Evaluation of PD-1 and interleukin-10-receptor expression by T lymphocytes in malignant and benign pleural effusions.

PD-1 (programmed cell death protein-1)/PD-L1 (programmed cell death ligand 1) as well as IL-10 (interleukin-10)/IL-10R (interleukin-10 receptor) interactions play a major role in tumor immune evasion in various malignancies. Several studies investigated the expression of PD-1 on T lymphocytes in pleural effusions (PE) in patients with malignant diseases. However, results in malignant pleural effusions (MPE) compared to benign PE (BPE) are underreported. In this prospective study, 51 patients (median age 66 years, IQR 54-78, 47% male) with PE of malignant or benign origin at the Medical University of Vienna between March 2021 and November 2022 were enrolled and divided into three groups according to the cytological results (group 1: MPE [n = 24, 47%]; group 2: BPE in malignant disease [n = 22, 43%]; group 3: BPE in benign disease [n = 5, 10%]). In the cytological samples, T cells were analyzed for the expression of PD-1 and IL-10R via flow cytometry. In MPE, the proportion of PD-1+ T lymphocytes on CD4+ cells was significantly lower than in BPE (40.1 vs. 56.3 in group 1 vs. 3, p = 0.019). Moreover, a significantly lower expression of PD-1+ IL-10R+ CD8+ (9.6 vs. 35.2 in group 1 vs. 2, p = 0.016; 9.6 vs. 25.0 in group 1 vs. 3, p = 0.032) and a significantly higher expression of PD-1-IL-10R-CD8+ T lymphocytes (43.7 vs. 14.0 in group1 vs. 2, p = 0.045; 43.7 vs. 23.3 in group 1 vs. 3, p = 0.032) were observed in MPE when compared to BPE. The frequency of T cells expressing PD-1 and IL-10R on CD8+ T cells is significantly lower in MPE compared to BPE regardless of the underlying disease indicating a different microenvironment in PE driven by the presence of tumor cells. Our observation spotlights the possible involvement of PD-1 and IL-10R in MPE.

PD-L1 expression in patients with non-small-cell lung cancer is associated with sex and genetic alterations: A retrospective study within the Caucasian population.

BACKGROUND: Programmed cell death-ligand 1 (PD-L1) expression is a well-established biomarker for predicting responses to immune checkpoint inhibitors and certain targeted therapies. As a result, treatment strategies for patients vary based on their PD-L1 expression status. Understanding the clinical features of patients with distinct PD-L1 levels is crucial for personalized treatment approaches. METHODS: Demographic and clinicopathological characteristics of 227 patients (54% male, mean age 67 ± 9.9 years) newly diagnosed with non-small-cell lung cancer (NSCLC) between April 2020 and December 2022 were retrospectively compared among three groups based on the PD-L1 expression: PD-L1 Tumor Proportion Score (TPS) negative, 1-50%, and ≥50%. Logistic regression analysis was performed to evaluate predictors for high PD-L1 expression ≥50%. RESULTS: PD-L1 expression levels were distributed as follows: negative in 29% of patients, between 1% and 50% in 41%, and greater than 50% (high) in 29%. In comparison to negative PD-L1 expression, low and high PD-L1 expression was associated with female sex (32.9% vs. 52.7% vs. 50.7%, p = 0.031), with the absence of epidermal growth factor receptor (EGFR) mutations (83.6% vs. 91.1% vs. 98.1% p = 0.029), and with the absence of ERBB2 (HER2) tyrosine kinase mutations (90.9% vs. 100% vs. 98.1% p = 0.007), respectively. Age, smoking status, histological subtype, and disease stage showed no significant differences among the three patient groups. In the univariate logistic regression, EGFR mutation appeared to be the only predictor for PD-L1 expression, although it did not reach statistical significance (p = 0.06). CONCLUSION: Although sex and genomic alterations are associated with PD-L1 expression in patients with NSCLC, no clinical characteristics seem to predict PD-L1 expression significantly.

