Based on Moos and Holahan’s “Coping With Chronic Illness and Disability” model, we examined the contribution of medical impairment, illness perception, sense of coherence (SOC), relationship with the professional team, and adherence to treatment to the psychosocial adaptation (social adjustment and life satisfaction) of young adults with cystic fibrosis (CF). We also examined adherence, an important goal in and of itself for patients with CF. Seventy-one participants completed the following questionnaires: Social Adjustment, Life Satisfaction, Perceived Illness Severity, SOC, Relationship With Team, and Compliance. The legal criteria for medical impairment were also examined. Findings indicate that female patients and patients with high SOC reported better psychosocial adaptation. Participants with more severe medical impairments reported higher levels of adherence, and those who perceived their illness to be less severe reported lower levels of adherence and greater satisfaction in life. Relationship with the team was found to contribute to social adjustment. Psychosocial adaptation is associated with internal and external resources, but not necessarily with adherence to treatment. The rehabilitation counselor’s role is, therefore, to help adults with CF bridge between the contrasting dimensions of their lives, namely adherence to strict treatment protocols and psychosocial adaptation.

Background: Palliative treatment of refractory neuroblastoma remains a significant clinical problem. Objectives: To retrospectively determine the clinical response to 131I-MIBG therapy at low doses in patients with refractory neuroblastoma. m ethods: We performed a retrospective chart review of 10 patients with neuroblastoma treated with 131I-MIBG at Rambam Health Care Campus from 1994 to 2012. Clinical data, number of 131I-MIBG courses delivered, toxicities, and clinical responses were reviewed. MIBG scan was performed after each course.

INTRODUCTION:Spirometry testing should include both expiratory and inspiratory measurements. Inspiratory forced maneuvers can demonstrate extrathoracic airway abnormalities, of which various symptoms may suggest asthma. However, the inspiratory portion of the forced flow/volume maneuver in young healthy children has not yet been described. OBJECTIVES:To document and analyze the forced inspiratory flow volume curve indices in healthy young children. SETTINGS AND PARTICIPANTS:Healthy preschool children (age 2.5-6.5 years) from community kindergartens around Israel. METHODS:The teaching method included multi-target, interactive spirometry games and accessory games for inspiration (e.g., inspiratory whistle). RESULTS:One hundred and fourteen out of a total of 157 children performed duplicate full adequate inspiratory maneuvers. Repeatability between two maneuvers was 5.6%, 4.0%, 5.1%, 7.3% for inspiratory capacity (IC), forced inspiratory vital capacity (FIVC), peak inspiratory flow (PIF), and mid inspiratory flow (FIF50). Inspiratory flow indices were significantly lower than the expiratory flow indices. The time to reach PIF was significantly longer (mean +/- SD; 229 +/- 21 msec) than the time to reach peak expiratory flow (92 +/- 8 msec; P < 0.0001). The shape of the inspiratory curve was parabolic and did not vary with age. The formed predicted equations were in agreement with the extrapolated values for older healthy children. CONCLUSIONS:The majority of healthy young children can perform reliable maximum inspiratory flow volume curves. Our results provide a framework of reference equations for maximum inspiratory flow volume curve in the young children. The clinical applications of these equations have to be explored.

OBJECTIVE:The use of flexible bronchoscopy (FOB) and bronchoalveolar lavage (BAL) in investigating pediatric patient with airway abnormalities and pulmonary infiltrates are indispensable and are now a routine procedure in many centers. Immunocompromised and cancer patients, especially after bone marrow transplantation, and children who have undergone surgery for congenital heart disease (CHD) are at high risk for pulmonary disease. Our aim was to study the diagnostic rate, safety, and clinical yield of FOB in critically ill pediatric patients.DESIGN:: Retrospective chart review.SETTING:Pediatric intensive care unit in a tertiary university hospital.PATIENTS:Three hundred nineteen children who underwent 335 FOB procedures. The indications for bronchoscopy included infectious agent identification in immune-competent patients with new pulmonary infiltrates seen on chest radiograph (46%) and in patients with fever and neutropenia with respiratory symptoms (18%), airway anatomy evaluation in patients with upper airway obstruction (16%), CHD (15%), and airway trauma (5%). Data were obtained by reviewing the patients' charts, bronchoscopy reports, and laboratory results.MEASUREMENTS AND MAIN RESULTS:The diagnostic rate of FOB procedures was 79%. FOB and BAL resulted in alteration of management (positive clinical yield) in 70 patients (23.9%). A definite infectious organism was identified in 56 patients (17.6%). The clinical yield in patients with cancer or primary immune deficiency (38.7%) was significantly higher compared with patients with CHD (20.4%, p < 0.01) and pneumonia (17%, p < 0.01). Major complications were observed in two procedures (prolonged apnea), and minor complications (transient desaturation, stridor, and minor bleeding) were observed in 45 patients (14%).CONCLUSIONS:FOB and BAL have an important role in the evaluation of airway abnormality and pulmonary infiltrate in pediatric patients, in whom rapid and accurate diagnosis is crucial for survival. We suggest that FOB should be considered as an initial diagnostic tool in those critically ill patients.

