Specific Patient Profiles Face Up to 30% Risk of Severe Asthma Progression

Identifying Asthma's Trajectory: Pinpointing Risk for Disease Progression

Asthma affects millions globally, and while many patients with mild-to-moderate disease achieve control, a subset progresses to a severe form characterized by persistent symptoms and frequent exacerbations [1, 2, 3]. This severe phenotype, which often requires high-dose inhaled corticosteroids (ICS) or systemic corticosteroids, imposes a significant burden on patients and healthcare systems [1]. A critical, yet poorly understood, clinical question is what drives this progression, particularly after a patient's first significant exacerbation, an event that may signal a turning point in the disease course [4, 5]. A recent large-scale observational study provides new data to help clinicians identify which patients are most likely to follow this adverse trajectory.

Study Design and Patient Cohort

To delineate the path from mild-to-moderate to severe asthma, investigators performed an observational cohort study using the NORdic Dataset for aSThmA Research (NORDSTAR) platform. The study identified adult patients with mild-to-moderate asthma who experienced their first exacerbation between 2000 and 2018. This cohort was then followed prospectively for five years to track the development of severe asthma, which was defined according to the rigorous European Respiratory Society/American Thoracic Society (ERS/ATS) guidelines. To isolate the most influential predictors of disease progression, the researchers analyzed baseline characteristics using multivariable logistic regression models, a statistical method that assesses the independent contribution of multiple potential risk factors simultaneously. This approach allowed them to not only calculate overall risk but also to construct specific high-risk patient profiles based on real-world clinical data.

Overall Progression Rates and Key Risk Factors

Among the 99,748 patients followed, the study found that the overall five-year risk of progressing to severe asthma after a first exacerbation was relatively low, at 4.1%. However, this aggregate figure conceals specific, potent risk factors that substantially elevate an individual's risk. The analysis revealed that an exacerbation occurring despite treatment with medium-dose ICS was the strongest predictor of progression (OR: 3.72; 95% CI: 3.39, 4.09), suggesting a more aggressive or treatment-refractory disease process. Other significant factors included a baseline blood eosinophil count ≥ 0.6 × 10^9/L (OR: 1.97; 95% CI: 1.47-2.61), a key marker of Type 2 inflammation. High use of short-acting beta agonists, a clinical indicator of poor underlying symptom control, was also associated with an increased risk of progression (OR: 1.76; 95% CI: 1.64, 1.90). Additionally, patients aged 40-49 years (OR: 1.62; 95% CI: 1.49, 1.77) and those with a history of two or more respiratory infections (OR: 1.61; 95% CI: 1.49-1.73) were more likely to develop severe disease.

Identifying High-Risk Patient Profiles

The study's primary clinical value lies in its ability to move beyond population averages and identify specific combinations of factors that create a high-risk phenotype. While the overall progression rate was low, the authors demonstrated that certain patient profiles face a dramatically higher likelihood of deterioration. For instance, the researchers constructed a profile of a 40 to 49-year-old patient with late-onset, eosinophilic asthma who experiences recurrent respiratory infections and has an exacerbation while already on medium-dose ICS. This specific combination of factors resulted in a 30.4% five-year risk of progressing to severe asthma. The identification of such high-risk profiles provides clinicians with a practical tool for risk stratification in the clinic. Recognizing these patients after a first exacerbation could prompt a more aggressive management strategy, including closer follow-up, optimization of therapy, or earlier referral to a specialist, with the goal of modifying their disease trajectory.

References

1. Chung KF, Wenzel SE, Brożek J, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. European Respiratory Journal. 2013. doi:10.1183/09031936.00202013

2. Zhou C, Shuai L, Hu H, et al. Applications of machine learning approaches for pediatric asthma exacerbation management: a systematic review.. BMC medical informatics and decision making. 2025. doi:10.1186/s12911-025-02990-0

3. Tadesse DB, Negash M, Kiros KG, et al. Uncontrolled asthma in Ethiopia: a systematic review and meta-analysis.. Advances in respiratory medicine. 2020. doi:10.5603/ARM.a2020.0162

4. Yamasaki A, Tomita K, Inui G, Okazaki R, Harada T. Differences in the effectiveness of single, dual, and triple inhaled corticosteroid therapy for reducing future risk of severe asthma exacerbation: A systematic review and network meta-analysis.. Heliyon. 2024. doi:10.1016/j.heliyon.2024.e31186

5. Noble JH, Warhurst S, Cullen R, et al. The Dose-Response of Inhaled Corticosteroids in Combination Inhaled Corticosteroid/Long Acting Beta₂-Agonist Maintenance Therapy for Asthma: A Systematic Review and Meta-Analysis.. Chest. 2025. doi:10.1016/j.chest.2025.08.014