RESUMO
BACKGROUND: Airflow limitation alone is unable to capture the complexity of chronic obstructive pulmonary disease (COPD), better explained by comprehensive disease-specific indexes. Frailty is a clinical condition characterized by high vulnerability to internal and external stressors and represents a strong predictor of adverse outcomes. AIMS: Primary objective was to test the association between indexes of lung function and COPD severity with frailty index (FI), and secondary to evaluate the association between FI and comorbidities, cognitive and physical function, BODE index, and mortality. METHODS: 150 stable COPD outpatients were enrolled and followed up to 4 years. At baseline, participants performed a geriatric multidimensional assessment, pulmonary function tests, arterial blood gas analysis, 6-min walking test, and bioimpedance analysis. BODE and FI were calculated. Spearman's ρ was used to assess correlations. Mortality was assessed using Kaplan-Meier curves. RESULTS: Participants were followed up for a median of 39 months. Mean age was 73 years and median frailty index 0.15 (IQR 0.11-0.19). FI was higher in frequent exacerbators (≥ 2/year) (mean 0.18 vs 0.15, p 0.01) and dyspnoeic patients (mMRC ≥ 2) (mean 0.21 vs 0.14, p < 0.01) and correlated with lung volumes, expiratory flows, and pressure of arterial oxygen. FI was positively correlated with the number of comorbidities, depressive symptoms, cognitive decline, and BODE index. Mortality was higher in patients with BODE higher than 3 (HR 3.6, 95% CI 1.2-10.9), and not associated with FI. DISCUSSION: FI positively correlates with all clinical drivers orienting the choice of treatment in COPD. CONCLUSIONS: FI associates with lung function and COPD severity, but does not associate with mortality.
Assuntos
Fragilidade , Doença Pulmonar Obstrutiva Crônica , Idoso , Humanos , Pulmão , Doença Pulmonar Obstrutiva Crônica/complicações , Testes de Função Respiratória , Índice de Gravidade de DoençaRESUMO
Since the outbreak of the SARS-CoV-2 pandemic in 2020, many governments have been imposing confinement and physical distancing measures. No data exist on the effects of lockdowns on the health status of patients affected by chronic pathologies, specifically those with Chronic Obstructive Pulmonary Disease (COPD). Our study aims to establish variations across the psychological and cognitive profile of patients during the isolation period in Italy, in a cohort of patients affected by COPD, between February and May 2020. Forty patients with established COPD were comprehensively evaluated by geriatric multidimensional assessment before the spread of the epidemic in Italy, and submitted to a second evaluation during the subsequent lockdown. We assessed functional ability, basic and instrumental Activities of Daily Living (ADL and IADL), cognition and mood status. We compared the scores obtained at baseline against those obtained during the pandemic, and used mean differences for correlation with major clinical and functional indexes. The score differences from MMSE, ADL and IADL were statistically significant. Such differences were correlated to the presence of a caregiver and to the total number of family members living together. Remarkably, the loneliness dimension, more than the restrictions themselves, seemed to represent the major determinant of altered health status and depressed psycho-cognitive profile in our population. Also remarkably, we detected no correlation between the score variation and the respiratory function indexes of disease severity. The isolation measures adopted during the SARS-CoV-2 pandemic have triggered the classic clinical string associated to geriatric isolation, which leads to a deterioration of cognitive functions, independence and frailty levels in a population affected by a chronic degenerative disease, such as COPD. If considered from a multidimensional geriatric point of view, the individual benefit of isolation measures could be small or non-existent.
