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Biomedical subjects

J Dosman

Publications and source records attributed to J Dosman.

16 recordsLinked to original sources

Effect of route of breathing on response to exposure in a swine confinement building.

Exposure of naive subjects to swine buildings results in acute nasal, lung, and peripheral blood inflammatory responses with an increase in nonallergic airway responsiveness. Because nasal passages filter large particles and soluble gases and because swine building exposure results in an acute inflammatory response at this level, we questioned what effect breathing through or avoiding this route would have on local and systemic inflammation. Nine normal young men 23 to 37 yr of age were exposed for 5 h to a swine building, once breathing normally and once with the mouth occluded (n = 8) (Protocol 1) or the nose occluded (n = 4) (Protocol 2); three subjects participated in both protocols. For each protocol each subject underwent a methacholine challenge for PC20 measurement, a nasal lavage, venous blood puncture, and a bronchoalveolor lavage (BAL) once before and once after each swine building exposure. Bronchial responsiveness as measured by PC20 decreased in most subjects after swine building exposure and was not influenced by the route of breathing. Nasal lavage neutrophils increased tenfold after each swine exposure, except when the nose was occluded where no alteration was observed. Total BAL cells significantly increased after each exposure to the swine building, this increase was not modified by the route of breathing. In Protocol 1, white blood cells increased from a baseline level of 7.0 to 10.5 x 10(9) cells/L after exposure with normal breathing and to 10.7 x 10(9) cells/L during nasal breathing exclusively. For Protocol 2, these respective values were: 5.6, 11.7 and 10.4 x 10(9)/L. Interleukins 6 and 8 levels in BAL, nasal washes, and serum were increased by swine building exposure, except in the nasal wash when the nose was occluded. In conclusion, the lung and blood responses to exposure in a swine confinement building are not modified by the route of breathing, suggesting that nasal inflammation and filtration are not important in the process and that small respirable particles and/or gases may be responsible for these responses.

Adult

Effects of repeated swine building exposures on normal naive subjects.

Exposure to swine confinement buildings has a negative impact on respiratory health. A short exposure to this environment results in an acute airway inflammatory response. The present study was performed to confirm and further define the acute effects of working in a swine building, and to determine whether these effects are reproducible. Seven previously nonexposed normal subjects underwent evaluations that included hourly measurement of forced expiratory volume in one second (FEV1), methacholine challenge (the provocative concentration producing a 20% fall in FEV1 (PC20)), bronchoalveolar lavage (BAL), nasal lavage (NL), and blood analyses, before (control) and after each of two 5 h exposures to a swine building environment. The exposures were conducted 8 days apart. The levels of total dust, endotoxins, and ammonia (NH3) in the confinement building were measured on each day of exposure. Both exposures resulted in a significant reduction in FEV1 (mean+/-SEM change in FEV1: control = 7+/-2%; exposure 1 = 15+/-3%; exposure 2 = 23+/-3%), decrease in PC20 (median value (25th-75th percentile): 223 (23-256), 20 (15-198) and 20 (11-71), respectively; p=0.05) and increase in BAL cells (129+/-20, 451+/-43 and 511+/-103x10(3) cells x mL(-1), respectively) and NL cells (6+/-4, 126+/-58 and 103+/-26x10(3) cells x mL(-1), respectively), mostly neutrophils. Levels of interleukin-8 (IL-8), but not interleukin-1 (IL-1) or tumour necrosis factors (TNF-alpha), increased both in BAL and nasal fluids with exposure. In normal naive subjects, repeated exposure to the environment of a swine building induced a marked and reproducible reduction in forced expiratory volume in one second, increase in airway responsiveness, and increased neutrophilic inflammatory response. These results could not be accounted for by any of the environmental factors measured.

Adult

Demonstration of regional phase differences in ventilation by breath sounds.

We measured phase and amplitude of compensated breath sounds (Ib/Tn), which are indexes of regional ventilation, with two microphones placed near the apex and base 10 cm apart on the chest wall, lateral to the right anterior axillary line in four seated normal subjects. We compared phase and amplitude of Ib/Tn with phase and amplitude of esophageal pressure changes (Pes) measured by two balloons positioned 10 cm apart and at approximately the same horizontal levels as the microphones. When breathing tidally below closing volume (CV), apical Ib/Tn was louder and earlier than basal Ib/Tn, whereas basal Pes was greater and earlier than apical Pes. Above CV basal Ib/Tn was louder than apical and the phase differences either disappeared or followed phase differences in PES. The results suggest that below CV, ventilation of lower zones lags behind upper ones probably due to airway closure. Pes measurements indicate that this may lead to an amplification of pleural pressure swings at the base. Above CV, all airways are open, the ventilation of lower zones is greater than that of upper zones, and the sequence of ventilation follows the sequence of pleural pressure changes.

Adult

The relations between structural changes in small airways and pulmonary-function tests.

To examine the relation between small-airways abnormalities and specific lung functions, we performed pulmonary-function tests in 36 patients, of whom two were nonsmokers, one to three days before open-lung biopsy for localized pulmonary lesions. The primary lesion in the small airways was a progressive inflammatory reaction leading to fibrosis with connective-tissue deposition in the airway walls. Increase in disease in small airways correlated with deterioration in lung function. Lesions could be reliably detected (P less than 0.05) by tests for closing capacity, the volume at which air and helium flow ere equal (a test of airway caliber and elastic recoil), and the slope of phase III of the single-breath washout curve (which tests evenness of ventilation). These tests showed abnormalities at a time when the pathologic changes were still potentially reversible and when other tests were not appreciably changed.

