Prevention Of Chronic Obstructive Pulmonary Disease Exacerbations Research Articles

Exploring the Prevalence of Respiratory Failure in Adults Presenting With Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) poses a significant global health burden and is a leading cause of morbidity and mortality. Acute exacerbations of COPD often lead to respiratory failure, necessitating a thorough understanding of its prevalence. This study aimed to investigate the prevalence of respiratory failure among adult patients experiencing acute exacerbations of COPD. A descriptive, cross-sectional study was conducted over a span of seven months at the internal medicine department of Hayatabad Medical Complex, Peshawar. A total of 255 adult patients with acute exacerbations of COPD were included, and their demographic data, as well as arterial blood gas (ABG) analysis results, were collected. The prevalence of respiratory failure was defined by specific arterial blood gas criteria. The study revealed a notable prevalence of respiratory failure (41.18%) among COPD patients presenting with acute exacerbations. Factors such as older age and male gender were identified as being associated with a heightened risk of respiratory failure. In conclusion, acute exacerbations of COPD predominantly affect middle-aged males (65.5%), with the 51-60 age group being the most impacted. Respiratory failure was present in over 41% of cases. ABG analysis indicated significant acid-base imbalances, hypoxemia, and hypercapnia, with compensatory chronic respiratory acidosis. These findings highlight the need for targeted interventions to manage and prevent COPD exacerbations, especially in middle-aged men.

LABA/LAMA versus LABA/ICS fixed-dose combinations in the prevention of COPD exacerbations: a modeling analysis of literature aggregate data.

This study aimed to quantitatively compare the efficacy and safety of long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) and LABA/inhaled corticosteroid (ICS) fixed-dose combinations (FDCs) in preventing moderate or severe chronic obstructive pulmonary disease (COPD) exacerbations. A literature search was performed using public databases. The time course characteristics of the probability of a moderate or severe exacerbation in stable COPD patients treated with LABA/LAMA and LABA/ICS FDCs were described by the parametric survival function. A random-effects model in a single-arm meta-analysis was used to analyze the incidence of serious adverse events (SAEs) and pneumonia. Twenty studies including 23,955 participants were included. The proportion of participants with a history of COPD exacerbation (%) in the previous year and the postbronchodilator forced expiratory volume in the first second (FEV1) (%predicted) were important factors affecting drug efficacy. After adjusting the above factors to median levels of 100% and 45.5%, respectively, the moderate or severe exacerbation rates at 52weeks for olodaterol/tiotropium, formoterol/budesonide, indacaterol/glycopyrronium, formoterol/glycopyrronium, vilanterol/fluticasone, salmeterol/fluticasone, and vilanterol/umeclidinium were 38.3%, 41.0%, 42.6%, 47.0%, 47.5%, 47.9%, and 53.0%, respectively. In terms of safety, significant differences were observed among drugs containing different LABA/LAMA FDCs. This study showed that not all LABA/LAMA FDCs were superior to LABA/ICS FDCs in safety and in preventing moderate or severe exacerbations in patients with stable COPD, providing important quantitative information for COPD-related guidelines.

The impact of COPD on the private healthcare system in Brazil: an economic analysis

Objective: To assess healthcare resource utilization and hospitalization costs of patients with chronic obstructive pulmonary disease (COPD) exacerbations in the Brazilian private healthcare system. Methods: A retrospective cohort study, considering data from an administrative database of a private company (Orizon). Patients aged ≥40 years old and with at least one COPD-related claim identified by the ICD-10 code (J40 to J44) at any time during the eligibility period (January/2010 to December/2013) were included in the analysis. Follow-up was performed until December/2014, death or inactivation of a health plan. Sociodemographic characteristics, number of emergency visits, hospital admissions (number and length of stay), length of hospital stay in an intensive care unit (ICU), number of severe COPD exacerbations, therapeutic approach, and hospitalization costs were assessed. Results: The analysis included 8,254 COPD patients. Emergency visits, hospital admission, and exacerbation rates were 0.4, 0.2, and 0.1 per person-year, respectively. The mean length of hospital stays and the length of stay of patients requiring or not ICU stay were 16.6 (SD = 77.0), 8.7 (SD = 36.9), and 27.6 (SD = 109.7), respectively. Mean costs associated to emergency department visits and hospitalizations were 258.2 BRL (SD = 383.1) and 38,165.4 BRL (SD = 124,683.5), respectively. Hospitalizations costs without ICU stay were 11,810.1 BRL (SD = 31,144.1) and 74,585.3 BRL (SD = 182,808.1) for those with ICU utilization. Conclusion: Costs for COPD management during disease exacerbation are very high and may reach almost 75 thousand BRL per hospitalization. The prevention of COPD exacerbations and better disease control may reduce the economic burden on the private healthcare system in Brazil.

