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Risk of progression of idiopathic pulmonary fibrosis to connective tissue disease: a long-term observational study in 527 patients

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A Correction to this article was published on 15 April 2021

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Abstract

Objective

Connective tissue disease (CTD) might occur during the course of idiopathic pulmonary fibrosis (IPF). Clinical factors associated with CTD development in IPF patients have still not been identified. We investigated which antibodies have a significant association with the development of CTD during the clinical course of IPF.

Methods

We retrospectively reviewed the records of 527 patients with a first diagnosis of IPF between January 2007 and March 2014 and investigated the time to CTD development after IPF diagnosis in these patients.

Results

CTD developed in 15 patients at a median of 2.1 years (range 1.2–4.8) after IPF diagnosis. All patients had anti-neutrophil cytoplasmic antibodies (ANCA) or autoantibodies that met the serology criteria for interstitial pneumonia with autoimmune features (IPAF). Survival duration for IPF patients with progression to CTD was 5.3 (3.8, 6.7) years, which was significantly longer than for IPF patients without progression to CTD [2.9 (1.7, 4.8), p = 0.001]. Independent risk factors for CTD development in IPF patients included female gender [adjusted hazard ratio (HR) 5.319, p = 0.0082], titer of rheumatoid factor (RF; adjusted HR, 1.006; p = 0.022), titer of anti-citrullinated protein antibody (ACPA; adjusted HR, 1.009; p = 0.0011), and titer of myeloperoxidase (MPO)-ANCA (adjusted HR, 1.02; p < 0.0001).

Conclusion

Progression to CTD is uncommon in IPF patients. However, a significant number of IPF patients with high titers of RF, ACPA, or MPO-ANCA progressed to CTD. RF, ACPA, and MPO-ANCA might be significantly associated with CTD development in IPF patients.

Key Points

• A significant number of IPF patients with high titers of RF, ACPA, or MPO-ANCA progressed to CTD.

• IPF/UIP with high titers of RF, ACPA, or MPO-ANCA might be the initial clinical manifestation of CTD.

• RF, ACPA, and MPO-ANCA may be significantly associated with the development of pulmonary fibrosis in patients with CTD.

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Acknowledgments

We would like to thank Hyojung Choi from the Department of Clinical Research Information at Asan Medical Center for her assistance in preparing this manuscript. We thank Dr. Joon Seo Lim from the Scientific Publications Team at Asan Medical Center for his editorial assistance.

Funding

This work was supported by the research fund of the Rheumatology Research Foundation (RRF-2018-04)

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Authors and Affiliations

  1. Division of Rheumatology, Jeju National University School of Medicine, Jeju National University Hospital, Jeju, Republic of Korea

    Byeongzu Ghang & Jinseok Kim

  2. Division of Rheumatology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea

    Byeongzu Ghang, So Hye Nam, Jungsun Lee, Soo Min Ahn, Ji Seon Oh, Seokchan Hong, Yong-Gil Kim, Bin Yoo & Chang-Keun Lee

  3. Division of Rheumatology, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea

    Doo-Ho Lim

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  1. Byeongzu Ghang
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Correspondence to Chang-Keun Lee.

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The authors have declared no conflicts of interest.

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The study was approved by the Institutional Review Board of Asan Medical Center (IRB number: 2016-0222), and conforms to the ethical guidelines of the Declaration of Helsinki.

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The original online version of this article was revised: Under the Discussion section of this article, "IPA patients" was changed to "IPF patients".

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Ghang, B., Nam, S.H., Lee, J. et al. Risk of progression of idiopathic pulmonary fibrosis to connective tissue disease: a long-term observational study in 527 patients. Clin Rheumatol 40, 2447–2456 (2021). https://doi.org/10.1007/s10067-021-05659-x

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