Background: The exercise challenge test (ECT) is a common tool for assessment of asthma in children. Many studies suggest that the "time to maximal bronchoconstriction" (Nadir-t) after exercise challenge in asthmatic children may be age-dependent, although this has never been systematically studied. Such findings may influence epidemiological surveys where the schedule of post-exercise measurements is trimmed. This study systematically assesses the relation between age and time to maximal bronchoconstriction post-ECT.Methods: Data were collected retrospectively from 131 subjects (87 male; 3-18 years) who were referred for ECT. The routine ECT was performed according to ATS recommendation of a 6-min run. Spirometry was measured at 1, 3, 5, 10, 15, and 20 min post-exercise. The post-exercise nadir of FEV1 (%baseline) (FEV1-nadir) and the time to maximal. fait in Nadir-t (minutes) were sought and values were related to age.Results. Baseline FEV1 values (mean +/- SD) were 90.5 +/- 13.8% predicted. FEV1-nadir was -23.6 +/- 11.7% from baseline values. The Nadir-t was reached at 5.1 +/- 2.6 min (range 2-12 min). A positive correlation between children's age and Nadir-t was observed (r(2) = 0.542; SD of residuals = 1.79; p < 0.001), regardless of FEV1-nadir, whether the cutoff of point was -10% or -15% of baseline FEV1. Children <10 years of age showed Nadir-t at 3.4 +/- 1.7 min post-exercise and older children at 6.6 +/- 2.5 min post-exercise (p < 0.0001).Conclusion: Our results indicate that the time to maximal bronchoconstriction is age-dependent in children and adolescents, and imply that the schedute of post-exercise FEV1 measurements should be cautiously trimmed. (C) 2009 Elsevier Ltd. All rights reserved.

Objectives The aims of this study were to determine the current pancreatic status of the entire cystic fibrosis (CF) population of Israel, to analyze the clinical characteristics of the pancreatic sufficient (PS) patients, and to characterize the correlation between pancreatic status, pancreatitis, and CIF genotype.Methods The Israeli CF database includes 505 patients. These patients were defined as being PS or insufficient according to their fecal pancreatic elastase level or by coefficient fat absorption findings. Mutations were categorized as severe (Delta F508, W1282X, G542X, S549R, N1303K, Q359K/T360K, 405 + 1G, and 1717) or mild/variable (3849 + 10 kb, D1152H, G85E, I1234V, R334W, and 5T) based on disease severity in patients carrying these mutations. Age at diagnosis, presenting symptoms, sweat-chloride concentrations, occurrence of pancreatitis, presence of diabetes, and liver disease were recorded.Results One hundred and thirty-nine (27.5%) of the CF patients were PS. None carried two mutations associated with severe disease. Over one third (34%) had normal or borderline sweat tests; 20 of these 139 patients had pancreatitis (14.3%) but none of the 366 pancreatic insufficient patients had it. Four initially PS patients became pancreatic insufficient: conversion followed several events of pancreatitis in three of them. Nasal potential differences were all pathological in 35 tested PS patients. None had either diabetes or liver disease.Conclusions A substantial number of CF patients are PS. All of them carry at least one mild mutation enabling production of a sufficient amount of normal mRNA to maintain exocrine pancreatic function. Pancreatitis occurs only in CF patients who are PS. These patients are at risk of progressing to pancreatic insufficiency.

