title: Diagnostic accuracy of methacholine challenge tests assessing airway hyperreactivity in asthmatic patients - a multifunctional approach.
abstract: There are few studies comparing diagnostic accuracy of different lung function parameters evaluating dose-response characteristics of methacholine (MCH) challenge tests (MCT) as quantitative outcome of airway hyperreactivity (AHR) in asthmatic patients. The aim of this retrospectively analysis of our database (Clinic Barmelweid, Switzerland) was, to assess diagnostic accuracy of several lung function parameters quantitating AHR by dose-response characteristics.
  
  
  
  Changes in effective specific airway conductance (sGeff) as estimate of the degree of bronchial obstruction were compared with concomitantly measured forced expiratory volume in 1 s (FEV1) and forced expiratory flows at 50% forced vital capacity (FEF50). According to the GINA Guidelines the patients (n = 484) were classified into asthmatic patients (n = 337) and non-asthmatic subjects (n = 147). Whole-body plethysmography (CareFusion, Würzburg, Germany) was performed using ATS-ERS criteria, and for the MCTs a standardised computer controlled protocol with 3 consecutive cumulative provocation doses (PD1: 0.2 mg; PD2: 1.0 mg; PD3: 2.2 mg) was used. Break off criterion for the MCTs were when a decrease in FEV1of 20% was reached or respiratory symptoms occurred.
  
  
  
  In the assessment of AHR, whole-body plethysmography offers in addition to spirometry indices of airways conductance and thoracic lung volumes, which are incorporated in the parameter sGeff, derived from spontaneous tidal breathing. The cumulative percent dose-responses at each provocation step were at the 1stlevel step (0.2 mg MCH) 3.7 times, at the 2ndlevel step (1 mg MCH) 2.4 times, and at the 3rdlevel step (2.2 mg MCH) 2.0 times more pronounced for sGeff, compared to FEV1. A much better diagnostic odds ratio of sGeff(7.855) over FEV1(6.893) and FEF50(4.001) could be found. Moreover, the so-called dysanapsis, and changes of end-expiratory lung volume were found to be important determinants of AHR.
  
  
  
  Applying plethysmographic tidal breathing analysis in addition to spirometry in MCTs provides relevant advantages. The absence of deep and maximal inhalations and forced expiratory manoeuvres improve the subject's cooperation and coordination, and provide sensitive and differentiated test results, improving diagnostic accuracy. Moreover, by the combined assessment, pulmonary hyperinflation and dysanapsis can be respected in the differentiation between "asthmatics" and "non-asthmatics".
authors.affiliation: Department of Clinical Research, University of Berne, Kirchenfeldstrasse 74, CH-3005, Berne, Switzerland. richard.kraemer@swissonline.ch.
authors.forename: Richard
authors.identifier: 0000-0002-2839-8829
authors.initials: R
authors.lastname: Kraemer
authors.affiliation: Medical Development, Research in Respiratory Diagnostics, Berlin, Germany.
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Smith
authors.affiliation: Division of Pulmonary Medicine, Clinic Barmelweid, CH-5017, Barmelweid, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Sigrist
authors.affiliation: Division of Pulmonary Medicine, Clinic Barmelweid, CH-5017, Barmelweid, Switzerland.
authors.forename: Gabi
authors.initials: G
authors.lastname: Giger
authors.affiliation: Division of Pulmonary Medicine, Clinic Barmelweid, CH-5017, Barmelweid, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: Keller
authors.affiliation: Division of Pulmonary Medicine, Clinic Barmelweid, CH-5017, Barmelweid, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Frey
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D001249:Asthma / Q000175:diagnosis* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000175:diagnosis* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage*; D002648:Child; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D005260:Female; D005540:Forced Expiratory Flow Rates; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage*; D008875:Middle Aged; D010993:Plethysmography, Whole Body; D011237:Predictive Value of Tests; D012372:ROC Curve; D015203:Reproducibility of Results; D012189:Retrospective Studies; D013147:Spirometry; D013557:Switzerland; D055815:Young Adult
chemical_list: D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride
keywords: (1) Airway hyperreactivity; (2) Bronchial asthma; (3) Methacholine challenge test; (4) Whole-body plethysmography; (5) Effective, specific airway conductance; (6) Diagnostic accuracy; (7) Dysanapsis