Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and morbidity worldwide, with high and growing prevalence. Its underdiagnosis and hence under-treatment is a general ...feature across all countries. This is particularly true for the mild or early stages of the disease, when symptoms do not yet interfere with daily living activities and both patients and doctors are likely to underestimate the presence of the disease. A diagnosis of COPD requires spirometry in subjects with a history of exposure to known risk factors and symptoms. Postbronchodilator forced expiratory volume in 1 second (FEV
)/forced vital capacity <0.7 or less than the lower limit of normal confirms the presence of airflow limitation, the severity of which can be measured by FEV
% predicted: stage 1 defines COPD with mild airflow limitation, which means postbronchodilator FEV
≥80% predicted. In recent years, an elegant series of studies has shown that "exclusive reliance on spirometry, in patients with mild airflow limitation, may result in underestimation of clinically important physiologic impairment". In fact, exercise tolerance, diffusing capacity, and gas exchange can be impaired in subjects at a mild stage of airflow limitation. Furthermore, growing evidence indicates that smokers without overt abnormal spirometry have respiratory symptoms and undergo therapy. This is an essential issue in COPD. In fact, on one hand, airflow limitation, even mild, can unduly limit the patient's physical activity, with deleterious consequences on quality of life and even survival; on the other hand, particularly in younger subjects, mild airflow limitation might coincide with the early stage of the disease. Therefore, we thought that it was worthwhile to analyze further and discuss this stage of "mild COPD". To this end, representatives of scientific societies from five European countries have met and developed this document to stimulate the attention of the scientific community on COPD with "mild" airflow limitation. The aim of this document is to highlight some key features of this important concept and help the practicing physician to understand better what is behind "mild" COPD. Future research should address two major issues: first, whether mild airflow limitation represents an early stage of COPD and what the mechanisms underlying the evolution to more severe stages of the disease are; and second, not far removed from the first, whether regular treatment should be considered for COPD patients with mild airflow limitation, either to prevent progression of the disease or to encourage and improve physical activity or both.
The interplay between purinergic receptors as well as pattern recognition receptors like Toll-like receptors (TLRs) and NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) might have a role in ...the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of this study was to determine and compare the concentrations of the damage-associated molecular patterns (DAMPs) heat shock protein 70 (Hsp70) and adenosine triphosphate (ATP), and gene expression of their respective receptors as well as NLRP3 inflammasome-related molecules in the peripheral blood of patients with end-stage COPD before and 1 year after lung transplantation (LT). Lung function was assessed by spirometry and diffusion capacity for carbon monoxide (DLCO). Quantitative polymerase chain reaction (qPCR) was applied for detection of TLR2, TLR4, P2X7R, P2Y2R, IL1B, CASP1, and NLRP3 expression. High-sensitivity ELISA kits were used for extracellular (e) Hsp70 and IL-1β, and luminescence assay for eATP measurements. Concentrations of eHsp70 and eATP as well as IL-1β were significantly increased in the plasma of end-stage COPD patients and significantly decreased after LT. In addition, TLR4, P2Y2R, IL1B, CASP1, and NLRP3 expression was up-regulated in COPD patients before LT, while it was significantly suppressed after LT. In conclusion, it could be assumed that NLRP3 inflammasome is activated in the peripheral blood of end-stage COPD patients and that eHsp70 and eATP could be responsible for its activation through triggering their receptors. On the other hand, previously enhanced pro-inflammatory reactions seem to be suppressed to the healthy population levels in lung recipients without allograft rejection.
The most commonly used topical hemostatic agents during flexible bronchoscopy (FB) are cold saline and adrenaline. Data on use of other agents such as tranexamic acid (TXA) for this purpose are ...limited.
Is TXA effective and safe in controlling iatrogenic bleeding during FB compared with adrenaline?
We conducted a cluster-randomized, double-blind, single-center trial in a tertiary teaching hospital. Patients were randomized in weekly clusters to receive up to three applications of TXA (100 mg, 2 mL) or adrenaline (0.2 mg, 2 mL, 1:10000) after hemostasis failure after three applications of cold saline (4 ° C, 5 mL). Crossover was allowed (for up to three further applications) before proceeding with other interventions. Bleeding severity was graded by the bronchoscopist using a visual analog scale (VAS; 1 = very mild, 10 = severe).
A total of 2,033 FBs were performed and 130 patients were randomized successfully to adrenaline (n = 65) or TXA (n = 65), whereas 12 patients had to be excluded for protocol violations (two patients from the adrenaline arm and 10 patients from TXA arm). Bleeding was stopped in 83.1% of patients (54/65) in both groups (P = 1). The severity of bleeding and number of applications needed for bleeding control were similar in both groups (adrenaline: mean VAS score, 4.9 ± 1.3 n = 1.8 ± 0.8; TXA: mean VAS score, 5.3 ± 1.4 n = 1.8 ± 0.8). Both adrenaline and TXA were more successful in controlling moderate bleeding (86.7% and 88.7%, respectively) than severe bleeding (40% and 58.3%, respectively; P = .008 and P = .012, respectively) and required more applications for severe bleeding (3.0 ± 0 and 2.4 ± 0.5, respectively) than moderate bleeding (1.7 ± 0.8 and 1.7 ± 0.8, respectively) control (P = .006 and P = .002, respectively). We observed no drug-related adverse events in either group.
