Frequency Of COPD Exacerbations Research Articles

The Effect of Opioids and Benzodiazepines on Exacerbation Rate and Overall Survival in Patients with Chronic Obstructive Pulmonary Disease on Long-Term Non-Invasive Ventilation.

Background: There is a growing concern that opioids and benzodiazepines can depress the respiratory drive and could contribute to worsening respiratory failure and higher exacerbation frequency in COPD. However, the relationship between the exacerbation rate and medication taken is poorly understood in patients with chronic respiratory failure due to COPD. Methods: As part of a service evaluation project, we analysed 339 patients with COPD who were established on long-term non-invasive ventilation (LT-NIV) at our tertiary centre. We investigated the relationship between benzodiazepine and opioid prescription and clinical outcomes as well as their impact on the exacerbation rate and overall survival following setup. Results: Before LT-NIV setup, 40 patients took benzodiazepines and 99 patients took opioids. Neither benzodiazepine nor opioid use was associated with changes in daytime blood gases, overnight hypoxia or annual exacerbations before NIV setup, but patients taking opioids were more breathless as assessed by modified Medical Research Council scores (3.91 ± 0.38 vs. 3.65 ± 0.73, p < 0.01). Long-term NIV significantly reduced the number of yearly exacerbations (from 3.0/2.0-5.0/ to 2.8/0.71-4.57/, p < 0.01) in the whole cohort, but the effect was limited in those who took benzodiazepines (from 3.0/2.0-7.0/ to 3.5/1.2-5.5/) or opioids (3.0/2.0-6.0/ to 3.0/0.8-5.5/). Benzodiazepine use was associated with reduced exacerbation-free survival and overall survival (both p < 0.05). However, after adjustment with relevant covariates, the relationship with exacerbation-free survival became insignificant (p = 0.12). Opioids were not associated with adverse outcomes. Conclusions: Benzodiazepines and opiates are commonly taken in this cohort. Whilst they do not seem to contribute to impaired gas exchange pre-setup, they, especially benzodiazepines, may limit the benefits of LT-NIV.

USE OF INDIVIDUAL PREDICTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE EXACERBATIONS IN OBESE PATIENTS DURING DISPENSARY OBSERVATION

COPD is one of the main public health problems. 40.0% of all COPD patients tolerate at least 1 moderate or severe exacerbation within a year, and up to 16.0% - 2 or more. GOLD (2022) proposed for clinical practice a strategy based on "treatable traits," the key of which are exacerbations and persistent shortness of breath, but there are other numerous pulmonary and extrapulmonary features, the definition and consideration of which is useful when leaving individual management algorithms for patients with COPD.&#x0D; Purpose. To evaluate the clinical effectiveness of the use of individual prediction of COPD exacerbations in obese patients during clinical observation.&#x0D; Materials and methods. 106 people diagnosed with COPD between the ages of 18 and 80 were examined. The patient examination included an assessment of the number of outpatient exacerbations and hospitalizations to medical organizations over the past 12 months, a BMI calculation, a comprehensive assessment of COPD symptoms with CAT, the functional status of patients, and an assessment of biochemical blood parameters. Results. According to the examination results and BMI calculation, 80 patients (75.5%) were overweight (55 patients) or obese of various degrees (grade 1 obesity - 21 patients, grade 2 - 1 patient and grade 3 - 3 patients). According to GOLD (2023), all patients were classified as "high risk of exacerbations" - group E. The probability index of COPD exacerbation was calculated over the next 12 months using regression analysis. To prevent predicted exacerbations of COPD, individual treatment and rehabilitation programs were developed for patients, designed for use for 12 months of follow-up: treatment modification, personalized programs for optimizing physical activity, dietary recommendations, vaccination against influenza and pneumococcal infection, course therapy with melatonin, consultation with an endocrinologist. At the end of 12 months, compliance with the recommendations of the index of the probability of exacerbation of COPD for the next 12 months was low.&#x0D; Conclusions. In patients with frequent exacerbations of COPD, in order to achieve disease control, it is advisable to develop individual treatment and rehabilitation programs within the framework of clinical observation, given the "treatable signs," the correction of which has a significant positive effect on the course of COPD, achievement of control and prognosis of the disease.

