Total Number Of Exacerbations Research Articles

N-acetylcysteine Treatment in Chronic Obstructive Pulmonary Disease (COPD) and Chronic Bronchitis/Pre-COPD: Distinct Meta-analyses

IntroductionN-acetylcysteine (NAC) is a mucolytic agent with antioxidant properties. Oxidative stress is a key pathogenic mechanism in chronic respiratory conditions such as COPD and chronic bronchitis (CB). In these meta-analyses we investigated the efficacy of NAC in subjects with COPD or CB, the latter being a potential pre-COPD condition (CB/pre-COPD). MethodsThe meta-analyses were conducted according to PRISMA guidelines. Exacerbations were assessed using total number of exacerbations. Improvement in patients’ respiratory symptoms and/or patients quality of life (QoL) were measured by validated tools or assessed at the end of the study. ResultsTwenty studies were included, of which seven evaluated NAC in patients with symptoms of CB/pre-COPD as entry criterion.NAC treated patients showed a significant reduction of the incidence of exacerbations as compared to placebo both in COPD (IRR=0.76; 95% confidence interval (CI) 0.59–0.99) and CB/pre-COPD (IRR=0.81; 95% CI 0.69–0.95). Sensitivity analyses in studies with duration higher than 5 months, confirmed the overall results.CB/pre-COPD patients treated with NAC were significantly more likely to experience an improvement in symptoms and/or QoL compared to placebo (odds ratio (OR)=3.47; 95% CI 1.92–6.26). A similar trend was observed in the few COPD studies evaluable.Sensitivity analyses showed a significant association of NAC with improvement in symptoms and/or QoL both in CB/pre-COPD and COPD patients. ConclusionsThese findings provide novel data of NAC on the improvement in symptoms and QoL in addition to prevention of exacerbations in COPD and CB/pre-COPD.PROSPERO registry no. CRD42023468154.

Experience of using omalizumab in patients with severe bronchial asthma

Introduction. New insights into the complex pathophysiology of severe asthma (SA) have led to the development of personalized treatment strategies using genetically engineered drugs, which is based not only on disease severity, but also on specific patient characteristics and asthma endotypes.Aim. Evaluation of the effectiveness of omalizumab in patients with severe bronchial asthma (SBA).Materials and methods. A prospective observational study (12 months) with the participation of 39 patients with TB (20 women and 19 men, average age 47.7 ± 14.2 years) who were treated at the Ochapovsky Regional Clinic Hospital of Krasnodar Region. All patients included in the study were prescribed the drug omalizumab.Results. After 6 months of follow-up, there was an improvement in asthma control in the form of an increase in the average number of points according to the ACT questionnaire: 15.9 (1.19) vs 10.7 (3.19); a decrease in the proportion of patients with an ACT score of ≤ 19 points by 15.6% (from 32 patients to 27), a decrease in the proportion of patients with the result of the ACT is less than 15 points by 16%. Within 12 months from the start of treatment with omalizumab, there was a decrease in asthma exacerbations regardless of the initial level of IgE and eosinophils, a decrease in the number of days of disability by 68.9%, the number of emergency calls by 50%, outpatient visits to a pulmonologist by 65.2%, the number of hospitalizations by 63.6%, the number of days spent in hospital – by 49.2, there was a significant decrease in daily doses of IGCS, oral GCS, the total number of exacerbations, the average score on the ACT test in all patients (p = 0.01).Conclusions. Use of the drug omalizumab in patients with SBA, in combination with a different spectrum of sensitization, it was possible to bring the treatment of such patients to a qualitatively new level, providing a pronounced clinical effect by minimizing symptoms, stopping exacerbations, and improving the quality of life. It is important to have a good safety and portability profile, as well as a convenient application mode.

