Endobronchial metastasis from renal cell carcinoma as a reason for recurrent pulmonary infections

Endobronchial metastases (EBM) secondary to extrathoracic malignancies are very rare. Breast cancer, colorectal cancer andrenal cell carcinoma represent the most common types of cancer leading to endobronchial metastases. They usually representa late manifestation of other types of cancer and their prognosis is generally poor averaging a survival of 1-2 years in most caseseries. Due to their rarity, they remain a challenge for clinicians regarding whether they are primary lung tumors or not. This casereport article intends to present a case of a young man with a left nephrectomy due to clear cell renal carcinoma, who developedEBM 7 years later and to summarize available data in the field. Furthermore, the utility of diathermic snare as a treatment approachfor this entity is highlighted

Measles pneumonitis

Measles is an acute febrile illness, potentially fatal and highly contagious, which is transmitted through the respiratory mode. Fevercombined with one of the following: cough, coryza, conjunctivitis are the first manifestations of the disease. Koplik’s spots mayalso appear on the buccal mucosa providing an opportunity to set the diagnosis even before the emergence of rash. Rash typicallyappears 3–4 days after the onset of fever, initially on the face and behind the ears, and its appearance is associated with the peakof the symptoms. Measles affects multiple systems, including the respiratory system, with pneumonia being one of the most lethalcomplications. Management involves best supportive care, correction of dehydration and nutritional deficiencies, treatment ofsecondary bacterial infections and provision of vitamin A. Importantly, given that measles present with lifelong immunity followinginfection or vaccination, prevention through measles vaccination has a cardinal role for measles’ elimination. Indeed, public educationand vaccination led to an estimated 79% decrease in global measles deaths from 2000 to 2015. Nonetheless, the last two years haveseen a measles outbreak in several countries, partially due to the anti-vaccination movement. This article aims to present two casesof measles in our hospital and highlight the pressing need for vaccination in order to eradicate a potentially fatal disease

Bleomycin Revisited: A Direct Comparison of the Intratracheal Micro-Spraying and the Oropharyngeal Aspiration Routes of Bleomycin Administration in Mice

Idiopathic Pulmonary Fibrosis (IPF) is a fatal disease characterized by exuberant deposition of extracellular matrix components, deterioration of lung architecture and impairment of lung functions. Its etiopathogenesis remains incompletely understood, as reflected in the lack of an appropriate therapy. Modeling the human disease in mice via the administration of bleomycin (BLM), despite the inherent limitations, has provided valuable insights into the underlying pathogenetic mechanisms, and has been instrumental for the development and validation of new pharmacologic interventions. Here we have directly compared the, most widely used, intratracheal (IT) route of administration with oropharyngeal aspiration (OA). Our results suggest that the OA route of BLM-administration can be used as a safe and effective alternative, minimizing peri-operative and experimental mortality, while preserving a solid fibrotic profile, as assessed with a plethora of standardized readout assays

Przerzuty raka nerkowokomórkowego do oskrzeli przyczyną nawracających infekcji dróg oddechowych

Przerzuty do oskrzeli nowotworów rozwijających się poza klatką piersiową występują niezwykle rzadko. Najczęstszymi typami raka, które do nich prowadzą, są rak sutka, rak jelita grubego i rak nerkowokomórkowy. Przerzuty do oskrzeli stanowią zazwyczaj późny objaw innych typów nowotworu i ich rokowanie jest zazwyczaj złe — średnie przeżycie w większości przypadków wynosi 1–2 lata. Z powodu swojej unikatowości pozostają wyzwaniem dla lekarzy oceniających, czy są one pierwotnym guzem płuc, czy mają charakter wtórny. W niniejszym artykule przedstawiono przypadek młodego mężczyzny po usunięciu lewej nerki z powodu raka jasnokomórkowego, u którego po 7 latach pojawiły się przerzuty do oskrzeli, oraz podsumowano dostępne dane literaturowe. Autorzy odnoszą się ponadto do stosowania pętli diatermicznej jako metody leczenia tej jednostki chorobowej.Przerzuty do oskrzeli nowotworów rozwijających się poza klatką piersiową występują niezwykle rzadko. Najczęstszymi typami raka, które do nich prowadzą, są rak sutka, rak jelita grubego i rak nerkowokomórkowy. Przerzuty do oskrzeli stanowią zazwyczaj późny objaw innych typów nowotworu i ich rokowanie jest zazwyczaj złe — średnie przeżycie w większości przypadków wynosi 1–2 lata. Z powodu swojej unikatowości pozostają wyzwaniem dla lekarzy oceniających, czy są one pierwotnym guzem płuc, czy mają charakter wtórny. W niniejszym artykule przedstawiono przypadek młodego mężczyzny po usunięciu lewej nerki z powodu raka jasnokomórkowego, u którego po 7 latach pojawiły się przerzuty do oskrzeli, oraz podsumowano dostępne dane literaturowe. Autorzy odnoszą się ponadto do stosowania pętli diatermicznej jako metody leczenia tej jednostki chorobowej

