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Background: The role of obesity on dyspnea in chronic obstructive pulmonary disease (COPD) patients remains unclear. We aimed to provide an assessment of dyspnea in COPD patients according to their Body Mass Index (BMI) and to investigate the impact of obesity on dyspnea according to COPD severity. Methods: One hundred and twenty seven COPD patients with BMI ≥ 18.5 kg/m² (63% male, median (interquartile range) post bronchodilator forced expiratory volume of 1 second (post BD FEV1) at 51 (34-66) % pred) were consecutively included. Dyspnea was assessed by mMRC (Modified medical research council) scale. Lung function tests were recorded, and emphysema was quantified on CT-scan (computed tomography-scan). Results: Twenty-five percent of the patients were obese (BMI ≥ 30kg/m²), 66% of patients experienced disabling dyspnea (mMRC ≥ 2). mMRC scores did not differ depending on BMI categories (2 (1-3) for normal weight, 2 (1-3) 1 for overweight and 2 (1-3) for obese patients; p = 0.71). Increased mMRC scores (0-1 versus 2-3 versus 4) were associated with decreased post BD-FEV1 (p < 0.01), higher static lung hyperinflation (inspiratory capacity/total lung capacity (IC/TLC), p < 0.01), reduced DLCO (p < 0.01) and higher emphysema scores (p < 0.01). Obese patients had reduced static lung hyperinflation (IC/TLC p < 0.01) and lower emphysema scores (p < 0.01) than non-obese patients. mMRC score increased with GOLD grades (1-2 versus 3-4) in non-obese patients but not in obese patients, in association with a trend towards reduced static lung hyperinflation and lower emphysema scores. Conclusion: By contrast with non-obese patients, dyspnea did not increase with spirometric GOLD grades in obese patients. This might be explained by a reduced lung hyperinflation related to the mechanical effects of obesity and a less severe emphysema in severe COPD patients with obesity.
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Índice de Masa Corporal , Disnea , Pulmón , Obesidad , Enfermedad Pulmonar Obstructiva Crónica , Índice de Severidad de la Enfermedad , Humanos , Masculino , Disnea/fisiopatología , Disnea/etiología , Disnea/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Obesidad/complicaciones , Obesidad/fisiopatología , Obesidad/diagnóstico , Femenino , Anciano , Persona de Mediana Edad , Volumen Espiratorio Forzado , Pulmón/fisiopatología , Pulmón/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Enfisema Pulmonar/fisiopatología , Enfisema Pulmonar/diagnóstico , Factores de Riesgo , EspirometríaRESUMEN
WHAT ARE THE INDICATIONS FOR CORTICOSTEROID THERAPY IN COPD? In stable state chronic obstructive pulmonary disease (COPD), inhaled corticosteroids (ICS) should be used in case of frequent exacerbation only, associated with long-term bronchodilators including long-acting beta-agonist (LABA) and long-acting muscarinic antagonist (LAMA). When frequent exacerbations persist despite dual inhaled therapy (LABA + CSI or LABA+LAMA), triple inhaled therapy (LAMA+LABA+CSI) is indicated. In COPD exacerbation, the level of evidence for systemic corticosteroids is very low, justifying not to systematically prescribe systemic corticosteroids and when used to restrict this use to short-term (5 days) and low doses.
QUELLES SONT LES INDICATIONS POUR LA CORTICOTHÉRAPIE DANS LA BPCO ? Dans la bronchopneumopathie chronique obstructive (BPCO) à l'état stable, les corticostéroïdes inhalés (CSI) ne sont à utiliser qu'en cas d'exacerbations fréquentes, en association avec des bronchodilatateurs de longue durée d'action de type bêta-2-agoniste de longue durée d'action (LABA) et anticholinergique de longue durée d'action (LAMA). En cas de persistance d'exacerbations fréquentes malgré une bithérapie inhalée (LABA-CSI ou LAMA-LABA), une triple thérapie (LAMA-LABA CSI) peut être proposée. En cas d'exacerbation de BPCO, le niveau de preuve de la corticothérapie systémique est faible, justifiant ne pas recourir à ce traitement de façon systématique ou de le réaliser en cures courtes (cinq jours) et à faibles doses quand il est prescrit.
