Investigating the effect of pretreatment with azithromycin on inflammatory mediators in bronchial epithelial cells exposed to cigarette smoke.

Purpose of the study: Macrolide therapy is effective in reducing chronic obstructive pulmonary disease (COPD) exacerbations. Our recent study has shown the effectiveness of taking azithromycin in COPD patients, not only ex-smokers but also current smokers. Beyond their anti-microbial effects, macrolides have anti-inflammatory and immunomodulatory properties. The aim of this study was to determine if pretreatment with azithromycin modulates cigarette smoke-induced inflammation in airway epithelial cells. We hypothesized that pretreatment with azithromycin decreases exacerbation frequency by modulating inflammation in human airway epithelial cells exposed to cigarette smoke. Materials and methods: BEAS-2B bronchial epithelial cells were incubated with 5% cigarette smoke extract (CSE) for 3 h, 6 h, and 24 h. Then, airway epithelial cells were pretreated with azithromycin and exposed to 5% CSE. In each stage, the expression and release of IL-6 and IL-8 mRNA were analyzed by quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results: There was a significant increase of IL-6 and IL-8 mRNA, as well as an increase in extracellular IL-8 protein following exposure to 5% CSE. When cells were pretreated with azithromycin and exposed to 5% CSE for 3 h, there was a significant dose-dependent decrease in the expression of IL-6 mRNA. A final concentration of 9 µg/mL of azithromycin was sufficient to decrease IL-6, IL-8 mRNA, and extracellular IL-8 levels. Conclusion: Pretreatment with azithromycin decreased the expression of IL-6 and IL-8 mRNA and the release of IL-8 in bronchial epithelial cells exposed to cigarette smoke. These results demonstrate the direct effect of azithromycin on inflammatory mediators in bronchial epithelial cells exposed to cigarette smoke.

Fractional Exhaled Nitric Oxide as an Inflammatory Biomarker in Chronic Obstructive Pulmonary Disease (COPD) with or without Concurrent Diagnosis of Asthma: The Canadian Cohort Obstructive Lung Disease (CanCOLD).

We studied whether fractional exhaled nitric oxide (FENO) can differentiate chronic obstructive pulmonary disease (COPD) with concurrent diagnosis of asthma from COPD-only as well as its ability to predict disease severity and progression. This study was embedded in the Canadian Cohort Obstructive Lung Disease (CanCOLD). Subjects of ≥40 years old completed FENO measurements were subdivided into four groups, including COPD (N = 86 [COPD-only (N = 35) and COPD with concurrent diagnosis of asthma (N = 51)], healthy (N = 72), and at risk (N = 151). Three of the most common clinical definitions were used for characterizing COPD with concurrent diagnosis of asthma: 1) atopy and self-reported physician diagnosis of asthma, 2) ≥12% and ≥200 ml post-bronchodilator FEV1; 3) self-reported physician diagnosis of asthma. FENO values were classified using quartiles and the American Thoracic Society (ATS) guideline 2011. Compared to COPD-only, more COPD with concurrent diagnosis of asthma had a significant FENO50 level of [Formula: see text] 33.5 ppb (fourth quartile) than COPD-only (p = 0.045, 0.011, and 0.006, for definition 1, 2, and 3, respectively). Considering the ATS guideline 2011, fewer COPD with concurrent diagnosis of asthma had FENO50 < 25 than COPD-only, which was statistically significant with definition 1 and 3 (p = 0.038 and 0.026, respectively). FENO as a biomarker has the potential to be used as a complementary value for differentiating COPD with concurrent diagnosis of asthma from COPD-only. Further studies should be conducted on validated definitions of COPD with concurrent diagnosis of asthma, which may include a reference to the type of airway inflammation in addition to the clinical definition.

Identification and definition of asthma-COPD overlap: The CanCOLD study.