Evaluation of PD-1 T lymphocytes in bronchoalveolar lavage in lung cancer compared to benign lung diseases.

The expression of the programmed cell death protein 1 (PD-1) has been shown to be markedly increased in tumor-infiltrating lymphocytes. However, the proportion of PD-1 + T cells in the bronchoalveolar lavage (BAL) of lung cancer patients has not been sufficiently evaluated so far. In this prospective study, the proportion of PD-1 + CD4 + as well as PD-1 + CD8 + T cells in BAL samples, isolated from patients with lung cancer, asthma or interstitial lung disease (ILD), were determined via flow cytometry and compared for differences. Bronchoalveolar lavage was performed in 34 patients (14 patients with lung cancer, 10 patients with asthma, 10 patients with ILD). The highest median proportion of PD-1 + CD4 + or PD-1 + CD8 + T cells were found in patients with ILD (83.1% [IQR 72.1; 87.5] and 73.8% [IQR 60.3; 86.3]) followed by patients with lung cancer (66.4% [IQR 59; 69] and 77.1% [IQR 35.8; 82.3]) and patients with asthma (61.3% [IQR 57.4; 70.5] and 57.3% [IQR 46; 65]). Thereby, the difference in the proportion of PD-1 + CD3 + CD4 + BAL cells between ILD patients and asthmatics was significantly different (p = 0.04). The proportion of PD-1 + CD4 + and PD-1 + CD8 + T cells in the BAL of patients with lung cancer did not differ significantly to patients with benign lung diseases. The highest proportion was observed in ILD patients suggesting further research to evaluate the role of the PD-1/PD-L1 pathway in ILD patients.

Correlation of PD-L1 expression on tumour cells between diagnostic biopsies and surgical specimens of lung cancer in real life with respect to biopsy techniques and neoadjuvant treatment.

PURPOSES: Programmed death-ligand 1 (PD-L1) testing is performed mainly on biopsy specimens in patients with advanced lung cancer. It is questionable whether the small amount of tissue analysed in biopsies may represent the true PD-L1 expression of a tumour. METHODS: In this retrospective study, PD-L1 expression on tumour cells derived from bronchoscopy brush cytology, endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA), endobronchial biopsy, transbronchial biopsy (TBB) and computed tomography (CT)-guided transthoracic biopsy was compared to the PD-L1 expression of the corresponding surgical resection in lung cancer patients with regard to neoadjuvant treatment in-between. RESULTS: A quantitative comparison between the diagnostic biopsy of the primary tumour with corresponding resected surgical specimens in a total of 113 lung cancer patients (60% male, mean age 65 ± 9 years) revealed a statistically significant correlation of PD-L1 expression on tumour cells (r = 0.58, p< 0.001), for patients without neoadjuvant treatment in-between and for patients who underwent neoadjuvant treatment (both p < 0.001). Using a cut-off value of ≥ 50% PD-L1 TPS for comparing the biopsy samples and resected specimens, the concordance rate was 78% with a Cohen's Kappa of 0.45. CONCLUSION: A statistically significant concordance for PD-L1 expression on tumour cells between biopsies from primary lung tumour and resected specimen was found, but of uncertain clinical accuracy. The use of a cut-off value of ≥ 50% PD-L1 TPS resulted only in a moderate agreement. Therefore, the interpretation of the PD-L1 determined form biopsy specimens status should only be considered with caution for treatment decisionsQuery.

[Recommendations for Performing Bronchoscopy in Times of the COVID-19 Pandemic - Update 12/2020]. / Empfehlungen zur Durchführung einer Bronchoskopie in Zeiten der COVID-19-Pandemie: Update 12/2020.

