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Celiprolol, atenolol and propranolol: a comparison of pulmonary effects in asthmatic patients.

Celiprolol, a new beta-adrenoceptor antagonist, blocks serotonin- and methacholine-mediated bronchoconstriction in animals, even in the presence of propranolol. In two, randomized, placebo-controlled, 5-way crossover trials, the pulmonary effects of celiprolol 200 and 400 mg, propranolol 40 mg and atenolol 100 mg were compared in 34 asthmatic patients. Pulmonary function was measured after single doses of each agent, and again following subsequent, graded doses of albuterol or isoproterenol aerosol. Changes in one-second forced expiratory volume (FEV1) and maximal midexpiratory flow rate (FEF25-75) prior to albuterol or isoproterenol were positive after placebo and both doses of celiprolol. Propranolol, and to a lesser extent, atenolol, caused significant reductions in both measures of pulmonary function. Overall changes in FEV1 following each drug plus isoproterenol or albuterol were positive, in the rank order, celiprolol approximately placebo greater than atenolol greater than propranolol. Propranolol pretreatment caused a significant reduction in the effect of bronchodilator. Unlike atenolol and propranolol, celiprolol was highly bronchosparing and did not antagonize sympathomimetic bronchodilators.

Adrenergic beta-Antagonists↗

Protease inhibitor variants in children and young adults with chronic asthma.

The results of systematic medical histories and pulmonary function tests on 26 children and young adults, 10 with Pi variant alpha1-antitrypsin phenotypes and 16 Pi normals, are reported. These subjects were selected from 57 consecutive patients who had chronic asthma. The incidence of Pi variants was 20.4% among 46 Caucasian subjects (ages seven to 21 years). The Pi variant patients required more bronchodilators and long-term corticosteroid therapy. Among the parents and siblings, 50% of those with abnormal Pi type had chronic obstructive lung disease. Grandparents of the Pi abnormal probands had greater incidence of chronic obstructive lung disease (P less than 0.05). Baseline specific airways conductance and maximal midexpiratory flow rates did not discriminat between the two groups. However, bronchodilator inhalation showed the Pi variant group to be significantly less responsive than the Pi normal group. Pi heterozygous state, particularly Pi MZ, should be considered when a young person with chronic asthma is unresponsive to adequate doses of bronchodilators and needs prolonged use of corticosteroids.

Adolescent↗

Tests of minimal obstruction in the small airways: interrelationships and physiologic significance.

Several technics have become popular to detect airway obstruction in the small (less than 2 mm diameter) peripheral bronchi which appear to be the site of the early lesions in chronic obstructive pulmonary disease (COPD). These include determining maximal midexpiratory flow rate (MMFR) from the expiration spirogram, maximum expiratory flows at low lung volumes from the maximum expiratory flow-volume (MEFV) curve, a comparison of flow-volume curves during air and helium/O2 breathing, demonstration of frequency dependence of compliance, and the measurement of closing volume (CV). This discussion attempts to interpret the literature relative to these tests, examining their physiologic basis and clinical significance while relating them to the standard spirometric tests. The aim is to provide the clinical anesthesiologist with a better understanding of the information they provide, since their physiologic basis relates well to the many aspects of abnormal lung function which appear during anesthesia and the entire perioperative period.

Airway Obstruction↗

Relations of smoking and diving experience to pulmonary function among U.S. Navy divers.

The relations of 4 pulmonary function parameters (measured from the forced expiratory spirogram) with diving experience (in years) and indices of cigarette smoking were examined in a group of 93 healthy U.S. Navy divers. Years of diving was not significantly related to lung function. The value for pack-years of smoking was inversely associated with both percentage of predicted forced expiratory volume in 1 s (FEV1) and percentage of predicted maximal midexpiratory flow rate (MMFR). Divers who have relatively heavy smoking histories may be at greater risk for developing significant decline in pulmonary function, and diving exposure factors other than years of diving may contribute to this risk.

Adult↗

[Pulmonary arterial hypertension of unknown etiology. Study of the cardiopulmonary function].

