Therapy Of Obstructive Pulmonary Disease Research Articles

Relationship between risk, cumulative burden of exacerbations and mortality in patients with COPD: modelling analysis using data from the ETHOS study

BackgroundThe major drivers of cost-effectiveness for chronic obstructive pulmonary disease (COPD) therapies are the occurrence of exacerbations and deaths. Exacerbations, including acute and long-term events, can cause worsening of COPD and lead to an increased risk of further exacerbations, and ultimately may elevate the risk of death. In contrast to this, health economic models are based on COPD severity progression. In this post hoc analysis of the ETHOS study, we focus on the progression of COPD due to exacerbations and deaths.MethodsWe fitted semi-parametric and fully parametric multi-state Markov models with the following five progressive states: State 1, no exacerbation; State 2, 1 moderate exacerbation; State 3, ≥ 2 moderate exacerbations; State 4, ≥ 1 severe exacerbations; State 5, death. The models only allowed a patient to transition to a worsened health state, and transitions did not necessarily have to be to the next adjacent state. We used the multi-state models to analyse data from ETHOS, a phase III, 52-week study assessing the efficacy and safety of triple therapy with budesonide/glycopyrronium/formoterol fumarate dihydrate in moderate-to-very severe COPD.ResultsThe Weibull multi-state Markov model showed good fit of the data. In line with clinical evidence, we found a higher mortality risk after a severe exacerbation (11.4-fold relative ratio increase [95% CI, 7.7–17.0], 6.4-fold increase [95% CI, 3.8–10.8] and 5.4-fold increase [95% CI, 2.9–10.3] relative to no exacerbations, 1 moderate exacerbation or ≥ 2 moderate exacerbations, respectively). One moderate exacerbation increased mortality risk 1.8-fold (95% CI, 1.1–2.9) vs no exacerbations. We also found a higher risk of severe exacerbation and mortality following ≥ 2 moderate exacerbations.ConclusionMulti-state modelling of patients with COPD in ETHOS found an acute and chronic effect of severe exacerbations on mortality risk. Risk was also increased after a moderate exacerbation. Clinical management with effective pharmacotherapies should be optimised to avoid even moderate exacerbations. Modelling with exacerbations could be an alternative to current COPD models focused on disease progression.Trial registrationNCT02465567

Features and significance of the early bronchodilatation effect of the first dose of a long-acting bronchodilator alone and in fixed combination in the treatment of chronic obstructive pulmonary disease

The early bronchodilatory effects of the first dose of long-acting anticholinergics (glycopyrronium and tiotropium) were compared with those of a fixed double combination of long-acting bronchodilators of various classes (indacaterol/glycopyrronium) in patients with stable chronic obstructive pulmonary disease. The possibility of using the results of an early bronchodilatory response to predict their effectiveness in the basic therapy of chronic obstructive pulmonary disease is evaluated. A total of 176 patients with chronic obstructive pulmonary disease were examined. The patients were randomized into three groups. The first group (n = 66) took glycopyrronium, the second group (n = 60) received a combination of indacaterol/glycopyrronium, and the third group (n = 50, control) took tiotropium. Broncholytic tests with the listed drugs were evaluated. The early bronchodilatory effect of the first dose of 110/50 mcg indacaterol/glycopyrronium was manifested by significant bronchodilation (p 0.001) from 30 min, reached its maximum value 60 min after drug intake, and persisted after a 28-day course of treatment. The combination of indacaterol/glycopyrronium provided rapid and prolonged bronchodilation in patients with stable chronic obstructive pulmonary disease, demonstrating advantages over the isolated use of glycopyrronium and tiotropium. Maximization of bronchodilation by the sequential use of glycopyrronium and salbutamol leads to an increase in the volume of forced exhalation in the first second on the 90th min, comparable with the results of indacaterol/glycopyrronium on the 60th min after drug intake, which indicates the clinical feasibility of maximizing bronchodilation with drugs both separately and in combination. Based on a direct positive correlation between the initial value of the forced expiratory volume in the first second and the value on day 28 of indacaterol/glycopyrronium therapy, an equation for predicting the individual effectiveness of the drug during treatment is derived.