Experience With Elexacaftor/Tezacaftor/Ivacaftor in Patients With Cystic Fibrosis and Advanced Disease

IntroductionElexacaftor/tezacaftor/ivacaftor (ETI) was used through the early access programme in Spain from December 2019 in cystic fibrosis (CF) patients with homozygous or heterozygous F508del mutation with advanced lung disease. MethodologyMulticentre, ambispective, observational, study in which 114 patients in follow-up in 16 national CF units were recruited. Clinical data, functional tests, nutritional parameters, quality of life questionnaires, microbiological isolates, number of exacerbations, antibiotic treatments and side effects were collected. The study also compared patients with homozygous and heterozygous F508del mutations. ResultsOf the 114 patients, 85 (74.6%) were heterozygous for F508del mutation, and the mean age was 32.2±9.96 years. After 30 months of treatment, lung function measured by FEV1% showed improvement from 37.5 to 48.6 (p<0.001), BMI increased from 20.5 to 22.3 (p<0.001), and all isolated microorganisms decreased significantly. The total number of exacerbations was also significantly reduced from 3.9 (±2.9) to 0.9 (±1.1) (p<0.001). All items in the CFQ-R questionnaire showed improvement, except for the digestive domain. Oxygen therapy use decreased by 40%, and only 20% of patients referred for lung transplantation remained on the active transplant list. ETI was well-tolerated, with only 4 patients discontinuing treatment due to hypertransaminemia. ConclusionsETI decreases the number of exacerbations, increases lung function and nutritional parameters, decrease in all isolated microorganisms, for 30 months of treatment. There is an improvement in the CFQ-R questionnaire score except for the digestive item. It is a safe and well-tolerated drug.

Clinical course of COPD in patients with Arg16Gly (rs1042713) polymorphism of ADRB2 gene.

The ADBR2 gene has been studied for its possible relationship with the development and clinical course of chronic obstructive pulmonary disease (COPD), including response to beta-2 agonists, with existing data being contentious on the subject. So, the purpose of this study was to look into the potential impact of the arginine-16-glycine (Arg16Gly) polymorphism on the clinical course and drug utilization in COPD patients. Data show that patients with Arg16Arg have a lower number of hospital admissions for exacerbations (p=0.048), but only in the total number of exacerbations, including those treated out-patients (p=0.086). Each glycine (Gly) copy was associated with a higher number of exacerbations (OR: 0.25; 95% CI: 0.00-055; p=0.048). The number of exacerbations after LABA/LAMA treatment was similar across groups, indicating that all ADRB2 variants responded well to the treatment. Furthermore, there were no statistically significant differences in mMRC and CAT values across all study visits. Interestingly, groups differed in their use of antibiotics (AB) at all visits, with Arg16Arg being associated with the least amount of AB use. There was also a link discovered between clycine copies and increased use of glucocorticoids. As a result, Arg16Gly is involved in the clinical course of COPD as well as the utilization of drug groups. Based on the findings, we can speculate that the cross-talk between the ADRB2 gene and the corticosteroid receptor is altered in patients with the Gly16Gly genotype.

Case-control study of corneal topography and specular microscopy parameters in JIA patients with and without ocular involvement.

To assess corneal topography and specular microscopy values in juvenile idiopathic arthritis-related uveitis (JIA-U). This case-control study included 30 eyes from JIA-U patients, 20 eyes from JIA patients, and 50 eyes from age- and gender-matched healthy subjects. Patients with a history of ocular diseases or intraocular surgery were excluded. Corneal topography maps (Pentacam HR) and specular microscopy images (CellChek SL) were obtained. The measurements of the groups were compared. Keratometric astigmatism was higher in the JIA-U group than in the control group (p = 0.040). Patients with astigmatism greater than 1.50D were more common in the JIA-U group than in the control group (p = 0.026). The JIA-U group had higher anterior and posterior elevation values than the control group (p = 0.006, p = 0.025). The density of endothelial cells, coefficient of variation, and hexagonality did not change across groups (p = 0.465, p = 0.096, p = 0.869). The total number of exacerbations and the duration of anterior chamber inflammation were both positively correlated with posterior elevation (r = 0.600, p 0.001; r = 0.583, p 0.001). The age of diagnosis was found to be negatively correlated with anterior elevation (r = -0.412, p = 0.021). Corneal astigmatism, as well as anterior and posterior elevation values, were all higher in JIA-U patients. Endothelial cell density and morphology, on the other hand, did not differ significantly between groups. Chronic inflammation's impact on stromal remodelling could explain these corneal alterations. The positive correlation between posterior elevation and the number of flares and duration of inflammation represents the importance of early diagnosis and effective treatment.

Long-term oxygen treatment need is less frequent in eosinophilic COPD patients.

