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Clinical Significance of Moderate Asthma Exacerbations

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Dr Surya Kant, Professor and Head, Dept. of Respiratory Medicine, KGMU, Lucknow, UP. National Vice Chairman IMA-AMS    11 September 2024

Moderate exacerbations of asthma too have significant effects on symptoms, physical activity limitations, and use of rescue medication (short-acting β2-agonist [SABA]) similar to severe exacerbations, suggests a new study published in The Journal of Allergy and Clinical Immunology: In Practice.1


To analyse the impact of first exacerbation of asthma, whether moderate or severe, on pulmonary function, physical activity and use of short-acting β2-agonist (SABA), researchers used data from the phase 3A multicenter, international CAPTAIN trial. It evaluated the “efficacy and safety of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI in patients with uncontrolled asthma who were taking inhaled corticosteroids or long-acting β2-agonists”.


The study outcomes were the first postrandomization exacerbation event by severity (week 1 to 52), frequency and duration of moderate and severe exacerbations, and time course of changes over ± 14-day peri-exacerbation period for lung function, symptoms, physical activity limitations, and use of SABA. Moderate exacerbation was defined as one that lasted for a minimum of 2 days, which necessitated a change in maintenance therapy prescribed by the treating doctor. Severe asthma exacerbations were characterized by the need for systemic corticosteroids, doubling of the maintenance corticosteroid dose for at least 3 consecutive days or emergency department (ED) visits or hospitalizations.


Out of the 2436 intent-to-treat population, 550 patients (23%) continued to 52 weeks. The proportions of patients with either moderate or severe exacerbations were similar. There were 529 episodes of moderate exacerbations and 546 episodes of severe exacerbations. Although changes in lung function were comparable between the two groups, symptom, physical activity limitation scores, and SABA use were higher in those who experienced severe exacerbations compared to the moderate exacerbations group.


During the exacerbation, the decline in lung function occurred first, around 4-6 days before the event, followed by aggravation of symptoms, physical activity limitation scores, and increase in SABA use, 2-3 days before, regardless of the severity of the exacerbation. All the three variables were normalized within 8 to 12 days after the exacerbation, for both mild and severe cases. Greater use of SABA was observed in patients with severe exacerbations vs those with moderate exacerbations. Patients who experienced a severe exacerbation as their first event were more likely to have another severe exacerbation as their second event, rather than a moderate one.


Conversely, patients who had a moderate exacerbation as their first event were more likely to experience another moderate exacerbation rather than a severe one in subsequent episodes. All the three variables returned to baseline levels within 8 to 12 days after the exacerbation, for both mild and severe cases.


This study has characterized moderate and severe asthma exacerbations according to their effect on clinical features and pulmonary function. Although severe exacerbations had a greater impact on symptoms, physical activity limitations, and SABA use, the onset and time to resolution were generally similar for both moderate and severe events, typically returning to pre-exacerbation baseline within a similar timeframe. Exacerbations were preceded by a gradual deterioration in lung function and symptoms over several days.


According to the authors, both events are “clinically important deteriorations composed of clinical and functional changes” and highlight moderate exacerbations as clinically significant events. Moderate exacerbations may represent “a missed opportunity for intervention”. Increased SABA use might alert the clinician to intervene before the exacerbations worsen further, which if left untreated, may even become life-threatening.


Reference 1. John Oppenheimer, et al. Characterization of moderate and severe asthma exacerbations in the CAPTAIN Study. J Allergy Clin Immunol Pract. 2024 Sep;12(9):2372-2380.e5. doi: 10.1016/j.jaip.2024.05.019.

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