所有成人哮喘患者都应考虑 OA。OA 的确诊要求临床医生根据临床病史和暴露史首先客观地确诊哮喘,然后再确认哮喘和工作之间的关系。要进行有效的评估,应在工人离开工作场所之前进行 OA 相关检查,因为避免暴露可能影响检查过程的可靠性。对于致敏剂诱发的 OA 患者尤其如此。由于长时间暴露于致敏剂可能导致较差的临床结局,因此及时诊断十分重要。但致敏剂诱发的 OA 的准确诊断也极为重要,因为该诊断可能导致非常显著的工作限制,这可能损害患者维持就业的能力。[22]Tarlo SM, Balmes J, Balkissoon R, et al. Diagnosis and management of work-related asthma: American College of Chest Physicians Consensus Statement. Chest. 2008;134(3 suppl):1S-41S.http://www.ncbi.nlm.nih.gov/pubmed/18779187?tool=bestpractice.com 如有可能,最好将患者转诊给有职业性哮喘专门知识的专科医生进行诊断。刺激物诱发的 OA 也需要仔细客观的诊断,以确保对疾病的正确管理和赔偿决策。
确立哮喘的诊断
基于以下因素诊断哮喘:
相符合的临床病史
显示不同程度的气流受限情况的检查。应采用推荐的检查方法和阳性反应的定义进行上述评估[30]Pellegrino R, Viegi G, Brusasco V, et al. Interpretative strategies for lung function tests. Eur Respir J. 2005;26:948-968.http://erj.ersjournals.com/cgi/content/full/26/5/948http://www.ncbi.nlm.nih.gov/pubmed/16264058?tool=bestpractice.com[31]Crapo RO, Casaburi R, Coates AL, et al. American Thoracic Society: guidelines for methacholine and exercise challenge testing - 1999. Am J Respir Crit Care Med. 2000;161:309-329.http://www.ncbi.nlm.nih.gov/pubmed/10619836?tool=bestpractice.com
排除其他呼吸系统病变
对于刺激物诱发的 OA 患者,排除既往呼吸系统疾病有助于诊断。征得同意后,应从患者的初级医疗保健医生处获取信息,确认患者过去从未接受过哮喘治疗。如果可以,应获取暴露事件前的任何既往肺功能试验结果。
明确哮喘的工作相关性
对于所有患者,应当获取完整的病史,包括任何公认的 OA 危险因素的详细信息(例如,高水平致敏剂暴露、特应质和吸烟)。还应获取全面的职业史。这应包括询问患者当前和既往工作情况,重点是确定是否有已知致敏剂暴露或者任何高水平刺激物呼吸道暴露史。Haz-Map: information on hazardous agents and occupational diseasesToxicology Data Network: data on hazardous chemicals[23]Baur X, Bakehe P. Allergens causing occupational asthma: an evidence-based evaluation of the literature. Int Arch Occup Environ Health. 2014;87:339-363.http://rd.springer.com/article/10.1007/s00420-013-0866-9/fulltext.htmlhttp://www.ncbi.nlm.nih.gov/pubmed/23595938?tool=bestpractice.com[32]Baur X. A compendium of causative agents of occupational asthma. J Occup Med Toxicol. 2013;8:15.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3665602/http://www.ncbi.nlm.nih.gov/pubmed/23706060?tool=bestpractice.com[33]Raulf M, Buters J, Chapman M, et al; European Academy of Allergy and Clinical Immunology. Monitoring of occupational and environmental aeroallergens-EAACI Position Paper. Allergy. 2014;69:1280-1299.http://onlinelibrary.wiley.com/doi/10.1111/all.12456/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24894737?tool=bestpractice.com[34]Rosenman KD, Beckett WS. Web based listing of agents associated with new onset work-related asthma. Respir Med. 2015;109:625-631.http://www.ncbi.nlm.nih.gov/pubmed/25863522?tool=bestpractice.com 然而,缺少公认的危险因素或已知致敏剂暴露史并不能排除致敏剂诱发的 OA,而且每年都会报告新的致敏剂。如果可用,应要求患者提供工作场所使用的物质材料安全数据表。在某些情况下,可能需要探访工作场所,以发现和评估任何潜在致敏剂暴露。如果需要这样,应确定同一工作场所中受呼吸道症状影响的其他工人。[22]Tarlo SM, Balmes J, Balkissoon R, et al. Diagnosis and management of work-related asthma: American College of Chest Physicians Consensus Statement. Chest. 2008;134(3 suppl):1S-41S.http://www.ncbi.nlm.nih.gov/pubmed/18779187?tool=bestpractice.com 该评估可由职业卫生人员进行。对于刺激物诱发的哮喘病例,有关急性工作暴露事件的任何记录(时间和暴露细节)都有助于诊断。
应系统地询问患者症状和工作暴露的时间关系,应特别询问急性刺激物暴露后症状发作的时间,对于疑似致敏剂诱发的 OA,还应询问在离开工作场所几天后症状是否有所改善。[35]Vandenplas O, Ghezzo H, Munoz X, et al. What are the questionnaire items most useful in identifying subjects with occupational asthma? Eur Respir J. 2005;26:1056-1063.http://erj.ersjournals.com/cgi/content/full/26/6/1056http://www.ncbi.nlm.nih.gov/pubmed/16319335?tool=bestpractice.com[36]Malo JL, Ghezzo H, L'Archeveque J, et al. Is the clinical history a satisfactory means of diagnosing occupational asthma? Am Rev Respir Dis. 1991 Mar;143(3):528-32.http://www.ncbi.nlm.nih.gov/pubmed/2001062?tool=bestpractice.com 但是应该注意的是,晚期致敏剂诱发的 OA 可能出现与症状之间的时间差异较小,而且一些患者的哮喘症状不是在工作中加重,而是在下班后加重。