Clinical improvement in Job syndrome following administration of co-trimoxazole, omalizumab and inhaled tobramycin

Established treatment regimens for the autosomal dominant hyperimmunoglobulin E syndrome, denominated Job syndrome, are lacking. Thus, Job syndrome still exerts a dramatic impact on patients’ quality of life. Our aim was to present safety and effectiveness of a regimen including co-trimoxazole, omalizumab and inhaled tobramycin in Job syndrome. A 26-year-old woman diagnosed with Job syndrome since infancy through sequencing revealing G342D mutation in STAT3 gene was initiated in the above mentioned treatment regimen; she was followed for 6 months, and to date, none recurrent pulmonary or skin infection was noticed. Furthermore, a considerable improvement in skin lesions was observed. A combination of anti-IgE and longitudinal use of inhaled antibiotics seems well-founded in Job syndrome

Cardiovascular Risk Assessment in a Cohort of Newly Diagnosed Patients with Obstructive Sleep Apnea Syndrome

Objectives. Obstructive sleep apnea syndrome (OSAS) is associated with increased cardiovascular morbidity and mortality. The aim of this study was to assess whether the 10-year risk for cardiovascular disease in newly diagnosed patients with OSAS is increased. Materials and Methods. Recently diagnosed, with polysomnography, consecutive OSAS patients were included. The Systematic Coronary Risk Evaluation (SCORE) and the Framingham Risk Score (FRS) were used to estimate the 10-year risk for cardiovascular disease. Results. Totally, 393 individuals (73.3% males), scheduled to undergo a polysomnographic study with symptoms indicative of OSAS, were enrolled. According to apnea-hypopnea index (AHI), subjects were divided in four groups: mild OSAS (AHI 5–14.9/h) was diagnosed in 91 patients (23.2%), moderate OSAS (AHI 15–29.9/h) in 58 patients (14.8%), severe OSAS (AHI > 30/h) in 167 patients (42.5%), while 77 individuals (19.6%) had an AHI < 5/h and served as controls. Increased severity of OSAS was associated with increased SCORE p<0.001 and FRS values p<0.001. More specifically, a significant correlation was observed both between AHI and SCORE r=0.251, p<0.001 and AHI and FRS values r=0.291, p<0.001. Furthermore, a negative correlation was observed between FRS values and sleep efficiency r=−0.224, p=0.006. Conclusions. The 10-year risk for cardiovascular morbidity and mortality seems to increase with severity of OSAS. Physicians should bear this finding in mind, in order to seek for and consecutively eliminate risk factors for cardiovascular disease and to prevent future cardiovascular events in OSAS patients

Increased lipocalin-2 expression in pulmonary inflammation and fibrosis

IntroductionIdiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive interstitial lung disease with dismal prognosis. The underlying pathogenic mechanisms are poorly understood, resulting in a lack of effective treatments. However, recurrent epithelial damage is considered critical for disease initiation and perpetuation, via the secretion of soluble factors that amplify inflammation and lead to fibroblast activation and exuberant deposition of ECM components. Lipocalin-2 (LCN2) is a neutrophil gelatinase-associated lipocalin (NGAL) that has been suggested as a biomarker of kidney damage. LCN2 has been reported to modulate innate immunity, including the recruitment of neutrophils, and to protect against bacterial infections by sequestering iron.MethodsIn silico analysis of publicly available transcriptomic datasets; ELISAs on human IPF patients' bronchoalveolar lavage fluids (BALFs); bleomycin (BLM)-induced pulmonary inflammation and fibrosis and LPS-induced acute lung injury (ALI) in mice: pulmonary function tests, histology, Q-RT-PCR, western blot, and FACS analysis.Results and discussionIncreased LCN2 mRNA expression was detected in the lung tissue of IPF patients negatively correlating with respiratory functions, as also shown for BALF LCN2 protein levels in a cohort of IPF patients. Increased Lcn2 expression was also detected upon BLM-induced pulmonary inflammation and fibrosis, especially at the acute phase correlating with neutrophilic infiltration, as well as upon LPS-induced ALI, an animal model characterized by neutrophilic infiltration. Surprisingly, and non withstanding the limitations of the study and the observed trends, Lcn2−/− mice were found to still develop BLM- or LPS-induced pulmonary inflammation and fibrosis, thus questioning a major pathogenic role for Lcn2 in mice. However, LCN2 qualifies as a surrogate biomarker of pulmonary inflammation and a possible indicator of compromised pulmonary functions, urging for larger studies

