Severe COPD Exacerbations Research Articles

Comparative Effectiveness and Safety of Different Types of Inhaled Long-Acting β2-Agonist Plus Inhaled Long-Acting Muscarinic Antagonist vs Inhaled Long-Acting β2-Agonist Plus Inhaled Corticosteroid Fixed-Dose Combinations in COPD A Propensity Score-Inverse Probability of Treatment Weighting Cohort Study

Despite multiple available fixed-dose combinations (FDCs) of inhaled long-acting β2-agonists (LABAs) plus long-acting muscarinic antagonists (LAMAs) and LABAs plus inhaled corticosteroids (ICS) for COPD, uncertainty remains regarding their comparative effects. Can comparative effectiveness and safety of LABA plus LAMA (LABA/LAMA) and LABA plus ICS (LABA/ICS) FDCs vary by different individual components of the dual combinations in COPD? We conducted a new user, propensity score-inverse probability of treatment weighting cohort study to compare the effectiveness and safety of two frequently used LABA/LAMA FDCs (indacaterol plus glycopyrronium [IND/GLY] and vilanterol plus umeclidinium [VI/UMEC]) vsthree commonly prescribed LABA/ICS FDCs (salmeterol plus fluticasone propionate [SAL/FP], formoterol fumarate plus budesonide [FF/BUD], and formoterol fumarate plus beclomethasone dipropionate [FF/BDP]) using the Taiwanese nationwide health care claims from 2014 through 2017. The primary effectiveness outcome was the annual moderate to severe exacerbation rate, and safety outcomes included risks of severe pneumonia and cardiovascular disease requiring hospitalization. Weighted generalized linear mixed models and Cox proportional hazard models were used to assess the effectiveness and safety outcomes, respectively. Patients with COPD initiating IND/GLY and VI/UMEC showed an 11%(incidence rate ratio [IRR], 0.89; 95%CI, 0.80-0.98) and 20%(IRR, 0.80; 95%CI, 0.71-0.90) reduced annual rate of moderate to severe exacerbations, respectively, than those initiating SAL/FP, but showed a similar rate as those initiating FF/BUD or FF/BDP. Both LABA/LAMA FDCs, compared with SAL/FP and VI/UMEC vsFF/BDP, were associated with a 27%(hazard ratio [HR], 0.73; 95%CI, 0.59-0.90) to 42%(HR, 0.58; 95%CI, 0.48-0.70) reduced pneumonia risk. Cardiovascular risk was comparable in five groups. An intraclass difference existed in rates of moderate to severe COPD exacerbation and risks of pneumonia among LABA/ICS FDCs, but not between LABA/LAMA FDCs. Both LABA/LAMAs vsSAL/FP are associated with a lower exacerbation rate and pneumonia risk, but exhibit similar effectiveness and safety outcomes compared with FF/BDP or FF/BUD, suggesting that comparative effects may differ by individual components of the dual therapies in COPD.

Impact of COVID-19 lockdown on the incidence and mortality of acute exacerbations of chronic obstructive pulmonary disease: national interrupted time series analyses for Scotland and Wales

BackgroundThe COVID-19 pandemic and ensuing national lockdowns have dramatically changed the healthcare landscape. The pandemic’s impact on people with chronic obstructive pulmonary disease (COPD) remains poorly understood. We hypothesised that the UK-wide lockdown restrictions were associated with reductions in severe COPD exacerbations. We provide the first national level analyses of the impact of the COVID-19 pandemic and first lockdown on severe COPD exacerbations resulting in emergency hospital admissions and/or leading to death as well as those recorded in primary care or emergency departments.MethodsUsing data from Public Health Scotland and the Secure Anonymised Information Linkage Databank in Wales, we accessed weekly counts of emergency hospital admissions and deaths due to COPD over the first 30 weeks of 2020 and compared these to the national averages over the preceding 5 years. For both Scotland and Wales, we undertook interrupted time-series analyses to model the impact of instigating lockdown on these outcomes. Using fixed-effect meta-analysis, we derived pooled estimates of the overall changes in trends across the two nations.ResultsLockdown was associated with 48% pooled reduction in emergency admissions for COPD in both countries (incidence rate ratio, IRR 0.52, 95% CI 0.46 to 0.58), relative to the 5-year averages. There was no statistically significant change in deaths due to COPD (pooled IRR 1.08, 95% CI 0.87 to 1.33). In Wales, lockdown was associated with 39% reduction in primary care consultations for acute exacerbation of COPD (IRR 0.61, 95% CI 0.52 to 0.71) and 46% reduction in COPD-related emergency department attendances (IRR 0.54, 95% CI 0.36 to 0.81).ConclusionsThe UK-wide lockdown was associated with the most substantial reductions in COPD exacerbations ever seen across Scotland and Wales, with no corresponding increase in COPD deaths. This may have resulted from reduced transmission of respiratory infections, reduced exposure to outdoor air pollution and/or improved COPD self-management.

