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Background Coronary heart disease occurs more frequently among patients with chronic obstructive pulmonary disease (COPD) compared to those without COPD. While some research suggests that long‐acting bronchodilators might confer an additional risk of acute coronary syndrome (ACS), information from real‐world clinical practice about the cardiovascular impact of using two versus one long‐acting bronchodilator for COPD is limited. We undertook a population‐based nested case–control study to estimate the risk of ACS in users of both a long‐acting muscarinic antagonist (LAMA) and a long‐acting beta2‐agonist (LABA) relative to users of a LAMA. Methods The study was based on the primary care PREDICT Cardiovascular Disease Cohort and linked data from regional laboratories and the New Zealand Ministry of Health's national data collections. The underlying cohort (n = 29,993) comprised patients aged 45–84 years, who initiated treatment with a LAMA and/or LABA for COPD between 1 February 2006 and 11 October 2016. 1490 ACS cases were matched to 13,550 controls by date of birth, sex, date of cohort entry (first long‐acting bronchodilator dispensing), and COPD severity. Results Relative to current use of LAMA therapy, current use of LAMA and LABA dual therapy was associated with a significantly higher risk of ACS (adjusted OR = 1.72; [95% CI: 1.28–2.31]). Conclusion Dual long‐acting bronchodilator therapy, rather than LAMA mono‐therapy, could increase the risk of ACS by more than 50%. This has important implications for decisions about the potential benefit/harm ratio of COPD treatment intensification, given the modest benefits of dual therapy.

Young-Jee Jeon,1,&ast; Sangyoung Han,2,&ast; Gyung-Min Park,2 Tae Young Lee,3 Soon Eun Park,4 Hyunho Lee,4 Byung Ju Kang2 1Department of Family Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea; 2Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea; 3Department of Radiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea; 4Department of Anesthesiology and Pain Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Byung Ju KangDepartment of Internal Medicine, Ulsan University Hospital, University of Ulsan, College of Medicine, 877, Bangeojinsunhwando-ro, Dong-gu, Ulsan, 44033, Republic of KoreaTel +82-52-250-8870Fax +82-52-250-8997Email pastnumber@naver.comPurpose: Low-attenuation muscle area (LAMA) and normal-attenuation muscle area (NAMA) indicate lipid-rich and lipid-poor skeletal muscle areas, respectively. Additionally, intermuscular adipose tissue (IMAT) indicates localized fat between muscle groups. In this study, we aimed to evaluate the intramuscular and intermuscular fat infiltration in individuals with chronic obstructive pulmonary disease (COPD) by performing quantitative assessment of the LAMA, NAMA, and IMAT observed on abdominopelvic computed tomography (APCT) images.Patients and Methods: We performed a cross-sectional study using data of subjects who underwent a general health examination with APCT at Ulsan University Hospital between March 2014 and June 2019. We classified the subjects into control and COPD groups based on age, smoking history, and pulmonary function results. We compared the attenuation and body mass index adjusted area of intra-abdominal components between the two groups using propensity score matching. We also evaluated these outcomes in COPD subgroups (mild and moderate stage subjects).Results: Overall, 6,965 subjects were initially enrolled, and 250 pairs of control and COPD subjects were selected after propensity score matching. The NAMA attenuation (unstandardized β=− 1.168, P< 0.001) was lower, and the IMAT (unstandardized β=0.042, P=0.006) and LAMA (unstandardized β=0.120, P< 0.001) indexes were greater in the COPD group than in the control group. In subgroup analysis, those with mild and moderate COPD also had high IMAT (unstandardized β=0.037, P=0.009 and unstandardized β=0.045, P< 0.001) and LAMA (unstandardized β=0.089, P=0.002 and unstandardized β=0.147, P< 0.001) indexes compared to the control subjects. However, the NAMA attenuation (unstandardized β=− 1.075, P< 0.001) and NAMA index (unstandardized β=− 0.133, P=0.015) were significantly lower in moderate COPD subjects only.Conclusion: Our study showed that intramuscular and intermuscular abdominal fat infiltration could be present in subjects with mild COPD, and it might be exacerbated in those with moderate COPD.Keywords: abdominal fat, abdominal muscles, chronic obstructive pulmonary disease, computed tomography

Therapeutical options for the treatment of chronic obstructive pulmonary disease (COPD) have significantly expanded in recent years, primarily due to market entry of new combination drugs. One of the commonly used therapeutic options for patients with frequent exacerbations of COPD is a triple combination, including LABA, LAMA and ICS, however, prescribing such therapy, doctors often face a decrease in treatment adherence, which ultimately leads to lack of effectiveness, as well as with an increased risk of adverse events. This article presents the current information on the clinical efficacy and safety profile of a fixed triple combination of beclomethasone dipropionate, glycopyrronium bromide and formoterol fumarate, available as extrafine aerosol inhaler, allows to optimize inhalation treatment for patients with frequent exacerbations of COPD.

