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Biomedical subjects

H A Boushey

Publications and source records attributed to H A Boushey.

At least 19 recordsLinked to original sources
PubMed1992

Mucus hypersecretion in bronchiectasis. The role of neutrophil proteases.

To investigate the role of neutrophil proteases in the pathogenesis of mucus hypersecretion in bronchiectasis, we collected sputum samples from seven patients with bronchiectasis and measured their secretagogue activity by examining secretion of radiolabeled macromolecules by bovine airway submucosal gland cells incubated with sputum supernatants. There was marked secretagogue activity in bronchiectasis sputum, reaching a maximum of 1,963 +/- 292% (mean +/- SEM) above baseline at 1:15 dilution. Addition of ICI 200,355 (10(-5) M), a selective human neutrophil elastase inhibitor, decreased the secretory response markedly (72.53 +/- 5.89% reduction). The combination of aprotinin, an inhibitor of cathepsin G, and ICI 200,355 caused significantly more reduction in the secretory response than ICI 200,355 alone (89.12 +/- 3.8 versus 72.53 +/- 5.89% reduction, p < 0.05). We conclude that bronchiectasis sputum causes a large secretory response from tracheal submucosal glands due mostly to neutrophil proteases.

Adult↗
PubMed1991

An experimental human model of metal fume fever.

OBJECTIVE: To examine the pathogenesis of metal fume fever in humans by studying functional, cellular, and biochemical responses after exposure to zinc welding fume. DESIGN: Clinical experimental study. PARTICIPANTS: We studied 14 welders recruited through public advertisements. INTERVENTIONS: Participants welded galvanized steel. MEASUREMENTS: We measured lung volumes, airflow, diffusing capacity for carbon monoxide, and airway reactivity at baseline as well as either 6 or 20 hours after welding. We carried out bronchoalveolar lavage either 8 hours (early follow-up, 5 participants) or 22 hours (late follow-up, 9 participants) after welding, assaying the fluid for total and differential cell counts and bronchoalveolar lavage supernatant concentrations of interleukin-1 and tumor necrosis factor (TNF). MAIN RESULTS: Changes in pulmonary function and airway reactivity were minimal. Cumulative zinc exposure and polymorphonuclear leukocyte count in bronchoalveolar lavage fluid at late (r = 0.87; P less than 0.01) and early (r = 0.93; P less than 0.05) follow-up were positively correlated. Among the late follow-up group, the mean proportion of polymorphonuclear leukocytes was 37% (range, 19% to 63%), a statistically greater proportion than the 9% (range, 2% to 21%) seen among the early follow-up group (P less than 0.05). We did not detect TNF or more than a trace amount of interleukin-1 in the bronchoalveolar lavage supernatant. CONCLUSIONS: Zinc oxide welding fume was associated with a marked dose-dependent increase in the number of polymorphonuclear leukocytes recovered in bronchoalveolar lavage fluid 22 hours after exposure but was not associated with a clinically significant change in pulmonary function or airway reactivity. Although we did not identify increases in either interleukin-1 or TNF levels in bronchoalveolar lavage fluid, cytokines or a cytokine-like mechanism may mediate the syndrome of metal fume fever.

Adult↗
PubMed1991

Effects of 0.60 PPM nitrogen dioxide on circulating and bronchoalveolar lavage lymphocyte phenotypes in healthy subjects.

