Introduction: The relationship between serum periostin and type 2 inflammation is well established in asthma. However, its association with asthma-COPD overlap (ACO) and COPD has not been demonstrated. Aims and objectives: In this cross-sectional study, we evaluated serum periostin in Japanese patients with asthma, ACO, or COPD. Methods: Serum periostin levels were measured using the Elecsys® Periostin assay (Roche) in asthma (194), ACO (78), and COPD (81) patients. The relevance of periostin levels was investigated to clinical parameters, including peripheral blood eosinophil counts, lung function, and fractional exhaled nitric oxide (FeNO). Asthma and COPD patients fulfilled the definition of GINA and GOLD guidelines, respectively. ACO was diagnosed if asthma patients had FEV1/FVC <0.7 and reduced diffusing capacity or a presence of low attenuation area on high-resolution CT, or COPD patients had a past history of asthma or FeNO >35 ppb. Results: Serum periostin levels were not significantly different between patients with asthma, ACO, and COPD (median values, ng/mL: 59.3, 57.2, and 54.0, respectively). Serum periostin levels correlated with eosinophils counts (rho: asthma, 0.34; ACO, 0.32; and COPD, 0.37) and FeNO (ACO, 0.28; and COPD, 0.24). Periostin high patients (≥57.5 ng/mL, median value) showed higher eosinophil counts and lower BMI and FEV1/FVC in asthma, higher eosinophil counts, total IgE, %FEV1, and FEV1/FVC in COPD than in respective periostin low patients. There was no difference in clinical parameters between periostin high and low ACO patients. Conclusions: Serum periostin levels were comparable among a Japanese population with asthma, ACO, and COPD.
Impaired epithelial barrier function renders the airway vulnerable to environmental triggers associated with the pathogenesis of bronchial asthma. We investigated the influence of protocadherin-1 (PCDH1), a susceptibility gene for bronchial hyperresponsiveness, on airway epithelial barrier function. We applied transepithelial electric resistance and dextran permeability testing to evaluate the barrier function of cultured airway epithelial cells. We studied PCDH1 function by siRNA-mediated knockdown and analyzed nasal or bronchial tissues from 16 patients with chronic rhinosinusitis (CRS) and nine patients with bronchial asthma for PCDH1 expression. PCDH1 was upregulated with the development of epithelial barrier function in cultured airway epithelial cells. Immunocytochemical analysis revealed that PCDH localized to cell-cell contact sites and colocalized with E-cadherin at the apical site of airway epithelial cells. PCDH1 gene knockdown disrupted both tight and adhesion junctions. Immunohistochemical analysis revealed strong PCDH1 expression in nasal and bronchial epithelial cells; however, expression decreased in inflamed tissues sampled from patients with CRS or bronchial asthma. Dexamethasone (Dex) increased the barrier function of airway epithelial cells and increased PCDH1 expression. PCDH1 gene knockdown eradicated the effect of Dex on barrier function. These results suggest that PCDH1 is important for airway function as a physical barrier, and its dysfunction is involved in the pathogenesis of allergic airway inflammation. We also suggest that glucocorticoids promotes epithelial barrier integrity by inducing PCDH1.
Adhesion molecules such as ICAM-1 and E-selectin have been shown to play important roles in the production of allergic inflammation. In the present study, we measured serum soluble ICAM-1 (sICAM-1) and soluble E-selectin (sE-selectin) levels by ELISA in 42 patients with bronchial asthma (22 atopic and 20 non-atopic) during asthma attacks and in stable conditions in order to assess the state of ICAM-1 and E-selectin in allergic inflammation. Both serum sICAM-1 levels and serum sE-selectin levels in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. These findings were observed regardless of atopic status. To examine the regulatory mechanism in the elevation of serum sICAM-1 and sE-selectin levels, serum tumour necrosis factor-alpha (TNF-alpha) levels were measured by ELISA. TNF-alpha levels in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. There was a correlation between the nature of change in serum TNF-alpha levels and the nature of change in serum sICAM-1 levels or serum sE-selectin levels, though serum TNF-alpha levels did not correlate with serum sICAM-1 levels or serum sE-selectin levels. These results suggest that higher levels of sICAM-1 and sE-selectin during asthma attacks may reflect the up-regulation of ICAM-1 and E-selectin expression in allergic inflammation, and that the soluble form of these adhesion molecules may be useful markers for the presence of allergic inflammation. TNF-alpha is shown to enhance the expression and release of ICAM-1 and E-selectin in vitro, however; the regulatory mechanism in the elevation of serum sICAM-1 and sE-selectin levels remains to be clarified.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)
