Proinflammatory cytokines Il-6 and TNF-α and the development of inflammation in obese subjects.

BACKGROUND: The development of obesity and related disorders, e.g., type II diabetes (T2D), hypertension, and metabolic disturbances is strongly related to increased levels in proinflammatory cytokines (IL-1, IL-6, and TNF-α). Both IL-6 and TNF-α are secreted by adipocytes and their concentration correlates with the percentage and distribution of fat tissue in the body. Both cytokines are the main factors responsible for the induction of acute phase proteins production (e.g., CRP) and to inflammatory state. OBJECTIVE: To compare of TNF-α and IL-6 concentrations in serum from obese subjects with those in subjects with normal BMI and to analyze the relation between TNF-α, IL-6, BMI and the inflammatory state as measured by the level of CRP. MATERIAL AND METHODS: The study included 80 obese subject (54 males and 26 females) BMI >25 kg/m⊃2. A control group consisted of 53 healthy subjects (24 males and 29 females) with BMI <25 kg/m⊃2. To determine the blood plasma concentration of IL-6 and TNF, commercial ELISA assay kits were used. RESULTS: The concentration of IL-6 was lower in the control compared with the obese patients, but a significance difference concerned only female subjects (P = 0.001). TNF-α concentration was significantly higher in all obese subjects (P<0.001). A higher level of this cytokine was also found in patients with obesity suffering from T2DM. A positive correlation was present between IL-6 and TNF-α concentrations. Only did the IL-6 level correlate with the concentration of CRP in serum. CONCLUSIONS: The study confirmed that increased inflammatory cytokines lead to the persistence of inflammation in obese subjects. However, some other factors, such as gender, may contribute to the development of obesity-related inflammatory states.

Frequency of distribution of leptin receptor gene polymorphism in obstructive sleep apnea patients.

Leptin is an adipocyte-derived hormone regulating energy homeostasis and body weight. Leptin concentration is increased in patients with the obstructive sleep apnea syndrome (OSAS). Leptin receptor (LEPR) is a single transmembrane protein belonging to the superfamily of cytokine receptors related by a structure to the hemopoietin receptor family. The aim of the present study was to evaluate the frequency of distribution of leptin receptor gene polymorphism GLN223ARG in OSAS patients compared with healthy controls. The examined group included 179 subjects: 102 OSAS patients (74 men and 28 women) and 77 non-apneic controls (39 men and 38 women). Genomic DNA was isolated with the use of a column method and genotyping of DNA sequence variation was carried out by restriction enzyme analysis of PCR-amplified DNA. The results revealed a significant correlation between the polymorphism of LEPR and OSAS. Carriers of Arg allele in homozygotic genotype Arg/Arg and heterozygotic genotype Gln/Arg were more often obese and developed OSAS than the group of carriers of homozygotic Gln/Gln genotype. This tendency was observed in the whole examined population and in the group of obese women. We also found the highest levels of total cholesterol, LDL, HDL, and triglycerides in the group of homozygotic Arg/Arg genotype carriers, lower in heterozygotic Gln/Arg genotype carriers, and the lowest in the group of persons carring homozygotic Gln/Gln genotype. The presence of Arg allel seems linked to a higher risk of obesity and higher lipid levels in OSAS patients. OSAS may have a strong genetic basis due to the effects from a variety of genes including those for leptin receptor.

Leptin measurement in urine is a reliable method of monitoring its secretion in patients with obstructive sleep apnea syndrome.

Leptin is believed to play a significant role in the pathogenesis of obstructive sleep apnea syndrome (OSAS) as well as progression of OSAS-related obesity. It is also known that other factors such as gender and diurnal variations in serum strongly affect the measurement results making repeated blood sampling necessary for leptin precise monitoring. Since renal metabolism and urine secretion are the main elimination mechanism for leptin, in this study we evaluated urine relevance for leptin secretion monitoring. Serum and urine (collected during the day and overnight) sampled from 169 OSAS patients and 41 controls were assayed by immunoenzymatic method specific for human leptin. Only 5 (17%) controls and 10 (5.8%) OSAS patients had undetectable urine leptin. We observed significant relationships between serum and urinary leptin in both day-time (r=0.656, P<0.001) and night-time (r=0.518, P<0.001) samples and between day and night-time urine leptin (r=0.811, P<0.001). Significance values did not alter when urinary leptin levels were expressed as the ratio to urinary creatinine. Gender-related differences in leptin concentrations were present both in serum (P<0.001) and overnight urine (P<0.01) in the OSAS group. However, mean night-time urine leptin was lower in the OSAS patients (P<0.05) and their subgroups stratified according to disease severity (P<0.01), while serum leptin levels were comparable in both groups. We conclude that assaying leptin in urine by immunoenzymatic method is a reliable and useful non-invasive alternative for its serum measurement. However, night-time urine leptin levels better reflect differences in its turnover due to gender and OSAS severity.