We found no significant difference between adrenaline and TXA for controlling noncatastrophic iatrogenic endobronchial bleeding after cold saline failure, adding to the body of evidence that TXA can be used safely and effectively during FB.
ClinicalTrials.gov; No.: NCT04771923; URL: www.clinicaltrials.gov
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Chronic obstructive pulmonary disease (COPD) is considered as the strongest independent risk factor for lung cancer (LC) development, suggesting an overlapping genetic background in both diseases. A ...common feature of both diseases is aberrant immunity in respiratory epithelia that is mainly regulated by Toll-like receptors (TLRs), key regulators of innate immunity. The function of the flagellin-sensing TLR5 in airway epithelia and pathophysiology of COPD and LC has remained elusive. We performed case−control genetic association and functional studies on the importance of TLR5 in COPD and LC development, comparing Caucasian COPD/LC patients (n = 974) and healthy donors (n = 1283). Association analysis of three single nucleotide polymorphisms (SNPs) (rs725084, rs2072493_N592S, and rs5744174_F616L) indicated the minor allele of rs2072493_N592S to be associated with increased risk for COPD (OR = 4.41, p < 0.0001) and NSCLC (OR = 5.17, p < 0.0001) development and non-small cell LC risk in the presence of COPD (OR = 1.75, p = 0.0031). The presence of minor alleles (rs5744174 and rs725084) in a co-dominant model was associated with overall survival in squamous cell LC patients. Functional analysis indicated that overexpression of the rs2072493_N592S allele affected the activation of NF-κB and AP-1, which could be attributed to impaired phosphorylation of p38 and ERK. Overexpression of TLR5N592S was associated with increased chemosensitivity in the H1299 cell line. Finally, genome-wide transcriptomic analysis on WI-38 and H1299 cells overexpressing TLR5WT or TLR5N592S, respectively, indicated the existence of different transcription profiles affecting several cellular pathways potentially associated with a dysregulated immune response. Our results suggest that TLR5 could be recognized as a potential biomarker for COPD and LC development with functional relevance.
Astma je kronična upalna bolest dišnih putova koja zahvaća i male dišne putove. Inhalacijski kortikosteroidi učinkoviti su lijekovi u liječenju astme, međutim slabo dopiru u male dišne putove. Nove ...formulacije inhalacijskih kortikosteroida s vrlo sitnim česticama, manjim od 5 μm, značajno se bolje odlažu u male dišne putove i alveole. Qvar HFA-beklometazon dipropionat, nova je formulacija beklometazona s vrlo sitnim česticama, što omogućava da se više od 50% lijeka raspodijeli u pluća te je na taj način potrebna 2,6 puta niža doza kortikosteroida da bi se ostvario jednak učinak u usporedbi s klasičnim inhalacijskim beklometazon dipropionatom. Pored toga Autohaler se vrlo jednostavno upotrebljava jer se aktivira udahom te eliminira problem koordinacije pritiska na inhaler i udaha. Qvar ostvaruje jednaku ili bolju učinkovitost uz značajno manje lokalnih nuspojava u usporedbi s klasičnim inhalacijskim kortikosteroidima te podjednaku učestalost sistemskih nuspojava. Zbog dobre raspodjele u plućima i djelovanja na male dišne putove te zbog inhalera koji se jednostavno upotrebljava, Qvar Autohaler omogućuje bolju kontrolu astme.
Lung cancer is one of the most diagnosed malignancies with increasing incidence worldwide. Immunotherapy is the main oncological treatment for advanced non-small cell lung cancer (NSCLC), for which ...the discovery of new efficient biomarkers is crucial. Scientific evidence points to the importance of the Lung Immune Prognostic Index (LIPI), but its predictive significance is unclear.
The aim of this study was to investigate the clinical significance and predictive role of LIPI in patients with advanced NSCLC and PD-L1 mutation who are eligible for immunotherapy in combination with chemotherapy. In addition, to our knowledge, this is the first time that the association between COVID-19 infection and the course and outcome of oncologic treatment of NSCLC has been investigated.
Patients were divided into four study groups according to strictly defined clinical parameters, therapeutic approach, and COVID-19 infection. LIPI was determined and its predictive power was evaluated in all studied groups, as well as overall survival (OS), progression-free survival (PFS), and disease control rate (DCR).
This study confirmed the understudied and uncertain predictive power and clinical relevance of LIPI as a biomarker in patients with advanced NSCLC. Patients infected with COVID-19 had a higher survival rate than uninfected patients despite the therapeutic approach, which may be attributed to their hospitalization and intensive medical management during the pandemic.
Findings obtained in this study may help to determine treatment options according to the clinical condition of the patient by using LIPI values as a non-invasive, readily available and economically acceptable predictive biomarker in lung oncology.