对于疑似致敏剂诱发的 OA,应进行相关检查,以便客观证明哮喘与暴露之间的关系。[22]Tarlo SM, Balmes J, Balkissoon R, et al. Diagnosis and management of work-related asthma: American College of Chest Physicians Consensus Statement. Chest. 2008;134(3 suppl):1S-41S.http://www.ncbi.nlm.nih.gov/pubmed/18779187?tool=bestpractice.com[37]Beach J, Russell K, Blitz S, et al. A systematic review of the diagnosis of occupational asthma. Chest. 2007;131:569-578.http://www.ncbi.nlm.nih.gov/pubmed/17296663?tool=bestpractice.com[38]Vandenplas O, Suojalehto H, Aasen TB, et al. Specific inhalation challenge in the diagnosis of occupational asthma: consensus statement. Eur Respir J. 2014;43:1573-1587.http://erj.ersjournals.com/content/43/6/1573.longhttp://www.ncbi.nlm.nih.gov/pubmed/24603815?tool=bestpractice.com[39]Beach J, Rowe BH, Blitz S, et al. Diagnosis and management of work-related asthma. Evid Rep Technol Assess (Summ). 2005;129:1-8.https://www.ncbi.nlm.nih.gov/books/NBK37917/http://www.ncbi.nlm.nih.gov/pubmed/16354102?tool=bestpractice.com
每种检查方法都有假阴性和假阳性;因此,可能需要联合多种检查以确诊。通常,最好尽早将患者转诊给具有该领域(肺、过敏或职业性疾病)专业知识的专科医生。
支持性检查包括:
连续呼气峰流速检测[40]Liss GM, Tarlo SM. Peak expiratory flow rates in possible occupational asthma. Chest. 1991;100:63-69.http://www.ncbi.nlm.nih.gov/pubmed/2060392?tool=bestpractice.com[41]Perrin B, Lagier F, L'Archeveque J, et al. Occupational asthma: validity of monitoring of peak expiratory flow rates and non-allergic bronchial responsiveness as compared to specific inhalation challenge. Eur Respir J. 1992;5:40-48.http://www.ncbi.nlm.nih.gov/pubmed/1577147?tool=bestpractice.com
FEV1 监测
NSBHR 的连续评估[22]Tarlo SM, Balmes J, Balkissoon R, et al. Diagnosis and management of work-related asthma: American College of Chest Physicians Consensus Statement. Chest. 2008;134(3 suppl):1S-41S.http://www.ncbi.nlm.nih.gov/pubmed/18779187?tool=bestpractice.com[42]Cote J, Kennedy S, Chan-Yeung M. Sensitivity and specificity of PC20 and peak expiratory flow rate in cedar asthma. J Allergy Clin Immunol. 1990;85:592-598.http://www.ncbi.nlm.nih.gov/pubmed/2179365?tool=bestpractice.com
采用免疫学检测以确定致敏性,例如皮肤点刺试验和 IgE 测定。[22]Tarlo SM, Balmes J, Balkissoon R, et al. Diagnosis and management of work-related asthma: American College of Chest Physicians Consensus Statement. Chest. 2008;134(3 suppl):1S-41S.http://www.ncbi.nlm.nih.gov/pubmed/18779187?tool=bestpractice.com[37]Beach J, Russell K, Blitz S, et al. A systematic review of the diagnosis of occupational asthma. Chest. 2007;131:569-578.http://www.ncbi.nlm.nih.gov/pubmed/17296663?tool=bestpractice.com[39]Beach J, Rowe BH, Blitz S, et al. Diagnosis and management of work-related asthma. Evid Rep Technol Assess (Summ). 2005;129:1-8.https://www.ncbi.nlm.nih.gov/books/NBK37917/http://www.ncbi.nlm.nih.gov/pubmed/16354102?tool=bestpractice.com
[Figure caption and citation for the preceding image starts]: 对患有职业性哮喘的护士使用天然橡胶胶乳进行皮肤点刺试验的结果来自 Tarlo SM, Wong L, Roos J, et al. Occupational asthma caused by latex in a surgical glove manufacturing plant. J Allergy Clin Immunol. 1990:85:626-631.经许可使用 [Citation ends].