Risk of major cardiovascular events and bleeding in atrial fibrillation patients with chronic obstructive pulmonary disease treated with low dose azithromycin prophylaxis

Abstract Background Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of cardiovascular events in patients with atrial fibrillation (AF). Low Dose Azithromycin Prophylaxis (LDAP) is associated with improved outcomes in people suffering frequent exacerbations of COPD, but the widespread use of macrolides in patients with underlying cardiovascular disease has been debated due to safety concerns. Aims and Objectives To investigate the safety and efficacy of LDAP in AF patients with COPD in a large global federated dataset. Methods We conducted a retrospective cohort study within the global TriNetX Platform, including AF patients with COPD exacerbations. Risks for all-cause death, major adverse cardiovascular events (MACE: acute coronary syndrome, thromboembolic events, severe ventricular arrhythmias, and heart failure), intracranial hemorrhage (ICH) and gastrointestinal (GI) bleeding were recorded up to 30 days post-COPD exacerbations and compared between LDAP users (at least 3 months use and using LDAP at index) and an active control group (non-Azithromycin users receiving inhaled corticosteroids (ICS)). Cox regression analyses compared outcomes between groups after propensity-score-matching (PSM) for cardiovascular risk factors. Results We identified 2791 LDAP users with COPD and AF (mean age 71.5±10.6 years, 48.9% female), and 61054 controls. Before PSM, LDAP users showed a lower prevalence of cardiovascular risk factors and were less likely to be prescribed oral anticoagulation (68.1% vs 76.1%, p&amp;lt;0.001). After PSM no significant baseline differences were found between two groups. After COPD exacerbation, LDAP users were associated with a lower 30-day risk of all-cause death (HR: 0.72, 95%CI 0.60-0.97), MACE (HR 0.72, 95%CI 0.57-0.90), ICH (0.48, 95%CI 0.27-0.88) and GI bleeding (HR 0.69,95%CI 0.46-0.89) compared to the conventional treatment with ICS. Analysing the different time frames, the lower risk of thrombotic events was observed during the second week after COPD exacerbation while the magnitude of the bleeding risk reduction was more evident in the first 7 days (Figure 1). Conclusion LDAP use is associated with a lower risk of all-cause death, MACE and bleeding in AF patients with COPD. Further studies are needed to investigate the possible role of LDAP as part of the integrated care management of AF patients with COPD.

Monocyte related haematological indices in acute exacerbations of COPD - a new biomarker?

C-reactive protein (CRP) and leukocyte count are standard tools for recognising inflammation in COPD patients. This study aimed to find if there is a pattern in monocyte related haematological indices - monocyte to neutrophil ratio (MNR) and monocyte to lymphocyte ratio (MLR) - which could be helpful in differentiating COPD patients in need for hospitalization due to acute exacerbation of COPD or differentiating frequent COPD exacerbators from non-frequent COPD exacerbators. The study included 119 patients with COPD and 35 control subjects, recruited at the Clinic for Respiratory Diseases Jordanovac, University Hospital Centre Zagreb, Croatia. Complete blood count was performed on Sysmex XN-1000, CRP on Cobas c501, and Fbg on BCS XP analyser. Data were analysed with MedCalc statistical software. The COPD patients were divided into three groups - frequent exacerbators (FE), non-frequent exacerbators (NFE), patients hospitalized for acute COPD exacerbations (HAE) and the control group were healthy smokers (HS). A statistically significant difference was found in the values of MNR while comparing these groups of patients: FE vs HAE (p<0.000), NFE vs HAE (p<0.000) and HS vs HAE (p<0.001); and for the values of MLR: FE vs HAE (p<0.022), NFE vs HAE (p<0.000) and HS vs HAE (p<0.000). As MLR and MNR have shown the statistical difference comparing the group of HAE to NFE, FE and HS, MLR and MNR could be valuable and available markers of acute COPD exacerbations and need for hospitalization.

