Homozygous loss-of-function mutations in MNS1 cause laterality defects and likely male infertility.

The clinical spectrum of ciliopathies affecting motile cilia spans impaired mucociliary clearance in the respiratory system, laterality defects including heart malformations, infertility and hydrocephalus. Using linkage analysis and whole exome sequencing, we identified two recessive loss-of-function MNS1 mutations in five individuals from four consanguineous families: 1) a homozygous nonsense mutation p.Arg242* in four males with laterality defects and infertility and 2) a homozygous nonsense mutation p.Gln203* in one female with laterality defects and recurrent respiratory infections additionally carrying homozygous mutations in DNAH5. Consistent with the laterality defects observed in these individuals, we found Mns1 to be expressed in mouse embryonic ventral node. Immunofluorescence analysis further revealed that MNS1 localizes to the axonemes of respiratory cilia as well as sperm flagella in human. In-depth ultrastructural analyses confirmed a subtle outer dynein arm (ODA) defect in the axonemes of respiratory epithelial cells resembling findings reported in Mns1-deficient mice. Ultrastructural analyses in the female carrying combined mutations in MNS1 and DNAH5 indicated a role for MNS1 in the process of ODA docking (ODA-DC) in the distal respiratory axonemes. Furthermore, co-immunoprecipitation and yeast two hybrid analyses demonstrated that MNS1 dimerizes and interacts with the ODA docking complex component CCDC114. Overall, we demonstrate that MNS1 deficiency in humans causes laterality defects (situs inversus) and likely male infertility and that MNS1 plays a role in the ODA-DC assembly.

Energy drinks in children and adolescents: demographic data and immediate effects.

Energy drinks consumption has become increasingly common in the last few years, despite evidence associating these products with vast adverse health effects. This led us to explore the phenomenon of energy drinks consumption in adolescents in the Israeli Arab population of the Nazareth area (Northern Israel), examining their awareness of risks associated with consumption of energy drinks, investigating their immediate effects on the body. Our study revealed that the consumption of energy drinks is very common in adolescents of both sexes, though more common in boys. Of 375 students who filled out the questionnaire, 206 reported that they consumed energy drinks (55%), 91 were male (44.4%), and 115 were female (55.6%). In the experimental stage of this study, we found that energy drinks significantly increased systolic blood pressure in most participants within a brief period of time after drinking.Conclusion: Given the prevalence of energy drinks consumption and their side effects, it is important to increase awareness of the risks associated with their regular use and to combat this phenomenon through the education system in schools. What is Known: • Energy drinks consumption has become popular and frequent among adolescents across the world. • The immediate effects of energy drinks in children and adolescents are poorly described. What is New: • Religious and social norms are not a barrier to ED consumption among the varied investigated population. • Our study describes the immediate effect of energy drinks during the first 2 h after consumption, revealing systolic blood pressure to be significantly increased.

[RECURRENT WANDERING PNEUMONIA AS AN UNUSUAL PRESENTATION OF FOREIGN BODY ASPIRATION].

INTRODUCTION: In cases of recurrent pneumonia that involved both lungs, foreign body aspiration (FBA) requires a high index of suspicion. BACKGROUND: A previously healthy one-year old boy, was admitted to our department, because of right lower lobe pneumonia with a moderate amount of pleural effusion. He was treated with IV Cefuroxime resulting in a good clinical response. Three weeks later, he was referred again due to left lower lobe pneumonia with a mild amount of pleural effusion. Due to two episodes of pneumonia involving two different lungs within a five week period, a suspicion of an underlying immunodeficiency or other systemic disease was raised and a broad investigation revealed no underlying disease. Despite the lack of a history of FBA and the inappropriate clinical presentation (recurrent pneumonia not in the same side), FBA was still highly considered as a potential diagnosis, mainly due to the fact that these two episodes of pneumonia occurred within a short period of time. A flexible bronchoscopy was performed which revealed a FB lodged at the entrance of the left main bronchus, the FB was extracted by rigid bronchoscopy. Since then the child is asymptomatic with no further signs of pneumonia. CONCLUSIONS: FBA should be highly considered in recurrent pneumonia that involves two lungs especially when the episodes of pneumonia occur within a short period of time. DISCUSSION: In cases of recurrent pneumonia that involve both lungs, FBA requires a high index of suspicion. Our assumption in this unusual case was that the FB was stuck in the carina, tilting and obstructing the entry of the right main bronchus leading to right side pneumonia; and in the second episode, later on, tilting to the left side and obstruction to the left main bronchus resulting in left sided pneumonia.

