Biomedical subjects

Adam Wanner

Publications and source records attributed to Adam Wanner.

At least 19 recordsLinked to original sources

PubMed2007

Aerosolized red-tide toxins (brevetoxins) and asthma.

BACKGROUND: With the increasing incidence of asthma, there is increasing concern over environmental exposures that may trigger asthma exacerbations. Blooms of the marine microalgae, Karenia brevis, cause red tides (or harmful algal blooms) annually throughout the Gulf of Mexico. K brevis produces highly potent natural polyether toxins, called brevetoxins, which are sodium channel blockers, and possibly histamine activators. In experimental animals, brevetoxins cause significant bronchoconstriction. In humans, a significant increase in self-reported respiratory symptoms has been described after recreational and occupational exposures to Florida red-tide aerosols, particularly among individuals with asthma. METHODS: Before and after 1 h spent on beaches with and without an active K brevis red-tide exposure, 97 persons >or= 12 years of age with physician-diagnosed asthma were evaluated by questionnaire and spirometry. Concomitant environmental monitoring, water and air sampling, and personal monitoring for brevetoxins were performed. RESULTS: Participants were significantly more likely to report respiratory symptoms after K brevis red-tide aerosol exposure than before exposure. Participants demonstrated small, but statistically significant, decreases in FEV(1), midexpiratory phase of forced expiratory flow, and peak expiratory flow after exposure, particularly among those participants regularly using asthma medications. No significant differences were detected when there was no Florida red tide (ie, during nonexposure periods). CONCLUSIONS: This study demonstrated objectively measurable adverse changes in lung function from exposure to aerosolized Florida red-tide toxins in asthmatic subjects, particularly among those requiring regular therapy with asthma medications. Future studies will assess these susceptible subpopulations in more depth, as well as the possible long-term effects of these toxins.

Adolescent↗

PubMed2006

Acute effect of cigarette smoke and nicotine on airway blood flow and airflow in healthy smokers.

Cigarette smoke contains irritants and vasoactive substances. We wanted to determine the effect of smoking a cigarette and of nasally or orally inhaled nicotine on airway blood flow (Q(aw)) and airflow in smokers. In ten healthy current smokers, Q(aw), FEV(1), and FEF(25-75) were measured before and at 5, 30, and 180 min after smoking a cigarette. The effects of systemic nicotine using a nicotine nasal spray and local nicotine using a nicotine inhaler were also studied. Mean (+/- SE) Q(aw) increased by 81% +/- 16% (p = 0.03) 5 min after smoking a cigarette and was no longer different from baseline at 30 and 180 min. Nicotine nasal spray and nicotine oral inhaler had no effect on Q(aw.) FEV(1) and FEF(25-75) remained unchanged after smoking a cigarette and after local or systemic nicotine administration. Smoking a cigarette is followed by a transient increase in airway blood flow but no changes in airflow. Nicotine, at the rate and dose provided by the nasal spray (systemic action) and oral inhaler (local and systemic action), does not appear to be involved in the Q(aw) change, suggesting a pharmacologic or nonspecific irritant effect of other cigarette smoke constituents.

Adult↗

PubMed2006

Epithelial organic cation transporters ensure pH-dependent drug absorption in the airway.

