Biologics (mepolizumab and omalizumab) induced remission in severe asthma patients.

BACKGROUND: Asthma remission has emerged as a potential treatment goal. This study evaluated the effectiveness of two biologics (mepolizumab/omalizumab) in achieving asthma remission. METHODS: This observational study included 453 severe asthma patients (41% male; mean age ± SD 55.7 ± 14.7 years) from two real-world drug registries: the Australian Mepolizumab Registry and the Australian Xolair Registry. The composite outcome clinical remission was defined as zero exacerbations and zero oral corticosteroids during the previous 6 months assessed at 12 months and 5-item Asthma Control Questionnaire (ACQ-5) ≤1 at 12 months. We also assessed clinical remission plus optimization (post-bronchodilator FEV1 ≥80%) or stabilization (post-bronchodilator FEV1 not greater than 5% decline from baseline) of lung function at 12 months. Sensitivity analyses explored various cut-offs of ACQ-5/FEV1 scores. The predictors of clinical remission were identified. RESULTS: 29.3% (73/249) of AMR and 22.8% (37/162) of AXR cohort met the criteria for clinical remission. When lung function criteria were added, the remission rates were reduced to 25.2% and 19.1%, respectively. Sensitivity analyses identified that the remission rate ranged between 18.1% and 34.9% in the AMR cohort and 10.6% and 27.2% in the AXR cohort. Better lung function, lower body mass index, mild disease and absence of comorbidities such as obesity, depression and osteoporosis predicted the odds of achieving clinical remission. CONCLUSION: Biologic treatment with mepolizumab or omalizumab for severe asthma-induced asthma remission in a subgroup of patients. Remission on treatment may be an achievable treatment target and future studies should consider remission as an outcome measure.

Mepolizumab decreases tissue eosinophils while increasing type-2 cytokines in eosinophilic chronic rhinosinusitis.

BACKGROUND: Eosinophilic chronic rhinosinusitis is an often treatment-resistant inflammatory disease mediated by type-2 cytokines, including interleukin (IL)-5. Mepolizumab, a monoclonal antibody drug targeting IL-5, has demonstrated efficacy and safety in inflammatory airway disease, but there is negligible evidence on direct tissue response. The study's aim was to determine the local effect of mepolizumab on inflammatory biomarkers in sinonasal tissue of eosinophilic chronic rhinosinusitis patients. METHODS: Adult patients with eosinophilic chronic rhinosinusitis received 100mg mepolizumab subcutaneously at four-weekly intervals for 24 weeks in this prospective phase 2 clinical trial. Tissue eosinophil counts, eosinophil degranulation (assessed as submucosal eosinophil peroxidase deposition by immunohistochemistry) and cytokine levels (measured in homogenates by immunoassay) were evaluated in ethmoid sinus tissue biopsies collected at baseline and at weeks 4, 8, 16 and 24. RESULTS: Twenty patients (47.7 ± 11.7 years, 50% female) were included. Sinonasal tissue eosinophil counts decreased after 24 weeks of treatment with mepolizumab (101.64 ± 93.80 vs 41.74 ± 53.76 cells per 0.1 mm2 ; p = .035), eosinophil degranulation remained unchanged (5.79 ± 2.08 vs 6.07 ± 1.20, p = .662), and type-2 cytokine levels increased in sinonasal tissue for IL-5 (10.84 ± 18.65 vs 63.98 ± 50.66, p = .001), IL-4 (4.48 ± 3.77 vs 9.38 ± 7.56, p = .004), IL-13 (4.02 ± 2.57 vs 6.46 ± 3.99, p = .024) and GM-CSF (1.51 ± 1.74 vs 4.50 ± 2.97, p = .001). CONCLUSION: Mepolizumab reduced eosinophils in sinonasal tissue, demonstrating that antagonism of IL-5 suppresses eosinophil trafficking. With reduced tissue eosinophils, a local type-2 inflammatory feedback loop may occur. The study exposes mechanistic factors which may explain incomplete treatment response.

