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Telomerase is a reverse transcriptase ribonucleo-protein (h-TERT) that synthesizes telomeric repeats using its RNA component (h-TERC) as a template. Telomerase dysfunction has been associated with both fibrogenesis and carcinogenesis. In this study, we aimed to evaluate the telomerase mRNA expression levels of both subunits (h-TERT and h-TERC) in lung tissue and bronchoalveolar lavage fluid (BALF) from patients with idiopathic pulmonary fibrosis (IPF) and non-small cell lung cancer (NSCLC), since there are indications of common pathogenetic pathways in these diseases. We prospectively examined lung tissue samples from 29 patients with IPF, 10 patients with NSCLC and 21 controls. Furthermore, we examined BALF samples from 31 patients with NSCLC, 23 patients with IPF and 12 control subjects. The mRNA expression for both h-TERT and h-TERC was measured by real-time RT-PCR. In the lung tissue samples, both h-TERT and h-TERC mRNA expression levels varied among the 3 groups (p=0.036 and p=0.002, respectively). h-TERT mRNA levels in the patients with IPF were lower compared with those in the controls (p=0.009) and patients with NSCLC (p=0.004). h-TERC mRNA levels in the patients with IPF were lower compared with those in the controls (p=0.0005) and patients with NSCLC (p=0.0004). In the BALF samples, h-TERT mRNA expression levels varied among the groups (p=0.012). More specifically, h-TERT mRNA levels in the patients with IPF were higher compared with those in the controls (p=0.03) and patients with NSCLC (p=0.007). The attenuation of telomerase gene expression in IPF in comparison to lung cancer suggests a differential role of this regulatory gene in fibrogenesis and carcinogenesis. Further functional studies are required in order to further elucidate the role of telomerase in these devastating diseases.

Idiopathic pulmonary fibrosis (IPF) is a progressively fibrotic disease with a median survival of 3-5 years. Despite recent advances the pathophysiology of the disease remains not fully understood. However, injury of type II alveolar epithelial cells is considered the key event for the initiation of the development of fibrosis. An accurate diagnosis is imperative because commencing treatment at an early stage may reduce disease progression. In this regard, the multidisciplinary disease meeting between pulmonologists, radiologists and pathologists has definitely improved the diagnostic confidence. Importantly, a milestone has been recently reached as the first IPF-specific drug namely pirfenidone has been licensed in Europe, Japan and Asia.

Distinguishing malignant from benign pleural effusions using routine cytology is a common diagnostic problem. Recently, genetic alterations, including microsatellite instability (MSI) and loss of heterozygosity (LOH), have been described in malignant pleural effusions and proposed as methods improving diagnostics. The purpose of this study was to evaluate a panel of molecular markers for the detection of genetic alterations of cells in pleural effusions and to determine their diagnostic value as an additional test to cytologic examination. Pleural fluid and peripheral blood from 48 patients (36 male and 12 female, median age 71 years) were analyzed. Twenty-six patients had malignant pleural effusion, including 23 lung cancer and three metastatic non-pulmonary carcinoma. The control group consisted of 22 patients with benign pleural effusions. Only 14 malignancy-associated pleural effusions were cytology-positive for malignant cells (54%), whereas all benign pleural effusions were negative. DNA was extracted from all the samples and analysed for MSI and/or LOH using the following microsatellite markers: D3S1234, D9S171, D12S363, D17S250, D5S346 and TP53Alu, located at five chromosomal regions: 3p, 9p, 12q, 17q, 5q. Microsatellite analysis of the pleural fluid pellet exhibited genetic alterations in two neoplastic pleural fluid cases and in one inflammatory case. Two out of 26 (7.6%) patients with malignant pleural effusion showed genetic alterations. One exhibited MSI in three different microsatellite markers (D17S250, D9S171, D3S134) and the other showed LOH in marker D3S134. One out of 22 (4.5%) patients with benign pleural effusion showed LOH in marker D3S134. In conclusion, genetic alterations at the level of microsatellite DNA, were detected only in very few cases of malignant pleural effusions, and in one case of benign pleural effusion. Thus, our data suggest that microsatellite DNA analysis does not facilitate the diagnosis of malignant pleural effusion.

Introduction: Near the end of a maximal voluntary breath-hold, re-inhalation of the expired gas allows an additional period of breath-holding, indicating that the breaking point does not depend solely on chemical drive. We hypothesized that afferents from respiratory muscle and/or chest wall are significant in breath-holding., Methods: Nineteen normal adults breathed room air through a mouthpiece connected to a pneumotachograph and were instructed to breath-hold with and without voluntary regular respiratory efforts against an occluded airway., Results: Fifty one trials with and 53 without respiratory efforts were analyzed. The mean number of efforts per minute was 19+/-2.3 and the mean lowest airway pressure (P(aw)) -16.6+/-5.4 cmH(2)O. Breath-holding time (BHT) did not differ without (33.0+/-18.2 s) and with (29.3+/-12.3 s) efforts. In five patients arterial blood gasses were measured before and at the end of breath-holding and they did not differ between trials without and with efforts, indicating similar chemical drive. Our results suggest that afferents from respiratory muscle and/or chest wall are not the major determinants of BHT.

