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Serial relationships between ventilation-perfusion inequality and spirometry in acute severe asthma requiring hospitalization.

Patterns of VA/Q distribution and their relationship to spirometric indices were studied in 10 patients with acute severe asthma requiring hospitalization (7 women and 3 men 41.0 +/- 5.6 yr of age, mean +/- SEM) on admission and during subsequent recovery. On admission, all patients received the standard therapeutic regimen for our hospital. Spirometry and essentially noninvasive multiple inert gas elimination measurements were obtained serially, approximately once every day, whereas conventional arterial blood gases were determined every 3 days. On admission, all patients showed severe air-flow obstruction (FEV1/FVC% = 34.1 +/- 4.3%) and moderate to severe hypoxemia without CO2 retention (PaO2 = 50.5 +/- 2.6 mm Hg; PaCO2 = 37.1 +/- 2.4 mm Hg; AaPO2 = 53.7 +/- 3.0 mm Hg). Nine of the 10 patients showed bimodal blood flow distributions (dispersion of blood flow distribution, log SD Q = 1.34 +/- 0.11; normal range, 0.3 to 0.6) with only small amounts of shunt (1.09 +/- 0.8%). However, no significant interindividual correlations were observed between maximal expiratory flow rates (FEV1 and FEF25(-75) and log SD Q (r2 = 0.14 and 0.006, respectively). This lack of correlation persisted throughout hospitalization. Despite both clinical and spirometric improvement in all patients, there was simultaneous improvement in VA/Q matching in only one patient. Statistically significant negative correlations between maximal expiratory flow rates and gas exchange did develop toward the end of the study (Weeks 3 and 4 after discharge) when maximal recovery of physiologic changes associated with the acute asthma attack was achieved.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Lung function over six years among professional divers.

AIMS: To analyse longitudinal changes in pulmonary function in professional divers and their relation with cumulative diving exposure. METHODS: The study included 87 men at the start of their education as professional divers. At follow up one, three, and six years later, 83, 81, and 77 divers were reexamined. The median number of compressed air dives in the 77 divers over the follow up period was 196 (range 37-2000). A group of non-smoking policemen (n = 64) were subjected to follow up examinations in parallel with the divers. Assessment of lung function included dynamic lung volumes, maximal expiratory flow rates, and transfer factor for carbon monoxide (Tl(CO)). The individual rates of change of the lung function variables were calculated by fitting linear regression lines to the data, expressed as percent change per year. RESULTS: The annual reductions in forced vital capacity (FVC) and forced expired volume in one second (FEV(1)) were 0.91 (SD 1.22) and 0.84 (SD 1.28) per cent per year in divers, which were significantly higher than the reductions in the policemen of 0.24 (SD 1.04) and 0.16 (SD 1.07) per cent per year (p < 0.001). The annual reduction in the maximal expiratory flow rates at 25% and 75% of FVC expired (FEF(25%) and FEF(75%)) were related to the log(10) transformed cumulative number of dives in a multiple regression analysis (p < 0.05). The annual reductions in Tl(CO) were 1.33 (SD 1.85) and 0.43 (SD 1.53) per cent per year in divers and policemen (p < 0.05). CONCLUSIONS: FVC, FEV(1), maximal expiratory flow rates, and Tl(CO) were significantly reduced in divers over the follow up period when compared with policemen. The contrasts within and between groups suggest that diving has contributed to the reduction in lung function.

Accidents, Occupational↗

Parenteral vs. inhaled atropine: density dependence of maximal expiratory flow.

Using forced vital capacity maneuvers, we measured maximal expiratory flow rates (Vmax) and static elastic recoil pressures of the lung [Pst(L)] using quasi-static maneuvers in normal nonsmoking human subjects who were breathing air and after a washing of 80% helium-20% oxygen before and after both inhaled and intravenously administered atropine sulfate. By both routes there were equivalent increases in Vmaxair but different effects on density dependence (DD) of Vmax (DD = ratio of VmaxHeO2 to Vmaxair) and on Pst(L). At 30% of vital capacity, DD decreased from an average of 1.47 to 1.32 (P less than 0.01, paired t test) after inhaled drug and did not change after parenteral administration [1.44 vs. 1.48 (P greater than 0.2)]. After inhalation Pst(L) did not change, but after parenteral administration Pst(L) significantly decreased. We interpret these findings to indicate a predominantly large-airway effect with the inhalation route and a more uniform dilatation after the parenteral dose. These results contrast with beta-adrenergic dilatation following which small-airway effects predominate regardless of route of administration.