Qing Song,1– 3 Yi-Yang Zhao,1– 3 Yu-Qin Zeng,1– 3 Cong Liu,1– 3 Wei Cheng,1– 3 Min-Hua Deng,4 Xin Li,5 Li-Bing Ma,6 Yan Chen,1– 3 Shan Cai,1– 3 Ping Chen1– 3 1Department of Respiratory and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 3Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 4Department of Respiratory, PLA Rocket Force Characteristic Medical Center, Beijing, 100088, People’s Republic of China; 5Division 4 of Occupational Disease, Hunan Occupational Disease Prevention and Treatment Hospital, Changsha, Hunan, 410000, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, 541000, People’s Republic of ChinaCorrespondence: Ping ChenDepartment of Respiratory and Critical Care Medicine, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, Hunan, 410011, People’s Republic of ChinaTel +86 731 8529 5248Fax +86 731 8529 5848Email pingchen0731@csu.edu.cnBackground: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 separated pulmonary function from combined assessment. We aimed to analyze the characteristics of airflow limitation and future exacerbations in different GOLD groups of chronic obstructive pulmonary disease (COPD) patients.Methods: For this prospective observational study, stable COPD outpatients were enrolled and divided into Groups A, B, C and D based on GOLD 2017, and followed-up for 18 months. Data on demographics, pulmonary function, COPD assessment test (CAT), Clinical COPD Questionnaire (CCQ), modified Medical Research Council (mMRC), exacerbations, mortality and treatments were collected. A post-bronchodilator ratio of forced expiratory volume in one second to forced vital capacity < 0.70 confirms the presence of airflow limitation.Results: A total of 993 subjects were classified into Groups A (n = 170, 17.1%), B (n = 360, 36.3%), C (n = 122, 12.3%), and D (n = 341, 34.3%). There were significant differences in mMRC, CAT, CCQ, exacerbations and hospitalizations rates among the different groups (P < 0.001). Groups B and D had more severe airflow limitation than Groups A and C (P < 0.05). In the same groups with different severity of airflow limitation, the differences were mainly observed in body mass index, CAT, CCQ and treatment with long-acting muscarinic antagonist (LAMA) and LAMA + long-acting β 2-agonist + inhaled corticosteroid (P < 0.05). After 18 months of follow-up, the exacerbations and hospitalizations rates were significantly different among different groups (P < 0.05). However, in the same groups with different airflow limitation severity, the mortality rates and number of exacerbations, hospitalizations and frequent exacerbators showed no differences.Conclusion: In the GOLD groups, different severity of airflow limitation had no impact on future exacerbations and mortality rate. It implies that pulmonary function is not a good indicator for predicting exacerbation.Keywords: chronic obstructive pulmonary disease, Global Initiative for Chronic Obstructive Lung Disease, pulmonary function, exacerbation

Leah B Sansbury,1 Chanchal Bains,2 David A Lipson,3,4 Afisi S Ismaila,5,6 Sarah H Landis5 1Value Evidence and Outcomes, GlaxoSmithKline, Research Triangle Park, NC, USA; 2Value Evidence and Outcomes, GlaxoSmithKline, Uxbridge, UK; 3Clinical Sciences, GlaxoSmithKline, Collegeville, PA, USA; 4Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 5Value Evidence and Outcomes, GlaxoSmithKline, Collegeville, PA, USA; 6Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, CanadaCorrespondence: Leah B SansburyValue Evidence and Outcomes, GlaxoSmithKline, Building 5, 42 Moore Drive, Research Triangle Park, NC, 27709, USATel +1 919 812 0719Email leah.b.sansbury@gsk.comIntroduction: Until recently, triple therapy for chronic obstructive pulmonary disease (COPD) has only been available through treatment with multiple inhalers. Evidence on real-world use of multiple-inhaler triple therapy (MITT), including duration of use and treatment patterns, is limited.Methods: A retrospective, observational study of electronic health records and hospital episodes in patients with COPD initiating MITT between 2013 and 2015 in the UK was performed. This study described patients initiating, treatment persistence and discontinuation, and prior and subsequent COPD treatments.Results: Eligible patients (N=3825) had a mean age of 69.5 years; most were former or current smokers (95%). The majority (86%) initiated MITT with two inhalers and 14% initiated with three inhalers. Mean duration of use was 5.1 (standard deviation: 4.6) months; 24% of patients persisted for 12 months. Patients who had significantly poorer lung function at baseline (12 months prior to initiating MITT) and had experienced significantly more moderate-to-severe acute exacerbation of COPD (AECOPD) and hospitalizations during the baseline period were more likely to persist for 12 months, compared with those who discontinued within 12 months. Most patients stepped down to an inhaled corticosteroid/long-acting β2-agonist combination (ICS/LABA; 48%) or a long-acting muscarinic antagonist (LAMA; 45%) after discontinuing MITT.Conclusion: Initiation of MITT occurred in patients with clinically relevant symptoms and a history of AECOPD. Persistence varied and was most likely linked to disease severity, although more research is required to fully understand why patients discontinue MITT, the subsequent clinical consequences of therapy discontinuation, and the potential impact of newly available single-inhaler triple therapies.Keywords: chronic obstructive pulmonary disease, COPD, multiple-inhaler triple therapy, MITT, general practice, real world, treatment patterns

