[When eosinophilia is not only a marker of asthma ]. / Cas clinique. Quand l'éosinophilie n'est pas qu'un marqueur d'asthme...

We report the case of a patient who has been hospitalized for dyspnea. Investigations revealed airway obstruction, eosinophilia, elevated IgE and elevated exhaled nitric oxide. Patient improved with oral corticosteroids (OCS). However, the patient presented two exacerbations requiring OCS during the next twelve months. Chest CT scan revealed two multiloculated parenchymal lesions. Lab test was positive for Echinococcus and Western-Blot confirmed infection with Echinococcus granulosus. Bronchoalveolar lavage confirmed the presence of 6 % eosinophils. Echinococcus granulosis is a zoonotic larval infection caused by a tapeworm larva. Patients with this disease may be asymptomatic for years. Early identification and management, in a multidisciplinary team, are essential and rely mainly on surgical intervention and antiparasitic treatments. This article presents the case of a young patient with pulmonary echinococcosis.

Nous rapportons le cas d'un patient ayant été hospitalisé dans un contexte d'obstruction bronchique, avec une légère éosinophilie, une élévation des IgE et du monoxyde d'azote dans l'air exhalé, qui a évolué favorablement sous corticostéroïdes oraux (CSO). L'évolution est marquée par deux exacerbations d'asthme d'évolution favorable sous CSO dans les douze mois de suivi. Une tomodensitométrie thoracique révèle la présence de deux lésions pulmonaires kystiques. Les sérologies infectieuses mettent en évidence une positivité pour l'espèce -Echinococcus et une confirmation pour l'Echinococcus granulosus. Le lavage broncho-alvéolaire retrouve une hyperéosinophilie à 6 %. L'échinococcose kystique est une infection larvaire zoonotique causée par une larve de taenia. Les patients atteints de cette maladie peuvent être asymptomatiques pendant de nombreuses années. Une identification précoce et une prise en charge adéquate, en équipe pluridisciplinaire, sont primordiales et reposent essentiellement sur une intervention chirurgicale et des traitements anti-parasitaires. Cet article présente le cas d'un jeune patient atteint d'une échinococcose kystique pulmonaire.

[The GOLD (Global Initiative for Chronic Obstructive Lung Disease) 2023 : a substantial revision]. / Le GOLD (Global Initiative for Chronic Obstructive Lung Disease) 2023 : une révision substantielle.

The GOLD is a consensus summarizing current evidence gathered to assess, diagnose and manage patients with chronic obstructive pulmonary disease (COPD). Each year, this GOLD document is enriched with new studies and articles. The year 2023 was special because more than 387 new references were added. These new developments have considerably modified the diagnostic and therapeutic approaches to COPD.

Le GOLD est un consensus résumant les preuves actuelles rassemblées pour évaluer, diagnostiquer et prendre en charge les patients atteints de bronchopneumopathie chronique obstructive (BPCO). Chaque année, ce document GOLD s'enrichit de nouvelles études et articles. L'année 2023 a été particulière puisque plus de 387 nouvelles références ont été ajoutées. Ces nouveautés ont considérablement modifié les approches diagnostique et thérapeutique de la BPCO.

Excess of blood eosinophils prior to therapy correlates with worse prognosis in mesothelioma.

Background: Only a fraction of patients with malignant pleural mesothelioma (MPM) will respond to chemo- or immunotherapy. For the majority, the condition will irremediably relapse after 13 to 18 months. In this study, we hypothesized that patients' outcome could be correlated to their immune cell profile. Focus was given to peripheral blood eosinophils that, paradoxically, can both promote or inhibit tumor growth depending on the cancer type. Methods: The characteristics of 242 patients with histologically proven MPM were retrospectively collected in three centers. Characteristics included overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR). The mean absolute eosinophil counts (AEC) were determined by averaging AEC data sets of the last month preceding the administration of chemo- or immunotherapy. Results: An optimal cutoff of 220 eosinophils/µL of blood segregated the cohort into two groups with significantly different median OS after chemotherapy (14 and 29 months above and below the threshold, p = 0.0001). The corresponding two-year OS rates were 28% and 55% in the AEC ≥ 220/µL and AEC < 220/µL groups, respectively. Based on shorter median PFS (8 vs 17 months, p < 0.0001) and reduced DCR (55.9% vs 35.2% at 6 months), the response to standard chemotherapy was significantly affected in the AEC ≥ 220/µL subset. Similar conclusions were also drawn from data sets of patients receiving immune checkpoint-based immunotherapy. Conclusion: In conclusion, baseline AEC ≥ 220/µL preceding therapy is associated with worse outcome and quicker relapse in MPM.

