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Biomedical subjects

B L Graham

Publications and source records attributed to B L Graham.

At least 37 records · Page 2Linked to original sources

Effect of breath-hold time on DLCO(SB) in patients with airway obstruction.

The single-breath diffusing capacity of the lung for CO [DLCO(SB)] is considered a measure of the conductance of CO across the alveolar-capillary membrane and its binding with hemoglobin. Although incomplete mixing of inspired gas with alveolar gas could theoretically influence overall diffusion, conventional calculations of DLCO(SB) spuriously overestimate DLCO(SB) during short breath-holding periods when incomplete mixing of gas within the lung might have the greatest effect. Using the three-equation method to calculate DLCO(SB) which analytically accounts for changes in breath-hold time, we found that DLCO(SB) did not change with breath-hold time in control subjects but increased with increasing breath-hold time in both patients with asthma and patients with emphysema. The increase in DLCO(SB) with increasing breath-hold time correlated with the phase III slope of the single-breath N2 washout curve. We suggest that in patients with ventilation maldistribution, DLCO(SB) may be decreased for the shorter breath-hold maneuvers because overall diffusion is limited by the reduced transport of CO from the inspired gas through the alveolar gas prior to alveolar-capillary gas exchange.

Adult↗

Reduction of the single breath CO diffusing capacity in cystic fibrosis.

The single breath diffusing capacity of the lung for carbon monoxide (Dsb) was measured using three equations to describe CO uptake separately during inhalation, breath holding, and exhalation in 24 patients with cystic fibrosis and 30 control subjects with similar age and height distributions. Using the control group, we developed two prediction equations for Dsb: one based on height, age, and sex; and another based on alveolar lung volume (VA) to the 2/3 power. We also developed a prediction for Dsb/VA (Kco) based on height. The Dsb as percent predicted (% pred) using either prediction equation decreased with increasing age and height as well as with decreasing % pred maximal midexpiratory flow rate (FEF25-75) in cystic fibrosis patients but not in controls. The Kco (% pred) also decreased in cystic fibrosis with increasing age and decreasing percent pred FEF25-75. We conclude that in patients with cystic fibrosis, Dsb decreases with variables that relate to increasing disease severity (age, height, and increasing airflow obstruction).

Adolescent↗

Fast vs. slow exhalation before O2 inhalation alters subsequent phase III slope.

We studied 10 symptom-free lifetime non-smokers and 17 smokers all with normal pulmonary function studies. All subjects performed single-breath N2 washout tests by either exhaling slowly ("slow maneuver") from end inspiration (EI) to residual volume (RV) or exhaling maximally ("fast maneuver") from EI to RV. After either maneuver, subjects then slowly inhaled 100% O2 to total lung capacity (TLC) and without breath holding, exhaled slowly back to RV. In the nonsmokers seated upright phase III slope of single-breath N2 test (delta N2/l) was lower (P less than 0.01) for the fast vs. the slow maneuver, but this difference disappeared when the subjects repeated the maneuvers in the supine position. In contrast, delta N2/l was higher for the fast vs. the slow maneuver (P less than 0.01) in smokers seated upright. For the slow maneuver, delta N2/l was similar between smokers and nonsmokers but for the fast maneuvers delta N2/l was higher in smokers than nonsmokers (P less than 0.01). We suggest that the fast exhalation to RV decreases delta N2/l in normal subjects by decreasing apex-to-base differences in regional ratio of RV to TLC (RV/TLC) but increases delta N2/l in smokers, because regional RV/TLC increases distal to sites of small airways obstruction when the expiratory flow rate is increased.

Adult↗

Overestimation of the single-breath carbon monoxide diffusing capacity in patients with air-flow obstruction.

It has been previously shown that conventional methods of measuring the single-breath diffusing capacity of the lung for carbon monoxide (DLCOsb) overestimate diffusion in normal subjects when the expiratory flow rate is reduced, when the collection of the exhaled alveolar gas sample is delayed, and/or when too large an alveolar gas sample is collected. Conventional methods use a single breathholding equation to analyze the entire single-breath maneuver, which consists of inhalation, breathholding, and exhalation. We previously developed a method of calculating DLCOsb using 3 separate equations, one for each phase of the single-breath maneuver. Using this method, DLCOsb measurements are unaffected by changes in expiratory flow rate or by the size and timing of the alveolar gas sample, as these parameters are analytically included in the analysis. We hypothesized that in patients with air-flow obstruction, conventional methods of measuring DLCOsb would overestimate diffusion. We examined the effects of measuring DLCOsb using rapid inhalation and exhalation maneuvers in a group of normal subjects and in 3 groups of patients with emphysema, asthma, and cystic fibrosis, respectively. First, we found that, whereas conventional methods specify 750 ml or 1 L of gas to be used for dead space washout, the washout volumes, as measured from a continuous monitor of the helium concentration in the exhaled gas in the single-breath maneuver, exceeded 1 L in 26% of the study group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Pulmonary function and respiratory symptoms in potash workers.

