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Effects of hyperoxia on maximal leg O2 supply and utilization in men.

We studied O2 transport in the leg to determine if hyperoxia will increase the maximal rate of O2 uptake (VO2max) in exercising muscle. An increase in inspired O2 fraction (FIO2) from 0.21 to 1.00 was postulated to have the following effects: 1) increase the leg VO2max by approximately 5-10%, 2) increase the maximal O2 delivery [arterial O2 concentration.flow (CaO2.Q] by approximately 10%, and 3) raise the leg VO2max in proportion to both the femoral venous PO2 and mean leg capillary PO2. To test these hypotheses, 11 men performed cycle exercise to the highest work rates (WRmax) they could achieve while breathing 100% O2 (hyperoxia), 21% O2 (normoxia), and 12% O2 (hypoxia). Leg VO2 was derived from duplicate measurements of femoral venous blood flow and CaO2 and femoral venous blood O2 concentrations (CVO2) at 20, 35, 50, 92, and 100% WRmax in each FIO2. Femoral venous leg Q (Qleg) was measured by the constant-infusion thermodilution technique, and leg O2 uptake (VO2) was determined by the Fick principle [VO2 = Qleg(CaO2-CVO2)]. Leg VO2max was the mean of duplicate values of VO2 at 100% WRmax for each FIO2. Hyperoxia increased leg VO2max by 8.1% (P = 0.016) and maximal O2 delivery by 10.9% (P = 0.05) without changing Qleg. There was a significant increase in femoral venous PO2 (P < 0.001) that was proportionally greater than the increase in leg VO2max. The results support our first and second hypotheses, providing direct evidence that in normal subjects leg VO2max is limited by O2 supply during normoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Influence of environmental temperature and humidity on bronchial responses during assessment of selectivity of beta-adrenoceptor antagonists in man.

1 The effects of beta-adrenoceptor antagonists given intravenously in single doses were examined in a double-blind, placebo controlled study performed in six healthy volunteers. Heart rate and peak expiratory flow rate (PEFR) were measured at rest and during standardised exercise. 2 Atenolol 0.2 mg/kg, betaxolol 0.15 mg/kg, practolol 1 mg/kg and propranolol 0.2 mg/kg all reduced heart rate to a similar extent during exercise at 2 and 4 h after administration; betaxolol 0.6 mg/kg had a significantly greater effect than the other treatments at all times. Only betaxolol 0.15 and 0.6 mg/kg significantly inhibited exercise tachycardia at 24 h. 3 None of the treatments studied had any effect on PEFR at rest or during exercise. 4 A second study was performed to determine whether this lack of effect of propranolol on exercise PEFR could have been due to the warm and humid conditions prevailing during the experiment. Eight healthy men underwent a standardised exercise test under alternately 'warm and humid' and 'cool and dry' conditions before and after propranolol 0.2 mg/kg or saline placebo intravenously. 5 Propranolol treatment did not influence resting or exercise PEFR in either environment, but did reduce FEV1 immediately after exercise under the cool and dry conditions but not under the warm and humid conditions. 6 Comparison of the effects of beta-adrenoceptor antagonists on exercise heart rate and PEFR is not a reliable or sensitive method of measuring the cardioselectivity of these drugs. 7 Environmental temperature and humidity should ideally be controlled when the action of any drug on airflow resistance is being studied.

Adrenergic beta-Antagonists↗

Respiratory and cardiac effects of metoprolol and bevantolol in patients with asthma.

The effects on standing heart rate and respiratory function of two relatively selective beta 1-adrenoceptor antagonists, metoprolol and bevantolol, were compared in a double-blind, randomized, crossover study of 16 patients with asthma. After control observations on 2 separate days, the patients received approximately equivalent cardiac beta-adrenoceptor antagonist doses of metoprolol, 12.5, 25, 50, and 100 mg, and bevantolol, 18.75, 37.5, 75 and 150 mg, at intervals of 2 hours. Dosing was stopped if symptoms warranted or if there was a fall of greater than or equal to 20% in the forced expiratory volume in 1 second. In general, the cumulative dosing regimen proved a safe and effective means of assessing bronchial responsiveness to these beta-blockers in asthma, but one patient had to be dropped from the study because of severe bronchoconstriction after the first dose. Of the 15 patients studied who were taking both drugs, seven patients were withdrawn prematurely. In these seven patients, the average maximum tolerated cumulative doses were 45.5 mg bevantolol and 26.8 mg metoprolol, doses that are much lower than those usually required for therapeutic activity. The respiratory response to either drug could not be predicted.

