Frequency Of Chronic Obstructive Pulmonary Disease Exacerbations Research Articles

CRP, Fibrinogen, White Blood Cells, and Blood Cell Indices as Prognostic Biomarkers of Future COPD Exacerbation Frequency: The TIE Cohort Study.

Background/Objective: Systemic inflammation is common in chronic obstructive pulmonary disease (COPD), and evidence suggests that inflammatory biomarkers can predict acute exacerbations (AECOPDs). The aim of this study was to analyse whether C-reactive protein (CRP), fibrinogen, white blood cell count (WBC), or the blood cell indices PLR (platelet-to-lymphocyte ratio), SII (systemic immune inflammation index), SIRI (systemic inflammation response index), and AISI (aggregate index of systemic inflammation) can predict future AECOPDs. Methods: In the Tools Identifying Exacerbations (TIE) cohort study, participants with spirometry-confirmed COPD were recruited from primary and secondary care in three Swedish regions and assessed during a stable phase of COPD. AECOPD frequency during the three-year follow-up was reviewed in medical records. Associations were analysed via ordinal logistic regressions. Results: Of the 571 participants, 46% had ≥1 AECOPD during follow-up, and the mean ± SD AECOPD frequency was 0.63 ± 1.2/year. In unadjusted analyses, high levels of CRP (odds ratio 1.86, 95% CI 1.29-2.67), fibrinogen (2.09, 1.38-3.16), WBCs (2.18, 1.52-3.13), SII (1.52, 1.05-2.19), SIRI (1.76, 1.23-2.52), and AISI (1.99, 1.38-2.87) were associated with a higher AECOPD frequency. After adjustment for AECOPD history, age, sex, smoking, body mass index, COPD Assessment Test score, lung function, and inhaled corticosteroid use, associations remained for high levels of CRP (adjusted odds ratio of 1.64; 95% CI of 1.08-2.49), fibrinogen (1.55; 1.07-2.24), and WBC (1.65; 1.10-2.47). Conclusions: CRP, fibrinogen, and WBC, assessed during stable-phase COPD, enhanced AECOPD prediction, whereas PLR, SII, SIRI, and AISI did not.

Outcomes among patients with chronic obstructive pulmonary disease after recovery from COVID-19 infection of different severity

While studies have suggested increased risks of severe COVID-19 infection in chronic obstructive pulmonary disease (COPD), the persistent and delayed consequences of COVID-19 infection on patients with COPD upon recovery remain unknown. A prospective clinical study was conducted in Hong Kong to investigate the persistent and delayed outcomes of patients with COPD who had COVID-19 infection of different severity (mild-moderate COVID-19 and severe COVID-19), compared with those who did not. Chinese patients with COPD ≥ 40 years old were recruited from March to September 2021. They were prospectively followed up for 24.9 ± 5.0 months until 31st August 2023. The primary outcome was the deterioration in COPD control defined as the change in mMRC dyspnea scale. The secondary outcomes included the change in exacerbation frequency and non-COVID-19 respiratory mortality (including death from COPD exacerbation or bacterial pneumonia). 328 patients were included in the analysis. Patients with mild-moderate and severe COVID-19 infection had statistically significant increased risks of worsening of mMRC dyspnoea scale by increase in 1 score from baseline to follow-up with adjusted odds ratios of 4.44 (95% CI = 1.95–10.15, p < 0.001) and 6.77 (95% CI = 2.08–22.00, p = 0.001) respectively. Patients with severe COVID-19 infection had significantly increased risks of increase in severe COPD exacerbation frequency with adjusted odds ratios of 4.73 (95% CI = 1.55–14.41, p = 0.006) non-COVID-19 respiratory mortality from COPD exacerbation or pneumonia with adjusted hazard ratio of 11.25 (95% CI = 2.98–42.45, p < 0.001). After recovery from COVID-19, worsening of COPD control from worsening of dyspnea, increase in severe exacerbation frequency to non-COVID-19 respiratory mortality (COPD exacerbation and pneumonia) was observed among patients with severe COVID-19. Mild to moderate COVID-19 was also associated with symptomatic deterioration.

