Perspectives in cystic fibrosis.
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Adolescent↗
Biomedical subjects
H Levison
Publications and source records attributed to H Levison.
Sodium cromoglycate-induced changes in the dose-response curve of inhaled methacholine and histamine in asthmatic children.
The effect of inhalation of 2 per cent solution of sodium cromoglycate compared to that of saline on the bronchial response to methacholine and histamine was studied in 30 asthmatic children. Seven of 17 children challenged with methacholine showed decreased sensitivity after pretreatment with sodium cromoglycate. In 4 of 13 children, sodium cromoglycate attenuated the response to inhaled histamine. We conclude that in some asthmatic children, sodium cromoglycate provides significant protection against these nonallergenic challenges. This may have some therapeutic implications in the management of these patients. Our findings raise the possibility that sodium cromoglycate might have an action on cholinergic or irritant receptor sites in addition to inhibition of mast cell degranulation.
Adolescent↗
Evaluation of the single-breath diffusing capacity in asthma and cystic fibrosis.
To explain why the single-breath carbon monoxide diffusing capacity (Dsb) was, on the average, elevated in 163 asthmatic subjects and 175 patients with cystic fibrosis, we simulated this elevation in ten normal subjects by having them perform the test for Dsb through an inspiratory obstruction. This resulted in an 18 percent increase in Dsb corrected for pulmonary volume. Inhalation of a bronchodilator drug was associated with relief of obstruction and a fall in the corrected Dsb in 31 asthmatic subjects but did not change either the obstruction or the corrected Dsb in 17 patients with cystic fibrosis. We suggest that elevated Dsb in asthma and cystic fibrosis is partly due to maximal inspiration against obstructed airways. This requires abnormally negative intrathoracic pressures, increasing the pulmonary capillary blood volume, and, thereby, increasing the Dsb.
Adolescent↗
Bronchial hyperreactivity to histamine and methacholine in asthmatic children after inhalation of SCH 1000 and chlorpheniramine maleate.
Nine asthmatic patients with a mean age of 14 yr received bronchial challenges with histamine and methacholine. The challenges were repeated after inhalation of 80 microgram of SCH 1000 (ipratropium bromide) and 5 mg of chlorpheniramine maleate. The provocation doses which produced a 20% fall in forced expiratory volume in 1 sec (FEV1) and the slopes of the dose-response curves were analyzed. SCH 1000 prevented methacholine-induced bronchoconstriction and chlorpheniramine prevented methacholine-induced bronchoconstriction. There was no significant change in the dose-response curve of histamine after SCH 1000 or in the dose-response curve of methacholine after chlorpheniramine. The findings indicate that the mechanisms and receptor sites involved in bronchial provocation by histamine and methacholine are distinctly different. The histamine response is unlikely to be vagally mediated because histamine-induced bronchoconstriction was not prevented by SCH 1000. Both SCH 1000 and chlorpheniramine caused significant bronchodilatation, suggesting the presence of both histamine- and vagal-dependent bronchomotor tone.
Adolescent↗
The response to exercise in normal and asthmatic children.
Twenty-five normal and 105 asthmatic children were exercised on a treadmill. Pulmonary function was assessed before and after exercise. The maximum fall from the resting value in normal subjects depended on the test used: PEFR 12.5%; FEV1 10%; MMEF 26%; V50 30%; V25 33%. Using these criteria, PEFR and FEV1 detected 99% of those asthmatic children who had a positive exercise response. The largest fall from the resting value was seen with the MMEF, but this test detected only 70% of the positive responders. The pre-exercise function did not affect the severity of the response but did have an effect on the incidence of exercise-induced bronchospasm.
Adolescent↗
Bronchial hyperreactivity in cystic fibrosis and asthma.
We studied 113 patients with CF and compared their responsiveness to inhaled methacholine to that of 50 asthmatic children and 26 normal children. Positive responses to MCh occurred in 51% of the patients with CF and 98% of those with asthma. There was a significant correlation between a positive response to MCh in CF and poor pulmonary function. There was no relationship between allergic rhinitis or positive allergen skin tests and a positive MCh response. Dose-response curves and time course to MCh challenge differed in CF and asthma. Bronchial hyperreactivity is thus common in CF but is different from that in asthma.
