Two siblings, a 14.5-year-old boy and his 11.5-year-old sister, with congenital nemaline myopathy... more Two siblings, a 14.5-year-old boy and his 11.5-year-old sister, with congenital nemaline myopathy presented with severe respiratory failure and, in the case of the older patient, with cor pulmonale and systemic hypertension. The children were treated initially by continuous mechanical ventilation, but after a few weeks they only required ventilation at night. At the start of treatment, both were found to have a decreased ventilatory response to CO2 which apparently improved during 4 to 5 years of follow-up treatment. It has not been possible to wean them from nocturnal mechanical ventilation, but during the daytime they attend school and function almost normally. It is postulated that respiratory failure in nemaline myopathy may not be related to the severity of the muscle weakness but may result from a disturbance of the feedback required for normal control of breathing.
During exercise, less additional CO2 is stored per kilogram body weight in children than in adult... more During exercise, less additional CO2 is stored per kilogram body weight in children than in adults, suggesting that children have a smaller capacity to store metabolically produced CO2. To examine this, tracer doses of [13C]bicarbonate were administered orally to 10 children (8-12 yr) and 12 adults (25-40 yr) at rest. Washout of 13CO2 in breath was analyzed to estimate recovery of tracer, mean residence time (MRT), and size of CO2 stores. CO2 production (VCO2) was also measured breath by breath using gas exchange techniques. Recovery did not differ significantly between children [73 +/- 13% (SD)] and adults (71 +/- 9%). MRT was shorter in children (42 +/- 7 min) compared with adults (66 +/- 15 min, P less than 0.001). VCO2 per kilogram was higher in the children (5.4 +/- 0.9 ml.min-1.kg-1) compared with adults (3.1 +/- 0.5, P less than 0.0001). Tracer estimate of CO2 production was correlated to VCO2 (r = 0.86, P less than 0.0001) and when corrected for mean recovery accurately pred...
The results of 92 bronchoscopic examinations and 18 bronchograms in infants and children performe... more The results of 92 bronchoscopic examinations and 18 bronchograms in infants and children performed during a two-year period were reviewed. Of 62 patients with suspected foreign-body aspiration, the diagnosis was confirmed in 36 (58%); of 18 patients mainly suspected of having congenital anomalies, a positive diagnosis was made in 12 (66%); but of nine patients with lobar atelectasis only two had abnormal findings. In three patients a transbronchial biopsy specimen did not provide diagnostic material. Bronchography for suspected localized bronchiectasis was performed in 11 patients and a positive diagnosis was made in seven. In all seven patients suspected of having congenital anomalies, bronchography provided a definitive diagnosis. There was no mortality and morbidity was minimal but three patients died of their primary disease. Nearly 60% of the investigations yielded abnormal results, but many of the normal findings were of equal clinical value.
Bronchial reactivity to inhaled methacholine was measured by the steady-state tidal breathing met... more Bronchial reactivity to inhaled methacholine was measured by the steady-state tidal breathing method in asthmatic children aged 1 to 17 yr. The children were divided into three clinical groups according to their minimal therapeutic requirements: mild asthma, children requiring infrequent treatment with inhaled beta-agonists (81 patients); moderate asthma, children requiring daily preventive treatment with either cromolyn sodium or slow-release theophylline (67 patients); and severe asthma, children requiring daily preventive treatment with oral or inhaled steroids (34 patients). They were also divided into three age groups: from 1 to 6 yr, tested by using bronchial provocation with tracheal auscultation (BPTA) to determine the methacholine concentration causing wheezing (PCW); and from 7 to 11 yr and 12 to 17 yr, using lung function testing to determine the concentration causing a 20% fall in FEV1 (PC20). For the whole group the mean level of bronchial reactivity to methacholine correlated inversely with the severity of bronchial asthma according to the minimal drug requirements (p less than 0.0001) and was similar over the whole age range (p less than 0.9965) for each severity grouping. In the older children the difference between moderate and severe asthma was not significant, but this may have been a result of the effect of corticosteroids in the severe group. We concluded that age has no significant effect on the methacholine response in asthmatic children over a wide age range.
This review considers whether there is a role for lung function tests in the clinical management ... more This review considers whether there is a role for lung function tests in the clinical management of infants with lung disease. The purpose of testing lung function in older subjects, the tests available for infants, and the practical problems of testing lung function in infants are considered. After reviewing all the facts, we suggest that there are four situations in which lung function testing should be recommended for infants, as follows: 1) the infant who presents with unexplained tachypnea, hypoxia, cough, or respiratory distress in whom a definitive diagnosis is not apparent from physical examination and other, less difficult investigations; 2) the infant with severe, continuous, chronic obstructive lung disease who does not respond to an adequate clinical trial of combined corticosteroid and bronchodilator therapy; 3) the infant with known respiratory disease of uncertain severity in whom there is need to justify management decisions; and 4) research and development. A review...
