The disparity of health facilities in an urban area discourages proposed treatment application in inoperable lung cancer patients

Georgios Hillas1, Petros Bakakos2, Miltiadis Trichas3, Fotis Vlastos11Department of Respiratory and Critical Care Medicine, “Sotiria” Chest Diseases Hospital, Athens, Greece; 21st Respiratory Medicine Department, University of Athens Medical School, “Sotiria” Chest Diseases Hospital, Athens, Greece; 3Radiotherapy Department, Metropolitan Hospital, Neo Faliro, GreeceObjectives: Patients with a newly diagnosed non-small cell lung cancer (NSCLC) stage IIIB are offered chemoradiotherapy, as proposed by the current guidelines. This combination treatment is facilitated by the coexistence of corresponding departments in the same establishment. The geographical disparity of these health facilities influences patients’ willingness to be treated and may influence their survival. This is an observational study that compares the survival of two groups of patients with NSCLC stage IIIB: those treated with chemoradiotherapy versus those treated only with chemotherapy. These two comparable groups were formed exclusively by patients’ and/or their families’ decisions.Methods: One hundred fifteen consecutive NSCLC stage IIIB patients were included in the study. All were hospitalized in the biggest Chest Disease Hospital in Athens and were offered sequential chemoradiotherapy. Only 54 patients opted for the proposed treatment, while 61 decided to be treated with chemotherapy only, denying continuing their treatment in another health care unit (radiotherapy). Their survival and related factors were analyzed.Results: Mean overall survival was estimated 10 months (95% confidence interval [CI]: 7.96–12.04). Patients treated with chemoradiotherapy had almost double overall survival compared to those under chemotherapy (P = 0.001): 13.6 months (95% CI: 12.3–14.9) versus 7.5 (95% CI: 6.1–8.9). Patients aged ≤ 65 years (P < 0.001), smokers (P < 0.001), and those without a cancer history (P < 0.001) survived longer.Conclusions: The lack of a radiotherapy department in a hospital providing chemotherapy impedes the application of current guidelines advocating combined radiochemotherapy. When recommended radiotherapy after six chemo cycles, half of the patients are unwilling to be displaced and do not follow the recommendations. This has an impact on patient survival.Keywords: non-small cell lung cancer, survival, radiotherapy, chemotherapy, health facilities&nbsp

Vascular endothelial growth factor and cysteinyl leukotrienes in sputum supernatant of patients with asthma

SummaryBackgroundVascular endothelial growth factor (VEGF) is considered to be the most important angiogenic factor in asthma. Cysteinyl leukotrienes (Cyst-LTs) have been implicated in vascular permeability in asthma. Cyst-LTs receptor antagonists modulate vascular permeability by reducing VEGF expression.ObjectiveWe aimed to determine the levels of VEGF and Cyst-LTs in sputum supernatants of patients with asthma and to investigate possible associations within them and with airway vascular permeability (AVP) index. Possible confounding factors were also assessed.MethodsOne hundred twenty one patients with asthma (38 with severe refractory asthma, 41 smokers) and 30 healthy subjects (15 smokers) were studied. All subjects underwent lung function tests, and sputum induction for cell count identification and VEGF, Cyst-LTs, measurement in supernatants. AVP index was also assessed.ResultsBoth VEGF & Cyst-LTs (pg/ml) levels were significantly elevated in patients with asthma compared to normal subjects (median, interquartile ranges 845 [487–1034] vs. 432 (327–654) and 209 [171–296] vs. 92 [75–114] respectively, p < 0.001 for both). Multivariate regression analysis in the whole group showed a significant association of Cyst-LTs levels in sputum supernatants with VEGF levels in sputum supernatants and AVP index. A similar positive association was observed between VEGF levels in sputum supernatants and AVP index. The presence of Severe asthma was a significant covariate for both associations.ConclusionOur results indicate that Cyst-LTs may modulate vascular permeability by up-regulating VEGF expression. The above effect seems to be affected by asthma severity

The cost-saving switch from inhaled corticosteroid-containing treatments to dual bronchodilation : a two-country projection of epidemiological and economic burden in chronic obstructive pulmonary disease

