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The role of hyperventilation in exercise-induced bronchoconstriction.

Significant bronchoconstriction, comparable in severity to that observed after moderate treadmill exercise, was induced in asthmatic children by voluntary isocapnic hyperventilation of 3-min and 10-min duration. In both hyperventilation and exercise, nasal breathing inhibited the bronchoconstrictive responses, whereas mouth breathing potentiated the bronchoconstrictive response. In the asthmatic children, 10 min of voluntary isocapnic hyperventilation did not represent a greater bronchoconstrictive stimulus than did 10 min of exercise or 3 min of isocapnic hyperventilation. This study also showed that in normal children there was no measurable airway response after either voluntary isocapnic hyperventilation or moderate exercise. Finally, this study indicates that it is the stimulation of upper airway receptors by relatively cold and dry air, rather than hyperventilation per se, that provokes exercise-induced bronchoconstriction.

Adolescent↗

Hypoxemia during exercise in patients with chronic obstructive pulmonary disease.

Arterial oxygenation at rest and during maximal treadmill exercise was studied in a group of 17 patients with chronic obstructive pulmonary disease. Patients who developed exertional hypoxemia (subgroup 1) were compared to others who did not (subgroup 2). There was no significant difference between the 2 subgroups at rest in terms of mixed venous PO2, cardiac output, or venous admixture. Subgroup 1 had more severe respiratory impairment than subgroup 2, but there was marked overlap of their respective lung volumes and flows. Both subgroups showed the same extent of desaturation of mixed venous blood during maximal treadmill exercise, so that exertional hypoxemia cannot be explained on the basis of low mixed venous O2. The marked difference between subgroup 1 and subgroup 2 was that the latter showed decreased venous admixture on exercise. Because of the relative constancy of mixed venous blood desaturation, arterial saturation was closely correlated with venous admixture both at rest (r = 0.931) and during exercise (r = 0.985).

Arteries↗

Forced expiratory spirometric parameters derived by feature-extraction techniques.

Spirometric data from 200 patients seen in the pulmonary function laboratory were analyzed retrospectively. Using standard criteria, the spirometric patterns of the subjects were classified as indeterminate, normal, restrictive, or obstructive; obstruction was further classified as mild, moderate, severe, or very severe. A formal feature-extraction technique was used to define 2 new parameters. These were linear combinations of the 5 standard spirometric parameters and explained 94% of the variation in the original parameters. The derived parameters provided better separation of the various classes than the combination of the normalized forced vital capacity and the ratio of the forced expiratory volume in 1 s to the forced vital capacity.

Forced Expiratory Flow Rates↗

The effects of H1 and H2 antihistamines on histamine inhalation challenges in asthmatic patients.

This study was designed to examine the effect of an H1 antihistamine, chlorpheniramine, an H2 antihistamine, cimetidine, and the combination of chlorpheniramine and cimetidine on histamine-induced bronchoconstriction in a double-blind, randomized protocol on 11 patients with asthma. Each patient underwent a histamine inhalation challenge on 5 separate days. After a control day, histamine inhalation challenges were performed 2 h after the administration of a single oral dose of 8 mg of chlorpheniramine, 300 mg of cimetidine, the combination of chlorpheniramine and cimetidine, or placebo. Baseline pulmonary function measurements were not significantly altered by the 4 treatments. Body plethysmography data and measurements from the forced vital capacity maneuver were obtained before and after the histamine inhalation challenges. The provocation dose of histamine that produced a 20% decrease in forced expiratory volume in one second, a 35% decrease in mean forced expiratory flow during the middle half of the forced vital capacity, and a 50% decrease in specific airway conductance was significantly increased after administration of chlorpheniramine (p less than 0.002) and decreased after administration of cimetidine (p less than 0.02), where as no significant effect was noted after the combination of chlorpheniramine and cimetidine. The results suggest the presence of both H1 and H2 receptors in the airways of asthmatic patients.

Adolescent↗

Airway responsiveness to cold air and hyperpnea in normal subjects and in those with hay fever and asthma.

Multiple aspects of pulmonary mechanics were measured before and after bronchial challenges consisting of hyperpnea with cold air inhalation in 20 normal control subjects, 16 subjects with hay fever, and 44 asymptomatic asthmatics. These challenges had no effect on the lung function of the normal subjects. In the hay fever group, however, postchallenge mechanics changed a small, but significant, amount, e.g., mean decrease in forced expiratory volume in one second (FEV1) was -5.1 +/- 1.7% (SEM). The asthmatics had a much more marked response (mean fall in FEV1, -32.7 +/- 2.6%). There was considerable overlap between the responses of the normal subjects and those with hay fever, but no overlap at all between asthmatic and normal subjects. The only subjects with hay fever whose responses overlapped the asthmatic response were those who had histories of occasional episodes of wheezing. This pattern of response suggests that the use of hyperpnea and subfreezing air is a very sensitive and highly specific means of detecting increased air reactivity.

