Increasing Vitamin D Serum Levels Is Associated With Reduced Pulmonary Exacerbations in Patients With Cystic Fibrosis.

CONTEXT: In 2012, The North American Cystic Fibrosis Foundation (NACFF) published new guidelines for the treatment of vitamin D deficiency in individuals with cystic fibrosis (CF). OBJECTIVE: The objectives of our study were to assess the efficacy of these guidelines, and to test the effect of increasing vitamin D dosage on pulmonary function and exacerbations. DESIGN: Pulmonary function tests and serum concentrations of 25-hydroxyvitamin D [25(OH)D] were measured 1 year before increasing vitamin D dosage according to the guidelines and at least 1 year later. In addition, days of hospitalization and pulmonary exacerbations were counted and an average per year (average number of days of hospitalization and average number of pulmonary exacerbations [PEA], respectively) was calculated. SETTING AND PARTICIPANTS: A total of 90 patients from The Cystic Fibrosis Clinic at Hadassah Mount-Scopus Hospital, Jerusalem, Israel. RESULTS: The mean serum concentration of vitamin D increased significantly from 20.97 ng/mL (52.34 nmol/L) at baseline to 25.41 ng/mL (63.42 nmol/L) at the end of follow-up (P < 0.001). The number of PEA decreased significantly from 2.79 ±â€Š3.96 to 2.15 ±â€Š2.91 (P = 0.007). The change in vitamin D levels was correlated with a decrease in PEA (correlation coefficient = -0.318, P = 0.002). CONCLUSIONS: The NACFF guidelines for management of vitamin D deficiency improve vitamin D levels in patients with CF but did not reach the normal values in most patients. The increase in vitamin D serum levels was, however, associated with a decrease in number of pulmonary exacerbations.

The impact of a national population carrier screening program on cystic fibrosis birth rate and age at diagnosis: Implications for newborn screening.

BACKGROUND: Population carrier screening (PCS) has been available in Israel since 1999 and universally subsidized since 2008. We sought to evaluate its impact. METHODS: A retrospective review of governmental databanks, the national CF registry and CF centers. RESULTS: CF rate per 100,000 live births has decreased from 14.5 in 1990 to 6 in 2011. From 2004-2011 there were 95 CF births: 22 utilized PCS; 68 (72%) had 2 known CFTR mutations; 37% were pancreatic sufficient. At diagnosis, age was 6 (0-98) months; 53/95 had respiratory symptoms, 41/95 failure to thrive and 19/95 pseudomonas. Thirty-four (36%) were Arabs and 19 (20%) orthodox Jews, compared to 20% and 8% respectively, in the general population. CONCLUSIONS: PCS markedly reduced CF birth rates with a shift towards milder mutations, but was often avoided for cultural reasons. As children regularly have significant disease at diagnosis, we suggest a balanced approach, utilizing both PCS and newborn screening.

Triphala (PADMA) extract alleviates bronchial hyperreactivity in a mouse model through liver and spleen immune modulation and increased anti-oxidative effects.

OBJECTIVES: Triphala (TRP), a herbal extract from Tibetan medicine, has been shown to affect lymphocytes and natural killer T (NKT) cell function. We hypothesize that TRP could ameliorate bronchial hyperreactivity through immune-cell modulations. METHODS: Asthma mouse models were generated through intraperitoneal (IP) injections of ovalbumin (OVA)/2 weeks followed by repeated intranasal OVA challenges. Mice were then treated with normal saline (OVA/NS) or Triphala (OVA/TRP). Data were compared with mice treated with inhaled budesonide. All groups were assessed for allergen-induced hyperreactivity; lymphocytes from lungs, livers and spleens were analyzed for OVA-induced proliferation and their alterations were determined by flow cytometry. Oxidative reactivity using chemiluminescence, serum anti-OVA antibodies level and lung histology were assessed. RESULTS: Both TRP and budesonide significantly ameliorated functional and histological OVA-induced bronchial hyperreactivity. TRP had no effect on serum anti-OVA antibodies as compared with decreased levels following budesonide treatment. Furthermore, a significant increase in lung and spleen CD4 counts and a decrease in the liver were noted after TRP treatments. Bronchoalveolar fluid from TRP-treated animals but not from the budesonide-treated animals showed anti-oxidative effects. CONCLUSION: TRP and budesonide caused a significant decrease in bronchial reactivity. TRP treatment altered immune-cell distributions and showed anti-oxidative properties. These findings suggest that immune-cell modulation with TRP can ameliorate lung injury.

Oxidized cellulose binding to allergens with a carbohydrate-binding module attenuates allergic reactions.

