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1.
PLoS One ; 15(12): e0243826, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33370308

RESUMO

PURPOSE: Recent studies suggest that occupational inhalant exposures trigger exacerbations of asthma and chronic obstructive pulmonary disease, but findings are conflicting. METHODS: We included 7,768 individuals with self-reported asthma (n = 3,215) and/or spirometric airflow limitation (forced expiratory volume in 1 second (FEV1)/ forced expiratory volume (FVC) <0.70) (n = 5,275) who participated in The Copenhagen City Heart Study or The Copenhagen General Population Study from 2001-2016. Occupational exposure was assigned by linking job codes with job exposure matrices, and exacerbations were defined by register data on oral corticosteroid treatment, emergency care unit assessment or hospital admission. Associations between occupational inhalant exposure each year of follow-up and exacerbation were assessed by Cox regression with time varying exposure and age as the underlying time scale. RESULTS: Participants were followed for a median of 4.6 years (interquartile range, IQR 5.4), during which 870 exacerbations occurred. Exacerbations were not associated with any of the selected exposures (high molecular weight sensitizers, low molecular weight sensitizers, irritants or low and high levels of mineral dust, biological dust, gases & fumes or the composite variable vapours, gases, dusts or fumes). Hazards ratios ranged from 0.8 (95% confidence interval: 0.7;1.0) to 1.2 (95% confidence interval: 0.9;1.7). CONCLUSION: Exacerbations of obstructive airway disease were not associated with occupational inhalant exposures assigned by a job exposure matrix. Further studies with alternative exposure assessment are warranted.


Assuntos
Asma/epidemiologia , Asma/patologia , Progressão da Doença , Exposição Ocupacional/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/patologia , Feminino , Humanos , Exposição por Inalação , Masculino , Pessoa de Meia-Idade
2.
Rev Mal Respir ; 37(9): 756-765, 2020 Nov.
Artigo em Francês | MEDLINE | ID: mdl-33169687

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality, especially in cases of chronic hypercapnic respiratory failure. Following a prolonged debate, the indication and benefits of noninvasive ventilation (NIV) have been recently established. Although improved ventilation and reduction in hyperinflation appear to underlie the positive effect on NIV in COPD, only a few studies have focused on specific ventilatory algorithms for improving PaCO2. METHODS: The main objective of this study is to analyze the impact of Löwenstein's ventilatory algorithms, supposed to allow a better management of hyperinflation and its consequences on alveolar ventilation and blood gas parameters. This is an interventional study in routine care, prospective, single blind, randomized with cross over. The primary endpoint will be the transcutaneous partial pressure of nocturnal carbon dioxide. Secondary endpoints will be: abnormal respiratory events occurring during nocturnal NIV; the objective quality of sleep via polysomnography; the tolerance of ventilation and the subjective quality of sleep evaluated by auto questionnaires. EXPECTED RESULTS: The results of this study will clarify whether is it necessary to explore more the impact of the ventilatory modes developed by Löwenstein, dedicated to hypercapnic COPD patients, requiring a long-term NIV.


Assuntos
Algoritmos , Hipercapnia/terapia , Ventilação não Invasiva , Doença Pulmonar Obstrutiva Crônica/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Dióxido de Carbono/análise , Dióxido de Carbono/sangue , Estudos Cross-Over , Serviços de Assistência Domiciliar , Humanos , Hipercapnia/complicações , Hipercapnia/patologia , Monitorização Fisiológica/métodos , Monitorização Fisiológica/normas , Ventilação não Invasiva/métodos , Seleção de Pacientes , Polissonografia , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Projetos de Pesquisa , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/patologia , Insuficiência Respiratória/terapia , Tamanho da Amostra , Índice de Gravidade de Doença , Método Simples-Cego , Sono/fisiologia
4.
Cytokine Growth Factor Rev ; 54: 32-42, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32747157

