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Introduction and ObjectivesMyeloid-derived suppressor cells (MDSCs) are immature cells with immunosuppressive properties, divided into polymorphonuclear (PMN-) and monocytic (M-) subpopulations. Based on a limited number of disease-specific studies, they appear to be involved in a wide spectrum of lung diseases. We aimed to standardise a simple measuring protocol of MDSCs in the lungs and the systemic circulation and to comparatively investigate their differences among distinct lung diseases.MethodsIn 16 patients with lung diseases, MDSCs were measured in peripheral blood (PB) and bronchoalveolar lavage (BAL) via flow cytometry and immunophenotypically defined as CD45+CD3−CD19−CD20−CD56−CD16−HLA-DR−CD33+CD11b+CD15+Lox-1+ PMN-MDSCs and CD45+CD3−CD19−CD20−CD56−CD16−HLA-DR−CD33+CD11b+CD14+ M-MDSCs, as shown in figure 1a. Total MDSCs were calculated as the sum of the two subpopulations. Their suppressive character was confirmed via T-cell suppression assay. BAL cell populations were also defined. Further clinical and laboratory data were collected, including diagnosis, stage of disease, findings from microbiological, cytological, and histological examinations, disease course, and end outcomes. The data were analysed with the non-parametric Wilcoxon signed ranks test for paired samples and the Kruskal-Wallis test for comparison between multiple groups.ResultsOur study population included 4 patients with bronchiectasis, 6 patients with lung cancer, and 6 patients with interstitial lung diseases (ILD). MDSCs from all study subgroups showed normal capacity to suppress T cells. All MDSC subsets, including total MDSCs, M-MDSCs, and PMN-MDSCs, were statistically significantly increased in BAL compared to PB, as depicted in figure 1b, indicating the lung accumulation of these cells (p-value: <0.05 in all disease groups). Interestingly, total MDSCs in the BAL were statistically significantly differentiated between the three patient groups, as depicted in figure 1c, with the group of patients with ILD presenting the higher counts (p-value: 0.001).Abstract P251 Figure 1[Image Omitted. See PDF.]ConclusionsOur preliminary data show for the first time that MDSCs could potentially be used as differential diagnostic biomarkers in lung diseases. Additional data are needed to develop disease- and sample-specific reference values of MDSCs and further investigate their quantitative alterations in different entities.

Introduction and ObjectivesMyeloid-derived suppressor cells (MDSCs) are immature cells of the myeloid lineage with immunosuppressive properties, divided into polymorphonuclear and monocytic subpopulations, and are commonly involved in chronic inflammatory diseases. We aimed to systematically review the literature to assess the quantitative and qualitative alterations of MDSCs and their involvement in allergic airway diseases, i.e. asthma and allergic rhinitis.MethodsThe systematic review protocol was registered in PROSPERO, and the PRISMA guidelines for systematic reviews were followed. The databases MEDLINE via PubMed, Embase, and Scopus were systematically searched for original research studies involving the measurement of human MDSCs in allergic airway diseases by the end of 2024. A narrative synthesis of the extracted data from the included studies was performed.ResultsAmong a total of 429 records screened, 8 studies were considered eligible to be included in the review. The studies were run from 2011 to 2021 and cumulatively included 212 patients with asthma and 90 patients with allergic rhinitis. Healthy controls (cumulatively 203) were included in 7 studies, while 4 studies also included patients with other respiratory diseases for comparison, i.e. chronic obstructive pulmonary disease (35 patients), pneumonia (65 patients), and respiratory viral infections (27 patients). Out of 6 studies about asthma, MDSC counts were found either increased or increasing after allergen challenge in bronchoalveolar lavage (2 studies) and in peripheral blood mononuclear cells (3 studies), while the monocytic MDSC subpopulation was found downregulated in isolated white blood cells in only 1 study. The 2 studies about allergic rhinitis used diverse experimental set-ups and were not comparable.ConclusionsIncreased counts of MDSCs are mostly found in asthma, pointing towards the role of these immunomodulatory cells in its pathogenesis, despite the heterogeneity of the methodology among the different studies. Further research and harmonisation of the markers and techniques for the identification of MDSCs is needed, as they may be used as novel biomarkers and therapeutic targets in these disease entities.

Background The 2005 guidelines of the American Thoracic Society-Infectious Diseases Society of America Guidelines for Hospital for managing hospital-acquired pneumonia classified patients according to time of onset and risk factors for potentially drug-resistant microorganisms to select the empirical antimicrobial treatment. We assessed the microbial prediction and validated the adequacy of these guidelines for antibiotic strategy. Methods We prospectively observed 276 patients with intensive care unit-acquired pneumonia. We classified patients into group 1 (early onset without risk factors for potentially drug-resistant microorganisms; 38 patients) and group 2 (late onset or risk factors for potentially drug-resistant microorganisms; 238 patients). We determined the accuracy of guidelines to predict causative microorganisms and the influence of guidelines adherence in patients' outcome. Results Microbial prediction was lower in group 1 than in group 2 (12 [50%] of 24 vs 119 [92%] of 129; P < .001) mainly because of potentially drug-resistant microorganisms in 10 patients (26%) from group 1. Guideline adherence was higher in group 2 (153 [64%] vs 7 [18%]; P < .001). Guideline adherence resulted in more treatment adequacy than did nonadherence (69 [83%] vs 45 [64%]; P = .013) and a trend toward better response to empirical treatment in group 2 only but did not influence mortality. Reclassifying patients according to the risk factors for potentially drug-resistant microorganisms of the former 1996 American Thoracic Society guidelines increased microbial prediction in group 1 to 21 (88%; P = .014); all except 1 patient with potentially drug-resistant microorganisms were correctly identified by these guidelines. Conclusions The 2005 guidelines predict potentially drug-resistant microorganisms worse than the 1996 guidelines. Adherence to guidelines resulted in more adequate treatment and a trend to a better clinical response in group 2, but it did not influence mortality.

