Skip header and navigation

Refine By

12 records – page 1 of 2.

Adding formoterol to budesonide in moderate asthma--health economic results from the FACET study.

https://arctichealth.org/en/permalink/ahliterature10200
Source
Respir Med. 2001 Jun;95(6):505-12
Publication Type
Article
Date
Jun-2001
Author
F. Andersson
E. Stahl
P J Barnes
C G Löfdahl
P M O'Byrne
R A Pauwels
D S Postma
A E Tattersfield
A. Ullman
Author Affiliation
AstraZeneca R&D Lund, Sweden. fredrik.l.andersson@astrazeneca.com
Source
Respir Med. 2001 Jun;95(6):505-12
Date
Jun-2001
Language
English
Publication Type
Article
Keywords
Acute Disease
Adolescent
Adult
Aged
Anti-Asthmatic Agents - economics - therapeutic use
Asthma - drug therapy - economics
Budesonide - economics - therapeutic use
Cost Savings
Cost-Benefit Analysis
Drug Therapy, Combination
Ethanolamines - economics - therapeutic use
Great Britain
Health Care Costs
Humans
Middle Aged
Normal Distribution
Research Support, Non-U.S. Gov't
Spain
Sweden
Abstract
The FACET (Formoterol and Corticosteroid Establishing Therapy) study established that there is a clear clinical benefit in adding formoterol to budesonide therapy in patients who have persistent symptoms of asthma despite treatment with low to moderate doses of an inhaled corticosteroid. We combined the clinical results from the FACET study with an expert survey on average resource use in connection with mild and severe asthma exacerbations in the U.K., Sweden and Spain. The primary objective of this study was to assess the health economics of adding the inhaled long-acting beta2-agonist formoterol to the inhaled corticosteroid budesonide in the treatment of asthma. The extra costs of adding the inhaled beta2-agonist formoterol to the corticosteroid budesonide in asthmatic patients in Sweden were offset by savings from reduced use of resources for exacerbations. For Spain the picture was mixed. Adding formoterol to low dose budesonide generated savings, whereas for moderate doses of budesonide about 75% of the extra formoterol costs could be recouped. In the U.K., other savings offset about half of the extra cost of formoterol. All cost-effectiveness ratios are within accepted cost-effectiveness ranges reported from previous studies. If productivity losses were included, there were net savings in all three countries, ranging from Euro 267-1183 per patient per year. In conclusion, adding the inhaled, long-acting beta2-agonist formoterol to low-moderate doses of the inhaled corticosteroid budesonide generated significant gains in all outcome measures with partial or complete offset of costs. Adding formoterol to budesonide can thus be considered to be cost-effective.
PubMed ID
11421509 View in PubMed
Less detail

Adoptive transfer of allergen-specific CD4+ T cells induces airway inflammation and hyperresponsiveness in brown-Norway rats.