RESUMO

The seventh human coronavirus SARS-CoV2 belongs to the cluster of extremely pathogenic coronaviruses including SARS-CoV and MERS-CoV, which can cause fatal lower respiratory tract infection. Likewise, SARS-CoV2 infection can be fatal as the disease advances to pneumonia, followed by acute respiratory distress syndrome (ARDS). The development of lethal clinical symptons is associated with an exaggerated production of inflammatory cytokines, referred to as the cytokine storm, is a consequence of a hyperactivated immune response aginst the infection. In this article, we discuss the pathogenic consequences of the cytokine storm and its relationship with COVID-19 associated risk factors. The increased pro-inflammatory immune status in patients with risk factors (diabetes, hypertension, cardiovascular disease, COPD) exacerbates the Cytokine-storm of COVID-19 into a 'Cytokine Super Cyclone'. We also evaluate the antiviral immune responses provided by BCG vaccination and the potential role of 'trained immunity' in early protection against SARS-CoV2.


Assuntos
Vacina BCG/uso terapêutico , Infecções por Coronavirus/prevenção & controle , Síndrome da Liberação de Citocina/prevenção & controle , Citocinas/sangue , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Antivirais/uso terapêutico , Betacoronavirus/imunologia , Doenças Cardiovasculares/patologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Diabetes Mellitus/patologia , Humanos , Hipertensão/patologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Mycobacterium bovis/imunologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Doença Pulmonar Obstrutiva Crônica/patologia , Fatores de Risco , Síndrome Respiratória Aguda Grave/imunologia , Vacinação
5.
Nat Commun ; 11(1): 4311, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32855420

RESUMO

Pulmonary disease increases the risk of developing abdominal aortic aneurysms (AAA). However, the mechanism underlying the pathological dialogue between the lungs and aorta is undefined. Here, we find that inflicting acute lung injury (ALI) to mice doubles their incidence of AAA and accelerates macrophage-driven proteolytic damage of the aortic wall. ALI-induced HMGB1 leaks and is captured by arterial macrophages thereby altering their mitochondrial metabolism through RIPK3. RIPK3 promotes mitochondrial fission leading to elevated oxidative stress via DRP1. This triggers MMP12 to lyse arterial matrix, thereby stimulating AAA. Administration of recombinant HMGB1 to WT, but not Ripk3-/- mice, recapitulates ALI-induced proteolytic collapse of arterial architecture. Deletion of RIPK3 in myeloid cells, DRP1 or MMP12 suppression in ALI-inflicted mice repress arterial stress and brake MMP12 release by transmural macrophages thereby maintaining a strengthened arterial framework refractory to AAA. Our results establish an inter-organ circuitry that alerts arterial macrophages to regulate vascular remodeling.


Assuntos
Lesão Pulmonar Aguda/complicações , Aneurisma da Aorta Abdominal/patologia , Proteína HMGB1/metabolismo , Macrófagos/metabolismo , Remodelação Vascular , Lesão Pulmonar Aguda/patologia , Animais , Aorta Abdominal/citologia , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/etiologia , Aneurisma da Aorta Abdominal/prevenção & controle , Células Cultivadas , Modelos Animais de Doenças , Dinaminas/antagonistas & inibidores , Dinaminas/metabolismo , Humanos , Macrófagos/citologia , Metaloproteinase 12 da Matriz/genética , Metaloproteinase 12 da Matriz/metabolismo , Camundongos , Camundongos Knockout , Dinâmica Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fosforilação , Cultura Primária de Células , Proteólise/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/patologia , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Estudos Retrospectivos , Regulação para Cima
6.
Am J Physiol Lung Cell Mol Physiol ; 319(4): L661-L669, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32783617

RESUMO

The past two decades have witnessed a resurgence in neutrophil research, inspired in part by the discovery of neutrophil extracellular traps (NETs) and their myriad roles in health and disease. Within the lung, dysregulation of neutrophils and NETosis have been linked to an array of diseases including pneumonia, cystic fibrosis, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and severe asthma. However, our understanding of pathologic neutrophil responses in the lung remains incomplete. Two methodologic issues have contributed to this gap: first, an emphasis on studying neutrophils from blood rather than the lung and second, the technical difficulties of interrogating neutrophil responses in mice, which has largely restricted basic murine research to specialized laboratories. To address these limitations, we have developed a suite of techniques for studying neutrophil effector functions specifically in the mouse lung. These include ex vivo assays for phagocytosis and NETosis using bronchoalveolar neutrophils and in situ evaluation of NETosis in a murine model of pneumonia. Throughout, we have prioritized technical ease and robust, quantitative readouts. We hope these assays will help to standardize research on lung neutrophils and improve accessibility to this burgeoning field.