Aim: To investigate whether there is a significant relationship between an increased frequency of exacerbations and the rate of forced expiratory volume in 1s (FEV(1)) decline in COPD patients. METHODS-MEASUREMENTS: About 102 COPD patients (44 smokers, 58 ex-smokers) participated in a 3-year prospective study. Exacerbations were identified as worsening of patient's respiratory symptoms as recorded on diary cards. Spirometry was performed every 6 months. The effect of frequent exacerbations on lung function was investigated using random effects models., Results: The median (mean(95% CI)) annual exacerbation rate was 2.85 (3.1 (2.7-3.6)). Patients with an annual exacerbation rate over the median rate had significantly lower baseline post-bronchodilation FEV(1)(%pred), higher MRC dyspnoea score and chronic cough compared to patients who had an annual exacerbation rate less than the median. The average annual rate of FEV(1)(%pred), adjusted for smoking decline (DeltaFEV(1)), was found significantly increased in frequent compared to infrequent exacerbators (P=0.017). The highest DeltaFEV(1) was observed in smokers frequent exacerbators and a significant interaction between exacerbation frequency and DeltaFEV(1) was also observed in ex-smokers., Conclusions: Our findings suggest that an increased frequency of exacerbations is significantly associated with FEV(1) decline even in ex-smokers. Thus, smoking and frequent exacerbations may have both negative impact on lung function. Smoking cessation and prevention of exacerbations should be a major target in COPD.

Smoking, the most prominent nongenetic factor contributing to mortality, remains the major public health problem throughout the world. There are nearly 1.1 billion users of nicotine and tobacco products worldwide while approximately one third to half of them will die from smoking-related disease. The habit of smoking is mainly propelled by nicotine, a strongly addictive substance, to which the vast majority of smokers fall victim. Except for the general and specific support and counseling strategies there are now effective treatments for nicotine addiction. Two types of pharmacological therapies have been approved and are now licensed for smoking cessation. The first therapy consists of nicotine replacement, substituting the nicotine from cigarettes with safer nicotine formulations. The second therapy is bupropion, an antidepressant of the aminoketone class, which has been demonstrated to be effective in smoking cessation. However, although some cigarette smokers are able to quit, many are not, and standard medications to assist smoking cessation are ineffective. Several agents used for other indications (e.g. neurological diseases, depression, alcoholism) might be used to treat this subgroup. In conclusion, new more effective drugs are needed in order to fight the panepidemic of smoking globally.

Objective: To study the potential effectiveness of tumor necrosis factor a (TNF-alpha) inhibitor treatment for pulmonary fibrosis associated with a collagen vascular disease, CVD (rheumatoid arthritis, RA and systemic sclerosis, SSc) refractory to conventional treatment., Methods: Four patients (three men with RA, one woman with SSc) were treated with infliximab. All patients received 3mg/kgr of infliximab at intervals 0, 2 and 6 weeks, and then maintenance infusions every 8 weeks afterwards for at least a 12-month period. Patients had active disease despite treatment with corticosteroids and other immunomodulatory agents., Results: Treatment was well-tolerated from all patients. Pulmonary fibrosis remained stable during treatment in terms of symptoms, pulmonary function tests (PFTs) and High resolution computed tomography (HRCT) appearance. As expected, a clinical response was observed in joint symptoms in patients with RA as evaluated by the DAS28 (Disease Activity Score, the 28 joint version)., Conclusion: This study suggests that inhibition of TNF-alpha with infliximab may stabilize the progression of pulmonary fibrosis associated with CVD. Prospective, controlled trials are necessary to determine the efficacy of infliximab in pulmonary fibrosis associated CVD.

Background: The aim of this study was to explore the possible association of the lung clearance of 99mTc-DTPA scan with HRCT lung abnormalities and with the pulmonary function tests [PFTs] in patients with sarcoidosis., Methods: We studied prospectively 15 patients [5 males, 10 females] of median age 46yr [range 27-67] with histologically proved sarcoidosis. HRCT scoring included the sum of the severity and extent of lymph node enlargement and parenchymal involvement., Results: The mean DTPA clearance half-time [tau 1/ <40 min] was found [mean [SD]] 38.3+/-4.5min. The lymph node enlargement was found 34% and the parenchymal involvement 12%. DTPA clearance was negatively correlated with the parenchymal involvement [r= -0.651, p=0.0091]. The HRCT parenchymal abnormalities were found significantly correlated with PFTs [FVC [r= -0.65, p=0.008] and TLCO [r= -0.76, p=0.02]., Conclusions: Our data suggest a moderate association between 99mTc-DTPA scan and HRCT in pulmonary sarcoidosis. However, further studies in large scale of sarcoid patients are needed to clarify the role of this novel methodology in the evaluation and follow-up of this disorder.

