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Peak flow variability, methacholine responsiveness and atopy as markers for detecting different wheezing phenotypes
R T Stein1, C J Holberg, W J Morgan
1Respiratory Sciences Center, University of Arizona, Tucson 85724, USA.
Insights
Childhood wheezing is diverse. Airway lability and atopy markers identify three phenotypes: transient early, non-atopic, and IgE-associated wheeze/asthma, aiding prognosis and treatment.
Area of Science:
- Pediatric Pulmonology
- Allergy and Immunology
- Respiratory Medicine
Background:
- Childhood wheezing is increasingly recognized as heterogeneous, with varying risk factors and prognoses.
- Identifying distinct wheezing phenotypes is crucial for understanding underlying mechanisms and guiding clinical management.
- Previous studies suggest airway lability and atopy may play roles in differentiating wheezing types.
Purpose of the Study:
- To determine if airway lability and atopy markers can identify distinct wheezing phenotypes in children.
- To investigate the association between wheezing patterns and objective measures of airway function and allergic sensitization.
- To classify childhood wheezing into clinically relevant subgroups based on physiological and immunological parameters.
Main Methods:
- A birth cohort study evaluated peak flow variability (n=600) and methacholine challenge responsiveness (n=397) at age 11.
- Wheezing history was recorded at ages three, six, and 11 years.
- Total serum IgE and skin prick test reactivity to allergens were assessed as markers of atopy.
Main Results:
- Neither peak flow variability nor methacholine hyperresponsiveness at age 11 predicted wheezing solely in the first three years.
- Both measures were associated with wheezing at ages six and 11.
- Non-atopic wheezing up to age six correlated with peak flow variability, while methacholine hyperresponsiveness at age 11 was linked to higher IgE and allergic sensitization, particularly in boys.
Conclusions:
- Three childhood wheezing phenotypes were identified: transient early wheezing, non-atopic wheezing, and IgE-associated wheeze/asthma.
- Transient early wheezing is unrelated to airway lability.
- Non-atopic wheezing is linked to peak flow variability, while IgE-associated wheeze/asthma involves persistent symptoms, airway hyperresponsiveness, and atopy markers.
Background:
There is increasing evidence that wheezing during childhood may be a heterogeneous condition, and that different forms of wheezing may be associated with different risk factors and prognosis. The aim of this study was to determine if measures of airway lability and of atopy could identify distinct wheezing phenotypes during childhood.
Method:
In a cohort of children followed from birth peak flow variability (n = 600) was evaluated and methacholine challenge responsiveness (n = 397) was measured at age 11 in relation to wheezing before the age of three, and at age six and 11 years total serum IgE and skin test reactivity to allergens were determined.
Results:
Neither positive peak flow variability nor methacholine hyperresponsiveness measured at age 11 were associated with wheezing occurring only during the first three years of life. Both methacholine hyperresponsiveness and positive peak flow variability were associated with wheezing at both ages six and 11 (OR 5.1 (95% CI 2.4 to 10.6) and 2.3 (1.2 to 4.5), respectively). In addition, positive peak flow variability was associated with wheezing up to the age of six but not at age 11 in non-atopic children (OR 2.9 (95% CI 1.0 to 8.8)). Methacholine hyperresponsiveness measured at age 11 was more frequently observed in boys (OR 2.1 (95% CI 1.2 to 3.5)) and was strongly associated with serum IgE levels measured at ages six and 11 (p < 0.001) and with positive skin test reactivity (OR 4.5 (95% CI 2.0 to 10.1)). Peak flow variability was unrelated to sex or markers of atopy (IgE and skin test reactivity).
Conclusions:
Methacholine responsiveness and peak flow variability assessed at age 11, together with markers of atopy (IgE and skin test reactivity to allergens) identify three different wheezing phenotypes in childhood: "transient early wheezing" limited to the first three years of life and unrelated to increased airway lability; "non-atopic wheezing" of the toddler and early school years associated with positive peak flow variability but not with methacholine hyperresponsiveness; and "IgE-associated wheeze/asthma" associated with persistent wheezing at any age and with methacholine hyperresponsiveness, peak flow variability, and markers of atopy.