Immunofluorescence Analysis and Diagnosis of Primary Ciliary Dyskinesia with Radial Spoke Defects.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder caused by several distinct defects in genes responsible for ciliary beating, leading to defective mucociliary clearance often associated with randomization of left/right body asymmetry. Individuals with PCD caused by defective radial spoke (RS) heads are difficult to diagnose owing to lack of gross ultrastructural defects and absence of situs inversus. Thus far, most mutations identified in human radial spoke genes (RSPH) are loss-of-function mutations, and missense variants have been rarely described. We studied the consequences of different RSPH9, RSPH4A, and RSPH1 mutations on the assembly of the RS complex to improve diagnostics in PCD. We report 21 individuals with PCD (16 families) with biallelic mutations in RSPH9, RSPH4A, and RSPH1, including seven novel mutations comprising missense variants, and performed high-resolution immunofluorescence analysis of human respiratory cilia. Missense variants are frequent genetic defects in PCD with RS defects. Absence of RSPH4A due to mutations in RSPH4A results in deficient axonemal assembly of the RS head components RSPH1 and RSPH9. RSPH1 mutant cilia, lacking RSPH1, fail to assemble RSPH9, whereas RSPH9 mutations result in axonemal absence of RSPH9, but do not affect the assembly of the other head proteins, RSPH1 and RSPH4A. Interestingly, our results were identical in individuals carrying loss-of-function mutations, missense variants, or one amino acid deletion. Immunofluorescence analysis can improve diagnosis of PCD in patients with loss-of-function mutations as well as missense variants. RSPH4A is the core protein of the RS head.

Foreign Body Aspiration in Children with Focus on the Role of Flexible Bronchoscopy: A 5 Year Experience.

BACKGROUND: Foreign body aspiration (FBA) is common in the pediatric population and if not diagnosed and treated properly can lead to major complications. OBJECTIVES: To define the clinical and radiological features of aspirated foreign bodies, characterize the incidence of FBA among the Israeli-Arab population, and evaluate flexible bronchoscopy as a diagnostic tool prior to performing rigid bronchoscopy. METHODS: We reviewed the e-files of 115 children who underwent bronchoscopy for suspected FBA between January 2006 and December 2010 in the pediatric department of the St. Vincent French Hospital, Nazareth. RESULTS: We identified 44 patients (38.3%) who had foreign body aspiration (mean age 31.2 ± 29 months, males 64%). Organic-type foreign body was seen in 70% of cases and location was equally distributed. Statistically significant correlations were found between the presence of a foreign body and a history of choking, abnormal lung auscultation, and abnormal chest X-ray (P < 0.05). The rate of negative finding in rigid bronchoscopy in our study was as low as 15% (in only 8 of 52 rigid bronchoscopies was the finding negative for FBA). Compared with other centers in our region where rigid bronchoscopy was performed without the preceding flexible procedure, we found that our protocol reduced the rate of negative rigid bronchoscopies. CONCLUSIONS: Introducing flexible bronchoscopy initially in FBA management reduced the rate of negative rigid bronchoscopies.

Physiological Impacts of Energy Drink Consumption: A Clinical Analysis in Adolescents.

Energy drink (ED) consumption among Israeli-Arab adolescents is widespread. This study aimed to investigate the acute glycemic and insulin effects of EDs in healthy adolescents. Seventy-one Israeli-Arab adolescents (56% girls, average age 16.04 ± 1.03 years) participated in a non-randomized, case-controlled, open-label study. Participants consumed ED (n = 36) or a volume- and carbohydrate-matched non-caffeinated soft drink (SD, n = 35), followed by a 2 h glucose tolerance test. Blood glucose was measured at baseline and 15, 30, 60, and 120 min post-consumption (T0, T15, T30, T60 and T120, respectively). Serum insulin concentration and caffeine relative intensity were determined 45 min post-consumption (T45). Blood glucose levels peaked significantly at T15 and remained significantly higher at T30 in the ED group compared to the SD group (p = 0.005, p = 0.017, respectively). Insulin concentrations were substantially higher at T45 in the ED group (t [64] = 2.794, p = 0.001). This pattern was especially prominent in heavy ED consumers. A positive correlation emerged between the amount of caffeine consumed (mg/kg), blood glucose levels at T15 and T30, and insulin concentration at T45. This study is the first to demonstrate the glycemic and insulin responses to ED consumption in adolescents, suggesting that regulatory measures limiting ED sales to adolescents could improve their health.

