New concepts in the pathogenesis of bronchial hyperresponsiveness and asthma

doi:10.1016/0091-6749(89)90441-7

Journal of Allergy and Clinical Immunology

Volume 83, Issue 6, June 1989, Pages 1013-1026

https://doi.org/10.1016/0091-6749(89)90441-7 Get rights and content

Abstract

Recent studies have suggested that inflammation may play an important role in the characteristic bronchial hyperresponsiveness and symptoms of chronic asthma. The mechanisms by which inflammatory cells, mediators, and nerves interact to produce the features of asthma are still uncertain, however. Although mast cells play an important role in the immediate response to allergen (and probably exercise), pharmacologic evidence argues against a critical role in the late response or bronchial hyperresponsiveness in which other cells, such as macrophages and eosinophils, may play a more important role. Many mediators have been implicated in asthma, but only PAF causes a prolonged increase in bronchial responsiveness. PAF attracts eosinophils into tissues and potently activates these cells, which may lead to epithelial damage, a key feature of asthmatic airways. PAF is also a potent induces of microvascular leakage in airways, which may result in submucosal edema and plasma exudation into the airway lumen in the future. PAF antagonists will reveal whether PAF plays an important role in the eosinophilic inflammation of asthma. Neural mechanisms may also make an important contribution. Inflammatory mediators may influence neurotransmitter release from airway nerves, and neurotransmitters may be proinfiammatory. Neural control is complex and cholinergic, adrenergic, and NANC mechanisms may contribute to bronchial hyperresponsiveness. Many neuropeptides, which may be the transmitters of NANC nerves, have been identified in airways. Neuropeptides in airway sensory nerves, such as substance P, have potent proinflammatory effects and, if these are released by an axon reflex, may amplify the inflammatory response in asthma. Since asthma may be chronic eosinophilic bronchitis, it is logical that the primary treatment should involve drugs that suppress this inflammatory response. At present, corticosteroids appear to be the most effective therapy; they have potent effects against eosinophils and macrophages (but not on mast cells) and reduce bronchial hyperresponsiveness and symptoms. By contrast, bronchodilators, such as β-agonists, although they reduce symptoms, do not reduce the chronic inflammatory response or bronchial hyperresponsiveness and may mask the underlying inflammation. New therapies should be directed toward controlling eosinophil infiltration and activation in airways.

References (115)

P.G.J. Burney
Asthma mortality in England and Wales: evidence for a further increase
Lancet
(1986)
P. Godard et al.
Functional assessment of alveolar macrophages: comparison of cells from asthmatics and normal subjects
J Allergy Clin Immunol
(1982)
D.W. Cockcroft et al.
Comparative effects of inhaled salbutamol, sodium cromoglycate, and beclomethasone dipropionate on allergen-induced early asthmatic responses, late asthmatic responses, and increased bronchial responsiveness to histandne
J Allergy Clin Immunol
(1987)
J. Kraan et al.
Changes in bronchial hyperreactivity induced by 4 weeks of treatment with antiasthmatic drugs in patients with allergic asthma: a comparison between budesonide and terbutaline
J Allergy Clin Immunol
(1985)
K.F. Kerrebijn et al.
Effect of long-term treatment with inhaled corticosteroids and betaagonists on the bronchial responsiveness in children with asthma
J Allergy Clin Immunol
(1987)
E. Frigas et al.
The eosinophil and the pathology of asthma
J Allergy Clin Immunol
(1986)
M.J. Holtzman et al.
Selective generation of leukotriene B, by tracheal epithelial cells from drugs
Biochem Biophys Res Commun
(1983)
J. Morley et al.
Platelet activation as a basis for asthma exacerbation
Lancet
(1984)
D.S. Silberstein et al.
The regulation of human eosinophil function by cytokines
Immunol Today
(1987)
S. Lam et al.
Effect of bronchial lavage volume on cellular and protein recovery
Chest
(1985)

P.J. Barnes

Inflammatory mechanisms and nocturnal asthma

Am J Med

(1988)

N.C. Barnes et al.

Actions of inhaled leukotrienes and their interactions with other allergic mediators

Prostaglandins

(1984)

J.R. Britton et al.

The effect of an oral leukotriene D, antagonist L-649,923 on the response to inhaled antigen in asthma

J Allergy Olin Immunol

(1987)

P.J. Barnes et al.

Platelet-activating factor as a mediator of allergic disease

J Allergy Clin Immunol

(1988)

F.M. Cuss et al.

