Bronchoalveolar lavage differential cell count on prognostic assessment of patients with stable or acute interstitial lung disease: A retrospective real-life study
Introduction
Analysis of cell differential counts in bronchoalveolar lavage (BAL) fluid has been regarded as useful, though not in itself sufficient, in the diagnosis of specific types of interstitial lung diseases (ILD) [1]. According to the current international guidelines on the diagnosis of IPF, BAL is recommended to be performed if high-resolution computed tomography (HRCT) reveals other patterns than definite usual interstitial pneumonia (UIP), namely probable UIP, indeterminate for UIP or some alternative diagnosis [2].
There is limited data on how valuable BAL is as a prognostic tool or its usefulness in predicting the response to therapy [1]. However, some previous studies have shown that BAL might be beneficial in risk prediction in terms of the occurrence of AE-ILD or mortality in different types of ILD, as presented in Table 1 [[3], [4], [5], [6], [7], [8], [9], [10], [11]], which also lists four studies which have described BAL cell differential counts examined during an AE-ILD [[12], [13], [14], [15]].
The importance of BAL in the diagnostics of AE-ILD has been a subject of debate in recent years. In addition to typical symptoms and new, bilateral alveolar changes in computed tomography (CT), the previous international recommendation on AE-IPF demanded the exclusion of infection which had to be performed by collecting either BAL or an endobronchial aspirate [16]. The present guideline does not recommend performing BAL during AE-IPF, since distinguishing an infection triggered AE-IPF from idiopathic cases is not supported by research data [17]. Even though the guidelines on AE were made originally for IPF, they have also been applied to other AE-ILDs with progressive phenotypes [18].
The aim of our study was to evaluate BAL differential cell counts in ILD patients at the time of the initial ILD diagnosis or/and AE-ILD. We investigated whether different BAL cellular profiles were associated with mortality and the risk and outcome of AE-ILD.
Section snippets
Patient and data collection
The study cohort consists of IPF and other ILD patients hospitalized in Oulu University Hospital and Oulaskangas Hospital in Northern Finland between 1/1/2008 and 31/12/2017. A total of 89 patients also belonged to the cohort of our recently published study [19]. The patients' data were collected from the hospital medical records by performing a search with the International Classification of Diseases version 10 codes J84.1, J84.8, J84.9. J61, J99, J99.0* and J99*M05.1. The patients with
Study subjects
We examined 133 therapy naive ILD patients for whom we had baseline BAL data and in addition, there were 43 patients in whom BAL had been obtained during AE-ILD (Table 2); of these, 20 patients had undergone two consecutive BALs, e.g. the first specimen had been gathered at time of the initial diagnosis and the second later during an AE-ILD. One out of 20 patients had baseline BAL differential cells analyzed only with PAPA staining. The majority of the subjects suffered from IPF, while the most
Discussion
We have examined a relatively large real-life material of BAL cell differential counts of IPF and non-IPF patients, with and without an AE-ILD. We found significant changes in BAL cell profiles caused by AE-ILD. We were also able to detect a correlation of AE-BAL TCC with survival and several correlations between BAL cell differential counts and survival time.
BAL cell profiles showed a more neutrophilic and lymphocytic pattern in AE-ILD than in the stable phase of the disease, while macrophages
Conclusions
To conclude, we detected significant changes in BAL-cell profiles in patients having undergone both BAL at baseline and AE-BAL. We detected several new prognostic markers, namely basophils in the stable phase of the ILD, and TCC, number of macrophages and BAL neutrophil count during AE-ILD. As a result, BAL might be a more functional tool in the prognostic evaluation of ILD patients than previously believed.
Funding source declaration
This work was supported by the Foundation of the Finnish Anti-Tuberculosis Association, Ryttylä, Finland; Research Foundation of the Pulmonary Diseases HES, Helsinki, Finland; Jalmari and Rauha Ahokas Foundation, Helsinki, Finland and the Research Foundation of North Finland, Oulu, Finland. The funding sources were not involved in the study design, collection, analysis and interpretation of data, in the writing of the report or in the decision to submit the article for publication.
Submission declaration and verification
This work has not been published previously, is not under consideration for publication elsewhere, is approved by all authors and by the responsible authorities where the work was carried out, and that, if accepted, it will not be published elsewhere in the same form, in English or in any other language, including electronically without the written consent of the copyright-holder.
