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2.
Expert Opin Investig Drugs ; 28(10): 827-833, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31474120

RESUMO

Introduction: A compound that simultaneously inhibits PDE3 and PDE4 should increase airway caliber by relaxing the smooth muscle and, simultaneously, suppress airway inflammatory responses. Ensifentrine (RPL554) is considered a PDE3/4 inhibitor, although its affinity for PDE3 is 3,440 times higher than that for PDE4, that is under clinical development for the treatment of asthma and COPD and, potentially, cystic fibrosis. Areas covered: We analyze the development of this molecule from its basic pharmacology to the present clinical Phase II studies. Expert opinion: Ensifentrine is an interesting drug but there is a lack of solid studies that still does not allow us to correctly allocate this molecule in the current COPD and even asthma therapeutic armamentarium. Furthermore, apparently ensifentrine has not yet entered Phase III clinical development and, in any case, there is no reliable evidence of its ability to elicit an anti-inflammatory activity in patients with COPD or asthma. Therefore, the real anti-inflammatory profile of ensifentrine must be clarified with new studies of basic pharmacology and adequate clinical studies specifically designed. However, at present the most intriguing perspective is linked to its possible use in the treatment of cystic fibrosis, also considering the lack of valid therapeutic options for this disease.


Assuntos
Asma/tratamento farmacológico , Isoquinolinas/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Pirimidinonas/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Asma/fisiopatologia , Fibrose Cística/tratamento farmacológico , Fibrose Cística/fisiopatologia , Desenvolvimento de Medicamentos/métodos , Humanos , Isoquinolinas/farmacologia , Inibidores da Fosfodiesterase 3/farmacologia , Inibidores da Fosfodiesterase 3/uso terapêutico , Inibidores da Fosfodiesterase 4/farmacologia , Inibidores da Fosfodiesterase 4/uso terapêutico , Pirimidinonas/farmacologia
3.
Georgian Med News ; (292-293): 68-71, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31560666

RESUMO

The aim of our study was a comparative description of the state of bronchial sensitivity to nonspecific stimuli in respiratory asymptomatic children and children with bronchial asthma. We investigated a total of 242 children aged between 7 and 14 years. The group of respiratory asymptomatic children included 100 examined and 142 had an established diagnosis of atopic bronchial asthma at the I, II, and III stages in the phase of remission. The study was conducted in accordance with the principles of bioethics. In order to investigate the nature of the reaction, bronchoprovocation test with the acetylcholine (bronchoconstrictor) was conducted in children. The test involved monitoring the state of bronchial patency under the effect of increasing concentrations of the stimulus. The acetylcholine test showed that the state of nonspecific bronchial hypersensitivity was expressed in the most of patients with asthma and in 5% of respiratory asymptomatic children. Comparison of the results of the nonspecific bronchial sensitivity and diagnosed airway obstruction did not reveal the relationship between these characteristics. The findings suggest that the presence of nonspecific bronchial hypersensitivity is a congenital and not an acquired phenomenon.


Assuntos
Obstrução das Vias Respiratórias/etiologia , Asma/fisiopatologia , Brônquios/fisiopatologia , Hiper-Reatividade Brônquica/fisiopatologia , Hipersensibilidade Imediata/complicações , Adolescente , Obstrução das Vias Respiratórias/diagnóstico , Obstrução das Vias Respiratórias/fisiopatologia , Asma/etiologia , Hiper-Reatividade Brônquica/diagnóstico , Testes de Provocação Brônquica , Criança , Humanos
4.
Expert Opin Investig Drugs ; 28(11): 931-940, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31549891