Relationship Between Helicobacter pylori IgG Seroprevalence and the Immune Response to Poliovirus Vaccine Among School-Age Children From a Population With Near-Universal Immunity Level.

OBJECTIVES: To examine the association between Helicobacter pylori seroprevalence and serum pepsinogens (PGs) as markers of gastric inflammation), with high neutralizing antibody titers to poliovirus type 1 and 3 vaccine strains among children age 3-4 years, subsequent to sub-clinical infection acquired during a wild-type poliovirus type 1 outbreak in Israel. METHODS: A serosurvey was conducted among 336 children aged 5-17 years who were vaccinated with both inactivated polio vaccine and oral polio vaccines. H. pylori serum IgG antibodies and PG concentrations were measured using ELISA. Neutralizing antibodies to poliovirus vaccine strains were measured and children with a titer ≥1:8 were considered immune. High-level immunity was defined as having a serum NA titer >1:2048. Propensity score inverse weighting was used to account for confounders. RESULTS: Neutralizing antibodies titers ≥1:8 to poliovirus type 1 and 3 vaccine strains were found in 99.4 and 98.2% of the children, respectively. An inverse association was found between H. pylori seropositivity accompanied by PGI:PGII ratio ≤6.5 (marker of gastric inflammation) and high-level immunity to poliovirus type 1: OR 0.39 (95% CI 0.68-0.91), p = 0.027. The association between H. pylori seropositivity of CagA virulent phenotype and polio high immunity was not significant. The association between H. pylori seropositivity and high neutralizing antibodies to type 3 poliovirus was of low magnitude and not significant. CONCLUSIONS: H. pylori seroprevalence accompanied by evidence of gastric inflammation was inversely correlated with high titers of neutralizing antibodies to poliovirus in children from a population with near universal polio immunity.

Associations of Helicobacter pylori seropositivity and gastric inflammation with pediatric asthma.

OBJECTIVE: Controversy exists regarding an association between Helicobacter pylori infection and asthma in children. We examined the hypotheses of inverse associations of H. pylori seroprevalence and pepsinogen (PG) levels, as markers of gastric inflammation, with asthma in children. METHODS: A hospital-based case-control study was conducted among children aged 4.8 to 17.3 years in Israel. Confirmed asthma cases (n = 75) were recruited through a pulmonary clinic, and controls (n = 160) without asthma were enrolled. Using enzyme-linked immunosorbent assays we measured the presence of H. pylori immunoglobulin G (IgG) antibodies, IgG antibodies to cytotoxin-associated gene A antigen (CagA) (virulent factor), serum PG levels and exposure to other enteric pathogens (Shigella flexneri). Multivariable logistic regression models were applied. RESULTS: H. pylori IgG seropositivity was 25% and 40% among cases and controls, respectively (P = .03). H. pylori CagA IgG seropositivity was associated with reduced risk of asthma (adjusted odds ratio [OR], 0.33 [95% CI, 0.11-0.95] but not for the CagA negative serology (adjusted OR, 0.70 [95% CI, 0.32-1.54]). Children who were H. pylori seropositive with a PGI:PGII of ≤6.78 (severe gastric inflammation) had a lower likelihood of asthma (adjusted OR, 0.31 [95% CI, 0.10-0.89]) than did seronegative children. Exposure to Shigella flexneri did not differ between cases and controls, nor according to H. pylori seropositivity. Among the asthmatic children, pulmonary function did not differ according to H. pylori seropositivity. CONCLUSIONS: H. pylori infection and its related gastric inflammation may have a protective role in the risk of pediatric asthma and further research into a potential causal pathway is required.

Computerized acoustic assessment of treatment efficacy of nebulized epinephrine and albuterol in RSV bronchiolitis.

