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Comparison of Clinical Characteristics and Outcomes Between Idiopathic and Secondary Pleuroparenchymal Fibroelastosis

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Comparison of Clinical Characteristics and Outcomes Between Idiopathic and Secondary Pleuroparenchymal Fibroelastosis Journal of Clinical Medicine Article Comparison of Clinical Characteristics and Outcomes between Idiopathic and Secondary Pleuroparenchymal Fibroelastosis Tsuneyuki Oda 1,*, Akimasa Sekine 1, Erina Tabata 1 , Tae Iwasawa 2, Tamiko Takemura 2 and Takashi Ogura 1 1 Kanagawa Cardiovascular and Respiratory Center, Department of Respiratory Medicine, Yokohama 236-8651, Japan; [email protected] (A.S.); [email protected] (E.T.); [email protected] (T.O.) 2 Kanagawa Cardiovascular and Respiratory Center, Department of Radiology, Yokohama 236-8651, Japan; [email protected] (T.I.); [email protected] (T.T.) * Correspondence: [email protected]; Tel.: +81-045-701-9581 Abstract: Background: Pleuroparenchymal fibroelastosis (PPFE) is a unique clinical, radiologic, and histopathologic entity for which several potential etiologies have been reported recently. How- ever, there has been no comprehensive study of secondary PPFE. Objective: Assessment of the clinical characteristics, outcomes, and prognostic factors of secondary and idiopathic PPFE. Methods: We retrospectively reviewed the medical records of consecutive PPFE patients between January 1999 and December 2018. We identified 132 idiopathic PPFE patients and 32 secondary PPFE patients. Results: The incidence of interstitial lung disease (ILD) pattern different from the usual interstitial pneumonia (UIP) pattern in the lower lobes was higher in secondary PPFE patients (38.5%) than in idiopathic PPFE patients (61.5%, p = 0.02). The idiopathic and secondary PPFE groups did not differ significantly in terms of laboratory data, respiratory complications, and survival (median: Citation: Oda, T.; Sekine, A.; Tabata, 5.0 years vs. 4.1 years, p = 0.95). The presence of UIP pattern was independently associated with E.; Iwasawa, T.; Takemura, T.; Ogura, increased mortality in multivariate analyses in idiopathic PPFE patients, but not in secondary PPFE T. Comparison of Clinical patients. Conclusions: The frequency and prognostic impact of UIP-pattern ILD differed between Characteristics and Outcomes idiopathic and secondary PPFE patients. Lung transplantation should be considered in secondary between Idiopathic and Secondary PPFE patients with low diffusing capacity of the lungs for carbon monoxide (DLCO) regardless of Pleuroparenchymal Fibroelastosis. J. lower-lobe ILD pattern. Clin. Med. 2021, 10, 846. https:// doi.org/10.3390/jcm10040846 Keywords: pleuroparenchymal fibroelastosis; UIP; hypersensitivity pneumonitis; interstitial lung dis- eases Academic Editor: Hiroshi Ishii Received: 20 January 2021 Accepted: 15 February 2021 1. Introduction Published: 18 February 2021 Pleuroparenchymal fibroelastosis (PPFE) was first reported as a unique pleuroparenchy- mal lung disease in 2004 [1]. Idiopathic PPFE has been reported to account for approximately Publisher’s Note: MDPI stays neutral 6–8% of all interstitial lung diseases; however, the true prevalence of PPFE is not known. with regard to jurisdictional claims in published maps and institutional affil- Several recent studies have explored and documented the possible etiologies of secondary iations. PPFE, including radiation [1], bone marrow or stem cell transplantation [2,3], lung trans- plantation [2,4], connective tissue diseases [5–7], asbestosis [8], pneumoconiosis [8,9], metal lung [10,11], recurrent infections (e.g., pulmonary aspergillus [12] or Mycobacterium avium intracellular complex [13]), chemotherapeutic agents [14,15], and chronic hypersensitivity pneumonitis (HP) [12,16,17]. The diagnosis of secondary PPFE is challenging because of the Copyright: © 2021 by the authors. contraindications for surgical lung biopsy. Surgical lung biopsy is associated with risks such Licensee MDPI, Basel, Switzerland. as a potentially prolonged period of post-operative iatrogenic pneumothorax [18,19]. There This article is an open access article distributed under the terms and has been no comprehensive study of secondary PPFE. Thus, the clinical differences between conditions of the Creative Commons idiopathic and secondary PPFE remain unknown. Attribution (CC BY) license (https:// Prognostic factors for PPFE reported in previous studies include the Krebs von den creativecommons.org/licenses/by/ Lungen 6 (KL-6) [20] levels, body mass index, predicted forced vital capacity (FVC) % [21], 4.0/). and the gender-age-physiology index score [21]. However, the presence of the usual J. Clin. Med. 2021, 10, 846. https://doi.org/10.3390/jcm10040846 https://www.mdpi.com/journal/jcm J. Clin. Med. 2021, 10, x FOR PEER REVIEW 2 of 12 Prognostic factors for PPFE reported in previous studies include