Mast cell–associated alveolar inflammation in patients with atopic uncontrolled asthma

doi:10.1016/j.jaci.2011.01.022

Journal of Allergy and Clinical Immunology

Volume 127, Issue 4, April 2011, Pages 905-912.e7

https://doi.org/10.1016/j.jaci.2011.01.022 Get rights and content

Background

A significant proportion of patients with asthma have persistent symptoms despite treatment with inhaled glucocorticosteroids.

Objective

We hypothesized that in these patients, the alveolar parenchyma is subjected to mast cell–associated alterations.

Methods

Bronchial and transbronchial biopsies from healthy controls (n = 8), patients with allergic rhinitis (n = 8), and patients with atopic uncontrolled asthma (symptoms despite treatment with inhaled glucocorticosteroids; mean dose, 743 μg/d; n = 14) were processed for immunohistochemical identification of mast cell subtypes and mast cell expression of FcεRI and surface-bound IgE.

Results

Whereas no difference in density of total bronchial mast cells was observed between patients with asthma and healthy controls, the total alveolar mast cell density was increased in the patients with asthma (P < .01). Division into mast cell subtypes revealed that in bronchi of patients with asthma, tryptase positive mast cells (MC_T) numbers decreased compared with controls (P ≤ .05), whereas tryptase and chymase positive mast cells (MC_TC) increased (P ≤ .05). In the alveolar parenchyma from patients with asthma, an increased density was found for both MC_T (P ≤ .05) and MC_TC (P ≤ .05). The increased alveolar mast cell densities were paralleled by an increased mast cell expression of FcεRI (P < .001) compared with the controls. The patients with asthma also had increased numbers (P < .001) and proportions (P < .001) of alveolar mast cells with surface-bound IgE. Similar increases in densities, FcεRI expression, and surface-bound IgE were not seen in separate explorations of alveolar mast cells in patients with allergic rhinitis.

Conclusion

Our data suggest that patients with atopic uncontrolled asthma have an increased parenchymal infiltration of MC_T and MC_TC populations with increased expression of FcεRI and surface-bound IgE compared with atopic and nonatopic controls.

Section snippets

Patients with atopic uncontrolled asthma, nonatopic and atopic control groups

The current study involved 14 nonsmoking patients with uncontrolled atopic asthma according to Global Initiative for Asthma guidelines and an asthma control test (ACT).6, 25 Eight healthy never-smoking nonatopic subjects who had a negative skin prick test (SPT) result, were not hyperresponsive to methacholine, and lacked any history of respiratory symptoms were used as controls. A separate control group, representing atopy without asthma, included 8 patients with clinically confirmed AR.²⁶

From

Clinical characteristics

An overview of the patient characteristics is presented in Table I.

Discussion

Accumulated evidence from physiological studies and tissue explorations suggests that inflammatory processes in the distal airways contribute to asthma pathogenesis.³⁹ The current study advances our insight about the nature of this inflammation by identifying an alveolar infiltration of altered MC_T and MC_TC populations as a novel histopathological feature.

The current study took advantage of our possibility to obtain bronchial as well as transbronchial biopsies, not only from patients with

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: Supported by the Heart and Lung Foundation, Sweden; the Swedish Medical Research Council; the Swedish Asthma and Allergy Associations Research Foundation; and the Crafoord Foundation.

: Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

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Asthma and lower airway diseaseMast cell–associated alveolar inflammation in patients with atopic uncontrolled asthma

Background

Objective

Methods

Results

Conclusion

Section snippets

Patients with atopic uncontrolled asthma, nonatopic and atopic control groups

Clinical characteristics

Discussion

J Allergy Clin Immunol

J Allergy Clin Immunol

Lancet

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Pathol Res Pract

J Allergy Clin Immunol

Blood

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Immunology of asthma and chronic obstructive pulmonary disease

Nat Rev Immunol

Asthma

N Engl J Med

The role of allergy in the development of asthma

Nature

Novel targets of therapy in asthma

Curr Opin Pulm Med

Inflammatory cell mapping of the respiratory tract in fatal asthma

Clin Exp Allergy

Time to death and mast cell degranulation in fatal asthma

Respirology

Alveolar tissue inflammation in asthma

Am J Respir Crit Care Med

Mast cells in human keloid, small intestine, and lung by an immunoperoxidase technique using a murine monoclonal antibody against tryptase

Am J Pathol

Mast-cell infiltration of airway smooth muscle in asthma

N Engl J Med

Novel site-specific mast cell subpopulations in the human lung

Thorax

Alterations in lung mast cell populations in patients with chronic obstructive pulmonary disease

Am J Respir Crit Care Med

Lower airways inflammation in allergic rhinitics: a comparison with asthmatics and normal controls

Clin Exp Allergy

Asthma and lower airway disease
Mast cell–associated alveolar inflammation in patients with atopic uncontrolled asthma