English

BACKGROUND Pulmonary hypertension (PH) and heart failure are common comorbidities in 20 – 30 % of chronic obstructive pulmonary disease (COPD) patients with acute exacerbation. Similarities in signs and symptoms and lack of objective measures to stratify them at emergency department makes the management difficult. Echocardiography though useful requires specialised training. Hence, B-Type Natriuretic Peptide (BNP) is a simple test that can prognosticate the severity and can influence management in such patients. The purpose of the study was to estimate the significance of BNP during acute exacerbation of chronic obstructive pulmonary disease (AECOPD) as an important marker of severity and to study its correlation with duration of hospital stay, place and mode of management in patients with severe and life-threatening exacerbation of COPD. METHODS This is a prospective longitudinal observational study conducted on 50 patients of severe and life-threatening COPD exacerbation admitted to General Medicine department of HSK hospital, Bagalkot and their outcomes were noted based on the BNP levels. RESULTS The study showed higher levels of BNP in patients admitted to ICU as compared to emergency ward (P = 0.001). Greater values among those on invasive mechanical ventilation vs. non-invasive ventilation (NIV). There was a positive correlation and statistical significance of BNP values with arterial blood gases (ABG) parameters like pulmonary hypertension (PH), partial pressure of carbondi-oxide (PaCO2), partial pressure of oxygen (PaO2), echo parameters like right ventricle (RV) diameter and pulmonary artery systolic pressure (PASP) and duration of hospital stay. CONCLUSIONS BNP is a simple, low cost and easily available blood test that can prognosticate oxygen requirement, mode of ventilation, place of management and can grade and reflect the severity in acute exacerbation of COPD. KEYWORDS AECOPD, BNP, Prognostic Marker, Outcome

Exploring the impact of number and type of comorbidities on the risk of severe COPD exacerbations in Korean Population: a Nationwide Cohort Study

BackgroundIt is difficult to assess the impact of multiple comorbidities on clinical outcomes in chronic obstructive pulmonary disease (COPD). In this study, we aimed to investigate exacerbation-associated comorbidities, determine whether the number of comorbidities is an independent risk factor for exacerbation, and identify other exacerbation-associated factors in a Korean COPD population using a nationwide population-based cohort. This study focused on severe exacerbations that required hospitalisation or emergency room visits.MethodsThe National Health Insurance Service-National Sample Cohort, version 2.0, data sampled between 2002 and 2015 were analysed. Data from two years after the diagnosis of COPD were analysed for each participant (N = 12,554, entire cohort). Moreover, 42% of the participants underwent additional health examinations (N = 5306, health-screening cohort). Fifteen comorbidities that were previously reported as risk factors for exacerbations were examined. A logistic regression model was used to analyse association with exacerbations.ResultsAsthma (1.57 [1.39–1.76] and 1.24 [1.06–1.44]), lung cancer (1.84 [1.30–2.59] and 2.28 [1.54–3.37]), and heart failure (1.39 [1.16–1.67] and 1.52 [1.18–1.97]) were associated with exacerbation in both cohorts (odds ratio [95% confidence interval] in the entire cohort and health-screening cohort, respectively). The number of comorbidities was an independent risk factor, and old age, male sex, low body mass index, and current smoking were also independent risk factors. High cholesterol levels and body mass index exerted protective effects against exacerbation.ConclusionsThe number of comorbidities, certain comorbidities such as asthma, lung cancer and heart failure, and low BMI were associated with an increased risk of severe exacerbation in COPD patients.