AIM: We evaluated the use of computerized quantification of wheezing and crackles compared to a clinical score in assessing the effect of inhaled albuterol or inhaled epinephrine in infants with RSV bronchiolitis. METHODS: Computerized lung sounds analysis with quantification of wheezing and crackles and a clinical score were used during a double blind, randomized, controlled nebulized treatment pilot study. Infants were randomized to receive a single dose of 1 mgr nebulized l-epinephrine or 2.5 mgr nebulized albuterol. Computerized quantification of wheezing and crackles (PulmoTrack) and a clinical score were performed prior to, 10 minutes post and 30 minutes post treatment. Results were analyzed with Student's t-test for independent samples, Mann-Whitney U test and Wilcoxon test. RESULTS: 15 children received albuterol, 12 received epinephrine. The groups were identical at baseline. Satisfactory lung sounds recording and analysis was achieved in all subjects. There was no significant change in objective quantification of wheezes and crackles or in the total clinical scores either within the groups or between the groups. There was also no difference in oxygen saturation and respiratory distress. CONCLUSION: Computerized lung sound analysis is feasible in young infants with RSV bronchiolitis and provides a non-invasive, quantitative measure of wheezing and crackles in these infants.

Inhaled corticosteroids in transient tachypnea of the newborn: A randomized, placebo-controlled study.

OBJECTIVE: Prenatal corticosteroids were shown to reduce the respiratory complication in late preterm infants. Our objective was to determine if early inhaled corticosteroids could alleviate the respiratory distress and morbidity in late preterm and term neonates with transient tachypnea of the newborn (TTN). STUDY DESIGN: Double-blind, randomized placebo-controlled, multicenter pilot study. Infants born at >34 weeks gestational age with TTN at 4 h of age were randomized to two doses, 12 h apart, of inhaled Budesonide 1000 µg/dose or placebo within 6 h from delivery. Analysis was done by intention to treat. RESULTS: The study (n = 24) and control (n = 25) groups were comparable in birth characteristics (gestational age: 36.8 ± 1.9 vs 36.4 ± 1.8 weeks) and clinical condition at the time of recruitment (vital signs, clinical score, ventilation support, and blood gases). There was no difference between the study and control groups in clinical score (based on grunting, retractions, ala nasi, and respiratory rate) at recruitment and at 12, 24, and 48 h after the first inhalation (4.3 ± 1.6 vs 4.1 ± 2.1; 1.9 ± 1.8 vs 1.5 ± 1.7; 1.1 ± 1.4 vs 1.3 ± 1.6; 0.5 ± 0.8 vs 0.6 ± 1.0; respectively). Respiratory support at each time point, time to spontaneous unsupported breathing (67.4 ± 74.1 vs 75.2 ± 95.2 h), time to full feeds (86.7 ± 68.7 vs 84.3 ± 66.6 h) and length of stay (9.9 ± 5.5 vs 12.4 ± 8.0 days) did not differ between the groups. We did not detect any side effects. CONCLUSIONS: Our pilot study was unable to detect a beneficial effect of early administration of inhaled steroids on the clinical course of TTN in late preterm and term infants.

Impaired gastric myolectrical activity in patients with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is frequently associated with gastrointestinal complaints that can be due to gastrointestinal dysmotility. Electrogastrography (EGG) is an attractive, non-invasive procedure to assess gastric electric activity. The aims of our study were to investigate EGG abnormalities in pancreatic sufficient and pancreatic insufficient CF patients, and to examine whether EGG correlates with gastric emptying as assessed by scintigraphy. METHODS: EGG was performed in 23 CF patients (12 pancreatic sufficient patients, 11 pancreatic insuffficient) by using cutaneous recording pre- and postprandialy. Pre- and postpostprandial EGG indexes were compared to 19 healthy control patients. Gastric emptying was assessed simultaneously by gastric scintigraphy in 11 of the 23 CF patients. Six patients underwent a repeated scintigraphy recording following a month of treatment with cisapride. RESULTS: Abnormal patterns of EGG were found in 78.3% of CF patients compared to 31.3% of controls during fasting (p

A Case of Infective Endocarditis and Pulmonary Septic Emboli Caused by Lactococcus lactis.

Infective endocarditis is a rare condition in children with normal hearts. We present here a case of previously healthy eleven-year-old girl with infective endocarditis and pulmonary septic emboli caused by a very rare bacterial etiology (Lactococcus lactis). Identification of this pathogen was only made by polymerase chain reaction.

Primary ciliary dyskinesia in Israel: Prevalence, clinical features, current diagnosis and management practices.