Acute exacerbation of idiopathic pulmonary fibrosis: International survey and call for harmonisation.

AIM Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is an often deadly complication of IPF. No focused international guidelines for the management of AE-IPF exist. The aim of this international survey was to assess the global variability in prevention, diagnostic and treatment strategies for AE-IPF. MATERIAL AND METHODS Pulmonologists with ILD expertise were invited to participate in a survey designed by an international expert panel. RESULTS 509 pulmonologists from 66 countries responded. Significant geographical variability in approaches to manage AE-IPF was found. Common preventive measures included antifibrotic drugs and vaccination. Diagnostic differences were most pronounced regarding use of KL-6 and viral testing, while HRCT, BNP and D-Dimer are generally applied. High dose steroids are widely administered (94%); the use of other immunosuppressant and treatment strategies is highly variable. Very few (4%) responders never use immunosuppression. Antifibrotic treatments are initiated during AE-IPF by 67%. Invasive ventilation or extracorporeal membrane oxygenation are mainly used as a bridge to transplantation. Most physicians educate patients comprehensively on the severity of AE-IPF (82%) and consider palliative care (64%). CONCLUSION Approaches to the prevention, diagnosis and treatment of AE-IPF vary worldwide. Global trials and guidelines to improve the prognosis of AE-IPF are needed

Study of the pathogenesis of idiopathic interstitial pneumonias with the use of microarrays

