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1.
Respir Res ; 22(1): 255, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34579722

RESUMO

INTRODUCTION: There is relatively little published on the effects of COVID-19 on respiratory physiology, particularly breathing patterns. We sought to determine if there were lasting detrimental effect following hospital discharge and if these related to the severity of COVID-19. METHODS: We reviewed lung function and breathing patterns in COVID-19 survivors > 3 months after discharge, comparing patients who had been admitted to the intensive therapy unit (ITU) (n = 47) to those who just received ward treatments (n = 45). Lung function included spirometry and gas transfer and breathing patterns were measured with structured light plethysmography. Continuous data were compared with an independent t-test or Mann Whitney-U test (depending on distribution) and nominal data were compared using a Fisher's exact test (for 2 categories in 2 groups) or a chi-squared test (for > 2 categories in 2 groups). A p-value of < 0.05 was taken to be statistically significant. RESULTS: We found evidence of pulmonary restriction (reduced vital capacity and/or alveolar volume) in 65.4% of all patients. 36.1% of all patients has a reduced transfer factor (TLCO) but the majority of these (78.1%) had a preserved/increased transfer coefficient (KCO), suggesting an extrapulmonary cause. There were no major differences between ITU and ward lung function, although KCO alone was higher in the ITU patients (p = 0.03). This could be explained partly by obesity, respiratory muscle fatigue, localised microvascular changes, or haemosiderosis from lung damage. Abnormal breathing patterns were observed in 18.8% of subjects, although no consistent pattern of breathing pattern abnormalities was evident. CONCLUSIONS: An "extrapulmonary restrictive" like pattern appears to be a common phenomenon in previously admitted COVID-19 survivors. Whilst the cause of this is not clear, the effects seem to be similar on patients whether or not they received mechanical ventilation or had ward based respiratory support/supplemental oxygen.


Assuntos
COVID-19/fisiopatologia , Hospitalização/tendências , Pulmão/fisiologia , Mecânica Respiratória/fisiologia , Espirometria/tendências , Sobreviventes , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , COVID-19/terapia , Feminino , Humanos , Pneumopatias/diagnóstico , Pneumopatias/fisiopatologia , Pneumopatias/terapia , Masculino , Pessoa de Meia-Idade , Alta do Paciente/tendências , Testes de Função Respiratória/métodos , Testes de Função Respiratória/tendências , Espirometria/métodos , Adulto Jovem
2.
Cells ; 10(7)2021 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206722

RESUMO

The lungs are affected by illnesses including asthma, chronic obstructive pulmonary disease, and infections such as influenza and SARS-CoV-2. Physiologically relevant models for respiratory conditions will be essential for new drug development. The composition and structure of the lung extracellular matrix (ECM) plays a major role in the function of the lung tissue and cells. Lung-on-chip models have been developed to address some of the limitations of current two-dimensional in vitro models. In this review, we describe various ECM substitutes utilized for modeling the respiratory system. We explore the application of lung-on-chip models to the study of cigarette smoke and electronic cigarette vapor. We discuss the challenges and opportunities related to model characterization with an emphasis on in situ characterization methods, both established and emerging. We discuss how further advancements in the field, through the incorporation of interstitial cells and ECM, have the potential to provide an effective tool for interrogating lung biology and disease, especially the mechanisms that involve the interstitial elements.


Assuntos
Dispositivos Lab-On-A-Chip , Pneumopatias/patologia , Pulmão/fisiologia , Regeneração/fisiologia , Mucosa Respiratória/citologia , COVID-19/patologia , COVID-19/terapia , COVID-19/virologia , Células Cultivadas , Matriz Extracelular/fisiologia , Humanos , Pulmão/citologia , Pulmão/patologia , Pneumopatias/fisiopatologia , Pneumopatias/terapia , Modelos Biológicos , Mucosa Respiratória/patologia , Mucosa Respiratória/fisiologia , SARS-CoV-2/patogenicidade , Técnicas de Cultura de Tecidos/instrumentação , Técnicas de Cultura de Tecidos/métodos
3.
Pediatr Rheumatol Online J ; 19(1): 104, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193201

