Moderate Chronic Obstructive Pulmonary Disease Exacerbations Research Articles

Nebulised interferon beta-1a (SNG001) in the treatment of viral exacerbations of COPD

BackgroundRespiratory viral infections are major drivers of chronic obstructive pulmonary disease (COPD) exacerbations. Interferon-β is naturally produced in response to viral infection, limiting replication. This exploratory study aimed to demonstrate proof-of-mechanism, and evaluate the efficacy and safety of inhaled recombinant interferon-β1a (SNG001) in COPD. Part 1 assessed the effects of SNG001 on induced sputum antiviral interferon-stimulated gene expression, sputum differential cell count, and respiratory function. Part 2 compared SNG001 and placebo on clinical efficacy, sputum and serum biomarkers, and viral clearance.MethodsIn Part 1, patients (N = 13) with stable COPD were randomised 4:1 to SNG001 or placebo once-daily for three days. In Part 2, patients (N = 109) with worsening symptoms and a positive respiratory viral test were randomised 1:1 to SNG001 or placebo once-daily for 14 days in two Groups: A (no moderate exacerbation); B (moderate COPD exacerbation [i.e., acute worsening of respiratory symptoms treated with antibiotics and/or oral corticosteroids]).ResultsIn Part 1, SNG001 upregulated sputum interferon gene expression. In Part 2, there were minimal SNG001–placebo differences in the efficacy endpoints; however, whereas gene expression was initially upregulated by viral infection, then declined on placebo, levels were maintained with SNG001. Furthermore, the proportion of patients with detectable rhinovirus (the most common virus) on Day 7 was lower with SNG001. In Group B, serum C-reactive protein and the proportion of patients with purulent sputum increased with placebo (suggesting bacterial infection), but not with SNG001. The overall adverse event incidence was similar with both treatments.ConclusionsOverall, SNG001 was well-tolerated in patients with COPD, and upregulated lung antiviral defences to accelerate viral clearance. These findings warrant further investigation in a larger study.Trial registrationEU clinical trials register (2017-003679-75), 6 October 2017.

Impact of the COVID-19 pandemic on COPD exacerbations in Japanese patients: a retrospective study

Various infection control measures implemented during the coronavirus disease (COVID-19) pandemic have reduced the number of respiratory infections, which are the most common cause of chronic obstructive pulmonary disease (COPD) exacerbations. Here, we investigated whether infectious disease prevention during the COVID-19 pandemic reduced COPD exacerbations and the characteristics of patients exhibiting exacerbations before and during the COVID-19 pandemic. We included outpatients and inpatients with moderate or severe COPD exacerbations who required systemic steroids between April 1, 2018 and March 31, 2022. Their medical records were retrospectively compared and analyzed in 2-year intervals (before and during the COVID-19 pandemic). During the 4-year observation period, 70,847 outpatients and 2,772 inpatients were enrolled; 55 COPD exacerbations were recorded. The number of COPD exacerbations decreased from 36 before to 19 during the COVID-19 pandemic. Regarding the characteristics of patients with exacerbations, the % forced expiratory volume in one second (52.3% vs. 38.6%, P = 0.0224) and body mass index (BMI) (22.5 vs. 19.3, P = 0.0127) were significantly lower during the COVID-19 pandemic than before the pandemic. The number of COPD exacerbations during the pandemic decreased. Additionally, the tendency for a reduction in COPD exacerbation was greatest in patients with preserved lung function or above-standard BMI patients.

Temporal Risk of Nonfatal Cardiovascular Events After Chronic Obstructive Pulmonary Disease Exacerbation: A Population-based Study.

