Bronchodilator effects of metaproterenol and oxtriphylline in asthma.
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We compared the effects of two histamine receptor blocking agents, chlorpheniramine (H1) and cimetidine (H2) on the airways of healthy and asthmatic subjects. Eleven healthy subjects and ten asthmatic patients underwent histamine aerosol challenge. A threshold dose (T) for response to histamine was determined for each subject using maximal expiratory flow rates on partial expiratory flow rates on partial expiratory flow volume curves (MEF40 %[P]). On subsequent study days, the subjects were pre-treated with 8 mg of chlorpheniramine, 300 mg of cimetidine or a lactose placebo. Histamine challenge was performed two hours later with the individual's own T dose and doses one dilution below (T-1) and one dilution above (T+1) that dose. In both asthmatic and healthy subjects chlorpheniramine significantly reduced the bronchoconstrictor responses to histamine (p less than 0.02 and 0.05, respectively) as measured by MEF40 percent (P) at the T dose. When treated with cimetidine asthmatic patients displayed significantly more bronchospasm at T than with placebo (p less than 0.035). By contrast, pretreatment with cimetidine did not alter airway responses to histamine in healthy subjects when compared to placebo. We conclude that H2 receptors mediating bronchodilatation can be demonstrated in asthmatic patients but not in healthy subjects.
Twenty-eight patients with advanced emphysema and/or chronic bronchitis and severe airflow obstruction were randomly assigned to receive either bitolterol or isoproterenol aerosol delivered by a metered dose device which was administered three times daily. Randomization resulted in similar patients with like degrees of airflow obstruction and responsiveness to a test dose of inhaled bronchodilator. Significantly greater improvement in airflow was achieved by administration of bitolterol compared to isoproterenol. Pharmacologic responses continued after 90 days of daily dosing. Both drugs were well tolerated and side effects included mild degrees of tachycardia for both drugs. Two patients assigned to isoproterenol stopped therapy during the study due to side effects. This study indicates that bitolterol is more effective than isoproterenol in degree and duration of bronchodilatation in patients with advanced chronic obstructive pulmonary disease.
Respiratory exercise physiology research has historically focused on male subjects. In the last 20 years, important physiological and functional differences have been noted between the male and female response to dynamic exercise where sex differences have been reported for most of the major determinants of exercise capacity. Female participation in competitive and recreational sport is growing worldwide and it is universally accepted that participation in regular physical activity is of health benefit for both sexes. Understanding sex differences is of potential importance to both the clinician-scientist and the exercise physiologist since differences could impact upon exercise rehabilitation programmes for patient populations, exercise prescription for disease prevention in healthy individuals and training strategies for competitive athletes. Sex differences have been shown in resting pulmonary function, which may impact on the respiratory response to exercise. Women typically have smaller lung volumes and maximal expiratory flow rates even when corrected for height relative to men. Differences in resting and exercising ventilation across the menstrual cycle and relative to men have also been reported, although the functional significance remains unclear. Expiratory flow limitation and a high work of breathing are seen in women. Pulmonary system limitations, in particular exercise-induced arterial hypoxia, have been reported in both men and women; however, the prevalence in women is not yet known. From the available literature, it appears that there are sex differences in some areas of respiratory exercise physiology. However, detailed sex comparisons are difficult because the number of subjects studied to date has been woefully small.
Eighteen patients with bronchial asthma were studied in a single-blind fashion. Each patient received an infusion of magnesium sulfate (MgSO4.7H2O 50% W/V) in a dose equivalent to 10 mmol of elemental magnesium. The airways resistance showed a significant decrease (p < 0.01) while SGaw increased significantly (p < 0.001) with MgSO4 infusion. FEV1 (p < 0.01), FEF25-75% (p < 0.05), and V50 (p < 0.05) also showed statistically significant increase (p < 0.001) with MgSO4 infusion. Significant changes in Raw (p < 0.01) and SGaw (p < 0.01) persisted at 10 and 20 min following MgSO4 infusion. No significant side effects were observed with MgSO4 infusion. It is concluded that modest improvement in airways resistance and specific conductance and only small improvement in maximal expiratory flow rates is consistent with a predominant effect of MgSO4 on large airways in patients with bronchial asthma.
Twenty-two males with asthma and 22 healthy males (7-18 years old) performed a Wingate Anaerobic Test. The subjects with asthma had a lower mid-maximal expiratory flow rate (78.3+/-25.3 vs. 100.1+/-24.5%, p < 0.01) than the controls. Aerobic and anaerobic exercise performance (peak power: PP; mean power: MP) were similar for the two groups whether expressed in absolute or relative terms to body weight. The subgroup with asthma with a lower percent body fat (<25%) had a higher PP and MP than the subjects with a higher percent body fat (>25%). Pulmonary function or maturation were not independent correlates of anaerobic power. Our results fail to show differences in anaerobic exercise performance in children with asthma compared to healthy controls. Nutrition appears to be an important factor for performance during this test.
