| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Division of Pulmonary and Critical Care Medicine, University of Miami School of Medicine at Mount Sinai Medical Center, Miami Beach, Florida 33140
 |
ABSTRACT |
|---|
 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
The purpose of the present study was to
determine the responsiveness of airway vascular smooth muscle (AVSM) as
assessed by airway mucosal blood flow (
aw) to inhaled
methoxamine (
1-agonist; 0.6-2.3 mg) and albuterol
(
2-agonist; 0.2-1.2 mg) in healthy [n = 11; forced expiratory volume in 1 s, 92 ± 4 (SE) % of predicted] and asthmatic (n = 11, mean
forced expiratory volume in 1 s, 81 ± 5%) adults.
Mean baseline values for aw were 43.8 ± 0.7 and 54.3 ± 0.8 µl · min
1 · ml1 of
anatomic dead space in healthy and asthmatic subjects, respectively (P < 0.05). After methoxamine inhalation, the maximal
mean change in aw was 
13.5 ± 1.0 µl · min1 · ml1 in
asthmatic and 7.1 ± 2.1 µl · min1 · ml1 in
healthy subjects (P < 0.05). After albuterol, the mean
maximal change in aw was 3.0 ± 0.8 µl · min1 · ml1 in
asthmatic and 14.0 ± 1.1 µl · min1 · ml1 in
healthy subjects (P < 0.05). These results demonstrate
that the contractile response of AVSM to 1-adrenoceptor
activation is enhanced and the dilator response of AVSM to
2-adrenoceptor activation is blunted in asthmatic subjects.
bronchial blood flow; asthma; adrenergic agonists
| |
INTRODUCTION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
BOTH AIRWAY SMOOTH
MUSCLE and airway vascular smooth muscle (AVSM) express
-adrenergic and -adrenergic receptors, but the receptor densities
have been shown to differ between the two types of smooth muscle
(2). Based on pharmacological observations, -adrenergic receptors predominate on AVSM, whereas airway
smooth muscle expresses mainly -adrenergic receptors (9,
11). Contraction is mediated primarily by the
1-adrenergic receptor (1-AR) and relaxation primarily by the 2-adrenergic receptor
(2-AR) (13, 19, 22).
There appear to be differences in the adrenergic responsiveness of
airway smooth muscle between healthy and asthmatic subjects. For
example, several investigators have reported that inhaled 1-adrenergic agonists cause airflow obstruction in
patients with asthma but not in healthy subjects (7, 23).
Conversely, 2-adrenergic agonist-induced bronchodilation
may be blunted in some patients with asthma, although the clinical
significance of this defect has been called into question (4, 6,
16, 24, 25). In contrast to airway smooth muscle, comparative
data on 1- and 2-AR-mediated responses of
ASVM have not been systematically examined in healthy and asthmatic subjects.
The aim of the present study was to determine whether the
responsiveness of AVSM tone to 1-AR and
2-AR activation is altered in asthmatic subjects. We
used airway mucosal blood flow (aw) as an index of AVSM tone,
and inhaled methoxamine and albuterol as 1-AR and
2-AR activators, respectively.
| |
METHODS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Test population.
Twenty-two nonsmokers participated in the study. They denied having
cardiovascular disease or taking vasoactive or anti-inflammatory medications. Subjects who had taken antibiotics or inhaled or systemic
glucocorticoids and subjects who had an acute respiratory infection
during the 6-wk period preceding the study were excluded. Eleven
subjects were healthy (mean age 36.5 yr, range 29-46 yr; 9 women),
and 11 had mild, intermittent asthma (mean age 33.1 yr, range
25-53 yr; 9 women) as defined by the American Thoracic Society and
National Asthma Education Program (1, 18). The asthmatic
subjects used a short-acting inhaled -adrenergic agonist on demand
as their only asthma treatment. The mean weekly -adrenergic agonist
use was 1.6 puffs (range 0-8). Nine of the 11 asthmatic subjects
had a baseline forced expiratory volume in 1 s
(FEV1) <90% of predicted; the albuterol-induced mean
increase in FEV1 for all asthmatic subjects was 10.2 ± 2.5%. The two asthmatic subjects with FEV1 >90%
of predicted had previously demonstrated methacholine
hyperresponsiveness. Cutaneous allergy testing was not performed.
Historically, five asthmatic subjects denied having allergies, four
reported known allergies (confirmed by previous skin testing in 3), and
two were not sure. Informed consent was obtained from all subjects, and
they received financial remuneration for their participation.