Rationale: Cardiovascular events after chronic obstructive pulmonary disease (COPD) exacerbations are recognized. Studies to date have been post hoc analyses of trials, did not differentiate exacerbation severity, included death in the cardiovascular outcome, or had insufficient power to explore individual outcomes temporally.Objectives: We explore temporal relationships between moderate and severe exacerbations and incident, nonfatal hospitalized cardiovascular events in a primary care-derived COPD cohort.Methods: We included people with COPD in England from 2014 to 2020, from the Clinical Practice Research Datalink Aurum primary care database. The index date was the date of first COPD exacerbation or, for those without exacerbations, date upon eligibility. We determined composite and individual cardiovascular events (acute coronary syndrome, arrhythmia, heart failure, ischemic stroke, and pulmonary hypertension) from linked hospital data. Adjusted Cox regression models were used to estimate average and time-stratified adjusted hazard ratios (aHRs).Measurements and Main Results: Among 213,466 patients, 146,448 (68.6%) had any exacerbation; 119,124 (55.8%) had moderate exacerbations, and 27,324 (12.8%) had severe exacerbations. A total of 40,773 cardiovascular events were recorded. There was an immediate period of cardiovascular relative rate after any exacerbation (1-14 d; aHR, 3.19 [95% confidence interval (CI), 2.71-3.76]), followed by progressively declining yet maintained effects, elevated after one year (aHR, 1.84 [95% CI, 1.78-1.91]). Hazard ratios were highest 1-14 days after severe exacerbations (aHR, 14.5 [95% CI, 12.2-17.3]) but highest 14-30 days after moderate exacerbations (aHR, 1.94 [95% CI, 1.63-2.31]). Cardiovascular outcomes with the greatest two-week effects after a severe exacerbation were arrhythmia (aHR, 12.7 [95% CI, 10.3-15.7]) and heart failure (aHR, 8.31 [95% CI, 6.79-10.2]).Conclusions: Cardiovascular events after moderate COPD exacerbations occur slightly later than after severe exacerbations; heightened relative rates remain beyond one year irrespective of severity. The period immediately after an exacerbation presents a critical opportunity for clinical intervention and treatment optimization to prevent future cardiovascular events.

The Role of the Cumulative Illness Rating Scale (CIRS) in Estimating the Impact of Comorbidities on Chronic Obstructive Pulmonary Disease (COPD) Outcomes: A Pilot Study of the MACH (Multidimensional Approach for COPD and High Complexity) Study.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous systemic syndrome that often coexists with multiple comorbidities. In highly complex COPD patients, the role of the Cumulative Illness Rating Scale (CIRS) as a risk predictor of COPD exacerbation is not known. The objective of this study was determine the effectiveness of the CIRS score in detecting the association of comorbidities and disease severity with the risk of acute exacerbations in COPD patients. In total, 105 adults with COPD (mean age 72.1 ± 9.0 years) were included in this prospective study. All participants at baseline had at least two moderate exacerbations or one leading to hospitalization. The primary outcome was a composite of moderate or severe COPD exacerbation during the 12 months of follow-up. The CIRS indices (CIRS total score, Severity Index and Comorbidity Index) showed a positive correlation with modified Medical Research Council (mMRC), COPD assessment test (CAT) and a negative correlation with forced expiratory volume in the first second (FEV1), Forced Vital Capacity (FVC), and FEV1/FVC. The three CIRS indices were able to predict the 12-month rate of moderate or severe exacerbation (CIRS Total Score: Hazard Ratio (HR) = 1.12 (95% CI: 1.08-1.21); CIRS Severity Index: HR = 1.21 (95% CI: 1.12-1.31); CIRS Comorbidity Index = 1.58 (95% CI: 1.33-1.89)). Among patients with COPD, the comorbidity number and severity, as assessed by the CIRS score, influence the risk in moderate-to-severe exacerbations. The CIRS score also correlates with the severity of respiratory symptoms and lung function.

The altered sputum microbiome profile in patients with moderate and severe COPD exacerbations, compared to the healthy group in the Indian population

Background: Microbial culture-independent sequencing techniques have advanced our understanding of host-microbiome interactions in health and disease. The purpose of this study was to explore the dysbiosis of airway microbiota in patients with moderate or severe chronic obstructive pulmonary disease (COPD) and compare them with healthy controls. Methods: The COPD patients were investigated for disease severity based on airflow limitations and divided into moderate (50%≤FEV1<80% predicted) and severe groups (FEV1<50% predicted). Spontaneous sputum samples were collected and, the V3-V4 regions of the 16S rRNA coding gene were sequenced to examine the microbiome profile of COPD and healthy participants. Results: A total of 45 sputum samples were collected from 17 severe COPD, 12 moderate COPD cases, and 16 healthy volunteers. The bacterial alpha diversity (Shannon and Simpson’s index) significantly decreased in the moderate and severe COPD groups, compared to healthy samples. A significantly higher proportion of Firmicutes and Actinobacteria were present in moderate COPD, and Proteobacteria numbers were comparatively increased in severe COPD. In healthy samples, Bacteroidetes and Fusobacteria were more abundant in comparison to both the COPD groups. Among the most commonly detected 20 bacterial genera, Streptococcus was predominant among the COPD sputum samples, whereas Prevotella was the top genus in healthy controls. Linear discriminant analysis (LDA>2) revealed that marker genera like Streptococcus and Rothia were abundant in moderate COPD. For severe COPD, the genera Pseudomonasand Leptotrichia were most prevalent, whereas Fusobacterium and Prevotella were dominant in the healthy group. Conclusions: Our findings suggest a significant dysbiosis of the respiratory microbiome in COPD patients. The decreased microbial diversity may influence the host immune response and provide microbiological biomarkers for the diagnosis and monitoring of COPD.

