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Efficacy and safety of roflumilast in patients with stable chronic obstructive pulmonary disease: A meta-analysis.

Currently, several large studies showed that roflumilast has been demonstrated efficacy during treatment chronic obstructive pulmonary disease (COPD) patients, but also caused some side effects. AIM: To assess the efficacy and safety of roflumilast in COPD patients.

METHODS: A computerized search through electronic databases included PubMed, EMBASE, CINAHL, the Cochrane clinical trials database, Physiotherapy Evidence Database and ClinicalTrials.gov was performed to identify randomized controlled trials. The primary outcomes were trough forced expiratory volume in one second (FEV1) (reported pre-bronchodilator values) and exacerbation rate. Secondary outcomes included other spirometric parameters, health-related quality of life, the overall mortality rate and adverse events. Weighted mean differences (WMDs), relative risks (RRs) and 95% confidence intervals (CIs) were calculated and pooled using a random effects model.

RESULTS: Eleven trials involving 9675 patients met the inclusion criteria. Roflumilast significantly reduced the mean exacerbation rate (mild, moderate or severe) (WMD = -0.23; 95% CI = -0.33 to -0.13; p < 0.00001) and improved trough FEV1 (WMD = 53.52 ml; 95% CI = 42.49 to 64.55; p < 0.00001), and other post-bronchodilator spirometric parameters (e.g., forced vital capacity, etc.). Roflumilast did not improve St George's Respiratory Questionnaire total score (WMD = -0.70 units; 95% CI = -2.65 to 1.26; p = 0.49) and decrease the overall mortality rate (RR = 0.90; 95% CI = 0.63 to 1.29; p = 0.56). Roflumilast increased some adverse events including diarrhea, headache, nausea, weight loss, and insomnia.

CONCLUSIONS: Roflumilast significantly reduces the mean exacerbation rate in COPD patients. Although there are insufficient clinical evidence on other clinical endpoints and high risk of some adverse events, roflumilast therapy may benefit COPD patients. Further studies are needed to pay more attention to the long-term efficacy and safety of roflumilast.

Chest wall volumes during inspiratory loaded breathing in COPD patients.

Chest wall volumes and breathing patterns of 13 male COPD patients were evaluated at rest and during inspiratory loaded breathing (ILB). The sternocleidomastoid (SMM) and abdominal muscle activity was also evaluated.

The main compartment responsible for the tidal volume at rest and during ILB was the abdomen. During ILB patients exhibited, in addition to increases in the ratio of inspiratory time to total time of the respiratory cycle and minute ventilation, increases (p<0.05) in the chest wall tidal volume by an increase in abdomen tidal volume as a result of improvement of end chest wall inspiratory volume without changing on end chest wall expiratory volume. The SMM and abdominal muscle activity increased 63.84% and 1.94% during ILB.

Overall, to overcome the load imposed by ILB, COPD patients improve the tidal volume by changing the inspiratory chest wall volume without modifying the predominant mobility of the abdomen at rest and without affecting the end chest wall expiratory volume.

Clinical asthma phenotypes and therapeutic responses.

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Asthma is a heterogeneous disease that means not all asthmatics respond to the same treatment. We hypothesize an approach to characterize asthma phenotypes based on symptomatology (shortness of breath (SOB), cough, and wheezy phenotypes) in correlation with airway inflammatory biomarkers and FEV1. We aimed to detect whether those clinical phenotypes have an impact on the response to asthma medications.

Two hundred three asthmatic children were allocated randomly to receive either montelukast (5 mg at bed time) or fluticasone propionate (100 ug twice daily) for 8 consecutive weeks. Serum concentrations of IL-2Rs, ICAM-1, VCAM-1, total IgE, eosinophilic %, eosinophil cationic protein (ECP), and FEV1 were done before and after treatment to patients and once to controls. Children who have SOB were found to have higher levels of total sIgE, older age, and longer disease duration, and they responded to fluticasone alone. Cough group was found to have higher levels of eosinophilic % and sECP, younger age, shorter disease duration and responded to montelukast alone. Wheezy group showed mixed pattern and responded to both medications.

Conclusion. Although there is variability in response to ICS and LTRAs, we did identify characteristics of patient that should guide the clinician in the choice of asthma medications.

Allergy and Inflammation: An Immunological and Therapeutic Approach.

All organisms are protected by their immune system but occasionally this system overreacts leading to allergic and inflammatory reactions in the body. These reactions are the starting points of various diseases like asthma, eczema and urticaria etc. They involve activation of T cells and release of histamines and toxic chemicals from mast cells and eosinophils respectively. Several chemically and naturally synthesized therapeutic agents are available for the treatment of these immunological diseases.

The present review provides a detailed account of mechanism of allergic and inflammatory reactions, its types and treatment strategies with a special focus on some recent patents in this field.

Influences of Smoking and Aging on Allergic Airway Inflammation in Asthma.

Asthma is a heterogeneous disease with varying phenotypes and numerous risk factors. This condition results from complex interactions between genetic and environmental factors, and active smoking is one of these risk factors. The effects of aging should also be taken into account in these interactions. From an epidemiological standpoint, smokers and/or elderly patients with asthma are not small part in the total population with asthma. Furthermore, both smoking and aging are important risk factors for severe asthma.

This review discusses the potential effects of smoking and aging on healthy subjects and patients with asthma, particularly from the perspective of inflammatory changes. First we show evidence that smokers and the elderly have increased neutrophil counts in their airways, which may have impacts on their clinical characteristics of elderly smokers with asthma. Secondly, on the basis of our recent findings on the interactions between smoking and aging in patients with asthma, we propose that IgE/eosinophilic inflammation should not be underestimated in elderly smokers with asthma, particularly those who are atopic.

This review may expand our understanding of the effects of smoking and aging on asthma with a new perspective of an old issue.

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