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Chronic Obstructive Pulmonary Disease (COPD) is very a common, with great morbidity and mortality, disease.Since the beginning of the disease cannot be detected with precision and by using only FEV1 to monitor the evolution of the disease, the Natural History of COPD is rather obscure and sometimes controvercial.Therefore, the terms EARLY COPD and MILD COPD have been used indistinguishably in the medical literature.In this review we discuss the two terms trying to clarify some of the definition issues, starting with a synopsis of the Naturel History of the disease.We recommend to use the term EARLY COPD for the pre-clinical stage of the disease (stage 0) and the term MILD COPD when the diagnosis is confirmed by spirometry and FEV1 is above 80% predicted. However, COPD is a complex disease and spirometric evaluation alone (MILD COPD, stage I), cannot fully describe the clinical status of the patient.We conclude that biomarkers to detect the starting point and been able to follow the natural history of the disease more accurately, beyond FEV, are urgently needed.

// Ismini Lasithiotaki 1, 2 , Eliza Tsitoura 2, 3 , Anastasios Koutsopoulos 4 , Eleni Lagoudaki 4 , Chara Koutoulaki 2 , George Pitsidianakis 1 , Demetrios A. Spandidos 3 , Nikolaos M. Siafakas 1 , George Sourvinos 3, * , Katerina M. Antoniou 1, 2, * 1 Department of Thoracic Medicine, University Hospital, Medical School, University of Crete, Heraklion 71110, Greece 2 Laboratory of Cellular and Molecular Pneumonology, Medical School, University of Crete, Heraklion Crete 71110, Greece 3 Laboratory of Clinical Virology, Medical School, University of Crete, Heraklion Crete 71110, Greece 4 Department of Pathology, Medical School, University of Crete, Heraklion Crete 71110, Greece * These authors have contributed equally to this work Correspondence to: George Sourvinos, email: sourvino@med.uoc.gr Keywords: merkel cell polyomavirus, non-small cell lung cancer, microRNAs, signalling pathways Received: April 23, 2016 Accepted: July 19, 2016 Published: August 11, 2016 ABSTRACT Merkel Cell Polyoma Virus (MCPyV) infection has been associated with non-small cell lung cancer (NSCLC). Viruses can manipulate cellular miRNAs or have a profound impact on cellular miRNA expression to control host regulatory pathways. In this study, we evaluated the expression profiles of cancer-associated and virally affected host microRNAs miR-21, miR-145, miR-146a, miR-155, miR-302c, miR-367 and miR-376c in a series of NSCLC tissue samples as well as in samples from “healthy” sites, distant from the tumour region that were either positive or negative for MCPyV DNA. miR-21 and miR-376c were significantly upregulated whereas miR-145 was significantly downregulated in the MCPyV+ve samples compared to the MCPyV-ve tumour samples. Overall, miR-21 and miR-376c expression was higher in tumour compared to healthy tissue samples. No association was observed between the miR-155, miR-146a, miR-302c and miR-367 levels and the presence of MCPyV. The expression of miR-21 target genes ( Pten, Bcl-2, Daxx, Pkr, Timp3) , miR-376c ( Grb2, Alk7 , Mmp9 ) and miR-145 ( Oct-4, Sox2 , Fascin1 ) and their associated pathways ( Braf, Akt-1, Akt-2, Bax, Hif1a, p53 ) was altered between MCPyV+ve tumor samples and their corresponding controls. These results show a novel association between miR-21, miR-376c and miR-145 and their host target genes with the presence of MCPyV, suggesting a mechanism of virus-specific microRNA signature in NSCLC.

Background Increased protein citrullination and peptidylarginine deiminases (PADIs), which catalyze the citrullination process, are central in Rheumatoid arthritis pathogenesis and probably involved in the initial steps towards autoimmunity. Approximately, 10% of RA patients develop clinically significantly ILD. A possible shared role of protein citrullination in rheumatoid arthritis associated interstitial lung disease (RA-ILD), and idiopathic pulmonary fibrosis (IPF) pathogenesis remains unclear. Methods We evaluated PADI2 and PADI4 mRNA expression in bronchoalveolar lavage fluid (BALF) cells of 59 patients with IPF, 27 patients RA-ILD and 10 healthy controls. PADI 2 and 4 expression was analyzed by western blot and immunohistochemistry. Citrullinated protein levels were also quantified. Results PADI4 mRNA and protein levels were higher in RA-ILD and IPF than controls. Furthermore, PADI4 mRNA levels showed an increase among smokers in RA-ILD. PADI4 expression was detected in granulocytes and macrophages in all groups, with the strongest cytoplasmic expression observed in granulocytes in RA-ILD and IPF. PADI2 mRNA and immunostaining of BAL cells, were similar in all groups among smokers. Overall, stronger staining was observed in current smokers. Citrullinated peptides were significantly increased in IPF compared to RA-ILD and controls. In RA-ILD, protein citrullination strongly correlated with PADI4 expression and anti-citrullinated protein antibodies (ACPAs). Conclusions These results suggest that the citrullination pathway is upregulated in IPF and in RA-ILD. Electronic supplementary material The online version of this article (10.1186/s12931-017-0692-9) contains supplementary material, which is available to authorized users.

Lung hyperinflation is the main pathophysiological mechanism significantly reducing the Quality of Life (QoL)and contributing to increased morbidity and mortality of the emphysematous patients. Therefore, the prime aim of the management of those patients is the deflation of their lungs. There are a number of treatments proven effective to reduce hyperinflation, such as,pharmacotherapy (bronchodilators/deflators), rehabilitation and surgical volume reduction. Recently, methods to reduce lung volume by a bronchoscopic approach had been developed. We review these methods and in particular the endobronchial valves, coils and the sclerosing therapies and provide the current status, as well as, an algorithm of selection of the appropriate patients. We conclude that further large studies are needed in order to verify the effectiveness of these methods and identify the appropriate group of patients that can be benefit by each of these bronchoscopic techniques.

Background Tiotropium bromide, once daily, long-acting anticholinergic bronchodilator is either administered by handihaler metered dose inhaler or by respimat soft mist inhaler. It has been proved to improve lung function, daily symptoms and quality of life and to decrease the exacerbation and hospitalisation rate of patients with Chronic Obstructive Pulmonary Disease (COPD). Although the efficacy of both formulations is undeniable, concerns have been raised on their effect on cardiovascular and general mortality. Methods Two independent authors systematically reviewed Medline, Scopus, Cochrane Library and ClinicalTrials.gov to collect clinical trials, observational studies and meta-analyses studying the safety of tiotropium. The reference list of all the included studies were also reviewed. Results Limited, early studies suggested a potential increase in cardiovascular and general mortality associated with tiotropium handihaler, but these data were outweighed by following larger trials, real-life studies and meta-analyses which proved the opposite. On the other hand, data on tiotropium respimat (5 μg) have been contradictory, with different studies suggesting increased cardiovascular and general mortality compared to handihaler (18 μg) or placebo, especially in patients with comorbid diseases. TIOSPIR trial suggests comparable safety of the two formulations. However the exclusion of patients with pre-existing unstable cardiovascular disease, moderate or severe kidney disease or any other significantly disease may limit the generizability of these results. Conclusion Although the two tiotropium formulations have similar efficacy, current data cannot prove safety equivalence, since respimat may be associated with increased cardiovascular and general mortality, especially in patients with comorbid diseases.