Over 94% of the workers in each of four Saskatchewan potash mines participated in a respiratory health surveillance program that included a questionnaire and pulmonary function tests. Compared with a nonexposed control group, potash workers had higher prevalences of cough, dyspnea, and chronic bronchitis but better pulmonary function. Prevalences of symptoms and pulmonary function abnormalities were similar among workers at the four mines tested and at the various job locations. Potash dust, diesel fumes, and other air contaminants may have an irritant effect that leads to the increased prevalences of cough and chronic bronchitis. Although we found no adverse effects of the potash mine environment on pulmonary function, these findings reflect a healthy worker effect or some selection process that makes the potash workers appear healthier in a cross-sectional study.

Adult↗

Effect of high negative inspiratory pressure on single breath CO diffusing capacity.

We measured the single breath diffusing capacity for carbon monoxide (DLcoSB) using a three-equation method to describe CO uptake in 10 normal seated subjects who either voluntarily inhaled slowly (0.5 L/sec) to total lung capacity (TLC), or inhaled slowly to TLC with maximal effort through a high inspiratory resistance which created high negative inspiratory pressure. Subjects then immediately exhaled slowly at a voluntarily controlled exhaled flow. Single breath maneuvers were performed in duplicate both with and without high negative inspiratory pressure while subjects were seated upright at rest and during steady-state bicycle exercise. We found that high negative inspiratory pressure increased DLcoSB by 10.5 +/- 4.9% (mean +/- 1 SD) at rest (P less than 0.001). In 7 subjects low level exercise alone increased DLcoSB by a similar amount (12.1 +/- 7.3%; P = 0.005). In six of the subjects there was a significant correlation between the increase in DLcoSB during high negative inspiratory pressure at rest and the increase in DLcoSB during steady-state exercise (r = 0.89; P less than 0.01). During steady-state exercise, high negative inspiratory pressure further increased DLcoSB 6.4 +/- 6.3% compared to exercise alone (P = 0.05). We conclude that the increase in DLcoSB with high negative inspiratory pressure at rest is a simple reproducible method of assessing recruitment of the pulmonary capillary bed in man.

Adult↗

Dynamic measurements of CO diffusing capacity using discrete samples of alveolar gas.

It has been shown that measurements of the diffusing capacity of the lung for CO made during a slow exhalation [DLCO(exhaled)] yield information about the distribution of the diffusing capacity in the lung that is not available from the commonly measured single-breath diffusing capacity [DLCO(SB)]. Current techniques of measuring DLCO(exhaled) require the use of a rapid-responding (less than 240 ms, 10-90%) CO meter to measure the CO concentration in the exhaled gas continuously during exhalation. DLCO(exhaled) is then calculated using two sample points in the CO signal. Because DLCO(exhaled) calculations are highly affected by small amounts of noise in the CO signal, filtering techniques have been used to reduce noise. However, these techniques reduce the response time of the system and may introduce other errors into the signal. We have developed an alternate technique in which DLCO(exhaled) can be calculated using the concentration of CO in large discrete samples of the exhaled gas, thus eliminating the requirement of a rapid response time in the CO analyzer. We show theoretically that this method is as accurate as other DLCO(exhaled) methods but is less affected by noise. These findings are verified in comparisons of the discrete-sample method of calculating DLCO(exhaled) to point-sample methods in normal subjects, patients with emphysema, and patients with asthma.

Adult↗

Characteristics of airway tone during exercise in patients with asthma.

In 10 nonasthmatic subjects and 11 patients with asthma, we measured pulmonary resistance (RL), functional residual capacity (FRC), and specific conductance (sGaw) before, during, and after submaximal treadmill exercise. Nonasthmatic subjects did not change RL, FRC, or sGaw from base-line resting values during or after exercise. In patients with asthma, RL decreased significantly during exercise, both when exercise was begun from the control resting state and from conditions of elevated RL after a preceding period of exercise. When asthmatic patients inhaled a standardized dose of aerosolized histamine, the increase in RL during exercise was significantly less than the increase in RL when they breathed histamine at rest. When patients hyperventilated at rest with tidal volumes, breathing frequencies, and end-tidal CO2 tensions similar to those during exercise conditions, bronchodilatation also occurred, and the increase in RL following inhaled histamine during isocapnic hyperventilation was also less than at rest. Since bronchodilatation and inhibition of histamine-induced bronchoconstriction occur during both exercise and isocapnic hyperventilation, we suggest that the mechanism of bronchodilatation during exercise may not necessarily be related to metabolic factors associated with exercise.

