Bronchodilator Dose Responsiveness in Children and Adolescents: Clinical Features and Association with Future Asthma Exacerbations

• Authors: Jocelyn Grunwell, Emory University; Kristopher M Nguyen, Emory University; Anne Fitzpatrick, Emory University; Alice C Bruce, Emory University
• Journal Title: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
• Volume: Volume 8, Number 3
• Publisher: ELSEVIER | 2020-03-01, Pages 953-964
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.jaip.2019.09.033
• Subjects: Health Sciences, Public Health; Health Sciences, Health Care Management
• Keywords: Science & Technology; Life Sciences & Biomedicine; Allergy; Immunology; Asthma in children; Exacerbation; Airway physiology; Phenotype; Lung function; Bronchodilator reversibility; Type 2 inflammation; Sensitization; NITRIC-OXIDE LEVELS; QUALITY-OF-LIFE; LUNG-FUNCTION; CHILDHOOD ASTHMA; INDUCED BRONCHOCONSTRICTION; WHEEZING PHENOTYPES; AIRWAY-OBSTRUCTION; REVERSIBILITY; SALMETEROL; PREDICTORS

Abstract

Background: Bronchodilator reversibility measures are often associated with poor asthma outcomes in children. Whether bronchodilator dose responsiveness is similarly useful in children is unclear. Objective: We hypothesized that children and adolescents requiring higher doses of bronchodilator to achieve maximal bronchodilation would have unique risk factors and increased risk of future exacerbation. Methods: Children (6-11 years, N = 299) and adolescents (12-21 years, N = 331) with confirmed asthma underwent clinical phenotyping procedures and a test of maximal bronchodilation with escalating doses of albuterol sulfate up to 720 mcg. Outcome measures were assessed at 12 months and included exacerbations treated with systemic corticosteroids, emergency department (ED) visits, and hospitalizations for asthma. Results: A total of 6.7% of children and 9.3% of adolescents had poor bronchodilator dose responsiveness, defined as attainment of maximal forced expiratory volume in 1 second with 720 mcg albuterol. Risk factors included type 2 inflammation, prior exacerbations, and greater asthma severity; historical pneumonia and tobacco exposure were also risk factors in children. Children and adolescents with poor bronchodilator dose responsiveness did not have increased current symptoms or impaired quality of life, but had approximately 2-fold increased odds of exacerbation or ED visit and approximately 3-fold increased odds of hospitalization by 12 months, independent of airflow obstruction. Conclusions: Bronchodilator dose responsiveness may be useful for phenotyping and may be of utility in practice and future studies focused on asthma outcomes or quantification of treatment responses. In children and adolescents, this phenotype of poor bronchodilator responsiveness may be associated with periods of relatively stable disease yet marked airway constriction in response to triggers, including tobacco smoke, respiratory infections/pneumonia, and aeroallergens.