Today, achieving clinical control in patients with chronic obstructive pulmonary disease (COPD) remains relevant. Thus, the results of a large multicenter study of clinical efficacy of dual bronchodilatory therapy in real practice conducted in Eastern Europe, including the Russian Federation, are of great interest.Aim. Assessment of changes in the clinical control in patients with COPD receiving treatment with LABA/LAMA combination (tiotropium/olodaterol 5/5 μg via the Respimat® inhaler) in real clinical practice.Methods. The study included patients (n = 1 476) with COPD older than 40 years who were prescribed tiotropium/olodaterol 5/5 μg via the Respimat® inhaler according to the current Russian and foreign clinical guidelines. The observation period was 6 weeks. The clinical control of COPD was assessed by the CCQ questionnaire, the patient’s general condition, the severity of dyspnea according to the mMRC scale, the incidence of using short-acting bronchodilators to relieve symptoms. The criterion for therapeutic success was a 0.4 point decrease in the CCQ score, the minimal clinically important differenceResults. The treatment with tiotropium/olodaterol 5/5 μg was successful, i.e., led to a decrease in the number of CCQ points by more than 0.4 points, in 89.84% of patients (95% CI 88.2 – 91.3 %; p < 0.0001). On average, the overall CCQ score between the first and second visit decreased by 1.31 ± 0.97 points, the severity of symptoms – by 1.39 ± 1.03 points, the functional state – by 1.2 ± 1.1 points, the mental condition – by 1.38 ± 1.31 CCQ points. Achievement of clinical control did not depend on comorbid pathology, disease severity, patient age, and the previous therapy.Conclusion. The results obtained on a wide sample of patients from real practice confirmed the high clinical efficacy of tiotropium/olodaterol 5/5 μg in achieving clinical control of COPD.

Background: Many chronic obstructive pulmonary disease (COPD) patients receiving monotherapy continue to experience symptoms, exacerbations and poor quality of life. This study aimed to assess the efficacy and safety of direct switch from once-daily tiotropium (TIO) 18 μg to indacaterol/glycopyrronium (IND/GLY) 110/50 μg once daily in COPD patients in Korea. Methods: This was a randomized, open-label, parallel group, 12-week trial in mild-to-moderate COPD patients who received TIO 18 μg once daily for ≥12 weeks prior to study initiation. Patients aged ≥40 years, with predicted post-bronchodilator forced expiratory volume in 1 second (FEV1) ≥50%, post-bronchodilator FEV1/forced vital capacity

This study presents a comparative morphological and morphometrical examination of the interosseous muscle (IOM), digital flexor tendons and associated structures of all four species of South American Camelids (SACs): Lama (Lama glama), alpaca (Vicugna pacos), guanaco (Lama guanicoe) and vicuna (Vicugna vicugna). Our findings show that the lamoid interosseous muscle and digital flexor tendons are very similar between species and differences, which have been reported previously, are possibly due to diverging examiner interpretation. Lumbricalis muscles were mostly found as single muscles in this study. The definition of the terminal and dorsal branches of the interosseous muscle is critically revised. The analysis of morphometric data indicates that the size of the individual has a substantial influence on the cross-sectional area (CSA) of the examined structures. Metacarpal/metatarsal bone width is a main predictor of CSA, while the factor species only shows significance in specific sample points. For lama and alpaca, no differences in CSA in relation to species as factor were found. The IOM shows the largest CSAs of the three examined structures in all species, which implies an important load-bearing function. Considerable individual variation remains unexplained by the mentioned factors. This lowers the prospect of CSA reaching diagnostic importance in SAC fetlock pathology.

Long-acting muscarinic antagonists (LAMAs) have a recognised role in the management of chronic obstructive pulmonary disease. In asthma, muscarinic antagonists (both short- and long-acting) were historically considered less effective than β2-agonists; only relatively recently have studies been conducted to evaluate the efficacy of LAMAs, as add-on to either inhaled corticosteroid (ICS) monotherapy or ICS/long-acting β2-agonist (LABA) combinations. These studies led to the approval of the first LAMA, tiotropium, as an add-on therapy in patients with poorly controlled asthma. Subsequently, a number of single-inhaler ICS/LABA/LAMA triple therapies have been approved or are in clinical development for the management of asthma. There is now substantial evidence of the efficacy and safety of LAMAs in asthma that is uncontrolled despite treatment with an ICS/LABA combination. This regimen is recommended by GINA as an optimisation step for patients with severe asthma before any biologic or systemic corticosteroid treatment is initiated. This narrative review summarises the potential mechanisms of action of LAMAs in asthma, together with the initial clinical evidence supporting this use. We also discuss the studies that led to the approval of tiotropium for asthma and the data evaluating the efficacy and safety of the various triple therapies, before considering other potential uses for triple therapy.

