Use Of Β2-agonists Research Articles

The Impact of Eliminating Out-of-Pocket Payments on Asthma Medication Use.

High costs of controller therapies may be a barrier to guideline-recommended asthma treatment. We determined whether eliminating out-of-pocket (OOP) payments among low-income patients with asthma impacted controller medication use. We applied a controlled interrupted time series design to administrative claims data in British Columbia, Canada from 2017-2020. Cases were individuals with an annual household income <$13,750 in whom copays were eliminated on January 2019; there was no change in public coverage for the control group with annual income >$45,000. We evaluated trends in asthma medication costs, use, the ratio of inhaled corticosteroid (ICS)-containing medications to all asthma medications, excessive use of short-acting β-agonists (SABA) (>1 canister/month), and the proportion of days (PDC) covered by controller therapies. There were 12,940 cases (62% female, mean age 30.3 years, SD 14.9), and 71,331 controls (55% female, mean age of 31.3 years, SD 16.3). Removal of OOP payments increased monthly mean medication costs by $3.32 (95% CI $0.08 - $6.56, 2020 Canadian dollars), days supply of controller medications by 1.50 days (95% CI 0.61 - 2.40), and the ratio of ICS-containing medications to total medications by 4.20% (95% CI 0.73% - 7.66%) compared to the control group. The policy had no effect on PDC by controller therapies (0.01, 95% CI -0.01 - 0.04), but non-significantly decreased the percentage of patients with excessive SABA use (-6.37%; 95% CI -12.90% - 0.16%). Removal of OOP payments increased the dispensation of controller therapies, suggesting cost-related non-adherence could impair optimal asthma management.

SABINA + Hong Kong: a territory wide study of prescribing trends and outcomes associated with the use of short-acting β2 agonists in the Chinese population

BackgroundExcessive use of short-acting β2 agonists (SABA) in patients with asthma continues to be a notable concern due to its link to higher mortality rates. Global relevance of SABA overuse in asthma management cannot be understated, it poses significant health risk to patients with asthma and imposes burden on healthcare systems. This study, as part of global SABINA progamme, aimed to describe the prescribing patterns and clinical outcomes associated with SABA use in the Chinese population.MethodsRetrospective cohort study was conducted using anonymized electronic healthcare records of Clinical Data Analysis and Reporting System (CDARS) from Hong Kong Hospital Authority (HA). Patients newly diagnosed with asthma between 2011 and 2018 and aged ≥12 years were included, stratified by SABA use (≤2, 3–6, 7–10, or ≥11 canisters/year) during one-year baseline period since asthma diagnosis date. Patients were followed up from one-year post-index until earliest censoring of events: outcome occurrence and end of study period (31 December 2020). Cox proportional regression and negative binomial regression were used to estimate the mortality risk and frequency of hospital admissions associated with SABA use respectively, after adjusting for age, sex, Charlson Comorbidity Index (CCI), and inhaled corticosteroid (ICS) dose. Outcomes include all-cause, asthma-related, and respiratory-related mortality, frequency of hospital admissions for any cause, and frequency of hospital admissions due to asthma.Results17,782 patients with asthma (mean age 46.7 years, 40.8% male) were included and 59.1% of patients were overusing SABA (≥ 3 canisters per year). Each patient was prescribed a median of 5.61 SABA canisters/year. SABA overuse during baseline period was associated with higher all-cause mortality risk compared to patients with ≤2 canisters/year. Association was dose-dependent, highest risk in those used ≥11 canisters/year (adjusted hazard ratio: 1.42, 95% CI: 1.13, 1.79) and 3–6 canisters/year (adjusted hazard ratio: 1.22, 95% CI: 1.00, 1.50). Higher SABA prescription volume associated with increased frequency of hospital admissions with greatest risk observed in 7–10 canisters/year subgroup (adjusted rate ratio: 4.81, 95% CI: 3.66, 6.37).ConclusionsSABA overuse is prevalent and is associated with increased all-cause mortality risk and frequency of hospital admissions among the patients with asthma in Hong Kong.

