BACKGROUND: An increasing number of β2-adrenergic agonists are illicitly used for growth promoting and lean meat increasing in animal husbandry in recent years, but the development of analytical methods has lagged behind these emerging drugs.
RESULTS: Here, we designed and developed an ultrasound probe enhanced enzymatic hydrolysis reactor for quick separation and simultaneously quantification of 22 β2-adrenergic agonists in animal urine and livestock wastewater. Owing to the enhancement of the conventional enzymatic digestion through the ultrasound acoustic probe power, only 2 min was required for the comprehensively separation of β2-adrenergic agonists from the sample matrices, making it a much more desirable alternative tool for high-throughput investigation. The swine, bovine and sheep urines (n = 287), and livestock wastewater (n = 15) samples, collected from both the north and south China, were examined to demonstrate the feasibility and capability of the proposed approach. Six kinds of β2-adrenergic agonists (clenbuterol, salbutamol, ractopamine, terbutaline, clorprenaline and cimaterol) were found in animal urines, with concentrations ranged between 0.056 μg/L (terbutaline) and 5.79 μg/L (clenbuterol). Up to nine β2-adrenergic agonists were detected in wastewater samples, of which four were found in swine farms and nine in cattle/sheep farms, with concentration levels from 0.069 μg/L (tulobuterol) to 2470 μg/L (clenbuterol).
CONCLUSIONS: Interestingly, since β2-adrenergic agonists are usually considered to be abused mainly in the pig farms, our data indicate that both the detection frequencies and concentrations of these agonists in the ruminant farms were higher than the pig farms. Furthermore, the findings of this work indicated that there is a widespread occurrence of β2-adrenergic agonists in livestock farms, especially for clenbuterol and salbutamol, which may pose both food safety and potential ecological risks. We recommend that stricter controls should be adopted to prevent the illegally usage of these β2-adrenergic agonists in agricultural animals, especially ruminants, and they should also be removed before discharging to the environment.

OBJECTIVE: This retrospective longitudinal cohort study aimed to explore the best therapeutic regimen and treatment duration of cough variant asthma (CVA) in children.
METHODS: A total of 314 children with CVA were divided into receive inhaled corticosteroids (ICS) combined with long-acting beta2-agonist (LABA) group, ICS combined with leukotriene receptor antagonists (LTRA) group, ICS monotherapy group and LTRA monotherapy group. All clinical data were statistically analyzed. Logistic regression model was used to compare the advantages and disadvantages of different treatment schemes at each follow-up time point and the best treatment scheme. The Cox proportional hazard regression model based on inverse probability weighting was used to compare the effects of different medication regimens on adverse outcomes with asthma recurrence or progression as the end point.
RESULTS: (1) After comprehensive analysis, ICS + LABA group was the preferred control regimen for CVA within 8 weeks. After 8 weeks of diagnosis, the efficacy of ICS group or LTRA group was comparable to that of ICS + LABA group and ICS + LTRA group. (2) The ICS + LABA group showed a significant improvement in cough at an early stage, particularly at 4 weeks; the symptoms of ICS + LTRA and ICS groups were significantly improved at 36 weeks. The LTRA group alone showed significant improvement at 20 weeks.
CONCLUSIONS: ICS + LABA, ICS + LTRA, ICS alone and LTRA alone can effectively treat CVA. ICS + LABA could improve the symptoms most quickly within 8 weeks after CVA diagnosis, followed by ICS + LATR group. After 8 weeks, it can be reduced to ICS alone to control CVA for at least 36 weeks based on the remission of symptoms in children.