RESUMO

BACKGROUND: H syndrome (HS) is a rare autoinflammatory disease caused by a mutation in the solute carrier family 29, member 3 (SCL29A3) gene. It has a variable clinical presentation and little phenotype-genotype correlation. The pathognomonic sign of HS is cutaneous hyperpigmentation located mainly in the inner thighs and often accompanied by other systemic manifestations. Improvement after tocilizumab treatment has been reported in a few patients with HS. We report the first patient with HS who presented cardiogenic shock, multiorgan infiltration, and digital ischemia. CASE PRESENTATION: 8-year-old boy born to consanguineous parents of Moroccan origin who was admitted to the intensive care unit during the Coronavirus Disease-2019 (COVID-19) pandemic with tachypnoea, tachycardia, and oliguria. Echocardiography showed dilated cardiomyopathy and severe systolic dysfunction compatible with cardiogenic shock. Additionally, he presented with multiple organ dysfunction syndrome. SARS-CoV-2 polymerase chain reaction (PCR) and antibody detection by chromatographic immunoassay were negative. A previously ordered gene panel for pre-existing sensorineural hearing loss showed a pathological mutation in the SCL29A3 gene compatible with H syndrome. Computed tomography scan revealed extensive alveolar infiltrates in the lungs and multiple poor defined hypodense lesions in liver, spleen, and kidneys; adenopathy; and cardiomegaly with left ventricle subendocardial nodules. Invasive mechanical ventilation, broad antibiotic and antifungal coverage showed no significant response. Therefore, Tocilizumab as compassionate use together with pulsed intravenous methylprednisolone was initiated. Improvement was impressive leading to normalization of inflammation markers, liver and kidney function, and stabilising heart function. Two weeks later, he was discharged and has been clinically well since then on two weekly administration of Tocilizumab. CONCLUSIONS: We report the most severe disease course produced by HS described so far in the literature. Our patient's manifestations included uncommon, new complications such as acute heart failure with severe systolic dysfunction, multi-organ cell infiltrate, and digital ischemia. Most of the clinical symptoms of our patient could have been explained by SARS-CoV-2, demonstrating the importance of a detailed differential diagnosis to ensure optimal treatment. Although the mechanism of autoinflammation of HS remains uncertain, the good response of our patient to Tocilizumab makes a case for the important role of IL-6 in this syndrome and for considering Tocilizumab as a first-line treatment, at least in severely affected patients.


Assuntos
Cardiomiopatia Dilatada/fisiopatologia , Doenças Hereditárias Autoinflamatórias/fisiopatologia , Isquemia/fisiopatologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Choque Cardiogênico/fisiopatologia , Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19 , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/terapia , Criança , Glucocorticoides/uso terapêutico , Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/genética , Doenças Hereditárias Autoinflamatórias/terapia , Humanos , Isquemia/terapia , Nefropatias/diagnóstico por imagem , Nefropatias/fisiopatologia , Nefropatias/terapia , Hepatopatias/diagnóstico por imagem , Hepatopatias/fisiopatologia , Hepatopatias/terapia , Pneumopatias/diagnóstico por imagem , Pneumopatias/fisiopatologia , Pneumopatias/terapia , Linfadenopatia/diagnóstico por imagem , Linfadenopatia/fisiopatologia , Linfadenopatia/terapia , Masculino , Metilprednisolona/uso terapêutico , Insuficiência de Múltiplos Órgãos/terapia , Proteínas de Transporte de Nucleosídeos/genética , Pulsoterapia , Respiração Artificial , SARS-CoV-2 , Choque Cardiogênico/terapia , Esplenopatias/diagnóstico por imagem , Esplenopatias/fisiopatologia , Esplenopatias/terapia , Dedos do Pé/irrigação sanguínea , Tomografia Computadorizada por Raios X , Resultado do Tratamento
4.
G Ital Cardiol (Rome) ; 22(8): 638-647, 2021 Aug.
Artigo em Italiano | MEDLINE | ID: mdl-34310567

RESUMO

In recent years, lung ultrasonography has acquired an important role as a valuable diagnostic tool in clinical practice. The lung is usually poorly explorable, but it provides more acoustic information in pathological conditions that modify the relationship between air, water and tissues. The different acoustic impedance of all these components makes the chest wall a powerful ultrasound reflector: this is responsible for the creation of several artifacts providing valuable information about lung pathophysiology. Lung ultrasonography helps in the diagnostic process of parenchymal and pleural pathologies, in the differential diagnosis of dyspnea and in the clinical and prognostic evaluation of the SARS-CoV-2 infection.


