The maximal aerobic capacity of adult Puerto Ricans.
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We have compared the effects of the leukotriene (LT) D4 antagonist L-649,923 and placebo on the airway response to antigen challenge in eight men with mild asthma known to have both an early and late response to inhaled antigen. Subjects ingested 1000 mg of L-649,923 or placebo in a randomized, double-blind protocol and, two hours later, inhaled the dose of antigen known to induce a 20% fall in FEV1. Pulmonary function (specific conductance, FEV1, peak expiratory flow rate, and maximal flow at 25% of vital capacity) was measured at intervals before and up to 9 hours after antigen. FEV1 fell in one subject after L-649,923 ingestion. L-649,923 in the other seven subjects caused no change in baseline pulmonary function, a small reduction in the early response to antigen for FEV1, peak expiratory flow rate, and maximal flow at 25% of vital capacity but not for specific airway conductance (six subjects only) and no effect on the late response. The mean maximum fall in FEV1 in the early response was 1.35 L after L-649,923 ingestion and 1.78 after placebo ingestion. This relatively small degree of protection by L-649,923 suggests either that L-649,923 is not a sufficiently potent antagonist to diminish the effect of endogenous LTD4 in vivo or that LTD4 does not play a major role in the airway response to antigen challenge.
Forced expiratory flows (FEF) can be measured in infants from lung volumes initiated near total lung capacity. In order to establish reference values and to evaluate lung growth, we obtained measurements in 155 healthy subjects between 3 and 149 wk of age. Forced vital capacity (FVC) was highly correlated with body length; however, after accounting for length, age was also significant. When subjects were divided at the median age (40 wk) younger compared with older subjects had a significantly larger slope for length (3.7 versus 2.8; p = 0.002). The flow parameters (FEF(50), FEF(75), FEF(85), and FEF(25-75)) were highly correlated with length, and those infants whose mothers smoked had lower flows. For FEF(75), male subjects had lower flows than female subjects. The relationship between FEF and volume was assessed using FEV(0.5)/FVC, which decreased with increasing length. Smaller subjects emptied their lung volume proportionately faster. We conclude that our study provides reference values for this age group and demonstrates that smoke-exposed infants and male subjects have decreased FEF. In addition, our findings indicate that lung volume increases most rapidly during the first year of life and that airways are large relative to lung volume very early in life.
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To assess the effect of an upper respiratory tract infection (URTI) on airway reactivity, histamine inhalation tests (HITs) were performed prospectively in 44 nonsmoking asthmatic (14) and nonasthmatic (30) volunteers. Fifteen of the subjects developed an URTI during the following 4 months. Pulmonary function-forced expiratory volume in one second (FEV1), maximal midexpiratory flow rates (MMEFR) and maximal flow at 50% vital capacity (V50), and HITs, were studied at onset and 2, 3, and 4 wk after infection. There were no significant changes in pulmonary function during the total study period. For the 15 subjects, the mean provocative concentration of histamine causing a 20% fall in FEV1, (PC20H) was 8.73 mg/ml prior to onset of URTI, and at 1, 2, 3, and 4 wk after URTI was 7.97, 8.68, 8.13, and 8.61 mg/ml. These were not significantly different for the group as a whole, nor for the subgroups of asthmatics and nonasthmatics. Small changes in PC20H outside the normal range of variability occurred in 5 of 15 subjects. These were short-lived and no predictive factor for change in PC20H was identified in this group. Thus, URTI was not associated with significant changes in PC20H in this group of asthmatic and nonasthmatic subjects.
