Number Of COPD Exacerbations Research Articles

A long-term follow-up study of noninvasive positive pressure ventilation on all-cause mortality in patients with chronic obstructive pulmonary disease-obstructive sleep apnea overlap syndrome

Objective: To investigate the effect of noninvasive positive pressure ventilation(NIPPV) on all-cause mortality in patients with chronic obstructive pulmonary disease-obstructive sleep apnea overlap syndrome(OVS) through long-term follow-up. Methods: A total of 187 OVS patients were divided into the NIPPV group(n=92) and the non-NIPPV group(n=95). Of these, 85 males and 7 females were in the NIPPV group with an average age of (66.5±8.5) years(range 47-80 years); 89 males and 6 females were in the non-NIPPV group with an average age of (67.4±7.8) years(range 44-79 years). Follow-up was performed from enrolment with an average duration of 39(20, 51) months. The all-cause mortality was compared between the two groups. Result: There were no significant differences in their baseline clinical characteristics(all P>0.05), indicating that the data from the two groups were comparable. The Kaplan-Meier curve showed no difference in all-cause mortality between the two groups(log rank P=0.229). However, deaths from cardio-cerebrovascular diseases were higher in the non-NIPPV than in the NIPPV group(15.8% vs. 6.5%,P=0.045). Age, BMI, neck circumference, PaCO2, FEV1, FEV1%, moderate to severe OSA(AHI>15 events/h), mMRC, CAT, number of acute exacerbations of COPD and number of hospitalizations were associated with all-cause death in OVS patients; among which, age(HR 1.067, 95%CI 1.017-1.119, P=0.008), FEV1(HR 0.378, 95%CI 0.176-0.811, P=0.013), and number of COPD exacerbations(HR 1.298, 95%CI 1.102-1.530, P=0.002) were independent risk factors for all-cause mortality in OVS patients. Conclusions: The combination of NIPPV and conventional treatment may reduce cardio-cerebrovascular disease-related mortality in OVS patients. The deceased OVS patients had severe airflow limitation and mild to moderate OSA. Old age, low FEV1 and COPD exacerbations were independent risk factors for all-cause mortality in OVS patients.

Effect of mesenchymal stromal cell infusions on lung function in COPD patients with high CRP levels

BackgroundWe previously reported a Phase 1/2 randomized placebo-controlled trial of systemic administration of bone marrow-derived allogeneic MSCs (remestemcel-L) in COPD. While safety profile was good, no functional efficacy was observed. However, in view of growing recognition of effects of inflammatory environments on MSC actions we conducted a post-hoc analysis with stratification by baseline levels of a circulating inflammatory marker, C-reactive protein (CRP) to determine the effects of MSC administration in COPD patients with varying circulating CRP levels.MethodsTime course of lung function, exercise performance, patient reported responses, and exacerbation frequency following four monthly infusions of remestemcel-L vs. placebo were re-assessed in subgroups based on baseline circulating CRP levels.ResultsIn COPD patients with baseline CRP ≥ 4 mg/L, compared to COPD patients receiving placebo (N = 17), those treated with remestemcel-L (N = 12), demonstrated significant improvements from baseline in forced expiratory volume in one second, forced vital capacity, and six minute walk distance at 120 days with treatment differences evident as early as 10 days after the first infusion. Significant although smaller benefits were also detected in those with CRP levels ≥ 2 or ≥ 3 mg/L. These improvements persisted variably over the 2-year observational period. No significant benefits were observed in patient reported responses or number of COPD exacerbations between treatment groups.ConclusionIn an inflammatory environment, defined by elevated circulating CRP, remestemcel-L administration yielded at least transient meaningful pulmonary and functional improvements. These findings warrant further investigation of potential MSC-based therapies in COPD and other inflammatory pulmonary diseases.Trial registration: Clinicaltrials.gov NCT00683722.

OM-85 in the prevention of respiratory infections: State-of-the-art and future perspectives in clinical practice.

Respiratory infections (RI) significantly burden patients, their families, and society. Respiratory infection recurrence (RRI) usually depends on a defect of the immune response, which can be more or less transient and/or selective. In particular, children, older people, heavy smokers, and patients with chronic diseases, characterized by an inadequate immune response, may be at risk of developing RRI. In this context, OM- 85 could represent a valuable option in the management of RRI. OM-85 is a bacterial lysate containing the extracts of some common pathogens, including Branhamella catarrhalis, Klebsiella pneumoniae, Klebsiella ozaenae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, and Staphylococcus aureus. Methodologically rigorous studies have documented the mechanism of action, efficacy, and safety of OM-85. OM-85 enhances the natural and acquired immune response through multifaceted mechanisms. Substantial evidence has shown that OM-85 can prevent respiratory infections, reduce the number of COPD exacerbations, and shorten the disease duration at home or in hospital. OM-85 can enhance the effectiveness of the 'flu vaccination without affecting the vaccine tolerability. The preventive use of OM-85 can reduce the use of antibiotics, contributing to contrast antibiotic resistance and saving the high cost of chronic respiratory diseases. Further studies should define the ideal candidate to OM-85 treatment.