Asthma control in the United States: Relationships between short-acting β2-agonist and systemic corticosteroid use

BackgroundAsthma control assessment is based on impairment (current symptoms) and risk (exacerbation history). ObjectiveTo understand the extent of uncontrolled asthma, we assessed relationships between prescription fills for systemic corticosteroids (SCS) and short-acting β2-agonists (SABA) as risk and impairment markers, respectively. MethodsAnnual SCS and SABA fills among US patients with asthma were evaluated by a retrospective analysis of the IQVIA Longitudinal Access and Adjudication Data. Patients' disease severity was assigned based on the Global Initiative for Asthma step-therapy level. Exacerbations were evaluated by SCS fills within 12 months of a first asthma prescription fill. Uncontrolled asthma was defined as 2 or more SCS and/or 3 or more SABA fills annually. Individual patient relationships between SCS and SABA fills were assessed using Pearson's correlation coefficients. ResultsA total of 4,506,527 patients were included; 15.1% had 2 or more SCS fills, 29.1% had 3 or more SABA fills, and 37.4% fulfilled either or both criteria. If only SCS use was assessed, 21.4% of cases that were treated as mild to moderate and 27.6% that were treated as severe asthma would have been misclassified as controlled. If only SABA use was evaluated, 7.8% of cases treated as mild to moderate and 11.2% treated as severe asthma would have been misclassified. Overall, 80.9% of uncontrolled asthma occurred in patients treated for mild to moderate disease. Among patients with 2 or more SCS fills, the mean SABA fills were 2.9; the correlation between SCS and SABA fills per patient was significant but weak (r = 0.18; P < .001). ConclusionHigh symptom burden and SCS exposures are not limited to severe asthma but are also characteristic of patients treated for mild to moderate disease. Both impairment and risk assessments are required to understand the full extent of uncontrolled asthma across disease severities.

Preschool impulse oscillometry predicts active asthma and impaired lung function at school age

Asthmatic symptoms often start during early childhood. Impulse oscillometry (IOS) is feasible in preschool children who may be unable to reliably perform spirometry measurements. We sought to evaluate the use of IOS in a multicenter, multiethnic high-risk asthma cohort titled the Vitamin D Antenatal Asthma Reduction Trial. The trial recruited pregnant women whose children were followed from birth to age 8 years. Lung function was assessed with IOS at ages 4, 5, and 6 years and spirometry at ages 5, 6, 7, and 8 years. Asthma status, respiratory symptoms, and medication use were assessed with repeated questionnaires from birth to age 8 years. In total, 220 children were included in this secondary analysis. Recent respiratory symptoms and short-acting β2-agonist use were associated with increased respiratory resistance at 5 Hz at age 4 years (β= 2.6; 95% CI, 1.0 to 4.4; P= .002 and β= 3.4; 95% CI, 0.7 to 6.2; P= .015, respectively). Increased respiratory resistance at 5 Hz at age 4 years was also associated with decreased lung function from ages 5 to 8 years (β= -0.3; 95% CI, -0.5 to -0.1; P< .001 for FEV1 at 8 years) and active asthma at age 8 years (β= 2.0; 95% CI, 0.2 to 3.8; P= .029). Increased respiratory resistance in preschool IOS is associated with frequent respiratory symptoms as well as school-age asthma and lung function impairment. Our findings suggest that IOS may serve as a potential objective measure for early identification of children who are at high risk of respiratory morbidity.

Effect of Buteyko breathing technique on clinical and functional parameters in adult patients with asthma: a randomized, controlled study