Assuntos
COVID-19/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Ultrassonografia/métodos , Cardiologistas , Diagnóstico Diferencial , Dispneia/diagnóstico por imagem , Humanos , Pulmão/virologia , Pneumopatias/diagnóstico por imagem , Pneumopatias/fisiopatologia , Prognóstico
5.
Pan Afr Med J ; 38: 298, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34178217

RESUMO

Introduction: the use of flexible bronchoscopy in developing countries is limited. We report our initial experience and outcome with the use of flexible bronchoscopy at the Tamale Teaching Hospital in Ghana. This is the first reported case series of flexible bronchoscopy in Ghana. Methods: a retrospective review of patients who had flexible bronchoscopy from 2017-2019 was analyzed. Patient demographics and outcomes were summarized using frequency distribution and percentages. Results: we performed flexible bronchoscopies in 33 patients with mean age of 43 years. All patients were symptomatic at the time of presentation with the most common symptoms being chest pain (63.6%), dyspnea (57.6%) and cough (48.5%). The indication for bronchoscopy in most of the cases were suspected malignancy in 16 (48.5%) followed by infection 9 (27.3%), trauma 4 (12.1%) and others 4 (12.1%). We observed abnormal bronchoscopic findings in 25 (75.8%) of the cases with most of the pathologies in the right main bronchus. Twelve patients had toilet bronchoscopy, 6 had biopsy, 5 had no intervention and 4 patients had bronchoalveolar lavage (BAL). Culture and sensitivity results were available for 11 patients, of which 7 patients had negative results. Thirteen (13) malignancies and 11 inflammatory/infectious diseases were diagnosed in this case series. The mean procedure time was 32 minutes with mean hospital stay of 7 days. There was no complication or mortality in our series. Conclusion: flexible bronchoscopy is a safe procedure and indispensable in Ghana where there is an increasing incidence of lung diseases.


Assuntos
Brônquios/patologia , Broncoscopia/métodos , Pneumopatias/diagnóstico , Adolescente , Adulto , Idoso , Biópsia , Lavagem Broncoalveolar/métodos , Feminino , Gana , Hospitalização/estatística & dados numéricos , Hospitais de Ensino , Humanos , Tempo de Internação , Pneumopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Centros de Atenção Terciária , Adulto Jovem
7.
J Med Microbiol ; 70(5)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33999797

RESUMO

Introduction. Mycobacterium avium complex (MAC) has been reported as the most common aetiology of lung disease involving nontuberculous mycobacteria.Hypothesis. Antimicrobial susceptibility and clinical characteristics may differ between Mycobacterium avium and Mycobacterium intracellulare.Aim. We aimed to evaluate the differences in antimicrobial susceptibility profiles between two major MAC species (Mycobacterium avium and Mycobacterium intracellulare) from patients with pulmonary infections and to provide epidemiologic data with minimum inhibitory concentration (MIC) distributions.Methodology. Between January 2019 and May 2020, 45 M. avium and 242 M. intracellulare isolates were obtained from Shanghai Pulmonary Hospital. The demographic and clinical characteristics of patients were obtained from their medical records. The MICs of 13 antimicrobials were determined for the MAC isolates using commercial Sensititre SLOWMYCO MIC plates and the broth microdilution method, as recommended by the Clinical and Laboratory Standards Institute (CLSI; Standards M24-A2). MIC50 and MIC90 values were derived from the MIC distributions.Results. M. intracellulare had higher resistance rates than M. avium for most tested antimicrobials except clarithromycin, ethambutol, and ciprofloxacin. Clarithromycin was the most effective antimicrobial against both the M. avium (88.89 %) and M. intracellulare (91.32 %) isolates, with no significant difference between the species (P=0.601). The MIC90 of clarithromycin was higher for M. avium (32 µg ml-1) than M. intracellulare (8 µg ml-1). The MIC50 of rifabutin was more than four times higher for M. intracellulare (1 µg ml-1) than M. avium (≤0.25 µg ml-1). The percentages of patients aged >60 years and patients with sputum, cough, and cavitary lesions were significantly higher than among patients with M. intracellulare infection than M. avium infections.Conclusions. The pulmonary disease caused by distinct MAC species had different antimicrobial susceptibility, symptoms, and radiographic findings.