Objective: To identify the characteristics of CF patients with hemoptysis in Israel and to compare clinical features and risk factors to a control group of CF patients without hemoptysis.Design: Retrospective chart review.Patients: All CF patients in Israel who experienced hemoptysis between 2001 and 2005 and a control group of sex- and age-matched patients with no history of hemoptysis.Results: 40/440 CF patients (9.1%) experienced hemoptysis during the study period, 50% were male. Ten patients (25%) were under 13 years old at the first hemoptysis episode. Pulmonary exacerbation was the precipitating factor in 90%. Twenty three patients showed moderate or major hemoptysis. 35/40 patients responded well to conservative therapy. Bronchial artery embolization (BAE) was performed in 5 patients with no recurrence of bleed within 24 h. However all of these patients experienced recurrent hemoptysis. One patient died during the follow-up period because of end stage lung disease. Pulmonary function tests, body-mass index, coagulation tests, pancreatic status, presence of bronchiectasis, Sputum Cultures and genetic mutations were similar in the two groups. A high incidence (57.5%) of associated diseases including cystic fibrosis related diabetes, cirrhosis and portal hypertension, and distal intestinal obstruction syndrome was found among hemoptysis patients, compared to only 5.2% in the control group (p<0.001).Conclusions: Hemoptysis, even major, did not seem to be a risk factor for mortality in our patients. A higher incidence of hemoptysis was found in our pediatric patients compared to other series. BAE shows a high immediate rate of success in controlling hemoptysis, but does not prevent future disease. (C) 2007 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Background: Diseases of the lungs and airways can be life-threatening in patients with congenital cardiac disease. External compression, and tracheobronchomalacia, as well as pathology of the large airways, can cause respiratory symptoms such as wheezing, stridor, fever, and dyspnoea, along with producing difficulty to wean the patient from mechanical ventilation. A definite diagnosis may be achieved by fibreoptic flexible bronchoscopy. Aims: To characterize the patients who underwent bronchoscopy for respiratory diseases associated with congenital cardiac disease, and to evaluate the safety, total diagnostic rate, and diagnostic rate, which yielded alteration of treatment in this group of patients. Methods: We reviewed retrospectively the records of 39 patients with congenital cardiac disease associated with abnormalities of the airways who underwent 49 fibreoptic bronchoscopies between 1999 and 2004. The patients were evaluated with regard to rate of diagnosis, the rate of procedures that resulted in alteration of management, and the rate of complications. Results: Fibreoptic flexible bronchoscopy was safe, and contributed to a specific diagnosis in almost nine-tenths of the procedures. A specific diagnosis that resulted in treatment alteration was achieved in one-fifth of the procedures. Conclusions: Fibreoptic flexible bronchoscopy has an important role in the evaluation of pulmonary abnormalities in patients with congenital cardiac diseases, and should be considered as an initial diagnostic tool that may guide the clinician with regard to the proper therapy.

Bilevel positive airway pressure ventilation (BIPAP) has been used in cystic fibrosis (CF) patients as a bridge to transplantation. Our aim was to evaluate the effect of BIPAP use before transplantation on post-transplantation morbidity and mortality. We performed a retrospective study at a tertiary care center. Twelve CF patients (9 males; mean age = 26 years) were assessed. Group 1 consisted of eight patients that did not use BIPAP before lung transplantation. Group 2 comprised four patients who used BIPAP for 3-15 months while awaiting transplantation. Patients were evaluated before and two to ten years after transplantation. All eight patients who did not use BIPAP died two months to ten years after transplantation. All four BIPAP users are alive with no evidence of bronchiolitis obliterans two to eight years after lung transplantation. We demonstrated a significant improvement in acid-base balance (p < 0.01) and body mass index (p < 0.05) and a tendency toward improvement in the work of breathing and number of hospitalizations. We conclude that improvement in nutritional status and respiratory muscle strength before lung transplantation in BIPAP users may prevent post lung transplantation infection and acute rejection rate, which in turn may reduce chronic rejection (bronchiolitis obliterans) and improve long-term survival after lung transplantation.

Background Patients with childhood cancer or primary immunodeficiencies (PID) are at high risk for developing pulmonary infections and non-infectious complications. The broad differential diagnoses and the critical condition of these patients often drive physicians to start broad-spectrum antibiotic therapy before a definite diagnostic procedure is performed. A definite diagnosis may be achieved in these situations by fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL). Patients and Methods. The records of 58 PIDs and cancer (immunocompromised group) pediatric patients who underwent 62 fiberoptic bronchoscopies between 2000 and 2004 were retrospectively reviewed and compared to 158 non-cancer patients who underwent 182 fiberoptic bronchoscopies during the same period. Results. The overall diagnostic rate achieved by macroscopic inspection of purulent secretions or hemorrhage, abnormal cell count, and infectious agent isolation in the immunocompromised patients was 84%. A definite organism was recovered in 53.2% of the patients. Probable infection defined as purulent secretions or abnormal cell count without infectious agent isolation was diagnosed in another 21% of the patients. The rate of complications was 30.6%. In the control group, the overall diagnostic rate was 76.9% (n.s) and an infectious agent was demonstrated in 12.1% (P < 0.001). Probable infection was diagnosed in 24.2% (n.s) while the rate of complications was lower (15%) (P < 0.01). Conclusions. Rapid and accurate diagnoses were achieved in most procedures performed on immunocompromised patienis. Although the rate of complications was higher in the immunocompromised group, they were usually very mild with no mortality. Based on these results, broncoalveolar lavage should be considered as an initial diagnostic tool in pediatric immunocompromised patients with pulmonary complications.