STUDY OBJECTIVES: To determine respective contributions of alveolar and proximal airway compartments in exhaled nitric oxide (NO) output (QNO) in pediatric patients with asthma and to correlate their variations with mild symptoms or bronchial obstruction. PATIENTS AND DESIGN: In 15 asthmatic children with recent mild symptoms, 30 asymptomatic asthmatic children, and 15 healthy children, exhaled NO concentration was measured at multiple expiratory flow (V) rates allowing the calculation of alveolar and proximal airway contributions in QNO, using two approaches, ie, linear and nonlinear models. MEASUREMENTS AND RESULTS: Asymptomatic and recently symptomatic patients were not significantly different regarding FEV(1) and maximum V between 25% and 75% of FVC (MEF(25-75)): FEV(1), 93.3 +/- 13.4% vs 90 +/- 7.5%; MEF(25-75), 70 +/- 22% vs 68 +/- 28% of predicted values, respectively (mean +/- SD). Maximal airway QNO output was significantly higher in recently symptomatic vs asymptomatic patients (p < 0.0001), and in asymptomatic patients vs healthy children (p < 0.02): 134 +/- 7 nl/min, 55 +/- 43 nl/min, and 19 +/- 8 nl/min, respectively. In a multiple regression analysis, variables that influenced airway QNO output were symptoms (p < 0.0001) and distal airway obstruction as assessed by MEF(25-75) (p < 0.05). Alveolar NO concentration (FANO) was significantly (p < 0.03) higher in recently symptomatic than in patients without symptoms, whereas it was not significantly different between asymptomatic patients and healthy children: 7.2 +/- 2.4 parts per billion (ppb), 5.5 +/- 2.7 ppb, and 4.2 +/- 2.0 ppb, respectively. CONCLUSIONS: An increase in FANO was observed in the presence of symptoms, and proximal airway NO output was correlated with distal obstruction during asthma.
Maximal expiratory flows at functional residual capacity were measured noninvasively from partial expiratory flow-volume curves in 65 awake, healthy children, 4 to 6 years of age. The variabilities within and between subjects were nearly identical to those reported for flows low in the vital capacity obtained from older subjects. This test of maximal expiratory flow at functional residual capacity has the advantage that the subject does not have to inspire to total lung capacity, exhale to residual volume, or make a maximal effort, and it is therefore applicable to the testing of young children who cannot perform a vital capacity maneuver. Measurement of this flow rate in 20 patients of the same age with lung disorders of varying severity revealed abnormal flow rates in more than 50 per cent of patients. Functional residual capacity was measured by the closed-circuit helium-equilibration method. When flow rates in liters per sec were compensated for lung size, girls had significantly larger flow rates than did boys. This suggests that the lungs of young children may grow differently according to genetic determinants related to sex.
Three studies of factors affecting variability of forced expiratory time (FET) have been carried out. In the first, different observers or repeated measurements over a few minutes were shown to make no significant contribution to FET variability. Time of day was also relatively unimportant. In the second study, FET was shown to vary considerably more than peak flow rate, forced expiratory volumes, and mid expiratory flow rates over the course of five days. In the third study, FET was shown to correlate with other measurements of airways obstruction though the correlation coefficients were relatively low. The measurement of FET is thought to be too variable to be of practical use as a screening test for small airways disease, though its clinical value is not questioned.
BACKGROUND: Obesity increases the risk of cardiovascular disease, hypertension, diabetes, digestive diseases, and some cancers. Several studies have shown that excess weight or weight gain is related to pulmonary dysfunction, but this issue needs to be further clarified. METHODS: The analysis was based on data of the Humboldt cohort study which was conducted in the town of Humboldt, Saskatchewan, Canada. The baseline survey in 1977 included 1202 adults, comprising 94% of all residents aged 25-59 years. Of these, 709 (59%) were followed up in 1983. Pulmonary function (forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and maximal mid expiratory flow rate (MMFR) and weight were measured in both surveys. Weight gain was determined by subtracting weight at baseline from weight at follow up. A residual analysis was used to examine the relationship between body mass index (BMI) at baseline, weight gain, and pulmonary function decline. RESULTS: Both BMI at baseline and weight gain were significantly related to pulmonary function at follow up. The effect of weight gain during the study period, however, was more prominent. The results showed that both mean residual FVC and FEV1 were highest in the group that gained < 1.0 kg, lowest in the group that gained > or = 4.0 kg, and intermediate in the group that gained 1.0-3.9 kg in both men and women after taking age, BMI at baseline, and smoking into account. The effect of weight gain on pulmonary function was greater in men than in women. Multiple regression analysis showed that each kilogram of weight gain was associated with an excess loss of 26 ml in FVC and 23 ml in FEV1 in men, and 14 ml and 9 ml respectively in women. CONCLUSIONS: Weight gain is significantly related to lung dysfunction. The effect of weight gain on pulmonary function is greater in men than in women.
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)
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.
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.
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.
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.
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.
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.