Conflict of interest statement KS, LSM, GH and MB received grants from Boehringer Ingelheim. GP, DV, JM and SS are employed by Boehringer Ingelheim.© Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-Non Commercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).Purpose: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2018 recommendations support maintenance treatment with long-acting bronchodilators in most symptomatic patients with chronic obstructive pulmonary disease (COPD). While restricting the overuse of inhaled corticosteroids (ICS) may influence healthcare utilization required to treat inadvertent respiratory (exacerbations and pneumonia) and diabetes-related events, it may also change the total medication cost. This analysis was performed to estimate the 5-year budget impact of switching from ICS-containing treatment combinations to dual bronchodilation, in line with the recommendations. Methods: The model quantified the budget impact of treatment and healthcare resource utilization when COPD patients were anticipated to switch from ICS-containing treatments to dual bronchodilation. Three switch scenarios were calculated with increasing proportions of patients on dual long-acting bronchodilators, to the detriment of ICS-containing double and triple combinations. Clinical and cost input data were based on results from clinical trials and Greek and Portuguese healthcare cost databases. Results: Healthcare resource use to manage exacerbations, pneumonia and diabetes-related events were projected to increase between 2019 and 2023 in parallel with the growing COPD patient population and associated costs were estimated at 52–57% of the total disease cost in the Greek and Portuguese base case scenarios. Total cost savings between 21 and 112million EUR were projected when the proportion of patients on double and triple ICS-containing treatments was gradually reduced to 50% in scenario A, 20% in scenario B and 7% in scenario C. Sensitivity analyses showed that none of the model assumptions had a major impact on the projected savings. Conclusion: The alignment of COPD treatment with current recommendations may bring clinical benefits to patients, without substantial cost increases and even cost savings for payers.The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was funded by Boehringer Ingelheim.info:eu-repo/semantics/publishedVersio

ROSE:radiology, obstruction, symptoms and exposure - a Delphi consensus definition of the association of COPD and bronchiectasis by the EMBARC Airways Working Group

Introduction: The coexistence of chronic obstructive pulmonary disease (COPD) and bronchiectasis (BE) seems to be common and associated with a worse prognosis than for either disease individually. However, no definition of this association exists to guide researchers and clinicians. // Methods: We conducted a Delphi survey involving expert pulmonologists and radiologists from Europe, Turkey and Israel in order to define the “COPD-BE association”. A panel of 16 experts from EMBARC selected 35 statements for the survey after reviewing scientific literature. Invited participants, selected on the basis of expertise, geographical and gender distribution, were asked to express agreement on the statements. Consensus was defined as a score of ≥6 points (scale 0 to 9) in ≥70% of answers across two scoring rounds. // Results: A-hundred-and-two (72.3%) out of 141 invited experts participated the first round. Their response rate in the second round was 81%. The final consensus definition of “COPD-BE association” was: “The coexistence of (1) specific radiological findings (abnormal bronchial dilatation, airways visible within 1 cm of pleura and/or lack of tapering sign in ≥1 pulmonary segment and in >1 lobe) with (2) an obstructive pattern on spirometry (FEV1/FVC<0.7), (3) at least two characteristic symptoms (cough, expectoration, dyspnoea, fatigue, frequent infections) and (4) current or past exposure to smoke (≥10 pack-years) or other toxic agents (biomass, etc.)”. These criteria form the acronym “ROSE” (Radiology, Obstruction, Symptoms, Exposure). // Conclusions: The Delphi process formulated a European consensus definition of “COPD-BE association”. We hope this definition will have broad applicability across clinical practice and research in the future

Post-COVID-19 interstitial lung disease: Insights from a machine learning radiographic model

IntroductionPost-acute sequelae of COVID-19 seem to be an emerging global crisis. Machine learning radiographic models have great potential for meticulous evaluation of post-COVID-19 interstitial lung disease (ILD).MethodsIn this multicenter, retrospective study, we included consecutive patients that had been evaluated 3 months following severe acute respiratory syndrome coronavirus 2 infection between 01/02/2021 and 12/5/2022. High-resolution computed tomography was evaluated through Imbio Lung Texture Analysis 2.1.ResultsTwo hundred thirty-two (n = 232) patients were analyzed. FVC% predicted was ≥80, between 60 and 79 and &lt;60 in 74.2% (n = 172), 21.1% (n = 49), and 4.7% (n = 11) of the cohort, respectively. DLCO% predicted was ≥80, between 60 and 79 and &lt;60 in 69.4% (n = 161), 15.5% (n = 36), and 15.1% (n = 35), respectively. Extent of ground glass opacities was ≥30% in 4.3% of patients (n = 10), between 5 and 29% in 48.7% of patients (n = 113) and &lt;5% in 47.0% of patients (n = 109). The extent of reticulation was ≥30%, 5–29% and &lt;5% in 1.3% (n = 3), 24.1% (n = 56), and 74.6% (n = 173) of the cohort, respectively. Patients (n = 13, 5.6%) with fibrotic lung disease and persistent functional impairment at the 6-month follow-up received antifibrotics and presented with an absolute change of +10.3 (p = 0.01) and +14.6 (p = 0.01) in FVC% predicted at 3 and 6 months after the initiation of antifibrotic.ConclusionPost-COVID-19-ILD represents an emerging entity. A substantial minority of patients presents with fibrotic lung disease and might experience benefit from antifibrotic initiation at the time point that fibrotic-like changes are “immature.” Machine learning radiographic models could be of major significance for accurate radiographic evaluation and subsequently for the guidance of therapeutic approaches

