Effect of allergen challenge on airway responsiveness to histamine and sodium metabisulphite in mild asthma.

To determine the characteristics and reproducibility of circadian rhythms of airway responsiveness to histamine and methacholine and their relationship to airway tone in patients with mild asthma, we studied nine subjects with complaints of nighttime awakening due to dyspnea and/or cough at least once a week. Their mean age was 31.4 yr (range 17–65) and their mean daytime FEV1 was 99 +/- 14 (SD) % predicted. Forced expiratory volume in 1 s (FEV1) and the provocative concentrations of histamine and methacholine necessary to decrease FEV1 by 20% (PC20FEV1) were determined every 4 h for 13 consecutive measurements. Three subjects were measured with histamine, three with methacholine, and three with both histamine and methacholine. Data were evaluated on an individual basis. PC20FEV1 to histamine and methacholine showed significant and reproducible circadian variations in all cases (P less than 0.01 each) with a mean amplitude of 1.00 +/- 0.17 (SD) doubling concentrations for histamine and 1.35 +/- 0.29 doubling concentrations for methacholine. The amplitude of PC20FEV1 was significantly larger (P less than 0.05) and the time of maximum responsiveness was significantly earlier (P less than 0.05) with methacholine compared with histamine. FEV1 showed significant (P less than 0.05) circadian variations in three of nine subjects, and peak expiratory flow rate showed variations in two subjects. Correlation between the variations of FEV1 and PC20FEV1 was significant (P less than 0.05) in 5 of 12 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

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Allergen Induced Increase in Nonallergic Airway Responsiveness: A Citation Classic Revisited

Canadian Respiratory Journal ◽

10.1155/2000/846798 ◽

2000 ◽

Vol 7 (2) ◽

pp. 182-187 ◽

Cited By ~ 8

Author(s):

Donald W Cockcroft

Keyword(s):

Airway Inflammation ◽

Airway Hyperresponsiveness ◽

Immunoglobulin E ◽

Allergen Challenge ◽

Airway Responsiveness ◽

Forced Expiration ◽

Citation Classic ◽

Poor Understanding ◽

The Times

BACKGROUND:The present paper revisits the 1977 paper by DW Cockcroft, RE Ruffin, the late J Dolovich and FE Hargreave entitled "Allergen-induced increase in nonallergic bronchial reactivity" (Clin Allergy1977;7:503-13) that became a citation classic. Although clinical types of asthma were recognized at the time, there was a poor understanding regarding the role of allergic reactions in causing increases in airway hyperresponsiveness. The objective was to study formally Dr Altounyan's observation that patients with asthma showed increases in airway responsiveness at the times of natural allergen exposure during pollen season. Thirteen atopic patients with asthma were studied over two days, following inhalation of diluent (control) and following doubling amounts of an allergen solution at 10-min intervals until forced expiration volume in 1 s fell by 20%. Methacholine and histamine challenges were performed before, at 8 h, at 32 h and seven days following the inhalations. A significant reduction (reduction of at least one doubling concentration) in the provocative concentration that causes a 20% fall in forced expiration volume in 1 s occurred in seven of 13 patients, and more often in subjects with a late bronchoconstrictor response to allergen challenge.IMPORTANCE:The study showed that large changes in airway responsiveness could occur in patients with asthma and suggested that allergens could cause, rather than trigger, asthma. The study also led to the concept of asthma inducers and inciters -- inducers causing airway inflammation and inciters provoking bronchospasm. The results led to a series of observations that have now implicated immunoglobulin E-mediated airway inflammation as perhaps the most important cause of airway hyperresponsiveness in asthma.

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RANTES (CCL5) Regulates Airway Responsiveness after Repeated Allergen Challenge

American Journal of Respiratory Cell and Molecular Biology ◽

10.1165/rcmb.2005-0394oc ◽

2006 ◽

Vol 35 (2) ◽

pp. 147-154 ◽

Cited By ~ 17

Author(s):

Toshiyuki Koya ◽

Katsuyuki Takeda ◽

Taku Kodama ◽

Nobuaki Miyahara ◽

Shigeki Matsubara ◽

...

