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Localization of the site of the bronchoconstrictor effects of leukotriene C4 compared with that of histamine in asthmatic subjects.

Although the sulfidopeptide leukotrienes are known to be potent bronchoconstrictors, the relative aerodynamic site of response to these compounds is controversial. We determined the decrease in maximal expiratory flow rates (Vmax) from partial and maximal flow-volume curves in seven asthmatic subjects after inhalation of aerosols of histamine or leukotriene C4 (LTC4) while breathing air or a mixture of 80% helium and 20% oxygen (He/O2). Density dependence (DD) of maximal expiratory flow was determined from partial expiratory flow volume curves by an isovolumic comparison of maximal expiratory flows with subjects breathing He/O2 with those obtained while breathing air. Measurements were made before and after inhalation of aerosols generated from graded concentrations of each constrictor agent. An aerodynamic site of response to LTC4 more central than for histamine was indicated by a significant (p less than 0.02) increase in DD with the former but not with the latter agonist. The ratio of Vmax at 30% vital capacity determined from maximal and partial maneuvers (M/P) was routinely higher at baseline while breathing He/O2 compared to the corresponding values with air, suggesting a degree of peripheral obstruction that was reversed by a deep inhalation. Obstruction induced by LTC4 inhalation resulted in a greater increase in M/P compared with baseline when air was the test gas (p less than 0.02). This was not observed when He/O2 was the test gas. Similar effects on M/P were not induced by histamine aerosol inhalation, consistent with a central airway response to LTC4 that was not affected by volume history.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Spirometry and flow-volume curves in healthy, normal Pakistanis.

Previous studies have indicated that lung volumes in healthy, normal Pakistani adults are smaller than measurements reported in comparable healthy European populations; in order to confirm these findings and to examine the relationship of maximal expiratory flow rates to lung volumes, we studied 250 non-smoking healthy subjects (116 men and 114 women) between the ages of 18 and 65 years. The population sample was drawn from urban and rural areas of Pakistan, with low levels of air pollution. The results indicate that the forced vital capacity (FVC) and forced expired volume in 1 second (FEV1) were lower in the Pakistani population compared to European populations and North American populations of European descent. These data are in conformity with previous studies; however, in Pakistani men the effects of age on FVC and FEV1 were slight so that, after the fourth decade, the FVC and FEV1 values are very comparable between the European and Pakistani populations. Amongst Pakistani women, on the other hand, FVC and FEV1 remained lower than in their European counterparts throughout adult life. Maximal expiratory flow rates amongst the men did not correlate with age, and these values were very similar to those reported in age-matched European populations. In women, however, there was a significant correlation of maximal flow rates with age and height, and the maximal expiratory flows were decreased compared to European populations. These data indicate that in Pakistani men pulmonary mechanics may be different to their European counterparts, allowing for higher maximal expiratory flows at any given lung volume.

Adolescent↗

Phosphorus trichloride toxicity. Preliminary report.

A railroad accident in Somerville, Massachusetts, led to spillage of phosphorus trichloride liquid. Attempted clean-up with water led to the liberation of phosphorus trichloride, phosphoric acid, hydrochloric acid, and phosphorus oxides. Seventeen people exposed to this mixture were studied. Patients experienced eye irritation, lacrimination, nausea, vomiting, and dyspnea. Six patients had transient elevation of lactic dehydrogenase. Although all patients had normal chest roentgenographic findings, pulmonary function tests showed statistically significant decreases in vital capacity (p = 0.02), maximal breathing capacity (p = 0.02), forced expiratory volume in one second (p = 0.02), and maximal expiratory flow rate at 25 percent of vital capacity (p = 0.05) in those closest to the accident site. Further, patients exposed for less than one and a half hours had significantly greater maximal expiratory flow rates at 25 percent of vital capacity when compared with patients who had been exposed longer (p = 0.02). In seven patients, repeated pulmonary function tests one month later showed improvement, suggesting strongly that the acute effects may have been due to phosphorus trichloride toxicity.

Accidents, Traffic↗

The UCLA population studies of chronic obstructive respiratory disease. I. Methodology and comparison of lung function in areas of high and low pollution.