BACKGROUND Spirometry data in cystic fibrosis (CF) patients in early childhood is scarce, and the ability of spirometry to detect airways obstruction is debatable. OBJECTIVE To evaluate the ability of spirometry to detect airflow obstruction in CF patients in early childhood. METHODS CF children (age range, 2.5 to 6.9 years) in stable clinical condition were recruited from five CF centers. The children performed guided spirometry (SpiroGame; patented by Dr. Vilzone, 2003). Spirometry indices were compared to values of a healthy early childhood population, and were analyzed with relation to age, gender, and clinical parameters (genotype, pancreatic status, and presence of Pseudomonas in sputum or oropharyngeal cultures). RESULTS Seventy-six of 93 children tested performed acceptable spirometry. FVC, FEV1, forced expiratory flow in 0.5 s (FEV0.5), and forced expiratory flow at 50% of vital capacity (FEF50) were significantly lower than healthy (z scores, mean +/- SD: - 0.36 +/- 0.58, - 0.36 +/- 0.72, - 1.20 +/- 0.87; and - 1.80 +/- 1.47, respectively; p < 0.01); z scores for FEV1 and FVC were similar over the age ranges studied. However, z scores for FEV0.5 and forced expiratory flow at 25 to 75% of vital capacity were significantly lower in older children compared to younger children (p < 0.001), and a higher proportion of 6-year-old than 3-year-old children had z scores that were > 2 SDs below the mean (65% vs 5%, p < 0.03). Girls demonstrated lower FEF50 than boys (z scores: - 2.42 +/- 1.91 vs - 1.56 +/- 1.23; p < 0.001). Clinical parameters evaluated were not found to influence spirometric indices. CONCLUSIONS Spirometry elicited by CF patients in early childhood can serve as an important noninvasive tool for monitoring pulmonary status. FEV0.5 and flow-related volumes might be more sensitive than the traditional FEV1 in detecting and portraying changes in lung function during early childhood.

RATIONALE:The exercise challenge test (ECT) is a common tool to assess exercise-induced asthma (EIA) in school-aged children. EIA has not been explored in the early childhood setting.OBJECTIVE:To assess the existence of EIA in children in this age group.MEASUREMENTS AND MAIN RESULTS:A 6-min, controlled, free-run test was performed in 55 children (age range, 3 to 6 years old) who were classified into the following groups: 30 children in whom asthma had been previously diagnosed (group A); and 25 children with prolonged coughing (group B). Spirometry measurements were obtained before the run, and at 1, 2, 3, 5, 10, and 20 min after the run. A positive finding of EIA was defined as a 13% decrease from baseline FEV(1) or baseline forced expiratory volume in the first 0.5 s (FEV(0.5)). The actual duration of each run was age-related (mean [+/- SD] duration, 4.8 +/- 0.8 min). The nadir in indexes occurred after a mean time of 2.98 +/- 1.31 min. A positive EIA finding determined by FEV(1) was present in 15 children, and by FEV(0.5) in 34 children. Twenty-six children were from group A, but only 8 children were from group B. Wheezing and/or prolonged expiration were associated with a positive test result in 31 of 34 children. Coughing was frequent in children with both negative and positive ECT findings.CONCLUSION:The present study documents for the first time the presence of EIA in response to a free-run test in early childhood. Our findings suggest that a free-run test for the presence of EIA is suitable, but that the running duration is limited by age. The duration of airflow limitation after exercise is significantly earlier and shorter in young children with asthma compared with older children. FEV(0.5) is a better index than the traditional FEV(1) for describing positive ECT results in young children. The association of wheezing and/or prolonged expiration may help in defining EIA in early childhood in the absence of a spirometer.