Effect of Broncho-Vaxom (OM-85) on the frequency of chronic obstructive pulmonary disease (COPD) exacerbations

BackgroundEfforts have been made to reduce the risk of chronic obstructive pulmonary disease (COPD) exacerbations using a variety of measures. Broncho-Vaxom (BV) is an immunomodulating agent that has shown potential benefit by balancing between immune stimulation and regulation in patients with COPD. In this study, we evaluated the clinical efficacy of BV for reducing the risk of COPD exacerbations.MethodsThis study was based on the Korean National Health Insurance database, which contains reimbursement information for almost the entire population of South Korea. We extracted data from 2016 to 2019 for patients started on BV during 2017–2018. We collected baseline data on demographics, comorbidities, inhaler use, hospital type, and insurance type 1 year before starting BV. We also analyzed exacerbation history, starting from the year before BV initiation.ResultsIn total, 238 patients were enrolled in this study. Their mean age was 69.2 ± 9.14 years, 79.8% were male, and 45% experienced at least one exacerbation. BV reduced the risk of moderate (odds ratio [OR] = 0.59, 95% confidence interval [CI]: 0.38–0.91) and moderate-to-severe exacerbations compared to pre- and post-BV (OR = 0.571, 95% CI: 0.37–0.89). BV use also reduced the incidence of moderate and moderate-to-severe exacerbations (incidence rate ratio [IRR] = 0.75, p = 0.03; and IRR = 0.77, p = 0.03, respectively). The use of BV was significantly delayed moderate exacerbations (hazard ratio = 0.68, p = 0.02), but not with moderate-to-severe or severe exacerbations.ConclusionThe use of BV was associated with fewer moderate and moderate-to-severe exacerbations. Additionally, BV was associated with a delay in moderate COPD exacerbations.

The altered sputum microbiome profile in patients with moderate and severe COPD exacerbations, compared to the healthy group in the Indian population.

Background: Microbial culture-independent sequencing techniques have advanced our understanding of host-microbiome interactions in health and disease. The purpose of this study was to explore the dysbiosis of airway microbiota in patients with moderate or severe chronic obstructive pulmonary disease (COPD) and compare them with healthy controls. Methods: The COPD patients were investigated for disease severity based on airflow limitations and divided into moderate (50%≤FEV1<80% predicted) and severe groups (FEV1<50% predicted). Spontaneous sputum samples were collected and, the V3-V4 regions of the 16S rRNA coding gene were sequenced to examine the microbiome profile of COPD and healthy participants. Results: A total of 45 sputum samples were collected from 17 severe COPD, 12 moderate COPD cases, and 16 healthy volunteers. The bacterial alpha diversity (Shannon and Simpson's index) significantly decreased in the moderate and severe COPD groups, compared to healthy samples. A significantly higher proportion of Firmicutes and Actinobacteria were present in moderate COPD, and Proteobacteria numbers were comparatively increased in severe COPD. In healthy samples, Bacteroidetes and Fusobacteria were more abundant in comparison to both the COPD groups. Among the most commonly detected 20 bacterial genera, Streptococcus was predominant among the COPD sputum samples, whereas Prevotella was the top genus in healthy controls. Linear discriminant analysis (LDA>2) revealed that marker genera like Streptococcus and Rothia were abundant in moderate COPD. For severe COPD, the genera Pseudomonasand Leptotrichia were most prevalent, whereas Fusobacterium and Prevotella were dominant in the healthy group. Conclusions: Our findings suggest a significant dysbiosis of the respiratory microbiome in COPD patients. The decreased microbial diversity may influence the host immune response and provide microbiological biomarkers for the diagnosis and monitoring of COPD.

Chronic Obstructive Pulmonary Disease Exacerbations and Pneumonia Hospitalizations Among New Users of Combination Maintenance Inhalers

