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Alveolar T-helper type-2 immunity in atopic asthma is associated with poor clinical control

Bergqvist, Anders LU ; Andersson, Cecilia LU ; Mori, Michiko LU ; Walls, Andrew F.; Bjermer, Leif LU and Erjefält, Jonas LU (2015) In Clinical Science 128(1). p.47-56
Abstract
Real-world evaluation studies have shown that many patients with asthma remain symptomatic despite treatment with inhaled corticosteroids (ICSs). As conventional ICSs have poor access to the peripheral airways, the aim of the present paper was to study the relationship between peripheral airway inflammation and clinical control in allergic asthma. Consequently, bronchial and transbronchial biopsies were obtained from patients with poorly controlled asthma [n=12, asthma control test (ACT) score < 20], patients with well-controlled asthma (n= 12, ACT score >= 20) and healthy controls (n= 8). Tissue sections were immunostained to assess multiple leucocyte populations. To determine the degree of T-helper type-2 (Th2) immunity, the... (More)
Real-world evaluation studies have shown that many patients with asthma remain symptomatic despite treatment with inhaled corticosteroids (ICSs). As conventional ICSs have poor access to the peripheral airways, the aim of the present paper was to study the relationship between peripheral airway inflammation and clinical control in allergic asthma. Consequently, bronchial and transbronchial biopsies were obtained from patients with poorly controlled asthma [n=12, asthma control test (ACT) score < 20], patients with well-controlled asthma (n= 12, ACT score >= 20) and healthy controls (n= 8). Tissue sections were immunostained to assess multiple leucocyte populations. To determine the degree of T-helper type-2 (Th2) immunity, the logarithmic value of the ratio between Th2 cells/mm(2) and Th1 cells/mm(2) was used as a surrogate score for Th2-skewed immunity. In the bronchi, the leucocyte infiltration pattern and the Th2-score were similar between patients with well-controlled asthma and those with poorly controlled asthma. In contrast, in the alveolar parenchyma, the expression of T-helper cells was significantly higher in patients with poorly controlled asthma than in patients with well-controlled asthma (P < 0.01). Furthermore, the alveolar Th2-score was significantly higher in patients with poorly controlled asthma (median 0.4) than in the controlled patients (median -0.10, P < 0.05). In addition, in contrast with bronchial Th2-score, the alveolar Th2-score correlated significantly with ACT score (r(s)=-0.62, P < 0.01) in the pooled asthma group. Collectively, our data reveal an alveolar Th2-skewed inflammation, specifically in asthmatic patients who are poorly controlled with ICSs, and suggest that pharmacological targeting of the peripheral airways may be beneficial in this large patient category. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
alveolar parenchyma, asthma control asthma, peripheral inflammation, T-helper type-2 (Th2)
in
Clinical Science
volume
128
issue
1
pages
47 - 56
publisher
Portland Press
external identifiers
  • wos:000349362800005
  • scopus:84906881517
ISSN
1470-8736
DOI
10.1042/CS20140309
language
English
LU publication?
yes
id
08807870-48da-4025-9528-cf944eed11bd (old id 5194627)
date added to LUP
2015-04-01 07:35:46
date last changed
2017-11-19 03:04:43
@article{08807870-48da-4025-9528-cf944eed11bd,
  abstract     = {Real-world evaluation studies have shown that many patients with asthma remain symptomatic despite treatment with inhaled corticosteroids (ICSs). As conventional ICSs have poor access to the peripheral airways, the aim of the present paper was to study the relationship between peripheral airway inflammation and clinical control in allergic asthma. Consequently, bronchial and transbronchial biopsies were obtained from patients with poorly controlled asthma [n=12, asthma control test (ACT) score &lt; 20], patients with well-controlled asthma (n= 12, ACT score &gt;= 20) and healthy controls (n= 8). Tissue sections were immunostained to assess multiple leucocyte populations. To determine the degree of T-helper type-2 (Th2) immunity, the logarithmic value of the ratio between Th2 cells/mm(2) and Th1 cells/mm(2) was used as a surrogate score for Th2-skewed immunity. In the bronchi, the leucocyte infiltration pattern and the Th2-score were similar between patients with well-controlled asthma and those with poorly controlled asthma. In contrast, in the alveolar parenchyma, the expression of T-helper cells was significantly higher in patients with poorly controlled asthma than in patients with well-controlled asthma (P &lt; 0.01). Furthermore, the alveolar Th2-score was significantly higher in patients with poorly controlled asthma (median 0.4) than in the controlled patients (median -0.10, P &lt; 0.05). In addition, in contrast with bronchial Th2-score, the alveolar Th2-score correlated significantly with ACT score (r(s)=-0.62, P &lt; 0.01) in the pooled asthma group. Collectively, our data reveal an alveolar Th2-skewed inflammation, specifically in asthmatic patients who are poorly controlled with ICSs, and suggest that pharmacological targeting of the peripheral airways may be beneficial in this large patient category.},
  author       = {Bergqvist, Anders and Andersson, Cecilia and Mori, Michiko and Walls, Andrew F. and Bjermer, Leif and Erjefält, Jonas},
  issn         = {1470-8736},
  keyword      = {alveolar parenchyma,asthma control asthma,peripheral inflammation,T-helper type-2 (Th2)},
  language     = {eng},
  number       = {1},
  pages        = {47--56},
  publisher    = {Portland Press},
  series       = {Clinical Science},
  title        = {Alveolar T-helper type-2 immunity in atopic asthma is associated with poor clinical control},
  url          = {http://dx.doi.org/10.1042/CS20140309},
  volume       = {128},
  year         = {2015},
}