Mepolizumab effectiveness and identification of super-responders in severe asthma.

Severe asthma is a high-burden disease. Real-world data on mepolizumab in patients with severe eosinophilic asthma is needed to assess whether the data from randomised controlled trials are applicable in a broader population.The Australian Mepolizumab Registry (AMR) was established with an aim to assess the use, effectiveness and safety of mepolizumab for severe eosinophilic asthma in Australia.Patients (n=309) with severe eosinophilic asthma (median age 60 years, 58% female) commenced mepolizumab. They had poor symptom control (median Asthma Control Questionnaire (ACQ)-5 score of 3.4), frequent exacerbations (median three courses of oral corticosteroids (OCS) in the previous 12 months), and 47% required daily OCS. Median baseline peripheral blood eosinophil level was 590 cells·µL-1 Comorbidities were common: allergic rhinitis 63%, gastro-oesophageal reflux disease 52%, obesity 46%, nasal polyps 34%.Mepolizumab treatment reduced exacerbations requiring OCS compared with the previous year (annualised rate ratio 0.34 (95% CI 0.29-0.41); p<0.001) and hospitalisations (rate ratio 0.46 (95% CI 0.33-0.63); p<0.001). Treatment improved symptom control (median ACQ-5 reduced by 2.0 at 6 months), quality of life and lung function. Higher blood eosinophil levels (p=0.003) and later age of asthma onset (p=0.028) predicted a better ACQ-5 response to mepolizumab, whilst being male (p=0.031) or having body mass index ≥30 (p=0.043) predicted a lesser response. Super-responders (upper 25% of ACQ-5 responders, n=61, 24%) had a higher T2 disease burden and fewer comorbidities at baseline.Mepolizumab therapy effectively reduces the significant and long-standing disease burden faced by patients with severe eosinophilic asthma in a real-world setting.

Effect of monoclonal antibody drug therapy on mucosal biomarkers in airway disease: A systematic review.

BACKGROUND: Monoclonal antibody therapies have a growing role in treating refractory airway disease. OBJECTIVE: The review aimed to summarize the response of respiratory mucosa to monoclonal antibody treatments in inflammatory airway conditions. DESIGN: We conducted a systematic review including risk of bias assessment. DATA SOURCES: MEDLINE, EMBASE and PubMed from 1 January 2000 to 16 November 2019 were searched. ELIGIBILITY CRITERIA: Eligible studies assessed the immunological and histological response of airway mucosa to monoclonal antibody therapy compared with baseline or a comparison group in patients with respiratory diseases (asthma, chronic rhinosinusitis and allergic rhinitis). Any prospective interventional studies, including randomized controlled trials (RCTs) and single-arm trials, were eligible. RESULTS: There were 4195 articles screened, and full-text analysis produced n = 11 studies with extractable data. Nine were RCTs, and two were single-arm trials. These studies focused on asthma (n = 9 articles), chronic rhinosinusitis (n = 1) and allergic rhinitis (n = 1). Five monoclonal antibody drugs were assessed (omalizumab, mepolizumab, dupilumab, benralizumab and tralokinumab). Risk of bias was low (n = 6) or unclear (n = 3) in the RCTs and moderate in the single-arm trials. Omalizumab reduced the mucosal concentration of its target, IgE. Dupilumab reduced the concentration of one of its targets, IL-13, but not IL-4. Omalizumab, mepolizumab and benralizumab reduced tissue eosinophil cell density. Dupilumab decreased mucosal eosinophil granule proteins. Tralokinumab did not affect airway mucosa. CONCLUSIONS: Knowledge of the expected biological response of monoclonal antibody therapy on biomarkers in disease tissue provides an important supplement to data about clinical outcomes. An understanding of the biological effect is essential to identify likely responders, reasons for treatment failure and necessary adjustments to monoclonal antibody treatment. Further investigation into the effect of monoclonal antibody therapy on disease mucosa and more precise endotyping are required to move closer to achieving personalized medicine.

Work-related asthma: A position paper from the Thoracic Society of Australia and New Zealand and the National Asthma Council Australia.

