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1.
Intern Med ; 60(13): 2027-2032, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34193773

RESUMO

Objective Bronchial thermoplasty (BT) is a bronchoscopic procedure for patients with severe asthma. Although it has been suggested that BT works by reducing airway smooth muscle, the detailed mechanism underlying its effects is still unknown. Methods We performed xenon ventilation computed tomography (Xe-CT) before each BT procedure and six weeks after the third treatment to assess the improvement in lung ventilation at each separate lung region. The air trapping index in each lobe was defined as the mean trapping value (0: none, 1: mild, 2: moderate, and 3: severe) of the included segments. Patients and Materials Four patients were included. Results Asthma symptoms were improved after BT. The comparison of the scores at baseline with those after the third treatment showed that the air trapping index was improved in both the treated and untreated regions. However, neither the pulmonary function nor the exhaled nitric oxide was improved. Conclusion Using Xe-CT, we successfully evaluated the air trapping in patients who underwent BT. The improvement in asthma symptoms by BT may be related to the amelioration of peripheral lung ventilation in both the treated and untreated regions.


Assuntos
Asma , Termoplastia Brônquica , Asma/diagnóstico por imagem , Asma/terapia , Humanos , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Tomografia Computadorizada por Raios X , Xenônio
2.
Int J Mol Sci ; 22(12)2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34204710

RESUMO

Autophagy is a major self-degradative process through which cytoplasmic material, including damaged organelles and proteins, are delivered and degraded in the lysosome. Autophagy represents a dynamic recycling system that produces new building blocks and energy, essential for cellular renovation, physiology, and homeostasis. Principal autophagy triggers include starvation, pathogens, and stress. Autophagy plays also a pivotal role in immune response regulation, including immune cell differentiation, antigen presentation and the generation of T effector responses, the development of protective immunity against pathogens, and the coordination of immunometabolic signals. A plethora of studies propose that both impaired and overactive autophagic processes contribute to the pathogenesis of human disorders, including infections, cancer, atherosclerosis, autoimmune and neurodegenerative diseases. Autophagy has been also implicated in the development and progression of allergen-driven airway inflammation and remodeling. Here, we provide an overview of recent studies pertinent to the biology of autophagy and molecular pathways controlling its activation, we discuss autophagy-mediated beneficial and detrimental effects in animal models of allergic diseases and illuminate new advances on the role of autophagy in the pathogenesis of human asthma. We conclude contemplating the potential of targeting autophagy as a novel therapeutic approach for the management of allergic responses and linked asthmatic disease.


Assuntos
Asma/complicações , Asma/patologia , Autofagia , Hipersensibilidade/complicações , Hipersensibilidade/patologia , Animais , Asma/imunologia , Autofagia/genética , Humanos , Hipersensibilidade/imunologia , Inflamação/patologia , Modelos Biológicos , Transcrição Genética
3.
Int J Mol Sci ; 22(12)2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34204767

RESUMO

Increased airway wall thickness and remodeling of bronchial mucosa are characteristic of asthma and may arise from altered integrin signaling on airway cells. Here, we analyzed the expression of ß1-subfamily integrins on blood and airway cells (flow cytometry), inflammatory biomarkers in serum and bronchoalveolar lavage, reticular basement membrane (RBM) thickness and collagen deposits in the mucosa (histology), and airway geometry (CT-imaging) in 92 asthma patients (persistent airflow limitation subtype: n = 47) and 36 controls. Persistent airflow limitation was associated with type-2 inflammation, elevated soluble α2 integrin chain, and changes in the bronchial wall geometry. Both subtypes of asthma showed thicker RBM than control, but collagen deposition and epithelial α1 and α2 integrins staining were similar. Type-I collagen accumulation and RBM thickness were inversely related to the epithelial expression of the α2 integrin chain. Expression of α2ß1 integrin on T-cells and eosinophils was not altered in asthma. Collagen I deposits were, however, more abundant in patients with lower α2ß1 integrin on blood and airway CD8+ T-cells. Thicker airway walls in CT were associated with lower α2 integrin chain on blood CD4+ T-cells and airway eosinophils. Our data suggest that α2ß1 integrin on inflammatory and epithelial cells may protect against airway remodeling advancement in asthma.