The interrelationship between markers of inflammation and oxidative stress in chronic obstructive pulmonary disease: modulation by inhaled steroids and antioxidant.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is accompanied by both airway and systemic inflammation and by oxidative stress. This study aimed to characterise the relationship between oxidative stress and inflammatory components in induced sputum and blood. MATERIAL & METHODS: We studied blood and sputum samples from stable COPD patients (mean FEV1 60.5+/-7.5% predicted) at baseline (no treatment) and after 10 weeks treatment with either inhaled steroid, fluticasone propionate (FP) (1000 microg/d) or 10 weeks treatment with N-acetylcysteine (600mg/d) (NAC). We assessed the inflammatory markers (IL-8, ECP, sICAM-1, NE) in sputum and serum and we compared them with blood markers of oxidative stress (SOD, GPx, TEAC, albumin, vitamin E and A). RESULTS: At baseline blood sICAM-1 correlated with IL-8 levels (P<0.01, r = 0.62) and negatively with GPx (P<0.01, r = -0.63) and with TEAC (P<0.05, r = -0.53). TEAC correlated positively with GPx (P<0.01, r = 0.70). Correlation between sICAM and IL-8 disappeared after NAC treatment. The correlation between sICAM and GPx disappeared after FP treatment. The correlation between TEAC and GPx was maintained after both NAC and FP. CONCLUSIONS: The relationship between markers of inflammation, adhesion and antioxidant capacity is significantly modulated by treatment with N-acetylcysteine or inhaled corticosteroids.

Captopril effects on pulmonary and systemic hemodynamics in chronic cor pulmonale.

A placebo-controlled single-blind study on acute effects of captopril on hypoxic pulmonary hypertension was performed in 15 patients with severe chronic obstructive lung disease recovering from right heart failure. Ten patients received active drug (25 mg captopril orally), five patients received placebo and served as control subjects. Before drug administration, there was no difference in lung function data and pulmonary hemodynamics between patients in both groups. Captopril produced highly significant fall in systemic arterial pressure. No change in breathing frequency, minute ventilation, and pulmonary gas exchange was observed. There was no significant change in studied variables after placebo. The presented data suggest that captopril does not decrease pulmonary vascular resistance in patients with hypoxic pulmonary hypertension. A fall in pulmonary wedge pressure reflects a decrease in left ventricular afterload.

The effects of cigarette smoking on pulmonary hemodynamics.

Neutrophils are delayed in transit in the pulmonary circulation during smoking which could reflect smoke-induced changes in local hemodynamics. The purpose of this study was to measure the changes in pulmonary hemodynamics during cigarette smoking in both healthy smokers and patients with COPD with and without pulmonary hypertension. In eight healthy smokers, cigarette smoking decreased the transit time of technetium-99m-labeled red blood cells, associated with an increase in cardiac output and a fall in the pulmonary blood volume index. In patients with COPD, the cardiac index also increased during smoking associated with a small increase in pulmonary arterial pressure only in those patients with pulmonary hypertension. However, pulmonary vascular resistance fell. These changes in pulmonary hemodynamics during cigarette smoking could not account for the increased neutrophil sequestration that has been observed previously in the lungs during smoking.

Cardiac arrhythmias in chronic obstructive pulmonary disease.