Long-Term Follow-Up of Intralobar Bullae After Endobronchial Valve Treatment for Emphysema.

Endoscopic lung volume reduction using unidirectional endobronchial valves is a new technique in the treatment of patients with severe emphysema. However, the movements of the thoracic structures after endobronchial valves insertion are still unpredictable We report the unusual outcome of six patients after valves insertion in the left upper lobe. They all developed a complete atelectasis of the target lobe, a pneumothorax and sequential genuine bullae in the treated left lung of unknown etiology. The chest CT scan prior to the valves insertion was unremarkable. Three patients developed an air-liquid level in the bullae the day before a bacterial infection of their left lower lobe. The three other patients had an uneventful spontaneous resolution of their bullae at long-term follow-up. Therefore, a conservative attitude should be followed in this particular setting.

HDAC Inhibition with Valproate Improves Direct Cytotoxicity of Monocytes against Mesothelioma Tumor Cells.

The composition of the tumor microenvironment (TME) mediates the outcome of chemo- and immunotherapies in malignant pleural mesothelioma (MPM). Tumor-associated macrophages (TAMs) and monocyte myeloid-derived immunosuppressive cells (M-MDSCs) constitute a major fraction of the TME. As central cells of the innate immune system, monocytes exert well-characterized functions of phagocytosis, cytokine production, and antibody-dependent cell-mediated cytotoxicity (ADCC). The objective of this study was to evaluate the ability of monocytes to exert a direct cytotoxicity by cell-to-cell contact with MPM cells. The experimental model is based on cocultures between human blood-derived monocytes sorted by negative selection and mesothelioma cell lines. Data show (i) that blood-derived human monocytes induce tumor cell death by direct cell-to-cell contact, (ii) that VPA is a pharmacological enhancer of this cytotoxic activity, (iii) that VPA increases monocyte migration and their aggregation with MPM cells, and (iv) that the molecular mechanisms behind VPA modulation of monocytes involve a downregulation of the membrane receptors associated with the M2 phenotype, i.e., CD163, CD206, and CD209. These conclusions, thus, broaden our understanding about the molecular mechanisms involved in immunosurveillance of the tumor microenvironment and open new prospects for further improvement of still unsatisfactory MPM therapies.

Asthma and COPD Are Not Risk Factors for ICU Stay and Death in Case of SARS-CoV2 Infection.

BACKGROUND: Asthmatics and patients with chronic obstructive pulmonary disease (COPD) have more severe outcomes with viral infections than people without obstructive disease. OBJECTIVE: To evaluate if obstructive diseases are risk factors for intensive care unit (ICU) stay and death due to coronavirus disease 2019 (COVID19). METHODS: We collected data from the electronic medical record from 596 adult patients hospitalized in University Hospital of Liege between March 18 and April 17, 2020, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. We classified patients into 3 groups according to the underlying respiratory disease, present before the COVID19 pandemic. RESULTS: Among patients requiring hospitalization for COVID19, asthma and COPD accounted for 9.6% and 7.7%, respectively. The proportions of asthmatics, patients with COPD, and patients without obstructive airway disease hospitalized in the ICU were 17.5%, 19.6%, and 14%, respectively. One-third of patients with COPD died during hospitalization, whereas only 7.0% of asthmatics and 13.6% of patients without airway obstruction died due to SARS-CoV2. The multivariate analysis showed that asthma, COPD, inhaled corticosteroid treatment, and oral corticosteroid treatment were not independent risk factors for ICU admission or death. Male gender (odds ratio [OR]: 1.9; 95% confidence interval [CI]: 1.1-3.2) and obesity (OR: 8.5; 95% CI: 5.1-14.1) were predictors of ICU admission, whereas male gender (OR 1.9; 95% CI: 1.1-3.2), older age (OR: 1.9; 95% CI: 1.6-2.3), cardiopathy (OR: 1.8; 95% CI: 1.1-3.1), and immunosuppressive diseases (OR: 3.6; 95% CI: 1.5-8.4) were independent predictors of death. CONCLUSION: Asthma and COPD are not risk factors for ICU admission and death related to SARS-CoV2 infection.