Clinical guidelines on chronic obstructive pulmonary disease (COPD) recommend inhalers containing long-acting muscarinic antagonists (LAMAs) and long-acting β-agonists (LABAs) over inhalers containing inhaled corticosteroids (ICSs) and LABAs. However, data from randomized clinical trials comparing these combination inhalers (LAMA-LABAs vs ICS-LABAs) have been conflicting and raised concerns of generalizability. To assess whether LAMA-LABA therapy is associated with reduced COPD exacerbations and pneumonia hospitalizations compared with ICS-LABA therapy in routine clinical practice. This was a 1:1 propensity score-matched cohort study using Optum's Clinformatics Data Mart, a large commercial insurance-claims database. Patients must have had a diagnosis of COPD and filled a new prescription for a combination LAMA-LABA or ICS-LABA inhaler between January 1, 2014, and December 31, 2019. Patients younger than 40 years were excluded, as were those with a prior diagnosis of asthma. The current analysis was performed from February 2021 to March 2023. Combination LAMA-LABA inhalers (aclidinium-formoterol, glycopyrronium-formoterol, glycopyrronium-indacaterol, tiotropium-olodaterol, or umeclidinium-vilanterol) and combination ICS-LABA inhalers (budesonide-formoterol, fluticasone-salmeterol, fluticasone-vilanterol, or mometasone-formoterol). The primary effectiveness outcome was first moderate or severe COPD exacerbation, and the primary safety outcome was first pneumonia hospitalization. Propensity score matching was used to control for confounding between the 2 groups. Logistic regression analysis was used to estimate propensity scores. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models stratified on matched pairs. Among 137 833 patients (mean [SD] age, 70.2 [9.9] years; 69 530 [50.4%] female) (107 004 new ICS-LABA users and 30 829 new LAMA-LABA users), 30 216 matched pairs were identified for the primary analysis. Compared with ICS-LABA use, LAMA-LABA use was associated with an 8% reduction in the rate of first moderate or severe COPD exacerbation (HR, 0.92; 95% CI, 0.89-0.96) and a 20% reduction in the rate of first pneumonia hospitalization (HR, 0.80; 95% CI, 0.75-0.86). These findings were robust across a range of prespecified subgroup and sensitivity analyses. In this cohort study, LAMA-LABA therapy was associated with improved clinical outcomes compared with ICS-LABA therapy, suggesting that LAMA-LABA therapy should be preferred for patients with COPD.

Antibiotic Stewardship und chronische Lungenerkrankungen

HintergrundDie Therapie akuter Exazerbationen von Patienten mit chronischen Lungenerkrankungen ist häufig mit der Gabe von Antibiotika vergesellschaftet. Wiederholte stationäre Aufenthalte, hohe Antibiotikaverbräuche sowie die Gefahr des Auftretens multiresistenter Keime stellen eine Belastung für das Gesundheitssystem dar.Ziel dieser ArbeitZiel dieser Arbeit ist es, einen Überblick über Antibiotic-Stewardship-Strategien für das Management von Patienten mit chronischen Lungenerkrankungen mit besonderem Fokus auf COPD („chronic obstructive pulmonary disease“) sowie Bronchiektasien und zystischer Fibrose (CF) zu geben.Material und MethodenDie Übersichtsarbeit basiert auf einer Literaturrecherche in PubMed.Ergebnisse und DiskussionPoint-of-Care-Tests (POCT) zum schnelleren Erregernachweis ergaben uneinheitliche Ergebnisse in Bezug auf die Reduktion antibiotischer Therapien. Als relativ einfaches Verfahren konnte mittels POCT C‑reaktives Protein (CRP) („cut off“ < 20 bzw. ≥ 40 mg/l) die Anwendung von Antibiotika bei Patienten mit exazerbierter COPD reduzieren, ohne die Sicherheit zu gefährden. Die Rolle von Procalcitonin bleibt unklar. Bei nichtpurulentem Sputum und einer leichten bis mittelschweren COPD-Exazerbation kann Leitliniengerecht auf eine Antibiotikatherapie verzichtet werden. Der Einsatz von Makroliden führt zu einer zunehmenden Resistenzentwicklung und birgt die Gefahr v. a. kardiovaskulärer Nebenwirkungen, sodass eine Dauertherapie bei Patienten trotz häufiger COPD-Exazerbationen kritisch gesehen werden muss. Bei der CF hat sich durch den Einsatz von CFTR(„cystic fibrosis transmembrane conductance regulator“)-Modulatoren das Management der Grunderkrankung so verbessert, dass weniger Antibiotikatherapien gebraucht wurden. Auch bei den Bronchiektasen gibt es Anlass zur Hoffnung, dass durch neue Therapien, wie z. B. Inhibitoren der neutrophilen Elastase, Antibiotika eingespart werden können. Jeder Einsatz von Antibiotika bei chronischen Lungenerkrankungen sollte leitliniengerecht erfolgen.

