American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · May 2014
ReviewMacrolide Antibiotics and the Risk of Cardiac Arrhythmias.
Randomized, controlled trials have demonstrated that chronic therapy with macrolide antibiotics reduces the morbidity of patients with cystic fibrosis, non-cystic fibrosis bronchiectasis, chronic obstructive pulmonary disease, and nontuberculous mycobacterial infections. Lower levels of evidence indicate that chronic macrolides are also effective in treating patients with panbronchiolitis, bronchiolitis obliterans, and rejection after lung transplant. Macrolides are known to cause torsade des pointes and other ventricular arrhythmias, and a recent observational study prompted the FDA to strengthen the Warnings and Precautions section of azithromycin drug labels. This summary describes the electrophysiological effects of macrolides, reviews literature indicating that the large majority of subjects experiencing cardiac arrhythmias from macrolides have coexisting risk factors and that the incidence of arrhythmias in absence of coexisting risk factors is very low, examines recently published studies describing the relative risk of arrhythmias from macrolides, and concludes that this risk has been overestimated and suggests an approach to patient evaluation that should reduce the relative risk and the incidence of arrhythmias to the point that chronic macrolides can be used safely in the majority of subjects for whom they are recommended.
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Am. J. Respir. Crit. Care Med. · May 2014
WHOLE EXOME SEQUENCING REVEALS TOPBP1 AS A NOVEL GENE IN IDIOPATHIC PULMONARY ARTERIAL HYPERTENSION.
Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening disorder characterized by progressive loss of pulmonary microvessels. Although mutations in the bone morphogenetic receptor 2 (BMPR2) are found in 80% of heritable and ∼15% of patients with IPAH, their low penetrance (∼20%) suggests that other unidentified genetic modifiers are required for manifestation of the disease phenotype. Use of whole-exome sequencing (WES) has recently led to the discovery of novel susceptibility genes in heritable PAH, but whether WES can also accelerate gene discovery in IPAH remains unknown. ⋯ WES led to the discovery of TopBP1, a gene whose deficiency may increase susceptibility to small vessel loss in IPAH. We predict that use of WES will help identify gene modifiers that influence an individual's risk of developing IPAH.
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Am. J. Respir. Crit. Care Med. · May 2014
Density and Duration of Pneumococcal Carriage is Maintained by TGFB1 and T Regulatory Cells.
Nasopharyngeal carriage of Streptococcus pneumoniae is a prerequisite for invasive disease, but the majority of carriage episodes are asymptomatic and self-resolving. Interactions determining the development of carriage versus invasive disease are poorly understood but will influence the effectiveness of vaccines or therapeutics that disrupt nasal colonization. ⋯ These data explain the mechanisms by which S. pneumoniae colonize the human nasopharynx without inducing damaging host inflammation and provide insight into the role of bacterial and host constituents that allow and maintain carriage.