Aspiration into the airways is one of the major causes of lung disease in infants and young child... more Aspiration into the airways is one of the major causes of lung disease in infants and young children. Unfortunately, the diagnosis of aspiration is often delayed due to unawareness and low sensitivity and specificity of existing diagnostic tests. We tested the efficacy of a new method, using a mixture of corn flour in milk instilled into the trachea, to diagnose aspiration in a hamster model. Forty‐five female hamsters were used for the experiments. Twenty hamsters underwent tracheal instillation of 0.1 ml of a mixture of 7.5% corn flour (containing starch granules with a diameter of 2–30 μm) in milk. Twenty control animals underwent tracheal instillation of saline. Five hamsters served as naive controls. Five animals from the corn flour and saline groups underwent bronchoalveolar lavage on days 1, 3, 7, and 14 after tracheal instillation. Starch granules were identified under light microscopy, using both iodine and Diff‐Quik staining in all the corn flour‐instilled animals and duri...
Flexible fiberoptic (FO) bronchoscopy can now be undertaken readily in children using topical ane... more Flexible fiberoptic (FO) bronchoscopy can now be undertaken readily in children using topical anesthesia and light sedation and has largely supplanted rigid open tube (OT) bronchoscopy for diagnostic purposes. The present study examined the contribution of the FO bronchoscope to clinical management in children presenting with specific types of problems. We examined the first 200 consecutive flexible bronchoscopies performed in 1995 in children under 18 years of age (median age, 2.27 years). Indications for bronchoscopy were noisy breathing (26.5%), recurrent pneumonia (21.0%), suspected pneumonia in an immunocompromised patient (10.5%), atelectasis or bronchial toilet (12.5%), possible foreign body aspiration (13.0%), and miscellaneous other reasons (16.5%). Inspection of the airway was abnormal in 67.0% of all investigations and made a clinically meaningful contribution to management in 67.5%, especially in those with noisy breathing (98.1%), possible foreign body aspiration (100%), and atelectasis (76.0%). Bronchoalveolar lavage (BAL) cytology was abnormal in 80.4% of the 107 lavages, but contributed little to management except in those with recurrent pneumonia (73.8%). Bacteria were isolated in 26.6% of the 109 specimens cultured, but this finding rarely affected management. Fungi were isolated in 47.4% of the 19 lavages in the immunocomprised group. Together, inspection, BAL and microbiology contributed to management in a mean of 90.5% (range, 76.2-100%) of patients in the various groups. We concluded that a high yield of clinically meaningful information can be expected from FO bronchoscopy in children when coupled with BAL and microbiological studies of lavage fluid.
To test the hypothesis that obese children are unfit (i.e., have abnormal responses to exercise t... more To test the hypothesis that obese children are unfit (i.e., have abnormal responses to exercise testing consistent with reduced levels of habitual physical activity), we used new analytic strategies in studies of 18 obese children performing cycle ergometry. The subjects' weight (mean +_ SD) was 168 _+ 24% that predicted by height, and the age range was 9 to 17 years. Size-independent measures of exercise (e.g., the ratio of oxygen uptake [Vo2] to work rate during progressive exercise and the temporal response of Vo2, carbon dioxide output [Vco=], and minute ventilation (~/E) at the onset of exercise) were used. The ability to perform external mechanical work was corrected for Vo2 at unloaded pedaling (change in maximum oxygen uptake [AVo2max] and in anaerobic threshold [AAT]. On average, obese children's responses were in the normal range: AVo2max, 104 _+ 41% (_+SD) predicted (by age); AAT, 85 _+ 51%, ratio of change in VE to change in Vco2, 111 _+ 21% and ratio of change in Vo2 to change in work rate, 100 +_ 24%, but six of the obese children had values of ~Vo2max or AAT that were more than 2 SD below normal. In addition, obese children did not have increased AVo2max or AAT with age as observed in nonobese children. Although the response time of Vo2 was normal (99 _+ 32% of predicted), those for both Vco2 and VE were prolonged. We conclude that the finding of obesity in a child is not a reliable indicator of poor fitness but that testing cardiorespiratory responses to exercise can be used to identify subjects with serious impairment and to individualize therapy.
