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Adoptive transfer of alveolar macrophages abrogates bronchial hyperresponsiveness.

https://arctichealth.org/en/permalink/ahliterature15196
Source
Am J Respir Cell Mol Biol. 2004 Jul;31(1):22-7
Publication Type
Article
Date
Jul-2004
Author
Eric Careau
Elyse Y Bissonnette
Author Affiliation
Centre de Recherche, Hôpital Laval, Institut universitaire de Cardiologie et de Pneumologie de l'Université Laval, Québec, Canada. eric.careau@crhl.ulaval.ca
Source
Am J Respir Cell Mol Biol. 2004 Jul;31(1):22-7
Date
Jul-2004
Language
English
Publication Type
Article
Keywords
Adoptive Transfer
Animals
Asthma - physiopathology
Bronchi - drug effects - immunology - physiopathology
Bronchial Hyperreactivity - genetics - physiopathology - therapy
Bronchial Provocation Tests
Clodronic Acid
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Resistance - physiology
Genetic Predisposition to Disease - genetics
Immunoglobulin E - blood
Immunoglobulin G - blood
Liposomes
Macrophages, Alveolar - drug effects - immunology - transplantation
Male
Methacholine Chloride - pharmacology
Ovalbumin - immunology
Rats
Rats, Sprague-Dawley
Reaction Time - drug effects - physiology
Research Support, Non-U.S. Gov't
Abstract
Increasing evidence suggests that alveolar macrophages (AM) are involved in asthma pathogenesis. To better understand the role that these cells play, we investigated the capacity of AM from allergy-resistant rat, Sprague Dawley (SD), to modulate airway hyperresponsiveness of allergy-susceptible rat, Brown Norway (BN). AM of ovalbumin (OVA)-sensitized BN rats were eliminated by intratracheal instillation of liposomes containing clodronate. AM from OVA-sensitized SD rats were transferred into AM-depleted BN rats 24 h before allergen challenge. Airway responsiveness to methacholine was measured the following day. Instillation of liposomes containing clodronate in BN rats eliminated 85% AM after 3 d compared with saline liposomes. Methacholine concentration needed to increase lung resistance by 200% (EC200RL) was significantly lower in OVA-challenged BN rats (27.9 +/- 2.8 mg/ml) compared with SD rats (63.9 +/- 8.6 mg/ml). However, when AM from SD rats were transferred into AM-depleted BN rats, airway responsiveness (64.0 +/- 11.3 mg/ml) was reduced to the level of naïve rats (54.4 +/- 3.7 mg/ml) in a dose-dependent manner. Interestingly, transfer of AM from BN rats into SD rats did not modulate airway responsiveness. To our knowledge, this is the first direct evidence showing that AM may protect against the development of airway hyperresponsiveness.
Notes
Comment In: Am J Respir Cell Mol Biol. 2004 Jul;31(1):1-215208095
Comment In: Am J Respir Cell Mol Biol. 2004 Jul;31(1):3-715208096
PubMed ID
14962974 View in PubMed
Less detail

Airway responses in Brown Norway rats following inhalation sensitization and challenge with trimellitic anhydride.

https://arctichealth.org/en/permalink/ahliterature80614
Source
Toxicol Sci. 2006 Dec;94(2):322-9
Publication Type
Article
Date
Dec-2006
Author
Zhang Xing-Dong
Andrew Michael E
Hubbs Ann F
Siegel Paul D
Author Affiliation
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA.
Source
Toxicol Sci. 2006 Dec;94(2):322-9
Date
Dec-2006
Language
English
Publication Type
Article
Keywords
Administration, Inhalation
Airway Resistance - drug effects - physiology
Allergens - immunology - toxicity
Animals
Antibodies, Anti-Idiotypic - blood
Bronchi - drug effects - pathology
Bronchial Hyperreactivity - chemically induced - immunology - pathology
Bronchial Provocation Tests
Female
Immunoglobulin E - blood - immunology
Inhalation Exposure
Phthalic Anhydrides - immunology - toxicity
Plethysmography, Whole Body
Rats
Rats, Inbred BN
Respiratory Hypersensitivity - chemically induced - immunology - pathology
Specific Pathogen-Free Organisms
Abstract
Trimellitic anhydride (TMA) is a cause of asthma in man. Dose-dependent TMA-specific IgE, histopathology, and airway responses after sensitization by inhalation were examined in the Brown Norway rat. Rats were exposed to 0.04, 0.4, 4, or 40 mg/m3 TMA aerosol for 10 min, once a week, over 10 weeks. All lower exposures were, subsequently, rechallenged to 40 mg/m3 TMA aerosol. All rats received a sham exposure 1 week prior to the first TMA exposure. Following the sham exposure and weekly after each TMA exposure, TMA-specific IgE and both early-phase airway response (EAR) and late-phase airway response (LAR) were measured using enhanced pause (Penh). All rats sensitized by 40 mg/m3 TMA developed specific IgE, EAR, and LAR to one or more of the challenges to 40 mg/m3 TMA. TMA of 4 mg/m3 induced a much lower, but stable, specific IgE response. EAR and LAR were observed only after a 40 mg/m3 TMA rechallenge in this group, but it was much larger than that observed in the 40 mg/m3 TMA-sensitized and challenged group. Exposure-dependent histopathological changes noted included eosinophilic granulomatous interstitial pneumonia, perivascular eosinophil infiltrates, bronchial-associated lymphoid tissue hyperplasia, and peribronchiolar plasma cell infiltrates.
PubMed ID
16982671 View in PubMed
Less detail