Assuntos
Armadilhas Extracelulares/metabolismo , Neutrófilos/patologia , Fagocitose/fisiologia , Doença Pulmonar Obstrutiva Crônica/patologia , Animais , Modelos Animais de Doenças , Pulmão/patologia , Camundongos , Pneumonia/diagnóstico , Pneumonia/patologia , /patologia
7.
Clin Chest Med ; 41(3): 307-314, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32800186

RESUMO

Chronic obstructive pulmonary disease (COPD) has been traditionally considered a self-inflicted disease caused by tobacco smoking. Current available evidence, however, indicates that the pathogenesis of COPD needs to consider the dynamic and cumulative nature of a series of environment (including smoking plus other exposures)-host interactions that eventually determine lung development, maintenance, repair, and aging. By doing so, these factors modulate the trajectory of lung function of the individual through life and the odds of developing COPD through different routes, which likely represent different forms of the disease that require different preventive and therapeutic strategies.


Assuntos
Doença Pulmonar Obstrutiva Crônica/patologia , Feminino , Humanos , Masculino
8.
Clin Chest Med ; 41(3): 339-345, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32800189

RESUMO

Alpha-1 antitrypsin deficiency (AATD) was the first genetic risk factor for chronic obstructive pulmonary disease (COPD) described. In the more than 50 years since its description, the disease continues to provide insights into more common forms of COPD. Although AATD is caused by a single genetic variant, the clinical manifestations of disease include panacinar emphysema, airway hyperresponsiveness, and bronchiectasis. With improved molecular understanding of the mechanisms of disease pathogenesis and progression, new therapies in addition to intravenous augmentation therapy are on the horizon.


Assuntos
Doença Pulmonar Obstrutiva Crônica/etiologia , Deficiência de alfa 1-Antitripsina/complicações , Humanos , Doença Pulmonar Obstrutiva Crônica/patologia , Deficiência de alfa 1-Antitripsina/patologia
9.
Clin Chest Med ; 41(3): 395-403, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32800194

RESUMO

The term asthma chronic obstructive pulmonary disease (COPD) overlap (ACO) has been popularized to describe people who simultaneously have features of both diseases. Analysis of the basis of disease classification and comparison of the clinical, pathophysiological, and therapeutic features of asthma and COPD concludes that it is not useful to use the term ACO. Rather, it is important to make the individual diagnoses, recognizing that both diseases may coexist. If a concurrent diagnosis of COPD is suspected in people with asthma, pharmacotherapy should primarily follow asthma guidelines, but pharmacologic and nonpharmacologic approaches also may be needed for COPD.


Assuntos
Asma/diagnóstico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Asma/patologia , Feminino , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/patologia
10.
Clin Chest Med ; 41(3): 421-438, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32800196

RESUMO

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are episodes of symptom worsening which have significant adverse consequences for patients. Exacerbations are highly heterogeneous events associated with increased airway and systemic inflammation and physiological changes. The frequency of exacerbations is associated with accelerated lung function decline, quality of life impairment and increased mortality. They are triggered predominantly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation. A proportion of patients appear to be more susceptible to exacerbations, with poorer quality of life and more aggressive disease progression than those who have infrequent exacerbations. Exacerbations also contribute significantly to healthcare expenditure. Prevention and mitigation of exacerbations are therefore key goals of COPD management.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Qualidade de Vida/psicologia , Progressão da Doença , Humanos , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/patologia , Doença Pulmonar Obstrutiva Crônica/terapia
11.
PLoS One ; 15(7): e0235709, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32650339

