Long-Term Natural History of Severe Asthma Exacerbations and Their Impact on the Disease Course

Rationale: The long-term natural history of asthma in terms of successive severe exacerbations and the influence of each exacerbation on the course of the disease is not well studied. Objectives: To investigate the long-term natural history of asthma among patients who are hospitalized for asthma for the first time in terms of the risk of future severe exacerbations and heterogeneity in this risk across patients. Methods: Using the administrative health databases of British Columbia, Canada (January 1, 1997 to March 31, 2016), we created an incident cohort of patients with at least one asthma exacerbation that required inpatient care. We estimated the 5-year cumulative incidence of severe exacerbations after successive numbers of previous events. We used a joint frailty model to investigate the extent of between-individual variability in exacerbation risk and the associations of each exacerbation with the rate of subsequent events. Analyses were conducted separately for pediatric (<14 years old) and adult (⩾14 years old) patients. Results: Analyses were based on 3,039 pediatric (mean age at baseline, 6.4; 35% female) and 5,442 (mean age at baseline, 50.8; 68% female) adult patients. The 5-year rates of severe exacerbations after the first three events were 0.16, 0.29, and 0.35 for the pediatric group, and 0.14, 0.33, and 0.49 for the adult group. Both groups exhibited substantial variability in patient-specific risks of exacerbation: the mid-95% interval of 5-year risk of experiencing a severe exacerbation ranged from 11% to 24% in pediatric patients and from 8% to 40% in adult patients. After controlling for potential confounders, the first follow-up exacerbation was associated with an increase of 79% (95% confidence interval [CI], 11-189%) in the rate of subsequent events in the pediatric group, whereas this increase was 188% (95% CI, 35-515%) for the adult group. The effects of subsequent exacerbations were not statistically significant. Conclusions: After the first severe exacerbation, the risk of subsequent events is substantially different among patients. The number of previous severe exacerbations carries nuanced prognostic information about future risk. Our results suggest that severe exacerbations in the early course of asthma detrimentally affect the course of the disease and risk of subsequent exacerbations.