Adult↗

Reference spirometric values using techniques and equipment that meet ATS recommendations.

Forced expiratory volumes and flows were measured in 251 healthy nonsmoking men and women using techniques and equipment that meet American Thoracic Society (ATS) recommendations. Linear regression equations using height and age alone predict spirometric parameters as well as more complex equations using additional variables. Single values for 95% confidence intervals are acceptable and should replace the commonly used method of subtracting 20% to determine the lower limit of normal for a predicted value. Our study produced predicted values for forced vital capacity and forced expiratory volume in one second that were almost identical to those predicted by Morris and associates (1) when the data from their study were modified to be compatible with the back extrapolation technique recommended by the ATS. The study of Morris and colleagues was performed at sea level in rural subjects, whereas ours was performed at an altitude of 1,400 m in urban subjects. Either the present study or the study of Morris and co-workers, modified to back extrapolation, could be recommended for predicting normal values.

Adolescent↗

Pulmonary function in identical twins raised apart.

As part of the Minnesota Study of Twins Raised Apart, we measured pulmonary function in 15 pairs of monozygotic twins and one set of monozygotic triplets who were separated at an average age of 3.8 months. Six pairs of twins were concordant for nonsmoking, 3 pairs and the triplets were concordant for cigarette smoking, and 6 pairs were discordant for respiratory problems (5 pairs for smoking, 1 pair for asthma). Thirteen pulmonary function tests were done on each twin; however, only 2 tests of pulmonary function, the FEF25-75% and V75, could separate smokers from nonsmokers to a statistically significant degree. One additional test, the FEV1, was the most sensitive way to separate smoking from nonsmoking twins when only paired data from twin pairs discordant for smoking were used. Intratwin differences between twins of a pair for these three pulmonary function tests were small and virtually identical for both concordant groups, whereas the intratwin differences in the discordant group were large and distinctly different from the concordant groups. These results, together with those of previous studies in identical twins raised together, support the conclusion that genetic factors are important in determining susceptibility to airway obstruction from cigarette smoke.

Adolescent↗

Changes in the glottic aperture during bronchial asthma.

We measured the cross-sectional area of the glottis in 12 asymptomatic asthmatic subjects before and after bronchoconstriction (BC) induced by histamine or ultrasonically nebulized water aerosol. The glottis was visualized using a fiberoptic bronchoscope attached to a video camera and tape recorder onto which flow and volume were simultaneously recorded. During induced asthma, measurements of forced expiratory flow fell to 36 +/- 3% (mean +/- SE) of control. Glottic area at mid-expiration (Age) fell from 75 +/- 14 mm2 by 45 +/- 8% (p less than 0.005). In some subjects, expiratory constriction of the supraglottic portion of the larynx and pharynx was also noted. Five subjects showed mild constriction (13 to 32%) of the glottis during inspiration. The administration of 10 cm H2O of continuous positive airway pressure (CPAP) during the induced asthma temporarily abolished expiratory constriction of the glottis and supraglottic structures; Age increased from 45 +/- 15 to 79 +/- 11 mm2 (p less than 0.01). The constriction returned when CPAP was stopped. After reversal of BC by salbutamol Age returned to values similar to those before BC. Although the mechanism for the expiratory glottic constriction is not known, it may be related to the different pattern of respiratory muscle activity seen in asthma. We speculate that the glottic constriction may contribute to hyperinflation by slowing expiratory flow and/or allowing a reduction in the persistent inspiratory muscle activity during expiration.

Adult↗

Risk factors associated with longitudinal change in pulmonary function.

In a longitudinal study of pulmonary function, we investigated the relationship between loss of forced expiration over time and a series of potential risk factors, as well as 4 other measures of pulmonary function at initial visit. Data on 1,912 adults tested twice, with an average of 4.7 yr between visits, were used. Of the potential risk factors examined, only age and smoking were consistently associated with increased loss of forced expiratory function in both men and women. Statistically significant differences among ABO blood types and among Pi types were also seen in women, although the direction of these differences was unexpected in that non-Z Pi variant phenotypes showed less decline in pulmonary function than did the most common Pi M phenotypes. Similar patterns of differences were seen in men, although these were not statistically significant. Of 4 initial-visit pulmonary function measures examined, only closing capacity at initial visit was consistently associated with subsequent loss of forced expiratory volume in one second (delta FEV1) in both men and women. The final predictive model for delta FEV1 accounted for a modest proportion of the total variation seen in this sample, however, limiting its potential use for predicting decline in pulmonary function over a 5-yr span in individual subjects.

ABO Blood-Group System↗

The UCLA population studies of chronic obstructive respiratory disease. VII. Relationship between parental smoking and children's lung function.

