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1.
Surg Pathol Clin ; 17(2): 173-192, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38692803

RESUMEN

Granulomas are frequently encountered by pathologists in all types of lung specimens and arise from diverse etiologies. They should always be reported as necrotizing or non-necrotizing, with microorganism stains performed to evaluate for infection. With attention to distribution, quality (poorly vs well-formed), associated features, and correlation with clinical, radiologic, and laboratory data, the differential diagnosis for granulomatous lung disease can usually be narrowed to a clinically helpful "short list." This review describes a practical approach to pulmonary granulomas and reviews the clinicopathological aspects of common entities, including infectious (mycobacteria, fungi) and noninfectious (hypersensitivity pneumonitis, sarcoid, and vasculitis) causes.


Asunto(s)
Enfermedades Pulmonares , Humanos , Diagnóstico Diferencial , Enfermedades Pulmonares/patología , Enfermedades Pulmonares/diagnóstico , Granuloma del Sistema Respiratorio/patología , Granuloma del Sistema Respiratorio/diagnóstico , Granuloma/patología , Granuloma/diagnóstico , Pulmón/patología , Alveolitis Alérgica Extrínseca/diagnóstico , Alveolitis Alérgica Extrínseca/patología , Sarcoidosis Pulmonar/patología , Sarcoidosis Pulmonar/diagnóstico , Enfermedades Pulmonares Fúngicas/diagnóstico , Enfermedades Pulmonares Fúngicas/patología
3.
Biometals ; 36(3): 603-615, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-35976499

RESUMEN

Lactoferrin (LTF), an iron binding protein, is known to exhibit immune modulatory effects on pulmonary pathology during insult-induced models of primary Mycobacterium tuberculosis (Mtb) infection. The effects of LTF correlate with modulation of the immune related development of the pathology, and altering of the histological nature of the physically compact and dense lung granuloma in mice. Specifically, a recombinant human version of LTF limits immediate progression of granulomatous severity following administration of the Mtb cell wall mycolic acid, trehalose 6,6'-dimycolate (TDM), in part through reduced pro-inflammatory responses known to control these events. This current study investigates a limited course of LTF to modulate not only initiation, but also maintenance and resolution of pathology post development of the granulomatous response in mice. Comparison is made to a fusion of LTF with the Fc domain of IgG2 (FcLTF), which is known to extend LTF half-life in circulation. TDM induced granulomas were examined at extended times post insult (day 7 and 14). Both LTF and the novel FcLTF exerted sustained effects on lung granuloma pathology. Reduction of pulmonary pro-inflammatory cytokines TNF-α and IL-1ß occurred, correlating with reduced pathology. Increase in IL-6, known to regulate granuloma maintenance, was also seen with the LTFs. The FcLTF demonstrated greater impact than the recombinant LTF, and was superior in limiting damage to pulmonary tissues while limiting residual inflammatory cytokine production.


Asunto(s)
Factores Cordón , Granuloma del Sistema Respiratorio , Lactoferrina , Enfermedades Pulmonares , Animales , Humanos , Ratones , Factores Cordón/metabolismo , Factores Cordón/toxicidad , Lactoferrina/uso terapéutico , Mycobacterium tuberculosis/metabolismo , Granuloma del Sistema Respiratorio/inducido químicamente , Granuloma del Sistema Respiratorio/tratamiento farmacológico , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/tratamiento farmacológico
4.
São Paulo; s.n; 2023. 27 p.
Tesis en Portugués | Coleciona SUS, Sec. Munic. Saúde SP, HSPM-Producao, Sec. Munic. Saúde SP | ID: biblio-1531123

RESUMEN

A granulomatose com poliangeíte (GPA) é uma vasculite de pequenos vasos, de acometimento sistêmico variável, sendo o trato respiratório superior, inferior e rins os órgãos mais afetados. O acometimento traqueobrônquico se dá por várias manifestações, sendo a estenose subglótica a manifestação mais comum. A apresentação da estenose pode ser independente das manifestações sistêmicas da GPA e nem sempre segue a mesma evolução e resposta ao tratamento dos demais órgãos acometidos por essa vasculite, podendo ser grave o suficiente para necessitar de traqueostomia. Este estudo tem como objetivo relatar um caso de GPA com evolução para estenose subglótica (ESG) de 60% da luz da traqueia e o comportamento desta complicação frente às opções terapêuticas utilizadas. É um estudo observacional, descritivo, do tipo relato de caso. O caso demonstra a complexidade dessa apresentação clínica frente às opções terapêuticas disponíveis, por vezes, necessitando da combinação de medidas farmacológicas e intervencionistas. O manejo bem-sucedido da ESG é essencial para evitar complicações graves, destacando a importância do diagnóstico precoce e do acompanhamento rigoroso para garantir a qualidade de vida dos pacientes afetados por essa condição desafiadora. Palavra-chave: Estenose subglótica. Granulomatose com poliangeíte. Granulomatose de Wegener.