Nitrogen dioxide (NO2) is a common oxidant air pollutant. Animal studies have suggested that NO2 exposure causes a decrease in the numbers of some splenic lymphocyte subtypes and impairs lymphocyte-dependent immune responses. To investigate whether ambient levels of NO2 alter circulating and bronchoalveolar lavage fluid (BALF) human lymphocytes, we studied five healthy nonsmoking adult volunteers. In each subject, blood and bronchoalveolar lavage fluid was obtained and then, more than 2 weeks later, volunteers were exposured to 0.60 ppm NO2 for 2 hr with intermittent light to moderate exercise on 4 separate days within a 6-day period. We measured standard tests of pulmonary function (airway resistance, thoracic gas volume, maximal expiratory flow) and had the subjects rate the severity of respiratory symptoms before and after each NO2 exposure. Circulating and BALF lymphocytes were labeled with fluorochrome-conjugated monoclonal antibodies to human lymphocyte antigens and a flow cytometer was used to count lymphocyte subtypes. Neither any single day's exposure nor all four exposures caused a change in symptoms or in the results of tests of pulmonary function. The total number of circulating lymphocytes obtained after NO2 exposure was slightly greater than at baseline (1792 +/- 544 vs 1598 +/- 549 cells/mm3 at baseline; P = not significant) but the proportions of lymphocyte subtypes did not differ. In the BALF obtained after NO2 exposure and in the baseline state, the total number of lymphocytes and the percentages of T cells (CD 3), B cells (CD 20), T cytotoxic-suppressor cells (CD 8), T helper-inducer cells (CD 4), and large granular lymphocytes (CD 57) also did not differ after NO2 exposure. A slightly but significantly greater proportion of natural killer cells (CD 16) was found in the BALF obtained after NO2 exposure (7.2 +/- 3.1 vs 4.2 +/- 2.4% of total lymphocytes). We conclude that repeated exposures of healthy nonsmoking adults to 0.60 ppm NO2 are not associated with clinically significant symptoms, changes in airway caliber, or alterations in circulating and BALF lymphocyte subtypes. We suggest that brief, daily exposures to NO2 at levels higher than those achieved in urban atmosphere are unlikely to provoke acute respiratory impairment in healthy, nonsmoking adults.

Adult↗
PubMed1991

Cough in hot pepper workers.

STUDY OBJECTIVE: To determine whether there is an effect on the prevalence of respiratory symptoms, an alteration in lung function, or an increase in the cough threshold to capsaicin among workers chronically exposed to hot chili (Capsicum) peppers. DESIGN: Cross-sectional study of responses to a structured questionnaire, lung function assessed by spirometry and cough threshold to inhalation of capsaicin aerosol in a group of occupationally-exposed Capsicum workers as compared to non-exposed employees of the same work site. SETTING: Spice manufacturing facility. PARTICIPANTS: Twenty-two Capsicum-exposed and 19 nonexposed workers. MEASUREMENTS AND MAIN RESULTS: When evaluated by questionnaire, 13 (59 percent) of the Capsicum-exposed workers reported cough as compared to 4 (21 percent) of the nonexposed workers (p less than 0.05). Baseline FEV1 and FVC did not differ between the two groups. Cough threshold, as assessed by the lowest concentration of inhaled capsaicin eliciting cough, was related to workplace exposure (p = 0.05), displaying a bimodal pattern of higher and lower cough thresholds among the Capsicum workers as compared to a unimodal distribution among the nonexposed workers. Within the exposed group, a higher cough threshold was significantly related to male gender (p = 0.03) and was associated to a lesser extent with dietary preference for hot food (p = 0.09) and cumulative cigarette smoking (p = 0.07). CONCLUSION: Chronic occupational exposure to chili peppers is associated with complaints of cough but does not alone lead to decreased responsiveness of capsaicin-sensitive nerves when assessed by cough threshold. The cough response to capsaicin inhalation may be modified by the effects of multiple, potentially interactive factors.

Adult↗
PubMed1990

Short-term exposure to 0.3 ppm nitrogen dioxide does not potentiate airway responsiveness to sulfur dioxide in asthmatic subjects.