https://arctichealth.org/en/permalink/ahliterature57604
Source
Immunology. 1997 Jun;91(2):176-85
Publication Type
Article
Date
Jun-1997
Author
A. Haczku
P. Macary
T J Huang
H. Tsukagoshi
P J Barnes
A B Kay
D M Kemeny
K F Chung
R. Moqbel
Author Affiliation
Department of Allergy and Clinical Immunology, Guy's Hospital, London, UK.
Source
Immunology. 1997 Jun;91(2):176-85
Date
Jun-1997
Language
English
Publication Type
Article
Keywords
Adoptive Transfer
Animals
Bronchial Hyperreactivity - immunology
Bronchoalveolar Lavage Fluid - immunology
CD4-Positive T-Lymphocytes - immunology - transplantation
CD8-Positive T-Lymphocytes - immunology - transplantation
Cell Culture Techniques
Cell Division - immunology
Eosinophils - immunology
Leukocyte Count
Lymphocyte Transfusion
Male
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Spleen - immunology
Abstract
Following allergen exposure, sensitized Brown-Norway rats develop airway hyperresponsiveness (AHR) and eosinophilic inflammation together with an increase in activated T cells (CD25+) in the airways. We tested the hypothesis that CD4+ T cells are involved directly in the acquisition of AHR. Spleen T cells from animals that were injected intraperitoneally on three consecutive days with ovalbumin/Al(OH)3, showed a dose-dependent proliferative response in vitro to ovalbumin, but not to bovine serum albumin, as measured by [3H]thymidine uptake. For total T-cell transfer, spleen cells obtained from donor rats 4 days after sensitization were depleted of adherent cells by a nylon wool column separation. CD4+ and CD8+ T cells were purified by immunomagnetic beads cell separation. Recipient naive rats were injected intravenously with 50 x 10(6) total T cells, 20 x 10(6) and 5 x 10(6) CD4+ cells, and 5 x 10(6) CD8+ cells, and were exposed to ovalbumin aerosol 24 hr afterwards. After a further 24 hr, airway responsiveness to acetylcholine (ACh) was measured and provocative concentration (PC) values PC100, PC200 and PC300) (the ACh concentration needed to achieve 100, 200 and 300% increase in lung resistance above baseline) were calculated. Airway responsiveness was significantly increased in recipients of sensitized total T cells compared with recipients of cells from saline-injected donor rats (P
PubMed ID
9227314 View in PubMed
Less detail

Airway hyperresponsiveness, elevation of serum-specific IgE and activation of T cells following allergen exposure in sensitized Brown-Norway rats.

https://arctichealth.org/en/permalink/ahliterature15906
Source
Immunology. 1995 Aug;85(4):598-603
Publication Type
Article
Date
Aug-1995
Author
A. Haczku
K F Chung
J. Sun
P J Barnes
A B Kay
R. Moqbel
Author Affiliation
Department of Allergy and Clinical Immunology, National Heart and Lung Institute, London, UK.
Source
Immunology. 1995 Aug;85(4):598-603
Date
Aug-1995
Language
English
Publication Type
Article
Keywords
Allergens - immunology
Animals
Bronchial Hyperreactivity - immunology
Bronchial Provocation Tests
Bronchoalveolar Lavage Fluid - immunology
Female
Immunoglobulin E - blood
Lymphocyte Activation - immunology
Ovalbumin - immunology
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
T-Lymphocyte Subsets - immunology
Abstract
T lymphocytes may play a regulatory role in the development of allergic airway hyperresponsiveness (AHR). We have studied the relationship between airway responsiveness and a number of immunological changes in Brown-Norway rats sensitized intraperitoneally and repeatedly exposed to ovalbumin (OVA) aerosol. Acetylcholine provocation concentration (PC)150 (the concentration of acetylcholine causing a 150% increase of base-line lung resistance) was measured and peripheral blood and bronchoalveolar lavage (BAL) cells were collected 18-24hr after the final exposure. Total and OVA-specific IgE in serum was measured by enzyme-linked immunosorbent assay (ELISA). Mononuclear cells were analysed by flow cytometry after labelling with monoclonal antibodies against CD2 (pan T-cell marker), CD4, CD8 (T-cell subsets) or CD25 (interleukin-2 receptor). There were significant differences in PC150 (P
PubMed ID
7558155 View in PubMed
Less detail

Characterization of allergen-induced bronchial hyperresponsiveness and airway inflammation in actively sensitized brown-Norway rats.