Inflammation in severe exacerbation of chronic obstructive pulmonary disease: correlation to phenotypic characteristics and impact of mechanical ventilation

Aim: Resistive breathing, due to airflow limitation, is observed during the natural course of Chronic Obstructive Pulmonary Disease (COPD), especially during acute exacerbations of COPD (AECOPD) and induces an inflammatory response, characterized by elevated cytokine plasma levels. Τhe aim of this study is to test the hypothesis that elevated cytokine plasma levels in patients with severe AECOPD most probably originate from respiratory muscles (especially the contracting diaphragm) and/or the mechanically stressed "inflammatory" lung. We also hypothesized that plasma cytokine levels would be decreased after respiratory muscles relaxing, due to mechanical ventilation. Methods: Thirty patients with severe AECOPD that led to endotracheal intubation and mechanical ventilation were studied. Blood samples were collected during three phases of observation: Just before intubation, 20 minutes and 6 hours after intubation and application of mechanical ventilation. Seven patients with COPD in steady state, which were intubated and mechanically ventilated for elective surgery procedures were used as the control group. Blood samples were collected during two phases of observation: Just before and 20 minutes after intubation. Luminex 100 IS technique (Luminex Corporation, Austin, TX, USA) was used to access the plasma levels of the cytokines: IL-1α, IL-1β, IL-5, IL-6, IL-8, IL-10, Interferon-γ (IFN-γ), Tumor Necrosis Factor-α (TNF-α), Epidermic Growth Factor (EGF), Eotaxin, Monocyte Chemotactic Protein-1 (MCP-1), and Regulated And Normal T cell Expressed and Secreted (RANTES). Measurements were done with the Human Cytokine/Chemokine Milliplex MAP Kit (MPXHCYTO-60K, Millipore Corporation, Billerica, MA, USA). Results Patients IL-6 plasma levels 6 hours after intubation were found statistically significantly lower compared to IL-6 levels before and 20 minutes after intubation (p=0.043 and p=0.048 respectively). IL-10 plasma levels 6 hours after intubation were found statistically significantly lower compared to IL-10 levels 20 minutes after intubation (p=0.05). Eotaxin plasma levels 20 minutes and 6 hours after intubation were found statistically significantly lower compared to Eotaxin plasma levels before intubation (p=0.012 and p=0.019 respectively). EGF plasma levels 20 minutes and 6 hours after intubation were found statistically significantly lower compared to EGF levels before intubation (p=0.009 and p=0.012 respectively). IL-5, IL-8, TNF-α, INF-γ, MCP-1 and RANTES plasma levels didn't change statistically significantly over time. Controls: Plasma levels of all measured cytokines did not change significantly over time in the control group.IL-1α and IL-1β plasma levels were found below the lower detectable limit in both groups (patients with AECOPD and controls). Conclusions: Application of mechanical ventilation in patients with AECOPD that results in endotracheal intubation, leads to decreased plasma levels for circulating IL-6, IL-10, Eotaxin and EGF. These findings suggest that the origin of these cytokines could be the respiratory muscles and especially the contracting diaphragm and/or the mechanically stressed "inflammatory" lung.H εργώδης αναπνοή παρατηρείται κατά τη φυσική πορεία της Χρόνιας Αποφρακτικής Πνευμονοπάθειας (ΧΑΠ) και ιδιαίτερα κατά τη διάρκεια των παροξύνσεων της νόσου και επάγει μια φλεγμονώδη απάντηση που χαρακτηρίζεται από αυξημένα επίπεδα κυτταροκινών στο πλάσμα. Στόχος της μελέτης είναι να ελέγξει: την υπόθεση ότι η αύξηση των επιπέδων των κυτταροκινών στο πλάσμα ασθενών με σοβαρή παρόξυνση ΧΑΠ πιθανώς προέρχεται από τους