Gatal Lake is located in the Kotawaringin Lama District, West Kotawaringin Regency, Central Kalimantan, Indonesia. The government and the surrounding communities use Gatal Lake for recreation, irrigation, livestock, and fisheries. Geographically, Gatal Lake, is close to oil palm plantations and palm oil processing factories that contributed to water pollution, especially the pollutants originating from plantation activities in the form of large-scale use of fertilizers and pesticides. This study aimed to determine the status of the water quality of Gatal Lake, Kotawaringin Lama based on the physicochemical parameters. The samples from five stations were analyzed based on the following parameters: temperature, TDS, TSS, pH, BOD, COD, DO, nitrate, nitrite, phosphate, Pb, Cd, H2S, oil and grease, detergent, and phenol. The study was conducted using a purposive sampling method and determining the status of water quality based on Government Regulation No. 82/2001. The results of the physicochemical analysis of Gatal Lake showed that the water quality parameters which exceeded the water quality standards, are BOD (6.94 to 8.65 mg L), COD (9.58 to 15.7 mg/L), and DO (4.20 to 5.10 mg/L), while the parameters that did not exceed the water quality standards for Class I, II, III, and IV are temperature, TDS, TSS, pH, nitrate, nitrite, phosphate, Pb, Cd, H2S, oils and fats, detergents and phenols. On the basis of the STORET method, the water quality of Gatal Lake for Class I, II, and III are included in the highly polluted category, and for Class IV is in the moderate category.

Taraneh Bahremand,1 Mahyar Etminan,2 Nardin Roshan-Moniri,1 Mary A De Vera,1 Hamid Tavakoli,1 Mohsen Sadatsafavi1 1Collaboration for Outcomes Research and Evaluation, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada; 2Department of Ophthalmology, Faculty of Medicine, The University of British Columbia, Vancouver, BC, CanadaCorrespondence: Mohsen SadatsafaviFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, CanadaEmail msafavi@mail.ubc.caBackground: In contemporary guidelines for the management of Chronic Obstructive Pulmonary Disease (COPD), the history of acute exacerbations plays an important role in the choice of long-term inhaled therapies. This study aimed at evaluating population-level trends of filled inhaled prescriptions over the time course of COPD and their relation to the history of exacerbations.Methods: We used administrative health databases in British Columbia, Canada (1997– 2015), to create a retrospective incident cohort of individuals with diagnosed COPD. We quantified long-acting inhaled medication prescriptions within each year of follow-up and documented their trend over the time course of COPD. Using generalized linear models, we investigated the association between the frequent exacerbator status (≥ 2 moderate or ≥ 1 severe exacerbation(s) in the previous 12 months) and filling a prescription after a physician visit.Results: 132,004 COPD patients were included (mean age 68.6, 49.2% female). The most common medication class during the first year of diagnosis was inhaled corticosteroids (ICS, used by 49.9%), followed by long-acting beta-2 adrenoreceptor agonists (LABA, 31.8%). Long-acting muscarinic receptor antagonists (LAMA) were the least commonly prescribed (10.4%). ICS remained the most common prescription throughout follow-up, being used by approximately 50% of patients during each year. 39.0% of patients received combination inhaled therapies in their first year of diagnosis, with ICS+LABA being the most common (30.7%). The association with exacerbation history was the most pronounced for triple therapy with an odds ratio (OR) of 2.68 for general practitionersand 2.02 for specialists (p< 0.001 for both). Such associations were generally stronger among GPs compared with specialists, with the exception of monotherapy with LABA or ICS.Conclusion: We documented low utilization of monotherapies (specifically LAMA) and high utilization of combination therapies (particularly ICS containing). Specialists were less likely to consider exacerbation history in the choice of inhaled therapies compared with GPs.Keywords: COPD, prescription, medication, exacerbation, time trend

Background Which patients should receive dual therapy as initial treatment for chronic obstructive pulmonary disease (COPD) is only loosely defined. We evaluated if a lower forced expiratory volume in 1 s (FEV1) identifies a population more likely to benefit from dual therapy than monotherapy among group B COPD patients in whom Global initiative for Chronic Obstructive Pulmonary Disease (GOLD) recommends monotherapy as initial treatment. Methods This was a patient-level pooled analysis of phase-3 randomized controlled trials involving dual bronchodilators. Study patients were classified into two groups based on the FEV1 of 50% of the predicted value (GOLD I/II versus GOLD III/IV). We evaluated the efficacy of dual versus monotherapy (long-acting beta-2 agonist [LABA] or long-acting muscarinic antagonist [LAMA]) between these two groups in the following outcomes: changes in trough FEV1, the St. George’s Respiratory Questionnaire (SGRQ) score, the proportion of SGRQ responders, time to first exacerbation, and risk of adverse events. Results A total of 14,449 group B patients from 12 studies were divided into GOLD III/IV (n = 8043) or GOLD I/II group (n = 6406). In the GOLD III/IV group, dual therapy was significantly more effective in improving FEV1, reducing SGRQ scores, and achieving a higher proportion of SGRQ responders compared with either LABA or LAMA. Dual therapy also showed a significantly longer time to first exacerbation compared with LABA in the GOLD III/IV group. In contrast, in the GOLD I/II group, the benefits of dual therapy over monotherapy were less consistent. Although dual therapy resulted in significantly higher FEV1 than either LABA or LAMA, it did not show significant differences in the SGRQ score and proportion of SGRQ responders as compared with LABA. The time to first exacerbation was also not significantly different between dual therapy and either LABA or LAMA in the GOLD I/II group. Conclusions Dual therapy demonstrated benefits over monotherapy more consistently in patients with lower FEV1 than those with higher FEV1.