BACKGROUND AND OBJECTIVE: Lack of consensus on diagnosis of ACO limits our understanding of the impact, management and outcomes of ACO. The present observational study aims to describe the prevalence, clinical characteristics and course of individuals with ACO based on various definitions used in clinical practice. METHODS: We included individuals with COPD from the prospective, multisite CanCOLD study and defined subjects with ACO using seven definitions commonly used in the literature. RESULTS: Data including questionnaires, lung function and CT scans were analysed from 522 individuals with COPD who were randomly recruited from the population. Among them, 264 fulfilled at least one of the seven definitions of ACO. Prevalence of ACO varied from 3.8% to 31%. Regardless of the definition, individuals with ACO had worse outcomes (lung function and higher percentage of fast decliners, symptoms and exacerbations, health-related quality of life and comorbidities) than the remaining patients with COPD. Conversely, patients with non-ACO had higher emphysema and bronchiolitis scores. The three definitions that included atopy and/or physician diagnosis of asthma identified subjects who differed significantly from patients with COPD. The two ACO definitions with post-bronchodilator reversibility were concordant with COPD and were the least stable, with less than 50% of the patients from each group maintaining reversibility over visits. CONCLUSION: Atopy and physician-diagnosed asthma are more distinguishing characteristics to identify ACO. This finding needs to be validated using measures of airway inflammation and other specific biomarkers.

Investigating Fractional Exhaled Nitric Oxide in Chronic Obstructive Pulmonary Disease (COPD) and Asthma-COPD Overlap (ACO): A Scoping Review.

Chronic obstructive pulmonary disease (COPD) is the most common fixed airflow limitation. Individuals may present with the features of both asthma and COPD called asthma-COPD overlap (ACO) with more severity and worse health-related quality of life than COPD or asthma. One of the promising biomarkers that could be used in clinical practice to differentiate ACO from COPD is fractional exhaled nitric oxide (FENO). The role of Fractional exhaled nitric oxide (FENO) in COPD/ACO remains unknown. This scoping review aims to investigate the role of FENO measurement to differentiate COPD from ACO, to anticipate disease severity/progression and treatment response. A structured comprehensive literature search was performed in major databases including Medline, EMBASE, CINAHL, Cochrane Library, Web of Science, and BIOSIS from 2005 onwards. Thirty-eight studies were retrieved. Based on the synthesis of the reviewed literature, six themes emerged. Thirty-four articles covered more than one theme. From which, 24 articles were on modifying factors in FENO measurement, 18 on FENO in COPD compared with healthy subjects, and seven on FENO in ACO compared with COPD, 22 on FENO and disease severity/progression,12 on FENO and biomarkers, and eight on FENO and treatment response. FENO measurement cannot be used alone in the clinical settings of COPD patients. Although FENO level is higher in ACO patients than COPD-only, it is still unclear if there is a FENO cut-off that can be used to make the diagnosis of ACO and/or to guide therapy with inhaled corticosteroids/glucocorticoids in COPD patients.

Long-term azithromycin therapy to reduce acute exacerbations in patients with severe chronic obstructive pulmonary disease.

RATIONALE: According to clinical trials, azithromycin taken daily for 1 year, decreased exacerbations of chronic obstructive pulmonary disease (COPD). OBJECTIVES: Effectiveness evaluation of long-term azithromycin to reduce exacerbations in severe COPD patient on optimal therapy in real-life practice. METHODS: We conducted a retrospective observational study of severe COPD patients who were prescribed azithromycin (PA)(250 mg, at least 3 times weekly for at least 6 months). Comparison group included severe COPD patients not prescribed azithromycin (NPA). Data were extracted from clinical chart review. MAIN RESULTS: Study included 126 PA and 69 NPA patients. They had severe airflow obstruction, mostly emphysema and one-third bronchiectasis. A predominant feature in the PA group was respiratory tract colonization with Pseudomonas aeruginosa. The mean number of exacerbations per patient per year in the PA group was 3.2 ±â€¯2.1 before initiating azithromycin, and 2.3 ±â€¯1.6 during following year on therapy (p < 0.001). Patients in the NPA group had 1.7 ±â€¯1.3 and 2.5 ±â€¯1.7 exacerbations during first and second follow-up year respectively (p < 0.001). Exacerbation changes from pre to post differed between groups (p < 0.001). Decrease in emergency visits and hospital admissions was significant in PA group. Exacerbation reductions and patient proportions having ≥2 exacerbations extended to the second year of treatment. CONCLUSION: These data showed that long-term azithromycin reduces exacerbation numbers in severe COPD patients, and benefits persist beyond one year. Desirable effects are more likely to outweigh the risks and adverse events in patients colonized with Pseudomonas aeruginosa.

