Specific inhalation challenge in the diagnosis of occupational asthma: consensus statement

This consensus statement provides practical recommendations for specific inhalation challenge (SIC) in the diagnosis of occupational asthma. They are derived from a systematic literature search, a census of active European centres, a Delphi conference and expert consensus. This article details each step of a SIC, including safety requirements, techniques for delivering agents, and methods for assessing and interpreting bronchial responses. The limitations of the procedure are also discussed. Testing should only be carried out in hospitals where physicians and healthcare professionals have appropriate expertise. Tests should always include a control challenge, a gradual increase of exposure to the suspected agent, and close monitoring of the patient during the challenge and for at least 6 h afterwards. In expert centres, excessive reactions provoked by SIC are rare. A positive response is defined by a fall in forced expiratory volume in 1 s o15% from baseline. Equivocal reactions can sometimes be clarified by finding changes in nonspecific bronchial responsiveness, sputum eosinophils or exhaled nitric oxide. The sensitivity and specificity of SIC are high but not easily quantified, as the method is usually used as the reference standard for the diagnosis of occupational asthma. @ERSpublications ERS Task Force: a statement on specific inhalation challenges in the diagnosis of occupational asthma http://ow.ly/tCvFG Copyright ERS 2014 ERS TASK FORCE REPORT OCCUPATIONAL ASTHMA Eur Respir J 2014; 43: 1573–1587 | DOI: 10.1183/09031936.00180313 1573 Introduction In this context, specific inhalation challenge (SIC) testing is the controlled exposure of a patient, under laboratory conditions, to an agent encountered in their workplace. In this article we are concerned with the use of SIC to identify immunologically mediated (or sensitiser-induced) occupational asthma in patients with a history of work-related symptoms [1–4]. A similar approach is used in the evaluation of hypersensitivity pneumonitis, but this is not discussed below. Common synonyms for SIC include specific ‘‘bronchial provocation testing’’ and ‘‘occupational-type challenge tests’’. Although there are earlier, sporadic reports of its use, the procedure for SIC with occupational agents was formally developed in the early 1970s by PEPYS et al. [5], and initially performed in a corridor of the Royal Brompton Hospital (London, UK). In the intervening 40 years the practice has spread and become more sophisticated. In many centres, primarily in Canada and mainland Europe, SIC is regarded as a ‘‘first-line’’ procedure for diagnosing asthma arising from exposure to a respiratory sensitising agent in the workplace. In other centres it is reserved for cases where alternative methods have failed to identify, with sufficient accuracy, a specific causal exposure. SIC remains the best method of recognising the human sensitising potential of new agents, particularly chemical agents, encountered by persons in their work. In 2011, the European Respiratory Society (ERS) formed a Task Force on SIC with occupational agents, comprising 15 specialist respiratory physicians from 10 European countries. Its principal aim was to issue guidance on the indications, methodology, interpretation and drawbacks of SIC. From the start, we recognised that several review articles [5–10], textbooks [11] and guidelines [12, 13] had covered similar ground but none of them were comprehensive and many were very dated. We did not aim to formulate a single, standardised approach to the use of SIC, recognising that there are important historical, jurisdictional and cultural determinants of its use that cannot, and need not, be included under a guise of ‘‘harmony’’. We suggest that the information contained in this article will be of interest to those: 1) currently using SIC in the assessment of occupational asthma in Europe and elsewhere; 2) who are concerned with the risk assessment of (chemical) agents used in the workplace, particularly new such agents; and 3) planning to introduce SIC to their clinical practice. This latter audience is, we believe, especially important. Although SIC is still acknowledged as the ‘‘reference standard’’ for demonstrating the causal relationship between exposure to an occupational agent and asthma [1, 2, 4, 14], recent information indicates that it is underused in the diagnostic evaluation of work-related asthma [15–19]. Task Force methodology We undertook a variety of approaches to produce this guidance. First, we performed a systematic bibliographic search through the library services at the Finnish Institute of Occupational Health, Helsinki, Finland (Appendix A in the online supplementary material). The retrieved abstracts were carefully explored by two Task Force members (P. Cullinan and H. Suojalehto) to identify relevant information on the performance of SIC with occupational agents. In addition, the reference lists of relevant articles and previous reviews were screened to identify any additional publications. The results of this systematic search were made available to all members of the Task Force. Secondly, using a structured questionnaire, we surveyed the current practice of SIC with occupational agents in European centres among the members of the Occupational and Environmental Group of the ERS. A summary of this survey is published elsewhere [19]. Thirdly, we completed a two-stage Delphi exercise that aimed to judge the consistency of the Task Force member’s views. The findings from this and the survey mentioned above were used in the preparation of the guidance. Finally, we held four face-to-face meetings with the Task Force members between 2011 and 2013. Through these we prepared a list of ‘‘statements’’ pertaining to each step of SIC and considered the available evidence