Luigino Calzetta,1 Angelo Coppola,2 Beatrice Ludovica Ritondo,3 Matteo Matino,3 Alfredo Chetta,1 Paola Rogliani2,3 1Department of Medicine and Surgery, Respiratory Disease and Lung Function Unit, University of Parma, Parma, Italy; 2Division of Respiratory Medicine, University Hospital “Policlinico Tor Vergata”, Rome, Italy; 3Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome “Tor Vergata”, Rome, ItalyCorrespondence: Paola Rogliani Department of Experimental MedicineUniversity of Rome “Tor Vergata”, Via Montpellier 1, Rome 00133, ItalyTel +39 06 2090 4656Email paola.rogliani@uniroma2.itAbstract: Long-acting muscarinic receptor antagonists (LAMAs) are the cornerstone for the treatment of chronic obstructive pulmonary disease (COPD); furthermore, tiotropium is approved as add-on therapy in severe asthmatic patients. Accumulating evidence suggests that LAMAs may modulate airway contractility and airway hyperresponsiveness not only by blocking muscarinic acetylcholine receptors (mAchRs) expressed on airway smooth muscle but also via anti-inflammatory mechanisms by blocking mAchRs expressed on inflammatory cells, submucosal glands, and epithelial cells. The aim of this systematic review, performed according to the PRISMA-P guidelines, was to provide a synthesis of the literature on the anti-inflammatory impact of muscarinic receptor antagonists in the airways. Most of the current evidence originates from studies on tiotropium, that demonstrated a reduction in synthesis and release of cytokines and chemokines, as well as the number of total and differential inflammatory cells, induced by different pro-inflammatory stimuli. Conversely, few data are currently available for aclidinium and glycopyrronium, whereas no studies on the potential anti-inflammatory effect of umeclidinium have been reported. Overall, a large body of evidence supports the beneficial impact of tiotropium against airway inflammation. Further well-designed randomized controlled trials are needed to better elucidate the anti-inflammatory mechanisms leading to the protective effect of LAMAs against exacerbations via identifying suitable biomarkers.Keywords: muscarinic receptor antagonist, LAMA, tiotropium, inflammation, systematic review

Objective The aim of this study was to evaluate the quality of diagnosis and treatment of COPD using Big Data methodology on the Savana Manager 2.1 clinical platform. Materials and methods A total of 59,369 patients with a diagnosis of COPD were included from a population of 1,219,749 adults over 40 years of age. Results In total, 78% were men. Spirometry data were available for only 26,453 (43.5%) subjects. Disease severity was classified in 18,172 patients: 4396 mild, 7100 moderate, and 6676 severe, although only 27%, 34%, and 28%, respectively, presented obstructive spirometry. The clinical management of COPD is mainly the responsibility of the primary care and pulmonology departments, while internal medicine and, to a lesser extent, geriatrics also participate. Drug treatment was based on bronchodilators and inhaled corticosteroids (ICS). A marked decline in the use of long-acting beta-2 agonists (LABA) in monotherapy and a slight reduction in ICS/LABA combinations, associated with a long-acting anticholinergic (LAMA) in 74% of cases, were observed. All-cause in-hospital mortality among the overall population was 5.6% compared to 1% of the general population older than 40 years. In total, 35% were admitted to hospital, with an average stay of 6.6 days and an in-hospital mortality rate in this group of 10.74%. Discussion This study identifies the main features of an unselected COPD population and the main errors made in the management of the disease.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality. Early detection and appropriate treatment and management of COPD can lower morbidity and perhaps mortality. Clinicians in the primary care setting provide the majority of COPD care and are pivotal in the diagnosis and management of COPD. In this review, we provide an overview of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2020 report, with a focus on the management of COPD in the primary care setting. We discuss the pathophysiology of COPD; describe COPD risk factors, signs, and symptoms that may facilitate earlier diagnosis of COPD; and reinforce the importance of spirometry use in establishing the diagnosis of COPD. Disease monitoring, as well as a review of the 2020 GOLD treatment recommendations, is also discussed. Patients and families are important partners in COPD management; therefore, we outline simple steps that may assist them in caring for those affected by COPD. Finally, we discuss nonpharmacological treatment options for COPD, COPD monitoring tools that may aid in the evaluation of disease progression and response to therapy, and the importance of developing a COPD action plan on an individualized basis.