RESUMO

BACKGROUND: Since 2005, the Smoking Treatment for Ontario Patients (STOP) program has provided smoking cessation treatment of varying form and intensity to smokers through 11 distinct treatment models, either in-person at partnering healthcare organizations or remotely via web or telephone. We aimed to characterize the patient populations reached by different treatment models. METHODS: We linked self-report data to health administrative databases to describe sociodemographics, physical and mental health comorbidity, healthcare utilization and costs. Our sample consisted of 107,302 patients who enrolled between 18Oct2005 and 31Mar2016, across 11 models operational during different time periods. RESULTS: Patient populations varied on sociodemographics, comorbidity burden, and healthcare usage. Enrollees in the Web-based model were youngest (median age: 39; IQR: 29-49), and enrollees in primary care-based Family Health Teams were oldest (median: 51; IQR: 40-60). Chronic Obstructive Pulmonary Disease and hypertension were the most common physical health comorbidities, twice as prevalent in Family Health Teams (32.3% and 30.8%) than in the direct-to-smoker (Web and Telephone) and Pharmacy models (13.5%-16.7% and 14.7%-17.7%). Depression, the most prevalent mental health diagnosis, was twice as prevalent in the Addiction Agency (52.1%) versus the Telephone model (25.3%). Median healthcare costs in the two years up to enrollment ranged from $1,787 in the Telephone model to $9,393 in the Addiction Agency model. DISCUSSION: While practitioner-mediated models in specialized and primary care settings reached smokers with more complex healthcare needs, alternative settings appear better suited to reach younger smokers before such comorbidities develop. Although Web and Telephone models were expected to have fewer barriers to access, they reached a lower proportion of patients in rural areas and of lower socioeconomic status. Findings suggest that in addition to population-based strategies, embedding smoking cessation treatment into existing healthcare settings that reach patient populations with varying disparities may enhance equitable access to treatment.


Assuntos
Aceitação pelo Paciente de Cuidados de Saúde , Fumantes/psicologia , Adulto , Comorbidade , Estudos Transversais , Depressão/epidemiologia , Depressão/patologia , Feminino , Custos de Cuidados de Saúde , Humanos , Hipertensão/epidemiologia , Hipertensão/patologia , Internet , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/patologia , Abandono do Hábito de Fumar , Inquéritos e Questionários , Telefone
12.
Viruses ; 12(7)2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32698440

RESUMO

The coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects almost everyone in the world in many ways. We previously predicted antivirals (atazanavir, remdesivir and lopinavir/ritonavir) and non-antiviral drugs (tiotropium and rapamycin) that may inhibit the replication complex of SARS-CoV-2 using our molecular transformer-drug target interaction (MT-DTI) deep-learning-based drug-target affinity prediction model. In this study, we dissected molecular pathways upregulated in SARS-CoV-2-infected normal human bronchial epithelial (NHBE) cells by analyzing an RNA-seq data set with various bioinformatics approaches, such as gene ontology, protein-protein interaction-based network and gene set enrichment analyses. The results indicated that the SARS-CoV-2 infection strongly activates TNF and NFκB-signaling pathways through significant upregulation of the TNF, IL1B, IL6, IL8, NFKB1, NFKB2 and RELB genes. In addition to these pathways, lung fibrosis, keratinization/cornification, rheumatoid arthritis, and negative regulation of interferon-gamma production pathways were also significantly upregulated. We observed that these pathologic features of SARS-CoV-2 are similar to those observed in patients with chronic obstructive pulmonary disease (COPD). Intriguingly, tiotropium, as predicted by MT-DTI, is currently used as a therapeutic intervention in COPD patients. Treatment with tiotropium has been shown to improve pulmonary function by alleviating airway inflammation. Accordingly, a literature search summarized that tiotropium reduced expressions of IL1B, IL6, IL8, RELA, NFKB1 and TNF in vitro or in vivo, and many of them have been known to be deregulated in COPD patients. These results suggest that COVID-19 is similar to an acute mode of COPD caused by the SARS-CoV-2 infection, and therefore tiotropium may be effective for COVID-19 patients.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Brometo de Tiotrópio/uso terapêutico , Transcriptoma , Brônquios/virologia , Infecções por Coronavirus/etiologia , Infecções por Coronavirus/patologia , Células Epiteliais/virologia , Humanos , Pandemias , Pneumonia Viral/etiologia , Pneumonia Viral/patologia , Doença Pulmonar Obstrutiva Crônica/patologia , Transdução de Sinais/fisiologia
14.
JAMA ; 323(22): 2268-2280, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32515814

