Association between dynamic hyperinflation and emphysema ...
The impact of homogeneous versus heterogeneous emphysema on dynamic hyperinflation in patients with severe COPD assessed for lung volume reductionRunning title: Dynamic hyperinflation and emphysema patternAfroditi K. Boutou1, Zaid Zoumot1,2, Arjun Nair1, Claire Davey1, David M. Hansell1 , Athanasios Jamourtas3, Michael I. Polkey1, Nicholas S. Hopkinson1 1NIHR Biomedical Research Unit at Royal Brompton and Harefield NHS Foundation Trust and Imperial College, London U.K.2Respiratory and Critical Care Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE.3Department of Sports Education and Physical Science, University of Thessaly, Trikala, Greece Corresponding author: Dr Nicholas S HopkinsonNIHR Respiratory Biomedical Research Unit at Royal Brompton and Harefield NHS Foundation Trust and Imperial College London.Royal Brompton Hospital, Fulham Rd, London, UK SW3 6NP n.hopkinson@ic.ac.uk +44 2073497775Keywords: Chronic Obstructive Pulmonary Disease; Dynamic Hyperinflation; Heterogeneous emphysema;Homogeneous emphysema;Cardiopulmonary Exercise TestingAbstractDynamic hyperinflation (DH) is a pathophysiologic hallmark of Chronic Obstructive Pulmonary Disease (COPD). The aim of this study was to investigate the impact of emphysema distribution on DH during a maximal cardiopulmonary exercise testing (CPET) in patients with severe COPD.This was a retrospective analysis of prospectively collected data among severe COPD patients who underwent thoracic high-resolution computed tomography, full lung function measurements and maximal CPET with inspiratory manouvers as assessment for a lung volume reduction procedure. ΔIC was calculated by subtracting the end-exercise inspiratory capacity (eIC) from resting IC (rIC) and expressed as a percentage of rIC (ΔIC %). Emphysema quantification was conducted at 3 predefined levels using the syngo PULMO-CT (Siemens AG); a difference >25% between best and worse slice was defined as heterogeneous emphysema. Fifty patients with heterogeneous (62.7% male; 60.9±7.5 years old; FEV1%=32.4±11.4) and 14 with homogeneous emphysema (61.5% male; 62.5±5.9 years old; FEV1%=28.1±10.3) fulfilled the enrolment criteria. The groups were matched for all baseline variables. ΔIC% was significantly higher in homogeneous emphysema (39.8%±9.8% vs.31.2%±13%, p=0.031), while no other CPET parameter differed between the groups. Upper lobe predominance of emphysema correlated positively with peak oxygen pulse, peak oxygen uptake and peak respiratory rate, and negatively with ΔIC%.Homogeneous emphysema is associated with more DH during maximum exercise in COPD patients.IntroductionExpiratory flow limitation is the pathophysiologic hallmark of Chronic Obstructive Pulmonary Disease (COPD). One of the consequences of airflow limitation and permanent parenchymal destruction is lung hyperinflation. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"ExmyfyeV","properties":{"formattedCitation":"(1)","plainCitation":"(1)"},"citationItems":[{"id":724,"uris":[""],"uri":[""],"itemData":{"id":724,"type":"article-journal","title":"Why does the lung hyperinflate?","container-title":"Proceedings of the American Thoracic Society","page":"176-179","volume":"3","issue":"2","source":"NCBI PubMed","abstract":"Patients with chronic obstructive pulmonary disease (COPD) often have some degree of hyperinflation of the lungs. Hyperinflated lungs can produce significant detrimental effects on breathing, as highlighted by improvements in patient symptoms after lung volume reduction surgery. Measures of lung volumes correlate better with impairment of patient functional capabilities than do measures of airflow. Understanding the mechanisms by which hyperinflation occurs in COPD provides better insight into how treatments can improve patients' health. Both static and dynamic processes can contribute to lung hyperinflation in COPD. Static hyperinflation is caused by a decrease in elasticity of the lung due to emphysema. The lungs exert less recoil pressure to counter the recoil pressure of the chest wall, resulting in an equilibrium of recoil forces at a higher resting volume than normal. Dynamic hyperinflation is more common and can occur independent of or in addition to static hyperinflation. It results from air being trapped within the lungs after each breath due to a disequilibrium between the volumes inhaled and exhaled. The ability to fully exhale depends on the degree of airflow limitation and the time available for exhalation. These can both vary, causing greater hyperinflation during exacerbations or increased respiratory demand, such as during exercise. Reversibility of dynamic hyperinflation offers the possibility for intervention. Use of bronchodilators with prolonged durations of action, such as tiotropium, can sustain significant reductions in lung inflation similar in effect to lung volume reduction surgery. How efficacy of bronchodilators is assessed may, therefore, need to be reevaluated.","DOI":"10.1513/pats.200508-094DO","ISSN":"1546-3222","note":"PMID: 16565428","journalAbbreviation":"Proc Am Thorac Soc","language":"eng","author":[{"family":"Ferguson","given":"Gary T"}],"issued":{"date-parts":[["2006",4]]},"PMID":"16565428"}}],"schema":""} (1) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"yJUAZbbx","properties":{"formattedCitation":"(2)","plainCitation":"(2)"},"citationItems":[{"id":683,"uris":[""],"uri":[""],"itemData":{"id":683,"type":"article-journal","title":"Hyperinflation, dyspnea, and exercise intolerance in chronic obstructive pulmonary disease","container-title":"Proceedings of the American Thoracic Society","page":"180-184","volume":"3","issue":"2","source":"NCBI PubMed","abstract":"Expiratory flow limitation is the pathophysiologic hallmark of chronic obstructive pulmonary disease (COPD), but dyspnea (breathlessness) is its most prominent and distressing symptom. Acute dynamic lung hyperinflation, which refers to the temporary increase in operating lung volumes above their resting value, is a key mechanistic consequence of expiratory flow limitation, and has serious mechanical and sensory repercussions. It is associated with excessive loading and functional weakness of inspiratory muscles, and with restriction of normal VT expansion during exercise. There is a strong correlation between the intensity of dyspnea at a standardized point during exercise, the end-expiratory lung volume, and the increased ratio of inspiratory effort to volume displacement (i.e., esophageal pressure relative to maximum: Vt as a % of predicted VC). This increased effort-displacement ratio in COPD crudely reflects the neuromechanical dissociation of the respiratory system that arises as a result of hyperinflation. The corollary of this is that any intervention that reduces end-expiratory lung volume will improve effort-displacement ratios and alleviate dyspnea. In flow-limited patients, bronchodilators act by improving dynamic airway function, thus enhancing lung emptying and reducing lung hyperinflation. Long-acting bronchodilators have recently been shown to reduce hyperinflation during both rest and exercise in moderate to severe COPD. This lung deflation allows greater Vt expansion for a given inspiratory effort during exercise with consequent improvement in dyspnea and exercise endurance.","DOI":"10.1513/pats.200508-093DO","ISSN":"1546-3222","note":"PMID: 16565429","journalAbbreviation":"Proc Am Thorac Soc","language":"eng","author":[{"family":"O'Donnell","given":"Denis E"}],"issued":{"date-parts":[["2006",4]]},"PMID":"16565429"}}],"schema":""} (2) Static hyperinflation is due to the reduced elastic recoil of the lung. Dynamic hyperinflation (DH), which occurs independently or in addition to static hyperinflation, refers to the increase of lung volumes above their resting value that occurs with increases in respiratory rate due to expiratory flow limitation. It is associated both with excessive loading and mechanical disadvantage of inspiratory muscles and with restriction of normal tidal volume expansion during exercise. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"HFQ5FVIh","properties":{"formattedCitation":"(2)","plainCitation":"(2)"},"citationItems":[{"id":683,"uris":[""],"uri":[""],"itemData":{"id":683,"type":"article-journal","title":"Hyperinflation, dyspnea, and exercise intolerance in chronic obstructive pulmonary disease","container-title":"Proceedings of the American Thoracic Society","page":"180-184","volume":"3","issue":"2","source":"NCBI PubMed","abstract":"Expiratory flow limitation is the pathophysiologic hallmark of chronic obstructive pulmonary disease (COPD), but dyspnea (breathlessness) is its most prominent and distressing symptom. Acute dynamic lung hyperinflation, which refers to the temporary increase in operating lung volumes above their resting value, is a key mechanistic consequence of expiratory flow limitation, and has serious mechanical and sensory repercussions. It is associated with excessive loading and functional weakness of inspiratory muscles, and with restriction of normal VT expansion during exercise. There is a strong correlation between the intensity of dyspnea at a standardized point during exercise, the end-expiratory lung volume, and the increased ratio of inspiratory effort to volume displacement (i.e., esophageal pressure relative to maximum: Vt as a % of predicted VC). This increased effort-displacement ratio in COPD crudely reflects the neuromechanical dissociation of the respiratory system that arises as a result of hyperinflation. The corollary of this is that any intervention that reduces end-expiratory lung volume will improve effort-displacement ratios and alleviate dyspnea. In flow-limited patients, bronchodilators act by improving dynamic airway function, thus enhancing lung emptying and reducing lung hyperinflation. Long-acting bronchodilators have recently been shown to reduce hyperinflation during both rest and exercise in moderate to severe COPD. This lung deflation allows greater Vt expansion for a given inspiratory effort during exercise with consequent improvement in dyspnea and exercise endurance.","DOI":"10.1513/pats.200508-093DO","ISSN":"1546-3222","note":"PMID: 16565429","journalAbbreviation":"Proc Am Thorac Soc","language":"eng","author":[{"family":"O'Donnell","given":"Denis E"}],"issued":{"date-parts":[["2006",4]]},"PMID":"16565429"}}],"schema":""} (2) Previous studies have indicated that lung hyperinflation contributes significantly to exercise limitation, exertional dyspnoea and exercise desaturation in COPD patients. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"aGuGeSDC","properties":{"formattedCitation":"(3)","plainCitation":"(3)"},"citationItems":[{"id":1256,"uris":[""],"uri":[""],"itemData":{"id":1256,"type":"article-journal","title":"Dynamic hyperinflation is associated with a poor cardiovascular response to exercise in COPD patients","container-title":"Respiratory Research","page":"150","volume":"12","issue":"1","source":"PubMed Central","abstract":"Background\nPulmonary hyperinflation has the potential for significant adverse effects on cardiovascular function in COPD. The aim of this study was to investigate the relationship between dynamic hyperinflation and cardiovascular response to maximal exercise in COPD patients.\n\nMethods\nWe studied 48 patients (16F; age 68 yrs ± 8; BMI 26 ± 4) with COPD. All patients performed spirometry, plethysmography, lung diffusion capacity for carbon monoxide (TLco) measurement, and symptom-limited cardiopulmonary exercise test (CPET). The end-expiratory lung volume (EELV) was evaluated during the CPET. Cardiovascular response was assessed by change during exercise in oxygen pulse (ΔO2Pulse) and double product, i.e. the product of systolic blood pressure and heart rate (DP reserve), and by the oxygen uptake efficiency slope (OUES), i.e. the relation between oxygen uptake and ventilation.\n\nResults\nPatients with a peak exercise EELV (%TLC) ≥ 75% had a significantly lower resting FEV1/VC, FEF50/FIF50 ratio and IC/TLC ratio, when compared to patients with a peak exercise EELV (%TLC) < 75%. Dynamic hyperinflation was strictly associated to a poor cardiovascular response to exercise: EELV (%TLC) showed a negative correlation with ΔO2Pulse (r = - 0.476, p = 0.001), OUES (r = - 0.452, p = 0.001) and DP reserve (r = - 0.425, p = 0.004). Furthermore, according to the ROC curve method, ΔO2Pulse and DP reserve cut-off points which maximized sensitivity and specificity, with respect to a EELV (% TLC) value ≥ 75% as a threshold value, were ≤ 5.5 mL/bpm (0.640 sensitivity and 0.696 specificity) and ≤ 10,000 Hg · bpm (0.720 sensitivity and 0.783 specificity), respectively.\n\nConclusion\nThe present study shows that COPD patients with dynamic hyperinflation have a poor cardiovascular response to exercise. This finding supports the view that in COPD patients, dynamic hyperinflation may affect exercise performance not only by affecting ventilation, but also cardiac function.","DOI":"10.1186/1465-9921-12-150","ISSN":"1465-9921","note":"PMID: 22074289\nPMCID: PMC3225311","journalAbbreviation":"Respir Res","author":[{"family":"Tzani","given":"Panagiota"},{"family":"Aiello","given":"Marina"},{"family":"Elia","given":"Davide"},{"family":"Boracchia","given":"Luca"},{"family":"Marangio","given":"Emilio"},{"family":"Olivieri","given":"Dario"},{"family":"Clini","given":"Enrico"},{"family":"Chetta","given":"Alfredo"}],"issued":{"date-parts":[["2011"]]},"accessed":{"date-parts":[["2014",4,13]]},"PMID":"22074289","PMCID":"PMC3225311"}}],"schema":""} (3) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"phi86tao","properties":{"formattedCitation":"(4)","plainCitation":"(4)"},"citationItems":[{"id":726,"uris":[""],"uri":[""],"itemData":{"id":726,"type":"article-journal","title":"Dynamic hyperinflation correlates with exertional oxygen desaturation in patients with chronic obstructive pulmonary disease","container-title":"Lung","page":"177-182","volume":"191","issue":"2","source":"NCBI PubMed","abstract":"BACKGROUND: Dynamic hyperinflation (DH) causes exercise limitation and exertional dyspnea in patients with chronic obstructive pulmonary disease (COPD). Exertional desaturation (ED) also occurs commonly in COPD but neither routine physiologic parameters nor imaging predict ED accurately. In this study we evaluated the relationship between DH and ED during 6-min walk testing (6MWT).\nMETHODS: We measured ED and DH in patients with stable COPD. SpO2 was measured by continuous pulse oximetry during 6MWT. ED was defined as a decline in SpO2 (ΔSpO2) ≥4?%. DH was determined by measuring inspiratory capacity (IC) before and after the 6MWT using a handheld spirometer. DH was defined as ΔIC >0.0?L. We correlated DH and ED with clinical and pulmonary physiologic variables by regression analysis, χ (2), and receiver operator curve (ROC) analysis.\nRESULTS: Thirty males [age?=?65?±?9.4?years, FEV1 % predicted?=?48?±?14?%, and DLCO % predicted?=?50?±?21?% (mean?±?SD)] were studied. ΔSpO2 correlated with ΔIC (r?=?0.49, p?=?0.005) and age (r?=?0.39, p?=?0.03) by univariate analysis; however, only ΔIC correlated on multivariate regression analysis (p?=?0.01). ΔSpO2 did not correlate with FEV1, FVC, FEF25-75, RV, DLCO % predicted, BMI, smoking, BORG score, or distance covered in 6MWT. DH strongly correlated with ED (p?=?0.001). On ROC analysis, DH had an area under the curve of 0.92 for the presence of ED (sensitivity?=?90?%; specificity?=?77?%, p?<?0.001).\nCONCLUSION: Routine pulmonary function test results and clinical variables did not correlate with ED in patients with stable COPD. Dynamic hyperinflation strongly correlates with exertional desaturation and could be a reason for this desaturation.","DOI":"10.1007/s00408-012-9443-3","ISSN":"1432-1750","note":"PMID: 23283384","journalAbbreviation":"Lung","language":"eng","author":[{"family":"Zafar","given":"Muhammad Ahsan"},{"family":"Tsuang","given":"Wayne"},{"family":"Lach","given":"Laura"},{"family":"Eschenbacher","given":"William"},{"family":"Panos","given":"Ralph J"}],"issued":{"date-parts":[["2013",4]]},"PMID":"23283384"}}],"schema":""} (4) Thoracic computed tomography (CT) allows precise assessment of emphysema extent and distribution ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"jCjFfgXB","properties":{"formattedCitation":"(5)","plainCitation":"(5)"},"citationItems":[{"id":748,"uris":[""],"uri":[""],"itemData":{"id":748,"type":"article-journal","title":"Quantitative chest tomography in COPD research: chairman's summary","container-title":"Proceedings of the American Thoracic Society","page":"874-877","volume":"5","issue":"9","source":"NCBI PubMed","DOI":"10.1513/pats.200810-118QC","ISSN":"1546-3222","note":"PMID: 19137669 \nPMCID: PMC2720105","shortTitle":"Quantitative chest tomography in COPD research","journalAbbreviation":"Proc Am Thorac Soc","language":"eng","author":[{"family":"Coxson","given":"Harvey O"}],"issued":{"date-parts":[["2008",12,15]]},"PMID":"19137669","PMCID":"PMC2720105"}}],"schema":""} (5) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"s50tLyHD","properties":{"formattedCitation":"(6)","plainCitation":"(6)"},"citationItems":[{"id":743,"uris":[""],"uri":[""],"itemData":{"id":743,"type":"article-journal","title":"Densitometry for assessment of effect of lung volume reduction surgery for emphysema","container-title":"The European respiratory journal","page":"1138-1143","volume":"29","issue":"6","source":"NCBI PubMed","abstract":"To explore if change in the extent of emphysema correlated with change in lung function, the effect of resection of emphysematous tissue was studied by computed tomography (CT) densitometry. In addition, the current authors studied how surgery-induced change in emphysema related to lung density in control subjects. In total, 30 patients (14 females; mean+/-sd age 59+/-10 yrs) with severe emphysema before and 3 months after lung volume reduction surgery (LVRS), 48 patients with moderate emphysema and 76 control subjects were investigated. Lung density (15th percentile point) of both lungs and heterogeneity of lung density between 12 isovolumetric partitions in each lung were calculated from chest CT images. The 15th percentile point and its heterogeneity could distinguish controls from subjects with moderate emphysema with a sensitivity and specificity of >95%. LVRS significantly increased lung density by 5.0+/-10.9 g.L(-1) (n=30). Improvement in the diffusing capacity of the lung for carbon monoxide and in residual volume significantly correlated with an increase in lung density (n=20 and 28, respectively). Change in forced expiratory volume in one second did not correlate with change in lung density. In conclusion, lung density 15th percentile point is a valuable surrogate marker for detection of both the extent of and reduction in emphysema.","DOI":"10.1183/09031936.00056206","ISSN":"0903-1936","note":"PMID: 17331971","journalAbbreviation":"Eur. Respir. J.","language":"eng","author":[{"family":"Stolk","given":"J"},{"family":"Versteegh","given":"M I M"},{"family":"Montenij","given":"L J"},{"family":"Bakker","given":"M E"},{"family":"Grebski","given":"E"},{"family":"Tutic","given":"M"},{"family":"Wildermuth","given":"S"},{"family":"Weder","given":"W"},{"family":"el Bardiji","given":"M"},{"family":"Reiber","given":"J H C"},{"family":"Rabe","given":"K F"},{"family":"Russi","given":"E W"},{"family":"Stoel","given":"B C"}],"issued":{"date-parts":[["2007",6]]},"PMID":"17331971"}}],"schema":""} (6) and correlation of these parameters with functional and pathologic data. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"c9fAEX0M","properties":{"formattedCitation":"(7)","plainCitation":"(7)"},"citationItems":[{"id":766,"uris":[""],"uri":[""],"itemData":{"id":766,"type":"article-journal","title":"Lung CT density correlates with measurements of airflow limitation and the diffusing capacity","container-title":"The European respiratory journal","page":"141-146","volume":"4","issue":"2","source":"NCBI PubMed","abstract":"We studied 80 subjects (63 M, 17 F; 23-82 yrs) and related lung computerized tomography (CT) density with age, height, spirometry, lung volumes, diffusing capacity and arterial blood gas tensions. These subjects demonstrated a wide range of physiological impairment (forced expiratory volume in one second (FEV1) 8-116% predicted; diffusing capacity (Kco) 15-139% predicted; arterial oxygen tension (Pao2) 38-91 mmHg). They ranged from normal subjects to patients with chronic respiratory failure. Lung density was derived from CT density histograms measured as both mean Emergency Medical Information (EMI) number (EMI scale: 0 = water, -500 = air, EMI number of normal lung tissue range approximately -200 to -450) and the lowest 5th percentile EMI number, the latter value being more likely to represent the density of lung parenchyma. Lung CT density correlated most strongly with airflow obstruction (EMI 5th percentile versus FEV1/forced vital capacity (FVC) % predicted, r = 0.73, p less than 0.001) and diffusing capacity (EMI 5th percentile versus Kco, r = 0.77, p less than 0.001). This suggests that reduction in lung density, which reflects loss of the surface area of the distal airspaces, is a major index of respiratory function in patients with smoking related chronic obstructive pulmonary disease (COPD). These data provide no indication of other factors such as small and large airways disease, and loss of elastic recoil, which may contribute to airflow limitation, or disruption of the pulmonary vascular bed which may also affect CT lung density.","ISSN":"0903-1936","note":"PMID: 2044729","journalAbbreviation":"Eur. Respir. J.","language":"eng","author":[{"family":"Gould","given":"G A"},{"family":"Redpath","given":"A T"},{"family":"Ryan","given":"M"},{"family":"Warren","given":"P M"},{"family":"Best","given":"J J"},{"family":"Flenley","given":"D C"},{"family":"MacNee","given":"W"}],"issued":{"date-parts":[["1991",2]]},"PMID":"2044729"}}],"schema":""} (7) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"5UZGnAhj","properties":{"formattedCitation":"(8)","plainCitation":"(8)"},"citationItems":[{"id":768,"uris":[""],"uri":[""],"itemData":{"id":768,"type":"article-journal","title":"\"Density mask\". An objective method to quantitate emphysema using computed tomography","container-title":"Chest","page":"782-787","volume":"94","issue":"4","source":"NCBI PubMed","abstract":"We used a computed tomography (CT) scanner program (\"density mask\") that highlights voxels within a given density range to quantitate emphysema by defining areas of abnormally low attenuation. We compared different density masks, mean lung attenuation, visual assessment of emphysema and the pathologic grade of emphysema in 28 patients undergoing lung resection for tumor. In each patient, a single representative CT image was compared with corresponding pathologic specimens of tissue. There was good correlation between the extent of emphysema as assessed by the density mask and the pathologic grade of emphysema. The optimal attenuation level to define areas of emphysema may vary in different scanners, but, once determined for a particular scanner, the density mask accurately assesses the extent of emphysema and eliminates interobserver and intraobserver variability. It has the added advantage of determining the exact percentage of lung parenchyma showing changes consistent with emphysema.","ISSN":"0012-3692","note":"PMID: 3168574","journalAbbreviation":"Chest","language":"eng","author":[{"family":"Müller","given":"N L"},{"family":"Staples","given":"C A"},{"family":"Miller","given":"R R"},{"family":"Abboud","given":"R T"}],"issued":{"date-parts":[["1988",10]]},"PMID":"3168574"}}],"schema":""} (8)The distribution of parenchymal damage varies widely between individuals ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"QjLX0ZNT","properties":{"formattedCitation":"(9)","plainCitation":"(9)"},"citationItems":[{"id":737,"uris":[""],"uri":[""],"itemData":{"id":737,"type":"article-journal","title":"Computed tomographic emphysema distribution: relationship to clinical features in a cohort of smokers","container-title":"European Respiratory Journal","page":"536-542","volume":"33","issue":"3","source":"erj.","abstract":"Computed tomography (CT) scanning allows precise assessment of both the extent and distribution of emphysema. There has been little work on the relationship between the distribution of emphysema and clinical features of the disease. The current study investigated the association between clinical features and distribution of emphysema.\nA total of 129 patients with smoking-related chronic obstructive pulmonary disease underwent CT assessment of the extent and distribution of their emphysema (core/rind and upper/lower zone predominance).\nEmphysema was found predominantly in the upper/core zone and this distribution was related to the extent of disease. Core predominance was associated with lower forced expiratory volume in one second (FEV1), FEV1/forced vital capacity ratio and body mass index (BMI); and with higher BODE (BMI, airflow obstruction, dyspnoea and exercise capacity) index and Medical Research Council dyspnoea score. Upper-zone predominance was associated with female sex and an increased total St George’s Respiratory Questionnaire score. Using multiple linear regression age, sex and whole lung emphysema severity were independently associated with core/rind distribution, while sex and whole lung emphysema severity were independently related to upper/lower distribution.\nDistribution of emphysema related best to clinical features when divided into core/rind predominance. However, the effects were not independent of the extent of emphysema. Increased age and female sex were related to disease distribution independent of emphysema severity. These findings may be related to differences in development of emphysema.","DOI":"10.1183/09031936.00111808","ISSN":"0903-1936, 1399-3003","note":"PMID: 18829675","shortTitle":"Computed tomographic emphysema distribution","journalAbbreviation":"Eur Respir J","language":"en","author":[{"family":"Mair","given":"G."},{"family":"Miller","given":"J. J."},{"family":"McAllister","given":"D."},{"family":"Maclay","given":"J."},{"family":"Connell","given":"M."},{"family":"Murchison","given":"J. T."},{"family":"MacNee","given":"W."}],"issued":{"date-parts":[["2009",3,1]]},"accessed":{"date-parts":[["2014",3,12]]},"PMID":"18829675"}}],"schema":""} (9) and, its categorization in homogeneous and heterogeneous emphysema is of clinical significance, since it guides selection for surgical and bronchoscopic procedures of lung volume reduction (LVR). ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"055bOnyq","properties":{"formattedCitation":"(10)","plainCitation":"(10)"},"citationItems":[{"id":1415,"uris":[""],"uri":[""],"itemData":{"id":1415,"type":"article-journal","title":"Bronchoscopic and Percutaneous Approaches to Lung Volume Reduction:","container-title":"Clinical Pulmonary Medicine","page":"300-308","volume":"20","issue":"6","source":"CrossRef","DOI":"10.1097/CPM.0000000000000007","ISSN":"1068-0640","shortTitle":"Bronchoscopic and Percutaneous Approaches to Lung Volume Reduction","language":"en","author":[{"family":"McNulty","given":"William"},{"family":"Zoumot","given":"Zaid"},{"family":"Hopkinson","given":"Nicholas S."}],"issued":{"date-parts":[["2013",11]]},"accessed":{"date-parts":[["2014",5,14]]}}}],"schema":""} (10) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"ZWO3zQ2Y","properties":{"formattedCitation":"(11)","plainCitation":"(11)"},"citationItems":[{"id":1413,"uris":[""],"uri":[""],"itemData":{"id":1413,"type":"article-journal","title":"Noninvasive ventilation and lung volume reduction","container-title":"Clinics in chest medicine","page":"251-269","volume":"35","issue":"1","source":"NCBI PubMed","abstract":"As parenchymal lung disease in chronic obstructive pulmonary disease becomes increasingly severe there is a diminishing prospect of drug therapies conferring clinically useful benefit. Lung volume reduction surgery is effective in patients with heterogenous upper zone emphysema and reduced exercise tolerance, and is probably underused. Rapid progress is being made in nonsurgical approaches to lung volume reduction, but use outside specialized centers cannot be recommended presently. Noninvasive ventilation given to patients with acute hypercapnic exacerbation of chronic obstructive pulmonary disease reduces mortality and morbidity, but the place of chronic non-invasive ventilatory support remains more controversial.","DOI":"10.1016/m.2013.10.011","ISSN":"1557-8216","note":"PMID: 24507850","journalAbbreviation":"Clin. Chest Med.","language":"eng","author":[{"family":"Murphy","given":"Patrick Brian"},{"family":"Zoumot","given":"Zaid"},{"family":"Polkey","given":"Michael Iain"}],"issued":{"date-parts":[["2014",3]]},"PMID":"24507850"}}],"schema":""} (11) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"DPuNAbnJ","properties":{"formattedCitation":"(12)","plainCitation":"(12)"},"citationItems":[{"id":750,"uris":[""],"uri":[""],"itemData":{"id":750,"type":"article-journal","title":"National Emphysema Treatment Trial redux: accentuating the positive","container-title":"The Journal of thoracic and cardiovascular surgery","page":"564-572","volume":"140","issue":"3","source":"NCBI PubMed","abstract":"OBJECTIVE: Under the Freedom of Information Act, we obtained the follow-up data of the National Emphysema Treatment Trial (NETT) to determine the long-term outcome for \"a heterogeneous distribution of emphysema with upper lobe predominance,\" postulated by the NETT hypothesis to be optimal candidates for lung volume reduction surgery.\nMETHODS: Using the NETT database, we identified patients with heterogeneous distribution of emphysema with upper lobe predominance and analyzed for the first time follow-up data for those receiving lung volume reduction surgery and those receiving medical management. Furthermore, we compared the results of the NETT reduction surgery group with a previously reported consecutive case series of 250 patients undergoing bilateral lung volume reduction surgery using similar selection criteria.\nRESULTS: Of the 1218 patients enrolled, 511 (42%) conformed to the NETT hypothesis selection criteria and received the randomly assigned surgical or medical treatment (surgical = 261; medical = 250). Lung volume reduction surgery resulted in a 5-year survival benefit (70% vs 60%; P = .02). Results at 3 years compared with baseline data favored surgical reduction in terms of residual volume reduction (25% vs 2%; P < .001), University of California San Diego dyspnea score (16 vs 0 points; P < .001), and improved St George Respiratory Questionnaire quality of life score (12 points vs 0 points; P < .001). For the 513 patients with a homogeneous pattern of emphysema randomized to surgical or medical treatment, lung volume reduction surgery produced no survival advantage and very limited functional benefit.\nCONCLUSIONS: Patients most likely to benefit from lung volume reduction surgery have heterogeneously distributed emphysema involving the upper lung zones predominantly. Such patients in the NETT trial had results nearly identical to those previously reported in a nonrandomized series of similar patients undergoing lung volume reduction surgery.","DOI":"10.1016/j.jtcvs.2010.03.050","ISSN":"1097-685X","note":"PMID: 20723727","shortTitle":"National Emphysema Treatment Trial redux","journalAbbreviation":"J. Thorac. Cardiovasc. Surg.","language":"eng","author":[{"family":"Sanchez","given":"Pablo Gerardo"},{"family":"Kucharczuk","given":"John Charles"},{"family":"Su","given":"Stacey"},{"family":"Kaiser","given":"Larry Robert"},{"family":"Cooper","given":"Joel David"}],"issued":{"date-parts":[["2010",9]]},"PMID":"20723727"}}],"schema":""} (12) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"JcCI0eev","properties":{"formattedCitation":"(13)","plainCitation":"(13)"},"citationItems":[{"id":756,"uris":[""],"uri":[""],"itemData":{"id":756,"type":"article-journal","title":"Patient selection criteria for lung volume reduction surgery","container-title":"The Journal of thoracic and cardiovascular surgery","page":"957-964; discussion 964-967","volume":"114","issue":"6","source":"NCBI PubMed","abstract":"OBJECTIVE: Our intent was to refine the patient selection criteria for lung volume reduction surgery because various centers have different criteria and not all patients benefit from the procedure.\nMETHODS: Patient information, x-ray results, arterial blood gases, and plethysmographic pulmonary function tests in 154 consecutive patients who underwent bilateral thoracoscopic staple lung volume reduction surgery were compared with clinical outcome (change in forced expiratory volume in 1 second and dyspnea scale) with t tests and analysis of variance.\nRESULTS: Three hundred thirty-three of 487 (69%) patients evaluated for lung volume reduction surgery were rejected for lack of heterogeneous emphysema (n = 212), medical contraindications (n = 88), hypercapnia (n = 20), uncontrolled anxiety or depression (n = 10), or pulmonary hypertension (n = 1). Two patients died during the evaluation process. When tested by analysis of variance, there was no difference in clinical outcome associated with preoperative forced expiratory volume in 1 second, residual volume, total lung capacity, single-breath diffusing, and arterial oxygen or carbon dioxide tension. All patients selected for the operation had a heterogeneous pattern of emphysema. The upper lobe heterogeneous pattern of emphysema on chest computed tomography and lung perfusion scan was strongly associated with improved outcome with a mean (95% confidence interval) improvement in forced expiratory volume in 1 second of 73.2% (63.3 to 83.1) for the upper lobe compared with a mean (95% confidence interval) improvement of 37.9% (22.9 to 53.0) for the lower lobe or diffuse pattern of emphysema.\nCONCLUSION: The most important selection criteria for lung volume reduction surgery is the presence of a bilateral upper lobe heterogeneous pattern of emphysema on chest computed tomography and lung perfusion scan. After patients have been selected on the basis of a heterogeneous pattern of emphysema, clinical factors and physiology are not associated with clinical outcome well enough to further refine patient selection criteria. These results do not support the arbitrary patient selection criteria for lung volume reduction surgery reported in the literature.","ISSN":"0022-5223","note":"PMID: 9434691","journalAbbreviation":"J. Thorac. Cardiovasc. Surg.","language":"eng","author":[{"family":"McKenna","given":"R J, Jr"},{"family":"Brenner","given":"M"},{"family":"Fischel","given":"R J"},{"family":"Singh","given":"N"},{"family":"Yoong","given":"B"},{"family":"Gelb","given":"A F"},{"family":"Osann","given":"K E"}],"issued":{"date-parts":[["1997",12]]},"PMID":"9434691"}}],"schema":""} (13) Although there are some data regarding the association between emphysema distribution, clinical features and resting lung function values in COPD patients of various severities, ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"ioCszxUZ","properties":{"formattedCitation":"(9)","plainCitation":"(9)"},"citationItems":[{"id":737,"uris":[""],"uri":[""],"itemData":{"id":737,"type":"article-journal","title":"Computed tomographic emphysema distribution: relationship to clinical features in a cohort of smokers","container-title":"European Respiratory Journal","page":"536-542","volume":"33","issue":"3","source":"erj.","abstract":"Computed tomography (CT) scanning allows precise assessment of both the extent and distribution of emphysema. There has been little work on the relationship between the distribution of emphysema and clinical features of the disease. The current study investigated the association between clinical features and distribution of emphysema.\nA total of 129 patients with smoking-related chronic obstructive pulmonary disease underwent CT assessment of the extent and distribution of their emphysema (core/rind and upper/lower zone predominance).\nEmphysema was found predominantly in the upper/core zone and this distribution was related to the extent of disease. Core predominance was associated with lower forced expiratory volume in one second (FEV1), FEV1/forced vital capacity ratio and body mass index (BMI); and with higher BODE (BMI, airflow obstruction, dyspnoea and exercise capacity) index and Medical Research Council dyspnoea score. Upper-zone predominance was associated with female sex and an increased total St George’s Respiratory Questionnaire score. Using multiple linear regression age, sex and whole lung emphysema severity were independently associated with core/rind distribution, while sex and whole lung emphysema severity were independently related to upper/lower distribution.\nDistribution of emphysema related best to clinical features when divided into core/rind predominance. However, the effects were not independent of the extent of emphysema. Increased age and female sex were related to disease distribution independent of emphysema severity. These findings may be related to differences in development of emphysema.","DOI":"10.1183/09031936.00111808","ISSN":"0903-1936, 1399-3003","note":"PMID: 18829675","shortTitle":"Computed tomographic emphysema distribution","journalAbbreviation":"Eur Respir J","language":"en","author":[{"family":"Mair","given":"G."},{"family":"Miller","given":"J. J."},{"family":"McAllister","given":"D."},{"family":"Maclay","given":"J."},{"family":"Connell","given":"M."},{"family":"Murchison","given":"J. T."},{"family":"MacNee","given":"W."}],"issued":{"date-parts":[["2009",3,1]]},"accessed":{"date-parts":[["2014",3,12]]},"PMID":"18829675"}}],"schema":""} (9) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"u50FYUjH","properties":{"formattedCitation":"(14)","plainCitation":"(14)"},"citationItems":[{"id":741,"uris":[""],"uri":[""],"itemData":{"id":741,"type":"article-journal","title":"Emphysema presence, severity, and distribution has little impact on the clinical presentation of a cohort of patients with mild to moderate COPD","container-title":"Chest","page":"36-42","volume":"139","issue":"1","source":"NCBI PubMed","abstract":"BACKGROUND: Phenotypic characterization of patients with COPD may have potential prognostic and therapeutic implications. Available information on the relationship between emphysema and the clinical presentation in patients with COPD is limited to advanced stages of the disease. The objective of this study was to describe emphysema presence, severity, and distribution and its impact on clinical presentation of patients with mild to moderate COPD.\nMETHODS: One hundred fifteen patients with COPD underwent clinical and chest CT scan evaluation for the presence, severity, and distribution of emphysema. Patients with and without emphysema and with different forms of emphysema distribution (upper/lower/core/peel) were compared. The impact of emphysema severity and distribution on clinical presentation was determined.\nRESULTS: Fifty percent of the patients had mild homogeneously distributed emphysema (1.84; 0.76%-4.77%). Upper and core zones had the more severe degree of emphysema. Patients with emphysema were older, more frequently men, and had lower FEV(1)%, higher total lung capacity percentage, and lower diffusing capacity of the lung for carbon monoxide. No differences were found between the clinical or physiologic parameters of the different emphysema distributions.\nCONCLUSIONS: In patients with mild to moderate COPD, although the presence of emphysema has an impact on physiologic presentation, its severity and distribution seem to have little impact on clinical presentation.","DOI":"10.1378/chest.10-0984","ISSN":"1931-3543","note":"PMID: 20705800","journalAbbreviation":"Chest","language":"eng","author":[{"family":"de Torres","given":"Juan P"},{"family":"Bastarrika","given":"Gorka"},{"family":"Zagaceta","given":"Jorge"},{"family":"Sáiz-Mendiguren","given":"Ramón"},{"family":"Alcaide","given":"Ana B"},{"family":"Seijo","given":"Luis M"},{"family":"Montes","given":"Usua"},{"family":"Campo","given":"Arantza"},{"family":"Zulueta","given":"Javier J"}],"issued":{"date-parts":[["2011",1]]},"PMID":"20705800"}}],"schema":""} (14) no study has yet investigated the potential impact of emphysema distribution on DH among COPD patients.We therefore conducted a retrospective study in order to identify: a) differences in the degree of DH occurring during maximum cardiopulmonary exercise testing (CPET) between COPD patients with heterogeneous and matched COPD patients with homogeneous emphysema and b) associations between emphysema heterogeneity and CPET parameters in the two patient groups. The primary hypothesis was that patients with homogeneous emphysema hyperinflate more due to the diffuse distribution of the emphysematous lung tissue destruction.Material and MethodsStudy populationData were collected for COPD outpatients who had been assessed at the Respiratory Biomedical Research Unit of Royal Brompton Hospital between June 2009, and August, 2013 for potential eligibility to undergo a bronchoscopic lung volume reduction procedure. These included full lung function measurements, thoracic high resolution computed tomography (HRCT) and breath by breath data from maximal cycling CPET with inspiratory capacity manoeuvers every minute. The COPD patients were in stable clinical condition and optimally treated with combinations of β2-agonists, anticholinergic drugs and inhaled corticosteroids, according to guidelines. All patients had provided informed consent for their initial participation in the studies. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"E1hDiQHf","properties":{"formattedCitation":"(15)","plainCitation":"(15)"},"citationItems":[{"id":1299,"uris":[""],"uri":[""],"itemData":{"id":1299,"type":"article-journal","title":"Surgical approaches for lung volume reduction in emphysema","container-title":"Clinical medicine (London, England)","page":"122-127","volume":"14","issue":"2","source":"NCBI PubMed","abstract":"Lung volume reduction surgery (LVRS) for chronic obstructive pulmonary disease (COPD) is recommended in both British and international guidelines because trials have shown improvement in survival in selected patients with poor baseline exercise capacity and upper lobe-predominant emphysema. Despite this, few procedures are carried out, possibly because of historical concerns about high levels of morbidity and mortality associated with the operation. The authors reviewed data on lung volume reduction procedures at their institution between January 2000 and September 2012. There were no deaths within 90?days of unilateral LVRS (n = 81), bullectomy (n = 20) or intracavity drainage procedures (n = 14). These data suggest that concerns about surgical mortality should not discourage LVRS in selected patients with COPD, provided that it is undertaken within a multidisciplinary team environment involving appropriate patient selection.","DOI":"10.7861/clinmedicine.14-2-122","ISSN":"1470-2118","note":"PMID: 24715121","journalAbbreviation":"Clin Med","language":"eng","author":[{"family":"Clark","given":"Samuel J"},{"family":"Zoumot","given":"Zaid"},{"family":"Bamsey","given":"Olivia"},{"family":"Polkey","given":"Michael I"},{"family":"Dusmet","given":"Michael"},{"family":"Lim","given":"Eric"},{"family":"Jordan","given":"Simon"},{"family":"Hopkinson","given":"Nicholas S"}],"issued":{"date-parts":[["2014",4]]},"PMID":"24715121"}}],"schema":""} (15) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"4IZRBrb0","properties":{"formattedCitation":"(16)","plainCitation":"(16)"},"citationItems":[{"id":1297,"uris":[""],"uri":[""],"itemData":{"id":1297,"type":"article-journal","title":"Endobronchial coils for the treatment of severe emphysema with hyperinflation (RESET): a randomised controlled trial","container-title":"The lancet. Respiratory medicine","page":"233-240","volume":"1","issue":"3","source":"NCBI PubMed","abstract":"BACKGROUND: Few treatment options exist for patients with severe emphysema. We assessed the clinical benefits and safety of lung volume reduction coils (LVRCs) for the treatment of patients with severe emphysema with hyperinflation.\nMETHODS: In a randomised study, we recruited patients with severe emphysema (aged ≥35 years) from three centres in the UK. Using a computer-generated randomisation sequence, we randomly allocated patients in a one-to-one ratio (block sizes of four and stratified by centre) to either LVRC treatment (treatment group) or best medical care (usual care group). The primary endpoint was the difference in response in the St George's Respiratory Questionnaire (SGRQ) between treatment and usual care groups at 90 days after final treatment (by intention-to-treat analysis). The trial is registered with , number NCT01334307.\nFINDINGS: Between Jan 27, 2010, to Oct 25, 2011, we recruited and randomly allocated 47 patients: 23 to treatment and 24 to usual care (23 patients in each group were included in the intention-to-treat analysis). SGRQ response at 90 days after final treatment was greater in the treatment group than it was in the usual care group (between-group difference in change from baseline -8·36 points [95% CI -16·24 to -0·47]; p=0·04). We detected no between-group difference in serious adverse events.\nINTERPRETATION: Our findings suggest that treatment with endobronchial coils can improve quality of life for patients with severe emphysema and hyperinflation.\nFUNDING: PneumRx.","DOI":"10.1016/S2213-2600(13)70047-X","ISSN":"2213-2600","note":"PMID: 24429129","shortTitle":"Endobronchial coils for the treatment of severe emphysema with hyperinflation (RESET)","journalAbbreviation":"Lancet Respir Med","language":"eng","author":[{"family":"Shah","given":"Pallav L"},{"family":"Zoumot","given":"Zaid"},{"family":"Singh","given":"Suveer"},{"family":"Bicknell","given":"Stephen R"},{"family":"Ross","given":"Ewen T"},{"family":"Quiring","given":"John"},{"family":"Hopkinson","given":"Nicholas S"},{"family":"Kemp","given":"Samuel V"},{"family":"RESET trial Study Group","given":""}],"issued":{"date-parts":[["2013",5]]},"PMID":"24429129"}}],"schema":""} (16) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"75U7Jc89","properties":{"formattedCitation":"(17)","plainCitation":"(17)"},"citationItems":[{"id":1301,"uris":[""],"uri":[""],"itemData":{"id":1301,"type":"article-journal","title":"Bronchoscopic lung volume reduction with endobronchial valves for patients with heterogeneous emphysema and intact interlobar fissures (The BeLieVeR-HIFi trial): study design and rationale","container-title":"Thorax","source":"NCBI PubMed","abstract":"Although lung volume reduction surgery improves survival in selected patients with emphysema, there has been ongoing interest in developing and evaluating bronchoscopic approaches to try to reduce lung volumes with less morbidity and mortality. The placement of endobronchial valves is one such technique, and although some patients have had a significant improvement, responses have been inconsistent because collateral ventilation prevents lobar atelectasis. We describe the protocol of a trial (ISRCTN04761234) aimed to show that a responder phenotype, patients with heterogeneous emphysema and intact interlobar fissures on CT scanning, can be identified prospectively, leading to a consistent benefit in clinical practice.","DOI":"10.1136/thoraxjnl-2014-205127","ISSN":"1468-3296","note":"PMID: 24664535","shortTitle":"Bronchoscopic lung volume reduction with endobronchial valves for patients with heterogeneous emphysema and intact interlobar fissures (The BeLieVeR-HIFi trial)","journalAbbreviation":"Thorax","language":"ENG","author":[{"family":"Davey","given":"C"},{"family":"Zoumot","given":"Z"},{"family":"Jordan","given":"S"},{"family":"Carr","given":"D H"},{"family":"Polkey","given":"M I"},{"family":"Shah","given":"P L"},{"family":"Hopkinson","given":"N S"}],"issued":{"date-parts":[["2014",3,24]]},"PMID":"24664535"}}],"schema":""} (17) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"PQYcu4cU","properties":{"formattedCitation":"(18)","plainCitation":"(18)"},"citationItems":[{"id":1417,"uris":[""],"uri":[""],"itemData":{"id":1417,"type":"article-journal","title":"Bronchoscopic intrabullous autologous blood instillation: a novel approach for the treatment of giant bullae","container-title":"The Annals of thoracic surgery","page":"1488-1491","volume":"96","issue":"4","source":"NCBI PubMed","abstract":"The current standard therapy for patients with giant bullae is surgical bullectomy; however, high operative risk and comorbidities preclude surgical procedures in many patients. Autologous blood instilled directly into bullae can induce an inflammatory reaction, leading to scarring, fibrosis, and ultimately volume loss. We have treated 5 patients with this minimally invasive approach as day-case procedures using moderate sedation. Three of the 5 patients had shrinkage of the bullae, leading to large and clinically meaningful improvements in lung function, exercise capacity, and quality of life 3 months after treatment.","DOI":"10.1016/j.athoracsur.2013.03.108","ISSN":"1552-6259","note":"PMID: 24088475","shortTitle":"Bronchoscopic intrabullous autologous blood instillation","journalAbbreviation":"Ann. Thorac. Surg.","language":"eng","author":[{"family":"Zoumot","given":"Zaid"},{"family":"Kemp","given":"Samuel V"},{"family":"Caneja","given":"Cielito"},{"family":"Singh","given":"Suveer"},{"family":"Shah","given":"Pallav L"}],"issued":{"date-parts":[["2013",10]]},"PMID":"24088475"}}],"schema":""} (18) Study measurementsPulmonary Function TestingSpirometry, gas transfer and lung volumes measurements by body plethysmography were conducted using a Compact Lab System (Jaeger, Hoechberg, Germany). Arterialized capillary blood samples were used to measure arterial blood gases ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"3Z6iFd64","properties":{"formattedCitation":"(19)","plainCitation":"(19)"},"citationItems":[{"id":667,"uris":[""],"uri":[""],"itemData":{"id":667,"type":"article-journal","title":"Arterial versus capillary blood gases: a meta-analysis","container-title":"Respiratory physiology & neurobiology","page":"268-279","volume":"155","issue":"3","source":"NCBI PubMed","abstract":"A meta-analysis determined whether capillary blood gases accurately reflect arterial blood samples. A mixed effects model was used on 29 relevant studies obtained from a PubMed/Medline search. From 664 and 222 paired samples obtained from the earlobe and fingertip, respectively, earlobe compared to fingertip sampling shows that the standard deviation of the difference is about 2.5x less (or the precision is 2.5x better) in resembling arterial PO(2) over a wide range of arterial PO(2)'s (21-155 mm Hg ). The lower the arterial PO(2), the more accurate it is when predicting arterial PO(2) from any capillary sample (p<0.05). However, while earlobe sampling predicts arterial PO(2) (adjusted r(2)=0.88, mean bias=3.8 mm Hg compared to arterial), fingertip sampling does not (adjusted r(2)=0.48, mean bias=11.5 mm Hg compared to arterial). Earlobe sampling is slightly more accurate compared to fingertip sampling in resembling arterial PCO(2) (arterial versus earlobe, adjusted r(2)=0.94, mean bias=1.9 mm Hg ; arterial versus fingertip, adjusted r(2)=0.95, mean bias=2.2 mm Hg compared to arterial) but both sites can closely reflect arterial PCO(2) (880 total paired samples, range 10-114 mm Hg ). No real difference between sampling from the earlobe or fingertip were found for pH as both sites accurately reflect arterial pH over a wide range of pH (587 total paired samples, range 6.77-7.74, adjusted r(2)=0.90-0.94, mean bias=0.02). In conclusion, sampling blood from the fingertip or earlobe (preferably) accurately reflects arterial PCO(2) and pH over a wide range of values. Sampling blood, too, from earlobe (but never the fingertip) may be appropriate as a replacement for arterial PO(2), unless precision is required as the residual standard error is 6 mm Hg when predicting arterial PO(2) from an earlobe capillary sample.","DOI":"10.1016/j.resp.2006.07.002","ISSN":"1569-9048","note":"PMID: 16919507","shortTitle":"Arterial versus capillary blood gases","journalAbbreviation":"Respir Physiol Neurobiol","language":"eng","author":[{"family":"Zavorsky","given":"Gerald S"},{"family":"Cao","given":"Jiguo"},{"family":"Mayo","given":"Nancy E"},{"family":"Gabbay","given":"Rina"},{"family":"Murias","given":"Juan M"}],"issued":{"date-parts":[["2007",3,15]]},"PMID":"16919507"}}],"schema":""} (19). The European Coal and Steel Community predicted values were used for lung function measurements ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"uVJRt9yd","properties":{"formattedCitation":"(20)","plainCitation":"(20)"},"citationItems":[{"id":663,"uris":[""],"uri":[""],"itemData":{"id":663,"type":"article-journal","title":"Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society","container-title":"The European respiratory journal. Supplement","page":"5-40","volume":"16","source":"NCBI PubMed","ISSN":"0904-1850","note":"PMID: 8499054","journalAbbreviation":"Eur Respir J Suppl","language":"eng","author":[{"family":"Quanjer","given":"P H"},{"family":"Tammeling","given":"G J"},{"family":"Cotes","given":"J E"},{"family":"Pedersen","given":"O F"},{"family":"Peslin","given":"R"},{"family":"Yernault","given":"J C"}],"issued":{"date-parts":[["1993",3]]},"PMID":"8499054"}}],"schema":""} (20) and values of carbon monoxide diffusion capacity and transfer coefficient were adjusted for haemoglobin concentration (TLcoc and Kcoc, respectively). ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"3sPQdfuX","properties":{"formattedCitation":"(21)","plainCitation":"(21)"},"citationItems":[{"id":665,"uris":[""],"uri":[""],"itemData":{"id":665,"type":"article-journal","title":"Effect of blood transfusion on the carbon monoxide transfer factor of the lung in man","container-title":"Clinical science and molecular medicine","page":"627-631","volume":"54","issue":"6","source":"NCBI PubMed","abstract":"1. Ten studies were performed on nine patients with haematological disorders but with normal lungs, who required intermittent blood transfusions. The transfer factor for carbon monoxide and uptake of carbon monoxide per unit lung volume (KCO) were measured with the single breath technique before and at various intervals after transfusion. 2. The mean haemoglobin concentration increased from 7.7 to 11.1 g/dl. 3. The TLCO increased according to a formula based on the Roughton & Forster (1957) diffusion equations. TLCO (standardized) = TLCO (observed). (10.2 + Hb)/1.7 Hb, where haemoglobin (Hb) is expressed as g/dl. 4. The correlation between measured and predicted values was slightly better if changes in alveolar volume were taken into account, by using the KCO value.","ISSN":"0301-0538","note":"PMID: 657732","journalAbbreviation":"Clin Sci Mol Med","language":"eng","author":[{"family":"Clark","given":"E H"},{"family":"Woods","given":"R L"},{"family":"Hughes","given":"J M"}],"issued":{"date-parts":[["1978",6]]},"PMID":"657732"}}],"schema":""} (21) All pulmonary function testing (PFT) values used were measured prior to any bronchoscopic intervention and within a 6-month interval of both the HRCT and the maximal CPET. HRCT acquisition and interpretationImaging was performed for clinical indications on 4-slice multidetector CT (Volume Zoom, Siemens, Erlangen, Germany), or 64-slice CT (Somatom Sensation 64, Siemens, Erlangen, Germany). Images were either acquired at 10-mm intervals (4-slice CT) or using a volumetric acquisition (64-slice CT) in a supine position from the lung apices to the bases at full inspiration without the use of intravenous contrast. Images were reconstructed at thin section width (1.0mm to 1.5mm) using a high spatial resolution algorithm and reviewed on a workstation at appropriate window settings for viewing the lung parenchyma (window centre = ?500HU; window width = 1500HU).Images were transferred to a post-processing workstation (Leonardo, Siemens) and quantitative lung density analysis was performed using the Pulmo CT program (Siemens AG), which automatically segments the lung and calculates pixel attenuation coefficients as previously described ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"SyCziS3y","properties":{"formattedCitation":"(22)","plainCitation":"(22)"},"citationItems":[{"id":795,"uris":[""],"uri":[""],"itemData":{"id":795,"type":"article-journal","title":"Repeatability of quantitative CT indexes of emphysema in patients evaluated for lung volume reduction surgery","container-title":"Radiology","page":"448-454","volume":"220","issue":"2","source":"NCBI PubMed","abstract":"PURPOSE: To evaluate the repeatability of quantitative computed tomographic (CT) indexes of emphysema and the effect of spirometric gating of lung volume during CT in candidates for lung volume reduction surgery (LVRS).\nMATERIALS AND METHODS: Initial and same-day repeat routine inspiratory spiral chest CT studies were performed in 29 LVRS candidates (group 1, routine study vs repeat study). In a separate cohort of 29 LVRS candidates, spiral chest CT studies were performed both without and with spirometric gating by using a spirometer to trigger scanning at 90% of vital capacity (group 2, spirometric gating study). In each study, Pearson and intraclass correlation coefficients were calculated to determine the agreement between multiple pairs of whole-lung quantitative CT indexes of emphysema, and mean values were compared with two-tailed paired t tests.\nRESULTS: Pearson and intraclass correlation coefficients were high for all quantitative CT indexes (all > or = 0.92). No significant differences were found between mean values of quantitative CT indexes in group 1. Variation in quantitative CT results was small but more prominent in group 2 than in group 1. The variation in quantitative CT results was primarily related to differences in lung volume (r(2) as great as 0.83).\nCONCLUSION: Repeatability of quantitative CT test results in LVRS candidates is high and unlikely to improve by using spirometric gating.","DOI":"10.1148/radiology.220.2.r01au46448","ISSN":"0033-8419","note":"PMID: 11477250","journalAbbreviation":"Radiology","language":"eng","author":[{"family":"Gierada","given":"D S"},{"family":"Yusen","given":"R D"},{"family":"Pilgram","given":"T K"},{"family":"Crouch","given":"L"},{"family":"Slone","given":"R M"},{"family":"Bae","given":"K T"},{"family":"Lefrak","given":"S S"},{"family":"Cooper","given":"J D"}],"issued":{"date-parts":[["2001",8]]},"PMID":"11477250"}}],"schema":""} (22) with a minimum segmentation threshold of -1024HU. (Figure 1) Three representative slices of the lungs were analysed: (a) at the level where the superior border of the aortic arch appears; (b) at the level of the main carina, where clear separation of the right and left main bronchi becomes visible; and (c) at the lowest level where neither diaphragm nor any abdominal viscera are visible. At each level, the program provides a total emphysema index, defined as the percentage of whole lung with attenuation values below a threshold of -900 HU, as well as a severe emphysema index, defined as percentage of whole lung with attenuation values below a threshold of -950 HU. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"7RINs8tI","properties":{"formattedCitation":"(23)","plainCitation":"(23)"},"citationItems":[{"id":815,"uris":[""],"uri":[""],"itemData":{"id":815,"type":"article-journal","title":"Comparison of computed density and macroscopic morphometry in pulmonary emphysema","container-title":"American journal of respiratory and critical care medicine","page":"653-657","volume":"152","issue":"2","source":"NCBI PubMed","abstract":"High-resolution computed tomography (HRCT) scans were obtained at 1 cm intervals in 63 subjects referred for surgical resection of a cancer or for transplantation to find out whether the relative area of lung occupied by attenuation values lower than a threshold would be a measurement of macroscopic emphysema. Using a semiautomatic procedure, the relative areas occupied by attenuation values lower than eight thresholds ranging from -900 to -970 HU were calculated on the set of scans obtained through the lobe or the lung to be resected. The extent of emphysema was quantified by a computer-assisted method on horizontal paper-mounted lung sections obtained every 1 to 2 cm. The only level for which no statistically significant difference was found between the HRCT and the morphometric data was -950 HU. To determine the number of scans sufficient for an accurate quantification, we recalculated the relative area occupied by attenuation values lower than -950 HU on progressively fewer numbers of scans and investigated the departure from the results obtained with 1 cm intervals. Because of wide variations in this departure from patient to patient, a standard cannot be recommended as the optimal distance between scans.","DOI":"10.1164/ajrccm.152.2.7633722","ISSN":"1073-449X","note":"PMID: 7633722","journalAbbreviation":"Am. J. Respir. Crit. Care Med.","language":"eng","author":[{"family":"Gevenois","given":"P A"},{"family":"de Maertelaer","given":"V"},{"family":"De Vuyst","given":"P"},{"family":"Zanen","given":"J"},{"family":"Yernault","given":"J C"}],"issued":{"date-parts":[["1995",8]]},"PMID":"7633722"}}],"schema":""} (23) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"ZcwSCDaO","properties":{"formattedCitation":"(24)","plainCitation":"(24)"},"citationItems":[{"id":813,"uris":[""],"uri":[""],"itemData":{"id":813,"type":"article-journal","title":"Quantifying the extent of emphysema: factors associated with radiologists' estimations and quantitative indices of emphysema severity using the ECLIPSE cohort","container-title":"Academic radiology","page":"661-671","volume":"18","issue":"6","source":"NCBI PubMed","abstract":"RATIONALE AND OBJECTIVES: This study investigated what factors radiologists take into account when estimating emphysema severity and assessed quantitative computed tomography (CT) measurements of low attenuation areas.