RESUMO

Introduction: Thymic stromal lymphopoietin (TSLP) is overexpressed in the airways of severe asthmatics and is an upstream cytokine that orchestrates inflammatory responses in asthma. TSLP exerts its effects by binding to a high affinity heteromeric receptor complex composed of TSLPR and IL-7Rα. An association of polymorphisms in TSLP with airway hyperresponsiveness, IgE, eosinophilia and asthma has been documented. TSLP has been implicated in asthma pathophysiology. Tezepelumab is a first-in-class human monoclonal antibody that binds to TSLP, thus inhibiting its interaction with TSLP receptor complex. Tezepelumab given as an add-on-therapy to patients with severe uncontrolled asthma has shown safety, tolerability and efficacy. Several trials are evaluating the long-term safety and the efficacy of tezepelumab in adults and adolescents with severe uncontrolled asthma.Areas covered: We provide an overview of the monoclonal antibody therapeutics market for severe uncontrolled asthma, examine the underlying pathophysiology that drives TSLP and discuss the use of tezepelumab for the treatment of severe uncontrolled asthma,Expert opinion: TSLP is a promising target for T2-high and perhaps some patients with T2-low asthma. The results of preliminary clinical trials are encouraging. Several unanswered questions concerning basic pathophysiological aspects of TSLP variants, the long-term safety and efficacy of tezepelumab with different phenotypes/endotypes of asthma should be addressed.


Assuntos
Antiasmáticos/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Asma/tratamento farmacológico , Adolescente , Adulto , Animais , Antiasmáticos/efeitos adversos , Antiasmáticos/farmacologia , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacologia , Asma/imunologia , Asma/fisiopatologia , Citocinas/imunologia , Humanos , Índice de Gravidade de Doença
5.
Zhonghua Nei Ke Za Zhi ; 58(9): 680-684, 2019 Sep 01.
Artigo em Chinês | MEDLINE | ID: mdl-31461820

RESUMO

Objective: To analyze the clinical features and airway inflammatory phenotypes in patients with severe asthma. Methods: Patients with severe asthma were recruited in this cross-sectional study in our center. History of asthma, blood and sputum samples, and respiratory function were tested and recorded. The phenotypes of inflammation in airway were evaluated. Results: A total of 35 asthmatic patients with the mean age 41.4 years were involved in this study from January 2013 to December 2013. The disease duration were (14.3±13.6) years with mostly male in China-Japan Friendship Hospital. Thirteen patients reported the history of smoking. Twenty-one patients had the complications such as allergic rhinitis, followed by chronic rhinosinusitis of 11 cases, nasal polyp of 7 cases, gastroesophageal reflux disease of 5. The forced expiratory volume in one second/predicted value ratio (FEV(1)%pred) in 29 patients was lower than 80%.Twenty-one participants did not react in bronchial reversibility test. Sixteen patients were administrated with oral cortical steroids (OCS). The average annual cost per patient was 22 thousand RMB. Sixteenrefractory asthmatics were diagnosed as eosinophilic asthma. Conclusions: The clinical features associated with severe asthma include male gender, smoking, persistent airway limitation. Systemic use of corticosteroids is common and treatment costs are high. The eosinophilic asthma is the main inflammatory phenotype in patients with severe asthma.


Assuntos
Resistência das Vias Respiratórias , Asma , Eosinófilos , Inflamação , Adolescente , Adulto , Asma/patologia , Asma/fisiopatologia , China , Estudos Transversais , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Escarro , Adulto Jovem
6.
Neumol. pediátr. (En línea) ; 14(2): 105-110, jul. 2019. graf, ilust, tab
Artigo em Espanhol | LILACS | ID: biblio-1015136

RESUMO

Spirometry is better pulmonary function test for evaluating preschoolers with chronic lung disease and recurrent wheeze. It is useful, accessible and very good performance. For a correct interpretation it must be under the conditions specially controlled for this age group. In this review, product of the work done during the year 2018, by the Committee on pulmonary function in pediatric pulmonology Chilean society, will be showcased aspects for the realization and interpretation of spirometry in preschool children, with emphasis on the differences in the criteria typically described for older children and adults.


La espirometría es la prueba de función pulmonar más adecuada para evaluar a preescolares con enfermedades pulmonares crónicas y sibilancias recurrentes. Es útil, accesible y de buen rendimiento. Para una correcta interpretación debe realizarse bajo las condiciones especialmente normadas para este grupo etario. En esta revisión, producto del trabajo realizado durante el año 2018, por la comisión de función pulmonar de la sociedad Chilena de Neumología Pediátrica, se expondrán los aspectos actualizados para la realización e interpretación de la espirometría en preescolares, con énfasis en las diferencias de los criterios clásicamente descritos para niños mayores y adultos.