Clinical aspects of the use of erdosteine in respiratory diseases

Erdosteine is a drug based on thiol and used at the beginning only as a mucolytic. The main indication for it is the treatment of acute and chronic lung diseases, accompanied by difficult sputum discharge. The therapeutic effect of erdosteine is due to the action of thiol metabolites, which, in addition to mucoactive, have antioxidant, anti-inflammatory and antibacterial activities. Experimental studies have shown that this drug reduces the degree of damage to lung tissue caused by oxidative stress, primarily by reducing the production of reactive oxygen species. It increases the concentration of IgA in the respiratory mucosa, thereby reducing the damaging effect of tobacco smoke on endothelial and macrophage cells. In the RESTORE clinical study, which studied the effect of erdosteine on the frequency of exacerbations of chronic obstructive pulmonary disease, it was demonstrated that it significantly reduces the risk, frequency and severity of COPD exacerbations, regardless of patients taking inhaled corticosteroids and eosinophil levels. Recent experimental studies have shown that erdosteine also has the ability to slow the progression rate of fibrosis in pulmonary tissue. It has been shown to inhibit the development of bleomycin-induced fibrosis. The authors of the study suggested that this effect may be related to the suppression of neutrophil migration metabolite erastheine, the inhibition of lipid peroxidation and, in general, the regulation of antioxidant protection mechanisms Data obtained in recent studies also open up new possibilities for the use of erdosteine in patients with bronchial asthma and idiopathic pulmonary fibrosis, significantly expanding the indications for its use.

Possibilities of treatment of patients with chronic obstructive pulmonary disease: long-term follow-up results after the use of beta-glucans

Objective — to study long-term follow-up results after the use of beta-glucans in сhronic obstructive pulmonary disease (COPD) patients with frequent exacerbations. Materials and methods. 42 patients with COPD (group C according to the GOLD classification) were under our supervision for 2 years. Patients had 2 to 4 clinical exacerbations during the previous year. They have been randomized into 2 groups with beta-glucans treatment and without it. Results and discussion. In the patients with COPD a significant decrease in the indicators of cellular immunity was observed, which was manifested primarily by a decrease in the number of cells with natural killer activity and cells of the monocyte-macrophage series, as well as a significant decrease in the immunoregulatory ratio CD4+/CD8+. As a result, after 1 year of observation 2 patients progressed to a more severe COPD stage (from the second to the third due to repeated infectious exacerbations), and after 2 years — another 3 (15.0 %). The prescription of beta-glucans leads to the increasing of cells with the activity of natural killers (p &lt; 0.05) and cells of the monocyte-macrophage pull (CD14+, p &lt; 0.05), and to the normalization of the CD4+/CD8+ index (p &lt; 0.05). These changes were largely leveled off by the end of the second year of observation. The use of Immunsil D3 (Nutrimed, Ukraine) for 1 month reduced the number of exacerbations of COPD (p &gt; 0.05) and significantly reduced the need for antibiotics prescription in patients with COPD (p &lt; 0.05) within 1 year after treatment. During the next year of observation, the difference between the groups was significantly less pronounced. Conclusions. Prescription of beta-glucans can be recommended for patients with COPD with frequent clinical exacerbations (groups C and D). It is needful to repeat the course of treatment with beta-glucans annually in patients with frequent clinical exacerbations of COPD.

