T-cell subtypes in bronchoalveolar lavage fluid and in peripheral blood from patients with primary lung cancer.

The changes in local immunology play an important role in lung cancer development. We used bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) for the analysis of cell profiles in patients with primary lung cancer. Twenty-one patients with confirmed primary lung cancer and 13 healthy volunteers were investigated. All persons were smokers. The analysis of T-cell subsets was performed with a flow cytometry method and with the following antibodies: anti CD3, CD4, CD8, CD16, CD25, CD45, CD56, and HLA-DR. We found differences in the proportion of lymphocytes between BALF and PB, and a higher proportion of T cells and a lower proportion of B and natural-killer (NK) cells in BALF. There was a significant difference in the proportion of T-cytotoxic/suppressor lymphocytes, which was elevated in the BALF of patients and decreased in patients' PB. The T-helper:T-cytotoxic/suppressor (Th:Tc/s) ratio was significantly lower in the BALF of patients. These changes were visible in patients with a small cell type. The percentage of T cells with the alpha chain of receptor to IL-2 (IL -R) was lower in the BALF of patients than in the control group. Our observations reflect local changes in lung environment in patients affected with lung cancer.

Efficacy and safety of dofetilide in the prevention of symptomatic episodes of paroxysmal supraventricular tachycardia: a 6-month double-blind comparison with propafenone and placebo.

BACKGROUND: Existing drug therapies for paroxysmal supraventricular tachycardia (PSVT) have potentially serious adverse effects. Dofetilide, a pure class III antiarrhythmic agent, may offer an effective and safe alternative for treating PSVT. This study compared the efficacy and safety of dofetilide with that of propafenone and placebo in the prevention of PSVT. METHODS: This multicenter, randomized, placebo-controlled, parallel-group study compared the effectiveness of oral dofetilide 500 microg given twice daily with that of propafenone 150 mg given 3 times a day and placebo in preventing the recurrence of PSVT in 122 symptomatic patients. Episodes of PSVT were documented by symptom diaries and Hertcard (Hertford Medical, Hertfordshire, UK) event recorders. RESULTS: After 6 months of treatment, patients taking dofetilide, propafenone, and placebo had a 50%, 54%, and 6% probability, respectively, of remaining free of episodes of PSVT (P <.001 for both dofetilide and propafenone vs placebo). Both dofetilide and propafenone also decreased the frequency of episodes of PSVT; the median numbers of episodes in the dofetilide- and propafenone-treated groups were 1 and 0.5, respectively, compared with 5 in the placebo-treated group. Dofetilide was well tolerated; no proarrhythmia occurred. Three patients taking propafenone had serious treatment-related adverse effects that required drug discontinuation. CONCLUSIONS: Dofetilide and propafenone were equally effective in preventing the recurrence of or decreasing the frequency of PSVT.

[Anatomic abnormalities within upper airways in patients with obstructive sleep apnea syndrome]. / Nieprawidlowosci anatomiczne górnych dróg oddechowych u chorych z obturacyjnym bezdechem podczas snu.

In order to determine a proper method of the treatment of Obstructive Sleep Apnea Syndrome (OSAS) it is essential to demonstrate anatomical abnormalities of upper airways. In this study we would like to estimate how often these anatomical abnormalities occur and what is their influence on OSAS severity. 113 patients underwent laryngological examination, the nasal structure, palate and pharynx were evaluated. The anatomical abnormalities of upper airways were found in 86% patients. The most frequent abnormalities found were nasal disorders, however they were not correlated with OSAS severity. Anatomical abnormalities in more than one level of upper airways were found in 50% of the patients and in those patients OSAS symptoms were the most severe. This may explain why the most frequently performed operations in OSAS patients are not very effective.

[The effect of 6 week treatment with theophylline on spirometric parameters, nonspecific bronchial reactivity and the concentration of soluble interleukin 2 receptor in serum of asthmatic patients]. / Wplyw 6-tygodniowego leczenia teofilina o przedluzonym dzialaniu na parametry spirometryczne, nieswoista nadreaktywnosc oskrzeli i stezenie receptora dla interleukiny 2 w surowicy krwi u chorych na astme oskrzelowa.