Incubation of 5α-androstane-3α, 17β-diol with ovai’ian homogenate of immature rats treated with g... more Incubation of 5α-androstane-3α, 17β-diol with ovai’ian homogenate of immature rats treated with gonadotrophins exhibiting FSH-like activity resulted in the formation of 5α-androstane-3β,17β-diol. This epimerization reaction is reversible and needs the presence of NAD+ as cofactor. The reaction is catalyzed by an epimerization system that is inducible specifically by FSH. The reaction is optimal at pH 8.0, and at a temperature of 40 C. This epimerization system could not be detected in homogenates of hypophysis, hypothalamus, uterus and liver of normal or gonadotrophinstimulated rats, or in ovaries of nontreated rats. The mechanism of the epimerization is considered to be an oxidoreduction, with the production of 5α-androstan-17β-ol-3-one as an intermediate. The physiological importance of the induction of this enzyme system by FSH for the mechanism of the onset of puberty in the female rat is discussed. (Endocrinology 89: 347, 1971)
Background: In patients with COPD, oxygen therapy has been shown to improve exercise capacity and... more Background: In patients with COPD, oxygen therapy has been shown to improve exercise capacity and survival. Increase in barometric pressure at low altitude can serve as a simple way to improve arterial oxygenation in hypoxemic patients. We have tried to evaluate the elffect of staying at low altitude on arterial oxygenation and exercise performance in patients with COPD. Patients and method: Eleven patients with COPD (9 male, 2 female) aged 38 to 79 years (mean FEVl9 0.96 L; 36% predicted) with hypoxemia (mean Pa02, 54.2±8.9 mm Hg) at Jerusalem (altitude 800 m above sea level) were taken down to the Dead Sea area (altitude 402 m below sea level) for 3 weeks. At both locations we tested arterial blood gases, spirometry, progressive exercise, 6-minute walking distance, and sleep oximetry. The study was repeated 2 weeKs after returning to Jerusalem. Results: Spirometry results were unchanged. Mean arterial Pa02 rose from 54.2±8.9 mm Hg to 69.5±11 at the first week and to 66.6±11 at the third week of stay (p<0.001). PaC02 rose from 43.5±9.8 mm Hg to 47.7±9 and 49.5±8.4 (p<0.006). Six-minute walking distance rose from 337±107 m to 449±73 and 507±91 in the third week (p<0.005). Maximum oxygen consumption (Vo2max) rose from 901±257 mL/min to 1,099±255 and 1,063±250 mL/min (p=0.01). Sleep oximetry showed an increase in mean sleep arterial oxygen saturation from 86.0±4.3% to 89.9±4.2% and 88.3±3.0 at 1 and 3 weeks, respectively (p<0.05). Following the return to Jerusalem, arterial gases returned to their baseline levels (Pa02, 52.9±9.4 mm Hg) but 6-min walking distance remained significantly high, 453±47 (p<0.02), and Vo2max remained high as well (1,102±357 mL/min), although it did not reach statistical significance. Conclusions: Decline to low altitude or staying at high oxygen environment improves arterial oxygenation and exercise capacity in hypoxemic patients residing in moderate or high altitude. Low altitude (or pressurized wards) can improve pulmonary rehabilitation of hypoxemic patients
Beclomethasone dipropionate (BDP) and budesonide (BUD) were each given in a dose of 200 [tg twice... more Beclomethasone dipropionate (BDP) and budesonide (BUD) were each given in a dose of 200 [tg twice daily by metered dose inhaler to 10 asthmatic children already dependent on treatment with steroids. In a double blind randomised crossover study each course lasted one month. No clinically important differences were found between the two treatments when symptom scores, symptom free days, additional use of salbutamol, and results of lung function tests were considered. Metyrapone mildly reduced the plasma concentration of 11-deoxycortisol in two patients during treatment with budesonide, and in four during treatment with beclomethasone. It is concluded that although they are usually safe, both drugs may cause mild adrenal suppression when given in a dose of 200 [tg twice daily.
Among the simpler methods for measuring bronchial reactivity, the steady-state tidal breathing te... more Among the simpler methods for measuring bronchial reactivity, the steady-state tidal breathing technique using histamine or methacholine has proved very practicaM '2 However, this method needs full patient cooperation in
A randomized controlled study was done to determine whether the addition of heparin (1 U/mL) to p... more A randomized controlled study was done to determine whether the addition of heparin (1 U/mL) to peripheral intravenous alimentation solutions would affect the incidence of phlebitis and duration of patency of intravenous catheters in premature infants. Twenty-two-gauge Teflon catheters were uniformly used. One hundred five catheters infused with heparin were placed in 13 infants, and 122 catheters were placed in the control group of 13 infants. The time, nature, and incidence of complications were noted for each infusion site. Infusion of heparin was found to double the duration of patency of intravenous catheters and to reduce significantly the incidence of phlebitis. No complications related to the administration of heparin were noted. Heparinization of intravenous alimentation solutions should therefore be considered in premature infants as a means of reducing the work load and incidence of complications associated with peripheral lines.
<b><i>Background:</i></b> The prevalence of asthma has increased in weste... more <b><i>Background:</i></b> The prevalence of asthma has increased in western countries towards the end of the last century, but recently seems to have stabilized. <b><i>Objective:</i></b> To evaluate trends in the prevalence and severity of asthma that occurred in Israel over the past decade. <b><i>Methods:</i></b> The medical records of 17-year-old boys, eligible for national service, between 1999 and 2008 were reviewed. National annual hospitalization and death rates for asthma were extracted. <b><i>Results:</i></b> Three hundred thousand medical records were reviewed. During the study period, lifetime asthma prevalence decreased from 9.7 to 8.1% (p = 0.002). The point prevalence of moderate-to-severe and mild persistent asthma decreased significantly from 0.88 and 3.41% to 0.36 and 2.44%, respectively, during this period. The prevalence of intermittent asthma and asthma in clinical remission for more than 3 years did not change significantly. The annual hospitalization rate for asthma decreased from 13.0 to 7.5 per 10,000 population (p &lt; 0.0001), whilst the annual death rate due to asthma decreased between 1999 and 2008 from 2.1 to 1.4 per 100,000 population (p = 0.003). <b><i>Conclusions:</i></b> The prevalence of asthma in Israeli teenage boys decreased significantly over the last decade. In addition, asthma hospitalization and asthma-related death rates in the total population also decreased.