Abstract Background The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were analyzed in various carcinomas and their potential ...prognostic significance was determined. The objective of present study was to determine the correlation between these parameters and the survival of patients with small cell lung cancer (SCLC), since very few studies have been published on this type of carcinoma. Patients and methods One hundred and forty patients diagnosed with SCLC at University Hospital Center Zagreb, between 2012 and 2016 were retrospectively analyzed. Extensive-stage disease (ED) was verified in 80 patients and limited-stage disease (LD) in 60 patients. We analyzed the potential prognostic significance of various laboratory parameters, including NLR, PLR, and LMR, measured before the start of treatment. Results Disease extension, response to therapy, chest irradiation and prophylactic cranial irradiation (PCI), as well as hemoglobin, monocyte count, C-reactive protein (CRP), and lactate dehydrogenase (LDH) showed a prognostic significance in all patients. When we analyzed the patients separately, depending on the disease extension, we found that only skin metastases as well as LDH and NLR values, regardless of the cut-off value, had a prognostic significance in ED. Meanwhile, the ECOG performance status, chest irradiation, PCI, and hemoglobin and creatinine values had a prognostic significance in LD. Conclusions NLR calculated before the start of the treatment had a prognostic significance for ED, while PLR and LMR had no prognostic significance in any of the analyzed groups of patients.
COVID-19 i pneumonija Pavliša, Gordana; Ljubičić, Lidija; Turk, Lana ...
Medicus (Zagreb, Croatia : 1992),
09/2020, Letnik:
29, Številka:
2 COVID-19
Journal Article
Recenzirano
Odprti dostop
Bolest uzrokovana novim koronavirusom 2019 (COVID-19) postala je prijetnja cijeloj svjetskoj populaciji. Njena česta komplikacija je upala pluća. Najčešći simptomi bolesti su povišena tjelesna ...temperatura, suhi kašalj, umor, iskašljavanje, zaduha. Rjeđi simptomi su glavobolja, suho grlo, probavne tegobe, simptomi gornjega dišnog puta, promjene u osjetu njuha i okusa. Starija dob i komorbiditeti kao što je visoki krvni tlak, šećerna bolest, kronične plućne bolesti, kardiovaskularne bolesti, srčane bolesti, pretilost predstavljaju značajni rizični faktor za bolesnike inficirane koronavirusom SARS-CoV-2. Uobičajeni laboratorijski nalazi uključuju limfopeniju, povišenu razinu C-reaktivnog proteina, feritina, aminotransferaza, laktat dehidrogenaze. Bolesnici koji razviju tešku kliničku sliku obično imaju brojne laboratorijske poremećaje što sugerira da SARS-CoV-2 infekcija može uzrokovati ozljedu stanične imunosti, aktivaciju koagulacije, oštećenje miokarda, jetre i bubrega. Najčešće komplikacije su akutni respiratorni distres sindrom, šok, aritmije, akutna ozljeda miokarda, akutno oštećenje bubrežne funkcije. Kompjuterizirana tomografija (CT) može biti korisna kao komplementarna metoda polimeraznoj lančanoj reakciji u realnom vremenu za dijagnozu COVID-19 pneumonije. Njezine glavne CT karakteristike su infiltrati tipa mliječnog stakla periferne i subpleuralne distribucije. Ova područja uzorka mliječnog stakla mogu se miješati s područjima žarišne konsolidacije i/ili se na njih superponiraju zadebljale intralobularne septe, što daje uzorak ludog popločenja.
Abstract Background The standard first-line systemic treatment for patients with non-oncogene addicted advanced nonsquamous non-small cell lung cancer (NSCLC) is immunotherapy with immune checkpoint ...inhibitors (ICI) and/or chemotherapy (ChT). Therapy after failing ICI +/− ChT remains an open question, and docetaxel plus nintedanib represent a valid second line option. Patients and methods A multicenter retrospective trial of real-life treatment patterns and outcomes of patients with advanced lung adenocarcinoma treated with docetaxel plus nintedanib after the failure of ICI and/or ChT was performed. Patients from 2 Slovenian and 1 Croatian oncological center treated between June 2014 and August 2022 were enrolled. We assessed objective response (ORR), disease control rate (DCR), median progression free survival (PFS), median overall survival (OS), and safety profile of treatment. Results There were 96 patients included in the analysis, with ORR of 18.8%, DCR of 57.3%, median PFS of 3.0 months (95% CI: 3.0–5.0 months), and a median OS of 8.0 months (95% CI: 7.0–10.0 months). The majority of patients (n = 47,49%) received docetaxel plus nintedanib as third-line therapy. The ORR for this subset of patients was 19.1%, with a DCR of 57.4%. The highest response rate was observed in patients who received second-line docetaxel plus nintedanib after first-line combination of ChT-ICI therapy (n = 24), with an ORR of 29.2% and DCR of 66.7% and median PFS of 4.0 months (95% CI: 3.0–8.0 months). Fifty-three patients (55.2%) experienced adverse events (AEs), most frequently gastrointestinal; diarrhea (n = 29, 30.2%), and increased liver enzyme levels (n = 17, 17.7%). Conclusions The combination of docetaxel and nintedanib can be considered an effective therapy option with an acceptable toxicity profile for patients with advanced NSCLC after the failure of ICI +/− ChT.
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