Approach to treating cystic fibrosis pulmonary exacerbations varies widely across US CF care centers.

There is no standard definition of a CF pulmonary exacerbation universally accepted by clinicians. We aimed to investigate the variability of clinical practice among US CF clinicians in the diagnosis and treatment of exacerbations. Using clinical vignettes, we examined if variation in the identification and treatment of CF exacerbations is common, if practice patterns differ between CF care centers and what clinical factors determine treatment.

Improving care at cystic fibrosis centers through quality improvement.

Quality improvement (QI) using a clinical microsystems approach provides cystic fibrosis (CF) centers the opportunity to make a significant positive impact on the health of their patients. The availability of center-specific outcomes data and the support of the Cystic Fibrosis Foundation are important advantages for these quality improvement efforts. This article illustrates how the clinical microsystems methodology can improve care delivery and outcomes by describing the gradual application of quality improvement principles over the past 5 years by the CF team at the Lewis Walker Cystic Fibrosis Center at Akron Children's Hospital in Akron, Ohio.

Statin-mediated correction of STAT1 signaling and inducible nitric oxide synthase expression in cystic fibrosis epithelial cells.

The expression of the inducible form of nitric oxide synthase (NOS2) is reduced in cystic fibrosis (CF) epithelium despite the presence of aggressive inflammation. A potential mechanism for reduced NOS2 expression in CF is diminished signal transducer and activator of transcription-1 (STAT1) activity, possibly due to an increase in expression of protein inhibitor of activated STAT1 (PIAS1). Previous evidence also suggests that NOS2 expression can be negatively regulated by increased activation of the GTPase RhoA, leading to the hypothesis that CF-related increases in PIAS1 expression and altered STAT1 signaling may be mediated by Rho GTPase function.

Mechanisms of NOS2 regulation by Rho GTPase signaling in airway epithelial cells.

The aberrant dysregulation of the inducible form of nitric oxide synthase (NOS2) is thought to play a role in many inflammatory disorders including cystic fibrosis (CF). The complex regulation of NOS2 expression is the subject of intense investigation, and one intriguing regulatory pathway known to influence NOS2 expression is the Rho GTPase cascade. We examined NOS2 regulation in response to inflammatory cytokines in a human alveolar epithelial cell line treated with inhibitors of different upstream and downstream components of the Rho GTPase pathway to better define potential signaling mechanisms.