RESUMO
Purpose: Chronic obstructive pulmonary disease (COPD) phenotypes may introduce different characteristics that need to be known to improve treatment. Respiratory oscillometry provides a detailed analysis and may offer insight into the pathophysiology of COPD. In this paper, we used this method to evaluate the differences in respiratory mechanics of COPD phenotypes. Patients and Methods: This study investigated a sample of 83 volunteers, being divided into control group (CG = 20), emphysema (n = 23), CB (n = 20) and asthma-COPD overlap syndrome (ACOS, n = 20). These analyses were performed before and after bronchodilator (BD) use. Functional capacity was evaluated using the GlittreADL test, handgrip strength and respiratory pressures. Results: Initially it was observed that oscillometry provided a detailed description of the COPD phenotypes, which was consistent with the involved pathophysiology. A correlation between oscillometry and functional capacity was observed (r=-0.541; p = 0.0001), particularly in the emphysema phenotype (r = -0.496, p = 0.031). BD response was different among the studied phenotypes. This resulted in an accurate discrimination of ACOS from CB [area under the receiver operating curve (AUC) = 0.84] and emphysema (AUC = 0.82). Conclusion: These results offer evidence that oscillatory indices may enhance the comprehension and identification of COPD phenotypes, thereby potentially improving the support provided to these patients.
Assuntos
Asma , Enfisema , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Pulmão , Oscilometria/métodos , Força da Mão , Volume Expiratório Forçado , Broncodilatadores/uso terapêutico , Fenótipo , Desempenho Físico FuncionalRESUMO
Pulmonary emphysema is a primary component of chronic obstructive pulmonary disease (COPD), a life-threatening disorder characterized by lung inflammation and restricted airflow, primarily resulting from the destruction of small airways and alveolar walls. Cumulative evidence suggests that nicotinic receptors, especially the α7 subtype (α7nAChR), is required for anti-inflammatory cholinergic responses. We postulated that the stimulation of α7nAChR could offer therapeutic benefits in the context of pulmonary emphysema. To investigate this, we assessed the potential protective effects of PNU-282987, a selective α7nAChR agonist, using an experimental emphysema model. Male mice (C57BL/6) were submitted to a nasal instillation of porcine pancreatic elastase (PPE) (50 µl, 0.667 IU) to induce emphysema. Treatment with PNU-282987 (2.0 mg/kg, ip) was performed pre and post-emphysema induction by measuring anti-inflammatory effects (inflammatory cells, cytokines) as well as anti-remodeling and anti-oxidant effects. Elastase-induced emphysema led to an increase in the number of α7nAChR-positive cells in the lungs. Notably, both groups treated with PNU-282987 (prior to and following emphysema induction) exhibited a significant decrease in the number of α7nAChR-positive cells. Furthermore, both groups treated with PNU-282987 demonstrated decreased levels of macrophages, IL-6, IL-1ß, collagen, and elastic fiber deposition. Additionally, both groups exhibited reduced STAT3 phosphorylation and lower levels of SOCS3. Of particular note, in the post-treated group, PNU-282987 successfully attenuated alveolar enlargement, decreased IL-17 and TNF-α levels, and reduced the recruitment of polymorphonuclear cells to the lung parenchyma. Significantly, it is worth noting that MLA, an antagonist of α7nAChR, counteracted the protective effects of PNU-282987 in relation to certain crucial inflammatory parameters. In summary, these findings unequivocally demonstrate the protective abilities of α7nAChR against elastase-induced emphysema, strongly supporting α7nAChR as a pivotal therapeutic target for ameliorating pulmonary emphysema.
Assuntos
Benzamidas , Compostos Bicíclicos com Pontes , Camundongos Endogâmicos C57BL , Agonistas Nicotínicos , Elastase Pancreática , Enfisema Pulmonar , Receptor Nicotínico de Acetilcolina alfa7 , Animais , Receptor Nicotínico de Acetilcolina alfa7/agonistas , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Enfisema Pulmonar/tratamento farmacológico , Enfisema Pulmonar/induzido quimicamente , Enfisema Pulmonar/metabolismo , Enfisema Pulmonar/prevenção & controle , Camundongos , Benzamidas/farmacologia , Benzamidas/uso terapêutico , Masculino , Compostos Bicíclicos com Pontes/farmacologia , Compostos Bicíclicos com Pontes/uso terapêutico , Agonistas Nicotínicos/farmacologia , Agonistas Nicotínicos/uso terapêutico , Pulmão/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêuticoRESUMO
The aim of this review is to update and synthesize the molecular mechanisms that lead to the heterogeneous effect on tissue remodeling observed in the two most important clinical phenotypes of chronic obstructive pulmonary disease (COPD), pulmonary emphysema (PE) and chronic bronchitis (CB). Clinical and experimental evidence suggests that this heterogeneous response to promote PE, CB, or both, is related to differentiated genetic, epigenetic, and molecular conditions. Specifically, a tendency toward PE could be related to a variant in the DSP gene, SIRT1 downregulation, macrophage polarization to M1, as well as the involvement of the noncanonical Wnt5A signaling pathway, among other alterations. Additionally, in advanced stages of COPD, PE development is potentiated by dysregulations in autophagy, which promotes senescence and subsequently cell apoptosis, through exacerbated inflammasome activation and release of caspases. On the other hand, CB or the pro-fibrotic phenotype could be potentiated by the downregulated activity of HDAC2, the activation of the TGF-ß/Smad or Wnt/ß-catenin signaling pathways, macrophage polarization to M2, upregulation of TIMP-1, and/or the presence of the epithelial-mesenchymal transition (EMT) mechanism. Interestingly, the upregulated activity of MMPs, especially MMP-9, is widely involved in the development of both phenotypes. Furthermore, MMP-9 and MMP-12 enhance the severity, perpetuation, and exacerbation of COPD, as well as the development of autoimmunity in this disease.