IntroductionEosinophilic airway inflammation is a recognized inflammatory pattern in subgroups of patients with chronic obstructive pulmonary disease (COPD). However, there are still conflicting results between various studies concerning the effect of eosinophils in COPD patients. Our aim with this study was to evaluate eosinophilic inflammation and its relation to the clinical characteristics in a group of COPD patients.MethodsStable COPD patients with FEV1% predicted < 50 or with ≥ 1 exacerbation leading to hospital admission or ≥2 moderate or severe exacerbation history were consecutively enrolled from outpatient clinics.ResultsWe included 90 male COPD patients, with a mean age of 63.3 ± 9.2. Mean FEV1% predicted was 35.9 ± 11.3. Eosinophilic inflammation (eosinophil percentage ≥2%) was evident in 54 (60%) of the patients. Participants with eosinophilic inflammation were significantly older and had better FEV1 predicted % values. Eosinophilic COPD patients were characterized with better quality of life and fewer symptoms. COPD patients with noneosinophilic inflammation used supplemental long‐term oxygen therapy (LTOT) more frequently compared to patients with eosinophilic inflammation (36.1% vs. 14.8%, p = 0.01). Eosinophilic inflammation is associated with less dyspnea severity measured by mMRC (OR: 0.542 95% CI: 0.342–0.859, p = 0.009) and less LTOT use (OR: 0.334 95% CI: 0.115–0.968, p = 0.04) regardless of age, severity of airflow limitation, and having frequent exacerbation phenotype.ConclusionOur study supports the growing evidence for a potential role of eosinophilic inflammation phenotype in COPD with distinctive clinical characteristics. Eosinophilic inflammation is inversely associated with dyspnea severity measured by mMRC and LTOT use independently from age, total number of exacerbations, St. George Respiratory Questionnaire (SGRQ) total score and FEV1% predicted.

EHealth Program to Reduce Hospitalizations Due to Acute Exacerbation of Chronic Obstructive Pulmonary Disease: Retrospective Study.

BackgroundHospitalization for acute exacerbation of chronic obstructive pulmonary disease (COPD) is associated with poor prognosis. eHealth interventions might improve outcomes and decrease costs.ObjectiveThis study aimed to evaluate the effect of an eHealth program on COPD hospitalizations and exacerbations.MethodsThis was a real-world study conducted from April 2018 to December 2019 in the Bravis Hospital, the Netherlands. An eHealth program (EmmaCOPD) was offered to COPD patients at risk of exacerbations. EmmaCOPD consisted of an app that used questionnaires (to monitor symptoms) and a step counter (to monitor the number of steps) to detect exacerbations. Patients and their buddies received feedback when their symptoms worsened or the number of steps declined. Generalized estimating equations were used to compare the number of days admitted to the hospital and the total number of exacerbations 12 months before and (max) 18 months after the start of EmmaCOPD. We additionally adjusted for the potential confounders of age, sex, COPD severity, and inhaled corticosteroid use.ResultsThe 29 included patients had a mean forced expiratory volume in 1 second of 45.5 (SD 17.7) %predicted. In the year before the intervention, the median total number of exacerbations was 2.0 (IQR 2.0-3.0). The median number of hospitalized days was 8.0 days (IQR 6.0-16.5 days). Afterwards, there was a median 1.0 (IQR 0.0-2.0) exacerbation and 2.0 days (IQR 0.0-4.0 days) of hospitalization. After initiation of EmmaCOPD, both the number of hospitalized days and total number of exacerbations decreased significantly (incidence rate ratio 0.209, 95% CI 0.116-0.382; incidence rate ratio 0.310, 95% CI 0.219-0.438). Adjustment for confounders did not affect the results.ConclusionsThe eHealth program seems to reduce the number of total exacerbations and number of days of hospitalization due to exacerbations of COPD.

Impact of diabetes mellitus on the risk of severe exacerbation in patients with chronic obstructive pulmonary disease.

Suffering type 2 diabetes mellitus (T2DM) appears to promote the occurrence of respiratory infections. However, studies to evaluate the risk of hospital admission due to exacerbations in patients with chronic obstructive pulmonary disease (COPD) and concomitant T2DM are scarce. Prospective, observational study with a maximum follow-up of 18 months. Information on lung function, body mass index, degree of dyspnea, number of exacerbations, comorbidities and pneumococcal vaccination was obtained. Patients were classified into the categories COPD with (COPD/+T2DM) and without T2DM (COPD/-T2DM). A total of 121 patients with COPD were enrolled. Forty-seven (38%) of the study participants were diabetic. The presence of T2DM increased the risk of hospital admission due to COPD exacerbation (OR 2.66; P=0.031), but no significant difference in the total number of exacerbations was detected. The risk of hospital admission in the course of exacerbation seems to be higher in COPD/+T2DM patients than in COPD/-T2DM subjects.

