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Biomedical subjects

D J Cotton

Publications and source records attributed to D J Cotton.

At least 37 records · Page 2Linked to original sources
PubMed1991

Primary prophylaxis for Pneumocystis carinii pneumonia in HIV-infected people with CD4 counts below 200/mm3: a cost-effectiveness analysis.

We developed a decision-analytic model to assess the effectiveness and costs of dapsone, trimethoprim-sulfamethoxazole, or aerosolized pentamidine as initial prophylaxis for Pneumocystis carinii pneumonia in human immunodeficiency virus-infected people without prior symptoms AIDS and with CD4 counts less than 200/mm3. Each strategy increased life expectancy by about 18% compared with no prophylaxis; annual per-person costs were $440, $700, and $1,680 for dapsone, trimethoprim-sulfamethoxazole, and aerosolized pentamidine, respectively. These cost differences make a strategy beginning with dapsone most cost effective, with an incremental cost-effectiveness ratio of $13,400 per life year saved compared with no prophylaxis. Aerosolized pentamidine was substantially less cost effective, but the incremental cost effectiveness ratios were highly dependent on estimates for quality of life, efficacy, toxicity, and compliance. We conclude that, based on currently available data, initial prophylaxis with either dapsone or trimethoprim-sulfamethoxazole is most cost effective. For every 100,000 people treated, starting prophylaxis with trimethoprim-sulfamethoxazole or dapsone--with crossover to aerosolized pentamidine if oral therapy is not tolerated--may save between $98 million and $124 million per year.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Effect of a deep breath on gas mixing and diffusion in the lung.

We examined the effect of a previous deep breath on both inert gas mixing and the single breath diffusing capacity (DLCOSB) during submaximal single breath maneuvers in normal subjects. Single breath washouts were performed either immediately after a deep breath or after breathing tidally for 10 min. Maneuvers consisted of inhaling test gas from functional residual capacity to 50% inspiratory capacity and, after either 0 or 6 s of breath holding, exhaling slowly back to residual volume. We measured the Fowler dead space, the Phase III slope of the alveolar plateau of the He washout (delta He/L), the amplitude of the cardiogenic oscillations (Oc), closing capacity, mixing efficiency (Emix) and DLCOSB using the three equation method. For maneuvers immediately after a deep breath we found that delta He/L was steeper and the Oc were larger for washouts with 6 s but not 0 s of breath holding, while Emix was significantly lower and DLCOSB significantly higher for both the 0 s and the 6 s breath holding maneuvers. We conclude that a deep breath increases DLCOSB but simultaneously also increases convective-dependent inhomogeneity in the lung.

Adult↗
PubMed1990

Pulmonary diffusing capacity in adult cystic fibrosis: reduced positional changes are partially reversed by hyperoxia.

In seated adult cystic fibrosis (CF) patients, vascular recruitment of the relatively normal regions of the pulmonary circulation could occur in response to vascular destruction or hypoxia elsewhere in the pulmonary vasculature, thus limiting overall reductions in the single breath CO diffusing capacity (DLcoSB) with advancing disease. The purpose of this study was to determine the extent to which pulmonary capillary recruitment limits reductions in DLcoSB in seated adult cystic fibrosis patients, to define the role of hypoxia, and to develop strategies to improve detection of diffusion abnormalities in this disease. In normal subjects and adult CF patients breathing room air, and in a subgroup, after breathing both 40% and 100% O2 for 20 min, we measured changes (compared to sitting) in the three equation DLcoSB by changing transvascular pressure either with 15 degrees head down position (15 degrees HD), or with high negative inspiratory pressure (HNIP). In CF patients breathing room air, the changes in DLcoSB with both 15 degrees HD and HNIP were significantly smaller (p less than 0.01) than in controls and the positional changes correlated with the degree of airway obstruction. Although CF patients had no significant positional changes in diffusional resistance (1/DLcoSB) breathing room air, the positional changes in 1/DLcoSB after breathing 100% O2 for 20 min were similar in magnitude to the positional changes in normal subjects. We conclude that compensatory pulmonary capillary recruitment occurs in the relatively normal regions of the pulmonary vasculature breathing room air in the resting seated position in CF patients, thus minimizing reductions in DLcoSB in the seated position. This accounts for reduced responses of DLcoSB to both position and HNIP. The improved positional changes in 1/DLcoSB breathing hyperoxic gas mixtures in CF patients suggests that the vascular recruitment breathing room air is partly due to hypoxic vasoconstriction rather than due solely to fixed pathological changes in the pulmonary vasculature.

Adolescent↗
PubMed1989

Effect of lung volume on ventilation distribution.