Corrigendum to "Rheumatological Findings in Candidates for Valvular Heart Surgery".

[This corrects the article DOI: 10.5402/2012/927923.].

Investigating fractional exhaled nitric oxide (FeNO) in chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap (ACO): a scoping review protocol.

INTRODUCTION: During the last decade, many articles have been published, including reviews on fractional exhaled nitric oxide (FeNO) use and utility in clinical practice and for monitoring and identifying eosinophilic airway inflammation, especially in asthma, and evaluating corticosteroid responsiveness. However, the exact role of FeNO in patients with chronic obstructive pulmonary disease (COPD) and its ability to distinguish patients with COPD and those having concomitant asthma, that is, asthma-COPD overlap (ACO) is still unclear and needs to be defined. Due to the broad topics of FeNO in chronic airway disease, we undertook a scoping review. The present article describes the protocol of a scoping review of peer-reviewed published literature specific to FeNO in COPD/ACO over the last decade. METHODS AND ANALYSIS: We used Joanna Briggs Institute Reviewers' Manual scoping review methodology as well as Levac et al's and Arksey et al's framework as guides. We searched a variety of databases, including Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, Web of Science, and BioSciences Information Service (BIOSIS) on 29 June 2016. Additional studies will be recognised by exploring the reference list of identified eligible studies. Screening of eligible studies will be independently performed by two reviewers and any disagreement will be solved by the third reviewer. We will analyse the gathered data from article bibliographies and abstracts. ETHICS AND DISSEMINATION: To investigate the body of published studies regarding the role of FeNO in patients with COPD and its usefulness in the clinical setting, a scoping review can be used as a modern and pioneer model, which does not need ethics approval. By this review, new insights for conducting new research specific to FeNO in COPD/ACO population will emerge. The results of this study will be reported in the scientific meetings and conferences, which aim to provide information to the clinicians, primary care providers and basic science researchers.

Effect of milrinone on short term outcome of patients with myocardial dysfunction undergoing off-pump coronary artery bypass graft: a randomized clinical trial.

Myocardial dysfunction is a major complication in cardiac surgery that needs inotropic support. This study evaluates the effect of milrinone on patients with low ventricular ejection fraction undergoing off- pump coronary artery bypass graft (OPCAB). The present study is designed to evaluate the effect of milrinone on myocardial dysfunction. Eighty patients with low ventricular ejection fraction (<35%), candidate for elective OPCAB, were enrolled in this study. They were randomly assigned to two groups. One group received milrinone (50 µg/kg) intravenously and another group received a saline as placebo followed by 24 hours infusion of each agent (0.5 µg/kg/min). Short outcome of patients such as hemodynamic parameters and left ventricular ejection fraction were variables evaluated. Serum levels of creatine phosphokinase, the MB isoenzyme of creatine kinase, occurrence of arrhythmias and mean duration of mechanical ventilation were significantly lower in milrinone group (P<0.05). The mean post operative left ventricular ejection fraction was significantly higher in milrinone group (P=0.031). There were no statistical significant differences between the two groups in terms of intra-aortic balloon pump, inotropic support requirement, myocardial ischemia, myocardial infarction, duration of inotropic support, duration of intensive care unit stay, mortality and morbidity rate. Administration of milrinone in patients undergoing OPCAB with low ventricular ejection fraction is useful and effective.

Comparison of aspirin plus heparin with heparin alone on asymptomatic perioperative deep vein thrombosis in candidates for elective off-pump coronary artery bypass graft: a randomized clinical trial.