The accumulation of pleural effusion has important effects on respiratory system function. It changes the elastic equilibrium volumes of the lung and chest wall, resulting in a restrictive ventilatory effect, chest wall expansion and reduced efficiency of the inspiratory muscles. The magnitude of these alterations depends on the pleural fluid volume and the underlying disease of the respiratory system. The decrease in lung volume is associated with hypoxemia mainly due to an increase in right to left shunt. The drainage of pleural fluid results in an increase in lung volume that is considerably less than the amount of aspirated fluid, while hypoxemia is not readily reversible upon fluid aspiration.

Genetic alterations, such as loss of heterozygosity (LOH) or microsatellite instability (MI), have been reported in both malignant and benign disorders. In order to identify loci of deoxyribonucleic acid (DNA) mutation in asthma, MI and LOH were studied in sputum cells. DNA was extracted from cells in the sputum and blood cells of 22 patients with moderate asthma. Cells were analysed for MI and LOH using 18 polymorphic markers on chromosome 5q, 6p, 11q, 14q. Microsatellite analysis was also performed in six healthy subjects. None of the healthy individuals exhibited any genetic alteration. Genetic alterations were found in 16 of 22 asthmatic patients (73%). In total, 12 (54.5%) patients exhibited LOH only, one (4.5%) MI only, while three showed both MI and LOH. The highest incidence of LOH and MI was found on chromosome 14q. Mean immunoglobulin E and blood eosinophil levels were significantly higher in asthmatics with three or more genetic alterations. A high incidence of genetic alterations in the deoxyribonucleic acid of the sputum cells was found in asthmatic patients. Further studies are needed to identify the role of loss of heterozygosity and microsatellite instability in the investigation of genetic susceptibility of asthma and thus, in its pathogenesis.

During the last decade, the method of sputum induction (SI) has offered the opportunity to study inflammation in patients with chronic obstructive pulmonary disease (COPD). This paper reviews methodological aspects of SI and summarizes its uses in the research of inflammation in COPD, including sputum cellularity and soluble markers. SI is a relatively safe, reliable, and reproducible technique, used to investigate different aspects of airway inflammation. Although various methods of induction and processing have been proved safe and highly reproducible, a generally accepted method is needed. Sputum analysis has given evidence for increased numbers of macrophages and neutrophils in COPD patients compared to normal subjects. In some studies, increased numbers of eosinophils have been also reported. Changes in various mediators have been found in sputum supernatant of COPD patients (IL-8, LTB-4 and TNF-a). The clinical usefulness of the method in the follow-up of the disease has not been explored extensively. A number of observations in patients with different clinical characteristics could be proven useful in identifying patterns of inflammation associated with different prognosis. Finally, SI could also guide treatment; such as, sputum eosinophilia in COPD could predict response to inhaled corticosteroids.

Pulmonary sarcoidosis shares certain features with immune disease and neoplasia, and microsatellite DNA alterations are detectable in sputum specimens of pulmonary sarcoidosis patients. The biological basis and significance of these findings remain obscure, while information regarding the genetic basis of the disease is limited. Using multiplex PCR-based microsatellite analysis, we investigated 40 markers located on 1p, 1q, 2p, 2q, 3p, 5q, 6p, 7p, 9p, 11q, 14q and 17p in 38 sputum specimens of pulmonary sarcoidosis patients. Loss of heterozygosity (LOH) was found in 13 of 38 (34.2%) patients in at least one locus. These alterations occurred in the subset of markers located in or close to DNA mismatch repair (MMR) genes, hMSH2 (2p22.3-p16.1) and hMLH1 (3p2l.32-p21.1), as well as in CD48 (1q21-q23) and IRF4 (6p23-p25), genes associated with lymphocyte activation. Microsatellite instability (MIN) was observed in five cases (13.2%) in at least one locus. Our data suggest that genomic instability in pulmonary sarcoidosis could be due to MMR defects, while alterations of lymphocyte-specific agents could account for granuloma formation.

COPD is a common disease and its major risk factor, cigarette smoking, has been identified. However, only a minority of smokers develop clinically relevant disease. Although, the current understanding of the pathogenesis includes an "abnormal inflammation" as a response to various noxious agents, its various pathways are not clear. Oxidative stress, inflammation, tissue damage and tissue repair (remodeling) are parts of the complex procedure leading to COPD. This is a review of the available literature concerning the "susceptible" smoker. An epidemiological model is discussed, putting emphasis on the timing of the exposure to cigarette smoke. There are evidences that respiratory adenoviral infection in early life could be also an important factor. Differences in nutrition could also play a role in protecting against the oxidative stress. Airway hyperresponsiveness failed to clarify the whole picture and is still open for debate. Genetic differences are the most likely explanations to describe the "susceptible" smoker. However, the only well-established genetic risk factor is the alpha-l-antitrypsin. Other candidate genes were reviewed, alpha-l-antichymotrypsin, blood group antigens, vitamin-D binding protein, a2-macroglobulin, immunoglobulin deficiency, extracellular superoxide dismutase, secretory leukocyte proteinase inhibitor, cathepsin G, tumor necrosis factor-a gene and others. Microsatellite DNA instability in COPD could be a useful tool to identify the locus of genetic alterations leading to COPD. Thus, in addition to exposure to exogenous factors, host factors, most likely several genes, are involved and affect various pathways of the pathogenesis of COPD.