The SARS-CoV-19 pandemic continues to be globally related with significant morbidity and mortality, making protective measures to prevent transmission of the virus still necessary. Healthcare employees are exposed to a higher risk of infection and this is particularly true when performing aerosol-generating procedures such as bronchoscopy.Since the publication of recommendations for performing a bronchoscopy in the times of COVID-19 more than six months ago, the risk situation has not changed significantly, but due to the considerable gain in knowledge in the meantime, an update of the recommendations was necessary.The updated recommendations include the reduction of aerosol formation, the personal protection of the people involved in the procedure, as well as measures to better organize the processes in the endoscopy suite in order to perform bronchoscopic procedures securely even in times of COVID-19.

[Technological Innovations in Pulmonology - Examples from Diagnostics and Therapy]. / Expertentreffen COPD: Technologische Innovationen in der Pneumologie ­ Facetten aus Diagnostik und Therapie.

A significant proportion of the current technological developments in pneumology originate from the various areas of information technology. The spectrum ranges from smartphone apps to be used in daily life or in patient care to the use of artificial intelligence in screening and early detection of diseases. The diagnostic accuracy of apps for symptom analysis is currently very limited. Research projects are performed on the integration of symptoms and functional parameters into early detection, but also on mobility measurements as a prognostic marker in COPD. Lung cancer screening using computed tomography represents a major challenge. Here, artificial intelligence can help radiologists to cope with huge amounts of data. However, the quality of the software depends on the sufficient training of the system. Technological developments shape all fields of pneumology. For diagnostic and interventional endoscopy, they offer improved biopsy techniques and microstructural imaging. Advances in lung function measurements allow the differentiated analysis of respiratory mechanical disorders, and they could be transferred to ventilation technology. The translation of basic findings about the lung microbiome into patient care may perspectively help to better understand and treat COPD exacerbations.

[Recommendations for Performing Bronchoscopy in Times of the COVID-19 Pandemic]. / Empfehlungen zur Durchführung einer Bronchoskopie in Zeiten der COVID-19-Pandemie.

COVID-19, caused by coronavirus SARS-CoV-2 is a new and ongoing infectious disease affecting healthcare systems worldwide. Healthcare worker are at high risk for COIVD-19 and many have been infected or even died in countries severely affected by COVID-19 like China or Italy. Bronchoscopy causes cough and aerosol production and has to be considered a significant risk for the staff to get infected. Particular recommendations should guide to prevent spreading COVID-19 and to protect healthcare worker when performing a bronchoscopy.

The minimal important difference for target lobe volume reduction after endoscopic valve therapy.

Objective: Endoscopic valve therapy aims at target lobe volume reduction (TLVR) that is associated with improved lung function, exercise tolerance and quality of life in emphysema patients. So far, a TLVR of >350 mL was considered to be indicative of a positive response to treatment. However, it is not really known what amount of TLVR is crucial following valve implantation. Patients and methods: TLVR, forced expiratory volume in 1 second (FEV1), residual volume (RV) and 6-minute walk distance (6-MWD) were assessed before and 3 months after valve implantation in 119 patients. TLVR was calculated based on computed tomography (CT) scan analysis using imaging software (Apollo; VIDA Diagnostics). Minimal important difference estimates were calculated by anchor-based and distribution-based methods. Results: Patients treated with valves experienced a mean change of 0.11 L in FEV1, -0.51 L in RV, 44 m in 6-MWD and a TLVR of 945 mL. Using a linear regression and receiver operating characteristic analysis based on two of three anchors (ΔFEV1, ΔRV), the estimated minimal important difference for TLVR was between 890 and 1,070 mL (ie, 49%-54% of the baseline TLV). Conclusion: In future, a TLVR between 49% and 54% of the baseline TLV, should be used when interpreting the clinical relevance.

Clinical and radiological outcome following pneumothorax after endoscopic lung volume reduction with valves.