Spirometry was carried out with an Essential Medic unit (model 6200, Autbox DL, Yorba Linda, CA). The highest FEV1 of three
forced vital capacity maneuvers was determined and expressed as an
absolute value and as percent predicted (10).
aw.
A soluble inert-gas uptake method was used to measure aw
(15, 19, 21). The subjects were seated in front of a valve system that allowed them to inhale through a mouthpiece (with the nasal
passage occluded by a nose clip) room air or a gas mixture from a
Teflon bag containing 10% dimethylether (DME), 5% helium, and balance
oxygen and to exhale into a rolling seal spirometer (model 842; Ohio
Instruments, Houston, TX). The subjects first inhaled room air to, and
then exhaled 500 ml from, the total lung capacity position and
subsequently inhaled rapidly the same volume of gas mixture from the
Teflon bag. They held their breath for a predetermined duration and
then exhaled into the spirometer through a critical flow orifice to
standardize expiratory flow. The maneuver was performed with two
breath-hold times each of 5, 10, 15, and 20 s in random order.
During exhalation, the instantaneous concentrations of DME, nitrogen,
and helium were measured at the airway opening with a mass spectrometer
(Perkin-Elmer, Pomona, CA), along with the expired gas volume. The mass
spectrometer inlet was not heated, and no corrections were made for
water pressure. The resulting overestimation of DME concentration by
measuring it at the airway opening was considered to be negligible
(~0.3%). The mass spectrometer was also used to verify the gas
concentration in the Teflon bag before inhalation of the gas mixture.
Anatomic dead space (DS) was determined from the expired nitrogen
concentration curve as described by Fowler and co-workers
(12). The helium-corrected decrease in the DME
concentration over time was obtained by least squares fit using the two
measurements per gas for each of the four breath-hold times. This was
done in the expired volume fraction corresponding to the DS minus the
most proximal 50 ml. From the helium-corrected DME slope multiplied by
the DS (
DME), the mean DME concentration in the DS
(F
), and the solubility coefficient
for DME in blood and tissue (), aw was calculated using
Fick's principle (aw = DME/ · F). aw was normalized for DS and expressed as microliters per minute per milliliter.
Protocol.
The subjects were asked to come to the research laboratory in the
morning of the study day without having had any coffee or caffeinated
drinks. The subjects were asked to abstain from ingesting alcoholic
beverages the night before. The asthmatic subjects were asked not to
use their inhaled -adrenergic agonist for at least 12 h before
the study. After the measurement of baseline aw, the subjects
inhaled albuterol on 1 experiment day and methoxamine on another. A
dosimeter, consisting of a breath-activated solenoid valve, which
controlled flow of compressed air (45 lb./in.2) to a
DeVilbiss 644 nebulizer, was used. The mass median aerodynamic diameter
of the aerosol was 3.2 µm (geometric SD 2.0) as determined by a
cascade impactor. Different solutions of albuterol or methoxamine in
phosphate-buffered saline were freshly prepared. In a previous study,
our laboratory (19) found that inhalation of
phosphate-buffered saline aerosol had no effect on aw. In the
present investigation, the subjects inhaled the aerosol from functional
residual capacity to total lung capacity (inspiratory capacity).
They took the required number of breaths of different drug solutions
for the desired drug doses. During the first 0.6 s of each breath,
0.023 ml of solution was nebulized. Doses were 0.2, 0.4, 0.6, 0.8, and
1.2 mg for albuterol and 0.6, 1.2, 1.8, and 2.3 mg for methoxamine in
all subjects except for albuterol doses in asthmatic subjects (0.6 and
1.2 mg). Repeat measurements of aw were made 15 min after each
drug inhalation, and the interval between drug doses was 45 min. To
monitor airway caliber, FEV1 was determined before each
aw measurement.
Data analysis.
The mass spectrometer and spirometer signals were fed through
analog-to-digital converters to a computer and stored for data acquisition and calculation of aw. All aw data were
analyzed after completion of the study. Statistical comparisons between groups were made with ANOVA. A P value of <0.05 was
considered significant. The data are presented as means ± SE.
| |
RESULTS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
On the first experiment day, mean baseline aw was higher in
asthmatic than in healthy subjects (54.3 ± 0.8 vs. 43.8 ± 0.7 µl · min1 · ml1;
P < 0.05). The baseline values were comparable on the
second experiment day (Table 1). There
was no difference in mean dead space between groups and between the 2 experiment days within groups. Methoxamine caused a decrease in
aw at several doses in asthmatic subjects but only at the
highest dose in healthy subjects (Fig.