Introduction and objectivesBronchiectasis can contribute to severe and difficult to control asthma. It is important to recognise bronchiectasis in asthmatics and treat them accordingly. In order to estimate the presence of bronchiectasis in severe asthma, and the relation with the clinical and functional parameters we studied 40 patients with severe uncontrolled asthma, in a stable condition.MethodsThe symptoms, the duration of asthma diagnosis, the number of exacerbations/year, cycles of corticosteroids and antibiotic treatment/year, spirometry, and bronchial colonisation were estimated. High resolution computed tomography (HRCT) was performed to evaluate the presence and extent of bronchiectasis. HRCT were studied by an expert thoracic radiologist, according to Smith scale for bronchiectasis (score 0–24), taking a score≥3 as radiologically significant.ResultsForty patients were studied, 28 women, mean age (±SD) 57.9 years (±12.4), 32 non smokers. Mean ACT score was 14.2(±4.9).The main symptoms were: cough (92%), wheezing (95%), dyspnea (92%), sputum production (72%) of which mucoid (52%), mucopurulent and purulent (48%). Mean duration of asthma diagnosis was 16.5(±11.5) years, exacerbations: 4.4(±2.7)/year, corticosteroid per os cycles/year: 4.4 (±3.1), antibiotic cycles/year: 2.8(±2.2).In 27 patients (67,5%) bronchiectasis was diagnosed: Smith score: 5.2(±4.2).The mean FEV1 was 72.6% (±21.1) of predicted, FVC 79.1% (±19.4), FEV1/FVC ratio 67.3 (±9.7). Nine patients (22.5%) were colonised with pathogens, 6 of whom with Pseudomonas Aeruginosa. Patients with sputum production had a higher Smith score compared to those without expectoration (6.3 ± 4.2 vs 2.3 ± 2.2 respectively Z = 2.8, p = 0.005). In addition, patients with pathogens in sputum cultures had a higher Smith score compared to those with normal flora (10 ± 4.2 vs 3.8 ± 3 respectively, Z = 3.5, p < 0.0001) (Figure 1).Abstract P67 Figure 1Smith score in patients with pathogens in sputum cultures and in patients with normal floraNo correlation was found between the extent of bronchiectasis and the lung function parameters. The severity of bronchiectasis (Smith score) was correlated to the number of antibiotic cycles/year (p = 0.002, r = 0.48). In addition, a lower ACT score was related with a higher asthma exacerbation rate (r = -0.52, p = 0.001).ConclusionThe evidence of bronchiectasis on HRCT is common in patients with severe uncontrolled asthma. Sputum production and pathogen isolation in sputum culture may indicate the presence of this comorbidity and the need of antibiotics as an additional treatment.

Adamantia Liapikou,1 Catia Cillóniz,2 Antonio Torres216th Respiratory Department, Sotiria Chest Diseases Hospital, Athens, Greece; 2Pulmonology Department, Clinic Institute of Thorax (ICT), Hospital Clinic of Barcelona, Spain Insitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, SpainAbstract: Ceftobiprole, a new broad spectrum, parenteral cephalosporin, exhibits potent in vitro activity against a number of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae, and Gram-negative pathogens associated with hospital-acquired pneumonia (HAP) and community-acquired pneumonia (CAP). Ceftobiprole has demonstrated noninferiority in two large-scale pivotal studies comparing it to ceftriaxone with or without linezolid in CAP, with clinical cure rates 86.6% versus 87.4%, or ceftazidime in HAP, with clinical cure rates of 77% versus 76%, respectively. However, ceftobiprole was inferior in the subgroup of patients undergoing mechanical ventilation. Ceftobiprole has so far demonstrated a good safety profile in preliminary studies, with similar tolerability to comparators. The most commonly observed adverse events of ceftobiprole included headache and gastrointestinal upset. It is the first cephalosporin monotherapy approved in the EU for the treatment of both CAP and HAP (excluding ventilator-associated pneumonia).Keywords: antibiotic resistance, methicillin-resistant staphylococci, community-acquired pneumonia, hospital-acquired pneumonia, cephalosporins

Inoperable malignt tracheoesophageal fistula (TEF) is characterised by an extremely poor prognosis. Tracheal or double (tracheal-esophageal) stenting through rigid bronchoscopy has been suggested as a valuable therapeutic option. We report on a patient with a large TEF successfully sealed by deployment of a self-expandable stent through flexible bronchoscopy (FB) without fluoroscopy. Dramatically improved health status permitted him to undergo radiation, attaining further clinical improvement. Four months after stent placement no sequelae were observed. During the fifth month a new fistula developed distally to the stent filly leading to death from septic complication. Palliative magement of inoperable malignt TEF by tracheal stent placement through FB without fluoroscopy, is feasible, safe and rewarding leading to important clinical improvement.