Background: Acute chemical poisoning is a significant global health problem. Chemical poisons include agrochemical, household and industrial poison subtypes. The present study used a probabilistic model based on age, gender and type of poison consumed by the patient to predict the outcome in acute suicidal poisoning cases. Material and methods: A prospective observational study was conducted at emergency department of SMS Hospital, Jaipur, India, from January 2019 to February 2020. Patients over 15 years of age with poisoning severity score 2 or above were included in the study. Probabilistic model was used to predict the outcome measured in terms of cure, death and left against medical advice (LAMA) using Minitab 14. Results: Poisoning cases were 0.32 % of all emergency presentations. Out of them, 857 (59.6 %) had consumed chemical poison. Their mean age was 32 years and men to women ratio was 1.22. Agrochemical subtype was most common followed by household and industrial poisoning. Analysis by Probabilistic model showed that person between 30-60 years is more likely to be cured and chances of death and LAMA are highest in age group 60-75. Gender-wise, men have higher possibility for recovery. Besides, a person has highest chances of recovery in case of household poisons; death is most common in industrial poisons and LAMA in agrochemical poisons. Conclusion: The study concluded that in poisoning, patients' basic information like age, gender, type of poison consumed can be used to identify high death probability and LAMA risk patients. It will assist in designing and monitoring the most effective strategies for them.

Luca Richeldi,1 Alessio Piraino,2 Francesco Macagno,1 Gianluigi Micarelli,2 Eleonora Ingrassia2 1Unità Operativa Complessa di Pneumologia, Università Cattolica del Sacro Cuore, Fondazione Policlinico A, Gemelli, Rome; 2Chiesi Italia S.p.a., Parma, ItalyCorrespondence: Gianluigi MicarelliChiesi Italia S.p.a., Via Giacomo Chiesi 1, Parma 43122, ItalyTel +39 345 6350692Fax +39 0521 279592Email g.micarelli@chiesi.comBackground: The fixed triple combination Beclometasone dipropionate/Formoterol fumarate/Glycopyrronium (BDP/FF/G, Trimbow®), an extrafine formulation in a unique pressurized metered dose inhaler, is indicated for the maintenance treatment in adult patients with moderate to severe COPD, not adequately treated by ICS/LABA or LABA/LAMA. Besides the evidence from three randomized controlled trials, the impact of fixed triple therapy has not been extensively evaluated in a real-world population of COPD patients. TRITRIAL (TRIple Therapy in Real life: Impact on Adherence and HeaLth status) is a non-interventional study to assess the effect of BDP/FF/G in a real world setting in Italy.Design: TRITRIAL is a 12-month, multicenter, cohort, prospective, longitudinal observational study. Two follow-up visits will be performed at 6 and 12 months, respectively. The study includes the collection of anamnestic clinical and functional data before the start of BDP/FF/G. The study is built for digital conduction, from signature of the informed consent on a dedicated web platform, to the collection of questionnaires and clinical data on the eCRF.Population: A total of 800 patients with COPD ranging from Global Initiative for Obstructive Lung Disease (GOLD) stages 2 to 4, receiving therapy with BDP/FF/G according to the Summary of Product Characteristics and local clinical practice, will be recruited. All concomitant therapies will be permitted for the duration of the study.Evaluations: The primary endpoint is the change of CAT score at 12 months versus baseline. Secondary endpoints are adherence, health-related quality of life, sleep quality, disease-related outcomes (lung function and COPD exacerbations), device usability, economic resources consumption, and safety.Conclusion: TRITRIAL study is expected to give relevant information about effectiveness of BDP/FF/G fixed triple therapy in a real-life setting of patients with COPD, where adherence, usability of inhalers and patient’s preference of the device are crucial factors for the success of the therapy.Keywords: COPD, symptoms, health status, adherence, LAMA, LABA, ICS

Background: The increase in cesarean section delivery requires attention. Mortality and mor­bidity rates for mother and fetus increase in line with the increase in cesarean section delivery. This study aimed to analyze the factors affecting the delivery of cesarean section. Subjects and Method: This was an analytical observational study with a case-control design. The study was conducted at Tarakan Hospital, North Kalimantan, from 2018 to 2020. There were 200 study subjects as the sample of this study that was selected by purposive sampling. The dependent variable was cesarean section delivery. The independent variables were parity, age, history of the disease, medical indications, and ANC history. This study used medical records to collect the data with multiple logistic regression analysis. Results: Cesarean section delivery increased with multiparous (OR= 1.26; 95% CI= 1.67 to 7.45; p= 0.001), age

Background: Various combinations of inhaled corticosteroid (ICS), long-acting muscarinic antagonist (LAMA), and long-acting beta-agonist (LABA) have been used as triple therapy for stable chronic obstructive pulmonary disease (COPD). Objective: Our study was conducted to answer whether there were significant differences among various combinations in efficacy, for reducing exacerbation or mortality, and in safety, for increasing cardiovascular events or pneumonia. Method: We searched parallel-group randomized controlled trials (RCTs) comparing ICS/LAMA/LABA with other inhaled drugs in patients with stable COPD for at least 12 weeks in PubMed, EMBASE, the Cochrane Library, and clinical trial registries from inception to December 31, 2019. We conducted a network meta-analysis with Bayesian statistics using a random-effects model with heterogeneous variance structure (PROSPERO, CRD42019126757). Results: Nine different combinations of ICS/LAMA/LABA were identified in 21 RCTs containing 29,892 patients with moderate to very severe COPD. We could not find any significant evidence suggesting a better treatment for reducing total exacerbations or all-cause mortality among ICS/LAMA/LABA combinations. There were also no significant differences in moderate to severe exacerbation, COPD-related mortality, or cardiovascular disease-related mortality among ICS/LAMA/LABA combinations, and the risk of major adverse cardiovascular events was not different. A significantly lower risk of pneumonia was found in fluticasone propionate (FP)/glycopyrrolate/salmeterol (SAL) than FP/tiotropium/SAL {median odds ratio [OR] (95% credible interval [CrI]) = 0 [0–0.72]} and FP/umeclidinium/SAL {median OR (95% Crl) = 0 [0–0.97]}. Conclusion: There were no significant differences in clinical outcomes, including acute exacerbation and all-cause mortality among various ICS/LAMA/LABA combinations in patients with moderate to very severe COPD.

