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.