UNASSIGNED: Some systematic reviews (SRs) on triple therapy (consisting of long-acting β2-agonist, long-acting muscarinic antagonist, and inhaled corticosteroid, LABA/LAMA/ICS) for chronic obstructive pulmonary disease (COPD) have reported conflicting results. As the number of syntheses increases, the task of identifying and interpreting evidence becomes increasingly complex and demanding.
UNASSIGNED: To provide a comprehensive overview of the efficacy and safety of triple therapy for COPD.
UNASSIGNED: Overview of SRs.
UNASSIGNED: Two independent reviewers conducted comprehensive searches in PubMed, Embase, Web of Science, and the Cochrane Library to identify relevant SRs that compared triple therapy with any non-triple therapy for COPD, from the inception of these databases until 1 June 2023. The AMSTAR 2 and GRADE tools were utilized to assess the quality of the included studies and the evidence for each outcome.
UNASSIGNED: Eighteen SRs encompassing 30 original studies and involving 47,340 participants were analyzed. The overall AMSTAR 2 rating revealed that 3 SRs were of low quality, 13 SRs were of critically low quality, and 2 SRs were of high quality. No high-certainty evidence revealed a significant advantage of triple therapy in improving lung function or reducing acute exacerbations. However, all evidence, including one high certainty, supported the benefits of improving quality of life. Regarding all-cause mortality, no significant difference was found when compared to LAMA or ICS/LABA; however, high-certainty evidence confirmed its effectiveness when compared with LABA/LAMA. Notably, high-certainty evidence indicated that triple therapy was associated with a significant increase in the risk of pneumonia compared to LABA/LAMA.
UNASSIGNED: Triple therapy demonstrated notable benefits in improving lung function, reducing exacerbations, improving quality of life, and reducing all-cause mortality. However, it is important to note that it may also significantly increase the risk of pneumonia.
UNASSIGNED: This overview protocol was prospectively registered with PROSPERO (No. CRD42023431548).

BACKGROUND: Excessive 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.
METHODS: Retrospective 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.
RESULTS: 17,782 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).
CONCLUSIONS: SABA 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.

Although β2-agonists are crucial for treatment of chronic respiratory diseases, optimizing β2-agonistic activity and selectivity remains essential for achieving favorable therapeutic outcomes. A structure-based molecular design workflow was employed to discover a novel class of β2 agonists featuring a 5-hydroxy-4H-benzo[1,4]oxazin-3-one scaffold, which potently stimulated β2 adrenoceptors (β2-ARs). Screening for the β2-agonistic activity and selectivity led to the identification of compound A19 (EC50 = 3.7 pM), which functioned as a partial β2-agonist in HEK-293 cells containing endogenous β2-ARs. Compound A19 exhibited significant relaxant effects, rapid onset time (Ot50 = 2.14 min), and long duration of action (>12 h) on isolated guinea pig tracheal strips, as well as advantageous pharmacokinetic characteristics in vivo, rendering A19 suitable for inhalation administration. Moreover, A19 suppressed the upregulation of inflammatory cytokines and leukocytes and improved lung function in a rat model of COPD, thereby indicating that A19 is a potential β2 agonist candidate for further study.