\nMATERIALS AND METHODS: CT scans and spirometry were obtained on 1519 chronic obstructive pulmonary disease (COPD) subjects, 269 smoker controls, and 184 nonsmoker controls from the Evaluation of COPD Longitudinally to Indentify Surrogate Endpoints (ECLIPSE) study. CT scans were analyzed using the threshold technique (%<-950HU) and a low attenuation cluster analysis. Two radiologists scored emphysema severity (0 to 5 scale), described the predominant type and distribution of emphysema, and the presence of suspected small airways disease.\nRESULTS: The percent low attenuation area (%LAA) and visual scores of emphysema severity correlated well (r = 0.77, P < .001). %LAA, low attenuation cluster analysis, and absence of radiologist described gas trapping, distribution, and predominant type of emphysema were predictors of visual scores of emphysema severity (all P < .001). CT scans scored as showing regions of gas trapping had smaller lesions for a similar %LAA than those without (P < .001).\nCONCLUSIONS: Visual estimates of emphysema are not only determined by the extent of LAA, but also by lesion size, predominant type, and distribution of emphysema and presence/absence of areas of small airways disease. A computer analysis of low attenuation cluster size helps quantitative algorithms discriminate low attenuation areas from gas trapping, image noise, and emphysema.","DOI":"10.1016/j.acra.2011.01.011","ISSN":"1878-4046","note":"PMID: 21393027","shortTitle":"Quantifying the extent of emphysema","journalAbbreviation":"Acad Radiol","language":"eng","author":[{"family":"Gietema","given":"Hester A"},{"family":"Müller","given":"Nestor L"},{"family":"Fauerbach","given":"Paola V Nasute"},{"family":"Sharma","given":"Sanjay"},{"family":"Edwards","given":"Lisa D"},{"family":"Camp","given":"Pat G"},{"family":"Coxson","given":"Harvey O"},{"family":"Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) investigators","given":""}],"issued":{"date-parts":[["2011",6]]},"PMID":"21393027"}}],"schema":""} (24) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"o8lG4tlo","properties":{"formattedCitation":"(25)","plainCitation":"(25)"},"citationItems":[{"id":811,"uris":[""],"uri":[""],"itemData":{"id":811,"type":"article-journal","title":"Optimal threshold in CT quantification of emphysema","container-title":"European radiology","page":"975-984","volume":"23","issue":"4","source":"NCBI PubMed","abstract":"OBJECTIVES: To determine the optimal threshold by quantitatively assessing the extent of emphysema at the level of the entire lung and at the level of individual lobes using a large, diverse dataset of computed tomography (CT) examinations.\nMETHODS: This study comprises 573 chest CT examinations acquired from subjects with different levels of airway obstruction (222 none, 83 mild, 141 moderate, 63 severe and 64 very severe). The extent of emphysema was quantified using the percentage of the low attenuation area (LAA%) divided by the total lung or lobe volume(s). The correlations between the extent of emphysema, and pulmonary functions and the five-category classification were assessed using Pearson and Spearman's correlation coefficients, respectively. When quantifying emphysema using a density mask, a wide range of thresholds from -850 to -1,000 HU were used.\nRESULTS: The highest correlations of LAA% with the five-category classification and PFT measures ranged from -925 to -965 HU for each individual lobe and the entire lung. However, the differences between the highest correlations and those obtained at -950 HU are relatively small.\nCONCLUSION: Although there are variations in the optimal cut-off thresholds for individual lobes, the single threshold of -950 HU is still an acceptable threshold for density-based emphysema quantification.","DOI":"10.1007/s00330-012-2683-z","ISSN":"1432-1084","note":"PMID: 23111815 \nPMCID: PMC3573224","journalAbbreviation":"Eur Radiol","language":"eng","author":[{"family":"Wang","given":"Zhimin"},{"family":"Gu","given":"Suicheng"},{"family":"Leader","given":"Joseph K"},{"family":"Kundu","given":"Shinjini"},{"family":"Tedrow","given":"John R"},{"family":"Sciurba","given":"Frank C"},{"family":"Gur","given":"David"},{"family":"Siegfried","given":"Jill M"},{"family":"Pu","given":"Jiantao"}],"issued":{"date-parts":[["2013",4]]},"PMID":"23111815","PMCID":"PMC3573224"}}],"schema":""} (25) An alternative threshold for emphysema definition of -960 HU has also previously been reported and we included this threshold as an additional quantitative parameter. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"FdAUgp8q","properties":{"formattedCitation":"(26)","plainCitation":"(26)"},"citationItems":[{"id":809,"uris":[""],"uri":[""],"itemData":{"id":809,"type":"article-journal","title":"Pulmonary emphysema: comparison of preoperative quantitative CT and physiologic index values with clinical outcome after lung-volume reduction surgery","container-title":"Radiology","page":"235-242","volume":"205","issue":"1","source":"NCBI PubMed","abstract":"PURPOSE: To compare quantitative computed tomographic (CT) and preoperative physiologic values in emphysema with outcome after lung-volume reduction surgery.\nMATERIALS AND METHODS: In 46 patients, emphysema was quantified by measuring lung attenuation on preoperative CT scans. Quantitative CT and preoperative physiologic values and postoperative outcomes (1-second forced expiratory volume, PaO2, and 6-minute walk distance) were compared.\nRESULTS: Moderately strong correlations were found between several quantitative CT and preoperative physiologic values (magnitude of r = .29-.58, P < .05) and several quantitative CT and outcome measures (magnitude of r = .31-.47, P < .05). With stratification, postoperative outcome was better with mean lung attenuation greater than -900 HU; 75% or greater of upper lung below -900 HU (emphysema index); greater than 25% of lung below -960 HU (severe emphysema index); ratio of upper- and lower-lung emphysema indexes 1.5 or greater; volume of normally attenuated lung (-850 to -701 HU) greater than 1 L; and full width at half maximum of attenuation-frequency distribution 80 HU or less. Differences in outcome measures between groups stratified with quantitative CT values were often two- to threefold; patients with greater numbers of favorable quantitative CT values had better outcome. Correlations between preoperative physiologic measures and outcome were few.\nCONCLUSION: In emphysema, quantitative CT values correlate with outcome. Quantitative assessment of emphysema in candidates for lung-volume reduction surgery is potentially useful.","DOI":"10.1148/radiology.205.1.9314991","ISSN":"0033-8419","note":"PMID: 9314991","shortTitle":"Pulmonary emphysema","journalAbbreviation":"Radiology","language":"eng","author":[{"family":"Gierada","given":"D S"},{"family":"Slone","given":"R M"},{"family":"Bae","given":"K T"},{"family":"Yusen","given":"R D"},{"family":"Lefrak","given":"S S"},{"family":"Cooper","given":"J D"}],"issued":{"date-parts":[["1997",10]]},"PMID":"9314991"}}],"schema":""} (26) To enable us to classify subjects as having either homogeneous or heterogeneous emphysema, we defined heterogeneous emphysema as a difference of >25% between the highest and lowest quantitative emphysema scores obtained, based on previous precedents of visual analysis. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"UzMquitA","properties":{"formattedCitation":"(27)","plainCitation":"(27)"},"citationItems":[{"id":817,"uris":[""],"uri":[""],"itemData":{"id":817,"type":"article-journal","title":"Patients at High Risk of Death after Lung-Volume–Reduction Surgery","container-title":"New England Journal of Medicine","page":"1075-1083","volume":"345","issue":"15","source":"Taylor and Francis+NEJM","abstract":"Lung-volume–reduction surgery is a potentially valuable treatment for patients with advanced emphysema.1–8 During the operation, 20 to 35 percent of the emphysematous lung is resected by means of either a median sternotomy or video-assisted thoracoscopy. Generally, lung function, exercise capacity, and the quality of life improve after surgery, but the results vary.9 The surgical mortality rate ranges from 4 to 15 percent,3 and one-year mortality rates are as high as 17 percent,10 although follow-up has often been incomplete.11 A review of Medicare claims showed that the six-month mortality rate was 16.9 percent.12 Uncertainty about the risk of lung-volume–reduction surgery, . . .","DOI":"10.1056/NEJMoa11798","ISSN":"0028-4793","note":"PMID: 11596586","issued":{"date-parts":[["2001"]]},"accessed":{"date-parts":[["2014",3,23]]},"PMID":"11596586"}}],"schema":""} (27)In addition, emphysema was treated as a continuous variable and specifically as a ratio of average ES of the upper and middle slice versus ES of the lower slice (UM/L) for both the 950 and 960 emphysema thresholds. A high ratio therefore represented upper lobe predominance.Maximal CPETPatients performed incremental symptom-limited CPET on a cycle ergometer (Jaeger Ergoline 800), under continuous monitoring of pulse oximetry (SaO2), heart rate (HR), and a 12-lead electrocardiogram. The test consisted of three minutes of rest, one minute of unloaded pedaling at 50-60 rpm, and then a ramp protocol with work rate (WR) increasing either 5 or 10 watts/minute, followed by 2 minutes of recovery. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"dUynUQ1F","properties":{"formattedCitation":"(28)","plainCitation":"(28)"},"citationItems":[{"id":676,"uris":[""],"uri":[""],"itemData":{"id":676,"type":"article-journal","title":"ATS/ACCP Statement on cardiopulmonary exercise testing","container-title":"American journal of respiratory and critical care medicine","page":"211-277","volume":"167","issue":"2","source":"NCBI PubMed","DOI":"10.1164/rccm.167.2.211","ISSN":"1073-449X","note":"PMID: 12524257","journalAbbreviation":"Am. J. Respir. Crit. Care Med.","language":"eng","author":[{"family":"American Thoracic Society","given":""},{"family":"American College of Chest Physicians","given":""}],"issued":{"date-parts":[["2003",1,15]]},"PMID":"12524257"}}],"schema":""} (28)Gas exchange values and exercise parameters were collected breath-by-breath using a Jaeger Oxycon system , ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"tTZextzi","properties":{"formattedCitation":"(29)","plainCitation":"(29)"},"citationItems":[{"id":672,"uris":[""],"uri":[""],"itemData":{"id":672,"type":"book","title":"Principles of Exercise Testing and Interpretation: Including Pathophysiology and Clinical Applications","publisher":"Lippincott Williams & Wilkins","number-of-pages":"620","source":"Google Books","abstract":"Thoroughly updated in its Fourth Edition, this exceptional resource is the most comprehensive, current text on the physiology and pathophysiology of exercise testing available. It is the only reference to address those disorders that can be diagnosed only through cardiopulmonary exercise testing. Readers will find... Comprehensive presentation addressing cardiovascular, metabolic, and respiratory responses to exercise—in both health and disease states. Principles and rationale behind exercise testing, commonly used testing protocols, guidelines for normal and abnormal values, and tips for accurate interpretation of test results. Normal test values for a range of patient groups—including children, over- and underweight patients, and the elderly. More than 80 case histories, each accompanied by exercise physiology results, highlight differential diagnosis by applying basic physiological concepts to real-world examples. Coverage of disorders that can be diagnosed only through cardiopulmonary exercise testing. NEW to the Fourth Edition... New chapter covering regulation of arterial and mixed venous blood gases New nine-panel graphic array illustrating critical aspects of exercise testing Updated flow charts to help with clinical interpretation and differential diagnosis","ISBN":"9780781748766","shortTitle":"Principles of Exercise Testing and Interpretation","language":"en","author":[{"family":"Wasserman","given":"Karlman"}],"issued":{"date-parts":[["2005"]]}}}],"schema":""} (29) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"ZVyOLCVM","properties":{"formattedCitation":"(30)","plainCitation":"(30)"},"citationItems":[{"id":674,"uris":[""],"uri":[""],"itemData":{"id":674,"type":"article-journal","title":"A new method for detecting anaerobic threshold by gas exchange","container-title":"Journal of applied physiology (Bethesda, Md.: 1985)","page":"2020-2027","volume":"60","issue":"6","source":"NCBI PubMed","abstract":"Excess CO2 is generated when lactate is increased during exercise because its [H+] is buffered primarily by HCO-3 (22 ml for each meq of lactic acid). We developed a method to detect the anaerobic threshold (AT), using computerized regression analysis of the slopes of the CO2 uptake (VCO2) vs. O2 uptake (VO2) plot, which detects the beginning of the excess CO2 output generated from the buffering of [H+], termed the V-slope method. From incremental exercise tests on 10 subjects, the point of excess CO2 output (AT) predicted closely the lactate and HCO-3 thresholds. The mean gas exchange AT was found to correspond to a small increment of lactate above the mathematically defined lactate threshold [0.50 +/- 0.34 (SD) meq/l] and not to differ significantly from the estimated HCO-3 threshold. The mean VO2 at AT computed by the V-slope analysis did not differ significantly from the mean value determined by a panel of six experienced reviewers using traditional visual methods, but the AT could be more reliably determined by the V-slope method. The respiratory compensation point, detected separately by examining the minute ventilation vs. VCO2 plot, was consistently higher than the AT (2.51 +/- 0.42 vs. 1.83 +/- 0.30 l/min of VO2). This method for determining the AT has significant advantages over others that depend on regular breathing pattern and respiratory chemosensitivity.","ISSN":"8750-7587","note":"PMID: 3087938","journalAbbreviation":"J. Appl. Physiol.","language":"eng","author":[{"family":"Beaver","given":"W L"},{"family":"Wasserman","given":"K"},{"family":"Whipp","given":"B J"}],"issued":{"date-parts":[["1986",6]]},"PMID":"3087938"}}],"schema":""} (30), allowing measurement of: tidal volume (Vt), respiratory rate (RR), oxygen uptake (VO2), carbon dioxide production (VCO2), end-tidal oxygen (PETO2) and end-tidal carbon dioxide (PETCO2). The anaerobic threshold (AT), oxygen pulse (VO2/HR), respiratory exchange ratio (RER), minute ventilation (VE) and the ventilatory equivalent for carbon dioxide at peak VO2 (VE/VCO2@VO2 peak) were also calculated, as previously described. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"Ca8osNPA","properties":{"formattedCitation":"(29)","plainCitation":"(29)"},"citationItems":[{"id":672,"uris":[""],"uri":[""],"itemData":{"id":672,"type":"book","title":"Principles of Exercise Testing and Interpretation: Including Pathophysiology and Clinical Applications","publisher":"Lippincott Williams & Wilkins","number-of-pages":"620","source":"Google Books","abstract":"Thoroughly updated in its Fourth Edition, this exceptional resource is the most comprehensive, current text on the physiology and pathophysiology of exercise testing available. It is the only reference to address those disorders that can be diagnosed only through cardiopulmonary exercise testing. Readers will find... Comprehensive presentation addressing cardiovascular, metabolic, and respiratory responses to exercise—in both health and disease states. Principles and rationale behind exercise testing, commonly used testing protocols, guidelines for normal and abnormal values, and tips for accurate interpretation of test results. Normal test values for a range of patient groups—including children, over- and underweight patients, and the elderly. More than 80 case histories, each accompanied by exercise physiology results, highlight differential diagnosis by applying basic physiological concepts to real-world examples. Coverage of disorders that can be diagnosed only through cardiopulmonary exercise testing. NEW to the Fourth Edition... New chapter covering regulation of arterial and mixed venous blood gases New nine-panel graphic array illustrating critical aspects of exercise testing Updated flow charts to help with clinical interpretation and differential diagnosis","ISBN":"9780781748766","shortTitle":"Principles of Exercise Testing and Interpretation","language":"en","author":[{"family":"Wasserman","given":"Karlman"}],"issued":{"date-parts":[["2005"]]}}}],"schema":""} (29)Each patient performed a total of four inspiratory capacity (IC) maneuvers at the beginning and after 1, 2, and 3 minutes of rest as previously described; ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"Dapi2OUL","properties":{"formattedCitation":"(31)","plainCitation":"(31)"},"citationItems":[{"id":669,"uris":[""],"uri":[""],"itemData":{"id":669,"type":"article-journal","title":"Inspiratory Capacity during Exercise: Measurement, Analysis, and Interpretation","container-title":"Pulmonary Medicine","volume":"2013","source":"","abstract":"Cardiopulmonary exercise testing (CPET) is an established method for evaluating dyspnea and ventilatory abnormalities. Ventilatory reserve is typically assessed as the ratio of peak exercise ventilation to maximal voluntary ventilation. Unfortunately, this crude assessment provides limited data on the factors that limit the normal ventilatory response to exercise. Additional measurements can provide a more comprehensive evaluation of respiratory mechanical constraints during CPET (e.g., expiratory flow limitation and operating lung volumes). These measurements are directly dependent on an accurate assessment of inspiratory capacity (IC) throughout rest and exercise. Despite the valuable insight that the IC provides, there are no established recommendations on how to perform the maneuver during exercise and how to analyze and interpret the data. Accordingly, the purpose of this manuscript is to comprehensively examine a number of methodological issues related to the measurement, analysis, and interpretation of the IC. We will also briefly discuss IC responses to exercise in health and disease and will consider how various therapeutic interventions influence the IC, particularly in patients with chronic obstructive pulmonary disease. Our main conclusion is that IC measurements are both reproducible and responsive to therapy and provide important information on the mechanisms of dyspnea and exercise limitation during CPET.","URL":"","DOI":"10.1155/2013/956081","ISSN":"2090-1836","shortTitle":"Inspiratory Capacity during Exercise","language":"en","author":[{"family":"Guenette","given":"Jordan A."},{"family":"Chin","given":"Roberto C."},{"family":"Cory","given":"Julia M."},{"family":"Webb","given":"Katherine A."},{"family":"O'Donnell","given":"Denis E."