Evaluation of Clinically and Physiologically Atypical Asthma: If It Doesn’t Wheeze It May Still Be Asthma

Abstract

Investigators in this study (1) evaluated the relationship between the lack of clinical wheeze and lack of wheeze during positive bronchial challenge testing (BCT) in children suspected of having asthma and (2) evaluated the diagnostic value of provocation concentration respiratory rate (PCRR), oxygen saturation (PCO2-SAT), and wheezing (PCwheeze) and whether the value of these measures was influenced by age.Participants (n = 724) were recruited from children ages 3 months to 18 years without a diagnosis of asthma or conditions causing bronchial hyperresponsiveness or obstruction who were referred for possible asthma from 2009 to 2016.BCT was performed with methacholine (sensitive) to distinguish presence or absence of asthma or adenosine (specific) to distinguish asthma from other conditions. A positive BCT result was determined by the provocation concentration that resulted in a 20% decrease in forced expiratory volume in 1 second in children able to perform spirometry (group B) or a 50% increase in respiratory rate, a 5% decrease in oxygen saturation, or appearance of wheezing in those unable to perform spirometry (group A).BCT results were positive for 507 out of 724 children; 89 (17.6%) in group A (median age: 3 [interquartile range: 2.5–3.7] years) were unable to perform spirometry, and 418 (82.4%) in group B (median age: 10.7 [interquartile range: 6.8–15.6] years) were able to perform spirometry. Children without physician-documented wheeze in the whole population (groups A plus B) were more likely (65.5%) to have a positive BCT result without wheeze compared with those with physician-documented wheeze (41.0%, P < .001). In group A, adding PCRR and PCO2-SAT increased BCT sensitivity by 23.6%.Many children in both groups did not wheeze despite reaching BCT endpoints. Most children without physician-documented wheeze did not wheeze on BCT. In young children, adding PCRR and PCO2-SAT substantially increased BCT sensitivity.By documenting the possibility of absent wheezing during bronchial hyperresponsiveness diagnosed by positive BCT results, researchers in this study demonstrated that the presence of wheezing is not essential for a diagnosis of asthma. Inclusion of tachypnea and decreased oxygen saturation improved the sensitivity of asthma diagnosis in children too young to perform spirometry. Corresponding changes in specificity were not described, and the relative benefits of a sensitive or specific asthma definition in young children should be considered, depending on the circumstances. In children able to perform spirometry, a 20% decrease in forced expiratory volume in 1 second remained the more-sensitive measure. The combination of different BCT methods was a possible study limitation, despite similarities of the outcomes.