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Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Administración por Inhalación , Corticoesteroides/uso terapéutico , Corticoesteroides/administración & dosificación , Broncodilatadores/uso terapéutico , Broncodilatadores/administración & dosificación , Quimioterapia Combinada , Glucocorticoides/uso terapéutico , Glucocorticoides/administración & dosificaciónRESUMEN
Chronic obstructive pulmonary disease (COPD) is a condition characterized by chronic airway inflammation and obstruction, primarily caused by tobacco smoking. Although the involvement of immune cells in COPD pathogenesis is well established, the contribution of innate lymphoid cells (ILCs) remains poorly understood. ILCs are a type of innate immune cells that participate in tissue remodeling processes, but their specific role in COPD has not been fully elucidated. During COPD, the breakdown of pulmonary elastin generates elastin peptides that elicit biological activities on immune cells. This study aimed to investigate the presence of ILC in patients with COPD and examine the impact of elastin peptides on their functionality. Our findings revealed an elevated proportion of ILC2 in the peripheral blood of patients with COPD, and a general activation of ILC as indicated by an increase in their cytokine secretion capacity. Notably, our study demonstrated that serum from patients with COPD promotes ILC2 phenotype, likely due to the elevated concentration of IL-5, a cytokine known to favor ILC2 activation. Furthermore, we uncovered that this increase in IL-5 secretion is partially attributed to its secretion by macrophages upon stimulation by elastin peptides, suggesting an indirect role of elastin peptides on ILC in COPD. These findings shed light on the involvement of ILC in COPD and provide insights into the potential interplay between elastin breakdown, immune cells, and disease progression. Further understanding of the mechanisms underlying ILC activation and their interaction with elastin peptides could contribute to the development of novel therapeutic strategies for COPD management.NEW & NOTEWORTHY Elastin-derived peptides, generated following alveolar degradation during emphysema in patients with COPD, are able to influence the response of type 2 innate lymphoid cells. We show that the orientation of innate lymphoid cells in patients with COPD is shifted toward a type 2 profile and that elastin peptides are indirectly participating in that shift through their influence of macrophages, which in turn impact innate lymphoid cells.
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Elastina , Inmunidad Innata , Linfocitos , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Enfermedad Pulmonar Obstructiva Crónica/patología , Elastina/metabolismo , Elastina/inmunología , Linfocitos/inmunología , Linfocitos/metabolismo , Linfocitos/efectos de los fármacos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Interleucina-5/metabolismo , Interleucina-5/inmunología , Macrófagos/inmunología , Macrófagos/metabolismo , Péptidos/farmacología , Péptidos/inmunologíaRESUMEN
Purpose: The heterogeneity of clinical features in COPD at stable state has been associated with airway microbiota. Blood eosinophil count (BEC) represents a biomarker for a pejorative evolution of COPD, including exacerbations and accelerated FEV1 decline. We aimed to analyse the associations between BEC and airway microbiota in COPD at stable state. Patients and Methods: Adult COPD patients at stable state (RINNOPARI cohort) were included and characterised for clinical, functional, biological and morphological features. BEC at inclusion defined 2 groups of patients with low BEC <300/mm3 and high BEC ≥300/mm3. Sputa were collected and an extended microbiological culture was performed for the identification of viable airway microbiota. Results: Fifty-nine subjects were included. When compared with the low BEC (n=40, 67.8%), the high BEC group (n=19, 32.2%) had more frequent exacerbations (p<0.001) and more pronounced cough and sputum (p<0.05). The global composition, the number of bacteria per sample and the α-diversity of the microbiota did not differ between groups, as well as the predominant phyla (Firmicutes), or the gender repartition. Conclusion: In our study, high BEC in COPD at stable state was associated with a clinical phenotype including frequent exacerbation, but no distinct profile of viable airway microbiota compared with low BEC.