1). The mean maximum change (
max) in
aw was greater in asthmatic subjects (13.5 ± 1.0 µl · min1 · ml1) than in
healthy subjects (7.1 ± 2.1 µl · min1 · ml1;
P < 0.05; Fig. 2). After
albuterol, mean aw remained essentially unchanged in the dose
range of the study in asthmatic subjects and showed a dose-dependent
increase in healthy subjects (Fig. 1). Mean max in aw was
considerably greater in healthy subjects than in asthmatic subjects
(14 ± 1.1 vs. 3.0 ± 0.8 µl · min1 · ml1;
P < 0.05; Fig. 2).
|
|
|
Baseline mean FEV1 was lower in asthmatic than in healthy
subjects on both experiment days (Table 1). The mean max values in
FEV1 after methoxamine and albuterol are shown in Fig.
3. The drug-induced changes in DS were
minimal and statistically not different for the two adrenergic agents
in either group (Fig. 4).
|
|
Mean systemic blood pressure and pulse rate remained unchanged throughout the experiment with both drugs and in both groups of subjects.
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
This investigation disclosed enhanced 1-AR-mediated
contraction and blunted 2-AR-mediated relaxation of AVSM
in asthmatic compared with healthy subjects. We selected patients with
mild asthma for several reasons. First, we wanted to minimize the
difference in baseline aw between the asthmatic and healthy
subjects because baseline aw could have influenced the response
to the adrenergic agonists. Marked vasodilation associated with more
severe asthma could further attenuate vasodilation by albuterol,
although this has thus far not been demonstrated experimentally. In our
study, mean baseline aw was only 24% higher in asthmatic
subjects than healthy subjects. This difference is unlikely to explain
the observed differential responses to methoxamine and albuterol.
Because baseline aw varied among subjects, the methoxamine- and
albuterol-induced changes in aw were expressed in absolute terms
rather than as percent baseline. Second, the choice of mild asthmatic
subjects who did not use -adrenergic agonists regularly circumvented
the problem of agonist-induced tolerance to albuterol. Third, we were able to find a sufficient number of glucocorticosteroid-naive patients
by restricting the study to mild asthmatic subjects. Our laboratory has
previously made the observation that glucocorticosteroids restore
blunted -adrenergic AVSM responsiveness (8). Finally, the magnitude of methoxamine- and albuterol-induced changes in airway
caliber was minimized by studying individuals with a near-normal baseline FEV1. As a result, the maximum mean
FEV1 did not exceed 250 ml after either drug. The
relatively small changes in FEV1 and normalizing aw
for DS minimized a potential influence of airway caliber on the
measurement of aw. Furthermore, inhaled cholinergic agonists
have been shown to cause bronchoconstriction without changing airway
blood flow in sheep, indicating that airway blood flow is independent
of airway smooth muscle tone (9a, 21a). Finally, DS was only
minimally affected by the small changes in FEV1 induced by
methoxamine and albuterol in the present study.
Our laboratory (19) has previously shown that, in healthy
subjects, the vasoactive effects of a single inhaled dose of
methoxamine and albuterol are transient, waning by 30 min
postchallenge. Because 45 min elapsed between drug inhalations in the
present study, the dose-response curves were not cumulative for
aw. The drug doses used in this experiment (0.6-2.3 mg for
methoxamine, 0.2-1.2 mg for albuterol), for which we used
solutions nebulized only during inspiration by a dosimeter, are more
comparable to those of metered dose inhalers than constant-flow
nebulizers, in which a considerable fraction of the nebulized dose is
wasted during the expiratory phase (17). Within the dose
ranges of this study, differences in adrenergic responsiveness were
demonstrated without adverse drug reactions. Similarly, significant
systemic vascular changes as assessed by systemic blood pressure and
heart rate were not present at the drug doses used. Palpitations,
tachycardia, and tremor were observed at doses of albuterol exceeding
1.2 mg in preliminary experiments. The maximum dose was, therefore, set at 1.2 mg in the protocol.
Methoxamine caused bronchoconstriction in asthmatic subjects. The
lowest mean FEV1 value was 74.5 ± 4.1% of predicted,
and it is, therefore, unlikely that methoxamine caused hypoxia that was
severe enough to influence aw.