Asunto(s)
Humanos , Femenino , Adulto , Vasculitis/complicaciones , Granuloma del Sistema Respiratorio , Granulomatosis con Poliangitis/diagnóstico
6.
Adv Respir Med ; 89(4): 386-391, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34494242

RESUMEN

INTRODUCTION: Large vessels are often encountered during endobronchial ultrasound (EBUS). Safety of traversing the vessels weighed against a more invasive procedure can be a dilemma. MATERIAL AND METHODS: We describe a case series of 8 patients who underwent transvascular needle aspiration during EBUS, to access a lesion in the absence of an alternate safe window. A 21 gauge EBUS needle was used to traverse either the main or a major branch of the pulmonary artery. RESULTS: Malignancy was suspected at ROSE in five cases. Granuloma and necrosis noted in 2 cases were confirmed as tubercu-losis on culture. Diagnostic yield of EBUS-TVNA was 87.5% (7/8). No complications were noted in the immediate post-operative period as well as during 6 months of follow up. CONCLUSION: EBUS-TVNA in carefully selected patients is a feasible alternative to more invasive procedures with excellent yield. Appropriate intraoperative, perioperative and postoperative monitoring and care must be available in the case of fatal bleeds.


Asunto(s)
Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Biopsia Guiada por Imagen/métodos , Neoplasias Pulmonares/patología , Pulmón/patología , Ganglios Linfáticos/patología , Adulto , Femenino , Granuloma del Sistema Respiratorio/patología , Humanos , Masculino , Persona de Mediana Edad
7.
J Clin Invest ; 131(15)2021 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-34128839

RESUMEN

Tuberculosis (TB) is a persistent global pandemic, and standard treatment for it has not changed for 30 years. Mycobacterium tuberculosis (Mtb) has undergone prolonged coevolution with humans, and patients can control Mtb even after extensive infection, demonstrating the fine balance between protective and pathological host responses within infected granulomas. We hypothesized that whole transcriptome analysis of human TB granulomas isolated by laser capture microdissection could identify therapeutic targets, and that comparison with a noninfectious granulomatous disease, sarcoidosis, would identify disease-specific pathological mechanisms. Bioinformatic analysis of RNAseq data identified numerous shared pathways between TB and sarcoidosis lymph nodes, and also specific clusters demonstrating TB results from a dysregulated inflammatory immune response. To translate these insights, we compared 3 primary human cell culture models at the whole transcriptome level and demonstrated that the 3D collagen granuloma model most closely reflected human TB disease. We investigated shared signaling pathways with human disease and identified 12 intracellular enzymes as potential therapeutic targets. Sphingosine kinase 1 inhibition controlled Mtb growth, concurrently reducing intracellular pH in infected monocytes and suppressing inflammatory mediator secretion. Immunohistochemical staining confirmed that sphingosine kinase 1 is expressed in human lung TB granulomas, and therefore represents a host therapeutic target to improve TB outcomes.


Asunto(s)
Granuloma del Sistema Respiratorio/metabolismo , Pulmón/metabolismo , Modelos Biológicos , Mycobacterium tuberculosis/metabolismo , RNA-Seq , Tuberculosis Pulmonar/metabolismo , Adulto , Anciano , Femenino , Granuloma del Sistema Respiratorio/genética , Granuloma del Sistema Respiratorio/microbiología , Granuloma del Sistema Respiratorio/patología , Humanos , Pulmón/microbiología , Pulmón/patología , Masculino , Persona de Mediana Edad , Tuberculosis Pulmonar/genética , Tuberculosis Pulmonar/patología
8.
Sci Rep ; 11(1): 10687, 2021 05 21.
Artículo en Inglés | MEDLINE | ID: mdl-34021178