Assuntos
Antibacterianos/farmacologia , Pneumopatias/microbiologia , Complexo Mycobacterium avium/efeitos dos fármacos , Infecção por Mycobacterium avium-intracellulare/microbiologia , Mycobacterium avium/efeitos dos fármacos , Adulto , Idoso , China , Ciprofloxacina/farmacologia , Claritromicina/farmacologia , Tosse , Doxiciclina/farmacologia , Farmacorresistência Bacteriana , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pneumopatias/fisiopatologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium avium/isolamento & purificação , Complexo Mycobacterium avium/isolamento & purificação , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Infecção por Mycobacterium avium-intracellulare/fisiopatologia , Radiografia , Escarro
9.
Radiology ; 299(3): 508-523, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33825513

RESUMO

Over the past few decades, pulmonary imaging technologies have advanced from chest radiography and nuclear medicine methods to high-spatial-resolution or low-dose chest CT and MRI. It is currently possible to identify and measure pulmonary pathologic changes before these are obvious even to patients or depicted on conventional morphologic images. Here, key technological advances are described, including multiparametric CT image processing methods, inhaled hyperpolarized and fluorinated gas MRI, and four-dimensional free-breathing CT and MRI methods to measure regional ventilation, perfusion, gas exchange, and biomechanics. The basic anatomic and physiologic underpinnings of these pulmonary functional imaging techniques are explained. In addition, advances in image analysis and computational and artificial intelligence (machine learning) methods pertinent to functional lung imaging are discussed. The clinical applications of pulmonary functional imaging, including both the opportunities and challenges for clinical translation and deployment, will be discussed in part 2 of this review. Given the technical advances in these sophisticated imaging methods and the wealth of information they can provide, it is anticipated that pulmonary functional imaging will be increasingly used in the care of patients with lung disease. © RSNA, 2021 Online supplemental material is available for this article.


Assuntos
Pneumopatias/diagnóstico por imagem , Pneumopatias/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Inteligência Artificial , Meios de Contraste , Humanos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Testes de Função Respiratória
10.
Radiology ; 299(3): 524-538, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33847518

RESUMO

Pulmonary functional imaging may be defined as the regional quantification of lung function by using primarily CT, MRI, and nuclear medicine techniques. The distribution of pulmonary physiologic parameters, including ventilation, perfusion, gas exchange, and biomechanics, can be noninvasively mapped and measured throughout the lungs. This information is not accessible by using conventional pulmonary function tests, which measure total lung function without viewing the regional distribution. The latter is important because of the heterogeneous distribution of virtually all lung disorders. Moreover, techniques such as hyperpolarized xenon 129 and helium 3 MRI can probe lung physiologic structure and microstructure at the level of the alveolar-air and alveolar-red blood cell interface, which is well beyond the spatial resolution of other clinical methods. The opportunities, challenges, and current stage of clinical deployment of pulmonary functional imaging are reviewed, including applications to chronic obstructive pulmonary disease, asthma, interstitial lung disease, pulmonary embolism, and pulmonary hypertension. Among the challenges to the deployment of pulmonary functional imaging in routine clinical practice are the need for further validation, establishment of normal values, standardization of imaging acquisition and analysis, and evidence of patient outcomes benefit. When these challenges are addressed, it is anticipated that pulmonary functional imaging will have an expanding role in the evaluation and management of patients with lung disease.