Adolescent↗

Effects of grain dust exposure and smoking on respiratory symptoms and lung function.

In four groups of individually-matched subjects (nonsmoking grain workers, smoking grain workers, nonsmoking community controls, and smoking community controls) we measured pulmonary function variables from the spirogram, from the maximal expiratory flow-volume curve breathing air and helium, and from the single breath nitrogen test as well as symptom prevalences from a questionnaire in order to assess the relative effects of smoking and occupational exposure to grain dust in Saskatchewan country grain elevators. There were similar increased prevalences of respiratory symptoms and reductions in pulmonary function associated with either grain dust exposure or smoking, but the effects of smoking were slightly more pronounced. The combined effects of grain dust and smoking on lung function appeared to be additive except in the least exposed workers (five years or less) where a synergistic effect was observed in tests of peripheral airways dysfunction.

Adolescent↗

Effects of smoking and occupational exposure on peripheral airway function in young cereal grain workers.

We studied two groups of young male cereal grain elevator workers: 82 lifetime nonsmoking grain workers (2.5 +/- 1.2 yr of dust exposure) who were 22.7 +/- 3.5 yr of age, and 82 smoking grain workers (6.1 +/- 4.1 pack-years of smoking) individually matched to the nonsmoking grain workers for age (22.7 +/- 3.3 yr) and years of work in the grain industry (2.6 +/- 1.3 yr). We also studied the following groups of community control subjects: 82 nonsmoking community control subjects individually matched to the nonsmoking grain workers for age (22.8 +/- 3.7 yr), and 82 smoking community control subjects individually matched to the smoking grain workers for age (22.7 +/0 3.6 yr) and smoking history (6.0 +/- 4.0 pack-years). We measured forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC %, the maximal mid-expiratory flow rate (FEF25-75), the flow at 50% (Vmax50) and 25% (Vmax25) of a maximal expiratory flow-volume maneuver, the percent increase in the maximal expiratory flow at 50% FVC breathing a mixture of 80% helium-20% oxygen as compared with air (delta Vmax50), and the slope of Phase III of the single breath nitrogen test (delta N2/L). We also assessed the prevalence of respiratory symptoms from responses to a standardized questionnaire. Smoking was associated with an increased prevalence of cough, wheezing, and dyspnea, and a mildly decreased FEV1/FVC %. Two variables were used as indexes of small airway dysfunction, a lower delta Vmax50 and a higher delta N2/L. Only the group of workers who both smoked and were occupationally exposed to grain dust had evidence of small airway dysfunction. The differences in delta N2/L and delta Vmax50 were greater than was expected from an additive model, suggesting that the combined effects of occupational exposure to grain dust and inhalation of cigarette smoke may have a synergistic effect leading to small airway dysfunction in young cereal grain workers.

Adult↗

Effect of inspiratory flow rate on the esophageal pressure gradient in upright humans.

We measured pressures in 2 lung regions in 5 seated subjects with 2 esophageal balloons placed 7.2 +/- 0.6 cm (mean +/- SE) apart in the mid-thorax in order to obtain the esophageal pressure gradient (EPG). Pressure differences between the lower thoracic balloon and a balloon placed in the stomach were obtained to measure transdiaphragmatic pressure (pdi). Inspiratory maneuvers were made from functional residual capacity (FRC) at either low inspiratory flow rates (slow VI) (mean slow VI: 0.22 +/- 0.05 L/sec) or at rapid flow rates (fast VI) (2.15 +/- 0.15 L/s). At FRC the mean EPG was 0.19 +/- 0.04 cm H2O/cm. The mean EPG was consistently lower at 500 cc above FRC during fast VI (0.14 +/- 0.03 cm H2O/cm) than during slow VI (0.28 +/- 0.05 cm H2O/cm) (P less than 0.001, paired 't' test). Fast VI results in amplification of pressure in the lower as compared to the upper region wih reduction in EPG. Diaphragmatic contraction appears to influence alterations in EPG during fast VI.

Adult↗

Improved accuracy and precision of single-breath CO diffusing capacity measurements.