RESUMEN

Tuberculosis (TB) is still a major worldwide health threat and primarily a lung disease. The innate immune response against Mycobacterium tuberculosis (Mtb) is orchestrated by dendritic cells, macrophages, neutrophils, natural killer cells and apparently mast cells (MCs). MCs are located at mucosal sites including the lungs and contribute in host-defence against pathogens, but little is known about their role during Mtb infection. This study investigates the location and characteristics of MCs in TB lesions to assess their contribution to TB pathology. To this purpose, number, location and phenotype of MCs was studied in 11 necropsies of pulmonary TB and 3 necropsies of non-TB infected lungs that were used as controls. MCs were localised at pneumonic areas, in the granuloma periphery and particularly abundant in fibrotic tissue. Furthermore, MCs displayed intracellular Mtb and IL-17A and TGF-ß immunostaining. These findings were validated by analysing, post-mortem lung tissue microarrays from 44 individuals with pulmonary TB and 25 control subjects. In affected lungs, increased numbers of MCs expressing intracellularly both tryptase and chymase were found at fibrotic sites. Altogether, our data suggest that MCs are recruited at the inflammatory site and that actively produce immune mediators such as proteases and TGF-ß that may be contributing to late fibrosis in TB lesions.


Asunto(s)
Recuento de Leucocitos , Mastocitos/inmunología , Mastocitos/metabolismo , Mycobacterium tuberculosis/inmunología , Tuberculosis Pulmonar/inmunología , Tuberculosis Pulmonar/microbiología , Antígenos Bacterianos/inmunología , Fibrosis , Granuloma del Sistema Respiratorio/patología , Humanos , Inmunohistoquímica , Triptasas/metabolismo
9.
Pediatr Dev Pathol ; 24(3): 252-257, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33683986

RESUMEN

Immune dysregulation, polyendocrinopathy and enteropathy, X-linked (IPEX) syndrome is a rare disorder caused by loss-of-function mutations in the gene forkhead box protein 3 (FOXP3). IPEX patients frequently show chronic diarrhea (enteropathy) associated with villous atrophies in the small intestine. Our case is different from this classical information in the literature, since he presented with neonatal onset inflammatory bowel disease within the first months of life accompanied by deep ulcers throughout colonic mucosa. Moreover, he developed chronic lung disease during follow-up and histopathological examinations showed granulomas in both gastrointestinal tract and lung parenchyma. Genetic analysis revealed the diagnosis of IPEX syndrome with a germline mutation in FOXP3. Thus, our study provides an unusual presentation of IPEX syndrome with colitis and granulomas presence in histopathological examinations.


Asunto(s)
Colitis/patología , Diabetes Mellitus Tipo 1/congénito , Diarrea/patología , Enfermedades Genéticas Ligadas al Cromosoma X/patología , Granuloma del Sistema Respiratorio/patología , Enfermedades del Sistema Inmune/congénito , Colitis/genética , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/patología , Diarrea/genética , Duodeno/patología , Factores de Transcripción Forkhead/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Granuloma/genética , Granuloma/patología , Granuloma del Sistema Respiratorio/genética , Humanos , Enfermedades del Sistema Inmune/genética , Enfermedades del Sistema Inmune/patología , Recién Nacido , Masculino , Mutación
10.
Virchows Arch ; 478(2): 361-366, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32519036

RESUMEN

Drug adulterants containing contaminants have been known to cause lung disease by inhalation or intravenous intake. Talcosis due to intravenous talc injection has been widely described in the literature, whereas the hypothesis of granulomatosis due to asbestos related to adulterated cocaine injection has not yet been explored. Herein, a case of pulmonary granulomatosis due to asbestos fibres related to cocaine injection in a young woman is described. Inorganic material in the lung was first individuated by light microscopy and last was identified using the SEM-EDX method. This case is unique since the occupational and passive inhalation of asbestos was excluded with absolute certainty.