}],"issued":{"date-parts":[["2013",2,7]]},"accessed":{"date-parts":[["2014",2,23]]}}}],"schema":""} (31) resting IC (rIC) was calculated by averaging these values. End-exercise IC (eIC) was calculated by another inspiratory maneuver which was conducted during the last 30 seconds of peak exercise. ΔIC was utilized as a measure of DH and was calculated as rIC-eIC. For every patient, ΔIC was expressed as a percentage of rIC, that is: ΔIC%=(ΔIC/rIC) X100%. All exercise tests were performed before any bronchoscopic intervention took place and without oxygen supplementation.Statistical analysisStatistical analysis was conducted using the PASW (Predictive Analytics Software by SPSS Inc?) version 19 for Windows 2008. Distribution of values was assessed using the Shapiro-Wilk test of normality; continuous variables are described as mean±1 standard deviation or as median (minimum-maximum), accordingly. Group comparisons in PFTs, DH and exercise parameters were conducted utilizing either the independent samples t-test or the Mann-Whitney test, depending on the normality of their distribution. Pearson r or Spearman rho were used to describe parametric and non-parametric correlations between emphysema distribution indices, DH measures, and exercise parameters. Level of p<0.05 was considered significant.ResultsBaseline characteristicsSixty-four COPD patients (61.3±7.3 years old; FEV1 %predicted=31.5±11.2%, 61.8 male;) fulfilled the enrolment criteria and constituted the final study population. Fifty patients (78.1%) presented with heterogeneous and 14 patients (21.9%) with homogeneous emphysema (group Het and group Hom correspondingly). An initial attempt for patients in Hom group to match the same number of patients in Het group (1:1 matching) for age, FEV1 and TLcoc was made. However, the two patient groups (N1=14 patients in Hom group and N2=50 patients in Het group) were found to be already matched not only regarding these three selected variables, but also regarding gender, body mass index (BMI), rest pulmonary function testing variables (PFTs) and gas transfer parameters. Results were identical with the use of either emphysema threshold (-950 HU or -960 HU). The baseline demographic characteristics of the two groups are presented in Table 1.Exercise parametersExercise parameters for both groups are presented in Table 2. Dyspnoea was the reason for CPET termination for all patients, and the degree of breathlessness did not differ between groups. Only 15 patients (11 from Het group and 4 from Hom group) reached their AT during maximal CPET (data not shown); The rest terminated the exercise before reaching AT, due to respiratory reserve depletion.Patients in the Hom group displayed more DH during exercise, as ΔIC% was significantly higher among Hom group compared to Het group; 39.8% vs 31.2% (p=0.031). An additional analysis was undertaken, utilizing the change from rest to peak exercise values of End-Expiratory Lung Volume to Total lung capacity ratio (ΔEELV/TLC); Again, Hom group presented with significantly higher ratio, that is greater DH during exercise, compared to Het group (p=0.035). (Table 2) No other differences in CPET parameters were noted between the two groups (Table 2 and Table 3).Effect of upper lobe predominance of emphysema distribution The UM/L ratio of emphysema score for both the 950 and 960 emphysema thresholds was evaluated; a high ratio represents upper lobe predominance. As presented in Table 3, the UM/L ratio established a weak, inverse but significant correlation to ΔIC% for both emphysema thresholds (Spearman rho=-0.264, p=0.049; Spearman rho=-0.246, p=0.049, correspondingly). Moreover, peak VO2 %predicted, peak VO2/HR %predicted and peak RR were all positively correlated to UM/L ratio. (Table 3)DiscussionWe aimed to investigate whether the distribution of emphysema has any impact on dynamic lung volumes during exercise in patients with COPD. The primary hypothesis was confirmed; we found that patients with homogenous emphysema hyperinflated more than those with heterogeneous disease, although no differences in other exercise parameters were noted. Furthermore, a measure of upper lobe predominance (UM/L ratio) correlated inversely with DH, and positively with peak oxygen consumption, peak oxygen pulse and peak RR. Significance of findingsEmphysema distribution varies significantly among individuals and possibly represents different pathogenetic patterns of disease development. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"8GbAQKOW","properties":{"formattedCitation":"(9)","plainCitation":"(9)"},"citationItems":[{"id":737,"uris":[""],"uri":[""],"itemData":{"id":737,"type":"article-journal","title":"Computed tomographic emphysema distribution: relationship to clinical features in a cohort of smokers","container-title":"European Respiratory Journal","page":"536-542","volume":"33","issue":"3","source":"erj.","abstract":"Computed tomography (CT) scanning allows precise assessment of both the extent and distribution of emphysema. There has been little work on the relationship between the distribution of emphysema and clinical features of the disease. The current study investigated the association between clinical features and distribution of emphysema.\nA total of 129 patients with smoking-related chronic obstructive pulmonary disease underwent CT assessment of the extent and distribution of their emphysema (core/rind and upper/lower zone predominance).\nEmphysema was found predominantly in the upper/core zone and this distribution was related to the extent of disease. Core predominance was associated with lower forced expiratory volume in one second (FEV1), FEV1/forced vital capacity ratio and body mass index (BMI); and with higher BODE (BMI, airflow obstruction, dyspnoea and exercise capacity) index and Medical Research Council dyspnoea score. Upper-zone predominance was associated with female sex and an increased total St George’s Respiratory Questionnaire score. Using multiple linear regression age, sex and whole lung emphysema severity were independently associated with core/rind distribution, while sex and whole lung emphysema severity were independently related to upper/lower distribution.\nDistribution of emphysema related best to clinical features when divided into core/rind predominance. However, the effects were not independent of the extent of emphysema. Increased age and female sex were related to disease distribution independent of emphysema severity. These findings may be related to differences in development of emphysema.","DOI":"10.1183/09031936.00111808","ISSN":"0903-1936, 1399-3003","note":"PMID: 18829675","shortTitle":"Computed tomographic emphysema distribution","journalAbbreviation":"Eur Respir J","language":"en","author":[{"family":"Mair","given":"G."},{"family":"Miller","given":"J. J."},{"family":"McAllister","given":"D."},{"family":"Maclay","given":"J."},{"family":"Connell","given":"M."},{"family":"Murchison","given":"J. T."},{"family":"MacNee","given":"W."}],"issued":{"date-parts":[["2009",3,1]]},"accessed":{"date-parts":[["2014",3,12]]},"PMID":"18829675"}}],"schema":""} (9) Three different subtypes of emphysema have been recognized: a) centriacinar emphysema, which predominantly involves the upper lobes and is associated with long-standing cigarette smoking, b) panacinar emphysema, which mainly involves the lower lobes and is frequently found in patients with alpha-1 antitrypsin deficiency and c) distal acinar emphysema, which tends to occur adjacent to the pleura or the fibrous septa. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"Iszk5zQr","properties":{"formattedCitation":"(32)","plainCitation":"(32)"},"citationItems":[{"id":1240,"uris":[""],"uri":[""],"itemData":{"id":1240,"type":"article-journal","title":"Functional and morphological heterogeneity of emphysema and its implication for selection of patients for lung volume reduction surgery","container-title":"European Respiratory Journal","page":"230-236","volume":"14","issue":"1","source":"erj.","ISSN":"0903-1936, 1399-3003","note":"PMID: 10489857","journalAbbreviation":"Eur Respir J","language":"en","author":[{"family":"Russi","given":"E. W."},{"family":"Bloch","given":"K. E."},{"family":"Weder","given":"W."}],"issued":{"date-parts":[["1999",7,1]]},"accessed":{"date-parts":[["2014",4,13]]},"PMID":"10489857"}}],"schema":""} (32) These pathologic lesions are found in various combinations in each patient, comprising a heterogeneous or homogeneous emphysema pattern, as classified by CT imaging. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"HmwAgwml","properties":{"formattedCitation":"(32)","plainCitation":"(32)"},"citationItems":[{"id":1240,"uris":[""],"uri":[""],"itemData":{"id":1240,"type":"article-journal","title":"Functional and morphological heterogeneity of emphysema and its implication for selection of patients for lung volume reduction surgery","container-title":"European Respiratory Journal","page":"230-236","volume":"14","issue":"1","source":"erj.","ISSN":"0903-1936, 1399-3003","note":"PMID: 10489857","journalAbbreviation":"Eur Respir J","language":"en","author":[{"family":"Russi","given":"E. W."},{"family":"Bloch","given":"K. E."},{"family":"Weder","given":"W."}],"issued":{"date-parts":[["1999",7,1]]},"accessed":{"date-parts":[["2014",4,13]]},"PMID":"10489857"}}],"schema":""} (32) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"4wS5Ua3O","properties":{"formattedCitation":"(33)","plainCitation":"(33)"},"citationItems":[{"id":1244,"uris":[""],"uri":[""],"itemData":{"id":1244,"type":"article-journal","title":"Radiologic emphysema morphology is associated with outcome after surgical lung volume reduction","container-title":"The Annals of thoracic surgery","page":"313-319; discussion 319-320","volume":"64","issue":"2","source":"NCBI PubMed","abstract":"BACKGROUND: Lung volume reduction surgery is known to alleviate dyspnea and to improve pulmonary function, performance in daily activity, and quality of life in selected patients with severe pulmonary emphysema. We investigated the role of radiologically assessed emphysema morphology on functional outcome after a lung volume reduction operation.\nMETHODS: The preoperative chest computed tomograms in 50 consecutive patients who had undergone surgical lung volume reduction were retrospectively reviewed by 6 physicians blinded to the clinical outcome. Emphysema morphology was determined according to a simplified classification (ie, homogeneous, moderately heterogeneous, and markedly heterogeneous; lobe predominance). We studied the impact of these morphologic aspects on functional outcome at 3 months.\nRESULTS: We found a fair interobserver agreement applying our classification system. Functional improvement after surgical lung volume reduction was best in markedly heterogeneous emphysema with an increase in forced expiratory volume in 1 second of 81% +/- 17% (mean +/- standard error, n = 17) compared with 44% +/- 10% (n = 16) for intermediately heterogeneous emphysema. But also in patients with homogeneous emphysema clinical relevant improvement of function could be observed (increase in forced expiratory volume in 1 second = 34% +/- 6%; n = 17).\nCONCLUSIONS: The morphologic type of emphysema, assessed by a simplified surgically oriented classification, is an important predictor of surgical outcome. Lung volume reduction surgery may also improve dyspnea and lung function in homogeneous emphysema.","DOI":"10.1016/S0003-4975(97)00564-X","ISSN":"0003-4975","note":"PMID: 9262567","journalAbbreviation":"Ann. Thorac. Surg.","language":"eng","author":[{"family":"Weder","given":"W"},{"family":"Thurnheer","given":"R"},{"family":"Stammberger","given":"U"},{"family":"Bürge","given":"M"},{"family":"Russi","given":"E W"},{"family":"Bloch","given":"K E"}],"issued":{"date-parts":[["1997",8]]},"PMID":"9262567"}}],"schema":""} (33) Mair et al indicated that emphysema distribution is associated with several clinical features, such as FEV1, BMI, BODE index and health status; ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"WSD2NKrt","properties":{"formattedCitation":"(9)","plainCitation":"(9)"},"citationItems":[{"id":737,"uris":[""],"uri":[""],"itemData":{"id":737,"type":"article-journal","title":"Computed tomographic emphysema distribution: relationship to clinical features in a cohort of smokers","container-title":"European Respiratory Journal","page":"536-542","volume":"33","issue":"3","source":"erj.","abstract":"Computed tomography (CT) scanning allows precise assessment of both the extent and distribution of emphysema. There has been little work on the relationship between the distribution of emphysema and clinical features of the disease. The current study investigated the association between clinical features and distribution of emphysema.\nA total of 129 patients with smoking-related chronic obstructive pulmonary disease underwent CT assessment of the extent and distribution of their emphysema (core/rind and upper/lower zone predominance).\nEmphysema was found predominantly in the upper/core zone and this distribution was related to the extent of disease. Core predominance was associated with lower forced expiratory volume in one second (FEV1), FEV1/forced vital capacity ratio and body mass index (BMI); and with higher BODE (BMI, airflow obstruction, dyspnoea and exercise capacity) index and Medical Research Council dyspnoea score. Upper-zone predominance was associated with female sex and an increased total St George’s Respiratory Questionnaire score. Using multiple linear regression age, sex and whole lung emphysema severity were independently associated with core/rind distribution, while sex and whole lung emphysema severity were independently related to upper/lower distribution.\nDistribution of emphysema related best to clinical features when divided into core/rind predominance. However, the effects were not independent of the extent of emphysema. Increased age and female sex were related to disease distribution independent of emphysema severity. These findings may be related to differences in development of emphysema.","DOI":"10.1183/09031936.00111808","ISSN":"0903-1936, 1399-3003","note":"PMID: 18829675","shortTitle":"Computed tomographic emphysema distribution","journalAbbreviation":"Eur Respir J","language":"en","author":[{"family":"Mair","given":"G."},{"family":"Miller","given":"J. J."},{"family":"McAllister","given":"D."},{"family":"Maclay","given":"J."},{"family":"Connell","given":"M."},{"family":"Murchison","given":"J. T."},{"family":"MacNee","given":"W."}],"issued":{"date-parts":[["2009",3,1]]},"accessed":{"date-parts":[["2014",3,12]]},"PMID":"18829675"}}],"schema":""} (9) however, these associations were most evident among patients with core versus rind predominant, rather than upper versus lower predominant emphysema. Of note, the presence of heterogeneity has been repeatedly associated with improved outcomes and increased survival after a LVR procedure. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"hPG9MtsM","properties":{"formattedCitation":"(12)","plainCitation":"(12)"},"citationItems":[{"id":750,"uris":[""],"uri":[""],"itemData":{"id":750,"type":"article-journal","title":"National Emphysema Treatment Trial redux: accentuating the positive","container-title":"The Journal of thoracic and cardiovascular surgery","page":"564-572","volume":"140","issue":"3","source":"NCBI PubMed","abstract":"OBJECTIVE: Under the Freedom of Information Act, we obtained the follow-up data of the National Emphysema Treatment Trial (NETT) to determine the long-term outcome for \"a heterogeneous distribution of emphysema with upper lobe predominance,\" postulated by the NETT hypothesis to be optimal candidates for lung volume reduction surgery.\nMETHODS: Using the NETT database, we identified patients with heterogeneous distribution of emphysema with upper lobe predominance and analyzed for the first time follow-up data for those receiving lung volume reduction surgery and those receiving medical management. Furthermore, we compared the results of the NETT reduction surgery group with a previously reported consecutive case series of 250 patients undergoing bilateral lung volume reduction surgery using similar selection criteria.\nRESULTS: Of the 1218 patients enrolled, 511 (42%) conformed to the NETT hypothesis selection criteria and received the randomly assigned surgical or medical treatment (surgical = 261; medical = 250). Lung volume reduction surgery resulted in a 5-year survival benefit (70% vs 60%; P = .02). Results at 3 years compared with baseline data favored surgical reduction in terms of residual volume reduction (25% vs 2%; P < .001), University of California San Diego dyspnea score (16 vs 0 points; P < .001), and improved St George Respiratory Questionnaire quality of life score (12 points vs 0 points; P < .001). For the 513 patients with a homogeneous pattern of emphysema randomized to surgical or medical treatment, lung volume reduction surgery produced no survival advantage and very limited functional benefit.\nCONCLUSIONS: Patients most likely to benefit from lung volume reduction surgery have heterogeneously distributed emphysema involving the upper lung zones predominantly. Such patients in the NETT trial had results nearly identical to those previously reported in a nonrandomized series of similar patients undergoing lung volume reduction surgery.","DOI":"10.1016/j.jtcvs.2010.03.050","ISSN":"1097-685X","note":"PMID: 20723727","shortTitle":"National Emphysema Treatment Trial redux","journalAbbreviation":"J. Thorac. Cardiovasc. Surg.","language":"eng","author":[{"family":"Sanchez","given":"Pablo Gerardo"},{"family":"Kucharczuk","given":"John Charles"},{"family":"Su","given":"Stacey"},{"family":"Kaiser","given":"Larry Robert"},{"family":"Cooper","given":"Joel David"}],"issued":{"date-parts":[["2010",9]]},"PMID":"20723727"}}],"schema":""} (12) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"eaBbw8Du","properties":{"formattedCitation":"(13)","plainCitation":"(13)"},"citationItems":[{"id":756,"uris":[""],"uri":[""],"itemData":{"id":756,"type":"article-journal","title":"Patient selection criteria for lung volume reduction surgery","container-title":"The Journal of thoracic and cardiovascular surgery","page":"957-964; discussion 964-967","volume":"114","issue":"6","source":"NCBI PubMed","abstract":"OBJECTIVE: Our intent was to refine the patient selection criteria for lung volume reduction surgery because various centers have different criteria and not all patients benefit from the procedure.\nMETHODS: Patient information, x-ray results, arterial blood gases, and plethysmographic pulmonary function tests in 154 consecutive patients who underwent bilateral thoracoscopic staple lung volume reduction surgery were compared with clinical outcome (change in forced expiratory volume in 1 second and dyspnea scale) with t tests and analysis of variance.\nRESULTS: Three hundred thirty-three of 487 (69%) patients evaluated for lung volume reduction surgery were rejected for lack of heterogeneous emphysema (n = 212), medical contraindications (n = 88), hypercapnia (n = 20), uncontrolled anxiety or depression (n = 10), or pulmonary hypertension (n = 1). Two patients died during the evaluation process. When tested by analysis of variance, there was no difference in clinical outcome associated with preoperative forced expiratory volume in 1 second, residual volume, total lung capacity, single-breath diffusing, and arterial oxygen or carbon dioxide tension. All patients selected for the operation had a heterogeneous pattern of emphysema. The upper lobe heterogeneous pattern of emphysema on chest computed tomography and lung perfusion scan was strongly associated with improved outcome with a mean (95% confidence interval) improvement in forced expiratory volume in 1 second of 73.2% (63.3 to 83.1) for the upper lobe compared with a mean (95% confidence interval) improvement of 37.9% (22.9 to 53.0) for the lower lobe or diffuse pattern of emphysema.