Frequency of Hypomagnesemia in Patients with Chronic Obstructive Pulmonary Disease (COPD)

Objective: The purpose of this study is to assess the prevalence of hypomagnesemia among COPD patients (COPD). Study design: A cross sectional study. Place and duration of study: I have been offered a position in the Medicine & Pulmonology Department at Nishtar Hospital in Multan, Pakistan, which I will begin in March 2016 and remain in until February 2018. Methodology: The non-probabilistic sequential sampling technique used to choose the final pool of 137 cases. Quantitative variables' means and standard deviations were determined. Quantitative evaluation included frequency counts and percentages for qualitative factors. Several effect modifiers have been taken into consideration via stratification, including age, diabetes, body mass index, COPD, high blood pressure, smoking, socioeconomic status, place of residence (race/ethnicity), and gender. A chi-square test for stratification was used to examine the data, and a P value of 0.05 was considered statistically significant. Results: 30.81±14.74 Nearly eighty-one percent of the sample had illnesses that lasted more than 18 months, and the median duration of illness was also months (112). Fifty patients, or 36.5% of the total, were found to have low magnesium levels, with a mean blood magnesium level of 1.520.54 meq/liter. Practical Implementation: There is a lack of data on the function of magnesium in preventing COPD exacerbations. Hypomagnesemia may prove to be helpful in establishing COPD exacerbation as a predictive factor, according to the research that is now being conducted. This could lead to the development of COPD intervention strategies other than the standard treatments, enhancing COPD patients' life quality, morbidity, and mortality. Conclusion: Our results provide evidence that hypomagnesemia is common among people with COPD. Male gender, greater age, lower socioeconomic status, diabetes, hypertension, tobacco use, and longer disease duration were all associated with low magnesium levels. Keywords: Chronic Obstructive pulmonary disease (COPD), frequency, hypomagnesemia.

Оптимальное лечение инфекционного риносинусита как инструмент профилактики обострений ХОБЛ

Background: many studies report on the association between upper and lower respiratory infections. Various theories explain this association. In particular, some evidence demonstrates that nasal symptoms in diseases of the nasal cavity and paranasal sinuses affect exacerbations of chronic obstructive pulmonary disease (COPD). Therefore, treatment for rhinosinusitis improves the overall health and quality of life of these patients. Aim: to assess the clinical efficacy, tolerability, and safety of a combined antibacterial, anti-inflammatory, and vasoconstrictive drug in mild and moderate acute rhinosinusitis and concomitant COPD. Patients and Methods: this study enrolled 50 male and female patients aged 41–65 years. The primary examination included complaints and history taking, examination, instrumental tests for ENT organs, and pulmonary consultation. All patients underwent digital diaphanoscopy during the first visit to rule out acute exudative rhinosinusitis. In addition, all patients filled out a subjective assessment questionnaire. Treatment continued for 10 days with an interim examination on day 5±1 after starting treatment. Study group patients received a combined drug Polydexa with phenylephrine (1 injection into each nostril 4 times daily for 10 days) and irrigation with isotonic saline. The control group patients received 2 doses of mometasone furoate twice daily into each nostril for 10 days and irrigation with isotonic saline. Topical vasoconstrictors were allowed to be used as needed. Results: significant differences in the improvement of inflammatory symptoms between the groups were reported as early as by the second visit. The effect occurred earlier and was more significant at all treatment steps in the study group. A natural association between upper respiratory infection (acute rhinosinusitis), treatment strategy choice, and COPD exacerbation was revealed. Meanwhile, more COPD exacerbations were detected in the control group than in the study group (7 vs. 4). Conclusion: in mild and moderate acute rhinosinusitis and concomitant COPD, the combined drug Polydexa with phenylephrine reduces the rate and severity of COPD exacerbations. KEYWORDS: rhinosinusitis, nasal symptoms, upper and lower respiratory tract inflammation, Haemophilus influenzae, chronic obstructive pulmonary disease, phenylephrine, neomycin sulfate, polymixin B. FOR CITATION: Ovchinnikov A.Yu., Miroshnichenko N.A., Nikolaeva Yu.O., Zaitsev A.A. Optimal treatment for infectious rhinosinusitis as a tool to prevent COPD exacerbations. Russian Medical Inquiry. 2023;7(8):511–517 (in Russ.). DOI: 10.32364/2587-6821-2023-7-8-6.