Adult↗

The dependence of maximal expiratory flow on vital capacity: a theoretical analysis.

The decrease of maximal expiratory flow rates (Vmax) at the 50 or 25 per cent level of vital capacity (V50, V25) in idiopathic pulmonary fibrosis (IPF) has been reported by several investigators, and most of them simply concluded that small airway obstruction was associated with IPF. However, Jayamanne et al. (1978) stressed that the reduced airflow in this disease was due to the reduction of lung volume than to abnormally elevated resistance to airflow in small airways. Theoretical analysis on the influence of lung volume on Vmax using a mathematical model supported the opinion of Jayamanne et al.

Forced Expiratory Flow Rates↗

Respiratory abnormalities in employees of the hard rock mining industry.

Respiratory symptoms, forced vital capacity, and the single breath N2 test were assessed in male employees (25 to 54 yr of age) who had been employed for more than 5 yr in the mining industry in Manitoba. The results were compared with those in a similar group of men selected from the general population. The prevalence of cough and/or phlegm in both nonsmoking and smoking mining employees was significantly greater than that in the sample of the general population (p less than 0.05). In both nonsmokers and ex-smokers amongst the mining employees, the parameters derived from the single breath N2 test tended to be lower and maximal expiratory flow rates tended to be higher than in comparable groups in the general population sample. In smokers, FVC, FEV1, FEV1/FVC, maximal expiratory flow rates, RV/TLC, and the slope of phase III were significantly worse in smelter workers than in underground workers. Alterations in lung function in those who worked underground, but not in those who worked in the smelter, was related to the duration of employment in the industry. The data suggest that exposure to mining irritants may result in disorders of lung function, and that this effect is greater in cigarette smokers.

Adult↗

Smaller lungs in women affect exercise hyperpnea.

We subjected 29 healthy young women (age: 27 +/- 1 yr) with a wide range of fitness levels [maximal oxygen uptake (VO2 max): 57 +/- 6 ml . kg-1 . min-1; 35-70 ml . kg-1 . min-1] to a progressive treadmill running test. Our subjects had significantly smaller lung volumes and lower maximal expiratory flow rates, irrespective of fitness level, compared with predicted values for age- and height-matched men. The higher maximal workload in highly fit (VO2 max > 57 ml . kg-1 . min-1, n = 14) vs. less-fit (VO2 max < 56 ml . kg-1 . min-1, n = 15) women caused a higher maximal ventilation (VE) with increased tidal volume (VT) and breathing frequency (fb) at comparable maximal VT/vital capacity (VC). More expiratory flow limitation (EFL; 22 +/- 4% of VT) was also observed during heavy exercise in highly fit vs. less-fit women, causing higher end-expiratory and end-inspiratory lung volumes and greater usage of their maximum available ventilatory reserves. HeO2 (79% He-21% O2) vs. room air exercise trials were compared (with screens added to equalize external apparatus resistance). HeO2 increased maximal expiratory flow rates (20-38%) throughout the range of VC, which significantly reduced EFL during heavy exercise. When EFL was reduced with HeO2, VT, fb, and VE (+16 +/- 2 l/min) were significantly increased during maximal exercise. However, in the absence of EFL (during room air exercise), HeO2 had no effect on VE. We conclude that smaller lung volumes and maximal flow rates for women in general, and especially highly fit women, caused increased prevalence of EFL during heavy exercise, a relative hyperinflation, an increased reliance on fb, and a greater encroachment on the ventilatory "reserve." Consequently, VT and VE are mechanically constrained during maximal exercise in many fit women because the demand for high expiratory flow rates encroaches on the airways' maximum flow-volume envelope.

Adolescent↗

Maximal mid-inspiratory to maximal mid-expiratory flow rate ratio in upper airway obstruction.

