Production of leukotriene C4 by peripheral blood leukocytes stimulated with anti-fcepsilonRI antibody, PMA, and fMLP does not correlate with irreversible airway obstruction in asthmatics.

BACKGROUND: Airway remodeling has recently emerged as a major problem in an increasing percentage of patients with asthma. Reasons for great diversity in the progression of irreversible bronchoconstriction among asthmatics remain unclear. OBJECTIVE: The aim of this study was to assess whether the potential ability of leukocytes to produce cysteinyl leukotrienes in response to various stimuli is correlated with magnitude of irreversible airway obstruction in asthmatics. MATERIALS AND METHODS: The study sample comprised 76 asthmatics (34 males, mean +/- SD age 52 +/- 13 years), and 35 healthy controls (18 males, 38.2 +/- 15 years). Each subject underwent 2 pulmonary function tests: before and after bronchodilator administration. In addition, approximate annual decline in forced expiratory volume in 1 second (FEV1) (% of predicted) was calculated. Leukotriene C4 (LTC4) production was assessed combining a cellular antigen stimulation test and enzyme-linked immunosorbent assay using Bulhmann Laboratories AG kits. Leukocytes isolated from peripheral blood were stimulated with anti-FcepsilonRI antibody, N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol 12-myristate 13-acetate (PMA). In separate tubes each subject's leukocytes were tested for spontaneous LTC4 production. Finally, stimulated LTC4 production was expressed in pg/mL after subtraction of values of spontaneous production. RESULTS: In asthmatics, baseline FVC% and FEV% values ranged from 24.4% to 122.4% (mean, 75.5%) and from 23.4% to 126.6% (mean, 74.4%), respectively. There were no significant differences between asthmatics and controls in LTC4 production stimulated by anti-FcepsilonRI antibody (P = .79), fMLP (P = .33) or PMA (P = .86). We found no correlation between stimulated LTC4 production and spirometric parameters at baseline or after bronchodilator administration or annual decline in FEV1%. CONCLUSION: Our results do not confirm the hypothesis that airway remodeling in asthma might be related to enhanced ability of leukocytes to produce cysteinyl leukotrienes in response to various stimuli.

Relevance of the selected cytokine release (TNF-alpha, IL-6, IFN-gamma, and IFN-alpha) to the exacerbation of bronchial asthma from airway mycotic infections. Predominant role of TFN-alpha?

Airway fungal infections are often associated in asthmatics with the exacerbation of asthma symptoms. However, the pathomechanism of this phenomenon has not been fully understood. The aim of our study was to assess whether antimycotic treatment can influence the capacity of bronchoalveolar (BAL) leukocytes to release proinflammatory cytokines, which could contribute to increase in asthma severity. Ten patients with bronchial asthma complicated by airway fungal infections (Candida albicans and/or Aspergillus fumigatus) were included in the study. Seven asthmatics were treated with systemic and inhaled corticosteroids, whereas the remaining three with inhaled ones only. All subjects underwent several courses of therapy with antibiotics due to respiratory infections. BAL leukocytes obtained from the patients were cultured in the absence or presence of lipopolysaccharide E.coli (LPS) or Newcastle disease virus (NDV). The BAL procedure and measurement of the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (II-6), interferon-gamma (IFN-gamma), and interferon-alpha (IFN-alpha) by specific bioassays were performed twice: before antimycotic treatment and after 3 weeks of therapy with 8 mg of nebulized fluoconazole and 400 mg of oral ketoconazole per day. The elimination of fungi from respiratory tract resulted in an apparent clinical improvement. This coincided with diminished production of TNF-alpha in response to LPS and the production of IFN-alpha in response to NDV, which were initially high and subsided significantly after antimycotic therapy (p = 0.035, and 0.011, respectively). Such changes were not observed in the case of IFN-gamma and IL-6. This may suggest that TNF-alpha as well as IFN-alpha are secreted by fungi-prestimulated leukocytes from the lower respiratory tract and may be involved in the processes of exacerbation of asthma complicated by fungal infections. Further analyses of relationships between changes in cytokine levels and clinical parameters indicated that IFN-alpha seems to be of particular interest in fungal stimulation of asthma.

[Bronchial hyperreactivity to histamine and levels of serum eosinophil cationic protein in patients with non-atopic asthma]. / Nadreaktywnosc oskrzeli na histamine a stezenie eozynofilowego bialka kationowego w surowicy chorych na astme oskrzelowa nieatopowa.