Assuntos
Bronquite Crônica , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Humanos , Enfisema Pulmonar/patologia , Enfisema Pulmonar/metabolismo , Enfisema Pulmonar/genética , Doença Pulmonar Obstrutiva Crônica/patologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/genética , Bronquite Crônica/metabolismo , Bronquite Crônica/patologia , Bronquite Crônica/genética , Animais , Transdução de SinaisRESUMO
Introducción: la enfermedad periodontal y la enfermedad pulmonar obstructiva crónica son patologías de origen inflamatorio crónico y progresivo que afectan a pacientes de edad avanzada, fumadores con mal estado de salud oral, encontrándose una correlación por el grado de severidad en la enfermedad periodontal sobre aquellos individuos con presencia de enfermedad pulmonar obstructiva crónica (EPOC) y exacerbaciones. Objetivos: determinar la relación de la enfermedad periodontal y la enfermedad pulmonar obstructiva crónica, explicando los factores de riesgo que intervienen en estas enfermedades. Material y métodos: se realizó una búsqueda en los principales buscadores de datos digitales: PubMed, SciELO, Science Direct, BMC, Journal of Periodontology, Web of Science y Scopus. Se escogieron artículos publicados en los últimos cinco años; se excluyeron artículos incompletos y que no se relacionan al tema. En el resultado de la búsqueda, 45 artículos cumplieron con el propósito de la revisión bibliográfica. Resultados: en esta revisión bibliográfica, se obtuvo que 18 artículos comprueban la relación de la enfermedad periodontal y la enfermedad pulmonar obstructiva crónica. Conclusiones: se ha comprobado la relación entre la enfermedad periodontal y enfermedad pulmonar obstructiva crónica. Se requiere el análisis de más estudios para determinar una relación directa entre estas dos enfermedades e incluir variables como la edad y el tratamiento (AU)
Introduction: periodontal disease and chronic obstructive pulmonary disease are diseases of chronic and progressive inflammatory origin that affect elderly patients, smokers with poor oral health, finding a correlation by the degree of severity in periodontal disease on those individuals with the presence of chronic obstructive pulmonary disease (COPD) and exacerbations. Objectives: to determine the relationship between periodontal disease and chronic obstructive pulmonary disease explaining the risk factors involved in these diseases. Material and methods: a search was carried out in the main digital data search engines: PubMed, SciELO, Science Direct, BMC, Journal of Periodontology, Web of Science, and Scopus, articles published in the last 5 years were chosen, incomplete articles and those not related to the subject were excluded, in the result of the search 45 articles fulfilled the purpose of the bibliographic review. Results: in this literature review it was obtained that 18 articles, prove the relationship between periodontal disease and chronic obstructive pulmonary disease. Conclusions: the relationship between periodontal disease and chronic obstructive pulmonary disease has been proved. More studies are needed to determine a direct relationship between these two diseases and to include variables such as age and treatment (AU)
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Doenças Periodontais/microbiologia , Enfisema Pulmonar , Bronquite/complicações , Bases de Dados Bibliográficas/tendências , Doença Pulmonar Obstrutiva Crônica/microbiologia , Interações MicrobianasRESUMO
COPD, one of world's leading contributors to morbidity and mortality, is characterized by airflow limitation and heterogeneous clinical features. Three main phenotypes are proposed: overlapping asthma/COPD (ACO), exacerbator, and emphysema. Disease severity can be classified as mild, moderate, severe, and very severe. The molecular basis of inflammatory amplification, cellular aging, and immune response are critical to COPD pathogenesis. Our aim was to investigate EP300 (histone acetylase, HAT), HDAC 2 (histone deacetylase), HDAC3, and HDAC4 gene expression, telomere length, and differentiation ability to M1/M2 macrophages. For this investigation, 105 COPD patients, 42 smokers, and 73 non-smoker controls were evaluated. We identified a reduced HDAC2 expression in patients with mild, moderate, and severe severity; a reduced HDAC3 expression in patients with moderate and severe severity; an increased HDAC4 expression in patients with mild severity; and a reduced EP300 expression in patients with severe severity. Additionally, HDAC2 expression was reduced in patients with emphysema and exacerbator, along with a reduced HDAC3 expression in patients with emphysema. Surprisingly, smokers and all COPD patients showed telomere shortening. COPD patients showed a higher tendency toward M2 markers. Our data implicate genetic changes in COPD phenotypes and severity, in addition to M2 prevalence, that might influence future treatments and personalized therapies.
