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The effect of bronchoconstriction on airway remodeling in asthma

The effect of bronchoconstriction on airway remodeling in asthma
The effect of bronchoconstriction on airway remodeling in asthma
Background: asthma is characterized pathologically by structural changes in the airway, termed airway remodeling. These changes are associated with worse long-term clinical outcomes and have been attributed to eosinophilic inflammation. In vitro studies indicate, however, that the compressive mechanical forces that arise during bronchoconstriction may induce remodeling independently of inflammation. We evaluated the influence of repeated experimentally induced bronchoconstriction on airway structural changes in patients with asthma.

Methods: we randomly assigned 48 subjects with asthma to one of four inhalation challenge protocols involving a series of three challenges with one type of inhaled agent presented at 48-hour intervals. The two active challenges were with either a dust-mite allergen (which causes bronchoconstriction and eosinophilic inflammation) or methacholine (which causes bronchoconstriction without eosinophilic inflammation); the two control challenges (neither of which causes bronchoconstriction) were either saline alone or albuterol followed by methacholine (to control for nonbronchoconstrictor effects of methacholine). Bronchial-biopsy specimens were obtained before and 4 days after completion of the challenges.

Results: allergen and methacholine immediately induced similar levels of bronchoconstriction. Eosinophilic inflammation of the airways increased only in the allergen group, whereas both the allergen and the methacholine groups had significant airway remodeling not seen in the two control groups. Subepithelial collagen-band thickness increased by a median of 2.17 ?m in the allergen group (interquartile range [IQR], 0.70 to 3.67) and 1.94 ?m in the methacholine group (IQR, 0.37 to 3.24) (P<0.001 for the comparison of the two challenge groups with the two control groups); periodic acid–Schiff staining of epithelium (mucus glands) also increased, by a median of 2.17 percentage points in the allergen group (IQR, 1.03 to 4.77) and 2.13 percentage points in the methacholine group (IQR, 1.14 to 7.96) (P=0.003 for the comparison with controls). There were no significant differences between the allergen and methacholine groups

Conclusions: bronchoconstriction without additional inflammation induces airway remodeling in patients with asthma. These findings have potential implications for management
2006-2015
Grainge, Christopher L.
a83145e5-cfaf-4dae-a6d8-fb225f460136
Lau, Laurie C.K.
2af8045d-6162-4939-aba7-28dd2f60f6a8
Ward, Jonathan A.
a8107b98-069d-4263-bd70-d29d79f07edc
Dulay, Valdeep
acaa5235-244e-4049-b204-cc59c06c3f94
Lahiff, Gemma
b3cba880-68c4-42ab-8e07-1be2d65220c1
Wilson, Susan
21c6875d-6870-441b-ae7a-603562a646b8
Holgate, Stephen
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Howarth, Peter H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Grainge, Christopher L.
a83145e5-cfaf-4dae-a6d8-fb225f460136
Lau, Laurie C.K.
2af8045d-6162-4939-aba7-28dd2f60f6a8
Ward, Jonathan A.
a8107b98-069d-4263-bd70-d29d79f07edc
Dulay, Valdeep
acaa5235-244e-4049-b204-cc59c06c3f94
Lahiff, Gemma
b3cba880-68c4-42ab-8e07-1be2d65220c1
Wilson, Susan
21c6875d-6870-441b-ae7a-603562a646b8
Holgate, Stephen
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Howarth, Peter H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21

Grainge, Christopher L., Lau, Laurie C.K., Ward, Jonathan A., Dulay, Valdeep, Lahiff, Gemma, Wilson, Susan, Holgate, Stephen, Davies, Donna E. and Howarth, Peter H. (2011) The effect of bronchoconstriction on airway remodeling in asthma. New England Journal of Medicine, 364 (21), 2006-2015. (doi:10.1056/NEJMoa1014350).

Record type: Article

Abstract

Background: asthma is characterized pathologically by structural changes in the airway, termed airway remodeling. These changes are associated with worse long-term clinical outcomes and have been attributed to eosinophilic inflammation. In vitro studies indicate, however, that the compressive mechanical forces that arise during bronchoconstriction may induce remodeling independently of inflammation. We evaluated the influence of repeated experimentally induced bronchoconstriction on airway structural changes in patients with asthma.

Methods: we randomly assigned 48 subjects with asthma to one of four inhalation challenge protocols involving a series of three challenges with one type of inhaled agent presented at 48-hour intervals. The two active challenges were with either a dust-mite allergen (which causes bronchoconstriction and eosinophilic inflammation) or methacholine (which causes bronchoconstriction without eosinophilic inflammation); the two control challenges (neither of which causes bronchoconstriction) were either saline alone or albuterol followed by methacholine (to control for nonbronchoconstrictor effects of methacholine). Bronchial-biopsy specimens were obtained before and 4 days after completion of the challenges.

Results: allergen and methacholine immediately induced similar levels of bronchoconstriction. Eosinophilic inflammation of the airways increased only in the allergen group, whereas both the allergen and the methacholine groups had significant airway remodeling not seen in the two control groups. Subepithelial collagen-band thickness increased by a median of 2.17 ?m in the allergen group (interquartile range [IQR], 0.70 to 3.67) and 1.94 ?m in the methacholine group (IQR, 0.37 to 3.24) (P<0.001 for the comparison of the two challenge groups with the two control groups); periodic acid–Schiff staining of epithelium (mucus glands) also increased, by a median of 2.17 percentage points in the allergen group (IQR, 1.03 to 4.77) and 2.13 percentage points in the methacholine group (IQR, 1.14 to 7.96) (P=0.003 for the comparison with controls). There were no significant differences between the allergen and methacholine groups

Conclusions: bronchoconstriction without additional inflammation induces airway remodeling in patients with asthma. These findings have potential implications for management

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More information

Accepted/In Press date: May 2011
e-pub ahead of print date: 26 May 2011
Published date: May 2011

Identifiers

Local EPrints ID: 185841
URI: http://eprints.soton.ac.uk/id/eprint/185841
PURE UUID: 747af869-ef83-4812-889e-08bcd8acd52f
ORCID for Jonathan A. Ward: ORCID iD orcid.org/0000-0002-9278-0002
ORCID for Susan Wilson: ORCID iD orcid.org/0000-0003-1305-8271
ORCID for Donna E. Davies: ORCID iD orcid.org/0000-0002-5117-2991

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Date deposited: 11 May 2011 10:33
Last modified: 15 Mar 2024 02:57

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Contributors

Author: Christopher L. Grainge
Author: Laurie C.K. Lau
Author: Jonathan A. Ward ORCID iD
Author: Valdeep Dulay
Author: Gemma Lahiff
Author: Susan Wilson ORCID iD
Author: Stephen Holgate
Author: Donna E. Davies ORCID iD

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