Andreas Koulelidis

Effect and safety of mycophenolate mofetil or sodium in systemic sclerosis-associated interstitial lung disease: a meta-analysis.

Background. Interstitial lung disease (ILD) is the most common complication of systemic sclerosis (SSc) with treatment ineffective. Objective: The aim of this meta-analysis was to provide an estimate of the safety and efficacy profile of Mycophenolate Mofetil (MMF) or sodium (MMS) in SSc-ILD patients. Materials and Methods. All studies were reviewed systematically. The main end-points were safety and efficacy profile as estimated by forced vital capacity (FVC)% and diffusion capacity of the lung for carbon monoxide (DLCO)% of the predicted normal value (%pred.) before and after treatment in patients with SSc-ILD. Quality assessment and data extraction were performed independently by two reviewers. Results. Seventeen studies were reviewed systematically. Six studies, one prospective, were eligible for analysis encompassing 69 patients, including 10 subjects from our, yet unpublished, retrospective study. There was no statistically significant difference in both efficacy outcomes of interest, including FVC% pred. (weighted mean difference 1.48, 95% confidence interval (CI): −2.77 to 5.72, P = 0.49) and DLCO % pred. (weighted mean difference −0.83, 95% CI: −4.75 to 3.09, P = 0.93). No cases of clinically significant side effects were documented. Conclusions. Meta-analysis data suggest that MMF is a safe therapeutic modality which was associated with functional stabilization in patients with SSc-ILD.

Increased incidence of autoimmune markers in patients with combined pulmonary fibrosis and emphysema

BackgroundCombined pulmonary fibrosis and emphysema (CPFE) is an umbrella term encompassing upper lobe emphysema and lower lobe pulmonary fibrosis with pathogenesis elusive. The aim of our study was to investigate the incidence of autoimmune markers in patients with CPFE.MethodsIn this multicenter study we retrospectively evaluated records from patients with CPFE (n=40) and IPF (n=60) without emphysema. Baseline demographic characteristics, high-resolution computed tomography (HRCT), spirometry, histopathological, treatment, serum immunologic and survival data were investigated. B cell presence was estimated with CD20 immunostaining in representative lung biopsy samples from CPFE patients and control subjects.ResultsA statistically significant increased number of CPFE patients with elevated serum ANA with or without positive p-ANCA titers compared to patients with IPF without emphysema was observed. Patients with CPFE and positive autoimmune markers exhibited improved survival compared to patients with a negative autoimmune profile. A massive infiltration of clusters of CD20+ B cells forming lymphoid follicles within the fibrotic lung in CPFE patients with positive serum immunologic profile compared to patients with negative profile, was noted and positively correlated with improved survival.ConclusionsA significant proportion of patients with CPFE may present with underlying auto-immune disorders that may reside insidiously and be associated with favorable prognosis. Early identification of these patients using a panel of auto-antibodies may lead to more targeted and effective therapeutic applications.

Increased Expression of Epidermal Growth Factor Receptor (EGF-R) in Patients with Different Forms of Lung Fibrosis

Introduction. Emerging evidence supports the role of epidermal growth factor-receptor (EGFR) in fibrogenesis. The aim of our study was to investigate the expression profiles of EGFR in three forms of IIPs, including idiopathic pulmonary fibrosis (IPF), cryptogenic organizing pneumonia (COP), and nonspecific interstitial pneumonia (NSIP). Patients and Methods. Twenty newly diagnosed patients with IPF, 15 with COP, and 15 with NSIP (cellular, n = 4 and fibrotic, n = 11) were investigated. Fifteen paraffin blocks obtained from the normal part of lungs removed for benign lesions were used as controls. Immunohistochemistry was carried out using specific monoclonal antibody. Results were verified by qRT-PCR. Results. A significant EGFR upregulation, both in protein and mRNA level, was observed in IPF, COP, and fibrotic NSIP samples compared to controls. EGFR was primarily localized in the hyperplastic alveolar epithelium surrounding areas of fibrosis in IPF, COP, and fibrotic NSIP samples, as assessed by double immunohistochemistry analysis with surfactant protein-A. EGFR mRNA levels were positively associated with indicators of lung fibrosis (type 1 collagen mRNA levels) and negatively correlated with functional prognostic parameters. Conclusions. We conclude that EGFR is upregulated in the hyperplastic alveolar epithelium in all three fibrotic forms of IIPs indicating a potential role during abnormal reepithelization.

Expression of hypoxia-inducible factor (HIF)-1a-vascular endothelial growth factor (VEGF)-inhibitory growth factor (ING)-4- axis in sarcoidosis patients.

BackgroundSarcoidosis is a granulomatous disorder of unknown etiology. The term of immunoangiostasis has been addressed by various studies as potentially involved in the disease pathogenesis. The aim of the study was to investigate the expression of the master regulator of angiogenesis hypoxia inducible factor (HIF)-1a – vascular endothelial growth factor (VEGF)- inhibitor of growth factor 4-(ING4) - axis within sarcoid granuloma.MethodsA total of 37 patients with sarcoidosis stages II-III were recruited in our study. Tissue microarray technology coupled with immunohistochemistry analysis were applied to video-assisted thoracoscopic surgery (VATS) lung biopsy samples collected from 37 sarcoidosis patients and 24 controls underwent surgery for benign lesions of the lung. Computerized image analysis was used to quantify immunohistochemistry results. qRT-PCR was used to assess HIF-1a and ING4 expression in 10 sarcoidosis mediastinal lymph node and 10 control lung samples.ResultsHIF-1a and VEGF-ING4 expression, both in protein and mRNA level, was found to be downregulated and upregulated, respectively, in sarcoidosis samples compared to controls. Immunohistochemistry coupled with computerized image analysis revealed minimal expression of HIF-1a within sarcoid granulomas whereas an abundant staining of ING4 and VEGF in epithelioid cells was also visualized.ConclusionsOur data suggest an impairment of the HIF-1a – VEGF axis, potentialy arising by ING4 overexpression and ultimately resulting in angiostasis and monocyte recruitment within granulomas. The concept of immunoangiostasis as a possible protection mechanism against antigens of infectious origin needs further research to be verified.