We aimed to compare the effect of intensiveversusstandard interventions on continuous positive airway pressure (CPAP) adherence 2 years after CPAP initiation, as well as on sleepiness, quality of life, depression, hospitalisation and death rate due to cardiovascular disease (CVD).3100 patients with newly diagnosed sleep apnoea were randomised into the standard group, with usual follow-up care, or the intensive group, with additional visits, telephone calls and education. Subjective daytime sleepiness (Epworth Sleepiness Scale; ESS), quality of life (36-item Short Form Health Survey; SF-36) and the patient’s level of depression (Beck Depression Inventory; BDI) were recorded before and 2 years after CPAP initiation, together with CVD hospitalisations and death rate.2 years after CPAP initiation, the intensive group used CPAP significantly more than the standard group (6.9versus5.2 h per night; pCPAP usage can be improved by both intensive and standard patient support. However, the patients who received intensive CPAP support had significantly better ESS, BDI and SF-36 scores, and lower cardiovascular morbidity and mortality, suggesting that an intensive programme could be worthwhile.

Background and objective A combined pulmonary fibrosis/emphysema syndrome has been proposed, but the basis for this syndrome is currently uncertain. The aim was to evaluate the prevalence of emphysema in idiopathic pulmonary fibrosis (IPF) and rheumatoid lung (rheumatoid arthritis-interstitial lung disease (RA-ILD)), and to compare the morphological features of lung fibrosis between smokers and non-smokers. Methods Using high-resolution computed tomography, the prevalence of emphysema and the pack-year smoking histories associated with emphysema were compared between current/ex-smokers with IPF (n = 186) or RA-ILD (n = 46), and non-chronic obstructive pulmonary disease (COPD) controls (n = 103) and COPD controls (n = 34). The coarseness of fibrosis was compared between smokers and non-smokers. Results Emphysema, present in 66/186 (35%) patients with IPF and 22/46 (48%) smokers with RA-ILD, was associated with lower pack-year smoking histories than in control groups (P

Background Growth factors mediate various cellular responses to environmental stimuli. Specifically, exposure of lung epithelium to oxidative stress induced by cigarette smoke stimulates aberrant epidermal growth factor receptor (ERBB) family activation. This study's objective was to evaluate the expression of ERBB1–4 receptors in the lung tissue of smokers with or without chronic obstructive pulmonary disease (COPD). Materials and methods ERBBs expression was measured by microarray analysis in lung tissue samples from five patients with COPD and five non-COPD smokers, and by quantitative real-time PCR in additional 20 patients with COPD (GOLD stage II), 15 non-COPD smokers and 10 nonsmoker controls. Results Microarray data analysis revealed that ERBB receptors expression was elevated in patients with COPD compared to non-COPD smokers, ranging from 1·62- to 2·45-fold, (P

The multi-organ involvement of mitochondrial diseases means that patients are likely to be more vulnerable to sleep disturbances. We aimed to assess if early recognition and treatment of obstructive sleep apnea (OSA) in patients with Leigh disease may influence primary disease outcome. We describe a case of adult-onset Leigh disease presenting as severe brainstem encephalopathy of subacute onset. Based on the clinical symptoms that developed after the appearance of the neurological disease, an attended overnight polysomnography examination was performed. A marked clinical recovery was seen after administration of high doses of thiamine, coenzyme Q, L-carnitine, and vitamins C and E, combined with effective treatment with continuous positive airway pressure for the underlying severe obstructive sleep apnea (OSA). The latter condition was diagnosed on the basis of suggestive symptoms that appeared a few weeks before the establishment of the neurological disease. The improvement in the neurological disease (based on clinical and brain MRI features) with the appropriate medical treatment also resulted in a significant improvement in the OSA. Early recognition and treatment of sleep apnea may not only improve sleep and overall quality of life but also ameliorate the deleterious effects of nocturnal desaturations on the neurological features. This may be crucial for disease outcome when added to the generally advised pharmacological therapy.

According to the American Thorasic Society (ATS)/European Respiratory Society (ERS) Statement, chronic obstructive pulmonary disease (COPD) is defined as a preventable and treatable disease with a strong genetic component, characterized by airflow limitation that is not fully reversible, but is usually progressive and associated with an enhanced inflammatory response of the lung to noxious particles or gases. The main features of COPD are chronic inflammation of the airways and progressive destruction of lung parenchyma and alveolar structure. The pathogenesis of COPD is complex due to the interactions of several mechanisms, such as inflammation, proteolytic/antiproteolytic imbalance, oxidative stress, DNA damage, apoptosis, enhanced senescence of the structural cells and defective repair processes. This review focuses on the effects of oxidative DNA damage and the consequent immune responses in COPD. In susceptible individuals, cigarette smoke injures the airway epithelium generating the release of endogenous intracellular molecules or danger-associated molecular patterns from stressed or dying cells. These signals are captured by antigen presenting cells and are transferred to the lymphoid tissue, generating an adaptive immune response and enhancing chronic inflammation.

// Eliza Tsitoura 1,2 , Athol U. Wells 3 , Kostantinos Karagiannis 1 , Ismini Lasithiotaki 1 , Eirini Vasarmidi 1,4 , Eleni Bibaki 1,4 , Chara Koutoulaki 1 , Hiroe Sato 3 , Demetrios A. Spandidos 2 , Nikolaos M. Siafakas 1 , George Sourvinos 2 and Katerina M. Antoniou 1,4 1 Laboratory of Molecular and Cellular Pneumonology, Medical School, University of Crete, Heraklion, Crete, Greece 2 Department of Clinical Laboratory Medicine, Laboratory of Clinical Virology, Medical School, University of Crete, Heraklion, Crete, Greece 3 Interstitial Lung Disease Unit, Royal Brompton Hospital, Imperial College, SW3 6NP, London, UK 4 Department of Thoracic Medicine, Interstitial Lung Disease Unit, University Hospital of Heraklion, Heraklion, Crete, Greece Correspondence to: Katerina M. Antoniou, email: // Keywords : IPF, microRNA, bronchoalveolar lavage fluid, collagen, AKT, Immunology and Microbiology Section, Immune response, Immunity Received : August 02, 2016 Accepted : October 04, 2016 Published : October 18, 2016 Abstract MicroRNA signatures of BAL cells and alveolar macrophages are currently lacking in IPF. Here we sought to investigate the expression of fibrosis-related microRNAs in the cellular component of the BAL in IPF. We thus focused on microRNAs previously associated with fibrosis (miR-29a, miR-29b, miR-29c, let-7d, and miR-21) and rapid IPF progression (miR-185, miR-210, miR-302c-3p miR-376c and miR-423-5p). Among the tested microRNAs miR-29a and miR-185 were found significantly downregulated in IPF while miR-302c-3p and miR-376c were not expressed by BAL cells. Importantly, the downregulation of miR-29a inversely correlated with the significantly increased levels of COL1A1 mRNA in IPF BAL cells. Collagen 1 a was found mainly overexpressed in alveolar macrophages and not other cell types of the BAL by immunofluorescence. In view of the downregulation of miR-185, we tested the response of THP-1 macrophages to profibrotic cytokine TGFb and observed the downregulation of miR-185. Conversely, proinflammatory stimulation lead to miR-185 upregulation. Upon examination of the mRNA levels of known miR-185 targets AKT1, DNMT1 and HMGA2, no significant correlations were observed in the BAL cells. However, increased levels of total AKT and AKT ser473 phosphorylation were observed in the IPF BAL cells. Furthermore, miR-185 inhibition in THP-1 macrophages resulted in significant increase of AKT ser473 phosphorylation. Our study highlights the importance of BAL microRNA signatures in IPF and identifies significant differences in miR-185/AKT and miR-29a/collagen axes in the BAL cells of IPF patients.