RESUMO

Importance: Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD), yet much of COPD risk remains unexplained. Objective: To determine whether dysanapsis, a mismatch of airway tree caliber to lung size, assessed by computed tomography (CT), is associated with incident COPD among older adults and lung function decline in COPD. Design, Setting, and Participants: A retrospective cohort study of 2 community-based samples: the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study, which involved 2531 participants (6 US sites, 2010-2018) and the Canadian Cohort of Obstructive Lung Disease (CanCOLD), which involved 1272 participants (9 Canadian sites, 2010-2018), and a case-control study of COPD: the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), which involved 2726 participants (12 US sites, 2011-2016). Exposures: Dysanapsis was quantified on CT as the geometric mean of airway lumen diameters measured at 19 standard anatomic locations divided by the cube root of lung volume (airway to lung ratio). Main Outcomes and Measures: Primary outcome was COPD defined by postbronchodilator ratio of forced expired volume in the first second to vital capacity (FEV1:FVC) less than 0.70 with respiratory symptoms. Secondary outcome was longitudinal lung function. All analyses were adjusted for demographics and standard COPD risk factors (primary and secondhand tobacco smoke exposures, occupational and environmental pollutants, and asthma). Results: In the MESA Lung sample (mean [SD] age, 69 years [9 years]; 1334 women [52.7%]), 237 of 2531 participants (9.4%) had prevalent COPD, the mean (SD) airway to lung ratio was 0.033 (0.004), and the mean (SD) FEV1 decline was -33 mL/y (31 mL/y). Of 2294 MESA Lung participants without prevalent COPD, 98 (4.3%) had incident COPD at a median of 6.2 years. Compared with participants in the highest quartile of airway to lung ratio, those in the lowest had a significantly higher COPD incidence (9.8 vs 1.2 cases per 1000 person-years; rate ratio [RR], 8.12; 95% CI, 3.81 to 17.27; rate difference, 8.6 cases per 1000 person-years; 95% CI, 7.1 to 9.2; P < .001) but no significant difference in FEV1 decline (-31 vs -33 mL/y; difference, 2 mL/y; 95% CI, -2 to 5; P = .30). Among CanCOLD participants (mean [SD] age, 67 years [10 years]; 564 women [44.3%]), 113 of 752 (15.0%) had incident COPD at a median of 3.1 years and the mean (SD) FEV1 decline was -36 mL/y (75 mL/y). The COPD incidence in the lowest airway to lung quartile was significantly higher than in the highest quartile (80.6 vs 24.2 cases per 1000 person-years; RR, 3.33; 95% CI, 1.89 to 5.85; rate difference, 56.4 cases per 1000 person-years; 95% CI, 38.0 to 66.8; P<.001), but the FEV1 decline did not differ significantly (-34 vs -36 mL/y; difference, 1 mL/y; 95% CI, -15 to 16; P=.97). Among 1206 SPIROMICS participants (mean [SD] age, 65 years [8 years]; 542 women [44.9%]) with COPD who were followed up for a median 2.1 years, those in the lowest airway to lung ratio quartile had a mean FEV1 decline of -37 mL/y (15 mL/y), which did not differ significantly from the decline in MESA Lung participants (P = .98), whereas those in highest quartile had significantly faster decline than participants in MESA Lung (-55 mL/y [16 mL/y ]; difference, -17 mL/y; 95% CI, -32 to -3; P = .004). Conclusions and Relevance: Among older adults, dysanapsis was significantly associated with COPD, with lower airway tree caliber relative to lung size associated with greater COPD risk. Dysanapsis appears to be a risk factor associated with COPD.