Bayesian approach to investigate a two-statemixed model of COPD exacerbations

Chronic obstructive pulmonary disease (COPD) is a chronic obstructivedisease of the airways. An exacerbation of COPD is defined as shortness of breath,cough, and sputum production. New therapies for COPD exacerbations are examined inclinical trials frequently based on the number of exacerbations that implieslong-term study due to the high variability in occurrence and duration of theevents. In this work, we expanded the two-state model developed by Cook et al. wherethe patient transits from an asymptomatic (state 1) to a symptomatic state (state 2)and vice versa, through investigating different semi-Markov models in a Bayesiancontext using data from actual clinical trials. Of the four models tested, thelog-logistic model was shown to adequately characterize the duration and number ofCOPD exacerbations. The patient disease stage was found a significant covariate withan effect of accelerating the transition from asymptomatic to symptomatic state. Inaddition, the best dropout model (log-logistic) was incorporated in the finaltwo-state model to describe the dropout mechanism. Simulation based diagnostics suchas posterior predictive check (PPC) and visual predictive check (VPC) were used toassess the behaviour of the model. The final model was applied in three clinicaltrial data to investigate its ability to detect the drug effect: the drug effect wascaptured in all three datasets and in both directions (from state 1 to state 2 andvice versa). A practical design investigation was also carried out and showed thelimits of reducing the number of subjects and study length on the drug effectidentification. Finally, clinical trial simulation confirmed that the model canpotentially be used to predict medium term (6–12 months) clinical trial outcomeusing the first 3 months data, but at the expense of showing a non-significant drugeffect.

Mood disorders in elderly patients hospitalized for acute exacerbation of COPD

IntroductionChronic obstructive pulmonary disease (COPD) represents the most common cause of chronic respiratory failure and it's associated with several comorbidities such as depression. Depression is about four times more frequent in elderly patients with COPD compared to peers who are not affected and its prevalence increases with the degree of disease severity.ObjectiveTo assess mood and perception of the quality of life in elderly patients hospitalized for acute exacerbation of COPD.MethodsThirty-five elderly patients hospitalized for reactivation of COPD were examined; they were subjected to spirometry test for the calculation of FEV1 and to COPD Assessment Test (CAT) and Hamilton Rating Scale for Depression (HAM-D) to evaluate impact of COPD on patients’ quality of life and depressive symptomatology, respectively. The number of COPD exacerbations in the last year prior to hospitalization and the number of recovery days required for the stabilization of patients were also recorded.ResultsThere were strongly significative correlations (P < 0.001), positive between HAM-D scores, CAT scores, number of exacerbation in the last year and hospital length of stay and negative between HAM-D scores and FEV1 values. Furthermore, females were more depressed, with lower FEV 1 (P = 0.043) and with a longer length of stay (P = 0.039) as compared to males.ConclusionsA greater severity of depressive symptoms is related to a greater severity of COPD exacerbations, disability associated with it and perceived by the patient, as well as a higher number of recovery days and annual acute exacerbations, particularly in female gender.

Epidemiological characteristics of chronic respiratory diseases in patients vaccinated against pneumococcal infection

The purpose of this study was to analyze prospectively clinical and economic effects of vaccination of COPD patients using conjugated pneumococcal vaccine P С V13 (Prevenar 13). Methods. The study involved 39 4 male patients treated in the Teaching Hospital No.4 and Chelyabinsk Pulmonary Center in 2012 – 2016. Number of COPD exacerbations, hospitalizations and cases of pneumonia was analyzed; dyspnea and lung function were also measured; BODE, DOSE, and ADO prognostic indices were calculated. The cost-efficacy of vaccination was assessed. Results. Vaccination with P С V13 vaccine allowed stabilization basic respiratory functional parameters. In a year after the vaccination, BODE, DOSE, and ADO indices significantly decreased and this effect maintained during four years. Number of infectious exacerbations and pneumonia cases significantly decreased in 4 years after vaccination in non-smoking patients. Conclusion. The prognostic indices are a reliable tool to evaluate efficacy of treatment. Vaccination allowed saving up to RUR 394.3 million (78.5 % ) per a year due to reduction in number of COPD exacerbations and rate of pneumonia.

ADRB2 Polymorphisms and Budesonide/Formoterol Responses in COPD

Effects of β(2)-adrenergic receptor gene (ADRB2) polymorphism on therapeutic responses to long-acting β(2)-adrenergic agonists have not been evaluated in long-term COPD trials. We aimed to investigate the effects of the ADRB2 Gly16Arg polymorphism on response to formoterol alone or in combination with the inhaled corticosteroid budesonide in patients with COPD. Patients ≥ 40 years of age with moderate to very severe COPD from the 12-month trial I (NCT00206167) or the 6-month trial II (NCT00206154) were randomly assigned to bid budesonide/formoterol pressurized metered-dose inhaler (pMDI) 320/9 μg or 160/9 μg, budesonide pMDI 320 μg + formoterol dry powder inhaler 9 μg (trial II), budesonide pMDI 320 μg (trial II), formoterol dry powder inhaler 9 μg, or placebo. The effect of Gly16Arg on predose FEV(1) and 1-h postdose FEV(1), exacerbations, diary variables, and adverse events were analyzed. No significant interaction between genotype and treatment response was observed for predose (P ≥ .197) or postdose FEV(1) (P ≥ .125) in either pharmacogenetic study (n = 2,866). The number of COPD exacerbations per patient-treatment year was low and similar across genotypes for the active treatment groups (both studies). Percentages of patients with adverse events were similar across Gly16Arg genotype groups for each treatment. Therapeutic response and tolerability to long-term treatment with formoterol alone or in combination with budesonide was not modified by ADRB2 Gly16Arg genotype in two large independent pharmacogenetic studies in patients with moderate to very severe COPD.