S. Bella

Exhaled 8-isoprostane and prostaglandin E2 in patients with stable and unstable cystic fibrosis.

We measured 8-isoprostane, a biomarker of oxidative stress, and prostaglandin (PG) E(2) in exhaled breath condensate in 36 stable and 14 unstable cystic fibrosis (CF) patients, and in 15 healthy age-matched controls. We studied the relationships of these eicosanoids with clinical, radiological, and systemic inflammatory parameters. Compared with controls [15.5 (11.5-17.0) pg/ml] exhaled 8-isoprostane was increased in stable CF patients [30.5 (25.3-36.0) pg/ml, P<0.001]. Unstable CF patients had higher exhaled 8-isoprostane levels [47.5 (44.0-50.0) pg/ml, P<0.001] than stable CF patients. Unlike PGE(2), exhaled 8-isoprostane was negatively correlated with FEV(1) (r=-0.67; P<0.0001; r=-0.63; P<0.02) and Shwachman score (r=-0.43, P=0.012; r=-0.58, P=0.031) and positively correlated with Chrispin-Norman score (r=0.51, P<0.002; r=0.56, P=0.039) in stable and unstable CF patients, respectively. No correlation was observed with C-reactive protein. Compared with controls [41.0 (29.0-50.0) pg/ml], exhaled PGE(2) was also elevated in stable [72.0 (64.3-81.8) pg/ml, P<0.001) and, to a greater extent, in unstable CF patients [83.0 (74.3-91.3) pg/ml, P<0.001). In patients with CF, exhaled 8-isoprostane and PGE(2) could be a useful marker of disease severity.

Clinical effects of early treatment with insulin glargine in patients with cystic fibrosis and impaired glucose tolerance

Diabetes mellitus is an increasing complication of cystic fibrosis (CF), as a result of the improved life expectancy. There is clear association between diabetes and increased morbidity and mortality. Lung function and clinical status deteriorate up to 2–4 yr before the diagnosis of cystic fibrosis-related diabetes (CFRD). The aim of our study was to evaluate the effects, on glucose homeostasis and clinical status, of the early treatment with insulin glargine in CF patients with impaired glucose tolerance (IGT). We selected six subjects with IGT diagnosed at oral glucose tolerance test (OGTT). Median age was 18.12 yr (range 9.2–27.8). Insulin glargine was administered at the median dosage of 0.3 U/kg/day (range 0.2–0.5). After the initial adjustment of the dosage, no patient manifested hypoglycemia during treatment. Median glycosylated hemoglobin (HbAIc) did not show any significant variation during treatment: it was 5.9% at baseline (range 5.5–6.2) and 6.1% (range 5.0–6.7) at the end of follow-up (p = 0.496). Median body mass index (BMI) z-score significantly increased during treatment, from −0.95 (range −3.2–+0.6) at baseline to −0.5. (range −3.0–+0.9) at the end of follow-up (p = 0.026). Lung function, measured by median forced expiratory volume in the first second (FEV1%), showed a mild but significant improvement during insulin treatment. It was 72.7% at baseline (range 41.5–98.4) and 76.7% (range 42.0–106.8) at the end of follow-up (p = 0.027). No significant variation was found between the number of hospitalizations for clinical exacerbation (no./patient/yr) in the last 2 yr before treatment and during follow-up. Median number at baseline was 1.95/patient/yr (range 1–3) and 2.0/patient/yr (range 1–3) at follow-up (p = 0.715). Our data seem to indicate that early insulin therapy can be safe, no patient manifested hypoglycemia or other adverse effects during treatment. Insulin is an anabolic hormone implicated in both lipid and protein metabolism. The appearance of IGT out of infections can indicate an early insulin deficiency, with a potential impact on the nutritional and clinical status of the patient, even before the appearance of overt diabetes. Larger controlled trials are necessary to verify if early insulin therapy is able to reduce the deterioration of nutritional status and lung function associated with the onset of IGT. (J. Endocrinol. Invest. 29: RC1-RC4, 2006)

Bone and body composition analyzed by Dual-energy X-ray Absorptiometry (DXA) in clinical and nutritional evaluation of young patients with Cystic Fibrosis: a cross-sectional study

Backgroundthe improved general therapy has led to reduced morbidity and mortality from Cystic Fibrosis (CF), and bone status may have a potentially greater clinical impact.We investigated the correlation between the severity of the clinical condition, bone status and body composition parameters, in a group of children and young adults with CF.Methodswe measured lumbar spine bone density and total body composition by dual energy x-ray absorptiometry (DXA) in 82 consecutive CF patients (42 males; median age: 13 years - range: 5-30). Eighty-two healthy subjects, matched for age, gender, height and pubertal stage were recruited as a control group.Results37 patients (45.1%) had a normal bone mineral density (BMD). A BMD reduction were observed in 45 (54.8%) patients. Lumbar spine Z score was positively related to Body Mass Index (BMI) and a higher Shwachman-Kulczycki score, and negatively related to Crispin-Norman score. A positive and significant correlation was also observed between lumbar spine Z score and total body composition.Conclusiona significant BMD reduction can be present early in CF children and adolescents. A careful follow up of bone status is required starting in childhood.

Treatment of low bone density in young people with cystic fibrosis: a multicentre, prospective, open-label observational study of calcium and calcifediol followed by a randomised placebo-controlled trial of alendronate.