Most inhaled beta(2)-adrenergic agonist and anticholinergic bronchodilators have low lipid solubility because of their transient or permanent positive net charge at physiologic pH. Airway absorption of these cationic drugs is incompletely understood. We examined carrier-mediated mechanisms of cationic drug uptake by human airway epithelia. Airway tissues and epithelial cells, obtained from lung donors without preexisting lung disease, were evaluated for organic cation transporter expression by quantitative RT-PCR and immunofluorescence. For in vitro functional studies on primary airway epithelial cells, uptake of the cationic fluorophore 4-[4-(dimethylamino)-styryl]-N-methylpyridinium (ASP+) was characterized. Quantitative RT-PCR analysis demonstrated high mRNA levels for two polyspecific organic cation/carnitine transporters, OCTN1 and OCTN2, in human airway epithelia. Immunofluorescence of human airway sections confirmed OCTN1/2 protein expression, with a predominant localization to the apical portion of epithelial cells. Primary airway epithelial cells showed a carrier-mediated, temperature-sensitive and saturable uptake of ASP(+). Seventy-five to eighty percent of ASP(+) uptake was inhibited by L-carnitine, an OCTN2-carried zwitterion. The uptake was pH dependent, with approximately 3-fold lower rates at acidic (pH 5.7) than at alkaline (pH 8.2) extracellular pH. Albuterol and formoterol inhibited ASP(+) uptake, suggesting that all these molecules are carried by the same transport mechanism. These findings demonstrate the existence and functional role of a pH-dependent organic cation uptake machinery, namely OCTN1 and OCTN2, in human airway epithelia. We suggest that epithelial OCTN1/2 are involved in the delivery of inhaled cationic bronchodilators to the airway tissue.

Adrenergic beta-Agonists↗

PubMed2006

Inhaled corticosteroids reduce asthma-associated airway hyperperfusion through genomic and nongenomic mechanisms.

Inhaled corticosteroids have both genomic and nongenomic actions on the tracheobronchial (airway) vasculature in patients with bronchial asthma. Genomic actions involve the activation or repression of target genes associated with inflammation, and reduce inflammatory hyperperfusion in the airway. In contrast, nongenomic actions are mediated by rapid cellular mechanisms, and induce transient vasoconstriction. This article reviews recent progress on the mechanisms by which inhaled corticosteroids reverse inflammatory blood flow changes in the airway in asthma.

Administration, Inhalation↗

PubMed2006

Airway blood flow reactivity in smokers.

Cigarette smoking has been associated with impaired endothelium-dependent relaxation responses in the brachial and coronary arteries (endothelial dysfunction). The aim of the present study was to determine if the airway circulation is also affected and if airway treatment has an effect on endothelial function. Airway blood flow (Q(aw)) responses to inhaled albuterol as an index of endothelial function were measured in age-matched healthy current smokers, healthy ex-smokers, ex-smokers with COPD and healthy lifetime non-smokers; in the ex-smokers with COPD, the albuterol responsiveness was repeated after a 4-week treatment with an inhaled glucocorticoid/beta(2)-adrenergic agonist combination drug. Mean baseline Q(aw) was similar in the four groups. Albuterol inhalation increased mean Q(aw) in lifetime non-smokers (50.1+/-8.3%; p<0.05) and in healthy ex-smokers (37.2+/-3.4%; p<0.05) but not in healthy current smokers (13.9+/-3.2%; p=NS) and ex-smokers with COPD (9.7+/-4.5%; p=NS). While drug treatment per se did not change Q(aw) significantly, it restored albuterol responsiveness (+67.6+/-11.1%; p<0.05) in the ex-smokers with COPD. Thus, cigarette smoking is associated with endothelial dysfunction in the airway, with a partial recovery of endothelial function after smoking cessation in healthy ex-smokers but not in ex-smokers with COPD. In the latter, combined glucocorticoid/beta(2)-adrenergic agonist treatment restores albuterol responsiveness.

Administration, Inhalation↗

PubMed2006

A simplified noninvasive method to measure airway blood flow in humans.