Antigen-induced airway inflammation in the Brown Norway rat results in airway smooth muscle hyperplasia.

https://arctichealth.org/en/permalink/ahliterature15325
Source
J Appl Physiol. 2002 Nov;93(5):1833-40
Publication Type
Article
Date
Nov-2002
Author
K F Xu
R. Vlahos
A. Messina
T L Bamford
J F Bertram
A G Stewart
Author Affiliation
Bernard O'Brien Institute of Microsurgery, St. Vincent's Hospital, Fitzroy, Victoria 3065, Australia.
Source
J Appl Physiol. 2002 Nov;93(5):1833-40
Date
Nov-2002
Language
English
Publication Type
Article
Keywords
Acetylcholine - pharmacology
Airway Resistance
Animals
Bronchi - drug effects - pathology
Bronchial Hyperreactivity - immunology - physiopathology
Bronchitis - immunology - pathology - physiopathology
Cell Count
Hyperplasia
Hypersensitivity, Immediate - immunology - physiopathology
Male
Muscle, Smooth - pathology
Ovalbumin - immunology
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Abstract
Asthma is characterized by chronic airways inflammation, airway wall remodeling, and airway hyperresponsiveness (AHR). An increase in airway smooth muscle has been proposed to explain a major part of AHR in asthma. We have used unbiased stereological methods to determine whether airway smooth muscle hyperplasia and AHR occurred in sensitized, antigen-challenged Brown Norway (BN) rats. Ovalbumin (OA)-sensitized BN rats chronically exposed to OA aerosol displayed airway inflammation and a modest level of AHR to intravenously administered ACh 24 h after the last antigen challenge. However, these animals did not show an increase in smooth muscle cell (SMC) number in the left main bronchus, suggesting that short-lived inflammatory mechanisms caused the acute AHR. In contrast, 7 days after the last aerosol challenge, there was a modest increase in SMC number, but no AHR to ACh. Addition of FCS to the chronic OA challenge protocol had no effect on the degree of inflammation but resulted in a marked increase in both SMC number and a persistent (7-day) AHR. These results raise the possibility that increases in airway SMC number rather than, or in addition to, chronic inflammation contribute to the persistent AHR detected in this model.
PubMed ID
12381772 View in PubMed
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Are asthma-like symptoms in elite athletes associated with classical features of asthma?

https://arctichealth.org/en/permalink/ahliterature152734
Source
Br J Sports Med. 2009 Dec;43(14):1131-5
Publication Type
Article
Date
Dec-2009
Author
T K Lund
L. Pedersen
S D Anderson
A. Sverrild
V. Backer
Author Affiliation
Respiratory and Allergy Research Unit, Department of Respiratory Medicine, Bispebjerg Hospital, Copenhagen University Hospital, 2400 Copenhagen NV, Denmark. tclund@dadlnet.dk
Source
Br J Sports Med. 2009 Dec;43(14):1131-5
Date
Dec-2009
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Asthma - diagnosis - epidemiology - etiology - physiopathology
Breath Tests
Bronchi - drug effects
Bronchial Provocation Tests
Bronchodilator Agents - pharmacology
Cross-Sectional Studies
Denmark - epidemiology
Female
Forced Expiratory Volume - physiology
Humans
Male
Mannitol - pharmacology
Nitric Oxide - analysis
Sports - statistics & numerical data
Sputum - cytology
Vital Capacity - physiology
Young Adult
Abstract
Asthma is frequent in elite athletes and clinical studies in athletes have found increased airway inflammation.
To investigate asthma-like symptoms, airway inflammation, airway reactivity (AR) to mannitol and use of asthma medication in Danish elite athletes.
The study group consisted of 54 elite athletes (19 with doctor-diagnosed asthma), 22 non-athletes with doctor-diagnosed asthma (steroid naive for 4 weeks before the examination) and 35 non-athletes without asthma; all aged 18-35 years. Examinations (1 day): questionnaires, exhaled nitric oxide (eNO) in parts per billion, spirometry, skin prick test, AR to mannitol and blood samples. Induced sputum was done in subjects with asthma.
No significant difference was found in values for eNO, AR and atopy between 42 elite athletes with and 12 without asthma-like symptoms. Elite athletes with doctor-diagnosed asthma had less AR (response dose ratio 0.02 (0.004) vs 0.08 (0.018) p
PubMed ID
19201767 View in PubMed
Less detail