Determinination of the Frequency of Altered Cardiac Repolarization by Measuring the Heart rate Corrected QT Interval in COPD Patients

Objectives: To determine the frequency of altered cardiac repolarization by measuring the heart rate corrected QT interval in COPD patients.
 Setting: Department of Medicine at LUMHS hospital Hyderabad/Jamshoro.
 Study Design: Descriptive Cross sectional study. 
 Duration of Study: 6 months from 01-03-2019 to 31-08-2019.
 Methods: A total of 232 patients with severe acute exacerbation of COPD were included in this study. A 12 lead ECG was performed. QT intervals were measured on a resting ECG tracing in lead II. The QT interval was measured manually from the starting point of the QRS complex to the terminal point of the down slope of the T wave.
 Results: A total of 232 patients with COPD were included in this study. Most of the cases were above 50 years of age. The average age of the patients was 53.74±4.35 years. There were 92.67% (215/232) male and 7.33% (17/232) female. Out of 232 patients, 21.14% were current smoker and 75.86% were ex-smoker. A QTc interval >0.44 seconds was considered abnormally prolonged. Frequency of altered cardiac repolarization by measuring the heart rate corrected QT interval in COPD patients was 31.47% (73/232). Rate of altered cardiac repolarization was not significant among different age groups (p=0.641). Rate of altered cardiac repolarization was significantly high in male as compare to female (33.5% vs. 5.9%; p=0.018). This was not significant between obese and non-obese groups (p=0.100). Rate of altered cardiac repolarization was significantly high in former smoker (p=0.0005) and those patients whose duration of COPD was above 15 years (p=0.0005).
 Conclusion: Patients with hypoxic chronic obstructive pulmonary disease (COPD) have evidence of a subclinical parasympathetic autonomic neuropathy, with apparent preservation of sympathetic function. Measuring heart rate corrected QT interval (QTc) test is repeatable, easy to perform and a sensitive indicator for autonomic dysfunction in breathlessness individuals with COPD.

Correlation of Luminal Mucus Score in Large Airways with Lung Function and Quality of Life in Severe Acute Exacerbation of COPD: A Cross-Sectional Study.

Background and ObjectiveLuminal mucus plugging in small airways is associated with lung function decline and death of patients with chronic obstructive pulmonary disease (COPD). However, little attention has been paid to the possible role of mucus in large airways in acute exacerbation of COPD (AECOPD). Therefore, this study aimed to explore the relationship between the luminal mucus score of large airways and other physiological parameters of severe AECOPD.Subjects and MethodsA total of 74 AECOPD inpatients were enrolled in this cross-sectional study. All patients underwent lung function tests and bronchoscopy, and their luminal mucus was observed and scored through bronchoscopy. Four questionnaires, including the St. George Respiratory Questionnaire (SGRQ), modified Medical Research Council dyspnea scale (mMRC), COPD Assessment Test (CAT) and Exacerbation of Chronic pulmonary disease Tool (EXACT), were used to assess health-related quality of life (HRQoL).ResultsThe luminal mucus score of large airways was significantly correlated with spirometry parameters and HRQoL score. Both mMRC grade and SGRQ score were significantly positively correlated with luminal mucus score (ρ=0.527, P<0.001; ρ=0.441, P<0.001, respectively). Forced expiratory flow at 25% to 75% of the FVC (FEF25%-75%) and FEV1% predicted, as functional measures reflecting small airway disease, were significantly negatively correlated with luminal mucus score (ρ=−0.518, P<0.001; ρ=−0.498, P<0.001, respectively). The stepwise multiple linear regression model suggested that mMRC grade and FEV1% predicted could predict luminal mucus score (R2=0.348, F=18.960, P<0.001).ConclusionFor severe acute exacerbation of COPD, bronchoscopy-identified luminal mucus in large airways is associated with reduced lung function and worse health-related quality of life.