Asunto(s)
Amianto/efectos adversos , Estimulantes del Sistema Nervioso Central/efectos adversos , Trastornos Relacionados con Cocaína/complicaciones , Cocaína/efectos adversos , Contaminación de Medicamentos , Granuloma de Cuerpo Extraño/etiología , Granuloma del Sistema Respiratorio/etiología , Abuso de Sustancias por Vía Intravenosa/complicaciones , Adulto , Amianto/administración & dosificación , Autopsia , Estimulantes del Sistema Nervioso Central/administración & dosificación , Cocaína/administración & dosificación , Consumidores de Drogas , Resultado Fatal , Femenino , Granuloma de Cuerpo Extraño/patología , Granuloma del Sistema Respiratorio/patología , Humanos
11.
Chest ; 159(3): 1084-1093, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-32926872

RESUMEN

BACKGROUND: Chronic beryllium disease (CBD), a granulomatous disease with similarities to sarcoidosis, arises only in individuals exposed to beryllium. Inhaled beryllium can elicit a T-cell-dominated alveolitis leading nonnecrotizing granulomata. CBD can be distinguished from sarcoidosis by demonstrating beryllium sensitization in a lymphocyte proliferation test. RESEARCH QUESTION: Beryllium exposure usually occurs in an occupational setting. Because of the diagnosis of CBD in a patient without evident beryllium exposure, we performed a beryllium-lymphocyte proliferation test (BeLPT) among his work colleagues. STUDY DESIGN AND METHODS: This field study investigated a cohort of work colleagues without obvious beryllium exposure. Twenty-one of 30 individuals were assessed in our outpatient clinic for beryllium sensitization. Therefore, BeLPT was performed with freshly collected peripheral blood mononuclear cells. Data were extracted from clinical charts, including geographical data. Beryllium content in dust samples collected at the workplace was measured by graphite-furnace atomic absorption spectroscopy and was compared with samples from different areas of Germany. RESULTS: For the initial patient, the diagnosis of sarcoidosis was reclassified as CBD based on two positive BeLPT results. Assessment of his workplace did not identify a source of beryllium. However, BeLPTs performed on his workmates demonstrated beryllium sensitization in 5 of 21 individuals, suggesting a local beryllium source. Concrete dust obtained from the building yard, the workplace of the index patient, contained high amounts of beryllium (1138 ± 162 µg/kg), whereas dust from other localities (control samples) showed much lower beryllium content (range, 147 ± 18-452 ± 206 µg/kg). Notably, the control dust collected from different places all over Germany exhibit different beryllium concentrations. INTERPRETATION: We describe a cluster of beryllium-sensitized workers from an industry not related to beryllium caused by environmental exposure to beryllium-containing concrete dust, which exhibited markedly elevated beryllium content. Importantly, analyses of dust samples collected from different localities showed that they contain markedly different amounts of beryllium. Thus, besides workplace-related exposure, environmental factors also are capable of eliciting a beryllium sensitization.


Asunto(s)
Beriliosis , Berilio , Polvo/análisis , Exposición a Riesgos Ambientales , Granuloma del Sistema Respiratorio , Activación de Linfocitos/inmunología , Sarcoidosis Pulmonar/diagnóstico , Adulto , Beriliosis/diagnóstico , Beriliosis/etiología , Beriliosis/inmunología , Beriliosis/prevención & control , Berilio/análisis , Berilio/toxicidad , Industria de la Construcción , Diagnóstico Diferencial , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Femenino , Alemania/epidemiología , Granuloma del Sistema Respiratorio/inducido químicamente , Granuloma del Sistema Respiratorio/diagnóstico , Humanos , Pruebas Inmunológicas/métodos , Leucocitos Mononucleares , Masculino , Agrupamiento Espacio-Temporal , Lugar de Trabajo/normas
12.
J Clin Invest ; 131(3)2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33301427

RESUMEN

The mechanism by which only some individuals infected with Mycobacterium tuberculosis develop necrotic granulomas with progressive disease while others form controlled granulomas that contain the infection remains poorly defined. Mice carrying the sst1-suscepible (sst1S) genotype develop necrotic inflammatory lung lesions, similar to human tuberculosis (TB) granulomas, which are linked to macrophage dysfunction, while their congenic counterpart (B6) mice do not. In this study we report that (a) sst1S macrophages developed aberrant, biphasic responses to TNF characterized by superinduction of stress and type I interferon pathways after prolonged TNF stimulation; (b) the late-stage TNF response was driven via a JNK/IFN-ß/protein kinase R (PKR) circuit; and (c) induced the integrated stress response (ISR) via PKR-mediated eIF2α phosphorylation and the subsequent hyperinduction of ATF3 and ISR-target genes Chac1, Trib3, and Ddit4. The administration of ISRIB, a small-molecule inhibitor of the ISR, blocked the development of necrosis in lung granulomas of M. tuberculosis-infected sst1S mice and concomitantly reduced the bacterial burden. Hence, induction of the ISR and the locked-in state of escalating stress driven by the type I IFN pathway in sst1S macrophages play a causal role in the development of necrosis in TB granulomas. Interruption of the aberrant stress response with inhibitors such as ISRIB may offer novel host-directed therapy strategies.


