Maria Kraus-Filarska

Bronchial hyper-responsiveness, subepithelial fibrosis, and transforming growth factor-β1 expression in patients with long-standing and recently diagnosed asthma

Introduction:Chronic inflammation in asthmatic airways leads to bronchial hyper-responsiveness (BHR) and the development of structural changes. Important features of remodeling include the formation of subepithelial fibrosis due to increased collagen deposition in the reticular basement membrane. Transforming growth factor (TGF)-β might be a central mediator of tissue fibrosis and remodeling.Materials and Methods:Immunohistochemistry was used to measure collagen III deposition and TGF-β1 expression in biopsies from patients with long-standing asthma treated with inhaled corticosteroids, patients with recently diagnosed asthma, and control subjects. Computer-assisted image analysis was used to evaluate total basement membrane (TBM) thickness.Results:Asthmatics, particularly those with long-standing asthma, had thicker TBMs than healthy subjects. Collagen III deposition was comparable in the studied groups. BHR was not correlated with features of mucosal inflammation and was lower in steroid-treated patients with long-standing asthma than in subjects with newly diagnosed asthma untreated with steroids. Epithelial TGF-β1 expression negatively correlated with collagen III deposition and TBM thickness.Conclusions:The study showed that TBM thickness, but not collagen III deposition, could be a differentiating marker of asthmatics of different disease duration and treatment. The lack of correlation between BHR and features of mucosal inflammation suggests the complexity of BHR development. Corticosteroids can reduce BHR in asthmatics, but it seems to be less effective in reducing subepithelial fibrosis. The role of epithelial TGF-β1 needs to be further investigated since the possibility that it plays a protective and anti-inflammatory role in asthmatic airways cannot be excluded.

Fractioned exhaled nitric oxide (FENO) is not a sufficiently reliable test for monitoring asthma in pregnancy

It has been reported that fractioned exhaled nitric oxide (FENO) can be used for monitoring airway inflammation and for asthma management but conclusions drawn by different researchers are controversial. The aim of our study was to evaluate the clinical usefulness of FENO assessment for monitoring asthma during pregnancy. We monitored 72 pregnant asthmatics aged 18-38years (Me=29 years) who underwent monthly investigations including: the level of asthma control according to GINA (Global Initiative for Asthma), the occurrence of exacerbations, ACT (Asthma Control Test), as well as FENO and spirometry measurements. In 50 women, during all visits, asthma was well-controlled. In the remaining 22 women, asthma was periodically uncontrolled. FENO measured at the beginning of the study did not show significant correlation with retrospectively evaluated asthma severity (r=0.07; p=0.97). An analysis of data collected during all 254 visits showed that FENO correlated significantly but weakly with ACT scores (r=0.25; p=0.0004) and FEV1 (r=0.21; p=0.0014). FENO at consecutive visits in women with well-controlled asthma (N=50) showed large variability expressed by median coefficient of variation (CV)=32.0% (Min 2.4%, Max 121.9%). This concerned both: atopic and nonatopic groups (35.5%; and 26.7%, respectively). Large FENO variability (35.5%) was also found in a subgroup of women (N=11) with ACT=25 constantly throughout the study. FENO measured at visits when women temporarily lost control of asthma (N=22; 38 visits), showed an increasing tendency (64.2 ppb; 9.5 ppb-188.3 ppb), but did not differ significantly (p=0.13) from measurements taken at visits during which asthma was well-controlled (27.6 ppb; 6.2 ppb-103.4 ppb). The comparison of FENO in consecutive months of pregnancy in women who had well-controlled asthma did not show significant differences in FENO values during the time of observation. The assessment of asthma during pregnancy by means of monitoring FENO is of limited practical value due to this parameters considerable intrasubject variability, regardless of the degree of asthma control.

Treatment with Ebastine Changes Expression of Histamine H1 and H2 Receptor mRNA on Peripheral Blood Mononuclear Cells

AbstractBackground: Histamine H1 and H2 receptors both belong to a family of G protein-coupled receptors that often show opposite actions on cell activity. Ebastine, a piperidine derivative, and its active metabolite, carebastine, are very potent second-generation histamine H1 receptor antagonists. Objective: To investigate the influence of treatment with ebastine on the expression of histamine H1 receptor and H2 receptor mRNA on peripheral blood mononuclear cells (PBMC). Patients: The study was performed in five grass pollen-allergic individuals with seasonal allergic rhinitis. All subjects showed positive skin-prick tests with mixed grass pollen. The study was performed out of the grass pollen season. Methods: Blood samples were obtained before and after treatment with ebastine (Kestine®, Rhône-Poulenc-Rorer, France) 10 mg/day for 7 days. PBMC were isolated using density-gradient centrifugation. Histamine H1 and H2 receptor mRNA expression were determined using semiquantitative reverse transcription polymerase chain reaction. Results: Prior to ebastine treatment, mRNA expression measured by the peak area for histamine H1 and H2 receptors was 33, 323 (± 33, 269) relative fluorescence units (RFU)and 59, 511 (± 31, 621) RFU, respectively. After treatment, histamine H1 and H2 receptor mRNA expression increased to 42, 061 (± 28, 263 ) and 89, 913 (+ 13, 053) RFU, respectively, and this difference was statistically significant (p < 0.01) in contrast to the difference prior to the treatment. Ebastine-induced histamine H1 and H2 receptor upregulation, however, moved the balance towards histamine H2 receptor dominance. Conclusions: In conclusion, ebastine induced H1 and H2 receptor upregulation, but moved the balance towards H2 receptor dominance. This potent H1 receptor antagonist, in addition to reducing allergic symptoms, is able to influence inflammatory responses. Since H2 receptor stimulation shows suppressive effects on cell activation, this can contribute to long-term anti-inflammatory actions of anti-histamines.