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Background Idiopathic Pulmonary Fibrosis (IPF) represents a chronic lung disease with unpredictable course. Methods We aimed to investigate prognostic performance of complete blood count parameters in IPF. Treatment-naïve patients with IPF were retrospectively enrolled from two independent cohorts (derivation and validation) and split into subgroups (high and low) based on median baseline monocyte count and red cell distribution width (RDW). Results Overall, 489 patients (derivation cohort: 300, validation cohort: 189) were analyzed. In the derivation cohort, patients with monocyte count ≥ 0.60 K/μL had significantly lower median FVC%pred [75.0, (95% CI 71.3–76.7) vs. 80.9, (95% CI 77.5–83.1), (P = 0.01)] and DLCO%pred [47.5, (95% CI 44.3–52.3) vs. 53.0, (95% CI 48.0–56.7), (P = 0.02)] than patients with monocyte count P = 0.04)] and DLCO%pred [45.4, (95% CI 43.3–50.5) vs. 53.0, (95% CI 50.8–56.8), (P = 0.008)] than patients with RDW P P P = 0.09) and significantly lower median FVC%pred (P = 0.001), respectively. Kaplan–Meier analysis in the derivation cohort demonstrated higher all-cause mortality in patients with high (≥ 0.60 K/μL) vs. low monocyte count (P = 0.01)]. Conclusions Increased monocyte count and RDW may represent negative prognostic biomarkers in patients with IPF.

Background: Telomere-related genes (TRG) mutations are detected in 30% of familial pulmonary fibrosis (FPF) and are also associated with personal/familial extra-pulmonary disease suggestive of short telomere syndrome (STS). Aim: to evaluate the prevalence of TRG mutations in a national cohort of interstitial lung disease (ILD) with suspected genetic predisposition in Greece and to define patients’ characteristics and impact on outcome.Methods: Genetic diagnoses made between December 2014-September 2019 in patients with FPF, pulmonary fibrosis at young age or personal and/or family extra-pulmonary disease suggestive of STS were analyzed. Results: 150 ILD patients, 73% male, age-at-diagnosis 67 years old, 33% non-smokers, 75% with definite/probable UIP or CPFE, 93% with dyspnea/cough, FVC% pred 75%, DLCO% pred 49% were tested; FPF was 65%, 19% young age, 21% personal and 17% family extra-pulmonary disease suggestive of STS; 21% were tested for more than 1 indication. TRG pathogenic variations were detected in 19 (13%): 13 in a familial, 3 in young age and 3 in extra-pulmonary disease suggestive of STS context as follows: TERT, TERC, RTEL1, PARN, NOP10, NHP2 in 8,5,2,2,1 and 1 respectively. No difference was detected in epidemiological-clinical-radiologic-functional characteristics between patients without and with mutations apart from age-at-diagnosis [69 vs 62 years, p

Introduction: Alpha1-antitrypsin (A1AT) deficiency is an autosomal co-dominant disease related to SERPINA-1 gene mutations predisposing to pulmonary emphysema and/or liver disease. Aim: to examine the genotype and phenotype of a Greek cohort of A1AT-deficiency patients. Methods: This multicenter study enrolled A1AT-deficiency patients under augmentation treatment from 8 centers in Greece. Results: 23 adult patients, 61% male, 17.4% non-smokers, diagnosed at a median age (IQR) of 47(42-58) years with A1AT levels of 0.24 (0.04-0.4) g/L were identified. Indications for A1AT measurement were severe obstructive pulmonary disease at the age Conclusion: In contrast with the literature, where Z and S are the most common A1AT-deficiency alleles, the present study reveals extremely rare deleterious variants in Greek A1AT-deficiency patients under augmentation treatment. Further examination of phenotype-genotype associations and outcome is expected to unveil their clinical significance in the future.

During the lockdown, IPF patients experienced lower than expected COVID-19, suggesting that simple measures for the winter months, such as face masking, clean hands, physical distancing could be adopted as promising advances in non-pharmacological therapyhttps://bit.ly/2ISi2EV

Background Abundant evidence supports an association between Idiopathic Pulmonary Fibrosis (IPF) and lung cancer development. Data on diagnosis and management of patients with IPF and lung cancer are still scarce. Patients and methods This was a retrospective multicenter study, enrolling 1016 patients with IPF from eight different centers between 2011 and 2018 in Greece. Our aim was to estimate prevalence of lung cancer in patients with IPF in Greece. Results We identified 102 cases of patients with IPF and lung cancer (prevalence = 10.03% n = 102/1016, mean age±SD = 71.8 ± 6.9, 96 males, mean FVC±SD = 72.7 ± 19.7, mean DLCO±SD = 44.5 ± 16.3). We identified 85 cases (83.3%) of non-small cell lung cancer (35 squamous, 28 adenocarcinoma), and 15 cases (14.7%) of small cell lung cancer . Primary lesion was localized in lower lobes in 57.1% of cases. Lung cancer was diagnosed post IPF diagnosis (mean latency time + SD = 33.2 + 36.1 months) in 57.6% of patients and synchronously in 36.5% of patients. Chemotherapy was applied in 26.7% of cases, while 34.7% of patients underwent surgery. Median survival of patients with IPF and lung cancer was 27.4 months (95% CI: 20.6 to 36.8). Conclusions IPF is a risk factor for lung cancer development. In line with current literature, squamous cell carcinoma is the most common histologic subtype in patients with IPF. Large randomized controlled studies on the management of patients with IPF and lung cancer are sorely needed.

Background: Abundant evidence supports an association between Idiopathic Pulmonary Fibrosis (IPF) and lung cancer development. Data on diagnosis and management of patients with IPF and lung cancer are still scarce. Aim: To estimate prevalence of lung cancer in patients with IPF. Patients and Methods: This was a retrospective multicenter study, enrolling 835 patients with IPF from eight different centers between 2009 and 2018 in Greece. Results: We identified 88 cases of patients with IPF and lung cancer (prevalence=10.5% n=88/835, mean age±SD=71.8±7.1, 82 males, meanFVC±SD= 73.5±18.9, meanDLCO±SD= 45.3±15.6). Six patients (7%) had both lung and other type of cancer. We identified 68 cases (77.3%) of non-small cell lung cancer (32 squamous, 25 adenocarcinoma, 11 non-specified), and 13 cases (14.8%) of small cell lung cancer. An equal distribution of anatomic location of lung cancer between upper and lower lobes was observed. Lung cancer was diagnosed post IPF diagnosis (median latency time=15.9 months) in 68% of patients and synchronously in 29.3% of patients. Chemotherapy was applied in 31.8% of cases, while 33.3% of patients underwent surgery. Median survival of patients with IPF and lung cancer was 27.4 months (95% CI: 20.6 to 36.8). Conclusions: IPF is a risk factor for lung cancer development. Squamous cell carcinoma is the most common histologic subtype in patients with IPF. Large randomized controlled studies on the management of patients with IPF and lung cancer are sorely needed.

Introduction In sarcoidosis although no better drug therapy than corticosteroids (CS) has emerged, alternative immunosuppressive agents are used when indicated. Mycophenolate mofetil (MMF) presents rapid action, a considerable safety profile and absence of lung toxicity. Few data exist so far on its use in patients with sarcoidosis. This is a retrospective study on the effectiveness and safety of MMF in patients with sarcoidosis. Materials and methods All patients with biopsy proven sarcoidosis treated for at least 1 year with MMF from 2008 to 2017 in our department are evaluated. Results Eight patients with both pulmonary and extrapulmonary disease are included in the analysis. During follow-up, symptoms and chest radiological findings improved in all. A statistically significant improvement of FEV1 and FVC is reported (p = 0.010 and p = 0.021 respectively). Cardiac and renal disease resolved during treatment while dermal disease significantly improved. MMF permitted CS dose reduction from 15.0 (10.0, 35.0) to 2.5 (0.0, 5.0) mg prednisolone (or equivalent), p = 0.016. All patients but one, tolerated well MMF. Conclusion MMF as an alternative drug in systemic sarcoidosis, proved safe and effective, permitting the reduction of the dose of oral CS and leading to clinical, functional and radiological improvement.