The prevalence of symptoms of chronic obstructive respiratory disease and of functional respiratory impairment was determined in 3465 residents (70 per cent of enumerated) of an area historically exposed to photochemical/oxidant pollutants and 4509 residents (79 per cent of enumerated) of an area exposed to low levels of chemical pollutants. Tests administered included the NHLI questionnaire, electronic volume spirometry, whole body plethysmography, and the single-breath nitrogen test (deltaN2750-1250 and closing volume). Cough and cough with sputum were more frequently reported in the low-pollution area. Lung function was better among residents of the low-pollution area according to FEV1, FVC, maximal expiratory flow rates, closing volume fraction, thoracic gas volume, and airway resistance. Maximal mid-expiratory flow rate, considered to be a sensitive spirometric test for detection of small airways disease, was similar in residents of both areas. Mean deltaN2750-1250 was slightly worse among residents of the low-pollution area. Findings suggest that adverse effects of long-term exposure to photochemical/oxidant pollutants may occur primarily in the larger airways both among smokers and never smokers. The greatest differences between areas were observed in residents 18-59 years of age, suggesting that long-term exposure may be required to cause measurable impairment and that these differnces may be obliterated by such factors as smoking, differential out-migration and differential survival.

Adolescent↗

Ventilatory effects of atenolol and bevantolol in asthma.

The cardioequipotency of 400 mg bevantolol and 100 mg atenolol was determined by measuring the exercise heart rate in healthy subjects. The beta-blockers were then used in these doses to investigate their ventilatory effects in patients with asthma. The effects of both drugs on forced expiratory flow parameters for large and small airways were assessed at rest and during and after exercise. A dose-response curve was then plotted after inhalation of the beta 2-adrenoceptor agonist terbutaline. Bevantolol significantly decreased the forced expiratory volume in 1 second (FEV1) and the peak expiratory flow rate (PEFR) at rest, while there was no such change with placebo or atenolol. Both beta-blockers decreased the maximal expiratory flow rates at 50% of forced vital capacity (MEF50) and after expiration of 75% of the forced vital capacity (MEF25) at rest; the decrease was larger after bevantolol than after atenolol. During atenolol there was a decrease in FEV1 and in PEFR (P less than 0.01) 15 minutes after exercise in comparison with preexercise values. There was no significant difference between pre- and postexercise values of MEF50 and MEF25 during atenolol dosing. After bevantolol there was only a small change in PEFR after exercise, probably because of the low preexercise values of the ventilatory indices with this drug. Inhalation of terbutaline up to a dose of 2 mg significantly improved all ventilatory indices measured, but with bevantolol the values after 2 mg inhaled terbutaline were lower than the initial values.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

What are the best pulmonary function test parameters for early detection of post-lung transplant bronchiolitis obliterans syndrome in children?

Post-lung transplant bronchiolitis obliterans syndrome (BOS) is defined as an unexplained fall in forced expiratory volume in 1 s (FEV1) >or=20% of baseline (B). There have been reports in adults that FEF25-75% (>30% decline from B) is more sensitive than FEV1 for the early diagnosis of BOS. Yet, it is not known if other pulmonary function test (PFT) parameters - forced expiratory flow rates at 25-75% of vital capacity (FEF25-75%) and maximal expiratory flow rate at 80% (Vmax80%), 70% (Vmax70%) and 60% (Vmax60%) - are more sensitive indicators for early diagnosis of BOS than FEV1 in post-lung transplant children. We reviewed serial PFTs of 18 patients (ages 14.1 +/- 3.7 yr, 50% female) who had lung transplantation at our institution from 1993 to 1999, and who met the criteria for BOS diagnosis. There was no significant difference in post-transplant days when decline in FEV1 >or=20% of B, FEF25-75% >30% of B, and Vmax80%, Vmax70% and Vmax60% from normal occurred (635 +/- 431, 551 +/- 422 and 454 +/- 287 days, respectively; p = 0.4). However, a decline in FEV1 was the first abnormality in only 39% of the patients, while a decline in FEF25-75% and Vmax at specific lung volume were the first abnormality in 78% and 56% of the patients, respectively. The earliest signs of BOS would be missed in 61% of patients if FEV1 was the primary parameter used for the diagnosis. In order to improve the sensitivity of the diagnosis of post-lung transplant BOS; we speculate that the diagnosis should be based on decreases in FEF25-75% rather than on FEV1.

