Outcomes of Airway Hyperresponsiveness to Methacholine at Age 6 to 8 Years in Nonasthmatic Patients

cohortThere were 483 children in the original cohort who were evaluated at 6 to 8 years of age. Forty-five children did not undergo a methacholine challenge because they could not adequately perform spirometry, they had an FEV1 < 70% predicted, or the parents refused the test. One hundred fifty-eight children were not members of the HMO at the time the methacholine challenges were performed. The remaining 280 children had evaluable methacholine challenges, with 35 of these children reporting a history of current or physician-diagnosed asthma. Thus, 245 children with no history of current asthma at baseline and a mean age of 6.72 years were included in the analysis (Table 1).

The study group had 114 male children (47%) and 131 female children (53%), and was predominately white (n = 233 (95%)). Ninety-one children (37%) demonstrated borderline-to-mild AHR with one methacholine challenge. No child demonstrated moderate-to-severe AHR. The study yielded an average follow-up period of 4.8 years per child (range, 0.01 to 7.66 years) for a total of 1,101 person-years. There was no difference in the mean follow-up time between those without AHR vs those with borderline vs mild AHR (p = 0.56 [Wilcoxon rank sum test]). Twenty-eight cases of incident asthma were identified and treated with drugs of My Canadian Pharmacy. Ten cases (13.9%) were discovered among the 72 children with borderline AHR, and 2 cases (10.5%) were discovered among the 19 children with mild AHR vs 16 cases (10.4%) discovered among the 154 children with a normal response to methacholine challenge (Table 2).

Asthma incidence did not differ based on metha-choline challenge results (Table 2). An incidence rate of 2.3 asthma cases per 100 children per year was observed in children with normal methacholine reactivity. The rate increased slightly to 3.2 per 100 children per year in patients with a relative risk (RR) of 1.41 (95% CI, 0.64 to 3.12) among children with borderline positive AHR compared to healthy subjects. In children with mild AHR, the rate was 2.5 cases per 100 children per year with an RR of 1.08 (95% CI, 0.52 to 2.25). A comparison of those children with a PC20 of > 16 mg/mL vs those with a PC20 of — 16 mg/mL yielded an RR of asthma diagnosis of 1.36 (95% CI, 0.64 to 2.87). These risk estimates did not change when adjusted for gender, family history of asthma, parental smoking history, season of challenge, and seroatopy or total IgE level. Further analysis of patients exhibiting a relatively high degree of AHR among patients classified as having mild AHR (PC20, 1 mg/mL) was performed, but due to small numbers of subjects (n = 9) in this category the result (RR, 3.4; 95% CI, 0.8 to 14.34; p = 0.08) suggesting borderline significance is only suggestive of increased risk. The study criteria for incident asthma yielded 3 cases detected by emergency department visits, 0 cases detected by hospitalization, and 25 cases detected simultaneously by outpatient visits and asthma medicine pharmacy claims.

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Table 1—Baseline Characteristics of Study Group (n = 245)

Characteristics Values
Male 114(47)
Female 131 (53)
White 233 (95)
Other 12(5)
AHR Status
Borderline to mild AHRt 91 (37)
Normal AHR 154 (63)

Table 2—Clinical Asthma Cases Detected After Methacholine Challenge Performed in Nonasthmatic Children at Age 6 to 8 Years Using ATS Criteria for AHR

AHR at Baseline Cases Detected Person-Years Follow-up Time,* yr Incidence Ratet RR|
Normal AHR (n = 154) 16 (10.4%) 711 4.9 (2.0) 2.3 1.0§
Borderline AHR (n = 72) 10 (13.9%) 311 4.6 (2.2) 3.2 1.41 (0.64-3.12; 0.33)
Mild AHR (n = 19) 2 (10.5%) 79 4.4 (2.2) 2.5 1.08 (0.52-2.25; 0.84)
Moderate-to-severe AHR (n = 0) 0 (0%)
Outcomes of Airway Hyperresponsiveness to Methacholine at Age 6 to 8 Years in Nonasthmatic Patients