Asunto(s)
Granuloma del Sistema Respiratorio/inmunología , Pulmón/inmunología , Mycobacterium tuberculosis/inmunología , Estrés Fisiológico/inmunología , Tuberculosis Pulmonar/inmunología , Animales , Modelos Animales de Enfermedad , Granuloma del Sistema Respiratorio/microbiología , Granuloma del Sistema Respiratorio/patología , Pulmón/microbiología , Pulmón/patología , Ratones , Ratones SCID , Necrosis , Tuberculosis Pulmonar/patología
13.
Front Immunol ; 11: 606333, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33324422

RESUMEN

Background: Granulomatous-lymphocytic interstitial lung disease (GLILD) is a rare, potentially severe pulmonary complication of common variable immunodeficiency disorders (CVID). Informative clinical trials and consensus on management are lacking. Aims: The European GLILD network (e-GLILDnet) aims to describe how GLILD is currently managed in clinical practice and to determine the main uncertainties and unmet needs regarding diagnosis, treatment and follow-up. Methods: The e-GLILDnet collaborators developed and conducted an online survey facilitated by the European Society for Immunodeficiencies (ESID) and the European Respiratory Society (ERS) between February-April 2020. Results were analyzed using SPSS. Results: One hundred and sixty-one responses from adult and pediatric pulmonologists and immunologists from 47 countries were analyzed. Respondents treated a median of 27 (interquartile range, IQR 82-maximum 500) CVID patients, of which a median of 5 (IQR 8-max 200) had GLILD. Most respondents experienced difficulties in establishing the diagnosis of GLILD and only 31 (19%) had access to a standardized protocol. There was little uniformity in diagnostic or therapeutic interventions. Fewer than 40% of respondents saw a definite need for biopsy in all cases or performed bronchoalveolar lavage for diagnostics. Sixty-six percent used glucocorticosteroids for remission-induction and 47% for maintenance therapy; azathioprine, rituximab and mycophenolate mofetil were the most frequently prescribed steroid-sparing agents. Pulmonary function tests were the preferred modality for monitoring patients during follow-up. Conclusions: These data demonstrate an urgent need for clinical studies to provide more evidence for an international consensus regarding management of GLILD. These studies will need to address optimal procedures for definite diagnosis and a better understanding of the pathogenesis of GLILD in order to provide individualized treatment options. Non-availability of well-established standardized protocols risks endangering patients.


Asunto(s)
Alergia e Inmunología/tendencias , Inmunodeficiencia Variable Común/tratamiento farmacológico , Granuloma del Sistema Respiratorio/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Pediatría/tendencias , Pautas de la Práctica en Medicina/tendencias , Neumología/tendencias , Productos Biológicos/uso terapéutico , Inmunodeficiencia Variable Común/diagnóstico , Inmunodeficiencia Variable Común/inmunología , Europa (Continente) , Granuloma del Sistema Respiratorio/diagnóstico , Granuloma del Sistema Respiratorio/inmunología , Encuestas de Atención de la Salud , Disparidades en Atención de Salud/tendencias , Humanos , Inmunosupresores/efectos adversos , Internet , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/inmunología , Pediatras/tendencias , Pronóstico , Neumólogos/tendencias , Esteroides/uso terapéutico , Estados Unidos
16.
J Cardiothorac Surg ; 15(1): 331, 2020 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-33225977

