RESUMO
Characterization of lung sounds (LS) is indispensable for diagnosing respiratory pathology. Although conventional neural networks (NNs) have been widely employed for the automatic diagnosis of lung sounds, deep neural networks can potentially be more useful than conventional NNs by allowing accurate classification without requiring preprocessing and feature extraction. Utilizing the long short-term memory (LSTM) layers to reveal the sequence-based properties of the LS time series, a novel architecture consisting of a cascade of convolutional long short-term memory (ConvLSTM) and LSTM layers, namely ConvLSNet is developed, which permits highly accurate diagnosis of pulmonary disease states. By modeling the multichannel lung sounds through the ConvLSTM layer, the proposed ConvLSNet architecture can concurrently deal with the spatial and temporal properties of the six-channel LS recordings without heavy preprocessing or data transformation. Notably, the proposed model achieves a classification accuracy of 97.4 % based on LS data corresponding to three pulmonary conditions, namely asthma, COPD, and the healthy state. Compared with architectures consisting exclusively of CNN or LSTM layers, as well as those employing a cascade integration of 2DCNN and LSTM layers, the proposed ConvLSNet architecture exhibited the highest classification accuracy, while imposing the lowest computational cost as quantified by the number of parameters, training time, and learning rate.
Assuntos
Redes Neurais de Computação , Sons Respiratórios , Humanos , Sons Respiratórios/classificação , Sons Respiratórios/fisiopatologia , Asma/fisiopatologia , Asma/classificação , Asma/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/classificação , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Processamento de Sinais Assistido por Computador , Pulmão/fisiopatologiaRESUMO
OBJECTIVE: Asthma is the most frequent chronic airway illness in preschool children and is difficult to diagnose due to the disease's heterogeneity. This study aimed to investigate different machine learning models and suggested the most effective one to classify two forms of asthma in preschool children (predominantly allergic asthma and non-allergic asthma) using a minimum number of features. METHODS: After pre-processing, 127 patients (70 with non-allergic asthma and 57 with predominantly allergic asthma) were chosen for final analysis from the Frankfurt dataset, which had asthma-related information on 205 patients. The Random Forest algorithm and Chi-square were used to select the key features from a total of 63 features. Six machine learning models: random forest, extreme gradient boosting, support vector machines, adaptive boosting, extra tree classifier, and logistic regression were then trained and tested using 10-fold stratified cross-validation. RESULTS: Among all features, age, weight, C-reactive protein, eosinophilic granulocytes, oxygen saturation, pre-medication inhaled corticosteroid + long-acting beta2-agonist (PM-ICS + LABA), PM-other (other pre-medication), H-Pulmicort/celestamine (Pulmicort/celestamine during hospitalization), and H-azithromycin (azithromycin during hospitalization) were found to be highly important. The support vector machine approach with a linear kernel was able to diffrentiate between predominantly allergic asthma and non-allergic asthma with higher accuracy (77.8%), precision (0.81), with a true positive rate of 0.73 and a true negative rate of 0.81, a F1 score of 0.81, and a ROC-AUC score of 0.79. Logistic regression was found to be the second-best classifier with an overall accuracy of 76.2%. CONCLUSION: Predominantly allergic and non-allergic asthma can be classified using machine learning approaches based on nine features.Supplemental data for this article is available online at at www.tandfonline.com/ijas .