https://arctichealth.org/en/permalink/ahliterature57758
Source
J Allergy Clin Immunol. 1991 Dec;88(6):951-60
Publication Type
Article
Date
Dec-1991
Author
W. Elwood
J O Lötvall
P J Barnes
K F Chung
Author Affiliation
Department of Thoracic Medicine, National Heart and Lung Institute, London, England.
Source
J Allergy Clin Immunol. 1991 Dec;88(6):951-60
Date
Dec-1991
Language
English
Publication Type
Article
Keywords
Acetylcholine - administration & dosage
Aerosols
Airway Resistance - drug effects
Allergens - administration & dosage - immunology
Animals
Bronchial Hyperreactivity - etiology - immunology
Bronchial Provocation Tests - methods
Bronchitis - etiology - immunology
Bronchoalveolar Lavage Fluid - cytology
Comparative Study
Dose-Response Relationship, Immunologic
Immunization - methods
Male
Rats - immunology
Research Support, Non-U.S. Gov't
Time Factors
Abstract
Bronchial responsiveness to inhaled acetylcholine (ACh) and inflammatory cell recruitment in bronchoalveolar lavage fluid (BALF) were studied in inbred Brown-Norway rats actively sensitized to, and later exposed to, ovalbumin (OA). We examined animals 21 days after initial sensitization at 18 to 24 hours, or 5 days after a single challenge, or after the last of seven repeated exposures administered every 3 days. BALF was examined as an index of inflammatory changes within the lung. Animals repeatedly exposed to OA aerosols had an increased baseline lung resistance and a significant increase in bronchial responsiveness to inhaled ACh compared to control animals at both 18 to 24 hours and 5 days after the last OA exposure. Sensitized animals receiving a single OA aerosol also demonstrated bronchial hyperresponsiveness (BHR) to inhaled ACh (p less than 0.01) at 18 to 24 hours of a similar order as the multiple-exposed group. There was a significant increase in eosinophils, lymphocytes, and neutrophils in BALF at 18 to 24 hours but not at 5 days after single or multiple exposure to OA aerosol in the sensitized groups. Control animals demonstrated no changes in bronchial responsiveness, although a small but significant increase in inflammatory cells was observed compared to saline-only treated animals. There was a significant correlation between bronchial responsiveness and eosinophil counts in the BALF in the single allergen-exposed group (Rs = 0.68; p less than 0.05). We conclude that (1) BHR after allergen exposure in sensitized rats is associated with the presence of pulmonary inflammation but persists despite the regression of inflammatory cells in BALF after multiple OA exposures, and (2) this rat model has many characteristics of human allergen-induced BHR.
PubMed ID
1744366 View in PubMed
Less detail

Contribution of intercellular-adhesion molecule-1 in allergen-induced airway hyperresponsiveness and inflammation in sensitised brown-Norway rats.

https://arctichealth.org/en/permalink/ahliterature15953
Source
Int Arch Allergy Immunol. 1994 Jul;104(3):291-5
Publication Type
Article
Date
Jul-1994
Author
J. Sun
W. Elwood
A. Haczku
P J Barnes
P G Hellewell
K F Chung
Author Affiliation
Department of Thoracic Medicine, National Heart and Lung Institute, London, UK.
Source
Int Arch Allergy Immunol. 1994 Jul;104(3):291-5
Date
Jul-1994
Language
English
Publication Type
Article
Keywords
Allergens - immunology
Animals
Asthma - immunology - prevention & control
Bronchial Hyperreactivity - immunology - prevention & control
Bronchial Provocation Tests
Bronchoalveolar Lavage Fluid - cytology
Cell Adhesion Molecules - immunology
Eosinophils - immunology
Female
Inflammation - pathology
Intercellular Adhesion Molecule-1
Leukocyte Count
Lymphocytes - immunology
Ovalbumin
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Abstract
We investigated the potential role of intercellular-adhesion molecule-1 (ICAM-1) in allergen-induced bronchial hyperresponsiveness (BHR) and inflammation in sensitised Brown-Norway rats. Rats were sensitised with ovalbumin (OA) intraperitoneally and 21 days later they were either exposed to 0.9% NaCl or 1% OA aerosol for 15 min. Rats exposed to OA aerosol were pretreated either with ICAM-1 antibody (3 mg/kg i.p. and i.v., 45 min prior to OA exposure) or with the diluent for the antibody. Eighteen to twenty-four hours after OA or 0.9% NaCl exposure, rats were anaesthetised, tracheostomised and mechanically ventilated, and airway responsiveness to acetylcholine (ACh) aerosol was measured as the provocative concentration of ACh needed to increase pulmorary resistance by 100% (PC100). Mean -log PC100 was increased in rats exposed to OA but pretreated with diluent (2.75 +/- 0.06) compared to rats treated with ICAM-1 antibody (2.51 +/- 0.08;
PubMed ID
7913357 View in PubMed
Less detail