RESUMEN

BACKGROUND: This study aimed to report the experience of diagnosis and treatment of one rare case of mediastinal lymph node tuberculous abscess (MLNTA) using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). CASE PRESENTATION: An 18-year-old female patient was hospitalized in the Affiliated Hospital of Xuzhou Medical University in November 2017, due to intermittent left chest pain. She was suspected of infecting tuberculosis (TB) and thus received anti-TB treatment. Since April 1, 2018, she began to exhibit symptoms of chest distress. The patient was then admitted to Shanghai Pulmonary Hospital and continued receiving systemic anti-TB treatment during the whole course. On April 11, 2018, she received EBUS-TBNA to puncture pus and inject isoniazid. Simultaneously, the pus was sent for cytopathological and bacteriological examination, both supporting the diagnosis of TB in the patient. On April 24 and May 10, she received two times of EBUS-TBNA treatment. The symptoms of chest distress were relieved, but granulomatous neoplasm occurred at the EBUS-TBNA site on the trachea wall. The patient then received local clamp removal and cryotherapy on May 29 and Jul 19, respectively. Chest computed tomography (CT) reexamination on September 28 revealed that the MLNTA lesion had been completely absorbed, and electronic bronchoscopic reexamination on September 30 demonstrated that the granulomatous neoplasm on the trachea wall was entirely invisible. CONCLUSIONS: Using EBUS-TBNA to puncture and aspirate pus and inject drugs can be effectively used to diagnose and treat MLNTA, which provides a new, less invasive, safe and reliable method for diagnosis and treatment of MLNTA.


Asunto(s)
Absceso/diagnóstico , Absceso/terapia , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Tuberculosis Ganglionar/diagnóstico , Tuberculosis Ganglionar/tratamiento farmacológico , Absceso/microbiología , Adolescente , Antituberculosos/uso terapéutico , Broncoscopía , Femenino , Granuloma del Sistema Respiratorio/diagnóstico por imagen , Granuloma del Sistema Respiratorio/cirugía , Humanos , Inyecciones Intralesiones , Isoniazida/uso terapéutico , Ganglios Linfáticos/patología , Mediastino , Enfermedades de la Tráquea/diagnóstico por imagen , Enfermedades de la Tráquea/cirugía , Tuberculosis Ganglionar/complicaciones
17.
Chest ; 158(5): e241-e244, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33160545

RESUMEN

CASE PRESENTATION: A 52-year-old man, current smoker with a 50 pack-year history, presented to our department with cough, yellow sputum, and localized right chest pain. Chest radiograph revealed a large mass in the right upper lobe. He denied the presence of fever, night sweats, or weight loss. He has a medical history of COPD and anxiety disorder. He was receiving long-acting beta agonists/long-acting muscarinic antagonists as a treatment for COPD and quetiapine 100 mg for anxiety disorder.


Asunto(s)
Dolor en el Pecho , Tos , Granuloma del Sistema Respiratorio , Pulmón , Neumonectomía/métodos , Toracotomía/métodos , Biopsia/métodos , Dolor en el Pecho/diagnóstico , Dolor en el Pecho/etiología , Tos/diagnóstico , Tos/etiología , Diagnóstico Diferencial , Granuloma del Sistema Respiratorio/diagnóstico por imagen , Granuloma del Sistema Respiratorio/fisiopatología , Granuloma del Sistema Respiratorio/cirugía , Humanos , Inflamación , Pulmón/diagnóstico por imagen , Pulmón/patología , Masculino , Persona de Mediana Edad , Necrosis , Radiografía Torácica/métodos , Nódulo Pulmonar Solitario/diagnóstico , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento
18.
Artículo en Inglés | MEDLINE | ID: mdl-33093772

RESUMEN

BACKGROUND: Forms of interstitial pneumonia secondary to exposure to an air-contaminant are varied and so far, insufficiently described. OBJECTIVES/METHODS: We report here a case of a 57-year-old patient managed in our department for the exploration of MRC grade 2 dyspnoea and interstitial pneumonia. He mentioned multiple occupational and domestic exposures such as hens' excrements, asbestos and metal particles; he also had a previous history of smoking. RESULTS: High-resolution computed tomography showed ground glass opacities predominating in posterior territories and surrounding cystic lesions or emphysematous destruction. The entire etiological assessment revealed only macrophagic alveolitis with giant multinucleated cells on the bronchoalveolar lavage. A surgical lung biopsy allowed us to refine the diagnosis with evidence of desquamative interstitial pneumonia and pulmonary granulomatosis. Finally, the analysis of the mineral particles in the biopsy revealed abnormally high rates of Zirconium and Aluminium. We were therefore able to conclude to a desquamative interstitial pneumonia associated with pulmonary granulomatosis linked to metal exposure (Aluminium and Zirconium). The clinical, functional and radiological evolution was favorable after a systemic corticosteroid treatment with progressive decay over one year. CONCLUSION: This presentation reports the first case to our knowledge of desquamative interstitial pneumonitis related to exposure to Zirconium and the third one in the context of Aluminium exposure. The detailed analysis of the mineral particles present on the surgical lung biopsy allows for the identification of the relevant particle to refine the etiological diagnosis, to guide the therapeutic management and to give access to recognition as an occupational disease. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (1): 79-84).


