Symptom-pattern phenotype and pulmonary function in preschool wheezers

Abstract

Pulmonary function in preschool wheezing phenotypes based on wheeze onset and duration and atopic status has been extensively described but has not been studied in symptom-pattern phenotypes of episodic (viral) and multiple-trigger wheeze. We investigated whether multiple-trigger wheezers were more likely to have abnormal pulmonary function and increased fraction of exhaled nitric oxide (FeNO) than episodic (viral) wheezers and whether multiple-breath wash-out was more sensitive at detecting abnormal pulmonary function than specific airways resistance (sR(aw)) in preschool wheezers. FeNO, multiple-breath wash-out indices (lung clearance index [LCI] and conductive airways ventilation inhomogeneity [S(cond)]) and sR(aw) were measured in healthy children and those with recurrent wheeze aged 4 to 6 years. Subgroup analysis was performed according to current symptom-pattern (multiple-trigger vs episodic [viral]), atopic status (atopic vs nonatopic), and wheeze status (currently symptomatic vs asymptomatic). Seventy-two control subjects and 62 wheezers were tested. Multiple-trigger wheezers were associated with an average increase of 11% (95% CI, 7% to 18%; P < .001) in LCI, 211% (95% CI, 70% to 470%; P < .001) in S(cond), and 15% (95% CI, 3% to 28%; P = .01) in sR(aw) compared with episodic (viral) wheezers. Pulmonary function in episodic (viral) wheezers did not differ significantly from control subjects. The presence of current atopy or wheeze was associated with higher FeNO (P = .05) but did not influence pulmonary function significantly. On average, LCI was abnormal in 39% (95% CI, 32% to 45%), S(cond) was abnormal in 68% (95% CI, 61% to 74%), and sR(aw) was abnormal in 26% (95% CI, 16% to 35%) of multiple-trigger wheezers. Multiple-trigger wheeze is associated with pulmonary function abnormalities independent of atopic and current wheeze status. S(cond) is the most sensitive indicator of abnormal pulmonary function in preschool wheezers.