Identification of frequent acute exacerbations phenotype in COPD patients based on imaging and clinical characteristics

BackgroundChronic obstructive pulmonary disease (COPD) is a common disease with high morbidity, with acute exacerbations manifesting as a worsening of respiratory symptoms. This study aimed to identify the frequent acute exacerbation phenotype in patients with COPD based on imaging and clinical characteristics. MethodsPatients with COPD (n = 201) were monitored for acute exacerbations one year after their initial hospital admission and further divided into frequent and non-frequent exacerbation groups according to the frequency and severity of acute exacerbations. All patients underwent high resolution CT scans and low attenuation area less than −950Hu (LAA-950) in the whole lung was measured. Differences in visual subtypes, LAA-950, and clinical basic characteristics were compared between groups. The clinical factors influencing frequent exacerbation were determined using binary logistic regression. Finally, based on imaging and clinical factors, the receiver operating characteristic curve was used to identify the phenotype of COPD with frequent acute exacerbations. ResultsPatients with frequent exacerbations had a larger LAA-950 than those non-frequent exacerbations patients (p＜0.001). Frequent acute exacerbations were associated with worsening visual subtypes. Multivariate binary logistic regression illustrated that age, smoking status, BMI, FEV1 pred, and LAA-950 were associated with frequent exacerbations of COPD. The area under the receiver operating characteristic curve for predicting frequent exacerbations based on age, smoking status, BMI, FEV1 pred, and LAA-950 was 0.907 (p＜0.001). ConclusionThe combination of imaging and clinical characteristics reached high diagnostic efficacy in the identification of frequent acute exacerbations in patients with COPD.

EPOXID HYDROLASE SINGLE GENE POLYMORPHISM (RS1051740) AND SEVERITY OF CHRONIC OBSTRUCTIVE DISEASE.

The aim: The aim of the present study was to establish a link between polymorphic variants of the microsomal epoxide hydrolase gene and the severity of COPD in patients with COPD and coronary heart disease. Materials and methods: The study included 128 patients with COPD and IHD, who were divided into two groups: group 1 included 72 patients with in¬frequent exacerbations of COPD (0-1 per year) and group 2 included 56 patients with frequent exacerbations of COPD (exacerbation of COPD ≥2 per year). The control groups consisted of 15 smokers without COPD and IHD, 11 practically healthy non-smokers and 11 patients with IHD who do not smoke. All patients underwent DNA isolation and purification, followed by determination of the Tyr113His polymorphism of the EPHX1 microsomal epoxide hydrolase gene (rs1051740). Results: There was a significant association of the carriage of the CC genotype of the EPHX1 gene in patients with COPD and IHD (RO = 21.326 [95.0% CI 4.217-107.846], p <0.001) with a more severe course of COPD compared with the TT genotype of the EPHX1 gene. Conclusions: Patients with COPD and coronary heart disease who were carriers of a homozygous variant СС of the EPHX1 gene have a reliable association with a more severe course of COPD with frequent exacerbations (higher class according to GOLD classification and more severe symptoms of COPD according to the СAT questionnaire).

Inhaled Corticosteroids and the Lung Microbiome in COPD.

The Global Initiative for Chronic Obstructive Lung Disease 2021 Report recommends inhaled corticosteroid (ICS)-containing regimens as part of pharmacological treatment in patients with chronic obstructive lung disease (COPD) and frequent exacerbations, particularly with eosinophilic inflammation. However, real-world studies reveal overprescription of ICS in COPD, irrespective of disease presentation and inflammatory endotype, leading to increased risk of side effects, mainly respiratory infections. The optimal use of ICS in COPD therefore remains an area of intensive research, and additional biomarkers of benefit and risk are needed. Although the interplay between inflammation and infection in COPD is widely acknowledged, the role of the microbiome in shaping lower airway inflammation has only recently been explored. Next-generation sequencing has revealed that COPD disease progression and exacerbation frequency are associated with changes in the composition of the lung microbiome, and that the immunosuppressive effects of ICS can contribute to potentially deleterious airway microbiota changes by increasing bacterial load and the abundance of potentially pathogenic taxa such as Streptococcus and Haemophilus. Here, we explore the relationship between microbiome, inflammation, ICS use and disease phenotype. This relationship may inform the benefit:risk assessment of ICS use in patients with COPD and lead to more personalised pharmacological management.