Assuntos
Asma/metabolismo , Asma/patologia , Progressão da Doença , Integrina alfa2beta1/metabolismo , Pulmão/patologia , Substâncias Protetoras/metabolismo , Adulto , Idoso , Remodelação das Vias Aéreas , Asma/sangue , Asma/imunologia , Membrana Basal/patologia , Brônquios/diagnóstico por imagem , Brônquios/patologia , Brônquios/fisiopatologia , Lavagem Broncoalveolar , Feminino , Humanos , Inflamação/patologia , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Membrana Mucosa/patologia , Subunidades Proteicas/metabolismo , Ventilação Pulmonar , Solubilidade , Linfócitos T/metabolismo , Tomografia Computadorizada por Raios X
4.
Respir Res ; 22(1): 200, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34233672

RESUMO

BACKGROUND: The first step in SARS-CoV-2 infection is binding of the virus to angiotensin converting enzyme 2 (ACE2) on the airway epithelium. Asthma affects over 300 million people world-wide, many of whom may encounter SARS-CoV-2. Epidemiologic data suggests that asthmatics who get infected may be at increased risk of more severe disease. Our objective was to assess whether maintenance inhaled corticosteroids (ICS), a major treatment for asthma, is associated with airway ACE2 expression in asthmatics. METHODS: Large airway epithelium (LAE) of asthmatics treated with maintenance ICS (ICS+), asthmatics not treated with ICS (ICS-), and healthy controls (controls) was analyzed for expression of ACE2 and other coronavirus infection-related genes using microarrays. RESULTS: As a group, there was no difference in LAE ACE2 expression in all asthmatics vs controls. In contrast, subgroup analysis demonstrated that LAE ACE2 expression was higher in asthmatics ICS+ compared to ICS‾ and ACE2 expression was higher in male ICS+ compared to female ICS+ and ICS‾ of either sex. ACE2 expression did not correlate with serum IgE, absolute eosinophil level, or change in FEV1 in response to bronchodilators in either ICS- or ICS+. CONCLUSION: Airway ACE2 expression is increased in asthmatics on long-term treatment with ICS, an observation that should be taken into consideration when assessing the use of inhaled corticosteroids during the pandemic.


Assuntos
Corticosteroides/administração & dosagem , Enzima de Conversão de Angiotensina 2/metabolismo , Asma/tratamento farmacológico , Receptores Virais/metabolismo , Mucosa Respiratória/efeitos dos fármacos , Administração por Inalação , Corticosteroides/efeitos adversos , Adulto , Enzima de Conversão de Angiotensina 2/genética , Asma/diagnóstico , Asma/enzimologia , Asma/genética , COVID-19/enzimologia , COVID-19/virologia , Estudos de Casos e Controles , Feminino , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , Receptores Virais/genética , Mucosa Respiratória/enzimologia , SARS-CoV-2/patogenicidade , Fatores de Tempo , Regulação para Cima , Internalização do Vírus , Adulto Jovem
6.
J Allergy Clin Immunol Pract ; 9(7): 2939, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34246441
7.
Front Public Health ; 9: 674843, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249841