Markers Of Progression of Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a pressing problem in the modern world. Every year, COPD increasingly leads to temporary disability and death. This is why it is so important to predict the progression of COPD in time. Progression of the disease can lead to severe shortness of breath, frequent exacerbations of COPD, respiratory failure and death. This literature review examines radiological and functional markers, clinical manifestations, sputum and blood markers, and the lung microbiome. All of this may be useful for predicting the risk of COPD progression.

Effectiveness of immunoglobulin replacement therapy in preventing infections in patients with chronic obstructive pulmonary disease: a systematic review

PurposeImmunoglobulin replacement therapy is a standard treatment for patients with antibody production deficiencies, which is of interest in patients with chronic obstructive pulmonary disease (COPD). This systematic review, registered with PROSPERO (CRD42021281118), assessed the current literature regarding immunoglobulin replacement therapy on COPD clinical outcomes in patients with low immunoglobulin G (IgG) serum concentrations.MethodsLiterature searches conducted from inception to August 23, 2021, in databases including MEDLINE, EMBASE, and CINAHL. Population (sex, age, comorbidities), baseline clinical characteristics (pulmonary function testing results, IgG levels), and outcome (hospitalizations, emergency department visits) were extracted after title/abstract and full text screening. The Cochrane risk of bias assessment form was used for risk of bias assessment of randomized controlled trials and the National Heart, Lung, and Blood Institute (NHLBI) assessment was used for pre and post studies.ResultsA total of 1381 studies were identified in the preliminary search, and 874 records were screened after duplicates were removed. Screening 77 full texts yielded four studies that were included in the review.ConclusionIt is unclear whether immune globulin replacement therapy reduces acute exacerbation frequency and severity in COPD. Current evidence suggests that it is worth considering, but better developed protocols for administration of immune globulin supplementation is required for future randomized controlled trials.

RSV-related Community COPD Exacerbations and Novel Diagnostics: A Binational Prospective Cohort Study.

Respiratory syncytial virus (RSV) is a common global respiratory virus increasingly recognized as a major pathogen in frail older adults and as a cause of chronic obstructive pulmonary disease (COPD) exacerbations. There is no single test for RSV in adults with acceptable diagnostic accuracy. Trials of RSV vaccines have recently shown excellent safety and efficacy against RSV in older adults; defining the frequency of RSV-related community infections and COPD exacerbations is important for vaccine deployment decisions. This prospective study aimed to establish the frequency of outpatient-managed RSV-related exacerbations of COPD in two well-characterized patient cohorts using a combination of diagnostic methods. Participants were recruited at specialist clinics in London, UK and Groningen, NL from 2017 and observed for three consecutive RSV seasons, during exacerbations and at least twice yearly. RSV infections were detected by reverse transcription-polymerase chain reaction (RT-PCR) and serologic testing. 377 patients with COPD attended 1,999 clinic visits and reported 310 exacerbations. There were 27 RSV-related exacerbations (8·7% of total); of these, seven were detected only on PCR, 16 only on serology and 4 by both methods. Increases in RSV specific N-protein antibody were as sensitive as antibody to pre-F or post-F for serodiagnosis of RSV related exacerbations. RSV is associated with 8.7% of outpatient managed COPD exacerbations in this study. Antibodies to RSV-N protein may have diagnostic value, potentially important in a vaccinated population. The introduction of vaccines that prevent RSV is expected to benefit patients with COPD.

Analysis of the Comorbid Course of Chronic Obstructive Pulmonary Disease.

