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04-Fév-2008
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EDITORIAL FOR ASMANET
September
1997
Provided by:
avec le support de :
Previous abstracts : clik here
(partial) translation : | Français/French | :-) 
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Asthma
and airway remodeling
Louis-Philippe Boulet, MD, FRCPC
Unité
de recherche en pneumologie
Institut de Cardiologie et Pneumologie de l’Hôpital
Laval,
Université Laval, Sainte-Foy (Québec), Canada.
Although
asthma is mostly considered an airway inflammatory
disease, it is possible that some of the airway function
changes observed, particularly persistent airway
hyperresponsiveness are, largely due to airway
remodeling. Indeed, the bronchial structure of asthmatic
subjects is quite altered, the most evident features
being damaged epithelium, subepithelial collagen
deposition, increased goblet cell numbers, enlarged
bronchial smooth muscle layer area, and changes in
various extracellular matrix components such as
glycoproteins. These changes are probably part of an
abnormal repair process secondary to intense and/or
repeated inflammatory insults in subjects predisposed to
develop those alterations. This abnormal repair process
may be initiated or modulated by mediators and cytokines
released by lymphocytes, eosinophils, macrophages, mast
cells or other resident cells. Epithelial damage may also
be involved in the initiation of the fibrotic process,
since epithelial cells are able to release different
mediators and cytokines. A key-cell in extracelular
matrix changes is the fibroblast. Activated macrophages
and eosinophils produce TGF-ß1, which induces transformation of
fibroblasts into myofibroblasts, with actin expression.
Furthermore, according to some of our recent
observations, asthmatic bronchial fibroblasts synthesis
of collagen seems to be increased.
However,
many questions about this process remain unanswered:
What are its
most relevant components in regard to changes in airway
function and the development of symptomatic asthma?
Smooth
muscle changes or subepithelial fibrosis are two good
candidates.
How could those
changes alter airway function?
Thickened
airways may become more responsive but simply changing
the components of the different bronchial compartments
may alter its airway function, whatever its thickness.
However, the specific mechanims by which those changes
translate into aiway hyperresponsiveness are uncertain.
How do the
airway inflammatory and repair processes influence each
other?
This is a
complex area and they seem to influence each other in
many ways.
When do the
different airway structural changes appear during the
course of the disease and what are the factors
influencing their appearance ?
We
previously showed that airway remodeling precedes asthma
and is also seen, although to a lesser extent, in
non-asthmatic atopic subjects.
How can we
prevent or reverse inflammation-induced modifications in
bronchial structure ?
Epithelial
integrity may be restored by corticosteroids, but other
structural changes such as subepithelial collagen
deposition seem relatively refractory to corticosteroids
and to other forms of treatment ! In acting early in the
course of the disease with anti-inflammatory agents, we
may possibly prevent those alterations. We certainly need
to know more about this and in doing so, we may be able
to develop new therapeutic avenues or ways to prevent the
development of asthma.
Louis-Philippe Boulet, MD, FRCPC
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REFERENCES
(for Medline complete abstracts, see http://www.ncbi.nlm.nih.gov/PubMed/ or partial abstract below under abstract 01, 02 ... according to
the reference number)
1- Boulet LP. Airway remodeling. Clinical
Asthma Review. May 1997
2- Boulet LP, Laviolette M, Turcotte H,
Milot J, Côté J, Cartier
A, Dugas M, Malo JL, Boutet M. Bronchial
subepithelial fibrosis correlates with airway responsiveness
to methacholine. Chest.
112:45-52.
3- Bousquet
J, Vignola AM, Chanez P, Campbell AM, Bonsignore G, Michel
FB. Airways remodeling in asthma: no
doubt, no more ? Int Arch
Allergy Immunol 1995; 107: 211-4.
4- Chakir J, Laviolette M, Boutet M,
Laliberté R, Dubé J, Boulet
LP. Lower airways remodeling in non
asthmatic subjects with allergic rhinitis. Lab. Invest. 1996; 75:
735-744.
