title: Methacholine challenge testing: improved patient comfort with a 2-tiered protocol.
abstract: BACKGROUND
  The methacholine challenge test (MCT) is a test of bronchial hyperreactivity used as an aid in the diagnosis of asthma. MCT results are reported as the provocation concentration at which the forced expiratory volume in 1 second (FEV1) decreases 20% (PC20). The requirement for a 20% or greater decrease in FEV1 results in precipitous decreases in FEV1 in some patients.
  
  
  OBJECTIVE
  To improve MCT safety without compromising accuracy.
  
  
  METHODS
  We performed a retrospective analysis of 879 consecutive MCTs (derivation cohort). A novel protocol for MCT was developed and validated in a cohort of 564 MCTs performed in a second institution.
  
  
  RESULTS
  In comparison with a PC20 cutoff of less than 8 mg/mL, a provocation concentration at which the FEV1 decreases 10% (PC10) cutoff of 1 mg/mL or less has a sensitivity of 86%, a specificity of 98%, a positive predictive value (PPV) of 97%, and a negative predictive value (NPV) of 91%. We propose a novel 2-tiered protocol for MCT. If the PC10 is 1 mg/mL or less, bronchial hyperreactivity is present; if the PC10 is greater than 1 mg/mL, the test is continued until the provocative concentration is 8 mg/mL or a 20% decrease in FEV1 is achieved. Compared with the standard protocol, the proposed protocol has a sensitivity, specificity, PPV, NPV, and overall accuracy of 100%, 98%, 97.6%, 100%, and 99%, respectively. The modified protocol would have enabled us to avoid 26 of 42 cases (62%) in which a 40% or greater decrease in FEV1 occurred and would save 0.65 dose for every MCT performed. The 2-tiered protocol performed well in the validation cohort; sensitivity, specificity, PPV, NPV, and overall accuracy were 100%, 98%, 87%, 100%, and 98%, respectively.
  
  
  CONCLUSIONS
  The proposed 2-tiered protocol is accurate, saves time, and avoids precipitous decreases in FEV1.
authors.affiliation: Pulmonary Institute, Chaim Sheba Medical Center, Tel Hashomer, Israel. Michael.Segel@gmail.com
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Segel
authors.forename: Einat
authors.initials: E
authors.lastname: Rabinovich
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Schwarz
authors.forename: Issahar
authors.initials: I
authors.lastname: Ben-Dov
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000175:diagnosis / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000175:diagnosis / Q000503:physiopathology; D001985:Bronchial Provocation Tests / Q000009:adverse effects / Q000592:standards; D016085:Bronchoconstrictor Agents; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D015203:Reproducibility of Results; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride