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Best practice advice for asthma exacerbation prevention and management in primary care: an international expert consensus

Primary care clinicians play a key role in asthma and asthma exacerbation management worldwide because most patients with asthma are treated in primary care settings. The high burden of asthma exacerbations persists and important practice gaps remain, despite continual advances in asthma care. Lack of primary care-specific guidance, uncontrolled asthma, incomplete assessment of exacerbation and asthma control history, and reliance on systemic corticosteroids or short-acting beta2-agonist-only therapy are challenges clinicians face today with asthma care. Evidence supports the use of inhaled corticosteroids (ICS) + fast-acting bronchodilator treatments when used as needed in response to symptoms to improve asthma control and reduce rates of exacerbations, and the symptoms that occur leading up to an asthma exacerbation provide a window of opportunity to intervene with ICS. Incorporating patient perspectives and preferences when designing asthma regimens will help patients be more engaged in their therapy and may contribute to improved adherence and outcomes. This expert consensus contains 10 Best Practice Advice Points from a panel of primary care clinicians and a patient representative, formed in collaboration with the International Primary Care Respiratory Group (IPCRG), a clinically led charitable organization that works locally and globally in primary care to improve respiratory health. The panel met virtually and developed a series of best practice statements, which were drafted and subsequently voted on to obtain consensus. Primary care clinicians globally are encouraged to review and adapt these best practice advice points on preventing and managing asthma exacerbations to their local practice patterns to enhance asthma care within their practice.

Single-cell RNA transcriptomic analysis identifies Creb5 and CD11b-DCs as regulator of asthma exacerbations

Immune responses that result in asthma exacerbation are associated with allergen or viral exposure. Identification of common immune factors will be beneficial for the development of uniformed targeted therapy. We employed a House Dust Mite (HDM) mouse model of asthma and challenged allergic HDM mice with allergens (HDM, cockroach extract (CRE)) or respiratory syncytial virus (RSV). Purified lung immune cells underwent high-dimensional single-cell RNA deep sequencing (scRNA-seq) to generate an RNA transcriptome. Gene silencing with siRNA was employed to confirm the efficacy of scRNA-seq analysis. scRNA-seq UMAP analysis portrayed an array of cell markers within individual immune clusters. SCENIC R analysis showed an increase in regulon number and activity in CD11b DC cells. Analysis of conserved regulon factors further identified Creb5 as a shared regulon between the exacerbation groups. Creb5 siRNAs attenuated HDM, CRE or RSV-induced asthma exacerbation. scRNA-seq multidimensional analysis of immune clusters identified gene pathways that were conserved between the exacerbation groups. We propose that these analyses provide a strong framework that could be used to identify specific therapeutic targets in multifaceted pathologies.

Temporal trends in the prevalence of GP registrars’ long-term paediatric asthma control medications prescription

Asthma is one of the most common chronic illnesses affecting children. Long-term asthma control medications (LTACMs) are an important aspect of asthma management, with under-prescription associated with poor asthma control and increased asthma deaths. This study aimed to document temporal trends in the prescribing of LTACMs for paediatric patients for asthma-related presentations to Australian general practice registrars (trainees). Longitudinal analyses of data from 2010 to 2022 from the Registrars Clinical Encounters in Training study were undertaken. Proportions of paediatric presentations where LTACMs were prescribed were calculated, and temporal trends analysed and graphed. There was no change over time in registrar prescribing of LTACMs for paediatric asthma, although temporal changes were seen in the types of LTACMs prescribed. The lack of temporal increase in overall LTACMs prescription, despite evidence showing their importance in preventing asthma morbidity and mortality, has significant educational, clinical, and policy implications.

Over-the-counter short-acting β2-agonist purchase and asthma-related health outcomes: a post hoc analysis of the SABINA III study

This post-hoc analysis of the SABINA III study evaluated the association of short-acting β2-agonist (SABA) prescriptions and self-reported over-the-counter (OTC) SABA purchase in the previous 12 months with asthma-related outcomes using multivariable regression models in 4556 patients (mean age, 48.9 years). Of the 2810 patients prescribed ≥3 SABA canisters, 776 (27.6%) also purchased ≥1 SABA OTC. This subset of 776 patients reported the highest disease burden; 73.2% had ≥1 severe exacerbation and 55.7% had uncontrolled asthma. Asthma-related outcomes worsened with any SABA OTC purchase, regardless of SABA prescriptions; disease burden was the highest in patients with ≥3 SABA prescriptions and ≥1 SABA OTC purchase vs 1–2 SABA prescriptions only (86% lower odds of having at least partly controlled asthma and 124% increased incidence of severe asthma (both P < 0.001). These findings emphasize the need to implement policy changes to restrict SABA purchase without prescriptions and ensure access to affordable asthma care.

Asthma prescribing trends, inhaler adherence and outcomes: a Real-World Data analysis of a multi-ethnic Asian Asthma population

Inhaled corticosteroid (ICS) is the mainstay therapy for asthma, but general adherence is low. There is a paucity of real-world inhaler prescribing and adherence data from Asia and at the population level. To address these gaps, we performed a real-world data analysis of inhaler prescribing pattern and adherence in a multi-ethnic Asian asthma cohort and evaluated the association with asthma outcomes. We performed a retrospective analysis of adult asthma patients (aged ≥18 years) treated in the primary and specialist care settings in Singapore between 2015 to 2019. Medication adherence was measured using the medication possession ratio (MPR), and categorised into good adherence (MPR 0.75-1.2), poor adherence (MPR 0.75) or medication oversupply (MPR > 1.2). All statistical analyses were performed using R Studio. 8023 patients, mean age 57 years, were evaluated between 2015 and 2019. Most patients were receiving primary care (70.4%) and on GINA step 1–3 therapies (78.2%). ICS-long-acting beta-2 agonist (ICS-LABA) users increased over the years especially in the primary care, from 33% to 52%. Correspondingly, inpatient admission and ED visit rates decreased over the years. Between 2015 and 2019, the proportion of patients with poor adherence decreased from 12.8% to 10.5% (for ICS) and from 30.0% to 26.8% (for ICS-LABA) respectively. Factors associated with poor adherence included minority ethnic groups (Odds ratio of MPR 0.75–1.2: 0.73–0.93; compared to Chinese), presence of COPD (OR 0.75, 95% CI 0.59–0.96) and GINA step 4 treatment ladder (OR 0.71, 95% CI 0.61–0.85). Factors associated with good adherence were male gender (OR 1.14, 95% CI 1.01–1.28), single site of care (OR 1.22 for primary care and OR 1.76 for specialist care), GINA step 2 treatment ladder (OR 1.28, 95% CI 1.08–1.50). Good adherence was also associated with less frequent inpatient admission (OR 0.91, 95% CI 0.84–0.98), greater SABA overdispensing (OR 1.66, 95% CI 1.47–1.87) and oral corticosteroids use (OR 1.10, 95% CI 1.05–1.14). Inhaled corticosteroid (ICS) adherence has improved generally, however, poor adherence was observed for patients receiving asthma care in both primary and specialist care, and those from the minority ethnicities.

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