Thirty two cases of pulmonary arterial hypertension of unknown etiology (PAH-UE) were studied. The diagnosis was established by exclusion after the results of hemodinamics studies. Ninety percent of cases had severe PAH (100 mmHg). The end diastolic right ventricular pressure was elevated in 46% of cases. The total pulmonary vascular resistance was increased in the order of the 1700 dinas. seg. cm-5. The cardiac index was 3.3 1/m2 with a right ventricular work index of 3.96 K gm min. The total lung capacity (TLC) was normal, with a vital capacity (VC) of 78% of the predicted value. The residual volume was increased. The mean value of the maximal midexpiratory flow rate (MMFR) was 78%. The A-a gradient of O2 was 30 mmHg, with a venous mixture expressed as a percentage ratio of the cardiac output (Qva/Qt) of 26%. The mean paO2 mmHg and the anatomical pulmonary artery to vein shunt (Qs/Qt) was 9%, with a DLco normal. The clinical hemodinamic correlation was in good agreement. Our results suggested that PAH-UE "per se" has effect in pulmonary function changing slight lung mechanics, and in a moderate degree lung gas exchange. The hipoxemia results meanly from V/Q imbalance.

Adolescent↗

Lung function in tetralogy of Fallot after intracardiac repair.

Earlier studies have shown significant restrictive lung volume patterns in virtually all patients after shunt palliation and/or subsequent intracardiac repair (ICR) of tetralogy of Fallot. We have studied lung volumes and capacities, maximum voluntary ventilation (MVV), and maximum mid-expiratory flow (MEF[25-75]) at least 1 year after ICR in 123 patients, 91 males and 32 females, which included 54 who underwent primary ICR. All were evaluated by stress testing and 61 were studied serially from two to eight times at 12 to 18 months intervals. In contrast to the previous studies, we found a lower incidence and lesser degrees of restrictive lung volume patterns. Lung volumes may be entirely normal particularly after primary ICR but also when ICR is preceded by shunt palliation. After reoperation for ICR normal lung volumes are uncommon. These is a high correlation between abnormal lung volumes and poor surgical results of ICR as manifested by residual cardiac disease, notably pulmonic valve insufficiency and increased heart size. In primary repair we found no correlation between the presence of abnormal lung volumes and the age at ICR (range 1.87 to 15.4 years). Abnormal lung volumes correlate with reduced exercise performance, but the latter is limited by cardiovascular rather than pulmonary factors. Serial studies show stable lung volume patterns with time, and we found no evidence that the increased level of physical activity usually present after ICR results in increases of lung volumes in excess of those predicted from somatic growth. We conclude that an excellent surgical repair of tetralogy is the best guarantee against a significant restrictive lung volume pattern after repair.

Adolescent↗

[Acute altitude sickness and ventilatory function in subjects intermittently exposed to hypobaric hypoxia].

Aiming to assess the magnitude of acute mountain sickness symptoms and ventilatory function in subjects intermittently exposed to hypobaric hypoxia, we studied 48 healthy men aged 32.6 +/- 8.2 years old who worked in a gold mine at a altitude of 4600 m, using a schedule of 8-12 days of work at the mine followed by 4 days of rest at the sea level. Studies were performed at the sea level (A), during the first two days of ascension (B) and after three or four days of stay at 4600 m (C). Mountain sickness symptoms were evaluated with a questionnaire devised in the 1991 International Hypoxia Symposium and respiratory function was assessed with a Collins Eagle II respirometer, following American Thoracic Society recommendations. Subjects reported mild to moderate symptoms during the first 24 hours of ascending (mean score of 6.4 +/- 3.1 for a maximum of 15). Forced vital capacity fell significantly in period B and returned to normal in period C and forced expiratory volume in 1 s did not change in any period. However, maximal expiratory flow and maximal midexpiratory flow rate significantly increased and remained elevated during the four days stay at the mine. No correlation was found between acute mountain sickness symptoms and changes in ventilatory function.

Adult↗

The ventilatory response to carbon dioxide in asthmatic children, measured by the mouth-occlusion method (Pm100).