BACKGROUND: Primary Ciliary Dyskinesia (PCD) is rare and its features in Israel have not been described. AIMS: to assess prevalence utilizing state-of-the-art diagnostic techniques, and describe clinical features, diagnostic and management practices in Israel. METHODS: A national multicenter study from 2012 to 2013 recruited patients diagnosed or suspected of having PCD. Diagnosis was verified using: nasal Nitric Oxide (nNO); High-speed Video Microscope Analysis (HVMA); Transmission Electron Microscopy (TEM) of cilia; Immuno-fluorescence staining (IF) for ciliary proteins, and genetic analysis. RESULTS: Of the 203 patients recruited from 14 pediatric centers, 150 had a PCD diagnosis verified. Median age was 15.05y, with range 0.15-60.5y. PCD prevalence was 1:54,000 for the general population and 1:25,000 in children (5-14 y). For the non-Jewish (mainly Druze and Arab Moslem) compared to Jewish populations, prevalence was 1:16,500 and 1:139,000 respectively (p < 0.0001) and parental consanguinity was 85.4% and 21.9% respectively (p < 0.0001). Clinical features included bronchiectasis (88%), rhinitis (81%), recurrent pneumonia (78%), recurrent otitis (62%), neonatal pneumonia (60%) and situs inversus (42%). Prior diagnostic practices varied widely between centers with TEM assessed in 55% and abnormal in 61% of these. Management included antibiotics and airway clearance. Diagnostic verification revealed for 150 PCD patients: 81% nNO<233 ppb, 62% abnormal HVMA, 51% diagnostic TEM, 58% diagnostic IF and, 57% genetic diagnosis. CONCLUSIONS: PCD in Israel is rare, with comprehensive diagnostic tests showing prevalence in children similar to Europe. Prevalence was higher in non-Jews, associated with parental consanguinity. Diagnostic and management practices vary. Referral centers providing comprehensive diagnostic and care capabilities should be established.

Methacholine bronchial provocation measured by spirometry versus wheeze detection in preschool children.

BACKGROUND: Determination of PC20-FEV1 during Methacholine bronchial provocation test (MCT) is considered to be impossible in preschool children, as it requires repetitive spirometry sets. The aim of this study was to assess the feasibility of determining PC20-FEV1 in preschool age children and compares the results to the wheeze detection (PCW) method. METHODS: 55 preschool children (ages 2.8-6.4 years) with recurrent respiratory symptoms were recruited. Baseline spirometry and MCT were performed according to ATS/ERS guidelines and the following parameters were determined at baseline and after each inhalation: spirometry-indices, lung auscultation at tidal breathing, oxygen saturation, respiratory and heart rate. Comparison between PCW and PC20-FEV1 and clinical parameters at these end-points was done by paired Student's t-tests. RESULTS AND DISCUSSION: Thirty-six of 55 children (65.4%) successfully performed spirometry-sets up to the point of PCW. PC20-FEV1 occurred at a mean concentration of 1.70+/-2.01 mg/ml while PCW occurred at a mean concentration of 4.37+/-3.40 mg/ml (p < 0.05). At PCW, all spirometry-parameters were markedly reduced: FVC by 41.3+/-16.4% (mean +/-SD); FEV1 by 44.7+/-14.5%; PEFR by 40.5+/-14.5 and FEF25-75 by 54.7+/-14.4% (P < 0.01 for all parameters). This reduction was accompanied by de-saturation, hyperpnoea, tachycardia and a response to bronchodilators. CONCLUSION: Determination of PC20-FEV1 by spirometry is feasible in many preschool children. PC20-FEV1 often appears at lower provocation dose than PCW. The lower dose may shorten the test and encourage participation. Significant decrease in spirometry indices at PCW suggests that PC20-FEV1 determination may be safer.

Adenosine bronchial provocation with computerized wheeze detection in young infants with prolonged cough: correlation with long-term follow-up.