Effects of inhaled platelet-activating factor on pulmonary function and bronchial responsiveness in man

Lancet

(1986)

E. Henocq et al.

Accumulation of eosinophils in response to intracutaneous PAF-acether and allergens in man

Lancet

(1986)

T.C. Lee et al.

Increased biosynthesis of platelet-activating factor in activated human eosinophils

J Biol Chem

(1984)

K.F. Chung et al.

Effect of a ginkgolide mixture (BN 52063) in antagonising skin and platelet responses to platelet-activating factor in man

Lancet

(1987)

N.M. Roberts et al.

Effect of a PAF antagonists, BN52063, on antigen-induced, acute, and late-onset cutaneous responses in atopic subjects

J Allergy Clin Immunol

(1988)

P.J. Barnes

Neuropeptides in the lung: localization, function, and pathophysiologic implications [Aspen Allergy conference]

J Allergy Clin Immunol

(1987)

K.F. Chung et al.

Modulation of cholinergic neurotransmission in canine airways by thromboxane-mimetic U 46619

Eur J Pharmacol

(1985)

N. Grundstrom et al.

Prejunctional alpha₂-adrenoceptors inhibit contraction of tracheal smooth muscle by inhibiting cholinergic neurotransmission

Life Sci

(1981)

J.W. Bloom et al.

A muscarinic receptor with high affinity for pirenzepine mediates vagally induced bronchoconstriction

Eur J Pharmacol

(1987)

P.L. Barnes

Endogenous catecholamines and asthma

J Allergy Clin Immunol

(1986)

J.G. Ayres

Trends in asthma and hay fever in general practice in the United Kingdom

Thorax

(1986)

D.M. Fleming et al.

Prevalence of asthma and hay fever in England and Wales

Br Med J

(1987)

S.R. Benatar

Fatal asthma

N Engl J Med

(1986)

P.J. Barnes

Asthma deaths: the continuing problem

R.M. Sly

Increases in death from asthma

Ann Allergy

(1984)

E.F. Juniper et al.

Airway responsiveness to histamine and methacholine: relationship to minimum treatment to control symptoms of asthma

Thorax

(1981)

K.F. Chung

Role of inflammation in the hyperreactivity of the airways in asthma

Thorax

(1986)

M.S. Dunnill

The pathology of asthma with special reference to changes in the bronchial mucosa

J Clin Pathol

(1960)

L.A. Laitinen et al.

Damage of the airway epithelium and bronchial reactivity in patients with asthma

Am Rev Respir Dis

(1985)

K.C. Flint et al.

Bronchoalveolar mast cells in extrinsic asthma: a mechanism for the initiation of antigen-specific bronchoconstriction

Br Med J

(1985)

W.J. Metzger et al.

Local allergen challenge and bronchoalveolar lavage of allergic asthmatic lungs

Am Rev Respir Dis

(1987)

N.C. Thomson

In vivo versus in vitro human airway responsiveness to different pharmacologic stimuli

Am Rev Respir Dis

(1987)

J. Cerrina et al.

Comparison of human bronchial muscle responses to histamine in vivo with histamine and isoproterenol agonists in vitro

Am Rev Respir Dis

(1986)

R.G. Goldie et al.

In vitro responsiveness of human asthmatic blockers to carbachol, histamine, beta-receptor agonists, and theophylline

Br J Clin Pharmacol

(1986)

M.K. Church et al.

Inhibition of IgE-depedent histamine release from human dispersed lung mast cells by antiallergic drugs and salbutamol

Br J Pharmacol

(1987)

J.I. Dutoit et al.

Inhaled corticosteroids reduce the severity of bronchial hyperresponsiveness in asthma, but oral theophylline does not

Am Rev Respir Dis

(1987)

R.P. Schleimer et al.

Effects of dexamethasone on mediator release from human lung fragments and purified human lung mast cells

J Clin Invest

(1983)

M. Joseph et al.

Involvement of immunoglobulin E in the secretory process of alveolar macrophages from asthmatic patients

J Clin Invest

(1983)

R.W. Fuller et al.

Dexamethasone inhibits the production of thromboxane B₂ and leukotriene B, by human alveolar and peritoneal macrophages in culture

Clin Sci

(1984)

R.W. Fuller et al.

Human alveolar macrophage activation: inhibition by forskolin but not β-adrenoceptor stimulation or phosphodiesterase inhibition

P Pharmacol

(1989)

J.G.R. De Monchy et al.

Bronchoalveolar eosinophils during allergen-induced late asthmatic reactions

Am Rev Respir Dis

(1985)

A.J. Wardlaw et al.