This is a short review of the use of induced sputum in bronchial asthma. The clinical applications, the procedure of this method as well as the safety validity and reproducibility of the results are discussed in detail. It is shown that sputum induction is a practical and safe procedure and an important research tool of local inflammation of bronchial asthma.

Background: Genetic alterations at the microsatellite level have been detected in various human malignant tissues, but have also been found in chronically inflamed tissues. Sarcoidosis is a benign disease of unknown etiology characterized by chronic inflammation, which may be associated with an increased incidence of developing malignancy., Methods: We examined the microsatellite alterations in a sputum cytological specimen of a patient with sarcoidosis. The DNA electrophoretic pattern of sputum was compared with that of the peripheral blood. Thirty-two microsatellite markers located at chromosomes 2p, 3p, 8p, 9p, 9q, 17p, 17q were used to reveal genetic alterations., Results: Loss of heterozygosity (LOH) was detected in eleven markers in loci 2p, 9p, 9q and 17q. LOH was observed in all four markers spanning the chromosomal arm 17q11.2-q21, suggesting a potential chromosomal deletion., Conclusion: The observation of LOH in all four markers spanning the chromosomal arm 17q11.2-q21 may suggest a potential for malignancy development in this patient, or may be linked to the aetiopathogenesis of sarcoidosis. Further microsatellite fine mapping and clinical follow up of this patient are needed to clarify this.

This study investigates the effect of increased ventilation on the expression of messenger ribonucleic acid (mRNA) levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor-beta1 (TGF-beta1) in the diaphragm of intact, awake, spontaneously breathing rats, compared with responses in paralysed, mechanically-ventilated animals at similar blood gas and ventilatory levels. Four groups of intact, rats were studied in a body box, each group breathing one of four gases: room air, 12% oxygen (O2), 5% carbon dioxide (CO2), or 12% O2+5% CO2 for 1 h. Another 4 groups of paralysed, mechanically-ventilated animals were matched for arterial blood gas and ventilatory level. The results showed that VEGF mRNA abundance was increased three-fold and that of bFGF 1.5-fold when 12% O2+5% CO2 were breathed, but TGF-beta1 did not change. A significant linear relationship of VEGF and bFGF mRNA to minute ventilation was observed in awake animals (r=0.98, p<0.02 and r=0.87, p<0.03, respectively). The paralysed, mechanically-ventilated animals showed no mRNA increases for any probe. Systemic hypoxia had no additional effect on VEGF or bFGF levels in the diaphragm. It was concluded that messenger ribonucleic acid for vascular endothelial growth factor and basic fibroblast growth factor in the diaphragm rises significantly as a result of active ventilation and not due to blood gas/pH changes or to passive muscle shortening per se.

Study Objectives: We aimed to investigate the short-term respiratory effects of heavy, occupational wood smoke exposure among traditional charcoal production workers., Patients and Setting: A total of 22 charcoal workers (mean age, 41 years; 9 current smokers, 5 ex-smokers, and 8 nonsmokers) were studied and compared with a control group of 35 farmers residing in Perama, Rethymnon, Crete., Results: The charcoal workers were exposed to wood smoke for an average of 14 h/d during a mean of 23.7 days required for the burning of kilns. The workers under study were found to have significantly more cough (odds ratio [OR], 4.8; 95% confidence interval [CI], 1.2 to 19.7), sputum production (OR, 6; 95% CI, 1.4 to 26.5), wheezing (OR, 7.7; 95% CI, 1.4 to 41.5), dyspnea (OR, 28.7; 95% CI, 5.4 to 153), and hemoptysis (OR, 2.7; 95% CI, 0.7 to 55) than the control group. The prevalence of respiratory symptoms such as cough, sputum production, wheezing, and dyspnea in the charcoal workers was significantly elevated during the exposure period (OR, 5.4; 95% CI, 1.1 to 17.7; OR, 5.7; 95% CI, 1 to 31; OR, 9.8; 95% CI, 1 to 88; and OR, 36.7; 95% CI, 1 to 327, respectively). The mean +/- SD percent of predicted values of FVC, FEV(1), FEV(1)/FVC ratio, and forced expiratory flow at 25 to 75% of FVC during the exposure period were significantly lower than those before exposure: 106 +/- 10.8 vs 101 +/- 11.9, p < 0.01; 104 +/- 16 vs 97 +/- 15, p < 0.001; 81 +/- 9 vs 78 +/- 8, p < 0.001; and 95 +/- 27 vs 80 +/- 25, p < 0.01, respectively. The mean +/- SD value of peak expiratory flow at midday and in the evening during the exposure were significantly lower than before: 524 +/- 131 L/min vs 548 +/- 108 L/min, p = 0.03; and 521 +/- 135 L/min vs 547 +/- 131 L/min, p = 0.02, respectively., Conclusions: Our results suggest that wood smoke exposure in charcoal workers is associated with increased respiratory symptoms and decreased pulmonary function. Longitudinal studies are needed to determine potential long-term adverse respiratory effects.