Bronchial responsiveness in a Norwegian community.

https://arctichealth.org/en/permalink/ahliterature67886
Source
Am Rev Respir Dis. 1991 Feb;143(2):317-22
Publication Type
Article
Date
Feb-1991
Author
P S Bakke
V. Baste
A. Gulsvik
Author Affiliation
Department of Thoracic Medicine, University of Bergen, Norway.
Source
Am Rev Respir Dis. 1991 Feb;143(2):317-22
Date
Feb-1991
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Bronchi - drug effects
Female
Forced expiratory volume
Humans
Male
Methacholine Chloride - pharmacology
Middle Aged
Norway
Regression Analysis
Research Support, Non-U.S. Gov't
Sex Characteristics
Smoking
Abstract
Bronchial responsiveness to methacholine was examined in a Norwegian general population sample (n = 490) 18 to 73 yr of age. Altogether, 20 and 6% of the sample had PC20 less than or equal to 32 mg/ml and PC20 less than or equal to 8 mg/ml, respectively. The relationship of bronchial responsiveness to the following potential predictors were examined: sex, age, smoking habits, airway caliber (FEV1), FEV1 percent predicted (%FEV1), urban-rural area of residence, occupational airborne exposure in present job, and total serum IgE. After adjusting for age and FEV1, the odds ratio for PC20 less than or equal to 32 mg/ml was higher for men than for women in smokers and in ex-smokers, but did not vary by sex in nonsmokers, the adjusted odds ratio for PC20 less than or equal to 32 mg/ml in male compared with female smokers being 8.4 (95% Cl: 2.5-37.4). Irrespective of smoking status the sex- and FEV1-adjusted odds ratio for PC20 less than or equal to 32 mg/ml fell with increasing age. For every 10-yr increase in age the adjusted odds ratio for PC20 less than or equal to 32 mg/ml methacholine in nonsmokers decreased by 2.0 (95% Cl: 1.3-3.3). Also FEV1 and %FEV1 were predictors of PC20 less than or equal to 32 mg/ml after adjusting for sex and age irrespective of smoking status. Bronchial responsiveness (PC20 less than or equal to 8 mg/ml) was more prevalent in rural than in urban areas, the adjusted odds ratio being 2.5 (95% Cl: 1.1-5.9) for bronchial responsiveness in rural compared with urban residents after adjusting for sex, age, smoking habits, and FEV1.(ABSTRACT TRUNCATED AT 250 WORDS)
PubMed ID
1990946 View in PubMed
Less detail

[Clinical effectiveness of delayed-action theophylline preparations]

https://arctichealth.org/en/permalink/ahliterature16114
Source
Klin Med (Mosk). 1990 Sep;68(9):72-5
Publication Type
Article
Date
Sep-1990
Author
A N Tsoi
L N Gavrilenko
B P Bogovskii
L G Semenova
L I Iuldasheva
Source
Klin Med (Mosk). 1990 Sep;68(9):72-5
Date
Sep-1990
Language
Russian
Publication Type
Article
Keywords
Adult
Aged
Bronchi - drug effects
Comparative Study
Delayed-Action Preparations
Dose-Response Relationship, Drug
English Abstract
Female
Humans
Lung Diseases, Obstructive - drug therapy
Male
Middle Aged
Theophylline - administration & dosage - therapeutic use
Abstract
Clinical efficiency of course treatment has been assessed for 5 long-acting drugs of theophylline series: retaphylline (Finland), theo-dur (Sweden), durophylline (Yugoslavia), theopek and theobilong (USSR). The drugs were tested in 139 patients with chronic++ bronchial obstruction. It was established that first-line therapy with theophylline should be started with low doses (400 mg/day) and last for 3 days to define individual sensitivity to theophylline drugs followed by increasing doses. On day 7 serum theophylline levels were to be measured for control and dose correction. In cross administration and adequate doses the drugs activity was similar. For patients suffering from nocturnal asthma attacks it was an atypical doze regimen implying administration of two-thirds of the day, dose in the evening that produced the highest effect. The incidence and severity of CNS, cardiovascular and gastrointestinal side effects varied with the dose blood concentration and individual sensitivity to theophylline.
PubMed ID
2290338 View in PubMed
Less detail