RESUMO

The community health worker (CHW) asthma home-visiting model developed by Public Health-Seattle & King County (PHSKC) is an evidence-based approach proven to improve health outcomes and quality of life. In addition, it has been shown to be an effective and culturally appropriate approach to helping people with asthma understand the environmental and behavioral causes of uncontrolled asthma, while acquiring the skills they need to control their asthma. This paper describes the development and implementation of training curricula for CHWs and supervisors in the asthma home visiting program. To facilitate dissemination, this program took advantage of the current healthcare landscape in Washington State resulting from Centers for Medicare & Medicaid Services (CMS) approval of the 1115 Medicaid Waiver project. Key aspects of the training program development included: (1) Engagement: forming a Community Advisory Board with multiple stakeholders to help prioritize training content; (2) Curriculum Development: building the training on evidence-based home-visit protocols previously developed at PHSKC; (3) Implementation of the training program; (4) Evaluation of the training; and (5) Adaptation of the training based on lessons learned. We describe key factors in the training program's improvement including the use of a community-based participatory approach to engage stakeholders at multiple phases of the project and ensure regional adaption; combining in-person and online modules for delivery; and holding learning collaboratives for post-training and technical support. We also outline our training program evaluation plan and the planned evaluation of the home visit program which the trainees will deliver, both of which follow the RE-AIM framework. However, because the COVID-19 pandemic has curtailed training activities and prohibited the trainees from implementation of these CHW home visit practices, our evaluation is currently incomplete. Therefore, this case study provides insight into the adaptation of the training program, but not the delivery of the home visit program, the outcomes of which remain to be seen.


Assuntos
Asma , COVID-19 , Idoso , Asma/terapia , Agentes Comunitários de Saúde , Visita Domiciliar , Humanos , Medicare , Pandemias , Qualidade de Vida , SARS-CoV-2 , Estados Unidos , Washington
8.
BMJ Open Respir Res ; 8(1)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34193433

RESUMO

INTRODUCTION: Almost half of all school-age children with bronchopulmonary dysplasia (BPD) have asthma-like symptoms and more suffer from lung function deficits. While air pollution and indoor respiratory irritants are known to affect high-risk populations of children, few studies have objectively evaluated environmental contributions to long-term respiratory morbidity in this population. This study aimed to examine the role of indoor environmental exposures on respiratory morbidity in children with BPD. METHODS AND ANALYSIS: The Air quality, Environment and Respiratory Ouctomes in BPD (AERO-BPD) study is a prospective, single-centre observational study that will enrol a unique cohort of 240 children with BPD and carefully characterise participants and their indoor home environmental exposures. Measures of indoor air quality constituents will assess the relationship of nitrogen dioxide (NO2), particulate matter (PM2.5), nitric oxide (NO), temperature and humidity, as well as dust concentrations of allergens, with concurrently measured respiratory symptoms and lung function.Adaptations to the research protocol due to the SARS-CoV-2 pandemic included remote home environment and participant assessments. ETHICS AND DISSEMINATION: Study protocol was approved by the Boston Children's Hospital Committee on Clinical Investigation. Dissemination will be in the form of peer-reviewed publications and participant information products. TRIAL REGISTRATION NUMBER: NCT04107701.


Assuntos
Poluição do Ar/efeitos adversos , Displasia Broncopulmonar/epidemiologia , Exposição Ambiental/efeitos adversos , Material Particulado/efeitos adversos , Poluição do Ar em Ambientes Fechados/análise , Alérgenos , Asma/epidemiologia , Asma/fisiopatologia , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/fisiopatologia , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/virologia , Criança , Estudos de Coortes , Exposição Ambiental/estatística & dados numéricos , Feminino , Humanos , Umidade , Masculino , Óxido Nítrico/análise , Dióxido de Nitrogênio/análise , Estudos Prospectivos , Testes de Função Respiratória/métodos , SARS-CoV-2/genética , Temperatura
10.
Mayo Clin Proc ; 96(7): 1955-1969, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34218868

RESUMO

There are marked sex differences in asthma prevalence and severity. Sex hormones play a central role in these sex biases and directly interact with multiple key cells involved in the pathogenesis of asthma. Here we review the known effects of estrogen, progesterone, and testosterone on airway epithelial cells, airway smooth muscle cells, the mononuclear phagocyte system, innate lymphoid cells, eosinophils, mast cells, T cells, and B cells, all in the context of asthma. Furthermore, we explore unresolved clinical questions, such as the role of sex hormones in the link between asthma and obesity.