Adolescent↗

Pulmonary function abnormalities in thalassemia patients on a hypertransfusion program.

Pulmonary function tests were performed in 12 thalassemia patients on a hypertransfusion program (age 18.4 +/- 2.6 SEM years) to determine the presence of any abnormalities of lung function. These included spirometry, expiratory flow rates, body plethysmography, single-breath nitrogen washout, single breath carbon monoxide diffusing capacity, and arterial blood gases. Only one patient had normal pulmonary function. Arterial hypoxemia was present in ten of 12 patients at rest. The total lung capacity (TLC) was normal. The residual volume was abnormally increased in five of 12 patients. The slope of phase III of single breath nitrogen washout curve was abnormal in five of 12 patients, but the closing volume was normal. The maximal expiratory flow rate at 60% total lung capacity was decreased in four of 12 patients, suggesting the presence of small airway disease. The single breath carbon monoxide diffusing capacity was normal in all patients. These pulmonary function abnormalities did not correlate with age or the cumulative amount of iron via blood transfused. The small airway obstruction, hyperinflation; and hypoxemia observed in thalassemia patients on a hypertransfusion program may result from the basic disease, iron deposition in the lungs, or other factors.

Adolescent↗

Eglin-c prevents monocrotaline-induced ventilatory dysfunction.

The present study was carried out to investigate the relationship between elastase and monocrotaline (MCT)-induced ventilatory dysfunction in rats. To accomplish this, we used an elastase inhibitor eglin-c to suppress the activity of endogenous elastase. Thirty-five young Sprague-Dawley rats were randomly divided into six groups: control, MCT, eglin-c(1), eglin-c(2), eglin-c(1) + MCT, and eglin-c(2) + MCT. Rats in the control group received no treatment. Each MCT rat received a single subcutaneous injection of MCT (60 mg/kg) 1 wk before the functional test. Each eglin-c(1) rat was intratracheally instilled with eglin-c (9 mg/rat) twice in 1 wk. Each eglin-c(2) rat was intratracheally instilled with eglin-c (9 mg/rat) five times in 1 wk. Both eglin-c + MCT groups were treated with the combination of eglin-c(1) or eglin-c(2) and MCT. In the MCT group, there were significant decreases in dynamic respiratory compliance, maximal expiratory flow rate at 50% total lung capacity, and the slopes of the maximal expiratory flow-%total lung capacity curve and the maximal expiratory flow-static recoil pressure curve. However, in the eglin-c(1) + MCT and eglin-c(2) + MCT groups, all of the above-mentioned MCT-induced changes were prevented. All ventilatory values of the eglin-c(1) and eglin-c(2) groups were not significantly different from those of the control group. These results demonstrate that eglin-c treatment prevents MCT-induced ventilatory dysfunction and suggest that endogenous elastase may play an important role in MCT-induced inflammation-mediated ventilatory abnormality.

Animals↗

Anatomical dead space and airway resistance after glycopyrrolate or atropine premedication.

The effects of atropine and glycopyrrolate on anatomical dead space, one and three second forced expiratory volume, maximal expiratory flow rate, and total forced expiratory volume were determined in ten healthy volunteers. Using Fowler's single breath nitrogen analyzing technique, atropine was found to increase dead space by 19.2 per cent at one hour, declining to 11.02 per cent at four hours. Glycopyrrolate increased dead space by 21.57 per cent at one hour, 29.28 per cent at two hours, and 26.65 per cent at four hours. When compared to the effects of saline control injection, the dead space increases are significant. The difference between glycopyrrolate and atropine is significant only at four hours. Increases in maximal expiratory flow rate induced by atropine and glycopyrrolate were significant at one-half hour, while atropine alone induced a significant increase in one second forced expiratory volume. Three second forced expiratory volume and total forced expiratory volume were not significantly altered.

Adult↗

Clinical relevance of the flow rate response to low density gas breathing in asthmatics.