for each. A final consensus was reached through discussion. The recommendations in this document were based on published evidence when available or on the results of the survey and Delphi process when it was not. This article has supplementary material available from www.erj.ersjournals.com Received: Oct 16 2013 | Accepted after revision: Jan 26 2014 | First published online: Mar 6 2014 Conflict of interest: Disclosures can be found alongside the online version of this article at www.erj.ersjournals.com OCCUPATIONAL ASTHMA | O. VANDENPLAS ET AL. DOI: 10.1183/09031936.00180313 1574 In addition to this guidance, we developed a ‘‘handbook’’ of practical methods for performing SIC with individual workplace agents, under the direction of K. Suuronen (Finnish Institute of Occupational Health). The handbook contains a summary of the methods used by 22 European centres and is available in the online supplementary material. Rationale and indications for performing specific inhalation challenges SIC aims to investigate empirically the specific reactivity of the airways to occupational agents (of either highor low-molecular-weight (HMW and LMW, respectively)) in workers who have symptoms of workrelated asthma. The rationale for performing SIC is, therefore, to improve the diagnosis of work-related asthma. There is accumulating evidence that workplace exposures contribute substantially to the global burden of asthma, accounting for ,15% of all adult-onset disease [20, 21]. Up to 20% of adults with asthma report provocation of their symptoms in the workplace [22], although only a minority have immunologically or sensitiser-induced occupational asthma [23]. A timely and accurate diagnosis of occupational asthma is a key element in advising appropriate treatment or other interventions and minimising the adverse health and socioeconomic outcomes of the disease [4, 24, 25]. The accurate identification of an index case of occupational asthma and its aetiology is also important for implementing primary preventive measures for other exposed workers. The evidence-based guidelines issued by the British Occupational Health Research Foundation acknowledged that: ‘‘A carefully controlled SIC comes closest to a gold standard test for some agents causing OA [occupational asthma]’’, but ‘‘a negative test in a worker with otherwise good evidence of OA is not sufficient to exclude the diagnosis’’ [1]. The systematic review conducted by the Agency for Healthcare Research and Quality [14] concluded that ‘‘as yet there is no definitive diagnostic test for OA’’ and considered SIC to be a ‘‘reference standard’’ rather than the ‘‘gold standard’’. The expert-based consensus statement issued by the American College of Chest Physicians [2] recommended that: ‘‘In individuals with suspected sensitizer-induced OA, conducting SIC (where available) is suggested when the diagnosis or causative agent remains equivocal’’. This Task Force agreed that the broad categories of indications for performing SIC with an occupational agent include: 1) confirmation of the diagnosis of occupational asthma when other objective methods are not feasible, are less efficient or have failed to provide definitive results; 2) identification of the cause of occupational asthma when other objective methods are not feasible, are less efficient or have failed to provide definitive results; 3) the identification of a new (not formerly described) specific cause of occupational asthma; and 4) research into the mechanisms of work-related asthma. The place of SIC in the diagnostic evaluation of a patient with suspected occupational asthma is summarised in figure 1. Within these indications, the use of SIC is influenced by the final purpose of the diagnostic evaluation. For instance, the desired level of diagnostic accuracy may be different for clinical, research, compensatory or occupational health surveillance purposes. The use of SIC should also take into account patient important and societal outcomes. All of these may vary between jurisdictions and different countries. Methodology of specific inhalation challenges Key messages for performing reliable and safe SICs with occupational agents are summarised in table 1. General safety requirements SIC should only be carried out in hospital-based specialised centres [13]. Patients may be admitted to hospital for the duration of the SIC; where they are not, facilities for their management in the case of excessive reactions, including those in the late-phase, must be readily available. SIC should be conducted by trained personnel who have received precise training in the challenge protocol including when and how to stop further exposure, and in emergency procedures [13, 26]. SIC should be closely supervised by physicians who have expertise in the field and are readily available to manage acute asthmatic or anaphylactic reactions according to current guidelines [27, 28]. SIC should be performed in enclosed challenge rooms equipped with an adequate exhaust ventilation system or using closed-circuit devices [29–32], in order to prevent inadvertent exposure of the technicians and the tested patient after discontinuation of the challenge. Some patients with occupational asthma are extremely sensitive to very small quantities of the agent to which they are sensitised. During SIC, patients should wear protective overalls, caps, eye protection, shoes and non-latex gloves to avoid, as far as possible, direct skin exposure to the tested agent. The patient should receive detailed information on the purpose and procedures of the tests and on their potential adverse effects. Females of child-bearing age should be clearly informed that SIC is not advised OCCUPATIONAL ASTHMA | O. VANDENPLAS ET AL. DOI: 10.1183/09031936.00180313 1575 during pregnancy. There is a consensus that subjects undergoing an SIC procedure should be asked to sign a statement of informed consent.