A cluster-based analysis evaluating the impact of comorbidities in fibrotic interstitial lung disease
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RESEARCH
A cluster‑based analysis evaluating the impact of comorbidities in fibrotic interstitial lung disease Alyson W. Wong1,2*, Tae Yoon Lee3, Kerri A. Johannson4, Deborah Assayag5, Julie Morisset6, Charlene D. Fell4, Jolene H. Fisher7, Shane Shapera7, Andrea S. Gershon7,8,9,10, Gerard Cox11, Andrew J. Halayko12, Nathan Hambly11, Helene Manganas6, Mohsen Sadatsafavi3, Pearce G. Wilcox1,2, Teresa To8,9,10, Veronica Marcoux13, Nasreen Khalil1, Martin Kolb11 and Christopher J. Ryerson1,2
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. Keywords: Interstitial lung disease, Pulmonary fibrosis, Comorbidities, Outcomes
*Correspondence: [email protected] 1 Department of Medicine, University of British Columbia, Vancouver, BC, Canada Full list of author information is available at the end of the article
Introduction Interstitial lung disease (ILD) is a collection of diseases that lead to varying degrees of inflammation and fibrosis of the pulmonary parenchyma [1]. Common fibrotic ILDs include idiopathic pulmonary fibrosis (IPF), conne
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