Pediatric Allergy, Immunology, and Pulmonology, 2019
Background: To investigate the predictive factors associated with positive adenosine monophosphat... more Background: To investigate the predictive factors associated with positive adenosine monophosphate challenge using the auscultation method (AMP-PCW) test results. Methods: This is a prospective study of young children with suspected asthma who underwent AMP-PCW test. Patients with a positive AMP-PCW test were compared with those with a negative AMP-PCW. A multivariate logistic regression model was performed to identify the independent determinants of positive AMP-PCW. Results: A total of 159 patients completed the AMP-PCW test. The median age was 53 months. In total, 54.0% of patients had a positive AMP-PCW. The prevalence of atopic dermatitis and family history of asthma and allergy were significantly higher among the positive AMP-PCW group (P = 0.04, P = 0.02, and P = 0.007, respectively), as were the prevalences of elevated immunoglobulin E (IgE), peripheral blood eosinophils percentage (P = 0.003, P < 0.001, respectively), and number of emergency department (ED) visits/hospitalizations before AMP-PCW test (P = 0.006). A significant inverse correlation exists between peripheral blood eosinophils percentage and serum IgE levels with the AMP end-point concentrations (r =-0.302, P = 0.001, and r =-0.312, P = 0.001, respectively). In multivariate logistic regression model, peripheral blood eosinophils percentage, IgE levels, and the number of ED visits/hospitalizations before the AMP-PCW test were found as independent predictors for positive AMP-PCW test result. Conclusions: Our results suggest that bronchial responsiveness to AMP-PCW is related to proxy markers of airway inflammation (elevated eosinophils and IgE levels) and clinical exacerbation of asthma before the test. This may support the role of AMP-PCW in detecting inflammatory changes and monitoring their trend among young children with suspected asthma.
Aim: Our aim was to evaluate the correlation of Adenosine monophosphate challenge test (AMP-PCW) ... more Aim: Our aim was to evaluate the correlation of Adenosine monophosphate challenge test (AMP-PCW) results with the patients' subsequent clinical course. Methods: We performed a 6-year retrospective cohort study of young children with suspected asthma who underwent AMP-PCW test. Results: Fifty four children were included in the study (median age, 50.5 months; range, 26-90). AMP-PCW was positive in 35 (65%) children. During the 3-year follow-up period, among 22 of 35 patients in the positive AMP-PCW group and among 17 of 19 in the negative AMP-PCW group-prophylactic therapy was not changed. Prophylactic therapy was initiated or its dose was escalated in 12 of 13 (92.3%) of the children with a positive AMP-PCW test compared to none of the children with a negative challenge test (P < 0.001). Prophylactic therapy was discontinued in only one (7.6%) of the children with a positive test as compared to two (100%) of the children with a negative test (P < 0.001). There were significantly fewer severe asthma exacerbations during a 3-year follow-up period after the challenge test as compared to the preceding 3-year period both in children with a positive (from 34 to 9 total events, P = 0.01) or a negative challenge test (from 16 to 0 events P = 0.01). The severity of airway hyper responsiveness was found to associate with the number of severe asthma exacerbations (P = 0.04) and with a diagnosis of asthma during the following 3 years (P = 0.02). Conclusions: AMP-PCW test results correlates with the subsequent clinical course of young children with suspected asthma performing the test.
During breathing under sedation via a two-way valve, airflow (V), volume (delta V), and airway pr... more During breathing under sedation via a two-way valve, airflow (V), volume (delta V), and airway pressure (P) were recorded in eight normal (N) infants, seven with reversible obstructive airway disease (ROAD), and seven with chronic lung disease (CLD). Intermittently, expiratory volume clamping (EVC) was applied, involving selective occlusion of the expiratory valve for three to five breaths. The latter produced cumulative increases in delta V that, due to progressive recruitment of the Hering-Breuer reflex, were accompanied by increasing expiratory plateaus in P (i.e., apneas). The resultant passive inflation delta V-P relationships were closely approximated by the expression: delta V = aP2 + bP + c, wherein a represented the pressure-related changes in chord compliance (Crs), b the Crs at P = 0, and c the difference between the dynamic end-expiratory and relaxation volumes of the respiratory system. Relative to N, the ROAD and CLD infants had significantly reduced weight-specific va...
