The Prognostic Role of the Number of Involved Structures in Thymic Epithelial Tumors: Results from the ESTS Database.

BACKGROUND: The role of the number of involved structures (NIS) in thymic epithelial tumors (TETs) has been investigated for inclusion in future staging systems, but large cohort results still are missing. This study aimed to analyze the prognostic role of NIS for patients included in the European Society of Thoracic Surgeons (ESTS) thymic database who underwent surgical resection. METHODS: Clinical and pathologic data of patients from the ESTS thymic database who underwent surgery for TET from January 2000 to July 2019 with infiltration of surrounding structures were reviewed and analyzed. Patients' clinical data, tumor characteristics, and NIS were collected and correlated with CSS using Kaplan-Meier curves. The log-rank test was used to assess differences between subgroups. A multivariable model was built using logistic regression analysis. RESULTS: The final analysis was performed on 303 patients. Histology showed thymoma for 216 patients (71.3%) and NET/thymic carcinoma [TC]) for 87 patients (28.7%). The most frequently infiltrated structures were the pleura (198 cases, 65.3%) and the pericardium in (185 cases, 61.1%), whereas lung was involved in 96 cases (31.7%), great vessels in 74 cases (24.4%), and the phrenic nerve in 31 cases (10.2%). Multiple structures (range, 2-7) were involved in 183 cases (60.4%). Recurrence resulted in the death of 46 patients. The CSS mortality rate was 89% at 5 years and 82% at 10 years. In the univariable analysis, the favorable prognostic factors were neoadjuvant therapy, Masaoka stage 3, absence of metastases, absence of myasthenia gravis, complete resection, thymoma histology, and no more than two NIS. Patients with more than two NIS presented with a significantly worse CSS than patients with no more than two NIS (CSS 5- and 10-year rates: 9.5% and 83.5% vs 93.2% and 91.2%, respectively; p = 0.04). The negative independent prognostic factors confirmed by the multivariable analysis were incomplete resection (hazard ratio [HR] 2.543; 95% confidence interval [CI] 1.010-6.407; p = 0.048) and more than two NIS (HR 1.395; 95% CI 1.021-1.905; p = 0.036). CONCLUSIONS: The study showed that more than two involved structures are a negative independent prognostic factor in infiltrative thymic epithelial tumors that could be used for prognostic stratification.

Study protocol for Near-infrared molecular imaging for lung cancer detection and treatment during mini-invasive surgery (phase II Trial) - (the RECOGNISE study).

INTRODUCTION: To date, radical surgery remains the best curative option in patients with early-stage lung cancer. In patients with small lung lesions, video-assisted thoracic surgery (VATS) should be increasingly chosen as a fundamental alternative to thoracotomy as it is associated with less postoperative pain and better quality of life. This scenario necessarily increases the need for thoracic surgeons to implement new localization techniques. The conventional near-infrared (NIR) indocyanine green (ICG) method demonstrated a significant limitation in deep cancer recognition, principally due to its intrinsic low-depth tissue penetration. Similarly, the lymph-node sentinel approach conducted by the ICG method was demonstrated to be inefficient, mainly due to the non-specificity of the tracker and the irregular pathway of pulmonary lymph node drainage. Our study aims to evaluate the effectiveness of Cetuximab- IRDye800CW in marking lung nodules and mediastinal lymph nodes. METHODS AND ANALYSIS: This study is defined as an open-label, single-arm, single-stage phase II trial evaluating the effectiveness of Cetuximab-IRDye800CW in detecting tumors and lymph-node metastases in patients with lung cancer who are undergoing video-assisted thoracic surgery (VATS). Cetuximab is a monoclonal antibody that binds, inhibits, and degrade the EGFR. The IRDye® 800CW, an indocyanine-type NIR fluorophore, demonstrated enhanced tissue penetration compared to other NIR dyes. The combination with the clinical approved monoclonal antibody anti-epidermal growth factor EGFR Cetuximab (Cetuximab-IRDye800) has shown promising results as a specific tracker in different cancer types (i.e., brain, pancreas, head, and neck). The study's primary outcome is focused on the proportion of patients with lung nodules detected during surgery using an NIR camera. The secondary outcomes include a broad spectrum of items, including the proportion of patients with detection of unexpected cancer localization during surgery by NIR camera and the proportion of patients with negative surgical margins, the evaluation of the time spawns between the insertion of the NIR camera and the visualization of the nodule and the possible morbidity of the drug assessed during and after the drug infusion. ETHICS AND DISSEMINATION: This trial has been approved by the Ethical Committee of Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino (Torino, Italy) and by the Italian Medicines Agency (AIFA). Findings will be written as methodology papers for conference presentations and published in peer-reviewed journals. The Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, the University of Torino, and the AIRC Public Engagement Divisions will help identify how best to publicize the findings.Trial registration EudraCT 202,100,645,430. CLINICALTRIALS: gov NCT06101394 (October 23, 2023).