Cough is a common symptom in patients with chronic obstructive pulmonary disease (COPD). Patients with cough may exhibit various clinical characteristics and experience varying outcomes based on inhaled therapies they receive.
This study aimed to explore the clinical characteristics and outcomes of various inhaled therapies in COPD patients with frequent cough.
This was a multicenter, prospective cohort study. Of these patients, the median cough score in COPD assessment test (CAT) was two. Patients were classified into frequent cough group if they scored two or over in the first item of CAT and infrequent cough group otherwise. Patients with frequent cough were then divided into long-acting antimuscarinic (LAMA), long-acting beta2-agonist (LABA)/LAMA, inhaled corticosteroids (ICS)/LABA and ICS/LABA/LAMA groups. Minimum clinically important difference (MCID) (CAT scores decreased ≥2 from baseline) and the improvement of cough (cough score decreased ≥1 from baseline) were collected in the six-month follow-up. Frequent exacerbations (experiencing at least two exacerbations) were collected in the one-year follow-up.
Of 906 patients, 581 (64.1%) patients reported frequent cough at the initial visit. Frequent cough was associated with the current smokers and CAT scores (p < 0.05). The MCID showed no significant difference between frequent cough and infrequent cough groups in the follow-up. More patients with frequent cough experienced future frequent exacerbations compared to those with infrequent cough. After receiving inhaled therapies, 62% of patients with frequent cough got the cough improved. More patients with frequent cough treated with LABA/LAMA or ICS/LABA/LAMA attained MCID and fewer experienced exacerbations than those treated with LAMA or ICS/LABA (p < 0.05). The change in cough score showed no difference among various inhaled therapies in patients with frequent cough.
COPD patients with frequent cough were related to current smokers and higher CAT scores. These patients had a higher incidence of frequent exacerbations than those with infrequent cough. Patients with frequent cough who were treated with LABA/LAMA or ICS/LABA/LAMA were more likely to attain MCID and at a lower risk of exacerbation than those treated with LAMA or ICS/LABA.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a significant cause of mortality, with its prevalence projected to rise in Asia. The primary objective of this study was to describe clinical characteristics, maintenance treatment, and healthcare resource utilization (HCRU) among patients with COPD in Hong Kong. Secondary objectives were to assess patient demographics and clinical characteristics by eosinophil (EOS) levels, and compare the demographics, clinical characteristics, and treatment patterns of patients on multiple-inhaler triple therapy (MITT).
METHODS: This study analyzed a cohort of patients with COPD who had entered a previously initiated prospective cohort study involving patients with COPD and/or asthma at the Prince of Wales Hospital between 2017 and 2019.
RESULTS: Patients with COPD were enrolled (N = 220, mean age 74.3 years, 97 % male). Twelve months prior to baseline assessment, 66 % of patients were on MITT, 17 % on long-acting muscarinic antagonists (LAMAs)/long-acting beta-agonists (LABAs), and 7 % on inhaled corticosteroids (ICS)/LABA. Compared with ICS/LABA or LAMA/LABA, more patients on MITT experienced ≥1 exacerbation (26.7 %, 10.5 %, 39.7 %, respectively). Patients on MITT also had a higher mean (SD) COPD Assessment Test score (9.4 [5.9]) and modified Medical Research Council Dyspnea Scale score (1.7 [0.7]) and incurred the most COPD-related and total HCRU costs. Compared with patients with EOS ≤300 cells/μL, those with EOS >300 cells/μL had a higher number of exacerbations.
CONCLUSIONS: Patients with COPD in Hong Kong treated with MITT presented more severe disease profiles and incurred higher costs. These data can be used for decision making in patients with moderate-to-severe COPD in Hong Kong.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 report revised the combined assessment, merged the C and D groups into the E group, and revised the initial inhalation therapy recommendation.
This study aimed to analyze the future exacerbation and mortality of different inhalation therapies among patients with chronic obstructive pulmonary disease (COPD) in various groups based on the GOLD 2017 and GOLD 2023 reports.
This is a multicenter and retrospective study.
Stable COPD patients from the database setup by 12 hospitals were enrolled. The patients were divided into Groups A, B, C, D, and E according to the GOLD 2017 and GOLD 2023 reports. Then, the patients were classified into long-acting muscarinic antagonist (LAMA), long-acting β2-agonist (LABA) + inhaled corticosteroid (ICS), LABA + LAMA, and LABA + LAMA + ICS subgroups. Data on exacerbation and death during 1 year of follow-up were collected.
A total of 4623 patients were classified into Group A (15.0%), Group B (37.8%), Group C (7.3%), Group D (39.9%), and Group E (47.2%). The exacerbation, frequent exacerbation, and mortality showed no differences between different inhalation therapies in Groups A and C. Patients treated with LABA + LAMA or LABA + LAMA + ICS had a lower incidence of exacerbation and frequent exacerbation than patients treated with LAMA or LABA + ICS in Groups B, D, and E. The exacerbation, frequent exacerbation, and mortality showed no differences between different inhalation therapies after combining Groups A with C.
Patients in Group A should be recommended to undergo mono-LAMA, while patients in Groups B and E should be recommended treatment with LABA + LAMA, which is consistent with the GOLD 2023 report. However, it is worth considering merging Groups A and C into a single group and recommending mono-LAMA as the initial inhalation therapy.