Keyword(s):

Allergen Challenge ◽

Airway Responsiveness

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The effects of repeated allergen challenge on airway smooth muscle structural and molecular remodeling in a rat model of allergic asthma

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00142.2009 ◽

2009 ◽

Vol 297 (4) ◽

pp. L698-L705 ◽

Cited By ~ 31

Author(s):

Isabelle Labonté ◽

Muhannad Hassan ◽

Paul-André Risse ◽

Kimitake Tsuchiya ◽

Michel Laviolette ◽

...

Keyword(s):

Smooth Muscle ◽

Airway Smooth Muscle ◽

Ex Vivo ◽

Mrna Level ◽

Allergen Challenge ◽

Airway Responsiveness ◽

Brown Norway ◽

Contractile Phenotype ◽

The Relationship

The effects of remodeling of airway smooth muscle (SM) by hyperplasia on airway SM contractility in vivo are poorly explored. The aim of this study was to investigate the relationship between allergen-induced airway SM hyperplasia and its contractile phenotype. Brown Norway rats were sensitized with ovalbumin (OVA) or saline on day 0 and then either OVA-challenged once on day 14 and killed 24 h later or OVA-challenged 3 times (on days 14, 19, and 24) and killed 2 or 7 days later. Changes in SM mass, expression of total myosin, SM myosin heavy chain fast isoform (SM-B) and myosin light chain kinase (MLCK), tracheal contractions ex vivo, and airway responsiveness to methacholine (MCh) in vivo were assessed. One day after a single OVA challenge, the number of SM cells positive for PCNA was greater than for control animals, whereas the SM mass, contractile phenotype, and tracheal contractility were unchanged. Two days after three challenges, SM mass and PCNA immunoreactive cells were increased (3- and 10-fold, respectively; P < 0.05), but airway responsiveness to MCh was unaffected. Lower expression in total myosin, SM-B, and MLCK was observed at the mRNA level ( P < 0.05), and total myosin and MLCK expression were lower at the protein level ( P < 0.05) after normalization for SM mass. Normalized tracheal SM force generation was also significantly lower 2 days after repeated challenges ( P < 0.05). Seven days after repeated challenges, features of remodeling were restored toward control levels. Allergen-induced hyperplasia of SM cells was associated with a loss of contractile phenotype, which was offset by the increase in mass.

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Effect of triiodothyronine-induced thyrotoxicosis on airway hyperresponsiveness

Journal of Applied Physiology ◽

10.1152/jappl.1991.71.2.438 ◽

1991 ◽

Vol 71 (2) ◽

pp. 438-444 ◽

Cited By ~ 5

Author(s):

H. M. Hollingsworth ◽

M. R. Pratter ◽

J. M. Dubois ◽

L. E. Braverman ◽

R. S. Irwin

Keyword(s):

Lung Function ◽

Pulmonary Function ◽

Exercise Capacity ◽

Controlled Trial ◽

Pulmonary Function Tests ◽

Airway Responsiveness ◽

Mild Asthma ◽

Thyroid Function Tests ◽

Double Blind ◽

Function Tests

To determine whether thyrotoxicosis has an effect on the asthmatic state in subjects with mild asthma, airway responsiveness, lung function, and exercise capacity were measured in a randomized double-blind placebo-controlled trial before and after liothyronine (triiodothyronine, T3)-induced thyrotoxicosis. Baseline evaluation of 15 subjects with mild asthma included clinical evaluation, thyroid and routine pulmonary function tests, airway responsiveness assessment by methacholine inhalation challenge, and a symptom-limited maximal exercise test. For all subjects, the initial testing revealed that the dose of methacholine which provoked a 20% fall in forced expiratory volume in 1s (PD20) was in a range consistent with symptomatic asthma. There was no significant change in pulmonary function tests, airway reactivity (PD20), or exercise capacity in either the placebo or the T3-treated groups. Thyroid function tests confirmed mild sustained thyrotoxicosis in the T3-treated groups. We conclude that mild T3-induced thyrotoxicosis of 4-wk duration had no effect on lung function, airway responsiveness, or exercise capacity in subjects with mild asthma.