The aim of the study was to assess the discriminative power of cytokine interleukin 6 (IL-6) between transudative and exudative pleural and peritoneal effusions, and to compare IL-6 with common acute phase proteins in serous effusion differentiation. One hundred and forty-five consecutive patients with pleural or peritoneal effusion underwent diagnostic parecentesis. Patients were categorized in three groups. Malignant effusion (group A) 56 patients, non-malignant effusion (group B) 46 patients and transudate (group C) 43 patients. Serum and effusion levels of IL-6, C-reactive protein (CRP), alpha2-macroglobuline (alpha2-MG), alpha1-antitrypsin (alpha1-AT) and alpha1-acid glycoprotein (alpha1-AG) were determined. Serum IL-6 levels were significantly higher in groups A and B in comparison to group C (p<0.001 and 0.001, respectively). In addition, serum IL-6 levels were higher in group A compared to group B (p<0.001), while the studied acute phase proteins were not significantly different. All the studied parameters were higher in the effusions of groups A and B compared to group C. At a cut-off value of 72.1 fmol/ml IL-6 had a sensitivity of 82.6-89.3%, specificity of 88.4-90.7% and positive predictive value of 90.7-94.6% among the three groups. Our results suggest that IL-6 at levels > or =72.1 fmol/ml, alpha1-AT at > or =170 mg/dl and alpha1-AG at > or =52.3 mg/ml give strong evidences for malignancy in exudates.

Laser-assisted uvulopalatoplasty (LAUP) is an outpatient mode of treatment for snoring and perhaps for some mild cases of obstructive sleep apnea syndrome. LAUP results in severe throat pain that usually lasts for 8 to 14 days. Sucralfate adheres to proteins at the duodenal ulcer site, forming a protective coating against gastric acid, pepsin, and bile salts, that promotes healing. If a similar protective coating could be created at the area of LAUP trauma, morbidity may be diminished. Twenty-eight patients have undergone LAUP treatment-2 with mild obstructive sleep apnea syndrome and 26 with simple snoring. A block-randomized, single blind clinical study was performed. Sucralfate was administered in 14 patients (group A) every 6 hours for 15 days as a swish and swallow, whereas the other 14 patients (group B) received water for injection with a strawberry flavor as placebo with the same dosing. As a conclusion, sucralfate significantly lowered postoperative pain and the need for analgesic drug use as well as the total number of the days the patients needed to almost reach their normal diet quantity (> or = 80% of normal quantity).

Aim: To assess the level of knowledge for bronchial asthma of the primary healthcare physicians serving a rural population on the island of Crete, both before and immediately after a one-day educational course., Methods: Twenty-one primary health care physicians, randomly selected from a list of 14 Health Care Centres on the island of Crete were invited to participate in the study and attended an educational course. Nine of the 21 physicians were fully qualified general practitioners, while the remainder were non-specialized (NSs) physicians who had recently graduated from the University of Crete, Medical School. A questionnaire of 20 items based on current bronchial asthma clinical guidelines was used. Three scores, the mean total, knowledge subscore and attitudes subscore, were calculated for each group of physicians, both before and after the course., Results: At baseline mean total score and knowledge and attitudes subscores were higher for non-specialized physicians than for the general practitioners, but the differences were not statistically significant (p > 0.05). The knowledge subscore was improved in both groups, however the difference was statistically significant only for the non-specialized physicians (t = 2.628, d.f. = 11, p < 0.05). The mean total score after the course was significantly higher for the non-specialized physicians in comparison to that of the general practitioners (t=-2.688, d.f. = 19, p < 0.05)., Conclusions: This study adds to the information about the success of continuing medical education, and also demonstrates that the recent graduates in the studied population, could be educated with more positive results than the fully qualified practitioners

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology associated with DNA damage and malignancy. Bronchogenic carcinoma is the cause of death in 10% to 13% of IPF patients. Microsatellite instability (MSI) and loss of heterozygosity (LOH) are frequently detected in cancers. If these genetic alterations could be observed in IPF, they might explain the higher relative risk of lung cancer in this disease. We investigated the incidence of MSI and LOH in sputum cytologic specimens from 26 IPF patients and 26 healthy, matched subjects, using 10 highly polymorphic microsatellite markers. The electrophoretic pattern of each specimen was compared with that of corresponding peripheral blood. Thirteen (50%) patients showed genetic alterations, consisting either of MSI or LOH. Five (19%) patients exhibited MSI and 10 (39%) exhibited LOH in at least one microsatellite marker. Three (12%) patients showed LOH in more than one marker. None of the healthy subjects exhibited genetic alterations in the studied markers. No correlation was found between the detected genetic alterations and age, disease duration, blood gases, or spirometric parameters of the patients. Our findings suggest that the genetic alterations that we studied are frequent in IPF, are apparently unrelated to the severity of the disease, and may be related to tumorigenesis.