Grass and mite allergens are of the main causes of allergy and asthma. A carbohydrate-binding module (CBM) represents a common motif to groups I (ß-expansin) and II/III (expansin-like) grass allergens and is suggested to mediate allergen-IgE binding. House dust mite group II allergen (Der p 2 and Der f 2) structures bear strong similarity to expansin's CBM, suggesting their ability to bind carbohydrates. Thus, this study proposes the design of a carbohydrate-based treatment in which allergen binding to carbohydrate particles will promote allergen airway clearance and prevent allergic reactions. The aim of the study was to identify a polysaccharide with high allergen-binding capacities and to explore its ability to prevent allergy. Oxidized cellulose (OC) demonstrated allergen-binding capacities toward grass and mite allergens that surpassed those of any other polysaccharide examined in this study. Furthermore, inhalant preparations of OC microparticles attenuated allergic lung inflammation in rye grass-sensitized Brown Norway rats and OVA-sensitized BALB/c mice. Fluorescently labeled OC efficiently cleared from the mouse airways and body organs. Moreover, long-term administration of OC inhalant to Wistar rats did not result in toxicity. In conclusion, many allergens, such as grass and dust mite, contain a common CBM motif. OC demonstrates a strong and relatively specific allergen-binding capacity to CBM-containing allergens. OC's ability to attenuate allergic inflammation, together with its documented safety record, forms a firm basis for its application as an alternative treatment for prevention and relief of allergy and asthma.

Meconium ileus in patients with cystic fibrosis is not a risk factor for clinical deterioration and survival: the Israeli Multicenter Study.

OBJECTIVES: Patients with cystic fibrosis (CF) presenting with meconium ileus (MI) tend to have worse outcomes than those without MI. We evaluated the clinical characteristics and survival rates among Israeli patients with CF with and without MI after a prolonged follow-up (15-30 years). PATIENTS AND METHODS: A multicenter retrospective study. Forty-nine patients with CF, representing 13.8% of all patients with CF in Israel, presented with MI (current age 17.4 +/- 7.9 years) between 1975 and 2006. They were compared with 38 patients with CF (current age 19.3 +/- 6.5 years) without MI matched by sex and CF transmembrane conductance regulator mutation. RESULTS: A total of 66.2% of patients with MI and 73.6% without MI were followed for a prolonged period (24.9 +/- 2.7 years). Of the patients with MI, 31 were managed operatively, whereas 18 were treated successfully with gastrograffin enema, with similar clinical outcomes. Five patients in the MI group and 3 in the control group died during the study period. Bacterial colonization, z score of body mass index, and pulmonary function tests were similar in patients with and without MI in the long term. In younger patients, many clinical parameters were more prevalent in patients with MI (P = 0.004). However, these differences disappeared after the long-term follow-up (up to 31-years). CONCLUSIONS: Patients with CF presenting with MI had similar pulmonary function and nutritional status, as well as survival rates as did the control patients without MI. The distinct genetic mutation found in our population may explain in part the favorable results compared with other studies. In addition, it seems that early diagnosis and treatment of MI in patients with CF may be beneficial, subsequently lowering morbidity, and increasing survival.

Comparison of positive allergy skin tests among asthmatic children from rural and urban areas living within small geographic area.

BACKGROUND: Evidence of increased asthma and allergic response among urban versus rural residents has been reported. OBJECTIVE: To evaluate the prevalence of allergic response among asthmatic children from urban and rural areas living within close proximity. METHODS: In all, 448 asthmatic children from urban (363) and rural (85) areas were studied. The study group consisted of 234 9-year-olds and 214 12-year-olds. A health questionnaire was completed on each child who subsequently underwent allergic skin prick tests (SPTs). RESULTS: There was significantly more positive SPT response to house-dust mite, mold, cat, and cypress among asthmatic children from urban areas compared with children living in rural areas: 58.3% versus 37.6%, 46.1% versus 31.8%, 17.45 versus 5.9%, and 26.2% versus 15.3%, respectively. Positive SPT for indoor allergens were significantly greater among asthmatic urban residents than asthmatic rural residents: 63.3% versus 45.5%, respectively (P < 0.02). Positive SPT response to all the allergens checked was higher among the 12-year-old age group when compared with the 9-year-olds, 34.6% versus 22.7%, respectively (P = 0.05). CONCLUSIONS: Allergic response measured by SPT is significantly more common among asthmatic children from urban areas as opposed to rural, even though both areas are within small distance of one another. Further, asthmatic children living in urban areas demonstrated more allergic response to both indoor and outdoor allergens. The allergic response tends to increase with increased age in both urban and rural asthmatic children.