Introduction: COPD is a complex disease requiring multifaceted management. No data are available on the combined assessment of COPD severity in Greece. Aim: To assess the airflow obstruction severity and its impact on patient-centered outcomes in Greek COPD patients. Methods: Multicentre, observational study in COPD patients of any severity and treatment. Data were collected from July to November 2014 from medical records and patient interviews in a single visit by pulmonologists, in hospital and private practices. Anthropometric, spirometric and patient reported outcomes were collected. Results: Of 604 enrolled patients, 600 were analysed (men 79.3%; mean age 70.1±9.8 years, mean BMI 27.2±4.4 kg/m 2 ). Most patients had moderate or severe airflow obstruction (48.7% GOLD 2, 33.8% GOLD 3) and symptoms (mean mMRC 1.8±1.1, mean CCQ 2.1±1.1, mean BODEx 2.4±1.8). No exacerbations in the previous year were reported by 27% of patients. Of those reporting exacerbations, 38.3% reported one, 22.2% two and 12.5% three or more. Exacerbations were treated with corticosteroids (81.0% inhaled, 40.6% systemic) and antibiotics (89.8%). As per combined GOLD assessment, 23.3% of patients were Group A, 14.3% Group B, 18.8% Group C and 43.5% Group D. Almost all patients received treatment, mainly combinations (LABA+LAMA+ICS, 24.6%; LABA+LAMA, 17.2%). Patients reported healthcare resources use; 57.7% for COPD, 44.7% for comorbidities. Conclusion: The burden of COPD in Greece appears significant. Most diagnosed COPD patients suffer from moderate to severe airflow obstruction. These outcomes may help optimise patient identification, phenotyping and treatment personalisation.

Objective: SAA is frequently inadequately controlled despite intensive guideline-based therapy. Disease control can be improved by targeting allergic inflammatory processes underlying its pathogenesis. Methods: SMILE was a prospective, multicenter, observational, study designed to assess the clinical effects of omalizumab over a period of 18 months of treatment in everyday clinical practice. Clinical variables including quality of life (QoL), asthma symptoms, exacerbations, hospitalizations, visits to ER and lung function were evaluated at baseline and at pre-specified time points. Work productivity and activity impairment was measured through the WPAI-AA questionnaire. Safety data were also recorded. Results: Overall 169 SAA patients were recruited. Omalizumab therapy resulted in significant improvements in QoL; mean AQLQ score increase of 2.41; (p Conclusions: The results of the SMILE study (albeit being single-arm) suggest therapeutic benefits recorded in a “real-world” setting are consistent with the ones demonstrated in omalizumab9s randomized controlled trials, with a similar safety and tolerability profile. The study was sponsored by Novartis.

MicroRNA expression signatures of the BALF cells and in particular the alveolar macrophages are currently lacking despite the extensive characterisaion of microRNA expression in IPF tissues, isolated fibroblasts and mouse lungs. Here we sought to investigate the existence of IPF associated microRNA expression in the cellular component of the BAL fluid and we thus focused in the expression of microRNAs previously associated with fibrosis (miR-29a, b, c, let-7d, and miR-21) and rapid IPF progression (miR-185, miR-210, miR- 302c-3p miR-376c and 423-5p). IPF BAL fluid cells displayed a pro-fibrotic profile with miR-29a downregulation and increased expression of its target, COL1A1 mRNA. Furthermore, miR-29a downregulation was significantly associated with lower DLCO% and eosinophil infiltration of the alveolar spaces. Tumour-suppressor miR-185 was also significantly downregulated in IPF BAL fluid cells. MiR-185 downregulation was associated with significantly increased AKT total protein levels and AKT ser473 phosphorylation in the IPF group relative to the controls. The role of miR-185 in AKT activation was confirmed in THP-1 cells transfected with a miR-185 inhibitor that resulted in a significant increase in AKT1 mRNA and AKT ser473 phosphorylation. Our study identifies significant differences in miR-29a/collagen and miR-185/AKT axes in the BALF cells of IPF patients and highlight the relevance and importance of BALF microRNA signatures in IPF.

The classical definition of Chronic Obstructive Pulmonary Disease (COPD) as a lung condition characterized by irreversible airway obstruction is outdated. The systemic involvement in patients with COPD, as well as the interactions between COPD and its comorbidities, justify the description of chronic systemic inflammatory syndrome. The pathogenesis of COPD is closely linked with aging, as well as with cardiovascular, endocrine, musculoskeletal, renal, and gastrointestinal pathologies, decreasing the quality of life of patients with COPD and, furthermore, complicating the management of the disease. The most frequently described comorbidities include skeletal muscle wasting, cachexia (loss of fat-free mass), lung cancer (small cell or non-small cell), pulmonary hypertension, ischemic heart disease, hyperlipidemia, congestive heart failure, normocytic anemia, diabetes, metabolic syndrome, osteoporosis, obstructive sleep apnea, depression, and arthritis. These complex interactions are based on chronic low-grade systemic inflammation, chronic hypoxia, and multiple common predisposing factors, and are currently under intense research. This review article is an overview of the comorbidities of COPD, as well as their interaction and influence on mutual disease progression, prognosis, and quality of life.