Work-related asthma (WRA) is one of the most common occupational respiratory conditions, and includes asthma specifically caused by occupational exposures (OA) and asthma that is worsened by conditions at work (WEA). WRA should be considered in all adults with asthma, but especially those with new-onset or difficult to control asthma. Improvement in asthma symptoms when away from work is suggestive of WRA. Clinical history alone is insufficient to diagnose WRA; therefore, objective investigations are required to confirm the presence of asthma and the association of asthma with work activities. Management of WRA requires pharmacotherapy similar to that of non-WRA, however, also needs to take into account control of the causative workplace exposure. Ongoing exposure will likely lead to decline in lung function and worsening asthma control. WRA is a preventable condition but this does rely on increased awareness of WRA and thorough identification and control of all potential occupational respiratory hazards.

Treatable traits can be identified in a severe asthma registry and predict future exacerbations.

BACKGROUND AND OBJECTIVE: A new taxonomic and management approach, termed treatable traits, has been proposed for airway diseases including severe asthma. This study examined whether treatable traits could be identified using registry data and whether particular treatable traits were associated with future exacerbation risk. METHODS: The Australasian Severe Asthma Web-Based Database (SAWD) enrolled 434 participants with severe asthma and a comparison group of 102 participants with non-severe asthma. Published treatable traits were mapped to registry data fields and their prevalence was described. Participants were characterized at baseline and every 6 months for 24 months. RESULTS: In SAWD, 24 treatable traits were identified in three domains: pulmonary, extrapulmonary and behavioural/risk factors. Patients with severe asthma expressed more pulmonary and extrapulmonary treatable traits than non-severe asthma. Allergic sensitization, upper-airway disease, airflow limitation, eosinophilic inflammation and frequent exacerbations were common in severe asthma. Ten traits predicted exacerbation risk; among the strongest were being prone to exacerbations, depression, inhaler device polypharmacy, vocal cord dysfunction and obstructive sleep apnoea. CONCLUSION: Treatable traits can be assessed using a severe asthma registry. In severe asthma, patients express more treatable traits than non-severe asthma. Traits may be associated with future asthma exacerbation risk demonstrating the clinical utility of assessing treatable traits.

Nasal mucosal brushing as a diagnostic method for allergic rhinitis.

Background: Allergen specific immunoglobulin E (spIgE) in the nasal mucosa is a biomarker for local allergic rhinitis. Inferior turbinate tissue biopsy is a sensitive method to detect nasal spIgE but is invasive. Nasal brushing is a relatively noninvasive method to detect nasal spIgE that may be of comparable diagnostic utility. Objective: To assess the performance of nasal brushing to obtain a nasal spIgE sample compared with an inferior turbinate tissue biopsy among patients who underwent turbinate surgery. Methods: A diagnostic cross-sectional study that involved participants who were undergoing turbinate surgery was performed. Nasal brushing, inferior turbinate tissue biopsy, blood collection, and skin-prick test (SPT) were performed perioperatively and tested for house-dust allergens. A receiver operating curve was used to assess the performance of the nasal brushings to obtain nasal spIgE samples compared with the inferior turbinate tissue biopsy. The diagnostic utility of nasal brushings of spIgE compared with serum spIgE testing and SPT was also assessed. Results: A total of 157 patients (41.61 ± 14.83 years; 37.6% women) were included. Nasal brushing was an excellent method to sample for nasal spIgE compared with inferior turbinate tissue biopsy (Area under curve (AUC) 0.87 [95% confidence interval {CI}, 0.81-0.93], p < 0.01). Positive house-dust allergen spIgE results of nasal brushings was defined as > 0.1 kUA/L. Nasal brushings for spIgE sampling was also able to predict the presence of serum spIgE (AUC 0.93 [95% CI, 0.89-0.97], p < 0.01) and SPT (AUC 0.80 [95% CI, 0.72-0.87], p < 0.01). Conclusion: Nasal brushing constituted an easy and relatively noninvasive method to sample nasal epithelium. This sampling technique was comparable with an inferior turbinate tissue biopsy and may be developed as a diagnostic tool for the diagnosis of local allergic rhinitis.