This study allowed to investigate the effect of theophylline (Theo-Dur Astra) given 1 tablet á 200 mg per day in the evening for six weeks on histamine-induced airways responsiveness++ (PC20H), spirometric parameters and the concentration of soluble interleukin 2 receptor (sIL-2R) in serum. 21 patients with mild asthma (6 women, 15 men), average age 34.8 +/- 11.4 years were qualified for this study. PC20H was estimated according to Cockroft's method using pneumatic inhalator (Voyage-Secura Nova). Concentration of sIL-2R in serum was measured by Predicta Interleukin 2 Receptor Kit (Genzyme). Lung function test was measured by means of ABC PNEUMO (abc MED). Six week treatment with theophylline significantly increased PC20H in comparison with basal results (0.74 +/- 0.68 mg/ml before and 0.89 +/- 0.71 mg/ml after p < 0.04). The concentration of sIL-2R in serum did not change significantly during theophylline therapy. Treatment with theophylline significantly increased FEV1 (3.64 l/sec before and 3.84 l/sec after p < 0.001). The anti-inflammatory effect of theophilline is more clearly shown in the decrease of histamine-inducted airways responsiveness than in the decreased concentration of sIL-2R in serum.

Wegener's granulomatosis--clinical analysis of 18 patients group.

In observed, during 15 years group, of 18 patients with established Wegener's granulomatosis WG diagnosis, important is period of time from onset of the manifestations to WG diagnosis--very diversified, between 3 to 96 months and heterogenerosity of clinical manifestations during establishing of the diagnosis. Separated from clinical and histopathological features in most of the patients the presence of the titre of antineutrophil cytoplasmic antibody (ANCA) in blood serum examinations was established--75% among 16 observed patients in whom such examination was possible to perform. There was no significant correlation between ANCA titre and prognosis of the WG course. Most of the patients developed upper respiratory tract, ears, lungs and kidney disease involvement. Cyclophosphamide (CF) and prednisolone (P) treatment improves clinical remission in most of the patients (88.8%) and possibility of the course of the disease control. However often recurrences are observed (50%) and side effects due to the long term CF and P treatment (60%). 38.8% of patients achieve long term remission of the manifestations. 3 deaths of WG patients were observed during that period. Patients require during treatment close collaboration and careful periodical control of treatment.

[The role of methotrexate in the management of severe steroid-dependent asthma]. / Wartosc metotreksatu w leczeniu astmy oskrzelowej o ciezkim przebiegu.

Low-dose methotrexate therapy has been recently proposed as an alternative therapy for patients with severe steroid-dependent asthma. This study examined the role of low-dose methotrexate in the management of asthma. Fourteen subjects with stable, severe asthma were enrolled. Patients received orally methotrexate 15 mg/week. Only 2 of 14 patients responded to methotrexate 2 to 3 years after the study's termination. The doses of steroids could be reduced. Side effects were observed in nearly 50% of patients; 7 subjects required the discontinuation of treatment. Low-dose methotrexate therapy may have probably a role in small selected group of steroid-dependent asthmatics.

[Results of 30 days and 12 months treatment with salmeterol in patients with asthma and COPD]. / Wyniki 30-dniowego i 12-miesiecznego leczenia salmeterolem chorych na astme i przewlekla obturacyjna chorobe pluc.

148 outpatients with asthma and COPD were treated with inhaled steroids and salmeterol. 48 patients were estimated after 30 days treatment and other 100, who accepted salmeterol after 1 year treating. In these two groups of patients inhalations of other beta-mimethics, dyspnoe during the nights and early mornings, change of FEV1, side effects and acceptation of salmeterol were observed. After 1 months of treatment in 45% and after 1 year in 73% increase of FEV1 were noticed. In asthma group in 66% and in 15% COPD patients increase of MEV50 was observed. After 30 days 22% asthma patients and 30% COPD patients did not accept salmeterol. 6 persons had adverse effects/tachycardia, sore throat, exacerbation of dyspnoe/. After 12 months 87% accepted treatment with salmeterol. In 13 cases therapy with salmeterol was stopped, because results were poor.