The pharmacotherapy of professional serious bronchial asthma

In patients with severe bronchial asthma (BA) of professional origin, with the additional appointment of Tiotropium bromide on the background of combined therapy with inhaled glucocorticosteroids and long-acting b2-agonists, functional parameters improve, the proportion of days with good BA control increases, the total number of exacerbations decreases and the period increases to the first severe exacerbation.

Endotype-driven prediction of acute exacerbations in chronic obstructive pulmonary disease (EndAECOPD): protocol for a prospective cohort study

IntroductionCurrent strategies for the prevention of acute exacerbations in chronic obstructive pulmonary disease (COPD) are primarily based on clinical measurements but fail to target the pathophysiological mechanisms, namely endotypes, of...

The prevalence of bruxism and related factors in patients with multiple sclerosis: a comparative study.

To determine the prevalence of bruxism and related factors in patients with multiple sclerosis (MS). Diagnosed with relapsing-remitting MS under the 2010-revised McDonald diagnostic criteria, 182 patients without MS exacerbations during the previous three months were included in the patient group, and 145 healthy individuals made up the control group in the study. Demographic data of the participants in both groups were determined. In the patient and control groups, the diagnosis of definite bruxism was made using the International Classification of Sleep Disorders (Diagnosis and Coding Manual, Second Edition). Bruxism was found in 29.7% (n = 54) of the patients and in 12.4% (n = 18) of the controls, and the difference was statistically significant (p < 0.001). Of all patients, the onset of bruxism was found in 70.4% (n = 38) after the diagnosis and in 29.6% (n = 169) prior to the diagnosis of MS. Compared with those without bruxism, the mean age (p = 0.031) and the score of the Expanded Disability Status Scale (p = 0.001) were also significantly higher among MS patients with bruxism. Between MS patients with and without bruxism, no significant differences were found in terms of sex, marital status, educational status, employment, cigarette smoking, total number of exacerbations, number of exacerbations within the previous year, and drugs used. The frequency of bruxism was found to be higher in the patients with MS than in the controls. Bruxism is associated with age and the Expanded Disability Status Scale score in MS patients.

The associations between comorbidity and exacerbation risk in patients with chronic obstructive pulmonary disease

Objective: To study the association between comorbidity and acute exacerbation risk in patients with chronic obstructive pulmonary disease (COPD). Methods: This was a prospective cohort study with 64 stable COPD patients included. There were 64 males and 18 females with an average age of (68±9) years. Clinical characteristics, the number and type of comorbidities were recorded, and Charlson comorbidity index (CCI) was calculated. The patients were interviewed by phone calls every 3 months since baseline in which the number of acute exacerbations was recorded until 12 months. The impact of CCI, the number of comorbidities and certain comorbidities in the prediction of COPD exacerbation risk were analyzed. Results: Compared to patients with a lower CCI score, patients with a higher CCI score were older (75±6 vs 62±8), and had more severe lung function impairment [FEV(1)%pred: (40±18)% vs (52±18)% ], higher number of comorbidities [4(3, 7) vs 1(1, 3)] and higher frequency of hospital admission due to acute exacerbation [1(0, 2) vs 0(0, 0.25)]. In comparison with patients with lower number of comorbidities, patients with higher number of comorbidities were older (72±7 vs 64±10), and had higher mMRC score [2(1, 3) vs 2(1, 2)] and more severe lung function impairment [FEV(1)%pred: (42±15)% vs (53±19)% ], higher age adjusted CCI score [5(3, 5) vs 3(2, 3) ] and more courses of systemic corticosteroids [2(0, 3) vs 0(0, 0.75)] and/or antibiotics use [3(2, 4) vs 1.5(1, 2.75)]. The number of hospitalizations and total number of exacerbations were higher in COPD patients with bronchiectasis than those without (P<0.005). Conclusion: The inclusion of clinically meaningful comorbidities into the combined assessment of COPD for the prediction of disease prognosis deserves further study.

