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OBJECTIVES In this study, we sought to assess the validity of lung ultrasound (LUS) during the follow-up of patients with a wide spectrum of interstitial lung diseases (ILDs). METHODS Twenty-four patients (13 males, 11 females; mean age ± SD, 65.4 ± 14.3 years; age range, 40-84 years) with a diagnosis of ILDs who were admitted to the Interstitial Lung Disease Unit were prospectively enrolled. Patients were examined with a 56-lung intercostal space LUS protocol in lateral decubitus position, at baseline, 6-months, and 1-year. The LUS score was defined as the sum of B-lines counted in each intercostal space. All patients underwent complete pulmonary function tests at baseline and follow-up time-points. High-resolution computed tomography (HRCT) was performed at baseline and during follow-up, according to personalized patients' needs. All HRCT studies were graded according to the Warrick scoring system (WS). RESULTS Pooled data analysis showed a significant correlation between WS and LUS scores (P

The aim of this review was to summarize the recent data concerning interstitial lung disease after COVID-19, a field where knowledge is evolving very quickly.It has been found that a proportion of patients displayed fibrotic-like pattern on chest computed tomography shortly after COVID-19 pneumonia. Those lesions can potentially represent precursors of fibrosis, although most of them will resolve until 1 year postinfection. There was a wide range of the prevalence of post-COVID-19 interstitial lung disease detected in the literature, which can be attributed to the heterogeneous definition of lung abnormalities and the discrepancy of study design. The severity of acute COVID-19 disease has been linked to increased risk of residual imaging and functional abnormalities, while reduced DLco was the most common functional abnormality in long-term survivors. Studies indicated that pathophysiology of post-COVID interstitial lung disease shares common mechanisms with idiopathic pulmonary fibrosis. Regarding therapeutic strategies of post-COVID-19 interstitial lung disease, the role of immunosuppressive and antifibrotic treatment is currently under investigation.We still need to learn about the natural history of COVID-19 disease, allowing for a better targeting of therapeutic interventions through a multidisciplinary approach.

Patients diagnosed with coronavirus disease 2019 (COVID-19) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently experience symptom burden post-acute infection or post-hospitalisation. We aimed to identify optimal strategies for follow-up care that may positively impact the patient's quality of life (QoL). A European Respiratory Society (ERS) Task Force convened and prioritised eight clinical questions. A targeted search of the literature defined the timeline of "long COVID" as 1-6 months post-infection and identified clinical evidence in the follow-up of patients. Studies meeting the inclusion criteria report an association of characteristics of acute infection with persistent symptoms, thromboembolic events in the follow-up period, and evaluations of pulmonary physiology and imaging. Importantly, this statement reviews QoL consequences, symptom burden, disability and home care follow-up. Overall, the evidence for follow-up care for patients with long COVID is limited. ispartof: EUROPEAN RESPIRATORY JOURNAL vol:60 issue:2 ispartof: location:England status: published

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.

International audience; IPF is a devastating lung disease with limited therapeutic possibilities. FGF19, an endocrine FGF, was recently shown to decrease liver fibrosis. To ask whether FGF19 had anti-fibrotic properties in the lung and decipher its effects on common features associated with lung fibrogenesis. We assessed, by Elisa, FGF19 levels in plasma and bronchoalveolar lavage fluids (BALF)obtained from controls and IPF patients. In vivo, using an intravenously administered adeno11 associated virus (AAV), we overexpressed FGF19 at the fibrotic phase of two experimental models of murine lung fibrosis and assessed its effect on lung morphology, lung collagen content, fibrosis markers and pro fibrotic mediator expression, at mRNA and protein levels. In vitro, we investigated whether FGF19 could modulate the TGFβ-induced differentiation of primary human lung fibroblast into myofibroblast and the apoptosis of murine alveolar type II cell. While FGF19 was not detected in BALF, FGF19 concentration was decreased in the plasma of IPF patients compared to controls. In vivo, the overexpression of FGF19 was associated with a marked decrease of lung fibrosis and fibrosis markers, with a decrease of pro fibrotic mediator expression and lung collagen content. In vitro, FGF19 decreased alveolar type 2 epithelial cell apoptosis through the decrease of the proapoptotic BIM protein expression and prevented TGF-ß induced myofibroblast differentiation through the inhibition of JNK phosphorylation. Altogether these data identify FGF19 as an anti-fibrotic molecule with a potential therapeutic interest in fibrotic lung disorders.

