Background: The CAnadian REgistry for Pulmonary Fibrosis (CARE-PF) is a multi-center, prospective registry designed to study the natural history of fibrotic interstitial lung disease (ILD) in adults. The aim of this cross-sectional sub-study was to describe the baseline characteristics, risk factors, and comorbidities of patients enrolled in CARE-PF to date. Methods: Patients completed study questionnaires and clinical measurements at enrollment and each follow-up visit. Environmental exposures were assessed by patient self-report and comorbidities by the Charlson Comorbidity Index (CCI). Baseline characteristics, exposures, and comorbidities were described for the overall study population and for incident cases, and were compared across ILD subtypes. Results: The full cohort included 1285 patients with ILD (961 incident cases (74.8%)). Diagnoses included connective tissue disease-associated ILD (33.3%), idiopathic pulmonary fibrosis (IPF) (24.7%), unclassifiable ILD (22.3%), chronic hypersensitivity pneumonitis (HP) (7.5%), sarcoidosis (3.2%), non-IPF idiopathic interstitial pneumonias (3.0%, including idiopathic nonspecific interstitial pneumonia (NSIP) in 0.9%), and other ILDs (6.0%). Patient-reported exposures were most frequent amongst chronic HP, but common across all ILD subtypes. The CCI was ≤2 in 81% of patients, with a narrow distribution and range of values. Conclusions: CTD-ILD, IPF, and unclassifiable ILD made up 80% of ILD diagnoses at ILD referral centers in Canada, while idiopathic NSIP was rare when adhering to recommended diagnostic criteria. CCI had a very narrow distribution across our cohort suggesting it may be a poor discriminator in assessing the impact of comorbidities on patients with ILD.

Ongoing advances in precision cancer therapy have increased the number of molecularly targeted and immuno-oncology agents for a variety of cancers, many of which have been associated with a risk of pulmonary complications, among the most concerning being drug-induced interstitial lung disease/pneumonitis (DI-ILD). As the number of patients undergoing treatment with novel anticancer agents continues to grow, DI-ILD is expected to become an increasingly significant clinical challenge. Trastuzumab deruxtecan (T-DXd) is an antibody–drug conjugate targeting human epidermal growth factor receptor 2 that is gaining widespread use in the metastatic breast cancer setting and is undergoing exploration for other oncologic indications. ILD/pneumonitis is an adverse event of special interest associated with T-DXd, which has potentially fatal consequences if left untreated and allowed to progress. When identified in the asymptomatic stage (grade 1), T-DXd-related ILD can be monitored and treated effectively with the possibility of treatment continuation. Delayed diagnosis and/or treatment, however, results in progression to grade 2 or higher toxicity and necessitates immediate and permanent discontinuation of this active agent. Strategies are, therefore, needed to optimize careful monitoring during treatment to ensure patient safety and optimize outcomes. Several guidance documents have been developed regarding strategies for the early identification and management of T-DXd-related ILD, although none have been within the context of the Canadian health care environment. A Canadian multidisciplinary steering committee was, therefore, convened to evaluate existing recommendations and adapt them for application in Canada. A multidisciplinary approach involving collaboration among medical oncologists, radiologists, respirologists, and allied health care professionals is needed to ensure the proactive identification and management of T-DXd-related ILD and DI-ILD associated with other agents with a similar toxicity profile.

Previous studies have shown the importance of frailty in patients with fibrotic interstitial lung disease (ILD). Is the Clinical Frailty Scale (CFS) a valid tool to improve risk stratification in patients with fibrotic ILD? Patients with fibrotic ILD were included from the prospective multicenter Canadian Registry for Pulmonary Fibrosis. The CFS was assessed using available information from initial ILD clinic visits. Patients were stratified into fit (CFS 1-3), vulnerable (CFS 4), and frail (CFS 5-9) subgroups. Cox proportional hazards and logistic regression models with mixed effects were used to estimate time to death or lung transplantation. A derivation and validation cohort were used to establish prognostic performance. Trajectories of functional tests were compared using joint models. Of the 1587 patients with fibrotic ILD, 858 (54%) were fit, 400 (25%) vulnerable and 329 (21%) frail. Frailty was a risk factor for early mortality (HR 5.58, 95%CI 3.64-5.76, p<0.001) in the entire cohort, in individual ILD diagnoses, and after adjustment for potential confounders. Adding frailty to established risk prediction parameters improved the prognostic performance in derivation and validation cohorts. Frail patients had larger annual declines in forced vital capacity (FVC) %-predicted compared to fit patients (-2.32 (95%CI -3.39 to -1.17) vs. -1.55 (95%CI -2.04 to -1.15); p=0.02, respectively). The simple and practical CFS is associated with pulmonary and physical function decline in patients with fibrotic ILD and provides additional prognostic accuracy in clinical practice.

Extent of fibrosis, defined by the amount of honeycombing and traction bronchiectasis, was consistently associated with death or lung transplant across all interstitial lung disease subtypes in a dose-dependent fashion.