Our laboratory has previously developed and validated a noninvasive soluble gas uptake method to measure airway blood flow (Qaw) in humans (Onorato DJ, Demirozu MC, Breitenbücher A, Atkins ND, Chediak AD, and Wanner A. Am J Respir Crit Care Med 149: 1132-1137, 1994; Scuri M, McCaskill V, Chediak AD, Abraham WM, and Wanner A. J Appl Physiol 79: 1386-1390, 1995). The method has the disadvantage of requiring eight breath-hold maneuvers for a single Qaw measurement, a complicated data analysis, and the inhalation of a potentially explosive gas mixture containing dimethylether (DME) and O2. Because of these shortcomings, the method thus far has not been used in other laboratories. We now simplified the method by having the subjects inhale 500 ml of a 10% DME-90% N2 gas mixture to fill the anatomical dead space, followed by a 5- or 15-s breath hold, and measuring the instantaneous DME and N2 concentrations and volume at the airway opening during the subsequent exhalation. From the difference in DME concentration in phase 1 of the expired N2 wash-in curve multiplied by the phase 1 dead space volume and divided by the mean DME concentration and the solubility coefficient for DME in tissue, Qaw can be calculated by using Fick's equation. We compared the new method to the validated old method in 10 healthy subjects and found mean +/- SE Qaw values of 34.6 +/- 2.3 and 34.6 +/- 2.8 microl.min(-1).ml(-1), respectively (r = 0.93; upper and lower 95% confidence limit +2.48 and -2.47). Using the new method, the mean coefficient of variation for two consecutive measurements was 4.4% (range 0-10.4%); inhalation of 1.2 mg albuterol caused a 53 +/- 14% increase in Qaw (P = 0.02) and inhalation of 2.4 mg methoxamine caused a 32 +/- 7% decrease in Qaw (P = 0.07). We conclude that the new method provides reliable values of and detects the expected changes in Qaw with vasoactive drugs. The simplicity and improved safety of the method should improve its acceptability for the noninvasive assessment of Qaw in clinical research.

Administration, Inhalation↗

PubMed2006

Airway blood flow reactivity in healthy smokers and in ex-smokers with or without COPD.

STUDY OBJECTIVES: Cigarette smoking has been associated with impaired endothelium-dependent relaxation responses in the brachial and coronary arteries (endothelial dysfunction). The aim of the present study was to determine whether the airway circulation is also affected and whether pharmacologic treatment has an effect on endothelial function in patients with COPD. METHODS AND PATIENTS: Airway blood flow (Qaw) responses to therapy with inhaled albuterol, which causes endothelium-dependent vasodilation, were measured with a noninvasive soluble-gas-uptake technique in age-matched healthy current smokers (n = 10), healthy ex-smokers (n = 10), ex-smokers with COPD (n = 10), and healthy lifetime nonsmokers. In the ex-smokers with COPD, the albuterol responsiveness measurement was repeated after 4 weeks of treatment with fluticasone/salmeterol and after a drug washout period of 4 or 8 weeks. RESULTS: The mean (+/- SE) baseline Qaw values ranged between 40.7 +/- 3.9 and 50.9 +/- 2.8 microL/min/mL anatomic dead space in the four groups (differences were not significant). The mean FEV(1) was 53.4 +/- 2.3% predicted in the ex-smokers with COPD. Albuterol inhalation increased mean Qaw significantly in lifetime nonsmokers (50.1 +/- 8.3% predicted; p < 0.05) and healthy ex-smokers (37.2 +/- 3.4% predicted; p < 0.05), but not in healthy current smokers (13.9 +/- 3.2% predicted; difference was not significant) and ex-smokers with COPD (9.7 +/- 4.5% predicted; difference was not significant). While fluticasone/salmeterol did not change Qaw significantly, it restored albuterol responsiveness (67.6 +/- 11.1% predicted; p < 0.05) in the ex-smokers with COPD; this effect was no longer seen after the drug washout period. CONCLUSIONS: Cigarette smoking is associated with a blunted vasodilator response to inhaled albuterol in the airway as an expression of endothelial dysfunction, with a partial recovery of albuterol responsiveness after smoking cessation in healthy ex-smokers but not in ex-smokers with COPD. In the latter group, combined glucocorticoid/long-acting beta(2)-adrenergic agonist treatment restores albuterol responsiveness. The role of endothelial dysfunction in the physiopathology of COPD remains to be examined.

Adult↗

PubMed2005

Investigative bronchoprovocation and bronchoscopy in airway diseases.