Adult

Age and sex differences in lung elasticity, and in closing capacity in nonsmokers.

Static volume-pressure characteristics of the human lung, closing capacity (CC), closing pressure, and subdivisions of lung volumes were measured in 66 adult nonsmokers, aged 24-58 yr. There were systemic differences between the sexes as well as with age. Young females had less elastic recoil at any lung volume than young males. However, males lost elastic recoil with age faster than females so that in the older age groups the recoil was similar. There were no significant changes in compliance over the volume range containing most values of CC in either males or females. By comparing the age regression of CC and of elastic recoil pressures at 40 and 50% TLC we conclude that the increase in CC with age in males was attributable almost entirely to loss of recoil. In females none of the increase in closing capacity with age was attributable to loss of recoil. By exclusion, it is probably attributable to a change in the intrinsic properties of small airways or an increase in the pleural pressure gradient with age.

Adult

The relationship between symptoms and functional abnormalities in clinically healthy cigarette smokers.

Because a number of "early tests" may now be used to measure abnormalities of lung function in cigarette smokers with normal airflow rates, we evaluated the symptoms of cough, sputum, wheezing, and shortness of breath in 60 nonsmokers and 49 smokers to determine whether these symptoms correlated with measurements of lung function that are believed to be altered by mild obstruction. One or more symptoms were present in 5 per cent of the nonsmokers and 90 per cent of the smokers. Individual symptoms, sums of symptoms (symptoms score), and various combinations of symptoms correlated poorly or not at all to measured values for dynamic lung compliance, closing volume, closing capacity, slope of Phase III, and helium flow-volume curves. The symptoms score correlated negatively (P less than 0.05) with forced maximal expiratory flow at 50 per cent of vital capacity. Inasmuch as the serious consequences of chronic airway obstruction are related to abnormalities of lung function, it is likely the function tests will prove more useful than symptoms to reveal smokers at risk to develop chronic obstructive pulmonary disease. Symptoms cannot be used to detect smokers who are liable to have functional abnormalities suggestive of mild peripheral airway obstruction.

Adult

Effect of meperidine on occlusion pressure responses to hypercapnia and hypoxia with and without external inspiratory resistance.

In 5 normal subjects we measured ventilation and P0.1, the pressure generated by the first 0.1 sec of inspiratory effort against a closed airway, in response to hypercapnia and hypoxia with and without added inspiratory resistance before and after oral meperidine (1.1 to 1.3 mg per kg). CO2 responses were studied in the steady state, whereas progressive hypoxia was used to elicit hypoxic responses. In general, resistance decreased ventilatory responses to hypercapnia but increased P0.1 responses to both hypoxia and hypercapnia. Meperidine depressed both ventilatory and P0.1 responses, more so in hypoxia than in hypercapnia. The combination of resistance and merperidine was additive in depressing responses to hypercapnia but in hypoxia produced little more depression than did meperidine alone. In both hypercapnia and hypoxia, meperidine decreased the augmentation of P0.1 that was associated with increased resistance. Normal subjects responded to acute increases of inspiratory resistance by increasing inspiratory motor output; this increase was distinctly blunted by meperidine.

Adult

Reversibility of pulmonary function abnormalities in smokers. A prospective study of early diagnostic tests of small airways disease.

A prospective study of the reversibility of pulmonary function abnormalities in cigarette smokers was performed. Base line studies of 50 otherwise healthy cigarett smokers included lung volumes, static volume-pressure curves, closing volume, slope of phase III and maximum expiratory flow-volume curves while the subjects breathed air and while they breathed an 80 per cent helium-20 per cent oxygen mixture (He). Ten subjects, seven women and three men, ages 29 to 61, were restudied 6 to 14 weeks after they had stopped smoking. Two of these people had an abnormal closing volume, four had an abnormal slope of phase III and five had an abnormal response to helium. Static volume-pressure curves, slope of phase III and airflow rates were not improved on the repeat studies. There was increases in maximum expiratory flow rates with He at 50 and 25 per cent of vital capacity, reductions in the lung volume at which the maximum expiratory flow rate of air and He became identical, and decreases in closing volume. These reversible functional changes in smokers are thought to indicate improvement of peripheral airways obstruction.

Adult

Role of inertia in the measurement of dynamic compliance.

Dynamic compliance (Cdyn) was measured at different frequencies (breaths/min) in 30 nonsmoking males and females aged 30-59 yr. In those aged 30-49 yr Cydn at 90 breaths/min was significantly higher than at 15 breaths/min while those aged 50-59 yr showed no significant difference. Assuming an inertance of 0.01 cmH2O/l per s-2, and a sinusoidal breathing frequency, Cydn at 60 and 90 breaths/min was corrected for inertia. In the 30-49 yr age group corrected Cydn did not change with increasing frequency of breathing whereas in the 50-59 yr age group Cydn at 15 breaths/min was significantly higher than at 90 breaths/min (P is less than 0.05). In this age group, four of eight subjects were frequency dependent when corrected for inertia. These findings indicate that inertia influences Cydn at breathing frequencies of 60 per min and above. Unless this is taken into account, frequency dependence of compliance may be missed. The results also indicate that frequency dependence of compliance is normal in some older individuals but is not normal in the younger age group.

Adult