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The maximal mid-inspiratory to maximal mid-expiratory flow rate ratio (MMIF/MMEF) was measured in 16 patients with upper airway obstruction, in eight with pleural disease, in 25 with chest wall abnormalities, in 64 with various lung diseases and in 28 normal subjects. MMIF/MMEF ratio values of less than 1.0 were recorded in eight out of 16 patients with upper airway obstruction, in nine out of 25 patients with chest wall abnormalities and in one normal subject. Our findings show that a MMIF/MMEF ratio less than 1.0 although suggestive, is not diagnostic of upper airway obstruction. However, reduced MMIF/MMEF ratio in the presence of airflow obstruction is specific in localizing obstruction to the upper airway.
The purpose of this study was to evaluate the safety and efficacy of a new lowdose terbutaline sulfate aerosol (375 micrograms) over a six-week period. The question of drug tolerance was also evaluated. Twenty-four ambulant patients with chronic obstructive pulmonary disease with a component of reversible airway disease was evaluated. The patients were tested at two-week intervals during a six-week period. The patients abstained from all bronchodilatory medications for at least 10 hours prior to the time of evaluation. The evaluation consisted of baseline FEV1 and MMEFR determinations, ECG, CBC, urinalysis, and renal and liver function tests. After the terbutaline was administered, a rhythm strip and pulmonary function tests were repeated at 5, 15, 30, 60, 120, and 180 minutes. Throughout the six-week study there was a statistically significant increase in FEV1 and MMEFR, (P less than 0.001). No change was noted in the systolic blood pressures; however, heart rate and diastolic blood pressure decreased significantly. No drug tolerance, paradoxical bronchospasm, subjective side effects, no abnormal laboratory results were noted during the study period.
We have studied the effect of fenoterol, a selective beta-2 adrenergic agent, on airway obstruction in children with asthma. The drug was administered orally in single doses of 2.5, 5, and 7.5 mg to 20 children with chronic stable asthma of moderate severity. The mean age of the children was 11.6 yr. Pulmonary function tests were performed as baseline at zero time and at intervals over a 6-hour period after drug administration. Onset of action for all doses was within 1 hr with a peak effect noted at 1.5 to 3 hr, and sustained improvement was observed over the entire 6 hr. The doses of 5 mg and 7.5 mg were equally effective in producing significant improvement of pulmonary function compared to 2.5 mg (p less than 0.05). Side effects remained acceptable for all patients. The 5 and 7.5 mg doses produced significant adverse effects that involved the central nervous and musculoskeletal systems, whereas the 7.5 mg dose caused a significant incidence of tachycardia. Our findings indicate: (1) fenoterol is a potent oral bronchodilator for large and small airways in children, (2) the 7.5 mg dose does not achieve any additive effect over a 5 mg dose; and (3) 5 mg is the optimal oral dose of fenoterol for children from age 8 to 12 yr.
OBJECTIVE: To assess the effect of a training protocol on aerobic and anaerobic fitness in children with asthma. STUDY DESIGN: Sixteen boys (mean age: 13 years; range: 10-16 years) with mild-to-moderate asthma participated in a rehabilitation program that included 6 weeks of individualized training on a cycle ergometer. Two groups were randomly formed: the control group (CG, n = 7) and the training group (TG, n = 9), which exercised at an intensity set at the heart rate corresponding to the ventilatory threshold, with 1-minute sprints against the maximal aerobic power (MAP) every 4 minutes. Session duration was 45 minutes, 3 sessions per week. Changes in maximal oxygen uptake (VO(2)max), MAP, short-term peak power (PP), and pulmonary function were assessed. RESULTS: Two patients of the training group did not complete the study. Pulmonary function remained unchanged in both groups. Improvement in both aerobic and anaerobic fitness was significant only in the training group (TG vs CG): VO(2)max +18% +/- 2.1% versus +9% +/- 4.5% (P <.05), MAP +32% +/- 5% versus 12% +/- 7% (P <.05), PP +21% +/- 5.7% versus +8.8% +/- 10% (P <.01). CONCLUSION: Exercise training with high-intensity bouts is well tolerated in children with mild-to-moderate asthma. When included in a global rehabilitation program, this type of training improves both aerobic and anaerobic fitness. Anaerobic activities should be considered in sports rehabilitation programs for children with asthma.