Cellular changes in blood and bronchoalveolar lavage (BAL) and bron chial responsiveness after inhaled PAF in man

Am Rev Respir Dis

(1988)

T. Yukawa et al.

Bronchodilator agents do not inhibit oxygenfree radical release from guinea pig eosinophils

Am Rev Respir Dis

(1988)

A.J. Wardlaw et al.

Plateletactivating factor: a potent chemotactic and chemokinetic factor for human eosinophils

J Clin Invest

(1986)

G. Camussi et al.

Acute lung inflammation induced in the rabbit by local instillation of 1-O-octadecyl-2-acetyl-sn-glycerol-3-phosphorylcholine or of native platelet-activating factor

Am J Pathol

(1983)

C. Kroegel et al.

Platelet-activating factor induces eosinophil peroxidase release from purified human eosinophils

Immunology

(1988)

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^☆: Supported by the Medical Research Council and Asthma Research Council, U.K.

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Postgraduate courseNew concepts in the pathogenesis of bronchial hyperresponsiveness and asthma☆

Abstract

Lancet

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Biochem Biophys Res Commun

Lancet

Immunol Today

Chest

Am J Med

Prostaglandins

J Allergy Olin Immunol

J Allergy Clin Immunol

Lancet

Lancet

J Biol Chem

Lancet

J Allergy Clin Immunol

J Allergy Clin Immunol

Eur J Pharmacol

Life Sci

Eur J Pharmacol

J Allergy Clin Immunol

Trends in asthma and hay fever in general practice in the United Kingdom

Thorax

Prevalence of asthma and hay fever in England and Wales

Br Med J

Fatal asthma

N Engl J Med

Asthma deaths: the continuing problem

Increases in death from asthma

Ann Allergy

Airway responsiveness to histamine and methacholine: relationship to minimum treatment to control symptoms of asthma

Thorax

Role of inflammation in the hyperreactivity of the airways in asthma

Thorax

The pathology of asthma with special reference to changes in the bronchial mucosa

J Clin Pathol

Damage of the airway epithelium and bronchial reactivity in patients with asthma

Am Rev Respir Dis

Bronchoalveolar mast cells in extrinsic asthma: a mechanism for the initiation of antigen-specific bronchoconstriction

Br Med J

Local allergen challenge and bronchoalveolar lavage of allergic asthmatic lungs

Am Rev Respir Dis

In vivo versus in vitro human airway responsiveness to different pharmacologic stimuli

Am Rev Respir Dis

Comparison of human bronchial muscle responses to histamine in vivo with histamine and isoproterenol agonists in vitro

Am Rev Respir Dis

In vitro responsiveness of human asthmatic blockers to carbachol, histamine, beta-receptor agonists, and theophylline

Br J Clin Pharmacol

Inhibition of IgE-depedent histamine release from human dispersed lung mast cells by antiallergic drugs and salbutamol

Br J Pharmacol

Inhaled corticosteroids reduce the severity of bronchial hyperresponsiveness in asthma, but oral theophylline does not

Am Rev Respir Dis

Effects of dexamethasone on mediator release from human lung fragments and purified human lung mast cells

J Clin Invest

Involvement of immunoglobulin E in the secretory process of alveolar macrophages from asthmatic patients

J Clin Invest

Dexamethasone inhibits the production of thromboxane B2 and leukotriene B, by human alveolar and peritoneal macrophages in culture

Clin Sci

Human alveolar macrophage activation: inhibition by forskolin but not β-adrenoceptor stimulation or phosphodiesterase inhibition

P Pharmacol

Bronchoalveolar eosinophils during allergen-induced late asthmatic reactions

Am Rev Respir Dis

Cellular changes in blood and bronchoalveolar lavage (BAL) and bron chial responsiveness after inhaled PAF in man

Am Rev Respir Dis

Bronchodilator agents do not inhibit oxygenfree radical release from guinea pig eosinophils

Am Rev Respir Dis

Plateletactivating factor: a potent chemotactic and chemokinetic factor for human eosinophils

J Clin Invest

Acute lung inflammation induced in the rabbit by local instillation of 1-O-octadecyl-2-acetyl-sn-glycerol-3-phosphorylcholine or of native platelet-activating factor

Am J Pathol

Platelet-activating factor induces eosinophil peroxidase release from purified human eosinophils

Immunology

Postgraduate course
New concepts in the pathogenesis of bronchial hyperresponsiveness and asthma☆

Dexamethasone inhibits the production of thromboxane B₂ and leukotriene B, by human alveolar and peritoneal macrophages in culture