The potential for gene therapy to be an effective treatment for cystic fibrosis (CF) airway disease has been limited by inefficient gene transfer vector particle delivery and lack of persistent gene expression. We have developed an airway conditioning process that, when combined with a human immunodeficiency virus (HIV)-derived lentivirus (LV) vector, resulted in persistent in vivo expression of transgenes in airway epithelium. Pretreatment of mouse nasal epithelium with the detergent lysophosphatidylcholine (LPC) prior to instillation of a single dose of an LV vector carrying the LacZ marker gene produced significant LacZ gene expression in nasal airway epithelium for at least 92 days. Transduction of the cystic fibrosis transmembrane conductance regulator (CFTR) gene using the same LV vector system resulted in partial recovery of electrophysiologic function in the nasal airway epithelium of CF mice (cftr(tm1Unc) knockout) for at least 110 days. This first demonstration of LV-mediated in vivo recovery of CFTR function in CF airway epithelium illustrates the potential of combining a preconditioning of the airway surface with a simple and brief LV vector exposure to produce therapeutic gene expression in airway.

Cystic Fibrosis (CF) is a genetic disorder that arises due to mutations in the Cystic Fibrosis Transmembrane Conductance Regulator gene, which encodes for a protein responsible for ion transport out of epithelial cells. This leads to a disruption in transepithelial Cl-, Na + and HCO3− ion transport and the subsequent dehydration of the airway epithelium, resulting in infection, inflammation and development of fibrotic tissue. Unlike in CF, fibrosis in other lung diseases including asthma, chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis has been well characterised. One of the driving forces behind fibrosis is Epithelial Mesenchymal Transition (EMT), a process where epithelial cells lose epithelial proteins including E-Cadherin, which is responsible for tight junctions. The cell moves to a more mesenchymal phenotype as it gains mesenchymal markers such as N-Cadherin (providing the cells with migration potential), Vimentin and Fibronectin (proteins excreted to help form the extracellular matrix), and the fibroblast proliferation transcription factors Snail, Slug and Twist. This review paper explores the EMT process in a range of lung diseases, details the common links that these have to cystic fibrosis, and explores how understanding EMT in cystic fibrosis may open up novel methods of treating patients with cystic fibrosis.

Taping of the patellofemoral joint in the manner used in this study changed the timing of VMO and VL activity in subjects with patellofemoral pain during step-up and step-down tasks. The earlier activation of the VMO may alter the movement of the patella, and further research is needed to determine whether this occurs and whether it is beneficial.

Obstructive sleep apnea syndrome (OSAS) has been associated with reduced neurocognitive performance in children, but the underlying etiology is unclear. The aim of this study was to evaluate the relationship between hypoxemia, respiratory arousals, and neurocognitive performance in snoring children referred for adenotonsillectomy. Thirteen snoring children who were referred for evaluation regarding the need for adenotonsillectomy to a children's hospital otolaryngology/respiratory department underwent detailed neurocognitive and polysomnographic (PSG) evaluation. PSGs were evaluated for respiratory abnormalities and compared with 13 nonsnoring control children of similar age who were studied in the same manner. The snoring children had an obstructive respiratory disturbance index within normal range (mean obstructive apnea/hypopnea index, 0.6/hr). Despite this, several domains of neurocognitive function were reduced in the snoring group. These included mean verbal IQ scores (snorers 92.6 vs. nonsnorers 110.2, P < 0.001), mean global IQ scores (snorers 96.7 vs. nonsnorers 110.2, P < 0.005), mean selective attention scores (snorers 46.4 vs. nonsnorers 11.8, P < 0.001), mean sustained attention scores (snorers 8.0 vs. nonsnorers 2.2, P = 0.001), and mean memory index (snorers 95.2 vs. nonsnorers 112.1, P = 0.001). There was a direct relationship between number of mild oxygen desaturations of > or = 3%, obstructive hypopneas with > or = 3% oxygen desaturations, and respiratory arousals and severity of neurocognitive deficits, with the greatest effect being on memory scores. The disruption of sleep in snoring children produced by relatively mild changes in oxygen saturation or by increases in respiratory arousals may have a greater effect on neurocognitive function than hitherto appreciated. A possible explanation for these neurocognitive deficits may be the combination of the chronicity of sleep disruption secondary to snoring which is occurring at a time of rapid neurological development in the first decade of life. Future studies need to confirm the reversal of these relatively mild neurocognitive decrements post adenotonsillectomy.