Administration, Oral↗

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↗

Effect of body position on maximal expiratory pressure and flow in adults with cystic fibrosis.

Maximum expiratory pressure (MEP) and peak expiratory flow rate (PEFR) are used as surrogate measures of cough and huff strength. Some body positions (particularly head-down tilt) significantly affect these measures in people with normal respiratory function and with chronic obstructive pulmonary disease. This may have implications for people with cystic fibrosis (CF), who use coughing and huffing and may use gravity-assisted drainage positions for airway clearance. Previous research concluded that body position does not affect MEP in people with CF, although head-down tilt was not examined and PEFR was not measured. This study investigated the effect of body position on MEP and PEFR in 20 adults with stable CF. Repeated measures of MEP and PEFR were performed across seven positions (standing, chair-sitting, sitting in bed with backrest vertical, sitting in bed with backrest at 45 degrees , supine, side-lying, and side-lying with head-down tilt 20 degrees ) in random order. During testing, reflux sensation and oxygenation were monitored. MEP was significantly reduced in side-lying and in the head-down tilt position. PEFRs were significantly reduced in the three-quarters sitting, supine, side-lying, and head-down positions. Oxygenation and reflux scores were worst in the head-down position. Despite statistical significance, the differences observed between positions in this stable population were of small magnitude. The effect of body position on MEP and PEFR may be more relevant during airway clearance treatments of the acutely unwell person with CF.

Adolescent↗

Does Ramadan fasting affect expiratory flow rates in healthy subjects?

OBJECTIVE: To assess whether Ramadan fasting affects the expiratory flow rates in healthy subjects, and to know if these effects correlate to a change in other variables. METHODS: This unmatched case-control longitudinal study includes 46 non-smoking healthy subjects who undertook lung function testing at the Aga Khan University, Pakistan. Expiratory flow rates and body mass were measured in 3 Islamic months, corresponding to November 2001 to January 2002. RESULTS: There was a significant reduction in body mass in Ramadan compared to pre and post Ramadan. No significant changes in expiratory flows were seen during Ramadan as compared to the pre Ramadan period. However, forced expiratory flow rates at 75% of vital capacity (FEF(75)) and between 75% and 85% of vital capacity (FEF(75-85)) showed a significant increase in the post Ramadan period compared to Ramadan. Changes in FEF(75) were negatively correlated to changes in body mass between Ramadan and post Ramadan. CONCLUSION: This study shows that Ramadan fasting will not affect expiratory flow rates in healthy subjects. Post Ramadan values did show an increase in FEF(75) and FEF(75-85), possibly due to changes in body water and fat content. The reductions in body mass were most probably due to lack of nutrition and not dehydration as the fasts were performed in winter. Collection of reference values or early phase clinical trials measuring expiratory flow rates should not be affected by Ramadan fasting.

Adolescent↗

A study of twelve Southern California communities with differing levels and types of air pollution. II. Effects on pulmonary function.