\nCONCLUSION: The most important selection criteria for lung volume reduction surgery is the presence of a bilateral upper lobe heterogeneous pattern of emphysema on chest computed tomography and lung perfusion scan. After patients have been selected on the basis of a heterogeneous pattern of emphysema, clinical factors and physiology are not associated with clinical outcome well enough to further refine patient selection criteria. These results do not support the arbitrary patient selection criteria for lung volume reduction surgery reported in the literature.","ISSN":"0022-5223","note":"PMID: 9434691","journalAbbreviation":"J. Thorac. Cardiovasc. Surg.","language":"eng","author":[{"family":"McKenna","given":"R J, Jr"},{"family":"Brenner","given":"M"},{"family":"Fischel","given":"R J"},{"family":"Singh","given":"N"},{"family":"Yoong","given":"B"},{"family":"Gelb","given":"A F"},{"family":"Osann","given":"K E"}],"issued":{"date-parts":[["1997",12]]},"PMID":"9434691"}}],"schema":""} (13) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"dgkrc7L9","properties":{"formattedCitation":"(34)","plainCitation":"(34)"},"citationItems":[{"id":1419,"uris":[""],"uri":[""],"itemData":{"id":1419,"type":"article-journal","title":"Atelectasis and survival after bronchoscopic lung volume reduction for COPD","container-title":"The European respiratory journal","page":"1346-1351","volume":"37","issue":"6","source":"NCBI PubMed","abstract":"Bronchoscopic therapies to reduce lung volumes in chronic obstructive pulmonary disease are intended to avoid the risks associated with lung volume reduction surgery (LVRS) or to be used in patient groups in whom LVRS is not appropriate. Bronchoscopic lung volume reduction (BLVR) using endobronchial valves to target unilateral lobar occlusion can improve lung function and exercise capacity in patients with emphysema. The benefit is most pronounced in, though not confined to, patients where lobar atelectasis has occurred. Few data exist on their long-term outcome. 19 patients (16 males; mean±sd forced expiratory volume in 1 s 28.4±11.9% predicted) underwent BLVR between July 2002 and February 2004. Radiological atelectasis was observed in five patients. Survival data was available for all patients up to February 2010. None of the patients in whom atelectasis occurred died during follow-up, whereas eight out of 14 in the nonatelectasis group died (Chi-squared p=0.026). There was no significant difference between the groups at baseline in lung function, quality of life, exacerbation rate, exercise capacity (shuttle walk test or cycle ergometry) or computed tomography appearances, although body mass index was significantly higher in the atelectasis group (21.6±2.9 versus 28.4±2.9 kg·m(-2); p<0.001). The data in the present study suggest that atelectasis following BLVR is associated with a survival benefit that is not explained by baseline differences.","DOI":"10.1183/09031936.00100110","ISSN":"1399-3003","note":"PMID: 20947683","journalAbbreviation":"Eur. Respir. J.","language":"eng","author":[{"family":"Hopkinson","given":"N S"},{"family":"Kemp","given":"S V"},{"family":"Toma","given":"T P"},{"family":"Hansell","given":"D M"},{"family":"Geddes","given":"D M"},{"family":"Shah","given":"P L"},{"family":"Polkey","given":"M I"}],"issued":{"date-parts":[["2011",6]]},"PMID":"20947683"}}],"schema":""} (34) Although the theoretical background of these interventions is the restoration of lung elastic recoil and the improvement of lung mechanics, the impact of emphysema distribution itself on DH has not previously been assessed. Both the pathological hallmarks of COPD, airway inflammation and parenchymal destruction contribute to the development of DH. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"APHmZMhQ","properties":{"formattedCitation":"(35)","plainCitation":"(35)"},"citationItems":[{"id":1249,"uris":[""],"uri":[""],"itemData":{"id":1249,"type":"article-journal","title":"Hyperinflation and its management in COPD","container-title":"International Journal of Chronic Obstructive Pulmonary Disease","page":"381-400","volume":"1","issue":"4","source":"PubMed Central","abstract":"Chronic obstructive pulmonary disease (COPD) is characterized by poorly reversible airflow limitation. The pathological hallmarks of COPD are inflammation of the peripheral airways and destruction of lung parenchyma or emphysema. The functional consequences of these abnormalities are expiratory airflow limitation and dynamic hyperinflation, which then increase the elastic load of the respiratory system and decrease the performance of the respiratory muscles. These pathophysiologic features contribute significantly to the development of dyspnea, exercise intolerance and ventilatory failure. Several treatments may palliate flow limitation, including interventions that modify the respiratory pattern (deeper, slower) such as pursed lip breathing, exercise training, oxygen, and some drugs. Other therapies are aimed at its amelioration, such as bronchodilators, lung volume reduction surgery or breathing mixtures of helium and oxygen. Finally some interventions, such as inspiratory pressure support, alleviate the threshold load associated to flow limitation. The degree of flow limitation can be assessed by certain spirometry indexes, such as vital capacity and inspiratory capacity, or by other more complexes indexes such as residual volume/total lung capacity or functional residual capacity/total lung capacity. Two of the best methods to measure flow limitation are to superimpose a flow–volume loop of a tidal breath within a maximum flow–volume curve, or to use negative expiratory pressure technique. Likely this method is more accurate and can be used during spontaneous breathing. A definitive definition of dynamic hyperinflation is lacking in the literature, but serial measurements of inspiratory capacity during exercise will document the trend of end-expiratory lung volume and allow establishing relationships with other measurements such as dyspnea, respiratory pattern, exercise tolerance, and gas exchange.","ISSN":"1176-9106","note":"PMID: 18044095\nPMCID: PMC2707802","journalAbbreviation":"Int J Chron Obstruct Pulmon Dis","author":[{"family":"Puente-Maestu","given":"Luis"},{"family":"Stringer","given":"William W"}],"issued":{"date-parts":[["2006",12]]},"accessed":{"date-parts":[["2014",4,13]]},"PMID":"18044095","PMCID":"PMC2707802"}}],"schema":""} (35) During exercise, increased airway resistance and decreased elastic recoil result in increased time constants for alveolar units, so as RR and expiratory flow increase, the expiratory time available for exhalation becomes insufficient. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"MwU84Ccv","properties":{"formattedCitation":"(36)","plainCitation":"(36)"},"citationItems":[{"id":1246,"uris":[""],"uri":[""],"itemData":{"id":1246,"type":"article-journal","title":"Pathogenesis of hyperinflation in chronic obstructive pulmonary disease","container-title":"International Journal of Chronic Obstructive Pulmonary Disease","page":"187-201","volume":"9","source":"PubMed Central","abstract":"Chronic obstructive pulmonary disease (COPD) is a preventable and treatable lung disease characterized by airflow limitation that is not fully reversible. In a significant proportion of patients with COPD, reduced lung elastic recoil combined with expiratory flow limitation leads to lung hyperinflation during the course of the disease. Development of hyperinflation during the course of COPD is insidious. Dynamic hyperinflation is highly prevalent in the advanced stages of COPD, and new evidence suggests that it also occurs in many patients with mild disease, independently of the presence of resting hyperinflation. Hyperinflation is clinically relevant for patients with COPD mainly because it contributes to dyspnea, exercise intolerance, skeletal muscle limitations, morbidity, and reduced physical activity levels associated with the disease. Various pharmacological and nonpharmacological interventions have been shown to reduce hyperinflation and delay the onset of ventilatory limitation in patients with COPD. The aim of this review is to address the more recent literature regarding the pathogenesis, assessment, and management of both static and dynamic lung hyperinflation in patients with COPD. We also address the influence of biological sex and obesity and new developments in our understanding of hyperinflation in patients with mild COPD and its evolution during progression of the disease.","DOI":"10.2147/COPD.S38934","ISSN":"1176-9106","note":"PMID: 24600216\nPMCID: PMC3933347","journalAbbreviation":"Int J Chron Obstruct Pulmon Dis","author":[{"family":"Gagnon","given":"Philippe"},{"family":"Guenette","given":"Jordan A"},{"family":"Langer","given":"Daniel"},{"family":"Laviolette","given":"Louis"},{"family":"Mainguy","given":"Vincent"},{"family":"Maltais","given":"Francois"},{"family":"Ribeiro","given":"Fernanda"},{"family":"Saey","given":"Didier"}],"issued":{"date-parts":[["2014",2,15]]},"accessed":{"date-parts":[["2014",4,13]]},"PMID":"24600216","PMCID":"PMC3933347"}}],"schema":""} (36) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"ANcGWDKY","properties":{"formattedCitation":"(37)","plainCitation":"(37)"},"citationItems":[{"id":1252,"uris":[""],"uri":[""],"itemData":{"id":1252,"type":"article-journal","title":"The clinical importance of dynamic lung hyperinflation in COPD","container-title":"COPD","page":"219-232","volume":"3","issue":"4","source":"NCBI PubMed","abstract":"Lung hyperinflation commonly accompanies expiratory flow-limitation in patients with Chronic Obstructive Pulmonary Disease (COPD) and contributes importantly to dyspnea and activity limitation. It is not surprising, therefore, that lung hyperinflation has become an important therapeutic target in symptomatic COPD patients. There is increasing evidence that acute dynamic increases in lung hyperinflation, under conditions of worsening expiratory flow-limitation and increased ventilatory demand (or both) can seriously stress cardiopulmonary reserves, particularly in patients with more advanced disease. Our understanding of the physiological mechanisms of dynamic lung hyperinflation during both physical activity and exacerbations in COPD continues to grow, together with an appreciation of its serious negative mechanical and sensory consequences. In this review, we will discuss the basic pathophysiology of COPD during rest, exercise and exacerbation so as to better understand how this can be pharmacologically manipulated for the patient's benefit. Finally, we will review current concepts of the mechanisms of symptom relief and improved exercise endurance following pharmacological lung volume reduction.","ISSN":"1541-2555","note":"PMID: 17361503","journalAbbreviation":"COPD","language":"eng","author":[{"family":"O'Donnell","given":"Denis E"},{"family":"Laveneziana","given":"Pierantonio"}],"issued":{"date-parts":[["2006",12]]},"PMID":"17361503"}}],"schema":""} (37) In our study, patients with a heterogeneous pattern of emphysema, that is with unequally distributed parenchymal damage, experienced significantly less DH during maximal exercise. In patients with heterogeneous emphysema, lung areas with distinct destruction coexist with areas where lung parenchyma is relatively well preserved. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"KnS5rprV","properties":{"formattedCitation":"(32)","plainCitation":"(32)"},"citationItems":[{"id":1240,"uris":[""],"uri":[""],"itemData":{"id":1240,"type":"article-journal","title":"Functional and morphological heterogeneity of emphysema and its implication for selection of patients for lung volume reduction surgery","container-title":"European Respiratory Journal","page":"230-236","volume":"14","issue":"1","source":"erj.","ISSN":"0903-1936, 1399-3003","note":"PMID: 10489857","journalAbbreviation":"Eur Respir J","language":"en","author":[{"family":"Russi","given":"E. W."},{"family":"Bloch","given":"K. E."},{"family":"Weder","given":"W."}],"issued":{"date-parts":[["1999",7,1]]},"accessed":{"date-parts":[["2014",4,13]]},"PMID":"10489857"}}],"schema":""} (32) We speculate that this coexistence poses a mechanical barrier to the further increase of end expiratory lung volume in emphysematous lung areas, resulting in less DH during maximal exercise. On the contrary, patients with homogeneous emphysema have, by definition, more widespread disease and diffuse floppy airways, meaning that mechanical restriction to whole lung hyperinflation is less.Interestingly, no CPET parameter differed significantly between patients in the Het and Hom groups. It is well established that medical or other interventions targeting lung hyperinflation improve exercise tolerance among COPD patients. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"mTD6NMJd","properties":{"formattedCitation":"(38)","plainCitation":"(38)"},"citationItems":[{"id":1259,"uris":[""],"uri":[""],"itemData":{"id":1259,"type":"article-journal","title":"Improvements in symptom-limited exercise performance over 8 h with once-daily tiotropium in patients with COPD","container-title":"Chest","page":"1168-1178","volume":"128","issue":"3","source":"NCBI PubMed","abstract":"STUDY OBJECTIVES: We have previously shown that tiotropium at 18 mug reduces lung hyperinflation and dyspnea during exercise and improves exercise tolerance in patients with COPD. The present study was designed to gain further insight into the duration of improvements.\nDESIGN, PATIENTS, AND INTERVENTIONS: A randomized, double-blind, placebo-controlled, parallel-group study was conducted in 261 COPD patients (mean age, 62.5 +/- 7.4 years [+/- SD]; 189 men and 72 women; mean FEV1, 1.2 +/- 0.4 L [43 +/- 12.7% predicted]). On day 0 (first dose), day 21, and day 42 of treatment, pulmonary function tests were performed before and 1 h 20 min after dosing, followed by a constant work rate cycle ergometry test (75% maximum work capacity) to symptom limitation at 2.25 h after dosing. On day 42, an additional constant work rate cycle ergometry test was performed at 8 h after dosing.\nRESULTS: Adjusted mean (+/- SE) endurance time (ET) on day 42 was 803 +/- 40 s (tiotropium), vs 568 +/- 42 s (placebo) at 2.25 h after dosing (primary end point; treatment difference, 236 +/- 58 s; p = 0.0001) and 665 +/- 40 s (tiotropium) vs 494 +/- 42 s (placebo) at 8 h after dosing (treatment difference, 171 +/- 58 s; p = 0.0035). Adjusted mean dyspnea intensity at isotime on day 42 was 4.60 +/- 0.16 Borg units (tiotropium), vs 5.65 +/- 0.16 Borg units (placebo) at 2.25 h after dosing (p < 0.001), and 5.54 +/- 0.17 Borg units (tiotropium) vs 6.51 +/- 0.18 Borg units (placebo) at 8 h after dosing (p < 0.001). Adjusted mean pre-exercise inspiratory capacity (IC) on day 42 was 2.41 +/- 0.03 L (tiotropium) vs 2.19 +/- 0.03 L (placebo) at 2.25 h after dosing (p < 0.001), and 2.31 +/- 0.03 L (tiotropium) vs 2.16 +/- 0.03 L (placebo) at 8 h after dosing (p < 0.001). The significant increase in IC with tiotropium compared with placebo was maintained throughout exercise.\nCONCLUSIONS: The present study confirms that tiotropium reduces lung hyperinflation at rest and during exercise, reduces exertional dyspnea, and improves symptom-limited exercise tolerance in COPD patients. Furthermore, this study shows that this improvement is present at 2.25 h and at 8 h after dosing after 6 weeks of treatment.","DOI":"10.1378/chest.128.3.1168","ISSN":"0012-3692","note":"PMID: 16162703","journalAbbreviation":"Chest","language":"eng","author":[{"family":"Maltais","given":"Fran?ois"},{"family":"Hamilton","given":"Alan"},{"family":"Marciniuk","given":"Darcy"},{"family":"Hernandez","given":"Paul"},{"family":"Sciurba","given":"Frank C"},{"family":"Richter","given":"Kai"},{"family":"Kesten","given":"Steven"},{"family":"O'Donnell","given":"Denis"}],"issued":{"date-parts":[["2005",9]]},"PMID":"16162703"}}],"schema":""} (38) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"iYJPC0CG","properties":{"formattedCitation":"(39)","plainCitation":"(39)"},"citationItems":[{"id":1254,"uris":[""],"uri":[""],"itemData":{"id":1254,"type":"article-journal","title":"Effect of bronchoscopic lung volume reduction on dynamic hyperinflation and exercise in emphysema","container-title":"American journal of respiratory and critical care medicine","page":"453-460","volume":"171","issue":"5","source":"NCBI PubMed","abstract":"Endobronchial valve placement improves pulmonary function in some patients with chronic obstructive pulmonary disease, but its effects on exercise physiology have not been investigated. In 19 patients with a mean (SD) FEV(1) of 28.4 (11.9)% predicted, studied before and 4 weeks after unilateral valve insertion, functional residual capacity decreased from 7.1 (1.5) to 6.6 (1.7) L (p = 0.03) and diffusing capacity rose from 3.3 (1.1) to 3.7 (1.2) mmol . minute(-1) . kPa(-1) (p = 0.03). Cycle endurance time at 80% of peak workload increased from 227 (129) to 315 (195) seconds (p = 0.03). This was associated with a reduction in end-expiratory lung volume at peak exercise from 7.6 (1.6) to 7.2 (1.7) L (p = 0.03). Using stepwise logistic regression analysis, a model containing changes in transfer factor and resting inspiratory capacity explained 81% of the variation in change in exercise time (p < 0.0001). The same variables were retained if the five patients with radiologic atelectasis were excluded from analysis. In a subgroup of patients in whom invasive measurements were performed, improvement in exercise capacity was associated with a reduction in lung compliance (r(2) = 0.43; p = 0.03) and isotime esophageal pressure-time product (r(2) = 0.47; p = 0.03). Endobronchial valve placement can improve lung volumes and gas transfer in patients with chronic obstructive pulmonary disease and prolong exercise time by reducing dynamic hyperinflation.","DOI":"10.1164/rccm.200407-961OC","ISSN":"1073-449X","note":"PMID: 15579725","journalAbbreviation":"Am. J. Respir. Crit. Care Med.","language":"eng","author":[{"family":"Hopkinson","given":"Nicholas S"},{"family":"Toma","given":"Tudor P"},{"family":"Hansell","given":"David M"},{"family":"Goldstraw","given":"Peter"},{"family":"Moxham","given":"John"},{"family":"Geddes","given":"Duncan M"},{"family":"Polkey","given":"Michael I"}],"issued":{"date-parts":[["2005",3,1]]},"PMID":"15579725"}}],"schema":""} (39) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"R0Fi7zPC","properties":{"formattedCitation":"(40)","plainCitation":"(40)"},"citationItems":[{"id":1263,"uris":[""],"uri":[""],"itemData":{"id":1263,"type":"article-journal","title":"Measurement of symptoms, lung hyperinflation, and endurance during exercise in chronic obstructive pulmonary disease","container-title":"American journal of respiratory and critical care medicine","page":"1557-1565","volume":"158","issue":"5 Pt 1","source":"NCBI PubMed","abstract":"Changes in lung hyperinflation, dyspnea, and exercise endurance are important outcomes in assessing therapeutic responses in chronic obstructive pulmonary disease (COPD). Therefore, we studied the reproducibility of Borg dyspnea ratings, inspiratory capacity (IC; to monitor lung hyperinflation), and endurance time during constant-load symptom-limited cycle exercise in 29 patients with COPD (FEV1 = 40 +/- 2% predicted; mean +/- SEM). Responsiveness was also studied by determining the acute effects of nebulized 500 micrograms ipratropium bromide (IB) or saline placebo (P) on these measurements. During each of four visits conducted over an 8-wk period, spirometry and exercise testing were performed before and 1 h after receiving IB or P (randomized, double-blinded). Highly reproducible measurements included: endurance time (intraclass correlation R = 0.77, p < 0.0001); Borg ratings and IC at rest, at a standardized exercise time (STD), and at peak exercise (R > 0.6, p < 0.0001); and slopes of Borg ratings over time, oxygen consumption (V O2), and ventilation (R > 0.6, p < 0.0001). Responsiveness was confirmed by finding a significant drug effect for: change (Delta) in endurance time (p = 0.0001); DeltaBorgSTD and DeltaBorg-time slopes (p < 0.05); and DeltaIC at rest, at STD, and at peak exercise (p = 0.0001). With all completed visits, DeltaBorgSTD correlated better with DeltaICSTD than any other resting or exercise parameter (n = 115, r = -0.35, p < 0.001). We concluded that Borg dyspnea ratings, and measurements of IC and endurance time during submaximal cycle exercise testing are highly reproducible and responsive to change in severe COPD.","DOI":"10.1164/ajrccm.158.5.9804004","ISSN":"1073-449X","note":"PMID: 9817708","journalAbbreviation":"Am. J. Respir. Crit. Care Med.","language":"eng","author":[{"family":"O'Donnell","given":"D E"},{"family":"Lam","given":"M"},{"family":"Webb","given":"K A"}],"issued":{"date-parts":[["1998",11]]},"PMID":"9817708"}}],"schema":""} (40) Tzani et al reported that DH was associated with increased exertional dyspnea and reduced maximum exercise capacity in a cohort of COPD patients; ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"TDU25PjA","properties":{"formattedCitation":"(3)","plainCitation":"(3)"},"citationItems":[{"id":1256,"uris":[""],"uri":[""],"itemData":{"id":1256,"type":"article-journal","title":"Dynamic hyperinflation is associated with a poor cardiovascular response to exercise in COPD patients","container-title":"Respiratory Research","page":"150","volume":"12","issue":"1","source":"PubMed Central","abstract":"Background\nPulmonary hyperinflation has the potential for significant adverse effects on cardiovascular function in COPD. The aim of this study was to investigate the relationship between dynamic hyperinflation and cardiovascular response to maximal exercise in COPD patients.