Using three conventional methods and a new method we measured the single-breath diffusing capacity for carbon monoxide [DLCO(SB)] in a group of normal subjects. Whereas the conventional methods calculated DLCO(SB) from a single equation valid only for breath holding, the new method used three equations, one for each phase of the single-breath maneuver, i.e., inhalation, breath holding, and exhalation. We found that while the conventional methods of calculating DLCO(SB) were greatly affected by variations in the way in which the single-breath maneuver was performed and/or the way in which the alveolar gas sample was collected, these variations had little effect on the calculations of DLCO(SB) using the new method. These results were in close agreement with results from a computerized mathematical lung model in which the diffusing capacity did not change with lung volume. We concluded that the new method significantly improves the accuracy and precision of DLCO(SB) measurements while reducing the effects of maneuver variability. For these reasons comparisons of DLCO(SB) values between patients and normal subjects or between two groups with different pulmonary function may be more valid using the new method than using conventional methods.

Adult↗

Sensitivity and specificity of early diagnostic tests of lung function in smokers.

What are the relative sensitivities and specificities of the "early" tests of lung dysfunction? We describe the findings from a study of virtually the entire population of a rural pollution-free community. Using abnormal spirometry as a marker of obstructive disease, we evaluated the two tests obtained from the single-breath nitrogen curve, closing volume (CV/VC) and the slope of the alveolar plateau (delta N2/L), as well as combinations of the two tests. While CV/VC is highly specific (92.3 percent in male and 94.0 percent in female subjects), it lacks sensitivity (36.8 percent in male and 13.3 percent in female subjects) and is abnormal in only 10.0 and 6.5 percent of male and female smokers, respectively, a percentage not dissimilar from the percentage with abnormal spirometry. However, delta N2/L, abnormal in 24.1 percent of male smokers and 28.8 percent of female smokers, rates reasonably well with regard to both sensitivity (63.2 percent in male and 66.7 percent in female subjects) and specificity (79.3 percent in male and 74.0 percent in female subjects). The group of smokers with abnormal delta N2/L did include fair numbers with abnormal spirometry (20.7 percent in male and 16.1 percent in female subjects). A combination of the two tests (abnormal in either delta N2/L and/or CV/VC) has good sensitivity (68.4 and 80.0 percent for male and female subjects, respectively) and specificity (74.3 and 69.0 percent for male and female subjects, respectively).

Adult↗

Effect of ventilation and diffusion nonuniformity on DLCO (exhaled) in a lung model.

Recent studies have shown that diffusing capacities measured at multiple intervals during a single exhalation [DLCO(exhaled)] remained constant with lung volume in normal subjects, but decreased with decreasing lung volume in patients who may have had diffusion nonuniformity. We have examined the theoretical basis of these results by determining what factors affected DLCO(exhaled) in a computerized lung model in which diffusion in each compartment remained constant with lung volume. DLCO(exhaled) decreased with decreasing lung volume when a small lung region lacked diffusion. However, the change in DLCO(exhaled) with lung volume was also affected by nonuniform ventilation and these effects could not be eliminated by correcting the carbon monoxide decay and the simultaneous decay of helium. DLCO(exhaled) values were also influenced by the exhaled flow rate in the presence of nonuniform ventilation and/or nonuniform diffusion. However, prolonging the period of breath holding prior to exhalation reduced DLCO(exhaled) values at all lung volumes when non-uniform diffusion was simulated, but did not affect DLCO(exhaled) when only nonuniform ventilation was simulated.

Carbon Dioxide↗

Chronic bronchitis and decreased forced expiratory flow rates in lifetime nonsmoking grain workers.

To determine whether clinical symptoms and pulmonary function abnormalities were more common in lifetime nonsmoking grain elevator workers exposed to grain dust than in lifetime nonsmoking community control subjects who were not occupationally exposed to dust, we obtained an occupational health questionnaire, spirometric variables, and flow-volume curves on 90 lifetime nonsmoking grain workers and 90 lifetime nonsmoking community control subjects. For these groups we calculated the prevalence of chronic bronchitis, defined as daily production of phlegm for 3 months/yr for at least 2 yr. The prevalence of chronic bronchitis was higher in nonsmoking workers (23.1%) than in nonsmoking control subjects (3.3%) (p less than 0.01). Nonsmoking grain workers had lower mean values than did nonsmoking control subjects for maximal mid-expiratory flow rate (p less than 0.01) and for maximal expiratory flow at 50% of vital capacity (p less than 0.01). We conclude that exposure to grain dust inlifetime nonsmoking grain workers is associated with an increased prevalence of chronic bronchitis and evidence of airflow obstruction.

Adult↗