Supraventricular and ventricular dysrhythmias, as well as conduction disturbances of varying severity are frequently observed in chronic obstructive pulmonary disease (COPD). The type of arrhythmia that occurs in patients with COPD is influenced by their clinical state. Co-existing coronary heart disease, severe blood gas abnormalities and medication may precipitate the rhythm disturbances. Particularly in patients with acute respiratory failure, the presence of arrhythmias is associated with poor prognosis. However, more studies are needed to assess the importance of cardiac arrhythmias in stable COPD patients and their value in predicting survival.

Pulmonary haemodynamics in patients with OSAS or an overlap syndrome.

BACKGROUND: Alveolar hypoxia is the most important mechanism leading to pulmonary arterial vasoconstriction, remodelling and pulmonary hypertension. Patients with Obstructive Sleep Apnoea Syndrome (OSAS) experience multiple short periods of alveolar hypoxia during apnoeic episodes. However, the question as to whether these hypoxic episodes are responsible for the development of permanent pulmonary hypertension is still debatable. We aimed to investigate the relationship between the episodes of nocturnal desaturation and pulmonary haemodynamics in two distinct group patients: with pure OSAS or an overlap syndrome. METHODS: We studied 67 patients with severe OSAS (means: age 45+/-8 years, AHI 62+/-22, FEV1 3.6+/-0.8 L = 97+/-16% of predicted PaO2 72+/-10 mmHg, PaCO2 40+/-4 mmHg) and 17 patients with an overlap syndrome (OS), means: age 51+/-5 years, AHI 64+/-19, FEV1 1.5+/-0.7 = 43+/-16% of predicted PaO2 57+/-9 mmHg). All subjects underwent pulmonary artery catheterisation with pressure and flow recordings and an overnight full sleep study. RESULTS: On average patients with OSAS had nocturnal desaturation (mean overnight SaO2 = 87+/-5%) and normal PPA (15.8+/-4.6 mmHg). Only 11 out of 67 subjects (16%) presented with pulmonary hypertension. Patients with OS had nocturnal desaturation (mean overnight SaO2 = 80.2+/-8.5%) and mild pulmonary hypertension (PPA 24.2+/-7.4 mmHg). Only three out of 17 patients had normal pulmonary arterial pressure. CONCLUSIONS: In patients with severe OSAS, pulmonary hypertension is rare (16%) and is related best to the severity of the disease and to obesity. In OS patients diurnal pulmonary hypertension is frequent but does not correlate with the severity of nocturnal desaturation.

Psychological status of COPD patients before and after one year of long-term oxygen therapy.

Cognitive function, psychological status, and attitudes were investigated in 90 patients with chronic obstructive pulmonary disease before the initiation of long-term oxygen therapy and after one year of treatment. Assessment included clinical interview, Wechsler Intelligence Scale I.Q., Bourdon-Wiersma Test, Benton Verbal Retention Test, Rey's Test of Remembering 15 Words, Beck's Depression Scale, Taylor's Manifest Anxiety Scale, and Tylka's Psychological Evaluation Scale of the Effectiveness of Rehabilitation. The mean I.Q. of the patients studied was slightly above average at 107 points. Tests of cognitive function showed reduced performance. These included tests of repeating numbers, pictorial anecdotes and numerical symbols. Rey's Test of Word Memory was also below average but increased following treatment. In the Bourdon Test, there were 58 correct deletions and 7 omissions initially, improving to 67 and 8, respectively, after treatment. Poor visual and spatial memory did not improve after treatment. Before treatment, patients demonstrated depressed mood, low self-esteem with narrow interests, signs of anxiety, mental stress and depression. After a year of long-term oxygen therapy significant improvements in mood and attitudes were demonstrated. We conclude that long-term oxygen therapy may be capable of producing a significant improvement in emotional status. However, the effects of oxygen treatment are difficult to separate from effects of other aspects of care in producing a sense of increased security and well-being.

[Cough-syncope syndrome in tracheobronchomalacia]. / Zespól kaszlowo-omdleniowy na tle tracheobronchomalacji.

A 40-year-old man, referred for treatment of syncope due to cough, was found to have generalized tracheobronchomalacia. The diagnosis was based on an abnormal collapsibility of the trachea and bronchi on bronchoscopic examination. The detailed investigations confirmed the diagnosis of cough-syncope syndrome due to tracheobronchomalacia. Based on this case the causes, symptoms and possible treatment of those clinical entities are discussed.

