D. Shoseyov

Intravenous monthly pulse methylprednisolone treatment for ABPA in patients with cystic fibrosis

BACKGROUNDnAllergic bronchopulmonary aspergillosis (ABPA) in patients with CF is associated with frequent exacerbations and deterioration of lung function. Oral corticosteroids are standard therapy for ABPA and are associated with severe side effects. Monthly pulses of high-dose intravenous methylprednisolone (HDIVPM) are an effective therapy for autoimmune diseases with fewer side effects compared to oral prednisone, implicating its use for patients with CF who suffer from ABPA.nnnMETHODSn9 patients with CF and ABPA (4 male, 5 female, ages 7-36 years) received HDIVPM (10-15 mg/kg/d), for 3 days per month, and itraconazole, until clinical and laboratory resolution of ABPA.nnnRESULTSnAll patients showed clinical and laboratory improvement (FEV(1) increase, serum IgE levels and total eosinophil counts decrease) and treatment was discontinued after 6-10 pulses. Adverse effects were minor and disappeared shortly after each IV pulse therapy.nnnCONCLUSIONnHigh-dose IV-pulse methylprednisolone is an effective treatment for ABPA in CF with minor side effects.

Dexamethasone inhalations in RSV bronchiolitis: A double‐blind, placebo‐controlled study

OBJECTIVEnTo evaluate the effect of inhaled dexamethasone on hospitalization for respiratory syncytial virus (RSV) bronchiolitis.nnnSTUDY DESIGNnA double-blind, placebo-controlled study compared nebulization of dexamethasone versus nebulization of 0.9% saline. Both groups were treated with epinephrine nebulizations. Follow-up continued for 3 mo.nnnPATIENTS AND METHODSnSixty-one infants with bronchiolitis aged 3 to 12 mo were included. They were randomly allocated to nebulizations with 0.25 mg dexamethasone every 6 h (group 1) or an equivalent amount of normal saline (group 2).nnnRESULTSnNo statistically significant differences with respect to clinical score, oxygen saturation, or IV fluid requirement between the groups were noted. Using Kaplan-Meyers method, the cumulative proportion of in-hospital stay was significantly lower in group 1 compared with group 2, mainly in days 5 and 6 post-hospitalization (p<0.038). A subgroup of prematurely born children in group 1 had a shorter hospitalization period (6.5+/-1.7 d) compared with group 2 children (9.1+/-1.9) (p<0.018). Follow-up revealed similar wheeze and hospitalization rates in the two groups.nnnCONCLUSIONnInhaled dexamethasone may reduce the length of hospitalization among infants with acute viral bronchiolitis, especially among those born prematurely.

Differences in the Pattern of Structural Abnormalities on CT Scan in Patients With Cystic Fibrosis and Pancreatic Sufficiency or Insufficiency

BACKGROUNDnCystic fibrosis (CF) genotypes characterized by pancreatic sufficiency (PS) are generally associated with milder disease vs genotypes characterized by pancreatic insufficiency (PI); however, the correlation between pancreatic status and type and severity of structural lung changes has not been studied. We aimed to evaluate differences in the severity and distribution of pulmonary manifestations of CF in patients with PS vs PI.nnnMETHODSnWe retrospectively evaluated changes in individual lobes and the whole lung on chest CT scan with the modified Brody score. The study population included 84 (39 female, 45 male) patients with CF aged 4 to 68 years (mean, 20.5) treated from 2000 to 2010. Our institutional review board waived the requirement for informed consent. The severity of lung changes and distribution of pulmonary disease were compared by Student t test, nonparametric Pearson χ2 test, or mixed-design analysis of variance for 28 patients with CF-PS and 56 with CF-PI. Correlations were evaluated with the Pearson (continuous variables) or Spearman ρ (nonparametric variables) tests. A linear regression model was used for multivariate analyses.nnnRESULTSnCompared with patients with CF-PS, those with CF-PI had more-severe lung disease (P=.001) with predominant upper lobe involvement (P=.002) and significant differences in Brody scores for bronchiectasis and bronchial wall thickening. Lung manifestations in patients with CF-PS did not show predominant involvement of any one area (P=.133).nnnCONCLUSIONSnIn patients with CF-PI, structural lung changes are more severe with upper lobe predominance, prominent bronchiectasis, and bronchial wall thickening vs lower severity and more general distribution of changes in those with CF-PS.

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 (β-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 expansins 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. OCs 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.