Assuntos
COVID-19/prevenção & controle , Cognição/fisiologia , Solidão/psicologia , Saúde Mental , Distanciamento Físico , Doença Pulmonar Obstrutiva Crônica/psicologia , Atividades Cotidianas , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , COVID-19/psicologia , Estudos de Coortes , Feminino , Avaliação Geriátrica , Nível de Saúde , Humanos , Itália , Masculino , Testes de Estado Mental e Demência , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Inquéritos e QuestionáriosRESUMO
Background: Chronic obstructive pulmonary disease (COPD) is a common, preventable, and manageable lung disease characterized by large heterogeneity in disease presentation and grades impairment. Inhaled corticosteroids (ICS) are commonly used to manage COPD/COPD-exacerbation. The patient's response is characterized by interindividual variability without disease progression/survival modification. Objectives: We hypothesize that a therapeutic intervention may be more effective if single nucleotide polymorphisms (SNPs) are investigated. Methods: In 71 COPD patients under pulmonary rehabilitation, a small number of powerful SNPs, selected according to current literature, were analyzed; namely the glucocorticoid receptor gene NR3C1 (rs6190/rs6189/rs41423247), the glucocorticoid-induced transcript 1 gene (GLCCI1 rs37972), and the related co-chaperone FKBP5 gene (rs4713916). MDR1 rs2032582 was also evaluated. Lung function outcomes were assessed. Results: A significant association with functional outcomes, namely FEV1 (forced expiration volume/one second) and 6MWD (six-minutes walking distance), was found for rs4713916 and weakly for rs37972. The genotype rs4713916(GA) and, in a lesser extent, the genotype rs37972(TT), were more favorable than the wild-type. Conclusions: Our study supports a possible picture of pharmacogenomic control for COPD intervention. rs4713916 and, possibly, rs37972 may be useful predictors of clinical outcome. These results may help to tailor an optimal dose for individual COPD patients based on their genetic makeup.
Assuntos
Corticosteroides/uso terapêutico , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/genética , Proteínas de Ligação a Tacrolimo/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Administração por Inalação , Corticosteroides/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Glucocorticoides/genética , Resultado do TratamentoRESUMO
Background and Objectives: Obstructive sleep apnea syndrome (OSAS) represents an independent risk factor for cardiovascular, metabolic and neurological events. Polysomnography is the gold-standard for the diagnosis, however is expensive and time-consuming and not suitable for widespread use. Breath analysis is an innovative, non-invasive technique, able to provide clinically relevant information about OSAS. This systematic review was aimed to outline available evidence on the role of exhaled breath analysis in OSAS, taking into account the techniques' level of adherence to the recently proposed technical standards. Materials and Methods: Articles reporting original data on exhaled breath analysis in OSAS were identified through a computerized and manual literature search and screened. Duplicate publications, case reports, case series, conference papers, expert opinions, comments, reviews and meta-analysis were excluded. Results: Fractional exhaled Nitric Oxide (FeNO) is higher in OSAS patients than controls, however its absolute value is within reported normal ranges. FeNO association with AHI is controversial, as well as its change after continuous positive airway pressure (C-PAP) therapy. Exhaled breath condensate (EBC) is acid in OSAS, cytokines and oxidative stress markers are elevated, they positively correlate with AHI and normalize after treatment. The analysis of volatile organic compounds (VOCs) by spectrometry or electronic nose is able to discriminate OSAS from healthy controls. The main technical issues regards the dilution of EBC and the lack of external validation in VOCs studies. Conclusions: Exhaled breath analysis has a promising role in the understanding of mechanisms underpinning OSAS and has demonstrated a clinical relevance in identifying individuals affected by the disease, in assessing the response to treatment and, potentially, to monitor patient's adherence to mechanical ventilation. Albeit the majority of the technical standards proposed by the ERS committee have been followed by existing papers, further work is needed to uniform the methodology.
Assuntos
Testes Respiratórios , Óxido Nítrico/análise , Apneia Obstrutiva do Sono/diagnóstico , Compostos Orgânicos Voláteis/análise , Nariz Eletrônico , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Apneia Obstrutiva do Sono/fisiopatologia , Análise EspectralRESUMO