BURDEN OF ILLNESS IN PATIENTS WITH PULMONARY HYPERTENSION DUE TO COPD IN US ADMINISTRATIVE CLAIMS DATA

BURDEN OF ILLNESS IN PATIENTS WITH PULMONARY HYPERTENSION DUE TO COPD IN US ADMINISTRATIVE CLAIMS DATA

Withdrawal of inhaled corticosteroids from patients with COPD with mild or moderate airflow limitation in primary care: a feasibility randomised trial

BackgroundInhaled corticosteroids (ICS) are frequently prescribed outside guidelines to patients with chronic obstructive pulmonary disease (COPD) with mild/moderate airflow limitation and low exacerbation risk. This primary care trial explored the...

Diaphragmatic Movement at Rest and After Exertion: A Non-Invasive and Easy to Obtain Prognostic Marker in COPD.

IntroductionDiaphragmatic dysfunction is common in patients with chronic obstructive pulmonary disease (COPD). This study aimed to assess the prognostic significance of impaired diaphragmatic movement at rest and after exercise.MethodsThis was a prospective study of patients with stable COPD. Diaphragmatic movements were examined at rest and after a 6-minute walking test (6MWT) with a convex transducer with a frequency of 3.5-5-7.5 MHz. Maximal movement of the diaphragm was measured in both right and left diaphragm, and the side with higher amplitude was selected for further analysis. Measurements obtained were evaluated for their prognostic value for a composite endpoint of moderate and severe COPD exacerbations and death in 1 year time period was assessed. In addition, postbronchodilator spirometry, symptoms, quality of life, and demographic and clinical information were collected.ResultsA total of 96 patients were analyzed (62.5% male, mean age 65.1 years (standard deviation (SD): 8.1), mean FEV1 (% predicted): 55.8%, SD: 18.3%, mean CAT: 15.6 units, SD: 9.2). Sixty-four patients (67%) presented the composite endpoint. In the multivariate Cox analysis, FVC (HR = 0.944, p = 0.005), CAT score (HR = 1.133, p = 0.011), previous severe exacerbations (HR = 5.446, p = 0.004) and diaphragmatic movement at rest (HR = 0.932, p = 0.033) were found to be predictors of the composite endpoint. This model correctly classified 86.5% (83/96) of the patients.ConclusionNon-invasive assessment of diaphragmatic movement by ultrasound measurement both at rest and after exercise could contribute to the assessment of disease severity and prognosis of COPD.

Benefit of Prompt versus Delayed Use of Single-Inhaler Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) Following a COPD Exacerbation.

PurposeTriple therapy (TT; inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting β2-agonist) is recommended for patients with chronic obstructive pulmonary disease (COPD) at risk of exacerbation, although the optimum timing of TT initiation remains unclear. This study evaluated the impact of prompt versus delayed initiation of single-inhaler TT (fluticasone furoate, umeclidinium, and vilanterol [FF/UMEC/VI]) following a COPD exacerbation.Patients and MethodsThis retrospective cohort study used data from the IQVIA PharMetrics® Plus database. Patients initiating FF/UMEC/VI following a COPD exacerbation between September 18, 2017 and September 30, 2019 (exacerbation = index date) were categorized as prompt (within 30 days of index) or delayed (31–180 days after index) FF/UMEC/VI initiators. Patients were aged ≥40 years at index, had ≥12 months’ continuous health insurance coverage before index (baseline), and ≥6 months’ coverage after index (follow-up). Patients with a COPD exacerbation or claim for FF/UMEC/VI during baseline were excluded. Inverse probability weighting was used to adjust for differences in baseline characteristics between cohorts. Exacerbations (overall, moderate, and severe), healthcare costs, and readmissions were evaluated during follow-up.ResultsA total of 1904 patients (prompt: 529; delayed: 1375) were included. After weighting, baseline characteristics were well balanced between cohorts. Patients in the prompt cohort had significantly lower rates per person-year (PPY) of overall (0.98 vs 1.23; rate ratio [RR] [95% CI] = 0.79 [0.65–0.94], p = 0.004), moderate (0.86 vs 1.03; RR [95% CI] = 0.84 [0.69–0.99], p = 0.038), and severe (0.11 vs 0.20; RR [95% CI] = 0.57 [0.37–0.79], p = 0.002) exacerbations, compared with delayed initiators. Mean all-cause and COPD-related healthcare costs were significantly lower among prompt initiators (all-cause: $26,107 vs $32,400 PPY, p = 0.014; COPD-related: $12,694 vs $17,640 PPY, p = 0.002).ConclusionPrompt initiation of FF/UMEC/VI following a moderate or severe COPD exacerbation was associated with significant reductions in exacerbations and healthcare costs relative to delayed initiation.

Decalogue for the selection of oral antibiotics for lower respiratory tract infections.