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Living donor (LD) lobar lung transplantation is now an accepted alternative to cadaveric lung transplantation in selected patients with end-stage lung disease. This study reviews the Childrens Hospital Los Angeles LD experience of 17 patients (mean 13.2 +/- 2.7 yrs; range 9.3-18.5 yrs). 12 LD patients had end-stage cystic fibrosis, 4 had primary pulmonary hypertension, and 1 child had bronchiolitis obliterans. LD candidates must meet the same criteria as for cadaveric lung transplant candidates. Donor candidates are rigorously screened (physically and psychologically) prior to acceptance for lobectomy. LD patients receive the same triple immunosuppression regimen as our cadaveric recipients (prednisone, cyclosporine/FK506, and azathioprine/mycophenolate). Comparison of rejection episodes, incidence of bronchiolitis obliterans, pulmonary function tests, exercise stress tests, and cardiac catheterization data was made between LD and cadaveric lung transplantation (CL) pediatric recipients. Donor outcomes were also reviewed. In our pediatric program, the 1-year survival rate for LD recipients is currently 81%, which compares favorably with the ISHLT average of 70% for pediatric transplant patients. The incidence of rejection is about the same for LD and CL recipients, but the episodes are less severe for pediatric LD patients. There have been no histological cases of bronchiolitis obliterans syndrome in our LD recipients. Although there have been questions as to whether transplanted lobes can supply comparable pulmonary reserve to whole cadaveric lungs, the lung volumes (TLC and VC), expiratory flow rates, maximal exercise stress tests, and pulmonary artery pressures (no evidence of pulmonary hypertension) in LD patients are not significantly different to CL recipients in our institution. Besides pain from the thoracotomy, the donors have a decrease of 16% (right lower lobe donor) and 18% (left lower lobe donor) in their vital capacity. Otherwise, there have been no major complications to the donors and most have resumed their usual activities. Based on outcomes, pulmonary function tests, exercise stress tests, and hemodynamic studies as well as low donor morbidity, living donor double lobar lung transplantation is a viable alternative to cadaveric lung transplantation in selected pediatric patients with end-stage lung disease.
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The relative effectiveness of ephedrine, theophylline, hydroxyzine, and their combinations in relieving cycloergometer exercise-induced asthma were studied in 16 children and adolescents. Ephedrine had no effect on post-exercise asthma, hydroxyzine had weak effect on hastening recovery, while theophylline modified on the post-exercise response significantly. The three drugs together produced an additive effect superior to that of theohylline alone.
There are only a few studies that have established reference standards for pulmonary function of Indian children. Reference standards for pulmonary function that are reported for Indian children are mainly from northern and western parts of the country and there is a paucity of data on pulmonary function in normal South Indian children. Therefore, pulmonary function tests (spirometry and maximal expiratory flow rates) were carried out in 469 South Indian healthy children (246 boys and 223 girls) between 7-19 years of age to derive regression equations to predict pulmonary function. The correlations of forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were, in general highest with height followed by weight and age. Peak expiratory flow rate (PEFR), forced mid-expiratory flow (FMF) and forced expiratory flow rates at 25%, 50% and 75% of FVC (FEF25% FVC, FEF50%FVC and FEF75%FVC) were also significantly correlated with physical characteristics (age, height and weight). With a view to find out regression equations to predict spirometric functions based on physical characteristics (age, height and/or weight), the functions were regressed over all possible combinations of regressor variables, i.e. age, height and weight separately for boys and girls. The height influences the prediction equation in males to a great extent, whereas age and weight had greater influence in girls. Regression equations were derived for boys and girls for predicting normal pulmonary functions for children in South India. The pulmonary function measurements in South Indian children were similar to those reported for subjects from Western India and lower than those reported for Caucasians.
Airway obstruction is a prominent feature in coal workers' pneumoconiosis (CWP). However, many patients with CWP have even demonstrated a normal forced vital capacity (FVC) and forced expiratory volume in 1s (FEV1). The purpose of this study was to evaluate the ventilatory defect by spirometry and search for parameters, other than FVC and FEV1, suitable for early detection of pulmonary impairment in CWP. A sample of 227 coal miners was selected from the medical clinics of two teaching hospitals. Maximal expiratory flow volume measurement and determination of functional residual capacity (FRC) and residual volume (RV) were carried out with an automated plethysmograph. The prevalence of airway obstruction (FEV1/FVC < 70%) in this sample of miners was 52.9% (120/227). There was a progression of functional impairment with the transition from category 0 to categories 2 and 3, no matter what the miners smoking habits. All of the 107 non-obstructed miners had a normal FVC and FEV1. However, the mean values for FEF25-75% (mean forced expiratory flow during the middle half of FVC) and Vmax50 (maximal expiratory flow rate at 50% FVC) were abnormally low, and RV was already elevated, in those non-obstructed subjects with category 1 simple pneumoconiosis. A borderline abnormally elevated FRC in the miners with radiological category 3 of CWP was also noted. We conclude that the Vmax50, FEF25-75%, and RV appeared to be the discriminative indices for detecting early ventilatory defect in non-obstructed patients with simple CWP. Further studies is still needed to clarify the cause of small airway dysfunction.