BackgroundThe established therapy of asthma might be supported by additional non-pharmaceutical measures, such as the Buteyko breathing technique (BBT); however, the available data are mixed. To clarify the effects of BBT in patients with asthma, we investigated whether it led to clinical improvements with correlation to functional parameters.MethodsUsing a randomized, controlled design, we studied two groups (n = 30 each) of patients with asthma under either BBT or usual therapy (UT) w/o BBT over a period of 3 months. The primary outcome comprised the voluntary control pause (CP) after 3 months, secondary outcomes an additional breathhold parameter, forced expiratory volume in 1 s (FEV1), capnovolumetry, exhaled nitric oxide (FeNO), Asthma Control Questionnaire (ACQ) and Nijmegen Questionnaire (NQ), and the use of medication (β2-agonists; inhaled corticosteroids, ICS).ResultsCP showed significant time-by-group interaction [F(1,58.09) = 28.70, p < 0.001] as well as main effects for study group [F(1,58.27) = 5.91, p = 0.018] and time [F(1,58.36) = 17.67, p < 0.001]. ACQ and NQ scores were significantly (p < 0.05 each) improved with BBT. This was associated with reductions in the use of β2-agonists and ICS (p < 0.05 each) by about 20% each. None of these effects occurred in the UT group. While FEV1 and the slopes of the capnovolumetric expiratory phases 2 and 3 did not significantly change, the capnovolumetric threshold volume at tidal breathing increased (p < 0.05) with BBT by about 10 mL or 10%, compared to baseline, suggesting a larger volume of the central airways. No significant changes were seen for FeNO.ConclusionsBBT was clinically effective, as indicated by the fact that the improvement in symptom scores and the small increase in bronchial volume occurred despite the significant reduction of respiratory pharmacotherapy. As the self-controlled Buteyko breathing therapy was well-accepted by the participants, it could be considered as supporting tool in asthma therapy being worth of wider attention in clinical practice.Trial registration Retrospectively registered on 10 March 2017 at ClinicalTrials.gov (NCT03098849).

Key Characteristics of Asthma Patients with COVID-19 Vary Substantially by Age.

Assessing COVID-19 risk in asthma patients is challenging due to disease heterogeneity and complexity. We hypothesized that potential risk factors for COVID-19 may differ among asthma age groups, hindering important insights when studied together. We included a population-based cohort of asthma patients from the Swedish National Airway Register (SNAR) and linked to data from several national health registers. COVID-19 outcomes included infection, hospitalization, and death from Jan 2020 until Feb 2021. Asthma patients were grouped by ages 12-17, 18-39, 40-64, and ≥65 years. Characteristics of asthma patients with different COVID-19 outcomes were compared with those in their age-corresponding respective source population. Among 201,140 asthma patients studied, 11.2% were aged 12-17 years, 26.4% 18-39, 37.6% 40-64, and 24.9% ≥65 years. We observed 18,048 (9.0%) COVID-19 infections, 2172 (1.1%) hospitalizations, and 336 (0.2%) COVID-19 deaths. Deaths occurred only among patients aged ≥40. When comparing COVID-19 cases to source asthma populations by age, large differences in potential risk factors emerged, mostly for COVID-19 hospitalizations and deaths. For ages 12-17, these included education, employment, autoimmune, psychiatric, and depressive conditions, and use of short-acting β-agonists (SABA) and inhaled corticosteroids (ICS). In the 18-39 age group, largest differences were for age, marital status, respiratory failure, anxiety, and body mass index. Ages 40-64 displayed notable differences for sex, birth region, cancer, oral corticosteroids, antihistamines, and smoking. For those aged ≥65, largest differences were observed for cardiovascular comorbidities, type 1 diabetes, chronic obstructive pulmonary disease, allergic conditions, and specific asthma treatments (ICS-SABA, ICS-long-acting bronchodilators (LABA)). Asthma control and lung function were important across all age groups. We identify distinct differences in COVID-19-related risk factors among asthma patients of different ages. This information is essential for assessing COVID-19 risk in asthma patients and for tailoring patient care and public health strategies accordingly.

IPREDICT: proof-of-concept study to develop a predictive model of changes in asthma control.

The individualized PREdiction of DIsease Control using digital sensor Technology (iPREDICT) program was developed for asthma management using digital technology. Devices were integrated into daily lives of patients to establish a predictive model of asthma control by measuring changes from baseline health status with minimal device burden. To establish baseline disease characteristics of the study participants, detect changes from baseline associated with asthma events, and evaluate algorithms capable of identifying triggers and predicting asthma control changes from baseline data. Patient experience and compliance with the devices were also explored. This was a multicenter, observational, 24-week, proof-of-concept study conducted in the United States. Patients (⩾12 years) with severe, uncontrolled asthma engaged with a spirometer, vital sign monitor, sleep monitor, connected inhaler devices, and two mobile applications with embedded patient-reported outcome (PRO) questionnaires. Prospective data were linked to data from electronic health records and transmitted to a secure platform to develop predictive algorithms. The primary endpoint was an asthma event: symptom worsening logged by patients (PRO); peak expiratory flow (PEF) < 65% or forced expiratory volume in 1 s < 80%; increased short-acting β2-agonist (SABA) use (>8 puffs/24 h or >4 puffs/day/48 h). For each endpoint, predictive models were constructed at population, subgroup, and individual levels. Overall, 108 patients were selected: 66 (61.1%) completed and 42 (38.9%) were excluded for failure to respond/missing data. Predictive accuracy depended on endpoint selection. Population-level models achieved low accuracy in predicting endpoints such as PEF < 65%. Subgroups related to specific allergies, asthma triggers, asthma types, and exacerbation treatments demonstrated high accuracy, with the most accurate, predictive endpoint being >4 SABA puffs/day/48 h. Individual models, constructed for patients with high endpoint overlap, exhibited significant predictive accuracy, especially for PEF < 65% and >4 SABA puffs/day/48 h. This multidimensional dataset enabled population-, subgroup-, and individual-level analyses, providing proof-of-concept evidence for development of predictive models of fluctuating asthma control.