AVANT was a Phase 3, 24-week, randomized, parallel-group, double-blind, double-dummy, placebo-controlled study to assess the efficacy and safety of aclidinium/formoterol 400 μg/12 μg combination vs monotherapies and aclidinium vs placebo (1:1:1:1) in Asian patients (∼70% of whom were Chinese) with moderate-to-severe stable chronic obstructive pulmonary disease. Endpoints were analyzed hierarchically to incorporate type I error control. At Week 24, aclidinium/formoterol demonstrated improvements from baseline in 1-h morning post-dose forced expiratory volume in 1 s (FEV1) vs aclidinium (least squares [LS] mean 92 mL; 95% confidence interval [CI] 60, 124 mL; p < 0.001), and in trough FEV1 vs formoterol (LS mean 85 mL; 95% CI 53, 117 mL; p < 0.001). Furthermore, aclidinium provided improvements in trough FEV1 vs placebo (LS mean 134 mL; 95% CI 103, 166 mL; p < 0.001). There was an improvement in transition dyspnea index focal score at Week 24 for aclidinium/formoterol vs placebo (LS mean 0.8; 95% CI 0.2, 1.3; p = 0.005) but not for aclidinium vs placebo (LS mean 0.4; 95% CI -0.1, 1.0; p = 0.132). Improvements in St George\'s Respiratory Questionnaire total scores occurred for aclidinium/formoterol vs placebo (LS mean -4.0; 95% CI -6.7, -1.4; p = 0.003) and aclidinium vs placebo (LS mean -2.9; 95% CI -5.5, -0.3; p = 0.031). Aclidinium/formoterol and aclidinium were well tolerated and safety findings were consistent with known profiles; rates of treatment-emergent adverse events (AEs) (aclidinium/formoterol: 54.8%; aclidinium: 47.4%; placebo: 53.9%), serious AEs (7.2, 7.9, and 7.8%, respectively), and AEs leading to discontinuation of study medication (2.3, 1.5, and 2.2%, respectively) were similar between groups.

Asthma is a common chronic airway inflammation that produces a healthcare burden on the economy. We aim to obtain a better understanding of the clinical status and disease burden of patients with asthma in China. A retrospective study was carried out based on the computerized medical records in the Jinan Health Medical Big Data Platform between 2011 and 2019 (available data from 38 hospitals). The asthma severity of each patient was assessed retrospectively and categorized as mild, moderate, or severe according to Global Initiative for Asthma 2020 (GINA 2020). The results revealed that the majority (75.0%) of patients suffered from mild asthma. Patients treated with inhaled corticosteroids (ICS)/long-acting beta-agonists (LABA) at emergency department visits had lower frequencies of exacerbations compared with non-ICS/LABA-treated patients. The incidence rates for 1, 2, 3, and 4 exacerbation of the patients treated with ICS/LABA are lower than those treated without ICS/LABA (14.49 vs. 15.01%, 11.94% vs. 19.12%, 6.51% vs.12.92% and 4.10% vs. 9.35%). The difference got a statistical significance Chronic obstructive pulmonary disease (COPD) and gastroesophageal reflux disease (GERD), two comorbidities related to asthma, were risk factors for asthma exacerbation. Finally, patients who suffered from exacerbations produced a heavier economic burden compared to the patients who never suffered exacerbations (mean costs are ￥3,339.67 vs. ￥968.45 separately).  These results provide a reference for clinicians and patients to obtain a better treatment and therapy strategy management for people living with asthma.