Local specific Immunoglobulin E among patients with nonallergic rhinitis: a systematic review.

BACKGROUND: Allergen specific immunoglobulin can be present in the nasal mucosa of patients with non-allergic rhinitis (NAR). This condition is defined as local allergic rhinitis. However, the reported presence of nasal specific immunoglobulin E (nspIgE) among NAR is variable. The aim of this review was to summarize the studies which reported the presence of nspIgE among patients diagnosed as NAR. METHODS: Embase (1947- ) and Medline (1946-) were searched until 6th June 2017. A search strategy was utilized to identify studies on nspIgE among patients with NAR. The target population was patients with symptoms of rhinitis, but negative systemic allergen sensitization. Studies with original data on detectable nspIgE among the NAR population were included. Meta-analysis of single proportions as a weighted probability %(95%CI) was performed. Heterogeneity was explored amongst studies. RESULTS: A search strategy returned 2286 studies and 21 were included. These studies involved 648 participants with NAR. NspIgE was detected using either; 1. nasal secretions, 2. epithelial mucosa sampling, 3. tissue biopsies or 4. In-situ tests. Metaanalysis was performed on studies with nasal secretions. The weighted proportion of detectable nspIgE in nasal secretions within patients with NAR was 10.2 (7.4-13.4) %. Population definitions partly explained variability. Detection of nspIgE was lower in patients without a history suggestive of allergy compared to those with a positive allergic history (0 (0-3.1) % v 19.8 (14.5-25.6) %, p<0.01). CONCLUSION: NAR with positive allergy history suggests presence of nspIgE. These patients warrant further allergology evaluation to confirm localized nasal allergy, as they benefit from allergy therapy such as immunotherapy.

WITHDRAWN: Topical and systemic antifungal therapy for the symptomatic treatment of chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory disorder of the nose and sinuses. Since fungi were postulated as a potential cause of CRS in the late 1990s, there has been increasing controversy about the use of both topical and systemic antifungal agents in its management. Although interaction between the immune system and fungus has been demonstrated in CRS, this does not necessarily imply that fungi are the cause of CRS or that antifungals will be effective its management. OBJECTIVES: To assess the effectiveness of topical or systemic antifungal therapy in the treatment of CRS. SEARCH METHODS: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 8 March 2011. SELECTION CRITERIA: All randomised, placebo-controlled trials considering the use of topical or systemic antifungal therapy in the treatment of CRS and allergic fungal sinusitis (AFS). CRS was defined using either the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) or American Academy of Otolaryngology - Head and Neck Surgery (AAO-HNS) criteria. DATA COLLECTION AND ANALYSIS: We reviewed the titles and abstracts of all studies obtained from the searches and selected trials that met the eligibility criteria. We extracted data using a pre-determined data extraction form. There was significant heterogeneity of outcome data reporting with reports containing both parametric and non-parametric representations of data for the same outcomes. Means and standard deviations for change data were unavailable for a number of trials. Due to the limited reported data, we contacted authors and used original data for data analysis. MAIN RESULTS: Six studies were included (380 participants). Five studies investigated topical antifungals and one study investigated systemic antifungals. The risk of bias in all included studies was low, with all trials being double-blinded and randomised. Pooled meta-analysis showed no statistically significant benefit of topical or systemic antifungals over placebo for any outcome. Symptom scores in fact statistically favoured the placebo group. Adverse event reporting was statistically significantly higher in the antifungal group. AUTHORS' CONCLUSIONS: On the basis of this meta-analysis, there is no evidence to support the use of either topical or systemic antifungal treatment in the management of CRS.

Microgeographic factors and patterns of aeroallergen sensitisation.

