Several studies suggest that sex may affect cystic fibrosis (CF) disease severity, with females with CF being more severely affected. In this context, it has been suggested that sex hormones may influence the CF phenotype. A large proportion of females with CF regularly use oral contraceptives (OCs), but the effect of their use on disease severity is unclear. Here, we retrospectively assessed the effects of OCs on clinical outcomes in females with CF.Data from 681 females were available, of whom 42% had taken OCs for varying periods of time. We first performed an inter-patient analysis comparing annual change in % predicted forced expiratory volume in 1 s, body mass index and total days of intravenous antibiotic use over a 5-yr study period in 57 females exposed to and 57 females not exposed to OCs. There were no differences between the two groups. We next performed an intra-patient analysis of the same outcomes over a 3-yr period of OC exposure and a 3-yr period of no OC exposure in the same patient (exposure followed by non-exposure, n527; non-exposure followed by exposure, n523), but again did not detect any differences in any of the clinical outcomes.Our data suggests that the use of OCs does not affect CF disease severity.

Lung function has been traditionally accepted as the primary monitoring tool in cystic fibrosis. The rate of change in lung function however, is slowing and is now as low as 1% per annum. Alternative monitoring tools to assess disease severity are therefore required. Measuring neural respiratory drive (NRD) using diaphragm electromyography (EMG) provides a sensitive measure of load on the respiratory system. The invasive nature of this technique limits is application, however measurement of NRD by sEMGpara is non-invasive and has potential clinical application in monitoring respiratory function in cystic fibrosis (CF). Hypothesis That NRD measured by sEMGpara%max can be used to assess the change of ventilatory mechanics during an infective exacerbation in CF. Methods Eight patients [median (range) 20 (20e25) years old, three females] with CF, admitted to hospital with an acute chest infection were studied. The studies were performed within 48 h of admission and on the day of discharge. At both time points spirometry and sEMGpara were measured. sEMGpara was recorded from bipolar surface electrodes placed 3 cm bilaterally from the midpoint of the sternum in the second intercostal spaces (positive electrode on the right side of the chest). The reference electrode was placed on the lateral aspect of the clavicle. For EMG analysis the root mean square (RMS) was calculated and peak RMS of the resting EMG was expressed as a percentage of peak RMS of the maximum (EMG % max) obtained during inspiratory capacity manoeuvres. Results The median (range) length of stay was 10 (5e22) days. There was a significant reduction in median (range) sEMGpara% max between the first measurement and discharge [19.5 (8e28) We are interested in non-viral gene therapy for cystic fibrosis (CF). It is widely accepted that in addition to extracellular barriers responsible for inefficient uptake, there are key intracellular obstacles to the nuclear delivery of the therapeutic plasmid DNA (pDNA). Thus, we are investigating the intracellular fate of pDNA following transfection, using the clinically relevant cationic Genzyme Lipid (GL) 67 formulation, using three-dimensional Spinning-Disk realtime confocal, combined with transmission electron microscopy (TEM) to track, quantitate and provide high resolution 'snapshots' of pDNA at the single molecule level in transfected primaryhuman airway epithelial cells (AECs) grown at the aireliquid interface (hALI). The pDNA was tagged with fluorescent, photostable semiconductor quantum dots (Qdot-pDNA) or 1.4 nm gold nanoparticles (Au-pDNA) for use in fluorescence or TEM studies, respectively. Both confocal microscopy and TEM experiments demonstrate that Lipid GL67 was able to transfect AECs with Qdotand Au-pDNA. The number of gold spots in the nuclei of Au-pDNAtransfected AECs compared with those in unconjugated-pDNAtransfected control cells was significantly higher (p<0.05, n¼5 independent experiments). Approximately 50% of the total internalised pDNA localised to nuclei within 1 h post-transfection in both...