Asunto(s)
Aluminio/efectos adversos , Granuloma del Sistema Respiratorio/inducido químicamente , Exposición por Inhalación/efectos adversos , Enfermedades Pulmonares Intersticiales/inducido químicamente , Pulmón/efectos de los fármacos , Circonio/efectos adversos , Corticoesteroides/administración & dosificación , Aluminio/análisis , Biopsia , Granuloma del Sistema Respiratorio/diagnóstico , Granuloma del Sistema Respiratorio/tratamiento farmacológico , Granuloma del Sistema Respiratorio/metabolismo , Humanos , Pulmón/química , Pulmón/diagnóstico por imagen , Pulmón/patología , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/metabolismo , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Circonio/análisis
19.
Front Immunol ; 11: 1719, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32849608

RESUMEN

The inability to effectively model sarcoidosis in the laboratory or in animals continues to hinder the discovery and translation of new, targeted treatments. The granuloma is the signature pathological hallmark of sarcoidosis, yet there are significant knowledge gaps that exist with regard to how granulomas form. Significant progress toward improved therapeutic and prognostic strategies in sarcoidosis hinges on tractable experimental models that recapitulate the process of granuloma formation in sarcoidosis and allow for mechanistic insights into the molecular events involved. Through its inherent representation of the complex genetics underpinning immune cell dysregulation in sarcoidosis, a recently developed in vitro human granuloma model holds promise in providing detailed mechanistic insight into sarcoidosis-specific disease regulating pathways at play during early stages of granuloma formation. The purpose of this review is to critically evaluate current sarcoidosis models and assess their potential to progress the field toward the goal of improved therapies in this disease. We conclude with the potential integrated use of preclinical models to accelerate progress toward identifying and testing new drugs and drug combinations that can be rapidly brought to clinical trials.


Asunto(s)
Granuloma del Sistema Respiratorio , Pulmón , Sarcoidosis Pulmonar , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Granuloma del Sistema Respiratorio/genética , Granuloma del Sistema Respiratorio/inmunología , Granuloma del Sistema Respiratorio/metabolismo , Granuloma del Sistema Respiratorio/patología , Humanos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Pulmón/inmunología , Pulmón/metabolismo , Pulmón/patología , Macrófagos Alveolares/inmunología , Macrófagos Alveolares/metabolismo , Modelos Teóricos , Sarcoidosis Pulmonar/genética , Sarcoidosis Pulmonar/inmunología , Sarcoidosis Pulmonar/metabolismo , Sarcoidosis Pulmonar/patología
20.
Bull Exp Biol Med ; 169(1): 71-76, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32488784

RESUMEN

We studied the response of the extracellular matrix of the lungs and liver in mice with BCGinduced granulomatosis (3 months) after inhalation and intraperitoneal administration of liposome-encapsulated dextrazide (LEDZ): a conjugate of oxidized dextran (40 kDa) and isonicotinic acid hydrazide (INH). LEDZ inhalation proved to be more effective in reducing fibrosis severity, both in the lungs and liver. However, the mechanisms of the antifibrotic effect were different: increased degradation and reduced collagen synthesis in the lungs and reduced collagen synthesis and collagen degradation in the liver. This suggest that drug administration routes and delivery to the target organs are crucially important in the therapy of tuberculosis. The antifibrotic effect depended on LEDZ administration route and was more potent after LEDZ inhalation.


Asunto(s)
Antituberculosos/administración & dosificación , Granuloma del Sistema Respiratorio/tratamiento farmacológico , Liposomas/administración & dosificación , Fibrosis Pulmonar/tratamiento farmacológico , Animales , Antituberculosos/química , Vacuna BCG/efectos adversos , Dextranos/administración & dosificación , Dextranos/química , Composición de Medicamentos , Granuloma del Sistema Respiratorio/etiología , Isoniazida/administración & dosificación , Isoniazida/análogos & derivados , Isoniazida/química , Masculino , Ratones , Ratones Endogámicos BALB C , Oxidación-Reducción , Fibrosis Pulmonar/etiología , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/prevención & control
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