Background: Omalizumab and Mepolizumab are biologic drugs with proven efficacy in clinical trials. However, a better understanding of their real‐world effectiveness in severe asthma management is needed.Objectives: To better understand the real‐world effectiveness of Omalizumab and Mepolizumab, elucidate the clinical phenotypes of patients treated with these drugs, identify baseline characteristics associated with biologic response and assess the spectrum of responses to these medications.Methods: Using real‐world clinical data, we retrospectively phenotyped biologic naïve patients from the Wessex AsThma CoHort of difficult asthma (N = 478) commenced on Omalizumab (N = 105) or Mepolizumab (N = 62) compared to severe asthma patients not receiving biologics (SNB, N = 178). We also assessed multiple clinical endpoints and identified features associated with response.Results: Compared to SNB, Omalizumab patients were younger, diagnosed with asthma earlier, and more likely to have rhinitis. Conversely, compared to SNB, Mepolizumab patients were predominantly older males, diagnosed with asthma later, and more likely to have nasal polyposis but less dysfunctional breathing. Both treatments reduced exacerbations, Acute Healthcare Encounters [AHE] (emergency department or hospital admissions), maintenance oral corticosteroid dose, and improved Asthma Control Questionnaire 6 (ACQ6) scores. Omalizumab response was independently associated with more baseline exacerbations (p = .024) but fewer AHE (p = .050) and absence of anxiety (p = .008). Lower baseline ACQ6 was independently associated with Mepolizumab response (p = .007). A composite group of non‐responders demonstrated significantly more psychopathologies and worse baseline subjective disease compared to responder groups.Conclusions and Clinical Relevance: In a difficult asthma cohort, Omalizumab and Mepolizumab were used in distinct clinical phenotypes but were both multidimensionally efficacious. Certain baseline clinical characteristics were associated with poorer biologic responses, such as psychological co‐morbidity, which may assist clinicians in biologic selection. These characteristics also emphasize the need for comprehensive approaches to support these patients.

Background: Blood eosinophil measurement is essential for the phenotypic characterization of patients with difficult asthma and in determining eligibility for anti‐IL‐5/IL‐5Rα biological therapies. However, assessing such measures over limited time spans may not reveal the true underlying eosinophilic phenotype, as treatment, including daily oral corticosteroid therapy, suppresses eosinophilic inflammation and asthma is intrinsically variable.Methods: We interrogated the electronic healthcare records of patients in the Wessex AsThma CoHort of difficult asthma (WATCH) study (UK). In 501 patients being evaluated in this tertiary care centre for difficult to control asthma, all requested full blood count test results in a 10‐year retrospective period from the index WATCH assessment were investigated (n = 11,176).Results: In 235 biological therapy‐naïve participants who had 10 or more measures in this time period, 40.3% were eosinophilic (blood eosinophils ≥300 cells/µl) at WATCH enrolment whilst an additional 43.1%, though not eosinophilic at enrolment, demonstrated eosinophilia at least once in the preceding decade. Persistent eosinophilia was associated with worse post‐bronchodilator airway obstruction and higher Fractional exhaled Nitric Oxide (FeNO). In contrast, the 16.6% of patients who never demonstrated eosinophilia at this blood eosinophil threshold showed preserved lung function and lower markers of Type 2 inflammation.Conclusions: This highlights the central role that type 2 inflammation, as indicated by blood eosinophilia, has in difficult asthma and suggests that longitudinal electronic healthcare record analysis can be an important tool in clinical asthma phenotyping, providing insight that may help understand disease progression and better guide more specific treatment approaches.

Air pollution is associated with poor asthma outcomes. High-efficiency particulate air air purifiers may reduce air pollution and thus improve asthma outcomes. However, the efficacy of such devices for this purpose remains inconclusive. To investigate the effects of reducing the levels of pollutants on asthma outcomes in adults, using a novel Dyson high-efficiency particulate air air purifier. In a single-center, double-blinded, randomized controlled trial, participants (N = 50) were randomized at a 1:1 ratio to active filters (intervention) or to dummy filters (placebo) for a total of 78 weeks. The primary outcomes were the changes in Asthma Control Questionnaire 6 (ACQ6) and Asthma-specific Quality of Life Questionnaire (AQLQ) scores from baseline. The secondary outcomes were changes in indoor air pollution and lung function measurements. The coronavirus disease 2019 pandemic limited spirometry measurements to 2 time points and assessment of fractional exhaled nitric oxide and bronchial hyperresponsiveness to baseline only. Air pollutant levels were significantly lower in the intervention group compared with the placebo group (P = .0003). Both groups had a significant improvement in their ACQ6 and AQLQ. However, there were no significant between-group differences in ACQ6, AQLQ, or spirometry, compared with baseline in multivariable repeated measures models. The Dyson air purifier significantly improved air quality. However, there were no significant improvements in asthma control, quality of life, or measures of lung function in the intervention group compared with the control group despite improvements in indoor air quality. Larger, extended studies are required to confirm or refute these findings, especially given that the coronavirus disease 2019 pandemic prevented the procurement of detailed objective data. ClinicalTrials.gov identifier: NCT04729530; ttps://clinicaltrials.gov/ct2/show/NCT04729530.

Difficult asthma describes asthma in which comorbidities, inadequate treatment, suboptimal inhaler technique and/or poor adherence impede good asthma control. The association of anxiety and depression with difficult asthma outcomes (exacerbations, hospital admissions, asthma control, etc.) is unclear. This study assessed the clinical associations of anxiety and depression with difficult asthma outcomes in patients with a specialist diagnosis of difficult asthma. Using real-world data, we retrospectively phenotyped patients from the Wessex Asthma Cohort of Difficult Asthma (N = 441) using clinical diagnoses of anxiety and depression against those without anxiety or depression (controls). Additionally, we stratified patients by severity of psychological distress using the Hospital Anxiety and Depression Scale (HADS). We found that depression and/or anxiety were reported in 43.1% of subjects and were associated with worse disease-related questionnaire scores. Each psychological comorbidity group showed differential associations with difficult asthma outcomes. Anxiety alone (7.9%) was associated with dysfunctional breathing and more hospitalisations [anxiety, median (IQR): 0 (2) vs. controls: 0 (0)], while depression alone (11.6%) was associated with obesity and obstructive sleep apnoea. The dual anxiety and depression group (23.6%) displayed multimorbidity, worse asthma outcomes, female predominance and earlier asthma onset. Worse HADS-A scores in patients with anxiety were associated with worse subjective outcomes (questionnaire scores), while worse HADS-D scores in patients with depression were associated with worse objective (ICU admissions and maintenance oral corticosteroid requirements) and subjective outcomes. In conclusion, anxiety and depression are common in difficult asthma but exert differential detrimental effects. Difficult asthma patients with dual anxiety and depression experience worse asthma outcomes alongside worse measures of psychological distress. There is a severity-gradient association of HADS scores with worse difficult asthma outcomes. Collectively, our findings highlight the need for holistic, multidisciplinary approaches that promote early identification and management of anxiety and depression in difficult asthma patients.

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