(1) Background. Chronic obstructive pulmonary disease (COPD) has a heterogeneous natural history, manifested both in the variability of clinical features and in association with various comorbid pathologies. Atherosclerotic cardiovascular disease (ASCVD) is of great clinical importance and contributes significantly to the natural history and prognosis of COPD. The present study aimed to evaluate the nature of the comorbid course of COPD during a 15-year follow-up. (2) Methods: A total of 170 male COPD patients were included in this study. Spirometry values, symptom severity, presence of risk factors, and comorbidities were considered. Prognostic factors were evaluated using the Kaplan-Meier method. (3) Results: ASCVD was the most common comorbidity and the main cause of death in patients with COPD. Patients with comorbid COPD and ASCVD had more severe dyspnea, higher frequency of COPD exacerbations, and worse survival than patients without ASCVD (p < 0.01). Among patients with COPD, the risk of death from ASCVD was higher in those older than 60 years (OR 3.23, 95% CI [1.72, 6.07]), those with rapidly declining FEV1 (OR 4.35, 95% CI [2.28, 8.30]), those with more than two exacerbations per year (OR 3.21, 95% CI [1.71, 6.11]), and those with a pack year index greater than 30 (OR 2.75, 95% CI [1.38, 5.51]. High Charlson comorbidity index scores in patients with COPD were associated with a more severe disease course, including severity of dyspnea, frequency of exacerbations, and multivariate index scores. A high Charlson comorbidity index score was an adverse prognostic factor. (4) Conclusions: ASCVD influences the course of the disease and is a major cause of mortality in COPD patients.

Benralizumab Prevents Recurrent Exacerbations in Patients with Chronic Obstructive Pulmonary Disease: A Post Hoc Analysis.

Exacerbations in chronic obstructive pulmonary disease (COPD), which tend to occur in clusters and increase with disease severity, come with high societal and economic burdens. Prevention and delay of recurrent exacerbations is an unmet and significant therapeutic need for patients with COPD. GALATHEA (NCT02138916) and TERRANOVA (NCT02155660) were trials assessing efficacy of benralizumab in patients with frequent COPD exacerbations despite treatment. Although these studies found that benralizumab given as an add-on treatment did not significantly reduce annual rates of COPD exacerbations after 56 weeks of treatment, in the following exploratory post hoc analysis of the GALATHEA and TERRANOVA trials we identified a potential responder population in which treatment with benralizumab prevents recurrent COPD exacerbations during 30- and 90-day periods following an initial exacerbation, a vulnerable period for an exacerbation to occur. This responder population was characterized by high blood eosinophil counts and frequent previous exacerbations despite optimized triple therapy. These results highlight the importance of targeted therapies for high-risk populations and merit further research into the benefits of biologic therapies for COPD exacerbations.

Phase III, two arm, multi-centre, open label, parallel-group randomised designed clinical investigation of the use of a personalised early warning decision support system to predict and prevent acute exacerbations of chronic obstructive pulmonary disease: ‘Predict & Prevent AECOPD’ – study protocol

IntroductionWith 65 million cases globally, chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death and imposes a heavy burden on patients’ lives and healthcare resources worldwide. Around...

Curcumin effects on chronic obstructive pulmonary disease: A systematic review.

Chronic obstructive pulmonary disease (COPD) is a common disease of the lungs known as the third reason for death worldwide. Frequent COPD exacerbations compel health care workers to apply interventions that are not adverse effect free. Accordingly, adding or replacing Curcumin, a natural meal flavoring, may indicate advantages in this era by its antiproliferative and anti-inflammatory effects. The PRISMA checklist was employed for the systematic review study. On June 3,2022, PubMed/Medline, Scopus, and Web of Science were searched for studies associated with COPDand Curcumin in the last 10 years. Duplicate or non-English publications and articles with irrelevant titles and abstracts were excluded. Also, preprints, reviews, short communications, editorials, letters to the editor, comments, conference abstracts, and conference papers were not included. Overall, 4288 publications were found eligible, after the screening, 9 articles were finally included. Among them, one, four, and four in vitro, in vivo, and both in vivo and in vitro research exist respectively. According to the investigations, Curcumin can inhibit alveolar epithelial thickness and proliferation, lessen the inflammatory response, remodel the airway, produce ROS, alleviate airway inflammation, hinder emphysema and prevent ischemic complications. Consequently, the findings of the current review demonstrate that Curcumin's modulatory effects on oxidative stress, cell viability, and gene expression could be helpful in COPD management. However, for data confirmation, further randomized clinical trials are required.

