title: Diagnosing asthma in general practice with portable exhaled nitric oxide measurement--results of a prospective diagnostic study: FENO < or = 16 ppb better than FENO < or =12 ppb to rule out mild and moderate to severe asthma [added].
abstract: BACKGROUND
  To evaluate the sensitivity, specificity and predictive values of fractional exhaled nitric oxide (FENO) for the diagnosis of asthma in general practice.
  
  
  METHODS
  Prospective diagnostic study with 160 patients attending 10 general practices for the first time with complaints suspicious of obstructive airway disease (OAD). Patients were referred to a lung function laboratory for diagnostic investigation. The index test was FENO measured with a portable FENO analyser based on electrochemical sensor. The reference standard was the Tiffeneau ratio (FEV1/VC) as received by spirometric manoeuvre and/or results of bronchial provocation. Bronchial provocation with methacholine was performed to determine bronchial hyper-responsiveness (BHR) in the event of inconclusive spirometric results.
  
  
  RESULTS
  88 (55%) were female; their average age was 43.9 years. 75 (46.9%) patients had asthma, 25 (15.6%) had COPD, 8 (5.0%) had an overlap of COPD and asthma, and 52 (32.5%) had no OAD. At a cut-off level of 46 parts per billion (ppb) (n = 30; 18.8%), sensitivity was 32% (95%CI 23-43%), specificity 93% (95%CI 85-97%), positive predictive value (PPV) 80% (95%CI 63-91%), negative predictive value (NPV) 61% (95%CI 52-69%) when compared with a 20% fall in FEV1 from the baseline value (PC20) after inhaling methacholine concentration <or= 16 mg/ml. At 76 ppb (n = 11; 6.9%) specificity was 100% (95%CI 96-100%) and PPV was 100% (95%CI 72-100). At a cut-off level of 16 ppb (n = 68; 42.5%), sensitivity was 79% (95%CI 67-88), specificity 55% (95%CI 45-64), PPV 50% (95%CI 40-60), NPV 82% (95%CI 72-90 [corrected] when compared with a 20% fall of FEV1 after inhaling methacholine concentration <or= 4 mg/ml. Two [corrected] patients with unsuspicious spirometric results have to be tested with FENO to save one bronchial provocation test.
  
  
  CONCLUSIONS
  Asthma could be ruled in with FENO > 46 ppb. Mild and moderate to severe asthma could be ruled out with FENO <or= 16 ppb [corrected]. FENO measurement with an electrochemical sensor might be reasonable with respect to the time consuming procedure of bronchial provocation, which carries also some risk of severe bronchospasm. Further research is necessary to evaluate the effectiveness of this dual diagnostic strategy. The number needed to diagnose might be improved when the diagnostic precision could be enhanced by future technical developments.
authors.affiliation: Department of General Practice and Health Services Research, University Hospital, University of Heidelberg, Heidelberg, Germany. antonius.schneider@med.uni-heidelberg.de
authors.forename: Antonius
authors.initials: A
authors.lastname: Schneider
authors.forename: Lisa
authors.initials: L
authors.lastname: Tilemann
authors.forename: Tjard
authors.initials: T
authors.lastname: Schermer
authors.forename: Lena
authors.initials: L
authors.lastname: Gindner
authors.forename: Gunter
authors.initials: G
authors.lastname: Laux
authors.forename: Joachim
authors.initials: J
authors.lastname: Szecsenyi
authors.forename: Franz Joachim
authors.initials: FJ
authors.lastname: Meyer
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000175:diagnosis* / Q000378:metabolism / Q000503:physiopathology; D001944:Breath Tests / Q000295:instrumentation*; D016535:Bronchial Hyperreactivity; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents; D055664:Electrochemical Techniques / Q000295:instrumentation; D004867:Equipment Design; D045853:Exhalation; D005194:Family Practice; D005260:Female; D005541:Forced Expiratory Volume; D005858:Germany; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D009426:Netherlands; D009569:Nitric Oxide / Q000032:analysis*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D014797:Vital Capacity; D055815:Young Adult
chemical_list: D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D009569:Nitric Oxide