Combined pulmonary fibrosis and emphysema associated with microscopic polyangiitis

To the Editors: Microscopic polyangiitis (MPA) is a necrotising multiorgan vasculitis associated with a variety of circulating autoantibodies, such as anti-neutrophil cytoplasm antibodies (ANCAs) against myeloperoxidase (MPO) [1]. Typical and most common pulmonary involvement comprises of alveolar haemorrhage secondary to pulmonary capillaritis as well as interstitial lung fibrosis [2] and progressive obstructive lung disease [1, 3, 4]. The combination of pulmonary fibrosis and emphysema (CPFE) is a recently defined syndrome, encompassing a distinct radiology, revealing both upper-lobe emphysema and lower-lobe fibrosis on high-resolution computed tomography (HRCT) of the chest, as well as lung function profile, with apparently preserved lung volumes contrasting with disproportionally impaired gas exchange, as assessed by reduced diffusing capacity of the lung for carbon monoxide [5, 6]. CPFE has been recently described in the context of connective tissue diseases [7]. Nevertheless, it is still debatable whether CPFE represents a distinct syndrome or it is just a phenotype of pulmonary fibrosis with coincidental emphysema. Here, we describe for the first time, in a male patient, a novel type of pulmonary manifestation of MPA, the combination of pulmonary fibrosis and emphysema. In 2008, an 80-yr-old Greek-Caucasian male, heavy ex-smoker (80 pack-yrs), ex-farmer and coal worker with a history of idiopathic pulmonary fibrosis, based …

Mean Platelet Volume as a Surrogate Marker for Platelet Activation in Patients With Idiopathic Pulmonary Fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is associated with a prothrombotic state. Aim: To study mean platelet volume (MPV) and Platelet Distribution Width (PDW) as markers of platelet activation and their potential association with lung function in patients with recently diagnosed IPF. Materials and Methods: This study included 56 patients with IPF (age 64.9±7.4 years) and 79 controls (age 64.2 ± 5.9 years). Results: An inverse relation was demonstrated between platelet count and MPV in the control group but not among patients with IPF. Platelet count was significantly lower in patients with IPF compared with controls (230 ± 60 vs 256 ± 75 × 103/μL, P = .038). Conversely, MPV was higher in patients versus controls (10.3 ± 1.2 vs 9.8 ± 1.2 fl, P = .024), while there was no difference between the groups in PDW. Respiratory function was, as expected, significantly impaired in patients with IPF versus controls in terms of forced expiratory volume in first second (FEV1; 67.2 ± 23.1 vs 102.6 ± 15.9% of predicted value, P < .001), forced vital capacity (FVC; 65.3 ± 21 vs 95.2 ± 16.1% of predicted value, P < .001), FEV1/FVC (83.1 ± 15 vs 87.5 ± 6.4%, P = .041) and partial pressure of oxygen in arterial blood (PaO2; 67.1 ± 10.3 vs 81.5 ± 15.2 mm Hg, P < .001). No significant correlation was seen between MPV and FVC (r = −.1497, P = .275), MPV and lung diffusion capacity for carbon monoxide (r = .035, P = .798) and total lung capacity (r = .032, P = .820). Conclusions: Patients with IPF exhibit higher MPV values and lower platelet count. Further studies are needed to assess the clinical implications of these findings.

Dabigatran can cause eosinophilic pleural and pericardial effusion with blood eosinophilia.

Eosinophilic pleural effusions (EPE) account for 5%–8% of all exudative pleural effusions. A pleural effusion is defined as eosinophilic if it contains 10% or more eosinophils. We present the case of a 70‐year‐old man with EPE, blood eosinophilia and pericardial effusion due to dabigatran, a novel anti‐thrombin agent.

Bilateral empyema treated by sequential pleuroscopy

Bilateral empyema associated to infectious pericarditis is an extremely rare, yet life-threatening condition. Pleuroscopy-medical thoracoscopy has proved its efficacy in series of patients with empyema. Yet, all reported cases treated by this technique, concerned patients with pleural infection located to a single hemithorax. We present the case of a 71-year-old man with bilateral empyema treated successfully by sequential pleuroscopy, associated to infectious pericarditis.

AB 2. Impact of statins and ace inhibitors use on length of hospital stay in patients with community acquired pneumonia

Background Statins and angiotensin-converting enzyme (ACE) inhibitors are widely used in the treatment of cardiovascular diseases and arterial hypertension respectively, and several studies in experimental and animal models suggest their anti-inflammatory and immunomodulatory effect. However, we are lacking big trials that prove the potential benefit on clinical outcome and reduced hospital stay in community acquired pneumonia (CAP) patients. Aim of the study was to determine whether the use of statins and ACE inhibitors reduces the length of hospitalization in patients with CAP.