To examine the effect of preinspiratory lung volume (PILV) on ventilation distribution, we performed multiple-breath N2 washouts (MBNW) in seven normal subjects breathing 1-liter tidal volumes over a wide range of PILV above closing capacity. We measured the following two independent indexes of ventilation distribution from the MBNW: 1) the normalized phase III slope of the final breaths of the washout (Snf) and 2) the alveolar mixing efficiency during that portion of the washout where 80-90% of the lung N2 had been cleared. Three of the subjects also performed single-breath N2 washouts (SBNW) by inspiring 1-liter breaths and expiring to residual volume at PILV = functional residual capacity (FRC), FRC + 1.0, and FRC - 0.5, respectively. From the SBNW we measured the phase III slope over the expired volume ranges of 0.75-1.0, 1.0-1.6, and 1.6-2.2 liters (S0.75, S1.0, and S1.6, respectively). Between a PILV of 0.92 +/- 0.09 (SE) liter above FRC and a PILV of 1.17 +/- 0.43 liter below FRC, Snf decreased by 61% (P less than 0.001) and alveolar mixing efficiency increased from 80 to 85% (P = 0.05). In addition, Snf and alveolar mixing efficiency were negatively correlated (r = 0.74). In contrast, over a similar volume range, S1.0 and S1.6 were greater at lower PILV. We conclude that, during tidal breathing in normal subjects, ventilation distribution becomes progressively more inhomogeneous at higher lung volumes over a range of volumes above closing capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Effect of airway closure on ventilation distribution.

We examined the effect of airway closure on ventilation distribution during tidal breathing in six normal subjects. Each subject performed multiple-breath N2 washouts (MBNW) at tidal volumes of 1 liter over a range of preinspiratory lung volumes (PILV) from functional residual capacity (FRC) to just above residual volume. All subjects performed washouts at PILV below their measured closing capacity. In addition five of the subjects performed MBNW at PILV below closing capacity with end-inspiratory breath holds of 2 or 5 s. We measured the following two independent indexes of ventilation maldistribution: 1) the normalized phase III slope of the final breaths of the washout (Snf) and 2) the alveolar mixing efficiency of those breaths of the washout where 80-90% of the initial N2 had been cleared. Between a mean PILV of 0.28 liter above closing capacity and that 0.31 liter below closing capacity, mean Snf increased by 132% (P less than 0.005). Over the same volume range, mean alveolar mixing efficiency decreased by 3.3% (P less than 0.05). Breath holding at PILV below closing capacity resulted in marked and consistent decreases in Snf and increases in alveolar mixing efficiency. Whereas inhomogeneity of ventilation decreases with lung volume when all airways are patent (J. Appl. Physiol. 66: 2502-2510, 1989), airway closure increases ventilation inequality, and this is substantially reduced by short end-inspiratory breath holds. These findings suggest that the predominant determinant of ventilation distribution below closing capacity is the inhomogeneous closure of airways subtending regions in the lung periphery that are close together.

Adult↗
PubMed1988

Volume acceleration as an index of neuromuscular output.

At the transition from expiration to inspiration, when flow and volume changes are small, changes in the respiratory system driving pressure could determine the degree of volume acceleration (AI), which, in turn, could reflect the degree of respiratory center output. To test this hypothesis, we calculated AI occurring in each respiratory cycle at the transition from expiration to inspiration during CO2 rebreathing in 4 healthy supine subjects. To minimize the flow and volume change over the measurement interval, we measured AI just prior to inspiration within the limits of an expiratory flow of 0.2 L . sec -1 to zero flow using digital differentiation. We also measured mouth pressure 100 msec after the onset of inspiration (P0.1) during intermittent transient inspiratory airway occlusions. During CO2 rebreathing AI increased significantly with both increasing PCO2 and P0.1. We also compared pairs of rebreathing studies, performed without and with an alinear (16 cm H2O . L -1 . sec -1) inspiratory resistor (IR), repeated twice in the 4 subjects. IR markedly decreased delta VE/delta PCO2 and the slope of the increase in mean inspiratory flow rate with PCO2 (delta VT/TI/delta PCO2) but did not significantly alter either delta AI/delta PCO2 or the increase in P0.1 with PCO2 (delta P0.1/delta PCO2). However, the effects of IR on AI and P0.1 differed between the early and late phases of each rebreathing run; early in the rebreathing runs (PCO2 = 55 Torr) IR increased both AI and P0.1 by a similar amount, but near the end of rebreathing (PCO2 = 60 Torr) IR increased P0.1 but not AI. Our results are consistent with the possibility that AI reflects neuromuscular output under the conditions of the study. Hence this approach justifies further evaluation to determine its general applicability.

Adult↗
PubMed1987

Clinical features and therapeutic interventions in 17 cases of Bacillus bacteremia in an immunosuppressed patient population.