RATIONALE: Basic and clinical research strategies used for many lung diseases have depended on volunteer subjects undergoing bronchoscopy to establish access to the airways to collect biological specimens and tissue, perhaps with added bronchoprovocation in asthma syndromes. These procedures have yielded a wealth of important scientific information. Since the last critical review more than a decade ago, some of the techniques and applications have changed, and untoward events have occurred, raising safety concerns and increasing institutional review scrutiny. OBJECTIVES AND METHODS: To reappraise these investigational methods in the context of current knowledge, the National Heart, Lung, and Blood Institute and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health convened a working group to review these procedures used for airway disease research, emphasizing asthma and chronic obstructive pulmonary disease. MAIN RESULTS: The group reaffirmed the scientific importance of investigative bronchoscopy and bronchoprovocation, even as less invasive technologies evolve. The group also considered the safety of bronchoscopy and bronchoprovocation with methacholine and antigen to be acceptable for volunteer subjects and patients, but stressed the need to monitor this closely and to emphasize proper training of participating medical research personnel. Issues were raised about vulnerable volunteers, especially children who need surrogates for informed consent. CONCLUSION: This review of investigative bronchoscopy and bronchoprovocation could serve as the basis for future guidelines for the use of these procedures in the United States.

Asthma↗

PubMed2005

Proposal for a multidimensional staging system for chronic obstructive pulmonary disease.

The severity of chronic obstructive pulmonary disease (COPD) is currently assessed using a single physiological measurement, the forced expiratory volume in 1s (FEV1). COPD, however, has complex effects on other aspects of respiratory function, and in many patients is associated with important systemic changes. We hypothesized that a multidimensional staging system for COPD could provide a more complete assessment of the disease's impact. We considered over 40 potential staging variables, evaluating them according to sensitivity to change, measured reproducibly, independence of the information they provide and prognostic value. We finally selected three: FEV1 (including arterial blood gas measurements when FEV1 falls below 35% predicted), Medical Research Council dyspnea scale and body mass index (BMI). Each measure correlates independently with prognosis in COPD, is supported by a significant body of literature and serves as a surrogate for other potentially important variables. We then used principal components analysis (PCA) to determine the degree of association between 30 of the potential variables measured in 813 stable COPD patients. Using PCA, six groups of measurements defined independent categories of patient information: pulmonary function (including FEV1), symptoms of cough and sputum, dyspnea, health status, bronchodilator reversibility and BMI. These include the three principal variables selected for the staging system. Although the staging boundaries were based on existing literature, they have proven useful in predicting survival. We conclude that a multidimensional grading system is useful to assess the impact of COPD.

Age Factors↗

PubMed2005

The rationale for pharmacologic therapy in stable chronic obstructive pulmonary disease.

The structural changes in airways and alveoli that characterize chronic obstructive pulmonary disease (COPD) result from an abnormal and persistent inflammatory reaction to inhaled noxious particles or gases, notably tobacco smoke. This remodeling of the lung leads to irreversible airflow obstruction. However, COPD should be viewed by clinicians as a treatable condition, since most patients with COPD have an additional reversible component related to increased bronchomotor tone. The use of bronchodilators, especially anticholinergics and beta2-agonists, results in a reduction in airway smooth muscle tone and airflow resistance; this translates into marked improvement in significant clinical outcomes such as dyspnea, quality of life, and exercise capacity. An increasing amount of evidence supports the idea that long-acting agents have more significant impact in these parameters than the short-acting preparations.

Adrenal Cortex Hormones↗

PubMed2005

Initial evaluation of the effects of aerosolized Florida red tide toxins (brevetoxins) in persons with asthma.