The year 2020 is characterized by the COVID-19 pandemic that has resulted in more than half a million deaths in recent months. The high mortality is associated with acute severe respiratory failure that results in ICU admission and intubation. While facing this fatal disease, research and clinical observations need to be carried out in order to evaluate the long-term effects of the COVID-19 acute respiratory distress syndrome (ARDS). Potent clinical and laboratory biomarkers should be studied to be able to predict the subgroup of patients that are going to deteriorate or develop lung fibrosis. The opportunity of personalized medicine is a good way to consider for these patients.

Ανάμεσα στις Διάχυτες Διάμεσες Πνευμονοπάθειες (ΔΔΠ), η Ιδιοπαθής Πνευμονική Ίνωση (ΙΠΙ) αποτελεί την πιο συχνή ιδιοπαθή διάμεση πνευμονοπάθεια και την πιο σοβαρή νόσο λαμβάνοντας υπόψη την προοδευτική επιδείνωση της αναπνευστικής λειτουργίας που σχετίζεται με την ποιότητα ζωής, την πτωχή επιβίωση, και τις περιορισμένες θεραπευτικές επιλογές. Παρόλο που τα τελευταία έτη η ανακάλυψη των παθογενετικών μηχανισμών της νόσου όλο και περισσότερο κεντρίζει το ενδιαφέρον των ερευνητών, τα αίτια παθογένειας της ΙΠΙ παραμένουν εν πολλοίς άγνωστα. Το προτεινόμενο μοντέλο παθογένειας που επικρατεί έως σήμερα αναφέρεται σε βλάβες του επιθηλίου του βρογχικού δέντρου και των κυψελίδων που οφείλονται σε περιβαλλοντικούς παράγοντες, όπως την έκθεση σε καπνό, ιογενείς λοιμώξεις, γαστροοισοφαγική παλινδρόμηση, και όλα αυτά σε ένα υπόβαθρο ενός επιθηλίου γενετικά προδιαθετημένου σε ανώμαλη επιδιόρθωση. Απορρύθμιση των μηχανισμών επούλωσης, ανώμαλη επανα-επιθηλιοποίηση, υπέρμετρος πολλαπλασιασμός ινοβλαστών και μεγάλη παραγωγή εξωκυττάριας θεμέλιας ουσίας, αποτελούν τα στοιχεία που χαρακτηρίζουν την παθογένεια της ΙΠΙ. Μηχανισμοί οι οποίοι αποτελούν μονοπάτια της γήρανσης έχουν βρεθεί και στην ΙΠΙ , συμβάλλοντας στην ενίσχυση της άποψης ότι η νόσος αποτελεί μία νόσο πρώιμης γήρανσης. Σ’ αυτούς συμπεριλαμβάνεται το οξειδωτικό στρες, η δυσλειτουργία των μιτοχονδρίων, η μη αποτελεσματική αυτοφαγία και οι αλλαγές στην εξωκυττάρια ουσία. Η λεπτή ισορροπία μεταξύ αποικοδόμησης και βιογένεσης των μιτοχονδρίων έχει δειχθεί ότι είναι πολύ σημαντική για τη σωστή λειτουργία του κυττάρου. Συσσώρευση κατεστραμμένων πρωτεϊνών και οργανιδίων που οφείλεται σε μη αποτελεσματική αυτοφαγία οδηγεί σε αυξημένο κυτταρικό στρες και κυτταρικό θάνατο και έχει συσχετιστεί με νοσήματα της γήρανσης. Πρόσφατες μελέτες σε επιθηλιακά κύτταρα και ινοβλάστες σε πειραματικά μοντέλα ή/και ασθενείς με ΙΠΙ έδειξαν δυσλειτουργία των μιτοχονδρίων και μη αποτελεσματική αυτοφαγία των μιτοχονδρίων, δηλαδή μιτοφαγία. Σημαντικό ρόλο φαίνεται να διαδραματίζει το μόριο PINK1 (PTEN-induced kinase 1) που αποτελεί κύριο ρυθμιστή της διαδικασίας της μιτοφαγίας και τα επίπεδά του έχουν βρεθεί μειωμένα στα επιθηλιακά κύτταρα ασθενών με ΙΠΙ. Ο ρόλος των μακροφάγων αποτελεί τελευταία όλο και περισσότερο αντικείμενο έρευνας καθώς πολλά δεδομένα υποστηρίζουν την εμπλοκή των κυψελιδικών μακροφάγων στην ΙΠΙ. Τα κυψελιδικά μακροφάγα δεν αποτελούν μόνο κύτταρα του ανοσοποιητικού συστήματος επηρεάζοντας μέσω ανοσολογικών μηχανισμών, αλλά επίσης μέσω παραγωγής κυτταροκινών διαμορφώνουν το κατάλληλο μικροπεριβάλλον και αλληλεπιδρούν με τους υπόλοιπους κυτταρικούς πληθυσμούς στον πνεύμονα προάγοντας την ανάπτυξη της πνευμονικής ίνωσης. Έχει βρεθεί ότι τα μακροφάγα αποκτώντας ένα εναλλακτικά ενεργοποιημένο