Real-World Study of Single-Inhaler Triple Therapy with Fluticasone Furoate/Umeclidinium/Vilanterol on Asthma Control in the US.

Real-world asthma control data among patients initiating fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) are limited. This study assessed rescue medication use and asthma-related exacerbations in patients with asthma before and after initiating single-inhaler FF/UMEC/VI using administrative claims data. This retrospective, pre-post cohort study analyzed data from the IQVIA PharMetrics Plus database (September 18, 2016‒March 31, 2020). Patients aged ≥18 years that had ≥1 dispensing of single-inhaler FF/UMEC/VI 100/62.5/25 mcg (first dispensing = index date), ≥12 months of continuous health insurance enrollment prior to (pre-treatment) and following (post-treatment) FF/UMEC/VI initiation and ≥1 diagnosis of asthma during the pre-treatment period or on the index date were included. The primary endpoint was the number of oral corticosteroid (OCS) dispensings per patient per year during pre- and post-treatment periods. Secondary endpoints included asthma-related exacerbation rates and short-acting β2-agonist (SABA) use. Comparisons between pre- and post-treatment periods were made using risk and rate ratios. Overall, 890 patients with asthma initiating treatment with FF/UMEC/VI were included. The most recently dispensed controller medications prior to FF/UMEC/VI initiation were inhaled corticosteroids/long-acting β2-agonists (33.5%) and leukotriene modifiers (33.0%). Patients had a 29% reduction in the number of OCS dispensings (rate ratio [95% confidence interval (CI)]: 0.71 [0.65, 0.77], P < 0.001) during post-treatment versus pre-treatment, with a 23% reduction in the proportion of patients with ≥1 OCS dispensing post-treatment (risk ratio [95% CI]: 0.77 [0.73, 0.82], P < 0.001). Significant reductions in rates (rate ratio [95% CI]) of asthma-related exacerbations (0.59 [0.52, 0.67], P < 0.001) and SABA use (0.80 [0.74, 0.86], P < 0.001) were also observed. In this real-world study, patients with asthma had significantly lower OCS use, asthma-related exacerbations, and SABA use following treatment initiation with FF/UMEC/VI compared with their pre-treatment period. These results suggest better asthma control following initiation of FF/UMEC/VI in a routine clinical practice setting.

Asthma and the risk of cardiac events among patients with long QT Syndrome after age 40

Abstract Background The effect of asthma on the clinical course of long QT syndrome (LQTS) in the middle and old age population has not been studied. Purpose The present study was designed to investigate the association between asthma comorbidity, β2-agonist treatment and cardiac events among LQTS subjects after age 40 years. Methods The risk of cardiac events (comprising syncope, aborted cardiac arrest, implantable defibrillator shock, or sudden cardiac death) from age 40 through 75 years, by the presence of asthma and time-dependent β2-agonist use was assessed among 1020 LQTS patients from the LQTS Registry. Results Asthma was identified in 162 (16%) study patients and 63% of asthma patients received β2-agonist inhalers. Patients with asthma vs. no asthma had a higher cumulative rate of cardiac events during follow-up (44% vs. 26%, respectively; p&amp;lt;0.001 [Figure: left panel]). Consistently, multivariate analysis demonstrated that asthma was a powerful predictor of cardiac events with an associated 2-fold (HR=1.97, p=0.001) increased risk for cardiac events as compared to patients with no asthma. β2-agonist inhalers use was associated with a similar increased risk for cardiac events (HR =1.90, p=0.035) among all study patients (Figure: right panel]). Subgroup analysis did not show a statistically significant difference in the association of asthma with cardiac events by risk subsets of LQTS patients, including QTc duration, syncope prior to age 40 years, beta-blocker use, sex, and the LQTS genotype (all p-values for risk subset-by-asthma interaction &amp;gt;0.10). Conclusion The presence of asthma and β2-agonist treatment are associated with an increased risk of cardiac events among middle and old age patients with LQTS.

