Therapeutic advances in respiratory disease
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Asthma is characterized by recurrent and reversible airflow obstruction, which is routinely monitored by history and physical examination, spirometry and home peak flow diaries. As airway inflammation is central to asthma pathogenesis, its monitoring should be part of patient management plans. Fractional exhaled nitric oxide level (FeNO) is the most extensively studied biomarker of airway inflammation, and FeNO references were higher in Chinese (Asians) than Whites. ⋯ However, they will only form part of the clinical picture. Longitudinal studies with focused hypotheses and well-designed protocols are needed to establish the roles of these biomarkers in asthma management. The measurement of biomarkers in EBC remains a research tool.
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Ther Adv Respir Dis · Oct 2013
ReviewIvacaftor treatment of cystic fibrosis patients with the G551D mutation: a review of the evidence.
Cystic fibrosis (CF) is a recessive disorder caused by mutations in the gene that encodes the CF transmembrane conductance regulator (CFTR) protein. CFTR protein is a chloride and bicarbonate channel that is critical for normal epithelial ion transport and hydration of epithelial surfaces. Current CF care is supportive, but recent breakthroughs have occurred with the advent of novel therapeutic strategies that assist the function of mutant CFTR proteins. ⋯ The G551D mutation is reasonably common in the CF patient population and produces a CFTR protein that localizes normally to the plasma membrane, but fails to open in response to cellular cues. Ivacaftor treatment produces dramatic improvements in lung function, weight, lung disease stability, patient-reported outcomes, and CFTR biomarkers in patients with CF harboring the G551D CFTR mutation compared with placebo controls and patients with two copies of the common F508del CFTR mutation. The unprecedented success of ivacaftor treatment for the G551D CF patient population has generated excitement in the CF care community regarding the expansion of its use to other CF patient populations with primary or secondary gating defects.
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Ther Adv Respir Dis · Oct 2013
Randomized Controlled Trial Multicenter Study Comparative StudyComparison of the bronchodilator and systemic effects of AZD3199, an inhaled ultra-long-acting β₂-adrenoceptor agonist, with formoterol in patients with asthma.
Pharmacologically mediated bronchodilation is important in the management of asthma, and is primarily achieved with β₂-agonists. Novel compounds should preferably have a longer duration of action and a better systemic side effect profile than established alternatives at comparable peak bronchodilation. This single-dose crossover study was conducted to investigate and compare with formoterol the bronchodilatory and systemic effects, tolerability and safety of AZD3199, a novel ultra-long-acting β₂-agonist (uLABA). ⋯ AZD3199 480 µg and 1920 µg produced 24-hour bronchodilation. At comparable peak bronchodilator effect, AZD3199 was associated with a lower level of systemic side effects than formoterol. AZD3199 was well tolerated, with no safety concerns identified to preclude further investigation. ClinicalTrials.gov study identifier: NCT00736489.
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Recently it has been suggested that there is a causal association between the use of inhaled corticosteroids (ICSs) and the risk of developing pneumonia in patients with chronic obstructive pulmonary disease (COPD). An increased risk of pneumonia associated with ICS use has been seen in trials with different design, different study populations and with evidence of a dose-response relationship. However, as none of these clinical trials were originally designed to assess pneumonia risk, radiographic confirmation of pneumonia was not always obtained. ⋯ A number of mechanisms by which ICSs could increase the risk of pneumonia have been proposed, principally related to their immunosuppressive effect. Well-designed clinical trials with predefined endpoints and objective pneumonia definitions are needed before the real risk of pneumonia conferred by ICSs can be established. In the meantime, it seems reasonable to reduce ICSs given to COPD patients to the lowest effective doses, reduce the risk in individual patients by ensuring appropriate vaccination and to be vigilant for the possibility of pneumonia in patients with COPD on ICSs as they largely overlap with those of an acute exacerbation.
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Ther Adv Respir Dis · Aug 2013
ReviewDiagnosis and management of chronic lung disease in deployed military personnel.
Military personnel are a unique group of individuals referred to the pulmonary physician for evaluation. Despite accession standards that limit entrance into the military for individuals with various pre-existing lung diseases, the most common disorders found in the general population such as asthma and chronic obstructive pulmonary disease remain frequently diagnosed. Military personnel generally tend to be a more physically fit population who are required to exercise on a regular basis and as such may have earlier presentations of disease than their civilian counterparts. ⋯ Various respiratory hazards in the deployed environment include suspended geologic dusts, burn pits, vehicle exhaust emissions, industrial air pollution, and isolated exposure incidents and may give rise to both acute respiratory symptoms and chronic lung disease. In the evaluation of deployed military personnel, establishing the presence of actual pulmonary disease and the relationship of existing disease to deployment is an ongoing issue to both military and civilian physicians. This paper reviews the current evidence for chronic lung disease in the deployed military population and addresses any differences in diagnosis and management.