在患者工作中暴露于可疑物质并且有症状时,测定的 NSBHR 强度是该检测的高阴性预测值。[43]Pralong JA, Lemière C, Rochat T, et al. Predictive value of nonspecific bronchial responsiveness in occupational asthma. J Allergy Clin Immunol. 2016;137:412-416.http://www.ncbi.nlm.nih.gov/pubmed/26220529?tool=bestpractice.com 在病史提示致敏剂诱发的 OA 患者中,单次测定非特异性支气管高反应性 (NSBHR) 与特定皮肤点刺试验或 IgE 的联合检查似乎在预筛查的患者中具有高特异性。[37]Beach J, Russell K, Blitz S, et al. A systematic review of the diagnosis of occupational asthma. Chest. 2007;131:569-578.http://www.ncbi.nlm.nih.gov/pubmed/17296663?tool=bestpractice.com[39]Beach J, Rowe BH, Blitz S, et al. Diagnosis and management of work-related asthma. Evid Rep Technol Assess (Summ). 2005;129:1-8.https://www.ncbi.nlm.nih.gov/books/NBK37917/http://www.ncbi.nlm.nih.gov/pubmed/16354102?tool=bestpractice.com
[Figure caption and citation for the preceding image starts]: 职业性哮喘患者的呼气峰流速 (PEFR) 和乙酰甲胆碱激发试验结果来自 Tarlo SM, Wong L, Roos J, et al. Occupational asthma caused by latex in a surgical glove manufacturing plant. J Allergy Clin Immunol. 1990:85:626-631.经许可使用 [Citation ends].
针对致敏剂诱发的 OA 的其他检测
特异性吸入激发试验(暴露于特定物质)被认为是诊断标准性检查方法。但是,由于它只能在少数专业中心进行,因此不能将其视为常规检查。可以进行工作场所激发试验,存在多种潜在致敏剂时可能特别有用,但非常耗时且难以组织。[41]Perrin B, Lagier F, L'Archeveque J, et al. Occupational asthma: validity of monitoring of peak expiratory flow rates and non-allergic bronchial responsiveness as compared to specific inhalation challenge. Eur Respir J. 1992;5:40-48.http://www.ncbi.nlm.nih.gov/pubmed/1577147?tool=bestpractice.com[38]Vandenplas O, Suojalehto H, Aasen TB, et al. Specific inhalation challenge in the diagnosis of occupational asthma: consensus statement. Eur Respir J. 2014;43:1573-1587.http://erj.ersjournals.com/content/43/6/1573.longhttp://www.ncbi.nlm.nih.gov/pubmed/24603815?tool=bestpractice.com
近期被评估的诊断方法是诱导痰细胞学检查,如果可开展,也可采用。[22]Tarlo SM, Balmes J, Balkissoon R, et al. Diagnosis and management of work-related asthma: American College of Chest Physicians Consensus Statement. Chest. 2008;134(3 suppl):1S-41S.http://www.ncbi.nlm.nih.gov/pubmed/18779187?tool=bestpractice.com[27]Girard F, Chaboillez S, Cartier A, et al. An effective strategy for diagnosing occupational asthma: use of induced sputum. Am J Respir Crit Care Med. 2004;170:845-850.http://www.ncbi.nlm.nih.gov/pubmed/15271693?tool=bestpractice.com 呼出气一氧化氮分析也在研究过程中,但价值较不明确。[22]Tarlo SM, Balmes J, Balkissoon R, et al. Diagnosis and management of work-related asthma: American College of Chest Physicians Consensus Statement. Chest. 2008;134(3 suppl):1S-41S.http://www.ncbi.nlm.nih.gov/pubmed/18779187?tool=bestpractice.com[44]Piipari R, Piirila P, Keskinen H, et al. Exhaled nitric oxide in specific challenge tests to assess occupational asthma. Eur Respir J. 2002;20:1532-1537.http://erj.ersjournals.com/cgi/content/full/20/6/1532http://www.ncbi.nlm.nih.gov/pubmed/12503715?tool=bestpractice.com[45]Florentin A, Acouetey DS, Remen T, et al. Exhaled nitric oxide and screening for occupational asthma in two at-risk sectors: bakery and hairdressing. Int J Tuberc Lung Dis. 2014;18:744-750.http://www.ncbi.nlm.nih.gov/pubmed/24903948?tool=bestpractice.com