Metered-Dose Inhaler Spacer with Integrated Spirometer for Home-Based Asthma Monitoring and Drug Uptake.

This work introduces Spiromni, a single device incorporating three different pressurised metered-dose inhaler (pMDI) accessories: a pMDI spacer, an electronic monitoring device (EMD), and a spirometer. While there are devices made to individually address the issues of technique, adherence and monitoring, respectively, for asthma patients as laid out in the Global Initiative for Asthma's (GINA) global strategy for asthma management and prevention, Spiromni was designed to address all three issues using a single, combination device. Spiromni addresses the key challenge of measuring both inhalation and exhalation profiles, which are different by an order of magnitude. Moreover, the innovative design prevents exhalation from entering the spacer chamber and prevents medication loss during inhalation using umbrella valves without a loss in flow velocity. Apart from recording the peak exhalation flow rate, data from the sensors allow us to extract other key lung volume and capacities measures similar to a medical pulmonary function test. We believe this low-cost portable multi-functional device will benefit both asthma patients and clinicians in the management of the disease.

SABA prescriptions and asthma management practices in Singapore: results from a cross-sectional, observational SABINA III study.

OBJECTIVES: To evaluate asthma characteristics and treatment patterns, including short-acting ß2-agonist (SABA) prescriptions, in primary and specialist care in the Singapore cohort of the SABA use IN Asthma (SABINA III) study. DESIGN: Cross-sectional, observational study. SETTING: Multicentre study conducted at five sites across Singapore. METHODS: In patients with asthma (aged ≥12 years), data on demographics, disease characteristics and asthma treatment prescriptions were collected using electronic case report forms. Patients were classified by investigator-defined asthma severity (guided by 2017 Global Initiative for Asthma recommendations) and practice type (primary/specialist care). RESULTS: Of the 205 patients analysed (mean (SD) age, 53.6 (16.8) years; female, 62%), 55.9% were enrolled by specialists and 44.1% by primary care physicians. Most study patients (80.5%) had moderate-to-severe asthma (86.0% in specialist care and 74.4% in primary care). In the 12 months before study enrolment, 18.0% of patients experienced ≥1 severe exacerbation. Asthma was well or partly controlled in 78.0% of patients. Overall, 17.1% of all patients were overprescribed SABA (≥3 SABA canisters/year) in the preceding 12 months, and overprescription was greater in specialist versus primary care (26.3% vs 5.6%). Only 2.9% of patients were prescribed SABA monotherapy, while 41.0% received SABA in addition to maintenance therapy. Among the latter, 40.5% were overprescribed SABA. Overall, a higher percentage of patients prescribed ≥3 SABA canisters (vs 0-2 SABA canisters) were assessed as having uncontrolled asthma during the study visit (42.9% vs 17.6%). Maintenance therapy in the form of inhaled corticosteroids (ICS) or ICS/long-acting ß2 agonist fixed-dose combinations were prescribed to 14.1% and 84.9% of patients, respectively, in the 12 months before enrolment. CONCLUSIONS: In this Singapore cohort, ~17% of all patients and more than 40% of patients prescribed SABA in addition to maintenance therapy were overprescribed SABA. These findings emphasise the need to align clinical practices with the latest evidence-based treatment recommendations. TRIAL REGISTRATION: NCT03857178.

The increasing burden of asthma acute care in Singapore: an update on 15-year population-level evidence.

BACKGROUND: In Singapore, there is currently scarce population-based research informing the recent trends of asthma-related healthcare burdens. In this study, we investigated the past 25-year trends of asthma-related hospitalisations, emergency department (ED) visits and deaths in Singapore and projected the future burdens from 2023 to 2040. METHODS: We acquired annually-measured data from the Singapore Ministry of Health Clinical and National Disease Registry, containing 25-year asthma-related hospitalisation and death rates as well as 15-year ED visit rates. We conducted change-point analysis and generalised linear modelling to identify time intervals with stable trends and estimate asthma-related healthcare utilisation and mortality rates. To project future asthma-related burdens, we developed a probabilistic model which combined projections of future population size with the estimated rate outcomes from the last stable period. RESULTS: Our results show that the asthma hospitalisation rate in Singapore had remained at approximately 80 episodes per 100,000 from 2003 to 2019 and are likely to grow by 1.7% each year (95% CI: 0.7, 5.0%), leading to a total of 163,633 episodes from 2023 to 2040 which corresponds to an estimated $103,075,820 based on 2022 USD. Besides, Singapore's asthma-related ED visit rate was 390 per 100,000 in 2019 and is expected to decline by 3.4% each year (95% CI: - 5.8, 0.0%), leading to a total of 208,145 episodes from 2023 to 2040 which corresponds to USD$15,053,795. In contrast, the 2019 asthma-related mortality rate in Singapore was approximately 0.57 per 100,000 and is likely to stay stably low (change per year: -1.3, 95% CI: - 11.0, 4.3%). Between 2023 and 2040, Singapore's estimated total number of asthma-related deaths is 638 episodes. CONCLUSIONS: Currently, the burden of asthma acute care in Singapore is high; Singapore's asthma-related hospitalisation and ED visit rates are relatively higher than those of other developed economies, and its asthma admission rate is expected to increase significantly over time, possibly indicating excess resource use for asthma. The established national asthma programme in Singapore, together with recent efforts in reinforcing primary care at the national level, provides opportunities to reduce avoidable asthma admissions.

Impact of Guideline-Based Asthma Treatment on Health Services Use in Singapore Before and During COVID-19 Outbreak.