OBJECTIVE: To examine patterns of airborne allergen (aeroallergen) sensitisation in the Greater Sydney area (Sydney), and their relationships with climate, coastal proximity and environment (urban v regional). DESIGN, SETTING, PARTICIPANTS: Retrospective cross-sectional study of patients who underwent aeroallergen skin prick testing at three Sydney allergy clinics, January 2001 - October 2014. MAIN OUTCOME MEASUREMENTS: Proportions of patients sensitised to specific aeroallergen types; relationships between sensitisation patterns and climate and geography. RESULTS: Of 1421 patients who met the selection criteria (mean age, 28.3 years [SD, 21.3]; 53.3% were female), 1092 (76.8%) were sensitised to at least one aeroallergen. Those living less than 15 km from the coast were less commonly sensitised to cockroach (< 15 km, 15.1%; 15-30 km, 40.0%; > 30 km, 39.7%; P < 0.001) and grass aeroallergens (< 15 km, 36.5%; 15-30 km, 52.2%; > 30 km, 58.1%; P < 0.001) than patients further inland; the same applied to mould, weed and tree aeroallergens. Subtropical grass sensitisation was more common in temperate/warm summer climates (about 50%) than in temperate/hot summer (27.1%) or subtropical climates (15%) (P < 0.001), and less common in urban (36.7%) than in regional areas (54%; P = 0.014). 72.4% of grass-sensitised patients were co-sensitised to both temperate and subtropical grasses. A selected ten-aeroallergen skin prick test panel identified 98.5% of atopic patients in this Sydney sample. CONCLUSIONS: Environmental and geographic factors are associated with different patterns of allergic sensitisation in Sydney. Extensive co-sensitisation to subtropical and temperate grasses has implications for immunotherapy in Australia, where most currently available therapies are based on formulations directed at temperate grasses only.

Comparison of Allergen Immunotherapy Alone and in Conjunction With Turbinate Surgery for Nasal Obstruction in Perennial Allergic Rhinitis Patients.

BACKGROUND: Nasal obstruction, triggered by allergic rhinitis, often does not resolve with allergen-specific immunotherapy (AIT) alone, thus inferior turbinate reduction surgery (ITR) may be required. This study aims to investigate the impact of combined treatment on nasal obstruction, as evidence is currently limited. METHODOLOGY/PRINCIPAL: A retrospective cohort study of perennial allergic rhinitis patients experiencing nasal obstruction and undergoing ≥12 months AIT was conducted. Two groups were derived, those undergoing AIT-with or without an ITR. Patient reported nasal obstruction (evaluated with questionnaires) and nasal airway function (Nasal Peak Inspiratory Flow [NPIF] and Nasal Airflow Resistance [NAR]) were monitored. The change from baseline to 12 months post-treatment in each group were compared. RESULTS: A total of 118 patients (33.71 ± 14.43 years, 41.5% female) were recruited, 72% had AIT and 28% AIT&ITR. At baseline, the AIT&ITR group had a higher level of nasal obstruction (>moderate%; 63.6% vs 52.9%, P = .048). Post treatment, AIT&ITR group reported greater reduction in nasal obstruction (>1 category change: 75.8% vs 48.2%, P = .002). Similarly, the AIT&ITR group had greater improvement in nasal function by NPIF (-13.9 ± 110.3 L/minute vs -3.4 ± 78.1 L/minute, P = .049) and NAR (-0.120 ± 0.342 Pa/cm³/second vs -0.093 ± 0.224 Pa/cm³/second, P = .050). CONCLUSIONS: Allergic rhinitis patients, with moderate to severe nasal obstruction, who undergo combined AIT&ITR have greater relief of nasal obstruction and improved airflow analysis compared to AIT alone.

The future of allergic rhinitis management: A partnership between healthcare professionals and patients.

Allergic rhinitis (AR) is a chronic respiratory condition that internationally continues to be burdensome and impacts quality of life. Despite availability of medicines and guidelines for healthcare providers for the optimal management of AR, optimisation of its management in the community continues to be elusive. The reasons for this are multi-faceted and include both environmental and healthcare related factors. One factor that we can no longer ignore is that AR management is no longer limited to the domain of healthcare provider and that people with AR make their own choices when choosing how to manage their condition, without seeking advice from a health care provider. We must build a bridge between healthcare provider knowledge and guidelines and patient decision-making. With this commentary, we propose that a shared decision-making approach between healthcare professionals and people with AR be developed and promoted, with a focus on patient health literacy. As custodians of AR knowledge, we have a responsibility to ensure it is accessible to those that matter most-the people with AR.