Two siblings, a 14.5-year-old boy and his 11.5-year-old sister, with congenital nemaline myopathy... more Two siblings, a 14.5-year-old boy and his 11.5-year-old sister, with congenital nemaline myopathy presented with severe respiratory failure and, in the case of the older patient, with cor pulmonale and systemic hypertension. The children were treated initially by continuous mechanical ventilation, but after a few weeks they only required ventilation at night. At the start of treatment, both were found to have a decreased ventilatory response to CO2 which apparently improved during 4 to 5 years of follow-up treatment. It has not been possible to wean them from nocturnal mechanical ventilation, but during the daytime they attend school and function almost normally. It is postulated that respiratory failure in nemaline myopathy may not be related to the severity of the muscle weakness but may result from a disturbance of the feedback required for normal control of breathing.
During exercise, less additional CO2 is stored per kilogram body weight in children than in adult... more During exercise, less additional CO2 is stored per kilogram body weight in children than in adults, suggesting that children have a smaller capacity to store metabolically produced CO2. To examine this, tracer doses of [13C]bicarbonate were administered orally to 10 children (8-12 yr) and 12 adults (25-40 yr) at rest. Washout of 13CO2 in breath was analyzed to estimate recovery of tracer, mean residence time (MRT), and size of CO2 stores. CO2 production (VCO2) was also measured breath by breath using gas exchange techniques. Recovery did not differ significantly between children [73 +/- 13% (SD)] and adults (71 +/- 9%). MRT was shorter in children (42 +/- 7 min) compared with adults (66 +/- 15 min, P less than 0.001). VCO2 per kilogram was higher in the children (5.4 +/- 0.9 ml.min-1.kg-1) compared with adults (3.1 +/- 0.5, P less than 0.0001). Tracer estimate of CO2 production was correlated to VCO2 (r = 0.86, P less than 0.0001) and when corrected for mean recovery accurately pred...
The results of 92 bronchoscopic examinations and 18 bronchograms in infants and children performe... more The results of 92 bronchoscopic examinations and 18 bronchograms in infants and children performed during a two-year period were reviewed. Of 62 patients with suspected foreign-body aspiration, the diagnosis was confirmed in 36 (58%); of 18 patients mainly suspected of having congenital anomalies, a positive diagnosis was made in 12 (66%); but of nine patients with lobar atelectasis only two had abnormal findings. In three patients a transbronchial biopsy specimen did not provide diagnostic material. Bronchography for suspected localized bronchiectasis was performed in 11 patients and a positive diagnosis was made in seven. In all seven patients suspected of having congenital anomalies, bronchography provided a definitive diagnosis. There was no mortality and morbidity was minimal but three patients died of their primary disease. Nearly 60% of the investigations yielded abnormal results, but many of the normal findings were of equal clinical value.
Bronchial reactivity to inhaled methacholine was measured by the steady-state tidal breathing met... more Bronchial reactivity to inhaled methacholine was measured by the steady-state tidal breathing method in asthmatic children aged 1 to 17 yr. The children were divided into three clinical groups according to their minimal therapeutic requirements: mild asthma, children requiring infrequent treatment with inhaled beta-agonists (81 patients); moderate asthma, children requiring daily preventive treatment with either cromolyn sodium or slow-release theophylline (67 patients); and severe asthma, children requiring daily preventive treatment with oral or inhaled steroids (34 patients). They were also divided into three age groups: from 1 to 6 yr, tested by using bronchial provocation with tracheal auscultation (BPTA) to determine the methacholine concentration causing wheezing (PCW); and from 7 to 11 yr and 12 to 17 yr, using lung function testing to determine the concentration causing a 20% fall in FEV1 (PC20). For the whole group the mean level of bronchial reactivity to methacholine correlated inversely with the severity of bronchial asthma according to the minimal drug requirements (p less than 0.0001) and was similar over the whole age range (p less than 0.9965) for each severity grouping. In the older children the difference between moderate and severe asthma was not significant, but this may have been a result of the effect of corticosteroids in the severe group. We concluded that age has no significant effect on the methacholine response in asthmatic children over a wide age range.
This review considers whether there is a role for lung function tests in the clinical management ... more This review considers whether there is a role for lung function tests in the clinical management of infants with lung disease. The purpose of testing lung function in older subjects, the tests available for infants, and the practical problems of testing lung function in infants are considered. After reviewing all the facts, we suggest that there are four situations in which lung function testing should be recommended for infants, as follows: 1) the infant who presents with unexplained tachypnea, hypoxia, cough, or respiratory distress in whom a definitive diagnosis is not apparent from physical examination and other, less difficult investigations; 2) the infant with severe, continuous, chronic obstructive lung disease who does not respond to an adequate clinical trial of combined corticosteroid and bronchodilator therapy; 3) the infant with known respiratory disease of uncertain severity in whom there is need to justify management decisions; and 4) research and development. A review...