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.

Airway Obstruction↗

Airway responses to low concentrations of adrenaline and noradrenaline in normal subjects.

Airway, cardiovascular and metabolic responses were measured in six normal subjects during separate infusions of adrenaline and noradrenaline. Four incremental infusion rates of the catecholamines (4, 10, 25 and 62.5 ng X kg-1 X min-1) produced circulating levels of adrenaline and noradrenaline within the physiological range. Maximal expiratory flow rates at 25% of vital capacity measured from partial flow-volume curves increased sequentially with increasing adrenaline concentration. Increases in maximal expiratory flow rates at 25% and 50% of vital capacity measured from complete flow-volume curves were not statistically significant, nor were the changes in specific conductance. Small but insignificant changes were observed in heart rate and blood pressure during adrenaline infusion. Plasma glucose increased and serum potassium fell during adrenaline infusion. No significant airway, cardiovascular or metabolic responses were seen during noradrenaline infusion. These results suggest that adrenaline, at concentrations found in physiological circumstances, influences flow rates in small airways. Circulating noradrenaline does not appear to be important in the control of airway calibre in normal subjects.

Adult↗

Intrasubject variability of maximal expiratory flow volume curve.

Analysis of airflow in the terminal portion of the maximal expiratory flow volume curve has been suggested as a useful test for the early diagnosis of chronic airways obstruction. Whether such an analysis can identify early disease, and whether any subsequent action can prevent the progress of chronic airways obstruction, is unknown and will require prospective studies. As a precursor of such a study we have tried to establish the intrasubject variability of those tests of forced expiration which may be used for screening. We therefore measured expiratory flow volume curves of five healthy males and five healthy females aged 20-30 years as this is an age-group in which early detection of airways obstruction may be of value. Flow volume curves were obtained on the same day of the week for six weeks, and on three separate days during this period we carried out three flow volume curves every hour from 9 am to 6 pm. The data were subjected to analysis of variance to determine the variability of each measurement. Data were collected from forced expired volume in one second (FEV1) forced vital capacity (FVC), maximum expiratory flow rates at 50% and 75% of expired vital capacity, and forced expiratory time (FET). The results showed no consistent pattern of diurnal variation over the working day. The variation in any subject for FEV1 and FVC over the study period was considerably less than variations detected in the maximal expiratory flow rates at 50% and 75% of the expired vital capacity and FET. Our results suggest that the intrasubject variation found in flow rates of the terminal portion of the maximal expiratory flow volume curve and forced expiratory time may limit the usefulness of these tests in detecting early airways obstruction. FEV1 and FVC are more reproducible tests and are therefore particularly suited for cross-sectional screening. The more sensitive maximal expiratory flow volume curve may, however, be more useful for long-term studies in individuals when the onset of disease is sought, or for short-term challenge studies requiring the most sensitive index of change in airway characteristics.

Adult↗

Persistent small-airways dysfunction after exposure to hyperoxia.

To assess the contribution of hyperoxia to reduced pulmonary function after a deep saturation dive, a shallow saturation dive to a pressure of 0.25 MPa with the same profile of hyperoxic exposure as in a deep saturation dive to 3.7 MPa was conducted. The PO2 was 40 kPa, with periods of 75 kPa for 2 h every 2nd day during the first 14 days, 50 kPa the next 12 days, and a gradual fall to 21 kPa over the last 2 days in decompression. Seven submariners and one professional diver aged 22-27 yr participated. Pulmonary function, including static and dynamic lung volumes and flows and transfer factor for carbon monoxide (TLCO), were measured twice before, immediately after, 1 mo after, and 1 and 3 yr after the dive. As reported previously, there was a significant reduction in TLCO and in maximal expiratory flow rates at low lung volumes immediately after the dive. At the follow-up examinations 1 and 3 yr after, there was no recovery of the maximal expiratory flow rates. Forced midexpiratory flow rate was still reduced by 8.7 +/- 5.6% (P < 0.05) and 9.3 +/- 7.1% (P < 0.01), respectively. Forced expired volume in 1 s and forced vital capacity were not significantly reduced. There was a complete recovery of the TLCO. The findings are consistent with the studies indicating development of airway obstruction in divers, and the findings indicate that exposure to hyperoxia contributes to this effect.