Assuntos
Pneumopatias/diagnóstico por imagem , Pneumopatias/fisiopatologia , Meios de Contraste , Diagnóstico Precoce , Humanos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Melhoria de Qualidade , Testes de Função Respiratória
11.
Life Sci ; 278: 119496, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33894269

RESUMO

AIMS: Chronic lung allograft dysfunction (CLAD) after lung transplantation (Tx) is the clinical result of chronic airway rejection lesions (CARL), histomorphologically described as either obliterative remodeling of small airways or alveolar fibroelastosis, or as a combination of both. We here investigated the CD26-inhibitory effect on CD26-expressing CARL. MAIN METHODS: CARL were induced by BALB/c â†’ C57BL/6 mouse Tx under mild immunosuppression. CARL-related pro-fibrotic mediators were determined by RT-qPCR and western blotting (WB), EMT and ERK markers by WB. CD26 co-expression by immunofluorescence. CD26 was inhibited by Vildagliptin, gene depleted by CD26-/- mice. Primary lung fibroblasts were employed for ex vivo analyses. Samples from lung transplant patients with CLAD were analyzed by immunohistochemistry. KEY FINDINGS: CARL revealed a significantly higher expression of profibrotic proteins vs. normal lungs (p < 0.05). CD26 and EMT co-expressed in CARL with significantly higher Vimentin, Slug, Hif-1α, α-SMA expression vs. normal lungs (p < 0.05). Vildagliptin decreased the expression of α-SMA and N-cadherin in wild type (WT) lung fibroblasts (p < 0.05). Primary lung fibroblasts from WT and CD26-/- mice treated with TGF-ß1, IFN-γ, and FGF showed a reduction of EMT protein expression, proliferation, and reduced activation of ERK in CD26-/- mice vs. WT mice. CD26-positive cells were found in patient samples with CLAD in areas of loose fibrosis, but not in areas of dense fibrosis. SIGNIFICANCE: CD26 is expressed in CARL-developing lung transplants and CD26-inhibition downregulates fibrosis-forming mediators and fibroblast proliferation. CD26 thus qualifies as a target to attenuate the development of CARL mainly via modulation of ERK and the EMT pathway.


Assuntos
Dipeptidil Peptidase 4/metabolismo , Pneumopatias/fisiopatologia , Actinas/metabolismo , Animais , Caderinas/metabolismo , Doença Crônica , Fibroblastos/metabolismo , Fibrose/patologia , Rejeição de Enxerto , Imunossupressão , Pulmão/metabolismo , Transplante de Pulmão , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Fenótipo , Disfunção Primária do Enxerto , Vildagliptina/farmacologia
12.
Emerg Med Clin North Am ; 39(2): 257-271, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33863458

RESUMO

Geriatric trauma patients will continue to increase in prevalence as the population ages, and many specific considerations need to be made to provide appropriate care to these patients. This article outlines common presentations of trauma in geriatric patients, with consideration to baseline physiologic function and patterns of injury that may be more prevalent in geriatric populations. Additionally, the article explores specific evidence-based management practices, the significance of trauma team and geriatrician involvement, and disposition decisions.


Assuntos
Ferimentos e Lesões/epidemiologia , Acidentes por Quedas , Idoso , Envelhecimento/fisiologia , Doenças Cardiovasculares/fisiopatologia , Comorbidade , Fragilidade/fisiopatologia , Geriatras , Acesso aos Serviços de Saúde , Humanos , Pneumopatias/fisiopatologia , Doenças Musculoesqueléticas/fisiopatologia , Transtornos Neurocognitivos/fisiopatologia , Manejo da Dor , Alta do Paciente , Centros de Traumatologia , Sinais Vitais , Ferimentos e Lesões/fisiopatologia
13.
Emerg Med Clin North Am ; 39(2): 273-286, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33863459

RESUMO

In 30 years, adults 65 and older will represent 20% of the US population, with increased medical comorbidities leading to higher rates of critical illness and mortality. Despite significant acute illness, presenting symptoms and vital sign abnormalities may be subtle. Resuscitative guidelines are a helpful starting point but appropriate diagnostics, bedside ultrasound, and frequent reassessments are needed to avoid procrustean care that may worsen outcomes. Baseline functional status is as important as underlying comorbid conditions when prognosticating, and the patient's personal wishes should be sought early and throughout care with clear communication regarding prospects for immediate survival and overall recovery.