Adolescent↗
Ultrastructure of airways in children with asthma.
This study describes the histopathology and ultrastructure of bronchial mucosa in lung biopsies from two children with bronchial asthma in remission, and compares them with lung samples from two children who died in status asthmaticus. Light microscopy of all samples showed changes typical of bronchial asthma, e.g. mucus plugging, goblet cell hyperplasia, 'thickening of bronchial basement membrane', peribronchial smooth muscle hypertrophy and eosinophilic infiltration. Electron microscopy revealed that the mucus plugs consisted of moderately electron-dense floccular material containing degenerate epithelial cells, macrophages and cell fragments. The luminal surfaces of ciliated cells showed cytoplasmic blebs and abnormal cilia. Mast cells in various stages of degranulation were scattered between bronchial epithelial cells. The subepithelial hyaline layer, commonly referred to as "thickened basement membrane", consisted of collagen fibrils in plexiform arrangement. The basement membrane proper appeared intact. These electron microscopic changes, particularly the presence of mast cells and subepithelial collagen deposits, were also found in autopsy samples. This combined light and electron microscopic study shows that marked, possibly irreversible changes may be present in the lungs of patients with severe bronchial asthma, even when they are asymptomatic. These pulmonary changes could be the direct consequence of mast cell activation and the release of various mediators. No evidence of immune complex deposition was found.
Asthma↗
Cellular adaptations of the ventilatory muscles to a chronic increased respiratory load.
It is not known whether cellular adaptations of the ventilatory muscles are induced by increased respiratory loads. A chronic respiratory load was produced in rats by tracheal banding. Five weeks after the imposition of this increased load, biochemical and histochemical analyses were performed on the diaphragm and intercostal muscles. The oxidative capacity, as indicated by succinate dehydrogenase (SDH) activity, increased 38% in the diaphragm. The capacity for beta-oxidation fatty acids, as indicated by 3-hydroxy-acyl-CoA dehydrogenase (HADH) activity, increased 29%. The glycolytic capacity, as indicated by phosphofructokinase (PFK) activity, did not change. Similar enzymatic adaptations were observed in the intercostal muscles. The proportion of slow-twitch muscle fibers, as indicated by the myofibrillar adenosine triphosphatase (ATPase) stain, increased in the diaphragm, but not in the intercostal muscles. Thus, these ventilatory muscles responded with an increase in their oxidative capacity, and the diaphragm reponded with an increase in the proportion of muscle fibers having the myofibriller ATPase staining characteristic of slow-twich fibers. We conclude that cellular adaptations are induced in the ventilatory muscles by chronic increased respiratory loads.
3-Hydroxyacyl CoA Dehydrogenases↗
Developmental pattern of muscle fiber types in human ventilatory muscles.
Premature infants tolerate respiratory loads poorly. This may reflect incomplete development of the ventilatory muscles (VM) causing poor resistance to fatigue. To study the developmental pattern of human VM, 31 postmortem specimens of diaphragm and intercostal muscles were obtained. Individual muscle fibers were classified as type I (slow-twitch, high-oxidative) or type II (fast-twich, low-oxidative) using histochemical staining methods for myofibrillar adenosine triphosphatase (M-ATPase) (pH 10.30) and nicotinamide adenine dinucleotide (NADH) tetrazolium reductase. In the diaphragm, premature infants (less than 37 wk gestation) had only 9.7 +/- 1.3% type I fibers, full-term newborns 25.0 +/- 1.1%, and older subjects (greater than 2 yr of age) 54.9 +/- 1.3%. There was no further increase after 8 mo postpartum. In the intercostal muscles, premature infants had only 19.0 +/- 4.8% type I fibers, full-term newborns 45.7 +/- 1.3%, and older subjects 65.2 +/- 2.6%. There was no further increase after 2 mo postpartum. These findings suggest the ventilatory muscles of newborn infants are more susceptible to fatigue than those of older subjects. This may contribute significantly to respiratory problems in the neonate.
Adenosine Triphosphatases↗
Comparative study of histamine and exercise challenges in asthmatic children.