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We hypothesized that patients with chronic renal failure may present nonspecific bronchial hyperreactivity due to subclinical interstitial lung oedema. To assess lung function disturbances and methacholine (MTH) bronchial responsiveness in this condition, we studied 12 patients (9 men and 3 women; 41.8 +/- 13.3 yrs (SD] with chronic renal failure undergoing regular haemodialysis (HD). Before HD, mean results of conventional lung function tests were within the normal range: forced expiratory volume in one second (FEV1), 89 +/- 12.9% predicted; forced mid-expiratory flow (FEF25-75), 81 +/- 36.7% predicted; total lung capacity (TLC), 94 +/- 14.6% predicted, but 3 subjects presented mild reduction in lung volumes and 5 individuals showed mild obstructive ventilatory impairment. After HD, maximal expiratory flow rates increased significantly (FEV1, + 8.2 +/- 5.1% (p less than 0.005); FEF25-75, +26.2 +/- 25.9% (p less than 0.005]. Interestingly, these increases in FEV1 after HD correlated with body weight loss during HD (r = 0.74, p less than 0.01). In contrast, pre-HD bronchial reactivity was within the normal range (mean % change in FEV1 after MTH, -3.7 +/- 4.5%; range, +1- -14%) without significant changes in methacholine bronchial responsiveness after HD. We speculate that interstitial lung oedema may play a significant role in lung function impairment observed in patients with chronic renal failure. This study shows that nonspecific bronchial hyperreactivity is not present in clinically stable patients with this disorder.
Pulmonary function and respiratory muscle strength was assessed in 20 patients with mitral stenosis uncomplicated by other illness. Pulmonary function was evaluated by spirometry, flow-volume curves, functional residual capacity (FRC) and total lung capacity (TLC). Respiratory muscle strength was evaluated by measurement of maximal static inspiratory and expiratory mouth pressure (PIM, PEM cmH2O) at FRC and TLC respectively. Spirometric, FRC and TLC average values were normal. The maximal expiratory flow rate at 50 and 25% of vital capacity were decreased to 49.5 and 38.3% from predicted values. The values of PIM and PEM in patients (-93 +/- 17; 128 +/- 32 cmH2O, respectively) were similar to those of 12 normal subjects studied at comparable lung volume. Our results were similar to previous reports. There was no evidence of decreased respiratory muscle force, probably because the patients nutritional status and cardiac output were normal.
Parameters of total, nasal, and tracheobronchial airways resistance and other parameters of lung ventilation were measured in 55 patients with clinical signs of nasal obstruction. After successful surgical operation Rtot, Rn, Raw, functional residual capacity, minute volume of ventilation and breathing frequency decreased whereas maximal expiratory flow rate, one-second forced expiratory volume, vital capacity and tidal volume increased. These changes give evidence that the tracheal and bronchial tone improved and the efficacy of lung ventilation increased.
After one week theophylline therapy with a sustained release preparation (TheoDur 200 and 300 mg), a mean theophylline level of 10 mg/l was obtained in a group of ten patients with chronic asthmatic bronchitis with a mean dosage of 760 mg theophylline/24 h. A good improvement of the lung function was achieved, although only statistically significant for the mid maximal expiratory flow rate (MMEF) and the end expiratory specific airway conductance (sGaw) compared to placebo therapy. Tremor measurements and cyclic-AMP determinations showed a slight increase after theophylline therapy compared to placebo, although not statistically significant.
Forty-nine cardiac surgical patients had ventilatory function tests and measurements of maximum inspiratory (MIP) and maximum expiratory (MEP) pressures preoperatively. The differences between the values of various function tests were compared for patients requiring less than 24 hours of ventilator support and those requiring more than 24 hours. There was a significant difference in the mean values for the two groups in vital capacity (VC) first-second forced expired volume (FEV) midexpiratory flow between 50 and 75 (MMEF 50--75) and 75--85 percent of expired volume (MMEF 75--85), and MEP. The standard deviations of each of the variables were so large that the clinical usefulness was limited. However, when discriminant analysis was used for more than one variable, the combination of MMEF 75--85 and MEP predicted success or failure to wean in 24 hours correctly in 90 percent of instances. On the basis of these simple tests, patients predicted to succeed should be weaned from ventilator support on recovery from anesthesia. Those predicted to fail should be placed on intermittent mandatory ventilation (IMV) and should be weaned following a planned, logical process.