Efficacy of Low-Dose versus High-Dose Continuous Cyclic Azithromycin Therapy for Preventing Acute Exacerbations of COPD

Background: Long-term azithromycin therapy significantly reduces the frequency of COPD exacerbations (ECOPD). However, previous studies have used different dosing regimens, and the efficacy of these regimens has not been compared. Objective: Compare the efficacy of low-dose with high-dose continuous cyclic azithromycin (CC-A) in severe COPD. Methods: Patients with severe COPD and repeated exacerbations (ECOPD ≥4 or ≥3 with at least 1 hospital admission in the previous year) were prospectively recruited (January 2017 to December 2019) as a multicenter cohort (from 3 university hospitals in the Barcelona area) and treated with low-dose CC-A: 250 mg 3 times per week (250-CC-A group). This cohort was compared with a historical (January 2007 to December 2013) single-center cohort of severe COPD with frequent ECOPD treated with high-dose CC-A: 500 mg 3 times per week (500-CC-A group). To assess differences in ECOPD prevention according to the administration of low-dose or high-dose CC-A, moderate-to-severe ECOPD was evaluated during the 12-month period before and after starting CC-A therapy. Results: Fifty-eight patients with severe COPD were evaluated: 37 in the low-dose group and 21 in the high-dose group. The 250-CC-A therapy group achieved a mean reduction in moderate-to-severe ECOPD of 65.6% at 12 months after starting CC-A therapy (with a 61.5% reduction in hospitalizations), while the 500-CC-A group achieved a reduction of 60.5% (with a 44.8% reduction in hospitalizations). No significant differences between 250-CC-A and 500-CC-A dosages were observed in the mean annual reduction of moderate-to-severe ECOPD (p = 0.55) or hospitalizations (p = 0.07) with respect to the year prior to starting CC-A. Conclusions: Low-dose 250-CC-A therapy over a 1-year period is similar to high-dose 500-CC-A in reducing exacerbation frequency in severe COPD patients with frequent ECOPD despite maximal medical therapy.

Defective monocyte-derived macrophage phagocytosis is associated with exacerbation frequency in COPD

BackgroundLower airway bacterial colonisation (LABC) in COPD patients is associated with increased exacerbation frequency and faster lung function decline. Defective macrophage phagocytosis in COPD drives inflammation, but how defective macrophage function contributes to exacerbations is not clear. This study investigated the association between macrophage phagocytosis and exacerbation frequency, LABC and clinical parameters.MethodsMonocyte-derived macrophages (MDM) were generated from 92 stable COPD patients, and at the onset of exacerbation in 39 patients. Macrophages were exposed to fluorescently labelled Haemophilus influenzae or Streptococcus pneumoniae for 4 h, then phagocytosis measured by fluorimetry and cytokine release by ELISA. Sputum bacterial colonisation was measured by PCR.ResultsPhagocytosis of H. influenzae was negatively correlated with exacerbation frequency (r = 0.440, p < 0.01), and was significantly reduced in frequent vs. infrequent exacerbators (1.9 × 103 RFU vs. 2.5 × 103 RFU, p < 0.01). There was no correlation for S. pneumoniae. There was no association between phagocytosis of either bacteria with age, lung function, smoking history or treatment with inhaled corticosteroids, or long-acting bronchodilators. Phagocytosis was not altered during an exacerbation, or in the 2 weeks post-exacerbation. In response to phagocytosis, MDM from exacerbating patients showed increased release of CXCL-8 (p < 0.001) and TNFα (p < 0.01) compared to stable state.ConclusionImpaired COPD macrophage phagocytosis of H. influenzae, but not S. pneumoniae is associated with exacerbation frequency, resulting in pro-inflammatory macrophages that may contribute to disease progression. Targeting these frequent exacerbators with drugs that improve macrophage phagocytosis may prove beneficial.

