Advertisement
Research Article| Volume 89, P76-80, July 2021

Integrated approach to bronchoalveolar lavage cytology to distinguish interstitial lung diseases

Published:April 28, 2021DOI:https://doi.org/10.1016/j.ejim.2021.04.005

      Highlights

      • A new specific index called Bronchoalveolar Cytology Threshold (BCT), useful for distinguishing ILD has been analyzed.
      • Integrated approaches to BAL analysis can improve the interpretation of results without further cost or loss of time.
      • COP patients showed significantly higher BCT than IPF, f-HP and sarcoidosis. Moreover, COP patients were best distinguished by BCT.

      Abstract

      Background

      Broncho-alveolar lavage (BAL) is a safe diagnostic procedure, useful for differentiating fibrotic lung disorders and for excluding malignancy and infection. A recent multicenter study demonstrated a new, relatively sensitive, and specific index called Bronchoalveolar Cytology Threshold (BCT), useful for distinguishing healthy individuals from patients with lung diseases.

      Objectives

      In our study, BCT was applied for the first time to the analysis of interstitial lung diseases (ILDs), investigating its potential for differential diagnosis. Combinations of BAL cells that improve diagnostic accuracy for ILDs were studied and are proposed.

      Methods

      A retrospective analysis of BAL samples was performed. We considered more than 1000 BAL samples from patients investigated for ILD, performed at Siena University Hospital.
      The samples enrolled for the study included 468 patients: 413 with and 55 without ILD. BAL was performed for diagnostic purposes in line with international guidelines. BCT were calculated according to available literature.

      Results

      Among ILDs, patients with fibrotic hypersensitivity pneumonitis, idiopathic pulmonary fibrosis (IPF) and sarcoidosis showed significantly lower BCTs than unclassified ILD. Asbestosis patients showed significantly lower BCTs than nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP), connective tissue disease related ILD (CTD-ILD), sarcoidosis and unclassified ILD patients. COP patients showed significantly higher BCT than IPF, f-HP and sarcoidosis. Moreover, COP patients were best distinguished by BCT.

      Conclusion

      The analysis of BAL features is currently included in the diagnostic algorithm of ILDs. BAL cell patterns and BCT index can provide useful information for distinguishing ILDs, reducing the need for invasive procedures. Integrated approaches to BAL analysis can improve the interpretation of results without further cost or loss of time.

      Keywords

      Abbreviations:

