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Bronchoalveolar lavage fluid lymphocytosis in chronic hypersensitivity pneumonitis: a systematic review and meta-analysis

Nicola Adderley, Christopher J. Humphreys, Hayley Barnes, Brett Ley, Zahra A. Premji, Kerri A. Johannson
European Respiratory Journal 2020 56: 2000206; DOI: 10.1183/13993003.00206-2020
Nicola Adderley
1Faculty of Medicine, University of Calgary, Calgary, AB, Canada
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Christopher J. Humphreys
2Dept of Medicine, University of Calgary, Calgary, AB, Canada
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Hayley Barnes
3Dept of Allergy, Immunology and Respiratory Medicine, Alfred Hospital, Melbourne, Australia
4Dept of Medicine, University of California, San Francisco, San Francisco, CA, USA
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Brett Ley
4Dept of Medicine, University of California, San Francisco, San Francisco, CA, USA
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Zahra A. Premji
5Depts of Libraries and Cultural Resources, University of Calgary, Calgary, AB, Canada
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Kerri A. Johannson
2Dept of Medicine, University of Calgary, Calgary, AB, Canada
6Community Health Sciences, University of Calgary, Calgary, AB, Canada
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  • For correspondence: kerri.johannson@ahs.ca
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Abstract

Background The role of bronchoalveolar lavage fluid (BALF) lymphocyte percentage in diagnosing chronic hypersensitivity pneumonitis (CHP) is unclear. We conducted a systematic review and meta-analysis of bronchoalveolar lavage (BAL) lymphocyte percentage in the diagnosis of CHP.

Methods We searched Medline, Embase and the Cochrane Library from inception to August 2019. Individual patient data were obtained to test performance characteristics of BAL lymphocyte percentage at different thresholds. Random-effects models were used for pooled estimates, with comparisons made between CHP and non-CHP interstitial lung diseases (ILDs).

Results Fifty-three studies were included in the systematic review and 42 in the meta-analysis. The pooled estimate for BAL lymphocyte percentage was 42.8% (95% CI 37.7–47.8, I2=95.3%) in CHP, 10.0% (95% CI 6.9–13.1, I2=91.2%) in idiopathic pulmonary fibrosis (IPF), 23.1% (95% CI 3.0–43.2, I2=85.2%) in non-IPF idiopathic interstitial pneumonia (IIP), 23.4% (95% CI 11.0–35.9, I2=45.7%) in connective-tissue disease associated ILD (CTD-ILD) and 31.2% (95% CI 17.6–44.8, I2=95.2%) in sarcoidosis. Results differed between CHP and IPF (p<0.0001), non-IPF IIP (p=0.0309) or CTD-ILD (p=0.0824), but not between CHP and sarcoidosis (p=0.0966). Using individual patient data from eight studies, a lymphocyte percentage threshold of >20% provided a sensitivity of 68.1% and a specificity of 64.8% for CHP. Higher thresholds provided lower sensitivity with higher specificity. Older age and ever having smoked were associated with lower lymphocyte percentage in CHP.

Conclusions BAL lymphocyte percentage is higher in CHP compared to IPF and other IIPs, with higher thresholds providing improved specificity at the cost of sensitivity. However, the parent studies are at risk of incorporation bias and prospective studies should evaluate the additive discriminate value of BAL lymphocyte percentage to accurately diagnose CHP.

Abstract

BALF lymphocyte percentage is higher in patients with #CHP compared to #IPF, #IIP and #CTD-ILD, but studies available to fully address this question are limited in scope #AdvancesinILD https://bit.ly/2RntTMr

Footnotes

  • This article has supplementary material available from erj.ersjournals.com

  • This article has an editorial commentary: https://doi.org/10.1183/13993003.01534-2020

  • Data from the systematic review and meta-analysis are available upon reasonable request, as made to the corresponding author. Individual patient data may be available from the corresponding authors of the cited studies.

  • Author contributions: N. Adderley and K.A. Johannson conceived the study; all authors contributed to the study design and to protocol development; H. Barnes and K.A. Johannson conducted the statistical analyses; N. Adderley and K.A. Johannson drafted the manuscript; all authors contributed to, critically appraised and approved the final version of the manuscript.

  • Conflict of interest: N. Adderley has nothing to disclose.

  • Conflict of interest: C.J. Humphreys has nothing to disclose.

  • Conflict of interest: H. Barnes has nothing to disclose.

  • Conflict of interest: B. Ley has nothing to disclose.

  • Conflict of interest: Z.A. Premji has nothing to disclose.

  • Conflict of interest: K.A. Johannson reports personal fees for advisory board work, consultancy, lectures and travel to meetings from Boehringer Ingelheim, personal fees for advisory board work and lectures from Hoffman La Roche Ltd, personal fees for advisory board work and consultancy from Theravance and Blade Therapeutics, grants from the Chest Foundation, the University of Calgary School of Medicine, the Pulmonary Fibrosis Society of Calgary and UCB Biopharma SPRL, outside the submitted work.

  • Received January 30, 2020.
  • Accepted March 28, 2020.
  • Copyright ©ERS 2020
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Bronchoalveolar lavage fluid lymphocytosis in chronic hypersensitivity pneumonitis: a systematic review and meta-analysis
Nicola Adderley, Christopher J. Humphreys, Hayley Barnes, Brett Ley, Zahra A. Premji, Kerri A. Johannson
European Respiratory Journal Aug 2020, 56 (2) 2000206; DOI: 10.1183/13993003.00206-2020

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Bronchoalveolar lavage fluid lymphocytosis in chronic hypersensitivity pneumonitis: a systematic review and meta-analysis
Nicola Adderley, Christopher J. Humphreys, Hayley Barnes, Brett Ley, Zahra A. Premji, Kerri A. Johannson
European Respiratory Journal Aug 2020, 56 (2) 2000206; DOI: 10.1183/13993003.00206-2020
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