The spreading of Buddhism has implanted a profound effect on the social, political and ideological culture and tradition of the Mongolian. A vivid example of this can be seen in the relationship between the Tibetan monks such as Lama Pagba and the Mongol princes of the Yuan Dynasty. For example, Lama Pagba wrote numerous literary works on the basis of Buddhist teachings and sent them to the rulers of the Yuan Dynasty, such as Chingim, the prince, Mangal, Zevegtumur, Nomugan and Tumurbukh. The purpose of this article is to analyze these sources.

David Singer,1 Lindsay GS Bengtson,2 Caitlin Elliott,2 Ami R Buikema,2 Jessica Franchino-Elder1 1Health Economics and Outcomes Research, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA; 2Health Economics and Outcomes Research, Optum, Eden Prairie, MN, USACorrespondence: David SingerBoehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USATel +1-203-791-6409Email David_2.singer@Boehringer-Ingelheim.comBackground: Chronic obstructive pulmonary disease (COPD) is often managed with inhaled long-acting muscarinic antagonists (LAMAs), yet real-world data on healthcare resource utilization (HRU) by inhaler type are lacking. This study compared HRU after LAMA initiation with a soft mist inhaler (SMI) versus a dry powder inhaler (DPI).Patients and Methods: Inclusion criteria were COPD diagnosis, age ≥ 40 years, LAMA initiation (index date = first LAMA SMI or DPI claim 9/1/14— 6/30/18), and Medicare Advantage enrollment 1 year pre-index (baseline) to ≥ 30 days post-index (follow-up). Patients were followed to the earliest of discontinuation, switch, disenrollment, 1 year, or study end (7/31/18). Exclusion criteria were asthma, cystic fibrosis, or lung cancer diagnoses, unavailable demographics, multiple index LAMAs, or baseline LAMA use. Cohorts (SMI or DPI) were balanced on baseline characteristics using inverse probability of treatment weighting. Outcomes included per patient per month (PPPM) COPD-related HRU encounters, and exacerbations (defined as moderate [ambulatory visit with corticosteroid or antibiotic within ± 7 days] or severe [emergency visit or inpatient admission]); and 30-day readmissions following COPD-related hospitalizations.Results: After weighting, cohorts (SMI [n=5360] and DPI [n=22,880]) were similar in age (72 and 73 years, respectively), gender (both 52% female), and COPD severity score (31.3 and 31.5, respectively). Cohorts had similar counts of follow-up HRU encounters. However, the SMI cohort had fewer (mean ± standard deviation) COPD-related exacerbations (0.054± 0.082 vs DPI cohort 0.059± 0.088 PPPM, p< 0.001) overall. Moreover, the SMI cohort had fewer severe exacerbations (0.030± 0.058 vs DPI: 0.034± 0.065 PPPM, p< 0.001). Hospitalizations among SMI patients had a lower adjusted odds of readmission versus hospitalizations among DPI patients (odds ratio: 0.656, 95% confidence interval= 0.460, 0.937; p=0.020).Conclusion: SMI initiators had significantly fewer COPD-related exacerbations than DPI initiators. In addition, lower odds of readmissions were observed following COPD-related hospitalizations among the SMI cohort, as compared with the DPI cohort.Keywords: chronic obstructive pulmonary disease, COPD, long-acting muscarinic antagonist, LAMA, soft mist inhaler, SMI, dry powder inhaler, DPI, healthcare resource utilization, readmissions, exacerbations