We retrospectively examined episodes of Bacillus bacteremia at a hospital with a large proportion of immunosuppressed patients. Seventeen episodes in 9.5 years met our case definition: two of two bottles of one blood culture or one of two bottles of two or more separately obtained blood cultures drawn on the same date. During the same period, there were 59 additional episodes in which a single blood culture had only one of two bottles positive for Bacillus species. Only 2 of 59 such episodes resulted in recurrent bacteremia (3%), as compared with 5 of 17 episodes meeting our case definition (29%) (P = 0.004). In four of five episodes complicated by recurrent bacteremia and in which appropriate antibiotics were used, a Hickman-Broviac catheter was in place and was not removed. We suggest that our case definition permits the differentiation of infection from contamination based on outcome and that patients with Bacillus bacteremia have chronic venous catheters removed as well as receive antibiotic treatment.

Adolescent↗
PubMed1986

Pulmonary function in Pi M and MZ grainworkers.

Twenty-eight men with the Pi MZ phenotype who have been employed in the Saskatchewan country grain elevators and thus regularly exposed to high levels of grain dust, were case matched for age, years of employment, employment status, smoking status, and smoking history with grainworkers of type Pi M. Individuals answered a questionnaire, had a chest roentgenogram, skin tests, and performed a battery of pulmonary function tests. There were no differences between the two groups in prevalence of symptoms or atopy. Although not statistically significant, the MZ group had three times as many individuals with abnormal roentgenograms suggestive of COPD as the M group. The Pi MZ grainworkers had consistently poorer mean results for the pulmonary function tests with significantly lower mean values for FEV1, FEV1/FVC, MMFR, and Vmax50, leading us to suggest that Pi MZ individuals may be at higher risk of COPD than Pi M individuals, but only in the presence of other risk factors such as grain dust exposure.

Adult↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1984

Relationship between bronchial response to respiratory heat exchange and nonspecific airways reactivity in asthmatic patients.

In this study we have examined the relationship between the bronchial response to inhaled histamine and the bronchial response to breathing cold air at rest in nine control subjects and nine patients with asthma. Dried warm air (mean temp: +/- 1SD: 25.4 +/- 1.6 degrees C) and cold air (-19.7 +/- 2.6 degrees C) were breathed for 10 minutes each during quiet breathing at rest prior to as well as during both measurements of forced expired spirograms and the phase 3 slope of the single-breath oxygen test (delta N2/L). Subjects were also challenged with inhaled aerosolized histamine to determine the concentration required to reduce the forced expired volume in one second (FEV1) by 20 percent (PC20). Both asthmatic and control subjects had significantly greater respiratory heat exchange breathing cold as compared to warm air (p less than 0.01 in both cases). Control subjects did not change FEV1 or delta N2/L breathing cold air. Asthmatic patients increased delta N2/L from a mean warm air value of 2.41 +/- 1.31% N2/L to a mean cold air value of 5.39 +/- 4.55% N2/L (p less than 0.05). There was a significant linear correlation between the percent increase in delta N2/L from warm to cold air and 1/log10PC20 (r = -0.97, p less than 0.001) and also the percent decrease in FEV1 and log PC20 (r = -0.76, p less than 0.03) in the asthmatic patients. We conclude that cold air-induced alterations in ventilation/distribution and expired flow rates in asthmatic patients are related to pre-existing nonspecific airways reactivity.

Adolescent↗
PubMed1984

Nighttime ventilation improves respiratory failure in secondary kyphoscoliosis.

Four patients with cardiorespiratory failure caused by secondary kyphoscoliosis were studied. Polycythemia, cor pulmonale, restrictive lung pattern (functional residual capacity (FRC), 17 to 27% predicted; vital capacity (VC), 11 to 23% predicted), and abnormal arterial blood gases, primarily hypoventilation (PaO2, 31 to 44 mm Hg; PaCO2, 52 to 73 mm Hg), were seen in all. Supplementary oxygen, digoxin, diuretics, 15 min of intermittent positive-pressure breathing with inspired pressure (PI) 25 cm H2O 4 times daily, and tracheostomy failed to produce improvement. However, 12 h of nighttime ventilation (NTV) with PI 28 to 35 cm H2O through a permanent tracheostomy proved effective. Within 72 h, dyspnea at rest, restless sleep, and frequent waking resolved. Within 8 to 22 days, the PaO2 was approximately 58 mmHg and the PaCO2 was approximately 41 mm Hg while breathing 21% oxygen spontaneously during the day. The right heart failure resolved within 2 to 7 wk, and the hemoglobin count decreased to approximately 165 g/L within 2 to 6 months. There was a mean increase of 700 ml (72%) in functional residual capacity and 430 ml (49%) in vital capacity. The patients were discharged 2 days to 5 wk after NTV commenced. Daytime activity increased, approaching a normal life style. The improvement was sustained over a mean follow-up period of 3.4 yr. Problems included recurrent episodes of tracheobronchitis, mild self-limiting hemoptysis, and speech modification. Nighttime ventilation may be an effective alternative for long-term treatment of cardiorespiratory failure caused by secondary kyphoscoliosis.

Adult↗
PubMed1984

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↗
PubMed1983

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↗