Assuntos
Humanos , Pré-Escolar , Espirometria/métodos , Testes de Função Respiratória , Asma/diagnóstico , Asma/fisiopatologia , Índice de Gravidade de Doença , Capacidade Vital , Volume Expiratório Forçado , Fibrose Cística/diagnóstico , Fibrose Cística/fisiopatologia , Pneumopatias/diagnóstico , Pneumopatias/fisiopatologia
7.
Adv Exp Med Biol ; 1124: 381-422, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31183836

RESUMO

Airway smooth muscle (ASM) extends from the trachea throughout the bronchial tree to the terminal bronchioles. In utero, spontaneous phasic contraction of fetal ASM is critical for normal lung development by regulating intraluminal fluid movement, ASM differentiation, and release of key growth factors. In contrast, phasic contraction appears to be absent in the adult lung, and regulation of tonic contraction and airflow is under neuronal and humoral control. Accumulating evidence suggests that changes in ASM responsiveness contribute to the pathophysiology of lung diseases with lifelong health impacts.Functional assessments of fetal and adult ASM and airways have defined pharmacological responses and signaling pathways that drive airway contraction and relaxation. Studies using precision-cut lung slices, in which contraction of intrapulmonary airways and ASM calcium signaling can be assessed simultaneously in situ, have been particularly informative. These combined approaches have defined the relative importance of calcium entry into ASM and calcium release from intracellular stores as drivers of spontaneous phasic contraction in utero and excitation-contraction coupling.Increased contractility of ASM in asthma contributes to airway hyperresponsiveness. Studies using animal models and human ASM and airways have characterized inflammatory and other mechanisms underlying increased reactivity to contractile agonists and reduced bronchodilator efficacy of ß2-adrenoceptor agonists in severe diseases. Novel bronchodilators and the application of bronchial thermoplasty to ablate increased ASM within asthmatic airways have the potential to overcome limitations of current therapies. These approaches may directly limit excessive airway contraction to improve outcomes for difficult-to-control asthma and other chronic lung diseases.


Assuntos
Sinalização do Cálcio , Contração Muscular , Músculo Liso/fisiologia , Músculo Liso/fisiopatologia , Fenômenos Fisiológicos Respiratórios , Animais , Asma/fisiopatologia , Broncodilatadores , Humanos , Pulmão , Sistema Respiratório/fisiopatologia
8.
PLoS Genet ; 15(6): e1008164, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31194737

RESUMO

Chronic pain is highly prevalent worldwide and represents a significant socioeconomic and public health burden. Several aspects of chronic pain, for example back pain and a severity-related phenotype 'chronic pain grade', have been shown previously to be complex heritable traits with a polygenic component. Additional pain-related phenotypes capturing aspects of an individual's overall sensitivity to experiencing and reporting chronic pain have also been suggested as a focus for investigation. We made use of a measure of the number of sites of chronic pain in individuals within the UK general population. This measure, termed Multisite Chronic Pain (MCP), is a complex trait and its genetic architecture has not previously been investigated. To address this, we carried out a large-scale genome-wide association study (GWAS) of MCP in ~380,000 UK Biobank participants. Our findings were consistent with MCP having a significant polygenic component, with a Single Nucleotide Polymorphism (SNP) heritability of 10.2%. In total 76 independent lead SNPs at 39 risk loci were associated with MCP. Additional gene-level association analyses identified neurogenesis, synaptic plasticity, nervous system development, cell-cycle progression and apoptosis genes as enriched for genetic association with MCP. Genetic correlations were observed between MCP and a range of psychiatric, autoimmune and anthropometric traits, including major depressive disorder (MDD), asthma and Body Mass Index (BMI). Furthermore, in Mendelian randomisation (MR) analyses a causal effect of MCP on MDD was observed. Additionally, a polygenic risk score (PRS) for MCP was found to significantly predict chronic widespread pain (pain all over the body), indicating the existence of genetic variants contributing to both of these pain phenotypes. Overall, our findings support the proposition that chronic pain involves a strong nervous system component with implications for our understanding of the physiology of chronic pain. These discoveries may also inform the future development of novel treatment approaches.


