Biomedical subjects

M D Inman

Publications and source records attributed to M D Inman.

48 records · Page 3Linked to original sources

PubMed1995

Allergen-induced oxygen radical release from bronchoalveolar lavage cells and airway hyperresponsiveness in dogs.

Allergen inhalation causes airway hyperresponsiveness and airway inflammation in dogs. The purpose of this study was to determine whether allergen-induced airway hyperresponsiveness is associated with increases in oxygen radical production from bronchoalveolar lavage (BAL) cells. A group of 10 random-source dogs were studied twice, 4 wk apart. On each occasion, acetylcholine (ACh) airway responsiveness was measured before and 24 h after inhalation of Ascaris suum or its diluent, followed by BAL. The response to ACh was expressed as the concentration causing an increase in lung resistance of 5 cm H2/O/L/s above baseline. Spontaneous and phorbol myristate acetate (PMA)-stimulated (2.4 mumol/L) oxygen radical release were measured, for 10 min each, from washed BAL cells (4 x 10(6) cells/ml) by luminol-enhanced chemiluminescence in a luminometer at 37 degrees C. Superoxide anion production was measured using a cytochrome c assay. Allergen inhalation caused bronchoconstriction, airway inflammation, and airway hyperresponsiveness. The acetylcholine provocative concentration fell from 7.47 mg/ml (% SEM 1.61) before to 1.23 mg/ml (% SEM 1.62) after allergen (p < 0.0001). Allergen inhalation significantly increased absolute neutrophil (p = 0.03) and eosinophil (p = 0.02) counts in BAL. Spontaneous (p < 0.0003) and PMA-stimulated (p < 0.0005) chemiluminescence and superoxide anion production (p = 0.039) were increased after allergen inhalation. The allergen-induced increases in chemiluminescence were significantly correlated with the increases in ACh airway hyperresponsiveness (r = 0.75, p < 0.012). These results indicate that inhaled allergen increases oxygen radical release from bronchoalveolar lavage cells and supports the hypothesis that oxygen radicals are important in causing allergen-induced airway hyperresponsiveness.

Acetylcholine↗

PubMed1990

Methacholine airway responsiveness decreases during exercise in asthmatic subjects.

In many asthmatic subjects, bronchoconstriction develops 2 to 5 min after exercise, reaches a maximum at approximately 10 min, and declines over the next 60 min. However, bronchodilation is typically observed during and immediately after exercise. We measured the bronchoconstrictor responses to increasing concentrations of inhaled methacholine at rest and during two levels of exercise in seven asthmatic subjects to determine the protection against bronchoconstriction afforded by exercise. On the first day, an incremental Stage 1 exercise test was performed to determine the work capacity (Wcap) of each subject. On the second, third, and fourth days, methacholine was inhaled at rest or during steady-state exercise at one-third or two-thirds of Wcap. The bronchoconstrictor response to methacholine was significantly reduced during exercise (p less than 0.0001). The concentration of methacholine required to produce a 20% reduction in FEV1 (PC20) increased from 2.80 mg/ml (%SEM, 1.62) at rest to 7.29 mg/ml (%SEM, 1.43) during exercise at one-third Wcap, and to 31.03 mg/ml (%SEM, 1.74) during exercise at two-thirds Wcap (p less than 0.001). This study has demonstrated that there is greater than tenfold protection against bronchoconstriction by methacholine during exercise, and the magnitude of the protection depends on the intensity of exercise performed. The mechanism of this protection is not known, but may have clinical utility.

Adolescent↗

PubMed1988

Inspiratory muscles during exercise: a problem of supply and demand.

The capacity of inspiratory muscles to generate esophageal pressure at several lung volumes from functional residual capacity (FRC) to total lung capacity (TLC) and several flow rates from zero to maximal flow was measured in five normal subjects. Static capacity was 126 +/- 14.6 cmH2O at FRC, remained unchanged between 30 and 55% TLC, and decreased to 40 +/- 6.8 cmH2O at TLC. Dynamic capacity declined by a further 5.0 +/- 0.35% from the static pressure at any given lung volume for every liter per second increase in inspiratory flow. The subjects underwent progressive incremental exercise to maximum power and achieved 1,800 +/- 45 kpm/min and maximum O2 uptake of 3,518 +/- 222 ml/min. During exercise peak esophageal pressure increased from 9.4 +/- 1.81 to 38.2 +/- 5.70 cmH2O and end-inspiratory esophageal pressure increased from 7.8 +/- 0.52 to 22.5 +/- 2.03 cmH2O from rest to maximum exercise. Because the estimated capacity available to meet these demands is critically dependent on end-inspiratory lung volume, the changes in lung volume during exercise were measured in three of the subjects using He dilution. End-expiratory volume was 52.3 +/- 2.42% TLC at rest and 38.5 +/- 0.79% TLC at maximum exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

Estimate of mean tissue O2 consumption at onset of exercise in males.

