Clinical implications of reduced FEF25-75 in SARP patients

Reduced FEF25-75 in asthma. What does it mean and what are

the clinical implications?

Fernando Holguin MD MPH Director,

Asthma Clinical & Research Program Center for lungs and Breathing University of Colorado

Outline

? What is FEF 25 ? 75 ? What does it mean having a reduced FEF

25 ? 75 ? What are the potential clinical applications

associated with having a reduced FEF2575 ? Isolated FEF25-75, a different asthma phenotype? ? Limitation and future directions

FEF25-75

? Forced expiratory flow averaged over the middle portion of FVC, measured in L/s

? Historically thought to represent "small airways disease"

? Hypothesized to be a marker for peripheral airways obstruction; more sensitive to early involvement

Quanjer et al, ERJ 2014; 43: 1051-8

Defining FEF 25 - 75

? A physiological measure provided with every spirometry, for which everyone has a different opinion on what it measures and on its clinical relevance

? Unlike FEV1, a physiological measure for which there are no specific guidelines on how it should be interpreted.

Mid expiratory flow rates in the flow volume loop

0 ? 25% Effort dependent

25 ? 75% - Effort independent - Reflects flows from more

distal lung segments in which at lower lung volumes, elastic recoil and small airway resistances are major determinants of expiratory flow rates

Cross sectional analysis of 39 males and 14 females, which had MMF < 80% of predicted and an FEV1 > 80% on two consecutive occasions. (17 smokers)

FEV1 %

MEFR % MMF %

No hx of asthma 86% reported having ever wheezed 68% reported frequent coughing

Mc Fadden R, et al Am J Med 1972

From reduction in MMF to small airways disease

1. Reductions in MMF could be a normal variant. - Unlikely given that these patients had abnormal physiology

2. Reductions in MMF could be the result of loss of elastic recoil - Unlikely given that static pressure ? volume curves were within normal range

3. The small peripheral bronchioles explain the reductions in MMF -Supported by data showing: a) Cdyn was frequency dependent b) Reduced conductance of the small airways was low, and c) There were changes in gas exchange.

These changes must have been caused by marked time constant discrepancies AND, given that Raw was within normal limits, it is unlikely that larger airway ( 1 ? 4th generation) are the site of this process. THEREFORE...it must be in the peripheral airways. Because, 2mm airway diameters are the site of anatomical involvement in early COPD and the greater site of resistance at low lung volumes, reduced MMF represent obstruction in this site

Forced mid expiratory Are more sensitive to detect early changes in asthma & emphysema, Proposed ability to detect changes in more peripheral airways

CHEST, VOL. 64, NO. 6, DECEMBER, 1973

In 25 patients who developed bronchiolitis obliterans (BOS) after bilateral lung transplantation, both airway conductance and FEF25-75 were sensitive indicators

CHEST/111 7 6/JUNE, 1997

80 patients with asthma, mild to severe. FEF 25 ? 75 inversely related to bronchial thickening in major airway segments

Niimi A et al, Am J Respir Crit Care Med Vol 162. pp 1518?1523, 2000

FEF25-75, best correlation with air trapping index.

Allergy Asthma Immunol Res. 2011 April;3(2):111-117

In asthmatics, FEF25-75% is not associated with measures of distal airway inflammation

Sutherland R, J ALLERGY CLIN IMMUNOL VOLUME 113, NUMBER 6, 2004

Rao et al , J Asthma 2012

ORs for the association between a 10% reduction in FEF25-75% and long term asthma Persistence at follow up; adjusted for age, sex, body mass index, allergic sensitization, allergic rhinitis, age of asthma onset at baseline, and active smoking ever

337 participants (142 children and 225 adults) with current asthma (asthma attacks or treatment in the past 12 months) recruited to the Epidemiological Study on the Genetics and Environment of Asthma (EGEA1) and followed up at 12 and 20 year surveys

Siroux, et al . J ALLERGY CLIN IMMUNOL VOLUME 137, NUMBER 6

Adjusted association (ORs and 95% CIs) between FEF25-75 percent predicted at baseline and subsequent risk for uncontrolled asthma 10 years later. ORs are estimated for an FEF25-75 level reduced by 10% of predicted value.

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