Summary Background New lymphatic vessels are associated with tissue injury and repair. Recent studies have shown increased lymphatic follicles formation in the lungs of COPD patients. We hypothesized that lymphatic vascular remodeling could be part of COPD pathogenesis. Aim To investigate the lymphangiogenetic process in COPD we measured the lymphatic microvessel density (LMVD), the lymphatic invasion (L.I), and their correlation with clinical and laboratory parameters. Methods Lung tissue from 20 COPD patients and 20 non-COPD smokers was immunohistochemically stained for D2-40 (lymphatic endothelial cell marker), and LYVE-1 (lymphatic endothelial hyaluronan receptor 1). Both groups had similar age and smoking history. Results D2-40 and LYVE-1 were expressed in all specimens. Lymphatic invasion was presented only in COPD specimens. Lymphatic microvessel density (LMVD) as revealed by D2-40 and LYVE-1 markers was statistically significantly higher in COPD patients when compared with non-COPD smokers. Both markers (D2-40, LYVE-1) were correlated with FEV1 (% pred) ( R 2 = 0.415, R 2 = 0.605, respectively). Conclusions We report for the first time high lymphatic microvessel density and lymphatic invasion in COPD patients, related to the degree of airway obstruction. Our findings could provide novel insights in the pathogenesis of the disease.

Background Acquired somatic mutations induced by oxidative stress may contribute to the molecular pathogenesis of chronic inflammatory airway diseases. The objective of this study was to assess the intensity of oxidative DNA damage and the presence of microsatellite DNA instability (MSI), a marker of acquired somatic mutations, in patients with COPD, patients with noncystic fibrosis bronchiectasis, and control subjects. Methods Induced sputum and peripheral blood from 97 subjects were analyzed; 36 patients with COPD, 36 patients with bronchiectasis, 15 smokers without COPD, and 10 healthy control subjects. DNA was extracted and analyzed for MSI. 8-hydroxy-2′-deoxyguanosine (8-OHdG), a specific marker of oxidant-induced DNA damage, was measured in serum and sputum supernatants. Results None of the patients with bronchiectasis or control subjects (non-COPD smokers, healthy subjects) exhibited any genetic alteration. In contrast, MSI was found in 38% of COPD specimens. Sputum 8-OHdG was statistically significantly increased in COPD when compared with subjects with bronchiectasis ( P = .0002), smokers without COPD ( P = .0056), and healthy subjects ( P = .0003). Sputum 8-OHdG in MSI-positive patients with COPD differed significantly from that of MSI-negative patients with COPD ( P = .04) and smokers without COPD ( P = .008), but was not statistically different ( P = .07) among MSI-negative patients with COPD and smokers without COPD. Serum 8-OHdG was significantly increased in MSI-positive compared with MSI-negative patients with COPD ( P = .001), but was not statistically significant in smokers without COPD ( P = .09). Serum 8-OHdG was increased in smokers without COPD compared with MSI-negative patients with COPD ( P = .009). Conclusions There is a clear disparity in COPD regarding oxidant-induced DNA damage and somatic mutations. This may reflect a difference in the oxidative stress per se or a deficient antioxidant and/or repair capacity in the lungs of patients with COPD.

Background YKL-40 is an extracellular matrix glycoprotein with a significant role in tissue inflammation and remodeling. MIP-1a has chemotactic and pro-inflammatory properties, and is induced by YKL-40 in several lung disorders. The aim of this study was to determine the levels of YKL-40 and MIP-1a in blood serum and pleural fluids of various pulmonary diseases, and to evaluate their potential role as differential diagnosis biomarkers. Methods We recruited 60 patients (age: 62.5 ± 20.6 years) with pleural effusions: 49 exudates and 11 transudates (T). Exudates were further classified based on the underlying disease: ten with tuberculosis (TB), 13 with lung cancer (LCa), 15 with metastatic cancer (MCa) of non-lung origin and 11 with parapneumonic (PN) effusions. YKL-40 and MIP-1a levels were measured by ELISA. Results Pleural YKL-40 levels (ng/ml) were similar among all patient groups (TB: 399 ± 36, LCa: 401 ± 112, MCa: 416 ± 34, PN: 401 ± 50, T: 399 ± 42, p = 0.92). On the contrary, YKL-40 was significantly lower in the serum of TB patients (TB: 58 ± 22, LCa: 212 ± 106, MCa: 254 ± 140, PN: 265 ± 140, T: 229 ± 123, p

Asthma in older adults affects quality of life and results in a higher hospitalization rate and mortality. In common clinical practice, asthma in the elderly is underdiagnosed and undertreated or overdiagnosed and mistreated. The age-related reduction in perception of shortness of breath and the high incidence of comorbidities make the diagnosis and management more difficult and challenging for the physicians. Chronic obstructive pulmonary disease (COPD) is usually easy to distinguish from asthma, but sometimes the distinction from late-onset asthma in older patients, particularly in cigarette smokers, is difficult and may be impossible. Both diseases are characterized by the presence of airflow obstruction but have distinct pathogenesis, inflammatory pattern, and prognosis. The distinction between Asthma and COPD based simply on spirometric parameters is difficult especially in the elderly asthmatics. The combination of lung function testing, bronchial hyperresponsiveness (BHR) and atopy status, HRCT scans, and the newly developed biological techniques, allowing the assessment of biomarker profiles, could facilitate the distinction between these diseases.

Summary Background Experimental data have provided evidence that progenitor cells of bone marrow (BM) origin may play a role in the fibrogenic process of the lung. Objective To probe the possible involvement of BM mesenchymal stem cells (MSCs) in the pathophysiology of Idiopathic Pulmonary Fibrosis (IPF) by investigating the molecular profile of these cells. Design BM MSCs were studied in 10 IPF patients and 10 healthy controls. MSCs were identified by their immunophenotypic characteristics and their potential to differentiate towards adipocytes/osteocytes/chondrocytes. We evaluated the mRNA expression of genes involved in the lung injury of IPF, namely the vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), transforming growth factor beta-1 (TGF-β1) and the axis stromal-cell-derived factor-1 (SDF-1)/CXCR4 in BM MSCs using quantitative RT-PCR. Results The BM MSCs of IPF patients displayed normal immunophenotypic characteristics and differentiation potential. No statistically significant difference was found between patients and controls in VEGF and FGF mRNA expression. TGF-β1 was not expressed in either patients or controls. A significant increase in SDF-1-TR1 and CXCR4 mRNA expression was detected in IPF patients (1.6 × 10 25 ± 1.2 × 10 25 and 3.1 × 10 7 ± 3.1 × 10 7 , respectively) compared to controls (0.32 × 10 25 ± 0.07 × 10 25 and 1.67 × 10 7 ± 0.30 × 10 7 , respectively) ( p = 0.001 and p = 0.001, respectively) whereas SDF-1 levels in MSC supernatants were similar in patients and controls. Conclusions The increased CXCR4 expression by patient MSCs suggests that the BM is probably implicated in the pathophysiology of IPF by mobilizing MSCs in response to or preceding lung injury. The potential role of BM MSCs in IPF is another interesting field for further investigation.