Tanshinone increases Hemopexin expression in lung cells and macrophages to protect against cigarette smoke-induced COPD and enhance antiviral responses

ABSTRACT Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease, while respiratory infections can elicit exacerbations in COPD patients to mediate increased mortality. Administration of Tanshinones (TS) derivatives has been demonstrated to protect against cigarette smoking (CS) and lipopolysaccharide (LPS)-induced COPD progression. However, the underlying molecular mechanisms and the roles of TS in mitigating the severity of viral-mediated exacerbations of COPD have not been elucidated. Here, we found that TS treatments significantly attenuated lung function decline, inflammatory responses and oxidative stress in CS and LPS-induced COPD mice. Subsequent RNA-seq analysis revealed significantly upregulated Hemopexin expression and enriched interferons (IFNs) signaling pathways in lung tissues of COPD mice upon TS treatments. Moreover, TS administration demonstrated Hemopexin-dependent beneficial roles in BEAS-2B lung cells and RAW264.7 macrophages, which was associated with the suppression of oxidative stress and ERK, NF-κB, and NLRP3 inflammasome signaling pathways-mediated inflammation. Furthermore, TS promoted IFN signaling and rescued impaired antiviral responses in CS and LPS-exposed lung cells that were infected by influenza virus. Notably, hemopexin over-expression in lung cells and macrophages recapitulated the pharmacological activities of TS. Taken together, these results indicate that TS administration is a promising and potential therapeutic strategy for treating COPD and preventing COPD exacerbations.

Vitamin D supplementation in chronic obstructive pulmonary disease patients with low serum vitamin D: a randomized controlled trial

ABSTRACTBackgroundVitamin D deficiency is frequently found in patients with chronic obstructive pulmonary disease (COPD). Vitamin D has antimicrobial, anti-inflammatory, and immunomodulatory effects. Therefore, supplementation may prevent COPD exacerbations, particularly in deficient patients.ObjectivesWe aimed to assess the effect of vitamin D supplementation on exacerbation rate in vitamin D–deficient patients with COPD.MethodsWe performed a multicenter, double-blind, randomized controlled trial. COPD patients with ≥1 exacerbations in the preceding year and a vitamin D deficiency (15–50 nmol/L) were randomly allocated in a 1:1 ratio to receive either 16,800 International Units (IU) vitamin D3 or placebo once a week during 1 y. Primary outcome of the study was exacerbation rate. Secondary outcomes included time to first and second exacerbations, time to first and second hospitalizations, use of antibiotics and corticosteroids, pulmonary function, maximal respiratory mouth pressure, physical performance, skeletal muscle strength, systemic inflammatory markers, nasal microbiota composition, and quality of life.ResultsThe intention-to-treat population consisted of 155 participants. Mean ± SD serum 25-hydroxyvitamin D [25(OH)D] concentration after 1 y was 112 ± 34 nmol/L in the vitamin D group, compared with 42 ± 17 nmol/L in the placebo group. Vitamin D supplementation did not affect exacerbation rate [incidence rate ratio (IRR): 0.90; 95% CI: 0.67, 1.21]. In a prespecified subgroup analysis in participants with 25(OH)D concentrations of 15–25 nmol/L (n = 31), no effect of vitamin D supplementation was found (IRR: 0.91; 95% CI: 0.43, 1.93). No relevant differences were found between the intervention and placebo groups in terms of secondary outcomes.ConclusionsVitamin D supplementation did not reduce exacerbation rate in COPD patients with a vitamin D deficiency.This trial was registered at clinicaltrials.gov as NCT02122627.