Ventilatory responses to carbon dioxide vary widely in patients with bronchial asthma; some have a high response despite increased airway resistance. This paradoxical response was studied in 31 asthmatic children and 22 age-matched healthy children. Measurement of the ventilatory response to carbon dioxide with a conventional rebreathing method showed wide variation in the patients, paralleling the degree of their airway obstruction as measured by the one-second forced expiratory volume and maximal midexpiratory flow rate, but their mean response was similar to that in the control subjects. The ventilatory response was then determined with a new index (Pm100), which rises linearly with increasing carbon dioxide concentration. Despite wide variation in the slope of Pm100 in the patients, their mean response significantly exceeded normal, confirming that the neurochemical drive is increased in bronchial asthma.

Adolescent↗

Forced expiratory maneuvers in very young children. Assessment of flow limitation.

The application of negative expiratory pressure (NEP) to the airway opening during forced expiratory maneuvers has recently been described as a noninvasive method to assess whether flow limitation is achieved in adults. This methodology has great potential for extending the measurement of forced expiratory maneuvers to young children who may not produce maximal efforts as reproducibly as adults. We used NEP to assess flow limitation in 10 children between 3 and 5 yr of age. NEP was well tolerated by all subjects. With the application of NEP, there was not a step increase in flow, a finding consistent with flow limitation for the subjects. In addition to visual inspection, we proposed a method to quantify the change in flow during a short NEP. The flow-volume curves obtained with and without NEP were visually the same, other than the flow transients produced by NEP. The calculated values of FVC and FEF25-75 were not significantly different when measured from flow- volume curves with and without NEP. There was a statistically significant increase in FEV1 with NEP; however, the group mean increase in FEV1 was less than 2%. We conclude that NEP may be a useful technique to determine whether flow limitation has been achieved in young children performing forced expiratory maneuvers.

Child, Preschool↗

Effects of inhaled fenoterol on the circadian rhythm of expiratory flow in allergic bronchial asthma.

Metered-dose aerosol treatment with fenoterol for three consecutive days, in eight patients suffering from allergic asthma, caused the disappearance of FEV1 and MEF50 circadian rhythm. We attribute such behavior to the suppression of the bronchomotor tone induced by fenoterol. The administration on different days of a single dose of fenoterol aerosol in another group of eight patients pointed out the variability of the effects of the drug at different hours of the day. We believe the results obtained are important for a better dosage and time distribution of the therapy with beta2 agonists.

Adult↗

Maximum flow ratios at mid-vital capacity in young healthy adults.

Upper airway obstruction is usually diagnosed by visual examination of maximum expiratory and inspiratory flow-volume curves and by calculating a ratio of expiratory to inspiratory flow at 50 percent of vital capacity (mid-vital capacity flow ratio); however, reference values of this ratio have not been well established, and considerable variability exists. The purpose of this study was to examine the range of mid-vital capacity flow ratios in a group of healthy subjects and to determine if some of the variability is accounted for by different maximum inspiratory pressures. We measured maximum expiratory and inspiratory flows at 50 percent of vital capacity from the flow-volume curves, and maximum inspiratory pressures in a group of 60 healthy nonsmokers (30 men and 30 women) whose ages ranged from 21 to 40 years. We found that mid-vital capacity flow ratio (mean +/- SD) was 0.72 +/- 0.19 in men and 0.77 +/- 0.18 in women. The coefficient of variation of the mid-vital capacity flow ratio was 28 percent for men and 23 percent for women. The 95 percent confidence limits for the mid-vital capacity flow ratio were 0.65 to 0.79 for men and 0.70 to 0.84 for women. Maximum inspiratory pressures (mean +/- SD) were 129 +/- 30 cm H2O in men and 91 +/- 16 cm H2O in women, not significantly different from previous studies. Normalizing maximum inspiratory flow for maximum inspiratory pressure did not reduce the coefficient of variation, which became 29 percent in men and 30 percent in women. We conclude that the range of mid-vital capacity flow ratios is wide, and it cannot be reduced by standardizing it for maximum inspiratory pressures.

Adult↗