Pathogenesis of non-atopic bronchial asthma remains still an open question. Until now there have been very few studies concerning relationship between eosinophil activation and nonspecific bronchial hyperreactivity to histamine in this form of asthma. Sixteen subjects with mild nonatopic bronchial asthma entered the study. Evaluations of PC 20 for histamine and serum eosinophil cationic protein (ECP) concentration have been performed in all patients. In spite of fact that all patients were considered as mild asthmatic we have observed wide range of PC 20 and serum ECP concentration. Moreover we were able to find statistically significant inverse correlation between PC 20 for histamine and serum eosinophil cationic protein concentration: r = -0.498, p < 0.05. We conclude that eosinophil activation plays an important role in pathophysiology of nonspecific bronchial hyperreactivity in nonatopic bronchial asthma.

[Validation of the Polish version of St. George's respiratory questionnaire in patients with bronchial asthma]. / Ocena polskiej wersji St. George's respiratory questionnaire u chorych na astme oskrzelowa.

St George's Respiratory Questionnaire (SGRQ) has been widely used in the assessment of health related quality of life (HRQOL) in patients with asthma and chronic obstructive pulmonary disease. Introduction of the new language version of the HRQOL questionnaire needs to be preceded by a highly structured process of validation. We aimed to validate the Polish version of SGRQ in the group of 83 patients with asthma. Following the comprehension study, we thus evaluated reliability, validity, reproducibility, responsiveness, and measurement equivalence of the Polish version of SGRQ. Disease severity and health status were also concurrently assessed. The reliability was good, with Cronbach's alpha coefficient exceeding 0.75 for global and all subscale scores. There have been highly significant correlations between spirometric parameters, intensity of symptoms, health status self-assessment, and the degree of depression, and quality of life scores. Reproducibility, stability and responsiveness were confirmed in the follow-up study. Minimal clinically important difference was found to be 5.3 points. Polish version of SGRQ was found to be psychometrically equivalent to four other versions of SGRQ, which underscores its validity in the population of Polish asthmatics.

The distribution of nuchal translucency at 10-13 weeks of pregnancy.

There is a need for a simple method of expressing nuchal translucency measurement in early pregnancy that will allow for gestational age and be useful in screening for Down's syndrome. To achieve this objective, we conducted a prospective study of 561 women with singleton pregnancies that were not affected by Down's syndrome at 10-13 weeks of gestation. Nuchal translucency measurements and crown rump length measurements were determined. Nuchal translucency measurement increased by about 17 per cent per week. Expressing the result as a multiple of the median (MOM) nuchal translucency for a given crown rump length allowed for this increase with gestational age and yielded a distribution of values that was approximately Gaussian. About 96 per cent of values lay between 0.5 and 2.0 MOM. The variance and therefore the false-positive rate of nuchal translucency were significantly reduced by recording several measurements and using the average: for example, the false-positive rate reduced from 8.3 per cent to 5.0 per cent if the average of six measurements were used instead of one--a potential 40 per cent reduction in the false-positive rate if the test were used in screening. Estimating the distribution of nuchal translucency in MOM values will assist in specifying the statistical parameters to be used in prenatal screening for Down's syndrome and the use of repeated nuchal translucency measurements is expected to have a useful effect on reducing the screening false-positive rate at a given MOM cut-off level.

Results of routine fetal nuchal translucency measurement at weeks 10-13 in 4233 unselected pregnant women.

The aim of this study was to determine the value of nuchal translucency (NT) measurement for the detection of aneuploidies and other malformations in a low-risk population. In total, 4233 women who booked in our hospital for delivery were examined between the tenth and 13th week of gestation. Of the 17 chromosomal abnormalities that occurred, 11 were detected using the measurement of NT (65 per cent). Only three of the seven Down syndrome pregnancies were detected using this technique (43 per cent). The remaining four Down syndrome babies were diagnosed either because of positive biochemical testing or by amniocentesis because of maternal age. A total of 69 serious malformations including chromosomal defects were detected during the study period. In 18 of these cases, the NT measurement was > or = 2.5 mm (26 per cent). Most of the malformations without aneuploidies were of cardiac origin. The data show that the NT measurement is a valuable marker for aneuploidy even in a low risk-population. It is also of value in the diagnosis of other serious malformations, particularly cardiac defects.

Is mast cell activation during asthmatic reaction reflected in the circulation?

Allergic asthmatic patients were challenged with specific allergen that resulted in early asthmatic reaction (EAR). Serum tryptase concentration (STC) and neutrophil chemotactic activity (NCA) were measured before and during EAR. A significant increase in neutrophil chemotactic activity was noticed in the 60th min, without an accompanying increase in serum tryptase concentration. The rise in neutrophil chemotactic activity in our study confirms previous observations in this field. However, because of the numerous cellular sources for neutrophil chemotactic activity, it does not seem to be a gold standard for measurement of mast cell activation. Undetectable levels of serum tryptase concentration during EAR in our study do not exclude the role of the mast cell in its pathogenesis. To our knowledge, only massive mast cell degranulation is reflected in the circulation as an increased tryptase concentration. In the case of upper respiratory allergic reactions, mast cell degranulation definitely takes place, but does not result in evident changes in serum tryptase concentration. We conclude that mast cell activation during allergen-induced EAR is poorly represented in the circulation.