Chronic obstructive pulmonary disease and influenza vaccination effect in preventing outpatient and inpatient influenza cases

Evidence of influenza vaccine effectiveness in preventing confirmed influenza among persons diagnosed with chronic obstructive pulmonary disease (COPD) is scarce. We assessed the average effect of influenza vaccination in the current and prior seasons in preventing laboratory-confirmed influenza in COPD patients. We carried out a pooled test-negative case–control design in COPD patients hospitalized or presented to primary healthcare centres with influenza-like illness who were tested for influenza in 2015/2016 to 2019/2020 seasons in Navarre, Spain. Influenza vaccination status in the current and 5 prior seasons was compared between confirmed-influenza cases and test-negative controls. Vaccination effect was compared between target patients for vaccination with and without COPD. Out of 1761 COPD patients tested, 542 (31%) were confirmed for influenza and 1219 were test-negative controls. Average effect for current-season vaccination in preventing influenza was 40% (95% CI 20–54%), and for vaccination in prior seasons only was 24% (95% CI –10 to 47%). Point estimates seemed higher in preventing outpatient cases (60% and 58%, respectively) than inpatient cases (37% and 19%, respectively), but differences were no statistically significant. Influenza vaccination effect was similar in target population with and without COPD (p = 0.339). Influenza vaccination coverage in control patients with COPD was 68.3%. A 13.7% of the influenza cases in patients with COPD could be prevented by extending the influenza vaccine coverage. Average effect of current-season influenza vaccination was moderate to prevent influenza in COPD persons. The increase of influenza vaccination coverage can still prevent COPD exacerbations.

Effectiveness of Indacaterol-Glycopyrronium in preventing COPD exacerbations in comparison to Salmeterol-Fluticasone

COPD exacerbations are complex events usually associated with increased airway inflammation, increased mucus production and marked gas trapping. These changes contribute to increased dyspnoea that is the key symptom of an exacerbation. Inhaled long acting bronchodilators not only control symptoms but also prevent exacerbations of chronic obstructive pulmonary disease (COPD). The purpose of the study was to compare the efficacy between Indacaterol-Glycopyrronium and salmeterol fluticasone (SFC) in preventing COPD exacerbations during 24 weeks of treatment. This randomised active-controlled trial was conducted at Department of Respiratory Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka involving 200 patients with COPD exacerbations. Patients were randomly divided into two groups; & treated with Indacaterol- Glycopyrronium 110/50 ug o.d. & Salmeterol-Fluticasone (50/500 ug b.i.d.) (SFC) respectively; & follow-up was done after 12 and 24 weeks. The FEV1 was significantly higher at 12 and 24 weeks in the Indacateol- Glycopyrronium group compared with SFC. Statistically significant improvements in peak FVC was observed in Indacaterol- Glycopyrronium when compared to SFC at week 12 and week 24. Our study result showed that Indacaterol-Glycopyrronium was superior to Salmeterol-Fluticasone in terms of prevention and optimal management of COPD exacerbation. BSMMU J 2021; 14(3): 43-49

Advanced Dental Cleaning is Associated with Reduced Risk of COPD Exacerbations - A Randomized Controlled Trial.

