Prevalent comorbidity in patients with hypersensitivity pneumonitis: a UK primary care population study

<bold>Background:</bold> Existing data on the prevalence of comorbidities in patients prior to a diagnosis of hypersensitivity pneumonitis (HP) is sparse. <bold>Methods:</bold> Patients with two read codes of HP diagnosed between 01/01/1997 and 01/01/2019, were identified from the Clinical Practice Research Datalink GOLD database multiple registrations cohort. Included patients with a restrictive defect on pulmonary function testing were defined as probable fibrotic HP (pfHP). The incidence of a range of comorbidities was compared to age, gender and smoking matched patients with chronic obstructive pulmonary disease (COPD), and a second cohort of similarly matched patients without HP or COPD. <bold>Results:</bold> 210 pfHP patients (median age=62, male=59%) were identified. Compared to matched controls without COPD, 5 years prior to their HP diagnosis, pfHP patients had an increased risk of asthma (RR 2.9 [1.9-4.4], p<0.001), cardiac disease (RR 2.4 [1.4-4.0], p=0.002), atrial fibrillation (RR 3.1[1.5-6.4], p=0.002) and hypertension (RR 1.3 [1.0-1.7], p=0.04) and gastro-oesophageal reflux disease (RR 1.9 [1.1-3.4], p=0.02). Compared to matched COPD controls, pfHP patients were at higher risk of asthma (RR 1.6 [1.2-2.2], p=0.005) and death (log-rank test, p<0.001). Interpretation: The increased documentation of asthma prior to HP diagnosis suggests that individuals predisposed to HP may exhibit asthma-like prodromal symptoms a decade before a formal HP diagnosis. These findings have implications for our understanding of the early pathophysiological evolution of fibrotic HP and its early detection.