Assuntos
Estado Terminal/terapia , Ressuscitação/métodos , Diretivas Antecipadas , Idoso , Envelhecimento/fisiologia , Doenças Cardiovasculares/fisiopatologia , Humanos , Nefropatias/fisiopatologia , Pneumopatias/fisiopatologia , Sistemas Automatizados de Assistência Junto ao Leito , Insuficiência Respiratória/terapia , Choque/diagnóstico , Choque/terapia , Ultrassonografia
14.
Int J Mol Sci ; 22(5)2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806395

RESUMO

Alveolar type II (ATII) cells are a key structure of the distal lung epithelium, where they exert their innate immune response and serve as progenitors of alveolar type I (ATI) cells, contributing to alveolar epithelial repair and regeneration. In the healthy lung, ATII cells coordinate the host defense mechanisms, not only generating a restrictive alveolar epithelial barrier, but also orchestrating host defense mechanisms and secreting surfactant proteins, which are important in lung protection against pathogen exposure. Moreover, surfactant proteins help to maintain homeostasis in the distal lung and reduce surface tension at the pulmonary air-liquid interface, thereby preventing atelectasis and reducing the work of breathing. ATII cells may also contribute to the fibroproliferative reaction by secreting growth factors and proinflammatory molecules after damage. Indeed, various acute and chronic diseases are associated with intensive inflammation. These include oedema, acute respiratory distress syndrome, fibrosis and numerous interstitial lung diseases, and are characterized by hyperplastic ATII cells which are considered an essential part of the epithelialization process and, consequently, wound healing. The aim of this review is that of revising the physiologic and pathologic role ATII cells play in pulmonary diseases, as, despite what has been learnt in the last few decades of research, the origin, phenotypic regulation and crosstalk of these cells still remain, in part, a mystery.


Assuntos
Células Epiteliais Alveolares/patologia , Células Epiteliais Alveolares/fisiologia , Pneumopatias/fisiopatologia , Pulmão/fisiologia , Células Epiteliais Alveolares/citologia , Animais , COVID-19/fisiopatologia , Humanos , Imunidade Inata , Íons/metabolismo , Pulmão/anatomia & histologia , Pneumopatias/etiologia , Pneumopatias/patologia , Proteínas Associadas a Surfactantes Pulmonares/metabolismo , Regeneração
15.
Respiration ; 100(7): 594-599, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33878758

RESUMO

BACKGROUND AND OBJECTIVES: The 6-minute walk test (6MWT), as a clinical assessment tool for functional exercise capacity, is an integral component of lung allocation scores (LASs). In times of the coronavirus disease (COVID-19) pandemic, patients underwent 6MWTs wearing a surgical mask in ambulatory care. We investigated the impact of wearing a mask on 6-minute walk distances (6MWDs). METHOD: 6MWDs of 64 patients with end-stage lung diseases wearing an oronasal surgical mask were retrospectively compared to previously investigated 6MWDs of the same cohort, in a pre-COVID-19 pandemic era, without wearing a mask. Four patients were excluded due to a primary vascular disease, 29 patients due to clinically unstable pulmonary functions, and 1 patient due to a psychiatric disorder. RESULTS: The median age of the patients included was 55 (46-58) years; 15 (48%) were male. Ten (32.2%) were on the Eurotransplant lung transplant waiting list with a median LAS of 34.3 (31.9-36.2). Twenty (64.5%) patients had chronic obstructive pulmonary diseases, 7 (22.6%) had interstitial lung diseases, and 4 (12.9%) had other end-stage lung diseases. The mean 6MWD without versus with wearing a mask was 306.9 (101.9) versus 305.7 (103.8) m, with a mean difference of -1.19 m (95% confidence interval -13.4 to 11.03). The observed difference is statistically equivalent to zero (p < 0.001). No significant differences in 6MWDs were observed between the clinical groups. CONCLUSION: Wearing an oronasal surgical mask did not affect the 6MWDs of patients with advanced lung diseases. Therefore, a masked 6MWT appears to provide a reliable examination of functional exercise capacity in this cohort.


