Reproducibility of the airway response to an exercise protocol standardized for intensity, duration, and inspired air conditions, in subjects with symptoms suggestive of asthma

Abstract

Background: Exercise testing to aid diagnosis of exercise-induced bronchoconstriction (EIB) is commonly performed. Reproducibility of the airway response to a standardized exercise protocol has not been reported in subjects being evaluated with mild symptoms suggestive of asthma but without a definite diagnosis. This study examined reproducibility of % fall in FEV1 and area under the FEV1 time curve for 30 minutes in response to two exercise tests performed with the same intensity and duration of exercise, and inspired air conditions.

Methods: Subjects with mild symptoms of asthma exercised twice within approximately 4 days by running for 8 minutes on a motorized treadmill breathing dry air at an intensity to induce a heart rate between 80-90% predicted maximum; reproducibility of the airway response was expressed as the 95% probability interval.

Results: Of 373 subjects challenged twice 161 were positive (≥ 10% fall FEV1 on at least one challenge). The EIB was mild and 77% of subjects had <15% fall on both challenges. Agreement between results was 76.1% with 56.8% (212) negative (< 10% fall FEV1) and 19.3% (72) positive on both challenges. The remaining 23.9% of subjects had only one positive test. The 95% probability interval for reproducibility of the % fall in FEV1 and AUC0-30 min was ± 9.7% and ± 251% for all 278 adults and ± 13.4% and ± 279% for all 95 children. The 95% probability interval for reproducibility of % fall in FEV1 and AUC0-30 min for the 72 subjects with two tests ≥ 10% fall FEV1 was ± 14.6% and ± 373% and for the 34 subjects with two tests ≥ 15% fall FEV1 it was ± 12.2% and ± 411%. Heart rate and estimated ventilation achieved were not significantly different either on the two test days or when one test result was positive and one was negative.

Conclusions: Under standardized, well controlled conditions for exercise challenge, the majority of subjects with mild symptoms of asthma demonstrated agreement in test results. Performing two tests may need to be considered when using exercise to exclude or diagnose EIB, when prescribing prophylactic treatment to prevent EIB and when designing protocols for clinical trials.

Figure 1

Subject Disposition. Reproduced from Respiratory Research 2009, 10:4 (23 January 2009) with the permission of the authors.

Figure 2

Reproducibility of the % fall in FEV₁ and area under the FEV₁ curve following exercise. The difference between values for % fall FEV₁ and AUC_{0-30 min} % fall FEV₁ per min on the two exercise challenges in relation to the average value for the two challenges in adults (a and b) and children (c and d). The interval defines the 95% probability that the difference between a single measurement and the true value for the subject is within that range.

Figure 3

Reproducibility of the % fall in FEV₁ and area under the FEV₁ curve following exercise in subjects positive on both occasions. The difference between values for a) % fall in FEV₁; and b) AUC_{0-30 min} on the two challenges in relation to the average value on the two challenges for those who had a fall in FEV₁ ≥10% on both challenges. The interval defines the 95% probability that the difference between a single measurement and the true value for the subject is within that range.

Figure 4

% fall in FEV₁ in relation to NAEPPII severity score. Individual values for the maximum % fall in FEV₁ after exercise in relation to the NAEPPII severity grading for asthma.

Figure 5

Distribution of the maximum % fall in FEV₁. Distribution of the highest % fall in FEV₁ after exercise challenge in 375 subjects.

Figure 6

% fall in FEV₁ and AUC on the two exercise tests. The mean and standard deviation for:- a) average % fall FEV₁ on exercise; b) average AUC_{0-30 min} FEV₁ in 373 subjects and for 278 adults and 95 children. The groups are:- those negative, <10% fall in FEV₁ after exercise, those negative/positive and positive/negative on the 1^st and 2^nd challenge, and those with two positive challenges, i.e. ≥10% fall in FEV₁.

Figure 7

Distribution of the % of maximum voluntary ventilation during the 6^th minute of exercise. Distribution of the values estimated for percentage of maximum voluntary ventilation during exercise test on the test when the highest fall in FEV₁ was measured.