The function of the respiratory muscles (RM) is affected positively or negatively by a variety of surgical procedures. Cardiac, thoracic and upper abdominal surgery impair the RM function and lead to postoperative complications such as hypoxia, atelectasis, aspiration and infections. Preoperative assessment of RM function is cardinal to avoid or attenuate these complications. Three types of surgical procedures, lung transplantation, lung volume reduction surgery and surgery for obesity have been shown to improve RM function. A mechanism by which these types of operation have shown beneficial effects on RM function is multifactorial, depending on geometrical factors, from the reduction of hyperinflation and those depending on changes on the control of breathing. Physicians dealing with postoperative care of patients should be aware of the pathophysiological mechanisms that impair or improve respiratory muscle function as a result of a surgery as well as of the therapeutic modalities.

In the present study we investigated the incidence of microsatellite instability (MI) and loss of heterozygosity (LOH) in sarcoidosis, a multisystem disease of unknown origin. We examined sputum cytological specimens from 30 patients with sarcoidosis and 30 healthy, matched subjects, using 10 highly polymorphic microsatellite markers located at several chromosomal arms. The electrophoretic pattern of each specimen was compared with the corresponding pattern of peripheral blood and any difference in the mobility of the microsatellite alleles was interpreted as MI-positive. LOH was scored as decrease in intensity of one allele relative to the other as determined from comparison of sputum and normal (blood) DNA. We found that 14 (47%) sarcoidosis patients showed genetic alterations, either MI or LOH. Six (20%) patients exhibited MI and nine (30%) exhibited LOH in at least one microsatellite marker. One of the patients exhibited MI in two microsatellite markers and three (10%) showed LOH in more than one marker. One patient showed complete deletion of the chromosomal arm 17q11.2-q21. None of the healthy subjects exhibited any genetic alteration in the studied markers. No correlation was found between the genetic alterations detected and age, disease duration, blood gases, or spirometric parameters of the patients. Our findings suggest that MI is a detectable phenomenon in sarcoidosis and seems not to be related with the severity of the disease. The detection of LOH indicates the presence of putative tumor suppressor genes at loci examined, which may play an important role in the etiopathogenesis of sarcoidosis.

Study Objectives: Cigarette smoking is the prime cause of COPD; however, only a few smokers develop the disease. In a previous study, we demonstrated that microsatellite DNA instability (MSI) is a detectable phenomenon in sputum cells of COPD patients. Therefore, we hypothesize that this genetic alteration may indicate susceptibility to COPD., Design: In order to investigate this hypothesis, we compared smokers who developed COPD with smokers who did not develop COPD (referred to as non-COPD smokers)., Setting: Seven highly polymorphic microsatellite markers were targeted on the DNA of sputum cells and of WBCs., Patients and Participants: We studied 60 non-COPD smokers and 59 severe COPD patients with a similar smoking history (mean +/- SD) of 48+/-25 and 54+/-33 pack-years, respectively (p = 0.77). Non-COPD smokers were tested once; COPD smokers were tested twice, with an interval of 24 months between tests., Results: MSI was detected in 14 COPD patients (24%) but in none of the non-COPD smokers. In 10 COPD patients, MSI was exhibited by one microsatellite marker; in the remaining 4 COPD patients, MSI was exhibited by two different alleles. The most commonly affected marker was THRA1 on chromosome 17 (43%). No significant differences were found between MSI-positive and MSI-negative COPD patients for clinical or laboratory parameters, survival, and development of lung cancer. No change in the microsatellite alleles was found between the tests performed with a 24-month interval., Conclusions: This study demonstrated that MSI was found exclusively in the sputum cells of smokers with COPD. The results support the hypothesis that MSI could be part of the complex genetic basis of COPD, and it could be a marker of the genetic alteration caused by smoking that allows COPD to develop.

This review reports evidence showing that the function of the respiratory muscles (RMs) is affected in endocrinopathies and emphasizes that clinicians should look for RM weakness in hormone inbalances. Although there is a potential pathophysiological mechanism for affecting RM in diabetes insipidus, hypoparathyroidism, Cushing's disease, pheochromocytoma, adrenalin deficiency or androgen disorder, no study was found in the available literature. Therefore, investigations are urgently needed in these diseases. Controversial results have been reported in acromegaly, hypopituitarism, diabetes mellitus and steroid-induced (iatrogenic) RM myopathy. Obviously, these are areas for further research. Respiratory muscle dysfunction has been well documented in thyroid disease and there is general agreement that both hypo- and hyperthyroidism are associated with reversible respiratory muscle weakness.