Assuntos
Dor Crônica/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Herança Multifatorial/genética , Adulto , Idoso , Asma/genética , Asma/fisiopatologia , Bancos de Espécimes Biológicos , Índice de Massa Corporal , Dor Crônica/fisiopatologia , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurogênese/genética , Plasticidade Neuronal/genética , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Reino Unido
9.
Medicine (Baltimore) ; 98(18): e15313, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045768

RESUMO

BACKGROUND: Asthma is a chronic inflammatory disease characterized by recurrent attacks of breathlessness and wheezing, which often worsen at night or in the early morning and vary from person to person in severity and frequency. Sanao decoction (SAD), as a traditional Chinese medicine compound, has a long history of clinical application in the treatment of respiratory diseases. Whereas neither systematic nor meta-analysis of randomized controlled articles explain the efficacy of SAD in treating asthma. Therefore, we provide a protocol to evaluate the efficacy and safety of SAD for asthma. METHODS: From the beginning to December 2018, the following electronic databases will be searched for studies in English or Chinese: the Cochrane Library, Embase, PubMed, Web of Science, the Chinese National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the Chinese Scientific Journal Database, and the Wanfang Database. Total effective rate, peak expiratory flow (PEF), forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC will be measured as primary outcomes. Meta-analysis will be performed using the Stata 15. RESULTS: This study will provide the current evidence of asthma treated with SAD from the several points including PEF, FEV1, FVC, and FEV1/FVC. CONCLUSION: The consequence of this summary will furnish proof to evaluate if SAD is effective in the treatment of asthma. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42018117923.


Assuntos
Asma/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa/métodos , Asma/epidemiologia , Asma/fisiopatologia , Medicamentos de Ervas Chinesas/administração & dosagem , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Medicina Tradicional Chinesa/efeitos adversos , Avaliação de Resultados (Cuidados de Saúde) , Pico do Fluxo Expiratório/efeitos dos fármacos , Projetos de Pesquisa , Testes de Função Respiratória/métodos , Capacidade Vital/efeitos dos fármacos
10.
Ter Arkh ; 91(1): 60-63, 2019 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-31090373

RESUMO

AIM: To assess the functional status of the small Airways in patients with bronchial asthma associated with obesity, by body plethysmography. MATERIALS AND METHODS: 65 patients with bronchial asthma of mild severity, partially controlled course, including 30 patients with normal body weight and 35 patients with obesity of I degree were examined. Control group-30 healthy volunteers. Examined forced vital capacity (FVC), forced expiratory volume in first second (FEV1) ratio of FEV1 to FVC (FEV1/FVC), maximum volumetric exhalation rate after 25.50 and 75% FVC (MEF75, MEF50, MEF25), average flow velocity in the exhalation interval 25-75% of FVC (MMEF25-75). Method bodyplethysmography was evaluated in bronchial resistance, functional residual capacity (FRC), residual volume of the lungs (RV), total lung capacity (TLC), the percentage of RV/TLC. RESULTS: Patients with bronchial asthma with obesity showed a reduction of indicators of bronchial obstruction: FEV1 of 14% (p=0.02), FEV1/FVC by 14% (p=0.001), MEF75 30% (p=0.001), MEF50 by 35% (p=0.001), MEF25 by 44% (p=0.003), MMEF25-75 by 38% (p=0.001). The increase of bronchial resistance on inhalation in 2 times (p=0.001), on exhalation in 3.3 times (p=0.003) was found, which is typical for generalized bronchial obstruction at the proximal level. An increase in RV by 24% (p=0.03), TLC - by 9% (p=0.03), RV/TLC - by 18% (p=0.03), indicating the presence of "air traps" and dysfunction of the small respiratory tract. CONCLUSION: In patients with asthma of mild severity associated with obesity, both the central bronchis and the distal lung are affected, which are manifested by generalized bronchial obstruction, the formation of "air traps" and dysfunction of the small respiratory tract.