Assuntos
Asma , Hormônios Esteroides Gonadais/metabolismo , Mucosa Respiratória/metabolismo , Asma/imunologia , Asma/metabolismo , Asma/patologia , Humanos , Imunidade Celular , Imunidade Inata , Fatores Sexuais
11.
Se Pu ; 39(3): 281-290, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-34227309

RESUMO

Respiratory syncytial virus (RSV) can cause lower respiratory tract infections, such as bronchiolitis in infants. In China, traditional asthma-relieving medicine has numerous clinical applications in the treatment of RSV infections. However, due to the complexity of the traditional Chinese medicine system, its therapeutic mechanism and main pharmacological components remain unclear. Metabolomics can be used to analyze the efficacy of traditional Chinese medicine to provide modern scientific evidence for such treatments. In this study, an animal model experiment was performed with seven groups of three-week-old rats. The model group and five intervention groups were inoculated nasally with RSV for three consecutive days, and the normal group was treated with the same amount of saline for three consecutive days under the same conditions. In parallel, the five intervention groups were treated separately with the following via intragastric administration for seven consecutive days: asthma-relieving traditional Chinese medicine decoction, its three constituent agents (ascending (xuan) therapy, descending (jiang) therapy, pyretic clearing (qing) therapy), and ribavirin. Both normal group and RSV model group were administered with normal saline via intragastric administration as controls for seven consecutive days. The fundus plasma of rats in each group was collected on day 0, day 3, and day 7. Liquid chromatography-mass spectrometry-based untargeted metabolomics analysis was performed to investigate the changes in the metabolome after RSV infection, the effects of the asthma-relieving decoction on the regulation of metabolites related to RSV infection, and the primary source of efficacy. The detected metabolite ions were corrected using internal standards. Multivariate analysis of ions with an RSD value of less than 30% in quality control (QC) samples was used to construct principal component analysis models to monitor the overall metabolic changes of each group. The results showed that, during RSV infection and treatment, the asthma-relieving decoction and the positive control ribavirin had similar effects on the overall metabolic regulation of RSV-infected rats. Among the three asthma-relieving decoction constituent agents, the ascending (xuan) therapy agents which was composed of ephedra and ginkgo had a closer metabolic regulation effect with asthma-relieving decoction, and might be the main source of pharmacological efficacy. Based on the retention time, m/z value and tandem mass spectra in the database established by our laboratory, a total of 150 metabolites were identified. Paired t-tests were performed using data of the identified metabolites before and after RSV infection in each group, and it was found that 83 metabolite levels significantly changed after RSV infection, indicating that RSV infection could lead to disorders of multiple metabolic pathways in rats. The altered pathways included aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine, and tryptophan biosynthesis, primary bile acid biosynthesis, phenylalanine metabolism and sphingomyelin metabolism. On the third day, the asthma-relieving decoction had regulatory effects on several metabolites such as bile acids, amino acids, organic acids, lipids, etc. Among the three asthma-relieving decoction constituent agents, the ascending (xuan) therapy agents had more similar effects on the regulation of metabolites with the asthma-relieving decoction. On the other hand, the descending (jiang) therapy agents and pyretic clearing (qing) therapy agents down-regulated the abnormal increase in acylcarnitine caused by the RSV infection. Additionally, both asthma-relieving decoction and its constituent agents could maintain the stability of the immune system and metabolism of the intestinal flora in rats. This study used metabolomics to evaluate the efficacy of an asthma-relieving decoction and demonstrate the metabolites and the corresponding changes after asthma-relieving decoction-based treatment. It provides theoretical support for research on the therapeutic mechanism and active ingredients of asthma-relieving decoction.