Whether short-term exposure to low levels of nitrogen dioxide (NO2) enhances airway responsiveness in asthmatic subjects is controversial. Because it is well established that asthma is associated with increased airway responsiveness to another common air pollutant, sulfur dioxide (SO2), we examined whether short-term exposure of asthmatic subjects to 0.3 ppm NO2 potentiates airway responsiveness to inhaled SO2. We exposed nine subjects with clinically stable asthma to 0.3 ppm NO2 or filtered air in an environmental room for 30 min on 2 separate days at least 1 wk apart in a double-blind, randomized fashion. A questionnaire about common symptoms related to inhaled irritants was completed before and immediately after each exposure. Each subject exercised (60 to 80 W) on a cycloergometer during the first 20 min of each exposure. We measured specific airway resistance (SRaw) and FEV1/FVC before, 5 min after, and 1 h after completion of the air or NO2 exposure. The single-breath nitrogen test (SBN2) was also performed before and 1 h after completion of the air or NO2 exposures and closing volume was determined; subsequently, SO2 dose-response curves (0.25 to 4.0 ppm) were performed via a mouthpiece. Each dose of SO2 was inhaled at a minute ventilation of 20 L/min for 4 min and was doubled until SRaw increased by at least 8 U above baseline. The dose of SO2 required to provoke an increase in SRaw of 8 U above baseline was determined by linear interpolation from the dose-response curve (PD8Uso2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Local mediator release after antigen challenge of a bronchial segment in allergic dogs.

To investigate the local intraluminal bronchial response to an antigenic stimulus, we developed a bronchoscopic double-balloon system to challenge and lavage a segment of the left main-stem bronchus. We studied whether fluid from above or below the occlusion balloons leaked into the bronchial segment. Lavage was performed before and after placement of red and blue pigments proximal and distal to the inflated balloons, respectively, and the recovered lavage fluid was analyzed visually and spectrophotometrically in three experiments. There was no evidence for pigment leakage into the segment. In six anesthetized ragweed-allergic dogs, local ragweed antigen challenges were performed. After balloon inflation in the left main-stem bronchus, we performed two baseline lavages of the interballoon segment, introduced a ragweed antigen solution, and performed two postchallenge lavages. The recovered fluid was analyzed for the concentrations of prostaglandin D2 (PGD2; radioimmunoassay) and histamine (fluorometric technique) and for total and differential cell counts. Antigen challenge was associated with a significant increase in PGD2 concentration in the recovered fluid, rising from a median of 178 pg/ml (range, 157-647) before to 919 pg/ml (range, 149-2,452) after challenge. Median histamine concentrations were 3.1 ng/ml (range, 1-5.4 ng/ml) before and 5.6 ng/ml (range, 1-16.2) after challenge (P = not significant). In four dogs, a control challenge with the antigen vehicle alone showed no change in either mediator. Changes in cell counts after challenge were inconsistent.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗
PubMed1989

Effect of exercise, hyperpnea, and bronchoconstriction on plasma atrial natriuretic peptide.

To examine whether endogenous secretion of atrial natriuretic peptide (ANP) modifies the bronchomotor response to moderately strenuous exercise and, conversely, whether hyperpnea of exercise or bronchoconstriction alone modulates the release of ANP, we compared the rise in specific airway resistance and the rise in circulating immunoreactive ANP (IR-ANP) induced by a 5-min submaximal exercise and by eucapnic hyperpnea with cold dry air and exercise-matched minute ventilation in six healthy individuals and in five subjects with clinically stable asthma. As expected, the increase in specific airway resistance from base line provoked by exercise was greater in the asthmatic subjects (from 11.8 +/- 7.1 to 34.0 +/- 18.6 l.cmH2O.l-1.s-1) than in the healthy subjects (from 3.7 +/- 1.2 to 4.5 +/- 1.9 l.cmH2O.l-1.s-1). In both groups, exercise was associated with a similar and significant rise in plasma IR-ANP levels, ranging from 222 to 550% from base-line value in the healthy group and from 176 to 1,120% from base-line value in the asthmatic group. Peak plasma IR-ANP levels occurred from 3 to 15 min after completion of exercise with a return to base-line values within 60 min. Although eucapnic hyperpnea was associated with a similar increase in specific airway resistance as was exercise, it provoked an increase in circulating IR-ANP in only one subject.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Local cellular and humoral responses to antigenic and distilled water challenge in subjects with allergic rhinitis.