      BAL (Broncho-alveolar lavage), f-HP (fibrotic-hypersensitivity pneumonitis), CTD-ILD (connective tissue diseases associated with ILD), IPF (idiopathic pulmonary fibrosis), BCT (Bronchoalveolar Cytology Threshold), AM (alveolar macrophages)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Davidson KR
        • Ha DM
        • Schwarz MI
        • Chan ED.
        Bronchoalveolar lavage as a diagnostic procedure: a review of known cellular and molecular findings in various lung diseases.
        J Thorac Dis. 2020; 12: 4991https://doi.org/10.21037/jtd-20-651
        • Wells AU.
        The clinical utility of bronchoalveolar lavage in diffuse parenchymal lung disease.
        Eur Resp Rev. 2010; 19: 237-241https://doi.org/10.1183/09059180.00005510
        • Zaidi A
        • Kaur H
        • Gupta P
        • Gupta N
        • Srinivasan R
        • Dey P
        • et al.
        Role of bronchoalveolar lavage in diagnosing pulmonary infections and malignancies: experience from a tertiary care center.
        Diagn Cytopathol. 2020; 48: 1290-1299https://doi.org/10.1002/dc.24574
        • Rottoli P
        • Bargagli E.
        Is bronchoalveolar lavage obsolete in the diagnosis of interstitial lung disease?.
        Curr Opin Pulm Med. 2003; 9: 418-425https://doi.org/10.1097/00063198-200309000-00014
        • bargagli e
        Serum analysis of coagulation factors in IPF and NSIP.
        Inflammation. 2014; https://doi.org/10.1007/s10753-013-9706-z
        • Bergantini L
        • Cameli P
        • d'Alessandro M
        • Vagaggini C
        • Refini RM
        • Landi C
        • et al.
        NK and NKT-like cells in granulomatous and fibrotic lung diseases.
        Clin Exp Med. 2019; 19: 487-494https://doi.org/10.1007/s10238-019-00578-3
        • Landi C
        • Bargagli E
        • Carleo A
        • Bianchi L
        • Gagliardi A
        • Prasse A
        • et al.
        A system biology study of BALF from patients affected by idiopathic pulmonary fibrosis (IPF) and healthy controls.
        Proteomics Clin Appl. 2014; 8: 932-950https://doi.org/10.1002/prca.201400001
        • Prasse A
        • Binder H
        • Schupp JC
        • Kayser G
        • Bargagli E
        • Jaeger B
        • et al.
        BAL cell gene expression is indicative of outcome and airway basal cell involvement in idiopathic pulmonary fibrosis.
        Am J Respir Crit Care Med. 2019; 199: 622-630https://doi.org/10.1164/rccm.201712-2551OC
        • Bargagli E
        • Olivieri C
        • Nikiforakis N
        • Cintorino M
        • Magi B
        • Perari MG
        • et al.
        Analysis of macrophage migration inhibitory factor (MIF) in patients with idiopathic pulmonary fibrosis.
        Respir Physiol Neurobiol. 2009; 167: 261-267https://doi.org/10.1016/j.resp.2009.05.004
        • d'Alessandro M
        • Bergantini L
        • Cameli P
        • Vietri L
        • Lanzarone N
        • Alonzi V
        • et al.
        Krebs von den Lungen-6 as a biomarker for disease severity assessment in interstitial lung disease: a comprehensive review.
        Biomark Med. 2020; 14: 665-674https://doi.org/10.2217/bmm-2019-0545
        • d'Alessandro M
        • Carleo A
        • Cameli P
        • Bergantini L
        • Perrone A
        • Vietri L
        • et al.
        BAL biomarkers’ panel for differential diagnosis of interstitial lung diseases.
        Clin Exp Med. 2020; 20: 207-216https://doi.org/10.1007/s10238-020-00608-5
        • d'Alessandro M
        • Bergantini L
        • Cameli P
        • Lanzarone N
        • Perillo F
        • Perrone A
        • et al.
        BAL and serum multiplex lipid profiling in idiopathic pulmonary fibrosis and fibrotic hypersensitivity pneumonitis.
        Life Sci. 2020; 256117995https://doi.org/10.1016/j.lfs.2020.117995
        • d'Alessandro M
        • Bergantini L
        • Refini RM
        • Cameli P
        • Perillo F
        • Landi C
        • et al.
        Adiponectin and leptin levels in idiopathic pulmonary fibrosis: a new method for BAL and serum assessment.
        Immunobiology. 2020; 225151997https://doi.org/10.1016/j.imbio.2020.151997
        • Vietri L
        • Cameli P
        • Perruzza M
        • Cekorja B
        • Bergantini L
        • d'Alessandro M
        • et al.
        Pirfenidone in idiopathic pulmonary fibrosis: real-life experience in the referral centre of Siena.
        Ther Adv Respir Dis. 2020; 141753466620906326https://doi.org/10.1177/1753466620906326
        • cameli p