φαινότυπο, με αντίσταση στην απόπτωση, συμμετέχουν ενεργά στα μονοπάτια της παθογένειας της ίνωσης μέσω παραγωγής μεσολαβητών οι οποίοι σχετίζονται με την επιβίωση των μυοϊνοβλαστών, την ενεργοποίηση των επιθηλιακών κυττάρων και πιθανά στη μετατροπή των τελευταίων σε μεσεγχυματικά. Η δική μας μελέτη είχε ως στόχο την ανάλυση των μακροφάγων από βρογχοκυψελιδικό έκπλυμα ασθενών με ΙΠΙ, και συγκεκριμένα την εκτίμηση των μιτοχονδρίων τους. Απομόνωση των κυψελιδικών μακροφάγων πραγματοποιήθηκε από το βρογχοκυψελιδικό έκπλυμα το οποίο ελήφθη μέσω της διαδικασίας της βρογχοσκόπησης. Η λήψη του εκπλύματος αποτελεί μία ελάχιστα επεμβατική μέθοδο που οδηγεί σε συλλογή κυττάρων από τις κυψελίδες, που στο μεγαλύτερο ποσοστό τους αφορούν μακροφάγα (>80%). Οι ασθενείς (52 ασθενείς) που συμπεριελήφθησαν στη μελέτη υπεβλήθησαν σε βρογχοσκόπηση στο πλαίσιο διερεύνησης διάχυτης διάμεσης πνευμονοπάθειας (και έπειτα διαπιστώθηκε/επιβεβαιώθηκε ότι πρόκειται για ΙΠΙ) και συγκρίθηκαν με υγιείς μάρτυρες (19 άτομα) οι οποίοι υπεβλήθησαν σε βρογχοσκόπηση στο πλαίσιο διερεύνησης άτυπων μικροοζιδίων ή για αποκλεισμό πνευμονικής νόσου έπειτα από κάποιο επεισόδιο αιμόπτυσης, και με βάση τα αποτελέσματα της βρογχοσκόπησης (επισκόπηση βρογχικού δέντρου, καλλιέργειες, κυτταρολογικές εξετάσεις ) κρίθηκαν υγιείς. Τα κυψελιδικά μακροφάγα των ατόμων που συμπεριελήφθησαν στην παρούσα μελέτη αξιολογήθηκαν με βάση τα επίπεδα οξείδωσης των μιτοχονδρίων χρησιμοποιώντας κυτταρομετρία ροής, και διαπιστώθηκε ότι τα μακροφάγα ασθενών με ΙΠΙ εμφανίζουν σημαντικά υψηλότερα επίπεδα οξειδωμένων μιτοχονδρίων. Το αποτέλεσμα αυτό δεν συσχετίζεται με την καπνιστική συνήθεια των ασθενών, ενώ φάνηκε να σχετίζεται με στατιστική σημαντικότητα με τις κλινικές παραμέτρους της νόσου. Μελετήθηκαν ακολούθως τα επίπεδα αυτοφαγίας και μιτοφαγίας ώστε να διερευνηθεί εάν η αύξηση των οξειδωμένων μιτοχονδρίων οφείλεται σε μειωμένη διαδικασία αποικοδόμησης και ανακύκλωσης στα κύτταρα του βρογχοκυψελιδικού εκπλύματος, όμως δεν διαπιστώθηκαν σημαντικές διαφορές ανάμεσα σε ασθενείς και υγιείς μάρτυρες. Επιπλέον, εκτιμήθηκε η μορφολογία των μιτοχονδρίων στα κυψελιδικά μακροφάγα με τη χρήση ηλεκτρονικού μικροσκοπίου. Παρατηρήθηκε ότι τα μιτοχόνδρια στα μακροφάγα των ασθενών είναι δύσμορφα και έχουν αυξημένη διάμετρο υπονοώντας πιθανή δυσλειτουργία σύμφωνα με προηγούμενες μελέτες. Παράλληλα, επιβεβαιώθηκε ότι τα μακροφάγα στους ασθενείς με ΙΠΙ παρουσιάζουν δείκτες μάλλον υπέρ εναλλακτικής ενεργοποίησης-προϊνωτικό προφίλ. Τέλος, εκτιμήθηκε η έκφραση διαφόρων γονιδίων που σχετίζονται με την ανακύκλωση και την οξειδωτική φωσφορυλίωση που συμβαίνει στα μιτοχόνδρια, και βρέθηκε διαταραγμένη στους ασθενείς. Η μελέτη αυτή αποτελεί την πρώτη προσπάθεια χαρακτηρισμού της διαδικασίας της αυτοφαγίας, της μορφολογίας, και της οξείδωσης των μιτοχονδρίων στα μακροφάγα ασθενών με ΙΠΙ ρίχνοντας φως σε πιθανά παθογενετικά μονοπάτια της σοβαρής αυτής ασθένειας. Είναι σαφές από τα αποτελέσματα της μελέτης ότι τα μιτοχόνδρια των κυψελιδικών μακροφάγων των ασθενών με ΙΠΙ είναι δύσμορφα και δυσλειτουργικά, με αυξημένα επίπεδα οξείδωσης. Καθώς είναι αδιαμφισβήτητη η σημασία των μακροφάγων , όχι μόνο ως κύτταρα του ανοσοποιητικού, αλλά και ως ενορχηστρωτές της ινωτικής διεργασίας στον πνεύμονα, τα νέα δεδομένα αποτελούν σημαντικά στοιχεία που θα μπορούσαν να βοηθήσουν στον καλύτερο χαρακτηρισμό αυτού του αινιγματικού κυτταρικού πληθυσμού, σχετικά με τη λειτουργία, τη δράση και το μεταβολισμό τους.