Lymphadenectomy for lung carcinoids: Which factors may predict nodal upstaging? A multi centric, retrospective study.

OBJECTIVE: To investigate risk factors for nodal upstaging in patients with lung carcinoids and to understand which type of lymphadenectomy is most appropriate. METHODS: Data regarding patients with lung carcinoids, who underwent surgical resection and lymphadenectomy in five institutions from January 1, 2005 to December 31, 2019, were collected and retrospectively analyzed. Clinical and pathological tumor characteristics were correlated to analyze lymph node upstaging. RESULTS: The analysis was conducted on 283 patients. Pathology showed 230 typical and 53 atypical carcinoids. Nodal and mediastinal upstaging occurred in 33 (11.6%) and 16 (5.6%) patients, respectively. At the univariable analysis, nodal upstaging was significantly correlated with central location (p = 0.003), atypical histology (p < 0.001), pT dimension (p = 0.004), and advanced age (p = 0.043). The multivariable analysis confirmed atypical histology (odds ratio [OR]: 11.030; 95% confidence interval [CI]: 4.837-25.153, p < 0.001) and central location (OR: 3.295; 95% CI: 1.440-7.540, p = 0.005) as independent prognostic factors for nodal upstaging. Atypical histology (p < 0.001), pT dimension (p = 0.036), number of harvested lymph node stations (p = 0.047), and type of lymphadenectomy (p < 0.001) correlated significantly with mediastinal upstaging. The multivariable analysis confirmed atypical histology (OR: 5.408; 95% CI: 1.391-21.020, p = 0.015) and pT (OR: 1.052; 95% CI: 1.021-1.084, p = 0.001) as independent prognostic factors. CONCLUSION: Atypical histology, dimension, and central location are associated with a high-risk for occult hilo-mediastinal metastases, and mediastinal radical dissection may predict nodal upstaging. Thus, we suggest radical mediastinal lymph node dissection in high-risk tumors, reserving sampling, or lobe-specific dissection in peripheral, small typical carcinoids.

Does morbid obesity influence perioperative outcomes after video-assisted thoracic surgery (VATS) lobectomy for non-small cell lung cancer? Analysis of the Italian VATS group registry.

OBJECTIVES: Obesity in Europe, and worldwide, has been an increasing epidemic during the past decades. Moreover, obesity has important implications regarding technical issues and the risks associated with surgical interventions. Nevertheless, there is a lack of evidence assessing the influence of obesity on video-assisted thoracic surgery (VATS) lobectomy results. Our study aimed to assess the impact of morbid obesity on perioperative clinical and oncological outcomes after VATS lobectomy using a prospectively maintained nationwide registry. METHODS: The Italian VATS lobectomy Registry was used to collect all consecutive cases from 55 Institutions. Explored outcome parameters were conversion to thoracotomy rates, complication rates, intra-operative blood loss, surgical time, hospital postoperative length of stay, chest tube duration, number of harvested lymph-node, and surgical margin positivity. RESULTS: From 2016 to 2019, a total of 4412 patients were collected. 74 patients present morbid obesity (1.7%). Multivariable-adjusted analysis showed that morbid obesity was associated with a higher rate of complications (32.8% vs 20.3%), but it was not associated with a higher rate of conversion, and surgical margin positivity rates. Moreover, morbid obesity patients benefit from an equivalent surgical time, lymph-node retrieval, intraoperative blood loss, hospital postoperative length of stay, and chest tube duration than non-morbid obese patients. The most frequent postoperative complications in morbidly obese patients were pulmonary-related (35%). CONCLUSION: Our results showed that VATS lobectomy could be safely and satisfactorily conducted even in morbidly obese patients, without an increase in conversion rate, blood loss, surgical time, hospital postoperative length of stay, and chest tube duration. Moreover, short-term oncological outcomes were preserved.

Impact of High-Grade Patterns in Early-Stage Lung Adenocarcinoma: A Multicentric Analysis.