INTRODUCTION: Valve implantation has evolved as a therapy for patients with advanced emphysema. Although it is a minimally invasive treatment, it is associated with complications, the most common being pneumothorax. Pneumothorax occurs due to the rapid target lobe volume reduction and may be a predictor of clinical benefit despite this complication. OBJECTIVE: The objective of this study was to conduct an exploratory data analysis of patients who developed a pneumothorax following endoscopic valve therapy for emphysema. MATERIALS AND METHODS: This study performed a retrospective evaluation of pneumothorax management and the impact of pneumothorax on clinical outcomes in 70 patients following valve therapy in 381 consecutive patients. RESULTS: Pneumothorax rate following valve therapy was 18%. Pneumothorax management consisted of chest tube insertion, valve removal, and surgical intervention in 87% (61/70), 44% (31/70), and 19% (13/70) of the patients, respectively. Despite pneumothorax, patients experienced modest but significant improvements in lung function parameters (forced expiratory volume in 1 second: 55±148 mL, residual volume: -390±964 mL, total lung capacity: -348±876; all P<0.05). Persistent lobar atelectasis 3 months after recovering from pneumothorax, which was associated with relevant clinical improvement, was observed in only 21% (15/70) of the patients. CONCLUSION: Pneumothorax is a frequent severe complication following valve therapy that requires further intervention. Nevertheless, the pneumothorax does not impair the clinical status in the majority of patients. Patients with lobar atelectasis benefit after recovering from pneumothorax in terms of lung function parameters.

[Tracheobronchoplasty for Severe Diffuse Tracheomalacia]. / Tracheobronchoplastie bei schwerer diffuser Tracheobronchomalazie.

Patients with diffuse airway instability due to tracheobronchomalacia or excessive dynamic airway collapse are typically highly symptomatic, with marked dyspnoea, recurrent bronchopulmonary infections and excruciating intractable cough. Silicone stents achieve immediate symptom control, but are - due to the typical complications associated with stent treatment - usually not an option for long-term treatment. The aim of surgical intervention is definitive stabilisation of the trachea and of both main bronchi by posterior splinting of the Paries membranaceus with a polypropylene mesh. This operation is an appropriate treatment option for patients with documented severe tracheobronchomalacia or excessive dynamic airway collapse and is ultimately the only therapy that can achieve permanent symptom control. The success of the operation, however, depends on many factors and requires close interdisciplinary collaboration.

[Endoscopic interventions in pulmonology]. / Endoskopische Interventionen in der Pneumologie.

Bronchoscopy plays a significant role in the diagnosis and treatment of pulmonary diseases. Hemoptysis, or central airway obstruction, is a common indication for interventional bronchoscopy. In addition, the treatment of early lung cancer is the domain of bronchoscopy in inoperable patients. In recent years, endoscopic techniques have also been established as new therapeutic options in advanced chronic obstructive pulmonary disease and uncontrolled bronchial asthma.

Novel Endoscopic Approaches to Treating Chronic Obstructive Pulmonary Disease and Emphysema.

Chronic obstructive pulmonary disease (COPD) is a widespread disease associated with high morbidity and mortality. The principal aim of therapy is preventing disease progression. Besides rehabilitation and pharmacological treatment, different endoscopic approaches were developed in the past decade extending the therapeutic spectrum. Various endoscopic lung volume reduction (ELVR) techniques are available that differ in the implementation, mechanism of action, complication spectrum, and reversibility. So far, the data on efficacy and safety are variable and still very limited. The most comprehensive data are available for endoscopic valve therapy. This reversible technique leads to lobar atelectasis and thus significant lobar volume reduction in patients with severe emphysema and low collateral ventilation. Implantation of coils leading to parenchymal compression and bronchoscopic thermal vapor ablation inducing an inflammatory reaction are nonblocking ELVR techniques and thus independent of collateral ventilation. Besides ELVR techniques, targeted lung denervation has evolved as the latest development in the field of endoscopic therapy in COPD. The aim of this endoscopic method is sustainable bronchodilation by minimizing the influence of parasympathetic pulmonary nerves on smooth muscles of the airways. This review summarizes the different endoscopic procedures, their mechanism of action, and the results of the clinical trials including efficacy and safety.