The maximal expiratory flow rate response to low density gas breathing was examined at the mid-vital capacity point in 31 asthmatic patients. Clinical features and long-term follow-up date were documented to assess the clinical relevance of the various responses. Many of the patients with chronic asthma had not responded adequately to outpatient therapy, and they had been admitted to hospital for evaluation and management. With increased steroid doses and intensive bronchodilator therapy, all showed considerable improvement and were studied when this improvement occurred. The remainder of the patients were studied after recovery from acute asthmatic attacks or during maintenance management as outpatients. All patients with a forced expiratory volume in 1 second is greater than 75 per cent of the predicted value and mid-expiratory flow rate is greated than 50 per cent of the predicted value at the time of study showed a good response to helium. Those patients with more severe obstruction could be divided into 2 groups, responders and nonresponders. A qualitatively similar response to normal subjects (density-dependent flow rates) was a feature of those patients who in general showed further improvement in ventilatory function on follow-up. A qualitatively similar response to that seen in patients with chronic irreversible obstruction (density-independent flow rates) was a feature of those patients who in general showed no further improvement in ventilatory function on long-term follow-up. There were, however, exceptions to both groups. We conclude that in asthmatics with more than mild air flow obstruction, the assessment of helium response can be of value in identifying those patients who have, in addition to asthma, chronic irreversible obstruction due to concommitant chronic bronchitis and/or emphysema. Clinical assessment and measurement of single-breath diffusion of carbon monoxide provide additional support for the latter diagnoses and separate the few exceptions from the bulk of the nonresponders. Responders and nonresponders can be fairly reliably identified from the simply recorded exhaled flow volume curve, thus obviating the need for a volume displacement plethysmograph.

Acute Disease↗

Residual lung volume and ventilatory muscle strength changes following maximal and submaximal exercise.

In order to evaluate a mechanism which may be responsible for the often observed acute increase in residual lung volume (RV) following exercise, 12 non-smoking males (20-30 yrs) performed two bouts of exercise on separate days; one to maximal heart rate (HRmax) and one to 85% of HRmax for 20 min. Prior to exercise and at 5, 15, 30, 60 and 120 min post-exercise, the following parameters were measured: RV, forced vital capacity (FVC), forced expiratory volume (FEV1.0), forced expiratory flow (FEF75-85), maximal expiratory pressure (PEmax), and maximal inspiratory pressure (PImax). Significant (p < 0.05) increases occurred in RV at 5, 15 and 30 min following maximal exercise and at 5 and 30 min after submaximal exercise. Changes in RV between the two exercise bouts were generally greater (p < 0.05) for maximal exercise. Accompanying the increases in RV were significant (p < 0.05) decreases in PEmax and decreases in FVC, while FEV1.0 and FEF75-85 remained generally unchanged or were slightly elevated. The data suggest that decreases in expiratory muscle strength due to fatigue may in part be responsible for increases in RV.

Adult↗

[Forced expiration index, signal and noise].

Although forced expiration measurements are extensively used, there is no general agreement concerning the best way to quantify the data. In this context, it may be of interest to examine indices from the point of view of their signal/noise ratio. The signal depends upon the actual sensitivity of the index to the kind of abnormality which is to be detected. In general, the relationship between signal and degree of abnormality is strongly non-linear, so that sensitivity is not a constant. The noise depends upon the kind of investigation which is made. When a subject is compared to himself (bronchomotor challenge, follow-up studies, etc.), it is mainly due to intraindividual variability. FEV1 is an example of index with a low sensitivity to peripheral airway abnormality, but a high reproducibility, so that its signal/noise ratio for paired measurements is comparatively good. When two groups are to be compared, the relevant noise is interindividual variability. Coefficient of variation of transit times and slope ratios are quite effective in detecting abnormalities in young smokers, probably because their sensitivity to mild peripheral airway disease is large compared to their interindividual variability. It follows that, according to the type of study, as well as to the nature and extent of abnormality, many indices may qualify as being the best.

Forced Expiratory Flow Rates↗

Intraindividual variability in maximal expiratory flow-volume and closing volume in asymptomatic subjects.