Assuntos
Volume Expiratório Forçado , Pulmão/patologia , Doença Pulmonar Obstrutiva Crônica/patologia , Capacidade Vital , Idoso , Feminino , Humanos , Pulmão/anatomia & histologia , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Masculino , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Fumar/efeitos adversos , Espirometria , Tomografia Computadorizada por Raios X
15.
Arch Biochem Biophys ; 689: 108439, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32504553

RESUMO

Chronic obstructive pulmonary disease (COPD) and lung cancer are a major cause of morbidity and mortality worldwide, with cigarette smoking being the single most important risk factor for both. Emerging evidence indicates alterations in reverse cholesterol transport-mediated removal of excess cholesterol from lung, and intracellular cholesterol overload to be involved in smoke-promoted COPD and lung cancer development. Since there are currently few effective treatments for COPD and lung cancer, it is important to identify food-derived, biologically active compounds, which can protect against COPD and lung cancer development. High intake of the carotenoid lycopene, as one of phytochemicals, is associated with a decreased risk of chronic lung lesions. This review article summarizes and discusses epidemiologic evidence, in vitro and in vivo studies regarding the prevention of smoke-promoted COPD and lung carcinogenesis through dietary lycopene as an effective intervention strategy. We focus on the recent research implying that lycopene preventive effect is through targeting the main genes involved in reverse cholesterol transport. This review also indicates gaps in knowledge about the function of lycopene against COPD and lung cancer, offering directions for further research.


Assuntos
Anticarcinógenos/uso terapêutico , Antioxidantes/uso terapêutico , Fumar Cigarros/efeitos adversos , Neoplasias Pulmonares/prevenção & controle , Licopeno/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Animais , Anticarcinógenos/metabolismo , Antioxidantes/metabolismo , Colesterol/metabolismo , Suplementos Nutricionais , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Licopeno/metabolismo , Lycopersicon esculentum/metabolismo , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia
16.
Tunis Med ; 98(5): 378-395, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32548841

RESUMO

OBJECTIVE: The objective of this literature review is to gather all the LFT norms available for the Tunisian population, as well as QDV questionnaires specific to chronic respiratory patients that have been validated in Tunisia. METHODS: This review included a literature search using the PubMed and Sciencedirect databases. The reference lists of the retrieved English/French articles were searched for any additional reference. Specific research has been carried out for each stage of the natural evolution of chronic diseases. For LFT used in the exploration of deficiency, the key-words were ("respiratory function test" OR "spirometry" OR "plethysmography" OR "exhaled fraction of oxide nitric" OR "lung diffusion" OR "peak nasal inspiratory flow" OR "Lung age") AND ("Tunisia" OR "North Africa") AND ("reference equation" OR "reference value" OR "standard reference"). For LFT used in the exploration of incapacity, the key-words were ("exercise test" OR "maximal oxygen uptake" OR "cardiorespiratory test" OR "six minute walk distance" OR "six-minute walk distance" OR "6-minute walk distance" OR "six-min walk distance" OR "6-min walk distance" OR "six minute walking distance" OR "six-minute walking distance" OR "6MWD") AND ("Tunisia" OR "North Africa") AND ("reference equation" OR "reference value" OR "standard reference"). For the QOL questionnaires used in pneumology, the key-words were: ("quality of life" OR "QOL") AND ("respiratory" OR "pulmonology") AND ("Tunisia" OR "North Africa"). RESULTS: As part of deficiency exploration, 11 Tunisian norms are available. As part of incapacity exploration, three Tunisian norms are available for the 6-minute walk test. Only one QOL questionnaire specific to chronic respiratory patients has been validated in Tunisia. CONCLUSION: Despite its richness, the Tunisian "bank" of norms for LFT and QOL questionnaires has yet to be enriched.