[Effect of tobacco smoking on pulmonary function in employees of the Institute of Tuberculosis and Lung diseases in Warsaw]. / Wplyw palenia tytoniu na czynnosc pluc u pracowników Instytutu Gruzlicy i Chorób Pluc w Warszawie.

The effects of smoking habit on pulmonary function was studied prospectively (from 1987 to 1991) in a group of the staff in the Institute of Tuberculosis and Lung Diseases in Warsaw. The prevalence of smoking was the lowest among physicians (42% in 1987 and 24% in 1991). Nurses smoked more--51% in 1987 and 41% in 1991. A positive trend in quiting smoking was noted especially among physicians, nurses and technicians. Pulmonary function test were normal in all studied groups. The most pronounced decreases in lung function were noted in smokers.

[Effects of smoking tobacco on exercise tolerance in healthy subjects]. / Wplyw palenia tytoniu na wydolnosc wysilkowa u osób zdrowych.

The aim of the study was to investigate the effects of smoking on exercise tolerance in middle aged smokers. Sixty two healthy subjects 55 males and 7 females with mean age 35 +/- 7 years were studied. There were 47 smokers (smoking 21.5 cigarettes per day for a mean of 16 years) and 15 non-smokers (control group). Resting pulmonary function was normal in both groups, however smokers had significantly lower VC as well as MEF 50 and MEF 75. A maximal incremental exercise on cycloergometer using ramp protocol was performed. Ventilatory parameters (breath by breath method) together with transcutaneous oxygen saturation (every minute), heart rate (continuously) and blood pressure (every minute) were recorded. Significant differences in exercise tolerance in studied groups were observed. Smokers tolerated a lower maximal workload for a shorter time and deferred significantly in both maximal oxygen consumption and oxygen consumption at anaerobic threshold. Five persons, all smokers did not reach the anaerobic threshold. In five smokers a decrease in ECG ST segment was observed. No differences were found in breathing reserve, heart reserve or maximal oxygen pulse. It seems that a decreases exercise performance is due to cardiac limitation.

[Smoking habits, knowledge and attitude of pulmonologists concerning problems of smoking in Poland]. / Nalóg palenia, zasób wiadomosci i postawa lekarzy zatrudnionych w pionie gruzlicy i chorób pluc wobec problemu nikotynizmu w Polsce.

An analysis was carried out on 850 self-report questionnaires sent to Polish pulmonologists on their knowledge and attitude toward smoking. In the sampled population 38% of the males and 29% of females smoked. Smoking was dated as first among various noxious factors in human pathology. The knowledge of harmful effect of smoking was restricted to the cardio-respiratory system. Part of the responders, mainly smokers believe that smoking less than 15 cigarettes is harmless. ++Ex-smokers were most active in smoking cessation programs. Knowledge of harmful effect of smoking and cessation programs by physicians is unsatisfactory and teaching programs concerning this problem is mandatory.

[Evaluation of the effectiveness of medical consultation regarding smoking cessation]. / Ocena skutecznosci porady lekarskiej na porzucenie nalogu palenia.

Smoking habits were assessed by a questionnaire in workers of a small factory during their prophylactic medical check-up. In all subjects spirometry and CO levels in expired air were determined. In the studied group 43.8% were smokers. Respiratory indices were decreased in smokers in comparison to ex- and non-smokers. In all smokers higher (3x) levels of CO were found. After a year 5 subjects ceased to smoke (15.6% of the smokers).

[Effect of short-term home oxygen therapy on pulmonary artery pressure does not predict the survival of patients with chronic obstructive lung disease]. / Wplyw krótkotrwalej tlenoterapii na cisnienie w tetnicy plucnej nie okresla przezycia chorych na przewlekla obturacyna chorobe pluc leczonych tlenem w domu.