αναπνευστικούς μύες (ιδιαίτερα από το έντονα συσπώμενο διάφραγμα) ή/και από τον εκτιθέμενο σε μηχανικό στρες πνεύμονα και συνεπώς τα επίπεδα αυτά στο πλάσμα πιθανώς μειώνονται λόγω της κατάργησης των έντονων συσπάσεων των αναπνευστικών μυών (εφαρμογή μηχανικού αερισμού). Μεθοδολογία: Χρησιμοποιήθηκαν 30 ασθενείς με σοβαρή παρόξυνση ΧΑΠ που οδηγήθηκαν σε ενδοτραχειακή διασωλήνωση/εφαρμογή μηχανικού αερισμού. Ελήφθησαν δείγματα αίματος σε τρεις φάσεις παρατήρησης: Αμέσως πριν τη διασωλήνωση, 20 λεπτά και 6 ώρες μετά τη διασωλήνωση. Εφτά ασθενείς με ΧΑΠ σε σταθερή κατάσταση που οδηγήθηκαν σε διασωλήνωση/εφαρμογή μηχανικού αερισμού λόγω προγραμματισμένης χειρουργικής επέμβασης, αποτέλεσαν την ομάδα ελέγχου. Ελήφθησαν δείγματα αίματος σε δύο φάσεις παρατήρησης: Αμέσως πριν και 20 λεπτά μετά τη διασωλήνωση. Με τη τεχνική Luminex 100 IS πραγματοποιήθηκε ο ποσοτικός προσδιορισμός των κυτταροκινών: IL-1α, IL-1β IL-5, IL-6, IL-8, IL-10, IFN-γ, TNF-α, Εοταξίνη, MCP-1, RANTES και EGF. Χρησιμοποιήθηκε το Human Cytokine/Chemokine Milliplex MAP Kit (MPXHCYTO-60K) της εταιρίας Millipore. Αποτελέσματα: Ασθενείς. Τα επίπεδα της IL-6 στο πλάσμα 6 ώρες μετά τη διασωλήνωση ανευρέθηκαν στατιστικά σημαντικά χαμηλότερα σε σχέση με τα επίπεδα της πριν και 20 λεπτά μετά τη διασωλήνωση (p = 0.043, p = 0.048 αντίστοιχα). Τα επίπεδα της IL-10 στο πλάσμα 6 ώρες μετά τη διασωλήνωση ανευρέθηκαν στατιστικά σημαντικά χαμηλότερα σε σχέση με τα επίπεδα της 20 λεπτά μετά τη διασωλήνωση (p = 0.05). Τα επίπεδα της Εοταξίνης στο πλάσμα 20 λεπτά και 6 ώρες μετά τη διασωλήνωση ανευρέθηκαν στατιστικά σημαντικά χαμηλότερα σε σχέση με τα επίπεδα της πριν τη διασωλήνωση (p = 0.012, p = 0.019 αντίστοιχα). Τα επίπεδα του EGF στο πλάσμα 20 λεπτά και 6 ώρες μετά τη διασωλήνωση ανευρέθηκαν στατιστικά σημαντικά χαμηλότερα σε σχέση με τα επίπεδα του πριν τη διασωλήνωση (p = 0.009, p = 0.012 αντίστοιχα). Τα επίπεδα των IL-5, IL-8, TNF-α, INF-γ, MCP-1 and RANTES δεν μεταβλήθηκαν στατιστικώς σημαντικά με το χρόνο. Ομάδα ελέγχου: Τα επίπεδα όλων των κυτταροκινών που μετρήθηκαν δεν μεταβλήθηκαν στατιστικώς σημαντικά με το χρόνο. Τα επίπεδα των IL-1α και IL-1β ανευρέθηκαν κάτω από τα κατώτερα όρια ανίχνευσης (ασθενείς με παρόξυνση ΧΑΠ και ομάδα ελέγχου). Συμπεράσματα: Η εφαρμογή του μηχανικού αερισμού σε ασθενείς με ΧΑΠ και σοβαρή παρόξυνση, οδηγεί σε μείωση των επιπέδων στο πλάσμα των IL-6, IL-10, Εοταξίνης και EGF. Αυτά τα ευρήματα υποδεικνύουν πως πηγή προέλευσης αυτών των κυτταροκινών, μπορεί να είναι οι αναπνευστικοί μύες και ιδιαίτερα το έντονα συσπώμενο διάφραγμα ή/και ο εκτιθέμενος σε μηχανικό στρες και «φλεγμαίνων» πνεύμονας

Acute exacerbation of COPD: is it the “stroke of the lungs”?

Chronic obstructive pulmonary disease (COPD) is one of the top five major causes of morbidity and mortality worldwide. Despite worldwide health care efforts, costs, and medical research, COPD figures demonstrate a continuously increasing tendency in mortality. This is contrary to other top causes of death, such as neoplasm, accidents, and cardiovascular disease. A major factor affecting COPD-related mortality is the acute exacerbation of COPD (AECOPD). Exacerbations and comorbidities contribute to the overall severity in individual patients. Despite the underestimation by the physicians and the patients themselves, AECOPD is a really devastating event during the course of the disease, similar to acute myocardial infarction in patients suffering from coronary heart disease. In this review, we focus on the evidence that supports the claim that AECOPD is the “stroke of the lungs”. AECOPD can be viewed as: a Semicolon or disease’s full-stop period, Triggering a catastrophic cascade, usually a Relapsing and Overwhelming event, acting as a Killer, needing Emergent treatment