[Concentration of eosinophil cationic protein in blood serum during early and late asthmatic reaction]. / Stezenie eozynofilowego bialka kationowego w surowicy podczas wczesnej i póznej reakcji astmatycznej.

Eosinophil cationic protein (ECP) was measured in blood serum of 15 atopic asthmatics during early (EAR) and late (LAR) asthmatic reaction triggered by specific allergen provocation. Nonspecific bronchial hyperreactivity was evaluated in histamine provocation test before and 48 hours after the allergen challenge. We observed dual asthmatic reaction (DAR) in 8 and an isolated EAR in 7 patients. The ECP serum level and nonspecific bronchial hyperreactivity were significantly higher (p < 0.05) in the DAR group when compared to EAR responders. An inverse correlation between PC20 for histamine and ECP level was shown before and after the allergen challenge in all examined subjects (R = -0.5472, p < 0.05).

[Bronchial hyperreactivity in patients with bronchial asthma treated with salbutamol and salbutamol combined with beclocort or nedocromil]. / Nadreaktywnosc oskrzeli u chorych na astme, leczonych salbutamolem oraz salbutamolem skojarzonym z beklokortem lub nedokromilem.

Salbutamol alone (400 micrograms per day) or salbutamol together with beclocort (1 mg per day) was used in 20 patients with mild asthma. 12 patients received during a month salbutamol combined with nedocromil (Tilade 8 mg per day). Prior starting treatment and after concluding a histamine provocation challenge was performed allowing to assess the bronchodilating properties of salbutamol. We conclude that: salbutamol alone produced a statistically nonsignificant increase of bronchial hyperactivity; a combination of salbutamol with beclocort or nedocromil did not increase the bronchial hyperactivity; during the three month trial with salbutamol alone or in a combination with a antiinflammatory agent the bronchodilatatory effect of salbutamol remained the same.

[Spontaneous and allergen induced basophil histamine release and bronchial hyperreactivity]. / Spontaniczne i indukowane alergenem uwalnianie histaminy z granulocytów zasadochlonnych a nadreaktywnosc oskrzeli.

In this study we have measured spontaneous and allergen induced basophil histamine release before and 24 hours after specific allergen bronchoprovocation challenge. Non-specific bronchial hyperreactivity was estimated twice: before and after allergen challenge. 15 atopic asthmatic entered the study. 8 of them developed only early asthmatic reaction and 7 demonstrated dual asthmatic reaction. In dual responders group higher values of spontaneous basophil histamine release before and increase of allergen induced basophil histamine release after specific allergen bronchoprovocation challenge were observed. There was an inverse correlation between values of allergen induced basophil histamine release and values of PC20 for histamine.

[Granulocyte chemiluminescence during early and late asthmatic reaction]. / Chemiluminescencja granulocytów w trakcie wczesnej i póznej reakcji astmatycznej.

Allergic asthmatic patients were challenged with specific allergen resulting in early and dual asthmatic reaction. FMLP induced granulocyte chemiluminescence was measured before and in 10 min, 60 min, 4 hours and 24 hours after allergen challenge. We have observed significant decrease of granulocyte chemiluminescence in both groups. In patient with early asthmatic reaction decrease of luminescence was observed during first hour only. In patients with dual asthmatic reaction decrease of luminescence was observed during 24 hours after allergen challenge.

[Bronchial hyperreactivity after chronic use of salbutamol]. / Nadreaktywnosc oskrzeli po przewleklym stosowaniu salbutamolu.

15 patients with bronchial asthma received inhalations of salbutamol three times daily (200 mcg) for 2 months. Spirometry was carried out at the beginning of the study, one and two months after starting the study. The bronchodilating effect and non-specific bronchial hyperreactivity assessed with the histamine bronchoprovocation test were studied. Two month treatment with salbutamol decreased the bronchodilating effect and at the same time produced an increase of non-specific bronchial hyperreactivity.

[Nedocromil sodium in treatment of bronchial asthma]. / Nedokromil sodu w leczeniu astmy oskrzelowej.