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Eosinofilia , Microbiota , Enfermedad Pulmonar Obstructiva Crónica , Adulto , Humanos , Eosinófilos , Progresión de la Enfermedad , Sistema Respiratorio , Recuento de Leucocitos , Esputo/microbiologíaRESUMEN
BACKGROUND: Severe asthma is characterized by frequent exacerbations, altered lung function, and impaired quality of life. Tailored patient education allows for the improvement of both asthma management and quality of life. Our study aimed to assess the needs of severe asthma patient in therapeutic education, according to previous therapeutic patient education background and asthma phenotype. METHODS: Consecutive patients monitored for severe asthma in a tertiary referral center were considered for inclusion and answered a questionnaire detailing their patient education needs and the topics they would like to discuss. Asthma history, clinical and biological data, and lung function results were recorded. RESULTS: Fifty-three patients were included and 47 (88.7%) expressed at least one need. The most frequently selected topics were "life with asthma" (83%), "treatment use" (68%), and "exacerbation management" (60%), independent of previous participation in a patient education program dedicated to asthma. Patients of older age at inclusion, uncontrolled asthma, and T2-high phenotypes were associated with different profiles of patient education needs. CONCLUSION: Our study identified frequent and various patient educational needs among severe asthmatics, highlighting the importance of an in-depth assessment of severe asthmatics expectations and the crucial need for the development of dedicated educational tools.
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Asma , Calidad de Vida , Humanos , Proyectos Piloto , Educación del Paciente como Asunto , Asma/tratamiento farmacológico , FenotipoRESUMEN
BACKGROUND AND OBJECTIVE: EpiGETIF is a web-based, multicentre clinical database created in 2019 aiming for prospective collection of data regarding therapeutic rigid bronchoscopy (TB) for malignant central airway obstruction (MCAO). METHODS: Patients were enrolled into the registry from January 2019 to November 2022. Data were prospectively entered through a web-interface, using standardized definitions for each item. The objective of this first extraction of data was to describe the population and the techniques used among the included centres to target, facilitate and encourage further studies in TB. RESULTS: Overall, 2118 patients from 36 centres were included. Patients were on average 63.7 years old, mostly male and smokers. Most patients had a WHO score ≤2 (70.2%) and 39.6% required preoperative oxygen support, including mechanical ventilation in 6.7%. 62.4% had an already known histologic diagnosis but only 46.3% had received any oncologic treatment. Most tumours were bronchogenic (60.6%), causing mainly intrinsic or mixed obstruction (43.3% and 41.5%, respectively). Mechanical debulking was the most frequent technique (67.3%), while laser (9.8%) and cryo-recanalization (2.7%) use depended on local expertise. Stenting was required in 54.7%, silicone being the main type of stent used (55.3%). 96.3% of procedure results were considered at least partially successful, resulting in a mean 4.1 points decrease on the Borg scale of dyspnoea. Complications were noted in 10.9%. CONCLUSION: This study exposes a high volume of TB that could represent a good source of future studies given the dismal amount of data about the effects of TB in certain populations and situations.