PurposeInfections from the oral microbiome may lead to exacerbations of chronic obstructive pulmonary disease (COPD). We investigated whether advanced dental cleaning could reduce exacerbation frequency. Secondary outcomes were disease-specific health status, lung function, and whether the bacterial load and composition of plaque microbiome at baseline were associated with a difference in outcomes.Patients and MethodsOne-hundred-one primary and secondary care patients with COPD were randomized to intervention with advanced dental cleaning or to dental examination only, repeated after six months. At baseline and at 12 months, data of exacerbations, lung function, COPD Assessment Test (CAT) score, and periodontal status were collected from questionnaires, record review, and periodontal examination. Student’s t-test and Mann–Whitney-U (MWU) test compared changes in outcomes. The primary outcome variable was also assessed using multivariable linear regression with adjustment for potential confounders. Microbiome analyses of plaque samples taken at baseline were performed using Wilcoxon signed ranks tests for calculation of alpha diversity, per mutational multivariate analysis of variance for beta diversity, and receiver operating characteristic curves for prediction of outcomes based on machine learning models.ResultsIn the MWU test, the annual exacerbation frequency was significantly reduced in patients previously experiencing frequent exacerbations (p = 0.020) and in those with repeated advanced dental cleaning (p = 0.039) compared with the non-treated control group, but not in the total population including both patients with a single and repeated visits (p = 0.207). The result was confirmed in multivariable linear regression, where the risk of new exacerbations was significantly lower in patients both in the intention to treat analysis (regression coefficient 0.36 (95% CI 0.25–0.52), p < 0.0001) and in the population with repeated dental cleaning (0.16 (0.10–0.27), p < 0.0001). The composition of microbiome at baseline was moderately predictive of an increased risk of worsened health status at 12 months (AUC = 0.723).ConclusionAdvanced dental cleaning is associated with a reduced frequency of COPD exacerbations. Regular periodontal examination and dental cleaning may be of clinical importance to prevent COPD exacerbations.

Effects of simvastatin on tissue factor pathway of blood coagulation in STATCOPE (Simvastatin in the prevention of COPD exacerbations) trial

BackgroundStatins are widely used to lower lipids and reduce cardiovascular events. In vitro studies and small studies in patients with hyperlipidemias show statins inhibit tissue factor (TF) and blood coagulation mechanisms. We assessed the effects of simvastatin on TF and coagulation biomarkers in patients entered in STATCOPE, a multicenter, randomized, placebo‐controlled trial of simvastatin (40 mg daily) versus placebo on exacerbation rates in patients with chronic obstructive pulmonary disease (COPD). MethodsIn 227 patients (114 simvastatin, 113 placebo; mean [± standard error of the mean] age 62 ± 0.53 years, 44.5% women) we measured (baseline, and 6 and 12 months): whole blood membrane TF‐procoagulant activity (TF‐PCA) and plasma factors VIIa, VII, VIII, fibrinogen, TF antigen, tissue factor pathway inhibitor (TFPI), thrombin‐antithrombin complexes (TAT), and D‐dimer. We excluded patients with diabetes, cardiovascular disease, and those taking or requiring a statin. ResultsIn the statin group, there was a small increase in TF‐PCA (from 25.18 ± 1.08 to 30.36 ± 1.10 U/ml; p = .03) over 12 months; factors VIIa and VIII, fibrinogen, TAT, and D‐dimer did not change. Plasma TFPI (from 52.4 ± 1.75 to 44.7 ± 1.78 ng/ml; p < .0001) and FVIIC (1.23 ± 0.04 to 1.15 ± 0.03 U/ml; p = .03) decreased and correlated with total cholesterol levels. No changes in biomarkers were observed with placebo. ConclusionsIn contrast to previous studies on statins, in COPD patients without diabetes, cardiovascular disease, or requiring a statin treatment, simvastatin (40 mg per day) did not decrease TF or factors VIIa and VIII, fibrinogen, TAT, or D‐dimer. The decreases in TFPI and factor VII reflect the decrease in serum lipids.

