A cluster-based analysis evaluating the impact of comorbidities in fibrotic interstitial lung disease

Abstract

Background Comorbidities are frequent and have been associated with poor quality of life, increased hospitalizations, and mortality in patients with interstitial lung disease (ILD). However, it is unclear how comorbidities lead to these negative outcomes and whether they could influence ILD disease progression. The goal of this study was to identify clusters of patients based on similar comorbidity profiles and to determine whether these clusters were associated with rate of lung function decline and/or mortality. Methods Patients with a major fibrotic ILD (idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis, connective tissue disease-associated ILD, and unclassifiable ILD) from the CAnadian REgistry for Pulmonary Fibrosis (CARE-PF) were included. Hierarchical agglomerative clustering of comorbidities, age, sex, and smoking pack-years was conducted for each ILD subtype to identify combinations of these features that frequently occurred together in patients. The association between clusters and change in lung function over time was determined using linear mixed effects modeling, with adjustment for age, sex, and smoking pack-years. Kaplan Meier curves were used to assess differences in survival between the clusters. Results Discrete clusters were identified within each fibrotic ILD. In IPF, males with obstructive sleep apnea (OSA) had more rapid decline in FVC %-predicted (− 11.9% per year [95% CI − 15.3, − 8.5]) compared to females without any comorbidities (− 8.1% per year [95% CI − 13.6, − 2.7]; p = 0.03). Females without comorbidities also had significantly longer survival compared to all other IPF clusters. There were no significant differences in rate of lung function decline or survival between clusters in the other fibrotic ILD subtypes. Conclusions The combination of male sex and OSA may portend worse outcomes in IPF. Further research is required to elucidate the interplay between sex and comorbidities in ILD, as well as the role of OSA in ILD disease progression.

Cost drivers in the pharmacological treatment of interstitial lung disease

“…Age has been identified as a risk factor for ILD progression [ 35 ]. Furthermore, older age is particularly known in to increase the likelihood of progression and mortality in progressive fibrosing phenotypes [ 12 ].…”

“…We considered the baseline covariates age (in years), sex, duration of disease (in years), smoking status (current or former and never-smoker), study center, comorbidity burden and physician-reported information on forced vital capacity (FVC) % predicted. In addition, we considered four different ILD subtypes: (1) Sarcoidosis, (2) IPF, (3) PF-ILD (determined by a decrease of at least 10% in either FVC %predicted or DLCO %predicted values after 12 months [ 12 ]), as well as (4) other ILD subtypes. Other ILD subtypes comprised of idiopathic interstitial pneumonias, hypersensitivity pneumonitis, rheumatic and connective tissue diseases with pulmonary involvement, drug-related ILD, combined pulmonary fibrosis and emphysema, non-classifiable ILD and other forms.…”

“…We disregarded information on diffusing capacity of carbon monoxide (DLCO) % predicted in our analyses because this led to multicollinearity problems [ 12 ].…”

“…Within the various non-IPF ILDs, a proportion of patients can develop a progressive, fibrosing phenotype. This phenotype is characterized by declining lung function and high mortality [ 11 , 12 ]. In contrast to IPF however, progressive fibrosing ILDs (PF-ILD) are often accompanied by inflammation.…”

“…In contrast to IPF however, progressive fibrosing ILDs (PF-ILD) are often accompanied by inflammation. Around 20–30% of ILDs may develop into a PF-ILD [ 12 ]. ILDs that are associated with this phenotype include sarcoidosis, non-specific interstitial pneumonia (NSIP), CTD-ILD, HP and unclassifiable ILD [ 11 ].…”