Hyaluronic acid as a predictor of exacerbation of occupational chronic obstructive pulmonary disease

The frequency of exacerbations of chronic obstructive pulmonary disease (COPD) is one of the main factors determining the outcome. The search for biomarkers which reflect the risk of exacerbations is one of the urgent scientific and practical objectives. Aim. The study aimed to analyze the relationship between the serum concentration of hyaluronic acid (HA) and the frequency of exacerbations of occupational COPD caused by exposure to silica dust and to substantiate the use of HA as a predictor of exacerbations of COPD. Methods. 78 individuals with a diagnosis of occupational COPD were examined. Respiratory function was assessed based on forced vital capacity of the lungs (FVC, %), the forced expiratory volume in 1 second (FEV1, %) and the calculated ratio of these parameters (FEV1/FVC, %), i.e., modified Tiffno index. The serum concentration of hyaluronic acid (ng/ml) was determined in all individuals using solid-phase enzyme-linked immunosorbent assay (ELISA). The absolute blood level of eosinophils (cell/μl) was determined by a unified method of morphological study of hemocytes with white blood cell differential count. Results. Serum HA concentration in patients with occupational COPD with frequent exacerbations was 25% higher than in the patients with rare exacerbations (the difference was statistically significant; р = 0,004). The analysis of the obtained data showed that the most significant moderate correlation was found between the level of HA and the frequency of COPD exacerbations (direct relationship, r = 0.32; p &lt; 0.05), and FEV1 and the frequency of COPD exacerbations (feedback, r = -0.32;p &lt; 0.05). A weak relationship was found between the relative number of eosinophils and the frequency of COPD exacerbations (direct relationship, r = 0.2; p &lt; 0.05). Weak correlations were also found between the level of HA and FEV1 (feedback, r = -0.23; p &lt; 0.05), between the level of HA and the relative number of eosinophils (direct relationship, r = 0.18; p &lt; 0.05). Conclusion. Quantitative analysis of serum HA in patients with occupational COPD can be used in clinical practice as a biochemical marker for assessing the risk of exacerbations and progression of bronchopulmonary pathology.

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.

Relationship Between Episodic Nocturnal Hypercapnia and History of Exacerbations in Patients with Advanced Chronic Obstructive Pulmonary Disease

PurposeAn episodic increase in transcutaneous carbon dioxide pressure (PtcCO2) is often recognized in patients with advanced chronic obstructive pulmonary disease (COPD) by overnight PtcCO2 monitoring. This phenomenon, called episodic nocturnal hypercapnia (eNH), mainly corresponds to rapid eye movement (REM) sleep-related hypoventilation. However, it is unclear whether eNH is associated with the frequency of COPD exacerbation. We aimed to investigate whether a relationship exists between COPD exacerbation and eNH.Patients and MethodsWe enrolled consecutive patients with stable, severe, or very severe COPD with a daytime arterial carbon dioxide pressure (PaCO2) <55.0 mmHg who underwent overnight PtcCO2 monitoring from April 2013 to January 2017. We retrospectively analyzed the prevalence of eNH and sleep-associated hypoventilation (SH) as defined by the American Academy of Sleep Medicine. Moreover, we compared the relationship between the frequency of COPD exacerbations in the previous year and eNH or SH.ResultsTwenty-four patients were included in this study. The study patients had a mean daytime PaCO2 and nocturnal PtcCO2 of 43.3 ± 6.8 mmHg and 42.9 ± 9.6 mmHg, respectively. Six (25.0%) and 11 (45.9%) of the 24 patients met the SH and eNH criteria, respectively. The odds ratios of SH and eNH for at least one annual exacerbation were 1.0 [95% confidence interval (CI): 0.16–6.00] and 11.1 [95% CI: 1.39–87.7], respectively. The odds ratios of SH and eNH for at least two annual exacerbations were 0.3 [95% CI: 0.04–2.64] and 6.6 [95% CI: 1.06–39.4], respectively.ConclusionIn patients with advanced COPD and a daytime PaCO2 <55.0 mmHg, eNH may be associated with a history of more frequent exacerbations than SH. Further studies are required to validate these findings.