        Long-Term Follow-Up of Patients With Idiopathic Pulmonary Fibrosis Treated With Pirfenidone or Nintedanib: A Real-Life Comparison Study.
        Front Mol Biosci. 2020; https://doi.org/10.3389/fmolb.2020.581828
        • Meyer KC
        • Raghu G
        • Baughman RP
        • Brown KK
        • Costabel U
        • du Bois RM
        • et al.
        An official american thoracic society clinical practice guideline: the clinical utility of bronchoalveolar lavage cellular analysis in interstitial lung disease.
        Am J Respir Crit Care Med. 2012; 185: 1004-1014https://doi.org/10.1164/rccm.201202-0320ST
        • Heron M
        • Grutters JC
        • ten Dam-Molenkamp KM
        • Hijdra D
        • van Heugten-Roeling A
        • Claessen AME
        • et al.
        Bronchoalveolar lavage cell pattern from healthy human lung.
        Clin Exp Immunol. 2012; 167: 523https://doi.org/10.1111/j.1365-2249.2011.04529.x
        • Crouser ED
        • Maier LA
        • Wilson KC
        • Bonham CA
        • Morgenthau AS
        • Patterson KC
        • et al.
        Diagnosis and detection of sarcoidosis. an official american thoracic society clinical practice guideline.
        Am J Respir Crit Care Med. 2020; 201: e26-e51https://doi.org/10.1164/rccm.202002-0251ST
        • Raghu G
        • Remy-Jardin M
        • Ryerson CJ
        • Myers JL
        • Kreuter M
        • Vasakova M
        • et al.
        Diagnosis of hypersensitivity pneumonitis in adults. An official ATS/JRS/ALAT clinical practice guideline.
        Am J Respir Crit Care Med. 2020; 202: e36-e69https://doi.org/10.1164/rccm.202005-2032ST
        • Kowal-Bielecka O
        • Kowal K
        • Highland KB
        • Silver RM.
        Bronchoalveolar lavage fluid in scleroderma interstitial lung disease: technical aspects and clinical correlations: review of the literature.
        Semin Arthritis Rheum. 2010; 40: 73-88https://doi.org/10.1016/j.semarthrit.2008.10.009
        • Bargagli E
        • Prasse A.
        Sarcoidosis: a review for the internist.
        Intern Emerg Med. 2018; 13: 325-331https://doi.org/10.1007/s11739-017-1778-6
        • Cameli P
        • Gonnelli S
        • Bargagli E
        • d'Alessandro M
        • Bergantini L
        • Favetta V
        • et al.
        The role of urinary calcium and chitotriosidase in a cohort of chronic sarcoidosis patients.
        Respiration. 2020; 99: 207-212https://doi.org/10.1159/000505653
        • cameli p
        Hypercalciuria in Sarcoidosis: A Specific Biomarker With Clinical Utility..
        Front Med (Lausanne). 2020; https://doi.org/10.3389/fmed.2020.568020
        • Hoffman AM
        Bronchoalveolar lavage: sampling technique and guidelines for cytologic preparation and interpretation.
        Veterinary Clin North Am: Equine Pract. 2008; 24: 423-435https://doi.org/10.1016/j.cveq.2008.04.003
        • Dohn MN
        • Baughman RP.
        Effect of changing instilled volume for bronchoalveolar lavage in patients with interstitial lung disease1–3.
        Am Rev Respir Dis. 2015;
        • Lam S
        • Leriche JC
        • Kijek K
        • Phillips D.
        Effect of bronchial lavage volume on cellular and protein recovery.
        Chest. 1985; 88: 856-859https://doi.org/10.1378/chest.88.6.856
        • bergantini l
        Regulatory and Effector Cell Disequilibrium in Patients with Acute Cellular Rejection and Chronic Lung Allograft Dysfunction after Lung Transplantation: Comparison of Peripheral and Alveolar Distribution.
        cells. 2021; https://doi.org/10.3390/cells10040780
        • Karimi R
        • Tornling G
        • Grunewald J
        • Eklund A
        • Sköld CM.
        Cell recovery in bronchoalveolar lavage fluid in smokers is dependent on cumulative smoking history.
        PLoS One. 2012; 7: e34232https://doi.org/10.1371/journal.pone.0034232
        • Meyer KC
        • Soergel P.
        Variation of bronchoalveolar lymphocyte phenotypes with age in the physiologically normal human lung.
        Thorax. 1999; 54: 697-700https://doi.org/10.1136/thx.54.8.697
        • Welker L
        • Jörres RA
        • Costabel U
        • Magnussen H.
        Predictive value of BAL cell differentials in the diagnosis of interstitial lung diseases.
        Eur Respir J. 2004; 24: 1000-1006https://doi.org/10.1183/09031936.04.00101303
        • Korkmaz C
        • Demircioglu S.
        The association of neutrophil/lymphocyte and platelet/lymphocyte ratios and hematological parameters with diagnosis, stages, extrapulmonary involvement, pulmonary hypertension, response to treatment, and prognosis in patients with sarcoidosis.
