Interplay of Type 2 Inflammation, Small Airway Dysfunction, and Patient-Reported Outcomes in Treatment-Naive Uncontrolled Asthma: A Retrospective Primary Care Analysis

BackgroundEffective initial asthma treatment in primary care requires a comprehensive assessment of airway inflammation and lung function impairment, including small airway dysfunction (SAD). We investigated the prevalence of type 2 (T2) inflammation and SAD in treatment-naive patients with uncontrolled asthma who received primary care, and assessed the utility of the Asthma Control Questionnaire-5 (ACQ-5) as a potential indicator of these factors. MethodsThis single-center retrospective study enrolled treatment-naive adults who presented with uncontrolled asthma (ACQ-5 score [&ge;] 1.5) between April 2020 and March 2022. T2 inflammation was assessed using blood eosinophil count (bEOS), fractional exhaled nitric oxide (FeNO), and total immunoglobulin E (IgE) levels. Patients with bEOS [&ge;] 300 cells/L and FeNO [&ge;] 50 ppb were designated "T2-high." SAD was defined as a forced expiratory flow between 25% and 75% of the vital capacity percentage predicted value (FEF25-75%pred) < 65%. ResultsAmong 192 patients, 87% exhibited an elevation in at least one T2 biomarker, with 47% meeting the T2-high criteria. An ACQ-5 score [&ge;] 3.0 significantly predicted T2-high status (odds ratio: 2.62, 95% confidence interval: 1.46-4.69, p = 0.00127). SAD was identified in 52% of patients, with ACQ-5 scores showing a strong negative correlation with FEF25-75%pred ({rho} = -0.583, p < 0.0001), particularly for nocturnal awakening score ({rho} = -0.728, p < 0.0001). ConclusionsOur findings revealed a high prevalence of T2 inflammation and SAD in treatment-naive patients with uncontrolled asthma who received primary care. The ACQ-5 demonstrates potential as a practical screening tool for these pathophysiological features, offering valuable guidance for initial treatment decisions where advanced diagnostic capabilities may be limited. Data availability statementData are available upon reasonable request. The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed in accordance with the Creative Commons Attribution Noncommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work noncommercially, and license their derivative works on different terms, provided that the original work is properly cited, appropriate credit is given, any changes are indicated, and the use is noncommercial. See: http://creativecommons.org/licenses/by-nc/4.0/. https://doi.org/10.5061/dryad.j6q573np9 What is already known on this topicDespite therapeutic advances, optimal asthma control remains elusive in many adult patients, particularly in primary care settings, where most treatments occur. Our understanding of type 2 inflammation and small airway dysfunction in treatment-naive patients with uncontrolled asthma remains limited. This knowledge gap hinders the development of enhanced management strategies among primary care practitioners. What this study addsThis study revealed high prevalence rates of type 2 inflammation (87%) and small airway dysfunction (52%) in treatment-naive patients with uncontrolled asthma receiving primary care, with 47% showing high-grade type 2 inflammation. An Asthma Control Questionnaire-5 (ACQ-5) score [&ge;] 3.0, predicted high-grade type 2 inflammation, while nocturnal symptoms correlated with small airway dysfunction. How this study might affect research, practice, or policyThese findings underscore the importance of considering type 2 inflammation and small airway dysfunction when initiating asthma treatment in primary care. ACQ-5 could serve as a practical tool for more targeted treatment decisions, while future research should focus on developing primary care-specific algorithms that combine ACQ-5 scores with biomarker profiles.