BACKGROUND: Chronic cough in babies is often associated with bronchial hyperreactivity (BHR). The objective documentation of BHR in babies is difficult, and acoustic methods have been described (provocative concentration of a substance causing wheeze) for conducting bronchial provocation tests (BPTs). We conducted a study to evaluate automatic computerized wheeze detection (CWD) in determining BHR in young infants with prolonged cough, and its correlation with the subsequent development of wheezing. METHODS: Infants aged < 24 months with prolonged cough (ie, > 2 months) underwent acoustic BPTs with the response determined by CWD and auscultation by a physician. Telephone interviews with parents were conducted after 1 month and yearly for the next 3 years. RESULTS: A total of 28 infants who were 4 to 24 months old with prolonged cough were included in the study. Twenty of these infants (71.4%) had BHR as determined by a positive acoustic BPT result. In 11 of these 20 tests, the CWD occurred earlier, and in 9 tests it occurred at the same step as auscultation by a physician. Rhonchi or whistles often preceded wheezes. Seventeen of the 20 patients with BHR completed 3 years of follow-up. Of these, 14 had recurrent episodes of wheezing and shortness of breath, and 3 were well. Six of the eight adenosine-negative patients completed 3 years of follow-up and had no symptoms of BHR. CONCLUSIONS: Acoustic BPT is a technically feasible test for the detection of BHR in young infants. CWD provides an earlier detection of wheeze than stethoscope auscultation. In our group of infants, a positive acoustic BPT result had high correlation with symptoms compatible with BHR over the next 3 years.

Measurement of inspiratory flow in children with acute asthma.

Dry-powder inhalers (DPIs) have been proposed for treatment of acute asthma. Different DPIs vary in their inspiratory resistance and have different recommended optimal peak inspiratory flows (PIFs). Reduced PIF during acute asthma may result in inadequate drug delivery to the lungs. Our aim was to measure the inspiratory flow in relation to inspiratory resistance during acute asthma in children presenting to the emergency room. School-age (range, 6-18 years) children were referred to the emergency room for acute asthma. PIF measurements were performed by In-Check Dial trade mark device with simulated airflow resistances equivalent to Turbuhaler, Diskus, and free flow. Percent change in PIF between remission and acute asthma (%Delta) was correlated with percent change in clinical score (CS) and percent change in spirometry in children <9 and >9 years old. Thirty-three children (21 males) participated. PIF with simulated Turbuhaler resistance was significantly lower than with simulated Diskus resistance in both acute and remission states (P < 0.0001). PIF with simulated Turbuhaler resistance increased from 62.1 +/- 15.3 (acute) to 74.4 +/- 16.5 l/min (remission, P < 0.0001), while with Diskus it rose from 72.6 +/- 20.5 to 91.1 +/- 18.9 l/min (P < 0.0001). Turbuhaler %Delta PIF correlated with %Delta FEV(1) (P = 0.01) and with %Delta CS (P = 0.0001). A lesser degree of correlation was observed while using Diskus resistance and in children above 9 years old. During acute asthmatic attacks, PIF is reduced; this reduction is particularly prominent in young children who use a high-resistance device. However, the PIF generated is generally within the values considered compatible with adequate lung deposition with both Diskus and Turbuhaler.

Duplication in CHIT1 gene and the risk for Aspergillus lung disease in CF patients.

BACKGROUND: Aspergillus often persists in the respiratory tract of patients with Cystic Fibrosis (CF) and may cause allergic broncho-pulmonary aspergillosis (ABPA). Chitinases are enzymes that digest the chitin polymer. Plants use chitinase as a defense mechanism against fungi. Chitotriosidase (CHIT1) is the major chitinase in human airways. Variation in the coding region with 24-bp duplication allele results in reduced CHIT1 activity. Recently, CHIT1 duplication heterozygocity was found in 6/6 patients with severe asthma and fungal sensitization (SAFS). AIM: Our aim was to evaluate the link between CHIT1 duplication in CF patients and the predisposition to Allergic broncho-pulmonary mycosis (ABPM) or persistent Aspergillus positive sputum (APS). PATIENTS AND METHODS: CHIT1 duplication was assessed in three CF groups. Group 1: patients who had neither ABPM nor APS in the past (control group). Group 2: patients with persistent APS (≥2/year), without ABPA. Group 3: patients with current or past ABPM. RESULTS: Forty patients with CF were included in the analysis, CHIT1 duplication heterozygocity was found in 3/6 (50%) of the patients in the ABPM group, 3/12 (25%) in the APS group, and 7/22 (31.8%) in the control group (P > 0.05). Eleven patients carried W1282X mutation, 90.9% were negative for CHIT1 duplication, five of them were homozygous for W1282X; none of them had CHIT1 duplication or ABPM. CONCLUSIONS: CHIT1 duplication is not found in all CF patients with ABPM in contrast to patients with SAFS. These results suggest that CHIT1 duplication cannot be the sole explanation for Aspergillus positive sputum in CF patients.