Background: Abundant evidence supports an association between Idiopathic Pulmonary Fibrosis (IPF) and lung cancer development. Nevertheless, epidemiological data on IPF and cancer are scarce. Aim: To estimate prevalence of lung and other types of cancer in patients with IPF. Patients and Methods: This was a retrospective multicenter study, enrolling 608 patients with IPF from six different centers between 2009 and 2018. Results: We identified 63 cases of patients with IPF and cancer (prevalence=10.3%, n=63/608, mean age±SD=72.8±7.5, 57 males, meanFVC±SD= 75.9±21.5, meanDLCO±SD= 47.2±15.8). We recorded 50 cases of lung cancer and 16 patients with other types of cancer (colon n=6, stomach n=2, breast n=2, chronic lymphocytic leukemia n=2, other=4). Three patients had both lung and other type of cancer. Prevalence of lung cancer in patients with IPF was 8.2%. Most cases (74%, n=37) were non-small cell lung cancer (20 squamous, 12 adenocarcinoma, 5 non-specified), while in 7 patients (14%) small cell lung cancer was diagnosed. Primary lesion was localized in upper lobes in 52% (n=26) of cases. In 64%(n=32) of patients, lung cancer was diagnosed post IPF diagnosis (median latency time= 14.6 months), 30%(n=15) of patients were diagnosed with IPF and lung cancer synchronously and 6%(n=3) of cases developed lung cancer prior IPF diagnosis(median latency time=23.8 months). Chemotherapy was applied in 36% of cases, while 20% of patients underwent surgery. Median survival of patients with IPF and lung cancer was 24.0 months (95% CI: 18.6 to 38.0). Conclusions: Our epidemiologic data validates IPF as risk factor for cancer development. Further studies are greatly anticipated.

Introduction: Short telomeres are a risk factor for idiopathic pulmonary fibrosis (IPF). Few data exist for telomere length (TL) in acute exacerbation of IPF (AE-IPF) as well as in other fibrotic interstitial lung diseases (ILD). Aim: To measure TL in sporadic fibrotic ILDs including IPF, AE-IPF, Collagen-Vascular-Disease (CVD), Combined pulmonary fibrosis-emphysema (CPFE) and compare them with age-matched healthy controls in the Greek population. Methods: Consecutive ILD patients were enrolled. TL was measured from peripheral white blood cells using a multiplex quantitative polymerase chain reaction (qPCR). The relative TL was estimated from the ratio of the telomere repeat copy number to a single gene (human b-globin gene) copy number (telomere/single-copy gene [T/S] ratio). Results: 84 participants were studied [mean age (68.6±0.71) years], 24 stable IPF (69.7±1.2), 18 ΑE-IPF (70.0±1.6), 7 CTD-ILDs (68.8±3,4), 10 CPFE (69.7±1.4) and 25 age-matched healthy controls (66.0±1.2). TL in all ILD patients was significantly shortened compared to controls [mean T/S ratio (SE) (0.79±0.05) vs (2.11±0.29), p 0.72, 7.0±1.68 months vs 14.4±4.3), no significant association was observed in overall survival. Conclusion: Short TL was detected across all fibrotic groups of ILD. Further shortening of TL during AE-IPF was not found. “Grant of Hellenic Thoracic Society”

Diffuse idiopathic skeletal hyperostosis (DISH), also known as Forestier’s disease, is a systemic non inflammatory disease of unknown cause. It is characterized by the presence of osteophytes due to calcification and ossification of spinal ligaments and entheses. Moreover, diffuse idiopathic skeletal hyperostosis has been associated with a variety of metabolic disorders. However, to the best of our knowledge no association with non small cell lung cancer (NSCLC) has been reported so far. In the present study we report a case of a patient with NSCLC and DISH.

Introduction Nocturnal pulse oximetry (NPO) has not been widely used in idiopathic pulmonary fibrosis (IPF). Daytime functional tests are common tools of evaluation of the disease. Aims and objectives We investigated whether NPO in association with 6Minute Walking Test (6MWT) and pulmonary function tests (PFTs) could assess the clinical course in IPF. Methods We prospectively investigated consecutive IPF outpatients at the start of Pirfenidone treatment and after 1 year follow-up. Included patients had PFTs, 6MWT and NPO. Results 16 patients of 70.7±6.5 years old, 12 male, 10 with a BMI less than 30, 14 with an index of Gender, Age and Physiology (GAP) I, II. After 1 year of Pirfenidone, there was no significant change in FVC (p=0.82) and DLCO (p=0.08). The Walking Distance decreased (p=0.02). Regarding NPO there was no change in lowest SPO2(p=0.32) nor in desaturation ≤90% for more than 10% of recording time (≤90%≥10%) (p=0.06). The change in desaturation during 6MWT did not correlate with lowest SPO2 (p=0.06) or desaturation ≤90%≥10% (p=0.60). The change in DLCO, did not correlate with lowest SPO2(p=0.53), or desaturation ≤90%≥10% (p=0.65). The change in FVC did not correlate with lowest SPO2 (p=0.48) or desaturation ≤90%≥10% (p=0.06). Conclusions This cohort of IPF patients were stable regarding PFTs but their walking distance in 6MWT was worse after 1 year of follow up. There was a trend towards statistical significance of worsening desaturation of ≤90% for more than ≥10% of recording sleep time. Worsening of desaturation during 6MWT tended to correlate with lowest baseline nocturnal SPO2.