[Extracellular components of bronchoalveolar lavage fluid (BALF) as a marker of the activity of interstitial pulmonary diseases. III: Phospholipids to protein concentration ratio]. / Pozakomórkowe skladniki plynu z plukania oskrzelowo-pçherzykowego (BALF) jako marker aktywnosci sródmiazszowych chorób pluc. Czesc III: Stosunek stezenia fosfolipidów do stezenia bialka.

In interstitial pulmonary diseases investigations are conducted to find markers of the activity of the interstitial processes so that noninvasive monitoring of the disease might be possible. In 188 patients divided into 9 groups: 42 with active sarcoidosis, 24 with inactive sarcoidosis, 16 with active sarcoidosis treated with steroids and 22 with inactive sarcoidosis after corticotherapy, 17 with avian fanciers' lung exposed to the antigen, 16 with avian fanciers' lung after a year interval in exposure to the antigen, 20 with advanced and 13 with moderate idiopathic pulmonary fibrosis, and 18 healthy persons the BAL was performed. In the BALF concentrations of protein and phospholipids were assayed by colorimetric method. The results indicate usefulness of the studied biochemical parameters in BALF in evaluation of the activity of interstitial pulmonary diseases. Significant differences were found between the results in the active group of patients compared to the control group and to the inactive forms of interstitial pulmonary diseases. Particularly valuable is phospholipids to protein concentration ratio in BALF.

Flow cytometric evaluation of lymphocyte subpopulations in BALF of healthy smokers and nonsmokers.

The purpose of this work was to evaluate the normal lymphocyte phenotype in the bronchoalveolar lavage fluid (BALF). BAL was carried out in 12 untreated healthy nonsmoking volunteers and in 9 cigarette smokers. For the analysis of lymphocyte subsets by two-color flow cytometry, the monoclonal antibodies used were directed anti: CD3, CD4, CD8, CD16, CD19, D25, CD45, CD56 and anti HLA-DR. An increase in the total number of cells in BALF of smoking persons and increased proportion of macrophages was observed. The percentage of CD8+ lymphocytes was 1.7 times higher, whereas the proportions of CD4+ cells, and a CD4+/CD8+ ratio were lower 1.5 and 2.6 times, respectively, in the BALF of cigarette smoking persons when compared with nonsmoking volunteers. The changes did not depend on the age of the person. In conclusion, we suggest that the decreased CD4/CD8 ratio and the elevated CD8 T cell subset may be regarded as a potential risk factor associated with clinically asymptomatic lung cancer. Moreover, in the interpretation of BALF from patients with pulmonary diseases cell proportions of nonsmoking and of smoking persons should be compared with the respective controls.

[Drivers with obstructive sleep apnea as potential authors of car accidents]. / Kierowcy chorzy na obturacyjny bezdech podczas snu (OBPS) jako potencjalni sprawcy wypadków komunikacyjnych.

The aim of this work was to estimate excessive somnolence and frequency of episodes of dozing off during driving a car in patients with obstructive sleep apnea. Result of questionnaire and polysomnographic investigations were analysed in a group of 503 patients. Mean age for the whole group was 49.2 +/- 9.7 of years, BMI 32.1 +/- 1.4 kg/m2 and the value for apnea and hypopnea index 45.4 +/- 24.8. Excessive somnolence during driving was reported by 49.1% of patients. 31.2% of the group notified at least one episode of falling asleep while driving a car. Sleepy drivers (group A) were significantly younger (46.5 +/- 9.2 vs 50 +/- 9.8 years) and had higher values of BMI (34.1 +/- 7 vs 31.1 +/- 5.5 kg/m2) than the others (group B) Results of polysomnographic investigation showed more severe sleep apnea in the group A. Mean value of AHI for this group was 52.5 +/- 26.1 vs 41.6 +/- 23.5 in the group B. Besides, somnolence in many other practical situations was more often considered as a serious problem in the group A.

[Evaluation of the incidence of clinical symptoms and risk factors for COPD based on the monitoring of refinery workers in Piock (1993-1996)]. / Ocena czestosci wystepowania objawów klinicznych i zmian w badaniach czynnosciowych w pochp na podstawie badan pracowników elektrocieplowni petrochemii plockiej (1993-1996).