Florida red tides annually occur in the Gulf of Mexico, resulting from blooms of the marine dinoflagellate Karenia brevis. K. brevis produces highly potent natural polyether toxins, known as brevetoxins, that activate voltage-sensitive sodium channels. In experimental animals, brevetoxins cause significant bronchoconstriction. A study of persons who visited the beach recreationally found a significant increase in self-reported respiratory symptoms after exposure to aerosolized Florida red tides. Anecdotal reports indicate that persons with underlying respiratory diseases may be particularly susceptible to adverse health effects from these aerosolized toxins. Fifty-nine persons with physician-diagnosed asthma were evaluated for 1 hr before and after going to the beach on days with and without Florida red tide. Study participants were evaluated with a brief symptom questionnaire, nose and throat swabs, and spirometry approved by the National Institute for Occupational Safety and Health. Environmental monitoring, water and air sampling (i.e., K. brevis, brevetoxins, and particulate size distribution), and personal monitoring (for toxins) were performed. Brevetoxin concentrations were measured by liquid chromatography mass spectrometry, high-performance liquid chromatography, and a newly developed brevetoxin enzyme-linked immunosorbent assay. Participants were significantly more likely to report respiratory symptoms after Florida red tide exposure. Participants demonstrated small but statistically significant decreases in forced expiratory volume in 1 sec, forced expiratory flow between 25 and 75%, and peak expiratory flow after exposure, particularly those regularly using asthma medications. Similar evaluation during nonexposure periods did not significantly differ. This is the first study to show objectively measurable adverse health effects from exposure to aerosolized Florida red tide toxins in persons with asthma. Future studies will examine the possible chronic effects of these toxins among persons with asthma and other chronic respiratory impairment.

Adolescent↗

PubMed2005

Occupational exposure to aerosolized brevetoxins during Florida red tide events: effects on a healthy worker population.

Karenia brevis (formerly Gymnodinium breve) is a marine dinoflagellate responsible for red tides that form in the Gulf of Mexico. K. brevis produces brevetoxins, the potent toxins that cause neurotoxic shellfish poisoning. There is also limited information describing human health effects from environmental exposures to brevetoxins. Our objective was to examine the impact of inhaling aerosolized brevetoxins during red tide events on self-reported symptoms and pulmonary function. We recruited a group of 28 healthy lifeguards who are occupationally exposed to red tide toxins during their daily work-related activities. They performed spirometry tests and reported symptoms before and after their 8-hr shifts during a time when there was no red tide (unexposed period) and again when there was a red tide (exposed period). We also examined how mild exercise affected the reported symptoms and spirometry tests during unexposed and exposed periods with a subgroup of the same lifeguards. Environmental sampling (K. brevis cell concentrations in seawater and brevetoxin concentrations in seawater and air) was used to confirm unexposed/exposed status. Compared with unexposed periods, the group of lifeguards reported more upper respiratory symptoms during the exposed periods. We did not observe any impact of exposure to aerosolized brevetoxins, with or without mild exercise, on pulmonary function.

Adolescent↗

PubMed2005

Trends in the diagnosis of symptomatic patients with alpha1-antitrypsin deficiency between 1968 and 2003.

BACKGROUND: Alpha1-antitrypsin deficiency (AATD) is usually underrecognized, with only 5% of cases being diagnosed in the estimated 100,000 affected individuals in the United States. To support current guidelines recommending AATD testing of all individuals with COPD, we analyzed the diagnostic experience of a large cohort of symptomatic patients with AATD. METHODS: A total of 1,020 members of AlphaNet, a not-for-profit health management company devoted to patients with AATD, provided information regarding their AATD diagnostic experience as part of a larger survey-based outcome study. RESULTS: The average age at diagnosis was 45.5 +/- 9.5 years, and the average interval between the onset of symptoms and diagnosis was 8.3 +/- 6.9 years (+/- SD); 30.8% were diagnosed in patients > 50 years old. Two thirds of the diagnoses were made by the first or second physician, and 20% by the fourth or more physicians. From 1968 to 2003, there was a steady increase in age at diagnosis (p < 0.05), the number of physicians required for diagnosis (p > 0.05), and years with symptoms before diagnosis (p > 0.05), while the proportion of cases diagnosed by the first or second physician decreased (p < 0.001). Individuals with a diagnosis at < 35 years of age saw fewer physicians than other age groups (p < 0.05), and show a tendency toward a shorter diagnostic interval over time (p > 0.05). Diagnoses were made in men earlier than in women (p < 0.05), and the proportion of individuals in whom AATD was detected because of asthma or COPD has increased (p < 0.05). CONCLUSION: There has not been a significant improvement in earlier disease diagnosis between 1968 and 2003. There has been improved AATD detection in older individuals. The diagnostic delay is still significant, and efforts should be directed to increase early AATD detection by health-care providers and patients.