\n\nMethods\nWe studied 48 patients (16F; age 68 yrs ± 8; BMI 26 ± 4) with COPD. All patients performed spirometry, plethysmography, lung diffusion capacity for carbon monoxide (TLco) measurement, and symptom-limited cardiopulmonary exercise test (CPET). The end-expiratory lung volume (EELV) was evaluated during the CPET. Cardiovascular response was assessed by change during exercise in oxygen pulse (ΔO2Pulse) and double product, i.e. the product of systolic blood pressure and heart rate (DP reserve), and by the oxygen uptake efficiency slope (OUES), i.e. the relation between oxygen uptake and ventilation.\n\nResults\nPatients with a peak exercise EELV (%TLC) ≥ 75% had a significantly lower resting FEV1/VC, FEF50/FIF50 ratio and IC/TLC ratio, when compared to patients with a peak exercise EELV (%TLC) < 75%. Dynamic hyperinflation was strictly associated to a poor cardiovascular response to exercise: EELV (%TLC) showed a negative correlation with ΔO2Pulse (r = - 0.476, p = 0.001), OUES (r = - 0.452, p = 0.001) and DP reserve (r = - 0.425, p = 0.004). Furthermore, according to the ROC curve method, ΔO2Pulse and DP reserve cut-off points which maximized sensitivity and specificity, with respect to a EELV (% TLC) value ≥ 75% as a threshold value, were ≤ 5.5 mL/bpm (0.640 sensitivity and 0.696 specificity) and ≤ 10,000 Hg · bpm (0.720 sensitivity and 0.783 specificity), respectively.\n\nConclusion\nThe present study shows that COPD patients with dynamic hyperinflation have a poor cardiovascular response to exercise. This finding supports the view that in COPD patients, dynamic hyperinflation may affect exercise performance not only by affecting ventilation, but also cardiac function.","DOI":"10.1186/1465-9921-12-150","ISSN":"1465-9921","note":"PMID: 22074289\nPMCID: PMC3225311","journalAbbreviation":"Respir Res","author":[{"family":"Tzani","given":"Panagiota"},{"family":"Aiello","given":"Marina"},{"family":"Elia","given":"Davide"},{"family":"Boracchia","given":"Luca"},{"family":"Marangio","given":"Emilio"},{"family":"Olivieri","given":"Dario"},{"family":"Clini","given":"Enrico"},{"family":"Chetta","given":"Alfredo"}],"issued":{"date-parts":[["2011"]]},"accessed":{"date-parts":[["2014",4,13]]},"PMID":"22074289","PMCID":"PMC3225311"}}],"schema":""} (3) however a relatively high value of end expiratory lung volume (≥75% TLC) was used as a threshold for group categorization, while resting TLC was significantly higher between patients who hyperinflated compared to those who did not. In another study ΔIC was associated with exercise desaturation among male COPD patients with severe disease; nevertheless, this study utilized six-minute walking test, that is a submaximal exercise testing and not maximal CPET, so results are not easily comparable. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"7L4HKLaZ","properties":{"formattedCitation":"(4)","plainCitation":"(4)"},"citationItems":[{"id":726,"uris":[""],"uri":[""],"itemData":{"id":726,"type":"article-journal","title":"Dynamic hyperinflation correlates with exertional oxygen desaturation in patients with chronic obstructive pulmonary disease","container-title":"Lung","page":"177-182","volume":"191","issue":"2","source":"NCBI PubMed","abstract":"BACKGROUND: Dynamic hyperinflation (DH) causes exercise limitation and exertional dyspnea in patients with chronic obstructive pulmonary disease (COPD). Exertional desaturation (ED) also occurs commonly in COPD but neither routine physiologic parameters nor imaging predict ED accurately. In this study we evaluated the relationship between DH and ED during 6-min walk testing (6MWT).\nMETHODS: We measured ED and DH in patients with stable COPD. SpO2 was measured by continuous pulse oximetry during 6MWT. ED was defined as a decline in SpO2 (ΔSpO2) ≥4?%. DH was determined by measuring inspiratory capacity (IC) before and after the 6MWT using a handheld spirometer. DH was defined as ΔIC >0.0?L. We correlated DH and ED with clinical and pulmonary physiologic variables by regression analysis, χ (2), and receiver operator curve (ROC) analysis.\nRESULTS: Thirty males [age?=?65?±?9.4?years, FEV1 % predicted?=?48?±?14?%, and DLCO % predicted?=?50?±?21?% (mean?±?SD)] were studied. ΔSpO2 correlated with ΔIC (r?=?0.49, p?=?0.005) and age (r?=?0.39, p?=?0.03) by univariate analysis; however, only ΔIC correlated on multivariate regression analysis (p?=?0.01). ΔSpO2 did not correlate with FEV1, FVC, FEF25-75, RV, DLCO % predicted, BMI, smoking, BORG score, or distance covered in 6MWT. DH strongly correlated with ED (p?=?0.001). On ROC analysis, DH had an area under the curve of 0.92 for the presence of ED (sensitivity?=?90?%; specificity?=?77?%, p?<?0.001).\nCONCLUSION: Routine pulmonary function test results and clinical variables did not correlate with ED in patients with stable COPD. Dynamic hyperinflation strongly correlates with exertional desaturation and could be a reason for this desaturation.","DOI":"10.1007/s00408-012-9443-3","ISSN":"1432-1750","note":"PMID: 23283384","journalAbbreviation":"Lung","language":"eng","author":[{"family":"Zafar","given":"Muhammad Ahsan"},{"family":"Tsuang","given":"Wayne"},{"family":"Lach","given":"Laura"},{"family":"Eschenbacher","given":"William"},{"family":"Panos","given":"Ralph J"}],"issued":{"date-parts":[["2013",4]]},"PMID":"23283384"}}],"schema":""} (4) In our study, the highly selective patient population, the relatively small absolute difference of ΔIC (approximately 8.5%), and the presence of similarly increased resting lung volumes between the groups are the most probable causes for this lack of difference in measures of dyspnea and exercise capacity between patients with homogeneous and those with heterogeneous emphysema.When emphysema distribution was treated as a continuous variable, weak but significant correlations were established with several CPET parameters. The higher the emphysema heterogeneity with upper lobe predominance, as manifested by increased UM/L ratio, the lower the ΔIC%, and the higher the peak O2 consumption and the peak oxygen pulse. Lung hyperinflation is an important cause of circulatory impairment during exercise, through several mechanisms. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"CwXqDMcK","properties":{"formattedCitation":"(3)","plainCitation":"(3)"},"citationItems":[{"id":1256,"uris":[""],"uri":[""],"itemData":{"id":1256,"type":"article-journal","title":"Dynamic hyperinflation is associated with a poor cardiovascular response to exercise in COPD patients","container-title":"Respiratory Research","page":"150","volume":"12","issue":"1","source":"PubMed Central","abstract":"Background\nPulmonary hyperinflation has the potential for significant adverse effects on cardiovascular function in COPD. The aim of this study was to investigate the relationship between dynamic hyperinflation and cardiovascular response to maximal exercise in COPD patients.\n\nMethods\nWe studied 48 patients (16F; age 68 yrs ± 8; BMI 26 ± 4) with COPD. All patients performed spirometry, plethysmography, lung diffusion capacity for carbon monoxide (TLco) measurement, and symptom-limited cardiopulmonary exercise test (CPET). The end-expiratory lung volume (EELV) was evaluated during the CPET. Cardiovascular response was assessed by change during exercise in oxygen pulse (ΔO2Pulse) and double product, i.e. the product of systolic blood pressure and heart rate (DP reserve), and by the oxygen uptake efficiency slope (OUES), i.e. the relation between oxygen uptake and ventilation.\n\nResults\nPatients with a peak exercise EELV (%TLC) ≥ 75% had a significantly lower resting FEV1/VC, FEF50/FIF50 ratio and IC/TLC ratio, when compared to patients with a peak exercise EELV (%TLC) < 75%. Dynamic hyperinflation was strictly associated to a poor cardiovascular response to exercise: EELV (%TLC) showed a negative correlation with ΔO2Pulse (r = - 0.476, p = 0.001), OUES (r = - 0.452, p = 0.001) and DP reserve (r = - 0.425, p = 0.004). Furthermore, according to the ROC curve method, ΔO2Pulse and DP reserve cut-off points which maximized sensitivity and specificity, with respect to a EELV (% TLC) value ≥ 75% as a threshold value, were ≤ 5.5 mL/bpm (0.640 sensitivity and 0.696 specificity) and ≤ 10,000 Hg · bpm (0.720 sensitivity and 0.783 specificity), respectively.\n\nConclusion\nThe present study shows that COPD patients with dynamic hyperinflation have a poor cardiovascular response to exercise. This finding supports the view that in COPD patients, dynamic hyperinflation may affect exercise performance not only by affecting ventilation, but also cardiac function.","DOI":"10.1186/1465-9921-12-150","ISSN":"1465-9921","note":"PMID: 22074289\nPMCID: PMC3225311","journalAbbreviation":"Respir Res","author":[{"family":"Tzani","given":"Panagiota"},{"family":"Aiello","given":"Marina"},{"family":"Elia","given":"Davide"},{"family":"Boracchia","given":"Luca"},{"family":"Marangio","given":"Emilio"},{"family":"Olivieri","given":"Dario"},{"family":"Clini","given":"Enrico"},{"family":"Chetta","given":"Alfredo"}],"issued":{"date-parts":[["2011"]]},"accessed":{"date-parts":[["2014",4,13]]},"PMID":"22074289","PMCID":"PMC3225311"}}],"schema":""} (3) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"C1ono1F3","properties":{"formattedCitation":"(41)","plainCitation":"(41)"},"citationItems":[{"id":1265,"uris":[""],"uri":[""],"itemData":{"id":1265,"type":"article-journal","title":"Effects of hyperinflation on the oxygen pulse as a marker of cardiac performance in COPD","container-title":"European Respiratory Journal","page":"1275-1282","volume":"32","issue":"5","source":"erj.","abstract":"A decreased inspiratory capacity (IC)/total lung capacity (TLC) ratio is associated with dynamic hyperinflation and decreased exercise capacity. The present authors hypothesised that static (low IC/TLC) and dynamic hyperinflation impair cardiac function as assessed by oxygen pulse at rest and during cardiopulmonary exercise testing (CPET).\nLung function, body mass index, hand grip strength and CPET parameters were measured (oxygen uptake (mL·kg?1·min?1) and oxygen pulse (mL·beat?1)) in 87 chronic obstructive pulmonary disease (COPD) patients (American Thoracic Society/European Respiratory Society/Global Initiative for Chronic Obstructive Lung Disease stage 3–4) and 46 controls. The patients were divided into those with IC/TLC >25% or ≤25%.\nThe IC/TLC ratio at rest and at peak exercise was associated significantly with oxygen pulse. Patients with IC/TLC ≤25% (n = 45) had significantly lower exercise capacity, peak oxygen pulse, peak minus baseline oxygen pulse, peak IC, peak IC/TLC ratio and % change from baseline to peak IC/TLC ratio compared with patients with IC/TLC >25% and controls. During CPET, the oxygen pulse was lower at iso-work in patients with IC/TLC ≤25% than in those with IC/TLC >25%.\nResting hyperinflation (inspiratory capacity/total lung capacity) is associated with lower oxygen pulse, peak exercise inspiratory capacity/total lung capacity and exercise capacity in patients with severe chronic obstructive pulmonary disease. The present results support an interaction between hyperinflation and decreased cardiac function that may contribute to exercise limitation in these patients.","DOI":"10.1183/09031936.00151707","ISSN":"0903-1936, 1399-3003","note":"PMID: 18550609","journalAbbreviation":"Eur Respir J","language":"en","author":[{"family":"Vassaux","given":"C."},{"family":"Torre-Bouscoulet","given":"L."},{"family":"Zeineldine","given":"S."},{"family":"Cortopassi","given":"F."},{"family":"Paz-Díaz","given":"H."},{"family":"Celli","given":"B. R."},{"family":"Pinto-Plata","given":"V. M."}],"issued":{"date-parts":[["2008",11,1]]},"accessed":{"date-parts":[["2014",4,13]]},"PMID":"18550609"}}],"schema":""} (41) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"mBGT6hg6","properties":{"formattedCitation":"(42)","plainCitation":"(42)"},"citationItems":[{"id":1271,"uris":[""],"uri":[""],"itemData":{"id":1271,"type":"article-journal","title":"Effects of augmented respiratory muscle pressure production on locomotor limb venous return during calf contraction exercise","container-title":"Journal of applied physiology (Bethesda, Md.: 1985)","page":"1802-1815","volume":"99","issue":"5","source":"NCBI PubMed","abstract":"We determined effects of augmented inspiratory and expiratory intrathoracic pressure or abdominal pressure (Pab) excursions on within-breath changes in steady-state femoral venous blood flow (Qfv) and net Qfv during tightly controlled (total breath time = 4 s, duty cycle = 0.5) accessory muscle/\"rib cage\" (DeltaPab <2 cmH2O) or diaphragmatic (DeltaPab >5 cmH2O) breathing. Selectively augmenting inspiratory intrathoracic pressure excursion during rib cage breathing augmented inspiratory facilitation of Qfv from the resting limb (69% and 89% of all flow occurred during nonloaded and loaded inspiration, respectively); however, net Qfv in the steady state was not altered because of slight reductions in femoral venous return during the ensuing expiratory phase of the breath. Selectively augmenting inspiratory esophageal pressure excursion during a predominantly diaphragmatic breath at rest did not alter within-breath changes in Qfv relative to nonloaded conditions (net retrograde flow = -9 +/- 12% and -4 +/- 9% during nonloaded and loaded inspiration, respectively), supporting the notion that the inferior vena cava is completely collapsed by relatively small increases in gastric pressure. Addition of inspiratory + expiratory loading to diaphragmatic breathing at rest resulted in reversal of within-breath changes in Qfv, such that >90% of all anterograde Qfv occurred during inspiration. Inspiratory + expiratory loading also reduced steady-state Qfv during mild- and moderate-intensity calf contractions compared with inspiratory loading alone. We conclude that 1) exaggerated inspiratory pressure excursions may augment within-breath changes in femoral venous return but do not increase net Qfv in the steady state and 2) active expiration during diaphragmatic breathing reduces the steady-state hyperemic response to dynamic exercise by mechanically impeding venous return from the locomotor limb, which may contribute to exercise limitation in health and disease.","DOI":"10.1152/japplphysiol.00278.2005","ISSN":"8750-7587","note":"PMID: 16051714","journalAbbreviation":"J. Appl. Physiol.","language":"eng","author":[{"family":"Miller","given":"Jordan D"},{"family":"Pegelow","given":"David F"},{"family":"Jacques","given":"Anthony J"},{"family":"Dempsey","given":"Jerome A"}],"issued":{"date-parts":[["2005",11]]},"PMID":"16051714"}}],"schema":""} (42) The development of an intrinsic positive end-expiratory pressure (PEEP) during active expiration and the high intrathoracic pressure swings that have to be generated to overcome the increased high elastic and resistive loads result in functional hypovolemia during exercise among COPD patients, which may have an impact on stroke volume. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"bHu0OmYc","properties":{"formattedCitation":"(35)","plainCitation":"(35)"},"citationItems":[{"id":1249,"uris":[""],"uri":[""],"itemData":{"id":1249,"type":"article-journal","title":"Hyperinflation and its management in COPD","container-title":"International Journal of Chronic Obstructive Pulmonary Disease","page":"381-400","volume":"1","issue":"4","source":"PubMed Central","abstract":"Chronic obstructive pulmonary disease (COPD) is characterized by poorly reversible airflow limitation. The pathological hallmarks of COPD are inflammation of the peripheral airways and destruction of lung parenchyma or emphysema. The functional consequences of these abnormalities are expiratory airflow limitation and dynamic hyperinflation, which then increase the elastic load of the respiratory system and decrease the performance of the respiratory muscles. These pathophysiologic features contribute significantly to the development of dyspnea, exercise intolerance and ventilatory failure. Several treatments may palliate flow limitation, including interventions that modify the respiratory pattern (deeper, slower) such as pursed lip breathing, exercise training, oxygen, and some drugs. Other therapies are aimed at its amelioration, such as bronchodilators, lung volume reduction surgery or breathing mixtures of helium and oxygen. Finally some interventions, such as inspiratory pressure support, alleviate the threshold load associated to flow limitation. The degree of flow limitation can be assessed by certain spirometry indexes, such as vital capacity and inspiratory capacity, or by other more complexes indexes such as residual volume/total lung capacity or functional residual capacity/total lung capacity. Two of the best methods to measure flow limitation are to superimpose a flow–volume loop of a tidal breath within a maximum flow–volume curve, or to use negative expiratory pressure technique. Likely this method is more accurate and can be used during spontaneous breathing. A definitive definition of dynamic hyperinflation is lacking in the literature, but serial measurements of inspiratory capacity during exercise will document the trend of end-expiratory lung volume and allow establishing relationships with other measurements such as dyspnea, respiratory pattern, exercise tolerance, and gas exchange.","ISSN":"1176-9106","note":"PMID: 18044095\nPMCID: PMC2707802","journalAbbreviation":"Int J Chron Obstruct Pulmon Dis","author":[{"family":"Puente-Maestu","given":"Luis"},{"family":"Stringer","given":"William W"}],"issued":{"date-parts":[["2006",12]]},"accessed":{"date-parts":[["2014",4,13]]},"PMID":"18044095","PMCID":"PMC2707802"}}],"schema":""} (35) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"aHfNkDzm","properties":{"formattedCitation":"(41)","plainCitation":"(41)"},"citationItems":[{"id":1265,"uris":[""],"uri":[""],"itemData":{"id":1265,"type":"article-journal","title":"Effects of hyperinflation on the oxygen pulse as a marker of cardiac performance in COPD","container-title":"European Respiratory Journal","page":"1275-1282","volume":"32","issue":"5","source":"erj.","abstract":"A decreased inspiratory capacity (IC)/total lung capacity (TLC) ratio is associated with dynamic hyperinflation and decreased exercise capacity. The present authors hypothesised that static (low IC/TLC) and dynamic hyperinflation impair cardiac function as assessed by oxygen pulse at rest and during cardiopulmonary exercise testing (CPET).\nLung function, body mass index, hand grip strength and CPET parameters were measured (oxygen uptake (mL·kg?1·min?1) and oxygen pulse (mL·beat?1)) in 87 chronic obstructive pulmonary disease (COPD) patients (American Thoracic Society/European Respiratory Society/Global Initiative for Chronic Obstructive Lung Disease stage 3–4) and 46 controls. The patients were divided into those with IC/TLC >25% or ≤25%.\nThe IC/TLC ratio at rest and at peak exercise was associated significantly with oxygen pulse. Patients with IC/TLC ≤25% (n = 45) had significantly lower exercise capacity, peak oxygen pulse, peak minus baseline oxygen pulse, peak IC, peak IC/TLC ratio and % change from baseline to peak IC/TLC ratio compared with patients with IC/TLC >25% and controls. During CPET, the oxygen pulse was lower at iso-work in patients with IC/TLC ≤25% than in those with IC/TLC >25%.