Meir Mei-Zahav

Long term nutritional rehabilitation by gastrostomy in Israeli patients with cystic fibrosis: clinical outcome in advanced pulmonary disease.

Objectives: Several studies have shown a linear correlation between nutritional status and pulmonary function in patients with cystic fibrosis. Our study aims were: 1) To evaluate the effect of nutritional supplementation via gastrostomy on nutritional, clinical, and pulmonary parameters, and 2) To identify predicting factors for success of long-term nutritional rehabilitation. Methods: Twenty-one Israeli patients, aged 8 months to 20 years, underwent gastrostomy insertion from 1992 to 2001. All patients were pancreatic insufficient, and all carried severe mutations (W1282X in 62% of the patients). Anthropometric and clinical data were obtained for each patient: 0−12 months before and 6−12 months and 18−24 months after gastrostomy placement. Standard deviation scores (SDS) for height, weight, and body mass index as well as percent of height-appropriate body weight were calculated. Results: The mean percent-of-predicted forced expiratory volume in 1 second (FEV1) decreased significantly during the first year of gastrostomy feeding (n = 16), from 44.2% ± 13.9 to 41% ± 13.3 (P = 0.05). However, during the second year of therapy (n = 10), a trend toward improvement was observed (from 39.4 ± 12.1 to 41.4 ± 16.1). Weight, and BMI z-scores as well as weight percent-of ideal body weight increased significantly. Height z-score for age decreased during the first year (from −1.9 ± 1.3 to −2.1 ± 1.4), However, a trend toward improvement was observed during the second year. A significant correlation was found between the change in weight z-score and height z-score during the first (r = 0.488, P = 0.016) and the second (r = 0.825, P < 0.001) years. There was no difference between compliers and noncompliers regarding height, weight, and BMI either before or after gastrostomy placement. A significant correlation between age at insertion of gastrostomy and improvement in height z-score (r = 0.52, P = 0.016) was observed. Cystic fibrosis related diabetes (n = 8) did not affect the response to supplemental feeding. Conclusions: We observed a trend toward improvement of pulmonary disease during the second year, and a significant improvement in weight, height, and BMI z-scores. Compliance, diabetes, and young age prior to tube insertion did not predict success of nutritional rehabilitation.

Screening for pulmonary and cerebral arteriovenous malformations in children with hereditary haemorrhagic telangiectasia

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterised by vascular dysplasia complicated by visceral arteriovenous malformations (AVMs). To date, the diagnostic yield of screening procedures for pulmonary and cerebral AVMs in children with definite or potential HHT is not well defined. The aim of the present study was to prospectively evaluate the diagnostic yield of a screening protocol for pulmonary and cerebral AVMs in children with either a definite or potential HHT diagnosis. All children referred for evaluation for HHT between 1996 and 2008 were included in the present analysis. Screening tests for AVMs included chest computed tomography and brain magnetic resonance imaging. 61 children with a definite clinical and/or genetic diagnosis of HHT were asymptomatic for visceral AVMs at their first baseline assessment (mean±sd age 8.7±4.7 yrs; range 0–17.0 yrs). Of these, 15 (25%) had pulmonary and/or cerebral AVMs diagnosed on initial screening tests. Pulmonary AVMs predominated in paediatric HHT patients (14 out of 15 patients) and were found in eight children aged <10 yrs. 55 children had a potential HHT diagnosis as they fulfilled only one or two HHT clinical diagnostic criteria and did not have a confirmatory genetic diagnosis (age 10.9±4.8 yrs; range 0–17.9 yrs). None of these children had pulmonary or cerebral AVMs on initial screening tests. The present data suggest that children with a definite HHT diagnosis have a high frequency of pulmonary AVMs even when clinically asymptomatic. In contrast, no AVMs were observed in children not fulfilling HHT diagnostic criteria. Genetic testing appears to be useful in defining an at-risk group for pulmonary AVMs in childhood.

Encouraging Pulmonary Outcome for Surviving, Neurologically Intact, Extremely Premature Infants in the Postsurfactant Era

OBJECTIVE The aim of this study was to determine the long-term pulmonary outcome of extreme prematurity at a single tertiary-care center from 1997 to 2001 in the postsurfactant era. METHODS We assessed symptoms, exhaled nitric oxide, spirometry, methacholine challenge (provocative concentration of methacholine required to decrease FEV₁ by 20% [PC(20)]), lung volumes, diffusion, and cardiopulmonary exercise tolerance. RESULTS Of 279 infants born, 192 survived to discharge, and 79 of these developed bronchopulmonary dysplasia (BPD) (65 mild, 12 moderate, two severe). We studied a subgroup of 53 neurologically intact preterm subjects aged 10 ± 1.5 years (28 with BPD [born, 26.2 ± 1.4 weeks; birth weight, 821 ± 164 g] and 25 without BPD [born, 27.2 ± 1 weeks; birth weight, 1,050 ± 181 g]) and compared them with 23 term control subjects. Of the BPD cases, 21 were mild, seven were moderate, and none was severe; 77.4% of subjects received antenatal steroids, and 83% received postnatal surfactant. Sixty percent of the preterm subjects wheezed at age < 2 years compared with 13% of the control subjects (P < .001), but only 13% wheezed in the past year compared with 0% of control subjects (not significant). For preterm and control subjects, respectively (mean ± SD), FEV₁ % predicted was 85% ± 10% and 94% ± 10% (P < .001), with limited reversibility; residual volume/total lung capacity was 29.3% ± 5.5% and 25% ± 8% (P < .05); diffusing capacity/alveolar volume was 89.6% ± 9.2% and 97% ± 10% (P < .005); and PC(20) was 6.5 ± 5.8 mg/mL and 11.7 ± 5.5 mg/mL (P < .001). PC(20) was < 4 mg/mL in 49% of preterm subjects despite normal exhaled nitric oxide. Most measurements were similar in premature subjects with and without BPD. Peak oxygen consumption and breathing reserve were normal, but % predicted maximal load (measured in Watts) was 69% ± 15% for subjects with BPD compared with 88% ± 23% for subjects without and 86% ± 20% for control subjects (P < .01). CONCLUSIONS Pulmonary outcome was encouraging at mid-childhood for neurologically intact survivors in the postsurfactant era. Despite mechanical ventilation and oxygen therapy, most had no or mild BPD. Changes found probably reflect the hypoplastic lungs of prematurity.