Lack of efficacy of Lactobacillus GG in reducing pulmonary exacerbations and hospital admissions in children with cystic fibrosis: A randomised placebo controlled trial

BackgroundIntestinal dysbiosis has been described in Cystic Fibrosis (CF) and probiotics have been proposed to restore microbial composition. Aim of the study was to investigate the effects of Lactobacillus rhamnosus GG (LGG) on clinical outcomes in children with cystic fibrosis (CF). MethodsA multicentre, randomised double-blind, clinical trial was conducted in children with CF. After 6months of baseline assessment, enrolled children (2 to 16years of age) received Lactobacillus GG (6×109CFU/day) or placebo for 12months. Primary outcomes were proportion of subjects with at least one pulmonary exacerbation and hospitalisation over 12months. Secondary endpoints were total number of exacerbations and hospitalisations, pulmonary function, and nutritional status. ResultsNinety-five patients were enrolled (51/95 female; median age of 103±50months). In a multivariate GEE logistic analysis, the odds of experiencing at least one exacerbation was not significantly different between the two groups, also after adjusting for the presence of different microbial organisms and for the number of pulmonary exacerbations within 6months before randomisation (OR 0.83; 95% CI 0.38 to 1.82, p=0.643). Similarly, LGG supplementation did not significantly affect the odds of hospitalisations (OR 1.67; 95% CI 0.75 to 3.72, p=0.211). No significant difference was found for body mass index and FEV1. ConclusionsLGG supplementation had no effect on respiratory and nutritional outcomes in this large study population of children with CF under stringent randomised clinical trial conditions. Whether earlier interventions, larger doses, or different strains of probiotics may be effective is unknown.

Influenza and pneumococcus vaccination: current recommendations

Acute asthmatic exacerbation and hospital admission may be associated with severe influenza infection. It has been reported that immunization with inactivated influenza vaccine in patients with persistent asthma decreased respiratory illnesses and asthmarelated events. Evidence from more recently published randomized trials indicated that there is no significant increase in asthma exacerbations immediately after influenza vaccination. Similarly, inactivated influenza vaccine in chronic obstructive pulmonary disease (COPD) patients resulted in a significant reduction in the total number of exacerbations when compared with placebo. The highest incidence of invasive pneumococcal disease occurs in children <5 years of age, immunocompromised persons such as HIV, and those ≥65 years of age. Therefore, pneumococcal vaccine has been recommended for all adults ≥65 years of age and in younger patients who have a condition that increases the risk of invasive pneumococcal disease or pneumococcal pneumonia. The development of pneumococcal conjugate vaccines represents a major advance, and the use of such vaccine has reduced the incidence of pneumococcal disease and acute exacerbation in COPD patients. There are limited data about the effect of pneumococcal vaccine on asthmatic patients.

Caffeine consumption and exacerbations of chronic obstructive pulmonary disease: Retrospective study

BackgroundThe modulation of adenosine receptors has been proposed as new therapeutic target for chronic obstructive pulmonary disease, but studies in humans were negative. Caffeine is widely consumed and acts by non-selective modulation of these receptors, allowing for a non-interventional evaluation of the purinergic effects on COPD. We evaluated the effects of chronic caffeine consumption on the risk for COPD exacerbations. MethodsRetrospective study including patients with COPD. The total number of exacerbations during a three-year period and the mean daily caffeine consumption in the last twenty years were evaluated. A univariate and multiple regression analysis were performed for evaluation of the significant predictors of exacerbations. ResultsA total of 90 patients were included. Most were males (82.2%) and had a mean forced expiratory volume in the first second (FEV1) of 57.0±17.1% predicted. The mean daily caffeine consumption was 149.7±140.9mg. There was no correlation between the mean caffeine consumption and exacerbations (p>0.05). DiscussionOur results suggest that caffeine has no significant effect on the frequency of COPD exacerbations. These conclusions are limited by the sample size and the retrospective nature of the study.