Pneumoconiosis among dental technicians has recently emerged as an area of research in interstitial lung disease. This study was carried out to estimate the prevalence of pneumoconiosis in Greek dental technicians on the island of Crete. Fifty-one of the 58 dental technicians of the Heraklion Dental Technicians' Association completed an exposure history questionnaire and underwent a clinical examination, including chest radiographs, and spirometric assessment of lung volume and diffusing capacity. Values were compared with 51 control subjects. Five dental technicians showed radiological evidence of pneumoconiosis. Mean lung function values of the dental technicians, even in those with pneumoconiosis, were not significantly different from controls. No significant changes in lung function parameters were associated with smoking, exposure to metals and other contaminants. Dental technicians, however, reported more respiratory symptoms than controls (p = 0.008). Symptoms were associated to the absence of a ventilation system. We concluded that occupational exposure in dental technicians in Crete did not affect lung function. The prevalence of pneumoconiosis in this study was 9. 8%.

Chronic obstructive pulmonary disease (COPD) is a very common disorder caused primarily by cigarette smoking. Recently national and international guidelines were produced in order to standardize the management of the disease. It became apparent that only a few items in these documents are based on evidence-based studies. Diagnosis should be made in relation to the definitions, symptoms, signs and routine investigation. Spirometry is essential for the diagnosis of COPD. The two well documented modes of treatment, namely cessation of smoking and long-term oxygen therapy are discussed in detail.

During maximal exercise, ventilation-perfusion inequality increases, especially in athletes. The mechanism remains speculative. We hypothesized that, if interstitial pulmonary edema is involved, prolonged exercise would result in increasing ventilation-perfusion inequality over time by exposing the pulmonary vascular bed to high pressures for a long duration. The response to short-term exercise was first characterized in six male athletes [maximal O2 uptake (V(O2)max) = 63 ml x kg-1 x min-1] by using 5 min of cycling exercise at 30, 65, and 90% V(O2) max. Multiple inert-gas, blood-gas, hemodynamic, metabolic rate, and ventilatory data were obtained. Resting log SD of the perfusion distribution (log SDQ) was normal [0.50 +/- 0.03 (SE)] and increased with exercise (log SDQ = 0.65 +/- 0.04, P < 0.005), alveolar-arterial O2 difference increased (to 24 +/- 3 Torr), and end-capillary pulmonary diffusion limitation occurred at 90% V(O2)max. The subjects recovered for 30 min, then, after resting measurements were taken, exercised for 60 min at approximately 65% V(O2)max. O2 uptake, ventilation, cardiac output, and alveolar-arterial O2 difference were unchanged after the first 5 min of this test, but log SDQ increased from 0.59 +/- 0.03 at 5 min to 0. 66 +/- 0.05 at 60 min (P < 0.05), without pulmonary diffusion limitation. Log SDQ was negatively related to total lung capacity normalized for body surface area (r = -0.97, P < 0.005 at 60 min). These data are compatible with interstitial edema as a mechanism and suggest that lung size is an important determinant of the efficiency of gas exchange during exercise.

The aim of this study was to investigate the extent of use, the selection criteria for usage and the conditions under which long-term oxygen therapy (LTOT) is provided on the island of Crete, Greece. A total of 545 patients using oxygen therapy at home in Crete were found from the records held by local hospitals, health insurance offices and oxygen supply companies. After randomization, 100 patients were selected, and finally 79 patients (64 males, 15 females), with a mean age of 71 yrs, were contacted and completed a questionnaire. The majority of patients (n = 57, 72%) using LTOT had a diagnosis of chronic obstructive pulmonary disease (COPD). In 67 (85%) patients LTOT was prescribed by a chest physician. All patients used large oxygen cylinders. The duration of daily oxygen use was significantly longer in the group of patients prescribed it by chest physicians than in those who was prescribed it by doctors from other specialities (8.8 h versus 4.7 h, p < 0.05). Of the patients, 47 (60%) fulfilled the criteria for LTOT. However, only 33 (43%) had accurate written instructions on how to use their home oxygen. A significant number of patients (n = 24, 29%) were still smokers and 63 (80%) had had a follow-up assessment. Our results suggest that COPD is the major grounds for LTOT. The daily duration of the oxygen therapy was longer in the group prescribed it by chest physicians. It is a concern that difficulties in setting up oxygen cylinders resulted in some ineffective usage. Physicians should stress the advantages of O2 concentrators.