Assuntos
Asma/fisiopatologia , Obesidade/complicações , Capacidade Pulmonar Total/fisiologia , Asma/complicações , Estudos de Casos e Controles , Volume Expiratório Forçado/fisiologia , Humanos , Pletismografia/métodos , Capacidade Vital/fisiologia
11.
Ter Arkh ; 91(3): 31-35, 2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31094456

RESUMO

AIM: The aim of the research was to study the state of the bronchial mucosa epi-thelium in relation to the severity of clinical manifestations in severe uncon-trolled asthma depending on the pattern of inflammation and the presence of cold airway hyperresponsiveness. MATERIALS AND METHODS: In 48 patients with severe uncontrolled asthma, there were assessed asthma symptoms, clinical signs of cold airway hyperre-sponsiveness, and lung function; the samples of slides were analyzed in the cytological examination of the sputum; the degree of damage to epithelial cells and granulocytes was estimated using the total cell destruction index (CDI). RESULTS: According to the analysis of sputum cytograms, the patients were divided into two groups: group I (22 patients) included persons with eosin-ophilic inflammation pattern (31.0±3.1% of eosinophils and 22.0±2.2% of neutrophils), group II (26 patients) was with mixed inflammation pattern (7.2±1.4 and 71.8±4.2%, respectively). The patients of group II had lower disease control according to Asthma Control Test (ACT; 12.1±0.7 and 17.8±0.2 points, respectively; р<0.05), a greater frequency of exacerbations (4.1±0.3 and 3.2±0.2 per year, respectively; р<0.05), greater incidence of clinical signs of cold airway hyperresponsiveness (79 and 19%, respectively; χ2=14.18; р<0.001); lower lung function (midexpiratory flow rate MEF25-75 was 14.6±1.6 and 20.7±1.9%, respectively; р<0.05); they received a higher dose of the combined medications of inhaled glucocorticosteroid in controller anti-inflammatory therapy (salmeterol/fluticasone at a dose of 705.3±19.7 and 650.7±14.8 µg/day for fluticasone propionate; р<0.05) In patients of group II the correlations of epithelial CDI with neutrophil CDI (r=0.61; p<0.01) and eosinophil CDI (r=0.48; p<0.05), as well as correlation of ACT with neutrophil CDI (r=-0.71; p<0.01) and eosinophil CDI (r=-0.53; p<0.05) were found. CONCLUSION: The degree of destruction of the epithelium and granulocytes in the inflammatory patterns has diagnostic relevance for the assessment of the severity of the disease, clinical manifestations of the airway response to the cold trigger, and the inertia of achieving control in patients with severe un-controlled asthma.


Assuntos
Asma/fisiopatologia , Hiper-Reatividade Brônquica/fisiopatologia , Síndromes Periódicas Associadas à Criopirina , Brônquios , Hiper-Reatividade Brônquica/imunologia , Temperatura Baixa/efeitos adversos , Eosinófilos , Humanos , Inflamação/imunologia , Inflamação/fisiopatologia , Índice de Gravidade de Doença , Escarro/citologia
12.
Ter Arkh ; 91(3): 93-100, 2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31094466

RESUMO

This review presents an analysis of the literature on the topic of respiratory muscle (RM) dysfunction in various forms of respiratory pathology: chronic obstructive pulmonary disease (COPD), asthma, community-acquired pneumonia, idiopathic pulmonary fibrosis (IPF), sarcoidosis and interstitial lung diseases (ILD), associated with systemic connective tissue diseases (polymyositis, dermatomyositis and systemic lupus erythematosus - SLE). Various clinical and pathophysiological aspects of RM dysfunction and general patterns of its pathogenesis were examined. It was proved that the role of RM in the development of respiratory failure depends on the form and stage of the pulmonary pathology and the severity of systemic manifestations of these diseases: excessive proteolysis, oxidative stress, hypoxia, chronic systemic inflammation. These factors modify the morphofunctional status of RM, worsens their contractile function, which is contributed to the development of respiratory failure. In some cases, the primary weakness of RM precedes the clinical manifestation of pulmonary pathology, which is distinctive for some variants of myositis-associated ILD and SLE. Endogenous intoxication syndrome plays a significant role in the development of RM dysfunction during community-acquired pneumonia. It is noted that sarcoid pulmonary ventilation disorders associate with the RM weakness, but not with the degree of lung damage. In most cases, secondary RM dysfunction predominates that contributes to respiratory failure progression, which is especially noticeable in case of COPD, asthma and IPF.