Assuntos
Asma , Medicamentos de Ervas Chinesas , Metabolômica , Infecções por Vírus Respiratório Sincicial , Animais , Asma/tratamento farmacológico , China , Cromatografia Líquida , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Espectrometria de Massas , Medicina Tradicional Chinesa , Ratos , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico
12.
J Allergy Clin Immunol Pract ; 9(7): 2567-2576, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34246433

RESUMO

Acute exacerbations cause significant morbidity and mortality in children with asthma worldwide. Although exacerbations can be minor and transient, in some children they are recurrent and significantly adversely impact quality of life. Children with frequent exacerbations account for a disproportionate amount of unscheduled care in nonprimary health facilities. Frequent exacerbators are often prescribed controller medications, but poor adherence is common. Major predictors for asthma exacerbations include genetic, social, comorbid, biological, and environmental factors. Although virus infections are a key trigger for exacerbations, other environmental factors also significantly increase risk. A previous exacerbation is a major risk factor for future exacerbations and thus identifies children to target for prevention of future episodes. In this review, we discuss both modifiable and fixed factors associated with asthma exacerbations, how to assess children for risk, and which pharmacological and nonpharmacological interventions may be of benefit. Finally, we review the current evidence around treatment within the outpatient setting for an emerging exacerbation.


Assuntos
Asma , Qualidade de Vida , Assistência Ambulatorial , Asma/tratamento farmacológico , Asma/epidemiologia , Criança , Progressão da Doença , Humanos , Pacientes Ambulatoriais
13.
J Allergy Clin Immunol Pract ; 9(7): 2578-2586, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34246434

RESUMO

Asthma exacerbations are major contributors to disease morbidity in patients of all ages. To develop strategies that reduce the disease burden from exacerbations, it is helpful to review current concepts about the risk factors for asthma attacks and current approaches for prevention and treatment. Multiple factors contribute as risks and to the development of asthma exacerbations, including allergic and infectious processes. Viral respiratory infections, primarily from rhinoviruses, are the dominant exacerbating cause for most asthma patients. Allergic sensitization and allergen exposure contribute directly and enhance susceptibility for respiratory viral infections. Respiratory viruses infect airway epithelium to promote underlying type 2 inflammation with eosinophils, the predominant cellular component of increased inflammation. Deficiencies of antiviral interferon responses and generation have been identified that increase susceptibility to viral infections in asthma. Exacerbation treatment focuses on reducing airflow obstruction and suppressing inflammation, followed by improving long-term asthma control. Increasing concern exists regarding the side effects associated with frequent systemic corticosteroid use. A major advance has been the selective use of biologics to prevent exacerbations, primarily in patients with existing type 2 inflammation. Future research to prevent exacerbations is being directed toward antiviral activity and a more encompassing regulation of underlying airway inflammation.


Assuntos
Asma , Hipersensibilidade , Viroses , Adulto , Asma/tratamento farmacológico , Asma/prevenção & controle , Humanos , Sistema Respiratório , Rhinovirus
14.
J Allergy Clin Immunol Pract ; 9(7): 2588-2597, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34246435

RESUMO

There have been considerable advances in our understanding of asthmatic airway inflammation, resulting in a paradigm shift of classifying individuals on the basis of either the presence or the absence of type 2 (T2) inflammatory markers. Several novel monoclonal antibody therapies targeting T2 cytokines have demonstrated significant clinical effects including reductions in acute exacerbations and improvements in asthma-related quality of life and lung function for individuals with T2-high asthma. However, there have been fewer advancements in developing therapies for those without evidence of T2 airway inflammation (so-called non-T2 asthma). Here, we review the heterogeneity of molecular mechanisms responsible for initiation and regulation of non-T2 inflammation and discuss both current and potential future therapeutic options for individuals with non-T2 asthma.