A mathematical model has been developed that permitted the calculation of the flow-weighted mean tissue O2 consumption (VO2T) at the onset of a step increase in work rate. From breath-by-breath measurements of alveolar O2 consumption (VO2A) and cardiac output (Q) by impedance cardiography and assumptions about the site of depletion of O2 stores, the rate of change in O2 stores (VO2s) was determined. The sum of VO2A + VO2s = VO2T. Six very fit males performed six repetitions of each of two step increases in work rate. STlo was a transition from rest to 100-W cycling; SThi was a transition from 100- to 200-W cycling. For each work rate transition, the responses of VO2A and Q were averaged over the six repetitions of each subject and the model was solved to yield VO2T. The responses of VO2A, VO2T, and Q after the increase in work rate were fit with a monoexponential function. This function included a time constant and time delay, the sum of which gave the mean response time (MRT). In the STlo test, the MRT of VO2A (24.9 +/- 1.1 s, mean +/- SE) was longer than that of VO2T (15.3 +/- 1.3 s) and of Q (16.5 +/- 6.5 s) (P less than 0.05). The MRT of VO2T and Q did not differ significantly. Also for SThi, the MRT of VO2A (34.4 +/- 3.3 s) was significantly longer than that of VO2T (30.0 +/- 3.4 s) (P less than 0.05). The MRT of VO2T and Q (30.3 +/- 5.5 s) were not significantly different at this work rate either.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1986

Oxygen uptake kinetics from ramp work tests: variability of single test values.

The variability in the estimation of the mean response time (MRT) of O2 uptake (VO2) kinetics from single ramp work rate exercise tests was examined in six repetitions by five fit subjects. Work rate increased at 50 W/min from a base line of 25 W to a work rate of 120% ventilatory threshold. Breath-by-breath data were analyzed by linear regression from 2 min after the onset of the ramp to the 120% work rate. Individual subjects showed approximately twofold differences in estimates of MRT; the coefficient of variation from individuals ranged from 18.5 to 29.3%. The MRT obtained as the mean from the individual repetitions did not differ from the MRT obtained from pooled within-subject data. Analysis of variance on the individual MRT estimates showed 53.9% of the variability was attributable to the slope of the regression, whereas only 2.4% could be attributed to baseline VO2. It was concluded that several repetitions of the ramp work rate tests should be pooled prior to estimation of kinetics parameters.

Adult↗

PubMed1985

Gas exchange analysis of immediate CO2 storage at onset of exercise.

The immediate storage of CO2 at the onset of exercise was estimated in 5 subjects as the difference between measured and predicted CO2 production at work rates of 33, 53 and 75% VO2max. Three time varying models of respiratory exchange ratio (RER) were used to obtain an expected range of predicted CO2 production. Calculated CO2 storage in the transition from rest to 33% VO2max ranged from 0.33 to 0.38 ml X kg-1 X torr-1; from 33 to 53% VO2max, corresponding values were -0.04 to 0.14 ml X kg-1 X torr-1; and, from 53 to 75% VO2max, values ranged from -0.25 to 0.16 ml X kg-1 X torr-1. In two models, CO2 storage decreased significantly at the highest work rate. Estimates of CO2 storage by hyperventilation in the steady state of exercise yielded significantly greater storage. It was concluded that immediate CO2 storage at the onset of exercise was less than hyperventilation estimates, and that it tended to decrease with metabolic acidosis.

Adult↗

PubMed1985

Comparison of cardiac output during exercise by single-breath and CO2-rebreathing methods.