Basal-bolus insulin therapy fails to control glucocorticoidinduced hyperglycemia in patients with severe COPD exacerbation

Basal-bolus insulin therapy fails to control glucocorticoidinduced hyperglycemia in patients with severe COPD exacerbation

Ability of procalcitonin to distinguish between bacterial and nonbacterial infection in severe acute exacerbation of chronic obstructive pulmonary syndrome in the ICU

BackgroundTo assess the ability of procalcitonin (PCT) to distinguish between bacterial and nonbacterial causes of patients with severe acute exacerbation of COPD (AECOPD) admitted to the ICU, we conducted a retrospective analysis of two prospective studies including 375 patients with severe AECOPD with suspected lower respiratory tract infections. PCT levels were sequentially assessed at the time of inclusion, 6 h after and at day 1, using a sensitive immunoassay. The patients were classified according to the presence of a documented bacterial infection (including bacterial and viral coinfection) (BAC + group), or the absence of a documented bacterial infection (i.e., a documented viral infection alone or absence of a documented pathogen) (BAC- group). The accuracy of PCT levels in predicting bacterial infection (BAC + group) vs no bacterial infection (BAC- group) at different time points was evaluated by receiver operating characteristic (ROC) analysis.ResultsRegarding the entire cohort (n = 375), at any time, the PCT levels significantly differed between groups (Kruskal–Wallis test, p < 0.001). A pairwise comparison showed that PCT levels were significantly higher in patients with bacterial infection (n = 94) than in patients without documented pathogens (n = 218) (p < 0.001). No significant difference was observed between patients with bacterial and viral infection (n = 63). For example, the median PCT-H0 levels were 0.64 ng/ml [0.22–0.87] in the bacterial group vs 0.24 ng/ml [0.15–0.37] in the viral group and 0.16 ng/mL [0.11–0.22] in the group without documented pathogens. With a c-index of 0.64 (95% CI; 0.58–0.71) at H0, 0.64 [95% CI 0.57–0.70] at H6 and 0.63 (95% CI; 0.56–0.69) at H24, PCT had a low accuracy for predicting bacterial infection (BAC + group).ConclusionDespite higher PCT levels in severe AECOPD caused by bacterial infection, PCT had a poor accuracy to distinguish between bacterial and nonbacterial infection. Procalcitonin might not be sufficient as a standalone marker for initiating antibiotic treatment in this setting.

Reduction of Severe Exacerbations of COPD during COVID-19 Pandemic in Portugal: A Protective Role of Face Masks?

Viral infections are known to be the main trigger for Chronic obstructive pulmonary disease (COPD) exacerbations. Face masks are acknowledged for effective viral aerosol shedding reduction. COVID-19 pandemic generated an opportunity to study the impact of face masks and confinement on droplet transmission diseases, usually implicated in acute exacerbations of COPD (AECOPD). We aimed to evaluate the variation on severe AECOPD (sAECOPD) rate in a Portuguese COPD cohort during the first COVID-19 lockdown and following months. This retrospective self-controlled study enrolled 322 adult patients followed at COPD-specialized consultation in a tertiary hospital from February 2016 to July 2020, of whom 286 met inclusion criteria. Severe AECOPD events were registered from March 2020 (beginning of state of emergency) until July 2020. From 2016 to 2019 there was a mean of 38 patients per year with sAECOPD. During 2020, 11 patients experienced sAECOPD. Over the course of 2020 there was a 73.4% (p < 0.001) decrease in sAECOPD events comparing with previous years’ average. After the end of State of Emergency, the rate of sAECOPD events also declined by 74.6% (p < 0.001) comparing with the same timeline of previous years. Results were consistent and statistically significant when comparing 2020 with each of previous years for every period of analysis. Our findings suggest a sustained decrease in the rate of sAECOPD during confinement and in the following months. The widespread use of face mask and social distancing during COVID-19 pandemic may play an important role in preventing the transmission of respiratory infections and consequently reducing sAECOPD.

Predicting Hospitalization Due to COPD Exacerbations in Swedish Primary Care Patients Using Machine Learning - Based on the ARCTIC Study.