Wen-Chien Cheng,1– 6 Biing-Ru Wu,1,3,5,6 Wei-Chih Liao,1,2,4,7 Chih-Yu Chen,1 Wei-Chun Chen,1,3– 6 Te-Chun Hsia,1,4,8 Chih-Yen Tu,1– 3 Chia-Hung Chen,1,2,7 Wu-Huei Hsu1 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; 2School of Medicine, China Medical University, Taichung, Taiwan; 3Department of Life Science, National Chung Hsing University, Taichung, Taiwan; 4Department of Internal Medicine, Hyperbaric Oxygen Therapy Center, China Medical University Hospital, Taichung, Taiwan; 5Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan; 6Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan; 7Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; 8Department of Respiratory Therapy, China Medical University, Taichung, TaiwanCorrespondence: Chia-Hung Chen; Chih-Yu ChenDepartment of Internal Medicine, China Medical University Hospital, No. 2, Yude Road, Taichung, TaiwanEmail hsnu758@gmail.com; cychen0808@gmail.comPurpose: Triple therapy versus dual therapy for chronic pulmonary obstructive disease (COPD) can reduce symptoms, limit the risk of acute exacerbations (AEs) as well as improve lung function. Currently, studies that feature clinically important deterioration (CID) as a composite endpoint to assess the need for treatment intensification for patients maintained on dual therapy remained to be scarce.Patients and Methods: This study is a retrospective analysis (January 2014 to January 2018) of COPD patients that presented with moderate to severe AEs during the previous year with blood eosinophil counts ≥ 100 cells/μL. The first line of therapy included a combination of inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA). Composite CID was used in assessing the response to treatment after 24 weeks of therapy.Results: This study included 110 patients, of which 49 patients reportedly experienced CID. The most common events of CID include a decline in forced expiratory volume in 1 second (FEV1) ≥  100 mL from baseline (25/49, 51%) and an increase in COPD Assessment Test (CAT) scores ≥ 2 (13/49, 26.5%); many of these patients respond to the addition of a long-acting muscarinic antagonist (LAMA). Seven patients (7/110, 6.3%) experienced moderate to severe exacerbations while undergoing treatment with ICS/LABA. Univariate and multivariate analyses have identified low baseline FEV1 (OR = 0.81, p = 0.004), high CAT score (OR = 1.89, p = 0.004), and the frequency of AE (OR = 19.86, p = 0.021) as independent predictors of CID. A baseline FEV1 of ≤ 42%, an initial CAT score ≥ 18, and AE ≥ 2 last year were considered the optimal cut-off values, which were identified via receiver operating characteristics (ROC) curve analysis.Conclusion: Triple therapy (ICS/LABAs/LAMAs) may be considered as first-line treatment in patients experiencing more than 2 times moderate to severe AEs of COPD in the previous year and who have blood eosinophil counts ≥ 100 cells/μL, reduced lung function (FEV1 ≤ 42%), and more symptoms (CAT score ≥ 18).Keywords: inhaled corticosteroid, ICS, long-acting muscarinic antagonist, LAMA, long-acting β2 agonist, LABA, triple therapy, chronic pulmonary obstructive disease, COPD, clinically important deterioration, CID

Background There is a large gap in the treatments for patients with COPD according to the Global Initiative for COPD (GOLD) recommendations. Determining the situation of therapies in the real world is necessary. This study aimed to characterize the real-world practical therapies of COPD and prognosis of patients after treatment for 1 year. Methods This study was a multicenter prospective observational study performed using a database set up by the Second Xiangya Hospital of Center South University. Detailed usage information for pharmacotherapies and nonpharmacotherapies for patients was collected, as well as the consistency of recommendations and patient adherence. Moreover, the effect of therapies after 1 year was calculated by comparing lung function and symptoms. Results Ultimately, 4,796 patients with COPD from 12 hospitals in China were eligible. LAMA (39.1%), LAMA + LABA/ICS (39.0%) and LABA/ICS (14.4%) were the top three inhalants. We found that 42.7% of Group A patients, 61.6% of Group B patients and 30% of Group C patients were following inappropriate therapy, especially overuse of ICS. Only 3.9% (95% CI 2.4, 5.4) of patients used oxygen therapy, and 1.8% (95% CI 1.5, 2.3) used noninvasive positive pressure ventilation at home. Among these patients, 33.2% had poor adherence. A total of 452 patients completed 1 year of follow-up. After 1 year of treatment, the lung function of FEV1/FVC decreased (P=0.001) and the mMRC score increased (P 0.05). Conclusion This study highlights a significant discrepancy between recommendations for managing patients with COPD in GOLD report, and in real-world clinical practice in China. Over-prescription of ICS and under-prescription of nonpharmacologic therapy were common. The adherence to treatment of patients was poor, and the real-life treatment effectiveness was unsatisfactory. More attention should be paid to the implementation of recommendations and standardized administration of therapies.

The aim of this study was to review clinical evidence supporting the use of fixed-dose combination of tiotropium and olodaterol, a long-acting muscarinic antagonist (LAMA) and a long-acting βFor this narrative review, the available literature was searched to identify studies including patients with COPD receiving tiotropium and olodaterol as either monotherapy or combination therapy and studies including patients with COPD receiving inhaled corticosteroids (ICS) in addition to long-acting bronchodilators. Relevant studies were included in the review.Patients with COPD are often prescribed ICS therapy, which, when used over a long term, can be associated with local and systemic adverse effects. The GOLD 2020 report recommends dual bronchodilator therapy as both an initial and follow-up treatment option. A LABA + LAMA combination is mechanistically synergistic, and cumulative evidence surrounding the efficacy and safety of fixed-dose combination of tiotropium and olodaterol supports therapeutic advantages over monotherapy in most patients with COPD.The early stages of COPD may represent a "window of therapeutic opportunity" during which initiation of tiotropium and olodaterol dual bronchodilator therapy may improve lung function and quality of life and reduce exacerbations in patients with COPD.