Lower respiratory tract infections, including chronic obstructive pulmonary disease exacerbations (COPD-E) and community acquired pneumonia (CAP), are one of the most frequent reasons for consultation in primary care and hospital emergency departments, and are the cause of a high prescription of antimicrobial agents. The selection of the most appropriate oral antibiotic treatment is based on different aspects and includes to first consider a bacterial aetiology and not a viral infection, to know the bacterial pathogen that most frequently cause these infections and the frequency of their local antimicrobial resistance. Treatment should also be prescribed quickly and antibiotics should be selected among those with a quicker mode of action, achieving the greatest effect in the shortest time and with the fewest adverse effects (toxicity, interactions, resistance and/or ecological impact). Whenever possible, antimicrobials should be rotated and diversified and switched to the oral route as soon as possible. With these premises, the oral treatment guidelines for mild or moderate COPD-E and CAP in Spain include as first options beta-lactam antibiotics (amoxicillin and amoxicillin-clavulanate and cefditoren), in certain situations associated with a macrolide, and relegating fluoroquinolones as an alternative, except in cases where the presence of Pseudomonas aeruginosa is suspected.

COPD EXACERBATIONS AND PNEUMONIA HOSPITALIZATIONS IN NEW USERS OF COMBINATION MAINTENANCE INHALERS: A COMPARATIVE EFFECTIVENESS AND SAFETY STUDY

TOPIC: Obstructive Lung Diseases TYPE: Original Investigations PURPOSE: Current guidelines recommend inhalers containing long-acting muscarinic antagonists (LAMA) and long-acting beta agonists (LABA) over inhalers containing inhaled corticosteroids (ICS) and LABAs as first-line dual therapy for chronic obstructive pulmonary disease (COPD). However, recent data from randomized controlled trials examining the efficacy and safety of LAMA-LABA versus ICS-LABA inhalers have been conflicting and raised concerns of generalizability. The purpose of this study was to determine whether LAMA-LABA therapy is associated with reduced COPD exacerbations and pneumonia hospitalizations compared to ICS-LABA therapy in real-world clinical practice. METHODS: A 1:1 propensity-score matched observational cohort study was conducted using a large US commercial insurance database. The study included patients with COPD who filled a new prescription for a combination LAMA-LABA or ICS-LABA inhaler between January 1, 2014 to December 31, 2019. Patients with a prior diagnosis of asthma were excluded. The primary effectiveness outcome was first moderate or severe COPD exacerbation, and the primary safety outcome was first pneumonia hospitalization. RESULTS: Among 138,395 patients (107,518 new ICS-LABA users and 30,877 new LAMA-LABA users), 30,772 matched pairs were identified for the primary analysis. The propensity-score matched cohort had a mean age of 70 years and 47% were women. Compared to ICS-LABA use, LAMA-LABA use was associated with a 10% reduction in the rate of first moderate or severe COPD exacerbation (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.87, 0.94) and a 24% reduction in the rate of first pneumonia hospitalization (HR 0.76, 95% CI 0.70, 0.84). These findings were robust across a range of prespecified sensitivity and subgroup analyses. CONCLUSIONS: LAMA-LABA therapy was associated with improved clinical outcomes compared to ICS-LABA therapy in a cohort of patients treated in routine clinical practice. CLINICAL IMPLICATIONS: In keeping with current guidelines, LAMA-LABA therapy should be preferred to ICS-LABA therapy for most patients with COPD. DISCLOSURES: No relevant relationships by Jerry Avorn, source=Web Response Consultant relationship with Alosa Health Please note: 2019-present Added 04/14/2021 by William Feldman, source=Web Response, value=Consulting fee Consultant relationship with Aetion Please note: 2019-2020 Added 04/14/2021 by William Feldman, source=Web Response, value=Consulting fee Consultant relationship with Blue Cross Blue Shield of Massachusetts Please note: 2019-2020 Added 04/14/2021 by William Feldman, source=Web Response, value=Honoraria no disclosure on file for Joshua Gagne; No relevant relationships by Aaron Kesselheim, source=Web Response

The outcomes and acceptance of pressurized metered-dose inhaler bronchodilators with venturi mask modified spacer in the outpatient emergency department during the COVID-19 pandemic.