Effect of dexamethasone and cyclosporin A on allergen-induced airway hyperresponsiveness and inflammatory cell responses in sensitized Brown-Norway rats.

https://arctichealth.org/en/permalink/ahliterature16053
Source
Am Rev Respir Dis. 1992 Jun;145(6):1289-94
Publication Type
Article
Date
Jun-1992
Author
W. Elwood
J O Lötvall
P J Barnes
K F Chung
Author Affiliation
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
Source
Am Rev Respir Dis. 1992 Jun;145(6):1289-94
Date
Jun-1992
Language
English
Publication Type
Article
Keywords
Acetylcholine - diagnostic use
Aerosols
Animals
Bronchial Hyperreactivity - physiopathology
Bronchial Provocation Tests
Bronchoalveolar Lavage Fluid - pathology
Comparative Study
Cyclosporine - pharmacology
Dexamethasone - pharmacology
Eosinophils - immunology
Immunization
Lymphocyte Activation - drug effects
Male
Ovalbumin - immunology
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
T-Lymphocytes - immunology
Abstract
We studied the effects of dexamethasone and cyclosporin A on the airway hyperresponsiveness (AHR) and the influx of inflammatory cells into the bronchoalveolar lavage (BAL) fluid seen 18 to 24 hr after exposure to aerosolized ovalbumin in actively ovalbumin-sensitized Brown-Norway rats. Allergen exposure resulted in an approximately sevenfold increase in bronchial responsiveness to inhaled acetylcholine associated with a significant increase in eosinophils and lymphocytes in BAL fluid. Dexamethasone (0.5 mg/kg administered intraperitoneally for 3 days) abolished the AHR and the increase in eosinophil and lymphocyte counts. However, cyclosporin A at two doses (5 and 50 mg given orally for 5 days) did not significantly prevent the induction of AHR while producing a significant inhibition of the eosinophil and lymphocyte influx. Dexamethasone (0.5 mg/kg for 3 days) or cyclosporin A (5 mg/kg for 5 days) on their own had no effect on airway responsiveness. We conclude that specific inhibition of T-lymphocyte activation in this Brown-Norway rat model is not sufficient to inhibit the induction of AHR despite suppressing allergen-induced eosinophilia in BAL fluid. However, corticosteroids, which have inhibitory effects on a wider range of inflammatory cells, are more effective. Our observations are in line with the potent effect of corticosteroids in airway inflammatory conditions such as asthma.
PubMed ID
1595993 View in PubMed
Less detail

Effect of interleukin-1 beta on airway hyperresponsiveness and inflammation in sensitized and nonsensitized Brown-Norway rats.

https://arctichealth.org/en/permalink/ahliterature57706
Source
J Allergy Clin Immunol. 1994 Feb;93(2):464-9
Publication Type
Article
Date
Feb-1994
Author
H. Tsukagoshi
T. Sakamoto
W. Xu
P J Barnes
K F Chung
Author Affiliation
Department of Thoracic Medicine, National Heart and Lung Institute, Royal Brompton Hospital, London, England.
Source
J Allergy Clin Immunol. 1994 Feb;93(2):464-9
Date
Feb-1994
Language
English
Publication Type
Article
Keywords
Acetylcholine - pharmacology
Airway Resistance - drug effects - physiology
Animals
Bradykinin - pharmacology
Bronchial Hyperreactivity - etiology - pathology - physiopathology
Bronchoalveolar Lavage Fluid - cytology
Immunization
Inflammation - etiology - physiopathology
Interleukin-1 - pharmacology
Male
Ovalbumin - immunology
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Time Factors
Abstract
Airway responsiveness (AR) to inhaled acetylcholine and bradykinin and inflammatory cell recruitment in bronchoalveolar lavage fluid (BALF) were studied in inbred male Brown-Norway rats actively sensitized to ovalbumin and later given 500 U interleukin-1 beta (IL-1 beta) intratracheally. We examined animals 14 to 21 days after initial sensitization at 18 to 24 hours after the intratracheal administration of IL-1 beta. We evaluated AR to acetylcholine as -log PC200, which is -log10 transformation of provocative concentration of acetylcholine producing 200% increase in lung resistance, and to bradykinin as percent increase in lung resistance. BALF was examined as an index of inflammatory changes within the lung. Although there was no significant difference in baseline lung resistance, nonsensitized and sensitized animals that were given IL-1 beta demonstrated a significant increase of AR to bradykinin at 18 to 24 hours and a significant increase of neutrophil counts in BALF, which was already observed by 4 to 6 hours. There was a significant correlation between AR to bradykinin and neutrophil counts in BALF in all animals (r = 0.644; p
PubMed ID
8120273 View in PubMed
Less detail