Background: Microsatellite instability (MI) and loss of heterozygosity (LOH) are described in lung cancer specimens. However, their importance in tumorigenesis remains unknown. The aim of this study was to identify the presence of MI and LOH in human tumor and normal bronchial mucosa DNA., Methods: We performed biopsies with fiberoptic bronchoscopy and took specimens from the tumor and from the opposite site normal bronchial mucosa in 20 patients with non-small-cell lung cancer (NSCLC). Four patients had an adenocarcinoma, while 16 had a squamous cell carcinoma. Also, 6 patients had an early-stage disease (stages I and II), while 14 patients had an advanced-stage disease (stages III and IV). All paired specimens were studied for MI and LOH on chromosome 17p, 17q, 9p, and 9q, with 10 polymorphic markers., Results: Sixteen of 20 tumors displayed genetic alterations (80%). Six tumors (30%) exhibited MI, five tumors (25%) exhibited LOH, while five tumors exhibited MI and LOH concurrently. The marker HBX had the most frequent incidence of LOH (4/20, 20%), indicating that the hbx gene becomes a strong candidate tumor suppressor gene, whereas of MI it was D17S515 (4/20, 20%). No relationship was observed between the presence of LOH or MI and the histologic subtype of NSCLC or the stage of the disease., Conclusion: Results suggest that genetic alterations exist in tumor, compared with the normal mucosa DNA. They may have a role in carcinogenesis as they exist in all stages and in both NSCLC histologic subtypes studied.

It has been reported that in patients with inflammatory bowel disease (IBD), the airways are involved, and a number of clinical manifestations have been described. The aim of this study was to investigate the function of the small airways in IBD. Thirty patients with IBD (mean age, 47 yr), 12 with Crohn's disease and 18 with ulcerative colitis, were studied and compared with a control group of 16 normal subjects. Maximal expiratory flow-volume curves were performed breathing room air and a mixture of 80% helium, 20% oxygen. The differences of flows at 50% of FVC (delta Vmax50) and the volume of equal flows (Visov) were calculated as indices of small airways function. In addition, spirometry, lung volumes, and diffusing capacity were measured. Visov was statistically significantly greater in patients with either CD or UC than in control subjects (x +/- SD) (24.99 +/- 1.35 and 25.95 +/- 1.5 versus 20.1 +/- 1.39), (p < 0.01 and p < 0.001, respectively). A reduction in TL(CO) was noticed in the active stage of the disease in both groups of patients (p < 0.05). This may indicate that lung parenchyma is also involved in active IBD. Our results suggest that the function of the small airways and diffusion capacity of the lungs are affected in patients with IBD.

Pneumothorax is a rare manifestation of sarcoidosis, occurring usually late in the course of the disease. We report five cases of pneumothorax as a presenting manifestation of sarcoidosis. In two patients, thoracotomy showed extensive pleural infiltration by noncaseating granulomas. High-resolution CT scans showed cavitated subpleural nodules and subpleural bullae in one case. These findings support that necrosis of subpleural granulomas or rupture of a subpleural bullae, or both, are the mechanisms of pneumothorax in sarcoidosis. Three patients with a lung function impairment were treated with oral corticosteroids. One nontreated patient died due to progression of the disease.

This study investigated 22 patients with histologically proven primary bronchial carcinoids and in particular the relationship between assessment parameters and survival. In each patient, age, sex, smoking habits, mode of presentation, results of diagnostic investigations, methods of treatment and pathological examination of resected specimens were recorded. Follow-up was possible in all patients for at least 5 years. Patients with atypical carcinoids were 10 years older than patients with typical ones. Eleven patients were smokers, all the patients with atypical and 4 patients with typical carcinoid. The most common presenting mode was pneumonia. Fiberoptic bronchoscopy was diagnostic in 11 cases. The survival rate for patients with typical carcinoid was 100%, while it was 57% in patients with atypical carcinoids. Patients with limited disease had a survival of 100%, while in stage III/IV patients showed a lower survival rate (50%). In conclusion, carcinoid tumors of the lung are tumors showing a good prognosis. Five-year survival indicated a significant difference between typical and atypical carcinoids and between limited and extensive disease. A precise staging is recommended for a better treatment and follow-up.

A 47 year old woman developed idiopathic bronchiolitis obliterans organizing pneumonia (BOOP) presenting with haemoptysis and diffuse multiple cavitary nodules. The disease was histologically confirmed by open lung biopsy after other entities had been excluded. The patient responded to a course of corticosteroids. This BOOP should be added to the list of diseases with multiple cavitary nodules.

The case of a 60-year-old male patient, who survived severe organophosphorus poisoning, and subsequently developed platypnoea and orthodeoxia is described. The patient was mechanically ventilated for a long period of time in the intensive care unit. During the weaning trial, he developed platypnoea and orthodeoxia (PaO2 85 mmHg in recumbency, and 40 mmHg in upright position). Interestingly, the patient's orthodeoxia was alleviated on continuous positive airway pressure (CPAP) treatment. This is a newly described cause of the platypnoea-orthodeoxia syndrome. The possible pathophysiological mechanisms are discussed and a review of the reported abnormal states associated with this condition is presented.