No abstract

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.

No abstract

We conclude that continuous or thrice-daily dosing of intravenous ceftazidime, both combined with once-daily tobramycin, are equally effective application regimens for elective antipseudomonal therapy in clinically stable patients with CF.

S U M M A R YThe hereditary disease cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Understanding of the consequences of CFTR gene mutations is derived chiefly from in vitro studies on heterologous cell cultures and on cells hyperexpressing CFTR. Data from ex vivo studies on human tissue are scarce and contradictory, a fact which is in part explained by secondary tissue destruction in most affected organs. The purpose of this study was to establish conditions under which wild-type and mutated CFTR can be studied in affected human tissue. Sweat glands carry the basic defect underlying CF and are not affected by tissue destruction and inflammation. Therefore, we used this tissue to test a panel of eight different CFTR antibodies under various fixation techniques. The antibodies were tested on skin biopsy sections from healthy controls, from CF patients homozygous for the most common mutation, ⌬ F508, and from patients carrying two nonsense mutations. Of the eight CFTR antibodies, only three-M3A7, MATG 1104, and cc24-met the criteria necessary for immunolocalization of CFTR in sweat glands. The labeling pattern in the CF sweat glands was consistent with the postulated processing defect of ⌬ F508 CFTR. The antibodies exhibited different sensitivities for detecting ⌬ F508 CFTR.

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.

We conclude that tobramycin given in a daily single dose (with the advantage of being more practical in a home environment) has an efficacy equal to that of three daily doses in terms of elective antipseudomonal therapy in clinically stable patients with CF.

The geographic distribution and origin of CFTR mutations in Germany was evaluated in 658 three-generation families with cystic fibrosis (CF). Fifty different mutations were detected on 1305 parental CF chromosomes from 22 European countries and overseas. The major mutation. delta F508 was identified on 71.5% of all CF chromosomes, followed by R553X (1.8%), N1303K (1.3%), G542X (1.1%), G551D (0.8%) and R347P (0.8%). According to the grandparents' birthplace, 74% of CF chromosomes had their origin in Germany; the delta F508 percentage was 77%, 75%, 70% and 62% in northern, southern, western and eastern Germany, respectively. Ten or more mutant alleles in the investigated CF gene pool originated from Austria, the Czech Republic, Poland, Russia, Turkey and the Ukraine. This widespread geographic origin of CFTR mutations in today's Germany reflects the many demographic changes and migrations in Central Europe during the 20th century.