Prevalence and Impact of Comorbidities in Individuals with Chronic Obstructive Pulmonary Disease: A Systematic Review

This study aimed to describe the prevalence of comorbidities associated with chronic obstructive pulmonary disease (COPD) and their relation with relevant outcomes. A systematic review based on the PRISMA methodology was performed from January 2020 until July 2021. The MEDLINE, Lilacs, and Scielo databases were searched to identify studies related to COPD and its comorbidities. Observational studies on the prevalence of comorbidities in COPD patients and costs with health estimates, reduced quality of life, and mortality were included. Studies that were restricted to one or more COPD pain assessments and only specific comorbidities such as osteoporosis, bronchitis, and asthma were excluded. The initial search identified 1,409 studies and after applying the inclusion and exclusion criteria, 20 studies were finally selected for analysis (comprising data from 447,459 COPD subjects). The most frequent COPD comorbidities were: hypertension (range, 17%–64.7%), coronary artery disease (19.9%–47.8%), diabetes (10.2%–45%), osteoarthritis (18%–43.8%), psychiatric conditions (12.1%–33%), and asthma (14.7%–32.5%). Several comorbidities had an impact on the frequency and severity of COPD exacerbations, quality of life, and mortality risk, in particular malignancies, coronary artery disease, chronic heart failure, and cardiac arrhythmias. Comorbidities, especially cardiovascular diseases and diabetes, are frequent in COPD patients, and some of them are associated with higher mortality.

Dual bronchodilation for the treatment of COPD: From bench to bedside.

Because there is a solid pharmacological rationale based on positive interactions between long-acting muscarinic receptor antagonists (LAMAs) and long-acting β-agonists (LABAs) for their ability to relax human airway smooth muscle in vitro alongside several randomised controlled trials (RCTs) and real-world observational studies that support the use of LAMA/LABA fixed-dose combinations (FDCs) for the treatment of patients with chronic obstructive pulmonary disease (COPD), in this narrative review we discuss the preclinical and clinical proofs supporting the use of LAMA + LABA therapy in COPD and why this therapeutic approach optimises bronchodilation. Robust evidence indicates that all LAMA/LABA FDCs are consistently more effective than LAMA or LABA administered alone in improving lung function, dyspnoea, quality of life and exercise capacity in patients with COPD. However, the ability of dual bronchodilation with FDCs of LAMA/LABA to prevent or reduce the risk of COPD exacerbations remains unclear due to conflicting data from large RCTs, despite several mechanisms explaining why such combinations should be of value in decreasing the frequency of COPD exacerbations. Both LABAs and LAMAs mechanistically can affect the cardiovascular system, but from clinical studies to date, LAMA/LABA FDCs have an acceptable cardiovascular safety profile, at least in the COPD population enrolled in RCTs. Indirect evidence suggests that some FDCs may even exert a protective role against serious cardiovascular adverse events compared to monotherapies. Consequently, several LAMA/LABA FDCs have been developed and approved for clinical use as treatments for patients with COPD. However, to date, there are unfortunately very few head-to-head studies comparing the safety and efficacy of different LAMA/LABA FDCs, making it difficult to choose the most appropriate combination, although the use of meta-analyses has provided some information in this regard. Endurance time Exercise time until exhaustion measured by a standard endurance test. Inspiratory capacity The maximum volume of air that can be inspired after reaching the end of a normal, quiet expiration. It is the sum of the tidal volume and the inspiratory reserve volume. St George's Respiratory Questionnaire (SGRQ) A tool to measure health status in patients with respiratory disease. It has three domains: symptoms, activity and impacts. A total score is also calculated. A minimal important difference (range) of ∼4 (2.4-5.6) units in the SGRQ total score is supported by published studies. Surface under the cumulative ranking curve analysis (SUCRA) A numerical representation of the overall rating that displays a single value for each treatment. SUCRA levels vary from 0% to 100%. The higher the SUCRA value and the closer it is to 100%, the more likely therapy is in the top rank or one of the top rankings; the lower the SUCRA value and the closer it is to 0%, the more likely therapy is in the bottom rank or one of the bottom ranks. Transition dyspnoea index (TDI) Widely used in clinical studies of COPD to measure shortness of breath, indicating change in response to an intervention. The total score ranges from -9 to 9; the negative value indicates deterioration, whereas a positive value indicates improvement. There is sufficient evidence to suggest that the minimal important difference for the TDI score is 1 unit. Trough FEV1 The mean volume of air that can be forced out in 1 second approximately 12 (with a twice-daily agent) or 24 (with a once-daily agent) hours after the last administration of bronchodilator.