Eur J Clin Invest 2010; 40 (11): 968–975 Abstract Background C-reactive protein (CRP) is recognized as a potential factor implicated in atherogenesis and associated cardiovascular morbidity. The aim of our study was to assess the CRP evolution during 1-year follow-up period in obstructive sleep apnoea (OSA) patients under CPAP treatment. Methods Five hundred and twenty-eight patients with newly diagnosed moderate to severe OSA were included. CRP was assessed before CPAP initiation and at the 3rd, 6th and 12th month of the follow-up period. Patients were divided into good and poor CPAP compliance groups. Results A significant reduction in CRP levels was observed after CPAP therapy (0·74 ± 0·62 mg dL−1 vs. 0·31 ± 0·29 mg dL−1, P

Purpose of the study: Several studies in patients with lung cancer have shown that epidermal growth factor receptor regulates various tumorigenic processes through the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin and Ras/Raf/Mek/Erk (mitogen-activated protein kinase (MAPK)) signalling pathways. The aim of our study is to evaluate whether these pathways are implicated in the pathogenesis of idi- opathic pulmonary fibrosis (IPF) and to seek indirect evidence of a common pathogenetic pathway with lung cancer. m-RNA expression of oncogenes participating in these two signaling pathways, as well as the combined m-RNA expression of the suppressor genes R-kip and p53 in lung tissue of patients with IPF were evaluated. Basic procedures: The study population was composed by two distinct groups. Patients with IPF (n = 25) and control subjects who underwent thoracic surgery for reasons other than interstitial lung disease (n = 10). Expression analysis of the aforementioned oncogenes and suppressor genes was performed using real-time reverse transcription polymerase chain reaction. Main findings: We found no difference in the overall m- RNA expression between controls and IPF in both investigated pathways. However, Braf has been overexpressed in IPF samples (P = 0.01) in contrast with K-ras that has been found downregulated (P < 0.001) in comparison with controls. Principal conclusions: These findings cannot exclude the hypothesis of involvement of Akt and MAPK sig- nalling pathways in pathogenesis of IPF. However, further investigation is needed in order to verify these data.

Background Instability of the Microsatellite DNA Instability (MSI) and Loss of Heterozygosity (LOH) have been previously detected in sputum cells of COPD patients. However, the particular cell subpopulation exhibiting genetic instability in COPD was uncertain. The aim of this study was to determine which cell type expresses Microsatellite DNA Instability in sputum and BALF samples from COPD patients. Methods Thirty-five COPD patients and 30 non-COPD smokers were studied. Sputum was induced from 20 COPD patients and 20 non-COPD smokers and BALF was obtained from 15 COPD patients and 10 non-COPD smokers. The sputum cell pellet and BALF samples were processed using immunomagnetic technology to separate antibody-specific cell subpopulations, using CD45 + for leukocytes, Epithelial enrich (MACS) for sputum epithelial cells and HEA-human epithelial antigen-(Dynal) for BAL epithelial cells. Microsatellite DNA amplification was performed using specific primers, namely G29802, D6S2223, D6S344, D6S263, D5S207, D13S71, RH70958, and D17S250. The presence of MSI and/or LOH was analyzed with LI-COR Saga GT Microsatellite Analysis Software. Measurements and main results None of the non-COPD smokers exhibited any genetic alteration. MSI and LOH were found in 15 cases (8 MSI and 7 LOH) in sputum and BAL samples. MSI and/or LOH were revealed only in the epithelial barrier cells. LOH was detected in D5S207, D6S344, G29802 and D17S250 microsatellite markers, while MSI in D13S71, D5S207 and D6S344. The entire leukocyte subpopulation exhibited no genetic alteration. Conclusions Our results support the hypothesis that chronic inflammation and oxidative burden in COPD can lead to DNA damage of the lung epithelial barrier cells, detected at the Microsatellite DNA level. Further studies are required to investigate the significance of these findings in the pathogenesis of COPD.

Background Little is known about sleep quality in patients with acute coronary syndromes (ACS) admitted to the coronary care unit (CCU). The aim of this study was to assess nocturnal sleep in these patients, away from the CCU environment, and to evaluate potential connections with the disease process. Methods Twenty-two patients with first ever ACS, who were not on sedation or inotropes, underwent a full-night polysomnography (PSG) in our sleep disorders unit within 3 days of the ACS and follow-up PSGs 1 and 6 months later. Results PSG parameters showed a progressive improvement over the study period. There was a statistically significant increase in total sleep time (TST), sleep efficiency, slow wave sleep (SWS), and rapid eye movement (REM) sleep, while arousal index, wake after sleep onset (WASO) and sleep latency decreased. Six months after the acute event, sleep architecture was within the normal range. Conclusions Patients with ACS have marked alterations in sleep macro- and micro-architecture, which have a negative influence on sleep quality. The changes tend to disappear over time, suggesting a relationship with the acute phase of the underlying disease.

SummaryEndothelin-1 (ET-1) has been implicated in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD) for establishing an inflammatory loop in the respiratory mucosa that could become independent from the initial irritant factor. Common causes of COPD exacerbations are associated with elevated ET-1 sputum concentrations. Genetic variants of the ET-1 gene, that lead to elevated ET-1 peptide levels, have not been investigated in COPD.We performed a case control, genetic study to assess possible associations of two polymorphisms of the ET-1 gene, an adenine insertion (+134 insA/delA) and a guanine to thymine transversion (G198T) with the COPD phenotype and disease severity.The genotypes of 209 subjects, 107 COPD smokers (patients) and 102 non-COPD smokers (controls) were examined. Statistical analysis revealed that the 3A/4A and 4A/4A genotypes were more common (P

Objectives High incidence of genetic alterations at the microsatellite (MS) DNA level has been reported in asthmatic adults. Working Hypothesis The aim of this study was to investigate whether microsatellite instability (MSI) and loss of heterozygosity (LOH) were detectable phenomena in children with asthma. Methodology DNA was extracted from sputum and blood cells of 27 children (10.8 ± 2.5 years) with mild to moderate asthma, and from 8 healthy, never-smoked young adults. Fourteen polymorphic MS markers, namely D5S207, D5S820, D5S637, D6S344, D6S2223, D6S263, SGC35231, D11S1253, D11S1337, D11S97, USAT24G1, D13S273, D14S258, and D14S292, located on chromosomes (chr) 5q, 6p, 11q, 13q, and 14q were used to assess MSI and LOH. Results None of the healthy subjects exhibited any genetic alteration. Five out of 27 children (18.5%) exhibited MSI or LOH in sputum cells versus blood samples from which 3 in the marker USAT24G1 (chr 13q14.1), 1 in the marker D14S258 (chr 14q23-q24.3), and 1 in the marker D5S637 (chr 5q12-q13). Compared to a previous study, with asthmatic adults, whereas MSI and/or LOH was exhibited in ∼60% of the cases, the current study reported