[Comparative evaluation of the clinical action of a series of beta-adrenergic blockaders]

https://arctichealth.org/en/permalink/ahliterature13208
Source
Kardiologiia. 1976 Jul;16(7):75-81
Publication Type
Article
Date
Jul-1976
Author
I P Zamotaev
L G Lozinskii
B L Sandomirskii
L N Maksimova
Source
Kardiologiia. 1976 Jul;16(7):75-81
Date
Jul-1976
Language
Russian
Publication Type
Article
Keywords
Adrenergic beta-Antagonists - administration & dosage - therapeutic use
Angina Pectoris - drug therapy
Arrhythmia - drug therapy
Bronchi - drug effects
Clinical Trials
Comparative Study
Drug Evaluation
England
English Abstract
Humans
Pindolol - therapeutic use
Practolol - therapeutic use
Propranolol - therapeutic use
Sweden
Switzerland
Abstract
A comparative clinical study of the efficacy of Benzoral, Trasicor, Viskene, Aptene, Eraldine and Inderal was conducted in the ischaemic heart disease patients. Their antiarrhythmic and antianginal effect was determined, as well as their optimum therapeutic dosages, the activity of their specific beta-adrenolytic properties, the effect of the drugs on the bronchi and the peripheral venous tone. Apart from the clinical study, electro- and polycardiography, functional pulmonary tests and the Schellong orthostatic test were used. All the drugs in question were found to produce a distinct specific beta-blocking effect. They are effective in cases of atrial and ventricular extrasystole, paroxysmal tachycardia, sinus tachycardia and tachyarrhythmic fibrillation, as well as for the prevention of anginal attacks and arrhythmic fibrillation. All the drugs produce a negative inotropic effect, Inderal--the strongest, Viskene and Benzoral--the weakest. All beta-blockers can impair bronchial patency in patients with bronchial obstruction. This effect is least pronounced with Eraldine that may be used as the drug of choice in such cases. In most cases the beta-blockers do not affect the peripheral venous tone, but in some cases they may reduce it.
PubMed ID
10463 View in PubMed
Less detail

A controlled study on the effect of treatment with cromolyn sodium pressurized aerosol on bronchial reactivity in patients with asthma.

https://arctichealth.org/en/permalink/ahliterature16195
Source
Ann Allergy. 1986 Mar;56(3):270-3
Publication Type
Article
Date
Mar-1986
Author
L A Laitinen
K. Venho
H. Poppius
Source
Ann Allergy. 1986 Mar;56(3):270-3
Date
Mar-1986
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aerosols
Asthma - physiopathology
Bronchi - drug effects
Child
Child, Preschool
Climate
Clinical Trials
Cold
Cromolyn Sodium - administration & dosage
Female
Histamine - pharmacology
Humans
Male
Middle Aged
Skin Tests
Abstract
The effect of cromolyn sodium (CS) pressurized aerosol on bronchial hyperreactivity was assessed by comparison with placebo in a double-blind crossover study of 14 adult patients with clinically stable asthma. The trial was performed in a cold climate during the pollen-free winter months and the patient's risk of exposure to clinically relevant allergens was judged to be low. The dose was two puffs, each of 1 mg CS or placebo, four times daily over two successive 4-week periods, the order of treatment being decided by random allocation. No significant difference between treatments was observed in bronchial reactivity to histamine, determined as PC15. There was no difference between treatments with regard to symptoms, which were slight, or daily peak expiratory flow recordings, which showed minimal circadian variation. The results suggest that, although prolonged treatment with CS may decrease bronchial reactivity by reducing airway inflammation secondary to the assault of allergic stimuli, the drug probably has little or no effect on the basal bronchial reactivity in asthma.
PubMed ID
3082257 View in PubMed
Less detail

Effect of the selective leukotriene B4 antagonists U-75302 and Ly255283 on bronchoalveolar eosinophilia induced by inhalation of leukotriene B4 or allergen in brown-Norway rats.

