Exacerbation of idiopathic pulmonary fibrosis and connective tissue disease-related interstitial lung disease outcomes: a systematic review and meta-analysis

Kamonpun Ussavarungsi; Samapon Duangkham; Poemlarp Mekraksakit; Narut Prasitlumkum; Jakrin Kewcharoen; Christopher A Childs; Kenneth Nugent

doi:10.6084/m9.figshare.30331037

Acute exacerbations (AE) of idiopathic pulmonary fibrosis (IPF) and connective tissue disease-related interstitial lung disease (CTD-ILD) lack standardized treatments, and outcomes based on ILD etiology remain unclear. Whether adding immunosuppressive drugs to corticosteroids in IPF provides similar benefits as in CTD-ILD remains unknown. This study evaluates mortality and medical therapy effects on AE-IPF and AE-CTD-ILD outcomes. A systematic search was conducted on August 21, 2020, across the Embase, PubMed, and Cochrane databases. Pooled incidence of mortality, mechanical ventilator use, and noninvasive ventilation use in AE-IPF and AE-CTD-ILD was calculated. A random effects model compared different treatment regimens. This meta-analysis included 28 studies with 3,148 patients, 1,253 patients had AE (983 IPF and 270 CTD-ILD). The 30-day and 90-day mortality rates for AE-IPF were 36% and 57%, respectively, and for AE-CTD-ILD were 34% and 44%. AE-IPF treated with corticosteroids alone had a 90-day mortality of 63%, while AE-CTD-ILD had 17%. In the corticosteroid with immunosuppressive therapy subgroup, 90-day mortality was 44% for AE-IPF and 61% for AE-CTD-ILD. AEs have a poor prognosis regardless of etiology, with no compelling evidence for a definitive treatment regimen. Addressing these uncertainties is crucial for improving outcomes and optimizing care for AE-ILD patients. Acute exacerbations occur in patients with both idiopathic pulmonary fibrosis (IPF) and connective tissue disease-related interstitial lung disease (CTD-ILD), and both have a poor prognosis and no established definitive treatment regimen.This meta-analysis revealed high 30-day mortality rates in acute exacerbations (AE) for both IPF (36%) and CTD-ILD (34%). The 90-day mortality rates were also high with AE-IPF at 57% and CTD-ILD at 44%.No significant differences in mortality rates between treatment regimens were found due to limited subgroup data, underscoring research gaps in ILD treatment and the need for further studies.Interest is growing in therapies beyond corticosteroids for managing excessive inflammation during AE, particularly with combination immunosuppressive therapy. For AE-IPF patients, mortality rates were 16% at 30 days and 44% at 90 days with corticosteroids plus immunosuppressant medication.The role of adding immunosuppressants during acute exacerbations (AE) in IPF needs further study before clinical application. Adaptive immunological abnormalities suggest that acute antibody-mediated exacerbations may resist corticosteroids. The PANTHER trial found increased mortality with the combination of prednisone, azathioprine, and N-acetylcysteine. Similarly, the EXAFIP study showed higher 3-month mortality with cyclophosphamide added to high-dose methylprednisolone, highlighting the need for caution with intensive combination therapies.Mortality rates for AE-CTD-ILD patients on corticosteroids and immunosuppressants can reach 61%. It remains unclear whether this high mortality is due to treatment-related side effects or systemic CTD manifestations leading to multi-organ involvement. Further research is needed to clarify these factors.Approximately half of the exacerbations in patients in both IPF and CTD-ILD required ventilatory support.Uncertainties remain about the best treatments and risks for acute exacerbations in IPF and CTD-ILD. Research in real-world settings is difficult, and no standard treatment regimen has been established.Ongoing randomized studies in IPF hold promise, with potential future expansion to non-IPF patients. Individualized management and precise identification of patient phenotypes responsive to specific regimens are crucial for advancing treatment outcomes. Acute exacerbations occur in patients with both idiopathic pulmonary fibrosis (IPF) and connective tissue disease-related interstitial lung disease (CTD-ILD), and both have a poor prognosis and no established definitive treatment regimen. This meta-analysis revealed high 30-day mortality rates in acute exacerbations (AE) for both IPF (36%) and CTD-ILD (34%). The 90-day mortality rates were also high with AE-IPF at 57% and CTD-ILD at 44%. No significant differences in mortality rates between treatment regimens were found due to limited subgroup data, underscoring research gaps in ILD treatment and the need for further studies. Interest is growing in therapies beyond corticosteroids for managing excessive inflammation during AE, particularly with combination immunosuppressive therapy. For AE-IPF patients, mortality rates were 16% at 30 days and 44% at 90 days with corticosteroids plus immunosuppressant medication. The role of adding immunosuppressants during acute exacerbations (AE) in IPF needs further study before clinical application. Adaptive immunological abnormalities suggest that acute antibody-mediated exacerbations may resist corticosteroids. The PANTHER trial found increased mortality with the combination of prednisone, azathioprine, and N-acetylcysteine. Similarly, the EXAFIP study showed higher 3-month mortality with cyclophosphamide added to high-dose methylprednisolone, highlighting the need for caution with intensive combination therapies. Mortality rates for AE-CTD-ILD patients on corticosteroids and immunosuppressants can reach 61%. It remains unclear whether this high mortality is due to treatment-related side effects or systemic CTD manifestations leading to multi-organ involvement. Further research is needed to clarify these factors. Approximately half of the exacerbations in patients in both IPF and CTD-ILD required ventilatory support. Uncertainties remain about the best treatments and risks for acute exacerbations in IPF and CTD-ILD. Research in real-world settings is difficult, and no standard treatment regimen has been established. Ongoing randomized studies in IPF hold promise, with potential future expansion to non-IPF patients. Individualized management and precise identification of patient phenotypes responsive to specific regimens are crucial for advancing treatment outcomes. There is no single best treatment for sudden worsening of idiopathic pulmonary fibrosis (IPF), a disease that causes lung scarring of unknown cause, or for lung diseases related to connective tissue disease (CTD-ILD). We also don’t fully understand how outcomes differ between these types of lung disease. It’s unclear if adding certain drugs to steroids helps IPF patients like it does for CTD-ILD patients. This study looks at death rates and the effects of treatments on sudden worsening in both diseases. We searched several medical databases and combined data from different studies to find out how often patients died, needed machines to help them breathe, or used other breathing support when their conditions suddenly worsened. This analysis included 28 studies with 3,148 patients; 1,253 had sudden worsening (983 with IPF and 270 with CTD-ILD). For IPF, the death rates were 36% within 30 days and 57% within 90 days of worsening. For CTD-ILD, the death rates were 34% within 30 days and 44% within 90 days. IPF patients treated with only steroids had a 90-day death rate of 63%, while CTD-ILD patients had a death rate of 17%. In the group treated with steroids and other immune-suppressing drugs, the 90-day death rate was 44% for IPF and 61% for CTD-ILD. Sudden worsening of these diseases generally has a poor outcome, and there isn’t strong evidence for the best treatment. Understanding these uncertainties is important for improving care and outcomes for patients with these conditions.

Exacerbation of idiopathic pulmonary fibrosis and connective tissue disease-related interstitial lung disease outcomes: a systematic review and meta-analysis

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