A single home visit improves adherence and reduces healthcare utilization in patients with frequent exacerbations of Severe Asthma and COPD

BackgroundNonadherence to treatment recommendation, common in patients with COPD and Asthma, leads to poor disease control, frequent exacerbations and emergency room visits. We studied the effect of a single home visit (HV) on adherence and health care utilization in a cohort of non-compliant Asthma and COPD patients. MethodsPatients with severe Asthma and COPD with frequent exacerbations deemed non-compliant were subjected to a single home visit by a multidisciplinary team. Adherence to inhalers and office visits, and healthcare utilization were assessed a year prior to and after the home visit. ResultsA total of 60 patients had an attempted home visit. Contact was made with 36 patients during the home visits and these were subject to analyses. Mean age was 60, and 61% were women. Average FEV1 was 1.56 L (55% predicted). There was a significant increase in compliance with office visits in the year following the HV as compared to the year before HV (87 vs 145 visits post-HV). Similarly, there was a significant reduction in the ER visits (76 visits vs 34 visits post-HV), and hospital admission (39 visits vs 24 post HV) and this was associated with a significant improvement in patient adherence to maintenance inhaler use - 17% (6 of 36) vs 53% (19 of 36). ConclusionIn patients with frequent exacerbations of Asthma and COPD with confirmed non-compliance, a single home visit by a multidisciplinary team improved patient adherence to inhalers and office visits and reduced healthcare utilization.

Prevalence and consequences of Gastroesophageal Reflux Disease on COPD

Background The main determinants for COPD exacerbations are previous history of exacerbation, the severity of the disease, and the presence of comorbidities. However, the role of GER in this setting remains unclear. Aim To assess the impact of GER on COPD severity and exacerbation frequency. Methods Stable COPD patients were included.Diagnosis of GER was done by GERD questionnaire.Patients were classified into two groups (COPD with GERD & COPD without GERD). Associations of GERD with degree of airway obstruction, frequency of exacerbation ,ICU admission and mechanical ventilation in the previous year were assessed. Factors associated with exacerbation were analysed by regression analysis Results The current study included 233 COPD patients and were classified into two groups;Group A: COPD with GERD including 56 patients (24%) and Group B : COPD without GERD including 177 patients (76%).Group A had more ICU admission and mechanical ventilation events in the last year (P= 0.01&0.009 respectively).COPD patients with GERD had more severe degree of airway obstruction measured by FEV1 % (56% versus 62% in COPD patients without GERD.When comparing rate of COPD exacerbation in the last year before inclusion, 60% of COPD patients with GERD gave history of two or more exacerbations while in those without GERD, only 33% were exacerbators. . Current smoking, GERD and Severity of airway obstruction were the three independent predictors of excaerbation in the studied population. Conclusions The frequency of GER in COPD was 24%.COPD with GERD had lower FEV1%, more exacerbation and mechanical ventilation than those without GERD.

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.

Predictors of unfavorable long-term prognosis after percutaneous coronary intervention in patients with chronic obstructive pulmonary disease and acute coronary syndrome

Aim. Тo determine independent predictors of unfavorable cardiovascular long-term prognosis after percutaneous coronary intervention in patients with acute coronary syndrome and concomitant chronic obstructive pulmonary disease. Methods. 119 patients with acute coronary syndrome after percutaneous coronary intervention and concomitant chronic obstructive pulmonary disease were included in prospective cohort study. During follow-up up to 36 month the frequency of major cardiovascular events (cardiovascular death, myocardial infarction, stroke, repeat myocardial revascularization) were registered. The predictors of combined end point were identified by Cox regression through forward stepwise mode. Results. Independent variables as major cardiovascular events predictors were determined: main coronary arteries stenosis number, ankle-brachial index, glomerular filtration rate according to the CKD-EPI formula, frequent COPD exacerbations, functional residual lung capacity, 6-minute walk test distance. Conclusion. Functional residual lung capacity as a lung hyperinflation indicator and frequent COPD exacerbations are among independent predictors of major cardiovascular events in long-term follow-up period after percutaneous coronary intervention in patients with acute coronary syndrome and concomitant chronic obstructive pulmonary disease.