Predictors of chronic opioid therapy in Medicaid beneficiaries with HIV who initiated antiretroviral therapy

The factors associated with chronic opioid therapy (COT) in patients with HIV is understudied. Using Medicaid data (2002–2009), this retrospective cohort study examines COT in beneficiaries with HIV who initiated standard combination anti-retroviral therapy (cART). We used generalized estimating equations on logistic regression models with backward selection to identify significant predictors of COT initiation. COT was initiated among 1014 out of 9615 beneficiaries with HIV (male: 10.4%; female: 10.7%). Those with older age, any malignancy, Hepatitis C infection, back pain, arthritis, neuropathy pain, substance use disorder, polypharmacy, (use of) benzodiazepines, gabapentinoids, antidepressants, and prior opioid therapies were positively associated with COT. In sex-stratified analyses, multiple predictors were shared between male and female beneficiaries; however, chronic obstructive pulmonary disease, liver disease, any malignancy, and antipsychotic therapy were unique to female beneficiaries. Comorbidities and polypharmacy were important predictors of COT in Medicaid beneficiaries with HIV who initiated cART.

Efficacy and safety of single-inhaler extrafine triple therapy versus inhaled corticosteroid plus long-acting beta2 agonist in eastern Asian patients with COPD: the TRIVERSYTI randomised controlled trial

BackgroundA single-inhaler extrafine triple combination of beclometasone dipropionate (BDP), formoterol fumarate (FF) and glycopyrronium (G) has been developed for maintenance therapy of chronic obstructive pulmonary disease (COPD). This study evaluated the efficacy and safety of BDP/FF/G in patients in three eastern Asian areas: China, Republic of Korea and Taiwan.MethodsTRIVERSYTI was a double-blind, randomised, active-controlled, parallel-group study in patients with COPD, post-bronchodilator forced expiratory volume in 1 s (FEV1) < 50% predicted, ≥ 1 exacerbation in the previous 12 months, and receiving inhaled maintenance medication. Patients received either extrafine BDP/FF/G 100/6/10 µg via pressurised metered-dose inhaler, or non-extrafine budesonide/formoterol (BUD/FF) 160/4.5 µg via dry-powder inhaler, both administered as two puffs twice-daily for 24 weeks. The co-primary objectives (analysed in the overall population) were to demonstrate superiority of BDP/FF/G over BUD/FF for change from baseline in pre-dose morning and 2-h post-dose FEV1 at Week 24 (these were analysed as key secondary objectives in the China subgroup). The rate of moderate/severe COPD exacerbations was a secondary endpoint.ResultsOf 708 patients randomised, 88.8% completed. BDP/FF/G was superior to BUD/FF for pre-dose and 2-h post-dose FEV1 at Week 24 [adjusted mean differences 62 (95% CI 38, 85) mL and 113 (87, 140) mL; both p < 0.001]. The annualised moderate/severe exacerbation rate was 43% lower with BDP/FF/G [rate ratio 0.57 (95% CI 0.42, 0.77); p < 0.001]. Adverse events were reported by 61.1% and 67.0% patients with BDP/FF/G and BUD/FF. Results were similar in the China subgroup.ConclusionsIn patients with COPD, FEV1 < 50% and an exacerbation history despite maintenance therapy, treatment with extrafine BDP/FF/G improved bronchodilation, and was more effective at preventing moderate/severe COPD exacerbations than BUD/FF.Trial registration CFDA CTR20160507 (registered 7 Nov 2016, http://www.chinadrugtrials.org.cn/index.html).

Comparative analysis of medications for antibiotic therapy of chronic obstructive pulmonary disease in the pharmaceutical market of Ukraine and France

The aim of the work – comparative analysis of the assortment of registered medicines for antibiotic therapy of chronic obstructive pulmonary disease (COPD) in the domestic market and similar segment of the French market. Materials and methods. The study of drug assortment in Ukraine was carried out according to the State Register of Medicines of Ukraine , employing the directory of medicines Compendium online , Anatomical Therapeutic Chemical Classification , web-resource Tabletki.UA . Database Base de donnees publique des medicaments was consulted while studying the pharmaceutical market in France. The following methods were used: information search, marketing analysis, graphical, comparative and logical methods. Results . A comparative analysis of medicines employed in Ukraine and France for antibiotic therapy of chronic obstructive pulmonary disease (COPD) was performed. Conclusions . Pharmaceutical markets of drugs for antibiotic therapy of COPD in Ukraine and France are analyzed. As of January 2020, there are 43 brand names (BN) of medicines with 73 available range items registered in Ukraine, and 87 BN medicines with 150 available range items registered in France. The analysis of drugs assortment showed that foreign drugs predominate in Ukraine and France, their share is 84 % and 55 %, respectively. Among the drug-importing countries, the leaders in Ukraine are India and Germany, and in France they are Spain, England and Germany. The share of domestic drugs in Ukraine and France is lower – 16 % and 45 %, respectively. The leaders among domestic manufacturers in Ukraine are Yuria-Pharm LLC and Astrapharm LLC , in France they are Sanofi Winthrop Industrie , Mylan S.A.S. , Delpharm Tours , Delpharm Lille S.A.S. and Panpharma . In the two countries, the majority of drugs for COPD antibiotic therapy treatment is manufactured as powders for solutions and injections, and as tablets; their share in Ukraine is 41 % and 33 %, in France – 19 % and 59 %, respectively. Monocomponent drugs prevail in Ukraine and France. Since the Ukrainian pharmaceutical market, in comparison with the French drug market, is significantly dominated by foreign drugs, it is important to develop new domestic drugs that would be used in COPD treatment.