Probe-based confocal laser endomicroscopy for pleural malignancies diagnosis.

BACKGROUND AND OBJECTIVE: Probe based confocal laser endomicroscopy (pCLE) is an optical imaging technique allowing live tissue imaging at a cellular level. Currently, this tool remains experimental. Two studies regarding pleural disease have been published and suggest that pCLE could be valuable for pleural disease investigations. However, normal and malignant pleural pCLE features remain unknown. Therefore, we conducted a prospective trial of pCLE during medical thoracoscopy to study and describe the malignant and benign pleural pCLE features. METHODS: Every patient >18 years referred to our department for medical thoracoscopy was eligible. Medical thoracoscopy was performed under sedation, allowing spontaneous breathing. Five millilitres of fluorescein (10%) was intravenously administrated 5 min before image acquisition. The pCLE was introduced through the working channel of the thoracoscope and gently placed on the parietal pleura to record videos. Afterwards, biopsies were performed on the corresponding sites. Malignant and benign pleural pCLE features were precisely described and compared using 11 preselected criteria. RESULTS: A total of 62 patients were included in the analysis including 36 benign and 26 malignant pleura. Among our preselected criteria, 'abnormal tissue architecture' and 'dysplastic vessels' were strongly associated with malignancies (100% and 85% ss, 721% and 74% sp, respectively) whereas, the 'full chia seeds sign' and 'cell shape homogeneity' were associated with benignity (36% and 56% ss, 100% and 70% sp, respectively). No study-related adverse events occurred. CONCLUSION: Benign and malignant pleural involvement have clearly distinct pCLE features.

Usefulness of surgical lung biopsies after cryobiopsies when pathological results are inconclusive or show a pattern suggestive of a nonspecific interstitial pneumonia.

BACKGROUND: Although increasing data supports the use of transbronchial lung cryobiopsies (TBLCs) for the diagnosis of diffuse parenchymal lung diseases (DPLDs), its role as an alternative to surgical lung biopsy (SLB) is still under debate. The aim of this study was to assess the benefit of additional SLBs performed in selected patients after TBLCs. METHOD: We conducted a multicentric Belgian prospective trial in which SLBs were performed after TBLCs when the pathological diagnosis was uncertain or if a nonspecific interstitial pneumonia (NSIP) pattern was observed hypothesizing that SLB could provide additional information and that a co-existent UIP pattern could be missed. RESULTS: Eighty-one patients with TBLCs performed for a DPLD were included in the study between April 2015 and December 2019. A specific histological diagnosis was obtained in 52 patients (64%) whereas no pathological diagnosis following TBLCs was obtained in 13 patients (16%) and a pattern suggestive of a NSIP was observed in 16 patients (20%). Fourteen out of these 29 patients had SLBs after TBLCs. SLBs showed a UIP pattern in 11 (79%), a pattern suggestive of a hypersensitivity pneumonitis in two (14%) and a NSIP pattern in one patient (7%). Among the 16 patients with pathological NSIP following TBLCs, six underwent a SLBs showing a UIP in five and confirming a NSIP in one patient only. A retrospective pathological analysis of patients having both procedures showed a lower diagnostic confidence and agreement among pathologists for TBLCs compared to SLBs. Major factors underlying the added value of SLBs were the bigger size of the sample as well as the subpleural localization of the biopsies. CONCLUSIONS: TBLCs are useful in the setting of DPLDs with a good diagnostic yield. However, our study suggests that SLB provides critical additional information in case TBLCs are inconclusive or show a pattern suggestive of a NSIP, questioning the accuracy of TBLC to adequately identify this histological pattern.

Bronchial thermoplasty decreases airway remodelling by blocking epithelium-derived heat shock protein-60 secretion and protein arginine methyltransferase-1 in fibroblasts.

