Fractioned exhaled nitric oxide (FE(NO)) 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 parameter's considerable intrasubject variability, regardless of the degree of asthma control.

[Chlamydial infection in asthma. Macrolide treatment]. / Zakazenia chlamydiowe w astmie. Luczenie makrolidami.

Atypical microorganism infections, including Chlamydophila pneumoniae, play an important role in asthma course. A significant influence of chlamydial infection on severity of asthma exacerbations and increase in chronic asthma symptoms has been shown. The group of medication with high antibacterial activity against atypical microorganisms are macrolides, which also have anti-inflammatory and immunomodulatory effects. Macrolide treatment in patients with asthma can be connected with additional therapeutic benefits. Mechanism of action of these antibiotics is not ultimately clarified and further studies are required.

Bronchial hyper-responsiveness, subepithelial fibrosis, and transforming growth factor-beta(1) 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)-beta might be a central mediator of tissue fibrosis and remodeling. MATERIALS AND METHODS: Immunohistochemistry was used to measure collagen III deposition and TGF-beta(1) 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-beta(1) 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-beta(1) needs to be further investigated since the possibility that it plays a protective and anti-inflammatory role in asthmatic airways cannot be excluded.

Circadian variations of histamine binding to lymphocytes and neutrophils and skin reactivity to histamine in atopic and healthy subjects.

INTRODUCTION: Numerous pathophysiological conditions change during 24-hour periods. Histamine, the main mediator in allergic reactions, exerts a multiplicity of pathophysiological actions through binding to specific receptors on effector cells. Nocturnal exacerbation of symptoms occurs in many atopic diseases in which histamine is an important mediator. Nocturnal wheezing is a very common symptom of asthma. The aim of this study was to determine whether the binding of (fluorescein-labeled) histamine to cells participating in allergic-inflammatory processes (lymphocytes, neutrophils) and skin reactivity to histamine undergo circadian changes and to compare these phenomena in atopic asthmatic and healthy subjects. MATERIALS AND METHODS: Blood samples were collected at 8 am, 2 pm, 8 pm, 2 am, and 8 am the next day. Histamine skin-prick tests were performed at the same times. RESULTS: It was found that skin reactivity to histamine (wheal, erythema) in healthy subjects underwent significant circadian changes with acrophase at 8 am (wheal) or 8 pm (erythema), the lowest values being at night (2 am, p = 0.017), in contrast to atopics, in whom the highest reactivity was found at night (2 am, p = 0.002). Significant differences in the binding of fluorescein-labeled histamine between day (8 am-2 pm) and night (2 am) were observed for lymphocytes (p = 0.006) and neutrophils (p = 0.018). CONCLUSIONS: In the asthmatic group these changes were not significant. Circadian changes in both the binding of histamine by effector cells and skin reactivity to histamine were different in healthy and asthmatic subjects, and this may play a role in the pathomechanism, course, and chronopharmacotherapy of atopic diseases.

[Airway remodeling in asthma]. / Remodeling w astmie.

Asthma is a chronic inflammatory disease of the airways. Structural alteration of the airways and lung parenchyma, "remodeling", is a recognized feature of chronic asthma and a cause of irreversible airway obstruction. Airway and lung remodeling in asthma involves subepithelial fibrosis, but also alterations of bronchial epithelium, airway smooth muscle cells, myofibroblasts, extracellular matrix, mucous glands, blood vessels and nerves. Defining of morphological changes and correlating them with clinical features of the disease has been a major focus of research over the past decade. The results of these studies are often contradictory and there is still little understanding of the mechanisms underlying lung remodeling in asthma.

Skin reactivity to histamine and expression of histamine receptors mRNA in lymphocytes of healthy subjects and non-small-cell lung cancer patients before and after surgery.

Histamine modulates an immunological response through stimulation of appropriate receptor--H1R proinflammatory or H2R suppressive. The participation of histamine in regulation of an immunological response in the course of neoplastic disease is determined by the expression of particular receptor. The aim of our work was the investigation of the expression of mRNA of two types of histamine receptors in peripheral blood lymphocytes and the evaluation of skin-prick test with histamine in lung cancer patients before and after surgery. The investigation was performed on 15 patients qualified to surgery before and 7-10 days after treatment and on 12 healthy subjects. Reverse transcriptase polymerase chain reaction (RT-PCR) with primers labeled with fluorescent dyes was performed. Intensity of fluorescence was expressed as relative fluorescence units (RFU). The data were analysed using ABI Prism 310 GeneScan collection software Version 3.1. Skin-prick test with histamine was evaluated after 10 min by measuring the diameter of the weal. The expression of H1R and H2R mRNA in healthy subjects was not significantly different in contrast to the lung cancer patients in which a significant prevalence of H2R mRNA expression was observed before surgery and only slightly decreased after (P < 0.001). Skin-prick test--negative in one patient before surgery, after treatment was positive in all patients and the diameter of histamine weal was significantly increased (P < 0.001). One may assume that the prevalence of the expression of H2R mRNA in patients reflects the status of immunosuppression caused by cancer. Since histamine exerts its suppressive activity trough H2R it seems reasonably to include the antagonists of this receptor to the cancer therapy which may restore a relative balance between accessibility of both types of histamine receptors.

[Mechanisms of action of nebulized low molecular weights heparin in patients with bronchial asthma]. / Mechanizmy dzialania heparyny maloczasteczkowej nebulizowanej u chorych na astme oskrzelowa.

Bronchial asthma is a chronic disease of the respiratory tract. Search for alternative to presently used therapies seems to be the way to obtain a better control of asthma. Heparin is an acidic mucopolysaccharide and in the past years there has been a number of reports on the role of heparin and low-molecular-weight heparin (LMWH) in chronic inflammatory disorders of the respiratory tract. Our aim was to estimate the effect of long-time LMWH nebulization on selected parameters in asthmatic patients. Twenty-four patients entered the study. All of them were subjected to bronchoscopy with BAL, in 8 patients this procedure was performed twice: before and after heparin treatment. After 14 days of treatment we observed an increase in FEV1 (from 73.93 +/- 14.14% (in % of nominal value) to 89.62 +/- 10.08% (p = 0.0049). Additionally we noted a decrease in the percentage of eosinophils and lymphocytes in BAL sediments, from 4.86 +/- 3.48% to 1.25 +/- 2.76%; p = 0.0006 and from 5.39 +/- 2.25% to 2.94 +/- 1.23%; p = 0.0209, respectively. This changes were paralleled by a drop of EG2 in BAL supernatant from 1.00 +/- 0.99 to 0.13 +/- 0.35, p = 0.0256. In blood serum level of histamine 0.74 +/- 0.77 to 0.1 +/- 0.22; p = 0.0493. We did not observe significant changes in IL-5, sVCAM-1 or ECP concentrations in serum. Also different LMWH dosing (5-10 kUIC anti-Xa b.i.d.) did not produce any dose-response effect. We conclude, that LMWH in nebulization can be a valuable add-on treatment in bronchial asthma, and its most likely mechanisms of action are: prevention of mast cell degranulation (histamine decrease), decreased eosinophil activation (lower EG2), and modification of inflammatory cells influx (decreased percentages of eosinophils and lymphocytes in BAL).