Impact of income-based public drug coverage deductibles on adherence to asthma medications

BackgroundCost-related nonadherence to medications can be a barrier to asthma management. ObjectiveTo quantify the impact of public drug plan deductibles on adherence to asthma medications. MethodsWe used a quasi-experimental regression discontinuity analysis to determine whether thresholds in deductibles for public drug coverage, determined on the basis of annual household income, decreased medication use among lower-income children and adults with asthma in British Columbia from 2013 to 2018. Using dispensed medication records, we evaluated deductible thresholds at annual household incomes of $15,000 (a deductible increase from 0% to 2% of annual household income), and $30,000 (a deductible increase from 2% to 3% annual household income). We evaluated medication costs, use, the ratio of inhaled corticosteroids–containing controller medications to total medications, excessive use of short-acting β-agonists, and the proportion of days covered by controller therapies. All costs are reported in 2020 Canadian dollars. ResultsOverall, 88,935 individuals contributed 443,847 person-years of follow-up (57% of female sex, mean age 31 years). Public drug subsidy decreased by −$41.74 (95% CI, −$28.34 to −$55.13) at the $15,000-deductible threshold, a 28% reduction, and patient costs increased by $48.45 (95% CI, $35.37-$61.53). The $30,000 deductible threshold did not affect public drug costs (P = .31), but patient costs increased by $27.65 (95% CI, $15.22-$40.09), which is an 11% increase. Asthma-related medication use, inhaled corticosteroids–to–total medication ratio, excessive use of short-acting β-agonists, and proportion of days covered by controller therapies were not impacted by deductible thresholds. ConclusionIncome-based deductibles reduced public drug costs with no effect on asthma-related medication use, adherence to controller therapies, or excessive reliever therapy use in lower-income individuals with asthma.

Agonists and hydrogen peroxide mediate hyperoxidation of β2-adrenergic receptor in airway epithelial cells: Implications for tachyphylaxis to β2-agonists in constrictive airway disorders

Asthma and other airway obstructive disorders are characterized by heightened inflammation and excessive airway epithelial cell reactive oxygen species (ROS), which give rise to a highly oxidative environment. After decades of use, β2-adrenergic receptor (β2AR) agonists remain at the forefront of treatment options for asthma, however, chronic use of β2-agonists leads to tachyphylaxis to the bronchorelaxant effects, a phenomenon that remains mechanistically unexplained. We have previously demonstrated that β2AR agonism increases ROS generation in airway epithelial cells, which upholds proper receptor function via feedback oxidation of β2AR cysteine thiolates to Cys-S-sulfenic acids (Cys-SOH). Our previous results also demonstrate that prevention of normal redox cycling of this post-translational oxi-modification back to the thiol prevents proper receptor function. Given that Cys-S-sulfenic acids can be irreversibly overoxidized to Cys-S-sulfinic (Cys-SO2H) or S-sulfonic (Cys-SO3H) acids, which are incapable of further participation in redox reactions, we hypothesized that β2-agonist tachyphylaxis may be explained by hyperoxidation of β2AR to S-sulfinic acids. Here, using airway epithelial cell lines and primary small airway epithelial cells from healthy and asthma-diseased donors, we show that β2AR agonism generates H2O2 in a receptor and NAPDH oxidase-dependent manner. We also demonstrate that acute and chronic receptor agonism can facilitate β2AR S-sulfination, and that millimolar H2O2 concentrations are deleterious to β2AR-mediated cAMP formation, an effect that can be rescued to a degree in the presence of the cysteine-donating antioxidant N-acetyl-L-cysteine. Our results reveal that the oxidative state of β2AR may contribute to receptor functionality and may, at least in part, explain β2-agonist tachyphylaxis.