Educational interventions for health professionals managing chronic obstructive pulmonary disease in primary care.

Educational interventions for health professionals managing chronic obstructive pulmonary disease in primary care.

Relationship of COPD Exacerbation Severity and Frequency on Risks for Future Events and Economic Burden in the Medicare Fee-For-Service Population.

PurposeTo quantify the effects of moderate and/or severe chronic obstructive pulmonary disease (COPD) exacerbations on future exacerbations and healthcare costs in Medicare Fee-For-Service beneficiaries.Patients and MethodsA retrospective cohort study of patients ≥40 years of age, with continuous enrollment from 2015 to 2018, with an index COPD diagnosis defined as first hospitalization, emergency department visit, or first of two outpatient visits (≥30 days apart) in 2015 with a claim for chronic bronchitis, emphysema, or chronic airway obstruction. Patients were stratified by baseline exacerbation categories in year one (YR1) and subsequently evaluated in YR2 and YR3: (A) none; (B) 1 moderate; (C) ≥2 moderate; (D) 1 severe; and (E) ≥2, one being severe. Moderate exacerbations were defined as COPD-related outpatient/ED visits with a corticosteroid/antibiotic claim within ±7 days of the visit and severe exacerbations as hospitalizations with a primary COPD diagnosis. Total all-cause costs for Categories B-E were compared to reference Category A using generalized linear models and inflation adjusted to 2019 dollars.ResultsA total of 1,492,108 patients met study criteria with a mean (±SD) age of 70.9±10.9. In YR1, nearly 40% of patients experienced ≥1 moderate and/or severe exacerbations. Patients having multiple exacerbations, regardless of severity were 2–4 times more likely to experience an exacerbation during YR2 and YR3. Adjusted costs ranged between $24,000 and $26,600 for all categories for YR2 and YR3. Adjusted YR2 costs for Category D and E were $1421 and $1548 higher than those without an exacerbation (Category A YR2 $25,084, YR3 $24,282; p<0.0001). The respective YR3 adjusted costs were $2062 and $2117 higher than those without an exacerbation (Category A; p<0.0001), representing an increase of 6–8% and 8–9% for YR2 and YR3.ConclusionMedicare patients with recent moderate or severe exacerbations, or at least two exacerbations per year are at significant risk for future exacerbations and incur higher all-cause costs.

Short-Term Impact of the Frequency of COPD Exacerbations on Quality of Life.

Chronic obstructive pulmonary disease (COPD) patients in the Simvastatin for the Prevention of Exacerbations in Moderate-to-Severe COPD (STATCOPE) and Azithromycin for Prevention of Exacerbations of COPD (MACRO) trials provide an opportunity to prospectively study the short-term effect of acute exacerbations of COPD (AECOPDs). We hypothesized that those patients with frequent exacerbations (≥2 AECOPDs per patient year) would experience greater short-term decline in quality of life as measured by the St George's Respiratory Questionnaire (SGRQ). A total of 1934 COPD patients were randomized in STATCOPE or MACRO. Patients who were randomized to azithromycin in MACRO or were followed less than 180 days were excluded. A total of 1219 patients were included. Patients were divided into 2 groups: infrequent exacerbators (< 2 exacerbations per patient year), and frequent exacerbators (≥2 exacerbations per year.) Data were collected at baseline, measured over time, and compared between groups. Of the patients studied, 871 were in the infrequent exacerbators group. A total of 348 were in the frequent exacerbators group. Frequent exacerbators used more respiratory medications, were more likely to have used oxygen, steroids, or antibiotics in the 12 months preceding study entry, had more obstruction on spirometry, and had more severe symptoms as measured by SGRQ at baseline. Over at least 180 days, symptom scores worsened in frequent exacerbators and improved in infrequent exacerbators. Patients with frequent exacerbations of COPD experienced a short-term slight worsening of severely impaired SGRQ symptoms scores, while patients with infrequent exacerbations experienced improvement while on COPD therapies.