https://arctichealth.org/en/permalink/ahliterature12109
Source
Ann N Y Acad Sci. 1991;629:428-9
Publication Type
Article
Date
1991

Effect of tralokinumab, an interleukin-13 neutralising monoclonal antibody, on eosinophilic airway inflammation in uncontrolled moderate-to-severe asthma (MESOS): a multicentre, double-blind, randomised, placebo-controlled phase 2 trial.

https://arctichealth.org/en/permalink/ahliterature299756
Source
Lancet Respir Med. 2018 07; 6(7):499-510
Publication Type
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Date
07-2018
Author
Richard J Russell
Latifa Chachi
J Mark FitzGerald
Vibeke Backer
Ronald Olivenstein
Ingrid L Titlestad
Charlotte Suppli Ulrik
Timothy Harrison
Dave Singh
Rekha Chaudhuri
Brian Leaker
Lorcan McGarvey
Salman Siddiqui
Millie Wang
Martin Braddock
Lars H Nordenmark
David Cohen
Himanshu Parikh
Gene Colice
Christopher E Brightling
Author Affiliation
Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
Source
Lancet Respir Med. 2018 07; 6(7):499-510
Date
07-2018
Language
English
Publication Type
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Keywords
Adolescent
Adult
Aged
Antibodies, Monoclonal - therapeutic use
Asthma - drug therapy - physiopathology
Bronchi - drug effects - physiopathology
Canada
Denmark
Double-Blind Method
Eosinophilia - physiopathology
Female
Humans
Inflammation - drug therapy - physiopathology
Male
Middle Aged
Severity of Illness Index
Treatment Outcome
United Kingdom
Young Adult
Abstract
The role of interleukin 13 in airway inflammation and remodelling in asthma is unclear. Tralokinumab is a human monoclonal antibody that neutralises interleukin 13. We aimed to evaluate whether tralokinumab would have an effect on airway eosinophilic infiltration, blood and sputum eosinophil concentrations, eosinophil activation, and airway remodelling.
We did a multicentre, double-blind, randomised, placebo-controlled phase 2 trial at 15 centres across the UK, Denmark, and Canada. We enrolled participants of either sex aged 18-75 years with inadequately controlled moderate-to-severe asthma for 12 months or more, requiring treatment with inhaled corticosteroids at a stable dose. We randomly assigned participants (1:1) to receive tralokinumab (300 mg) or placebo by an interactive web-based system or voice response system. Participants and study personnel were masked to treatment allocation. Both tralokinumab and placebo were administered subcutaneously every 2 weeks. The primary outcome measure was change from baseline to week 12 in bronchial biopsy eosinophil count. Secondary outcome measures included change in blood and sputum eosinophil counts. Exploratory outcomes included fractional exhaled nitric oxide (FENO) and blood IgE concentrations. Safety analyses were carried out in all participants who received study drug. This trial is registered with ClinicalTrials.gov, number NCT02449473, and with the European Clinical Trials Database, EudraCT 2015-000857-19.
Between Sept 25, 2015, and June 21, 2017, 224 participants were enrolled and screened. Of these participants, 79 were randomly assigned to receive tralokinumab (n=39) or placebo (n=40). Tralokinumab did not significantly affect bronchial eosinophil count compared with placebo at week 12 (treatment effect ratio 1·43, 95% CI 0·63-3·27; p=0·39). Compared with placebo, tralokinumab did not significantly affect blood eosinophil count (treatment effect ratio 1·21, 95% CI 1·00-1·48; p=0·055) or sputum eosinophil count (0·57, 0·06-6·00; p=0·63), but FENO concentration (0·78, 0·63-0·96; p=0·023) and total blood IgE concentration (0·86, 0·77-0·97; p=0·014) were significantly reduced. 33 (85%) of 39 patients receiving tralokinumab and 32 (80%) of 40 receiving placebo reported at least one adverse event during the treatment period. No deaths in either treatment group were observed. Treatment-related adverse events occurred more frequently in the tralokinumab group than in the placebo group (11 [28%] of 39 vs seven [18%] of 40).
Tralokinumab did not significantly affect eosinophilic inflammation in bronchial submucosa, blood, or sputum compared with placebo, but did reduce FENO and IgE concentrations. These results suggest interleukin 13 is not crucial for eosinophilic airway inflammation control in moderate-to-severe asthma.
AstraZeneca.
Notes
CommentIn: Lancet Respir Med. 2018 Jul;6(7):480-481 PMID 29793858
PubMed ID
29793857 View in PubMed
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20 records – page 1 of 2.