Influenza Vaccine For Egyptian Elderly Patients With Chronic Obstructive Pulmonary Disease

Background: Acute exacerbations of chronic obstructive pulmonary disease are a major cause of morbidity and mortality worldwide. Most acute exacerbations are triggered by community-acquired respiratory infections.Influenza vaccines are currently recommended for all persons with COPD. Aim: To determine the effectiveness of influenza vaccination on influenza-related acute respiratory illness (ARI) and overall ARI in patients with COPD. Methods: A case control study was conducted on 90 elderly patients with COPD (58 years and older) recruited from the outpatient geriatric clinic of Ain shams university hospital. 90 patients with COPD were classified based on their FEV1 as having mild, moderate, and severe COPD. They were classified into two groups; 45 COPD patients (cases) who received the influenza vaccine & 45 COPD patients (controls) who refused to receive the influenza vaccine. We compared the two groups as regard exacerbation rates, hospitalizations, mortality, lung function and adverse effects. Results: Inactivated vaccine in COPD patients resulted in a significant reduction in the total number of exacerbations per vaccinated subject (1.8 i?½ 1.3)compared with those who did not receive the influenza vaccine(3.0i?½1.9).The exacerbations rate were (2.1i?½2.2), (3.2i?½1.9), and (3.7i?½1.2) in the patients with mild, moderate, and severe COPD, respectively in non-vaccinated group, and (1.6i?½1.4), (2.0i?½1.2), and (2.3i?½1.4) in the patients with mild, moderate, and severe COPD, respectively in the vaccinated group. The hospitalization rate was Lower in vaccinated subjects (44.4%) than non-vaccinated group (75.6%) p value 0.002 .Also mortality rate was lower in vaccinated subject (11.1%) than non-vaccinated group (26.7%). Conclusions: Influenza vaccination is highly effective in the prevention of influenza-related acute respiratory illness (ARI) regardless of the severity of COPD. Influenza vaccination should be recommended to all patients with COPD.

Clinical Effects of Vitamin D in Children with Asthma

Objective: Both asthma and vitamin D deficiency are common among children. The results from studies examining the relationship between them are contradictory. The aim of this study is to determine the relationship between the clinical parameters of asthma and vitamin D status in children. Methods: One hundred and twenty children diagnosed with asthma and followed-up in our hospital were included in the study. The control group included 74 children with no evidence of allergic disease. The eosinophil counts, IgE levels and serum 25 OH cholecalciferol [25(OH)D] levels were measured. Results: The patient group consisted of 73 (60.8%) males and 47 (39.2%) females with a mean age of 4.4 ± 1.2 years. There was no significant difference between the patient and control groups with respect to gender and age. The mean 25(OH)D level was 21.49 ± 7.74 ng/ml in the study group and 23.94 ± 8.97 ng/ml in the control group, and this difference was not significant (p = 0.094). The patients with asthma were grouped according to their vitamin D status as ‘deficient' (group 1), ‘insufficient' (group 2) and ‘normal' (group 3). The sociodemographic features, duration of illness, number of hospitalizations, number of sensitivities to allergens, eosinophil count and serum IgE levels were not found to be different between the groups. However, the total number of exacerbations, asthma severity and systemic glucocorticoid need in the previous year were significantly higher in the deficiency group (p < 0.05). Conclusion: Vitamin D levels were not significantly different in patients with asthma. Vitamin D deficiency was common in the study group as well as in the control group. The clinical severity of disease, the number of exacerbations and the systemic glucocorticoid need were related to vitamin D level. © 2014 S. Karger AG, Basel

Effect of High/Low Dose N-Acetylcysteine on Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis

Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and morbidity worldwide, charcterised by persistent airflow limitation, mucus hypersecretion, oxidative stress and airway inflammation. N-acetylcysteine (NAC) have anti-oxidant and anti-inflammatory properties, which have been shown an uncertain benefit in COPD patients. Method: Systematic searches were conducted in Cochrane, Medline and Embase electronic databases. A meta-analysis was performed to evaluate the different effect between high and low-dose NAC treatment on COPD exacerbation. Results: This review yielded 11 studies. The methodological quality of included studies were scored using the Jadad score, with a scale of 1 to 5 (score of 5 being the highest). Data showed high-dose NAC can reduce both the total number of exacerbations (RR = 0.59, 0.47 to 0.74, 95%CI, p < 0.001) and the proportion of patients with at least one exacerbation (RR = 0.76, 0.59 to 0.98, 95%CI, p = 0.03). In the low-dose group, subgroup with jadad ≤ 3 showed a significant decrease (RR = 0.69, 0.61 to 0.77, 95%CI, p < 0.001) in the proportion of patients with exacerbation, the other subgroup with Jadad score > 3 showed no significant decrease (RR = 0.98, 0.90 to 1.06, 95%CI, p = 0.59). And low-dose NAC showed no benifit in the total number of exacerbations (RR = 0.97, 0.68 to 1.37, 95%CI, p = 0.85). Neither high nor low-dose NAC treatment showed benifit in forced expiratory volume in one second(FEV1)(WMD = 1.08, −9.97 to 12.13, 95%CI, p = 0.85). Conclusion: Long-term high-dose NAC treatment may lead to a lower rate of exacerbations. But the effect of low-dose NAC treatment remains uncertain. Further researches are needed to confirm this outcome and to clarify its mechanisms.