Idiopathic interstitial pneumonias (IIPs) are a heterogeneous group of diseases comprising of seven distinct clinical and pathological entities. Idiopathic pulmonary fibrosis (IPF) and cryptogenic organizing pneumonia (COP) represent two of the most prevalent members of the disease group with major differences in pathogenesis, clinical course and prognosis. The incidence of IPF is estimated at 6.8-16.3 cases per 100.000 per year in the United States, and the mean survival from the time of diagnosis is 3-5 yr regardless of treatment. IPF is a refractory and lethal IIP characterized by fibroblast proliferation, extracellular matrix deposition and progressive lung scarring, comprising the histopathologic pattern of usual interstitial pneumonia (UIP). In UIP, areas of accumulated fibroblasts and myofibroblasts mainly distributed in subepithelial areas of the intersititium, termed fibroblastic foci represent the pathogenetic hallmark of fibrogenesis. On the other hand, COP, is a patchy process involving alveolar ducts and alveoli, characterized by distinct fibromyxoid lesions called Masson bodies that are susceptible to even complete reversal, in contrast to fibroblastic foci that represent collections of highly proliferative fibroblastic-like cells resistant to apoptosis. These lesions may reflect differential wound repair responses to lung injury; the active fibrosis of IPF mirrors the abnormal wound repair in response to multiple sites of ongoing alveolar epithelial injury, involving increased activity and possibly exaggerated responses by a spectrum of proinflammatory and profibrogenic factors whereas that of COP may reflect normal wound repair response to pulmonary injury. In IPF, due to the lack of a more effective alternative, the fundamental therapeutic approach has been use of corticosteroids, alone or in combination with other immunosuppressive agents; however, this has little impact on long-term survival and is effective only in a minority of affected individuals. While the treatment of IPF remains elusive, COP presents with excellent prognosis and corticosteroid treatment responsiveness. Several studies have attributed these differences to distinct pathogenetic characteristics reflected by regional differences in apoptotic and angiogenic profiles. In an attempt to elucidate pathogenetic differences between these two disease entities and delineate potential mechanisms explaining distinct regional apoptotic and angiogenic profiles we investigated the expression of HIF-1a and telomerase in experimental models of pulmonary fibrosis and in patients with IPF and COP. A. HIF-1a in the pathogenesis of pulmonary fibrosis HIF-1a is recognized as a master regulator of hypoxic signaling by activating gene transcription of genes encoding proteins that mediate the cellular adaptive response under hypoxic conditions. Hypoxia, the lack of oxygen, can modulate alveolar epithelial cell homeostasis by promoting significant and adverse effects on epithelial function, including VEGF and surfactant protein production, disruption of cytoskeleton integrity, and the triggering of apoptosis through induction of p53 expression. Alveolar hypoxia can also promote macrophage recruitment and enhanced expression of inflammatory mediators. Thus, hypoxia could represent a potential fibrotic stimulus through induction of epithelial apoptosis, angiogenesis and modulation of the inflammatory response. With the use of DNA microarrays we performed extensive expression profiling of disease progression in an animal model of the disease, compared our data with all publicly available expression profiles both from human patients and animal models and identified HIF-1a as one of the most deregulated genes. The mRNA levels of HIF-1a, as well as of HIF-1a target gene vegfa, were found upregulated upon administration of bleomycin and the development of pulmonary inflammation and fibrosis. Immunohistochemistry for HIF-1a confirmed overexpression of HIF-1a localizing it mainly at the epithelium. Notably, HIF-1a (and HIF-1 target gene vegfa) overexpression was observed early in the pathologic cascade, before any deterioration of lung architecture and consequent gas exchange problems, indicating an early role for HIF-1 in the development of the modeled disease. Since the bleomycin animal model is not fully representative of IPF due to its self limiting nature and rapidity of its development, we then investigated HIF-1a immunolocalization in lung samples from patients with IPF/UIP and COP/OP, two histopathologic patterns of pulmonary fibrosis with different clinical course and prognosis. We used the pioneering technology of tissue microarrays, which allowed us the simultaneous analysis of up to 250 samples in a single experiment under highly standardized conditions. ...