Cardiac output (Q) was estimated in supine rest and in upright cycling at several work rates up to 200 W in five male and one female subjects. At least four repetitions of both the CO2-rebreathing plateau method (Collier, J. Appl. Physiol. 9:25-29, 1956) and the Kim et al. (J. Appl. Physiol. 21: 1338-1344, 1966) single-breath method were performed at each work rate, in a steady state of O2 consumption and heart rate. At supine rest and low work rates, estimates of Q were similar by the two methods. However, at higher work rates, the single-breath method significantly (P less than 0.05) underestimated the value obtained by CO2 rebreathing. The reason for the difference in estimates of Q by the two methods was traced to the determination of arterial partial pressure of CO2 (PaCO2) and mixed venous partial pressure of CO2 (PvCO2). The estimate of PaCO2 from the single-breath method was approximately 88.5% of the estimate from end-tidal PCO2 used with the rebreathing method (P less than 0.001). The oxygenated PvCO2 calculated from the single-breath Q averaged approximately 92.5% of the PvCO2 from CO2 rebreathing (P less than 0.0001). The difference in estimates of Q was not eliminated by using a logarithmic form of the CO2 dissociation curve with the single-breath method.

Adult↗

PubMed1983

Pancreatic enzyme activity in obese and lean Zucker rats: a developmental study.

Exocrine pancreatic enzyme activities were measured in female, obese and lean Zucker rats at 1, 3, 6 and 12 months of age. When expressed per 100 g body weight, food intake, pancreatic weight, and activities of trypsin, chymotrypsin and lipase were highest at 1 month and showed a similar decline with age in both obese and lean rats. In contrast, amylase activity declined only in the obese and remained elevated in the lean. Expressed per milligram pancreas, amylase activity was lower in the obese after 3 months, trypsin was elevated in the obese at 6 and 12 months, lipase was lower at 1 month and elevated at 6 months, whereas chymotrypsin did not differ. Hyperinsulinemia was present in obese rats at all ages, and yet amylase levels were reduced. The inability of insulin to elevate amylase activity in obese animals may be a reflection of the insulin resistance of these animals.

Amylases↗

PubMedDate not supplied

Dose-response protective effect of salbutamol on methacholine airway responsiveness using pressurized metered dose inhalers and Turbuhalers.

The purpose of this study was to estimate the relative dose potency of salbutamol Turbuhaler compared with salbutamol pressurized metered dose inhaler (pMDI) with respect to the protective effect against methacholine bronchoconstriction. Twenty-three asthmatic subjects with stable asthma participated in the study. Baseline forced expiratory volume in 1 s (FEV1) was 70% or more of predicted, and baseline methacholine provocative concentration causing a 20% fall in FEV1 (PC20) was 4 mg/mL or less. The design was randomized, double-blind, double-dummy, crossover and placebo controlled and was conducted over seven study days. On each study day, the subjects inhaled 50 microg or 100 microg of salbutamol via Turbuhaler, 100 microg, 200 microg, 400 microg or 800 microg of salbutamol via pMDI, or placebo in randomized order. PC20 was determined 30 mins after inhalation. Increasing doses of salbutamol pMDI increased the PC20 in a dose-dependent fashion from 3.9 mg/mL after placebo to 13.3 mg/mL after pMDI 100 microg, 19.0 mg/mL after 200 microg, 32.6 mg/mL after 400 microg, and 35.1 mg/mL after 800 microg. The half-maximum response dose for pMDI (ED50) was 104 microg. Salbutamol Turbuhaler 50 microg increased the PC20 to 10.0 mg/mL and 100 microg to 12.6 mg/mL. Salbutamol pMDI 200 microg provided significantly greater protection to methacholine than pMDI 100 microg or Turbuhaler 100 microg and significantly less protection than pMDI 400 microg (P<0. 05). This study demonstrates that the relative protective dose potency of inhaled beta-agonists can be determined by comparing their effects on methacholine airway responsiveness. The estimated relative protective dose potency for salbutamol Turbuhaler in comparison with pMDI was 1.38 (95% CI 0.67 to 2.87) at 50 microg and was 0.96 (95% CI 0.56 to 1.64) at 100 microg.

Adrenergic beta-Agonists↗

PubMedDate not supplied

Management of exercise-induced bronchoconstriction.

