Background: The burden of symptoms varies markedly between patients with Chronic Obstructive Pulmonary Disease (COPD) and is only weakly correlated with lung function impairment. While heterogeneity in lung function decline and exacerbations have been previously studied, the extent of heterogeneity in symptoms and the factors associated with this heterogeneity are not well understood.

Methods: A sample of the general Canadian population ≥40 years with persistent airflow limitation was followed for up to 3 years. Participants reported whether they experienced chronic coughing, phlegm, wheezing, or dyspnea during visits at 18-month intervals. We used mixed10 effect logistic regression models (separately for each symptom) to assess overall heterogeneity in the occurrence of symptoms between individuals, and the proportion of variation in symptom burden explained by lung function versus all other clinical characteristics of participants.

Results: 548 participants (54% male, mean age 67 years) contributed 1,086 visits in total, and 82% of patients reported at least one symptom during follow-up. There was substantial heterogeneity in the individual-specific probabilities for the occurrence of symptoms. This heterogeneity was highest for dyspnea and lowest for phlegm (interquartile range of probabilities: 0.15-0.77 and <0.01-0.53, respectively). FEV1 explained 82% of the variation between individuals in the occurrence of phlegm, 26% for dyspnea, 3% for cough, and <0.1% for wheeze. All clinical characteristics of participants (including FEV1) explained between 86% of heterogeneity in the occurrence of phlegm to <1% for wheeze.

Conclusion: There is marked heterogeneity in the burden of respiratory symptoms between COPD patients. The ability of lung function and other commonly measured clinical characteristics to explain this heterogeneity differs between symptoms.