Effects of Age and Disease Severity on Systemic Corticosteroid Responses in Asthma

Abstract

Rationale: Phenotypic distinctions between severe asthma (SA) and nonsevere asthma (NONSA) may be confounded by differential adherence or incorrect use of corticosteroids.

Objectives: To determine if there are persistent phenotypic distinctions between SA (as defined by 2014 American Thoracic Society/European Respiratory Society guidelines) and NONSA after intramuscular triamcinolone acetonide (TA), and to identify predictors of a corticosteroid response in these populations.

Methods: A total of 526 adults age 18 years and older (315 SA) and 188 children age 6 to less than 18 years (107 SA) in the NHLBI Severe Asthma Research Program III were characterized before and 3 weeks after TA. The primary outcome for corticosteroid response was defined as greater than or equal to 10-point improvement in percent predicted FEV₁.

Measurements and main results: Adult asthma groups exhibited a small but significant mean FEV₁% predicted improvement after TA (SA group mean difference, 3.4%; 95% confidence interval, 2.2-4.7%; P = 0.001), whereas children did not. Adult SA continued to manifest lower FEV₁ and worse asthma control as compared with NONSA after TA. In children, after TA only prebronchodilator FEV₁ distinguished SA from NONSA. A total of 21% of adults with SA and 20% of children with SA achieved greater than or equal to 10% improvement after TA. Baseline bronchodilator response and fractional exhaled nitric oxide had good sensitivity and specificity for predicting response in all groups except children with NONSA.

Conclusions: One in five patients with SA exhibit greater than or equal to 10% improvement in FEV₁ with parenteral corticosteroid. Those likely to respond had greater bronchodilator responsiveness and fractional exhaled nitric oxide levels. In adults, differences in airflow obstruction and symptoms between SA and NONSA persist after parenteral corticosteroids, suggesting a component of corticosteroid nonresponsive pathobiology in adults with SA that may differ in children. Clinical trial registered with www.clinicaltrials.gov (NCT 01606826).

Trial registration: ClinicalTrials.gov NCT01606826.

Keywords: corticosteroid response phenotype; pediatric and adult asthma; severe asthma.

Figure 1.

(A–F) Distribution of intramuscular corticosteroid (triamcinolone) response in the population as quantified by absolute change in prebronchodilator FEV₁% predicted (A), post-bronchodilator FEV₁% predicted (B), Asthma Control Questionnaire-6 (C), fractional exhaled nitric oxide (D), and blood (E) and sputum (F; in adults only) eosinophils, comparing adults and children grouped by severity. Bars are histograms and lines are smooth density lines showing probabilities (area under the curve = 1.0). ACQ = Asthma Control Questionnaire; BD = bronchodilator; Fe_NO = fractional exhaled nitric oxide.

Figure 2.

(A–F) Intramuscular corticosteroid (triamcinolone) response in adult and pediatric participants by prebronchodilator FEV₁% predicted (A), post-bronchodilator FEV₁% predicted (B), Asthma Control Questionnaire-6 (C), fractional exhaled nitric oxide (D), and blood (E) and sputum (F; in adults only) eosinophils. Error bars represent 95% confidence intervals. ***P < 0.001; **P ≥ 0.001 to <0.01; *P ≥ 0.01 to <0.05. ACQ = Asthma Control Questionnaire; BD = bronchodilator; Eos = eosinophils; Fe_NO = fractional exhaled nitric oxide; Peds = pediatric; TA = triamcinolone acetonide.

Figure 3.

The receiver operating characteristic curve to depict sensitivity and specificity for a corticosteroid response (defined as absolute ∆ prebronchodilator FEV₁% predicted of at least 10%) for each of the baseline predictors including Asthma Control Questionnaire-6, age, bronchodilator response, body mass index, blood eosinophils, and fractional exhaled nitric oxide. ACQ = Asthma Control Questionnaire; BD = bronchodilator; BMI = body mass index; Fe_NO = fractional exhaled nitric oxide; ROC = receiver operating characteristic.