ABSTRACT Respiratory tract infections are a leading cause of morbidity and mortality worldwide. Even with the advancement of diagnostic tools, the causative agent of 20 to 30% of upper respiratory tract infections go undiagnosed. Recently, a newly identified human respiratory virus, human metapneumovirus (hMPV), was discovered in young children in The Netherlands. To study the prevalence of hMPV infections in Israeli children, respiratory specimens from 388 hospitalized children less than 5 years of age were evaluated for the presence of hMPV RNA, which was present in 42 (10.8%) of these samples. All hMPV-positive samples were negative for respiratory syncytial virus (RSV), influenza viruses (Flu) A and B, adenovirus, and parainfluenza viruses 1, 2, and 3. Conversely, hMPV RNA was not detected in 76 RSV-positive and 38 Flu A- or B-positive samples. Most hMPV activity was between the months February and April. Sequence analysis of 20 positive samples revealed that both of the hMPV genotypes (groups 1 and 2) have circulated in central Israel during the study period. Moreover, three of the four known hMPV subgroups (1A, 1B, and 2B) were detected among the tested samples. Seroprevalence of hMPV in 204 patients from the central part of Israel revealed that 100% of the children are hMPV seropositive by the age of 5 years old. We conclude that hMPV is a common respiratory pathogen in Israel, while mixed infections of hMPV with RSV or Flu in hospitalized children are apparently rare.

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.

STUDY OBJECTIVES:To explore the role of respiratory interactive computer games in teaching spirometry to preschool children, and to examine whether the spirometry data achieved are compatible with acceptable criteria for adults and with published data for healthy preschool children, and whether spirometry at this age can assess airway obstruction. DESIGN:Feasibility study. SETTINGS:Community kindergartens around Israel and a tertiary pediatric pulmonary clinic. PARTICIPANTS:Healthy and asthmatic preschool children (age range, 2.0 to 6.5 years). INTERVENTION:Multi-target interactive spirometry games including three targets: full inspiration before expiration, instant forced expiration, and long expiration to residual volume. MEASUREMENTS AND RESULTS:One hundred nine healthy and 157 asthmatic children succeeded in performing adequate spirometry using a multi-target interactive spirometry game. American Thoracic Society (ATS)/European Respiratory Society spirometry criteria for adults for the start of the test, and repeatability were met. Expiration time increased with age (1.3 +/- 0.3 s at 3 years to 1.9 +/- 0.3 s at 6 years [+/- SD], p < 0.05). FVC and flow rates increased with age, while FEV1/FVC decreased. Healthy children had FVC and FEV1 values similar to those of previous preschool studies, but flows were significantly higher (> 1.5 SD for forced expiratory flow at 50% of vital capacity [FEF50] and forced expiratory flow at 75% of vital capacity [FEF75], p < 0.005). The descending part of the flow/volume curve was convex in 2.5- to 3.5-year-old patients, resembling that of infants, while in 5- to 6-year-old patients, there was linear decay. Asthma severity by Global Initiative for Asthma guidelines correlated with longer expiration time (1.7 +/- 0.4 s; p < 0.03) and lower FEF50 (32 to 63%; p < 0.001) compared to healthy children. Bronchodilators improved FEV1 by 10 to 13% and FEF50 by 38 to 56% of baseline. CONCLUSIONS:Interactive respiratory games can facilitate spirometry in very young children, yielding results that conform to most of the ATS criteria established for adults and published data for healthy preschool children. Spirometric indexes correlated with degree of asthma severity.

BACKGROUND:Along with the increased life expectancy in cystic fibrosis and the remarkable progress in its management and therapy, issues of female fertility and pregnancy are frequently raised. These include infertility, severity of lung disease, pancreatic insufficiency, poor nutritional status, glucose intolerance and diabetes, drug safety, and long-term maternal and neonatal outcome.OBJECTIVE:To describe the experience of our CF center in the management of CF pregnant woman from 1977 to 2004.METHODS:We analyzed 27 years of records (1977-2004) of the national CF registry of all CF women who wished to conceive and became pregnant.RESULTS:Eight CF women (mean age 24 +/- 4.5 years) who wished to conceive had 11 pregnancies and delivered 12 neonates. The pregestational results of forced expiratory volume per 1 second varied significantly among patients (59 +/- 23%), yet most (10/11) stayed stable throughout the pregnancy course. Maternal deterioration in CF condition occurred in only one mother, necessitating cesarean section. In 9 of the 11 pregnancies the women were pancreatic-insufficient. Of the 11 pregnancies, 2 CF women had diabetes mellitus and 3 developed gestational diabetes. One pregnancy occurred in a mother with a transplanted lung. Of the 12 neonates, 3 were preterm and one was born with esophageal atresia. No miscarriages, terminations or neonatal mortalities occurred. Although most of the CF mothers had FEV1 below 55% before pregnancy, the maternal and neonatal outcome was favorable and lung function tests generally remained stable.CONCLUSIONS:We conclude that pregnancy in CF is feasible with a positive maternal and neonatal outcome. Early participation of the CF physician in the wish of the CF woman to reproduce is required. The integration of an intensive multidisciplinary approach during pregnancy, which includes close follow-up of maternal and fetal condition by the various specialists, should ensure an optimal outcome.