To study the possible chronic respiratory effects of air pollutants, we designed and initiated a 10-yr prospective study of Southern California public schoolchildren living in 12 communities with different levels and profiles of air pollution. The design of the study, exposure assessment methods, and survey methods and results related to respiratory symptoms and conditions are described in the accompanying paper. Pulmonary function tests were completed on 3,293 subjects. We evaluated cross-sectionally the effects of air pollution exposures based on data collected in 1986-1990 by existing monitoring stations and data collected by our study team in 1994. Expected relationships were seen between demographic, physical, and other environmental factors and pulmonary function values. When the data were stratified by sex, an association was seen between pollution levels and lower pulmonary function in female subjects, with the associations being stronger for the 1994 exposure data than the 1986-1990 data. After adjustment, PM10, PM2.5, and NO2 were each significantly associated with lower FVC, FEV1, and maximal midexpiratory flow (MMEF); acid vapor with lower FVC, FEV1, peak expiratory flow rate (PEFR), and MMEF; and O3 with lower PEFR and MMEF. Effects were generally larger in those girls spending more time outdoors. Stepwise regression of adjusted pulmonary function values for girls in the 12 communities showed that NO2 was most strongly associated with lower FVC (r = -0.74, p < 0.01), PM2.5 with FEV1 (r = -0.72, p < 0.01), O3 with PEFR (r = -0.75, p < 0.005), and PM2.5 with MMEF (r = -0.80, p < 0.005). There was a statistically significant association between ozone exposure and decreased FVC and FEV1 in girls with asthma. For boys, significant associations were seen between peak O3 exposures and lower FVC and FEV1, but only in those spending more time outdoors. These findings underline the importance of follow-up of this cohort.

Acids↗

Intravenous enprofylline in the treatment of patients with acute asthma.

The safety and efficacy of enprofylline were studied in 55 moderately severe asthmatic patients [forced expiratory volume in 1 s (FEV1) and peak expiratory flow rate (PEFR) no more than 50% of predicted values] presenting with an acute attack. A bolus injection of 1.5 mg/kg enprofylline was given over 20 min and then maintenance infusion of 0.4 mg/kg.h enprofylline for up to 24 h. On admission, 200 mg hydrocortisone was administered intravenously and additional oxygen and/or inhaled beta 2-agonist therapy was permitted after 1 h; this additional therapy was given to 39 patients. The bolus injection increased the PEFR from 121 +/- 44 l/min to 164 +/- 49 l/min at 20 min, with a further improvement during the maintenance infusion to 200 +/- 79 l/min at 24 h. Heart rate and blood pressure decreased towards normal in parallel with the improvement in lung function. The mean steady-state enprofylline plasma concentration was slightly higher than predicted. The mean renal clearance and recovery of enprofylline from urine were in good agreement with results previously obtained from healthy Caucasian subjects.

Acute Disease↗

Bronchoconstrictor effects of leukotriene E4 in normal and asthmatic subjects.

The bronchoconstrictor activity of an aerosol of leukotriene E4(LTE4) was compared with that of histamine in 5 normal and in 6 asthmatic subjects to define the relative potency of LTE4 between the groups using 3 indices of airway response. The FEV1 and the flow rate measured at 30% of vital capacity from partial and maximal expiratory maneuvers (V30-P and V30-M) were measured. The geometric mean (GSEM) concentration of LTE4 required to reduce the V30-P by 30% was 0.30 (1.46) mM in the normal subjects, and 0.058 (1.63) in the asthmatic subjects; LTE4 was 39-fold more potent than histamine in the former and 14-fold in the latter group. Further, we observed that when normal and asthmatic subjects were compared at a degree of bronchoconstriction resulting in a 30% decrement in the V30-P after inhaling LTE4, there was a greater response in the asthmatic group than in the normal group of the accompanying change in the FEV1. The decrements in the FEV1 were not significantly different between the 2 groups after inhaling histamine. This study demonstrates that LTE4 is a potent bronchoconstrictor agonist in humans and suggests that airway responsiveness to this agonist differs substantially with the index of bronchoconstriction used for assessment of airway response.

Aerosols↗

Subacute effects of heavy marihuana smoking on pulmonary function in healthy men.

To evaluate the subacute effects of heavy marihuana smoking on the lung, pulmonary function was tested in 28 healthy young male experienced cannabis users, before and after 47 to 59 days of daily ad-libitum marihuana smoking (mean of 5.2 marihuana cigarettes per day per subject, 2.2 per cent delta9-tetrahydrocannabinol). Base-line pulmonary-function studies were nearly all within normal limits, but after 47 to 59 days of heavy smoking, statistically significant decreases in forced expired volume in one second (3 +/- 1 per cent, S.E.), maximal mid-expiratory flow rate (11 +/- 2 per cent), plethysmographic specific airway conductance (16 +/- 2 per cent) and diffusing capacity (8 +/- 2 per cent) were noted as compared with the base-line studies. The decreases in maximal mid-expiratory flow rate and specific airway conductance were correlated with the quantity of marihuana smoked. These findings suggest that customary social use of marihuana may not result in detectable functional respiratory impairment in healthy young men, whereas very heavy marihuana smoking for six to eight weeks causes mild but statistically significant airway obstruction.