We examined aerobic and anaerobic exercise performance in 17 subjects with cystic fibrosis (CF) (age 25+/-10 [SD] yr; 47% females; FEV1 62+/-21% pred) and 17 age- and sex-matched control subjects (age 25+/-8 [SD] yr; 41% females; FEV1 112+/-15% pred) in relation to pulmonary function and nutritional status. Aerobic capacity was determined as maximal oxygen consumption (VO2max) (ml/kg/min) and anaerobic threshold (AT; ml VO2/kg/min) from a graded exercise stress test on an electronically braked bicycle ergometer. Anaerobic performance was assessed from the average work of two bouts of pedaling to exhaustion at a load corresponding to 130% Vo2max from graded exercise. Both aerobic and anaerobic performances were decreased in subjects with CF (p < 0.001). The duration of anaerobic exercise in subjects with CF was similar to control subjects. In control subjects, pulmonary function did not correlate to aerobic or anaerobic exercise. In subjects with CF significant relationships between FEV1, vital capacity, and FEF25-75% to AT were found, suggesting the pulmonary limitation to aerobic capacity. In both patients with CF and control subjects, lean body mass and arm muscle area significantly correlated with anaerobic performance but not with VO2max or AT. We conclude that nutritional status, rather than pulmonary function, is the major determinant of anaerobic exercise capacity in CF. The preserved duration of anaerobic exercise at equivalent workloads (corresponding to 130% of VO2max from graded exercise) suggests that readily available energy stores in muscle may be similar in CF and normal individuals.
High doses of inhaled salbutamol produce substantial improvements in airway response in patients with asthma, and are associated with dose-dependent systemic beta-adrenoceptor responses. The purpose of the present study was to investigate whether tachyphylaxis occurs during prolonged treatment with high dose inhaled salbutamol. Twelve asthmatic patients (FEV1, 81 +/- 4% predicted), requiring only occasional inhaled beta-agonists as their sole therapy, were given a 14-day treatment with high dose inhaled salbutamol (HDS), 4,000 micrograms daily, low dose inhaled salbutamol (LDS), 800 micrograms daily, or placebo (PI) by metered-dose inhaler in a double-blind, randomized crossover design. During the 14-day run-in and during washout periods, inhaled beta-agonists were withheld and ipratropium bromide was substituted for rescue purposes. At the end of each 14-day treatment, a dose-response curve (DRC) was performed, and airway (FEV1, FEF25-75) chronotropic (HR), tremor, and metabolic (K, Glu) responses were measured at each step (from 100 to 4,000 micrograms). Treatment had no significant effect on baseline values. There were dose-dependent increases in FEV1 and FEF25-75 (p less than 0.001), and pretreatment with HDS did not displace the DRC to the right. DRC for HR (p less than 0.001), K (p less than 0.001), and Glu (p less than 0.005) were attenuated after treatment with HDS compared with PI. There were also differences between HDS and LDS for HR (p less than 0.001) and Glu (p less than 0.05) responses. Frequency and severity of subjective adverse effects were also reduced after HDS: tremor (p less than 0.001), palpitations (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
The ability of atropine to inhibit exercise-induced bronchospasm was evaluated in 18 children with chronic, perennial asthma. In 17 of 18 patients, exercise-induced bronchospasm was blocked by prior inhalation of 0.1 mg per kg of atropine sulfate, administered in a randomized single blind fashion. In 14 of these 17 patients, significant bronchodilatation occured after the combination of atropine and exercise. Placebo failed to inhibit exercise-induced bronchospasm in any patient. These results suggest that the parasympathetic nervous system has a role in the mediation of exercise-induced bronchospasm in children.