Within the Interstitial Lung Diseases (ILD), patients with idiopathic pulmonary fibrosis (IPF) and a subset of those with non-IPF fibrotic ILD have a distinct clinical phenotype of progression despite management. This group of patients has been collectively termed the progressive fibrotic phenotype (PFP). Their early recognition may facilitate access to antifibrotic therapies to prevent or slow progression. Macrophages/monocytes within the lung orchestrate the progression and maintenance of fibrosis. A novel role for monocyte-derived macrophages during tissue damage and wound healing is the expression of collagens. We examined Collagen 1a1 expression in airway macrophages from ILD patients at diagnosis. COL1A1 mRNA levels from BAL cells were elevated in IPF and Non-IPF patients. The presence of a UIP pattern and a subsequent progressive phenotype were significantly associated with the higher BAL COL1A1 levels. In Non-IPF patients, higher COL1A1 levels were associated with a more than twofold increase in mortality. The intracellular localisation of COL1A1 in airway macrophages was demonstrated by confocal microscopy in CD45 and CD163 co-staining assays. Additionally, airway macrophages co-expressed COL1A1 with the profibrotic SPP1 gene product osteopontin. The levels of SPP1 mRNA and OPN in the BAL were significantly higher in IPF and Non-IPF patients relative to healthy. Our results suggest that profibrotic airway macrophages are increased in the BAL of patients with IPF and other ILDs and co-express COL1A1 and OPN. Importantly, COL1A1 expression by pro-fibrotic airway macrophages could be a marker of disease progression and poor survival in ILDs.

Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible fibrotic chronic lung disease affecting predominantly older adults, with a history of smoking. The current model of disease natural course is that recurrent injury of the alveolar epithelium in the context of advanced aging/cellular senescence is followed by defective re-epithelialization and scar tissue formation. Currently, two drugs, nintedanib and pirfenidone, that modify disease progression have been approved worldwide for the treatment of IPF. However, despite treatment, patients with IPF are not cured, and eventually, disease advances in most treated patients. Enhancing biogenomic and metabolic research output, its translation into clinical precision and optimal service delivery through patient-centeredness are key elements to support effective IPF care. In this review, we summarize therapeutic options currently investigated for IPF based on the major pathogenetic pathways and molecular targets that drive pulmonary fibrosis.

Airway Macrophages (AMs) are important in the pathogenesis of lung fibrosis. Inflammasomes (NLRP3,AIM2,NLRC4) are cytosolic receptors of the innate immune system responsible for cleavage of IL-1b, a proinflammatory,profibrotic cytokine. Inflammasomes respond to local microbiota changes. In IPF the bacterial burden is elevated and its composition is altered. AIM2 is increased and linked to exacerbation of fibrosis after Streptococcal infection (Cho,Thorax 2019). In IPF exacerbations, top upregulated genes in the BAL are IL-1b and NLRP3. MtROS drives NLRP3 activation and is elevated in IPF AMs (Tsitoura,RespRes 2019). We hypothesised that changes in lung microbiota in IPF may drive Inflammasome activation. As such, we studied the capacity of AMs to activate inflammasomes in relation to microbial burden and mtROS. We prospectively enrolled healthy and IPF subjects and isolated AMs from BAL. AMs were treated with specific inflammasome stimuli; ATP for NLRP3, dsDNA for AIM2, flagellin for NLRC4. IL-1b release was measured by ELISA, BAL microbial burden by 16S rRNA qPCR and mtROS by flow cytometry. The samples are sent for lung microbiome characterisation. Upon stimulation, IPF AMs over activate NLPR3 and AIM2 but not NLRC4. Baseline IL-1b release was similar between groups. Excessive inflammasome activation was linked to higher baseline mtROS. Microbial burden tended to be increased in IPF. Microbial burden correlated with baseline IL1b release. There was a strong association between the levels of 16S rRNA and relative AIM2 mRNA. Our results reveal a possible novel role of inflammasomes’ response to local microbiota changes which could be associated with the pathogenesis of IPF acute exacerbations.

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

SARS-coronavirus-2 (SARS-CoV-2), the etiologic agent of the new lung disease COVID-19 is closely related to SARS-CoV, and together with MERS-CoV are three new human coronaviruses that emerged in the last 20 years. The COVID-19 outbreak is a rapidly evolving situation with higher transmissibility and infectivity compared with SARS and MERS. Clinical presentations range from asymptomatic or mild symptoms to severe illness. The prevalent cause of mortality is pneumonia that progresses to ARDS. The ongoing pandemic has already resulted in more than 135,000 deaths and an unprecedented burden on national health systems worldwide. Pending the availability of a vaccine, there is a critical need to identify effective treatments and a number of clinical trials have been implemented worldwide. Trials are based on repurposed drugs that are already approved for other infections, have acceptable safety profiles or have performed well in animal studies against the other two deadly coronaviruses. Supportive care remains the mainstay of therapy at present, as it is still unclear how well these data can be extrapolated to SARS-CoV-2. Most of those emerging re-introduced drugs are administered to patients in the context of clinical trials. In this review, we summarize the strategies currently employed in the treatment of COVID-19.

Sarcoidosis is a disease characterized by granulomatous inflammation potentially affecting multiple organ systems. Although it can affect any organ, lungs, lymph nodes, skin and eyes are most commonly involved. Renal sarcoidosis, although rare, remains a challenging clinical issue requiring mandatory treatment, given the risk of developing renal failure. Taking into consideration the rarity of the disease, data regarding its diagnosis and treatment are scarce. This case series describes seven cases of sarcoidosis with predominantly renal manifestations, and moreover provides a review of the current literature on renal sarcoidosis.