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Enfisema , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Humanos , Macrófagos , Senescência Celular/genética , Expressão GênicaRESUMO
This study aimed to evaluate long-term exposure to conventional cigarette smoke (CC) and electronic cigarette (EC) aerosol in adult male and female C57BL/6 mice. Forty-eight C57BL/6 mice were used, male (n = 24) and female (n = 24), both were divided into three groups: control, CC and EC. The CC and EC groups were exposed to cigarette smoke or electronic cigarette aerosol, respectively, 3 times a day for 60 consecutive days. Afterwards, they were maintained for 60 days without exposure to cigarettes or electronic cigarette aerosol. Both cigarettes promoted an influx of inflammatory cells to the lung in males and females. All animals exposed to CC and EC showed an increase in lipid peroxidation and protein oxidation. There was an increase of IL-6 in males and females exposed to EC. The IL-13 levels were higher in the females exposed to EC and CC. Both sexes exposed to EC and CC presented tissue damage characterized by septal destruction and increased alveolar spaces compared to control. Our results demonstrated that exposure to CC and EC induced pulmonary emphysema in both sexes, and females seem to be more susceptible to EC.
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Sistemas Eletrônicos de Liberação de Nicotina , Enfisema Pulmonar , Produtos do Tabaco , Camundongos , Masculino , Animais , Feminino , Enfisema Pulmonar/induzido quimicamente , Enfisema Pulmonar/metabolismo , Camundongos Endogâmicos C57BL , Aerossóis e Gotículas Respiratórios , Pulmão/metabolismo , Produtos do Tabaco/efeitos adversos , NicotianaRESUMO
BACKGROUND: Several minimally invasive treatments have been offered to patients with severe emphysema over the last two decades. Currently, endobronchial valves (EBVs) are the only approved therapeutic option, but this method has drawbacks: only a few can undergo this therapy and the incidence of pneumothorax remains high. A minimally invasive technique, appropriate for a broader patient population and posing fewer risks, would represent a desirable alternative to improve lung function in these patients. OBJECTIVE: The objective of this study was to demonstrate whether a new prototype implantable artificial bronchus (IAB) releases trapped air from the lungs of recently deceased patients with emphysema. METHOD: Seven recently deceased patients with emphysema were mechanically ventilated and the respiratory rate increased from 12 bpm (resting) to 30 bpm (exercise), inducing air trapping and dynamic hyperinflation. This protocol was performed twice, before and after IAB placement. Ventilation parameters and the fraction of inspired oxygen were similar in all patients. Respiratory system plateau pressure (Pplat,rs) and intrinsic positive end-expiratory pressure (iPEEP) were measured. RESULTS: IAB implantation significantly reduced Pplat,rs (p = 0.017) in 6 of 7 deceased patients with emphysema and iPEEP (p = 0.03) in 5 of 7 patients. CONCLUSIONS: Placement of one or two IABs in segmental bronchi (up to 15th generation) proved to be feasible and improved lung function. These findings should provide a basis for subsequent clinical studies to assess the safety and efficacy of IAB in patients with emphysema, as well as identify short- and long-term effects of this innovative procedure.
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Enfisema , Enfisema Pulmonar , Humanos , Enfisema/cirurgia , Pulmão , Brônquios , Próteses e ImplantesRESUMO
OBJECTIVE: To estimate the prevalence of treatments used for the management of chronic obstructive pulmonary disease (COPD) in the Brazilian adult population. METHODS: A population-based cross-sectional study with data from the 2013 Brazilian National Survey of Health, including individuals aged 40 years or older, with a self-reported medical diagnosis of COPD, chronic bronchitis and/or emphysema, who were asked about treatments used for disease management. RESULTS: A total of 60,202 adults were interviewed, of which 636 were 40 years of age or older and had reported a medical diagnosis of COPD, emphysema, or chronic bronchitis. Less than half (49.4%) of the diagnosed population reported using some type of treatment, with differences regarding the macro-region of the country (South 53.8% - Northeast 41.2%, p = 0.007). Pharmacological treatment was the most reported, and emphysema patients had the highest proportion of those undergoing more than one type of treatment. Among the individuals who reported having only chronic bronchitis, 55.1% (95%CI: 48.7-61.4) used medication, 4.7% (95%CI: 2.6-8.3) underwent physical therapy, and 6.0% (95%CI: 3.6-9.9) oxygen therapy. On the other hand, among the emphysema patients, 44.1% (95%CI: 36.8-51.7) underwent drug treatment, 8.8% (95%CI: 5.4-14.2) physical therapy, and 10.0% (95%CI: 6.3-15.6) oxygen therapy. CONCLUSION: The prevalence of treatments for COPD management was below ideal in 2013. The pharmacological treatment was the main type of treatment, followed by oxygen therapy and physical therapy.