BACKGROUND: COPD is an inflammatory airway disease characterised by progressive airflow limitation and air trapping, leading to lung hyperinflation and exercise limitation. Acute worsening of symptoms, including dyspnea, cough and sputum production, occurs during exacerbations which are associated with significantly reduced health related quality of life, and increased morbidity and mortality. Chronic bronchial mucus production and productive cough are risk factors for exacerbations. Medicines targeting bronchoconstriction and airway inflammation are the current mainstays of COPD therapy. However, there is growing concern with an increased risk of pneumonia in patients with COPD receiving regular inhaled corticosteroids and there is therefore a need to find safer alternative treatments. Previous studies have indicated that inhalation of unfractionated heparin (UFH) treats local inflammation, mucus hypersecretion and lung injury, without systemic anticoagulation, and is safe. Therefore, our primary objective was to demonstrate that inhaled UFH significantly improves lung function (FEV1) over 21 days of treatment in patients with COPD receiving pulmonary rehabilitation and that UFH provides a novel, safe and effective way of treating this complex disease. METHODS: Forty patients with moderate to very severe COPD admitted to the IRCCS San Raffaele Pisana Hospital for 21 days pulmonary rehabilitation were randomised to receive nebulised inhaled UFH (75,000 or 150,000 IU BID) or placebo for 21 days. All patients also received nebulised salbutamol (1 mg) and beclomethasone dipropionate (400 µg) BID over the same period. Lung function was measured at day 0, 7, 14 and 21 of treatment and at a follow-up visit 7 days post-treatment. Exercise capacity (6MWT) and dyspnoea (Borg score) were measured before and after treatment. In pre-clinical studies, the ability of basic proteins found in COPD sputum to neutralise the anticoagulant activity of heparin was determined using the AMAX heparin assay kit. MAIN RESULTS: At both doses, UFH significantly increased FVC following 7 days of treatment and 150,000 IU BID significantly increased FEV1 (+249 ± 69 ml compared with placebo) at this time, an effect maintained to the 28 day follow-up. Clinically significant improvement in exercise capacity and dyspnoea were seen after 21 days of treatment with both doses of UFH. There were no serious adverse events or effects on systemic coagulation. Pre-clinical studies demonstrated that the basic proteins lactoferrin, platelet factor-4 (PF-4), IL-8 and polyarginine, as a model of the eosinophil cationic protein (ECP), found in COPD sputum neutralise the anticoagulant activity of heparin. CONCLUSION: Inhaled nebulised UFH is safe and provides additional clinical benefit for patients with moderate to very severe COPD through effects that are independent of its anticoagulant activity.
Assuntos
Albuterol/administração & dosagem , Beclometasona/administração & dosagem , Heparina/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Idoso , Idoso de 80 Anos ou mais , Animais , Broncodilatadores/administração & dosagem , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Seguimentos , Volume Expiratório Forçado , Glucocorticoides/administração & dosagem , Heparina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores , Projetos Piloto , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Qualidade de Vida , Testes de Função Respiratória , Índice de Gravidade de Doença , Suínos , Fatores de TempoRESUMO
Chronic obstructive pulmonary disease (COPD) is characterized by long-term airflow limitation. Early-onset COPD in non-smoker subjects is ≥60 years and in the elderly is often associated with different comorbidities. Cognitive impairment is one of the most common feature in patients with COPD, and is associated with COPD severity and comorbidities. Cognitive impairment in COPD enhances the assistance requirement in different aspects of daily living, treatment adherence, and effectual self-management.This review describes various bioactive compounds of natural marine sources that modulate different targets shared by both COPD and cognitive impairment and hypothesizes a possible link between these two syndromes.
Assuntos
Organismos Aquáticos/química , Produtos Biológicos/uso terapêutico , Disfunção Cognitiva/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Idoso , Produtos Biológicos/isolamento & purificação , Biomarcadores/análise , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Comorbidade , Humanos , Incidência , Fármacos Neuroprotetores/isolamento & purificação , Fatores de RiscoRESUMO
Metabolic disorder has been frequently observed in chronic obstructive pulmonary disease (COPD) patients. However, the exact correlation between obesity, which is a complex metabolic disorder, and COPD remains controversial. The current study summarizes a variety of drugs from marine sources that have anti-obesity effects and proposed potential mechanisms by which lung function can be modulated with the anti-obesity activity. Considering the similar mechanism, such as inflammation, shared between obesity and COPD, the study suggests that marine derivatives that act on the adipose tissues to reduce inflammation may provide beneficial therapeutic effects in COPD subjects with high body mass index (BMI).
Assuntos
Organismos Aquáticos/química , Fatores Biológicos/química , Fatores Biológicos/farmacologia , Doenças Metabólicas/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Animais , HumanosRESUMO
Most patients with chronic obstructive pulmonary disease (COPD) share many risk factors and similar aetiological agents with erectile dysfunction (ED). Both conditions also cause serious interference with quality of life and sexual relationships. In general, ageing and chronic illness decrease sexual interest, sexual function, and testosterone levels. This observational study included 66 male patients referred to our centre with different grades of COPD. We studied the different correlations between COPD and ED. The data collected from each patient regarded the following features: demographic and social condition; smoking status; clinical status; spirometric measurements. In this group, COPD was diagnosed in 78.8% and ED was present in 83.3% with increased severity in presence of LUTS and nicotinism.