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Obstrucción de las Vías Aéreas , Broncoscopía , Sistema de Registros , Humanos , Broncoscopía/métodos , Masculino , Obstrucción de las Vías Aéreas/diagnóstico , Obstrucción de las Vías Aéreas/terapia , Obstrucción de las Vías Aéreas/etiología , Persona de Mediana Edad , Femenino , Estudios Prospectivos , Anciano , Stents , Neoplasias Pulmonares/complicacionesRESUMEN
BACKGROUND: Bronchiectasis is a chronic airway disease characterized by permanent and irreversible abnormal dilatation of bronchi. Several studies have reported the development of bronchiectasis after renal transplantation (RT), but no prospective study specifically assessed bronchiectasis in this population. This study aimed to compare features of patients with bronchiectasis associated with RT to those with idiopathic bronchiectasis. METHODS: Nineteen patients with bronchiectasis associated with RT (RT-B group) and 23 patients with idiopathic bronchiectasis (IB group) were prospectively included in this monocentric cross-sectional study. All patients underwent clinical, functional, laboratory, and CT scan assessments. Sputum was collected from 25 patients (n = 11 with RT-B and n = 14 with IB) and airway microbiota was analyzed using an extended microbiological culture. RESULTS: Dyspnea (≥ 2 on mMRC scale), number of exacerbations, pulmonary function tests, total bronchiectasis score, severity and prognosis scores (FACED and E-FACED), and quality of life scores (SGRQ and MOS SF-36) were similar in the RT-B and IB groups. By contrast, chronic cough was less frequent in the RT-B group than in the IB group (68% vs. 96%, p = 0.03). The prevalence and diversity of the airway microbiota in sputum were similar in the two groups. CONCLUSION: Clinical, functional, thoracic CT scan, and microbiological characteristics of bronchiectasis are overall similar in patients with IB and RT-B. These results highlight that in RT patients, chronic respiratory symptoms and/or airway infections should lead to consider the diagnosis of bronchiectasis. Further studies are required to better characterize the pathophysiology of RT-B including airway microbiota, its incidence, and impact on therapeutic management.
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Bronquiectasia , Trasplante de Riñón , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Estudios Transversales , Trasplante de Riñón/efectos adversos , Calidad de Vida , Bronquiectasia/complicacionesAsunto(s)
Asma , Cilios , Fenotipo , Transcriptoma , Humanos , Asma/genética , Asma/metabolismo , Cilios/metabolismo , Cilios/patología , Inflamación/genética , Células Epiteliales/metabolismo , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/patología , Perfilación de la Expresión Génica , Regulación de la Expresión GénicaRESUMEN
Cilia are organelles emanating from the cell surface, consisting of an axoneme of microtubules that extends from a basal body derived from the centrioles. They are either isolated and nonmotile (primary cilia), or grouped and motile (motile cilia). Cilia are at the centre of fundamental sensory processes and are involved in a wide range of human disorders. Pulmonary cilia include motile cilia lining the epithelial cells of the conductive airways to orchestrate mucociliary clearance, and primary cilia found on nondifferentiated epithelial and mesenchymal cells acting as sensors and cell cycle keepers. Whereas cilia are essential along the airways, their regulatory molecular mechanisms remain poorly understood, resulting in a lack of therapeutic strategies targeting their structure or functions. This review summarises the current knowledge on cilia in the context of lung homeostasis and COPD to provide a comprehensive overview of the (patho)biology of cilia in respiratory medicine with a particular emphasis on COPD.