Assuntos
Pulmão/fisiopatologia , Insuficiência Respiratória/fisiopatologia , Músculos Respiratórios/fisiopatologia , Asma/fisiopatologia , Doenças do Tecido Conjuntivo/fisiopatologia , Humanos , Fibrose Pulmonar Idiopática/fisiopatologia , Pneumopatias Obstrutivas/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia
13.
Tuberk Toraks ; 67(1): 31-38, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31130133

RESUMO

Introduction: Understanding the difference of elderly asthma is essential to provide better healthcare for this vulnerable population. The aim of this study was to evaluate the differences between young and elderly asthma patients. Materials and Methods: This real-life study was designed as a cross-sectional analysis. All data collected with structured web based asthma program. In sum, 373 (89.9%) young asthma (YA, age < 65) and 42 (10.1%) elderly asthma (EA, age < 65) patients followed at least one year and compared statistically. Result: Cough is found higher in EA (p< 0.01) despite lower smoking rate in EA (p< 0.001). Allergic rhinitis and allergic conjunctivitis were more common in YA (p< 0.05, p< 0.01) which is consistent with higher allergy rate in YA (p< 0.05). On the other hand, diabetes and hypertension were determined significantly higher in EA (p< 0.01, p< 0.01). 52.4% of EA patients were found to have low diffusion capacity (DLCO < 80%). Although EA patients use combined therapies with inhaled corticosteroids and long acting beta agonists more than YA patients (p< 0.01), both emergency room visit (ERV) and hospitalization ratios are founded significantly higher in EA (p< 0.001, p< 0.001). Conclusions: EA patients were presented with cough in general. They possess an increased risk of hypertension, diabetes and low levels of diffusion capacity. ERV and hospitalization ratios have founded higher despite higher usage of combined therapies.


Assuntos
Corticosteroides/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Hospitalização/estatística & dados numéricos , Qualidade de Vida , Adulto , Idoso , Asma/fisiopatologia , Asma/psicologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória
14.
Expert Opin Drug Metab Toxicol ; 15(6): 517-520, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31104515

RESUMO

Background: To date, there is the strong need to compare the efficacy across the monoclonal antibodies (mAbs) approved to treat severe asthma. Research design and method: A quantitative synthesis has been performed to compare the impact of omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and placebo on the risk of exacerbation and change in forced expiratory flow in 1 s (FEV1) in severe asthmatic patients. Results: All the investigated mAbs were more effective than placebo in reducing the risk of exacerbation and improving lung function. Dupilumab showed a general superiority compared to the other mAbs, as it significantly reduced the risk of exacerbation vs. omalizumab, and significantly improved FEV1 when compared to omalizumab, mepolizumab, and benralizumab. The overall-marked placebo effect indicates that a better adherence to drug regimens in the context of RCTs may lead to noteworthy improvement in the clinical condition of severe asthmatic patients. Conclusions: Further extensive meta-analyses are needed to identify the factors influencing the efficacy profile of mAbs in severe asthma. This may also permit to identify the profile of patients that are specifically responsive to either anti-IgE, anti-IL-4Rα, anti-IL-5, or anti-IL-5Rα mAbs.


Assuntos
Antiasmáticos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Asma/tratamento farmacológico , Antiasmáticos/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Asma/fisiopatologia , Volume Expiratório Forçado , Humanos , Adesão à Medicação , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença
16.
Arch. bronconeumol. (Ed. impr.) ; 55(4): 208-213, abr. 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-181512