Adult↗

PubMed2004

Effect of montelukast and fluticasone propionate on airway mucosal blood flow in asthma.

Asthma is associated with an increase in airway blood flow (Qaw), presumably as a manifestation of airway inflammation. We therefore determined the effect of the antiinflammatory agents montelukast (ML) and fluticasone propionate (FP) on Qaw in 12 patients with mild intermittent asthma. Using a double-blind approach, Qaw along with FEV(1) and Vmax(50) were determined before and after a 2-week treatment period with either ML (10 mg/day), FP (440 microg/day), or 10 mg of ML plus 440 microg of FP daily, separated by 2-week washout periods. Mean (+/- SEM) Qaw ranged from 68 +/- 4.2 to 71.8 +/- 5.9 microl x minute(-1) x ml(-1) anatomic dead space before the treatment periods. ML, FP, and ML plus FP decreased mean Qaw by 21.5, 20.8, and 26.9%, respectively (p < 0.05 for all). No significant difference was observed among the three regimens. FEV(1) and Vmax(50) were not changed by any of the treatments. We conclude that at the dosages used, ML and FP are equipotent in reducing Qaw in patients with mild asthma, and that the magnitude of the response is not greater if the two drugs are combined. The results also suggest that the vascular effects of these agents can be assessed independent of their effects on airway function.

Acetates↗

PubMed2004

Parent-reported asthma in Puerto Rican children.

We conducted a survey to determine parent-reported asthma prevalence, morbidity, and healthcare utilization among 3527 children attending public schools (n = 2849) and private schools (n = 678) in San Juan, Puerto Rico. Schools were randomly selected from each of 12 geographic regions of the San Juan metropolitan area. Parents of children age 4-7 years old completed a 12-item questionnaire on asthma diagnosis, respiratory symptoms and morbidity, and healthcare utilization. Parents of children in public schools and private schools reported similar rates of a physician having previously diagnosed asthma in their children (43.2% vs. 39.4%); however, significantly more children in public schools were reported to still have asthma at the time of the survey (32.6% vs. 23.7%). Children attending public schools vs. private schools were reported to have missed significantly more school and to have had more hospitalizations and emergency department visits. Among children reported to still have asthma, significantly more children visited an emergency department, were hospitalized, and missed more school days due to respiratory symptoms in the past year. The high prevalence of parent-reported asthma, respiratory symptoms, and healthcare utilization among Puerto Rican children in San Juan calls for further studies using objective methods for ascertaining asthma and asthma-related morbidity. Differences in healthcare utilization between children attending public vs. private schools suggest that socioeconomic factors play a role in asthma management in Puerto Rico.

Absenteeism↗

PubMed2004

Nongenomic actions of glucocorticosteroids on the airway vasculature in asthma.