1-Adrenergic responsiveness.
Our study showed airway vascular hyperresponsiveness to methoxamine in
asthmatic subjects, similar to the previously demonstrated airway
hyperresponsiveness to -adrenergic agonists (7, 23). The mechanisms responsible for the asthma-associated smooth muscle hyperresponsiveness are not known. With respect to airway smooth muscle, methoxamine-induced vasoconstriction could have reduced the
washout of methoxamine from the airway tissue, leading to increased
airway smooth muscle contraction. In addition, 1-AR density has been reported to be increased in patients with obstructive lung disease (5); this may explain or contribute to the
enhanced 1-adrenergic smooth muscle responsiveness,
although it is not known which lung cells overexpress
1-ARs.
1-adrenergic AVSM
hyperresponsiveness to airway inflammation, systemic sensitization, or both. This has not been studied in humans. However, experiments conducted in animal models of allergic sensitization and airway inflammation support this notion. There are several possible mechanisms of inflammation-induced 1-adrenergic
hyperresponsiveness, including increased 1-AR expression
and function or altered postreceptor signal transduction in AVSM and
airway vascular endothelium, altered inactivation or cellular uptake of
1-adrenergic agonists, or a combination thereof. Some of
these possibilities have been investigated. For example, it has been
reported that antigen-sensitized and airway-challenged guinea pigs have
an increased pulmonary 1-AR density (3). In
addition, Zschauer et al. (26) showed that the contractile
sensitivity of AVSM to phenylephrine increased in bronchial artery
rings removed from ovalbumin-sensitized rabbits. In that model, the
1-adrenergic hyperresponsiveness induced by systemic
sensitization alone was related to an endothelial contractile factor.
The putative inflammatory products responsible for the potentiation of
1-AR-mediated AVSM contractions in asthma remain to be identified.
2-Adrenergic responsiveness.
We found a marked attenuation of 2-AR-mediated
relaxation of AVSM in asthmatic subjects compared with healthy
subjects. Healthy subjects had a dose-related increase in aw,
whereas in asthmatic subjects, aw remained unchanged within the
nebulized dose range of albuterol (0.2-1.2 mg). It is possible
that higher doses of albuterol would have increased aw in
asthmatic subjects as well, but we decided against exceeding a
nebulized dose of 1.2 mg to avoid acute toxic drug effects.
2-ARs. Pulmonary
2-AR density has been reported to be decreased in
patients with obstructive airway disease (5). Possibly
AVSM cells or endothelial cells are more susceptible than airway smooth
muscle cells, resulting in a demonstrable blunting of albuterol
responsiveness in the former but not the latter. Another hypothesis is
that airway smooth muscle has a greater 2-AR reserve and
that asthma-related loss of 2-AR density is of no or
little functional consequence. In contrast to airway smooth muscle, a
reduction of 2-AR density on blood lymphocytes has been
found in patients with asthma, and this was accompanied by a decreased
2-adrenergic responsiveness as assessed by cyclic AMP
production (14, 20). In this regard, AVSM seems to
resemble blood lymphocytes more than airway smooth muscle.
In a previous study, we showed that the vasodilator response in the
airway to 180 µg of albuterol administered by inhalation was restored
by a 2-wk treatment with an inhaled glucocorticosteroid (8). Assuming that this effect of the glucocorticosteroid
was related to its anti-inflammatory action, the observation suggests that the attenuated 2-adrenergic responsiveness of AVSM
is a consequence of the asthma-associated airway inflammation.
In summary, the results of this study demonstrate an enhanced
adrenergic constrictor response and blunted adrenergic dilator response
of the airway circulation in patients with asthma. This could be
considered an adrenergic adaptation to the asthma-associated inflammatory vasodilation in the airway.
| |
ACKNOWLEDGEMENTS |
|---|
This study was supported by National Heart, Lung, and Blood Institute Grant HL-58086.
| |
FOOTNOTES |
|---|
Address for reprint requests and other correspondence: A. Wanner, Division of Pulmonary and Critical Care Medicine, Univ. of Miami School of Medicine, P.O. Box 016960 (R-47), Miami, FL 33101 (E-mail: awanner{at}miami.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 8 May 2000; accepted in final form 25 August 2000.
| |
REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
American Thoracic Society.
Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma.
Am Rev Respir Dis
136:
225-244,
1987[ISI][Medline].
2.
Barnes, PJ.
Neural control of human airways in health and disease.