Introduction: To date, the role of standard asthma care in reducing asthma-related health services use (HSU) during the COVID-19 pandemic remains unclear. This study examined the impact of guideline-based asthma treatment on the use of asthma-related emergency department (ED) visits, polyclinic visits (total visits and urgent visits characterized by nebuliser use) before and during the pandemic. Methods: Data from April 2017 to October 2020 was obtained from the National University Health System, one of the three healthcare clusters in Singapore. Using generalized linear models, we estimated the joint effects of the ratio of preventer to reliever dispensations (PRR) and COVID-19 on asthma-related ED visits per hospital per month, total asthma-related polyclinic visits and asthma-related urgent polyclinic visits per clinic per month. Results: Findings show that before the onset of COVID-19, for every 0.5 unit increase in PRR, the number of asthma-related ED visits and urgent polyclinic visits decreased by 12.9% (95% CI: -13.0% to -12.9%) and 6.8% (95% CI: -6.9% to -6.7%), respectively, whereas total asthma-related polyclinic visits increased by 1.0% (95% CI: 0.9% to 1.0%). During the pandemic, a 0.5 unit increase of PRR decreased the number of asthma-related ED visits, urgent and total polyclinic visits by 16.9% (95% CI: -17.0% to - 16.9%), 9.3% (95% CI: -9.5% to -9.2%) and 0.7% (95% CI: -0.8% to -0.7%), respectively. Discussion: These findings suggest that regardless of the COVID-19 pandemic, an increase in PRR consistently reduced the frequency of asthma-related urgent and emergent care, although it barely influenced routine asthma follow-up visits.

Evaluation of short-acting Beta-2-agonist prescriptions and associated clinical outcomes: Findings from the SABA use IN Asthma (SABINA) study in Asia.

Background: The extent of short-acting Beta-2-agonist (ß2-agonist) (SABA) use across Asian countries is not well documented. As part of the SABA use IN Asthma (SABINA) III study, we assessed SABA prescriptions and clinical outcomes in patients with asthma from Asia. Methods: This cross-sectional study recruited patients (aged ≥12 years) with asthma from 8 Asian countries. Data on disease characteristics and asthma treatments were collected using electronic case report forms. Patients were classified by practice type (primary or specialist care) and investigator-defined asthma severity (per Global Initiative for Asthma [GINA] 2017 recommendations). The association of SABA prescriptions with clinical outcomes was analyzed using multivariable regression models. Results: Overall, 3066 patients were analyzed, with a mean (standard deviation) age of 51.8 (16.7) years; of these patients, 2116 (69%) were female, 2517 (82.1%) had moderate-to-severe asthma and 2498 (81.5%) and 559 (18.2%) were treated in specialist and primary care, respectively. In total, 1423 (46.4%) patients had partly controlled/uncontrolled asthma, with 1149 (37.5%) patients experiencing ≥1 severe asthma exacerbation in the previous year. Overall, 800 (26.7%) patients were prescribed ≥3 SABA canisters in the previous year, which is regarded as overprescription and was associated with a significantly decreased odds of at least partly controlled asthma and increased incidence rates of severe exacerbations (P < 0.01 for both associations). Conclusion: The findings from this cohort of predominantly specialist-treated patients with asthma indicate SABA overprescription in at least 1 in every 4 patients, and this overprescription is associated with poor clinical outcomes. These data highlight the need for adherence to recently updated asthma treatment recommendations in Asia.

Dexamethasone protects against Aspergillus fumigatus-induced severe asthma via modulating pulmonary immunometabolism.

Severe asthma is a difficult-to-treat chronic airway inflammatory disease requiring systemic corticosteroids to achieve asthma control. It has recently been shown that drugs targeting immunometabolism have elicited anti-inflammatory effects. The purpose of this study was to investigate potential immunometabolic modulatory actions of systemic dexamethasone (Dex) in an Aspergillus fumigatus (Af)-induced severe asthma model. Mice were repeatedly exposed to the Af aeroallergen before systemic treatment with Dex. Simultaneous measurements of airway inflammation, real-time glycolytic and oxidative phosphorylation (OXPHOS) activities, expression levels of key metabolic enzymes, and amounts of metabolites were studied in lung tissues, and in primary alveolar macrophages (AMs) and eosinophils. Dex markedly reduced Af-induced eosinophilic airway inflammation, which was coupled with an overall reduction in lung glycolysis, glutaminolysis, and fatty acid synthesis. The anti-inflammatory effects of Dex may stem from its immunometabolic actions by downregulating key metabolic enzymes including pyruvate dehydrogenase kinase, glutaminase, and fatty acid synthase. Substantial suppression of eosinophilic airway inflammation by Dex coincided with a specific escalation of mitochondrial proton leak in primary lung eosinophils. Besides, while our findings confirmed that inflammation corresponds with an upregulation of glycolysis, it was accompanied with an unexpectedly stable or elevated OXPHOS in the lungs and activated immune cells, respectively. Our findings reveal that the anti-inflammatory effects of Dex in severe asthma are associated with downregulation of pyruvate dehydrogenase kinase, glutaminase, and fatty acid synthase, and the augmentation of mitochondrial proton leak in lung eosinophils. These enzymes and biological processes may be valuable targets for therapeutic interventions against severe asthma.

Dominant Negative TRAF3 Variant With Recurrent Mycobacterium abscessus Infection and Bronchiectasis.

Host factors leading to pulmonary nontuberculous mycobacteria (PNTM) disease are poorly understood compared with disseminated NTM disease, which is linked to the interleukin 12-interferon gamma signaling pathway. We investigated the tumor necrosis factor receptor associated factor 3 (TRAF3) R338W variant in a patient with recurrent PNTM infection, demonstrating TRAF3- and TNF-α-deficient phenotypes via ex vivo immune and cloning-transfection cellular studies.