OBJECTIVE: The presence of micropapillary and solid adenocarcinoma patterns leads to a worse survival and a significantly higher tendency to recur. This study aims to assess the impact of pT descriptor combined with the presence of high-grade components on long-term outcomes in early-stage lung adenocarcinomas. METHODS: We retrospectively collected data of consecutive resected pT1-T3N0 lung adenocarcinoma from nine European Thoracic Centers. All patients who underwent a radical resection with lymph-node dissection between 2014 and 2017 were included. Differences in Overall Survival (OS) and Disease-Free Survival (DFS) and possible prognostic factors associated with outcomes were evaluated also after performing a propensity score matching to compare tumors containing non-high-grade and high-grade patterns. RESULTS: Among 607 patients, the majority were male and received a lobectomy. At least one high-grade histological pattern was seen in 230 cases (37.9%), of which 169 solid and 75 micropapillary. T1a-b-c without high-grade pattern had a significant better prognosis compared to T1a-b-c with high-grade pattern (p = 0.020), but the latter had similar OS compared to T2a (p = 0.277). Concurrently, T1a-b-c without micropapillary or solid patterns had a significantly better DFS compared to those with high-grade patterns (p = 0.034), and it was similar to T2a (p = 0.839). Multivariable analysis confirms the role of T descriptor according to high-grade pattern both for OS (p = 0.024; HR 1.285 95% CI 1.033-1.599) and DFS (p = 0.003; HR 1.196, 95% CI 1.054-1.344, respectively). These results were confirmed after the propensity score matching analysis. CONCLUSIONS: pT1 lung adenocarcinomas with a high-grade component have similar prognosis of pT2a tumors.

Italian survey on non-intubated thoracic surgery: results from INFINITY group.

BACKGROUND: Non-Intubated Thoracic Surgery (NITS) is becoming increasingly adopted all over the world. Although it is mainly used for pleural operations,, non-intubated parenchymal lung surgery has been less frequently reported. Recently, NITS utilization seems to be increased also in Italy, albeit there are no multi-center studies confirming this finding. The objective of this survey is to assess quantitatively and qualitatively the performance of NITS in Italy. METHODS: In 2018 a web-based national survey on Non-Intubated management including both thoracic surgeons and anesthesiologists was carried out. Reference centers have been asked to answer 32 questions. Replies were collected from June 26 to November 31, 2019. RESULTS: We raised feedbacks from 95% (55/58) of Italian centers. Seventy-eight percent of the respondents perform NITS but only 38% of them used this strategy for parenchymal surgery. These procedures are more frequently carried out in patients with severe comorbidities and/or with poor lung function. Several issues as obesity, previous non-invasive ventilation and/or oxygen therapy are considered contraindications to NITS. The regional anesthesia technique most used to provide intra- and postoperative analgesia was the paravertebral block (37%). Conversion to general anesthesia is not anecdotal (31% of answerers). More than half of the centers believed that NITS may reduce postoperative intensive care unit admissions. Approximately a quarter of the centers are conducting trials on NITS and, three quarters of the respondent suppose that the number of these procedures will increase in the future. CONCLUSIONS: There is a growing interest in Italy for NITS and this survey provides a clear view of the national management framework of these procedures.

Accuracy of 18F-FDG in Detecting Stage I Lung Adenocarcinomas According to IASLC/ATS/ERS Classification.

BACKGROUND: Only a small number of studies have explored the clinicopathological features of pulmonary adenocarcinoma (PA) associated with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) false-negative (FN) results. Herein, we investigated the FDG-PET diagnostic performance by stratifying PAs according to International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification. METHODS: From January 2002 to December 2016, all consecutive patients who underwent pulmonary resection for stage I PA at six thoracic surgery institutions were retrospectively reviewed. The diagnostic performance of FDG-PET was analysed according to IASLC/ATS/ERS classification and two validated subclassifications. Univariable and multivariable logistic analysis were used to identify predictors of FDG-PET FN results. RESULTS: Five hundred and fifty (550) patients with stage I PA were included in the analyses. Most of the patients were male (n=354 [64.4%]) and smokers (n=369 [67.1%]). Ninety-seven (n=97 [17.6%]) FN cases were observed at FDG-PET imaging. On multivariable analysis, a lepidic pattern was found to be independently associated with FDG-PET FN results (odds ratio [OR], 3.20; p<0.001), while a solid pattern more commonly presented with a positive finding (OR, 0.40; p=0.066). According to Nakamura's classification, we observed an independent association between lepidic pattern and FDG-PET FN results (OR, 3.17; p<0.001), while solid/micropapillary patterns were independently related with increased FDG uptake (OR, 0.35; p=0.021). According to Yoshizawa's classification, Intermediate-grade tumours were independently correlated with FN FDG-PET results (OR, 2.78; p=0.005). CONCLUSIONS: In our cohort, histopathological features were significantly associated with FDG uptake. In particular, some adenocarcinoma subtypes (mostly Lepidic pattern) have a tendency towards FN FDG-PET findings. The correlation between computed tomography findings, clinical characteristics, and FDG uptake is mandatory, in order to tailor the precise diagnostic and therapeutic pathway for each patient.