Nintedanib is a tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis (IPF). In a retrospective, real-world study across seven Greek hospitals, we evaluated the effectiveness and safety of nintedanib in routine clinical practice. Patients diagnosed with IPF, as per guideline criteria or multidisciplinary diagnosis, received nintedanib between January 2013 and January 2018. We evaluated 244 patients: mean±sd age 71.8±7.5 years, 79.1% male, 45.1% current smokers and 33.1% ex-smokers at treatment initiation. At baseline, predicted forced vital capacity (FVC) was 73.3±20.7% and predicted diffusing capacity of the lungs for carbon monoxide (DLCO) was 42.6±16.7%. On average, patients spent 23.6±15.0 months on nintedanib. At 3 years, 78 patients had died, equating to a 3-year survival rate of 59.4% (unaffected by treatment discontinuation or dose reduction). FVC% pred and DLCO% pred were largely stable at 3 years, with no significant difference from baseline (FVC 73.3±20.7% pred versus 78±20.1% pred, p=0.074; DLCO 42.6±16.7% pred versus 40.4±18.1% pred, p=0.334). Of the 244 patients, 55.7% reported an adverse event. Gastrointestinal events were the most common (173 (77.2%) out of 224 total events) and 45.0% of patients experienced diarrhoea. Only 32 (13.1%) patients had to permanently discontinue nintedanib due to an adverse event. This real-world study shows a 3-year survival rate of 59.4% and a low discontinuation rate due to adverse events. Our experience is consistent with previous findings in clinical trials of nintedanib in IPF., Findings from the largest registry of Greek patients with IPF receiving nintedanib in routine clinical practice show, over a 3-year period, a low discontinuation rate and efficacy data that support the results of the INPULSIS clinical trials http://bit.ly/35a2CS5

Background Impaired mitochondria homeostasis and function are established hallmarks of aging and increasing evidence suggests a link with lung fibrosis. Mitochondria homeostasis may be also affected in alveolar macrophages (AMs) in idiopathic pulmonary fibrosis (IPF). In this study, we used bronchoalveolar lavage (BAL), a tool for both clinical and research purposes, and a rich source of AMs. Methods BAL samples were examined from 52 patients with IPF and 19 healthy individuals. Measurements of mitochondria reactive oxygen species (mtROS), mitochondria morphology and related gene expression were performed. Additionally, autophagy and mitophagy levels were analysed. Results Mitochondria in AMs from IPF patients had prominent morphological defects and impaired transcription paralleled to a significant reduction of mitochondria homeostasis regulators PINK1, PARK2 and NRF1. mtROS, was significantly higher in IPF and associated with reduced expression of mitochondria-encoded oxidative phosphorylation (OXPHOS) genes. Age and decline in lung function correlated with higher mtROS levels. Augmentation of damaged, oxidised mitochondria in IPF AMs however was not coupled to increased macroautophagy and mitophagy, central processes in the maintenance of healthy mitochondria levels. Conclusion Our results suggest a perturbation of mitochondria homeostasis in alveolar macrophages in IPF.

The role of pulmonary macrophages in the pathogenesis of Idiopathic Pulmonary Fibrosis (IPF) remains poorly understood. CD163 a scavenger receptor expressed on monocyte/macrophage cells, increases during resolution of inflammation and has been proposed as a marker of anti-inflammatory (M2) macrophages. It is suggested that the alveolar macrophage population in IPF is complex and adopts a pro-fibrotic phenotype. A recent study performed on lung biopsies demonstrated increased CD163 positive macrophages in ILDs in comparison with controls, and higher CD163 expression in other fibrotic lung diseases compared with IPF. In this study we analysed fresh BAL cells of patients at the time of diagnosis. Patients with IPF (n=33) and other ILDs (n=17), as well as control subjects (n=12) were included. Patients’ characteristics were analysed, including pulmonary function tests and smoking history. CD163 expression was analysed in alveolar macrophages identified as FSChighSSChighCD45+CD11c+ cells by flow cytometry. Furthermore, we analysed the correlation between CD163 percentage and pulmonary function (FVC, DLco) at the time of diagnosis as well as during follow-up period. CD163 positive macrophages were significantly higher in IPF (62.4±20.4%) relative to controls (40.8±18.3%) while there was no significant difference among fibrotic ILDs. The percentage of CD163 did not show significant correlation with pulmonary function parameters. Our results showed elevated expression of CD163 on alveolar macrophages in the BAL in fibrotic lung diseases, however the heterogeneity of the alveolar macrophages warrants further evaluation in order to clarify the subtypes and activation of ILD macrophages.

