Feasible and simple exclusion criteria for pulmonary reference populations

International guidelines recommend that pulmonary reference populations consist of never-smokers without respiratory diseases or symptoms, but the diseases and symptoms are not clearly specified. The present study aimed to identify simple exclusion criteria for defining pulmonary reference populations.

Based on a random sample from a general population (the parent population), 2,358 subjects aged 26-82 years performed spirometric tests. From this sample, subjects were stepwise excluded according to self-reported obstructive lung diseases, symptoms and smoking history. Four increasingly more healthy respiratory reference populations were formed. Prediction equations for the median and lower limit of normal lung function were derived using quantile regression analysis.

Subjects without self-reported obstructive lung diseases or the cardinal respiratory symptoms of breathlessness, cough or wheeze (population B), never-smokers without cardinal symptoms (population C) and never-smokers without any respiratory symptoms (population D) constituted 50% (n = 1,184), 23% (n = 539) and 14% (n = 331) of the parent population (population A), respectively. The largest discrepancy between prediction equations was found between the parent population and the population without cardinal respiratory symptoms (population B) (p<0.05). Minor changes in the reference equations were also seen when excluding ever-smokers (population C). There was no additional change with exclusion of other respiratory symptoms (population D). Age-related decline in lung function was steepest in the parent population.

Obstructive lung diseases, smoking history, breathlessness, cough and wheeze are optimal exclusion criteria for a pulmonary reference population. Further validation of the exclusion criteria identified in this study is recommended with identical wording in other and larger multinational populations.