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Pulmón , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Depuración Mucociliar , Axonema/metabolismo , Cilios/metabolismo , Células Epiteliales/metabolismo , Homeostasis , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/terapia , Enfermedad Pulmonar Obstructiva Crónica/metabolismoRESUMEN
BACKGROUND: Cough and sputum are major symptoms in cystic fibrosis (CF) that contribute to the impairment of quality of life. METHODS: This prospective single centre cross-sectional pilot study aimed to evaluate the results of a self-administered questionnaire assessing cough and sputum symptoms (2 domains), and their impact (2 domains) on daily activities in the previous week, named the Cough and Sputum Assessment Questionnaire (CASA-Q) in CF adult patients at stable state, and to analyse associations with clinical, functional, microbiological, radiological data, and two quality of life scales: the Cystic Fibrosis Questionnaire Revised (CFQ-R) and the Saint George Respiratory Questionnaire (SGRQ). RESULTS: Forty-eight patients were included in this analysis (69% men; median age of 27.8 ± 8.1 years; median body mass index of 21.8 + 3.3 kg/m²; mean FEV1 of 64 ± 30% of the predicted value). The mean values of the CASA-Q domains were 58 ± 23 for cough symptoms, 77 ± 24 for cough impact, 62 ± 25 for sputum symptoms and 84 ± 21 for sputum impact. Impairment in CASA-Q cough and sputum domains was associated with dyspnea mMRC scale (p < 0.005 for all 4 domains of CASA-Q) and exacerbations in the previous year (p < 0.05 for CASA-Q symptoms domains). We also found correlations between all domains of the CASA-Q and quality of life questionnaires including SGRQ (p < 0.001) and to a lesser extend CFQ-R. We identified a clinical phenotype (female gender, ΔF508 heterozygous mutation, dyspnea mMRC scale) associated with an impairment of CASA-Q score and quality of life using a 2-step cluster analysis. CONCLUSIONS: CASA-Q allows the assessment of cough and sputum in CF adult patients and is associated with quality of life impairment. This simple easy-to-use tool could be used in routine clinical practice and in clinical studies to assess cough and sputum in CF patients. TRIAL REGISTRATION: The study was registered on ClinicalTrials.gov (NCT02924818, first posted on 5th October 2016).
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Fibrosis Quística , Calidad de Vida , Masculino , Adulto , Humanos , Femenino , Adulto Joven , Tos/etiología , Fibrosis Quística/complicaciones , Fibrosis Quística/diagnóstico , Esputo , Estudios Prospectivos , Estudios Transversales , Proyectos Piloto , Encuestas y Cuestionarios , DisneaRESUMEN
BACKGROUND: Dysregulated inflammation as seen in chronic obstructive pulmonary disease (COPD) is associated with impaired wound healing. IL-20 cytokines are known to be involved in wound healing processes. The purpose of this study was to use ex vivo and in vitro approaches mimicking COPD to evaluate the potential modulatory role of interleukin-20 (IL-20) on the inflammatory and healing responses to epithelial wounding. METHODS: The expression of IL-20 cytokines and their receptors was investigated in lung-derived samples collected from non-COPD and COPD patients, from mice chronically exposed to cigarette smoke and from airway epithelial cells from humans and mice exposed in vitro to cigarette smoke. To investigate the role of IL-20 cytokines in wound healing, experiments were performed using a blocking anti-IL-20Rb antibody. RESULTS: Of interest, IL-20 cytokines and their receptors were expressed in bronchial mucosa, especially on airway epithelial cells. Their expression correlated with the disease severity. Blocking these cytokines in a COPD context improved the repair processes after a lesion induced by scratching the epithelial layer. CONCLUSIONS: Collectively, this study highlights the implication of IL-20 cytokines in the repair of the airway epithelium and in the pathology of COPD. IL-20 subfamily cytokines might provide therapeutic benefit for patients with COPD to improve epithelial healing.