Adult↗

Effect of low dose adrenaline and noradrenaline infusions on airway calibre in asthmatic patients.

Airway, cardiovascular and metabolic responses were measured in six asthmatic patients with stable asthma during separate adrenaline, noradrenaline and control infusions. Four incremental infusion rates (4, 10, 25 and 62.5 ng min-1 kg-1) produced circulating catecholamine concentrations within the physiological range. Specific airways conductance and maximal expiratory flow rates measured from complete and partial flow-volume curves increased significantly (P less than 0.05) during adrenaline infusion, in a dose-response manner. No changes in specific airways conductance or maximal expiratory flow rates were seen during the noradrenaline or control infusion. The highest adrenaline infusion rate caused a rise in systolic blood pressure (P less than 0.05) and plasma glucose (P less than 0.05) and a fall in plasma potassium (P less than 0.05). Noradrenaline infusion caused a slight increase in diastolic blood pressure (P less than 0.05) but no metabolic changes. No cardiovascular or metabolic changes occurred during the control infusion. Infused adrenaline, producing circulating concentrations within the physiological range, caused dose-related bronchodilatation in asthmatic patients. Circulating noradrenaline does not appear to have a role in the control of basal airway tone in asthmatic patients.

Adolescent↗

Nonspecific bronchial hyperreactivity after exposure to Western Red Cedar.

A 55-year-old nonatopic man presented with a 2-year history of progressively severe conjunctivitis, rhinitis, and asthma related to exposure to freshly cut red cedar. Chest roentgenogram, lung volumes, diffusing capacity for carbon monoxide, and expiratory flow rates were normal. A histamine inhalation test demonstrated mild, nonspecific bronchial hyperreactivity. After a 35-min cumulative exposure to Western Red Cedar sawdust in the laboratory, the patient developed a late asthmatic response. Bronchial reactivity to inhaled histamine increased significantly after exposure to red cedar in the laboraotry and again after natural exposure to red cedar at work. However, on both occasions forced expiraotry volume in one sec was decreased when compared to control values. Exposure to red cedar sawdust for 15 min was repeated in the laboratory, and histamine inhalation tests were performed the day before, for 4 consecutive days after, and 11 days after exposure. Before each test, one-sec forced expiratory volume, lung volumes, specific conductance, maximal expiratory flow rates at 25 and 50 per cent of vital capacity, closing capacity, and the slope of phase III from the single-breath O2 test were measured. Six hours after exposure to cedar, all measurements documented significant airway obstruction that persisted until the second day. Bronchial responsiveness to inhaled histamine also increased on the first 2 days after exposure to cedar, but this increase persisted on the third and fourth day when all other pulmonary function tests had returned to control values. Eleven days later, the bronchial hyperreactivity to inhaled histamine had also returned to control values. In a sensitized subject, exposure to Western Red Cedar induced a transient increase in nonspecific bronchial reactivity that was present in the absence of airflow obstruction. Factors other than decreased airway caliber are probably important in this phenomenon.

Bronchi↗

Lung function in North American Indian children: reference standards for spirometry, maximal expiratory flow volume curves, and peak expiratory flow.

Reference standards of lung function was determined in 176 healthy North American Indian children (94 girls, 82 boys) 7 to 18 yr of age. Spirometry, maximal expiratory flow volume curves, and peak expiratory flow rate were measured using techniques and equipment recommended by the American Thoracic Society. Standing height was found to be an accurate predictor of lung function, and prediction equations for each lung function variable are presented using standing height as the independent variable. Lung volumes and expiratory flow rates in North American Indian children were similar to those previously reported for white and Mexican-American children but were greater than those in black children. In both boys and girls, lung function increased in a curvilinear fashion. Volume-adjusted maximal expiratory flow rates after expiring 50 or 75% of FVC tended to decrease in both sexes as age and height increased. Our maximal expiratory flow volume curve data suggest that as North American Indian children grow, lung volume increases at a slightly faster rate than airway size does.

Adolescent↗

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↗

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↗