Investigation and outcomes in patients with nonspecific pleuritis: results from the International Collaborative Effusion database

Our plain-English summary of Investigation and outcomes in patients with nonspecific pleuritis: results from the International Collaborative Effusion database, by A. Sundaralingam, A. Aujayeb, K.A. Jackson, et al (ERJ Open Research, 2023).

The study

• Authors: A. Sundaralingam, A. Aujayeb, K.A. Jackson, E.I. Pellas, I.I. Khan, M.T. Chohan, R. Joosten, A. Boersma, J. Kerkhoff, S. Bielsa, J.M. Porcel, A. Rozman, M. Marc-Malovrh, H. Welch, J. Symonds, S. Anevlavis, M. Froudrakis, F. Mei, L. Zuccatosta, S. Gasparini, F. Gonnelli, I. Dhaliwal, M.A. Mitchell, K. Fjaellegaard, J.K. Petersen, M. Ellayeh, N.M. Rahman, T. Burden, U. Bodtger, C.F.N. Koegelenberg, N.A. Maskell, J. Janssen, R. Bhatnagar
• Journal: ERJ Open Research
• Published: 2023;9(2)
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: We present findings from the International Collaborative Effusion database, a European Respiratory Society clinical research collaboration. Nonspecific pleuritis (NSP) is a broad term that describes chronic pleural inflammation. Various aetiologies lead to NSP, which poses a diagnostic challenge for clinicians. A significant proportion of patients with this finding eventually develop a malignant diagnosis.

Methods: 12 sites across nine countries contributed anonymised data on 187 patients. 175 records were suitable for analysis.

Results: The commonest aetiology for NSP was recorded as idiopathic (80 out of 175, 44%). This was followed by pleural infection (15%), benign asbestos disease (12%), malignancy (6%) and cardiac failure (6%). The malignant diagnoses were predominantly mesothelioma (six out of 175, 3.4%) and lung adenocarcinoma (four out of 175, 2.3%). The median time to malignant diagnosis was 12.2 months (range 0.8-32 months). There was a signal towards greater asbestos exposure in the malignant NSP group compared to the benign group (0.63 versus 0.27, p=0.07). Neither recurrence of effusion requiring further therapeutic intervention nor initial biopsy approach were associated with a false-negative biopsy. A computed tomography finding of a mass lesion was the only imaging feature to demonstrate a significant association (0.18 versus 0.01, p=0.02), although sonographic pleural thickening also suggested an association (0.27 versus 0.09, p=0.09).

Discussion: This is the first multicentre study of NSP and its associated outcomes. While some of our findings are reflected by the established body of literature, other findings have highlighted important areas for future research, not previously studied in NSP.

Copyright ©The authors 2023.

