Gregory G. King

Asthma is a heterogeneous syndrome featuring variable pathophysiology, clinical presentation and treatment response. This review examines a comprehensive endotype‐phenotype framework for asthma assessment with an emphasis on characteristics beyond T2 inflammatory status alone. Endo‐phenotype assessment can be performed across three domains: clinical (symptoms, exacerbations, co‐morbidities), structural and physiological, and inflammatory endotype. The clinical domain includes mucus hypersecretion, perception of airway narrowing, and obesity‐related asthma. Airway remodelling is the central, structural endo‐phenotype that defines asthma, given its relationship with fixed airflow limitation, airway hyperresponsiveness, small airway dysfunction, lung function decline, and asthma severity. However, it is the most difficult parameter to measure, and it is increasingly recognised that there is a critical need to be able to measure it longitudinally, beyond bronchial biopsy. Finally, T2‐high asthma is relatively well characterised with several effective anti‐inflammatory therapies available, including a range of biologics. In contrast, T2‐low asthma remains a heterogenous and potentially difficult to characterise endo‐phenotype, although some treatment studies have demonstrated benefit when subjects have been appropriately characterised and selected. Emerging multi‐omic approaches may enhance the detailed characterisation of patients in future. Adopting an endo‐phenotype framework allows clinicians and researchers to confront the complexity of asthma, better manage patients with a precision medicine approach and enhance mechanistic understanding, which is critical for new therapeutics to be developed for asthma.

Rationale: Strategies for asthma management need better tools to identify risk of exacerbations. In this prospective observational study, we investigated day-to-day variability of lung mechanics, measured using home telemonitored oscillometry, by examining relationships between current symptom control and future risk of exacerbation in asthma patients taking medium-/high-dose treatment, regardless of their level of asthma control. Methods: Participants underwent ≥24 weeks of telemonitoring during stable or stepped-down treatment, with once-daily self-recording of symptoms, and oscillometry (Resmon Pro Diary, Restech Srl, Milan, Italy). The 5-item Asthma Control Questionnaire and exacerbations were captured via weekly telephone calls. Mean inspiratory resistance and reactance at 5 Hz (R _insp and X _insp ), and their standard deviation and coefficient of variation over 7-day windows, were calculated; their associations with current symptom control were examined using linear mixed modelling, and their capacity to predict exacerbations in the following week was examined using logistic regression and receiver-operator characteristic (ROC) analysis, and conditional probability methods. Results: Data from 30 participants were analysed (19 female; mean± sd age 59±13 years, body mass index 30.1±6.6 kg·m ^-2 , percent predicted forced expiratory volume in 1 s 73.7±25.0), with mean monitoring adherence of 83.9±13.1%, and with 16 exacerbations recorded from 12 participants. Only X _insp was a significant predictor of current symptom control (p<0.001). Coefficient of variation of inspiratory resistance was the most accurate in predicting future exacerbations (area under the ROC curve (AUC)=0.664, p<0.001); accuracy was further enhanced using individual conditional probability (AUC=0.836, p<0.001). Conclusion: This proof-of-concept study shows that daily telemonitoring of oscillometry is useful for assessing current symptom control and future risk of exacerbations in asthma patients taking medium-/high-dose treatment.

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Editorial: Physiological phenotyping in respiratory diseases: New approaches