M. Cohen-Cymberknoh

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.

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.

Ivacaftor for the p.Ser549Arg (S549R) gating mutation – The Israeli experience

BACKGROUNDnIvacaftor is a drug that increases the probability of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel remaining open. Information about the efficacy of ivacaftor in patients carrying the rare p.Ser549Arg (S549R) CFTR mutation is sparse.nnnAIMnEfficacy of ivacaftor treatment in patients carrying the p.Ser549Arg (S549R) CFTR mutation.nnnMETHODSnData obtained from CF patients receiving ivacaftor for one year.nnnRESULTSnEight CF patients, mean age 21xa0±xa010 years, received ivacaftor. After one year, significant improvement was found in FEV1, increasing from 74% to 88% (pxa0<xa00.001), FVC, 89% to 101% (pxa0=xa00.019), and FEF25-75, 59%-76% (pxa0=xa00.019). Sweat chloride concentration decreased from 116xa0±xa08xa0mmol/L to 51xa0±xa017xa0mmol/L (pxa0<xa00.001), and BMI increased from 20xa0±xa03 to 22xa0±xa04 (pxa0=xa00.003). Glucose tolerance improved in five patients. There was no significant change in bacterial colonization.nnnCONCLUSIONSnIvacaftor therapy resulted in significant clinical improvement in patients carrying the p.Ser549Arg (S549R) CFTR mutation.