Assuntos
Disfunção Erétil/fisiopatologia , Sintomas do Trato Urinário Inferior/epidemiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Qualidade de Vida , Adulto , Fatores Etários , Idoso , Disfunção Erétil/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/etiologia , Fatores de Risco , Índice de Gravidade de Doença , Disfunções Sexuais Fisiológicas/epidemiologia , Fumar/epidemiologia , Espirometria , Testosterona/sangueRESUMO
In the present study, we examined whether there is a difference in the onset of bronchodilatation between formoterol/beclomethasone 12/200 µg Modulite and formoterol/budesonide 9/320 µg Turbuhaler in patients with COPD. We enrolled 28 patients with stable COPD. Both formoterol/beclomethasone and formoterol/budesonide elicited a larger mean FEV1-AUC0â15min than formoterol alone, whereas there was no significant difference between their FEV1-AUC0â15min. Also the change in FEV1 15 min after inhalation of formoterol/beclomethasone combination or formoterol/budesonide combination was greater than that induced by formoterol alone. This study confirms the rapid effect of the inhaled corticosteroid component when combined with formoterol and indicates that the onset of bronchodilation of formoterol/beclomethasone Modulite and formoterol/budesonide Turbuhaler are similar and greater than formoterol alone in patients with COPD.
Assuntos
Beclometasona/administração & dosagem , Broncodilatadores/farmacologia , Budesonida/administração & dosagem , Etanolaminas/farmacologia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Idoso , Estudos Cross-Over , Método Duplo-Cego , Etanolaminas/administração & dosagem , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Fumarato de Formoterol , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologiaRESUMO
Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with airways inflammation and lung parenchyma fibrosis. The primary goals of COPD treatment are to reduce symptoms and risk of exacerbations, therefore pulmonary rehabilitation is considered the key component of managing COPD patients. Oxidative airway damage, inflammation and reduction of endogenous antioxidant enzymes are known to play a crucial role in the pathogenesis of COPD. Recently, also natural antioxidants have been considered as they play an important role in metabolism, DNA repair and fighting the effects of oxidative stress. In this paper we evaluated the response of 105 elderly COPD patients to pulmonary rehabilitation (PR), based on high or low vegetable consumption, by analyzing clinical parameters and biological measurements at baseline and after completion of the three weeks PR. We found that daily vegetable intake in normal diet, without any specific intervention, can increase the probability to successfully respond to rehabilitation (65.4% of responders ate vegetables daily vs. 40.0% of non-responders, p = 0.033). The association was especially evident in subjects ≥ 80 year of age (OR = 17.0; p < 0.019). Three weeks of pulmonary rehabilitation are probably too short to reveal a reduction of the oxidative stress and DNA damage, but are enough to show an improvement in the patient's inflammatory state.
Assuntos
Dieta Saudável/métodos , Ingestão de Alimentos/fisiologia , Fenômenos Fisiológicos da Nutrição do Idoso/fisiologia , Doença Pulmonar Obstrutiva Crônica/reabilitação , Verduras , Administração por Inalação , Corticosteroides/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Broncodilatadores/administração & dosagem , Dano ao DNA/fisiologia , Inquéritos sobre Dietas , Feminino , Humanos , Inflamação , Pulmão/metabolismo , Masculino , Estresse Oxidativo/fisiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Resultado do TratamentoRESUMO
The "microbiome" is the operative term to refer to a collection of all taxa constituting microbial communities, such as bacteria, archaea, fungi and protists (originally microbiota). The microbiome consists of the indigenous microbial communities and of the host environment that they inhabit. Actually, it has been shown that there is a close relationship between the microbiome and human health and disease condition. Although, initially, the lung was considered sterile, actually, the existence of a healthy lung microbiome is usually accepted. Lung microbiome changes are reported in Chronic Obstructive Pulmonary Disease (COPD) and in its exacerbation. Viral and bacterial infections of the respiratory system are a major cause of COPD exacerbations (AECOPD) leading to increased local and systemic inflammation. Detection rates of virus in AECOPD are variable between 25-62% according to the detection method. The study of human airway and lung disease virome is quite recent and still very limited. The purpose of this review is to summarize recent findings on the lung microbiome composition with a special emphasis on virome in COPD and in AECOPD. Some drugs of natural origins active against resistant bacteria and virus are described.