Background Dendritic cells (DCs) have been reported to be increased in the small airways of patients with COPD, but the maturity status of these cells is unclear. We have quantified the numbers of cells expressing markers associated with DC maturation. Methods Lung tissue was obtained at resection for lung cancer from 41 patients with COPD (30 current smokers and 11 ex-smokers; 32 steroid-treated patients and 9 steroid-naive patients), 19 ex-smokers without COPD and 9 never-smokers without COPD. Tissue sections were immunostained for CD1a to mark immature DCs, and for CD83, fascin, and DC-lysosome-associated membrane protein (DC-LAMP) to delineate mature DCs. Results The volume density (ie, the volume of DCs as the percentage volume of the airway wall) comprising CD83+ DCs was significantly reduced in patients with COPD (median, 0; range, 0 to 5.1%) vs smokers (median, 2.8%; range, 0 to 10.2%) and never-smokers (median, 1.9%; range, 0.8 to 5.1%) without COPD (p = 0.000 and 0.012, respectively). Using a semiquantitative score for the alveolar wall, CD83+ DCs also were decreased in patients with COPD (median, 0; range, 0 to 2%) vs smokers (median, 1%; range, 0 to 2%) and never-smokers (median, 1%; range, 0.7 to 2%) without COPD (p = 0.004 and 0.04, respectively). No differences were detected in CD83+ DCs between current smokers and ex-smokers with COPD or between steroid-treated and steroid-naive patients. No differences were detected in CD1a+ DCs. Fascin and DC-LAMP were found to have poor specificity for mature DCs. Conclusions COPD is associated with decreased numbers of (mature) CD83+ DCs in small airways and alveoli. The relevance of such a reduction on pulmonary immune responses requires further investigation.

Chronic obstructive pulmonary disease (COPD) is generally thought to depend on an aberrant immune response to a noxious or infectious agent, which may cause chronic inflammation. However, the initiation of this abnormal response is not fully understood. Here, we propose a new hypothesis for the beginning of COPD, that the immune response to inhaled agents, mainly cigarette smoke, is directed toward the airway epithelium, due to oxidative DNA damage of the lung epithelial barrier cells (LEBCs). The steps of this model are as follows. 1) Cigarette smoke induces oxidative DNA damage of LEBCs. 2) The acquired mutations are expressed at the microsatellite DNA level of LEBCs. 3) The altered LEBCs are recognised by dendritic cells (DCs) as "nonself". DCs travel, with the new information, to the lymph nodes, presenting it to the naïve T-lymphocytes. 4) A predominant CD8+ cytotoxic T-lymphocyte proliferation occurs. The CD8+ cells, by releasing perforin and granzymes, attack the altered LEBCs activating cell death cascades. Obviously, the above scenario needs further experimental exploration. However, it is an attractive model for the initiation of the abnormal inflammation in COPD, comprising oxidative DNA damage of LEBCs and host immune response.

The prevalence of laryngopharyngeal reflux (LPR) has been constantly rising in the western world and affects today an alarmingly high percentage of the general population. Even though LPR and gastroesophageal reflux disease (GERD) are both the product of gastroesophageal reflux and seem to be sibling disorders, they constitute largely different pathological entities. While GERD has been for a long time identified as a source of esophageal disease, LPR has only recently been associated with head and neck disorders. Despite the high incidence of LPR and its great impact on patients' quality of life, little is known regarding its pathogenesis. On the other hand, studying the molecular and genetic basis of a disease is of fundamental importance in medicine as it offers better insight into the pathogenesis and opens new, disease-specific therapeutic trends. The aim of this study is to enlighten any known or suspected molecular mechanisms that contribute to the pathogenesis of LPR, and to suggest new trends for future research.

Objective: Genetic alterations, such as microsatellite instability (MSI) and loss of heterozygosity (LOH), have been detected in various inflammatory diseases, providing evidence that acquired somatic mutations might play a role in the aetiopathogenesis of chronic inflammatory conditions. The aim of this study is to assess the presence of MSI and/or LOH in nasal cytology of patients with nasal polyps. Study Design: Prospective case-controlled basic science experiment utilizing human blood and human nasal brush samples. Methods: Nasal brush samples and peripheral blood from 12 patients with nasal polyps were analyzed. DNA was extracted and analyzed for MSI and LOH using the following microsatellite markers: D2S2113, D6S344, D6S1002, D11S1253, D11S480, USAT24G1, and D13S273, harboring potential susceptibility genes for nasal polyposis. Microsatellite DNA analysis was also performed in 7 control subjects. Results: MSI or LOH were revealed in 3 specimens of the nasal polyps group. Among these there were 2 cases of LOH, one for marker D11S1273 and one for D13S273, and one case of MSI in marker USAT24G1. Each one of these alterations was detected in a different patient. None of the control subjects exhibited any genetic alterations in the 7 markers tested. Conclusions: This is the first time that microsatellite genetic alterations are reported in nasal disease. The presence of such alterations suggests that acquired genomic somatic mutations might play a role in the pathogenesis of nasal polyps. Laryngoscope, 2009

Pulmonary fibrosis is a devastating disease with few treatment options. Angiogenesis that leads to aberrant vascular remodeling is regulated by an opposing balance of angiogenic and angiostatic factors. The present study aims to evaluate the role of three angiogenic (IL-8, ENA-78 and GRO-a) and three angiostatic (MIG, IP-10, ITAC) chemokines in bronchoalveolar lavage fluid (BALF), before and after treatment with Interferon gamma-1b (IFN gamma-1b).We studied prospectively 20 patients (16 males, 4 females) of median age 68 years (range, 40-75) with histologically confirmed IPF/UIP. Patients were assigned to receive IFN gamma-1b 200 microg sc thrice a week. Angiogenic and angiostatic mediators' levels were measured by ELISA kits.The levels of the angiogenic chemokines significantly decreased after 12 months (mo) of IFN-gamma-1b treatment (median values in pg/ml, IL-8/CXCL8: 640 vs. 81, p0.05, ENA-78/CXCL5: 191 vs. 51, p0.005 and GRO-alpha: 1827 vs. 710, p0.005). No significant differences were detected in the levels of the angiostatic chemokines after therapy (median values in pg/ml, IP-10/CXCL10: 56 vs. 56.5, p=0.6, ITAC/CXCL11: 43 vs. 47, p=0.11). However, a significant decrease in the MIG/CXCL9: 66 vs. 31, p=0.006, has been detected.These findings support the notion that IFN gamma may be one of the important mediators regulating angiogenetic balance in IPF. However, IFN gamma-1b decreases MIG levels, finding that in association with no alteration in IP-10 and I-TAC levels, could explain in part the nonbeneficial effect of this drug in IPF.

Summary Microscopic polyangiitis is a non-granulomatous, systematic and small-vessel vasculitis in which necrotizing glomerulonephritis is very common and pulmonary capillaritis often occurs. We report a patient with fever, fatigue and dry cough who initially had been diagnosed as having pneumonia. A thoracic CT was performed showing widespread multiple nodular lesions, some with a central air-bronchogram and thickened bronchovascular bundles and some connected to nodules. No cavitation or ground glass opacities were observed. Fibreoptic bronchoscopy was normal and the cultures from the BAL were negative. Additionally, during his stay in the hospital his hematocrit was gradually falling, while the erythrocyte sedimentation rate increased. Urinanalysis revealed proteinuria and active urinary sediment. p-ANCA was positive and renal biopsy revealed focal pauci-immune necrotic glomerulonephritis. Pulmonary–renal syndrome was suspected and renal biopsy was performed. The diagnosis of microscopic polyangiitis was established and the patient began treatment with pulse intravenous methylprednisolone and cyclophosphamide. After induction of remission, the patient received maintenance therapy. Finally, an extensive review of the literature on microscopic polyangiitis is presented.