Assuntos
COVID-19/prevenção & controle , Doenças Pulmonares Intersticiais/fisiopatologia , Máscaras , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Insuficiência Respiratória/fisiopatologia , Teste de Caminhada/métodos , Gasometria , Doença Crônica , Tolerância ao Exercício , Feminino , Volume Expiratório Forçado , Humanos , Pneumopatias/fisiopatologia , Pneumopatias/cirurgia , Doenças Pulmonares Intersticiais/cirurgia , Transplante de Pulmão , Masculino , Pessoa de Meia-Idade , Diferença Mínima Clinicamente Importante , Pletismografia Total , Doença Pulmonar Obstrutiva Crônica/cirurgia , Reprodutibilidade dos Testes , Insuficiência Respiratória/cirurgia , Estudos Retrospectivos , SARS-CoV-2 , Capacidade Vital
16.
Cell Mol Life Sci ; 78(12): 5051-5068, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33864479

RESUMO

Mammalian lungs are metabolically active organs that frequently encounter environmental insults. Stress responses elicit protective autophagy in epithelial barrier cells and the supportive niche. Autophagy promotes the recycling of damaged intracellular organelles, denatured proteins, and other biological macromolecules for reuse as components required for lung cell survival. Autophagy, usually induced by metabolic defects, regulates cellular metabolism. Autophagy is a major adaptive response that protects cells and organisms from injury. Endogenous region-specific stem/progenitor cell populations are found in lung tissue, which are responsible for epithelial repair after lung damage. Additionally, glucose and fatty acid metabolism is altered in lung stem/progenitor cells in response to injury-related lung fibrosis. Autophagy deregulation has been observed to be involved in the development and progression of other respiratory diseases. This review explores the role and mechanisms of autophagy in regulating lung metabolism and epithelial repair.


Assuntos
Autofagia , Células Epiteliais/fisiologia , Pneumopatias/fisiopatologia , Pulmão/fisiologia , Animais , Células Epiteliais/citologia , Humanos , Pulmão/citologia
17.
Chest ; 159(3): e141-e145, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33678281

RESUMO

CASE PRESENTATION: A 51-year-old woman with a medical history of poorly controlled type 1 diabetes mellitus, hyperthyroidism, and tobacco abuse was admitted to the hospital with persistent nausea, vomiting, abdominal discomfort, dry cough, rhinorrhea, and sore throat. She denied fevers, chills, rigors, shortness of breath, hemoptysis, nasal congestion, postnasal drip, and facial pain. She denied any sick contacts, and there was no recent travel outside of Chicago.


Assuntos
Antifúngicos/administração & dosagem , Broncoscopia/métodos , Pneumopatias , Pulmão , Mucormicose , Nitrilas/administração & dosagem , Pneumonectomia/métodos , Piridinas/administração & dosagem , Triazóis/administração & dosagem , Anfotericina B/administração & dosagem , Diagnóstico Diferencial , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/microbiologia , Pulmão/patologia , Pneumopatias/diagnóstico , Pneumopatias/microbiologia , Pneumopatias/fisiopatologia , Pneumopatias/cirurgia , Pessoa de Meia-Idade , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Mucormicose/cirurgia , Respiração Artificial/métodos , Cirurgia Torácica Vídeoassistida/métodos , Resultado do Tratamento
18.
Pharmacol Ther ; 225: 107839, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33774068

RESUMO

Structural changes involving tissue remodelling and fibrosis are major features of many pulmonary diseases, including asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Abnormal deposition of extracellular matrix (ECM) proteins is a key factor in the development of tissue remodelling that results in symptoms and impaired lung function in these diseases. Tissue remodelling in the lungs is complex and differs between compartments. Some pathways are common but tissue remodelling around the airways and in the parenchyma have different morphologies. Hence it is critical to evaluate both common fibrotic pathways and those that are specific to different compartments; thereby expanding the understanding of the pathogenesis of fibrosis and remodelling in the airways and parenchyma in asthma, COPD and IPF with a view to developing therapeutic strategies for each. Here we review the current understanding of remodelling features and underlying mechanisms in these major respiratory diseases. The differences and similarities of remodelling are used to highlight potential common therapeutic targets and strategies. One central pathway in remodelling processes involves transforming growth factor (TGF)-ß induced fibroblast activation and myofibroblast differentiation that increases ECM production. The current treatments and clinical trials targeting remodelling are described, as well as potential future directions. These endeavours are indicative of the renewed effort and optimism for drug discovery targeting tissue remodelling and fibrosis.