BACKGROUND: Symptomatic or asymptomatic deep vein thrombosis (DVT) is a common complication following coronary artery bypass graft (CABG), in which less than 1% of these patients suffer from clinically evident pulmonary embolism (PE). DVT and PE can increase other morbidities of coronary revascularization from short to long period, but no clear consensus still exists regarding proper thromboprophylaxis strategy in the literatures. This study was designed to compare the anti-platelet prophylaxis of aspirin plus heparin with heparin alone on asymptomatic perioperative DVT in patients that are candidates for elective off-pump CABG. METHODS: One hundred and twenty patients, who are candidates for elective off-pump CABG, were randomly assigned to two groups: the aspirin plus heparin group (Group 1, n = 60) that received 80 mg daily aspirin orally and 5000 U unfractionated heparin per 8 h subcutaneously from admission to discharge time, and the heparin group (group 2, n = 60) that received same dose of heparin alone. All patients underwent right and left leg venous ultrasound examination during hospitalization, after which post-operative off-pump CABG complications such as deep vein thrombosis, bleeding and pulmonary embolism were evaluated in this study cases. RESULTS: The mean age of the patients was 62.10 ± 10.71 years with a male to female ratio of 2.24. Asymptomatic DVT occurred in 12 (10%) patients who underwent elective off-pump CABG. DVT was found more in Group 2 (16.6%) as compared to Group 1 (3.3%) with statistical significant difference (p = 0.015). Bleeding was detected in 5 (4.1%) cases in the patients sampled in this study (p = 0.34), 4 cases of which are from Group 1 and 1 case from Group 2. However, PE was shown in none of this study cases. CONCLUSIONS: The incidence of DVT decreased more with aspirin plus heparin as compared to heparin alone in patients who underwent elective off-pump CABG. As regards the results obtained in this study, more studies need to be conducted to establish this strategy for prophylaxis of DVT in CABG.

Cardiac manifestations of rheumatological conditions: a narrative review.

Cardiovascular diseases are common in systemic rheumatologic diseases. They can be presented at the time of diagnosis or after diagnosis. The cardiac involvements can be the first presentation of rheumatologic conditions. It means that a patient with rheumatologic disease may go to a cardiologist when attacked by this disease at first. These manifestations are very different and involve different structures of the heart, and they can cause mortality and morbidity of patients with rheumatologic diseases. Cardiac involvements in these patients vary from subclinical to severe manifestations. They may need aggressive immunosuppressive therapy. The diagnosis of these conditions is very important for choosing the best treatment. Premature atherosclerosis and ischemic heart disease are increased in rheumatoid arthritis and systemic lupus erythematosus, and may be causes of mortality among them. The aggressive control of systemic inflammation in these diseases can reduce the risk of cardiovascular disease especially ischemic heart disease. Although aggressive treatment of primary rheumatologic diseases can decrease mortality rate and improve them, at this time, there are no specific guidelines and recommendations, to include aggressive control and prevention of traditional risk factors, for them.

Rheumatological findings in candidates for valvular heart surgery.

Background and Objectives. Valvular heart diseases are among the frequent causes of cardiac surgery. Some patients have a well-known rheumatic condition. Heart valves are fragile connective tissues which are vulnerable to any systemic autoimmune diseases. This study was designed to evaluate the frequency of rheumatological background in patients candidate for valvular heart surgery in Afshar Cardiovascular Center, Yazd, Iran. Methods. One hundred and twenty (120) patients candidate for valvular heart surgery were selected for this study. Careful history and physical examination were undertaken from rheumatological stand points. The most sensitive screening serologic tests were also assayed. Results. The result of this study showed that 53.3% were male and 46.6% were female with mean age of 48.18 ± 17.65 years old. 45.8% of the patients had history of nonmechanical joint disease, 14.2% had history of rheumatological conditions in their family, and 30% had history of constitutional symptoms. 29.8% had positive joint dysfunction findings in their physical examination while 25.8% had anemia of chronic disease. Positive Rheumatoid factor (RF), anticyclic citrullinated peptide (CCP, ACPA), C-reactive protein (CRP), antinuclear antibody (ANA), abnormal urine and elevated erythrocyte sedimentation rate (ESR) were 34, 2.5, 26.7, 4.2, 5, and 36.7%, respectively. Antineutrophil cytoplasmic antibody (ANCA) and antiphospholipid (APL) were positive in a few cases. Conclusion. The findings of this study show immunologic bases for most patients with valvular heart diseases candidate for surgery. Undifferentiated connective tissue diseases may play an important role in the pathophysiology of valvular damage.