Fifty asthmatic children were tested with both a standardized treadmill exercise and a histamine inhalation on 2 separate days. Ninety per cent had a positive response to histamine, whereas 74 per cent had demonstrable exercise-induced bronchoconstriction. There was a close relationship between responsiveness to histamine and exercise, because all patients who responded to histamine had exercise-induced bronchoconstriction. Eight children (16 per cent) responded to histamine only. Although prechallenge pulmonary function has an effect on the incidence of exercise-induced bronchoconstriction, it does not appear to influence the responsiveness to histamine. Therefore, when provocation testing is being done for the purpose of diagnosing asthma, histamine is preferable to exercise.
Adolescent↗
Bronchial reactivity in cystic fibrosis.
There is considerable dispute regarding the prevalence of asthma in patients with cystic fibrosis (CF). We studied 50 patients with CF and compared their responsiveness to inhaled histamine with that of asthmatic children. The incidence of positive responses to inhaled histamine was 24% in the patients with CF and more than 90% in the asthmatic patients. We found no correlation, in the patients with CF, between the histamine response and several indexes of atopy (clinical allergic disease and positive allergen skin tests). Positive responders to histamine were not evenly distributed over the disease spectrum of CF. Instead, positive responses occurred only in those patients whose prechallenge pulmonary function was abnormal. We conclude that the heightened bronchial reactivity in patients with CF reflects the severity of their underlying lung disease rather than the presence of coexistent asthma.
Adolescent↗
Pulmonary function abnormalities in asymptomatic children after hydrocarbon pneumonitis.
To assess the effect of hydrocarbon pneumonitis on the developing lung, we studied the pulmonary function of 17 asymptomatic children, 8 to 14 years after the initial insult. Fourteen of the 17 subjects (82%) had one or more pulmonary function abnormalities, the most frequent being a high volume of isoflow. Volume of isoflow, ratio residual volume to total lung capacity, slope of phase III, flow rates at 50% and 25% of vital capacity and 60% of the total lung capacity, one-second forced expiratory volume, and maximum midexpiratory flow rate differed significantly (P less than .05) from values in control groups. Closing volume and closing capacity were not significantly different. Residual abnormalities present in children after hydrocarbon pneumonitis can be explained on the basis of small airway obstruction and/or loss of elastic recoil. These children may be at risk for the development of chronic lung disease as adults when they are exposed to exogenous factors such as air pollution or smoking.
Child, Preschool↗
Relationship of lung recoil to lung volume and maximum expiratory flow in normal children.
Thirty-one normal children, aged 6--18 yr, were studied by measurements of static lung volumes, static expiratory pressure-volume (PV) curves, and maximum expiratory flow-volume (MEFV) curves. A theoretical standard volume was used to compare children of differing size and this showed that total lung capacity (TLC) is also a valid standard volume. The shape of the PV curve was found to change so that static elastic recoil at a fixed proportion of TLC was higher in older than in younger children. This was also true of static recoil at functional residual capacity (FRC) and an associated increase in the ratio of FRC to TLC was interpreted as evidence for increase in outward recoil of the chest wall during childhood. Since static recoil at "closing capacity" (CC) remained constant, a decrease in the ratio of CC to TLC was quantitatively explained by the PV shift during childhood. Although maximum expiratory flow at various lung volumes increased in constant proportion to TLC, "upstream conductance" decreased relative to TLC. It was concluded that maturation of the respiratory system is disproportionate in several features during childhood and that these disproportions are likely to be even more prominent during infancy and early childhood.
Adolescent↗
Ventilatory muscle endurance training in normal subjects and patients with cystic fibrosis.