Work place environment plays an important role in development diseases because of the time spend in and different toxic factors placed in it. The aim of study was to assess the ventilatory efficiency in individuals employed in Generating Plant (GP) in relation to the pollution of the work place and the tobacco smoking habit during 3 years. The study covered a group of 144 male individuals employed at GP. (age 39.3 +/- 8.7 yrs, period of employment 20.3 +/- 8.6 yrs, smokers 53.5%. Lung function tests consisted of VC, FVC, FEV1, FEV1%VC, PEF, FEF50 counted from flow-volume curve and TGV, Rt measured using pletysmographic method. All tests were performed using pletysmograph (Masterlab) "Jaeger" placed on the ambulance near to the work place. The measurements were taken in May 1993 and 1996. Results were compared to with normal values (acc. ECSC). The anamnesis was obtained from all workers in the form of questionnaire projected for this study. All measurements were done during work time (9.00 a.m. to 2.00 p.m.). Mean values of the ventilation indices remained within the normal range but comparing results in smokers and non-smokers group significant differences in FEV1 and TGV were found. The symptoms of chronic bronchitis were present in 20.8% of persons. Spirometric criteria for the COPD diagnosis were found in 16 persons (11%). Only 5 persons (31%) were symptomatic. The mean decrease of FEV1 was 16.2 ml/yr, in the COPD group it was 82.5 ml/yr. The greater annual loss of FEV1 was found in the smokers and symptoms groups.

[Treatment with salmeterol and quality of life in patients with asthma]. / Leczenie salmeterolem, a jakosc zycia chorych na astme.

The aim of this study was to assess an influence of 4-week treatment with salmeterol on quality of life in asthmatic patients. It was a double blind, placebo controlled study. On the first visit spirometer parameters and PC20H were measured. Within one week of observation all patients recorded scores of asthma symptoms and after that time 22 patients were randomised to the treatment with salmeterol or placebo. On the fourth visit 4-week salmeterol or placebo therapy was finished and all parameters were carried out as on the first visit. Symptoms severity recorded in diary cards was reduced after 4-week of salmeterol therapy. Four week treatment with salmeterol did not change PC20H. Treatment with salmeterol reduced severity of asthma symptoms and use of short-acting beta 2-agonists. The reduction of asthma severity and the use of bronchodilators was more pronounced in the group of patients treated with salmeterol than in the placebo group, but the differences were not significant.

[Dyspnea and lung function. Results of a multicenter study]. / Dyspnoe und Lungenfunktion. Ergebnisse einer Multicenterstudie.

UNLABELLED: In seven pneumological centres 266 patients with different pneumological diseases were investigated. After having clarified several questions regarding the severity of the dyspnoea, cough intensity and the volume of sputum, as well as basic clinical investigation and after an x-ray of the thorax, the diagnosis was arrived at. Subsequently the lung function investigation with the flow-volume curve (including IVC, FVC, PEF, FEV1, MEF50%) and the body plethysmographic Rt and IGV were carried out. Different quality control procedures at and between the different centres ensured comparable results. All centres agreed to using methods well compatible with each other. The question as to which kind of parameters of lung function would agree best with the amount of the dyspnoea, was resolved. The causes for the large scatter of the results are described. Cough and sputum exercise an influence even on the degree of dyspnoea, but not by deteriorating the lung function. The results are shown for the entire collective (Part I) in respect of the different diagnoses (Part II). With different diagnosis the same significant correlations exist but the curves are positioned at different levels of the coordinate system. CONCLUSION: Significant correlations exist between the dyspnoea scale and function parameters. There are individual differences between the dyspnoea scale and disturbances of the function parameters. Carefully performed lung function analyse definitely important in any case.

Comparison of efficacy and ease of handling of salmeterol and terbutaline powder inhalers.