RESUMO

Introducción: El asma se caracteriza por una inflamación crónica de las vías respiratorias centrales y distales. El objetivo de este estudio ha sido evaluar la vía aérea pequeña (VAP) en niños con asma moderada y/o grave con FEV1 normal. Métodos: Estudio abierto, prospectivo, observacional y transversal con inclusión consecutiva de casos con asma moderada o grave, bajo tratamiento clínico habitual con FEV1 basal normal. Se ha determinado la FEno a flujos múltiples (CAno), resistencias y reactancia oscilatorias (R5-R20, X5), espirometría forzada (FEV1, FEF25-75), pletismografía corporal total (RV/TLC) y prueba de broncodilatación. La afectación de la VAP se definió por: Cano > 4,5 ppb, R5-R20 > 0,147kPa/L/s, X5 <-0,18kPa/L, FEF25-75 < -1,65 z-score, RV/TL > 33%. El mal control de asma se definió por ≤ 19 puntos en el cuestionario ACT o ≤ 20 en c-ACT. Resultados: Cohorte de 100 casos, 76 con asma moderada y 24 con asma grave, 71 niños clasificados como mal controlados y 29 bien controlados. El 77,78% del grupo con todas las determinaciones correctas (n =7 2) mostró ≥ 1 parámetro alterado de VAP y el 48,61% ≥ 2 parámetros. No hubo diferencias entre los casos bien y mal controlados. Conclusiones: Los niños con asma moderada y grave, con el FEV1 preservado, muestran un fenotipo de VAP disfuncionante. En nuestra muestra, la evaluación de la VAP mediante las técnicas descritas, no aporta información sobre el control habitual de la enfermedad


Introduction: Asthma is characterized by chronic inflammation of the central and distal airways. The aim of this study was to assess the small airway (SA) of children with moderate-severe asthma with normal FEV1. Methods: This was an open-label, prospective, observational, cross-sectional study with consecutive inclusion of patients with moderate-severe asthma, receiving standard clinical treatment, with normal baseline FEV1. We determined multiflow FEno (CAno), oscillatory resistance and reactance (R5-R20, X5), forced spirometry (FEV1, FEF25-75), total body plethysmography (RV/TLC) and bronchodilation test. SA involvement was defined as: Cano > 4.5 ppb, R5-R20 > 0.147kPa/L/s, X5< -0.18kPa/L, FEF25-75 < -1.65 z-score, RV/TLC > 33%. Poor asthma control was defined as ≤ 19 points on the ACT questionnaire or ≤ 20 on the c-ACT. Results: In a cohort of 100 cases, 76 had moderate asthma and 24 had severe asthma; 71 children were classified as poorly controlled and 29 were well-controlled. In total, 77.78% of the group with all the correct determinations (n=72) showed ≥ 1 altered SA parameter and 48.61% ≥ 2 parameters. There were no differences between well-controlled or poorly controlled cases. Conclusions: Children with moderate-severe asthma, with normal FEV1, show a phenotype of dysfunctional SA. In our series, the evaluation of SA using the techniques described above did not provide information on disease control


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Asma/fisiopatologia , Obstrução das Vias Respiratórias/fisiopatologia , Anormalidades do Sistema Respiratório , Volume Expiratório Forçado/fisiologia , Estudos Transversais , Estudos Prospectivos , Estudos de Coortes , Testes Respiratórios/métodos
17.
Immunity ; 50(4): 975-991, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30995510

RESUMO

Asthma is a chronic inflammatory airway disease associated with type 2 cytokines interleukin-4 (IL-4), IL-5, and IL-13, which promote airway eosinophilia, mucus overproduction, bronchial hyperresponsiveness (BHR), and immunogloubulin E (IgE) synthesis. However, only half of asthma patients exhibit signs of an exacerbated Type 2 response. "Type 2-low" asthma has different immune features: airway neutrophilia, obesity-related systemic inflammation, or in some cases, few signs of immune activation. Here, we review the cytokine networks driving asthma, placing these in cellular context and incorporating insights from cytokine-targeting therapies in the clinic. We discuss established and emerging paradigms in the context of the growing appreciation of disease heterogeneity and argue that the development of new and improved therapeutics will require understanding the diverse mechanisms underlying the spectrum of asthma pathologies.


Assuntos
Asma/imunologia , Citocinas/imunologia , Imunidade Adaptativa , Corticosteroides/uso terapêutico , Alérgenos/imunologia , Animais , Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Asma/classificação , Asma/tratamento farmacológico , Asma/fisiopatologia , Ensaios Clínicos como Assunto , Citocinas/antagonistas & inibidores , Células Epiteliais/imunologia , Humanos , Inflamação/imunologia , Interferons/imunologia , Camundongos , Camundongos Knockout , Modelos Imunológicos , Células Th2/imunologia
18.
Medicine (Baltimore) ; 98(15): e15226, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30985726

