COPD comorbidity and checkpoint inhibitor pneumonitis in a case-control study of patients with lung cancer.
Authors: Deyo Logan James , Norton Dustin Lee , Hunting John , Faucheux Andrew Thomas , Evans Joni , Amornmarn Amy , Rowland Courtney , Deery Erin , Lycan Thomas William 
Published: June 2024

e14700

Background: Checkpoint inhibitor pneumonitis (CIP) is the most common high-grade immune-related adverse event among patients with lung cancer. Risk factors for CIP include interstitial lung disease, fibrosis on pre-treatment CT imaging, and likely COPD. This study aims to compare COPD variables and CIP outcomes between cases of high and low-grade CIP, and controls without CIP. We hypothesized that the presence and severity of COPD would affect the evaluation, management, and outcomes of CIP. Methods: From a database of patients with lung cancer who received at least one dose of an immune checkpoint inhibitor between 2/1/11 and 4/7/22 at a comprehensive cancer center, we identified all CIP cases and randomly selected a larger number of controls without CIP. The study team reviewed routine clinical documentation and collected data on pre-treatment respiratory function (e.g., comorbidities, spirometry) and CIP outcomes (e.g., diagnostic testing, interventions, severity). Low-grade (grades 1-2) versus high-grade (grades 3-5) CIP were defined by the Common Terminology Criteria for Adverse Events. We tested categorical variables using Chi-squared or Fisher’s exact test depending on assumptions. We compared continuous variables using the Wilcoxon rank sum or the Kruskall-Wallis test. The database was maintained on a secure, cloud-based REDCap database, validated with data quality rules, and with IRB approval. Results: This study compared 84 cases of CIP (including high-grade CIP in 48/84 cases, 57%) with 252 controls. COPD was a commonly documented comorbidity in both groups (60% cases, 53% controls, p 0.28), although not all patients had spirometry (44% cases, 40% controls). Among the cases, CIP diagnosis occurred at a median of 3 months; at that time, 29% of cases were using a scheduled daily inhaled corticosteroid, and 18% continued to smoke tobacco. Between high-grade and low-grade CIP, there was similar COPD prevalence (64% vs. 56%, p 0.51), severity by forced expiratory volume in one second (FEV1) as a predicted percentage (64 ± 21% vs. 62 ± 16%, p 0.81), and diffusing capacity of the lungs for carbon monoxide as a predicted percentage (62 ± 19% vs. 61 ± 18%, p 0.82). In terms of CIP outcomes, COPD was not associated with the incidence of hospitalization (26/46, 57%, p 0.76), length of hospitalization (8.4 vs. 7.8 days, p=0.33), intensive care unit utilization (10/21, 48%, p 0.52), or death (5/9, 56%, p 0.94). Cardiac evaluation appeared slightly different among patients with COPD (e.g., more often ordered echo; less often ordered BNP or diuresis), although CIP management was overall similar. Conclusions: The presence or severity of pre-treatment COPD was not associated with differences in the management or outcomes of CIP when it occurred. The cardiac evaluation of CIP may have been different because COPD can decrease the specificity of BNP and be less responsive to diuretics.