Moua, Teng

Background/Objectives: Individual and increasing numbers of comorbidities have been associated with worse outcomes in patients with fibrotic interstitial lung disease (f-ILD). The association and impact of medical comorbidities on patient-reported outcome measures (PROMs) in f-ILD have yet to be reported. Methods: Analysis was conducted using data from a single-center prospective cohort involving 199 patients with f-ILD. All f-ILD diagnoses and severities were screened and enrolled over a three-year study period. Baseline demographics, pulmonary function test (PFT) measures, and survival status were collected. PROMs, including the Chronic Respiratory Questionnaire (CRQ) and the Self-Management Ability Scale (SMAS-30), were assessed at baseline and serially. Thirteen medical comorbidities were evaluated for their prevalence and impact on PROMs and all-cause mortality. Results: Mean age was 69 years, with a female-to-male ratio of 61% vs. 39%. Dyslipidemia (74%) and gastroesophageal reflux disease (GERD) (71%) were the most prevalent comorbidities. Hypertension, diabetes, GERD, pulmonary hypertension (PH), depression, congestive heart failure (CHF), and obstructive sleep apnea (OSA), were independently associated with lower PROM scores along with increasing numbers of concomitant comorbidities. Increasing numbers of comorbidities, as well as specifically diabetes, PH, hypertension, CHF, and OSA, were associated with greater all-cause mortality. Conclusions: Medical comorbidities may independently impact respiratory-related PROMs in patients with f-ILD. These findings highlight the importance of comprehensive comorbidity management in improving quality of life and survival outcomes in patients with f-ILD.

Background Antifibrotic (AF) therapy has been shown to potentially reduce the risk of lung cancer (LC) in patients with idiopathic pulmonary fibrosis (IPF). Our study further assesses the impact of AF use and LC incidence in a real-world cohort with patient-level data. Methods A retrospective multisite cohort study involving patients with IPF followed at Mayo Clinic between 2005 and 2022 was conducted. We identified individuals with new diagnoses of LC in the pre-AF and post-AF eras and defined AF use as continuous treatment for 6 months or more before LC diagnosis. Given the inclusion of LC cases prior to the wide availability of AF therapy and potential differences in patients exposed and unexposed to treatment, propensity score analysis with inverse probability of treatment weighting (IPTW) was used to balance comparator groups. Fine and Gray modelling was used to explore risk factors for developing LC, reported as parameter subdistribution HRs (SHR). Results A total of 3313 patients with IPF were included (1161 treated and 2152 non-treated). LC incidence rates were lower for treated patients in the post-AF era (0.34 vs 1.25 per 100 person-years, p<0.001). After IPTW, 2148 treated were compared with 2167 non-treated individuals. AF treatment was independently associated with reduced LC risk (SHR 0.36 (0.16–0.82), p=0.02), while smoking history and higher forced vital capacity were associated with increased risk. Conclusion AF use appears to be associated with a reduced incidence rate and risk of LC in patients with IPF.

Idiopathic pulmonary fibrosis (IPF) is a progressive and often fatal lung disease most commonly encountered in older individuals. Several decades of research have contributed to a better understanding of its pathogenesis, though only two drugs thus far have shown treatment efficacy, i.e., by slowing the decline of lung function. The pathogenesis of IPF remains incompletely understood and involves multiple complex interactions and mechanisms working in tandem or separately to result in unchecked deposition of extracellular matrix components and collagen characteristic of the disease. These mechanisms include aberrant response to injury in the alveolar epithelium, inappropriate communication between epithelial cells and mesenchymal cells, imbalances between oxidative injury and tissue repair, recruitment of inflammatory pathways that induce fibrosis, and cell senescence leading to sustained activation and proliferation of fibroblasts and myofibroblasts. Targeted approaches to each of these mechanistic pathways have led to recent clinical studies evaluating the safety and efficacy of several agents. This review highlights selected concepts in the pathogenesis of IPF as a rationale for understanding current or future therapeutic approaches, followed by a review of several selected agents and their recent or active clinical studies. Current novel therapies include approaches to attenuating or modifying specific cellular or signaling processes in the fibrotic pathway, modifying inflammatory and metabolic derangements, and minimizing inappropriate cell senescence.

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ABSTRACT Background and objective Criteria for interstitial pneumonia with autoimmune features (IPAF) were recently established for research purposes in a joint statement from the European Respiratory Society (ERS) and American Thoracic Society (ATS). We reviewed the utility of these criteria in patients previously diagnosed as broadly defined undifferentiated connective tissue disease (UCTD) and noted overlapping IPAF findings. Additional review was given to IPAF patients with usual interstitial pneumonia (UIP) on histopathology or radiology in terms of survival and outcome. Methods Patients with prior UCTD‐interstitial lung disease (ILD) were screened by ERS/ATS criteria for IPAF. Clinical data along with all‐cause mortality were collated and compared with selected idiopathic pulmonary fibrosis (IPF) patients from the same study period. Survival was compared between IPAF subgroups with and without UIP features. Results One hundred and one UCTD‐ILD subjects (91%) evaluated from 2005 to 2012 also met strict criteria for IPAF. Frequent clinical findings included Raynaud’s phenomenon, positive anti‐nuclear antibody (ANA) and non‐specific interstitial pneumonia (NSIP) pattern on chest computed tomography (CT). Nineteen had features of UIP either on histopathology or CT imaging. As compared with IPF, IPAF patients had overall better survival except in those with UIP features. Conclusion Current IPAF criteria encompassed the majority of broadly defined UCTD‐ILD and included those with UIP findings. Survival compared with IPF in those with UIP was similar. Further studies are necessary to refine IPAF definitions for clinical use and guide directed management strategies.