The frequency, degree, and pattern of bronchial reactivity to exercise were compared in 13 obese and 14 control children, ages 6 to 10 years, with no history of asthma. Spirometry was performed before and every three minutes after a seven-minute exercise challenge on a treadmill. There were 11 obese children and 6 controls who had at least a 15% fall in at least one of three monitored pulmonary function parameters (P < .05). The group mean percentage falls in FEV1 and FEF25%-75% were significantly greater in the obese group than in the controls. The pattern of bronchospasm, occurring soon after the exercise challenge, is consistent with that found in the known asthmatic population. A significant correlation was found between triceps skin-fold thickness and degree of fall in FEF25%-75% (r = .55, P < .005). This study demonstrated that significantly greater frequency and degree of bronchospasm of the smaller airways occur in obese children, partially related to the amount of subcutaneous fat. Whether exercise-induced bronchospasm leads to exercise avoidance and obesity or whether obesity causes or enhances bronchial hyperreactivity to exercise requires further study.
Since no information is available concerning the action of pirenzepine in vivo on human tracheobronchial tree, we evaluated the respiratory responses to pirenzepine in a group of healthy subjects. This clinical study suggests that pirenzepine exerts its bronchodilatory action on small airways (from 9th generation to distal airways), but not on larger airways, in normal subjects. These results are consistent with a probable presence of muscarinic high affinity receptors (M1 subtype) only in peripheral airways.
Albuterol (salbutamol) syrup was studied in 14 asthmatic children (three to six years of age) in a four-week, double-blind, crossover (with placebo) trial to determine efficacy, safety and tolerance. Albuterol was found to be more effective as evaluated by measurements of symptom scores (p less than .01) daily WPF meter (p less than .01) and need for additional medications. Albuterol provided a significant (p less than .01) increase in FEV1 and FEF 25%-75% over three hours. Clinically unimportant effects on heart rate, personality and tremors were noted in most subjects. The authors conclude that albuterol syrup is effective and safe in the young asthmatic.
To determine the effect of two forms of warm-up on postexercise bronchoconstriction in athletes with exercise-induced asthma, 12 moderately trained persons with asthma (age = 26.5 +/- 2.2 yr; height = 169.2 +/- 2.6 cm; weight = 64.3 +/- 2.6kg; VO2max = 52.7 +/- 1.3 ml.kg-1.min-1) were tested under three experimental conditions; continuous warm-up (CW), interval warm-up (IW), and control (C). CW consisted of 15 min of treadmill running at a velocity corresponding to 60% VO2max followed by an exercise challenge test (ET = 6 min at 90% VO2max). IW involved 8 x 30-s runs (1.5 min rest between bouts of exercise), at an intensity equivalent to 100% VO2max, followed by an ET. C consisted of only the ET. FEV1, FVC, and MMEFR were measured prior to the experimental conditions, repeated before the ET, and every 2 min during a 25-min passive recovery period, using a Breon spirometer. Postexercise changes in pulmonary function were recorded as the largest decrese in FEV1, FVC, and MMEFR during the recovery period, and expressed as a percentage of baseline values. Significant differences were detected in %FEV1 (34. 6,16.7,29.7: P = 0.009), %FVC (30.0,10.7,21.0: P = 0.03), and %MMEFR (50.0,30.2,43.4: P = 0.05), in comparing C, CW, and IW, respectively. Scheffe's test detected significance (P < 0.05) between C and CW for all three dependent variables; no statistical significance between C and IW or IW and CW occurred. These data indicate that a continuous warm-up of 15 min at 60% VO2max can significantly decrease postexercise bronchoconstriction in moderately trained athletes.
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Exercise-induced asthma was studied in 8 asthmatics using various conditions of inspired air during exercise. The exercise consisted of walking on a treadmill for 10 min, with a speed and grade elevation adjusted to achieve the target heart rate of approximately 90% of predicted maximum. Pulmonary function tests were performed pre- and post-exercise to determine exercise-induced asthma. With inspired air at 23 degrees C and 15% relative humidity (RH), the post-exercise forced expiratory volume in a sec (FEV1), maximal mid-expiratory flow rate (MMEF), and specific airway conductance (SGaw) decreased to an average of 69, 59 and 38% of the pre-exercise baseline, respectively. In contrast, the exercise-induced asthma was clearly prevented in all subjects by using inspired air at 37 degrees C and 100% RH, when the post-exercise FEV1, MMEF, and SGaw were 99, 100 and 91% of the baseline, respectively. Inspiration of warm, dry air or humid, room air reduced but did not prevent exercise-induced asthma. The results indicate that the primary stimulus for exercise-induced asthma may be heat loss and/or water loss from the airways during exercise.