Role of endobronchial and endoscopic ultrasound in pulmonary medicine.

In the last decade, endobronchial ultrasound (EBUS) has evolved into an important tool for diagnostic bronchoscopy in daily practice. EBUS has established as a standard for the diagnosis of hilar or mediastinal lymphadenopathy, as a guidance technique for peripheral pulmonary lesions and for the evaluation of tumor involvement of the tracheobronchial wall or mediastinum. In the meantime, EBUS has also taken a significant role in mediastinal staging in lung cancer patients. However, EBUS plays not only a role in the diagnosis of malignancies, it is also important for the diagnosis of benign disorders.

Interventional pulmonology procedures: an update.

Bronchoscopy is the most important tool in diagnosis of respiratory diseases, but also provides therapeutic options in various disorders. Besides hemoptysis, airway stenoses are a frequent indication for therapeutic bronchoscopy interventions. Thereby, a broad spectrum of endoscopic techniques including electrocautery, argon plasma coagulation, laser treatment, cryosurgery and stent implantation is available. In the last decade, development of new endoscopic modalities provides also treatment of patients with chronic obstructive pulmonary disease and uncontrolled asthma.

Collateral ventilation.

Although known for more than 80 years, 'collateral ventilation' (CV) became a focus of endoscopic research in the recent decade. Implantation of one-way valves presents an effective treatment option for patients with advanced heterogeneous emphysema optimizing symptoms and quality of life. However, this treatment modality is only successful in case of low interlobar CV. Based on this evidence, attempts to develop different approaches for the quantification of CV have been initiated. In this regard, it is crucial to illuminate the meaning and different aspects of CV.

Endobronchial ultrasound-guided lymph node biopsy with transbronchial needle forceps: a pilot study.

One limitation of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the size of the available needles, frequently yielding only cells for cytological examination. The aim of this pilot study was to evaluate the efficacy and safety of newly developed needle forceps to obtain tissue for the histological diagnosis of enlarged mediastinal lymph nodes. Patients with enlarged, positron emission tomography (PET)-positive lymph nodes were included. The transbronchial needle forceps (TBNF), a sampling instrument combining the characteristics of a needle (bevelled tip for penetrating through the bronchial wall) with forceps (two serrated jaws for grasping tissue) was used through the working channel of the EBUS-TBNA scope. Efficacy and safety was assessed. 50 patients (36 males and 14 females; mean age 51 yrs) with enlarged or PET-positive lymph nodes were included in this pilot study. In 48 (96%) patients penetration of the bronchial wall was possible and in 45 patients tissue for histological diagnosis was obtained. In three patients TBNF provided inadequate material. For patients in whom the material was adequate for a histological examination, a specific diagnosis was established in 43 (86%) out of 50 patients (nonsmall cell lung cancer: n=24; small cell lung cancer: n=7; sarcoidosis: n=4; Hodgkin's lymphoma: n=4; tuberculosis: n=2; and non-Hodgkin's lymphoma: n=2).No clinically significant procedure-related complications were encountered. This study demonstrated that EBUS-TBNF is a safe procedure and provides diagnostic histological specimens of mediastinal lymph nodes.

[Endoscopy of peripheral lung nodule]. / Endoskopie des peripheren Lungenrundherdes.

Pulmonary nodules of unknown dignity, often incidental findings, still present a diagnostic challenge. Next to operative resection, we find minimal invasive therapies such as transthoracal punctions and bronchoscopy with transbronchial as further options. By using modern navigation techniques, the validity of bronchoscopy in diagnosing pulmonary nodules, compared to x-ray fluoroscopy, has already been improved. Thus, the use of endobronchial ultrasound, electromagnetic navigation and virtual bronchoscopy--even without x-ray fluoroscopy--is possible and the combination augments sensitivity. These techniques already rate high in patients with unclear peripheral pulmonary nodules and high risk profiles to surgical operations, thus not to be operated, but still in need of further diagnostic procedures in order to plan therapy options. A future use of endoscopic therapies may possibly be a first approach.

