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1.
Pediatr Pulmonol ; 53(12): 1619-1626, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30353708

RESUMO

Marijuana use has risen dramatically over the past decade. Over this same time period, pediatric hospitals have seen an increase in presentation of adolescents with acute respiratory symptoms after recent marijuana inhalation. We report a case series of three adolescent males with significant findings of bilateral pulmonary nodules and ground glass opacities on chest imaging associated with recent marijuana inhalation. Lung biopsies in two of the three patients confirmed silica-induced pneumoconiosis. The third patient was diagnosed with acute hypersensitivity pneumonitis without lung biopsy. Improvement in clinical symptoms and lung function testing were noted in two of three patients after marijuana inhalation cessation. This case series highlights the variety of severe pulmonary presentations in adolescents following recent marijuana inhalation. Future studies are required to assess whether these presenting pulmonary complications are from direct marijuana exposure or indirect associations with marijuana inhalation injuries.


Assuntos
Alveolite Alérgica Extrínseca/etiologia , Fumar Maconha/efeitos adversos , Eosinofilia Pulmonar/etiologia , Silicose/etiologia , Adolescente , Alveolite Alérgica Extrínseca/diagnóstico por imagem , Alveolite Alérgica Extrínseca/patologia , Biópsia , Humanos , Pulmão/patologia , Masculino , Eosinofilia Pulmonar/diagnóstico por imagem , Eosinofilia Pulmonar/patologia , Radiografia , Testes de Função Respiratória , Silicose/diagnóstico por imagem , Silicose/patologia , Tomografia Computadorizada por Raios X
2.
Am J Physiol Lung Cell Mol Physiol ; 310(10): L928-39, 2016 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-26968770

RESUMO

Recently approved therapies that modulate CFTR function have shown significant clinical benefit, but recent investigations regarding their molecular mechanism when used in combination have not been consistent with clinical results. We employed micro-optical coherence tomography as a novel means to assess the mechanism of action of CFTR modulators, focusing on the effects on mucociliary clearance. Primary human airway monolayers from patients with a G551D mutation responded to ivacaftor treatment with increased ion transport, airway surface liquid depth, ciliary beat frequency, and mucociliary transport rate, in addition to decreased effective viscosity of the mucus layer, a unique mechanism established by our findings. These endpoints are consistent with the benefit observed in G551D patients treated with ivacaftor, and identify a novel mechanism involving mucus viscosity. In monolayers derived from F508del patients, the situation is more complicated, compounded by disparate effects on CFTR expression and function. However, by combining ion transport measurements with functional imaging, we establish a crucial link between in vitro data and clinical benefit, a finding not explained by ion transport studies alone. We establish that F508del cells exhibit increased mucociliary transport and decreased mucus effective viscosity, but only when ivacaftor is added to the regimen. We further show that improvement in the functional microanatomy in vitro corresponds with lung function benefit observed in the clinical trials, whereas ion transport in vitro corresponds to changes in sweat chloride. Functional imaging reveals insights into clinical efficacy and CFTR biology that significantly impact our understanding of novel therapies.


Assuntos
Aminofenóis/farmacologia , Agonistas dos Canais de Cloreto/farmacologia , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Fibrose Cística/tratamento farmacológico , Quinolonas/farmacologia , Amilorida/farmacologia , Animais , Células Cultivadas , Colforsina/farmacologia , Fibrose Cística/genética , Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada , Humanos , Potenciais da Membrana , Camundongos , Mutação de Sentido Incorreto , Células NIH 3T3
3.
Am J Respir Crit Care Med ; 190(4): 421-32, 2014 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-25029666

RESUMO

RATIONALE: The mechanisms underlying cystic fibrosis (CF) lung disease pathogenesis are unknown. OBJECTIVES: To establish mechanisms linking anion transport with the functional microanatomy, we evaluated normal and CF piglet trachea as well as adult swine trachea in the presence of selective anion inhibitors. METHODS: We investigated airway functional microanatomy using microoptical coherence tomography, a new imaging modality that concurrently quantifies multiple functional parameters of airway epithelium in a colocalized fashion. MEASUREMENTS AND MAIN RESULTS: Tracheal explants from wild-type swine demonstrated a direct link between periciliary liquid (PCL) hydration and mucociliary transport (MCT) rates, a relationship frequently invoked but never experimentally confirmed. However, in CF airways this relationship was completely disrupted, with greater PCL depths associated with slowest transport rates. This disrupted relationship was recapitulated by selectively inhibiting bicarbonate transport in vitro and ex vivo. CF mucus exhibited increased viscosity in situ due to the absence of bicarbonate transport, explaining defective MCT that occurs even in the presence of adequate PCL hydration. CONCLUSIONS: An inherent defect in CF airway surface liquid contributes to delayed MCT beyond that caused by airway dehydration alone and identifies a fundamental mechanism underlying the pathogenesis of CF lung disease in the absence of antecedent infection or inflammation.


Assuntos
Fibrose Cística/patologia , Fibrose Cística/fisiopatologia , Epitélio/fisiopatologia , Traqueia/patologia , Traqueia/fisiopatologia , Animais , Células Cultivadas , Modelos Animais de Doenças , Epitélio/patologia , Humanos , Técnicas In Vitro , Depuração Mucociliar/fisiologia , Suínos , Tomografia de Coerência Óptica/métodos
4.
PLoS One ; 8(1): e54473, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23372732

RESUMO

We demonstrate the use of a high resolution form of optical coherence tomography, termed micro-OCT (µOCT), for investigating the functional microanatomy of airway epithelia. µOCT captures several key parameters governing the function of the airway surface (airway surface liquid depth, periciliary liquid depth, ciliary function including beat frequency, and mucociliary transport rate) from the same series of images and without exogenous particles or labels, enabling non-invasive study of dynamic phenomena. Additionally, the high resolution of µOCT reveals distinguishable phases of the ciliary stroke pattern and glandular extrusion. Images and functional measurements from primary human bronchial epithelial cell cultures and excised tissue are presented and compared with measurements using existing gold standard methods. Active secretion from mucus glands in tissue, a key parameter of epithelial function, was also observed and quantified.


Assuntos
Brônquios/ultraestrutura , Cílios/ultraestrutura , Células Epiteliais/ultraestrutura , Mucosa Respiratória/ultraestrutura , Tomografia de Coerência Óptica/instrumentação , Tomografia de Coerência Óptica/métodos , Animais , Brônquios/fisiologia , Cílios/fisiologia , Células Epiteliais/fisiologia , Humanos , Depuração Mucociliar/fisiologia , Muco/metabolismo , Cultura Primária de Células , Mucosa Respiratória/fisiologia , Suínos
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