The relation between age and time to maximal bronchoconstriction following exercise in children.

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 fall 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 (r2=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 schedule of post-exercise FEV(1) measurements should be cautiously trimmed.

Forced inspiratory flow volume curve in healthy young children.

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.

Flexible bronchoscopy and bronchoalveolar lavage in pediatric patients with lung disease.

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.

Hemoptysis in Israeli CF patients--prevalence, treatment, and clinical characteristics.

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.

The changing face of the exocrine pancreas in cystic fibrosis: the correlation between pancreatic status, pancreatitis and cystic fibrosis genotype.

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 CF 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 (DeltaF508, 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.

Exercise challenge test in 3- to 6-year-old asthmatic children.

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.

Improved survival following lung transplantation with long-term use of bilevel positive pressure ventilation in cystic fibrosis.

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.

Spirometry in early childhood in cystic fibrosis patients.

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.

The role of flexible fibreoptic bronchoscopy in evaluation of pulmonary diseases in children with congenital cardiac disease.

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.

Characterization of human metapneumovirus infections in Israel.

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.

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.

The role of computer games in measuring spirometry in healthy and "asthmatic" preschool children.

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.

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.

Pregnancies and outcome in women with cystic fibrosis.

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.

Long-term non-invasive positive pressure ventilation among cystic fibrosis patients awaiting lung transplantation.

BACKGROUND: Pulmonary disease is the most frequent cause of morbidity and mortality in cystc fibrosis patients. New techniques such as non-invasive positive pressure ventilation have resulted in prolongation of life expectancy in CF patients with end-stage lung disease. OBJECTIVES: To determine the role of NIPPV in CF patients awaiting lung transplantation. METHODS: Between 1996 and 2001 nine CF patients (5 females) with end-stage lung disease were treated with bi-level positive airway pressure ventilation in the "spontaneous" mode. RESULTS: The patients' mean age at initiation of BiPAP was 15 years (range 13-40 years) and the mean duration of BiPAP usage was 8 months (range 3-16 months). Four patients underwent successful lung transplantation, three patients died while awaiting transplantation, and the remaining two are still on NIPPV while waiting for transplantation. Patients' body mass index increased significantly (P < 0.05) during BiPAP therapy (from 16.1 to 17.2 kg/m2). Blood pH, PaCO2, and bicarbonate improved significantly (from 7.31 to 7.38, 90.8 to 67.2 mmHg, and 48.9 to 40.3 mEq/L, respectively). Pulmonary function tests were not affected by BiPAP usage. The patients experienced a significant alleviation in morning headaches and improvement in quality of sleep (P < 0.003). There were no major complications during BiPAP usage. CONCLUSIONS: We demonstrated that long-term NIPPV can stabilize and improve physiologic parameters such as ventilation, arterial blood gases and body mass index, as well as subjective symptoms such as sleep pattern, daily activity level, and morning headaches in CF patients with end-stage lung disease. Further prospectively controlled studies are needed to evaluate the potential of BiPAP therapy and its influence on morbidity and mortality in the post-lung transplantation period.

Tracheal epinephrine or norepinephrine preceded by beta blockade in a dog model. Can beta blockade bestow any benefits?

Tracheal epinephrine (adrenaline) has been associated with two major deletorious side effects: increased heart rate (HR) and an initial decrease of blood pressure (BP). This prospective randomized animal study compared the haemodynamic responses to tracheally administered epinephrine or norepinephrine (nor adrenaline) alone versus each after pretreatment with propranolol for ameliorating those two untoward effects associated with epinephrine administration. Five anaesthetized mongrel dogs underwent 25 experiments of tracheal epinephrine or norepinephrine (0.02 mg/kg diluted with normal saline to 5 ml total volume) with or without an I/V non-selective beta-blocker (propranolol 0.1 mg/kg) pretreatment, and served as their own controls. Tracheal epinephrine alone produced a rise in both diastolic and mean arterial BP and an increase of HR. Tracheal norepinephrine alone produced the largest increase of diastolic and mean BP but this change was associated with a significant tachycardia (from 37 to 72/m, P<0.001). While both epinephrine or norepinephrine after pretreatment with propranolol produced a significant increase in both diastolic (from 106 to 166 mmHg and from 118 to 169 mmHg, respectively) (P<0.01) and mean BP (from 122 to 183 mmHg and from 133 to 188 mmHg, respectively) (P<0.01), only propranolol-pretreated tracheal epinephrine yielded a significant decrease in HR (from 52 to 33/m, P=0.002). Pretreatment with a beta-blocker protected against the deleterious tachycardia associated with epinephrine or norepinephrine and, by doing so, may improve the myocardial oxygen supply-and-demand balance. At the same time, the pretreatment augmented the relatively mild diastolic BP increase associated with the beta-adrenergic effect of epinephrine.

Endobronchial adrenaline: should it be reconsidered? Dose response and haemodynamic effect in dogs.