What is known and objectiveNebulizer use has been suspended in Malaysian public health facilities due to the potential to aggravate COVID‐19 nosocomial transmission. Currently, our facility uses the pressurized metered‐dose inhaler (pMDI) bronchodilator with Venturi mask modified spacer (VMMS) in patients visiting the Emergency Department (ED) for mild to moderate exacerbation of asthma and chronic obstructive pulmonary disease (COPD). We sought to assess the outcomes and acceptance of pMDI‐VMMS in the outpatient ED of a tertiary hospital in Malaysia.MethodsWe analysed the total visits and discharge rates during periods of using the nebulizer and current pMDI‐VMMS methods. The acceptance of pMDI‐VMMS by patients and assistant medical officers (AMOs) were assessed by questionnaire.Results and discussionWe analysed 3184 ED visits and responses from 103 patients and 32 AMOs. The direct discharge rate was similar for both nebulizer (n = 2162, 92.5%) and pMDI‐VMMS method (n = 768, 90.7%) (p‐value = 0.120). Twenty‐eight patients (27.2%) favoured the pMDI‐VMMS over the nebulizer, whereas 36 patients (35.0%) had no preference for either method. Sixty‐four patients (62.1%) felt that the current pMDI‐VMMS method was better or at least as effective in relieving their symptoms as a nebulizer. The current method was favoured over the nebulizer by twenty‐seven AMOs (84.4%). Twenty‐eight (87.5%) AMOs suggested that the current method was more effective than the nebulizer.What is new and conclusionThe bronchodilator delivered via pMDI‐VMMS appeared to be comparable to nebulizer in treating mild to moderate asthma and COPD exacerbations in the outpatient ED. Most patients and AMOs accepted the use of pMDI‐VMMS in the outpatient ED during the current COVID‐19 pandemic. The Venturi mask modified spacer can be a cheap and effective alternative to the commercial spacer in a resource‐limited situation.

Supplementation of curcumin and piperine plus standard therapy to prevent exacerbations in patients with Chronic Obstructive Pulmonary Disease (CUPISCO TRIAL: CUrcumin and PIperine Supplementation for COpd). A study protocol

Background: Chronic Obstructive Pulmonary Disease (COPD) is a highly prevalent condition that leads to a variety of complications that increase social and economic burdens. Although current treatment guidelines target symptomatic relief, including strategies to reduce future exacerbations and improve patients' quality of life, there is still a need for an effective intervention that also reduces the healthcare cost associated with this disease through reducing exacerbation-related hospitalization. Curcumin and piperine are natural and inexpensive components proven to inhibit the main inflammatory cascade responsible for COPD exacerbations. Objective: This trial aims to evaluate the supplementation of curcumin and piperine with COPD standard therapy to reduce the exacerbation rate in COPD patients compared to standard therapy alone. Methods: This will be a phase II multi-center, randomized, placebo-controlled, triple-blinded, parallel-group trial with COPD patients, classified in GOLD C and D groups, who are currently under standard treatment. Supplementation with 4g of curcumin combined with 20mg of piperine versus placebo will be evaluated during a period of 12 months. One thousand seven hundred and sixteen participants will be enrolled, with 858 participants for the control and intervention groups. The primary outcome will be the mean rate of moderate and severe exacerbations. Secondary outcomes will include time until first moderate or severe COPD exacerbation, St. George's Respiratory Questionnaire response, clinically significant change in post-bronchodilator forced expiratory volume, modification in the GOLD groups, and the presence of adverse events. Discussion: This will be the first randomized clinical trial to test curcumin plus piperine in COPD patients for twelve months. This intervention may improve patients’ quality of life and reduce the economic and social burden of this disease.

Triple Inhaled Therapy at Two Glucocorticoid Doses in Moderate-to-Very-Severe COPD