Interrelationships Among Small Airways Dysfunction, Neutrophilic Inflammation, and Exacerbation Frequency in COPD

Small airways disease (SAD) is a key component of COPD and is a main contributing factor to lung function decline. Is SAD a key feature of frequent COPD exacerbators and is this related to airway inflammation? Thirty-nine COPD patients defined as either frequent exacerbator (FE) group (≥ 2 exacerbations/y; n= 17) and infrequent exacerbator (IFE) group (≤ 1 exacerbation/y; n= 22) underwent the forced oscillation technique (resistance at 5Hz minus 19Hz [R5-R19], area of reactance [AX]), multiple breath nitrogen washout (conducting airways ventilation heterogeneity, acinar ventilation heterogeneity [Sacin]), plethysmography (ratio of residual volume to total lung capacity), single-breath transfer factor of the lung for carbon monoxide, spirometry (FEV1, FEV1/FVC), and paired inspiratory-expiratory CT scans to ascertain SAD. A subpopulation underwent bronchoscopy to enable enumeration of BAL cell proportions. Sacin was significantly higher in the COPD FE group compared with the IFE group (P= .027). In the FE group, markers of SAD were associated strongly with BAL neutrophil proportions, R5-R19 (P= .001, r= 0.795), AX (P= .049, ρ= 0.560), residual volume to total lung capacity ratio (P= .004, r= 0.730), and the mean lung density of the paired CT scans (P= .018, r= 0.639). Increased Sacin may be a consequence of previous exacerbations or may highlight a group of patients prone to exacerbations. Measures of SAD were associated strongly with neutrophilic inflammation in the small airways of FE patients, supporting the hypothesis that frequent exacerbations are associated with SAD related to increased cellular inflammation.

Aspiration and severe exacerbations in COPD: a prospective study.

RationaleSwallow may be compromised in COPD leading to aspiration and adverse respiratory consequences. However, prevalence and consequences of detectable aspiration in stable COPD are not known.ObjectivesWe tested the hypothesis that a significant number of patients with stable COPD will have detectable aspiration during swallow (prandial aspiration) and that they would experience more frequent severe acute exacerbations of COPD (AECOPD) over the subsequent 12 months.MethodsPatients (n=151) with verified and stable COPD of all severities were recruited at a tertiary care hospital. Videofluoroscopy was conducted to evaluate aspiration using Rosenbek's scale for penetration–aspiration during 100-mL cup drinking. AECOPD was documented as moderate (antibiotics and/or corticosteroid treatment) or severe (emergency department admission or hospitalisation) over the ensuing 12 months.Measurements and main resultsAspiration was observed in 30 out of 151 patients (19.9%, 18 males, 12 females; mean age 72.4 years). Patients with aspiration had more overall AECOPD events (3.03 versus 2 per patient; p=0.022) and severe AECOPD episodes (0.87 versus 0.39; p=0.032). Severe AECOPD occurred in more patients with aspiration (50% of patients versus 18.2%; OR 4.5, CI 1.9–10.5; p=0.001) and with silent aspiration (36.7% versus 18.2%; OR 2.6, CI 1.1–6.2; p=0.045). Aspiration was related to a shorter exacerbation-free period during the 12-month follow-up period (p=0.038).ConclusionsPrandial aspiration is detectable in a subset of patients with COPD and was predictive of subsequent severe AECOPD. Studies to examine if the association is causal are essential to direct strategies aimed at prevention of aspiration and AECOPD.