Intraoperative near-infrared molecular imaging for diagnostic thoracoscopy in difficult clinical scenario.

Precise diagnosis in intrathoracic malignancies is paramount for adequate treatment planning. Standard approach is histologic analysis from targeted biopsy obtained with different invasive procedures. Rarely, in difficult clinical scenarios, even gold standard diagnostic procedures can be ineffective in obtaining a satisfying result. Procedural developments and technological improvements applied to the chosen technique can be helpful to deal with such situation. We present two clinical cases of suspected intrathoracic malignancy in which repeated unsuccessful diagnostic procedures had already been attempted. We adopted a protocol based on intraoperative fluorescence during diagnostic thoracoscopy to increase diagnostic efficacy. In both cases we obtained a precise pathological diagnosis.

Prognostic impact of lung adenocarcinoma second predominant pattern from a large European database.

BACKGROUND AND OBJECTIVES: Adenocarcinoma patterns could be grouped based on clinical behaviors: low- (lepidic), intermediate- (papillary or acinar), and high-grade (micropapillary and solid). We analyzed the impact of the second predominant pattern (SPP) on disease-free survival (DFS). METHODS: We retrospectively collected data of surgically resected stage I and II adenocarcinoma. SELECTION CRITERIA: anatomical resection with lymphadenectomy and pathological N0. Pure adenocarcinomas and mucinous subtypes were excluded. Recurrence rate and factors affecting DFS were analyzed according to the SPP focusing on intermediate-grade predominant pattern adenocarcinomas. RESULTS: Among 270 patients, 55% were male. The mean age was 68.3 years. SPP pattern appeared as follows: lepidic 43.0%, papillary 23.0%, solid 14.4%, acinar 11.9%, and micropapillary 7.8%. The recurrence rate was 21.5% and 5-year DFS was 71.1%. No difference in DFS was found according to SPP (p = .522). In patients with high-grade SPP, the percentage of SPP, age, and tumor size significantly influenced DFS (p = .016). In patients with lepidic SPP, size, male gender, and lymph-node sampling (p = .005; p = .014; p = .038, respectively) significantly influenced DFS. CONCLUSIONS: The impact of SPP on DFS is not homogeneous in a subset of patients with the intermediate-grade predominant patterns. The influence of high-grade SPP on DFS is related to its proportion in the tumor.

Age and Clinical Presentation for Primary Spontaneous Pneumothorax.

Primary spontaneous pneumothorax (PSP) is a commonly known condition due to the accumulation of air in the pleural space in otherwise healthy people, without apparent underlying lung disease. To date, the exact pathogenesis of PSP is unclear, but it still represents a public health issue. We performed a review of the literature concerning the epidemiology of PSP, examining age of onset and presentation symptoms, in order to assess the possible correlation between these characteristics and its occurrence. Data concerning age, signs, and symptoms were collected. For description purposes, information regarding aetiological and anthropomorphic data was also gathered. In total, 265 papers were evaluated. Regarding age of onset, PSP is a disease that can occur in a broad age group with a double cluster (15-30 and 40-45 yr). Regarding symptoms, pain and dyspnoea (in its various forms) are the most described in PSP. Pain was recorded in 69.25% (range, 9-100%) of the population studied, whereas dyspnoea was present in an average of 54.55% (range, 27-77.1%). Tobacco exposure seems to play an important role in the early onset of PSP. Concerning age at presentation, this review highlights that PSP can occur over a broad age range. The literature appears to be consistent in reporting PSP occurrence mostly below 45 years of age. Asymptomatic PSP is an almost unseen entity. Finally, of pollutants, cigarette smoking should be considered as the most significant exogenous risk factor in the development of PSP.

Anatomical Resections Improve Survival Following Lung Metastasectomy of Colorectal Cancer Harboring KRAS Mutations.