Assuntos
Antiasmáticos , Asma , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Citocinas , Humanos , Inflamação , Qualidade de Vida
18.
Acta Biomed ; 92(3): e2021206, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34212923

RESUMO

BACKGROUND: Asthma is a chronic inflammatory disease of airways which accounts for a huge economic, morbidity and mortality burden. There are different cytokines that contribute to asthma pathophysiology. Learning about these cytokines leads to attaining novel anti-inflammatory treatments for asthma control. OBJECTIVES: The objective of this study is to investigate the association between interleukin-9 serum level and gene polymorphism with asthma susceptibility. METHODS: This was a case-control study of 70 asthmatic patients and 77 healthy control adults aged 18-60. Asthma diagnosis and severity were based on physician diagnosis, pulmonary function test (PFT) and 2016 guild line of Global Initiative for Asthma (GINA). Interleukin 9(IL -9) serum level was measured using sandwich enzyme linked immunosorbent assay.  IL9 promoter single nucleotide polymorphism (SNP) (rs2069882) was also assessed using Real-Time PCR System. RESULTS: There was no significant association between IL-9 SNP polymorphism and asthma. IL-9 serum level was significantly associated with asthma susceptibility (p value= 0.016) and absolute eosinophil count (AEC) (P value=0.033) however its corelation with atopic asthma type, asthma sivierity and Immunoglubin E serum level were not statistically significant. CONCLUSION: Although there was no association between IL-9 SNP and asthma, but IL-9 serum level was significantly correlated with asthma susceptibility and AEC.


Assuntos
Asma , Interleucina-9/sangue , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Asma/genética , Estudos de Casos e Controles , Humanos , Pessoa de Meia-Idade , Testes de Função Respiratória , Adulto Jovem
19.
Int J Mol Sci ; 22(13)2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206847

RESUMO

Recently, we clarified the function of mediastinal fat-associated lymphoid clusters (MFALCs) in the progression of several respiratory diseases. However, their role has not yet been identified in the lung asthmatic condition. Hence, we compared the immune cells in lung and MFALCs of C57BL/6N mice on days 3 and 7 following intranasal instillation of either papain (papain group "PG") or phosphate buffer saline (PBS) (vehicle group "VG"). The PG showed significantly prominent MFALCs, numerous goblet cells (GCs), and higher index ratios of different immune cells (macrophages, natural helper cells (NHC), B- and T-lymphocytes) within the MFALCs and lung than in the VG on both days 3 and 7. Interestingly, a tendency of decreased size of MFALCs and a significant reduction in the number of GCs and immune cells were observed within the MFALCs and lung in the PG on day 7 than on day 3. Furthermore, the quantitative parameters of these immune cells in MFALCs were significantly and positively correlated with the size of MFALCs and immune cells in the lung. This suggested that the possible crosstalk between immune cells within MFALCs and the lung could play a critical role in the progression and recovery of the acute inflammatory lung asthma.


Assuntos
Asma/imunologia , Pulmão/imunologia , Tecido Linfoide/imunologia , Macrófagos/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Tecido Adiposo/imunologia , Animais , Células Cultivadas , Células Caliciformes/imunologia , Imunidade Inata , Masculino , Mediastino , Camundongos , Camundongos Endogâmicos C57BL
20.
Acta Biomed ; 92(3): e2021165, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34212932

RESUMO

To date, there is still a lack of unanimity regarding the definition of exacerbation of asthma and COPD and about objective measurements in the currently used criteria. The aim of our study was to conduct a survey among general practitioners (GPs) and pulmonologists regarding the clinical criteria arbitrarily considered as important to start a course of systemic corticoids and/or antibiotics in asthma and COPD. We conducted a survey enrolling 50 general practitioners (GPs) and 50 pulmonologists, that evaluated the clinical criteria arbitrated as essential to start a course of systemic corticosteroids or antibiotics during asthma and/or COPD exacerbations. Our results demonstrated incongruities between GPs and pulmonologist and within the same professional category concerning systemic corticosteroids. Conversely, we showed higher consensus between and within the groups about criteria to prescribe antibiotics.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Corticosteroides/uso terapêutico , Antibacterianos/uso terapêutico , Asma/tratamento farmacológico , Humanos , Itália , Prescrições , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Pneumologistas
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