Aspiration into the airways is one of the major causes of lung disease in infants and young child... more Aspiration into the airways is one of the major causes of lung disease in infants and young children. Unfortunately, the diagnosis of aspiration is often delayed due to unawareness and low sensitivity and specificity of existing diagnostic tests. We tested the efficacy of a new method, using a mixture of corn flour in milk instilled into the trachea, to diagnose aspiration in a hamster model. Forty‐five female hamsters were used for the experiments. Twenty hamsters underwent tracheal instillation of 0.1 ml of a mixture of 7.5% corn flour (containing starch granules with a diameter of 2–30 μm) in milk. Twenty control animals underwent tracheal instillation of saline. Five hamsters served as naive controls. Five animals from the corn flour and saline groups underwent bronchoalveolar lavage on days 1, 3, 7, and 14 after tracheal instillation. Starch granules were identified under light microscopy, using both iodine and Diff‐Quik staining in all the corn flour‐instilled animals and duri...
Flexible fiberoptic (FO) bronchoscopy can now be undertaken readily in children using topical ane... more Flexible fiberoptic (FO) bronchoscopy can now be undertaken readily in children using topical anesthesia and light sedation and has largely supplanted rigid open tube (OT) bronchoscopy for diagnostic purposes. The present study examined the contribution of the FO bronchoscope to clinical management in children presenting with specific types of problems. We examined the first 200 consecutive flexible bronchoscopies performed in 1995 in children under 18 years of age (median age, 2.27 years). Indications for bronchoscopy were noisy breathing (26.5%), recurrent pneumonia (21.0%), suspected pneumonia in an immunocompromised patient (10.5%), atelectasis or bronchial toilet (12.5%), possible foreign body aspiration (13.0%), and miscellaneous other reasons (16.5%). Inspection of the airway was abnormal in 67.0% of all investigations and made a clinically meaningful contribution to management in 67.5%, especially in those with noisy breathing (98.1%), possible foreign body aspiration (100%), and atelectasis (76.0%). Bronchoalveolar lavage (BAL) cytology was abnormal in 80.4% of the 107 lavages, but contributed little to management except in those with recurrent pneumonia (73.8%). Bacteria were isolated in 26.6% of the 109 specimens cultured, but this finding rarely affected management. Fungi were isolated in 47.4% of the 19 lavages in the immunocomprised group. Together, inspection, BAL and microbiology contributed to management in a mean of 90.5% (range, 76.2-100%) of patients in the various groups. We concluded that a high yield of clinically meaningful information can be expected from FO bronchoscopy in children when coupled with BAL and microbiological studies of lavage fluid.
To test the hypothesis that obese children are unfit (i.e., have abnormal responses to exercise t... more To test the hypothesis that obese children are unfit (i.e., have abnormal responses to exercise testing consistent with reduced levels of habitual physical activity), we used new analytic strategies in studies of 18 obese children performing cycle ergometry. The subjects' weight (mean +_ SD) was 168 _+ 24% that predicted by height, and the age range was 9 to 17 years. Size-independent measures of exercise (e.g., the ratio of oxygen uptake [Vo2] to work rate during progressive exercise and the temporal response of Vo2, carbon dioxide output [Vco=], and minute ventilation (~/E) at the onset of exercise) were used. The ability to perform external mechanical work was corrected for Vo2 at unloaded pedaling (change in maximum oxygen uptake [AVo2max] and in anaerobic threshold [AAT]. On average, obese children's responses were in the normal range: AVo2max, 104 _+ 41% (_+SD) predicted (by age); AAT, 85 _+ 51%, ratio of change in VE to change in Vco2, 111 _+ 21% and ratio of change in Vo2 to change in work rate, 100 +_ 24%, but six of the obese children had values of ~Vo2max or AAT that were more than 2 SD below normal. In addition, obese children did not have increased AVo2max or AAT with age as observed in nonobese children. Although the response time of Vo2 was normal (99 _+ 32% of predicted), those for both Vco2 and VE were prolonged. We conclude that the finding of obesity in a child is not a reliable indicator of poor fitness but that testing cardiorespiratory responses to exercise can be used to identify subjects with serious impairment and to individualize therapy.
