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Reliable estimates of hospitalization costs for severe respiratory syncytial virus (RSV) infection are necessary to perform economic analyses of preventive strategies of severe RSV disease. We aimed to develop a model that predicts anticipated mean RSV hospitalization costs of groups of young children at risk for hospitalization, but not yet hospitalized, based on readily available child characteristics.

Cystic fibrosis (CF) disease severity is characterized by a broad variability that has been attributed, in addition to the CF transmembrane conductance regulator (CFTR) genotype, to modulating factors such as CFTR-mediated residual chloride (Cl−) secretion. Moreover, CFTR has been suggested to function as a receptor for Pseudomonas aeruginosa(PA). In this study, we investigated whether or not the presence of residual Cl−secretion protects against early chronic PA colonization of patients’ airways. Excluding influences on the phenotype caused by different CFTRmutations, we evaluated a cohort of F508del homozygous individuals with respect to the correlation between residual Cl−secretion and the age of onset of PA colonization as an important marker of clinical phenotype. A group with early chronic PA colonization before the age of 7 y (n14) was compared with a cohort that had no initial PA detection at least until the age of 13 y (n10). We determined the Cl−transport properties by using the intestinal current measurement in rectal suction biopsies. Residual Cl−secretion, most likely due to the CFTR Cl−channel, was observed in 63 of subjects, more frequently in early chronically PA colonized than among late or not colonized patients. These results demonstrate the presence of some active F508del-CFTR in the apical cell membrane and imply that factors other than the CFTR-mediated residual Cl−secretion determine the age of onset of PA colonization.

Cystic fibrosis (CF) disease severity is characterized by a broad variability that has been attributed, in addition to the CF transmembrane conductance regulator (CFTR) genotype, to modulating factors such as CFTR-mediated residual chloride (Cl-) secretion. Moreover, CFTR has been suggested to function as a receptor for Pseudomonas aeruginosa (PA). In this study, we investigated whether or not the presence of residual Cl-secretion protects against early chronic PA colonization of patients' airways. Excluding influences on the phenotype caused by different CFTR mutations, we evaluated a cohort of F508del homozygous individuals with respect to the correlation between residual Cl-secretion and the age of onset of PA colonization as an important marker of clinical phenotype. A group with early chronic PA colonization before the age of 7 y (n = 14) was compared with a cohort that had no initial PA detection at least until the age of 13 y (n = 10). We determined the Cl-transport properties by using the intestinal current measurement in rectal suction biopsies. Residual Cl-secretion, most likely due to the CFTR Cl-channel, was observed in 63% of subjects, more frequently in early chronically PA colonized than among late or not colonized patients. These results demonstrate the presence of some active F508del-CFTR in the apical cell membrane and imply that factors other than the CFTR-mediated residual Cl-secretion determine the age of onset of PA colonization.

Background & Aims:Cholinergic stimulation of chloride secretion is impaired in the intestines of patients with cystic fibrosis (CF). However, intestinal chloride secretion has been observed in patients with mild CF mutations. The aim of this study was to investigate residual Cl−secretion in the intestine of ΔF508 homozygous CF patients, and examine the contribution of cystic fibrosis transmembrane conductance regulator (CFTR) and alternative Cl−conductances. Twins and siblings with identical CFTRgenotypes were investigated to determine the impact of factors other than CFTRon chloride secretion. Methods:Chloride secretion in rectal tissue was investigated by applying Ca2+and adenosine 3',5'-cyclic monophosphate (cAMP)-linked agonists before and after the inhibition of alternative Cl−conductances with 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). Results:cAMP-mediated Cl−secretion was observed in 73% of patients, and 20% showed DIDS-sensitive Ca2+-activated Cl−secretion. This DIDS-sensitive alternative chloride conductance was seen only in CF patients who also responded to cAMP agonists. Chloride secretion was more concordant within monozygous twins than within dizygous pairs. Conclusions:These results suggest the presence of CFTR-mediated Cl−secretion in a subgroup of patients, implying that a portion of ΔF508 CFTR can be processed in vivo and function as a chloride channel in the apical membrane of intestinal cells. Moreover, a considerable number of ΔF508 homozygous patients express chloride conductances other than CFTR in their intestinal epithelia.

Abnormalities in transepithelial electrolyte transport in cystic fibrosis rectum were analyzed by short-circuit current measurements on 11 control subjects and 11 subjects with cystic fibrosis in a modified Ussing chamber. As judged by the amiloride-sensitive component of the short-circuit current, electrogenic sodium absorption appeared unmodified in cystic fibrosis. In contrast, the shortcircuit current response to specific stimuli of both cyclic adenosine monophosphate (cAMP)- and calcium-mediated chloride secretion was drastically altered in all of the cystic fibrosis biopsy specimens examined. Stimulation of the cAMP pathway by 8-bromo cAMP or forskolin resulted in a sustained increase in short-circuit current in control tissues (+2.51 ± 0.63 μA/cm2) but in a slight change in the opposite direction in cystic fibrosis (−0.56 ± 0.49 μA/cm2; P< 0.05). Carbachol, a calcium-linked secretagogue, provoked a transient increase in short-circuit current in all of the control tissues (peak response, +26.69 ± 3.63 μA/cm2) but a transient change in the opposite direction in 6 of 11 cystic fibrosis tissues (−12.46 ± 4.64 μA/cm2; P< 0.05). In 2 of 11 patients with cystic fibrosis, however, a significant but subnormal and transient increase in short-circuit current was observed (+2.62 ± 0.04 μA/cm2; P< 0.05), whereas in 3 of 11 patients with cystic fibrosis a transient change in the opposite direction (−9.83 ± 2.20 μA/cm2; P< 0.05) was followed by a small and transient increase (+2.89 ± 0.83 μA/cm2; P< 0.05). Using the calcium-mediated secretory response therefore, patients with cystic fibrosis could be divided into two categories: a major population showing defective anion secretion but active cation secretion and a subclass (including three siblings) showing residual but subnormal anion secretion. The easy accessibility of rectal samples and the inversed direction of the cAMP- or calcium-provoked short-circuit current is of considerable advantage in the diagnosis of cystic fibrosis.

Maturity-onset diabetes of the young (MODY) and type 2 diabetes are often misdiagnosed in children and adolescents.