Risks of adverse respiratory outcomes in adults with cancer over the course of survivorship compared with cancer-free individuals: a matched cohort study using linked English electronic health records.

Background: We aimed to compare the risks of developing new chronic respiratory conditions, or exacerbating existing ones in survivors of 20 common cancers vs. cancer-free individuals. Methods: We conducted a population-based matched cohort study using English electronic primary care records, linked to cancer registry, hospital admissions, and death records data from 1999 to 2019. Adults aged ≥ 18 years with incident cancer were matched 1:10 to cancer-free individuals on age, sex and general practice. Outcomes included new-onset and exacerbations of asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, and interstitial lung disease (ILD) ascertained from electronic health record (EHR) data throughout follow-up. Relative risks were estimated using Cox models, adjusted for confounders, like smoking. Absolute risks were estimated using adjusted incident rate differences and standardised cumulative incidence curves for new-onset disease and mean cumulative count for exacerbations. Findings: 789,254 adults with incident cancer were included. Compared with cancer-free individuals, ILD risk was raised in 18 cancers (adjusted hazard ratio [adjHR] > 5 in CNS, oesophageal and lung cancers, and adjHR > 2 in seven further cancers); raised risks persisted beyond five years after diagnosis in 11 cancers. Elevated risks of developing COPD were observed in 11 cancers (adjHR 4.69 increased risk for lung cancer; other adjHRs 1.08-1.71); for seven of these cancers, raised risks persisted beyond five years. New-onset bronchiectasis risk was increased in oesophageal, lung and haematological cancers while new-onset asthma risk was raised in non-Hodgkin lymphoma only. Exacerbations rates of pre-existing respiratory diseases were raised in survivors of oesophageal, liver, lung, pancreatic, central nervous system, and haematological cancers. Interpretation: Survivors of most types of cancer had substantial and sometimes prolonged raised risk of a range of respiratory conditions. Future research should explore the mechanisms underlying these associations, including the roles of post-cancer tobacco use and specific anti-cancer treatments. Targeted management, smoking cessation, and vaccination may be warranted for those at highest risk. Funding: Medical Research Council and Wellcome trust.