Airway Obstruction and Bronchodilator Responsiveness in Adults With Acute Cough

Main Findings

In adult patients without preexisting physician diagnosed asthma or COPD who consulted for acute cough in primary care and who underwent pre- and postbronchodilator spirometry 4 weeks later, 13% showed bronchodilator responsiveness, together with a history of recurrent airway symptoms. People with repeated episodes of acute cough and reversible airway obstruction may have undiagnosed asthma. Obstructive spirometry according to the GOLD definition was present in 10% and according to the LLN definition in 6% of the patients. The GOLD definition classified more participants with an obstructive condition than did the LLN definition, especially among older participants. Although these findings are necessary but not sufficient to diagnose COPD and asthma, patients with these findings are at higher risk of having (yet undetected) chronic obstructive lung disease and might benefit from ongoing treatment.

Strengths and Limitations

We studied a clinically relevant population, namely, those consulting their family physician for respiratory complaints (acute cough), whereas most previous studies included only asymptomatic volunteers (open-population studies).^17-19 Moreover, we studied the prevalence of lung function abnormalities in 12 European countries, whereas most other studies were from a single country. Reviews mention considerable variation in reported prevalence of obstructive lung disease, attributed to differences in risk exposure, population characteristics, methods, and definitions used to measure disease.^18,20 In our pan-European study, standardized measurements were used, and population differences were taken into account in analyses, increasing generalizability of the results. Finally, we measured spirometry results 4 weeks after an index consultation, when most acute episodes of cough had resolved.

A limitation of our study is that a formal clinical diagnosis of asthma and COPD could not be established within our research design. We were merely able to identify those with high risk of these disorders. Persistent airway obstruction is a hallmark of COPD (but can also develop in asthma, especially in smokers), and bronchodilator responsiveness suggests asthma and is common in COPD. There is no single reference standard to diagnose asthma and COPD; these diagnoses should be based on clinical history and physical examination combined with spirometry results. Repeat spirometry and additional tests, such as body plethysmography for COPD and histamine- or methacholine-provocation tests for asthma, can increase diagnostic certainty. We therefore considered that the diagnostic categories we used (bronchodilator responsiveness and airway obstruction) were most appropriate for reporting our results. Diagnostic certainty in our identified study participants could also have been be increased by specific questionnaires for asthma and COPD; however, the diagnostic value of such questionnaires is uncertain. Our findings reinforce the need for more objective criteria to define asthma or COPD.

The differences in prevalence of airway obstruction and bronchodilator responsiveness that we found between countries might represent real differences, possibly caused by variation in air pollution or demographic characteristics. Moreover, the differences could also partly be explained by varying definitions and guidelines between countries, because an active detection policy for asthma and COPD reduces the number of undetected cases (Supplemental Appendix 2). A further limitation of our study is that differential patient selection (selection bias) between countries cannot be excluded, as we were not able to gather data on the eligible participants who were not included in the study. Another problem is the high number of missing or incomplete spirometry results for some countries (eg, Italy, Supplemental Appendixes 1 and 2), resulting in unreliable prevalence estimates in those countries. We did not record whether missing spirometry data (19%) arose from uninterpretable results or whether spirometry was not performed in these patients. Moreover, there was no additional standardized reassessment of all spirometry curves in our study, and the individual judgment of quality by the individual research staff members may have led to misclassification.

Participants were assessed using the equipment already available in the participating practices and so were assessed using a range of models and makes of spirometer (list available on request). Spirometry was performed according to a uniform protocol at all study sites, however, and all general practice staff members performing spirometry were trained to analyze spirometry curves. A primary care study has shown that spirometry tests in a primary care setting conducted by staff with adequate training are comparable in quality to pulmonary function laboratory measurements.²¹ Finally, participants were included who were using inhaled lung medication, which may have influenced their spirometry results. Even so, it is common for primary care patients to be treated with inhaled medication without first undergoing diagnostic work-up for asthma or COPD.

Comparison With Other Studies

The prevalence of abnormal spirometry patterns in our study was lower than in other studies. The diagnostic outcomes we used, however, differed from those used in these previous studies. Thiadens and colleagues⁶ found asthma in 39% and COPD in 7% of the cases, and Broekhuizen and colleagues⁷ found previously undetected COPD in 30%. Apart from the older age of participants in Broekhuizen's study, the most likely explanation is that the average duration of cough was shorter in our study (8.7 days, with a self-reported recovery rate of 70% at 14 days). In an open-population study of the presence of chronic lung diseases in 169 smokers, 18% had COPD, increasing to 27% among those with chronic cough.¹

There was no notable variation in prevalence of airway obstruction among nonsmokers (9%), past-smokers (10%), and current smokers (13%) in our study, which is possibly related to the large number of missing results on smoking status. Alternatively, smokers may have been more likely to have had COPD previously diagnosed.

Studies in the general population found prevalence of obstructive lung disease that varied from 23% to 29%, depending on diagnostic criteria.^17-19 Likewise, findings from our study show that differences in age, sex, smoking status, and geographical population, as well as the definition that is used, can result in systematic differences in international prevalence rates. The increasing airway obstruction GOLD prevalence with older age, ie, when using the fixed ratio, is in line with recent warnings for overdiagnosis of airway obstruction in older adults. Also, the higher prevalence according to the LLN definition in younger participants is consistent with previous studies.¹³

Clinical Implications and Conclusions

An important proportion (approximately one-fifth) of adult patients without an established diagnosis of asthma or COPD consulting their family physician with acute cough showed subsequent airway obstruction or bronchodilator responsiveness, which suggests undetected asthma or COPD. Given effective pharmacological and lifestyle modification interventions, especially interventions to assist in quitting smoking, identifying and providing appropriate treatment and advice to these patients is likely to improve their quality of life and reduce exacerbations. Moreover, an accurate diagnosis could help to motivate smokers to quit.²² Finally, detection of asthma and COPD may help to reduce unnecessary use of antibiotics in patients with acute cough, because a noninfectious cause (obstruction) will also be considered.

Different methods to define airway obstruction resulted in twofold differences in the prevalence estimates among participants aged 50 years or more. Our results from symptomatic patients seeking health care uniquely confirm findings from open-population studies that a fixed cutoff value of 0.70 (GOLD) should be used to define obstruction with caution in the extremes of age.^12,13