Incubation of 5α-androstane-3α, 17β-diol with ovai’ian homogenate of immature rats treated with g... more Incubation of 5α-androstane-3α, 17β-diol with ovai’ian homogenate of immature rats treated with gonadotrophins exhibiting FSH-like activity resulted in the formation of 5α-androstane-3β,17β-diol. This epimerization reaction is reversible and needs the presence of NAD+ as cofactor. The reaction is catalyzed by an epimerization system that is inducible specifically by FSH. The reaction is optimal at pH 8.0, and at a temperature of 40 C. This epimerization system could not be detected in homogenates of hypophysis, hypothalamus, uterus and liver of normal or gonadotrophinstimulated rats, or in ovaries of nontreated rats. The mechanism of the epimerization is considered to be an oxidoreduction, with the production of 5α-androstan-17β-ol-3-one as an intermediate. The physiological importance of the induction of this enzyme system by FSH for the mechanism of the onset of puberty in the female rat is discussed. (Endocrinology 89: 347, 1971)
Background: In patients with COPD, oxygen therapy has been shown to improve exercise capacity and... more Background: In patients with COPD, oxygen therapy has been shown to improve exercise capacity and survival. Increase in barometric pressure at low altitude can serve as a simple way to improve arterial oxygenation in hypoxemic patients. We have tried to evaluate the elffect of staying at low altitude on arterial oxygenation and exercise performance in patients with COPD. Patients and method: Eleven patients with COPD (9 male, 2 female) aged 38 to 79 years (mean FEVl9 0.96 L; 36% predicted) with hypoxemia (mean Pa02, 54.2±8.9 mm Hg) at Jerusalem (altitude 800 m above sea level) were taken down to the Dead Sea area (altitude 402 m below sea level) for 3 weeks. At both locations we tested arterial blood gases, spirometry, progressive exercise, 6-minute walking distance, and sleep oximetry. The study was repeated 2 weeKs after returning to Jerusalem. Results: Spirometry results were unchanged. Mean arterial Pa02 rose from 54.2±8.9 mm Hg to 69.5±11 at the first week and to 66.6±11 at the third week of stay (p<0.001). PaC02 rose from 43.5±9.8 mm Hg to 47.7±9 and 49.5±8.4 (p<0.006). Six-minute walking distance rose from 337±107 m to 449±73 and 507±91 in the third week (p<0.005). Maximum oxygen consumption (Vo2max) rose from 901±257 mL/min to 1,099±255 and 1,063±250 mL/min (p=0.01). Sleep oximetry showed an increase in mean sleep arterial oxygen saturation from 86.0±4.3% to 89.9±4.2% and 88.3±3.0 at 1 and 3 weeks, respectively (p<0.05). Following the return to Jerusalem, arterial gases returned to their baseline levels (Pa02, 52.9±9.4 mm Hg) but 6-min walking distance remained significantly high, 453±47 (p<0.02), and Vo2max remained high as well (1,102±357 mL/min), although it did not reach statistical significance. Conclusions: Decline to low altitude or staying at high oxygen environment improves arterial oxygenation and exercise capacity in hypoxemic patients residing in moderate or high altitude. Low altitude (or pressurized wards) can improve pulmonary rehabilitation of hypoxemic patients
Beclomethasone dipropionate (BDP) and budesonide (BUD) were each given in a dose of 200 [tg twice... more Beclomethasone dipropionate (BDP) and budesonide (BUD) were each given in a dose of 200 [tg twice daily by metered dose inhaler to 10 asthmatic children already dependent on treatment with steroids. In a double blind randomised crossover study each course lasted one month. No clinically important differences were found between the two treatments when symptom scores, symptom free days, additional use of salbutamol, and results of lung function tests were considered. Metyrapone mildly reduced the plasma concentration of 11-deoxycortisol in two patients during treatment with budesonide, and in four during treatment with beclomethasone. It is concluded that although they are usually safe, both drugs may cause mild adrenal suppression when given in a dose of 200 [tg twice daily.
Among the simpler methods for measuring bronchial reactivity, the steady-state tidal breathing te... more Among the simpler methods for measuring bronchial reactivity, the steady-state tidal breathing technique using histamine or methacholine has proved very practicaM '2 However, this method needs full patient cooperation in
A randomized controlled study was done to determine whether the addition of heparin (1 U/mL) to p... more A randomized controlled study was done to determine whether the addition of heparin (1 U/mL) to peripheral intravenous alimentation solutions would affect the incidence of phlebitis and duration of patency of intravenous catheters in premature infants. Twenty-two-gauge Teflon catheters were uniformly used. One hundred five catheters infused with heparin were placed in 13 infants, and 122 catheters were placed in the control group of 13 infants. The time, nature, and incidence of complications were noted for each infusion site. Infusion of heparin was found to double the duration of patency of intravenous catheters and to reduce significantly the incidence of phlebitis. No complications related to the administration of heparin were noted. Heparinization of intravenous alimentation solutions should therefore be considered in premature infants as a means of reducing the work load and incidence of complications associated with peripheral lines.
<b><i>Background:</i></b> The prevalence of asthma has increased in weste... more <b><i>Background:</i></b> The prevalence of asthma has increased in western countries towards the end of the last century, but recently seems to have stabilized. <b><i>Objective:</i></b> To evaluate trends in the prevalence and severity of asthma that occurred in Israel over the past decade. <b><i>Methods:</i></b> The medical records of 17-year-old boys, eligible for national service, between 1999 and 2008 were reviewed. National annual hospitalization and death rates for asthma were extracted. <b><i>Results:</i></b> Three hundred thousand medical records were reviewed. During the study period, lifetime asthma prevalence decreased from 9.7 to 8.1% (p = 0.002). The point prevalence of moderate-to-severe and mild persistent asthma decreased significantly from 0.88 and 3.41% to 0.36 and 2.44%, respectively, during this period. The prevalence of intermittent asthma and asthma in clinical remission for more than 3 years did not change significantly. The annual hospitalization rate for asthma decreased from 13.0 to 7.5 per 10,000 population (p &lt; 0.0001), whilst the annual death rate due to asthma decreased between 1999 and 2008 from 2.1 to 1.4 per 100,000 population (p = 0.003). <b><i>Conclusions:</i></b> The prevalence of asthma in Israeli teenage boys decreased significantly over the last decade. In addition, asthma hospitalization and asthma-related death rates in the total population also decreased.