Am Rev Respir Dis
134:
1289-1314,
1986[ISI][Medline].
3.
Barnes, PJ,
Dollery CT,
and
MacDermot J.
Increased pulmonary -adrenergic and reduced -adrenergic receptors in experimental asthma.
Nature
285:
569-571,
1980[Medline].
4.
Barnes, PJ,
FitzGerald GA,
and
Dollery CT.
Circadian variation in adrenergic responses in asthmatic subjects.
Clin Sci (Colch)
62:
349-354,
1982[Medline].
5.
Barnes, PJ,
Karliner JS,
and
Dollery CT.
Human lung adrenoceptors studied by radioligand binding.
Clin Sci (Colch)
58:
457-461,
1980[Medline].
6.
Barnes, PJ,
and
Pride NB.
Dose-response curves to inhaled -adrenoreceptor agonists in normal and asthmatic subjects.
Br J Clin Pharmacol
15:
677-682,
1983[ISI][Medline].
7.
Black, JL,
Salome C,
Yan K,
and
Shaw J.
The action of prazosin and propylene glycol on methoxamine-induced bronchoconstriction in asthmatic subjects.
Br J Clin Pharmacol
18:
349-353,
1984[ISI][Medline].
8.
Brieva, JL,
Danta I,
and
Wanner A.
Effect of an inhaled glucocorticosteroid on airway mucosal blood flow in mild asthma.
Am J Respir Crit Care Med
161:
293-296,
2000
9.
Carstairs, JR,
Nimmo AJ,
and
Barnes PJ.
Autoradiographic visualization of -adrenoreceptor subtypes in human lung.
Am Rev Respir Dis
132:
541-547,
1985[ISI][Medline].
9a.
Charan, NB,
Carvalho P,
Johnson SR,
Thompson WH,
and
Lakshminarayan S.
Effect of aerosolized acetylcholine on bronchial blood flow.
J Appl Physiol
85:
432-436,
1998
10.
Crapo, RO,
Morris AH,
and
Gardner RM.
Reference spirometric values using techniques and equipment that meet ATS recommendations.
Am Rev Respir Dis
123:
659-664,
1981[ISI][Medline].
11.
Dey, RD,
Shannon WA,
and
Said SI.
Localization of VIP-immunoreactive nerves in airways and pulmonary vessels of dogs, cats and human subjects.
Cell Tissue Res
220:
231-238,
1981[ISI][Medline].
12.
Fowler, WS,
Cornish JER,
and
Kety SS.
Lung function studies. VIII. Analysis of alveolar ventilation by pulmonary N2 clearance curves.
J Clin Invest
31:
40-50,
1952.
13.
Goldie, RG,
Paterson JW,
Spira D,
and
Wade JL.
Classification of -adrenoceptors in human isolated bronchus.
Br J Pharmacol
81:
611-615,
1984[ISI][Medline].
14.
Kariman, K.
-Adrenergic receptor binding in lymphocytes from patients with asthma.
Lung
158:
41-51,
1980[ISI][Medline].
15.
Kumar, SD,
Emery MJ,
Atkins ND,
Danta I,
and
Wanner A.
Airway mucosal blood flow in bronchial asthma.
Am J Respir Crit Care Med
158:
153-156,
1998
16.
Larsson, S,
Svedmyr N,
and
Thiringer G.
Lack of bronchial -adrenoreceptor resistance in asthmatics during long-term treatment with terbutaline.
J Allergy Clin Immunol
59:
93-100,
1977[ISI][Medline].
17.
Lewis, RA,
Fleming JS,
Balachandran W,
and
Tattersfield AE.
Particle size distribution and deposition from a jet nebulizer: influence of humidity and temperature.
Clin Sci (Colch)
62:
5P,
1981.
18.
National Heart, Lung, and Blood Institute, and National Asthma Education Program.
Guidelines for the diagnosis and management of asthma.
J Allergy Clin Immunol
88:
425-534,
1991[Medline].
19.
Onorato, DJ,
Demirozu MC,
Breitenbücher A,
Atkins ND,
Chediak AD,
and
Wanner A.
Airway mucosal blood flow in man: response to adrenergic agonists.
Am J Respir Crit Care Med
149:
1132-1137,
1994[Abstract].
20.
Parker, CW,
and
Smith JW.
Alterations in cyclic adenosine monophosphate metabolism in human bronchial asthma.
J Clin Invest
52:
48-59,
1973.
21.