Ventilatory muscles can become fatigued, and this can contribute to respiratory failure. Patients with chronic obstructive lung disease may benefit from improving their ventilatory muscle endurance to improve resistance to fatigue. Ventilatory muscle endurance was measured in 30 normal subjects and 55 patients with cystic fibrosis by finding the highest level of normocapnic hyperpnea that could be sustained for 15 min. Subjects with cystic fibrosis had 36 per cent higher ventilatory muscle endurance than normal subjects, reflecting the chronic training stress of breathing against increased respiratory loads. Four normal subjects and 4 subjects with cystic fibrosis participated in a specific ventilatory muscle endurance training program consisting of 25 min per day of maximal normocapnic hyperpnea 5 days per week for 4 weeks. The cystic fibrosis patients who trained improved their ventilatory muscle endurance by 51.6 per cent, whereas the normal subjects who trained showed a 22.1 per cent increase in ventilatory muscle endurance. Seven subjects with cystic fibrosis participated in a 4-week physical activity training program consisting of at least 1.5 hours per day of intensive swimming and canoeing at summer camp. They increased their ventilatory muscle endurance by 56.7 per cent. There were no other pulmonary function changes. Ventilatory muscle endurance can be readily improved in cystic fibrosis equally well by specific ventilatory muscle endurance exercise.
Adolescent↗
Occult pulmonary abnormalities in asymptomatic asthmatic children.
The pulmonary status of 178 asymptomatic asthmatic children with normal time-volume spirograms was further evaluated using flow-volume loops, body plethysmographic studies, and blood gas tensions in arterialized capillary blood. Residual volume (RV) was abnormal in 26%, total lung capacity (TLC) in 33%, RV/TLC% in 41%, and arterial oxygen pressure in 23% of them. All values for expiratory flow measured relative to observed vital capacity (VC), (ie, the forced expiratory volume in one second [FEV1], the mean forced expiratory flow during the middle half of the forced vital capacity [FEF25-75%; FVC], FEV1/VC, and the instantaneous forced expiratory flow after 75% and after 50% of the FVC has been exhaled) were normal, and VC was subnormal in only five instances, but flow rates measured relative to TLC were abnormal in 26% of the patients. Some abnormality of pulmonary function was present in all but 13% of these asymptomatic children. Reliance upon conventional evaluation of pulmonary function by forced expiratory spirograms and freedom from wheezing may frequently give the clinician a false impression of the true conditon of the lungs of the asthmatic child.
Adolescent↗
Pulmonary function abnormalities in symptom-free children after bronchiolitis.
Twenty-three children less than 18 months old who had clinical and radiological evidence of bronchiolitis and remained symptom-free thereafter were studied to determine pulmonary function ten years later. Abnormal Pao2, Viso V and RV/TLC ratio were found in the majority of subjects, and 31.3% had abnormalities in all three tests; four and one-half percent had exercise-induced bronchospasm. These changes indicate a residual parenchymal or airways lesion following bronchiolitis.
Asthma↗
Effects of gravity on tracheal mucus transport rates in normal subjects and in patients with cystic fibrosis.
A noninvasive, radionuclide imaging technique for measuring the rate of mucus clearance in the trachea (RT), was used to study gravitational effects on mucus clearance in 13 patients with cystic fibrosis (CF), average age 17 years; 7 normal, nonsmoking adults, average age 26 years; and a normal subject who was recovering from an acute upper respiratory tract infection (URTI). In the upright position, nine of the CF patients and the subject with URTI demonstrated abnormal tracheal mucus clearance which approached normal when they were placed in 25 degrees headdown position. The normal subjects and two of the CF patients showed no significant difference in the RT measured in the two positions. The results of the study indicate that the force of gravity can be a major influence on tracheal mucus clearance in CF and URTI subjects. This conclusion supports the use of postural drainage as an effective form of therapy in patients with cystic fibrosis.
Adolescent↗
Components of respiratory depression after narcotic premedication in adolescents.
The effects of narcotics on ventilatory control were assessed in 13 adolescents and young adults. Both a narcotic and narcotic-phenothiazine significantly depressed the CO2 response curve. Using an occlusion pressure technique (Pm100) to evaluate those neuromuscular processes that generate forces acting on the ventilatory pump, it was found that narcotic agents reduced neuromuscular drive. In most subjects, narcotics had an additional action that contributed to the overall ventilatory depression. Using carbon dioxide to vary neuromuscular drive before and after drug administration at constant levels of neuromuscular drive the drugs reduced tidal-volume responsiveness of the pump. We conclude that narcotics impair ventilation through a combination of two effects; first, reduced neuromuscular drive, most probably due to central depression, and second, increased impedance of the ventilatory pump, most probably due to a decrease in chest-wall compliance.
Adolescent↗