A multicentre, randomised, open, parallel-group study was performed to compare the efficacy, tolerability and ease of handling of salmeterol xinafoate 50 micrograms twice daily via the Diskus inhaler with terbutaline sulphate 500 micrograms four times daily via the Turbuhaler inhaler. Two hundred and sixty-three patients (aged 18-79 years, baseline FEV1 50-90% predicted, mean PEFR 85% of response to salbutamol) were randomised to treatment with salmeterol (n = 136) or terbutaline (n = 127). A statistically significant difference in favour of salmeterol was seen between treatment groups for the primary efficacy variable, mean morning PEFR (difference in adjusted means 25.4 l/min, p < 0.001). Within the groups randomised to each device, ease of handling assessments favoured the Diskus inhaler over the Turbuhaler inhaler. More patients liked the Diskus inhaler than the Turbuhaler inhaler (98% vs 72%, p < 0.001). The Diskus inhaler received better scores than the Turbuhaler inhaler for all features assessed in the device questionnaire.

Interstitial lung disease in systemic sclerosis: comparison of BALF lymphocyte phenotype and DLCO impairment.

Patients with scleroderma (systemic sclerosis-SSc) frequently develop an interstitial lung disease. The role of lymphocytes in fibrosing alveolitis preceding lung fibrosis has been established. The purpose of this work was to evaluate cell profiles and lymphocyte phenotypes in the bronchoalveolar lavage (BAL) fluid and to correlate them with depression in lung function tests detected by depletion of diffusing capacity (DLCO). BAL was carried out in 25 untreated, non-smoking patients suffering from diffuse scleroderma and in 12 healthy non-smoking volunteers. For the analysis of lymphocyte sub-sets flow cytometry and monoclonal antibodies were used. The following cell sub-types were counted: T lymphocytes, B lymphocytes, helper lymphocytes, suppressor/cytotoxic lymphocytes, natural killer cells, cytotoxic T lymphocytes and activated T lymphocytes. The total cell count was higher in the group of patients with mild and moderate impairment in DLCO. The percentage of lymphocytes was greater in patients with DLCO lower than 65% of the predicted value since neutrophilia was found in patients with severe DLCO depletion, i.e. significant when compared with healthy subjects. The proportions of suppressor/cytotoxic lymphocytes and of activated T lymphocytes were higher in patients than in controls. The statistical analysis revealed significant differences between patients with moderate and mild changes in DLCO and the healthy volunteers. A decreased helper/suppressor ratio was noticed in these patients. We concluded that the BALF lymphocyte phenotype analysis may reflect the features of alveolitis in patients with SSc.

[Extracellular components of broncho-alveolar lavage fluid (BALF) as markers of interstitial pulmonary disease activity. II. Phospholipid concentration]. / Pozakomórkowe skladniki plynu z plukania oskrzelowo-pecherzykowego (BALF) jako marker aktywnosci sródmiazszowych chorób pluc. Czesc II: Stezenie fosfolipidów.

Phospholipids found in the alveolar space come from the surfactant which is produced by type II pneumocytes and whose surplus is eliminated from lungs by macrophages. In 188 patients with interstitial pulmonary diseases bronchoalveolar lavage was performed. Phospholipids from the supernatant of BALF were extracted using of Folch method and their concentration was measured colorimetrically assaying inorganic phosphorus after prior mineralization by Fiske-Subbarov method. The persons were divided into 7 groups: active sarcoidosis, inactive sarcoidosis, avian fancier's lung in the period of contact with the antigen, and after stopping the contact with the antigen, advanced idiopathic pulmonary fibrosis, moderate idiopathic pulmonary fibrosis, and a control group of healthy persons. Apart from that, the patients were divided into untreated and treated with corticosteroids. In every group of patients we have noticed increased concentration and total amount of phospholipids in BALF. Particularly distinct increase of the total number of phospholipids in BALF in pulmonary fibrosis was observed. However, this parameter does not permit to estimate disease activity in interstitial lung disease. Corticotherapy increases phospholipids concentration in BALF in patients with idiopathic pulmonary fibrosis and avian fancier's lung but decreases in sarcoidosis patients.