CCAD or eCRS: Defining Eosinophilic Subpopulations in Chronic Rhinosinusitis.

BACKGROUND: Central compartment atopic disease (CCAD) and eosinophilic chronic rhinosinusitis (eCRS) are two clinical phenotypes of primary diffuse type 2 chronic rhinosinusitis (CRS) defined in the European Position Paper on Rhinosinusitis 2020 classification. Currently, the distinction between these subtypes relies on phenotypic features alone. OBJECTIVE: This study aimed to investigate whether eosinophil activation differed between CCAD and eCRS. METHODS: A cross-sectional study was conducted of adult patients presenting with CCAD and eCRS who had undergone functional endoscopic sinus surgery. Routine pathology results were obtained from clinical records. Eosinophils were counted on haematoxylin and eosin-stained formalin-fixed paraffin-embedded sinonasal tissue. Eotaxin-3, eosinophil peroxidase and immunoglobulin E levels were assessed using immunohistochemistry. RESULTS: 38 participants were included (51.7 ± 15.6 years, 47.4% female), of whom 36.8% were diagnosed with CCAD and 63.2% with eCRS. The eCRS group was characterised by older age (55.8 ± 16.3 vs 44.5 ± 11.8 years, p = 0.029), and on histology exhibited a higher degree of tissue inflammation (τb = 0.409, p = 0.011), greater proportion of patients with >100 eosinophils/high power field (87.5% vs 50%, p = 0.011), and higher absolute tissue eosinophil count (2141 ± 1947 vs 746 ± 519 cells/mm2, p = 0.013). Eotaxin-3 scores were higher in the eCRS group (5.00[5.00-6.00] vs 6.00[6.00-6.75], p = 0.015). Other outcomes were similar. CONCLUSIONS: Eosinophil and eotaxin-3 levels were elevated in eCRS compared with CCAD, suggesting a greater degree of eosinophil stimulation and chemotaxis. Patients with CCAD were younger. Future investigation and biomarkers may better distinguish CRS subpopulations.

Bacterial colonization differences between central compartment atopic disease and eosinophilic chronic rhinosinusitis.

KEY POINTS: Culturable bacterial colonization is similar between type 2 CRS phenotypes Staphylococcus aureus coinfection is similar between eosinophilic CRS and CCAD Patients with CCAD were younger, consistent with current knowledge of the disease.

A Scoping Review of Artificial Intelligence Research in Rhinology.

BACKGROUND: A considerable volume of possible applications of artificial intelligence (AI) in the field of rhinology exists, and research in the area is rapidly evolving. OBJECTIVE: This scoping review aims to provide a brief overview of all current literature on AI in the field of rhinology. Further, it aims to highlight gaps in the literature for future rhinology researchers. METHODS: OVID MEDLINE (1946-2022) and EMBASE (1974-2022) were searched from January 1, 2017 until May 14, 2022 to identify all relevant articles. The Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews checklist was used to guide the review. RESULTS: A total of 2420 results were identified of which 62 met the eligibility criteria. A further 17 articles were included through bibliography searching, for a total of 79 articles on AI in rhinology. Each year resulted in an increase in the number of publications, from 3 articles published in 2017 to 31 articles published in 2021. Articles were produced by authors from 22 countries with a relative majority coming from the USA (19%), China (19%), and South Korea (13%). Articles were placed into 1 of 5 categories: phenotyping/endotyping (n = 12), radiological diagnostics (n = 42), prognostication (n = 10), non-radiological diagnostics (n = 7), surgical assessment/planning (n = 8). Diagnostic or prognostic utility of the AI algorithms were rated as excellent (n = 29), very good (n = 25), good (n = 7), sufficient (n = 1), bad (n = 2), or was not reported/not applicable (n = 15). CONCLUSIONS: AI is experiencing an increasingly significant role in rhinology research. Articles are showing high rates of diagnostic accuracy and are being published at an almost exponential rate around the world. Utilizing AI in radiological diagnosis was the most published topic of research, however, AI in rhinology is still in its infancy and there are several topics yet to be thoroughly explored.