The bronchodilator effect of three successive stable plasma terbutaline levels was studied in 10 children with asthma. Each terbutaline plateau was achieved by giving a rapid intravenous infusion of terbutaline, 0.9 microgram/kg, followed by a continuous infusion for 2 hours. Mean plasma terbutaline concentrations (18, 36, and 53 nmol/L at the three plateaus) were found to correlate linearly with the maintenance dose of terbutaline (2.4, 4.5, and 6.3 micrograms/kg/hr, respectively). Mean forced expiratory volume in 1 second increased from 65% to 96%, and mean forced mid-expiratory flow from 32% to 71% of the predicted normal value during the study (p less than 0.01); maximum bronchodilation was obtained at mean terbutaline levels of about 30 nmol/L (range 20 to 60). Effective plasma terbutaline levels were associated with side effects such as headache and tremor in all patients. In addition, heart rate increased from 84 to 116 beats/min, systolic blood pressure rose from 115 to 129 mm Hg, and diastolic blood pressure dropped from 72 to 61 mm Hg during the study. We conclude that a loading dose of 2 micrograms terbutaline per kilogram of body weight over 5 minutes, followed by a continuous infusion of 4.5 micrograms terbutaline per kilogram per hour, is suitable for treatment of severe bronchoconstriction in children. Because of interindividual variations in drug metabolism and clinical effect, dose adjustment should be evaluated at regular intervals.
OBJECTIVE: We have previously found that beta2-adrenoceptor downregulation and bronchodilator desensitization to albuterol occurred at 36 hours after stopping regular treatment with twice daily salmeterol. In this study we have evaluated these same effects with formoterol given once or twice daily on a regular basis. METHODS: In a randomized, placebo-controlled, double-blind, double-dummy crossover study, 16 subjects with mild-to-moderate stable asthma (mean [SD] age, 32.5 [15.3] years; mean [SD] FEV1, 73.2 [12.1] percent predicted) receiving regular inhaled corticosteroid therapy received 1 week of treatment with formoterol dry powder (24 microg twice daily [8 AM/8 PM]), formoterol (24 microg once daily [8 PM]), or identical placebo. Lymphocyte beta2-adrenoceptor parameters and a dose-response curve to inhaled albuterol (200 to 1600 microg) were evaluated at 36 hours after the last dose of each treatment period. RESULTS: There were no significant differences in the mean values for albuterol dose-response effects among the three treatment regimens. Comparison of maximal bronchodilator responses between treatments (mean and SEM as change from baseline) revealed no significant differences between treatments for FEV1 (0.47 L [0.06 L] for placebo vs 0.48 L [0.07 L] for 24 microg once daily formoterol vs 0.51 L [0.08 L] for 24 microg twice daily formoterol) or for forced expiratory flow, mid-expiratory phase (FEF25-75) (0.80 L/sec [0.12 L/sec] for placebo vs 0.80 L/sec [0.16 L/sec] for 24 microg once daily formoterol vs 0.89 L/sec [0.14 L/sec] for 24 microg twice daily formoterol). Formoterol also had no significant effect on mean lymphocyte beta2-adrenoceptor density. However, in five of seven patients with the homozygous Gly-16 polymorphism, beta2-adrenoceptor density was downregulated by twice daily formoterol, whereas only two such cases exhibited a reduction in maximal FEV1 response to albuterol. CONCLUSIONS: The results of this study showed that for patients taking inhaled corticosteroids, overall beta2-adrenoceptor regulation and associated bronchodilator sensitivity to inhaled albuterol were unaltered at 36 hours after stopping regular treatment with formoterol. However, in a subset of patients who were Gly-16 homozygous, there was a tendency towards downregulation but not desensitization. Further studies in subjects with more severe asthma are required to assess the clinical relevance of these findings.