Οι ιδιοπαθείς διάμεσες πνευμονίες (IIPs) αποτελούν μια ετερογενή ομάδα νοσημάτων αποτελούμενες από επτά διακριτές κλινικές και παθολογοανατομικές οντότητες. Η ιδιοπαθής πνευμονική ίνωση (IPF) και η κρυπτογενής οργανοποιός πνευμονία (COP) είναι δύο από τα πιο συχνά απαντώμενα στην κλινική πράξη νοσήματα αυτής της κατηγορίας. Η IPF είναι μια περιοριστική και θανατηφορός διάμεση πνευμονία που χαρακτηρίζεται από πολλαπλασιασμό των ινοβλαστών, εναπόθεση εξωκυττάριας θεμέλιας ουσίας που συνθέτουν το παθολογοανατομικό πρότυπο της συνήθους διάμεσης πνευμονίας (UIP). Η επίπτωση της IPF κυμαίνεται περίπου σε 6.8-16.3 περιπτώσεις ανά 100.000 ανά χρόνο στις Ηνωμένες Πολιτείες της Αμερικής ενώ ο μέσος χρόνος επιβίωσης από τη στιγμή της διάγνωσης είναι 3-5 έτη ανεξαρτήτου θεραπείας. Στην UIP, συναθροίσεις ινοβλαστών και μυοϊνοβλαστών εντοπιζόμενες κυρίως στις υποϋπεζωκοτικές ζώνες του διάμεσου χώρου, που ονομάζονται ινοβλαστικές εστίες (fibroblastic foci), αποτελούν το παθογενετικό ορόσημο και ένα από τα κριτήρια για την διάγνωση της νόσου. Aπό την άλλη μεριά, η κρυπτογενής οργανοποιός πνευμονία (COP) αποτελεί μια διάχυτη ινωτική διεργασία που προσβάλλει τους κυψελιδικούς σάκους και τις κυψελίδες και χαρακτηρίζεται από διακριτές ινομυξωματώδεις βλάβες, που λέγονται σωμάτια Masson (Masson bodies), και τα οποία σε αντίθεση με τις ινοβλαστικές εστίες της IPF υπόκεινται πλήρη ίαση και υποστροφή. Οι διεργασίες αυτές μπορεί να αντιπροσωπεύουν διαφορετικές ανταποκρίσεις του κυψελιδικού επιθηλίου σε βλαπτικά ερεθίσματα; Οι εστίες ενεργού ίνωσης της IPF αντανακλούν παθολογική ανταπόκριση του επιθηλίου σε επαναλαμβανόμενα βλαπτικά ερεθίσματα και η παθογένεια τους περιλαμβάνει την ενεργοποίηση μιας σειράς προ-φλεγμονωδών και προ-ινωτικών παραγόντων, ενώ αντίθετα εκείνες της COP (Masson bodies) πιθανόν να αντιπροσωπεύουν φυσιολογική απόκριση του επιθηλίου σε ένα βλαπτικό ερέθισμα. Στην IPF λόγω της έλλειψης αποτελεσματικής θεραπείας, η τρέχουσα θεραπευτική στρατηγική περιλαμβάνει τη χρήση κορτικοστεροειδών σε συνδυασμό με ανοσοκατασταλτικά και ανοσοτροποιητικά. Ωστόσο, όλα αυτά έχουν περιορισμένο αποτέλεσμα στην μακροχρόνια επιβίωση των ασθενών με IPF και είναι ευεργετικά στη μειοψηφία τους. Αντίθετα με την IPF, η COP παρουσιάζεται με πολύ καλή πρόγνωση, κλινική πορεία και ανταπόκριση στη θεραπεία με κορτικοστεροειδή. Αρκετές μελέτες απέδωσαν τις διαφορές αυτές σε σημαντικές παθογενετικές διαφορές αντανακλώμενες σε διακριτά εκφραστικά πρότυπα απόπτωσης και αγγειογένεσης. Σε μια προσπάθεια να αποσαφηνίσουμε τις παθογενετικές αυτές διαφορές και να σχεδιάσουμε μηχανισμούς που να εξηγούν τα διακριτά αποπτωτικά και αγγειογενετικά εκφραστικά πρότυπα, μελετήσαμε την έκφραση του HIF-1a και της τελομεράσης στο πειραματικό μοντέλο της πνευμονικής ίνωσης αλλά και σε δείγματα ασθενών με IPF και COP. Α. Ο ρόλος του HIF-1a στην παθογένεια της πνευμονικής ίνωσης Ο HIF-1a αναγνωρίζεται ως ο κυρίαρχος ρυθμιστικός παράγοντας της κυτταρικής υποξικής σήμανσης επάγοντας τη μεταγραφή γονιδίων στόχων τα οποία κωδικοποιούν πρωτεΐνες που καθορίζουν την κυτταρική απάντηση στην υποξία. H υποξία, η έλλειψη δηλαδή οξυγόνου, μπορεί να τροποποιήσει την κυτταρική ομοιόσταση του κυψελιδικού επιθηλίου με την επαγωγή σημαντικών προστατευτικών αλλά και ανεπιθύμητων-βλαβερών λειτουργιών της επιθηλιακής λειτουργίας όπως η έκφραση του VEGF και η παραγωγή επιφανειοδραστικού παράγοντα (surfactant factor) καθώς και η καταστροφή της ακεραιότητας του κυτταροσκελετού και η πυροδότηση της απόπτωσης. Η κυψελιδική υποξία μπορεί επίσης να προάγει τη συστράτευση μακροφάγων και άλλων φλεγμονωδών κυττάρων και να οδηγήσει στην αυξημένη παραγωγή φλεγμονωδών μεσολαβητών. Για τους παραπάνω λόγους η υποξία δύναται να αντιπροσωπεύει ένα ινωτικό ερέθισμα μέσω επαγωγής της επιθηλιακής απόπτωσης και ρύθμισης της αγγειογένεσης και της φλεγμονώδους απάντησης. Mε τη χρήση μικροσυστοιχιών γενετικού υλικού (DNA microarrays) πραγματοποιήσαμε συγκριτική μελέτη μοριακής αποτύπωσης της εξέλιξης της νόσου στο πειραματικό μοντέλο της πνευμονικής ίνωσης και αναδείξαμε τον επαγόμενο από την υποξία παράγοντα (HIF-1a) ως ένα από τα γονίδια με τις μεγαλύτερες διαταραχές στην έκφραση τους. Τα επίπεδα mRNA του HIF-1a καθώς και γονιδίων στόχων του συμπεριλαμβανομένων του vegfa, βρέθηκαν αυξημένα μετά τη χορήγηση μπλεομυκίνης και την ανάπτυξη πνευμονικής φλεγμονής και ίνωσης. Η ανοσοϊστοχημική μελέτη του HIF-1a αποκάλυψε υπερέκφραση του παράγοντα κυρίως στο κυψελιδικό επιθήλιο των ποντικιών. ..