[Extracellular components of bronchoalveolar lavage fluid (BALF) as a marker of interstitial pulmonary disease activity. I. Protein concentration]. / Pozakomórkowe skladniki plynu z plukania oskrzelowo-pecherzykowego (BALF) jako marker aktywnosci sródmiazszowych chorób pluc. Czesc I. Stezenie bialka.

In interstitial pulmonary diseases a passive transudation of protein into an alveolar space takes place as well as local synthesis of protein by cells in alveolar space and protein leaking out of destroyed cells. Concentration of protein in BALF was assessed in 170 patients with interstitial pulmonary diseases and in 18 healthy persons by means of colorimetric method with Coomassie Blue. Patients were divided into 8 groups: active untreated sarcoidosis, inactive untreated sarcoidosis, active sarcoidosis after corticotherapy, inactive sarcoidosis after corticotherapy, avian fanciers' lung in the period of contact with the antigen, avian fanciers' lung after one year's interval in exposure to the antigen, advanced idiopathic pulmonary fibrosis, and moderate idiopathic pulmonary fibrosis. In the group with active forms of diseases the increase of protein concentration in BALF was observed. The increase was statistically significant compared with the results in the control group and in the groups with inactive forms of the diseases. Protein concentration in BALF may play the role as marker of activity in interstitial pulmonary diseases.

[The usefulness of a computer program Oxygen Status Algorithm (OSA) with particular consideration of oxygen parameters in the Clinic of Chest Diseases]. / Przydatnosc programu komputerowego Oxygen Status Algorithm (OSA) ze szczególnym uwzglednieniem wskazników tlenowych w Klinice Chorób Pluc.

The traditional parameters such as the oxygen tension (pO2) and the haemoglobin oxygen saturation (sO2) obtained from arterial blood samples are not always sufficient in clinical practice. The purpose of the study is to present the examples where pO2 and sO2 even in combination may provide misleading information. We examined patients with bronchial asthma, respiratory insufficiency and with extrinsic allergic alveolitis who had been admitted to the Chest Disease Department. We used the Oxygen Status Algorithm (OSA) to calculate the new oxygen parameters. These new parameters are: 1) oxygen extraction tension px defined as the tension required to extract 2.3 mmol of oxygen per liter of blood, 2) the concentration of extractable oxygen cx defined as the concentration of oxygen extracted per liter of blood at a tension of 5.0 kPa, 3) the oxygen compensation factor (Qx), derived as 2.3 mmol/l/cx. This data defines the blood oxygen availability. Additional parameters such as effective hemoglobin concentration ceHb (equivalent of oxygen capacity) and the hemoglobin oxygen affinity (p50) inform us of the oxygen supply to the tissue. The results show that the new oxygen parameters are helpful in undertaking decisions of starting therapy and its duration.

Lymphocyte phenotyping in systemic sclerosis: a flow cytometry analysis of lymphocytes in bronchoalveolar lavage fluid.

OBJECTIVE: Patients with scleroderma (systemic sclerosis [SSc]) frequently develop interstitial lung disease. The purpose of this work was to evaluate the cell profile in the bronchoalveolar lavage fluid (BALF) in patients suffering from a diffuse form of systemic sclerosis as compared with healthy controls. STUDY DESIGN: Bronchoalveolar lavage was carried out in the right middle lobe of 25 untreated, nonsmoking patients with SSc and 12 healthy, nonsmoking volunteers. For the analysis of lymphocyte subsets, the following monoclonal antibodies were used: anti-CD3, anti-CD4, anti-CD8, anti-CD14, anti-CD16, anti-CD19, anti-CD25, anti-CD45, anti-CD56. Also, anti-HLA-DR and flow cytometry were used. RESULTS: We found an increase in the total number of cells with an increase in the percentage of lymphocytes and neutrophils in BALF from patients when compared with controls (P < .05). The proportion of lymphocytes, cytotoxic/suppressor CD8+ and activated lymphocytes T CD25+ were higher in patients' BALF (P < .05). The CD4+/CD8+ ratio in BALF from subjects was significantly lower than in controls. These findings were characteristic of patients with early-stage disease. CONCLUSION: Analysis of the BALF lymphocyte phenotype may be useful in the early detection of lung involvement in patients with SSc.