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

BackgroundThe extent of short-acting Beta-2-agonist (β2-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. MethodsThis 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. ResultsOverall, 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). ConclusionThe 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.

Regular (up to 10 puffs 4-hourly) inhaled salbutamol should be prescribed at discharge after an asthma attack: myth or maxim?

Over the past 20 years, the concept of asthma weaning plans on discharge after an attack has crept into common practice, although the precise origin of these plans is unclear. High use of short-acting β2-agonists (SABAs) may result in tolerance to their bronchodilator effects, thus diminishing their efficacy, particularly when they are most needed at the time of an acute attack. Furthermore, key warning signs of a deterioration in asthma control may be masked and the weaning plan may encourage the over-use and over-reliance on SABAs. Side-effects from over-use may also occur, including lactic acidosis, downregulation of the β2-adrenoreceptor, increased allergen response and pro-inflammatory effects. The need for asthma education at discharge, a personal asthma action plan and vigilance about prescribing and ensuring adherence to maintenance therapy are definitely important. However, the current authors conclude that the benefit of prescribing regular salbutamol (up to 10 puffs every 4 h) at discharge after an acute asthma attack is a myth, and a very dangerous one.

Online Survey to Investigate Asthma Medication Prescription and Adherence from the Perspective of Patients and Healthcare Practitioners in England.

High short-acting β2-agonist (SABA) use and/or inhaled corticosteroid (ICS) underuse are common and are associated with poor asthma outcomes. This study explored patients' and healthcare practitioners' (HCPs') perspectives to contextualize asthma treatment patterns observed in real-world studies. Data were collected using online surveys from HCPs and people with asthma (≥18 years old with a confirmed asthma diagnosis of any severity) who had consented to research participation through the Clinical Practice Research Datalink. Data were analysed using descriptive statistics. In total, 76 HCPs and 63 patients were invited to take part. Of 48 valid HCP responders, 54.2% (n=26) reported scheduling an annual asthma treatment review with their patients and 83.3% of general practitioners (n=40) had prescribed repeated inhalers at the patient's request. Of 47 valid patient responders, 57.4% (n=27) reported using their reliever (SABA) inhaler daily and 55.3% of patients (n=26) reported being prescribed a preventer inhaler. Of the total patient responders, 31.9% (n=15) reported that they never used their preventer inhaler. Consistent annual adherence with preventer inhalers was reported by 44.7% of all valid responders (n=21), while other patients admitted to using preventers intermittently. SABA and ICS prescription patterns are driven by a combination of HCP and patient factors. Opportunities exist to improve asthma control and behaviours around inhaler use.

Acute Effects of Single Versus Combined Inhaled β2-Agonists Salbutamol and Formoterol on Time Trial Performance, Lung Function, Metabolic and Endocrine Variables

BackgroundHigh prevalence rates of β2-agonist use among athletes in competitive sports makes it tempting to speculate that illegitimate use of β2-agonists boosts performance. However, data regarding the potential performance-enhancing effects of inhaled β2-agonists and its underlying molecular basis are scarce.MethodsIn total, 24 competitive endurance athletes (12f/12m) participated in a clinical double-blinded balanced four-way block cross-over trial to investigate single versus combined effects of β2-agonists salbutamol (SAL) and formoterol (FOR), to evaluate the potential performance enhancement of SAL (1200 µg, Cyclocaps, Pb Pharma GmbH), FOR (36 µg, Sandoz, HEXAL AG) and SAL + FOR (1200 µg + 36 µg) compared to placebo (PLA, Gelatine capsules containing lactose monohydrate, Pharmacy of the University Hospital Ulm). Measurements included skeletal muscle gene and protein expression, endocrine regulation, urinary/serum β2-agonist concentrations, cardiac markers, cardiopulmonary and lung function testing and the 10-min time trial (TT) performance on a bicycle ergometer as outcome variables. Blood and urine samples were collected pre-, post-, 3 h post- and 24 h post-TT.ResultsMean power output during TT was not different between study arms. Treatment effects regarding lung function (p < 0.001), echocardiographic (left ventricular end-systolic volume p = 0.037; endocardial global longitudinal strain p < 0.001) and metabolic variables (e.g. NR4A2 and ATF3 pathway) were observed without any influence on performance. In female athletes, total serum β2-agonist concentrations for SAL and FOR were higher. Microarray muscle gene analysis showed a treatment effect for target genes in energy metabolism with strongest effect by SAL + FOR (NR4A2; p = 0.001). Of endocrine variables, follicle-stimulating hormone (3 h Post–Post-TT), luteinizing hormone (3 h Post–Pre-TT) and insulin (Post–Pre-TT) concentrations showed a treatment effect (all p < 0.05).ConclusionsNo endurance performance-enhancing effect for SAL, FOR or SAL + FOR within the permitted dosages compared to PLA was found despite an acute effect on lung and cardiac function as well as endocrine and metabolic variables in healthy participants. The impact of combined β2-agonists on performance and sex-specific thresholds on the molecular and cardiac level and their potential long-term performance enhancing or health effects have still to be determined.Trial registration: Registered at Eudra CT with the number: 2015-005598-19 (09.12.2015) and DRKS with number DRKS00010574 (16.11.2021, retrospectively registered).