Pharmacotherapies for chronic obstructive pulmonary disease: a multiple treatment comparison meta-analysis

Background:Most patients with moderate and severe chronic obstructive pulmonary disease (COPD) receive long-acting bronchodilators (LABA) for symptom control. It is, however, unclear if and what drug treatments should be added to LABAs to reduce exacerbations, which is an important goal of COPD management. Since current guidelines cannot make strong recommendations yet, our aim was to determine the relative efficacy of existing treatments and combinations to reduce the risk for COPD exacerbations.Methods:We included randomized clinical trials (RCTs) evaluating long-acting β2 agonists (LABA), long-acting muscarinic antagonists (LAMA), inhaled glucocorticosterioids (ICS), and the phosphodiesterase-4 (PDE4) inhibitor roflumilast, and combinations of these interventions in moderate to severe COPD populations. Our primary outcome was the event rate of exacerbations. We conducted a random-effects Bayesian mixed-treatment comparison (MTC) and applied several sensitivity analyses. In particular, we confirmed our findings using a binomial MTC analysis examining whether a patient experienced at least one exacerbation event or not during the trial. We also used an additive assumption to calculate the combined effects of treatments that were not included in the systematic review.Results:Twenty-six studies provided data on the total number of exacerbations and/or the mean annual rate of exacerbations among a combined 36,312 patients. There were a total of 10 treatment combinations in the MTC and 15 in the additive analysis. Compared with all other treatments, the combination of roflumilast plus LAMA exhibited the largest treatment effects, and had the highest probability (45%) of being the best first-line treatment. This was consistent whether applying the incidence rate analysis or the binomial analysis. When applying the additive assumption, most point estimates suggested that roflumilast may provide additional benefit by further reducing exacerbations.Conclusions:Using various meta-analytic approaches, our study demonstrates that depending on the choice of drug, combined treatments offer a therapeutic advantage.

Cough and Sputum Production Are Associated With Frequent Exacerbations and Hospitalizations in COPD Subjects

Epidemiologic studies indicate that chronic cough and sputum production are associated with increased mortality and disease progression in COPD subjects. Our objective was to identify features associated with chronic cough and sputum production in COPD subjects. Cross-sectional analysis of data were obtained in a multicenter (17 university hospitals in France) cohort of COPD patients. The cohort comprised 433 COPD subjects (65 +/- 11 years; FEV(1), 50 +/- 20% predicted). Subjects with (n = 321) and without (n = 112) chronic cough and sputum production were compared. No significant difference was observed between groups for age, FEV(1), body mass index, and comorbidities. Subjects with chronic cough and sputum production had increased total mean numbers of exacerbations per patient per year (2.20 +/- 2.20 vs 0.97 +/- 1.19, respectively; p < 0.0001), moderate exacerbations (1.80 +/- 2.07 vs 0.66 +/- 0.85, respectively; p < 0.0001), and severe exacerbations requiring hospitalizations (0.43 +/- 0.95 vs 0.22 +/- 0.56, respectively; p < 0.02). The total number of exacerbations per patient per year was the only variable independently associated with chronic cough and sputum production. Frequent exacerbations (two or more per patient per year) occurred in 55% vs 22% of subjects, respectively, with and without chronic cough and sputum production (p < 0.0001). Chronic cough and sputum production and decreased FEV(1) were independently associated with an increased risk of frequent exacerbations and frequent hospitalizations. Chronic cough and sputum production are associated with frequent COPD exacerbations, including severe exacerbations requiring hospitalizations.