Pediatric Allergy, Immunology, and Pulmonology, 2019
Background: To investigate the predictive factors associated with positive adenosine monophosphat... more Background: To investigate the predictive factors associated with positive adenosine monophosphate challenge using the auscultation method (AMP-PCW) test results. Methods: This is a prospective study of young children with suspected asthma who underwent AMP-PCW test. Patients with a positive AMP-PCW test were compared with those with a negative AMP-PCW. A multivariate logistic regression model was performed to identify the independent determinants of positive AMP-PCW. Results: A total of 159 patients completed the AMP-PCW test. The median age was 53 months. In total, 54.0% of patients had a positive AMP-PCW. The prevalence of atopic dermatitis and family history of asthma and allergy were significantly higher among the positive AMP-PCW group (P = 0.04, P = 0.02, and P = 0.007, respectively), as were the prevalences of elevated immunoglobulin E (IgE), peripheral blood eosinophils percentage (P = 0.003, P < 0.001, respectively), and number of emergency department (ED) visits/hospitalizations before AMP-PCW test (P = 0.006). A significant inverse correlation exists between peripheral blood eosinophils percentage and serum IgE levels with the AMP end-point concentrations (r =-0.302, P = 0.001, and r =-0.312, P = 0.001, respectively). In multivariate logistic regression model, peripheral blood eosinophils percentage, IgE levels, and the number of ED visits/hospitalizations before the AMP-PCW test were found as independent predictors for positive AMP-PCW test result. Conclusions: Our results suggest that bronchial responsiveness to AMP-PCW is related to proxy markers of airway inflammation (elevated eosinophils and IgE levels) and clinical exacerbation of asthma before the test. This may support the role of AMP-PCW in detecting inflammatory changes and monitoring their trend among young children with suspected asthma.
Aim: Our aim was to evaluate the correlation of Adenosine monophosphate challenge test (AMP-PCW) ... more Aim: Our aim was to evaluate the correlation of Adenosine monophosphate challenge test (AMP-PCW) results with the patients' subsequent clinical course. Methods: We performed a 6-year retrospective cohort study of young children with suspected asthma who underwent AMP-PCW test. Results: Fifty four children were included in the study (median age, 50.5 months; range, 26-90). AMP-PCW was positive in 35 (65%) children. During the 3-year follow-up period, among 22 of 35 patients in the positive AMP-PCW group and among 17 of 19 in the negative AMP-PCW group-prophylactic therapy was not changed. Prophylactic therapy was initiated or its dose was escalated in 12 of 13 (92.3%) of the children with a positive AMP-PCW test compared to none of the children with a negative challenge test (P < 0.001). Prophylactic therapy was discontinued in only one (7.6%) of the children with a positive test as compared to two (100%) of the children with a negative test (P < 0.001). There were significantly fewer severe asthma exacerbations during a 3-year follow-up period after the challenge test as compared to the preceding 3-year period both in children with a positive (from 34 to 9 total events, P = 0.01) or a negative challenge test (from 16 to 0 events P = 0.01). The severity of airway hyper responsiveness was found to associate with the number of severe asthma exacerbations (P = 0.04) and with a diagnosis of asthma during the following 3 years (P = 0.02). Conclusions: AMP-PCW test results correlates with the subsequent clinical course of young children with suspected asthma performing the test.
During breathing under sedation via a two-way valve, airflow (V), volume (delta V), and airway pr... more During breathing under sedation via a two-way valve, airflow (V), volume (delta V), and airway pressure (P) were recorded in eight normal (N) infants, seven with reversible obstructive airway disease (ROAD), and seven with chronic lung disease (CLD). Intermittently, expiratory volume clamping (EVC) was applied, involving selective occlusion of the expiratory valve for three to five breaths. The latter produced cumulative increases in delta V that, due to progressive recruitment of the Hering-Breuer reflex, were accompanied by increasing expiratory plateaus in P (i.e., apneas). The resultant passive inflation delta V-P relationships were closely approximated by the expression: delta V = aP2 + bP + c, wherein a represented the pressure-related changes in chord compliance (Crs), b the Crs at P = 0, and c the difference between the dynamic end-expiratory and relaxation volumes of the respiratory system. Relative to N, the ROAD and CLD infants had significantly reduced weight-specific va...
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Papers by Chaim Springer