the Krebs von den Lungen 6 (KL-6) [20] levels, body mass index, predicted forced vital capacity (FVC) % [21], J. Clin. Med. 2021and, 10 ,the 846 gender-age-physiology index score [21]. However, the presence of the usual in- 2 of 11 terstitial pneumonia (UIP) pattern as a predictor remains controversial. Several studies have shown that the UIP pattern in the lower lobes was a poor prognostic factor in idio- pathic PPFE [20,22,23],interstitial whereas pneumonia others (UIP) determined pattern as it a to predictor be insignificant remains controversial. [16,24,25]. Several studies In this retrospectivehave shown study, that we the aimed UIP pattern to determine in the lower and elucidate lobes was the a poor clinical prognostic charac- factor in teristics, outcomes,idiopathic and prognostic PPFE [20,22 factors,23], whereas of secondary others determined PPFE compared it to be insignificantwith idiopathic [16,24 ,25]. PPFE in a large populationIn this retrospectiveof patients. study, we aimed to determine and elucidate the clinical character- istics, outcomes, and prognostic factors of secondary PPFE compared with idiopathic PPFE in a large population of patients. 2. Materials and Methods 2.1. Patient Selection2. Materials and Data and Collection Methods 2.1. Patient Selection and Data Collection From the Kanagawa Cardiovascular and Respiratory Center research database, we retrospectively identifiedFrom the68 PPFE Kanagawa patients Cardiovascular who underwent and Respiratory surgical lung Center biopsy research or database,au- we retrospectively identified 68 PPFE patients who underwent surgical lung biopsy or autopsy topsy between January 1999 and December 2018 and 96 PPFE patients who did not un- between January 1999 and December 2018 and 96 PPFE patients who did not undergo dergo surgical lungsurgical biopsy lung or biopsy autops ory autopsy between between January January 2012 2012and December and December 2018. 2018. Patients who metPatients the radiologic who met theand radiologic the pathologic and the criteria pathologic (if biopsy criteria specimens (if biopsy specimens were were available) for theavailable) diagnosis for of the PPFE, diagnosis as described of PPFE, asbelow, described were below, subjected were to subjected an evaluation to an evaluation and multidisciplinaryand multidisciplinary discussion discussioninvolving involving radiologists, radiologists, pathologists, pathologists, and pulmonologists.pul- monologists. PatientsPatients were were di dividedvided into into two two subgroups: IdiopathicIdiopathic PPFE PPFE group group and and secondary sec- PPFE ondary PPFE groupgroup with with a aknown known cause cause or associationassociation (Figure (Figure1). 1). FigureFigure 1. Flow 1. sheet.Flow sheet. ILD, ILD,interstitial interstitial lung lung disease; disease; PPFE, PPFE, pleuroparenchymal pleuroparenchymal fibroelastosis.fibroelastosis. Individual differentiatedIndividual connective differentiated tissue connective diseases, tissue such diseases, as Sjögren’s such as syndrome, Sjögren’s syndrome, sys- sys- temic sclerosis, andtemic rheumatoid sclerosis, and arthritis, rheumatoid we arthritis,re diagnosed were diagnosed using stan usingdard standard criteria criteria [26–28].[26 –28]. HP was diagnosed based on the official criteria of the American Thoracic Society, the Japanese HP was diagnosed based on the official criteria of the American Thoracic Society, the Jap- Respiratory Society, and the Latin American Thoracic Association clinical practice guide- anese Respiratoryline Society, [29]. Clinical and the and Latin laboratory American data, pulmonary Thoracic functionAssociation test (PFT) clinical data, practice and bronchoalve- guideline [29]. Clinicalolar lavage and (BAL)laboratory fluid findings data, pulmonary on initial examination function test were (PFT) collected data, retrospectivelyand bron- from choalveolar lavagethe (BAL) medical fluid records. findings Data on regarding initial examination the clinical course were of collected each patient retrospec- after diagnosis, tively from the medicalincluding records. complications Data andregarding prognosis, the were clinical also recorded.course of each patient after diagnosis, including Thecomplications protocol for and this prognosis, study was approvedwere also byrecorded. the institutional review board at the Kanagawa Cardiovascular Respiratory Center (approval number KCRC-19-0006). The Eth- J. Clin. Med. 2021, 10, 846 3 of 11 ical Committee waived the requirement for informed consent due to the retrospective nature of the study. The study cohort overlapped partially with the cohort described in a previous publication [20,30]. 2.2. High-Resolution Computed Tomography Evaluation A pulmonary radiologist (T.I.) and a pulmonologist (T.O.) reviewed the chest com- puted tomography (CT) data collected from all patients on initial examination. The review-
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