Inhalation glucocorticosteroids in the treatment of chronic obstructive pulmonary disease

The main objectives of chronic obstructive pulmonary disease (COPD) therapy are to reduce the severity of symptoms and the risk of exacerbations. The article discusses the role of local and systemic inflammation in the pathogenesis of COPD as well as various mechanisms of pharmacological influence on it. Approaches to prescribing basic therapy for patients with COPD, recommended by various national and global guidelines (clinical recommendations of the Russian respiratory society, criteria of the Global Initiative for Chronic Obstructive Lung Disease (GOLD), guidelines of the National Institute for Health and Clinical Excellence (NICE)), as well as recommendations on the therapy frequency review are considered. Currently, so-called triple combinations – fixed combinations of double bronchodilators with inhaled glucocorticosteroids – are being developed and registered in the world, and their place and significance in the treatment of COPD raise many discussions. The paper discusses the role of fixed triple combinations in reducing the incidence of COPD exacerbations, the impact on functional and patient-reported outcomes, and provides recommendations for the use of triple combinations in patients with COPD, taking into account the benefit/risk ratio.

Dose dependent effects of tadalafil and roflumilast on ovalbumin-induced airway hyperresponsiveness in guinea pigs

ABSTRACT Introduction: Chronic obstructive diseases of airways associated with cough and/or airway smooth muscle hyperresponsiveness are usually treated with bronchodilating and anti-inflammatory drugs. Recently, selective phosphodiesterase (PDE) 4 inhibitors have been introduced into the therapy of chronic obstructive pulmonary disease. Several studies have demonstrated their ability to influence the airway reactivity and eosinophilic inflammation by increasing the intracellular cAMP concentrations also in bronchial asthma. Furthermore, the expression of PDE5 in several immune cells suggests perspectives of PDE5 inhibitors in the therapy of inflammation, as well. Purpose: The aim of this study was to assess the dose-dependent effects of PDE4 and PDE5 inhibitors in allergic inflammation. Therefore, the effects of 7-days administration of PDE4 inhibitor roflumilast and PDE5 inhibitor tadalafil at two different doses in experimentally-induced allergic inflammation were evaluated. Materials and Methods: In the study, male adult guinea pigs were used. Control group was non-sensitized. Other animals were sensitized with ovalbumin over two weeks and thereafter treated intraperitoneally for 7 days with roflumilast or tadalafil (daily dose 0.5 mg/kg or 1.0 mg/kg b.w.), or with vehicle. Results: Both roflumilast and tadalafil reduced specific airway resistance after nebulization of histamine (marker of in vivo airway reactivity) at both doses used. The in vitro airway reactivity to cumulative doses of acetylcholine was significantly reduced for roflumilast at higher dose, predominantly in the lung tissue strips. Histamine-induced contractile responses were significantly influenced in both lung and tracheal tissue strips, predominantly at the higher doses. Tadalafil led to a decrease in contractile responses induced by both acetylcholine and histamine, with more significant effects in the lung tissue strips. These changes were associated with decreased numbers of circulating leukocytes and eosinophils and concentrations of interleukin (IL)-4, IL-5 and TNF-α in the lung homogenate. Conclusions: The selective PDE4 and PDE5 inhibitors alleviated allergic airway inflammation, with more significant effects at the higher doses.