We studied nasal responses to allergen, saline, and distilled water aerosol in 7 subjects with allergic rhinitis to determine whether they caused a similar release of mediators and influx of inflammatory cells into the nasal lumen. The subjects were challenged first with allergen and then with aerosols of distilled water and of normal saline in random order on separate days. We measured nasal airway resistance (Rn) by posterior rhinomanometry, measured the concentrations of protein, histamine, leukotrienes (LT) B4, C4, and D4, and platelet-activating factor (PAF-acether) and performed total and differential cell counts in nasal lavage fluid obtained before and after each challenge. Allergen challenge provoked a 2-fold or greater increase in nasal airway resistance in all subjects (mean increase = 12.2-fold). This response was associated with significant increases in protein, histamine, LTB4, and sulfidopeptide leukotrienes. 2-lyso-PAF-acether increased significantly, indicating activation of phospholipase A2, but PAF-acether was detected in only one subject. The total cell count increased from 55 +/- 44 x 10(3)/ml to 200 +/- 168 x 10(3)/ml; polymorphonuclear neutrophils increased from 11 +/- 22 x 10(3)/ml to 108 +/- 96 x 10(3)/ml, and eosinophils increased from 1.3 +/- 1.8 x 10(3)/ml to 10.6 +/- 15.3 x 10(3)/ml (p less than 0.05). Saline insufflation provoked insignificant changes in mean Rn, in the levels of protein and all inflammatory mediators, and in the number and types of cells in nasal lavage fluid. Distilled water insufflation also provoked an insignificant increase in mean Rn, but there was a 14-fold increase in one subject.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Indomethacin blocks airway tolerance to repetitive exercise but not to eucapnic hyperpnea in asthmatic subjects.

We have examined the effects of indomethacin (I) on tolerance to the bronchomotor effects of repetitive challenge with exercise (EX) and eucapnic hyperpnea (EH) in 7 asthmatic subjects. Each subject was studied on 4 separate days. EH was performed for 4 min at a minute ventilation found previously to increase specific airway resistance (SRaw) by 8 units (cm H2O/L/s). All exercise challenges were performed on a cycle ergometer for 5 min at a constant work load. Subjects breathed room temperature, dry air for both stimuli. SRaw was serially measured before and after each stimulus. Tolerance was examined by giving up to 3 repetitions of EH or EX, allowing a return of SRaw to within 1 unit of baseline between repetitions. Placebo (P) or I (25 mg four times a day for 7 doses) was administered in a single-blind manner. The timing between stimulus repetitions on the P day was matched to that of the I day. After P, the initial rise in SRaw was similar for both EX and EH, with a significant and progressive decrease in this rise after each stimulus repetition (p = 0.032 for EX, p = 0.006 for EH). After I, tolerance was still demonstrated to EH (p = 0.002), but not to EX (p = 0.231). This finding indicates that EH and EX are not identical stimuli, since there is an I-sensitive mechanism (possibly a bronchodilating prostaglandin) associated with the development of tolerance to EX but not to EH. Our data also suggest a possible additional bronchoconstricting mechanism associated with EX and not with EH.

Adaptation, Physiological↗
PubMed1988

Sulfur dioxide does not acutely increase nasal symptoms or nasal resistance in subjects with rhinitis or in subjects with bronchial responsiveness to sulfur dioxide.