Introduction: Several similarities and differences have been detected between idiopathic pulmonary fibrosis (IPF) and lung cancer (LC) on the ground of key pathogenic mechanisms. The implication of alveolar macrophages (AMs) in their pathogenesis continually recovers ground. M2 macrophages orchestrate the resolution of inflammation and are linked with tissue repair and fibrosis, while have been implicated in tumor immune surveillance. Aims and Objectives: The aim of this study was to evaluate the expression of an M2 marker, CD163 on alveolar macrophages from BAL samples collected from 12 controls, 34 IPF and 17 LC patients. Patients with LC were further analysed relative to the adjacency of the BAL cells with the malignant lesion. (SS: same side, OS: opposite side). Methods: Cell surface marker CD163 was used for phenotypic characterization of BAL derived AMs (FSChighSSChighCD45+CD11c+ cells) by flow cytometry. Results: CD163 expression on AMs was higher in IPF group compared with both control and LC group. The difference between IPF and LC was more pronounced. Higher levels of CD163 positive AMs were observed in the subgroup of LC patients where BAL procedure was performed close to the malignant lesion (SS), compared with the cases of LC that the BAL was performed at the opposite side. Conclusion: The distinct expression of CD163+ AMs between IPF and LC may reflect a disease-specific effect of the microenvironment on AMs polarization. The proximity of AMs with the tumor may also influence the intense of M2 functional status of AMs in LC.

Background: Varenicline is used at a standard dose as a first line pharmacotherapy in smoking cessation, as proposed by international guidelines. Aim: To assess the short and long term abstinence rate from smoking with low dose of varenicline in the second and third month of treatment. Design: A retrospective non-randomized clinical trial was conducted at a stop-smoking center of University Hospital of Heraklion, Crete, Greece during economic crisis, from January 1, 2016 to December 29, 2016. Participants were 143 smokers (> 30 pack years) with mean age of 48, 64% men and 36% women. Method: All participants received standard dose varenicline for 4 weeks (0.5mg for 3 days, 0.5mg twice daily for 3 days, and 1mg twice daily from 8th to 28th day). 78 were lost to follow up and 65 were finally analyzed. At 29th day 31 participants received low dose (1mg once daily) and 34 received standard dose (1mg twice daily). Main Outcome: Compliance to treatment (exhaled carbn monoxide Results: For weeks 1 through 6, the 6-week continuous abstinence rates were 91,2% for low dose varenicline vs 51.6% for standard dose varenicline (p=0.004). Abstinence rate at 2 years was 31.6% for low dose varenicline vs 38,9% for standard dose (p=0.388). Patients attending the 4th and 5th visits had higher abstinence rate at 2 years (p=0.005). Conclusion: Low dose of varenicline is non inferior to standard dose both at the short term and long term period. We also showed that the close follow up of patients results to higher abstinence rate at 2 years.

Interstitial Lung Diseases (ILDs) encompass a complex group of pulmonary disorders with varying prognosis and clinical behavior. Idiopathic pulmonary fibrosis(IPF) is the most common and most lethal among the fibrosing ILDs. The role of pulmonary macrophages in the pathogenesis of IPF remains poorly understood however, macrophages within the lung may orchestrate the progression and maintenance of fibrosis. In this study we analysed the expression of microRNA Let7c, required for the differentiation of alternatively activated macrophages, in BAL cells from IPF patients and other f-ILDs (CHP, fNSIP, RA-ILD, SSc-ILD, and SLE-ILD ) relative to controls, at the time of diagnosis, as a possible marker for disease progression. Alternatively activated alveolar macrophages were phenotypically characterized by CD45, CD11c, CD14, and CD163. Let7c was significantly lower in IPF as compared to other f-ILDs although it was not different from controls. In contrast CD163 positive macrophages were significantly higher in IPF and fibrotic ILDs relative to controls. Low Let7c levels were significantly associated with lower survival in patients with fibrotic lung disease, while a similar trend was observed within the non-IPF f-ILDs group. Additionally, disease progression at 6, 12 and 24 months following diagnosis was moderately negatively correlated with the levels of Let7c at baseline through the pulmonary fibrosis groups. Transcription in BAL cells in IPF is significantly affected in IPF relative to other f-ILDs, and gene expression related to alveolar macrophage activation may serve as diagnostic and disease progression marker.