Research priorities for exacerbations of COPD

Research priorities for exacerbations of COPD

The Toll-Like Receptor 5 agonist flagellin prevents Non-typeable Haemophilus influenzae-induced infection in cigarette smoke-exposed mice

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. The major bacterial cause of COPD exacerbations is non-typeable Haemophilus influenzae (NTHi). 25 to over 80% of cases are associated with NTHi. This susceptibility to infection involves a defective production of interleukin (IL)-22 which plays an important role in mucosal defense. Prophylactic administration of flagellin, a Toll-like receptor 5 (TLR5) agonist, protects healthy mice against respiratory pathogenic bacteria. We hypothesized that TLR5-mediated stimulation of lung immunity might prevent COPD exacerbations. Mice chronically exposed to cigarette smoke (CS), which presented COPD symptoms, were infected with NTHi and intraperitoneally treated with recombinant flagellin following a prophylactic or therapeutic protocol. Compared with control, cigarette smoke-exposed mice treated with flagellin showed a lower bacterial load in the airways, the lungs and the blood. This protection was associated with an early neutrophilia, a lower production of pro-inflammatory cytokines and an increased IL-22 production. Flagellin treatment decreased the recruitment of inflammatory cells and the lung damages related to exacerbation. Morover, the protective effect of flagellin against NTHi was altered by treatment with anti-IL-22 blocking antibodies in cigarette smoke-exposed mice and in Il22-/- mice. The effect of flagellin treatment did not implicated the anti-bacterial peptides calgranulins and defensin-β2. This study shows that stimulation of innate immunity by a TLR5 ligand is a potent antibacterial treatment in CS-exposed mice, suggesting innovative therapeutic strategies against acute exacerbation in COPD.

Evaluation of Hospital Admission Status for Emergency Department Patients Seen for Chronic Obstructive Pulmonary Disease Exacerbation: A Retrospective Observational Study.

Background: Chronic obstructive pulmonary disease (COPD) is a common and preventable condition. The disease accounts for a large economic burden in the US health care system. Better control and prevention of COPD exacerbations can help prevent presentations to already-crowded emergency departments (EDs) and hospitals. The objective of our study was to identify variables associated with hospital admission status in ED patients presenting with COPD exacerbation.Methods: We conducted a retrospective observational study of patients seen at 1 of 3 US EDs from 2012 to 2014 with a primary diagnosis related to COPD exacerbation. Hospital admission status was modeled using patient characteristic data via adaptive least absolute shrinkage and selection operator logistic regression. Study results are presented as adjusted odds ratios with 95% CIs. Planned post hoc model dependency and external data sensitivity analyses were conducted.Results: The study sample included 1,165 unique patients with COPD with an ED encounter related to exacerbation at 1 of the 3 reviewed hospitals. Approximately half of these patients had a hospital admission. Variables inversely associated with an admission included oxygen saturation and number of prior ED encounters for COPD exacerbation. Variables positively associated with admission were initial ED heart rate, patient age, and documented comorbidities of anxiety and/or depression. These mental health comorbidities had the strongest association with admission status.Conclusion: Understanding the characteristics of admitted patients may help direct resources and outpatient services to prevent encounters. Of note, the study revealed mental health variables as being strongly associated with admission status.

Beta-blockers in chronic obstructive pulmonary disease: the good, the bad and the ugly.

Several observational studies have suggested that β-blockers, especially cardioselective ones, are well tolerated and associated with a lower risk of acute exacerbations and death in patients with chronic obstructive pulmonary disease (COPD). However, there are dissenting studies. This review provides an update on the use of β-blockers in COPD, focusing on results of recent prospective studies and randomized controlled trials. In totality, cohort studies indicate that β-blockers are generally well tolerated and effective in COPD patients who also have a clear cardiovascular indication for these medications. Although β-blockers on average reduce lung function acutely in COPD patients, the absolute decrease is relatively small, especially if cardioselective β-blockers are used. The results of two large randomized controlled trials suggest that β-blocker use does not reduce the therapeutic benefits of inhaled bronchodilators in COPD patients. The use of β-blockers in COPD patients, who do not have overt cardiovascular disease, does not prevent COPD exacerbations and may paradoxically increase the risk of COPD-related hospitalization and mortality. The use of β-blockers is generally well tolerated and effective in COPD patients, who also have a clear cardiovascular indication for these drugs. However, they should not be used in patients who do not have overt cardiovascular disease as β-blockers can reduce lung function, worsen health status and increase the risk of COPD-related hospitalization.

