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Sensitivity of Methacholine Testing in Occupational Asthma

1986; Elsevier BV; Volume: 89; Issue: 3 Linguagem: Inglês

10.1378/chest.89.3.324

1931-3543

Russell Dodge,

Allergic Rhinitis and Sensitization

Physicians use the methacholine inhalation test to diagnose asthma in patients with atypical symptoms. But, perhaps because physicians don't agree among themselves exactly what asthma is, heightened bronchial responsiveness to methacholine is not a specific test for asthma. Townley and his co-workers1Townley RG Ryo UY Kolotkin BM Kang B Bronchial sensitivity to methacholine in current and former asthmatic and allergic rhinitis and control subjects.J Allerg Clin Immun. 1975; 56: 429-442Abstract Full Text PDF PubMed Scopus (277) Google Scholar found that persons with hay fever and those with asthma overlapped when their responses to methacholine were plotted. Patients with chronic bronchitis and emphysema can also react to relatively low doses of methacholine.2Klein RC Salvaggio JE Nonspecificity of the bronchoconstricting effect of histamine and acetyl-beta-methylcholine in patients with obstructive airway disease.J Allergy. 1966; 37: 158-168Abstract Full Text PDF PubMed Scopus (33) Google Scholar, 3Ramsdell JW Nachtwey FJ Moser KM Bronchial hyperreactivity in chronic obstructive bronchitis.Am Rev Respir Dis. 1982; 126: 829-832PubMed Google Scholar There has been general agreement, however, that a person who fails to respond to methacholine does not have asthma.4Boushey HA Holtzman MJ Sheller JR Nadel JA Bronchial hyperreactivity.Am Rev Respir Dis. 1980; 121: 389-413PubMed Google Scholar Townley et al,1Townley RG Ryo UY Kolotkin BM Kang B Bronchial sensitivity to methacholine in current and former asthmatic and allergic rhinitis and control subjects.J Allerg Clin Immun. 1975; 56: 429-442Abstract Full Text PDF PubMed Scopus (277) Google Scholar for example, reported positive tests in all their asthmatic subjects. Even so, as reported in this issue of Chest (see page 389) evidence that methacholine testing is not a 100 percent sensitive test for asthma is growing. Chan-Yeung and co-workers5Chan-Yeung M Immunologic and nonimmunologic mechanisms in asthma due to western red cedar (Thuja plicata).J Allergy Clin Immunol. 1982; 70: 32-37Abstract Full Text PDF PubMed Scopus (60) Google Scholar have studied asthmatic workers exposed to western red cedar and discovered that, among 16 workers who left the industry and became asymptomatic, eight lost their hypersensitivity to methacholine. Hargreave and co-workers6Hargreave FE Ramsdale EH Pugsley SO Occupational asthma without bronchial hyperresponsiveness.Am Rev Respir Dis. 1984; 130: 513-515PubMed Google Scholar have reported a worker with asthma secondary to exposure to toluene diisocyanate (TDI) who, after two months off work, became asymptomatic, and lost his reactivity to methacholine. With return to work, his responsiveness returned, weeks after delayed asthmatic attacks recurred. Smith and co-workers7Smith BS Brooks SM Blanchard J Bernstein EL Gallagher J Absence of airway hyperreactivity to methacholine in a worker sensitized to toluene diisocyanate (TDI).J Occup Med. 1980; 22: 327-331Crossref PubMed Scopus (24) Google Scholar reported a similar worker, who had an immediate-type reaction to TDI. Butcher and colleagues,8Butcher BT Jones RN O'Neill CC Glindmeyer HW Diem JE Dharmarajan V et al.Longitudinal study of workers employed in the manufacture of toluene diisocyanate.Am Rev Respir Dis. 1977; 116: 411-421Crossref PubMed Scopus (105) Google Scholar in a publication describing longitudinal study of TDI workers which did not relate testing to current exposures, found three of 11 symptomatic workers did not respond to 25 mg/ml of methacholine. Now the same researchers who have been following the TDI workers have reported a worker who failed to respond to methacholine despite a positive methylene diphenylisocyanate challenge test.9 This worker, too, had sporadic exposure to isocyanates. The likelihood of a positive methacholine test in isocyanate asthma, as the authors conjecture, seems to relate to the intensity and duration of work exposure. Since the precise mechanism by which methacholine produces hyperreactivity is unknown, an explanation of why the test produces variable results in asthmatic workers can only be speculation. Did the described workers receive a sufficient test dose of methacholine? The worker reported by Banks et al inhaled 64 mg/ml of methacholine. Hypersensitivity is generally regarded as a response to less than 8 mg/ml. Can differences in baseline airway caliber or distribution of inhaled methacholine explain the results? Normal pulmonary function prior to methacholine testing and positive specific agent challenges in the reported workers make these explanations unlikely. Do pathologic changes in airway smooth muscle or permeability gradually develop or disappear, depending on work exposures? And does the response to methacholine mirror these changes? Does the type of asthma—immediate, delayed, or dual—reflect the degree of airway injury and likelihood of a positive methacholine test? A longitudinal study, with methacholine testing at frequent intervals and quantification of exposures, is needed to define correlations among worker exposures, symptoms, and methacholine test results. Because methacholine testing has limited application, symptomatic workers who appeal to their employers for protection from exposures or who apply for compensation due to work-related illness should not be arbitrarily dismissed because of a negative methacholine test. Occupational medicine physicians and others who treat or evaluate workers with airways complaints may need to perform specific agent challenges in workers whose exposure history and symptoms suggest the methacholine test is falsely negative.