Assuntos
Pneumopatias/tratamento farmacológico , Pneumopatias/fisiopatologia , Remodelação das Vias Aéreas/fisiologia , Asma/tratamento farmacológico , Asma/fisiopatologia , Proteínas de Ligação ao Cálcio/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos , Fibrose/fisiopatologia , Glicoproteínas/metabolismo , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/fisiopatologia , Metaloproteinases da Matriz/metabolismo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fator de Crescimento Transformador beta
19.
Expert Opin Drug Metab Toxicol ; 17(5): 611-625, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33759677

RESUMO

INTRODUCTION: The lungs possess many xenobiotic metabolizing enzymes which influence the pharmacokinetics and safety of inhaled medicines. Anticipating metabolism in the lungs provides an opportunity to optimize new inhaled medicines and overcome challenges in their development. AREAS COVERED: This article summarizes current knowledge on xenobiotic metabolizing enzymes in the lungs. The impact of metabolism on inhaled medicines is considered with examples of how this impacts small molecules, biologics and macromolecular formulation excipients. Methods for measuring and predicting xenobiotic lung metabolism are critically reviewed and the potential for metabolism to influence inhalation toxicology is acknowledged. EXPERT OPINION: Drugs can be optimized by molecular modification to (i) reduce systemic exposure using a 'soft drug' approach, (ii) improve bioavailability by resisting metabolism, or (iii) use a prodrug approach to overcome pharmacokinetic limitations. Drugs that are very labile in the lungs may require a protective formulation. Some drug carriers being investigated for PK-modification rely on lung enzymes to trigger drug release or biodegrade. Lung enzyme activity varies with age, race, smoking status, diet, drug exposure and preexisting lung disease. New experimental technologies to study lung metabolism include tissue engineered models, improved analytical capability and in silico models.


Assuntos
Sistemas de Liberação de Medicamentos , Pulmão/metabolismo , Xenobióticos/metabolismo , Administração por Inalação , Animais , Disponibilidade Biológica , Simulação por Computador , Portadores de Fármacos/química , Humanos , Pulmão/enzimologia , Pneumopatias/fisiopatologia , Pró-Fármacos , Engenharia Tecidual , Xenobióticos/administração & dosagem , Xenobióticos/efeitos adversos
20.
Elife ; 102021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33720009

RESUMO

Measures of lung function are heritable, and thus, we sought to utilise genetics to propose drug-repurposing candidates that could improve respiratory outcomes. Lung function measures were found to be genetically correlated with seven druggable biochemical traits, with further evidence of a causal relationship between increased fasting glucose and diminished lung function. Moreover, we developed polygenic scores for lung function specifically within pathways with known drug targets and investigated their relationship with pulmonary phenotypes and gene expression in independent cohorts to prioritise individuals who may benefit from particular drug-repurposing opportunities. A transcriptome-wide association study (TWAS) of lung function was then performed which identified several drug-gene interactions with predicted lung function increasing modes of action. Drugs that regulate blood glucose were uncovered through both polygenic scoring and TWAS methodologies. In summary, we provided genetic justification for a number of novel drug-repurposing opportunities that could improve lung function.


Assuntos
Reposicionamento de Medicamentos/métodos , Hiperglicemia/genética , Pneumopatias/tratamento farmacológico , Pneumopatias/genética , Glicemia/metabolismo , Causalidade , Bases de Dados Genéticas , Estudo de Associação Genômica Ampla/métodos , Humanos , Hiperglicemia/metabolismo , Hiperglicemia/fisiopatologia , Pulmão/efeitos dos fármacos , Pulmão/fisiologia , Pulmão/fisiopatologia , Pneumopatias/metabolismo , Pneumopatias/fisiopatologia , Herança Multifatorial , Fenótipo , Polimorfismo de Nucleotídeo Único , Testes de Função Respiratória/métodos , Transcriptoma
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