BACKGROUND: Tracheal drug administration is a route for drug delivery during cardiopulmonary resuscitation when intravenous access is not immediately available. However, tracheal adrenaline (epinephrine) injection has been recently shown to be associated with detrimental decrease in blood pressure. This was attributed to exaggerated early beta2 mediated effects unopposed by alpha-adrenergic vasoconstriction. We hypothesized that endobronchial adrenaline administration is associated with better drug absorption, which may abolish the deleterious drop of blood pressure associated with tracheal drug administration. OBJECTIVE: To determine haemodynamic variables after endobronchial adrenaline administration in a non-arrest canine model. DESIGN: Prospective, randomized, laboratory study. METHODS: Adrenaline (0.02, 0.05, 0.1 mg/kg) diluted with normal saline was injected into the bronchial tree of five anaesthetized dogs. Injection of 10-ml saline served as control. Heart rate, blood pressure and arterial blood gases were monitored for 60 min after drug instillation. The protocol was repeated after 1 week. RESULTS: Adrenaline at a dose of 0.02 mg/kg produced only a minor initial decrease in diastolic (from 90 +/- 5 to 78 +/- 3 mmHg, P=0.05), and mean blood pressure (from 107 +/- 4 to 100 +/- 3 mmHg, P=0.05), in all dogs. This effect lasted less then 30 s following the drug administration. In contrast, higher adrenaline doses (0.05 and 0.1 mg/kg) produced an immediate increase in diastolic (from 90 +/- 5 to 120 +/- 7 mmHg; and from 90 +/- 5 to 170 +/- 6 mmHg, respectively), and mean blood pressure (from 107 +/- 4 to 155 +/- 10 mmHg; and from 107 +/- 4 to 219 +/- 6 mmHg, respectively). All adrenaline doses resulted in an immediate increase in systolic blood pressure and pulse. Endobronchial administration of saline (control) affected none of the haemodynamic variables. CONCLUSIONS: In a non-arrest model, endobronchial adrenaline administration, as opposed to the effect of tracheal adrenaline, produced only a minor decrease in diastolic and mean blood pressure. We suggest that endobronchial adrenaline administration should be investigated further in a CPR low-flow model when maintaining adequate diastolic pressure may be crucial for survival.

Liver cirrhosis and portal hypertension in cystic fibrosis.

OBJECTIVES: Liver disease is the second cause of death in cystic fibrosis. The most deleterious complication of liver disease is portal hypertension, which has an estimated prevalence of up to 8%. Portal hypertension may manifest itself by splenomegaly, hypersplenism, gastro-oesophageal bleeding and ascites. The aim of our study was to determine the prevalence, risk factors and invasive management of portal hypertension at our centre. METHODS: One hundred and fifty patients with cystic fibrosis were followed up between 1975 and 2000 in the national cystic fibrosis centre in Israel. Forty patients (27%) had liver disease. All underwent clinical evaluation and laboratory and imaging studies. RESULTS: Portal hypertension was diagnosed in 10 patients (7%), of whom eight were male. The mean age at diagnosis was 11 years (range, 4-17 years). All had severe mutations of the cystic fibrosis transmembrane conductance regulator gene (the CFTR gene), pancreatic insufficiency, meconium ileus or distal intestinal obstruction syndrome and variceal bleeding. Seven patients underwent sclerotherapy to control acute bleeding. Four underwent portosystemic shunting (functioning up to 37 years). Two patients with severe lung and liver disease underwent transjugular intrahepatic portosystemic shunting, which provided bleeding control, but both died while waiting for lung/liver transplantation. One patient underwent liver transplantation due to liver failure and still had good liver and lung function 10 years later. CONCLUSIONS: Portal hypertension is more common among Israeli patients with cystic fibrosis. The unique genetic composition of our population may explain this phenomenon. Risk factors include male gender, pancreatic insufficiency, severe CFTR mutations, meconium ileus and meconium ileus equivalent. Sclerotherapy is the main option to control oesophageal variceal bleeding, while portosystemic shunts offer a prolonged alternative treatment for refractory bleeding. A transjugular intrahepatic portosystemic shunt and liver transplantation may also be effective, but further research is required in order to establish their role.

Should vasopressin replace adrenaline for endotracheal drug administration?

OBJECTIVE: Arginine vasopressin was established recently as a drug of choice in the treatment of cardiac arrest and in retractable ventricular fibrillation; however, the hemodynamic effect of vasopressin following endotracheal drug administration has not been fully elucidated. We compared the effects of endotracheally administered vasopressin vs. adrenaline on hemodynamic variables in a canine model, and we investigated whether vasopressin produces the same deleterious immediate blood pressure decrease as did endotracheal adrenaline in the canine model. DESIGN: Prospective controlled study. SETTING: Animal laboratory in Tel-Aviv University, Israel. SUBJECTS: Five adult mongrel dogs weighing 6.5-20 kg. INTERVENTIONS: Dogs were anesthetized; each dog was intubated orally, and both femoral arteries were cannulated for the measurement of arterial pressure and for sampling blood gases. Each dog was studied four times, 1 wk apart, by using the same protocol for injection and anesthesia: endotracheal placebo (10 mL NaCl 0.9%,), endotracheal vasopressin (1 units/kg), endobronchial adrenaline (0.1 mg/kg), and endotracheal adrenaline (0.1 mg/kg). Following placebo, vasopressin, and adrenaline instillation, five forced manual ventilations were delivered with an Ambu bag. Each dog was its own control. MEASUREMENTS AND MAIN RESULTS: Following placebo or drug administration, heart electrocardiography and arterial pressures were continuously monitored with a polygraph recorder for 1 hr. Endotracheal vasopressin produced an immediate increase of diastolic blood pressure (from 83 +/- 10 mm Hg [baseline] to 110 +/- 5 mm Hg at 1 min postinjection). This response lasted >1 hr. In contrast, both endotracheal and endobronchial administration of adrenaline produced an early and significant (p <.05) decrease in diastolic and mean blood pressures. The diastolic blood pressure increase from 85 +/- 10 mm Hg to 110 +/- 10 mm Hg took an ill-afforded 55 secs following endotracheal adrenaline. Diastolic blood pressure was significantly (p <.05) higher following vasopressin compared with adrenaline administration in both routes. CONCLUSIONS: Vasopressin accomplishes its hemodynamic effect, particularly on diastolic blood pressure, more rapidly, vigorously, and protractedly and to a significant degree compared with both endotracheal and endobronchial adrenaline. Evaluation of the effects of endotracheal vasopressin in a closed chest cardiopulmonary resuscitation model is recommended.