Assuntos
Asma , Aprendizado de Máquina , Pré-Escolar , Humanos , Asma/classificação , Asma/diagnóstico , Azitromicina/uso terapêutico , Budesonida/uso terapêutico , Doença Crônica , HospitalizaçãoAssuntos
Asma/diagnóstico , Eosinofilia Pulmonar/complicações , Adulto , Asma/classificação , Asma/epidemiologia , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Eosinofilia Pulmonar/diagnóstico , Eosinofilia Pulmonar/epidemiologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The inflammatory phenotypes of asthma predict the treatment response and prognosis. The phenotype distributions differ depending on the geographical region. This study aimed to assess the distribution of different inflammatory phenotypes among asthma patients in Jilin Province, China. METHODS: A total of 255 patients with asthma were recruited from Jilin Province, China for this cross-sectional study. Each patient underwent sputum induction following clinical assessment and peripheral blood collection. Inflammatory phenotypes were classified according to the inflammatory cell counts in the sputum. RESULTS: Paucigranulocytic asthma (PGA) was the most common inflammatory phenotype (52.2%), followed by eosinophilic asthma (EA, 38.3%), mixed granulocytic asthma (MGA, 5.2%), and neutrophilic asthma (NA, 4.3%). NA was more common among patients over 45 years old and those who were treated with higher doses of inhaled corticosteroids (ICS), but was less common following antibiotics treatment (p < 0.05). The proportion of patients with EA decreased as the ICS treatment dose and time increased (p = 0.038). Patients with uncontrolled asthma had higher numbers of sputum eosinophils and neutrophils (p < 0.05). Patients with severe asthma had a higher percentage of sputum neutrophils (p < 0.05). A greater proportion of patients with NA had severe asthma (60%) compared to those with EA (18.2%) (p = 0.016). CONCLUSIONS: The most common asthma inflammatory cell phenotype in Jilin Province, China is PGA, followed by EA, MGA, and NA. The low prevalence of NA in Jilin Province compared to other countries and also other regions in China might be due to excessive antibiotic use and irregular ICS treatment in this region.
Assuntos
Asma/classificação , Asma/epidemiologia , Inflamação/complicações , Inflamação/epidemiologia , Fenótipo , Administração por Inalação , Corticosteroides/uso terapêutico , Adulto , Idoso , Asma/sangue , Asma/tratamento farmacológico , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Inflamação/tratamento farmacológico , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Asthma is a complex disorder characterized by expiratory airflow limitation, wheeze, shortness of breath, chest tightness and cough, which can vary over time and in intensity. Being highly heterogeneous, asthma was characterized and classified in several asthma phenotypes and endotypes from 1947 until today. The present systematic review aims to summarize and describe evidence that was published in the last ten years in the field of asthma phenotyping and endotyping. EVIDENCE ACQUISITION: The systematic review resumed high-quality evidence (clinical trials and randomized control trials) retrieved on MEDLINE and EMBASE databanks and involving adult asthmatic populations. Analyses of literature were conducted according to PRISMA and CASP guidelines. EVIDENCE SYNTHESIS: Querying MEDLINE and EMBASE databanks, 5019 and 12261 entries were retrieved, respectively. Applying limitations for year of publication, age of participants, and type of publication, the search results were reduced to 98 and 132 articles, respectively. After data abstraction and resolution of duplications, only 50 articles were further evaluated. The research products were then classified first in macro-areas of interest (phenotypes or endotypes) and then in detailed micro-areas. CONCLUSIONS: This systematic review overviews the principal findings available from high-quality literature in the last decade concerning asthma phenotypes and endotypes. Asthma has been described from different points of view, characterizing symptoms, microbiota composition, comorbidities, viral infections, and airway and/or systemic inflammatory status. The comprehension of precise mechanisms underlying asthma pathogenesis is thereby the basis for the development of novel therapeutic strategies, likely essential to the development of precision medicine.
Assuntos
Asma/classificação , Asma/etiologia , Fenótipo , Adulto , Fatores Etários , Asma/tratamento farmacológico , Produtos Biológicos/farmacologia , Ensaios Clínicos como Assunto , Comorbidade , Tosse/etiologia , Progressão da Doença , Resistência a Medicamentos , Humanos , Microbiota , Obesidade/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Sons Respiratórios , Escarro/microbiologia , Esteroides , Resultado do TratamentoRESUMO
Rationale: Preschool wheezing is heterogeneous, but the underlying mechanisms are poorly understood.Objectives: To investigate lower airway inflammation and infection in preschool children with different clinical diagnoses undergoing elective bronchoscopy and BAL.Methods: We recruited 136 children aged 1-5 years (105 with recurrent severe wheeze [RSW]; 31 with nonwheezing respiratory disease [NWRD]). Children with RSW were assigned as having episodic viral wheeze (EVW) or multiple-trigger wheeze (MTW). We compared lower airway inflammation and infection in different clinical diagnoses and undertook data-driven analyses to determine clusters of pathophysiological features, and we investigated their relationships with prespecified diagnostic labels.Measurements and Main Results: Blood eosinophil counts and percentages and allergic sensitization were significantly higher in children with RSW than in children with a NWRD. Blood neutrophil counts and percentages, BAL eosinophil and neutrophil percentages, and positive bacterial culture and virus detection rates were similar between groups. However, pathogen distribution differed significantly, with higher detection of rhinovirus in children with RSW and higher detection of Moraxella in sensitized children with RSW. Children with EVW and children with MTW did not differ in terms of blood or BAL-sample inflammation, or bacteria or virus detection. The Partition around Medoids algorithm revealed four clusters of pathophysiological features: 1) atopic (17.9%), 2) nonatopic with a low infection rate and high use of inhaled corticosteroids (31.3%), 3) nonatopic with a high infection rate (23.1%), and 4) nonatopic with a low infection rate and no use of inhaled corticosteroids (27.6%). Cluster allocation differed significantly between the RSW and NWRD groups (RSW was evenly distributed across clusters, and 60% of the NWRD group was assigned to cluster 4; P < 0.001). There was no difference in cluster membership between the EVW and MTW groups. Cluster 1 was dominated by Moraxella detection (P = 0.04), and cluster 3 was dominated by Haemophilus or Staphylococcus or Streptococcus detection (P = 0.02).Conclusions: We identified four clusters of severe preschool wheeze, which were distinguished by using sensitization, peripheral eosinophilia, lower airway neutrophilia, and bacteriology.