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Fumar Cigarrillos , Enfermedad Pulmonar Obstructiva Crónica , Animales , Humanos , Ratones , Fumar Cigarrillos/efectos adversos , Citocinas/metabolismo , Interleucinas/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/patología , Mucosa Respiratoria/metabolismoRESUMEN
Lung cancer remains the first cause of cancer-related death despite many therapeutic innovations, including immune checkpoint inhibitors (ICI). ICI are now well used in daily practice at late metastatic stages and locally advanced stages after a chemo-radiation. ICI are also emerging in the peri-operative context. However, all patients do not benefit from ICI and even suffer from additional immune side effects. A current challenge remains to identify patients eligible for ICI and benefiting from these drugs. Currently, the prediction of ICI response is only supported by Programmed death-ligand 1 (PD-L1) tumor expression with perfectible results and limitations inherent to tumor-biopsy specimen analysis. Here, we reviewed alternative markers based on liquid biopsy and focused on the most promising biomarkers to modify clinical practice, including non-tumoral blood cell count such as absolute neutrophil counts, platelet to lymphocyte ratio, neutrophil to lymphocyte ratio, and derived neutrophil to lymphocyte ratio. We also discussed soluble-derived immune checkpoint-related products such as sPD-L1, circulating tumor cells (detection, count, and marker expression), and circulating tumor DNA-related products. Finally, we explored perspectives for liquid biopsies in the immune landscape and discussed how they could be implemented into lung cancer management with a potential biological-driven decision.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Biomarcadores de Tumor , Linfocitos/metabolismoRESUMEN
INTRODUCTION: From 2018 single inhaler triple therapy (SITT) became available in France to treat moderate-to-severe chronic obstructive pulmonary disease (COPD). Given its simplified inhaler use compared with multiple inhaler triple therapy (MITT), this therapeutic option has the potential to offer benefit in terms of improved persistence and adherence. Given the lack of real-world evidence of the effectiveness of triple therapy, this study was designed to evaluate the use of MITT and SITT in France and compare persistence. METHODS: A retrospective cohort study was performed. Patients with COPD who initiated triple therapy between 1 July 2017 and 31 December 2019 were included from The Health Improvement Network, a large electronic medical database in France, which includes pharmacy data. A 60-day treatment gap defined discontinuation and thereby persistence. RESULTS: A total of 3134 patients initiated triple therapy for COPD in the study period, among them 485 with SITT. In 2019, the rate of use of SITT was 28.2%. The mean age (67.3 years) and sex (44.2% female) of patients initiating triple therapy was similar between MITT and SITT, and most patients had escalated from dual therapy (84.1%). However, SITT was more frequently initiated by a pulmonologist (59.8%) and a higher prevalence of comorbid asthma was observed for SITT (47.0% vs 37.9%). Persistence was assessed among patients who did not discontinue after a single dispensation of triple therapy (n=1674). Median persistence was 181 days for SITT and 135 days for MITT, and the covariate-adjusted HR for persistence was 1.47 (p<0.001) and the estimated persistence at 1 year was 33% for SITT compared with 18% for MITT. DISCUSSION: This study suggests that persistence was higher for the patients treated with SITT compared with MITT in France. Moreover, most patients initiated with triple therapy were previously treated with dual therapy and had exacerbations in the previous year.
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Broncodilatadores , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Femenino , Anciano , Masculino , Estudios Retrospectivos , Administración por Inhalación , Resultado del Tratamiento , Agonistas de Receptores Adrenérgicos beta 2/efectos adversos , Nebulizadores y VaporizadoresRESUMEN
Anti-PD-1/PD-L1 therapy indications are broadened in non-small cell lung cancer (NSCLC) although immune checkpoint inhibitors (ICI) do not provide benefits for the entire population. Texture features based on positron emission tomography/computed tomography (PET/CT), especially entropy (based on a gray-level co-occurrence matrix (GLCM)), could be interesting as predictors in NSCLC. The aim of our retrospective study was to evaluate the association between GLCM-entropy and response to anti-PD-1/PD-L1 monotherapy at the first evaluation in stage III or IV NSCLC, comparing patients with progressive disease (PD) and non-progressive disease (non-PD). In total, 47 patients were included. Response Evaluation Criteria in Solid Tumors (RECIST 1.1) were used to evaluate the response to ICI treatment (nivolumab, pembrolizumab, or atezolizumab). At the first evaluation, 25 patients were PD and 22 were non-PD. GLCM-entropy was not predictive of response at the first evaluation. Furthermore, GLCM-entropy was not associated with progression-free survival (PFS) (p = 0.393) or overall survival (OS) (p = 0.220). Finally, GLCM-entropy measured in PET/CT performed before ICI initiation in stage III or IV NSCLC was not predictive of response at the first evaluation. However, this study demonstrates the feasibility of using texture parameters in routine clinical practice. The interest of measuring PET/CT texture parameters in NSCLC remains to be evaluated in larger prospective studies.