A portable automated chip for simultaneous rapid point-of-care testing of multiple β-agonists

Abusive use of β-agonists as feed additives for animals and medication is detrimental to human health and food safety. Conventional assays are restricted to a single type of β-agonists detection and cannot match the multiplexing features to perform automated, high throughput, and rapid quantitative analysis in real samples. In this research, we develop a portable automated chip system (PACS) with highly integrated automated devices in conjunction with portable microfluidic chips to provide simultaneous point-of-care testing of multiple β-agonists in the field, simplifying complex manual methods, shortening assay times, and improving sensitivity. Specifically, silicon film is used as reaction substrates for immobilizing the conjugates of β-agonists to increase the sensitivity of the assay result. Then, the PACS with a chemiluminescence imaging detector is established for automatic high-throughput and sensitive detection of Clenbuterol, Ractopamine, and Salbutamol based on the indirect immunoassay. Newly developed chip with high mixing performance can improve the sensitivity of target determination. Multiplex assays were carried out using the developed system for Clenbuterol, Ractopamine, and Salbutamol with a limit of detection of 54 pg mL−1,59 pg mL−1, and 93 pg mL−1, respectively. Except for sample preparation and coating, the detection in the PACS takes less than 47 min. A satisfactory sample recovery (86.33%–108.12%) was obtained, validating the reliability and practical applicability of this PACS. Meanwhile, the PACS enables sensitive and rapid detection of multiple β-agonists in farms or markets where lacking advanced laboratory facilities.

Emergency department course of patients with asthma receiving initial emergency medical services care-Perspectives From the National Hospital Ambulatory Medical Care Survey.

Although 911 calls for acute shortness of breath are common, the role of emergency medical services (EMS) in acute asthma care is unclear. We sought to characterize the demographics, course, and outcomes of adult emergency department (ED) patients with asthma in the United States receiving initial EMS care. We analyzed data from the 2016-2019 National Hospital Ambulatory Medical Care Survey (NHAMCS). We included patients aged ≥18 years with an ED visit diagnosis of asthma, stratifying the cases according to initial EMS care. Accounting for the survey design of NHAMCS, we generated nationalized estimates of the number of EMS and non-EMS asthma visits. Using logistic regression, we determined the associations between initial EMS care and patient demographics (age, sex, race, and insurance type), ED course (initial vital signs, triage category, testing, medications), and outcomes (hospital admission, ED length of stay). Of 435million adult ED visits during 2016-2019, there were ≈5.3million related to asthma (1.3million annually, 1.2%; 95% confidence interval [CI], 1.1%-1.4%). A total of 602,569 (150,642 annually, 11.3%; 95% CI, 8.6%-14.8%) ED patients with asthma received initial EMS care. Compared with non-EMS asthma patients, EMS asthma patients were more likely to present with an "urgent" ED triage category (odds ratio [OR], 22.2; 95% CI, 6.6-74.9) and to undergo laboratory (OR, 2.78; 95% CI, 1.41-5.46) or imaging tests (OR, 2.42; 95% CI, 1.21-4.83). ED patients with asthma receiving initial EMS care were almost 3 times more likely to be admitted to the hospital (OR, 2.81; 95% CI, 1.27-6.25). There were no differences in demographics, ED use of β-agonists or corticosteroids, or ED length of stay between EMS and non-EMS asthma patients. Approximately 1 in 10 adult ED patients with asthma receive initial care by EMS. EMS asthma patients present to the ED with higher acuity, undergo more diagnostic testing in the ED, and are more likely to be admitted. Although limited in information regarding the prehospital course, these findings highlight the more severe illness of asthma patients transported by EMS and underscore the importance of EMS in emergency asthma care.

