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Background COPD prevalence is highly variable and geographical altitude has been linked to it, yet with conflicting results. We aimed to investigate this association, considering well known risk factors. Methods A pooled analysis of individual data from the PREPOCOL-PLATINO-BOLD-EPI-SCAN studies was used to disentangle the population effect of geographical altitude on COPD prevalence. Post-bronchodilator FEV1/FVC below the lower limit of normal defined airflow limitation consistent with COPD. High altitude was defined as >1500 m above sea level. Undiagnosed COPD was considered when participants had airflow limitation but did not report a prior diagnosis of COPD. Results Among 30,874 participants aged 56.1 ± 11.3 years from 44 sites worldwide, 55.8% were women, 49.6% never-smokers, and 12.9% (3978 subjects) were residing above 1500 m. COPD prevalence was significantly lower in participants living at high altitude with a prevalence of 8.5% compared to 9.9%, respectively (p < 0.005). However, known risk factors were significantly less frequent at high altitude. Hence, in the adjusted multivariate analysis, altitude itself had no significant influence on COPD prevalence. Living at high altitude, however, was associated with a significantly increased risk of undiagnosed COPD. Furthermore, subjects with airflow limitation living at high altitude reported significantly less respiratory symptoms compared to subjects residing at lower altitude. Conclusion Living at high altitude is not associated with a difference in COPD prevalence after accounting for individual risk factors. However, high altitude itself was associated with an increased risk of undiagnosed COPD.

We are grateful to Aggarwal and colleagues for their interest in our paper [1]. They are correct to point out the limitations of cross-sectional studies, particularly when they rely on recalled information, and we discussed these at some length in the paper. However, evidence needs to be evaluated in the round. Not all error is biased; the outcomes (lung function) that we used were measured objectively and, as the results were not shared with the participants at the time, are unlikely to have influenced their answers to questions about a past history of tuberculosis. We agree, of course, that objective measures of tuberculosis would have been preferable, but it seems more likely that these would have reduced random error and so strengthened the current findings. We hope to add these to future investigations in the Burden of Obstructive Lung Disease (BOLD) cohort. A history of tuberculosis is an important risk factor for obstructive disease and low lung function

The most popular way to define asthma based on questionnaires is to use definitions taken from cross-sectional international studies on asthma. These definitions may not, however, be optimal for future studies focusing on risk factors of asthma. The current authors, therefore, compared the performance of different operational definitions of asthma. The European Community Respiratory Health Study I was a cross-sectional study of 21,924 subjects aged between 25-44 yrs in 18 countries. Operational definitions of asthma compared included different combinations of symptoms of asthma and bronchial hyperresponsiveness. A continuous asthma score, ranging from 0-8, was defined as the sum of positive answers to eight main symptom questions. There was no threshold in the associations of asthma symptoms with severity or risk factors of asthma, which would have suggested a dichotomous definition of asthma. Using dichotomous definitions requiring the presence of several asthma symptoms strengthened associations with studied risk factors, and also increased the estimated specificity and positive predictive value. Using a continuous asthma score also improved the power of the analyses. In conclusion, dichotomous definitions of asthma yielding higher odds ratios are achieved by requiring positive responses to several questions on symptoms. However, symptoms of asthma are possibly best analysed as a continuous asthma score.

The European Community Respiratory Health Survey (ECRHS) was planned to answer specific questions about the distribution of asthma and health care given for asthma in the European Community. Specifically, the survey is designed to estimate variations in the prevalence of asthma, asthma-like symptoms and airway responsiveness; to estimate variations in exposures to known or suspected risk factors for asthma, and assess to what extent these variations explain the variations in the prevalence of disease; and to estimate differences in the use of medication for asthma. The protocol provides specific instructions on the sampling strategy adopted by the survey teams, as well as providing instructions on the use of questionnaires, the tests for allergy, lung function measurements, tests of airway responsiveness, and blood and urine collection. The principal data collection sheets and questionnaires are provided in the appendices, together with information on coding and quality control. The protocol is published as a reference for those who wish to know more of the methods used in the study, and also to give other groups who wish to collect comparable data access to the detailed methodology.