PurposeChronic obstructive pulmonary disease (COPD) exacerbations can negatively impact disease severity, progression, mortality and lead to hospitalizations. We aimed to develop a model that predicts a patient’s risk of hospitalization due to severe exacerbations (defined as COPD-related hospitalizations) of COPD, using Swedish patient level data.Patients and MethodsPatient level data for 7823 Swedish patients with COPD was collected from electronic medical records (EMRs) and national registries covering healthcare contacts, diagnoses, prescriptions, lab tests, hospitalizations and socioeconomic factors between 2000 and 2013. Models were created using machine-learning methods to predict risk of imminent exacerbation causing patient hospitalization due to COPD within the next 10 days. Exacerbations occurring within this period were considered as one event. Model performance was assessed using the Area under the Precision-Recall Curve (AUPRC). To compare performance with previous similar studies, the Area Under Receiver Operating Curve (AUROC) was also reported. The model with the highest mean cross validation AUPRC was selected as the final model and was in a final step trained on the entire training dataset.ResultsThe most important factors for predicting severe exacerbations were exacerbations in the previous six months and in whole history, number of COPD-related healthcare contacts and comorbidity burden. Validation on test data yielded an AUROC of 0.86 and AUPRC of 0.08, which was high in comparison to previously published attempts to predict COPD exacerbation.ConclusionOur work suggests that clinically available information on patient history collected via automated retrieval from EMRs and national registries or directly during patient consultation can form the basis for future clinical tools to predict risk of severe COPD exacerbations.

Safety of denervation following targeted lung denervation therapy for COPD: AIRFLOW-1 3-year outcomes

BackgroundTargeted lung denervation (TLD) is a novel bronchoscopic therapy that disrupts parasympathetic pulmonary nerve input to the lung reducing clinical consequences of cholinergic hyperactivity. The AIRFLOW-1 study assessed safety and TLD dose in patients with moderate-to-severe, symptomatic COPD. This analysis evaluated the long-term impact of TLD on COPD exacerbations, pulmonary function, and quality of life over 3 years of follow up.MethodsTLD was performed in a prospective, energy-level randomized (29 W vs 32 W power), multicenter study (NCT02058459). Additional patients were enrolled in an open label confirmation phase to confirm improved gastrointestinal safety after procedural modifications. Durability of TLD was evaluated at 1, 2, and 3 years post-treatment and assessed through analysis of COPD exacerbations, pulmonary lung function, and quality of life.ResultsThree-year follow-up data were available for 73.9% of patients (n = 34). The annualized rate of moderate to severe COPD exacerbations remained stable over the duration of the study. Lung function (FEV1, FVC, RV, and TLC) and quality of life (SGRQ-C and CAT) remained stable over 3 years of follow-up. No new gastrointestinal adverse events and no unexpected serious adverse events were observed.ConclusionTLD in COPD patients demonstrated a positive safety profile out to 3 years, with no late-onset serious adverse events related to denervation therapy. Clinical stability in lung function, quality of life, and exacerbations were observed in TLD treated patients over 3 years of follow up.

Neutrophil-to-Lymphocyte Ratio Predicts Clinical Outcome of Severe Acute Exacerbation of COPD in Frequent Exacerbators

PurposeFrequent exacerbators are a specific phenotype of chronic obstructive pulmonary disease (COPD), whose clinical characteristics and prognostic biomarkers during severe acute exacerbation (AECOPD) have not yet been fully elucidated. The aim of this study was to investigate the clinical features of severe AECOPD in frequent exacerbators and explore the predictive value of the neutrophil-to-lymphocyte ratio (NLR) for outcome in this phenotype during severe exacerbation.Patients and MethodsA total of 604 patients with severe AECOPD were retrospectively included in the study. Subjects were defined as frequent exacerbators if they experienced two or more exacerbations in the past year. Clinical characteristics and worse outcome (ICU admission, or invasive ventilation, or in-hospital mortality) during severe AECOPD were compared between frequent exacerbators and non-frequent ones. Furthermore, the relationship between NLR and worse outcome in frequent exacerbators was analyzed using logistic regression and receiver operating characteristic (ROC).ResultsAmong 604 patients with severe AECOPD, 282 (46.69%) were frequent exacerbators and 322 (53.31%) were non-frequent exacerbators. Compared with the non-frequent ones, frequent exacerbators presented higher levels of NLR (5.93 [IQR, 3.40–9.28] vs 4.41 [IQR, 2.74–6.80]; p<0.001), and more worse outcome incidence (58 [20.57%] vs 38 [11.80%]; p=0.003). Moreover, among the frequent exacerbators, NLR levels in the patients with worse outcome were much higher than in those without worse outcome (11.09 [IQR, 7.74–16.49] vs 5.28 [IQR, 2.93–7.93]; p<0.001). Increased NLR was significantly associated with a higher risk of worse outcome in frequent exacerbators (OR, 1.43; 95% CI, 1.28–1.64; p<0.001). Furthermore, ROC analysis revealed that a cut-off value of 10.23, NLR could predict worse outcome of severe AECOPD in frequent exacerbators (sensitivity 62.1%, specificity 92.0%, AUC 0.833).ConclusionFrequent exacerbators exhibited an increased level of NLR and a higher proportion of worse outcome during severe AECOPD. NLR is expected to be a promising predictive biomarker for the prognosis of severe AECOPD in frequent exacerbators.

