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20-12-2016 | Asthma | News | Article

Severe asthma exists despite suppressed tissue inflammation

medwireNews: Researchers have found that patients with asthma receiving recommended treatment can have severe disease despite suppressed endobronchial tissue inflammation in the proximal airways.

“This suggests that additional mechanisms in central airways or altered peripheral airway changes are contributing to asthma severity,” they write in the European Respiratory Journal.

Analyzable bronchial biopsies were obtained from 137 of 158 participants at a mean of 1.4 per participant and a success rate of 87%. The participants included 41 healthy controls and 96 patients with asthma, who were divided into three groups based on severity: 16 current or ex-smokers with severe asthma, 46 nonsmokers with severe asthma, and 34 with mild-to-moderate asthma.

All the asthma patients had significantly fewer mast cells in the bronchial submucosa than the healthy individuals.

The median number of mast cells was 33.6 cells/ mm2 in healthy individuals versus 22.2 cells/ mm2 for smokers with severe asthma, 17.4 cells/mm2 for non-smokers with severe asthma, and 21.2 cells/ mm2 for patients with mild-to-moderate asthma.

Smokers with severe asthma also had significantly reduced CD4+ lymphocyte counts compared with their nonsmoking peers, patients with mild-to-moderate asthma, and healthy controls, with respective values of 4.7 cells/mm2 versus 11.6 cells/ mm2, 10.1 cells/mm2, and 10.6 cells/mm2.

Susan Wilson (Southampton General Hospital, UK) and fellow researchers say that the reduction in mast cells is likely to be due the effects of the inhaled corticosteroid treatment that all the asthma patients were taking.

“There was a lack of any other asthma-related airway inflammatory signal at this proximal airway site, including significant airway eosinophilia,” they add.

Most of the patients had tissue eosinophil counts within the defined normal range of 2 standard deviations above the average for healthy controls, indicating effective glucocorticoid-related anti-inflammatory effects, the researchers note. Eleven participants, nine with asthma, had a high eosinophil count above the 12.63 eosinophils/mm2 cutoff. These individuals showed a typical type 2 inflammatory response not seen in patients in the low eosinophil group, but otherwise clinical characteristics were similar.

Bronchial epithelial brushings were also collected and transcriptomic analysis revealed seven gene probes positively related to biopsy eosinophilia, after taking into account age, gender, and correction for false discovery rate.

Five of these probes mapped to known genes – COX-2, ADAM-7, SLCO1A2, TMEFF2, and TRPM-1 – and the remaining two to unnamed genes. The enzyme COX-2 is induced during inflammation and increased expression has been reported in mild asthma, although not severe asthma, the researchers note, adding that the relevance of the other genes is less clear.

They conclude: “These data indicate that those with stable severe asthma on adequate therapy do not have major changes in cell infiltration within the bronchial mucosa of their large airways, suggesting that disease severity is mostly driven by other mechanisms, such as cellular activation status or inflammation elsewhere.”

By Lucy Piper

medwireNews is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2016

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