Extended Bacteria Culture-Based Clustering Identifies a Phenotype Associating Increased Cough and Enterobacterales in Stable Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by airflow limitation. This chronic respiratory disease represents the third leading cause of death worldwide. Alteration of the airway microbiota has been reported to be associated with exacerbation frequency in COPD, but its role on the symptoms in patients at stable state is still incompletely described. This study aimed to determine whether bacteria isolated in sputum can be associated with the clinical features of COPD patients within stable state. Our study highlights, for the first time, that altered microbiota with Enterobacterales is associated with pejorative clinical symptoms in stable COPD patients. The airway microbiota of 38 patients was analyzed using an extended culture approach and mass spectrometry identification. Cluster analysis by principal coordinate analysis of the bacterial communities showed that the patients could be classified into three distinct clusters in our cohort. The clusters showed no differences in proportions of the phylum, but one of them was associated with a high prevalence of Enterobacterales (71.4% in cluster 1 vs. 0% in cluster 3), loss of microbiota diversity, and higher bacterial load (107 vs. 105 CFU/ml, respectively) and characterized by predominant cough and impact on mental health. These novel findings, supported by further studies, could lead to modifying the processing of COPD sputum in the everyday practice of clinical microbiology laboratories.

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.

Beta-blocker treatment in atrial fibrillation with chronic obstructive pulmonary disease: a Danish nationwide study from 1995 to 2015

Abstract Background Atrial fibrillation (AF) and chronic obstructive pulmonary disease (COPD) often coexist. Beta-blockers are a mainstay of treatment in AF and are considered safe in COPD patients after myocardial infarction, though real-life studies have demonstrated significant under-use. Little is known on the utilization patterns in patients with AF and COPD. Purpose To investigate the temporal trends of beta-blocker utilization in patients following first diagnosis of AF in a hospital setting, with and without concomitant COPD, and determine clinical factors associated with beta-blocker use. Methods A nationwide study from 1995 to 2015 using data from the comprehensive Danish health registers. All patients with first registered AF diagnosis in a hospital setting were included. Beta-blocker use was identified by claimed prescriptions within 90 days following AF diagnosis. Factors associated with beta-blocker use or non-use in COPD patients during the most recent period (2010–2015) was examined using multivariable logistic regression and presented as odds ratios (OR) with 95% confidence intervals (95% CI). Results A total of 264 180 patients were included, of these 31 981 (12.1%) had COPD. Patients with concurrent COPD were older than those without COPD (median age 76 vs. 74 years), the proportion of males was similar (54%) and patients with COPD had more comorbidities, particularly cardiovascular disease. Across the 21-year study period, fewer patients with COPD used beta-blockers after AF diagnosis, than those without COPD (38.8% vs. 53.2%, p&amp;lt;0.001). Beta-blocker use increased in both groups during the study period (Figure 1). Nevertheless, the proportion of users was consistently lower among patients with COPD, although the difference was smaller during the most contemporary year (2015: 55.5% vs. 61.6% in COPD vs. non-COPD respectively). Predictors for decreased beta-blocker use included high age, COPD severity represented by use of triple inhaled therapy (OR 0.84 [95% CI 0.77–0.92]), and a history of frequent COPD exacerbations (OR 0.80 [95% CI 0.74–0.86]) (Figure 2). In a subgroup of COPD patients with complete clinical data from the Danish Register of COPD, severe airflow limitation (Forced Expiratory Volume in 1 second &amp;lt;30% of predicted) and high grade of dyspnoea (Modified Medical Research Council Dyspnoea scale 3–4) were associated with decreased odds for beta-blocker use (OR 0.48 [95% CI 0.38–0.59] and OR 0.67 [95% CI 0.55–0.80], respectively). Conclusions Beta-blocker use in patients with AF and concurrent COPD have increased considerably over a 21-year period yet remained less used than in patients without COPD. The severity of COPD was a strong negative predictor for beta-blocker use following AF diagnosis, suggesting a fear for adverse effects. The lower use of beta-blocker treatment in patients with severe COPD and AF might suggest underuse and warrants further evaluation. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Naestved - Slagelse - Ringsted Hospitals, Region Sjaelland, Denmark Figure 1. Temporal trends of beta-blocker useFigure 2. Factors associated with beta-blocker use