Assuntos
Doença Pulmonar Obstrutiva Crônica/diagnóstico , Qualidade de Vida , Testes de Função Respiratória/normas , Insuficiência Respiratória/diagnóstico , Inquéritos e Questionários/normas , Doença Crônica , Pessoas com Deficiência , Progressão da Doença , Teste de Esforço/métodos , Teste de Esforço/normas , Humanos , Doença Pulmonar Obstrutiva Crônica/patologia , Valores de Referência , Testes de Função Respiratória/métodos , Insuficiência Respiratória/patologia , Índice de Gravidade de Doença , Tunísia , Estudos de Validação como Assunto
17.
PLoS One ; 15(6): e0234808, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555678

RESUMO

Tobacco use after lung transplantation is associated with adverse outcome. Therefore, active smoking is regarded as a contraindication for lung transplantation and should be excluded prior to placement on the waiting list. The aim of the study was to compare self-reporting with a systematic cotinine based screening approach to identify patients with active nicotine abuse. Nicotine use was systematically assessed by interviews and cotinine test in all lung transplant candidates at every visit in our center. Patients were classified according to the stage prior to transplantation and cotinine test results were compared to self-reports and retrospectively analyzed until June 2019. Of 620 lung transplant candidates, 92 patients (14.8%) had at least one positive cotinine test. COPD as underlying disease (OR 2.102, CI 1.110-3.981; p = 0.023), number of pack years (OR 1.014, CI 1.000-1.028; p = 0.047) and a time of cessation less than one year (OR 2.413, CI 1.410-4.128; p = 0.001) were associated with a positive cotinine test in multivariable regression analysis. The majority of non-COPD patients (n = 13, 72.2%) with a positive test had a cessation time of less than one year. 78 patients (84.7%) falsely declared not consuming any nicotine-based products prior to the test. Finally, all never smokers were test negative. In conclusion, our data demonstrate that active nicotine use is prevalent in transplant candidates with a high prevalence of falsely declaring nicotine abstinence. COPD was the main diagnosis in affected patients. Short cessation time and a high number of pack years are risk factors for continued nicotine abuse.


Assuntos
Cotinina/urina , Transplante de Pulmão , Fumar/epidemiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Doença Pulmonar Obstrutiva Crônica/patologia , Análise de Regressão , Estudos Retrospectivos , Autorrelato , Abandono do Hábito de Fumar
18.
Am J Physiol Lung Cell Mol Physiol ; 319(1): L48-L60, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32460521

RESUMO

Chronic obstructive pulmonary disease (COPD) is associated with features of accelerated aging, including cellular senescence, DNA damage, oxidative stress, and extracellular matrix (ECM) changes. We propose that these features are particularly apparent in patients with severe, early-onset (SEO)-COPD. Whether fibroblasts from COPD patients display features of accelerated aging and whether this is also present in relatively young SEO-COPD patients is unknown. Therefore, we aimed to determine markers of aging in (SEO)-COPD-derived lung fibroblasts and investigate the impact on ECM. Aging hallmarks and ECM markers were analyzed in lung fibroblasts from SEO-COPD and older COPD patients and compared with fibroblasts from matched non-COPD groups (n = 9-11 per group), both at normal culture conditions and upon Paraquat-induced senescence. COPD-related differences in senescence and ECM expression were validated in lung tissue. Higher levels of cellular senescence, including senescence-associated ß-galactosidase (SA-ß-gal)-positive cells (19% for COPD vs. 13% for control) and p16 expression, DNA damage (γ-H2A.X-positive nuclei), and oxidative stress (MGST1) were detected in COPD compared with control-derived fibroblasts. Most effects were also different in SEO-COPD, with SA-ß-gal-positive cells only being significant in SEO-COPD vs. matched controls. Lower decorin expression in COPD-derived fibroblasts correlated with higher p16 expression, and this association was confirmed in lung tissue. Paraquat treatment induced cellular senescence along with clear changes in ECM expression, including decorin. Fibroblasts from COPD patients, including SEO-COPD, display higher levels of cellular senescence, DNA damage, and oxidative stress. The association between cellular senescence and ECM expression changes may suggest a link between accelerated aging and ECM dysregulation in COPD.