We wanted to verify if the acute effect of oxygen on pulmonary arterial pressure (PPA) is related to survival on LTOT as was suggested recently in the literature. We studied 46 COPD patients qualified for LTOT. The acute effects of O2 on pulmonary haemodynamics were assessed by pressure and flow measurements before and after 30 mins of O2 breathing via 28% Ventimask. Thirty nine patients reacted with a fall of the mean PPA of less than 5 mm Hg. These were termed nonresponders (NR). In seven patients mean PPA fell > 5 mm Hg. They were called responders (R). After the initial investigations patients were followed up on LTOT for 2 years or until death. During two years of LTOT 15 patients died (12 from NR and 3 from R groups). The first two years survival rate was 69% in NR and 57% in R groups respectively. We conclude that survival on LTOT is not related to the acute effect of oxygen on the pulmonary arterial pressure in COPD patients investigated in the steady-state period of the disease.

[Effects of spirometric screening in the community on smoking cessation]. / Wplyw wczesnego srodowiskowego wykrywania POCHP na ograniczenie nalogu palenia tytoniu.

UNLABELLED: In the years 1998-2000 in the Centre of COPD and Respiratory Failure in Bydgoszcz a group of tobacco smokers at risk of COPD (over 40 years of age, with smoking history of more than 10 packyears) were studied. Every patient filled-in a simple questionnaire on clinical signs of COPD and tobacco habit, had a spirometry performed according to ATS standards and received a short antitobacco counseling together with a booklet on how to quit smoking. Out of 1072 patients studied in 1998, airway obstruction was found in 200. Eighty seven of these were current smokers (studied group-S). Another 90 current smokers with normal spirometry served as a control group-C. Both groups of smokers were invited in 1999 and 2000 to perform spirometry. Changes in smoking habit were recorded at each yearly visit. After one year 13 patients (15%) from the S group and 4 (4.5%) from the C group permanently stopped smoking. In 2000 24 patients (28%) in S group and 13 (14.7%) in C group permanently quit smoking. CONCLUSION: Spirometric screening in smokers at risk of COPD together with a minimal antismoking intervention seems to be a promising method of smoking cessation.

[Eight years of experience in Warsaw with domiciliary long term oxygen therapy]. / Osiem lat doswiadczen Warszawskiego osrodka domowego leczenia tTlenem.

Between August 1986-July 1994 45 1 patients with chronic hypoxaemia were referred to us for evaluation. 315 of them (70%) were qualified for LTOT according to national guidelines. There were 189 pts with COPD (60%), 40 with late sequelae of pulmonary tuberculosis (TB), 21 with interstitial pulmonary fibrosis (IPF), 15 with bronchiectasis (BE), 15 with severe kyphoscoliosis (KS) and 35 with other disease leading to chronic respiratory failure. All patients received oxygen from an oxygen concentrator and have been regularly followed-up. The best survival rate in patients followed up for at least 3 years was observed in KS (68%) and COPD pts (50%). The worst survival was seen in BE (9%) and IPF (21%). 183 pts died during the follow-up and in 3 pts (1%) LTOT was withdrawn. The most frequent cause of death were either acute (58%) or chronic (21%) cardiorespiratory failure.

[Early, targeted population based screening for COPD. Preliminary study]. / Wczesne, srodowiskowe, celowane wykrywanie POCHP. Doniesienie wstepne.

COPD is the fourth leading cause of death in Poland, unfortunately diagnosed not early enough. The aim of the study was to establish prevalence of COPD in chronic smokers. Therefore, using daily press and TV, smokers with at least 10 year history of smoking, over 40 years of age, were invited for a free spirometry. 263 subjects (177 M and 86 F) mean age 54 +/- 0.6 years were examined. Most of them (97.7%) were smokers with a history of 32.2 +/- 0.9 pack-years, 6 persons (2.3%) were passive smokers. 110 persons (41.8%) presented bronchial obstruction, the remaining (58.2%) had normal spirometric values. Following recommendations of the Polish Society of Physio-pneumonology bronchial obstruction was classified as mild in 25.1%,- moderate in 12.1% and severe in 4.6% subjects. Majority of examined subjects presented with COPD symptoms, cough (62.7%), expectoration (68.8%) and dyspnoea (50.2%). The presence of those symptoms did not differ among groups with different severity of bronchial obstruction. However, there were significant differences in age (p < 0.05) and years of smoking habit (p < 0.01). The great efficacy of targeted screening for COPD (40%) should be an incentive to perform routine spirometric examination in smokers with more than 20 years of smoking history.