The variability of the parameters derived from analysis of the forced vital capacity and the expired nitrogen trace after a vital capacity inhalation of oxygen (closing volume) within a day, from day to day, and from week to week, has been determined. Effort-dependent tests as vital capacity and peak expiratory flow showed the least variability. The greatest variability was seen in effort-independent tests of function such as the maximal expiratory flow rate at 25 per cent (75 per cent of expired vital capacity) and 50 per cent of vital capacity, as well as closing volume. The degree of variability in the tests used was uninfluenced by the periodicity of the tests or the age or smoking habits of the subjects tested. It is suggested that variability of tests of respiratory function should be taken into account in their interpretation.

Adolescent↗

Monitoring of expiratory flow rates and lung volumes during a high altitude expedition.

BACKGROUND: Data on lung volumes and changes in flow-volume spirometry at high altitude are few and do not provide comprehensive assessment of the occurring changes. This study characterizes alterations of the forced expiratory flow-volume curve (FEFV-curve) and lung volumes at increasing altitude. METHODS: FEFV-curve and lung volumes at increasing altitude were characterized by daily assessment of peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and maximal expiratory flow rates (MEF 25, 50, 75) at 25%, 50% and 75% of the FEFV-curve with a portable spirometer (turbinometric method) three times a day during an expedition to Mustagh Ata (7545m) in 15 healthy mountaineers. RESULTS: With increasing altitude FVC and FEV1 were reduced by up to 25% (74.8% / 74.6% of baseline) and MEF25 was reduced to 81.5% of baseline values. PEF initially increased up to 4451m and returned to baseline values above 5000m. After descent below 2000m, all values normalized within one day. There were weak negative correlations between AMSS and FEV1, FVC and PEF (r = -0.23, p<0.001). CONCLUSIONS: We found increasing pulmonary restriction at high altitude without a marked reduction of PEF. Assessment of the FEFV-curve at high altitudes with a portable spirometer is a practical method reflecting the true field situation and may provide clinically relevant information (impending pulmonary edema).

Adult↗

Amantadine effect on peripheral airways abnormalities in influenza. A study in 15 students with natural influenza A infection.

Amantadine HCl administration has resulted in accelerated resolution of influenza A illness. Prolonged abnormalities in pulmonary function have been described in uncomplicated influenza A. To study the effect of amantadine on these changes, we evaluated young adults with documented natural influenza A with clear chest examinations and X rays. Subjects received placebo or amantadine in random, double-blind fashion. Physiologic studies included maximal expiratory flow volume curves with air and helium-oxygen mixtures. Air flow rates were unchanged in all subjects throughout. Initially, both groups showed comparable decreases in mean helium-oxygen maximal expiratory flow rates. The amantadine group showed accelerated physiologic improvement: significant increase in helium-oxygen flow rates occurred within 7 days (P less than 0.05). The rate of improvement in the helium-oxygen flow rates in the placebo group was not statistically significant. These studies confirm peripheral airways dysfunction after uncomplicated influenza A and suggest that amantadine is associated with accelerated resolution of this dysfunction.

Adult↗

Effects of theophylline on pulmonary function in patients with traumatic tetraplegia.

BACKGROUND/OBJECTIVES: To assess the effects of theophylline on pulmonary function in patients with chronic traumatic tetraplegia, we conducted a double-blind placebo-controlled crossover study in 10 patients. METHODS: The patients (age: 41 +/- 3 years; time from injury: 16 +/- 3 years; neurological levels: C3 to C7-T1) were randomized to receive oral theophylline or placebo for 6 weeks. After 2 months of washout, the patients received the medication not taken in the first trial for an additional 6 weeks. We measured lung volumes, expiratory flow rates, maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) at both baseline and at the end of each treatment arm. Theophylline blood serum assays were measured during the first week of the treatment and on the day of respiratory measurements. RESULTS: Mean theophylline level on the day of treatment completion was 12.6 +/- 1.4 microg/mL. In analyzing the data from the group of 10 patients, the percent changes from baseline in total lung capacity, forced vital capacity, forced expiratory volume at 1 second, MIP, and MEP did not differ significantly between the two treatment arms (P > 0.05 in all). CONCLUSION: These data show that in this small group of 10 subjects with chronic tetraplegia, administration of oral theophylline did not improve pulmonary function.

Adult↗