Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Apr;33(4):e13767.
doi: 10.1111/pai.13767.

Wheeze is an unreliable endpoint for bronchial methacholine challenges in preschool children

Lora Stewart  1 , Naomi Miyazawa  1   2 , Ronina Covar  1   2 , Christopher Mjaanes  1 , Reed Shimamoto  1 , Melanie Gleason  1   2 , Diego Peroni  3 , Joseph D Spahn  1   2 , Pasquale Comberiati  3
Affiliations

Wheeze is an unreliable endpoint for bronchial methacholine challenges in preschool children

Lora Stewart et al. Pediatr Allergy Immunol. 2022 Apr.

Abstract

Background: Onset of wheeze is the endpoint often used in the determination of a positive bronchial challenge test (BCT) in young children who cannot perform spirometry. We sought to assess several clinical endpoints at the time of a positive BCT in young children with recurrent wheeze compared to findings in school-aged children with asthma.

Methods: Positive BCT was defined in: (1) preschool children (n = 22) as either persistent cough, wheeze, fall in oxygen saturation (SpO2 ) of ≥5%, or ≥50% increase in respiratory rate (RR) from baseline; and (2) school-aged children (n = 22) as the concentration of methacholine (MCh) required to elicit a 20% decline in FEV1 (PC20 ).

Results: All preschool children (mean age 3.4 years) had a positive BCT (median provocative MCh concentration 1.25 mg/ml [IQR, 0.62, 1.25]). Twenty (91%) school-aged children (mean age 11.3 years) had a positive BCT (median PC20 1.25 mg/ml [IQR, 0.55, 2.5]). At the time of the positive BCT, the mean fall in SpO2 (6.9% vs. 3.8%; p = .001) and the mean % increase in RR (61% vs. 22%; p < .001) were greater among preschool-aged than among school-aged children. A minority of children developed wheeze at time of positive BCT (23% preschool- vs. 15% school-aged children; p = .5).

Conclusions: The use of wheeze as an endpoint for BCT in preschool children is unreliable, as it rarely occurs. The use of clinical endpoints, such as ≥25% increase in RR or fall in SpO2 of ≥3%, captured all of our positive BCT in preschool children, while minimizing undue respiratory distress.

Keywords: asthma; bronchial hyper-responsiveness; lung function; methacholine challenge; preschool children; spirometry; wheezing.

PubMed Disclaimer

Conflict of interest statement

Dr Spahn is currently employed by AstraZeneca. This study was designed, implemented, funded, and written before his employment with AstraZeneca. AstraZeneca had no involvement in any phase of this study. The remaining authors have no conflict of interest to report.

Figures

FIGURE 1
FIGURE 1
(A) Serial FEV1 values for each school‐aged subject during the methacholine challenge. Open squares represent FEV1 values at each methacholine dose prior to a fall in FEV1 of ≥20%, while closed squares represent the FEV1 values at the time of a positive methacholine challenge. (B) Mean FEV1 values at baseline and at the time of a positive methacholine challenge. Data are presented as mean ± SEM
FIGURE 2
FIGURE 2
Percentage of children remaining in the challenge as the methacholine dose is escalated
FIGURE 3
FIGURE 3
Change in SpO2 from baseline with increasing doses of methacholine in preschool (A) and school‐aged (B) children. Open circles and squares represent the SpO2 values of each child at methacholine doses prior to the development of a positive response, while closed circles (preschool‐aged children) and closed squares (school‐aged children) represent SpO2 values of each child at the time of a positive methacholine challenge. Dashed blue lines represent the mean SpO2 values at each dose of methacholine in children who did not develop a positive reaction, while the solid red lines represent the mean SpO2 values at each concentration of methacholine where children developed a positive response to methacholine challenge
See this image and copyright information in PMC

References

    1. Martinez FD, Wright AL, Taussig LM, et al. Asthma and wheezing in the first six years of life. N Engl J Med. 1995;332:133‐138. - PubMed
    1. Illi S, Von Mutius E, Niggemann B, Gruber C, Wahn U, on behalf of the Multicentre Allergy Study . Perennial allergen sensitization early in life and chronic asthma in children: a birth cohort study. Lancet. 2006;368:763‐770. - PubMed
    1. Spahn JD, Covar R. Clinical assessment of asthma progression in children and adults. J Allergy Clin Immunol. 2008;121:548‐557. - PubMed
    1. Palmer LJ, Rye PJ, Gibson NA, Burton PR, Landau LI, LeSouef PN. Airways responsiveness in early infancy predicts asthma, lung function and respiratory symptoms of school age. Am J Respir Crit Care Med. 2001;163:37‐42. - PubMed
    1. Avital A, Noviski N, Bar‐Yishay E, Springer C, Levy M, Godfrey S. Nonspecific bronchial reactivity in asthmatic children depends on severity but not on age. Am Rev Respir Dis. 1991;144:36‐38. - PubMed

Publication types

Substances