        Can Respir J. 2020; 2020https://doi.org/10.1155/2020/1696450
        • D'alessandro M
        • Bergantini L
        • Carleo A
        • Cameli P
        • Perrone A
        • Fossi A
        • et al.
        Neutrophil-to-lymphocyte ratio in bronchoalveolar lavage from IPF patients: a novel prognostic biomarker?.
        Minerva Med. 2020; https://doi.org/10.23736/S0026-4806.20.06614-8
        • Frye BC
        • Schupp JC
        • Rothe ME
        • Köhler TC
        • Prasse A
        • Zissel G
        • et al.
        The value of bronchoalveolar lavage for discrimination between healthy and diseased individuals.
        J Intern Med. 2020; 287: 54-65https://doi.org/10.1111/joim.12973
        • Lanzarone N
        • Gentili F
        • Alonzi V
        • Bergantini L
        • d'Alessandro M
        • Rottoli P
        • et al.
        Bronchoalveolar lavage and serum KL-6 concentrations in chronic hypersensitivity pneumonitis: correlations with radiological and immunological features.
        Intern Emerg Med. 2020; https://doi.org/10.1007/s11739-020-02281-8
        • Gogali A
        • Wells AU.
        Diagnostic approach to interstitial lung disease.
        Curr Respir Care Rep. 2012; 1: 199-207https://doi.org/10.1007/s13665-012-0029-6
        • Bargagli E
        • Cameli P
        • Carleo A
        • Refini RM
        • Bergantini L
        • D'alessandro M
        • et al.
        The effect of cigarette smoking on bronchoalveolar lavage protein profiles from patients with different interstitial lung diseases.
        Panminerva Med. 2019; https://doi.org/10.23736/S0031-0808.19.03754-6
        • Domagała-Kulawik J
        • Skirecki T
        • Maskey-Warzechowska M
        • Grubek-Jaworska H
        • Chazan R.
        Bronchoalveolar lavage total cell count in interstitial lung diseases–does it matter?.
        Inflammation. 2012; 35: 803-809https://doi.org/10.1007/s10753-011-9378-5
        • Efared B
        • Ebang-Atsame G
        • Rabiou S
        • Diarra AS
        • Tahiri L
        • Hammas N
        • et al.
        The diagnostic value of the bronchoalveolar lavage in interstitial lung diseases.
        J Negat Results Biomed. 2017; 16: 4https://doi.org/10.1186/s12952-017-0069-0
        • Costa E Silva M
        • Rolo R.
        The role of bronchoalveolar lavage in interstitial lung diseases.
        Rev Port Pneumol (2006). 2017; 23: 360-362https://doi.org/10.1016/j.rppnen.2017.10.003
        • Yoshizawa T
        • Sugino K
        • Shibuya K
        • Uekusa T
        • Homma S.
        Fibrocellular non-specific interstitial pneumonia with favourable prognosis in clinically amyopathic dermatomyositis.
        Respirol Case Rep. 2016; 4 (https://doi.org/10.1002/rcr2.180): e00180
        • Usagawa Y
        • Komiya K
        • Yamasue M
        • Hashinaga K
        • Mizukami E
        • Umeki K
        • et al.
        Risk factors for disease-related deterioration following diagnostic bronchoalveolar lavage procedures in diffuse lung disease: a case-control study.
        PeerJ. 2020; 8: e9864https://doi.org/10.7717/peerj.9864
        • Bennett D
        • Salvini M
        • Fui A
        • Cillis G
        • Cameli P
        • Mazzei MA
        • et al.
        Calgranulin B and KL-6 in bronchoalveolar lavage of patients with IPF and NSIP.
        Inflammation. 2019; 42: 463-470https://doi.org/10.1007/s10753-018-00955-2
        • Poletti V
        • Cazzato S
        • Minicuci N
        • Zompatori M
        • Burzi M
        • Schiattone ML.
        The diagnostic value of bronchoalveolar lavage and transbronchial lung biopsy in cryptogenic organizing pneumonia.
        Eur Respir J. 1996; 9: 2513-2516https://doi.org/10.1183/09031936.96.09122513
        • Sartorelli P
        • Indini S
        • Bianchi F
        • D'Alessandro M
        • Bergantini L
        • Cameli P
        • et al.
        Cytological analysis of bronchoalveolar lavage fluid in asbestos-exposed workers.
        Med Lav. 2020; 111: 379-387https://doi.org/10.23749/mdl.v111i5.9170
        • Meyer KC
        • Raghu G.
        Bronchoalveolar lavage for the evaluation of interstitial lung disease: is it clinically useful?.
        Eur Respir J. 2011; 38: 761-769https://doi.org/10.1183/09031936.00069509
        • Wells AU
        • Kokosi MA.
        POINT: should BAL be routinely performed in the diagnostic evaluation of idiopathic pulmonary fibrosis?.
        Yes. Chest. 2017; 152: 917-919https://doi.org/10.1016/j.chest.2017.08.1173