A rapid dosimetric methacholine challenge in asthma diagnostics: a clinical study of 230 patients with dyspnoea, wheezing or a cough of unknown cause

J Hedman, T Poussa, M M Nieminen
Respiratory Medicine 1998, 92 (1): 32-9
The rapid methacholine challenge test using a pocket turbine spirometer (Micro Spirometer) and the Spira Elektro 2 dosimeter was performed with 230 consecutive patients who had dyspnoea, wheezing or a prolonged cough of unknown cause. Patients with previous asthma diagnoses as well as those who had used inhaled steroids during the preceding 4 weeks were excluded. Seventy-eight patients (34%) were methacholine positive (PD20FEV1 < or = 6900 micrograms) 47 (60%) of whom had a final diagnosis of American Thoracic Society (ATS) criteria fulfilling bronchial asthma. One hundred and fifty-two patients (66%) were methacholine negative (PD20FEV1 > 6900 micrograms) 14 (9%) of whom had bronchial asthma according to clinical evaluation. Increased bronchial responsiveness was strongly associated with ATS criteria fulfilling asthma (P < 0.0001). When PD20FEV1 was used, 47 (77%) of the asthmatic patients were hyper-responsive (range 40-6900 micrograms) compared to 31 (18%) of the non-asthmatic patients (range 160-6900 micrograms). When using PD15FEV1, 51 (84%) of the asthmatic patients (range 28-6900 micrograms) and 52 (31%) of the non-asthmatic patients (range 100-6900 micrograms) were hyper-responsive. The level of bronchial responsiveness measured by both PD20FEV1 and PD15FEV1 differed significantly between asthmatic and non-asthmatic patients (P < 0.0001). Hyper-responsiveness was associated with an increased daily variation in peak expiratory flow (PEF) (P < 0.0001) and an increased number of blood eosinophils (P < 0.0001). Hyper-responsiveness was also associated with decreased levels of FEV1 and percentages of predicted FEV1 (P = 0.04 and P < 0.0001, respectively). Stepwise logistic regression analysis showed that the number of positive prick results (OR = 1.15, 95% CI 1.01-1.31), blood eosinophils (1.004, 1.00-1.01), level of FEV1 (0.56, 0.36-0.87) and current smoking (2.36, 1.00-5.59) were factors significantly associated with the probability of hyper-responsiveness. Age, gender, atopy, pets and a history of ex-smoking were not significantly associated with hyper-responsiveness, neither in univariate nor in multivariate analyses. The Bayesian analysis was used to investigate the diagnostic value of the rapid methacholine challenge test. A receiver operator characteristic curve demonstrated that PD20FEV1 separated asthmatic and non-asthmatic patients better than PD15FEV1. The best cutoff value of PD20FEV1 was 6000 micrograms, but the difference from 6900 micrograms was minimal. The best results of the test using a PD20FEV1 cutoff point of 6900 micrograms (PPV: 0.80, NPV: 0.79) were obtained when the pre-test probability was 0.48. The interval security of the test was established by a pre-test probability between 0.19 and 0.78. Maximal positive (0.34) and negative (0.31) final gains were achieved when pre-test probabilities were 0.33 and 0.65, respectively. The cutoff level of 150 micrograms gave 100% of specificity and predictive value of a positive test for clinical asthma diagnosis. The Bayesian analysis approach demonstrated that the test is useful in asthma diagnostics if not performed on patients with lowest or highest probabilities of asthma.

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