Assuntos
Microbiota , Doença Pulmonar Obstrutiva Crônica , Infecções Bacterianas , Produtos Biológicos , Humanos , PulmãoRESUMO
Despite remarkable therapeutic advances have been made in the last few decades, non-small cell lung cancer (NSCLC) is still one of the leading causes of death worldwide. Brain metastases are a common complication of a wide range of human malignancies and in particular NSCLC. Brain-derived neurotrophic factor (BDNF), binding its high-affinity tyrosine kinase B receptor, has been shown to promote cancer progression and metastasis. We hereby investigated the expression of the BDNF and its TrkB receptor in its full-length and truncated isoform T1, in samples from primary adenocarcinomas (ADKs) of the lung and in their metastasis to evaluate if their expression was related to preferential tumor entry into the central nervous system (CNS). By immunohistochemistry, 80% of the ADKs that metastasize to central nervous system expressed TrkB receptor compared to 33% expressing of ADKs without CNS metastasis. Moreover, ADKs with CNS metastasis showed an elevated expression of the full-length TrkB receptor. The TrkB receptor FL/T1 ratio was statistically higher in primary ADKs with brain metastasis compared to ADKs without brain metastasis. Our data indicate that TrkB full-length isoform expression in primary ADK cells may be associated with higher risk to develop brain metastasis. Therefore, TrkB receptor may possess prognostic and therapeutic implications in lung ADK.
Assuntos
Neoplasias Encefálicas/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Mutação/genética , Receptor trkB/genética , Idoso , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Adesão Celular , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Receptor trkB/metabolismo , Esferoides Celulares/metabolismo , Esferoides Celulares/patologiaRESUMO
BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) and Cardiovascular Diseases (CV) Often Coexist. COPD and CVD are complex diseases characterized by a strict interaction between environment and genetic. The mechanisms linking these two diseases are complex, multifactorial and not entirely understood, influencing the therapeutic approach. COPD is characterized by several comorbidities, it hypothesized the treatment of cardiovascular co-morbidities that may reduce morbidity and mortality. Flavonoids are an important class of plant low molecular weight Secondary Metabolites (SMs). Convincing data from laboratory, epidemiological, and human clinical studies point the important effects on CVD risk prevention. OBJECTIVE: This review aims to provide up-to-date information on the ability of Flavonoids to reduce the CVD risk. CONCLUSION: Current studies support the potential of Flavonoids to prevent the risk of CVD. Well-designed clinical studies are suggested to evaluate advantages and limits of Flavonoids for managing CVD comorbidity in COPD.
Assuntos
Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Flavonoides/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Animais , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , HumanosRESUMO
BACKGROUND: The morbidity and mortality associated with tobacco smoking is well established. Nicotine is the addictive component of tobacco. Nicotine, through the non-neuronal α7nicotinic receptor, induces cell proliferation, neo-angiogenesis, epithelial to mesenchymal transition, and inhibits drug-induced apoptosis. OBJECTIVE: To understand the genetic, molecular and cellular biology of addiction, chronic obstructive pulmonary disease and lung cancer. METHODS: The search for papers to be included in the review was performed during the months of July- September 2018 in the following databases: PubMed (http://www.ncbi.nlm.nih.gov), Scopus (http://www.scopus.com), EMBASE (http://www.elsevier.com/online-tools/embase), and ISI Web of Knowledge (http://apps.webofknowledge.com/). The following searching terms: "nicotine", "nicotinic receptor", and "addiction" or "COPD" or "lung cancer" were used. Patents were retrieved in clinicaltrials.gov (https://clinicaltrials.gov/). All papers written in English were evaluated. The reference list of retrieved articles was also reviewed to identify other eligible studies that were not indexed by the above-mentioned databases. New experimental data on the ability of nicotine to promote transformation of human bronchial epithelial cells, exposed for one hour to Benzo[a]pyrene-7,8-diol-9-10-epoxide, are reported. RESULTS: Nicotinic receptors variants and nicotinic receptors upregulation are involved in addiction, chronic obstructive pulmonary disease and/or lung cancer. Nicotine through α7nicotinic receptor upregulation induces complete bronchial epithelial cells transformation. CONCLUSION: Genetic studies highlight the involvement of nicotinic receptors variants in addiction, chronic obstructive pulmonary disease and/or lung cancer. A future important step will be to translate these genetic findings to clinical practice. Interventions able to help smoking cessation in nicotine dependence subjects, under patent, are reported.