Assuntos
Asma/classificação , Asma/diagnóstico , Asma/genética , Sons Respiratórios/classificação , Sons Respiratórios/diagnóstico , Sons Respiratórios/genética , Avaliação de Sintomas , Asma/fisiopatologia , Pré-Escolar , Feminino , Variação Genética , Genótipo , Humanos , Lactente , Masculino , Fenótipo , Sons Respiratórios/fisiopatologia , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Specific allergy sensitization pattern, using "component-resolved diagnosis" (CRD), is a central component of allergy and asthma in childhood. Besides this, allergic asthma has been characterized by a Th2-shifted endotype with elevation of classical Th2 cytokines. Recently, other endotypes with distinct mechanisms focusing on cytokine regulation evolved, yet those pathways are still not well understood. OBJECTIVE: (a) To define reproducible immunological endotypes using cytokine expression in an asthma cohort and (b) to characterize their sensitization profile and clinical phenotype. METHODS: Supernatants from PBMCs of 234 children (median age 10 years) of an asthma cohort were analysed for cytokine expressions. The children were split into a training (n = 49) and validation (n = 185) group. The training group was used to identify immunological endotypes by clustering cytokine expressions, which were then assessed regarding clinical characteristics and specific IgE of recombinant allergen components. Next, our findings were validated in the validation group. RESULTS: We identified novel endotypes based on primarily unstimulated cytokine expression. One endotype showed an IFN-γ/Interleukin (IL)-17/IL-5 predominance, a different sensitization pattern (high in birch/apple; p < .01), and inferior lung function (p < .01). A second endotype grouped young children with food allergy and reduced lung function. Our findings were reproducible in the validation group. CONCLUSION AND CLINICAL RELEVANCE: We identified two novel clinical asthma endotypes via cytokine expression pattern with distinct sensitization patterns. These novel findings are critical for clinical guidance and open avenues for identifying underlying mechanisms and more patient-specific therapies.
