In this study, among adults enrolled in an integrated health care organization, airflow obstruction among those without a known COPD diagnosis was not associated with a discernible increased likelihood of subjective respiratory symptoms, poorer self-reported health status, or decrements in functioning including the Short Physical Performance Battery (SPPB) and distance walked in 6 minutes (SMWT).
Notably, obesity was associated with a lower likelihood of airflow obstruction as defined by an FEV1
/FVC ratio <0.7, an effect that has been seen in prior cross-sectional studies of previously undiagnosed airflow obstruction.5,10–12
This stands in contrast to those with established COPD, where a positive association between COPD and increased
BMI has been reported,13
an effect that was previously reported by our group among those with diagnosed COPD in the study arm of the FLOW cohort not included in this analysis.36
The mechanism(s) of any protective effect of obesity on the presence of non-clinically diagnosed airflow obstruction remain to be elucidated. Clearly, there appears to be a difference between the relationship of obesity in non-clinically diagnosed airflow obstruction and clinically diagnosed COPD. Once COPD has been clinically diagnosed, there is a subset of patients who evolve to manifest lower BMI and have worse outcomes overall.37–40
Therefore, persons with concomitant clinically diagnosed COPD and obesity may reflect a survival bias leading to a higher proportion of patients with established COPD who are obese. Nonetheless, extrapolating from this sample to persons with non-clinically diagnosed airflow obstruction without clinical disease would be overly speculative at this time.
Obesity, but not airflow obstruction, was associated with productive cough, dyspnea on exertion, and self-assessed poorer health status. In addition, SPPB was impaired and SMWT distance was reduced in the presence of obesity. These associations are consistent with the existing literature documenting a convincing link between obesity and poorer functional status.41–43
Furthermore, the lack of association of decreased lung function to either respiratory symptoms or subjective quality of life decrements seen in our study is also well established in the existing literature. Many previous studies have shown the relatively weak association between decrements in lung function per se
and decreased health-related qualify of life or decreased functional status.44–47
Our study re-confirms this observation, suggesting that obesity is more strongly associated with the increased respiratory symptoms and decreased functional capacity that were manifested in our cohort.
In our cohort, obesity was less strongly and not significantly associated with obstruction as defined by the lower limit of normal (LLN) of the FEV1/FVC ratio and we observed no significant obesity-associated difference in the median FEF25–75. Redefining airflow obstruction based on the LLN reduced the prevalence of abnormality in this cohort (12.4% vs. 19%). Although our power to detect significant associations was compromised by the restricted numbers with obstruction thus defined, the point estimate of the obesity risk for obstruction was similar and in the direction of less likely odds (0.7 compared to 0.5), as was the weak association of obstruction with dyspnea on exertion (1.4 compared to 1.2).
Taken together, our results suggest that among those without previously diagnosed COPD, airflow obstruction, per se, is not contributing to respiratory symptoms, functional capacity, or self-rated global health status in a statistically significant or clinically meaningful way. Rather, we found that obesity in this group was playing a larger and more meaningful explanatory role. Thus, it may be possible that interventions intended to improve dyspnea may achieve greater impact by reducing obesity rather than by overly focusing on labeling airflow obstruction detected through screening as COPD and treating this with medications.
Strengths and Limitations of the Study
A particular strength of this analysis is in the systematic characterization of symptoms and the objective measures of physiologic functioning (pulmonary function, SMWT, and SPPB) in a sample recruited from a large integrated health care organization generalizable to other primary care settings. In addition, for our analysis we dichotomized BMI (obese vs. non-obese) rather than treating this as a linear variable. Even though this may result in some loss of statistical power, obesity so defined is the accepted and more clinically relevant measure. Moreover, including non-smokers as well as smokers in our study group is more relevant to the mixed general primary care population. By the same token, symptoms were not used as a screening criterion for entry into the study; limiting spirometric screening to only symptomatic populations is likely to introduce selection bias, both in regard to airflow obstruction and obesity.
Limitations of this analysis include its relatively narrow adult age range, modest sample size, geographic concentration in northern California and the absence of post-bronchodilator measurements of lung function. Subjects were intentionally chosen within a specific age range (40–65) because the focus of the parent FLOW study was disability among persons of working age; this may limit generalizability to older populations where airflow obstruction may be more prevalent and may have differing relationships to obesity. Some of the associations we observed did not achieve statistical significance, but might have done so with larger study numbers. Nonetheless, other weak associations, such as the change in SMWT linked to obstruction, are in the opposite direction to an adverse effect and do not suggest a larger study size alone would have led to an adverse effect being observed. Selection of referents may have contributed a source of bias in our study; overall we were able to recruit 649 subjects from 1558 eligible (42%), with 373 subjects participating (57% of the total recruited). Comparing individuals who participated in our study to those who did not, however, revealed a higher incidence of current or former smoking in the non-participation group. Had these non-participants been included in our study, this likely would have increased the incidence of AO, given the observed relationship between smoking and AO.
We studied subjects recruited from northern California; this geographic limitation should be kept in view when generalizing to other regions. We did not administer bronchodilators prior to lung function assessment, which may have falsely labeled some subjects with airflow obstruction who may have had reversible obstruction; this is particularly relevant because a subset of the subjects with obstruction were likely to have asthma. We addressed this issue by carrying out sensitivity analyses for all key models excluding such subjects. These demonstrated similar associations. We recognize the possibility that persons with obstruction who did not carry a prior diagnosis of asthma (and thus were not excluded from sensitivity analyses based on that diagnosis) nonetheless had that condition, which could influence the results seen in our study. Our study primarily focused on obstruction defined by an FEV1
/FVC ratio <0.7. The LLN approach, which we tested secondarily, may be more precise, but the fixed ratio approach is far more widely used and better understood in general primary care settings.48,49
Finally, in the setting of concomitant obesity and airflow obstruction, obesity may lower the FVC, which can appear to “normalize” the FEV1
/FVC ratio in the presence of a decreased FEV1
. This effect, to the extent operative, would tend to misclassify those with obstruction and concomitant obesity into the non- airflow obstruction group, making obesity appear to be less frequent in airflow obstruction. Of note, the FVC as a percent predicted, indeed was lower among obese compared to non-obese subjects. Were misclassified obstruction to have accounted for the relationship between obesity and respiratory symptoms in our cohort, however, we would have expected a strong association between increased BMI and abnormal FEF25–75
, which was not the case.
In summary, although airflow obstruction is relatively common in adults without an established COPD diagnosis and even though this impairment is related to cumulative smoking history, it may not be associated with respiratory symptoms or functional status. In contrast, obesity is negatively associated with the presence of obstruction and is strongly linked both to symptoms and functional impairment, even taking airflow obstruction into account. Strategies to manage respiratory symptoms and functional impairment among those with airflow limitation should consider the contribution of obesity to such abnormalities.