Involvement of cysteinyl leukotrienes in airway smooth muscle cell DNA synthesis after repeated allergen exposure in sensitized Brown Norway rats.

https://arctichealth.org/en/permalink/ahliterature15646
Source
Br J Pharmacol. 1999 Jul;127(5):1151-8
Publication Type
Article
Date
Jul-1999
Author
M. Salmon
D A Walsh
T J Huang
P J Barnes
T B Leonard
D W Hay
K F Chung
Author Affiliation
Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, UK.
Source
Br J Pharmacol. 1999 Jul;127(5):1151-8
Date
Jul-1999
Language
English
Publication Type
Article
Keywords
Acetylcholine - pharmacology
Allergens - immunology
Animals
Arachidonate 5-Lipoxygenase - physiology
Bronchi - drug effects - metabolism
Cell Count
Cysteine - physiology
DNA - biosynthesis
Eosinophils - physiology
Leukotrienes - physiology
Male
Muscle, Smooth - metabolism
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Abstract
Airway smooth muscle thickening is a characteristic feature of airway wall remodelling in chronic asthma. We have investigated the role of the leukotrienes in airway smooth muscle (ASM) and epithelial cell DNA synthesis and ASM thickening following repeated allergen exposure in Brown Norway rats sensitized to ovalbumin. There was a 3 fold increase in ASM cell DNA synthesis, as measured by percentage bromodeoxyuridine (BrdU) incorporation, in repeatedly ovalbumin-exposed (4.1%, 3.6-4.6; mean, 95% c.i.) compared to chronically saline-exposed rats (1.3%, 0.6-2.1; P
PubMed ID
10455261 View in PubMed
Less detail

Mechanisms of impaired beta-adrenoceptor-induced airway relaxation by interleukin-1beta in vivo in the rat.

https://arctichealth.org/en/permalink/ahliterature11157
Source
J Clin Invest. 1996 Oct 15;98(8):1780-7
Publication Type
Article
Date
Oct-15-1996
Author
H. Koto
J C Mak
E B Haddad
W B Xu
M. Salmon
P J Barnes
K F Chung
Author Affiliation
Thoracic Medicine, National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, London, United Kingdom.
Source
J Clin Invest. 1996 Oct 15;98(8):1780-7
Date
Oct-15-1996
Language
English
Publication Type
Article
Keywords
Animals
Autoradiography
Bronchi - drug effects - physiology
Cyclic AMP - metabolism
Forskolin - pharmacology
GTP-Binding Proteins - analysis
Interleukin-1 - pharmacology
Isoproterenol - pharmacology
Muscle Relaxation - drug effects
RNA, Messenger - analysis
Rats
Rats, Inbred BN
Receptors, Adrenergic, beta - analysis - genetics - physiology
Research Support, Non-U.S. Gov't
Trachea - drug effects - physiology
Abstract
We studied the in vivo mechanism of beta-adrenergic receptor (beta-AR) hyporesponsiveness induced by intratracheal instillation of interleukin-1beta (IL-1beta, 500 U) in Brown-Norway rats. Tracheal and bronchial smooth muscle responses were measured under isometric conditions ex vivo. Contractile responses to electrical field stimulation and to carbachol were not altered, but maximal relaxation induced by isoproterenol (10(-6)-10(-5) M) was significantly reduced 24 h after IL-1beta treatment in tracheal tissues and to a lesser extent, in the main bronchi. Radioligand binding using [125I]iodocyanopindolol revealed a 32+/-7% reduction in beta-ARs in lung tissues from IL-1beta-treated rats, without any significant changes in beta2-AR mRNA level measured by Northern blot analysis. Autoradiographic studies also showed significant reduction in beta2-AR in the airways. Isoproterenol-stimulated cyclic AMP accumulation was reduced by IL-1beta at 24 h in trachea and lung tissues. Pertussis toxin reversed this hyporesponsiveness to isoproterenol but not to forskolin in lung tissues. Western blot analysis revealed an IL-1beta-induced increase in Gi(alpha) protein expression. Thus, IL-1beta induces an attenuation of beta-AR-induced airway relaxation through mechanisms involving a reduction in beta-ARs, an increase in Gi(alpha) subunit, and a defect in adenylyl cyclase activity.
PubMed ID
8878428 View in PubMed
Less detail