The impact of implementing an allergic rhinitis clinical management pathway (AR-CMaP) in the community pharmacy.

Background: The Allergic Rhinitis Clinical Management Pathway (AR-CMaP) was developed to overcome the challenge of implementing current AR guidelines in the Australian community pharmacy practice and support pharmacists in optimally managing patients' AR. Objectives: To evaluate the impact of AR-CMaP on patients' behaviour and pharmacists' needs in managing AR in the pharmacy. Methods: This study used a cross-sectional, pre-post study design in which the primary outcome was the appropriateness of medications purchased from community pharmacies in Australia. Patient data were collected before and after the implementation of AR-CMaP. Pharmacist needs were recorded before and after AR-CMaP training. Data were analysed descriptively. Results: Six pharmacies, 19 pharmacists and a total of 416 patients were included in the study; 206 pre-AR-CMaP implementation and 210 post-AR-CMaP implementation. Pre-AR-CMaP, 22.4% of patients purchased appropriate AR medication compared with 29.0% post-AR-CMaP implementation. Over half the patient cohort (52%) consulted a pharmacist pre-AR-CMaP and 37% consulted a pharmacist post-AR-CMaP implementation. Post-AR-CMaP, pharmacists reported increased awareness of barriers such as patients' lack of time, patients' perceptions about the pharmacist's role and patient choice to self-manage. Pharmacists also rated an increased desire to interact with other health care providers (HCPs) in caring for patients with AR. Conclusions: While there was a non-statistically significant increase in the proportion of patients purchasing optimal AR medication, AR-CMaP did empower patients to self-select their own medication without further detriment. Moreover, following the implementation of AR-CMaP, pharmacists developed a greater awareness of their role in AR management, exemplified by their increased desire to be actively involved in AR management and increased interaction with other HCPs. Future research needs to explore more effective tools to support pharmacists' clinical decision-making and target patients' self-selection of AR medications. This study highlights that there is an ingrained self-reliance of AR decision-making that has become a habit for people living with AR.

Comorbidities Modify the Phenotype but Not the Treatment Effectiveness to Mepolizumab in Severe Eosinophilic Asthma.

BACKGROUND: Comorbidities in severe asthma are common and contribute to disease burden. The severe asthma phenotype and treatment response can be impacted by comorbid conditions. Real-world data on the use of mepolizumab in severe eosinophilic asthma (SEA) in the presence of comorbidities are needed to inform clinical practice. OBJECTIVE: To investigate the impact of comorbid conditions on baseline phenotype in patients with SEA and assess the mepolizumab treatment effect by comorbidity status in SEA. METHODS: Patients enrolled in the Australian Mepolizumab Registry (n = 309) were classified into subgroups defined by the presence or absence of comorbidities, including nasal polyps, aspirin-exacerbated airway disease, asthma-chronic obstructive pulmonary disease overlap (ACO), fungal sensitization, and obesity. Patient baseline characteristics were compared, and the impacts of comorbidity on phenotype, identified by differences in patient age and/or baseline biomarker levels and/or asthma severity, were assessed. The mepolizumab treatment effects on clinical and biological outcomes at 12 months were assessed. RESULTS: Across comorbidity subgroups, mepolizumab reduced the rate of clinically significant exacerbations (range: 47%-77%), maintenance oral corticosteroid use (dose reduction: 4.2-13.3 mg/d), and improved symptom control (Asthma Control Questionnaire-5 score: 1.9-2.4 point reduction) and lung function (mean: 3.4-9.3 post-bronchodilator percent predicted forced expiratory volume in 1 second). Peripheral blood eosinophils were reduced (mean: 480-780 cells/µL). Comorbidities (nasal polyps, obesity, ACO, and fungal sensitization) modified the baseline phenotype. CONCLUSIONS: Mepolizumab treatment is associated with comparable clinical improvements in patients with SEA and comorbidities. Mepolizumab effectively minimizes the disease impact and corticosteroid burden in patients with SEA.

