UNASSIGNED: Triple therapy (long-acting muscarinic antagonist/long-acting β2-agonist/inhaled corticosteroid) is recommended for patients with chronic obstructive pulmonary disease (COPD) who experience recurrent exacerbations. Multiple-inhaler triple therapy (MITT) is associated with poor adherence and persistence. This study assessed comparative adherence and persistence to single-inhaler triple therapy (SITT) versus MITT among patients with COPD in a real-world setting in Germany.
UNASSIGNED: This retrospective analysis using the WIG2 benchmark database identified patients with COPD newly initiating triple therapy with MITT or SITT (fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI] or formoterol/beclomethasone/glycopyrronium bromide [FOR/BDP/GLY]) November 2017-June 2019. Eligible patients were ≥35 years with 1 year\'s continual insurance prior to triple therapy initiation and no previous record of triple therapy. Inverse probability of treatment weighting was used to balance baseline characteristics. Adherence was measured using proportion of days covered (PDC) at 6, 12, and 18 months post-treatment initiation; persistence (time until treatment discontinuation) was measured at 6, 12, and 18 months, with a gap of >30 days used to define non-persistence.
UNASSIGNED: Of 5710 patients included in the analysis (mean age 66 years), 71.4% initiated MITT and 28.6% initiated SITT (FF/UMEC/VI: 41.4%; FOR/BDP/GLY: 58.6%). Mean PDC was higher among SITT versus MITT users at all time points; at each time point, mean PDC was highest among FF/UMEC/VI users. During the first 6 months following treatment initiation, higher adherence was exhibited by FF/UMEC/VI (29%) and FOR/BDP/GLY (19%) users versus MITT users. Over the entire observation period, FF/UMEC/VI users had the highest proportion of persistent patients; at 18 months, 16.5% of FF/UMEC/VI users were persistent versus 2.3% of MITT users.
UNASSIGNED: Patients initiating SITT in Germany had significantly higher adherence and persistence compared with patients initiating MITT over 6 to 18 months following treatment initiation. Among SITT, FF/UMEC/VI users had the highest proportion of adherence and persistence.

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.

暂无摘要。

UNASSIGNED: COPD causes substantial economic burden on healthcare. Alternative treatment strategies for COPD can be associated with different costs dependent upon their relative safety and effectiveness. We compared costs and healthcare resource utilization (HCRU) associated with LAMA or LABA/ICS initiation.
UNASSIGNED: Using the Korean National Health Insurance Service database, we enrolled COPD patients initiating treatment with LAMA or LABA/ICS between January 2005 and April 2015. Propensity score matched individuals were compared on all-cause and COPD-related medical costs and HCRU over a three-year follow-up period.
UNASSIGNED: A total of 2444 patients were enrolled in each treatment group. LAMA group was associated with significantly lower costs than LABA/ICS group, both in all-cause (403.08 vs 474.50 USD per patient per month [PPPM], cost ratio 1.18, 95% confidence interval [CI]=1.10-1.26, p<0.0001) and COPD-related (216.37 vs 267.32 USD PPPM, cost ratio 1.24, 95% CI=1.13-1.35, p<0.0001) medical costs. All-cause HCRU was not significantly different between groups, while COPD-related HRCU was higher in LAMA group (0.66 vs 0.60 medical visits PPPM, p<0.0001).
UNASSIGNED: COPD patients initiating treatment with LAMA were associated with lower all-cause and COPD-related medical costs than those starting with LABA/ICS despite the similar all-cause HCRU and higher COPD-related HCRU. Initiation with LAMA is a cost-efficient option for the treatment of COPD.

UNASSIGNED: The extrafine single inhaler triple therapy (efSITT) containing beclomethasone dipropionate/formoterol fumarate/glycopyrronium 87/5/9 μg has proved to be efficacious in patients with chronic obstructive pulmonary disease (COPD) in randomized control trials.
UNASSIGNED: TRIWIN study evaluated the effectiveness of efSITT delivering beclomethasone dipropionate/formoterol fumarate/glycopyrronium 87/5/9 μg in COPD patients previously treated with multiple-inhaler triple therapy (MITT) in a real-world study in Greece.
UNASSIGNED: Prospective, multicenter, observational, non-interventional study was conducted over 24 weeks.
UNASSIGNED: A total of 475 eligible patients had moderate-to-severe COPD, an indication for treatment with efSITT, and were symptomatic despite receiving MITT. COPD Assessment Test (CAT) score, pulmonary function parameters, use of rescue medication, and adherence to inhaler use were recorded at baseline (Visit 1), 3 (Visit 2), and 6 months (Visit 3) after treatment.
UNASSIGNED: Mean CAT score decreased from 21.4 points at Visit 1, to 16.6 at Visit 2 and 15.1 at Visit 3 (p < 0.001 for all pair comparisons). At Visit 3, 79.8% of patients reached a CAT improvement exceeding minimal clinically important difference (⩾2), compared to baseline. Mean forced expiratory volume in 1 s (%pred.) increased from 55.4% at Visit 1 to 63.5% at the end of study period (p < 0.001), while mean forced vital capacity (%pred.) increased from 71.1% at Visit 1, to 76.7% at Visit 3 (p < 0.001). The mean Test of Adherence to Inhalers score increased from 42.5 to 45.3 and 46.3 points, for the three visits, respectively (p < 0.001 comparing Visits 1/2 and Visits 1/3; p = 0.006 comparing Visits 2/3). The percentage of patients showing good adherence rose from 33.7% at baseline to 58.3% at Visit 3. The percentage of patients using rescue medication during the last month dropped from 16.2% to 7.4% at the end of study period (p < 0.001). Pulmonary function parameters also improved.
UNASSIGNED: The TRIWIN results suggest that extrafine beclomethasone dipropionate/formoterol fumarate/glycopyrronium is effective in improving health status, pulmonary function, and adherence and in reducing rescue medication use in COPD patients previously treated with MITT, in a real-world setting in Greece.