Blood neutrophil counts are associated with exacerbation frequency and mortality in COPD

BackgroundIdentifying patients with COPD at increased risk of poor outcomes is challenging due to disease heterogeneity. Potential biomarkers need to be readily available in real-life clinical practice. Blood eosinophil counts are widely studied but few studies have examined the prognostic value of blood neutrophil counts (BNC).MethodsIn a large population-based COPD registry in the East of Scotland (TARDIS: Tayside Allergic and Respiratory Disease Information System), BNC were compared to measures of disease severity and mortality for up to 15 years follow-up. Potential mechanisms of disease modification by BNC were explored in a nested microbiome substudy.Results178,120 neutrophil counts were obtained from 7220 people (mean follow up 9 years) during stable disease periods. Median BNC was 5200cells/μL (IQR 4000-7000cells/μL). Mortality rates among the 34% of patients with elevated BNCs (defined as 6000-15000cells/μL) at the study start were 80% higher (14.0/100 person years v 7.8/100py, P < 0.001) than those with BNC in the normal range (2000-6000cells/μL). People with elevated BNC were more likely to be classified as GOLD D (46% v 33% P < 0.001), have more exacerbations (mean 2.3 v 1.3/year, P < 0.001), and were more likely to have severe exacerbations (13% vs. 5%, P < 0.001) in the following year. Eosinophil counts were much less predictive of these outcomes. In a sub-cohort (N = 276), patients with elevated BNC had increased relative abundance of Proteobacteria and reduced microbiome diversity.ConclusionHigh BNC may provide a useful indicator of risk of exacerbations and mortality in COPD patients.

The airway microbiota and exacerbations of COPD.

AimThe aim of this study was to investigate whether the compositionality of the lower airway microbiota predicts later exacerbation risk in persons with COPD in a cohort study.Materials and methodsWe collected lower airways microbiota samples by bronchoalveolar lavage and protected specimen brushes, and oral wash samples from 122 participants with COPD. Bacterial DNA was extracted from all samples, before we sequenced the V3-V4 region of the 16S RNA gene. The frequency of moderate and severe COPD exacerbations was surveyed in telephone interviews and in a follow-up visit. Compositional taxonomy and α and β diversity were compared between participants with and without later exacerbations.ResultsThe four most abundant phyla were Firmicutes, Bacteroidetes, Proteobacteria and Fusobacteria in both groups, and the four most abundant genera were Streptococcus, Veillonella, Prevotella and Gemella. The relative abundances of different taxa showed a large variation between samples and individuals, and no statistically significant difference of either compositional taxonomy, or α or β diversity could be found between participants with and without COPD exacerbations within follow-up.ConclusionThe findings from the current study indicate that individual differences in the lower airway microbiota in persons with COPD far outweigh group differences between frequent and nonfrequent COPD exacerbators, and that the compositionality of the microbiota is so complex as to present large challenges for use as a biomarker of later exacerbations.

Clinical efficacy of mechanical bacterial lysate in the prevention of infectious exacerbations of chronic obstructive pulmonary disease

To evaluate the efficacy of mechanical bacterial lysate on the prevention of infectious exacerbations of chronic obstructive pulmonary disease in patients with frequent exacerbations. The study included patients (n=60) with frequent exacerbations of COPD (groups C and D according to the GOLD classification). All COPD patients were divided into two groups by blind method. The first group (n=30) received conventional therapy for COPD plus MBL (the course included 3 cycles of 10 days therapy with 20-day intervals between them). The second group of patients (control, n=30) received conventional therapy for COPD without MBL.We evaluated the severity of symptoms, frequency of recurrence of COPD exacerbations, readmissions, need for emergency care and changes in basic therapy of COPD. Evaluations were done on 10 days, 1, 3 and 6 months from the start of the study. Adding of MBL to the therapy list of COPD resulted in a significant decrease of biomarkers of systemic inflammation and sputum purulence during compared to the control group. After 6 months of observation MBL group demonstrated statistically significant improvement of respiratory function, decrease in frequency of COPD exacerbations, needs for emergency medical service, reduced changes in basic therapy and hospitalization for exacerbation of COPD. Therapy with MBL showed a high degree of safety and low incidence of adverse events. The results of the study indicate that MBL may be used for the prevention of severe infectious exacerbations of COPD.