Assuntos
Senescência Celular , Matriz Extracelular/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Adulto , Idade de Início , Biomarcadores/metabolismo , Células Cultivadas , Dano ao DNA , Feminino , Fibroblastos/patologia , Regulação da Expressão Gênica , Humanos , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Pessoa de Meia-Idade , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Estresse Oxidativo , Paraquat/toxicidade , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/fisiopatologia
19.
Am J Respir Cell Mol Biol ; 63(3): 293-305, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32338993

RESUMO

Chronic exposure to cigarette smoke (CS) causes chronic inflammation, oxidative stress, and apoptosis of epithelial cells, which results in destruction of the lung matrix. However, the mechanism by which the lung fails to repair the CS-induced damage, thereby succumbing to emphysema, remains unclear. Alveolar type 2 (AT2) cells comprise the stem cells of the alveolar compartments and are responsible for repairing and maintaining lung tissues. In this study, we examined the effect of chronic CS on AT2 stem cells. Adult mice expressing GFP in their AT2 cells were exposed to CS for > 3 months. Histological assessment showed that CS not only induced emphysematous changes but also increased the number of AT2 cells compared with that of air-exposed lungs. Assessment of sorted GFP+/AT2 cells via the stem cell three-dimensional organoid/colony-forming assay revealed that the number and size of the colonies formed by the CS-exposed AT2 stem cells were significantly higher than those of air-exposed control AT2 cells. Although CS-exposed lungs had more apoptotic cells, examination of the surviving AT2 stem cells in two-dimensional in vitro culture revealed that they developed a higher ability to resist apoptosis. Microarray analysis of CS-exposed AT2 stem cells revealed the upregulation of genes related to circadian rhythm and inflammatory pathways. In conclusion, we provide evidence that AT2 stem cells respond to chronic CS exposure by activating their stem cell function, thereby proliferating and differentiating faster and becoming more resistant to apoptosis. Disturbances in expression levels of several circadian rhythm-related genes might be involved in these changes.


Assuntos
Células Epiteliais Alveolares/efeitos dos fármacos , Enfisema Pulmonar/patologia , Fumaça/efeitos adversos , Tabaco/toxicidade , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/patologia , Animais , Apoptose/efeitos dos fármacos , Pulmão/patologia , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/patologia , Fumar
20.
Clin Sci (Lond) ; 134(7): 751-763, 2020 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-32227160

RESUMO

The numbers of macrophages are increased in the lungs of chronic obstructive pulmonary disease (COPD) patients. COPD lung macrophages have reduced ability to phagocytose microbes and efferocytose apoptotic cells. Inhaled corticosteroids (ICSs) are widely used anti-inflammatory drugs in COPD; however, their role beyond suppression of cytokine release has not been explored in COPD macrophages. We have examined the effects of corticosteroids on COPD lung macrophage phenotype and function. Lung macrophages from controls and COPD patients were treated with corticosteroids; effects on gene and protein expression of CD163, CD164, CD206, MERTK, CD64, CD80 and CD86 were studied. We also examined the effect of corticosteroids on the function of CD163, MERTK and cluster of differentiation 64 (CD64). Corticosteroid increased CD163, CD164, CD206 and MERTK expression and reduced CD64, CD80 and CD86 expression. We also observed an increase in the uptake of the haemoglobin-haptoglobin complex (CD163) from 59 up to 81% and an increase in efferocytosis of apoptotic neutrophils (MERTK) from 15 up to 28% following corticosteroid treatment. We observed no effect on bacterial phagocytosis. Corticosteroids alter the phenotype and function of COPD lung macrophages. Our findings suggest mechanisms by which corticosteroids exert therapeutic benefit in COPD, reducing iron available for bacterial growth and enhancing efferocytosis.


Assuntos
Corticosteroides/farmacologia , Dexametasona/farmacologia , Pulmão/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Idoso , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Apoptose/efeitos dos fármacos , Estudos de Casos e Controles , Células Cultivadas , Técnicas de Cocultura , Feminino , Regulação da Expressão Gênica , Humanos , Ferro/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Neutrófilos/patologia , Fenótipo , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Receptores de IgG/genética , Receptores de IgG/metabolismo , Transdução de Sinais , c-Mer Tirosina Quinase/genética , c-Mer Tirosina Quinase/metabolismo
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