Results of previous studies of the impact of parents' smoking on children's lung function have been conflicting. To evaluate further the effect of passive smoking on the lung function of children, we analyzed respiratory questionnaire and lung function results obtained during field testing of residents (aggregated according to household) of 4 census tracts in the Los Angeles area. We report here on 971 white, non-Hispanic, nonsmoking, nonasthmatic children residing in households in which the smoking status of both parents was known; households with ex-smoking parents were excluded from analysis. We divided these children into 3 categories related to parental smoking status: (1) at least mother smokes , (2) only father smokes , and (3) neither parent smokes . Prediction equations for several indexes of forced expired volume and flow were derived separately for boys and girls 7 to 17 yr of age. Analysis of variance was used to compare lung function residuals of children in the 3 different passive smoking categories. Analysis was performed separately on younger (7 to 11 yr of age) and older (12 to 17 yr of age) children of each sex. Among younger male children, residual values were significantly lower in the maternal smoking category than in the other 2 household categories for maximal flow and maximal flow after exhalation of 25% of forced vital capacity (FVC) (p less than or equal to 0.05); no differences were noted between the paternal-smoking only and nonsmoking household categories. A trend toward similar results was found in older male children, which approached significance (p less than 0.1). Among females, forced expiratory flow during the middle half of the FVC and maximal flow after exhalation of 75% of FVC were significantly lower in relation to maternal smoking in the older children only (p less than or equal to 0.05). ANOVA revealed no decrement in lung function in relation to passive smoking among children with asthma or bronchitis (n=138).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Airways responsiveness in a population sample of adults and children.

Nonspecific bronchial responsiveness was assessed with eucapneic hyperpnea to subfreezing air in a population-based sample of 134 adults and 213 children in East Boston, Massachusetts. Increased responsiveness was considered to be present if the decrease in forced expiratory volume in one second with cold air divided by the initial vital capacity was greater than 9%. Men and women had similar bronchial responsiveness, but children and young adults (24 yr of age and younger) were significantly more likely to be responders than were older subjects (p less than 0.001). Children with a doctor's diagnosis of asthma at any time in the past were twice as likely (42.9%) to be responders as were nonasthmatic children (19%) (p = 0.004). Ninety-two percent (11/12) of currently active asthmatics were responders. However, a large percentage of asymptomatic children had increased levels of bronchial responsiveness (18.9%). This cross-sectional study demonstrates the feasibility of measurement of nonspecific bronchial responsiveness in epidemiologic studies, and its relationship to age and wheeze symptoms in children.

Adult↗

A method for comparing the peak intensity and duration of action of aerosolized bronchodilators using bronchoprovocation with methacholine.

The effects of aerosolized metaproterenol (1.30 mg) and isoetharine (1.02 mg) on nonspecific airway responsiveness to inhaled methacholine were quantitated and compared in 6 asthmatic subjects for 4 h after dosing. Both metaproterenol and isoetharine demonstrated bronchodilatation and reduced airway responsiveness during the first hour. Isoetharine had lost its bronchodilator effects and its effects on airway responsiveness by 2.25 h. The effects of metaproterenol on airway responsiveness had decreased by half at 2.25 h, while its bronchodilator effect remained maximal. Metaproterenol had no effect on airway responsiveness by 4 h, despite persisting bronchodilatation. Thus, for metaproterenol, there is disparity between duration of bronchodilation and suppression of airway responsiveness. Because methacholine sensitivity is a measure of nonspecific airway responsiveness, which appears to correlate with the severity of asthma, this methodology may provide more relevant information for assessment of duration of effect and estimation of appropriate dosing intervals for maintenance therapy than do more traditional methods.

Adolescent↗

Time domain spirogram indices. Their variability and reference values in nonsmokers.

A cross-sectional population survey of dynamic ventilatory lung function was performed to determine the variability of and reference values for time domain spirogram indices. The reference population comprised 83 men and 143 women who were healthy nonsmokers. The time domain indices were derived from the blow with the largest sum of FVC and FEV1. Prediction equations for FEV1 and mean flow between 25 and 75% FVC were little influenced by methods for selecting the data from the 3 blows recorded. The variability of the first 2 moments of the spirogram increased with age, requiring a log transformation for regression analysis. Prediction equations for conventional and time domain spirometric indices are presented and reference values are proposed based on an estimated percentile derived from the predicted value and the residual standard deviation from regression. Two time domain indices are identified that may prove better suited than conventional indices for identifying abnormalities in the tail of the spirogram.

Adult↗

The effect of inhaled clonidine in patients with asthma.

To study the effect of inhaled clonidine on broncho-obstruction in asthmatics, 10 patients with extrinsic asthma were broncho-provoked twice with an allergen that had been shown to give positive skin prick test results. Before the provocations, saline or clonidine (75 micrograms) was inhaled via a DeVilbiss no. 40 nebulizer. Clonidine slightly improved the basal respiratory function without significantly influencing the blood pressure. There was a reduction in the allergen-evoked broncho-obstruction by 42 to 65% after pretreatment with clonidine. The eosinophilic leukocytes in peripheral blood had a slight tendency to leave the circulatory system during the provocation preceded by the clonidine treatment. These data add further evidence to the finding that clonidine may be of interest in the treatment of broncho-obstructive diseases.

Administration, Intranasal↗