Home parasternal electromyography tracks patient-reported and physiological measures of recovery from severe COPD exacerbation.

Physiological phenotyping using daily home-based assessments reveals early improvement in load–capacity–drive imbalance following #AECOPD and feasibility of home parasternal electromyography measurement, which tracks symptoms, health status and spirometry https://bit.ly/3o6I0Ty

COMBINED THERAPY WITH MEDICAL GASES AND RESPIRATORY SUPPORT IN PATIENTS WITH HYPERCAPNIC RESPIRATORY FAILURE WITH EXACERBATION OF COPD

COPD is one of the leading causes of morbidity and mortality in the Russian Federation. The prevalence reaches 6-10% of the general population. Severe and frequent exacerbations of COPD lead to acute hypercapnic DN requiring NIV. In 30% of patients with severe exacerbation of COPD, NIV does not lead to the desired results. To optimize NIV in this group of patients, we used inhalations of thermal heliox (t-He/O2) and nitric oxide (iNO), which significantly improved O2 transport, CO2 elimination, hemodynamics and stabilized lactate levels.

ASSESMENT OF INFECTIOUS ETHYOLOGY IN SEVERE EXACERBATIONS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE; RELATIONSHIP WITH RESPIRATORY FAILURE

Acute exacerbation of chronic obstructive pulmonary disease (COPD) is a negative event in disease evolution which leads to higher morbidity and mortality of patients. Infectious agents are the main cause of exacerbations and they can be easily obtained using new molecular methods. Our objective was to detect respiratory pathogens in patients hospitalized for severe acute exacerbation of COPD and to analyze their relationship with respiratory failure. We examined sputum from 49 patients (male, n=32) older than 40 years, using multiplex PCR microarray for 34 targets of which 18 bacteria, 9 viruses and 7 markers of antibiotic resistance. Blood gas analyses and other clinical and laboratory measures were provided. Infectious etiology was found in 51% of acute exacerbations in hospitalized patients. Of all sputum samples, influenza A was the most frequently detected respiratory pathogen (n = 9, 18.4%) followed by Haemophilis influenzae (n = 7, 14.3 %). We found a significant negative correlation between the presence of the type of detected pathogens and the level of pCO2 in the blood (r = -0.437; p = 0.029); thus, the higher the level of pCO2, the greater likelihood that it is a bacterial infection. Detection of sputum bacteria in patients with severe acute exacerbation of COPD can be an independent risk factor for acute hypercapnic respiratory failure. Keywords: acute exacerbation, COPD, respiratory pathogens, PCR, blood gas analyses

Inhaled Corticosteroids Do Not Adversely Impact Outcomes in COVID-19 Positive Patients with COPD: An Analysis of Cleveland Clinic's COVID-19 Registry