RESUMO

BACKGROUND: Morbidity of asthma in children is increasing, which is significantly affecting children's life quality. Despite the medication therapy, physical therapies, including breathing exercises, inspiratory muscle training and physical training, are widely used to improve children's condition. However, the effectiveness of physical therapy remains unclear. This systematic review and meta-analysis is aiming to evaluate the effects of physical therapy on lung function in children with asthma and to assess which physical therapy is more effective. METHODS: Three main databases (PubMed, Embase, and the Cochrane Library) will be searched from inception to November 30, 2018 for randomized controlled trials investigating the effects of physical therapy on lung function in children (age < 18 years old) with asthma published in English. In addition, a manual search of the references of relevant published studies in English will also be considered.Two independent reviewers will conduct studies selection, data extraction, and risk of bias assessment. Outcome measures will be the Peak Expiratory Flow (PEF), the Forced Expiratory Volume in the first second (FEV1), and the Forced Vital Capacity (FVC). Subgroup analyses will be performed according to the physical therapy (breathing exercises, inspiratory muscle training, and physical training) and the outcome (PEF, FEV1, FVC). RESULTS: The results will provide useful information about the effect of physical therapy on lung function in children with asthma and demonstrate which physical therapy is more effective. CONCLUSION: The findings of this study will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42019121627.


Assuntos
Asma/fisiopatologia , Asma/terapia , Pulmão/fisiopatologia , Modalidades de Fisioterapia , Criança , Humanos , Projetos de Pesquisa
19.
Expert Opin Drug Saf ; 18(5): 369-380, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30983432

RESUMO

INTRODUCTION: The treatment of asthma in older ages follows the recommendations of international guidelines for the management of asthma in younger ages, although older age has always represented an exclusion criterion for eligibility to pharmacological trials. This poses a clinical challenge when deciding whether elderly severe asthmatics are candidates for biological drugs. AREAS COVERED: The current article has a narrative structure to review the current literature on efficacy and safety of novel pharmacological drugs against immunoglobulins and interleukins that mediate and orchestrate the main inflammatory pathways in severe asthma, in order to explore whether older subjects (i.e. > 65 years of age) are included. EXPERT OPINION: Asthma in older ages is not a rare entity, and loss of symptom control is common in most advanced ages. Current evidence from randomized clinical trials (RCTs) on the safety of biological drugs in elderly asthmatics is scarce and does not allow drawing definitive conclusions. An urgent call for studies specifically designed for elderly populations is needed, with the purpose to assess the efficacy and safety of target biological therapies in advanced ages. We envision the design of large multi-center clinical trials to decide whether and when geriatric population could benefit from biological therapies.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Fatores Etários , Idoso , Antiasmáticos/efeitos adversos , Asma/fisiopatologia , Produtos Biológicos/efeitos adversos , Humanos , Imunoglobulinas/metabolismo , Interleucinas/metabolismo , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença
20.
Int J Mol Sci ; 20(7)2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30965592

RESUMO

Mast cells play a critical role in the pathogenesis of allergic asthma. Histamine is a central mediator released from mast cells through allergic reactions. Histamine plays a role in airway obstruction via smooth muscle contraction, bronchial secretion, and airway mucosal edema. However, previous clinical trials of H1 receptor antagonists (H1RAs) as a treatment for asthma were not successful. In recent years, type 2 innate immunity has been demonstrated to be involved in allergic airway inflammation. Allergic asthma is defined by IgE antibody-mediated mast cell degranulation, while group 2 innate lymphoid cells (ILC2) induce eosinophilic inflammation in nonallergic asthma without allergen-specific IgE. Anti-IgE therapy has demonstrated prominent efficacy in the treatment of severe allergic asthmatics sensitized with specific perennial allergens. Furthermore, recent trials of specific cytokine antagonists indicated that these antagonists were effective in only some subtypes of asthma. Accordingly, H1RAs may show significant clinical efficacy for some subtypes of allergic asthma in which histamine is deeply associated with the pathophysiology.


Assuntos
Asma/metabolismo , Asma/fisiopatologia , Histamina/metabolismo , Animais , Antagonistas dos Receptores Histamínicos/uso terapêutico , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade/imunologia , Hipersensibilidade/metabolismo , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Linfócitos/metabolismo , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo
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