Clinical study on efficiency of the nedocromil sodium (Tilade, Fisons) was performed in 20 patients with atopic and nonatopic bronchial asthma. The drug was administrated in dose of 8 mg per day for 2 months which allowed to renounce regular using of Beclocort forte after 7 days of the treatment. In both types of bronchial asthma the positive effect of nedocromil sodium was confirmed, causing increase of pulmonary ventilation and decrease of bronchial hyperactivity. Especially profitably effect was noticed in atopic bronchial asthma in which statistically important increase of peak expiratory flow (PEF) was obtained and decrease of bronchial hyperreactivity by PC20 for histamine was observed (p < 0.05). Mentioned above spirometric parameters did not differ in statistically important pattern in patients with nonatopic bronchial asthma, when Beclocort forte group with Tilade group compared. Neither important differences in general number of cells nor percentage composition of cell smears were observed in bronchoalveolar lavage fluid.

[A comparative study on skin tests and allergen-specific IgE levels determined by enzyme allergo-sorbent testing (EAST)]. / Badania porównawcze zgodnosci testów skórnych ze stezeniem swoistych prezeciwcial IgE oznaczanych metoda enzyme allergo-sorbent testing (EAST).

Ninety seven randomly selected subjects with bronchial asthma and allergic rhinitis were classified for the comparative studies. The level of allergen specific IgE determined by Enzyme Allergo-Sorbent Testing (EAST) was compared with skin tests. The statistically significant correlation was found for 9 selected allergens. However, the Spearman's rank correlation coefficient values varied largely, depending on a given allergen. They ranged from 0.74 (Dermatophagoides pteronyssinus) to 0.33 (Birch pollen) what might be, in the authors' opinion, a result of Bencard allergens use for skin tests and Kallestad allergens for EAST.

[Evaluating the safety of bronchoalveolar lavage in patients with bronchial asthma in light of gasometric and spirometric examinations]. / Ocena bezpieczenstwa plukania oskrzelowo-pecherzykowego u chorych na astme oskrzelowa w swietle badan gazometrycznych i spirometrycznych.

Gasometric parameters were performed before, during and after bronchoalveolar lavage (BAL) in 21 patients with mild bronchial asthma. In addition, spirometric parameters were performed before and after BAL. Decrease of pO2, SaO2 and increase of pCO2 which kept within the limits of normal values were observed. After BAL gasometric parameters returned to baseline values. Bronchoalveolar lavage caused statistically significant fall in FEV1 and PEF. BAL was well tolerated and did not worse the clinical state of patients.

Inhaled natural human interferon alpha induces bronchospastic reactions in asthmatics.

There is a relationship between viral infection and aggravation of bronchial asthma symptoms. Viruses belong to the strongest and fast acting inducers of interferon (IFN), which, in turn, may enhance histamine release from effector cells. We have administered IFN intrabronchially to 49 patients suffering from bronchial asthma. The impairment of lung ventilation with significant decrease of forced expiratory volume in one second (FEV1) have been observed in majority of the patients who inhaled crude or purified IFN preparations.

[Interferon as a bronchospastic factor in patients with bronchial asthma]. / Interferon jako czynnik spazmogenny oskrzeli u chorych na dychawice oskrzelowa.

Twenty three asthmatics were examined during the symptoms free period. Each subject inhaled aerolised human interferon alpha (Hu IFN-alpha, Le) in increasing doses 4000 and 8000 units. IFN inhalation provoked significant decline in FEV1 (by 9.9% after the 1st dose and 6.6% after the 2nd dose on average). This results indicate that inhaled interferon induces bronchospastic reactions in asthmatics.

[Circulating immune complexes in patients treated with Pollinex vaccine]. / Krazace kompleksy immunologiczne u chorych leczonych szczepionka Pollinex.

Twenty six patients with rhinitis were desensitized with Pollinex. Circulating immune complexes were determined in these patients before and after immunotherapy. Two assay techniques - precipitation and PEG-CCT were applied to assay circulating immune complexes. It was found that specific immunotherapy with Pollinex does not produce circulating immune complexes in patients with hay fever.

[Hyperreactivity of the bronchial tree in patients with hay fever before and after immunotherapy]. / Nadreaktywnosc oskrzeli u chorcych na katar sienny przed immunoterapia i po jej zastosowaniu.

Immunotherapy with Pollinex was performed in 46 patients with hay fever. Hyperreactivity of the bronchi determined with inhalation histamine test was noted in 36% of the patients. Histamine test was positive in 24% of patients treated with Pollinex. The difference was statistically insignificant.

Binding of histamine by gastric juice.

Ability of in vitro histamine binding by gastric juice was tested in aspirates from 10 normal subjects, collected during basal acid output (BAO) as well as after pentagastrin stimulation (maximal acid output - MAO). Histamine binding by 1 ml of gastric juice averaged 218.7 micrograms and after stimulation with pentagastrin was about 31% higher.