Interleukin-1 beta is a potential mediator of airway nitric oxide deficiency in cystic fibrosis.

Airway nitric oxide (NO) deficiency is a hallmark of cystic fibrosis (CF), but the reasons for the reduced NO production in CF airways are unclear. Interleukin (IL)-1 pathway activation plays a role in early CF lung disease and is also involved in the regulation of NO synthase activity. Treatment of CF patients with the CFTR-targeting drug ivacaftor, among other beneficial effects, results in an increase in airway NO levels. In this longitudinal observational trial, we show that ivacaftor therapy leads to a significant reduction in sputum IL-1ß concentration but not in other IL-1- or Th17-associated cytokines. IL-1ß concentrations were closely linked to improvement in pulmonary function, measures of NO metabolism in sputum and exhaled NO. These data therefore suggest a potential interaction between transepithelial chloride conductance, IL-1ß and airway NO production.

How abnormal is the normal? Clinical characteristics of CF patients with normal FEV1.

BACKGROUND: Normal values (>80%) of Forced Expiratory Volume in one second (FEV1 ) in patients with cystic fibrosis (CF) may lead to the interpretation that there is no lung disease. This study is a comprehensive analysis of lung involvement in CF patients having normal FEV1 . METHODS: Patients were recruited from two CF centers: Hadassah Medical Center, Jerusalem and Vall d' Hebron Hospital, Barcelona. Lung disease was assessed by lung clearance index (LCI), chest CT-Brody score, respiratory cultures, number of pulmonary exacerbations (PEx), and days of antibiotic treatment in the year before the assessment. RESULTS: Of the 247 patients, 89 (36%) had FEV1 ≥80% and were included in the study (mean age, 17.6; range, 4.25-49 years). Chronic Pseudomonas aeruginosa infection was found in 21%, and 31% had at least one major PEx in the year before the study. Abnormally elevated LCI was found in 86% of patients, ranging between 7.52 and 18.97, and total Brody score (TBS) was abnormal in 92% (range, 5.0-96.5). Patients with chronic P. aeruginosa had significantly higher LCI (p = .01) and TBS (p = .02) which were associated with more major PEx (p < .01 and p = .01, respectively) and more days of intravenous (IV) antibiotic treatment in the preceding year (p = .03 and p = .001, respectively). CONCLUSIONS: Most CF patients with normal FEV1 have already physiological and structural lung abnormalities which were associated with more PEx and IV antibiotic treatment. Further studies are needed to determine if better adherence to the currently used therapies and the new cystic fibrosis transmembrane modulators will prevent the progression of lung disease.

Neonatal Cervical Osteomyelitis With Bilateral Upper Limb Paresis.

Neonatal cervical osteomyelitis is extremely rare, with only a few cases having been reported. We report a neonate with cervical osteomyelitis and extensive inflammation of the surrounded tissues that caused nerve root compression and upper limb paresis.

Circulating angiogenic factors in monochorionic twin pregnancies complicated by twin-to-twin transfusion syndrome and selective intrauterine growth restriction.

OBJECTIVE: To determine maternal plasma levels of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), placental growth factor (PLGF), and soluble endoglin (sEng) in monochorionic diamniotic (MC/DA) twin pregnancies complicated by twin-to-twin transfusion syndrome (TTTS) or selective intrauterine growth restriction (sIUGR). STUDY DESIGN: A longitudinal cohort study of pregnant women with MC/DA twins who were classified into 3 groups: (1) uncomplicated MC/DA twins (n = 22), (2) TTTS (n = 23), and (3) sIUGR (n = 15). Maternal plasma samples were obtained between 13-20 and 21-28 weeks of gestation and cord blood samples were collected at delivery. Maternal plasma concentrations of sVEGFR-1, PLGF, and sEng, as well as cord blood levels of sVEGFR-1 were measured by enzyme-linked immunoassay. RESULTS: Maternal plasma levels of sVEGFR-1 and sEng were significantly higher in patients with TTTS at the early and late second trimester compared with normal monochorionic pregnancies (P < .01). In contrast, in the sIUGR group, sVEGFR-1 and sEng levels were significantly higher only at the late second trimester (P < .05). PLGF levels were significantly lower at the early and late second trimester in both TTTS and sIUGR compared with controls (P < .01). Plasma concentrations of sVEGFR-1 were significantly higher among TTTS pregnancies compared with sIUGR at the late second trimester (P = .027). Cord blood levels of sVEGFR-1 were significantly higher in the smaller intrauterine growth restricted twin compared with the normal cotwin. CONCLUSION: Monochorionic pregnancies complicated by TTTS and sIUGR are characterized by decreased angiogenic activity. The disparity in severity of the antiangiogenic state between TTTS and sIUGR suggests that these 2 conditions may represent a continuum.