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

BACKGROUND Allergic 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. METHODS 9 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. RESULTS All 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. CONCLUSION High-dose IV-pulse methylprednisolone is an effective treatment for ABPA in CF with minor side effects.

Computerised paediatric asthma quality of life questionnaires in routine care

Background: Asthma quality of life questionnaires are not readily incorporated into clinical care. We therefore computerised the Paediatric Asthma Quality of Life Questionnaire (standardised) (PAQLQ(S)) and the Paediatric Asthma Caregivers Quality of Life Questionnaire (PACQLQ), with a colour-coded printed graphical report. Objectives: To (a) assess the feasibility of the electronic questionnaires in clinical care and (b) compare the child’s PAQLQ scores with the parent’s score, physician’s clinical score and spirometry. Methods: Children with asthma were given a clinical severity score of 1–4 (increasing severity) and then completed the PAQLQ(S) electronically (scores 1–7 for increasing quality of life in emotional, symptoms and activity limitation domains) followed by spirometry and physician review. Parents completed the PACQLQ. Inclusion criteria required fluent Hebrew and reliable performance of spirometry. Children with additional chronic diseases were excluded. Results: 147 children with asthma aged 7–17 years completed PAQLQs and 115 accompanying parents completed PACQLQs, taking 8.3 (4.3–15) and 4.4 (1.5–12.7) min, respectively (mean (range)). Graphical reports enabled physicians to address quality of life during even brief visits. Children’s (PAQLQ) and parents’ (PACQLQ) total scores correlated (r = 0.61, p<0.001), although the children’s median emotional score of 6.3 was higher than their parents’ 5.7 (p<0.001), whereas median activity limitation score was lower than their parents’: 5.0 and 6.8, respectively (p<0.001). No correlation was found with physician’s clinical score or spirometry. Conclusions: Electronic PAQLQs are easy to use, providing additional insight to spirometry and physician’s assessment, in routine asthma care. Future studies must assess impact on asthma management.

Reference percentiles for FEV1 and BMI in European children and adults with cystic fibrosis

BackgroundThe clinical course of Cystic Fibrosis (CF) is usually measured using the percent predicted FEV1 and BMI Z-score referenced against a healthy population, since achieving normality is the ultimate goal of CF care. Referencing against age and sex matched CF peers may provide valuable information for patients and for comparison between CF centers or populations. Here, we used a large database of European CF patients to compute CF specific reference equations for FEV1 and BMI, derived CF-specific percentile charts and compared these European data to their nearest international equivalents.Methods34859 FEV1 and 40947 BMI observations were used to compute European CF specific percentiles. Quantile regression was applied to raw measurements as a function of sex, age and height. Results were compared with the North American equivalent for FEV1 and with the WHO 2007 normative values for BMI.ResultsFEV1 and BMI percentiles illustrated the large variability between CF patients receiving the best current care. The European CF specific percentiles for FEV1 were significantly different from those in the USA from an earlier era, with higher lung function in Europe. The CF specific percentiles for BMI declined relative to the WHO standard in older children. Lung function and BMI were similar in the two largest contributing European Countries (France and Germany).ConclusionThe CF specific percentile approach applied to FEV1 and BMI allows referencing patients with respect to their peers. These data allow peer to peer and population comparisons in CF patients.

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.

Propranolol treatment for infantile hemangioma does not increase risk of childhood wheezing

Propranolol is the treatment of choice for infantile hemangiomas requiring medical intervention. Although contraindicated in asthma, its bronchoconstrictive effect in infants and children has not been extensively studied. We aimed to assess the incidence of wheezing episodes in infants and children treated with propranolol for infantile hemangiomas.

Feasibility of multiple breath washout measurements in infants with bronchiolitis: A pilot study: Multiple Breath Washout in Bronchiolitis

Lung clearance index (LCI) reflects ventilation inhomogeneity and is raised in obstructive airway disease. Feasibility of multiple breath washout (MBW) measurement during acute lung disease in infants is unknown. As a further measure of disease, exhaled nitric oxide (eNO) may paradoxically decrease in acute bronchiolitis. We hypothesized that MBW measurements were attainable in infants with bronchiolitis and that LCI was raised and eNO reduced, compared to normal controls.

Nationwide genetic analysis for molecularly unresolved cystic fibrosis patients in a multiethnic society: implications for preconception carrier screening

Preconception carrier screening for cystic fibrosis (CF) is usually performed using ethnically targeted panels of selected mutations. This has been recently challenged by the use of expanded, ethnically indifferent, pan‐population panels. Israel is characterized by genetically heterogeneous populations carrying a wide range of CFTR mutations. To assess the potential of expanding the current Israeli preconception screening program, we sought the subset of molecularly unresolved CF patients listed in the Israeli CF data registry comprising ~650 patients.