To the Editor:
We read with great interest the research article by Sgalla and colleagues (1) regarding the coronavirus disease (COVID-19) vaccine and acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). We appreciate the authors’ valuable contribution to understanding that COVID-19 vaccination may act as a potential trigger of AE-IPF. However, there are still concerns worth further discussion.
First, this study involved a total of 26 patients diagnosed with IPF. However, the small number of cases in this study may lead to a series of biases and not be able to reveal the influence of the COVID-19 vaccine on patients with IPF. Hence, more patients are suggested to be involved to have a solid research result.
Second, this study categorized the patients into two groups: “triggered” and “idiopathic” AE-IPF. However, according to the protocol, the two groups of cases were not well matched. For example, patients with idiopathic AE-IPF had a higher CRP (C-reactive protein). The higher use of long-term oxygen therapy rate may be associated with an increased mortality rate. Therefore, the two groups of cases should be matched to reduce bias.
Third, previous studies showed that patients with interstitial lung disease had a higher prevalence of other autoimmune diseases, such as rheumatoid arthritis and progressive systemic sclerosis (2–4). However, they also had similar phenotypes of usual interstitial pneumonia. Glucocorticoids are best suited for the initial management or treatment of acute exacerbations while transitioning to other therapies with more favorable long-term safety profiles. It is possible that vaccine-associated acute exacerbation is characterized by better steroid responsiveness, and some patients might have both IPF and subclinical autoimmune diseases. Before we generalize the results of this trial to all patients with IPF, we recommend a post hoc analysis of baseline immune profiles, such as RF (rheumatoid factor), ACPA (anti-cyclic citrullinated peptide antibodies), ANA (antinuclear antibody), and ENA (extractable nuclear antigen antibody).
Above all, this study contributes to understanding that COVID-19 vaccination may act as a potential trigger of AE-IPF. Further studies are suggested to involve more patients in the study, match the study groups, and conduct a post hoc analysis.
Footnotes
Contributions: All authors contributed to writing this letter and approved the final version.
Originally Published in Press as DOI: 10.1164/rccm.202205-0877LE on May 25, 2022
Author disclosures are available with the text of this letter at www.atsjournals.org.
References
- 1. Sgalla G, Magrì T, Lerede M, Comes A, Richeldi L. COVID-19 vaccine in patients with exacerbation of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med . 2022;206:219–221. doi: 10.1164/rccm.202112-2765LE. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Yoo H, Hino T, Han J, Franks TJ, Im Y, Hatabu H, et al. Connective tissue disease-related interstitial lung disease (CTD-ILD) and interstitial lung abnormality (ILA): evolving concept of CT findings, pathology and management. Eur J Radiol Open . 2020;8:100311. doi: 10.1016/j.ejro.2020.100311. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
- 3. England BR, Hershberger D. Management issues in rheumatoid arthritis-associated interstitial lung disease. Curr Opin Rheumatol . 2020;32:255–263. doi: 10.1097/BOR.0000000000000703. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Jung JH, Lim JH, Bang CH, Seok H, Song GG, Choi SJ. Prevalence of chronic obstructive pulmonary disease in patients with rheumatoid arthritis: a cross-sectional study. Int J Rheum Dis . 2021;24:774–780. doi: 10.1111/1756-185X.14129. [DOI] [PubMed] [Google Scholar]