We examined whether brief exposures to moderately high concentrations of sulfur dioxide (SO2) causes acute increases in nasal symptoms and nasal resistance in subjects with chronic rhinitis. We studied 19 subjects with allergic rhinitis and 3 subjects with chronic intermittent rhinorrhea, nasal congestion, and sneezing without any other manifestation of allergy. We found that the change in nasal resistance and symptoms caused by nasal inhalation of 4 ppm of SO2 for 10 min was no greater than the changes caused by nasal inhalation of conditioned room air. In a second set of experiments, we examined whether allergic subjects with demonstrable bronchomotor responsiveness to SO2 also had nasal responsiveness to the gas. We studied 8 subjects with a history of both asthma and allergic rhinitis. Each subject developed symptoms of dyspnea or wheezing and an increase in specific airway resistance of at least 8 L x cm H2O/L/s after breathing 1 or 2 ppm of SO2 by mouthpiece at 20 L/min, and did not develop these changes after breathing room air under the same conditions. No subject, however, developed more nasal symptoms or a greater increase in nasal airway resistance after tidally breathing SO2 through the nose than after breathing room air, even when the concentration of SO2 delivered to the nose was double the concentration delivered through the mouthpiece to the lower airways. We conclude that brief exposure to SO2 at a concentration of 4 ppm or less is unlikely to cause significant nasal dysfunction in most subjects with chronic rhinitis, and that in subjects with both allergic rhinitis and asthma, responsiveness to SO2 is not uniform throughout the respiratory tract.

Administration, Inhalation↗
PubMed1988

Nasal response to substance P and methacholine in subjects with and without allergic rhinitis.

We compared the rise in nasal airway resistance (NAR) provoked by topical application of substance P (SP) and of methacholine (MCH) in seventeen patients suffering from rhinitis and fourteen control subjects. Challenges with SP or MCH were separated by a week or more. NAR was measured by posterior rhinomanometry before and 10 min after intranasal administration of SP (10-40 nmol) or MCH (3-12 mumol). The two groups of subjects had similar baseline levels of NAR and similar small responses to buffered saline. Substance P but not MCH provoked cutaneous flushing in all subjects. Both SP and MCH provoked a significantly greater increase in NAR in patients suffering from rhinitis than in control subjects. The increase in NAR was dose-dependent, and on a molar basis, SP was 375-500-fold more potent than MCH. Pretreatment with 200 micrograms of a topically active anticholinergic agent, oxytropium bromide, prevented the rise in NAR caused by 12 mumol of MCH but not that caused by 40 nmol of SP in six patients suffering from rhinitis. We conclude that SP is absorbed across the nasal mucosa and causes cutaneous vasodilation, that MCH and SP cause a greater rise in NAR in patients suffering from rhinitis than in control subjects, that SP is about 500-fold more potent than MCH in increasing NAR, and that the rise in NAR caused by SP is not mediated by postganglionic parasympathetic mechanisms.

Administration, Intranasal↗
PubMed1987

Hypotonic and isotonic aerosols increase bronchial reactivity in basenji-greyhound dogs.

Because basenji-greyhound dogs have greater bronchial reactivity to a range of inhaled stimuli than mongrel dogs do, and because bronchial hyperreactivity to nonspecific stimuli is characteristic of asthma, we asked whether basenji-greyhound dogs have greater bronchial reactivity to hypotonic and isotonic aerosols than mongrel dogs do. We assessed bronchial reactivity by measuring both the total pulmonary resistance and the bronchial response to an acetylcholine aerosol, before and after delivery of hypotonic and isotonic aerosols. Bronchial reactivity as measured by a change in total pulmonary resistance increased 9-fold after delivery of hypotonic and 5-fold after delivery of isotonic aerosols in 5 anesthetized basenji-greyhound dogs, but not in 3 similarly challenged mongrel dogs (p less than 0.01). Bronchial reactivity as measured by an increased bronchial response to acetylcholine aerosol increased 3-fold in basenji-greyhound dogs but not in mongrel dogs. Thus, hypotonic and isotonic aerosols increase bronchial reactivity in basenji-greyhound dogs. We also asked whether vagal or nonvagal pathways are involved in the increase in total pulmonary resistance induced by a hypotonic aerosol. Both vagal and nonvagal pathways appear to be involved, since blockade of the vagal pathway by intravenously administered atropine only partially inhibited the bronchoconstriction induced by a hypotonic aerosol (54%). Disodium cromoglycate, which inhibits vagal and nonvagal pathways, partially inhibited the bronchoconstriction (57%), but even in combination with atropine, did not completely inhibit it (68%). Our observations in basenji-greyhound dogs are similar to results in asthmatic subjects, suggesting that basenji-greyhound dogs are useful experimental animals in which to study the mechanisms by which hypotonic and isotonic aerosols increase bronchial reactivity.