[Corynebacterium pseudodiphtheriticum causing severe pneumonia in secondary immunoglobulin deficiency]. / Corynebacterium pseudodiphtheriticum als Erreger einer schwerwiegenden Pneumonie bei sekundärem Immunglobulinmangel.

BACKGROUND: Corynebacterium pseudodiphtheriticum is of increasing importance because of the rising number of immunocompromised patients. Pneumonia, but also endocarditis, urinary tract infections or keratitis can be caused by this bacteria in case of immunosuppression. Taking corynebacterium pseudodiphtheriticum into consideration as causitive agent provides for a fast onset of targeted antibiotic therapy. HISTORY AND FINDINGS: A 69-year-old man with immunoglobulin deficiency due to a chronic lymphocytic leukemia presented with typical clinical, laboratory and imaging evidence of pneumonia. DIAGNOSIS, TREATMENT AND COURSE: Corynebacterium pseudodiphtheriticum was detected as causative agent. After a prolongated course targeted antibiotic therapy and immunoglobulin substitution resulted in full recovery of the patient. CONCLUSION: In immunocompromised patients Corynebacterium pseudodiphtheriticum should be taken into consideration as causative bacterium of pneumonia. Especially, immunoglobuline deficiency seems to be associated with pneumonia caused by Corynebacterium pseudodiphtheriticum. Therefore, immunoglobulin substitution as well as a targeted antibiotic therapy should be considered.

Treatment of advanced emphysema with emphysematous lung sealant (AeriSeal®).

BACKGROUND: This report summarizes initial tests of an emphysematous lung synthetic polymer sealant (ELS) designed to reduce lung volume in patients with advanced emphysema. OBJECTIVES: The primary study objective was to define a therapeutic strategy to optimize treatment safety and effectiveness. METHODS: ELS therapy was administered bronchoscopically to 25 patients with heterogeneous emphysema in an open-label, noncontrolled study at 6 centers in Germany. Treatment was performed initially at 2-4 subsegments. After 12 weeks, patients were eligible for repeat therapy to a total of 6 sites. Safety and efficacy were assessed after 6 months. Responses were evaluated in terms of changes from baseline in lung physiology, functional capacity, and health-related quality of life. Follow-up is available for 21 of 25 patients. RESULTS: Treatment was well tolerated. There were no treatment-related deaths (i.e., within 90 days of treatment), and an acceptable short- and long-term safety profile. Physiological and clinical benefits were observed at 24 weeks. Efficacy responses were better among Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage III patients [n = 14; change in residual volume/total lung capacity (ΔRV/TLC) = -7.4 ± 10.3%; Δ forced expiratory volume in 1 s (ΔFEV(1)) = +15.9 ± 22.6%; change in forced vital capacity (ΔFVC) = +24.1 ± 22.7%; change in carbon monoxide lung diffusion capacity (ΔDLCO) = +19.3 ± 34.8%; change in 6-min walk test (Δ6MWD) = +28.7 ± 59.6 m; change in Medical Research Council Dyspnea (ΔMRCD) score = -1.0 ± 1.04 units; change in St. George's Respiratory Questionnaire (ΔSGRQ) score = -9.9 ± 15.3 units] than for GOLD stage IV patients (n = 7; ΔRV/TLC = -0.5 ± 6.4%; ΔFEV(1) = +2.3 ± 12.3%; ΔFVC = +2.6 ± 21.1%; ΔDLCO = -2.8 ± 17.2%; Δ6MWD = +28.3 ± 58.4 m; ΔMRCD = 0.3 ± 0.81 units; ΔSGRQ = -6.7 ± 7.0 units). CONCLUSIONS: ELS therapy shows promise for treating patients with advanced heterogeneous emphysema. Additional studies to assess responses in a larger cohort with a longer follow-up are warranted.