Small Airway Disease
COPDGene was an observational study that enrolled more than 10,000 cigarette users with and without chronic obstructive pulmonary disease (COPD). The study was designed to explore genetic associations with COPD and to refine our understanding of COPD phenotypes. All patients had expiratory and inspiratory CT of the chest. The resulting dataset has provided insights into COPD physiology and genetics.
I have been writing a lot recently about small airway disease (SAD)—its measurement and significance in the setting of asthma or COPD. The CHEST journal just published more data from COPDGene that evaluated markers for SAD. The study is important for several reasons. First, the investigators compared measures of SAD using more than one modality. They also expanded on what we already know about the forced expiratory volume in 3 seconds (FEV3). Perhaps of greatest importance, they correlated small airway dysfunction with functional outcomes.
For the past 40 years it has been dogma that SAD can affect respiratory function. It has also been acknowledged that these patients are hard to assess, and that standard spirometric measures won't detect SAD until it has progressed. For a long time, the forced expiratory flow at mid-expiration (FEF25%-75%) was considered a surrogate for SAD, but this measure shows wide variability and overlap between normal and abnormal values. Impulse oscillometry (iOS), plethysmography, FEV3, and CT imaging with air-trapping/mosaicism have all been used to establish SAD. Unfortunately, little in the way of comparative research between modalities has been done, and little correlation with clinical outcomes has been found.
FEV3, the SAD Measure of Choice
Enter the most recent installment from the COPDGene study published in CHEST. The investigators compared FEV3 with CT and established good correlation. It's reassuring that the two modalities are measuring the same phenomenon. In addition to what we already know about FEV3 and SAD,[5,6] they found that FEV3/FVC6 was superior to FEV3/FVC for predicting clinical outcomes in patients with COPD. Among patients with otherwise normal spirometry, the 15.4% with a low FEV3/FVC6 had increased symptoms (St George's Respiratory Questionnaire and modified Medical Research Council [mMRC] dyspnea score) and BODE index score, as well as shorter 6-minute walk distance compared with those with normal FEV3/FVC6. The importance of the relationship with functional status and symptoms cannot be overstated. All of the modalities used to measure SAD are short on clinical outcomes data; without those data, how do we know whether the deficits we believe we are identifying are clinically relevant?
This is more evidence that SAD is clinically relevant and supports using FEV3 as the small airway measure of choice. It's easy; it has already been reported with spirometry and, in my opinion, is backed by the best data.[2,4,7] There is no radiation risk and it doesn't require advanced equipment like iOS or plethysmography. For all you pulmonologists out there, start looking at the FEV3 when you get spirometry on your tobacco users and patients with unexplained dyspnea.
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Cite this: Assess Those Small Airways With FEV3 - Medscape - Sep 13, 2016.