Cough in fibrotic lung disease

Abstract

Background: Idiopathic pulmonary fibrosis and other progressive fibrotic lung diseases are associated with significant mortality and morbidity. Cough has previously been described to be associated with worsening outcomes in IPF. The pathogenesis of cough in fibrotic interstitial lung disease (FILD) is unknown and as such few effective treatment options are available to treat this disabling symptom. Methods: Two cohorts of patients were studied – the PROFILE cohort of 579 patients recruited between two major teaching hospitals. A second prospective cohort of 53 patients was collected for the purpose of measuring both subjective and objective cough. Patients in the latter cohort underwent fiberoptic bronchoscopy and bronchoalveolar lavage to allow measures of inflammation and microbiome to be taken. Blood was taken for genetic analysis to evaluate the MUC5B promoter polymorphism and its role in cough. Results: The impact of cough on quality of life in the PROFILE cohort is significant with a median Leicester cough questionnaire score (LCQ) of 16.32. Objective cough was similarly elevated with a median cough count of 10.6/hr/24hrs. This burden is comparable to that seen in lung cancer and more than that seen in airways disease. Of various subjective measures of cough, cough visual analogue scale (VAS) best correlates with objective cough recording. The cough of FILD correlates only weakly with measures of lung function and not with the MUC5B promoter polymorphism or bacterial burden suggesting its independence 3 from disease process. Current treatments for FILD do not seem to reduce cough burden significantly. Conclusion: Cough in fibrotic lung disease remains a therapeutic challenge with little change in cough burden through the duration of the illness. Targeting neuronal pathways seems a promising strategy, but more data is required to evaluate this. In particular cough challenge studies examining the heterogeneity of neuronal hypersensitivity would be prudent prior to embarking on trials of treatment.