Summary of Korean Asthma Guideline.

Asthma is a chronic inflammatory airway disease that is characterized by variable airflow obstruction. The Korean Asthma Study Group of the Korean Academy of Tuberculosis and Respiratory Diseases has recently updated the Korean Asthma Guideline. This review summarizes the updated Korean Asthma Guideline. Asthma prevalence is increasing worldwide, and in Korea. Variable airflow obstruction can be confirmed by bronchodilator response or other tests, and should be established prior to the controller medication. A low-dose inhaled corticosteroid-formoterol is used to alleviate symptoms in all treatment step, and it can be used as a controller as well as reliever in steps 3-5. This approach is preferred, because it reduces the risk of severe exacerbations, compared to the use of short-acting β2-agonist as reliever. In severe asthma, phenotype/endotype based on the underlying inflammation should be evaluated. For type 2 severe asthma, the biologics should be considered.

Pulmonary exacerbations in insured patients with bronchiectasis over 2 years.

Patients with bronchiectasis experience persistent symptoms and frequent pulmonary exacerbations; this study investigated the frequency of exacerbations and all-cause hospitalisation. This longitudinal, retrospective, claims database study (IBM® MarketScan®) identified patients aged ≥18 years from 1 July 2015 through 30 September 2018. Exacerbations were identified by bronchiectasis inpatient claim or a healthcare interaction, followed by antibiotic prescription within 7 days. Patients with ≥36 months of continuous health plan enrolment (12 months preceding the first bronchiectasis claim, i.e., baseline period and ≥24 months of follow-up) were included. Patients with cystic fibrosis at baseline were excluded. A multivariable logistic regression model identified baseline factors associated with having ≥2 exacerbations over the 2-year follow-up period. In total, 14 798 patients with bronchiectasis were identified; 64.5% were female, 82.7% were aged ≥55 years and 42.7% had ≥2 exacerbations at baseline. Having ≥2 exacerbations after 2 years was positively associated with chronic macrolide use, long-acting β2 agonist use, gastro-oesophageal reflux disease, heart failure and Pseudomonas aeruginosa. Frequent exacerbations (≥2) at baseline were significantly associated with greater likelihood of experiencing ≥2 exacerbations during the first and second year's follow-up (unadjusted odds ratios 3.35 (95% CI 3.1-3.6) and 2.96 (95% CI 2.8-3.2), respectively). The proportion of patients experiencing ≥1 all-cause hospitalisation cumulatively increased from 41.0% in the first year of follow-up to 51.1% over 2 years' follow-up. Frequent exacerbations in patients with bronchiectasis may increase the likelihood of future exacerbations over 2 years of follow-up, with increased hospitalisation rates over time.

Suboptimally controlled asthma in patients treated with inhaled ICS/LABA: prevalence, risk factors, and outcomes

This observational claims-linked survey study assessed the prevalence of and risk factors for suboptimal asthma control and healthcare utilization in adults with asthma receiving fixed-dose combination (FDC) inhaled corticosteroid/long-acting β2-agonist (ICS/LABA). Commercially insured adults from the Optum Research Database were invited to complete the Asthma Control Test (ACT) and Asthma Control Questionnaire-6 (ACQ-6). Among participants (N = 428), 36.4% (ACT-assessed) and 55.6% (ACQ-6-assessed) had inadequately controlled asthma. Asthma-related quality of life was worse and asthma-related healthcare resource utilization was higher in poorly controlled asthma. Factors associated with ACT-defined suboptimal asthma control in multivariate analysis included: frequent short-acting β2-agonist (SABA) use, asthma-related outpatient visits, lower treatment adherence, and lower education levels. During follow-up, factors associated with asthma exacerbations and/or high SABA use included: inadequately controlled asthma (ACT-assessed), body mass index ≥30 kg/m2, and high-dose ICS/LABA. Approximately 35–55% of adults with asthma were inadequately controlled despite FDC ICS/LABA; poor control was associated with worse disease outcomes.