BackgroundTriple fixed-dose regimens of an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting β2-agonist (LABA) for chronic obstructive pulmonary disease (COPD) have been studied at single dose levels of inhaled glucocorticoid, but studies at two dose levels are lacking.MethodsIn a 52-week, phase 3, randomized trial to evaluate the efficacy and safety of triple therapy at two dose levels of inhaled glucocorticoid in patients with moderate-to-very-severe COPD and at least one exacerbation in the past year, we assigned patients in a 1:1:1:1 ratio to receive twice-daily inhaled doses of triple therapy (inhaled glucocorticoid [320 μg or 160 μg of budesonide], a LAMA [18 μg of glycopyrrolate], and a LABA [9.6 μg of formoterol]) or one of two dual therapies (18 μg of glycopyrrolate plus 9.6 μg of formoterol or 320 μg of budesonide plus 9.6 μg of formoterol). The primary end point was the annual rate (the estimated mean number per patient per year) of moderate or severe COPD exacerbations, as analyzed in the modified intention-to-treat population with the use of on-treatment data only.ResultsThe modified intention-to-treat population comprised 8509 patients. The annual rates of moderate or severe exacerbations were 1.08 in the 320-μg–budesonide triple-therapy group (2137 patients), 1.07 in the 160-μg–budesonide triple-therapy group (2121 patients), 1.42 in the glycopyrrolate–formoterol group (2120 patients), and 1.24 in the budesonide–formoterol group (2131 patients). The rate was significantly lower with 320-μg–budesonide triple therapy than with glycopyrrolate–formoterol (24% lower: rate ratio, 0.76; 95% confidence interval [CI], 0.69 to 0.83; P<0.001) or budesonide–formoterol (13% lower: rate ratio, 0.87; 95% CI, 0.79 to 0.95; P=0.003). Similarly, the rate was significantly lower with 160-μg–budesonide triple therapy than with glycopyrrolate–formoterol (25% lower: rate ratio, 0.75; 95% CI, 0.69 to 0.83; P<0.001) or budesonide–formoterol (14% lower: rate ratio, 0.86; 95% CI, 0.79 to 0.95; P=0.002). The incidence of any adverse event was similar across the treatment groups (range, 61.7 to 64.5%); the incidence of confirmed pneumonia ranged from 3.5 to 4.5% in the groups that included inhaled glucocorticoid use and was 2.3% in the glycopyrrolate–formoterol group.ConclusionsTriple therapy with twice-daily budesonide (at either the 160-μg or 320-μg dose), glycopyrrolate, and formoterol resulted in a lower rate of moderate or severe COPD exacerbations than glycopyrrolate–formoterol or budesonide–formoterol. (Funded by AstraZeneca, ETHOS ClinicalTrials.gov number, NCT02465567.)

COPD exacerbation costs in the IMPACT study: a within-trial analysis

Exacerbations account for the greatest proportion of costs associated with chronic obstructive pulmonary disease (COPD). Here we aimed to evaluate, from the US payer perspective, the costs associated with moderate and severe COPD exacerbation events for patients treated with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) compared with FF/VI or UMEC/VI. This post hoc, within-trial economic analysis used data derived from the InforMing the PAthway of COPD Treatment (IMPACT) study (NCT02164513). Treatment groups within the IMPACT trial received either triple therapy with FF/UMEC/VI (100/62.5/25 mcg) or dual therapy (FF/VI [100/25 mcg] or UMEC/VI [62.5/25 mcg]). The primary end point for this IMPACT post hoc analysis was cost differences between the treatment arms related to 1-year on-treatment combined moderate and severe COPD exacerbation events. The final study sample for this within-trial analysis consisted of 10,355 patients, 49% of whom experienced an on-treatment moderate or severe exacerbation during the study. The mean 1-year on-treatment cost estimate associated with combined moderate and severe exacerbations was highest with UMEC/VI and lowest with FF/UMEC/VI ($6205 vs $4913, respectively). Mean cost differences were statistically significant for all pairwise comparisons of FF/UMEC/VI with FF/VI or UMEC/VI (-$549 [95% CI, -$565 to -$533] and -$1292 [95% CI, -$1313 to -$1272], respectively; both P <.0001). Treatment with FF/UMEC/VI compared with FF/VI or UMEC/VI in the US healthcare system resulted in lower exacerbation-related costs for combined moderate/severe exacerbation events, as well as moderate and severe exacerbations separately.

Moderate and severe exacerbations have a significant impact on health-related quality of life, utility, and lung function in patients with chronic obstructive pulmonary disease: A meta-analysis.

Exacerbations of chronic obstructive pulmonary disease (COPD) may increase the risk of morbidity and mortality as well as pulmonary complications after surgery among patients with COPD. This meta-analysis was designed to explore the impact of moderate and severe exacerbations of COPD on health-related quality of life (HRQoL), utility, and lung function in patients with COPD. The individual impacts of moderate and severe exacerbations on St George's Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT), and EuroQoL-5 dimensions 5 level (EQ-5D-5L) scores, and on forced expiratory volume in 1s (FEV1) were assessed. Adjustments were applied to account for differences in study design. Outcomes were measured at specific time points across a 12-month study period, for all patients and for subsets with either no or ≥1 severe exacerbations in the year before study entry. The proximity of each measurement in relation to a specific exacerbation was also assessed. A total of seven randomized clinical trials (RCTs) ≥12-month interventional/observational studies with 18,746 COPD patients were assessed. Overall, 4,483 (24%) patients had ≥1 severe exacerbation in the previous year. Moderate and severe exacerbations were associated with worsening from baseline in SGRQ, CAT, EQ-5D-5L, and FEV1 measures; severe exacerbations had greater impact than moderate exacerbations. Moderate and severe exacerbations have a substantial and lasting impact on HRQoL, utility, and lung function in patients with COPD, highlighting a need for effective exacerbation prevention.