Authors' contributions
JS collected the study material and interpreted and analyzed the data. JS and HL prepared the draft of the manuscript. HL participated substantially in the BAL data collection. EK participated in planning BAL data collection form, provided methodological assistance concerning the BAL procedure and participated in the interpretation of the data. HV planned and participated in the statistical analysis. RK and MP participated in planning the data collection, study design and in the interpretation
Data statement
The datasets generated and analyzed during the current study are not publicly available due to the relatively small population of Northern Finland since we could not guarantee individuals' anonymity as the data was collected in a detailed manner, but it is available from the corresponding author on reasonable request.
Declaration of Competing Interest
JS reports congress fees and travel subsidy from Boehringer-Ingelheim, GlaxoSmithKline, Novartis, Orion Pharma, Ratiopharm and Roche, and lecture fees from Boehringer-Ingelheim, Chiesi, GlaxoSmithKline, Mundipharma, Orion Pharma and Roche outside the submitted work. EK reports congress fee and travel subsidy from Orion Pharma outside the submitted work. HL and HV have nothing to disclose. MP reports a lecture fee from Boehringer-Ingelheim Finland Ltd. and a congress fee and travel subsidy from
Acknowledgements
The authors would like to thank for Dr. Ewen MacDonald for language and editorial assistance.
References (34)
- et al.
Baseline BAL neutrophilia predicts early mortality in idiopathic pulmonary fibrosis
Chest.
(2008) - 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) - et al.
Diagnosis of idiopathic pulmonary fibrosis. An Official ATS/ERS/JRS/ALAT clinical practice guideline
Am J Respir Crit Care Med.
(2018) - et al.
Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors and outcome
Eur Respir J.
(2011) - et al.
Heterogeneity of incidence and outcome of acute exacerbation in idiopathic interstitial pneumonia
Respirology.
(2016) - et al.
Risk factors for an acute exacerbation of idiopathic pulmonary fibrosis
Respir Res.
(2016) - et al.
Impact of lymphocyte differential count >15% in BALF on the mortality of patients with acute exacerbation of chronic fibrosing idiopathic interstitial pneumonia
BMC Pulm Med.
(2017) - et al.
Prognosis of patients with idiopathic pulmonary fibrosis
Med Sci Monit.
(2019) - et al.
Relationship between cells obtained by bronchoalveolar lavage and survival in idiopathic pulmonary fibrosis patients
Throrax
(1995) - et al.
Cell profiles of bronchoalveolar lavage fluid as prognosticators of idiopathic pulmonary fibrosis/usual interstitial pneumonia among Japanese patients
Respiration.
(2005)
Bronchoalveolar lavage in fibrotic idiopathic interstitial pneumonias
Respir Med.
Bronchoalveolar lavage pepsin in acute exacerbation of idiopathic pulmonary fibrosis
Eur Respir J.
Macrophage activation in acute exacerbation of idiopathic pulmonary fibrosis
PLoS ONE.
Bronchoscopy assessment of acute respiratory failure in interstitial lung disease
Respirology.
The utility of the Japanese Association for Acute Medicine DIC scoring system for predicting survival in acute exacerbation of fibrosing idiopathic interstitial pneumonia
PLoS One.
Acute exacerbations of idiopathic pulmonary fibrosis
Am J Respir Crit Care Med.
Acute exacerbation of idiopathic pulmonary fibrosis. An International Working Group Report
Am J Respir Crit Care Med.
Cited by (4)
Prognostic significance of bronchoalveolar lavage cellular analysis in patients with acute exacerbation of interstitial lung disease
2021, Respiratory MedicineCitation Excerpt :These data suggest that BALF cellular analysis is a potential biomarker for predicting prognosis in AE-ILD. AE can occur during the clinical course of fibrotic ILD [3–9], and BALF cell patterns at the time of AE have been examined in several reports [6,7,13–16,24,25]. Most of these studies showed that lymphocytes and/or neutrophils were predominant in the BALF in AE-ILD, including AE-IPF [14–16,24,25], AE-IIPs [6,7,13], and AE-CTD-ILD [6,7].
Clinical utility of heparin-binding protein as an acute-phase inflammatory marker in interstitial lung disease
2022, Journal of Leukocyte BiologyAcute exacerbation of interstitial lung disease associated with rheumatic disease
2022, Nature Reviews Rheumatology