Inhaled glucocorticosteroids (corticosteroids) continue to be the standard treatment for nonexacerbated asthma because of their anti-inflammatory actions. These include effects on the airway vasculature, which participates in the inflammatory process. Corticosteroids are now known to have genomic as well as nongenomic effects that involve different mechanisms of action. The genomic vascular effects of inhaled corticosteroids include a decrease in airway wall hypervascularity (inhibition of angiogenesis), reversal of the increased airway blood flow, and inhibition of vascular hyperpermeability and leukocyte recruitment. In addition, inhaled corticosteroids decrease airway blood flow acutely (within minutes) and reversibly through a nongenomic action that involves noradrenergic neurotransmission. This effect is likely related to the binding of inhaled corticosteroids to the plasma membrane of and the inhibition of the extraneuronal monoamine transporter on airway vascular smooth muscle cells, thereby increasing norepinephrine concentrations at alpha(1)-adrenoceptors and causing airway vascular smooth muscle contraction and a decrease in airway blood flow. Inasmuch as vascular hyperperfusion is a manifestation of airway inflammation, the acute vasoconstriction could also be considered an anti-inflammatory effect of inhaled corticosteroids.

Administration, Inhalation↗

PubMed2003

Norepinephrine transport by the extraneuronal monoamine transporter in human bronchial arterial smooth muscle cells.

Inhaled glucocorticosteroids (GSs) cause acute, alpha1-adrenoreceptor (AR)-mediated bronchial vasoconstriction. After release from sympathetic nerves, norepinephrine (NE) must be taken up into cells for deactivation by intracellular enzymes. Because postsynaptic cellular NE uptake is steroid sensitive, GSs could increase NE concentrations at alpha1-AR, causing vasoconstriction. We therefore evaluated mRNA expression of different NE transporters in human bronchial arterial smooth muscle and pharmacologically characterized NE uptake into these cells. RT-PCR demonstrated mRNA expression of the extraneuronal monoamine transporter (EMT) and organic cation transporter 1 (OCT-1). Fluorometric uptake assay showed time (within minutes)- and concentration-dependent NE uptake by freshly isolated bronchial arterial smooth muscle cells (SMC) with an estimated Km of 240 microM. Corticosterone and O-methylisoprenaline (1 microM each), but not desipramine, inhibited NE uptake, a profile indicative of NE uptake by EMT, but not OCT-1. Budesonide and methylprednisolone inhibited uptake with IC50 values of 0.9 and 5.6 microM, respectively. Corticosterone's action was reversible and not sensitive to RU-486 (GS receptor antagonist), actinomycin D (transcription inhibitor), or cycloheximide (protein synthesis inhibitor). Corticosterone made membrane impermeant by coupling to BSA also blocked NE uptake. Immunocytochemistry indicated a specific membrane binding site for corticosterone on bronchial arterial SMC. These data demonstrate that although human bronchial arterial SMC express OCT-1 and EMT, EMT is the predominant plasma membrane transporter for NE uptake. This process can be inhibited by GSs, likely via a specific membrane binding site. This nongenomic GS action (increasing NE concentrations at alpha1-AR) could explain acute bronchial vasoconstriction caused by inhaled GSs.

Arteries↗

PubMed2002

Montelukast prevents antigen-induced mucociliary dysfunction in sheep.

The cysteinyl leukotrienes are potent proinflammatory mediators that, in addition to their bronchospastic actions, can also contribute to mucociliary dysfunction, a central component of the pathophysiology of asthma. In this study, we determined whether montelukast, a cysteinyl leukotriene 1 receptor antagonist, could prevent and/or reverse antigen-induced mucociliary dysfunction in allergic sheep. We measured tracheal mucus velocity, a marker of mucociliary clearance, before and for 8 hours after antigen challenge in six animals treated with montelukast (0.15 mg/kg, intravenously) 30 minutes before, 1 hour after, or 4 hours after antigen challenge. In the control trial, the sheep received 0.9% saline intravenously at each of the previously mentioned time points. The maximum decrease in tracheal mucus velocity seen in the control trial was 56 +/- 4% (mean +/- SE) of baseline at 8 hours. Pretreatment with montelukast significantly protected against this reduction. However, treatment at 1 and 4 hours neither protected against nor reversed the allergen-induced fall in tracheal mucus velocity. We conclude that the early release of cysteinyl leukotrienes may contribute to the fall in tracheal mucus velocity that follows acute antigen challenge and that pretreatment with montelukast reduces this impairment.

Acetates↗