Scuri, M,
McCaskill V,
Chediak AD,
Abraham WM,
and
Wanner A.
Measurement of airway mucosal blood flow with dimethylether: validation with microspheres.
J Appl Physiol
79:
1386-1390,
1995
21a.
Scuri, M,
McCaskill V,
Chediak AD,
Abraham WM,
and
Wanner A.
Effect of inhaled and intravenous acetylcholine on bronchial blood flow in anesthetized sheep.
J Appl Physiol
80:
341-350,
1996
22.
Simonsson, BG,
Svedmyr N,
Skoogh BE,
Anderson R,
and
Bergh NP.
In vivo and in vitro studies on -adrenoreceptors in human airways. Potentiation with bacterial endotoxin.
Scand J Respir Dis
53:
227-236,
1972[ISI][Medline].
23.
Snashall, R,
Boother FA,
and
Sterling GM.
The effect of -adrenergic stimulation on the airways of normal and asthmatic man.
Clin Sci (Colch)
54:
283-289,
1978.
24.
Tattersfield, AE,
Holgate ST,
Harvey JE,
and
Gribbin HR.
Is asthma due to partial-blockade of airways?
Agents Actions
13:
265-271,
1983[ISI][Medline].
25.
Weber, RW,
Smith JA,
and
Nelson HS.
Aerosolized terbutaline in asthmatics: development of subsensitivity with chronic administration.
J Allergy Clin Immunol
70:
417-422,
1982[ISI][Medline].
26.
Zschauer, AOA,
Sielczak MW,
and
Wanner A.
Altered contractile sensitivity of isolated bronchial artery to phenylephrine in ovalbumin-sensitized rabbits.
J Appl Physiol
86:
1721-1727,
1999
This article has been cited by other articles:
|
|
 |
|
  A. Wanner, E. S. Mendes, and N. D. Atkins A simplified noninvasive method to measure airway blood flow in humans J Appl Physiol, May 1, 2006; 100(5): 1674 - 1678. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. S. Mendes, M. A. Campos, and A. Wanner Airway Blood Flow Reactivity in Healthy Smokers and in Ex-Smokers With or Without COPD. Chest, April 1, 2006; 129(4): 893 - 898. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Yun, P. Y. Lee, and A. N. Gerber Integrating systems biology and medical imaging: understanding disease distribution in the lung model. Am. J. Roentgenol., April 1, 2006; 186(4): 925 - 930. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Horvath and A. Wanner Inhaled corticosteroids: effects on the airway vasculature in bronchial asthma Eur. Respir. J., January 1, 2006; 27(1): 172 - 187. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Rhen and J. A. Cidlowski Antiinflammatory action of glucocorticoids--new mechanisms for old drugs. N. Engl. J. Med., October 20, 2005; 353(16): 1711 - 1723. [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Rodrigo Comparison of Inhaled Fluticasone with Intravenous Hydrocortisone in the Treatment of Adult Acute Asthma Am. J. Respir. Crit. Care Med., June 1, 2005; 171(11): 1231 - 1236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Wanner, G. Horvath, J. L. Brieva, S. D. Kumar, and E. S. Mendes Nongenomic Actions of Glucocorticosteroids on the Airway Vasculature in Asthma Proceedings of the ATS, November 1, 2004; 1(3): 235 - 238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Busse, S. Banks-Schlegel, P. Noel, H. Ortega, V. Taggart, and J. Elias Future Research Directions in Asthma: An NHLBI Working Group Report Am. J. Respir. Crit. Care Med., September 15, 2004; 170(6): 683 - 690. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Horvath, Z. Sutto, A. Torbati, G. E. Conner, M. Salathe, and A. Wanner Norepinephrine transport by the extraneuronal monoamine transporter in human bronchial arterial smooth muscle cells Am J Physiol Lung Cell Mol Physiol, October 1, 2003; 285(4): L829 - L837. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E.S. Mendes, A. Pereira, I. Danta, R.C. Duncan, and A. Wanner Comparative bronchial vasoconstrictive efficacy of inhaled glucocorticosteroids Eur. Respir. J., June 1, 2003; 21(6): 989 - 993. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Horvath, A. Torbati, G. E. Conner, M. Salathe, and A. Wanner Systemic Ovalbumin Sensitization Downregulates Norepinephrine Uptake by Rabbit Aortic Smooth Muscle Cells Am. J. Respir. Cell Mol. Biol., December 1, 2002; 27(6): 746 - 751. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