Adult↗

Late pulmonary sequelae of bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia is a chronic lung disease that often develops after mechanical ventilation in prematurely born infants with respiratory failure. It has become the most common form of chronic lung disease in infants in the United States. The long-term outcome for infants with bronchopulmonary dysplasia has not been determined. METHODS: We studied the pulmonary function of 26 adolescents and young adults, born between 1964 and 1973, who had bronchopulmonary dysplasia in infancy. We compared the results with those in two control groups: 26 age-matched adolescents and young adults of similar birth weight and gestational age who had not undergone mechanical ventilation, and 53 age-matched normal subjects. RESULTS: Sixty-eight percent of the subjects with bronchopulmonary dysplasia in infancy (17 of the 25 tested) had airway obstruction, including decreases in forced expiratory volume in one second, forced expiratory flow between 25 and 75 percent of vital capacity, and maximal expiratory flow velocity at 50 percent of vital capacity, as compared with both control groups (P less than 0.0001 for all comparisons). Twenty-four percent of the subjects with bronchopulmonary dysplasia in infancy had fixed airway obstruction, and 52 percent had reactive airway disease, as indicated by their responses to the administration of methacholine or a bronchodilator. Hyperinflation (an increased ratio of residual volume to total lung capacity) was more frequent in the subjects with a history of bronchopulmonary dysplasia than in either the matched cohort (P less than 0.0006) or the normal controls (P less than 0.0004). Six of the subjects who had bronchopulmonary dysplasia in infancy had severe pulmonary dysfunction or current symptoms of respiratory difficulty. CONCLUSIONS: Most adolescents and young adults who had bronchopulmonary dysplasia in infancy have some degree of pulmonary dysfunction, consisting of airway obstruction, airway hyperreactivity, and hyperinflation. The clinical consequences of this dysfunction are not known.

Adolescent↗

Severe acute asthma: a comparison of three methods of inhaling salbutamol.

The effects of salbutamol inhaled by three different methods were compared in groups of adult patients with severe acute asthma. 2 x 400 micrograms Rotacaps was the optimum dose of dry powder but about 40% of patients failed to respond to it. 5 mg salbutamol nebulized with IPPB resulted in a significant increase in peak expiratory flow rate when given before or after either Rotacaps or salbutamol nebulized without IPPB, whereas neither the dry powder nor the nebulized drug without IPPB resulted in significant change when given after salbutamol nebulized with IPPB. The extra benefit derived with IPPB is only slight and requires a device of appropriate characteristics. Occasional patients fail to respond to salbutamol inhaled by any means, generally those with the most severe airflow limitation.

Acute Disease↗

Overreactivity of the psyche or the soma? Interindividual associations between psychosomatic symptoms, anxiety, heart rate, and end-tidal partial carbon dioxide pressure.

Current research has all but refuted previous suggestions about the role of hyperventilation as a proximal, common cause of psychosomatic symptoms. As an alternative, it has been proposed that the experience of psychosomatic symptoms is primarily associated with psychological mechanisms, i.e., with enhanced tendencies of distressed individuals to focus their attention on bodily sensations and to evaluate these in a catastrophic manner. Although this hypothesis has received considerable empirical support, physiological influences on symptom reporting have not, as yet, been fully explored. In this study, contributions of psychological and physiological factors were studied among a group of 83 normal healthy male subjects by an assessment of the interindividual relationships between symptom experience in daily life, situational and dispositional anxiety, baseline end-tidal partial carbon dioxide pressure (PCO2), and heart rate. Trait anxiety and end-tidal PCO2 each contributed separately to the prediction of the psychosomatic symptom score. Trait anxiety explained nearly one third of the symptom variance, and an additional 4% was explained by PCO2. Psychological symptoms were more strongly associated with anxiety and somatic symptoms, more strongly with PCO2. Heart rate only tended to be correlated with symptom reporting. Analysis of covariance among subgroups of extreme-symptom reporters supported the correlational findings by demonstrating that the association between hyperventilation and symptom reporting remained intact when psychological influences were factored out. The findings suggest that reports of psychosomatic symptoms represent two distinct components: one that is primarily psychological (and is unrelated to physiological factors) and a second that reflects objective variance in physiological functioning. The influence of the first component is probably greater than that of the second.

