Altered pulmonary interleukin-6 signaling in preterm infants developing bronchopulmonary dysplasia.

Interleukin (IL)-6 signaling depends on the soluble IL-6 receptor (sIL-6R) and the soluble glycoprotein 130 (sgp130). To investigate the impact of IL-6 signaling on the pathogenesis of bronchopulmonary dysplasia of prematurity (BPD), IL-6, sIL-6R, and sgp130 were measured by enzyme-linked immunosorbent assay (ELISA) technique in tracheal aspirates of mechanically ventilated preterm infants. Infants developing BPD showed increased concentrations of IL-6, sIL-6R, and sgp-130 in their first week of life. These infants also had significantly higher molar ratios for IL-6/sIL-6R and IL-6/sgp130. The authors conclude that altered interleukin-6 signaling via the soluble receptors sIL-6R and sgp130 may play an important role in pulmonary inflammation of preterm infants.

Non-invasive tension time index in relation to severity of disease in children with cystic fibrosis.

The non-invasive tension-time index of the inspiratory muscles at rest (TTMUS) can be used for assessing respiratory muscle function in children with cystic fibrosis (CF). This study aimed to investigate how TTMUS becomes altered with increasing pulmonary impairment, and which factors determine TTMUS changes in CF. We assessed TTMUS in 47 patients with stable CF ranging in age from 9 to 26 years and in 47 controls of same age and gender. Pulmonary impairment was assessed by the pulmonary function score (PFS) according to Cropp (PFS 0-2 = no, 3-7 = mild, 8-12 = moderate, and 13-18 = severe dysfunction). Median TTMUS was significantly higher in the entire CF-group than in controls ((0.112 (0.079-0.174) vs. 0.07 (0.052-0.094), P < 0.001)). It was nearly identical in CF-patients without (0.079 (0.056-0.114)) and mild (0.080 (0.059-0.128)) pulmonary dysfunction. It was non-significantly higher in subjects with moderate (0.118 (0.103-0.173)) and grossly elevated in individuals with severe (0.232 (0.211-0.31), P < 0.001)) respiratory impairment when compared to the other PFS-groups. TTMUS was significantly related to percent predicted airway resistance (Raw%pred) (r = 0.60, P < 0.001), percent predicted Forced Expiratory Volume in 1 sec (r = -0.49, P < 0.001), percent predicted Vital Capacity (-0.57, P < 0.001), Functional Residual Capacity in percent Total Lung Capacity (r = 0.42, P = 0.003), and transcutaneous oxygen saturation (r = -0.49, P < 0.001). By contrast, Raw%pred was the only variable that had a significant effect on TTMUS (P = 0.01), when a multivariate logistic regression was applied, using the median of the entire CF-cohort to dichotomise TTMUS. These findings suggest that subjects with stable CF and severe pulmonary dysfunction are prone to respiratory muscle fatigue, and that airway obstruction is an important factor contributing to the increase of TTMUS in CF. Regular determination of TTMUS may be clinically useful during course of disease, and may aid the decision to institute therapies like respiratory muscle training or non-invasive intermittent ventilation.

CFTR protein analysis of splice site mutation 2789+5 G-A.

Ex vivo biochemical analysis of rectal biopsies of a carrier of the mild 2789+5 G-A CFTR frameshift splice site mutation revealed mutant truncated CFTR of expected size and an imbalance of more core-glycosylated and less mature full-length CFTR. This first immunoblot analysis of a non-F508del CFTR mutant protein derived from human tissue demonstrates that splice site mutations should not only be investigated at the mRNA, but also at the protein level to properly interpret the associations between genotype, molecular pathology and disease.