β2-adrenergic receptor (β2AR) agonists are the clinical gold standard for treatment and prophylaxis of airway constriction in pulmonary obstructive diseases such as asthma and COPD. Inhaled β2-agonists elicit rapid bronchorelaxation of the airway smooth muscle, yet, clinical tachyphylaxis to this response can occur over repeated and chronic use, which reduces the bronchodilatory effectiveness. Several mechanisms have been proposed to impart β2-agonist tachyphylaxis, most notably β2AR desensitization. However, airway tissue is known to be highly oxidative, particularly in obstructive disease states where reactive oxygen species (ROS) generation is upregulated and ROS degradation is suboptimal yielding a large oxidative burden. Recent evidence demonstrates that β2AR can regulate ROS generation and that ROS can post-translationally alter β2AR cysteine residues via oxidation, leading to distinct functional receptor outcomes. Herein, we discuss the growing evidence for β2AR mediated ROS generation in airway cells and the role of ROS in regulating β2AR via cysteine-oxidation of the receptor. Given the functional consequence of the β2AR-ROS signaling axis in the airways, we also discuss the potential role of ROS in mediating β2-agonist tachyphylaxis.

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).

OBJECTIVE: To evaluate asthma characteristics and treatment patterns, including short-acting β2-agonist (SABA) prescriptions, in primary and specialist care in the Singapore cohort of the SABA use IN Asthma (SABINA III) study.
METHODS: Cross-sectional, observational study.
METHODS: 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 β2 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.
BACKGROUND: NCT03857178.

This study aimed to define real-world prescription patterns in Korea and compare the effectiveness of chronic obstructive pulmonary disease (COPD) medications. We used national claims data provided by the Health Insurance Review and Assessment Service in Korea and examined patients who were first diagnosed with COPD and started treatment between May 1, 2017, and April 30, 2018, with no change in drug regimen. Among 30,784 patients with COPD, long-acting β2 agonist (LABA) combined with long-acting muscarinic antagonist (LAMA) (32.7%), inhaled corticosteroid-LABA (ICS-LABA) (25.6%), LAMA (18.3%), ICS (5.8%), or LABA (4.6%) were prescribed as the first-choice inhalers. The use of LABA-LAMA (hazard ratio [HR], 0.248-0.584), LAMA (HR, 0.320-0.641), ICS-LABA (HR, 0.325-0.643), and xanthine (HR, 0.563-0.828) significantly reduced the total and severe exacerbation rates compared with no use of each medication. However, the use of ICS or LABA individually did not yield such effects. The continued use of LABA-LAMA, LAMA, and ICS-LABA showed a significant effect on exacerbation rate, whereas the long-term use of ICS, LABA, and xanthine did not. Moreover, some high doses of ICS-LABA did not show significant effects. This real-world study revealed that LAMA and/or LABA could be the first choice of therapy, as recommended by recent guidelines. However, ICS, xanthine, and high-dose ICS-LABA are still being prescribed frequently as first-line drugs in Korea.

BACKGROUND: COPD is associated with the development of lung cancer. A protective effect of inhaled corticosteroids (ICS) on lung cancer is still controversial. Hence, this study investigated the development of lung cancer according to inhaler prescription and comorbidties in COPD.
METHODS: A retrospective cohort study was conducted based on the Korean Health Insurance Review and Assessment Service database. The development of lung cancer was investigated from the index date to December 31, 2020. This cohort included COPD patients (≥ 40 years) with new prescription of inhalers. Patients with a previous history of any cancer during screening period or a switch of inhaler after the index date were excluded.
RESULTS: Of the 63,442 eligible patients, 39,588 patients (62.4%) were in the long-acting muscarinic antagonist (LAMA) and long-acting β2-agonist (LABA) group, 22,718 (35.8%) in the ICS/LABA group, and 1,136 (1.8%) in the LABA group. Multivariate analysis showed no significant difference in the development of lung cancer according to inhaler prescription. Multivariate analysis, adjusted for age, sex, and significant factors in the univariate analysis, demonstrated that diffuse interstitial lung disease (DILD) (HR = 2.68; 95%CI = 1.86-3.85), a higher Charlson Comorbidity Index score (HR = 1.05; 95%CI = 1.01-1.08), and two or more hospitalizations during screening period (HR = 1.19; 95%CI = 1.01-1.39), along with older age and male sex, were independently associated with the development of lung cancer.
CONCLUSIONS: Our data suggest that the development of lung cancer is not independently associated with inhaler prescription, but with coexisting DILD, a higher Charlson Comorbidity Index score, and frequent hospitalization.