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RATIONALE: Pomalidomide is an immunomodulatory imide drug used in multiple myeloma and in Kaposi sarcoma. PATIENT CONCERNS: A 72-years-old male, treated for multiple myeloma with dexamethasone, pomalidomide and daratumumab, presented dyspnea, hypoxemia, biological inflammatory syndrome, ground glass opacities on computed tomography scan (CT-scan) and lymphocytic and eosinophilic alveolitis, with no specific cytologic or microbiological findings, 2 months after pomalidomide initiation. INTERVENTION AND OUTCOME: Antibiotics were started after bronchoscopy. No improvement was noted in dyspnea and biological inflammatory syndrome after 5 days of treatment. Pomalidomide was then discontinued, with continuation of Daratumumab-Dexamethasone, resulting in a rapid recovery of symptoms and CT-scan anomalies. No recurrence of dyspnea was observed during the 15 months of follow-up. DIAGNOSES: Pomalidomide-induced lung injury. LESSONS: Pomalidomide-induced lung injury is a rare and serious adverse event that can occur early after Pomalidomide introduction. As pomalidomide use is increasing, the identification of drug toxicity as a possible cause of lung injury appears important. We report a rapid recovery of symptoms and CT-scan anomalies after pomalidomide discontinuation.
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Lesión Pulmonar , Mieloma Múltiple , Masculino , Humanos , Anciano , Mieloma Múltiple/tratamiento farmacológico , Lesión Pulmonar/etiología , Dexametasona/uso terapéutico , Disnea/etiología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Survival improvement in cystic fibrosis (CF) is associated with more frequent long-term complications, including CF related bone disease (CFBD). Impact of CFBD on global health outcome remains poorly described. We aimed to assess the relationship between low bone mineral density (BMD) and spinal pain, disability, and quality of life in CF adult patients. This monocentric cross-sectional study with prospective data collection was conducted from November 2016 to December 2019 in the Department of Respiratory Diseases at the University Hospital of Reims (NCT02924818). BMD was assessed by X-ray absorptiometry (DXA). Disability was assessed by the Health Assessment Questionnaire (HAQ). Quality of life was assessed by both the St George's Respiratory Questionnaire and the Cystic Fibrosis Questionnaire for teenagers and adults (CFQ 14+). Forty patients were analyzed, 68% of men, with a median age of 25 years, a median body mass index of 21 kg/m² and a median FEV1% of 54%. Nine patients (23%) had spinal pain. Ten patients (25%) had a low BMD. Compared with patients with normal BMD, patients with low BMD had a significantly lower BMI (22 vs 19 kg/m²; Pâ =â .006) and less vitamin D supplementation (33% vs 0%; Pâ =â .035). Low BMD was not associated with spinal pain, disability and quality of life. Low BMD is frequent in CF, affecting 1-quarter of adult patients. No significant association was found between low BMD and spinal pain, disability or quality of life.
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Enfermedades Óseas Metabólicas , Fibrosis Quística , Masculino , Adolescente , Humanos , Adulto , Fibrosis Quística/complicaciones , Densidad Ósea , Proyectos Piloto , Estudios Transversales , Relevancia Clínica , Calidad de Vida , Enfermedades Óseas Metabólicas/complicaciones , Absorciometría de FotónRESUMEN
Lung transplantation (LTx) is a steadily expanding field. The considerable developments have been driven over the years by indefatigable work conducted at LTx centers to improve donor and recipient selection, combined with multifaceted efforts to overcome challenges raised by the surgical procedure, perioperative care, and long-term medical complications. One consequence has been a pruning away of contraindications over time, which has, in some ways, complicated the patient selection process. The Francophone Pulmonology Society (Société de Pneumology de Langue Française, SPLF) set up a task force to produce up-to-date working guidelines designed to assist pulmonologists in managing end-stage respiratory insufficiency, determining which patients may be eligible for LTx, and appropriately timing LTx-center referral. The task force examined the most recent literature and evaluated the risk factors that limit patient survival after LTx. Ideally, the objectives of LTx are to prolong life while also improving quality of life. The guidelines developed by the task force apply to a limited resource and are consistent with the ethical principles described below.