5- Roberts C. Asthma as a fibrotic
disease. Chest 1995;
107:111S-8S.
Abstract 02 :Title : Bronchial subepithelial fibrosis correlates with
airway responsiveness to methacholine.
Author : Boulet LP; Laviolette M; Turcotte H; Cartier A; Dugas
M; Malo JL; Boutet M
Address : Centre québécois d'excellence en santé respiratoire:
Unité de Recherche, Centre de Pneumologie de l'Hôpital Laval,
Université Laval, Sainte-Foy, QC, Canada.
Source : Chest, 112(1):45-52 1997 Jul
Abstract
OBJECTIVES: To evaluate the relationships between airway
subepithelial collagen
deposition and epithelial desquamation with airflow obstruction
and hyperresponsiveness in
different types of asthma and other respiratory conditions such
as chronic cough and allergic
rhinitis. DESIGN AND PARTICIPANTS: We compared the
histopathologic features
observed on bronchial biopsy specimens obtained from 80 subjects:
38 with different types of
asthma, 19 with chronic cough, 13 with allergic rhinitis, and 10
normal control subjects. Each
subject had a questionnaire on respiratory symptoms and
medication needs, measurements of
expiratory flows and methacholine responsiveness, allergy skin
prick tests, and a
bronchoscopy with bronchial biopsies. None of the subjects
studied used bronchial
anti-inflammatory agents. RESULTS: ......
Abstract 03 : Asthma:
no doubt, no more?
Author : Bousquet J; Vignola AM; Chanez P; Campbell AM;
Bonsignore G; Michel FB
Address : Clinique des Maladies Respiratoires, CHU Montpellier,
France.
Source : Int Arch Allergy Immunol, 107(1-3):211-4 1995 May-Jun
Abstract
Asthma is a chronic inflammatory disease of the airways
invariably associated with healing.
Remodelling of the airways can be demonstrated by the activation
of airways
macrophages, the release of growth factors and fibrogenic
cytokines, the activation of
fibroblasts and myofibroblast, elastolysis and elastosynthesis,
collagen deposition, increased
synthesis and release of extracellular matrix components, and an
increased mass of smooth
muscle and mucous glands. However, the control of remodelling is
still poorly understood.
Abstract 04 : Lower
airways remodeling in nonasthmatic subjects with allergic
rhinitis.
Author : Chakir J; Laviolette M; Boutet M; LalibertÍe R;
DubÍe J; Boulet LP
Address : UnitÍe de Recherche, Centre de Pneumologie de
l'HÍopital Laval, UniversitÍe Laval, Sainte-Foy, QuÍebec,
Canada.
Source : Lab Invest, 75(5):735-44 1996 Nov
Abstract
We analyzed by immunohistochemistry the distribution of types I,
II, III, IV, V, and VII
collagens, laminin, and fibronectin in the bronchial biopsy
specimens of nonasthmatic subjects
with seasonal allergic rhinitis (n = 8) and compared these
results with those found in mild
stable allergic asthmatics (n = 6) and normal controls (n = 5).
The content of type I and III
collagens was increased in rhinitic subjects compared with
controls. These collagens were
focally deposited in the reticular basement membrane area. Three
subjects with allergic rhinitis
had no fibronectin deposition in their basement membrane, as in
controls, whereas the other
five had a focal fibronectin deposition. In asthmatic patients,
type I and III collagens and
fibronectin were more abundant and more uniformly distributed
underneath the basement
membrane than they were in rhinitic subjects. Expression of type
II, IV, V, and VII collagens
and laminin were similar in the three groups.....
Abstract 05 :
Is asthma a fibrotic disease?
Author : Roberts CR
Address : University of British Columbia, UBC Pulmonary Research
Laboratory, St. Pauls Hospital, Vancouver, Canada.
Source : Chest, 107(3 Suppl):111S-117S 1995 Mar