OBJECTIVE: The aim of this study was to evaluate the benefit of anatomical resection (AR) in lung metastasectomy (LM) of colorectal cancer (CRC) harboring KRAS mutations SUMMARY BACKGROUND DATA:: KRAS mutations are related to high aggressiveness in the lung metastasis of CRC. It is unknown whether AR can lead to better outcomes than can non-AR (NAR) in KRAS patients. METHODS: We retrospectively reviewed the data from 574 consecutive patients who underwent a LM for CRC. We focused on patients exhibiting 1 lung metastasis who underwent an AR (segmentectomy) or an NAR (wedge) and for whom the KRAS mutational status was known. Overall survival (OS) and time to pulmonary recurrence (TTPR) were analyzed. RESULTS: We included 168 patients, of whom 95 (56.5%) harbored KRAS mutations. An AR was performed in 74 patients (44%). The type of resection did not impact the median OS in wild-type (WT) patients (P = 0.67) but was significantly better following AR in KRAS patients (101 vs 45 months, P = 0.02) according to the multivariate analysis [hazard ratio (HR): 6.524; 95% confidence interval (CI), 2.312-18.405; P < 0.0001). TTPR was not affected by the type of resection in WT patients (P = 0.32) but was significantly better for AR in KRAS patients (50 vs 15 months, P = 0.01) in the multivariate analysis (HR: 5.273; 95% CI, 1.731-16.064; P = 0.003). The resection-margin recurrence rate was significantly higher for NAR in KRAS patients (4.8% vs 54.2%, P = 0.001) but not in WT patients (P = 0.97). CONCLUSION: AR seems to improve both the OS and TTPR in LM of CRC harboring KRAS mutations.

Large Cell Neuroendocrine Tumor Size >3 cm Negatively Impacts Long-Term Outcomes After R0 Resection.

BACKGROUND: Minimal knowledge exists regarding the outcome, prognosis and optimal treatment strategy for patients with pulmonary large cell neuroendocrine carcinomas (LCNEC) due to their rarity. We aimed to identify factors affecting survival and recurrence after resection to inform current treatment strategies. METHODS: We retrospectively reviewed 72 patients who had undergone a curative resection for LCNEC in 8 centers between 2000 and 2015. Univariable and multivariable analyses were performed to identify the factors influencing recurrence, disease-specific survival and overall survival. These included age, gender, previous malignancy, ECOG performance status, symptoms at diagnosis, extent of resection, extent of lymphadenectomy, additional chemo- and/or radiotherapy, tumor location, tumor size, pT, pleural invasion, pN and pStage. RESULTS: Median follow-up was 47 (95%CI 41-79) months; 5-year disease-specific and overall survival rates were 57.6% (95%CI 41.3-70.9) and 47.4% (95%CI 32.3-61.1). There were 22 systemic recurrences and 12 loco-regional recurrences. Tumor size was an independent prognostic factor for systemic recurrence [HR: 1.20 (95%CI 1.01-1.41); p = 0.03] with a threshold value of 3 cm (AUC = 0.71). For tumors ≤3 cm and >3 cm, 5-year freedom from systemic recurrence was 79.2% (95%CI 43.6-93.6) and 38.2% (95%CI 20.6-55.6) (p < 0.001) and 5-year disease-specific survival was 60.7% (95%CI 35.1-78.8) and 54.2% (95%CI 32.6-71.6) (p = 0.31), respectively. CONCLUSIONS: A large proportion of patients with surgically resected LCNEC will develop systemic recurrence after resection. Patients with tumors >3 cm have a significantly higher rate of systemic recurrence suggesting that adjuvant chemotherapy should be considered after complete resection of LCNEC >3 cm, even in the absence of nodal involvement.

"Characteristics of patients admitted to emergency department for asthma attack: a real-LIFE study".