Acute exacerbations of chronic obstructive pulmonary disease: in search of diagnostic biomarkers and treatable traits

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are associated with a significant mortality, health and economic burden. Their diagnosis, assessment and management remain suboptimal and unchanged for decades. Recent...

LABA/LAMA fixed-dose combinations versus LAMA monotherapy in the prevention of COPD exacerbations: a systematic review and meta-analysis.

Background:Long-acting muscarinic antagonist (LAMA) monotherapy is recommended for chronic obstructive pulmonary disease (COPD) patients with high risk of exacerbations. It is unclear whether long-acting β2-agonist (LABA)/LAMA fixed-dose combinations (FDCs) are more effective than LAMAs alone in preventing exacerbations. The aim of this study was to systematically review the literature to investigate whether LABA/LAMA FDCs are more effective than LAMA monotherapy in preventing exacerbations.Methods:We searched several databases and manufacturers’ websites to identify relevant randomized clinical trials comparing LABA/LAMA FDC treatment with LAMAs alone ⩾24 weeks. Outcomes of interest were time to first exacerbation and rates of moderate to severe, severe and all exacerbations.Results:We included 10 trials in 9 articles from 2013 to 2018 with a total of 19,369 patients for analysis in this study. Compared with LAMA monotherapy, LABA/LAMA FDCs demonstrated similar efficacy in terms of time to first exacerbation [hazard ratio, 0.96; 95% confidence interval (CI) 0.79–1.18; p = 0.71], moderate to severe exacerbations [risk ratio (RR), 0.96; 95% CI 0.90–1.03; p = 0.28], severe exacerbations (RR, 0.92; 95% CI 0.81–1.03; p = 0.15), and a marginal superiority in terms of all exacerbations (RR, 0.92; 95% CI 0.86–1.00; p = 0.04). The incidence of all exacerbation events was lower in the LABA/LAMA FDC group for the COPD patients with a history of previous exacerbations and those with a longer treatment period (52–64 weeks).Conclusion:This study provides evidence that LABA/LAMA FDCs are marginally superior in the prevention of all exacerbations compared with LAMA monotherapy in patients with COPD. The reviews of this paper are available via the supplemental material section.

Building Hope by Restoring Breathing in Airways Diseases

Prof Agustí opened the session by explaining the new challenges in airway diseases including the changing paradigm of our understanding of chronic obstructive pulmonary disease (COPD) that considers the entire lung function trajectory from birth to death, the complexity and heterogeneity of the disease, and the need to diagnose and treat COPD earlier in life. Prof Siddiqui then explained that all of the airways, including small airways, are critically important in the pathophysiology of asthma and COPD. The world’s largest multi-centre ATLANTIS study focussed on small airways dysfunction (SAD) confirmed that a simple combination of different assessments like oscillometry and spirometry could identify patients with the SAD phenotype. The prevalence of airway dysfunction in the full asthma cohort was 91%. Prof Papi discussed that exacerbations are a crucial event in the natural history of COPD and that they drive several health-related outcomes. He reviewed the clinical evidence to demonstrate the benefits of triple therapy in general and specifically of the extrafine fixed triple combination (beclometasone dipropionate, formoterol fumarate, glycopyrronium bromide) to consistently reduce the risk of exacerbations, and improve lung function and quality of life (QoL) with a favourable benefit-to-harm ratio. Furthermore, triple therapy showed promising signals in terms of improved survival. Prof Celli debated that inhaled corticosteroid (ICS) should be given to many patients because scientific trials have shown that: 1) ICS combined with bronchodilator (BD) are effective in improving health status and reducing exacerbations; 2) they also impact lung function decline and mortality; 3) ICS increase pneumonia risk (depending on type, dose, airflow limitation, BMI, and age) but have no untoward effect on mortality or hospitalisations for pneumonia; 4) blood eosinophil count (BEC) (&lt;100 cell/µL) helps select patients unlikely to respond to ICS; and 5) ‘many’ COPD patients benefit from ICS combined with BD. Prof Singh focused on the fact that the magnitude of clinical benefit in preventing COPD exacerbations varies between individual patients, underlining the importance for clinicians of making the right decision for each patient when prescribing ICS, by balancing the potential risk/benefit. He concluded the debate by outlining that ICS have benefits in patients at increased exacerbation risk, and that the size of the benefits varies with BEC and the number/type of exacerbation.