Idiopathic pulmonary fibrosis (IPF) is a poorly understood disease that usually leads to death within 5 years of diagnosis. Despite our better understanding of IPF pathogenesis, the etiology and the precise cellular and molecular mechanisms involved are not well known. Current therapies are of unproven benefit. The aim of this review is to identify possible candidate pathways that might offer novel therapeutic targets changing the natural course of this disease. Current therapeutic approaches target at apoptosis, epithelial replacement, fibroblasts/myofibroblasts, procoagulant activity, growth factors production, angiogenesis, Th1 and Th2 cytokines and oxidative stress. Increased epithelial cells apoptosis can contribute to fibrosis, while on the other hand, decreased fibroblast or myofibroblast apoptosis promotes fibrosis. Recent findings support the notion that therapy directed at either inhibition of angiogenic or augmentation of angiostatic CXC chemokines may be a novel approach in the treatment of IPF. Additionally, there is little doubt that the development of novel therapeutic strategies for pulmonary fibrosis should target some profibrotic growth factors and key type II cytokines, such as inteleukin-13. Importantly, persistent activation of intra-alveolar procoagulant activity and subsequent abnormal fibrin turnover enhances a fibrotic response. Furthermore, increased procoagulant activity may interfere with fibrin accumulation and lack of activation of some matrix metalloproteinases responsible for an imbalance in matrix turnover. Finally, oxidative stress with increased production of oxidants in IPF is an additional mechanism proposed to explain epithelial cell apoptosis in this disease. The challenge of future targets for therapeutic intervention is to reconcile different pathogenetic pathways, and we strongly suspect that no single approach will be sufficient for a lethal disease with few therapeutic options.

The extent of pupillary miosis during 5 min in darkness is a simple, recently introduced alertness test which may become useful in the clinical assessment of normal and pathological sleepiness.In this study, we further validated this test by testing its sensitivity to the effects of modafinil, a non-stimulant, alertness-promoting drug.Twelve unmedicated patients recently diagnosed with obstructive sleep apnea (OSA) after polysomnography, received placebo or modafinil (200 mg), according to a double-blind, cross-over design. The patients' resting pupil diameter (RPD) was sampled over 5 min in darkness before (10:00 A.M.) and after treatment (2:00 P.M.), and their light reflexes were elicited and recorded in darkness with an infrared video pupillometer.We found a circadian miosis at 2:00 P.M. in the placebo treatment condition, which was reversed by modafinil. This effect correlated with modafinil-induced increase in subjective alertness, and it was greater in the most severely affected patients in terms of lowest oxygen saturation, independently of body mass index, age, or apneic episodes during sleep. Modafinil reduced the light reflex amplitude, suggesting an increase in the inhibitory input at the pupilloconstrictor Edinger-Westphal nucleus.These effects of modafinil are best explained via an activation of the hypoxia-sensitive nucleus locus coeruleus. The 5-min pupillary alertness test has promising predictive validity, and it holds promise as a fast and sensitive method for the objective assessment of excessive daytime sleepiness, monitoring of disease progression, and response to treatment.

Background Genetic alterations, including microsatellite instability (MSI) and loss of heterozygosity (LOH), have been described in both malignant and benign diseases. Previous studies have successfully detected such alterations in sputum samples of patients with bronchial asthma (BA). The aim of this study was to assess the presence of MSI and/or LOH in nasal cytology samples of patients with allergic rhinitis (AR). Methods Nasal brush samples and peripheral blood from 20 patients with AR were analyzed. DNA was extracted and analyzed for MSI and LOH using the following microsatellite markers: D16S289, D4S2394, D4S1651, DXS8039, D3S3606, and D2S2113, harboring potential susceptibility genes for AR and atopy. Microsatellite analysis was performed also in eight control subjects. Results No MSI and/or LOH were noted in either the AR or the control group. Conclusion Although MSI and LOH are detectable phenomena in sputum samples of patients with BA, this seems not to be the case for nasal cytology samples of patients with AR. Additional studies are needed, using a larger number of polymorphic markers, to assess if such a difference exists among two diseases otherwise very closely related.

Mitophagy is the selective digestion of damaged mitochondria. Mitochondria dysfunction and impaired mitophagy in AECIIs may play a role in the pathogenesis of IPF. PINK1 is a major regulator of mitophagy, while PINK1 deficiency promotes the accumulation of dysfunctional mitochondria in AECIIs in IPF. There have been no studies to date evaluating mitophagy in macrophages in IPF. However, an autophagy defect in alveolar macrophages of smokers resulting in mitochondrial dysfunction has been demonstrated. The purpose of this study was the evaluation of mitochondrial homeostasis in BALF cells in IPF and RA-ILD. 55 IPF patients, 20 healthy controls and 23 RA-ILD patients were included in the study. We tested the expression of AKT3, a major regulator of mitochondria homeostasis. AKT3 was up-regulated in RA-ILD versus IPF patients. Furthermore, we observed a significant down-regulation of PINK1 in IPF and RA-ILD patients versus controls. Interestingly, PINK1 and AKT3 expression positively correlated only in IPF but not in RA patients. Autophagy levels were also analysed through the expression of Beclin1, p62 and LC3. A positive correlation for all groups was demonstrated between AKT3 and p62 as well as between PINK1 and p62 in IPF. A trend for lower levels of p62 protein in IPF patients versus controls was indicated by Western Blot. LC3B levels tended to be higher in IPF versus control. Moreover, mitosox analysis was performed in order to define the oxidative status of macrophages and hence the levels of mitochondrial dysfunction in fibrotic disorders. Our results demonstrate changes in the mitophagy status in IPF macrophages relative to control and RA-ILD patients.

Lung cancer cells continuously interact with local and systemic immune cells, thus guiding tumor evasion, tissue injury and progressive cellular pathology. Moreover, a number of studies provide evidence that infectious products are associated with lung cancer tissue recovered from a significant number of patients, so we aimed to investigate the inducibility of the NLRP3 pathway in Bronchoalveolar Lavage macrophages and peripheral blood leukocytes from patients with primary lung cancer compared to healthy individuals. The presence or absence of mediators (NLRP3, Caspase-1) and outcomes (TNF-α, IL-1β, IL-6, IL-18) after inflammasome activation via LPS plus ATP were evaluated with RT-PCR, Western Blotting and ELISA kits. IL-1β protein production is severely inhibited in lung cancer macrophages and leukocytes compared to controls, while only macrophages showed a reversible inducibility of NLRP3 inflammasome. In addition, TNFα secretion after inflammasome activation is significantly prohibited in lung cancer samples, while IL-1β secretion profile in lung cancer suggest reversibility of NLRP3 induction in blood samples but not in lung macrophages. IL-6 remains the only reversible outcome, in both BAL and blood, in lung cancer compared to controls. IL-6 pronounced systemic inducibility leads to the possibility that systemic inflammation in lung cancer could be mediated via NLRP3 inflammasome, while immunosuppression or immunodepletion could explain TNFα profiling in the activation of NLRP3 inflammasome.