In plain English

This multicentre retrospective cohort study, part of the European Respiratory Society's International Collaborative Effusion database, studied patients diagnosed between 2009 and 2020 with nonspecific pleuritis (NSP). NSP is a biopsy finding of chronic pleural inflammation with no specific diagnosis. Twelve centres in nine countries submitted 187 cases, and 175 were analysed. Of these patients, 30% reported asbestos exposure. The cause was recorded as idiopathic (no clear cause identified) in 44%, pleural infection in 15% and benign asbestos-related disease in 12%. Eleven patients (6%, 95% confidence interval 3% to 11%) later developed a pleural malignancy: six malignant pleural mesothelioma, four lung adenocarcinoma and one of unknown type. Among the nine with known timing, the median time to diagnosis was 12.2 months (range 0.8 to 32 months). Asbestos exposure was more common in the malignant group than in the benign group (63% versus 27%), but the difference did not reach statistical significance (p=0.07). A mass lesion on CT was the only imaging feature significantly associated with a later malignant diagnosis (p=0.02). The authors said the study was underpowered, partly because of the COVID-19 pandemic.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Multicentre retrospective cohort study using data from the International Collaborative Effusion (ICE) database, a European Respiratory Society clinical research collaboration
• Who was studied: Patients given a diagnosis of nonspecific pleuritis between 2009 and 2020. Twelve centres in nine countries submitted 187 cases between October 2019 and July 2021. Twelve were removed as mislabelled, leaving 175 for analysis. Median age was 72 years and 142 (81%) were male.
• Exposure: Reported asbestos exposure, as recorded in clinical records: 52 of the 175 patients (30%). No fiber types, jobs or doses are given. Asbestos exposure was one of several baseline characteristics compared between patients who did and did not later develop malignancy.
• Main results:
  • Among the 175 patients, the eventual cause of NSP was idiopathic in 44%, followed by pleural infection (15%), benign asbestos-related disease (12%), malignancy (6%) and cardiac failure (6%).
  • 11 patients (6%) developed a pleural malignancy during follow-up. Of these, 6 out of 11 had malignant pleural mesothelioma, 4 out of 11 had lung adenocarcinoma, and in 1 the cancer type was not known.
  • The incidence of eventual pleural malignancy after an NSP result in this dataset was 6% (95% CI 3–11%).
  • All 11 missed malignant diagnoses were in patients whose biopsy was by local-anaesthetic thoracoscopy (LAT).
  • In patients later diagnosed with malignancy, the median time to diagnosis was 12.2 months (range 0.8 to 32 months). Timing was known for 9 of the 11 patients.
  • Asbestos exposure was reported by 7 of 11 patients (63%) in the eventual malignant group and 45 of 164 (27%) in the benign disease-course group. This difference did not meet statistical significance (p=0.07).
  • A mass lesion on CT was seen in 2 of 11 (18%) patients with an eventual malignancy versus 2 of 164 (1%) with a benign course (p=0.02). It was the only significant association with a false-negative biopsy.
  • Pleural thickening on ultrasound was seen in 3 of 11 (27%) patients in the malignant group versus 15 of 164 (9%) in the benign group (p=0.09). This was described as a signal, not a statistically significant result.
  • Needing more than one thoracocentesis after the NSP result was not significantly associated with later malignancy: 5 of 11 (46%) in the malignant group versus 51 of 159 (32%) in the benign group (p=0.51).
  • Comparing patients diagnosed early (under 3 months) with those diagnosed later (3 months or more) gave no statistically significant results. Mesothelioma appeared more likely among late progressors: 5 of 6 mesothelioma cases were late.
• The authors' conclusion: The authors concluded that asbestos exposure was the only baseline characteristic showing a signal towards association with eventual malignancy, but it did not reach statistical significance. A CT mass lesion was the only imaging feature associated with a false-negative biopsy. Much of the planned hypothesis testing did not reach significance, although the authors said associations worthy of further research were shown.
• Limitations the authors state:
  • Retrospective design, with incomplete data and variation in definitions between sites, causing heterogeneity, including in how causes of NSP were assigned.
  • The study was underpowered for several of its research questions, largely because the COVID-19 pandemic disrupted centres' participation.
  • Patients were recruited mainly from clinical databases used by pulmonologists rather than from pathology databases, which may have caused selection bias.
  • Fewer patients than expected developed pleural malignancy, so much of the hypothesis testing did not reach statistical significance.
  • The study did not specifically look at BAP-1 and p16 testing, which the authors describe as instrumental in diagnosing mesothelioma.
  • Very few patients had a surgical biopsy, so the finding that all false-negative biopsies were in the LAT group is difficult to interpret.

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, Idiopathic, Mesothelioma, Lung Adenocarcinoma, Asbestos Exposure, Biopsy, Pleural Thickening.

Related studies

• Outcome of patients with nonspecific pleuritis/fibrosis on thoracoscopic pleural biopsies — H.E. Davies, J.E. Nicholson, et al. (2010)
• Outcome of patients with nonspecific pleuritis at thoracoscopy — J.M. Wrightson, H.E. Davies (2011)
• How useful is GLUT-1 in differentiating mesothelial hyperplasia and fibrosing pleuritis from epithelioid and sarcomatoid mesotheliomas? An international collaborative study — A.N. Husain, M.K. Mirza, et al. (2014)
• Nonspecific pleuritis: optimal duration of follow-up — Z.S. DePew, A. Verma, et al. (2014)
• Chronic follicular pleuritis: a B cell-rich form of nonspecific pleuritis/fibrosis — S.A. Yousem (2019)
• Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for limited peritoneal metastasis. The PSOGI international collaborative registry — A. Arjona-Sanchez, O. Aziz, et al. (2021)

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