Heterogeneity in the respiratory symptoms of patients with mild-moderate COPD

Abstract

1Background: The burden of symptoms varies markedly between patients with Chronic 2 Obstructive Pulmonary Disease (COPD) and is only weakly correlated with lung function 3 impairment. While heterogeneity in lung function decline and exacerbations have been 4 previously studied, the extent of heterogeneity in symptoms and the factors associated with this 5 heterogeneity are not well understood. 6 Methods: A sample of the general Canadian population ≥ 40 years with persistent airflow 7 limitation was followed for up to 3 years. Participants reported whether they experienced chronic 8 coughing, phlegm, wheezing, or dyspnea during visits at 18-month intervals. We used mixed-9 effect logistic regression models (separately for each symptom) to assess overall heterogeneity in 1 0 the occurrence of symptoms between individuals, and the proportion of variation in symptom 1 1 burden explained by lung function versus all other clinical characteristics of participants. 1 2 Results: 548 participants (54% male, mean age 67 years) contributed 1,086 visits in total, and 1 3 82% of patients reported at least one symptom during follow-up. There was substantial 1 4 heterogeneity in the individual-specific probabilities for the occurrence of symptoms. This 1 5 heterogeneity was highest for dyspnea and lowest for phlegm (interquartile range of 1 6 probabilities: 0.15-0.77 and <0.01-0.53, respectively). FEV 1 explained 82% of the variation 1 7between individuals in the occurrence of phlegm, 26% for dyspnea, 3% for cough, and <0.1% for 1 8 wheeze. All clinical characteristics of participants (including FEV 1 ) explained between 86% of 1 9 heterogeneity in the occurrence of phlegm to <1% for wheeze. 2 0 Conclusion: There is marked heterogeneity in the burden of respiratory symptoms between 2 1 COPD patients. The ability of lung function and other commonly measured clinical 2 2characteristics to explain this heterogeneity differs between symptoms. 2 3 2 4 3 Word count: 262 2 5 2 6

Animal Models Reflecting Chronic Obstructive Pulmonary Disease and Related Respiratory Disorders: Translating Pre-Clinical Data into Clinical Relevance

“…Chronic bronchitis (productive cough that lasts for 3 months or more per year, for at least 2 years) can occur separately or combined with emphysema in COPD, where the latter diagnosis is based on spirometry. Decline in respiratory function is heterogeneous amongst patients, with some experiencing rapid, almost immediate reduction in lung function whilst others experience a more gradual decline [34][35][36][37][38][39]. The resultant airway damage, lack of elastic lung recoil, and pulmonary obstruction is irreversible, with no cure currently available.…”