Exercise-induced bronchoconstriction (EIB) is a common clinical manifestation of asthma, occurring in 70% to 80% of asthmatics. Evidence suggests that exercise and the ensuing bronchoconstriction do not contribute to a worsening of asthmatic inflammation. Asthmatics should not be discouraged from exercising, and, with adequate management, most patients should be able to exercise regularly with only minor symptoms. The first step in the management of patients with EIB should be to obtain optimum control of the underlying asthma, often requiring regular treatment with inhaled steroids. Regular treatment with inhaled corticosteroids usually reduces the extent of EIB by 50% or more. Frequently, despite optimal management of the underlying asthma, patients develop EIB symptoms requiring additional treatment. Short and long acting inhaled beta2-agonists are highly effective at reducing the magnitude of EIB, although there are concerns that the extent of protection diminishes during periods of regular use of these agents. Inhaled cromolyn and nedocromyl are effective at reducing the extent of EIB in some patients, although this protection does not extend beyond 2 to 3 h after treatment. The recently developed leukotriene receptor antagonists are effective at reducing the extent of EIB by 40% to 70%, and have the advantage that this protection lasts throughout the day and does not appear to diminish with regular use. Other agents, including anticholinergics and antihistamines, have been shown to offer partial protection against EIB, suggesting the possibility of using a combination treatment to manage some patients' symptoms. Finally, there is encouraging evidence suggesting that modifications of the pattern of exercise can markedly reduce the extent of EIB.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

Protective effects of fluticasone on allergen-induced airway responses and sputum inflammatory markers.

BACKGROUND: A direct comparison of the protective effects of single and regular doses of inhaled glucocorticoid on allergen-induced asthmatic responses and inflammation has not been made. OBJECTIVE: To compare the effects of pretreatment with fluticasone 250 microg 30 min before allergen inhalation and two weeks of 250 microg twice daily (last dose 24 h before challenge) with single and regular (twice daily) placebo doses on early and late asthmatic responses, induced sputum cell counts and measures of eosinophil activation at 7 h and 24 h, and methacholine airway responsiveness at 24 h. PATIENTS AND METHODS: Ten mild asthmatic patients were studied in a randomized, double-blind, placebo controlled crossover study. RESULTS: Regular fluticasone increased the baseline mean provocative concentration of methacholine to cause a 20% fall (PC20) in forced expiratory volume in 1 s (FEV1) from 2.6 to 6.4 mg/mL (P<0.05) and lowered the eosinophil count from 3.1% to 0.4% (P<0.05) compared with regular placebo. Neither single nor regular fluticasone had any effect on the early asthmatic response. Single fluticasone attenuated the late asthmatic response, the mean +/- SEM maximum percentage fall in FEV1 (10.8+/-3.6 compared with single placebo 18. 8+/-3.5, P=0.03), the allergen-induced increase of airway responsiveness (P<0.05), and the eosinophilia (P<0.005) and activated eosinophils at 7 h (P<0.01) but not at 24 h. Regular fluticasone also attenuated the late asthmatic response (11.1+/-2.5) compared with regular placebo (19.6+/-4.5), but this was not statistically significant and did not protect against the induced increase in airway responsiveness or the sputum eosinophilia. CONCLUSION: Two weeks of regular inhaled fluticasone discontinued 24 h before allergen challenge does not offer any additional protection against the early or late asthmatic responses, increased airway responsiveness or sputum eosinophilia compared with a single dose of 250 microg immediately before allergen challenge, despite increasing baseline PC20 and decreasing sputum eosinophilia prechallenge. The significance of the protective effect of a single dose of inhaled steroid before an allergen inhalation and the duration of the protective effect need further investigation.

Administration, Topical↗

PubMedDate not supplied

Bone marrow progenitors in allergic airways diseases: studies in canine and human models.

In a canine model of Ascaris suum-inducible bronchial hyperresponsiveness, we previously demonstrated that bone marrow-derived myeloid progenitors rise within 24 h of allergen inhalation; this effect is abolished by pretreatment with inhaled budesonide. We now report that this allergen-induced bone marrow response is observable in human asthmatics, and involves increases in both neutrophil-macrophage and eosinophil-basophil progenitors, within 6 h of allergen inhalation, as measured either by hematopoietic colony assays or by flow cytometric analyses of CD34+, IL-3R alpha+, and/or IL-5-responsive cell populations. In dogs, but not in humans, a transferrable serum hematopoietic activity accounts for the marrow response to inhaled allergen. These findings suggest that allergen-induced increases in bone marrow progenitor formation depend either on a serum hematopoietic factor(s) released after allergen challenge, or upon constitutive marrow upregulation of specific progenitors in allergic airway disease. Further studies to characterize the serum hematopoietic factor(s) and to determine the nature of any atopy-related progenitor profile are in progress.

Animals↗