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Allergen-induced airway hyperresponsiveness in Brown-Norway rat: role of parasympathetic mechanisms

Journal of Applied Physiology ◽

10.1152/jappl.1993.75.1.279 ◽

1993 ◽

Vol 75 (1) ◽

pp. 279-284 ◽

Cited By ~ 13

Author(s):

W. Elwood ◽

T. Sakamoto ◽

P. J. Barnes ◽

K. F. Chung

Keyword(s):

Airway Hyperresponsiveness ◽

Allergen Challenge ◽

Electrical Field Stimulation ◽

Airway Responsiveness ◽

Brown Norway ◽

Field Stimulation ◽

Electrical Field ◽

Norway Rat

Enhanced parasympathetic mechanisms may contribute to airway hyperresponsiveness. The present study examined whether the in vivo increase in airway responsiveness seen 18–24 h after either a single or chronic aerosolized allergen challenge protocol in actively sensitized Brown-Norway rats was due to altered parasympathetic mechanisms. The roles of central and reflex vagal mechanisms were studied by performing bilateral cervical vagotomy before measurement of airway responsiveness. Bilateral vagotomy failed to reduce the increase in airway responsiveness after either a single or chronic allergen challenge. The roles of increased neural release of acetylcholine (ACh) and increased end organ responsiveness were studied in vitro. The isometric responses of tracheal and bronchial strips to both electrical field stimulation and exogenously applied ACh from rats exposed both to single and chronic allergen challenges were compared with those from saline-exposed rats. The responses to electrical field stimulation and to exogenous ACh were not significantly enhanced 18–24 h after either protocol. We conclude that the airway hyperresponsiveness observed in this allergic rat model is not mediated through an enhancement of parasympathetic mechanisms.

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Protective Effects of Fluticasone on Allergen-Induced Airway Responses and Sputum Inflammatory Markers

Canadian Respiratory Journal ◽

10.1155/2000/254213 ◽

2000 ◽

Vol 7 (4) ◽

pp. 313-319 ◽

Cited By ~ 29

Author(s):

Krishnan Parameswaran ◽

Mark D Inman ◽

Rick M Watson ◽

Marilyn M Morris ◽

Ann Efthimiadis ◽

...

Keyword(s):

Single Dose ◽

Protective Effect ◽

Allergen Challenge ◽

Airway Responsiveness ◽

Protective Effects ◽

Asthmatic Response ◽

Sputum Eosinophilia ◽

Late Asthmatic Response ◽

Cell Counts ◽

Allergen Inhalation

BACKGROUND:A direct comparison of the protective effects of single and regular doses of inhaled glucocorticoid on allergen-induced asthmatic responses and inflammation has not been made.OBJECTIVE:To compare the effects of pretreatment with fluticasone 250 µg 30 min before allergen inhalation and two weeks of 250 µg twice daily (last dose 24 h before challenge) with single and regular (twice daily) placebo doses on early and late asthmatic responses, induced sputum cell counts and measures of eosinophil activation at 7 h and 24 h, and methacholine airway responsiveness at 24 h.PATIENTS AND METHODS:Ten mild asthmatic patients were studied in a randomized, double-blind, placebo controlled crossover study.RESULTS:Regular fluticasone increased the baseline mean provocative concentration of methacholine to cause a 20% fall (PC20) in forced expiratory volume in 1 s (FEV1) from 2.6 to 6.4 mg/mL (P<0.05) and lowered the eosinophil count from 3.1% to 0.4% (P<0.05) compared with regular placebo. Neither single nor regular fluticasone had any effect on the early asthmatic response. Single fluticasone attenuated the late asthmatic response, the mean ± SEM maximum percentage fall in FEV1(10.8±3.6 compared with single placebo 18.8±3.5, P=0.03), the allergen-induced increase of airway responsiveness (P<0.05), and the eosinophilia (P<0.005) and activated eosinophils at 7 h (P<0.01) but not at 24 h. Regular fluticasone also attenuated the late asthmatic response (11.1±2.5) compared with regular placebo (19.6±4.5), but this was not statistically significant and did not protect against the induced increase in airway responsiveness or the sputum eosinophilia.CONCLUSION:Two weeks of regular inhaled fluticasone discontinued 24 h before allergen challenge does not offer any additional protection against the early or late asthmatic responses, increased airway responsiveness or sputum eosinophilia compared with a single dose of 250 µg immediately before allergen challenge, despite increasing baseline PC20and decreasing sputum eosinophilia prechallenge. The significance of the protective effect of a single dose of inhaled steroid before an allergen inhalation and the duration of the protective effect need further investigation.

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