Subcutaneous emphysema and pneumomediastinum due to foreign body aspiration in children with asthma.

Pneumomediastinum (PM) and subcutaneous emphysema (SCE) are well recognized as complications of acute asthma exacerbation in children with asthma. We present herein a report of three cases of asthmatic children who presented with PM and SCE found to be secondary to foreign body aspiration. The cases highlight that clinicians must remain vigilant for co-morbidities in an asthma exacerbation, and less common etiologies of PM and SCE, such as foreign body aspiration, should also be carefully considered in asthmatic children.

The potential use of spirometry during methacholine challenge test in young children with respiratory symptoms.

BACKGROUND: The concentration of methacholine that causes a fall of 20% from baseline forced expiratory volume in the first second (PC20-FEV1) in the methacholine challenge test (MCT) is not usually considered a diagnostic tool in preschool children since PC20-FEV1 may not be achievable <6 years of age. AIM: To assess the usefulness of various spirometry indices obtained during MCT in a large group of 3- to 6-year-old children with respect to their clinical diagnosis. METHODS: Standardized MCT (inhaled triple-concentration increments [0.057-13.925 mg] of methacholine solution) was performed by 84 children previously diagnosed with asthma (asthmatics) and 48 with prolonged cough (coughers). Spirometry was determined at baseline and between inhalations; PC20-FEV1 and PC25-FEV0.5 were calculated. RESULTS: PC20-FEV1 values were significantly less in the asthmatics than in the coughers (mean +/- SD was 3.21 +/- 4.32 vs. 22.35 +/- 3.66 ml/mg). Similarly, PC25-FEV0.5 was 1.48 +/- 3.08 in the asthmatics and 9.45 +/- 12.59 mg/ml/Mch in the coughers, P < 0.0001. A cut-off at 4.0 mg/ml for PC20-FEV1 had 77.4% sensitivity and 75.0% specificity, a cut-off at 2.2 mg/ml for PC25-FEV0.5 had 73.8% sensitivity and 72.9% specificity, for clinical diagnosis of asthma. PC25-FEV0.5 also showed a correlation with age. CONCLUSIONS: Our findings suggest that MCT can be performed in preschool children with various respiratory symptoms. PC25-FEV0.5 may be a better end-point parameter. Children with a clinical diagnosis of asthma respond to a lower MCT concentration than children with cough. Further studies are needed to determine airway responsiveness in healthy young children and to further assess the contribution of MCT to the clinical diagnosis in this age group.

The role of alpha-, beta-, and gamma-ENaC subunits in distal lung epithelial fluid absorption induced by pulmonary edema fluid.

Edema fluid (EF) increases epithelial Na(+) transport by rat fetal distal lung epithelia (FDLE) and induces net lung fluid absorption in fetal mouse lung explants [Rafii B, Gillie DJ, Sulowski C, Hannam V, Cheung T, Otulakowski G, Barker PM, O'Brodovich H. J Physiol (Lond) 544: 537-548, 2002]. We now show that EF increases fluid absorption across monolayers of rat FDLE in a dose-dependent manner. To study the role of subunits of the epithelial Na(+) channel (ENaC) in the phenomena, we cultured explants from the distal lungs of 16-day gestational age wild-type (WT) or alpha-, beta-, or gamma-ENaC knockout or heterozygote (HT) mice. WT explants cultured in media continuously expanded over time as a result of net fluid secretion. In contrast, when explants were exposed to EF for 24 h, net fluid absorption occurred. EF-exposed explants had normal histology, but marked changes were seen after Triton X-100 or staurosporine exposure. Transmission electron microscopy showed EF promoted lamellar body formation and abundant surfactant in the explants' lumens. EF-induced changes in explant size were similar in alpha-ENaC knockout, WT, and HT littermate fetal lung explants (P > 0.05). In contrast, EF's effect was attenuated in beta- and gamma-ENaC knockouts (P < 0.05) vs. WT and HT littermate fetal lung explants. EF exposure slightly decreased or had no effect on mRNA levels for alpha-ENaC in various mouse genotypes but decreased expression of beta- and gamma-ENaC subunit mRNAs (P < 0.01) across all genotype groups. We conclude that beta- and gamma-, but not alpha-, ENaC subunits are essential for EF to exert its maximal effect on net fluid absorption by distal lung epithelia.