American journal of respiratory and critical care medicine
-
Am. J. Respir. Crit. Care Med. · Jan 2013
Multicenter StudyAn association between L-arginine/asymmetric dimethyl arginine balance, obesity, and the age of asthma onset phenotype.
Increasing body mass index (BMI) has been associated with less fractional exhaled nitric oxide (Fe(NO)). This may be explained by an increase in the concentration of asymmetric dimethyl arginine (ADMA) relative to L-arginine, which can lead to greater nitric oxide synthase uncoupling. ⋯ In late-onset asthma phenotype, plasma ratios of L-arginine to ADMA may explain the inverse relationship of BMI to Fe(NO). In addition, these lower L-arginine/ADMA ratios are associated with reduced lung function and increased respiratory symptom frequency, suggesting a role in the pathobiology of the late-onset phenotype.
-
Am. J. Respir. Crit. Care Med. · Jan 2013
Neutrophil elastase degrades cystic fibrosis transmembrane conductance regulator via calpains and disables channel function in vitro and in vivo.
Cystic fibrosis transmembrane conductance regulator (CFTR) protein is a chloride channel regulating fluid homeostasis at epithelial surfaces. Its loss of function induces hypohydration, mucus accumulation, and bacterial infections in CF and potentially other lung chronic diseases. ⋯ These data provide a new mechanism and show for the first time a link between NE-calpains activation and CFTR loss of function in bacterial lung infections relevant to CF and to other chronic inflammatory lung conditions.
-
Am. J. Respir. Crit. Care Med. · Jan 2013
Cytotoxic cells and granulysin in pulmonary arterial hypertension and pulmonary veno-occlusive disease.
Pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease (PVOD) both display occlusive remodeling of the pulmonary vasculature responsible for increased pulmonary vascular resistances. Cytotoxic T (CTL), natural killer (NK), and natural killer T (NKT) cells play a critical role in vascular remodeling in different physiological and pathological conditions. Granulysin (GNLY) represents a powerful effector protein for all these subpopulations. ⋯ PVOD is characterized by alterations of circulating cytotoxic cell subpopulations and by epigenetic dysregulation within the GNLY gene. Our findings may be helpful in the quest to develop needed diagnostic tools, including flow cytometry analyses, to screen for suspected PVOD in patients with pulmonary hypertension.
-
Am. J. Respir. Crit. Care Med. · Jan 2013
Patients with nontuberculous mycobacterial lung disease exhibit unique body and immune phenotypes.
Among patients with nontuberculous mycobacterial lung disease is a subset of previously healthy women with a slender body morphotype, often with scoliosis and/or pectus excavatum. We hypothesize that unidentified factors predispose these individuals to pulmonary nontuberculous mycobacterial disease. ⋯ This is the first study to comprehensively compare body morphotype, adipokines, and cytokine responses between patients with NTM lung disease and demographically matched controls. Our findings suggest a novel, predisposing immunophenotype that should be mechanistically defined.