Issues of triple therapy of chronic obstructive pulmonary disease. Comments to the algorithm. A resolution of expert panel, June 13, 2018, Vladivostok

Minimizing the risk of exacerbations of chronic obstructive pulmonary disease (COPD) along with symptoms control are the most important therapeutic tasks in COPD. The effective solution of this problem is still being discussed. The prevention of COPD exacerbations is of social and economic importance and should be the primary concern in the treatment of this disease. Unresolved problems in the treatment of COPD are low patient compliance to therapy and side effects of medication. According to recent guidelines, in case of persistent COPD exacerbations with patients receiving long-acting bronchodilators (LABA), the use of inhaled corticosteroids (ICS) must be considered; this reduces the incidence of moderate and severe COPD exacerbations, especially if a patient has a history of bronchial asthma or blood and/or sputum eosinophilia. Availability of LABA/LAMA and ICS/LABA fixed combinations in Russia provides two possible options to administer a free triple combination consisting of a single LAMA plus ICS/LABA or ICS plus LAMA/LAMA. According to multiple trials, the use of fixed combinations could provide twice improvement in the patient adherence to the therapy, which therefore leads to higher efficiency. The main complaint about ICS with COPD patients is an increased risk of pneumonia as well as the development of systemic adverse reactions typical for corticosteroids. However, the use of extra-fine ICS could significantly reduce the risk of pneumonia compared with fine-particle inhalators and also increases the effectiveness of therapy as the pathological process in COPD mainly involves the small airways.

Effects of long-term macrolide therapy at low doses in stable COPD.

Background: Chronic obstructive pulmonary disease (COPD) is currently the fourth largest fatal disease in the world, and is expected to rise to third place by 2020. Frequent acute exacerbations lead to increased mortality. Some suggestions for prophylactic use of macrolides in preventing COPD exacerbations have been raised, but there are still several issues that need to be addressed, such as target population, the course of treatment, therapeutic dose, and so on.Objective: To evaluate, via exploratory meta-analysis, the efficacy of long-term macrolide therapy at low doses in stable COPD.Methods: A systematic literature search was performed in PubMed, Embase, and Cochrane database from inception to March 28, 2019. Randomized controlled trials (RCT) which reported long-term use of macrolides in prevention of COPD were eligible.Results: A total of 10 articles were included in this study. It was found that there was a 23% relative risk reduction in COPD exacerbations among patients taking macrolides compared to placebo (P<0.01). The median time to first exacerbation was effectively prolonged among patients taking macrolides vs placebo (P<0.01). Sub-group analysis showed erythromycin was advantageous and older patients were less responsive to macrolides.Conclusions: Long-term low dose usage of macrolides could significantly reduce the frequency of the acute exacerbation of COPD. The treatment was well tolerated, with few adverse reactions, but it was not suitable for the elderly. It is recommended that this treatment regimen could be used in patients with GOLD grading C or D, because they have a higher risk of acute exacerbation and mortality. It needs to be further discussed whether this treatment should last for 12 months or longer.