BACKGROUND: Asthma is a chronic disease affecting 30 million people in Europe under 45y. Poor control of Asthma is the main cause of emergency-department (ED) access, becoming the strongest determinant of the economic burden of asthma management. OBJECTIVE: To examine the characteristics of adult patients admitted to ED for acute asthma attack, focusing on previous diagnosis of asthma (DA) and current therapy. METHODS: During a one-year period, a structured questionnaire, assessing asthma diagnosis and management, was administered to all patients admitted for asthma attack, to the ED of a South-Italy town. Only patients with subsequently confirmed asthma were enrolled. The data on oxygen saturation (Sat.O2), heart and respiratory-rate, severity code ED-admission, hospitalization or discharge, had been obtained. RESULTS: Two hundred one patients (mean 50.3ys), were enrolled. One hundred eighteen had a DA, made 17.5 ± 5.88 years before, and 35.6% had a specialist-examination in the last year. 53.3% of DA-patients used a self-medication before ED access with short-acting-beta-2-agonist and oral-corticosteroids, although none had a written-asthma-action-plan (WAAP). Almost all DA-patients were on regular therapy: inhaled-corticosteroids (ICS) in 61%, associated with LABA in 85%. 16.7% of DA-patients had previous DA-access. The overall hospitalization-rate was 39%, higher in DA compared to unknown asthmatic patients (UA)(p = 0.017). Significant risk factors for hospitalization were Sat-O2 ≤ 94% breathing ambient air (OR9.91, p < 0.001), inability-to-complete a sentence (OR9.42,p < 0.001) and the age (OR1.02,p = 0.049). CONCLUSION: Despite the asthma guidelines-recommendation, up to 40% of patients received the asthma diagnosis in ED, only 61% of DA-patients were taking ICS. It is disappointing that DA-patients did not have a WAAP, which could explain the poor patient-self-medication at ED admission.

Prognostic Value of Exon 19 Versus 21 EGFR Mutations Varies According to Disease Stage in Surgically Resected Non-small Cell Lung Cancer Adenocarcinoma.

BACKGROUND: The prognostic value of exon 19 and 21 EGFR mutations in stage IV non-small cell lung cancer (NSCLC) is well established. OBJECTIVE: We aimed to evaluate the prognostic value of the mutations in surgically resected NSCLC. METHODS: We retrospectively reviewed data from 1798 surgically resected NSCLC adenocarcinomas between 2007 and 2017 in three departments of thoracic surgery (Nancy/Strasbourg, France, and Torino, Italy) for whom mutational status was known. Overall survival (OS) was evaluated using log-rank and Cox proportional hazard models. RESULTS: EGFR exon 19 deletion was observed in 108 patients (55.1%) and exon 21 L858R mutations were observed in 88 patients (44.9%). In stage I, the median OS was not significantly different between exons 19 and 21 (p = 0.54), while, in stage II, the median OS reached 65 months [95% confidence interval (CI) 41.67-88.33] for exon 19 mutations and decreased to 48 months for exon 21 mutations (95% CI 44.21-51.79; p = 0.027). In multivariate analysis, exon 19 deletion remained a favorable prognostic factor [hazard ratio (HR) 0.314, 95% CI 0.098-0.997; p = 0.05]. In stage III, the median OS reached 66 months (95% CI 44.67-87.32) for exon 19 mutations and decreased to 32 months for exon 21 mutations (95% CI 29.86-34.14; p = 0.03). In multivariate analysis, exon 19 deletion remained a significantly favorable prognostic factor (HR 0.165, 95% CI 0.027-0.999; p = 0.05). CONCLUSION: The prognostic value of EGFR exon 19 and 21 mutations appears to be different according to disease stage in surgically resected NSCLC.

Basophil Membrane Expression of Epithelial Cytokine Receptors in Patients with Severe Asthma.

BACKGROUND: Severe asthma is a heterogeneous disease, which is characterized by airway damage and remodeling. All triggers of asthma, such as allergens, bacteria, viruses, and pollutants, interact with the airway epithelial cells, which drive the airway inflammatory response through the release of cytokines, particularly IL-25, IL-33, and thymic stromal lymphopoietin (TSLP). OBJECTIVES AND METHODS: To investigate whether the expression of the IL-25, IL-33, and TSLP receptors on the basophil membrane are associated with asthma severity. Twenty-six patients with asthma (11 severe and 15 moderate/mild) and 10 healthy subjects (controls) were enrolled in the study. The results of the basophil activation test and flow cytometry analysis were assessed to investigate basophil membrane expression of IL-25, TSLP, and IL-33 receptors before and after IgE stimulation. RESULTS: IL-25 and IL-33 receptor expression on the basophil membrane at baseline were significantly higher in patients with severe asthma than in those with mild/moderate asthma or healthy subjects, independent of atopy, eosinophilia, asthma control, and exacerbation frequency. Following IgE stimulation, a significantly higher increase in the IL-25 and IL-33 receptors was observed in mild/moderate versus severe asthma. CONCLUSIONS: The high expression of the IL-25 and IL-33 receptors on the basophil membrane of patients with severe asthma indicates an overstimulation of basophils by these cytokines in severe asthma. This finding can possibly be used as a biomarker of asthma severity.