Patient preferences for dry powder inhaler attributes in asthma and chronic obstructive pulmonary disease in France: a discrete choice experiment

BackgroundDry powder inhalers (DPIs) are often used in asthma and chronic obstructive pulmonary disease (COPD) therapies. Using the discrete choice experiment (DCE) methodology, this study conducted in France was designed to assess patients’ preferences for different attributes of DPIs.MethodsAttributes of DPIs were defined based on a literature review, patient focus group discussions and interviews with healthcare professionals (qualitative phase of the study). An online survey was then conducted among French patients with asthma or COPD to elicit patient preferences and willingness to pay (WTP) for these attributes using the DCE methodology (quantitative phase). A fractional factorial design including three blocks of 12 choice sets was created. Each choice set comprised three alternatives: two fictitious inhalers and the patient’s current inhaler. Marginal utilities were estimated using a ranked ordered logit model. Interactions between attributes and disease (asthma or COPD) were tested.ResultsSix DPI attributes were defined based on the qualitative phase: ease of use/fool-proof priming; accurate and easy-to-read dose counter; dose confirmation; hygiene of the mouthpiece; flexibility of the device handling; ability to use the inhaler with breathing difficulties. Overall, 201 patients with asthma and 93 with COPD were included in the online survey. Patients with asthma placed most value on an inhaler that requires one step for dose preparation (WTP €4.83 [95% CI: €3.77–€5.90], relative to an inhaler requiring four steps) and one that could be used during episodes of breathing difficulties (WTP €4.49 [95% CI: €2.95–€6.02]). Patients with COPD placed most value on an inhaler that could be used during episodes of breathing difficulties (WTP €7.70 [95% CI: €5.65–€9.76]) and on the accuracy of the dose counter (WTP €5.87 [95% CI: €3.98–€ 7.77]).ConclusionThis study suggests that asthma and COPD patients would be willing to change their inhaler if they were offered the option of a new inhaler with improved characteristics and they place a high value on an inhaler with ease of use during breathing difficulty episodes.

A role of long-acting bronchodilator tiotropium / olodaterol fixed combination as the first-line therapy of chronic obstructive pulmonary disease. A Consensus of Expert Board of Russian Respiratory Society

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NEW POSSIBILITIES OF MILD BRONCHIAL ASTHMA THERAPY

In the bronchial asthma structure the mild form of the disease takes the leading place: from 50 to 75% of patients suffer from mild asthma. Modern diagnostics of disease in these patients and adequate therapy allow preventing the disease progress. This article discusses issues of determination of the bronchial asthma gravity, incidence rate, disease burden and standard approaches to therapy of the mild bronchial asthma. Particular attention is given to a new possibility of therapy of mild asthma in adult patients with the help of the combined drug Salbutamol/Beclomethazone represented in the form of an aerosol inhaler and intended for arrest of symptoms and permanent therapy of bronchial asthma and chronic obstructive pulmonary disease in adults from the age of 18. Use of fixed combination Salbutamol/Beclomethazone in the regime “on demand” in adult patients with mild bronchial asthma leads to increase of the time to the first exacerbation and reduction of the disease exacerbations, at the same time it is accompanied by the minimum cumulative dosage of the inhalation corticosteroid and allows overcoming the low commitment of patients to therapy by inhalation corticosteroids.

Living in the Wake of Chronic Obstructive Pulmonary Disease and Long-Term Oxygen Therapy

Background: Chronic Obstructive Pulmonary Disease (COPD) is the fourth leading cause of death in the world. COPD is a progressive disease that could lead to chronic hypoxemia, which requires treatment as domiciliary Long-Term Oxygen Therapy (LTOT). There is a need for increased knowledge about self-care strategies used by individuals living with COPD and LTOT. Objective: The aim was to explore experiences and self-care strategies in patients living with both COPD and LTOT. Sample: The sample consisted of five men and five women diagnosed with COPD being prescribed LTOT for more than one year. Method: Ten interviews were undertaken and analyzed for both manifest and latent content. Results: Living with COPD and LTOT was associated with experiences of guilt although there were doubts about what had caused the lung disease. Both the lung disease and the oxygen therapy had a negative impact on their self-image. Anxiety was expressed when thoughts about the remaining time occurred. There was a constant balance between diminishing abilities and increasing restrictions related to the lung disease and the therapy. In order to compensate for arising imbalance, self-care strategies had been initiated aimed at preserving the present state of health, enabling and facilitating physical activity and promoting a positive attitude. Conclusion: The current study suggests that individuals living with COPD and LTOT are encouraged to adopt self-care strategies directed towards maintaining stability with regard to the lung disease, the oxygen therapy, physical capability and emotional reactions.