Assuntos
Asma/imunologia , Citocinas/imunologia , Hipersensibilidade Alimentar/imunologia , Pulmão/fisiopatologia , Animais , Antígenos de Dermatophagoides/imunologia , Asma/classificação , Asma/fisiopatologia , Betula/imunologia , Gatos , Criança , Alérgenos Animais/imunologia , Cães , Feminino , Volume Expiratório Forçado , Humanos , Imunoglobulina E/imunologia , Interferon gama/imunologia , Interleucina-17/imunologia , Interleucina-5/imunologia , Masculino , Malus/imunologia , Fenótipo , Phleum/imunologia , Reprodutibilidade dos Testes , Hipersensibilidade Respiratória/imunologia , Hipersensibilidade Respiratória/fisiopatologia , Células Th2/imunologia , Capacidade VitalRESUMO
BACKGROUND: Blood eosinophil measurement is essential for the phenotypic characterization of patients with difficult asthma and in determining eligibility for anti-IL-5/IL-5Rα biological therapies. However, assessing such measures over limited time spans may not reveal the true underlying eosinophilic phenotype, as treatment, including daily oral corticosteroid therapy, suppresses eosinophilic inflammation and asthma is intrinsically variable. METHODS: We interrogated the electronic healthcare records of patients in the Wessex AsThma CoHort of difficult asthma (WATCH) study (UK). In 501 patients being evaluated in this tertiary care centre for difficult to control asthma, all requested full blood count test results in a 10-year retrospective period from the index WATCH assessment were investigated (n = 11,176). RESULTS: In 235 biological therapy-naïve participants who had 10 or more measures in this time period, 40.3% were eosinophilic (blood eosinophils ≥300 cells/µl) at WATCH enrolment whilst an additional 43.1%, though not eosinophilic at enrolment, demonstrated eosinophilia at least once in the preceding decade. Persistent eosinophilia was associated with worse post-bronchodilator airway obstruction and higher Fractional exhaled Nitric Oxide (FeNO). In contrast, the 16.6% of patients who never demonstrated eosinophilia at this blood eosinophil threshold showed preserved lung function and lower markers of Type 2 inflammation. CONCLUSIONS: This highlights the central role that type 2 inflammation, as indicated by blood eosinophilia, has in difficult asthma and suggests that longitudinal electronic healthcare record analysis can be an important tool in clinical asthma phenotyping, providing insight that may help understand disease progression and better guide more specific treatment approaches.
Assuntos
Asma/sangue , Eosinofilia/sangue , Adulto , Antiasmáticos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/classificação , Asma/tratamento farmacológico , Asma/fisiopatologia , Estudos de Coortes , Registros Eletrônicos de Saúde , Eosinófilos , Feminino , Volume Expiratório Forçado , Teste da Fração de Óxido Nítrico Exalado , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulina E/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Omalizumab/uso terapêutico , Seleção de Pacientes , Escarro/citologia , Capacidade VitalRESUMO
Asthma is a heterogeneous condition, but firm identification of heterogeneity-focused treatments is still lacking. Dividing patients into subgroups of asthma pheno-/endotypes based on combined clinical and cellular biological characteristics and linking them to targeted treatments could be a potentially useful approach to personalize therapy for better outcomes. Nonetheless, there are still many problems related to the identification and validation of asthma phenotypes and endotypes. Alternatively, a precision-medicine strategy for the management of patients with airways disease that is free from the traditional diagnostic labels and based on identifying "treatable traits" in each patient might be preferable. However, it would represent a quite unsophisticated approach because the definition of a treatable trait is too imprecise. In fact, there is still no understanding of the mechanisms underlying treatable traits that allow directing any targeted therapies against any particular treatable trait. Fortunately, in-depth identification of underlying molecular pathways to guide targeted treatment in individual patients is in progress thanks to the improvement in big data management obtained from '-omic' sciences that is greatly increasing knowledge concerning asthma.
Assuntos
Asma/genética , Genoma Humano/genética , Medicina de Precisão , Asma/classificação , Asma/patologia , Asma/terapia , Genômica , Genótipo , Humanos , Fenótipo , ProteômicaRESUMO