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Trasplante de Pulmón , Calidad de Vida , Humanos , Francia/epidemiología , Factores de Riesgo , ContraindicacionesRESUMEN
Lung cancer stands as the first cause of death by cancer in the world. Despite the improvement in patients' outcomes in the past decades through the development of personalized medicine approaches, a substantial portion of patients remains ineligible for targeted therapies due to the lack of a "druggable" molecular target. HER2, a receptor tyrosine kinase member of the EGFR/ErbB family, is known to show oncogenic properties. In this review, we focus on the different HER2 dysregulation mechanisms that have been observed in non-small cell lung cancer (NSCLC): gene mutation, gene amplification, protein overexpression and protein hyper-phosphorylation, the latter suggesting that HER2 dysregulation can occur independently of any molecular aberration. These HER2 alterations inevitably have consequences on tumor biology. Here, we discuss how they are not only involved in abnormal proliferation and survival of cancer cells but also potentially in increased angiogenic properties, mesenchymal features and tumor immune escape. Finally, we review the impact of these HER2 alterations in various therapeutic approaches. While standard chemotherapy and groundbreaking immunotherapy seem rather ineffective for HER2-altered NSCLCs, the development of HER2-targeted therapies such as tyrosine kinase inhibitors, anti-HER2 antibodies and especially antibody-drug conjugates could provide new hopes for patients.
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Introduction: In recent decades, the development of immunotherapy and targeted therapies has considerably improved the outcome of non-small cell lung cancer (NSCLC) patients. Despite these impressive clinical benefits, new biomarkers are needed for an accurate stratification of NSCLC patients and a more personalized management. We recently showed that the tumor suppressor fragile histidine triad (FHIT), frequently lost in NSCLC, controls HER2 receptor activity in lung tumor cells and that tumor cells from NSCLC patients harboring a FHITlow/pHER2high phenotype are sensitive to anti-HER2 drugs. Here, we sought to identify the transcriptomic signature of this phenotype and evaluate its clinical significance. Materials and methods: We performed RNA sequencing analysis on tumor cells isolated from NSCLC (n=12) according to FHIT/pHER2 status and a functional analysis of differentially regulated genes. We also investigated the FHITlow/pHER2high signature in The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LUAD) (n=489) and lung squamous cell carcinoma (LUSC) (n=493) cohorts and used the tumor immune dysfunction and exclusion (TIDE) model to test the ability of this signature to predict response to immune checkpoint inhibitors (ICI). Results: We showed that up-regulated genes in FHITlow/pHER2high tumors were associated with cell proliferation, metabolism and metastasis, whereas down-regulated genes were related to immune response. The FHITlow/pHER2high signature was associated with the higher size of tumors, lymph node involvement, and late TNM stages in LUAD and LUSC cohorts. It was identified as an independent predictor of overall survival (OS) in LUAD cohort. FHITlow/pHER2high tumors were also predictive of poor response to ICI in both LUAD and LUSC cohorts. Conclusion: These data suggest that ICI might not be a relevant option for NSCLC patients with FHITlow/pHER2high tumors and that anti-HER2 targeted therapy could be a good therapeutic alternative for this molecular subclass with poorer prognosis.
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Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Transcriptoma , Adenocarcinoma del Pulmón/genética , Carcinoma de Células Escamosas/genética , InmunoterapiaRESUMEN
This study shows that TLD reduces airway epithelial expression of genes related to acetylcholine processing and airway inflammation, which may help to elucidate the mechanism for its effect of reducing severe exacerbations in COPD https://bit.ly/3dWcqZk.