Lack of time or economic difficulties prevent chronic obstructive pulmonary disease patients from communicating with their physicians, thus inducing exacerbation of their chronic condition and possible hospitalization. In this paper we propose a platform that integrates mobile application technologies and cloud computing to provide secure, robust, scalable and distributed backend for hosting health services that improve life quality in a cost effective way.

Inflammation is supposed to play a great role in the pathogenesis of the most common diseases of the respiratory system. In Chronic Obstructive Pulmonary Disease (COPD), which is a major cause of morbidity and mortality all around the world, smoking mainly causes the initiation of the inflammatory process that leads to an impaired respiratory function. Moreover, in bronchial asthma there are numerous proinflammatory mediators that are responsible for the onset and the progression of the disease. Finally, pulmonary infections and especially tuberculosis result in the orchestration of an inflammatory process that targets the causative agent in order to protect the host. L. M. O. Caram et al. have evaluated the levels of vitamin A in the serum and sputum and attempted to correlate it with known inflammatory markers, such as tumor necrosis factor alpha (TNF-α), interleukin- (IL-) 6, IL-8, and C-reactive protein (CRP) in 50 COPD patients and 50 individuals without COPD. The authors concluded that serum concentration of vitamin A is negatively associated with the presence of COPD and that it is positively associated with smoking status. Although COPD patients exhibited increased inflammation, these inflammatory markers were not associated with serum retinol concentrations. The manuscript of W. Zhang et al. tested the effect of a novel γ-secretase inhibitor to promote Th17 cell differentiation in a mouse model of allergic asthma. Their findings suggest that the inhibitor directly regulates Th17 responses in the mouse model of allergic asthma that they used, making it potentially efficacious. In their study, R. Rajajendram et al. tried a synthetic chalcone analogue in a murine model of asthma. Their results demonstrate a potential role of the substance in asthma, as the treatment with it inhibited eosinophilia, goblet cell hyperplasia, peripheral blood total IgE, and airway hyperresponsiveness in ovalbumin-sensitized and challenged mice. However, the tested nonsteroid potentially anti-inflammatory substance is far away from clinical use. In the manuscript entitled “Binding of CXCL8/IL-8 to Mycobacterium tuberculosis Modulates the Innate Immune Response,” A. Krupa et al. illustrate the role of IL-8 in the pathogenesis of tuberculosis (TB). The authors investigated the contribution of IL-8 in the inflammatory processes that are typically elicited in patients with TB. Their findings show that IL-8 seems to be the major chemokine responsible for recruiting T lymphocytes (CD3+, CD4+, and CD8+ T cells) and plays important role in the innate immunity against Mycobacterium tuberculosis. Last but not least, the study of R. Baumann et al. investigated the IgA and IgG responses to mycobacterial protein antigens in subjects with latent tuberculosis, active tuberculosis, and healthy individuals. In their conclusions they present a new biomarker for the diagnosis of active pulmonary tuberculosis.

Background The health status of patients with sarcoidosis has rarely been studied, despite the increasing numbers of health-related quality of life publications on other respiratory diseases. The aim of this cross-sectional study was to investigate whether sarcoidosis affects quality of life (QoL), using specifically designed questionnaires for respiratory diseases as well as general health measures, and to compare these with pulmonary function indices. Our secondary aim was to determine whether these measurements are correlated with pulmonary function tests and duration of the disease. Methods Included in the study were 75 consecutive patients with histologically confirmed active sarcoidosis. Self-completed dyspnea scales (Borg's scale, oxygen cost diagram, modified MRC questionnaire) and health-related quality of life (HRQoL) questionnaires (St George's Respiratory Questionnaire, Quality of Well-Being, and Anxiety and Depression) were used. Pulmonary function tests, measurements of arterial blood gases at rest and after exercise, chest radiographs, and duration of disease were used for correlation. Results We found that QoL was affected in sarcoidosis patients in comparison with healthy controls. Secondly, we found that the duration of the disease was correlated with all three dyspnea scales under evaluation, as well as with the SGRQ questionnaire. Furthermore, a significant correlation was shown between lung function tests (FVC, % pred and FEV 1 , % pred) and both the BORG dyspnea scale and the SGRQ questionnaire. Conclusion Quality of life is affected in patients with active sarcoidosis. The SGRQ questionnaire could be a useful tool for the investigation of HRQoL in an active sarcoid population with varying degrees of lung function impairment. Future studies are needed to address the ability of these instruments to measure HRQoL in the course of this chronic disease.

Recent evidence has shown that several chemokines--including those involved in angiogenesis--have been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and sarcoidosis. We speculated that these differences could be attributed to distinct angiogenic and angiostatic profiles. This hypothesis was investigated by estimating the levels of three angiogenic chemokines (growth-related gene [GRO]-alpha, epithelial neutrophil-activating protein [ENA]-78, and interleukin [IL]-8), and three angiostatic chemokines (monokine induced by interferon (IFN)-gamma [MIG], IFN-gamma-inducible protein [IP]-10, and IFN-gamma-inducible T-cell alpha chemoattractant) in serum and BAL fluid (BALF).We studied prospectively 20 patients with sarcoidosis (median age, 46 years; range, 25 to 65 years), 20 patients with IPF (median age, 68 years; range, 40 to 75 years), and 10 normal subjects (median age, 39 years; range, 26 to 60 years).The GRO-a serum and BALF levels of IPF patients were found significantly increased in comparison with healthy subjects (799 pg/mL vs 294 pg/mL [p = 0.022] and 1,827 pg/mL vs 94 pg/mL [p0.001], respectively) and sarcoidosis patients (799 pg/mL vs 44 pg/mL [p0.001] and 1,827 pg/mL vs 214 pg/mL [p0.001], respectively). Moreover, ENA-78 and IL-8 BALF levels in IPF patients were significantly higher compared with sarcoidosis patients (191 pg/mL vs 30 pg/mL [p0.001] and 640 pg/mL vs 94 pg/mL [p = 0.03], respectively). MIG serum levels in IPF patients were found significantly upregulated in comparison with sarcoidosis patients and healthy control subjects. However, MIG and IP-10 BALF levels (1,136 pg/mL vs 66 pg/mL [p0.001] and 112 pg/mL vs 56 pg/mL [p = 0.037], respectively) were significantly higher in sarcoidosis patients compared with IPF patients.Our data suggest distinct angiogenic profiles between IPF and sarcoidosis, indicating a potential different role of CXC chemokines in the local immunologic response in IPF and pulmonary sarcoidosis.