Assuntos
Neoplasias Pulmonares/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Agentes de Cessação do Hábito de Fumar/metabolismo , Fumar Tabaco/metabolismo , Tabagismo/metabolismo , Animais , Humanos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Antagonistas Nicotínicos/metabolismo , Antagonistas Nicotínicos/farmacologia , Antagonistas Nicotínicos/uso terapêutico , Patentes como Assunto , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Receptores Nicotínicos/metabolismo , Fatores de Risco , Abandono do Hábito de Fumar/métodos , Agentes de Cessação do Hábito de Fumar/farmacologia , Agentes de Cessação do Hábito de Fumar/uso terapêutico , Fumar Tabaco/tratamento farmacológico , Tabagismo/tratamento farmacológicoRESUMO
BACKGROUND: We report a comprehensive overview of current Chronic Obstructive Lung Disease (COPD) therapies and discuss the development of possible new pharmacological approaches based on "new" knowledge. Specifically, sensitivity/resistance to corticosteroids is evaluated with a special focus on the role of gene mutations in drug response. OBJECTIVE: Critically review the opportunities and the challenges occurring in the treatment of COPD. CONCLUSION: Findings from "omics" trials should be used to learn more about biological targeted drugs, and to select more specific drugs matching patient's distinctive molecular profile. Specific markers of inflammation such as the percentage of eosinophils are important in determining sensitivity/resistance to corticosteroids. Specific gene variations (Single nucleotide polymorphisms: SNPs) may influence drug sensitivity or resistance. Clinicians working in a real-world need to have a suitable interpretation of molecular results together with a guideline for the treatment and recommendations. Far more translational research is required before new results from omics techniques can be applied in personalized medicine in realworld settings.
Assuntos
Corticosteroides/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/genética , Resistência a Medicamentos/genética , Eosinófilos , Estudo de Associação Genômica Ampla , Humanos , Metabolômica , Mutação , Medicina de Precisão , Proteômica , Doença Pulmonar Obstrutiva Crônica/classificação , Doença Pulmonar Obstrutiva Crônica/terapiaRESUMO
BACKGROUND: We report a comprehensive overview of current COPD therapies from a real-world experience. OBJECTIVE: Critically review the opportunities and the challenges occurring in the real-world treatment of COPD. METHODS: This is a review that also report results from COPD patients treated with standardized therapy including pulmonary rehabilitation (Real World Data - RWD). CONCLUSION: Comprehensive assessment of COPD management requires strategies able to evaluate efficacy and usefulness in a real-world population, that take into account the interaction between experience and academic training, research, adherence to guidelines and judgments in order to plan the appropriate and optimum use of available strategies.
Assuntos
Doença Pulmonar Obstrutiva Crônica/terapia , Adulto , Idoso , Comorbidade , Análise de Dados , Prática Clínica Baseada em Evidências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Estudos RetrospectivosRESUMO
Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by severe respiratory symptoms. COPD shows several hallmarks of aging, and an increased oxidative stress, which is responsible for different clinical and molecular COPD features, including an increased frequency of DNA damage. The current pharmacological treatment options for COPD are mostly symptomatic, and generally do not influence disease progression and survival. In this framework, pulmonary rehabilitation is the most effective therapeutic strategy to improve physical performance, reducing hospital readmissions and mortality. Response to rehabilitation may greatly differ among patients calling for a personalized treatment. In this paper we will investigate in a group of COPD patients those variables that may predict the response to a program of pulmonary rehabilitation, integrating clinical parameters with cellular and molecular measurements, offering the potential for more effective and individualized treatment options. A group of 89 consecutive COPD patients admitted to a 3-weeks Pulmonary Rehabilitation (PR) program were evaluated for clinical and biological parameters at baseline and after completion of PR. DNA fragmentation in cryopreserved lymphocytes was compared by visual scoring and using the Comet Assay IV analysis system. The comparison of DNA damage before and after PR showed a highly significant increase from 19.6 ± 7.3 at admission to 21.8 ± 7.2 after three weeks of treatment, with a significant increase of 2.46 points (p < 0.001). Higher levels of DNA damage were observed in the group of non- responders and in those patients receiving oxygen therapy. The overall variation of %TI during treatment significantly correlated with the level of pCO2 at admission and negatively with the level of IL-6 at admission. Measuring the frequency of DNA damage in COPD patients undergoing pulmonary rehabilitation may provide a meaningful biological marker of response and should be considered as additional diagnostic and prognostic criterion for personalized rehabilitation programs.
