Respirology : official journal of the Asian Pacific Society of Respirology
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This review details some of the advances that have been made in the recent decade in the diagnosis, treatment and epidemiology of pulmonary fungal infections. These advances have occurred because of increasing knowledge regarding the fungal genome, better understanding of the structures of the fungal cell wall and cell membrane and the use of molecular epidemiological techniques. The clinical implications of these advances are more rapid diagnosis and more effective and less toxic antifungal agents. ⋯ The newest agents, the echinocandins, are especially safe as they interfere with the metabolism of the fungal cell wall, a structure not shared with humans cells. Epidemiological advances include the description of the emergence of Cryptococcus gattii in North America and the increase in pulmonary mucormycosis and pneumonia due to Fusarium and Scedosporium species in transplant recipients and patients with haematological malignancies. The emergence of azole resistance among Aspergillus species is especially worrisome and is likely related to increased azole use for treatment of patients, but also to agricultural use of azoles as fungicides in certain countries.
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Pneumonia Severity Index (PSI) predicts mortality better than Confusion, Urea >7 mmol/L, Respiratory rate >30/min, low Blood pressure: diastolic blood pressure <60 mm Hg or systolic blood pressure <90 mm Hg, and age >65 years (CURB-65) for community-acquired pneumonia (CAP) but is more cumbersome. The objective was to determine whether CURB enhanced with a small number of additional variables can predict mortality with at least the same accuracy as PSI. ⋯ An enhanced CURB score predicted 30-day mortality with at least the same accuracy as PSI class did among older adults hospitalized for CAP. External validation of this score in other populations is the next step to determine whether it can be used more widely.
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Cigarette smoking is the main risk factor for the development of chronic obstructive pulmonary disease (COPD). Recently, toll-like receptor 3 (TLR3) was shown to recognize pathogen-associated molecular patterns, especially viral-derived double-stranded RNA, and to be involved in immune responses. However, the effects of cigarette smoke on TLR3 remain unclear. In this study, it was examined whether cigarette smoke affects the expression and responses of TLR3 in human macrophages. ⋯ These data suggest that cigarette smoke augments the expression and responses of TLR3 in human macrophages, and this may contribute to neutrophilic airway inflammation and parenchymal destruction in the lungs of smokers and patients with COPD.
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Moxifloxacin (MXF) has been shown to possess immunomodulatory properties in addition to its antimicrobial effects. We investigated the effects of MXF on cytokine secretion and signal transduction mechanisms in naive control and allergen-exposed airway smooth muscle cell (ASMC) stimulated with tumour necrosis factor (TNF)-α. ⋯ MXF suppressed the secretion of pro-inflammatory cytokines by allergen-exposed rat ASMC, partly by inhibiting NF-κB and ERK activation. DXM may have additional or synergistic effects with MXF.
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Bronchiectasis is a chronic disorder characterized by impaired mucociliary clearance and a relentless cycle of infection, inflammation and bronchial wall injury, which has a debilitating impact on the patient's quality of life and results in increased morbidity and mortality. It is a disease for which there are no currently registered therapeutic products, limited epidemiological data and no validated endpoints that have been accepted by the majority of regulatory authorities. This article reviews the evidence base for the efficacy of inhaled dry powder mannitol in patients with non-cystic fibrosis (CF) bronchiectasis. ⋯ It is designed to hydrate the lungs and restore normal mucociliary clearance mechanisms in the lungs. Based on the available evidence, mannitol inhalation is well tolerated and improves the quality of life of patients with non-CF bronchiectasis. There is a need for well designed and adequately powered multicentre trials to establish the potential usefulness of mannitol as a treatment for non-CF bronchiectasis.