Bronchial thermoplasty (BT) is to date the only therapy that provides a lasting reduction in airway wall remodelling. However, the mechanism of action of BT is not well understood. This study aimed to characterise the changes of remodelling regulating signalling pathways by BT in asthma.Bronchoalveolar lavage fluid (BALF) was obtained from eight patients with severe asthma before and after BT. Primary bronchial epithelial cells were isolated from 23 patients before (n=66) and after (n=62) BT. Epithelial cell culture supernatant (Epi.S) was collected and applied to primary fibroblasts.Epithelial cells obtained from asthma patients after BT proliferated significantly faster compared with epithelial cells obtained before BT. In airway fibroblasts, BALF or Epi.S obtained before BT increased CCAAT enhancer-binding protein-ß (C/EBPß) expression, thereby downregulating microRNA-19a. This upregulated extracellular signal-regulated kinase-1/2 (ERK1/2) expression, protein arginine methyltransferase-1 (PRMT1) expression, cell proliferation and mitochondrial mass. BALF or Epi.S obtained after BT reduced the expression of C/EBPß, ERK1/2, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), PRMT1 and mitochondrial mass in airway fibroblasts. Proteome and transcriptome analyses indicated that epithelial cell-derived heat shock protein-60 (HSP60) is the main mediator of BT effects on fibroblasts. Further analysis suggested that HSP60 regulated PRMT1 expression, which was responsible for the increased mitochondrial mass and α-smooth muscle actin expression by asthmatic fibroblasts. These effects were ablated after BT. These results imply that BT reduces fibroblast remodelling through modifying the function of epithelial cells, especially by reducing HSP60 secretion and subsequent signalling pathways that regulate PRMT1 expression.We therefore hypothesise that BT decreases airway remodelling by blocking epithelium-derived HSP60 secretion and PRMT1 in fibroblasts.

[Bronchial thermoplasty: a real advancement in the treatment of asthma]. / Thermoplastie bronchique: une réelle avancée dans le traitement de l'asthme.

New treatments are needed to improve the care of severe asthmatic patients. Bronchial thermoplasty aims to lessen the airway smooth muscles via the heating of bronchial walls by radiofrequency. The preliminary studies showed a good tolerance and some good efficacy. Randomized controlled trials have been undertaken on moderate to severe asthmatic patients, demonstrating an improvement in quality of life, rate of severe exacerbations and unscheduled medical visits. The main side-effects consist of asthma exacerbations, atelectasis and infections. Bronchial thermoplasty is an innovative treatment with good efficacy and acceptable tolerance for moderate to severe asthmatic patients. More studies are needed to better understand its mechanism of action and more clearly delineate the precise indications of this innovative technique.

Diagnostic value of neurotrophin expression in malignant pleural effusions.

Neurotrophins (NTs) modulate the growth of human malignancies, including lung cancers. Our prospective study evaluated the accuracy of pleural NTs [nerve growth factor, brain-derived neurotrophic factor (BDNF), neurotrophin 3 (nT3) and 4 (nT4)] levels for differentiating benign from malignant pleural exudates. Levels of NTs were measured by ELISA in 170 patients with non-neutrophilic (<50%) exudative benign or malignant pleurisies diagnosed by pleuroscopy. Fifty-nine benign (9 infections and 50 inflammatory diseases) and 111 malignant (50 extrathoracic tumors, 51 lung cancers and 10 mesotheliomas) pleural exudates were diagnosed by thoracoscopy. Levels of BDNF were significantly higher in malignant than in benign effusions [17 pg/ml (0-367) vs. 8 pg/ml (0-51), p<0.05]. ROC analysis showed an area under the curve of 0.609 (p=0.012; best threshold 44 pg/ml). Pleural BDNF levels were significantly higher in pleural metastasis of pulmonary tumors and in mesothelioma than in pleural benign effusions. Finally, a higher proportion of pleural nT3 was detected in squamous cell lung carcinoma in comparison to that in non-squamous cell lung carcinoma (72.7 vs. 10%, p<0.0001). NTs and particularly BDNF may play a role in the pathogenesis of malignant pleural effusions.