Report of ERS Task Force: guidelines for measurement of acellular components and standardization of BAL

Abstract

The investigatory technique of bronchoalveolar lavage(BAL) has become one of the most valuable research toolsfor studying inflammatory mechanisms in a wide range ofdiseases that affect the lungs and airways in humans, andseveral thousand peer review papers are published eachyear. In addition, cytological and microbiological testing ofBAL samples are of established value for assisting inclinical diagnosis and management of many lung diseases,and these procedures are available routinely in most mod-ern specialist respiratory centres. Yet despite its undoubtedvalue, the interpretation of BAL findings is still hinderedbecause the procedure cannot be precisely standardized. Inparticular, there is still no satisfactory method of deter-mining the dilution factor during lavage. This preventsaccurate quantification of all components in BAL fluidsand causes especial difficulty in interpreting the results ofmeasurements of soluble acellular components.A number of Task Force reports have been publishedthat have provided guidelines for the clinical application ofBAL, and on technical aspects mainly related to evaluationof cells and other cytological features [1–4]. However, noguidelines are currently available for evaluation of acell-ular components, nor are any firm recommendationsavailable for standardization of BAL procedure. Thepurpose of this editorial is to inform that this omission isnow addressed by a new report of a European RespiratorySociety (ERS) Task Force which is currently being pub-lished in the European Respiratory Review [5]. ThisReport provides a comprehensive review of the currentstatus of techniques for measurement of acellular com-ponents in human BAL samples, and gives guidelines andrecommendations to define standard procedures for thegeneral conduct of BAL. It updates previous guidelinesand gives recommendations on how to comply with theincreasing demands for more effective quality control.The Task Force was established by the BAL ScientificGroup of the ERS in September 1995. The authors wereprivileged to be the task force co-ordinators and editors ofthe report, to which 49 authors and 21 invited reviewersfrom 15 countries contributed. It contains a series of det-ailed critical reviews which give recommendations accord-ing to the consensus view on 17 topics. These include threesections concerned with the general problems of BALstandardization [6–8] and one section dealing with thespecial problems relating to children [9]; while the re-maining 13 sections provide detailed information on spe-cific considerations that apply to the measurement ofdifferent categories of specific components including pul-monary surfactant components [10], immunoglobulins[11], proteases and antiproteases [12], angiotensin-con-verting enzyme [13], antioxidants, oxidants and oxidationproducts [14], lipid mediators [15], cytokines [16], solu-ble adhesion molecules [17], markers of fibrosis [18],granulocyte derived markers [19], tumour markers [20],markers of cell death [21], and other acellular compo-nents [22]. Those beginning work on lavage will findinformation about problems and pitfalls and how best toavoid them, while those experienced in the field will findcomprehensive critical reviews to assist with selectingoptimal approaches. All are encouraged to agree to therecommendations for better standardization procedures,in order to facilitate multicentre studies and the clearercomparison of findings between different workers to aidclinical interpretation.Early BAL studies were focused mainly on defining thepredominant types of inflammatory cells associated withdifferent lung diseases. Despite concerns about the lack ofstandardization, it soon became apparent that the findingsfrom independent groups of workers were remarkablysimilar, provided that results were expressed as differentialBAL cell counts. This is because differential proportions ofcells, unlike concentrations per millilitre, are unaffected byvariable BAL dilution. The situation is more difficult foracellular components, because quantitative measurementsper millilitre are the main approach to expression of results.Despite the inaccuracies in quantification, the Task Forcereport shows that a great deal of valuable information hasbeen obtained about numerous acellular components inBAL samples and that reproducibility can be improved bya more informed approach to the methods used for expres-sion of results and by improvements in assay standard-ization. The current frequent variability of approaches usedby different workers may explain why the clinical utility ofmeasurements of acellular components in BAL remainspoorly defined compared to that of cellular components.This may change if future studies are conducted accordingto the guidelines proposed in the Task Force report toimprove the reproducibility and reliability of quantitativemeasurements. These are summarized in table 1.Applications of BAL have diversified into many fieldsof respiratory medicine, and it mu