Out Hospital Drug Consumption in Therapy of Obstructive Pulmonary Disease in Serbia in the Period from 2007 to 2012

Out Hospital Drug Consumption in Therapy of Obstructive Pulmonary Disease in Serbia in the Period from 2007 to 2012

MECHANISMS OF ANTICHOLINERGIC EFFECTS AND PROBABLE MECHANISMS OF THEIR POTENTIATION USING BETA-2-AGONISTS

Current basic therapy of chronic obstructive pulmonary disease includes inhaled long-acting bronchodilators. This article reviews mechanisms of action of anticholinergic drugs and their potentiation with beta-2-agonists. There are several upcoming fixed combinations of anticholinergics and beta-2-agonists. In 2013, the first fixed combination of anticholinergic glycopyrronium and beta-2-agonist indacaterol has been registered. A beta-2-agonist decreases acetylcholine release due to changes in the cholinergic neuronal transmission via presynaptic beta-2-adrenoreceptors that leads to better smooth muscle relaxation in bronchi caused by anticholinergics. Moreover, anticholinergic drug could reduce acetylcholineinduced constriction and amplify bronchodilation caused by beta-2-agonist. The combination of anticholinergic glycopyrronium and beta-2-agonist indacaterol is to be effective.

Anticholinergics for therapy of chronic obstructive pulmonary disease: focus on tiotropium

Recently, there is a progressive growth in new drugs and combinations for treatment of chronic obstructive pulmonary disease (COPD) that, on the one hand, promotes therapeutic opportunities but, on the other hand, impedes the best choice of the drug. Bronchodilators have been still the cornerstone of the pharmacotherapy of COPD. Anticholinergics as monotherapy or in combination with other drugs, such as long - acting beta - 2 - agonists, inhaled steroids, or roflumilast, are widespread therapeutic approach for these patients. A huge body of evidence has been accumulated about the safety and efficacy of long - acting anticholinergic tiotropium bromide which has been successfully used worldwide for more than 10 years. Longacting anticholinergics are one of the most actively developed and highly efficient drugs for management of COPD. There is limited evidence regarding clinical efficacy and safety of novel anticholinergics mostly obtained from phase III clinical trials which did not involve the real - life population of COPD patients; this fact prevents considering new long - acting anticholinergics as a definitive alternative for tiotropium bromide.

Long term therapy and outcome of chronic obstructive pulmonary disease with or without co-morbidity: the TORCH study

BACKGROUND COPD affects over 5% of the adult population, and it is the only major cause of mortality that is increasing worldwide. Patients with COPD don’t die usually of respiratory failure: indeed lung cancer and cardiovascular diseases are the leading causes of mortality in patients with mild to moderate COPD. Pulmonary and systemic inflammations are prominent. Inhaled corticosteroids have little effect on the rate of decline of lung function, but they reduce the frequency of exacerbations, especially when combined with an inhaled long-acting beta-agonist. AIM OF THE STUDY The combination of the long-acting beta-agonist salmeterol (SM) and the inhaled corticosteroid fluticasone propionate (FP) would reduce mortality among patients with COPD, as compared with usual care. The primary end-point was the time to death from any cause by 3 years. Secondary end-points were the frequency of exacerbations and health status. PATIENTS AND METHODS Of 8,554 patients recruited, 6,184 underwent randomization; the mean age was 65 years, and the mean value of postbronchodilator FEV1 was 44% of the predicted value. This double-blind study was conducted in 444 centers of 42 countries. After a 2-week run-in period, eligible patients were randomly assigned to treatment with the combination of SM at a dose of 50 μg and FP at a dose of 500 μg or SM alone at a dose of 50 μg, FP alone at a dose of 500 μg, or placebo, all taken as a dry powder with the use of an inhaler bid for 3 years. RESULTS There were 875 deaths within 3 years after randomization. The proportions of deaths from any cause at 3 years were 12.6% in the combination therapy group, 15.2% in the placebo group, 13.5% in the SM group, and 16.0% in the FP group. The absolute risk reduction for death in the combination-therapy group as compared with the placebo group was 2.6%, and the hazard ratio was 0.825 (95% confidence interval [CI], 0.681 to 1.002; p = 0.052), corresponding to a reduction in the risk of death at any time in the 3 years of 17.5% (95% CI, –0.2 to 31.9). DISCUSSION In this trial, the reduction in mortality from any cause did not meet the level of statistical significance (p = 0.052), but the treatment with the combination regimen resulted in significantly fewer exacerbations and improved health status and lung function, as compared with placebo. Mortality could be influenced mainly by factors unresponsive to the study drugs, or it is possible that this study was underpowered to detect this effect. There was also a high withdrawal rate, which was highest among patients in the placebo group. CONCLUSIONS Even though p = 0.052 is not statistically significant, 126 deaths for every 1,000 treated in the combination-therapy group, after 3 years, instead of 152 in the placebo group, is anyway an important result? Further investigation is needed in future large, prospective trials.