Background: Inhaled Corticosteroids (ICS) are commonly prescribed to patients with severe COPD and recurrent exacerbations. Given the concern for increased viral shedding by corticosteroids, as observed with previous coronavirus strains, it is not known what impact ICS cause in terms of COVID-19 positivity or disease severity in COPD patients. Methods: This study examined 27,810 patients with COPD from the Cleveland Clinic COVID-19 registry between March and September 2020. Electronic health records (EHR) were used to determine diagnosis of COPD, ICS use, and clinical outcomes. Multivariate logistic regression was used to adjust for demographics and comorbidities known to be associated with increased risk for severe Coronavirus disease-19 disease. Findings: Amongst the COPD patients who were tested for COVID-19, 44.1% of those taking an ICS-containing inhaler tested positive for COVID-19 versus 47.2% who tested negative (p=0.033). Of those who tested positive, (n=1288), 371 (28.8%) required hospitalization. In-hospital outcomes were not significantly different when comparing ICS versus no ICS in terms of developing sepsis (28.4% vs 26.5%, p=0.77), ICU admission (36.8% vs 31.2%, p=0.30), endotracheal intubation (21.9% vs 16.5%, p=0.24), or mortality (18.4% vs 20.0%, p=0.80). Multivariate logistic regression demonstrated no significant differences in hospitalization (adj OR 1.12, CI: 0.90-1.38), ICU admission (adj OR: 1.31, CI: 0.82-2.10), need for mechanical ventilation (adj OR 1.65, CI: 0.69-4.02), or mortality (OR: 0.80, CI: 0.43-1.49). Interpretations: ICS therapy did not increase COVID-19 related healthcare utilization or mortality outcome in patients with COPD. These findings should encourage clinicians to continue ICS maintenance therapy for COPD patients during the COVID-19 pandemic. Funding: No sources of funding were used.Declaration of Interests: The authors certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.Ethics Approval Statement: This study and the registry were both approved by the Cleveland Clinic Institutional Review Board (IRB#20-391).

Polycythemia is Associated with Lower Incidence of Severe COPD Exacerbations in the SPIROMICS Study.

Secondary polycythemia has long been recognized as a consequence of chronic pulmonary disease and hypoxemia and is associated with lower mortality and fewer hospitalizations among individuals with chronic obstructive pulmonary disease (COPD)-prescribed long-term oxygen therapy. This study investigates the association of polycythemia with COPD severity, phenotypic features, and respiratory exacerbations in a contemporary and representative sample of individuals with COPD. Current and former smokers with COPD (forced expiratory volume in 1 second [FEV1] to forced vital capacity [FVC] ratio <70%) without a history of hematologic/oncologic disorders were selected from the SubPopulations and InteRmediate Outcomes Measures In COPD Study (SPIROMICS), a multi-center observational cohort. Participants with polycythemia (hemoglobin ≥15g/dL [females] or ≥17g/dL [males]), were compared to individuals without anemia (hemoglobin ≥12g/dL [females] or ≥13g/dL [males]). Cross-sectional outcomes including percent predicted FEV1, respiratory symptoms, quality of life, exercise tolerance, and percentage and distribution of emphysema (voxels<-950 Hounsfield units [HU] at total lung capacity) were evaluated using linear or logistic regression. Longitudinal acute exacerbation of COPD (AECOPD) and severe AECOPD (requiring an emergency department visit or hospitalization) were assessed using zero-inflated negative binomial models. Among 1261 participants, 148 (11.7%) had polycythemia. Average follow-up was 4.2±1.7 years and did not differ by presence of polycythemia. In multivariate analysis, compared to participants with normal hemoglobin, polycythemia was associated with a reduced rate of severe AECOPD (adjusted incidence rate ratio 0.57, 95% CI: 0.33-0.98), lower percent predicted FEV1, lower resting oxygen saturation, increased upper to lower lobe ratio of emphysema, and a greater degree of emphysema, though the latter was attenuated after adjusting for lung function. There were no significant differences in total AECOPD, patient-reported outcomes, or exercise tolerance. These findings suggest that polycythemia, while associated with less favorable physiologic parameters, is not independently associated with symptoms, and is associated with fewer severe exacerbations. Future studies should explore the potentially protective role of increased hemoglobin beyond the correction of anemia.

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.

Clinical Relevance of the Anti-inflammatory Effects of Roflumilast on Human Bronchus: Potentiation by a Long-Acting Beta-2-Agonist.