Assuntos
Proteína C-Reativa/análise , Ensaio Cometa , Dano ao DNA , Instabilidade Genômica , Interleucina-6/sangue , Doença Pulmonar Obstrutiva Crônica/genética , Terapia Respiratória , Corticosteroides/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Broncodilatadores/uso terapêutico , Terapia Combinada , Quebras de DNA de Cadeia Simples , Fragmentação do DNA , Progressão da Doença , Feminino , Humanos , Linfócitos/química , Masculino , Antagonistas Muscarínicos/uso terapêutico , Oxigenoterapia , Medicina de Precisão , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/reabilitação , Doença Pulmonar Obstrutiva Crônica/terapia , Índice de Gravidade de DoençaRESUMO
PURPOSE: There is a lack of consensus on the most appropriate early diagnostic strategy, criteria for early access to treatment and follow-up approach for patients with COPD. MATERIALS AND METHODS: A Delphi consensus project investigated the early management of COPD. We formulated two questionnaires for completion by pneumologists in Italy. RESULTS: A total of 207 specialists completed questionnaire 1 and 184 of them questionnaire 2, between November 2016 and October 2017. Early diagnosis of COPD was considered uncommon for 93.2% of the expert panel. Regardless of the definition of "early diagnosis" - a diagnosis made before the clinical manifestation of the disease for most responders (60.4%) - experts were confident of the positive effects of early disease management, which they consider is effective in modifying the natural history of the disease. Lack of awareness of the disease was considered the first limiting factor to early COPD management for 78% of respondents. The most effective steps to reduce functional decline were considered to be smoking cessation, followed by long-acting ß2-agonist (LABA)/long-acting muscarinic antagonist (LAMA), LAMA, LABA, and finally inhaled corticosteroid/LABA (P<0.01 for each paired comparison). Specialists considered it "inappropriate" for general practitioners to perform both the early diagnosis and therapy of COPD without the involvement of a specialist. CONCLUSION: Early management of COPD is uncommon, and although data on the effects of early disease management on long-term outcomes are limited, Italian experts are confident of the clinical efficacy of this approach.
Assuntos
Corticosteroides/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Broncodilatadores/administração & dosagem , Intervenção Médica Precoce/normas , Antagonistas Muscarínicos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Adulto , Consenso , Técnica Delphi , Combinação de Medicamentos , Diagnóstico Precoce , Medicina Baseada em Evidências , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto/normas , Valor Preditivo dos Testes , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Inquéritos e Questionários , Resultado do TratamentoRESUMO
BACKGROUND: To investigate the efficacy of an inpatient Pulmonary Rehabilitation program (i-PR) after lung resection (LR) for Non-Small Cell Lung Cancer (NSCLC). PATIENTS AND METHODS: From January 2001 to December 2004, 211 out of 618 patients who underwent LR were considered eligible for i-PR. Twenty-five patients accepted the i-PR and were included in the case group. The remaining 186 who refused i-PR were taken as controls. RESULTS: The two study groups were comparable for demographic and surgical characteristics, as well as for the peri-operative morbidity (4% in the controls and 3% among patients undergoing i-PR). Most functional parameters among treated patients were improved when baseline versus 1-month figures were compared, despite the strong correction for multiple comparison limited statistical significance to Borg scale dyspnoea on exertion - median - (2 versus 0; p<0.01); pH (7.45 versus 7.42; p<0.05); timed walk-6MWD (297.8m versus 393.4m; p<0.01) and Hb saturation during 6MWD (95.4% versus 93.9%; p<0.05). On the contrary, global function in the group of controls was homogeneously decreased (FEV(1) and PEF p<0.01) after operation. The comparison of treated and untreated patients 1 month after the operation did not show any significant difference in terms of FEV(1), FVC, PEF, distance, Hb saturation, and KCO that instead were homogeneously and significantly worse at baseline (before the surgical operation) in the case group. CONCLUSIONS: Respiratory Function and exercise capacity significantly improve following a post-operative 4-week i-PR in lung resected patients. i-PR could be regarded as a component of the management of patients who have undergone LR for cancer.
Assuntos
Neoplasias Pulmonares/reabilitação , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Carcinoma Pulmonar de Células não Pequenas , Dispneia/etiologia , Dispneia/fisiopatologia , Seguimentos , Volume Expiratório Forçado , Humanos , Neoplasias Pulmonares/fisiopatologia , Período Pós-Operatório , Troca Gasosa Pulmonar , Estudos Retrospectivos , Espirometria , Taxa de Sobrevida , Fatores de Tempo , CaminhadaRESUMO
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