Aerosols↗
PubMed1987

Combination therapy with anticholinergic agents for airflow obstruction.

The availability of long-acting, locally effective anticholinergic agents that can be delivered by aerosol and that have little systemic toxicity offers an alternative or additional form of therapy for relief of airflow obstruction. Most studies of combination therapy have examined the interaction of anticholinergic drugs with beta-adrenergic agents. For patients with asthma, combination treatment appears not to increase significantly the maximal bronchodilatation achievable with beta-agonists alone but does appear to prolong bronchodilatation and to permit reductions in the dose of beta-agonists without loss of efficacy. For patients with chronic obstructive bronchitis and emphysema, combination therapy may also increase the bronchodilatation achievable with beta-adrenergic agents alone. Anticholinergic agents have been shown also to increase the inhibitory effect of sodium cromoglycate on the bronchospastic response to exercise, eucapnic hyperpnoea and sulphur dioxide.

Airway Obstruction↗
PubMed1987

Asthma mortality.

These discussions are selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from transcriptions, they are prepared by Drs Homer A. Boushey, Professor of Medicine, and David G. Warnock, Associate Professor of Medicine, under the direction of Dr Lloyd H. Smith, Jr, Professor of Medicine and Associate Dean in the School of Medicine. Requests for reprints should be sent to the Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, CA 94143.

Aged↗
PubMed1986

Emotionally triggered asthma as a predictor of airway response to suggestion.

Twenty-nine male and female adults with asthma were tested to determine the relationship between perceived response to emotional triggers of asthma and bronchoconstrictive suggestion. Subjects were told that they were inhaling a bronchoconstricting agent in four increasingly potent concentrations, when in fact the solution the subjects inhaled was nebulized isotonic saline. Ten subjects responded to suggestion with a greater than 20% increase in specific airway resistance, but this response could not be predicted by the report of perceived emotional triggers of asthma. The finding that perception of asthmatic response to emotional arousal does not predict airway response to bronchoconstrictive suggestion may mean that suggestion is an invalid proxy variable for studying the role of psychological factors in provocation of asthma.

Adult↗
PubMed1986

O3-induced change in bronchial reactivity to methacholine and airway inflammation in humans.

The increase in airway responsiveness induced by O3 exposure in dogs is associated with airway epithelial inflammation, as evidenced by an increase in the number of neutrophils (polymorphonuclear leukocytes) found in epithelial biopsies and in bronchoalveolar lavage fluid. We investigated in 10 healthy, human subjects whether O3-induced hyperresponsiveness was similarly associated with airway inflammation by examining changes in the types of cells recovered in bronchoalveolar lavage fluid obtained after exposure to air or to O3 (0.4 or 0.6 ppm). We also measured the concentrations of cyclooxygenase and lipoxygenase metabolites of arachidonic acid in lavage fluid. We measured airway responsiveness to inhaled methacholine aerosol before and after each exposure and performed bronchoalveolar lavage 3 h later. We found more neutrophils in the lavage fluid from O3-exposed subjects, especially in those in whom O3 exposure produced an increase in airway responsiveness. We also found significant increases in the concentrations of prostaglandins E2, F2 alpha, and thromboxane B2 in lavage fluid from O3-exposed subjects. These results show that in human subjects O3-induced hyperresponsiveness to methacholine is associated with an influx of neutrophils into the airways and with changes in the levels of some cyclooxygenase metabolites of arachidonic acid.

Adult↗