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màj 23/07/98 |
Bronchial
inflammation in patients with Status Asthmaticus
P. Gosset, I. Tillie, C. Lamblin, B.
Wallaert and A.B. Tonnel.
INSERM U416, Institut
Pasteur and Clin. de Pneumologie, CHRU, Lille -France.
Airway
inflammation in asthma play an essential role to the
pathogenesis of clinical manifestations and has been
largely assessed by analysis of bronchoalveolar lavage
and bronchial biopsy findings. In contrast, little is
known about the inflammatory process in asthmatic
patients presenting an acute respiratory failure defined
as status asthmaticus (SA). Most of post-mortem studies
emphasized about the presence of eosinophils and of
inflammatory cells in the bronchial wall or lumen. In
addition, they also demonstrated extensive tissu
destruction and remodeling; these pathological changes,
although more severe, ressembled those described in mild
asthma. Nonetheless, the respective role of inflammatory
cells and the dynamic cellular events occurring during
the course of SA remain poorly investigated.
|
Diffuse bronchial obstruction
with viscid secretions is almost a constant feature in SA. In
some patients, well characterized atelectasis and/or acute
respiratory failure may ensue despite optimal medical treatment
and ventilatory support. In such circumstances of refractory SA,
bronchial lavage (BL) may be helpful to remove the viscid plugs.
In an attempt to elucidate cell effectors and mediators playing a
role in the setting of SA, we studied BL samples (n=18) from 9
patients with SA obtained at different time intervals from the
onset of mechanical ventilation (MV) and compared the results to
those obtained from 4 controls under MV without respiratory
disease (V), from 11 patients with mild asthma (A) and from 10
healthy non-asthmatic controls (C). We investigated the
contribution of different cell types and cell mediators
(neutrophil elastase, eosinophil cationic protein (ECP),
histamine and interleukin-8 (IL-8)) to the pathogenesis of SA. In
a second set of experiments, we evaluated on these BL the level
of cytokines and related mediators which have the ability to
modulate inflammation either positively (IL-1ß, Tumor Necrosis
Factor (TNF)-a), or negatively (IL-10, TGFß, IL1Ra, sTNF RI and
RII).
SA exhibited higher number and
percentage of neutrophils (81.5 ± 4.5 %) than V (44.3 ± 12.2)
(p<0.05), A (6.9 ± 2.7) and C (9.5 ± 3.8) (p<0.0001), and
higher number of eosinophils than V, A and C (p<0.01).
Neutrophil elastase, ECP and IL-8 levels were dramatically
increased in SA. Histamine was higher in SA than in C and V
(p<0.05). Bronchial neutrophilia was not related to
concommitant bacterial infection as bacteriological cultures were
positive in only 3 BL. Concerning mediators involved in
inflammation, the concentrations of IL-1, TNFa and of the active
form of TGFß were significantly higher in SA compared with the
other groups. IL-1Ra and IL-10 and total fraction of TGFß, sTNF
RI and RII were not different between SA and V, although higher
in the patients with SA than in controlled asthmatics and healthy
volunteers. The ratio between IL-1Ra and IL-1ß was significantly
higher in patients with SA compared with the other groups,
whereas there is no difference for the ratio between both types
of sTNFR and TNFa.
In conclusion, bronchial
inflammation in SA implicated large infiltrate mainly composed of
activated granulocytes. High levels of both pro- and
anti-inflammatory cytokines were detected in BL fluids from SA.
However, a significant difference between patients with SA and V
was only observed for pro-inflammatory cytokines.
These data raised some questions.
First, several studies have shown
in animal models that MV induces lung inflammation. Although MV
in patients without respiratory disease induced lung
neutrophilia, the intensity of the inflammatory reaction and
particularly the level of proinflammatory cytokines is higher in
patients with SA than in V.
2) Moreover, it seems important
to determine the participation of each trigerring factor
(allergen exposure, irritants, bronchial infection, stress, ...)
in the development of lung inflammation.
3) Whereas IL-8 secretion may be
implicated in neutrophil recruitment, the involvement of
mediators such as ß-chemokines in the migration of eosinophils
was not evaluated.
4) Concerning the mechanism of
transmigration, we can define the role of the proinflammatory
mediators such as TNFa and IL-1ß in epithelial and in
endothelial activation. The role of other cytokines such as IL-10
and TGFß particularly in the remodelling phase, is not defined.
Lastly, our results reinforced the interest of therapeutic
strategies able to limit the burst in cytokines during the
development of SA.
References
Ref (1): Lamblin C, Gosset P, Tillie-Leblond I,
Saulnier F, Marquette CH, Wallaert B and Tonnel AB. Bronchial neutrophilia in patients with
non infectious satus asthmaticus. Am Rev Respir Crit Care Med. In Press.
(partial abstract from http://www.healthy.net/library/search/medline.htm
)
in press
... for the complete abstract, please enquire http://www.healthy.net/library/search/medline.htm
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