Introduction Controversy exists about the pathogenesis of idiopathic pulmonary fibrosis acute exacerbations (IPF-AEs). According to one hypothesis IPF-AEs represent the development of any etiology diffuse alveolar damage (DAD) upon usual interstitial pneumonia (UIP), whilst other researchers argue that an accelerated phase of the intrinsic fibrotic process of unknown etiology prevails, leading to ARDS. Different cytokines might be involved in both processes. The aim of this study was to assess pro-inflammatory and pro-fibrotic cytokines in the peripheral blood from stable and exacerbated IPF patients. Methods Consecutive IPF patients referred to our department were included. Diagnoses of IPF and IPF-AE were based on international guidelines and consensus criteria. The interleukins (IL)-4, IL-6, IL-8, IL-10, and IL-13 as well as active transforming growth factor-beta (TGF-β) were measured in blood from both stable and exacerbated patients on the day of hospital admission for deterioration. Subjects were followed for 12 months. Mann-Whitney test as well as Tobit and logistic regression analyses were applied. Results Among the 41 patients studied, 23 were stable, and 18 under exacerbation; of the latter, 12 patients survived. The IL-6 and IL-8 levels were significantly higher in exacerbated patients (p = 0.002 and p = 0.046, respectively). An increase in either IL-6 or IL-8 by 1 pg/ml increases the odds of death by 5.6% (p = 0.021) and 6.7% (p = 0.013), respectively, in all patients. No differences were detected for the other cytokines. Conclusion High levels of IL-6 and IL-8 characterize early-on IPF-AEs and an increase in the levels of IL-6 and IL-8 associates with worse outcome in all patients. However, as the most representative pro-fibrotic cytokines, TGF-β, IL-10, IL-4 and IL-13 were not increased and given the dualistic nature, both pro-inflammatory and pro-fibrotic of IL-6 further studies are necessary to clarify the enigma of IPF-AEs etiopathogenesis.

The precise pathogenetic mechanisms and the potential role of uncontrolled fibroblastic proliferation or occult infection in IPF acute exacerbations need clarification. The aim of the study was the assessment of profibrotic and proinflammatory profile in both stable and excacerbated patients and their association to outcome. Stable or exacerbated patients referred to our department from October 2013 until November 2014 were included. IL-6, IL-8 and TGF-b were measured. All patients were followed up for 12 months. Tobit and logistic regression analysis were applied. Forty-one patients were included in the study [18 exacerbated, median age (IQR) 68.5 (67.0, 78.0) and 23 with stable IPF, median age (IQR) 71.0 (69.0, 74.0)]. Exacerbated patients presented higher plasma levels of IL-6 and IL-8 compared to those with stable IPF [median (IQR) 6.2 (3.2, 26.5) vs 2.1 (1.0, 4.4) pg/ml, p=0.002; median (IQR) 16.5 (12.9, 44.8) vs 10.1 (7.9, 13.2) pg/ml, p=0.046, respectively]. Most of the differences were independent to age, smoking status, procalcitonin, CRP, corticosteroid and oxygen treatment. No significant differences were observed in the profibrotic cytokine TGF-b between the two groups. An increase of IL-6 or IL-8 by 1 pg/ml increased the odds of death by 5,6% (p=0.021) and 6,7% (p=0.013) respectively in all patients and by 3,8% (p=0.093) and 4,3% (p=0.078) in exacerbated patients. The increased plasma levels of IL-6 and IL-8 found in exacerbated patients compared to stable suggest the presence of inflammation that may also relate to occult infection. Furthermore, our results indicate that plasma levels of IL-6 and IL-8 are associated with increased risk of death in all.