Pharmacogenetic effect of ADRB2 gene polymorphism on therapeutic response in chronic obstructive pulmonary disease

Summary. The purpose of this study was to evaluate effect of β2-adrenergic receptor gene polymorphisms on therapeutic response to β2-agonists and inhaled corticosteroids during 6-month therapy of chronic obstructive pulmonary disease (COPD). In 146 patients with stable COPD, polymorphisms of the amino acid positions 16 (Arg16/Gly16) and 27 (Gln27/Glu27) in the ADRB2 gene were assessed by allele-specific polymerase chain reaction. Gly16-Glu27-haplotype was associated with improvements in lung function, quality of life, and exercise tolerance after 6 months of combined treatment with long-acting β2-agonists and inhaled corticosteroids.

Novel effects of antiinflammatory therapy of chronic obstructive pulmonary disease

Novel effects of antiinflammatory therapy of chronic obstructive pulmonary disease

Candida esophagitis with fever alone in a patient with stroke

Background: Candida esophagitis is a rare disease, but its incidence is higher in patients with impaired immunity due to an underlying disease. Patients with candida esophagitis usually present with lower retrosternal pain or dysphagia, but they are sometimes asymptomatic. Several risk factors, including diabetes mellitus, malignancies, chronic obstructive pulmonary disease (COPD) and steroid therapy, have been shown to be associated with candida esophagitis. Candida esophagitis may mimic other disease processes and can thus be misdiagnosed.Case study: This study describes a case of candida esophagitis with fever alone in the patient with stroke. After a stroke attack, a 53-year-old man was hospitalized for rehabilitation. He had a fever unexpectedly, but the cause could not be found for 2 weeks. Esophagogastroduodenoscopy (EGD) was performed to find the cause of the fever and it was diagnosed as candida eosphagitis. Fever decreased respectively 4 days after anti-fungal therapy begun.Conclusion: Dysphagia, unexplained anaemia, loss of appetite and dyspepsia may require EGD to make a confirmative diagnosis. If unexplained fever is persistent without any of these symptoms, it is advisable to consider EGD in patients with stroke.

Joint Guideline Focuses on COPD Care

ANEW JOINT GUIDELINE FROM THE American College of Physicians (ACP), the American College of Chest Physicians (ACCP), the American Thoracic Society, and the European Respiratory Society highlights new information on the best use of diagnostic techniques for patients with signs and symptoms suggestive of chronic obstructive pulmonary disease (COPD) and recommends therapies for patients with stable COPD. COPD, a disabling condition that involves progressive airflow obstruction, is most often linked to long-term smoking. It is a common condition, which affects more than 5% of adults in the United States and contributes to $29.5 billion in medical costs each year. Because of the disease’s considerable impact, it was important to bring together all of the major professional organizations with expertise in caring for patients with COPD to reach a consensus on any areas where there is controversy and to avoid the confusion that could be caused by multiple guidelines, said Amir Qaseem, MD, PhD, director of clinical policy at the ACP in Philadelphia. “It’s the third leading cause of death in the United States and the 12th leading cause of morbidity,” Qaseem noted. “But there are still many patients not getting appropriate care.”

Issues on Safety of Long-Acting Muscarinic Antagonist

The prevention of and the controlling of symptoms, reductions in the frequency of exacerbations, and disease severity are central to the pharmacologic therapy of chronic obstructive pulmonary disease (COPD). COPD patients are inclined to be older, have more comorbidities, and use polypharmacy as a result. Long-acting inhaled muscarinic antagonists (LAMAs) is a preferred treatment modality. However, the cardiovascular (CV) safety of anti-cholinergics, including LAMA, has been an issue. In contrast, the results of the UPLIFT trial and a pooled analysis of data from 30 trials of tiotropium illustrates the association of tiotropium with reductions in the risk of all cause mortality, CV mortality and CV events. And, the UPLIFT trial provides clues regarding the additive advantages of tiotropium in COPD patients who already are using long-acting inhaled β2 agonists and inhaled corticosteroids. Following the contribution of tiotropium as a first LAMA, new LAMAs such as aclidinium and glycopyrrolate (NVA-237) seem to be emerging.