This analysis examined data from the Lung Health Study to determine whether post-bronchodilator lung function predicts mortality. Overall, we found that the pre- and post-bronchodilator measures of lung function, whether used categorically (as stages of COPD) or continuously (as FEV1 % predicted) predicted mortality similarly. This finding suggests that post-bronchodilator lung function data may not be needed for studies that look at long term outcomes in COPD.
Most guidelines defining COPD say that spirometry should be performed after the administration of an adequate dose of an inhaled bronchodilator in order to minimize variability [4, 21]. These same guidelines, however, state that "neither bronchodilator nor oral glucocorticosteroid reversibility testing predicts disease progression, whether judged by decline in FEV1, deterioration of health status, or frequency of exacerbations in patients with a clinical diagnosis of COPD and abnormal spirometry. Small changes in FEV1 (e.g., < 400 ml) after administration of a bronchodilator do not reliably predict the patient's response to treatment" . Others have suggested that one cannot use prebronchodilator lung function to define COPD, the reason being that airflow limitation can be variable and that this component can be easily reverse with a bronchodilator . Other research, though, has suggested that bronchodilator responsiveness is highly variable and that "over half the patients initially classified as reversible by the ATS/GOLD definition would be reclassified had they attended on another occasion" .
In population-based studies, one would expect that post-bronchodilator lung function measurement would reduce the prevalence of COPD. For example, in the PLATINO study, bronchodilator testing reduced the overall prevalence of FEV1/FVC% < 0.70 from 21.7% to 14% . In our analysis the prevalence of severe COPD was lower in the post- compared to the pre-bronchodilator lung function in both the year 1 (0.4% vs. 1.3%) and the year 5 (3.4% vs. 6.4%) cohorts. The finding of a lower prevalence, however, does not necessarily mean that this is the correct prevalence.
Others have looked at this problem in different ways. For example, Hansen et al studied 985 patients with COPD and found that the response to a bronchodilator was a positive prognostic factor along with FEV1 at baseline. However, if baseline FEV1 was substituted with post-bronchodilator FEV1, the bronchodilator reversibility became nonsignificant . Compared to our population, that population had much lower lung function (mean FEV1 38.5% of predicted compared to our mean FEV1 of 74.7%) and was much older (mean age 61.8 years at baseline compared to our mean age of 48.5 years). Still, the predictive value for FEV1 in their study was similar in the pre- (relative risk [RR] 0.60, 95% CI 0.54, 0.81) and post- bronchodilator (RR 0.62, 95% CI 0.56, 0.69) models.
Burrows acknowledged the complexity of the relation between bronchodilator responsiveness and outcomes in obstructive lung disease . He noted that different studies had varying results [27, 28] and suggested that several factors, such as how baseline lung function is determined, how responsiveness is measured, and the prevalence of "asthma" in the studied population, may be important determinants of outcomes. His conclusion that mortality is "related to age and to a low initial post-bronchodilator FEV1" provides, in part, the historic rationale for using post-bronchodilator lung function to define COPD.
This study has limitations that are important to its interpretation. The most important was that it was not a true "population-based" study but was a clinical intervention trial that targeted early COPD. Study participants had to be current smokers at entry with lung function that was mildly abnormal, and subjects who regularly used bronchodilators were excluded. Although asthma history was not a specific exclusion criterion, excluding people with regular bronchodilator use had the net effect of eliminating subjects with clinically significant asthma from the population. Thus, these findings may not necessarily apply to a population that includes never smokers or where a large proportion of the population has asthma that is symptomatic. Also, a more inclusive population of smokers where reversibility is more common may have yielded different results. This limitation is decreased by our study design that looked at data from the year 1 and year 5 follow-up, at which point some subjects had stopped smoking and many developed symptoms consistent with asthma or COPD. In addition, one would not expect the post-bronchodilator FEV1 of never smokers (in the absence of asthma) to differ significantly from the pre-bronchodilator value. Finally, the dose of bronchodilator used in this study (two inhalations, 200-μg total dose, of isoproterenol) is less than what has been used in other clinical trials, some of which have used 400 μg of isoproterenol and 400 μg of albuterol . Thus, it is unknown whether the findings would be similar if a "maximal bronchodilitation" protocol was used.
Another limitation was the absence of other important measures of COPD, such as an impaired exercise testing, impaired diffusion capacity or abnormal imaging. Recent work [30–32] in COPD has highlighted that measures other than lung function are important predictors of impaired function and poor outcomes. Lung function remains, however, the primary means of diagnosing and classifying COPD at the present time and this is unlikely to change in the foreseeable future.