Adult↗

Controlled exposures of volunteers with chronic obstructive pulmonary disease to sulfur dioxide.

Twenty-four volunteers with chronic obstructive pulmonary disease (COPD) were exposed to sulfur dioxide (SO2) at 0, 0.4, and 0.8 ppm in an environmental control chamber. Exposures lasted 1 hr and included two 15-min exercise periods (mean exercise ventilation rate 18 liter/min). Pulmonary mechanical function was evaluated before exposure, after initial exercise, and at the end of exposure. Blood oxygenation was measured by ear oximetry before exposure and during the second exercise period. Symptoms were recorded throughout exposure periods and for 1 week afterward. No statistically significant changes in physiology or symptoms could be attributed to SO2 exposure. Older adults with COPD seem less reactive to a given concentration of SO2 than heavily exercising young adult asthmatics. This may be due to lower ventilation rates (i.e., lower SO2 dose rates) and/or to lower airway reactivity in the COPD group.

Aged↗

Sauna to transiently improve pulmonary function in patients with obstructive lung disease.

The influence of sauna on pulmonary functioning in patients with an obstructive pulmonary disease was studied in 12 male patients by measuring forced vital capacity (FVC) and forced expiratory volume in one second on seven measure points the day of the sauna program. Despite the fact that body cooling and changes in osmolality of bronchial liquid can induce bronchoconstriction, we measured a significant improvement of the lung function parameters: FVC values were 3.22 +/- 0.89 and 3.6 +/- 0.99 before and after the sauna program, respectively. It is concluded that patients with an obstructive pulmonary disease can take part in sauna programs without eliciting bronchoconstriction; sauna even causes transient improvement of the lung function.

Adult↗

The effect of body position on maximal expiratory pressure and flow.

Positioning combined with coughing and huffing is frequently used to promote secretion clearance. Maximum expiratory pressure (MEP) and peak expiratory flow rate (PEFR) have been used as surrogate measures of cough and huff strength. This study investigated the effect of body position on MEP and PEFR. Repeated measures of MEP and PEFR were performed across seven randomised positions (standing, chair sitting, sitting in bed with backrest vertical, sitting in bed with backrest at 45 degrees, supine, side lying, and side lying with head down tilt 20 degrees) on 25 adults with normal respiratory function (NRF) and 11 adults with chronic airflow limitation (CAL). For the NRF group, MEP in standing (143+/-10cmH2O, mean+/-SEM) was significantly higher than MEP in chair sitting (133+/-10cmH2O) which in turn was significantly higher than in the remaining positions. The MEP in head down tilt (108+/-9cmH2O) was significantly lower than in all other positions. The PEFR in standing (571+/-24L/min) was significantly higher and head down tilt (486+/-23L/min) was significantly lower than in all other positions. For the CAL group, MEP in standing (134+/-18cmH2O) was significantly higher, while in head down tilt (96+/-15cmH2O) was significantly lower, than in most other positions. For the CAL group, PEFR in standing (284+/-40ml/sec) was significantly higher, while in head down tilt (219+/-38ml/sec) was significantly lower, than in most other positions. Body position has a significant effect on MEP and PEFR in NRF and CAL subjects, with the lowest values in the head down position. Thus, to maximise the strength of expiratory manoeuvres during treatments that use the head down position, patients should be encouraged to adopt a more upright position when coughing or huffing.

Adolescent↗