Metaplastic breast carcinoma: clinical-pathologic characteristics and HER2/neu expression.

https://arctichealth.org/en/permalink/ahliterature174989
Source
Breast Cancer Res Treat. 2005 May;91(2):173-8
Publication Type
Article
Date
May-2005
Author
P J Barnes
R. Boutilier
D. Chiasson
D. Rayson
Author Affiliation
Department of Pathology, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia B3H 2Y9, Canada.
Source
Breast Cancer Res Treat. 2005 May;91(2):173-8
Date
May-2005
Language
English
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
Breast Neoplasms - epidemiology - pathology
Carcinoma - epidemiology - pathology
Female
Humans
Immunohistochemistry
Metaplasia
Middle Aged
Nova Scotia - epidemiology
Receptor, erbB-2 - metabolism
Abstract
Metaplastic breast carcinomas (MBC) are rare primary breast malignancies characterized by the co-existence of carcinoma with non-epithelial cellular elements. They can be classified as monophasic spindle cell (sarcomatoid) carcinoma, biphasic carcinosarcoma, adenocarcinoma with divergent stromal differentiation (osseous, chondroid and rarely rhabdoid) as well as adenosquamous and pure squamous cell carcinomas. There is a paucity of information on clinically relevant pathologic features and clinical outcomes for these rare tumors. The aim of this study was to review the pathologic features and clinical outcomes of all cases of MBC seen at a single institution between 1971 and 2000.
A computerized search of the Queen Elizabeth II Health Sciences Center (QEII HSC) surgical pathology files was performed for the years 1971-2000. Tumor blocks from identified cases were reviewed and immunohistochemistry was performed for estrogen and progesterone receptors (ER/PR), HER2/neu protein overexpression and cytokeratin profile. Clinical outcome information was obtained from hospital files and telephone contact with treating physicians.
Twenty-six (26) cases were retrieved with only one case identified before 1990. All tumors were high grade with a median tumor size of 3.7 cm (range 1.4-9.5 cm). Thirteen cases had lymph node dissections available for evaluation, with 4 demonstrating nodal metastases. Five of 26 cases were ER positive within the adenocarcinomatous component, only two of which also expressed PR. Associated ductal carcinoma in situ (DCIS) was present in 11 cases. HER2/neu over-expression was seen in only one (1/26) adenosquamous carcinoma (3 + membranous staining of the malignant glandular component). At 23 months median follow-up, disease free survival (DFS) for the entire group was 53%.
Although a rare breast cancer subtype, MBC is of considerable interest due to its pathological heterogeneity and differences in clinical behavior compared to typical breast carcinomas. Increasing pathologic recognition of MBC as a discrete entity is suggested by the number of MBC diagnoses in the last decade compared to previous years. The poor DFS associated with MBC suggests that further research exploring mechanisms of carcinogenesis and identifying clinically relevant prognostic factors is needed to direct optimum clinical care. Importantly, MBC variants appear to rarely overexpress the HER2/neu oncoprotein.
PubMed ID
15868445 View in PubMed
Less detail

12 records – page 1 of 2.