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• Challenges in Interpreting High-Dose Corticosteroid Efficacy in Non-IPF AE-ILD
  Wei Chiang, Chih-Hsin Lee
  Published on: 17 February 2025

• Published on: 17 February 2025

  Challenges in Interpreting High-Dose Corticosteroid Efficacy in Non-IPF AE-ILD

  • Wei Chiang, Internal Medicine Physician Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University
  • Other Contributors:
    • Chih-Hsin Lee, Professor

  We read with great interest the systematic review by Srivali et al., titled “Corticosteroid Therapy for Treating Acute Exacerbation of Interstitial Lung Diseases: A Systematic Review,” published in Thorax [1].The topic of corticosteroid use in acute exacerbations (AE) of interstitial lung diseases (ILD) is of immense clinical relevance, and we commend the authors for their comprehensive evaluation of the current evidence base. However, we would like to draw attention to several critical limitations of the existing literature that may impact the robustness of the conclusions drawn in this review.

  The authors synthesized data from nine retrospective observational studies, encompassing over 18,000 patients. While this large sample size is notable, it is essential to recognize that the heterogeneity across the included studies significantly limits the ability to draw definitive conclusions. The AE definitions, corticosteroid regimens, and grouping criteria varied considerably across studies, precluding a meta-analysis and necessitating a narrative synthesis. This inherent heterogeneity presents a challenge in interpreting the pooled findings.

  One of the key findings of the review is that high-dose corticosteroid therapy (>1 mg/kg prednisolone) may be beneficial for non-idiopathic pulmonary fibrosis (IPF) ILD patients experiencing AE. However, this conclusion primarily stems from the study by Jang et al. [2], which included 131 patients, of whom only 57 were no...

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  We read with great interest the systematic review by Srivali et al., titled “Corticosteroid Therapy for Treating Acute Exacerbation of Interstitial Lung Diseases: A Systematic Review,” published in Thorax [1].The topic of corticosteroid use in acute exacerbations (AE) of interstitial lung diseases (ILD) is of immense clinical relevance, and we commend the authors for their comprehensive evaluation of the current evidence base. However, we would like to draw attention to several critical limitations of the existing literature that may impact the robustness of the conclusions drawn in this review.

  The authors synthesized data from nine retrospective observational studies, encompassing over 18,000 patients. While this large sample size is notable, it is essential to recognize that the heterogeneity across the included studies significantly limits the ability to draw definitive conclusions. The AE definitions, corticosteroid regimens, and grouping criteria varied considerably across studies, precluding a meta-analysis and necessitating a narrative synthesis. This inherent heterogeneity presents a challenge in interpreting the pooled findings.

  One of the key findings of the review is that high-dose corticosteroid therapy (>1 mg/kg prednisolone) may be beneficial for non-idiopathic pulmonary fibrosis (IPF) ILD patients experiencing AE. However, this conclusion primarily stems from the study by Jang et al. [2], which included 131 patients, of whom only 57 were non-IPF cases. In contrast, the study by Koshy et al. reported a higher mortality risk in non-IPF AE-ILD patients who received corticosteroids at a dose >0.5 mg/kg compared to those who did not receive corticosteroids [3]. This study included 76 non-IPF patients, and while the difference did not reach statistical significance, the trend raises important questions about the variability in corticosteroid response among different subtypes of ILD.

  The discrepancy between these findings could be attributed to several factors, including differences in corticosteroid dosing, the underlying mechanisms of ILD in the cohorts studied, or the triggers of AE. For example, the proportion of patients with connective tissue disease-associated ILD (CTD-ILD) versus hypersensitivity pneumonitis (HP) could influence the observed outcomes, as these subtypes have differing immune-mediated pathophysiology. Additionally, the cause of AE (e.g., infection, aspiration, or non-triggered exacerbation) likely plays a critical role in determining the effectiveness of corticosteroid therapy. These factors underscore the complexity of managing AE-ILD and highlight the need for more precise, prospective studies to better elucidate the role of corticosteroids in different ILD subtypes and AE triggers.

  Given these limitations, we urge caution in interpreting this review's findings as definitive evidence supporting high-dose corticosteroid therapy in non-IPF AE-ILD. The current evidence base remains fragile, and the variability in study design and patient populations across the included studies warrants further investigation through randomized controlled trials. These trials should aim to stratify patients by ILD subtype and AE trigger to provide more granular insights into the effectiveness of corticosteroid therapy.

  In conclusion, while the review by Srivali et al. provides valuable insights into the potential benefits of corticosteroid therapy in AE-ILD, the limitations of the included studies highlight the need for further research to strengthen the evidence base. We appreciate the authors' efforts in addressing this important clinical question and look forward to future studies that will help clarify the optimal management strategies for AE-ILD.

  References

  1. Srivali N, De Giacomi F, Moua T, et al. Corticosteroid therapy for treating acute exacerbation of interstitial lung diseases: a systematic review. Thorax 2024 doi: 10.1136/thorax-2024-222636 [published Online First: 20241225]

  2. Jang HJ, Yong SH, Leem AY, et al. Corticosteroid responsiveness in patients with acute exacerbation of interstitial lung disease admitted to the emergency department. Sci Rep 2021;11(1):5762. doi: 10.1038/s41598-021-85539-1 [published Online First: 20210311]

  3. Koshy K, Barnes H, Farrand E, et al. Steroid therapy in acute exacerbation of fibrotic interstitial lung disease. Respirology 2024;29(9):795-802. doi: 10.1111/resp.14763 [published Online First: 20240602]

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  Conflict of Interest:
  None declared.

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