Background: Roflumilast is an option for treating patients with severe COPD and frequent exacerbations despite optimal therapy with inhaled drugs. The present study focused on whether the phosphodiesterase (PDE) 4 inhibitor roflumilast and its active metabolite roflumilast N-oxide affect the release of tumor necrosis factor (TNF)-α and chemokines by lipopolysaccharide (LPS)-stimulated human bronchial explants. We also investigated the interactions between roflumilast, roflumilast N-oxide and the β2-agonist formoterol with regard to cytokine release by the bronchial preparations. Methods: Bronchial explants from resected lungs were incubated with roflumilast, roflumilast N-oxide and/or formoterol and then stimulated with LPS. An ELISA was used to measure levels of TNF-α and chemokines in the culture supernatants. Results: At a clinically relevant concentration (1 nM), roflumilast N-oxide and roflumilast consistently reduced the release of TNF-α, CCL2, CCL3, CCL4, CCL5 and CXCL9 (but not CXCL1, CXCL5, CXCL8 and IL-6) from human bronchial explants. Formoterol alone decreased the release of TNF-α, CCL2, and CCL3. The combination of formoterol with roflumilast (1 nM) was more potent than roflumilast alone for inhibiting the LPS-induced release of TNF-α, CCL2, CCL3, CCL4, and CXCL9 by the bronchial explants. Conclusions: At a clinically relevant concentration, roflumilast N-oxide and its parent compound, roflumilast, reduced the LPS-induced production of TNF-α and chemokines involved in monocyte and T-cell recruitment but did not alter the release of chemokines involved in neutrophil recruitment. The combination of formoterol with roflumilast enhanced the individual drugs’ anti-inflammatory effects.

Use of antidiabetic medications and risk of chronic obstructive pulmonary disease exacerbation requiring hospitalization: a disease risk score-matched nested case\u2013control study

BackgroundExacerbation of chronic obstructive pulmonary disease (COPD) severely impacts the quality of life and causes high mortality and morbidity. COPD is involved with systemic and pulmonary inflammation, which may be attenuated with antidiabetic agents exerting anti-inflammatory effects. Real-world evidence is scant regarding the effects of antidiabetic agents on COPD exacerbation. Accordingly, we conducted a disease risk score (DRS)-matched nested case–control study to systemically assess the association between each class of oral hypoglycemic agents (OHAs) and risk of severe COPD exacerbation in a nationwide COPD population co-diagnosed with diabetes mellitus (DM).MethodsWe enrolled 23,875 COPD patients receiving at least one OHA for management of DM by analyzing the Taiwan National Health Insurance claims database between January 1, 2000, and December 31, 2015. Cases of severe exacerbation were defined as those who had the first hospital admission for COPD. Each case was individually matched with four randomly-selected controls by cohort entry date, DRS (the estimated probability of encountering a severe COPD exacerbation), and COPD medication regimens using the incidence density sampling approach. Conditional logistic regressions were performed to estimate odds ratios (OR) of severe COPD exacerbation for each type of OHAs.ResultsWe analyzed 2700 cases of severe COPD exacerbation and 9272 corresponding controls after DRS matching. Current use of metformin versus other OHAs was associated with a 15% (adjusted OR [aOR], 0.85; 95% confidence interval [CI] 0.75–0.95) reduced risk of severe COPD exacerbation, whereas the reduced risk was not observed with other types of antidiabetic agents. When considering the duration of antidiabetic medication therapy, current use of metformin for 91–180 and 181–365 days was associated with a 28% (aOR, 0.72; 95% CI 0.58–0.89) and 37% (aOR, 0.63; 95% CI 0.51–0.77) reduced risk of severe COPD exacerbation, respectively. Similarly, 91–180 days of sulfonylureas therapy led to a 28% (aOR, 0.72; 95% CI 0.58–0.90) lower risk, and longer treatments consistently yielded 24–30% lower risks. Current use of thiazolidinediones for more than 181 days yielded an approximately 40% decreased risk.ConclusionsDuration-dependent beneficial effects of current metformin, sulfonylurea, and thiazolidinedione use on severe COPD exacerbation were observed in patients with COPD and DM.