Predictors of persistent disease in biologic treated type 2 diffuse/eosinophilic chronic rhinosinusitis undergoing surgery.

BACKGROUND: Biologic therapy targeting type 2 chronic rhinosinusitis with nasal polyps (CRSwNP) has greatly improved disease control but nonresponders exist in a proportion of patients in phase 3 trials and clinical practice. This study explores the serum and histologic changes in biologic treated CRSwNP that predict disease control. METHODS: A cross-sectional study was performed of patients with CRSwNP on biologics for their asthma, who underwent endoscopic sinus surgery while on biologic therapy. At the 6-month postoperative assessment, patients with poorly controlled CRSwNP while on biologic therapy were compared to patients who were controlled. Blood and mucosal samples taken at the time of surgery 6 months prior were assessed to predict disease control. RESULTS: A total of 37 patients were included (age 47.8 ± 12.4 years, 43.2% female). Those with poorly controlled disease had reduced tissue eosinophils (% >100 cells/high-powered field: 8.3% vs. 50.0%, p < 0.001) and increased serum neutrophils (5.2 ± 2.7 vs. 3.7 ± 1.1 × 109 cells/L, p = 0.02). Logistic regression analysis demonstrated that reduced tissue eosinophil was predictive for poorly controlled disease (OR = 0.21, 95% CI [0.05, 0.83], p = 0.03). Receiver-operating characteristic analysis showed that need for rescue systemic corticosteroid was predicted at a serum neutrophil cut-off level of 5.75 × 109 cells/L (sensitivity = 80.0%, specificity = 96.9%, AUC = 0.938, p = 0.002). CONCLUSION: Low tissue eosinophils and increased serum neutrophils while on biologics predict for poor response in the biological treatment of with CRSwNP. A serum neutrophil level of ≥5.75 × 109 cells/L predicts for poor response to current biologic therapy.

Impact of Landscape Fire Smoke Exposure on Patients With Asthma With or Without Laryngeal Hypersensitivity.

BACKGROUND: Individuals with asthma experienced severe and prolonged symptoms after the Australian 2019 to 2020 landscape fire. Many of these symptoms, such as throat irritation, occur in the upper airway. This suggests that laryngeal hypersensitivity contributes to persistent symptoms after smoke exposure. OBJECTIVE: This study examined the relationship between laryngeal hypersensitivity and symptoms, asthma control, and health impacts on individuals exposed to landscape fire smoke. METHOD: The study was a cross-sectional survey of 240 participants in asthma registries who were exposed to smoke during the 2019 to 2020 Australian fire. The survey, completed between March and May 2020, included questions about symptoms, asthma control, and health care use, as well as the Laryngeal Hypersensitivity Questionnaire. Daily concentration levels of particulate matter less than or equal to 2.5 µm in diameter were measured over the 152-day study period. RESULTS: The 49 participants with laryngeal hypersensitivity (20%) had significantly more asthma symptoms (96% vs 79%; P = .003), cough (78% vs 22%; P < .001), and throat irritation (71% vs 38%; P < .001) during the fire period compared with those without laryngeal hypersensitivity. Participants with laryngeal hypersensitivity had greater health care use (P ≤ .02), more time off work (P = .004), and a reduced capacity to participate in usual activities (P < .001) during the fire period, as well as poorer asthma control during the follow-up (P = .001). CONCLUSIONS: Laryngeal hypersensitivity is associated with persistent symptoms, reports of lower asthma control, and increased health care use in adults with asthma who were exposed to landscape fire smoke. Management of laryngeal hypersensitivity before, during, or immediately after landscape fire smoke exposure might reduce the symptom burden and health impact.