BACKGROUND Long-term complications of cystic fibrosis include osteoporosis and fragility fractures, but few data are available about effective treatment strategies, especially in young patients. We investigated treatment of low bone mineral density in children, adolescents, and young adults with cystic fibrosis. METHODS We did a multicentre trial in two phases. We enrolled patients aged 5-30 years with cystic fibrosis and low bone mineral density, from ten cystic fibrosis regional centres in Italy. The first phase was an open-label, 12-month observational study of the effect of adequate calcium intake plus calcifediol. The second phase was a 12-month, double-blind, randomised, placebo-controlled, parallel group study of the efficacy and safety of oral alendronate in patients whose bone mineral apparent density had not increased by 5% or more by the end of the observational phase. Patients were randomly assigned to either alendronate or placebo. Both patients and investigators were masked to treatment assignment. We used dual x-ray absorptiometry at baseline and every 6 months thereafter, corrected for body size, to assess lumbar spine bone mineral apparent density. We assessed bone turnover markers and other laboratory parameters every 3-6 months. The primary endpoint was mean increase of lumbar spine bone mineral apparent density, assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01812551. FINDINGS We screened 540 patients and enrolled 171 (mean age 13·8 years, SD 5·9, range 5-30). In the observational phase, treatment with calcium and calcifediol increased bone mineral apparent density by 5% or more in 43 patients (25%). 128 patients entered the randomised phase. Bone mineral apparent density increased by 16·3% in the alendronate group (n=65) versus 3·1% in the placebo group (n=63; p=0·0010). 19 of 57 young people (33·3%) receiving alendronate attained a normal-for-age bone mineral apparent density Z score. In the observational phase, five patients had moderate episodes of hypercalciuria, which resolved after short interruption of calcifediol treatment. During the randomised phase, one patient taking alendronate had mild fever versus none in the placebo group; treatment groups did not differ significantly for other adverse events. INTERPRETATION Correct calcium intake plus calcifediol can improve bone mineral density in some young patients with cystic fibrosis. In those who do not respond to calcium and calcifediol alone, alendronate can safely and effectively increase bone mineral density. FUNDING Telethon Foundation (Italy).

Severe reaction in a child with asymptomatic codfish allergy: Food challenge reactivating recurrent pancreatitis

An 8-year-old child during the first year of life manifested severe atopic dermatitis and chronic diarrhea with mucorrhea and rectal bleeding; a fish-free diet was started based on weakly positive skin-prick tests to codfish extract. At the age of 4 years the child began to suffer of recurrent pancreatitis. When he came to our attention for the evaluation of his fish allergy, he was asymptomatic; a weak reactivity to codfish was observed (SPTs: cod, 4 mm, sIgE ImmunoCAP: cod, 1.30kU/l). The food challenge test with cod was negative. When the child ate cod again, within 5 minutes, developed anaphylactic reaction and complained of abdominal pain compatible with pancreatitis (enzyme serum levels risen and parenchymal oedema at ultrasonography), that resolved within 7 days after specific therapy. This case raises two issues: the elimination diet in asymptomatic food allergy on the basis only of SPT and the ethicality of food challenge in gastrointestinal chronic disease.

Diagnosis of atypical CF: a case-report to reflect.

Non-classic Cystic Fibrosis (CF) still represents a difficult entity to diagnose. We present a case of two sisters affected by mild pulmonary symptoms started at puberty, carriers of the F508del mutation associated with the T5TG13 combination. We discuss the clinical utility of TG repeat testing in individuals carrying the T5 variant. Furthermore, this case-report leads to reflect on the natural history of CF and the correct management of its atypical forms.

47 CFTR gene mutations and the risk for developing a pancreatic cancer: is it only a consequence of chronic inflammation?

Background: Ten to 15% of CF infants present with meconium ileus (MI), that sometimes can lead to intestinal malformation. Serum immunoreactive trypsin (IRT) levels may be normal and newborn screening (NBS) could be erroneously considered negative. In our CFNBS protocol newborn babies presenting problems with meconium passage (delay in meconium emission − MD − included) undergo sweat test also if IRT is negative Aim: The aim of this study is to investigate the incidence of CF in neonates with MI and MD to determine if infants with this last condition have to be submitted to CF diagnostic test. Patients and Method: A retrospective 5-year study examines neonates screened in our Center that presented problems in meconium passage, with regard to IRT values and CF diagnosis. Results: In a 5-year period (2006–2010) we screened 172,185 newborns and diagnosed 50 CF. Eigthy-two newborns were reported having some problems related to meconium passage: 13 were referred as MI (group 1), 7 as intestinal atresia (IA) (group 2), 62 as MD (group 3). In group 1 8/13 had IRT positive, 6/13 were diagnosed as CF and one of them had IRT normal value; 2 died without diagnosis. In group 2 6/7 had IRT negative, 2/7 had CF and one of them was IRT negative. In group 3 nobody out 62 had IRT positive, nor positive sweat test. Conclusion: In this series 12% of CF neonates presented with MI and/or IA, and 2 of them were IRT negative confirming that CF with MI and IA can have negative NBS. Delay in meconium pass is therefore, asscociated neither with positive screening nor with CF, suggesting that newborns with MD and IRT negative don’t require further analysis for CF.

43 Atypical forms of cystic fibrosis (CF): The emerging diagnostic challenge for diagnosing CF in children and adolescents with a single-organ involvement

42* Do false positive test results for newborn screening for cystic fibrosis lead to long term parental anxiety? A.M. Vernooij-van Langen1,2, S.J. Reijntjens2, S.M. van der Pal3, J.G. Loeber1, E. Dompeling4, J.E. Dankert-Roelse2, CHOPIN Study Group. 1RIVM, Bilthoven, Netherlands; 2Atrium Medical Center, Heerlen, Netherlands; 3TNO Quality of Life, Leiden, Netherlands; 4Maastricht University Medical Center, Maastricht, Netherlands