Cystic fibrosis pulmonary inflammation

Yu H, Hanes M, Chrisp CE, Boucher JC, Deretic V. Microbial pathogenesis in cystic fibrosis pulmonary clearance of mucoid Pseudomonas aeruginosa and inflammation in a mouse model of repeated respiratory challenge. Infect Immun 1998 66 280. 

Diabetes melUtus Vital function monitoring in intensive care/anesthetics/ prolonged surgery Inflammation and oxidative stress Asthma, cystic fibrosis Pulmonary allograft dysfunction, lung cancer... 

Colonization with P. aeruginosa is a sentinel event in the course of cystic fibrosis. Chronic infection with this organism is associated with progressive loss of lung function attributed to chronic inflammation and recurrent pulmonary exacerbations. Thus, there is interest in strategies that may delay the acquisition of this organism. 

Cystic fibrosis patients may suffer from pulmonary inflammation that is treatable with NSAIDs. In 38 pediatric patients suffering from cystic fibrosis, the enantioselective pharmacokinetics of ibuprofen have been studied (Table 1) [288]. The S R mean ratio of concentrations was 2.0 in... 

Wagener J8, Kahn TZ, Copenhaver 8C, Accurso FJ. Early inflammation and the development of pulmonary disease in cystic fibrosis. Pediatr Pulmonol 1997 16 267-268. 

Two major but conflicting hypotheses have been proposed to explain the connection between abnormal CFTR activity in cystic fibrosis and the chronic neutrophil-dominated pulmonary inflammation and colonization with common bacteria. These hypotheses have been referred to as the high-salt hypothesis proposed by Michael Welsh and his colleagues at the University of Iowa, and the reduced pericellular volume hypothesis proposed by Richard Boucher and colleagues at the University of North Carolina. 

Many of the clinical studies into the mechanisms of pulmonary inflammation in cystic fibrosis have centered on determining the presence (or absence) of candidate mediators that may contribute to the pathogenesis of lung inflammation. Studies of both sputum specimens and BAL fluid obtained from adolescents and adults with cystic fibrosis have established that a plethora of pro-inflammatory mediators are present in airway surface liquid in patients with the disease. 

Studies of BAL and sputum have provided important insights into the early development of pulmonary inflammation in cystic fibrosis and, in particular, the role of the CFTR in promoting inflammation. However, the data have to be interpreted with caution. On the one hand, the findings could be interpreted as evidence that the airway environment in cystic fibrosis is able to support or induce a neutrophil-dominated inflammatory response in the absence of airway infection. Alternatively, the data could be interpreted as evidence that early pulmonary inflammation is a consequence of an abnormal response to exogenous stimuli within the airways resulting in a potentiation of responses that, by themselves, would not result in inflammation in normal subjects. Obviously, this could include augmented inflammatory responses to airway bacteria that might not induce an overt inflammatory response in the airways of a normal individual, but could include other noninfectious injurious events. 

The possible functional role of decreased expression of IL-10 in pulmonary inflammation and bacterial clearance in cystic fibrosis has also been investigated in animal models. As might be surmised from the known properties of IL-10, these studies have collectively suggested that the reduced levels of IL-10 seen in adults with cystic fibrosis are associated with a potentiation of pulmonary inflammation and with an impairment of the clearance of P. aeruginosa. In a... 

However, while these findings are of potential significance to the amplification and perpetuation of the airway inflammation in adult cystic fibrosis patients, other studies, especially studies in children with cystic fibrosis, have not consistently detected the marked reductions in IL-10 (73). The reason for these inconsistencies is not immediately apparent, though the discrepancies may in part reflect the time course of evolution of pulmonary inflammation. 

D. Neutrophil Involvement in Pulmonary Inflammation in Cystic Fibrosis... 

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