\nResting hyperinflation (inspiratory capacity/total lung capacity) is associated with lower oxygen pulse, peak exercise inspiratory capacity/total lung capacity and exercise capacity in patients with severe chronic obstructive pulmonary disease. The present results support an interaction between hyperinflation and decreased cardiac function that may contribute to exercise limitation in these patients.","DOI":"10.1183/09031936.00151707","ISSN":"0903-1936, 1399-3003","note":"PMID: 18550609","journalAbbreviation":"Eur Respir J","language":"en","author":[{"family":"Vassaux","given":"C."},{"family":"Torre-Bouscoulet","given":"L."},{"family":"Zeineldine","given":"S."},{"family":"Cortopassi","given":"F."},{"family":"Paz-Díaz","given":"H."},{"family":"Celli","given":"B. R."},{"family":"Pinto-Plata","given":"V. M."}],"issued":{"date-parts":[["2008",11,1]]},"accessed":{"date-parts":[["2014",4,13]]},"PMID":"18550609"}}],"schema":""} (41) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"4tWIPArp","properties":{"formattedCitation":"(36)","plainCitation":"(36)"},"citationItems":[{"id":1246,"uris":[""],"uri":[""],"itemData":{"id":1246,"type":"article-journal","title":"Pathogenesis of hyperinflation in chronic obstructive pulmonary disease","container-title":"International Journal of Chronic Obstructive Pulmonary Disease","page":"187-201","volume":"9","source":"PubMed Central","abstract":"Chronic obstructive pulmonary disease (COPD) is a preventable and treatable lung disease characterized by airflow limitation that is not fully reversible. In a significant proportion of patients with COPD, reduced lung elastic recoil combined with expiratory flow limitation leads to lung hyperinflation during the course of the disease. Development of hyperinflation during the course of COPD is insidious. Dynamic hyperinflation is highly prevalent in the advanced stages of COPD, and new evidence suggests that it also occurs in many patients with mild disease, independently of the presence of resting hyperinflation. Hyperinflation is clinically relevant for patients with COPD mainly because it contributes to dyspnea, exercise intolerance, skeletal muscle limitations, morbidity, and reduced physical activity levels associated with the disease. Various pharmacological and nonpharmacological interventions have been shown to reduce hyperinflation and delay the onset of ventilatory limitation in patients with COPD. The aim of this review is to address the more recent literature regarding the pathogenesis, assessment, and management of both static and dynamic lung hyperinflation in patients with COPD. We also address the influence of biological sex and obesity and new developments in our understanding of hyperinflation in patients with mild COPD and its evolution during progression of the disease.","DOI":"10.2147/COPD.S38934","ISSN":"1176-9106","note":"PMID: 24600216\nPMCID: PMC3933347","journalAbbreviation":"Int J Chron Obstruct Pulmon Dis","author":[{"family":"Gagnon","given":"Philippe"},{"family":"Guenette","given":"Jordan A"},{"family":"Langer","given":"Daniel"},{"family":"Laviolette","given":"Louis"},{"family":"Mainguy","given":"Vincent"},{"family":"Maltais","given":"Francois"},{"family":"Ribeiro","given":"Fernanda"},{"family":"Saey","given":"Didier"}],"issued":{"date-parts":[["2014",2,15]]},"accessed":{"date-parts":[["2014",4,13]]},"PMID":"24600216","PMCID":"PMC3933347"}}],"schema":""} (36) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"FEy9p2sg","properties":{"formattedCitation":"(43)","plainCitation":"(43)"},"citationItems":[{"id":1273,"uris":[""],"uri":[""],"itemData":{"id":1273,"type":"article-journal","title":"Respiratory muscle and cardiopulmonary function during exercise in very severe COPD","container-title":"American journal of respiratory and critical care medicine","page":"1284-1289","volume":"154","issue":"5","source":"NCBI PubMed","abstract":"Chronic obstructive pulmonary disease (COPD) is thought to limit exercise capacity through a decreased ventilatory reserve, with cardiovascular factors playing a minimal role. We assessed respiratory muscle (RM) and cardiopulmonary function during exercise in very severe COPD (FEV1 0.79 +/- 0.17 L). We determined minute ventilation (VE), oxygen consumption (VO2), carbon dioxide production (VCO2), heart rate (HR), respiratory rate (RR), and O2 pulse with a metabolic cart. RM function was assessed from esophageal and gastric pressures. Dyspnea was assessed with a visual analog scale (VAS). Exercise capacity (peak VO2 = 36 +/- 31%), ventilatory reserve (VE/maximum voluntary ventilation [MW] = 89 +/- 31%), HR = 76 +/- 15%, and O2 pulse (O2Pmax = 45 +/- 15%) were abnormal. Peak VO2 correlated with O2Pmax(r = 0.82), the change in end-inspiratory pleural pressure (deltaPpli) (r = -0.74), maximal transdiaphragmatic pressure (Pdimax) (r = 0.68), and VEmax (r = 0.58). There were similar correlations with exercise endurance time. Multiple regression analysis revealed O2Pmax to be the best predictor of peak VO2. Thereafter, only VEmax and deltaPpli remained significant (r2 = 0.87). O2Pmax correlated with inspiratory muscle function (Pplimax, r = -0.58; Pdimax, r = 0.53; deltaPpli, r = -0.47; and PImax, r = -0.47). By multiple regression analysis, the predictors of O2Pmax were Pplimax and deltaPpli (r2 = 0.47). In very severe COPD, the impressive swings in intrathoracic pressure resulting from deranged ventilatory mechanics are the most likely cause of exercise limitation and reduced O2 pulse. The contributions of factors such as deconditioning, hypoxemia, and concurrent heart disease remain unknown.","DOI":"10.1164/ajrccm.154.5.8912737","ISSN":"1073-449X","note":"PMID: 8912737","journalAbbreviation":"Am. J. Respir. Crit. Care Med.","language":"eng","author":[{"family":"Montes de Oca","given":"M"},{"family":"Rassulo","given":"J"},{"family":"Celli","given":"B R"}],"issued":{"date-parts":[["1996",11]]},"PMID":"8912737"}}],"schema":""} (43) Whether the unequal distribution of parenchymal destruction itself, as seen in heterogeneous emphysema, compromises cardiac functions less, irrespectively from the degree of DH, due to the potential compensatory effect of preserved lung areas, is a hypothesis that remains to be tested. Methodological issuesAlthough data were analyzed retrospectively, they were collected prospectively minimizing recall bias. COPD patients who were included in the study were followed-up in a single tertiary hospital and were pre-screened for assessment as potential patients for a LVR procedure. Thus, they presented with severe disease and with a higher proportion of heterogeneous emphysema than expected. Testing was performed by an experienced and highly trained team of physiologists and researchers with strict quality control measures in place to minimize testing variability. Moreover, patients were matched for other parameters which could potentially affect DH, such as resting lung function. Although the categorization of emphysema distribution was performed using a well-established technique, the use of UM/L ratio as a continuous variable to describe upper-lobe predominance in sub analysis has not been reported previously and needs to be further validated; Nevertheless its correlation with parameters of exercise capacity and DH is in accordance with published literature on emphysema heteroneneity, ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"HPHrJvJu","properties":{"formattedCitation":"(3)","plainCitation":"(3)"},"citationItems":[{"id":1256,"uris":[""],"uri":[""],"itemData":{"id":1256,"type":"article-journal","title":"Dynamic hyperinflation is associated with a poor cardiovascular response to exercise in COPD patients","container-title":"Respiratory Research","page":"150","volume":"12","issue":"1","source":"PubMed Central","abstract":"Background\nPulmonary hyperinflation has the potential for significant adverse effects on cardiovascular function in COPD. The aim of this study was to investigate the relationship between dynamic hyperinflation and cardiovascular response to maximal exercise in COPD patients.\n\nMethods\nWe studied 48 patients (16F; age 68 yrs ± 8; BMI 26 ± 4) with COPD. All patients performed spirometry, plethysmography, lung diffusion capacity for carbon monoxide (TLco) measurement, and symptom-limited cardiopulmonary exercise test (CPET). The end-expiratory lung volume (EELV) was evaluated during the CPET. Cardiovascular response was assessed by change during exercise in oxygen pulse (ΔO2Pulse) and double product, i.e. the product of systolic blood pressure and heart rate (DP reserve), and by the oxygen uptake efficiency slope (OUES), i.e. the relation between oxygen uptake and ventilation.\n\nResults\nPatients with a peak exercise EELV (%TLC) ≥ 75% had a significantly lower resting FEV1/VC, FEF50/FIF50 ratio and IC/TLC ratio, when compared to patients with a peak exercise EELV (%TLC) < 75%. Dynamic hyperinflation was strictly associated to a poor cardiovascular response to exercise: EELV (%TLC) showed a negative correlation with ΔO2Pulse (r = - 0.476, p = 0.001), OUES (r = - 0.452, p = 0.001) and DP reserve (r = - 0.425, p = 0.004). Furthermore, according to the ROC curve method, ΔO2Pulse and DP reserve cut-off points which maximized sensitivity and specificity, with respect to a EELV (% TLC) value ≥ 75% as a threshold value, were ≤ 5.5 mL/bpm (0.640 sensitivity and 0.696 specificity) and ≤ 10,000 Hg · bpm (0.720 sensitivity and 0.783 specificity), respectively.\n\nConclusion\nThe present study shows that COPD patients with dynamic hyperinflation have a poor cardiovascular response to exercise. This finding supports the view that in COPD patients, dynamic hyperinflation may affect exercise performance not only by affecting ventilation, but also cardiac function.","DOI":"10.1186/1465-9921-12-150","ISSN":"1465-9921","note":"PMID: 22074289\nPMCID: PMC3225311","journalAbbreviation":"Respir Res","author":[{"family":"Tzani","given":"Panagiota"},{"family":"Aiello","given":"Marina"},{"family":"Elia","given":"Davide"},{"family":"Boracchia","given":"Luca"},{"family":"Marangio","given":"Emilio"},{"family":"Olivieri","given":"Dario"},{"family":"Clini","given":"Enrico"},{"family":"Chetta","given":"Alfredo"}],"issued":{"date-parts":[["2011"]]},"accessed":{"date-parts":[["2014",4,13]]},"PMID":"22074289","PMCID":"PMC3225311"}}],"schema":""} (3) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"cyVvdNPN","properties":{"formattedCitation":"(41)","plainCitation":"(41)"},"citationItems":[{"id":1265,"uris":[""],"uri":[""],"itemData":{"id":1265,"type":"article-journal","title":"Effects of hyperinflation on the oxygen pulse as a marker of cardiac performance in COPD","container-title":"European Respiratory Journal","page":"1275-1282","volume":"32","issue":"5","source":"erj.","abstract":"A decreased inspiratory capacity (IC)/total lung capacity (TLC) ratio is associated with dynamic hyperinflation and decreased exercise capacity. The present authors hypothesised that static (low IC/TLC) and dynamic hyperinflation impair cardiac function as assessed by oxygen pulse at rest and during cardiopulmonary exercise testing (CPET).\nLung function, body mass index, hand grip strength and CPET parameters were measured (oxygen uptake (mL·kg?1·min?1) and oxygen pulse (mL·beat?1)) in 87 chronic obstructive pulmonary disease (COPD) patients (American Thoracic Society/European Respiratory Society/Global Initiative for Chronic Obstructive Lung Disease stage 3–4) and 46 controls. The patients were divided into those with IC/TLC >25% or ≤25%.\nThe IC/TLC ratio at rest and at peak exercise was associated significantly with oxygen pulse. Patients with IC/TLC ≤25% (n = 45) had significantly lower exercise capacity, peak oxygen pulse, peak minus baseline oxygen pulse, peak IC, peak IC/TLC ratio and % change from baseline to peak IC/TLC ratio compared with patients with IC/TLC >25% and controls. During CPET, the oxygen pulse was lower at iso-work in patients with IC/TLC ≤25% than in those with IC/TLC >25%.\nResting hyperinflation (inspiratory capacity/total lung capacity) is associated with lower oxygen pulse, peak exercise inspiratory capacity/total lung capacity and exercise capacity in patients with severe chronic obstructive pulmonary disease. The present results support an interaction between hyperinflation and decreased cardiac function that may contribute to exercise limitation in these patients.","DOI":"10.1183/09031936.00151707","ISSN":"0903-1936, 1399-3003","note":"PMID: 18550609","journalAbbreviation":"Eur Respir J","language":"en","author":[{"family":"Vassaux","given":"C."},{"family":"Torre-Bouscoulet","given":"L."},{"family":"Zeineldine","given":"S."},{"family":"Cortopassi","given":"F."},{"family":"Paz-Díaz","given":"H."},{"family":"Celli","given":"B. R."},{"family":"Pinto-Plata","given":"V. M."}],"issued":{"date-parts":[["2008",11,1]]},"accessed":{"date-parts":[["2014",4,13]]},"PMID":"18550609"}}],"schema":""} (41) which strengthens the rationale of its use. ConclusionsIn conclusion, we found that patients with homogeneous emphysema hyperinflate significantly more during maximum exercise compared to those with heterogeneous emphysema. Upper lobe predominance was also associated with less DH and with a higher peak VO2, peak VO2/HR and peak RR. Therefore CT assessed emphysema pattern and degree of heterogeneity may have a role to play when phenotyping COPD; however, further prospective studies are needed to that direction. AbbreviationsBMI: Body Mass Index COPD: chronic obstructive pulmonary diseaseCPET: Cardio pulmonary exercise testDH: Dynamic hyperinflationES: Emphysema scoreEELV: End Expiratory Lung VolumeFEV1: Forced Expiratory Volume in 1 secondFRC: Functional Residual CapacityFVC: Forced Vital CapacityHR: Heart RateHU: Hounsfield unitHRCT: High resolution computed tomographyIC: End-exercise Inspiratory Capacity Kcoc: Carbon Dioxide transfer coefficient corrected for haemoglobinpBorg: peak Borg scale scorePaO2: arterial Oxygen Partial PressurePaCO2: arterial Carbon Dioxide Partial PressurePETCO2: End Expiratory Carbon Dioxide partial pressure PETO2: End Expiratory Oxygen partial pressurepSPO2: peak arterial Oxygen Saturation rBorg: rest Borg scale scoreRER: Respiratory Exchange RatiorIC: rest Inspiratory CapacityrSPO2: rest arterial Oxygen SaturationRV: Residual Volume TLC: Total Lung CapacityTLcoc: Carbon Dioxide transfer factor corrected for haemoglobinUM/L: Ratio of upper and middle lobe emphysema score to lower lobeVCO2: Carbon Dioxide ProductionVE: Minute ventilation VE/VCO2: Ventilatory Equivalent for Carbon DioxideVO2: Oxygen ConsumptionVO2/HR: Oxygen PulseVt: Tidal VolumeWR: Work Rate Authors’ contribution: AKB contributed to study design, data acquisition, analysis and interpretation and manuscript drafting. ZZ, AN, CD and DMH contributed to data acquisition and interpretation and they critically revised the manuscript. AJ contributed to study design and critically revised the manuscript. MIP and NSH contributed to study conception and design, data acquisition and interpretation and critically revised the manuscript. All authors approved the final version of the manuscript to be published and agree to be accountable for all aspects of the work.AcknowledgementsWe would like to thank the clinical physiologists in the Respiratory BRU at Royal Brompton Hospital, London, UK who performed the pulmonary function tests and conducted the cardiopulmonary exercise tests described in this paper.During the conduction of this work AKB was a recipient of an ERS Short-Term Research peting interestsThe authors declare that they have no competing interests.References ADDIN ZOTERO_BIBL {"custom":[]} CSL_BIBLIOGRAPHY 1. Ferguson GT. Why does the lung hyperinflate? Proc Am Thorac Soc. 2006;3(2):176–9. 2. 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Baseline characteristics of the study populationHeterogeneous(n=50)Homogenous(n=14)pAge60.9±7.562.5±5.90.471Gender (%)-male-female62.737.361.538.50.936BMI (kg/m2)24±4.525.6±3.60.243FEV1 %predicted32.4±11.428.1±10.30.213FEV1/FVC29.1±726.5±6.40.216rIC (lit)2.2±0.72.2±0.50.932rIC /TLC0.18±0.050.17±0.050.660rEELV (lit)6.1±1.46±1.50.840rEELV/TLC0.73±0.070.72±0.060.660TLC %predicted137±16.4132.4±9.40.198RV %predicted232.8±44.6220.7±320.365RV/TLC (%)61.6±8.560.8±5.20.757FRC %predicted189.9±31.5168.8±47.40.059TLCOc %predicted34.1±1033.3±11.50.867KCOc %predicted45.8±1240±12.10.300PaO2 (kPa)9.6±1.39.2±10.527PaCO2 (kPa)4.8±0.75.1±1.50.398BMI: Body Mass Index; FEV1: Forced Expiratory Volume in 1 second; FVC: Forced Vital Capacity; TLC: Total Lung Capacity; EELV: End-Expiratory Lung Volume; RV: Residual Volume; FRC: Functional Residual Capacity; TLcoc: Carbon monoxide transfer factor corrected for haemoglobin; Kcoc: Carbon monoxide transfer coefficient corrected for haemoglobin; PaO2: arterial Oxygen Partial Pressure; PaCO2: arterial Carbon Dioxide Partial PressureTable 2. Comparison of exercise parameters between patients with heterogeneous and homogeneous emphysemaHeterogeneous(n=50)Homogenous(n=14)PeIC (lit)1.5±0.51.3±0.30.240eIC/TLC0.18±0.050.17±0.050.385ΔIC %31.2±1339.8±9.80.031eEELV (lit)6.8±1.46.9±1.50.833eEELV/TLC0.82±0.050.83±0.050.385ΔEELV/TLC0.079(0.01-0.21)0.119(0.06-0.15)0.035eIRV (lit)0.4±0.30.3±0.30.352rBorg1(0-5)2(0-2)0.441pBorg7(4-10)7(5-7)0.807ΔBorg5(1-9)5(3-7)0.852Peak VE (lit/min)34(15-47)32(18-84)0.593Peak Vt (lit/min)1.1(1.8)1(0.8)0.739Peak VO2 (ml/kg/min)13.3(7.9-26.2)12.5(7.8-26)0.349Peak VO2 %predicted49(13-99)44(14-67)0.246Peak WR %predicted26(5-73)34(12-59)0.361Peak VCO2 (ml/min)780.6(404-2023.4)934.6(361-1025)0.944RER0.9(0.4-1.3)0.9(0.4-1.5)0.662Peak HR %predicted75.5(42-106)75.5(65-86)0.802PETO2 (kPa)14.9(13-18)14.9(11.4-16)0.441PETCO2 (kPa)4.7(2.3-6.7)4.6(3.6-8.3)0.687Peak VE/VCO239.4(26.9-72.2)41.6(21-48.3)0.834Peak VO2/HR %predicted66.6(14.4-112.3)59(20.4-82)0.131RR (breaths/min)32.9±8.931.2±9.40.545rSPO2 (%)94.5(88-99)96(91-98)0.323pSPO2 (%)89(79-98)89(80-95)0.869ΔSPO2 (%)6(0-12)6.5(3-11)0.674rIC: rest Inspiratory Capacity; eIC: end-exercise Inspiratory Capacity; EELV: End-Expiratory Lung Volume; TLC: Total Lung Capacity; IRV: Inspiratory Residual Volume; rBorg: rest Borg scale score; pBorg: peak Borg scale score; VE: Minute ventilation; Vt: Tidal Volume; VO2: Oxygen Consumption; WR: Work Rate; VCO2: Carbon Dioxide Production; RER: Respiratory Exchange Ratio; HR: Heart Rate; PETO2: End Expiratory Oxygen partial pressure; PETCO2: End Expiratory Carbon Dioxide partial pressure; VE/VCO2: Ventilatory Equivalent for Carbon Dioxide; VO2/HR: Oxygen Pulse; rSPO2: rest arterial Oxygen Saturation; pSPO2: peak arterial Oxygen Saturation Table 3. Correlations between emphysema distribution and exercise parameters, for both emphysema thresholdsExercise parameter950UM/L960UM/LΔIC %-0.264*-0.246*rBorg-0.0180.016pBorg0.0960.068ΔBorg0.0780.030Peak VE (lit/min)0.1860.040Peak Vt (lit/min)0.0250.053Peak VO2 (ml/kg/min)0.0500.033Peak VO2 %predicted0.340**0.341**Peak WR %predicted0.0870.040Peak VCO2 (ml/min)0.1300.128RER0.0750.110Peak HR %predicted-0.074-0.086Peak PETO2 (kPa)0.1930.197Peak PETCO2 (kPa)-0.097-0.109Peak VE/VCO2-0.0060.010Peak VO2/HR %predicted0.398** 0.390**Peak RR (breaths/min)0.300*0.266*rSPO2 (%)0.0460.030pSPO2 (%)0.0790.069ΔSPO2 (%)-0.099-0.091Emphysema distribution is expressed as the UM/L ratio of emphysema score for both the 950 and 960 emphysema thresholds; a high ratio represents upper lobe predominance. IC: Inspiratory Capacity; rBorg: rest Borg scale score; pBorg: peak Borg scale score; VE: Minute ventilation; Vt: Tidal Volume; VO2: Oxygen Consumption; WR: Work Rate; VCO2: Carbon Dioxide Production; RER: Respiratory Exchange Ratio; HR: Heart Rate; PETO2: End Expiratory Oxygen partial pressure; PETCO2: End Expiratory Carbon Dioxide partial pressure; VE/VCO2: Ventilatory Equivalent for Carbon Dioxide; VO2/HR: Oxygen Pulse; rSPO2: rest arterial Oxygen Saturation; pSPO2: arterial Oxygen Saturation at peak exercise* Significant correlation at 0.05 level**Significant correlation at 0.01 levelFigure legendA. Upper slice (at the superior border of the aortic arch) transferred to the post-processing workstation, where quantitative lung density analysis was performed using the Pulmo CT program. B. Histogram of distribution of lung attenuation values, measured in HU in the upper slice (at the superior border of the aortic arch) for several potential emphysema thresholds. ................
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