Asthma is a chronic disease with major public health ramifications owing to its high morbidity and mortality rates, especially in severe and recurrent cases. Conventional therapeutic options could partially alleviate the burden of asthma, yet a novel approach is needed to completely control this condition. To do so, a comprehensive understanding of the molecular mechanism underlying asthma is essential to recognize and treat the major pathways that drive its pathophysiology. In this review, we will discuss the molecular mechanism of asthma, in particular focusing on the type of inflammatory responses it elicits, namely type 2 and non-type 2 asthma. Furthermore, we will discuss the novel therapeutic options that target the aberrant molecules found in asthma pathophysiology. We will specifically focus on the role of novel monoclonal antibody therapies recently developed, such as the anti-IgE, IL-5, IL-5Rα, and IL-4Rα antibodies, drugs that have been extensively studied preclinically and clinically.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Asma/tratamento farmacológico , Asma/genética , Terapia de Alvo Molecular , Asma/classificação , Feminino , Humanos , Imunoglobulina E/imunologia , Inflamação , Subunidade alfa de Receptor de Interleucina-4/imunologia , Interleucina-5/imunologia , Subunidade alfa de Receptor de Interleucina-5/imunologia , Masculino , Recidiva , Índice de Gravidade de DoençaAssuntos
Obstrução das Vias Respiratórias/diagnóstico por imagem , Aspergilose/diagnóstico , Influenza Humana/complicações , Obstrução das Vias Respiratórias/diagnóstico , Obstrução das Vias Respiratórias/microbiologia , Aspergilose/diagnóstico por imagem , Aspergilose/microbiologia , Asma/classificação , Asma/diagnóstico , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To evaluate the diagnostic value of fractional exhaled nitric oxide (FeNO) and maximum mid-expiratory flow (MMEF) for differentiating cough variant asthma (CVA) from chronic cough in patients with or without allergic rhinitis. METHODS: In total, 328 patients with chronic cough who underwent spirometry and FeNO testing were consecutively included in the retrospective analysis. Patients were divided into the CVA (n = 125) or NCVA (n = 203) groups according to the diagnostic criteria of CVA. Receiver operating characteristic (ROC) curves were established to assess the diagnostic efficiency and optimal cutoff points of FeNO and MMEF for the prediction of CVA. RESULTS: The optimal cutoff values of FeNO and MMEF to discriminate CVA from chronic cough were 24.5 ppb (AUC, 0.765; sensitivity, 69.60%; specificity 72.91%; PPV, 61.27%; NPV, 79.57%) and 66.2% (AUC, 0.771; sensitivity, 67.20%; specificity 78.33%; PPV, 65.63%; NPV, 79.50%). The optimal cutoff values of combining FeNO with MMEF to discriminate CVA from chronic cough were >22 ppb for FeNO and <62.6% for MMEF (AUC, 0.877). In patients with and without allergic rhinitis, the optimal cutoff point of FeNO to discriminate CVA from chronic cough was 24.5 ppb (AUC, 0.820) and 33.5 ppb (AUC, 0.707), respectively. CONCLUSIONS: FeNO and MMEF might have greater value as negative parameters for differentiating CVA from chronic cough. Combining FeNO and MMEF provided a significantly better prediction than either alone. The diagnostic accuracy of FeNO for predicting CVA in chronic cough patients with allergic rhinitis was higher than in chronic cough patients without allergic rhinitis.
Assuntos
Asma/diagnóstico , Asma/fisiopatologia , Tosse/diagnóstico , Tosse/fisiopatologia , Testes de Função Respiratória/métodos , Rinite Alérgica/fisiopatologia , Adolescente , Adulto , Idoso , Asma/classificação , Asma/epidemiologia , Tosse/epidemiologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/análise , Curva ROC , Valores de Referência , Estudos Retrospectivos , Rinite Alérgica/epidemiologia , Adulto JovemRESUMO
PURPOSE OF REVIEW: The aim of this study was to highlight the phenotypes and endotypes of asthma as a tool for selection of the Food and Drug Administration approved biologic therapies. RECENT FINDINGS: An evolving concept of asthma has led to the identification of distinct phenotypes and endotypes in this disease. Asthma endotypes are defined as the biological mechanism and are often categorized as T2-high and T2-low based on the influence of T helper type 2 (T2) cells and type 2 cytokines, including interleukin (IL)-4, IL-5, IL-9 and IL-13. Biomarkers such as peripheral blood absolute eosinophil count, total IgE, specific IgE and fractional exhaled nitric oxide may be used as indicators of asthma endotypes and help predict response to biologic therapies. There are currently five biologic therapies approved as a treatment option for T2-high asthma: omalizumab, benralizumab, mepolizumab, reslizumab and dupilumab. SUMMARY: Here, we explore the current understandings of asthma endotypes and review their associated phenotypes. We provide practical and evidence-based guidance for clinicians considering a biologic for asthma add-on maintenance therapy.
Assuntos
Antiasmáticos/farmacologia , Asma/tratamento farmacológico , Produtos Biológicos/farmacologia , Células Th2/efeitos dos fármacos , Antiasmáticos/uso terapêutico , Asma/sangue , Asma/classificação , Asma/diagnóstico , Produtos Biológicos/uso terapêutico , Biomarcadores/sangue , Humanos , Fenótipo , Índice de Gravidade de Doença , Células Th2/imunologia , Células Th2/metabolismo , Resultado do TratamentoRESUMO
BACKGROUND: Current biologic therapies target allergic, eosinophilic or type 2 inflammation phenotypic asthma. However, frequency and degree of overlap among these subtypes is unclear. OBJECTIVE: To characterize overlap among allergic, eosinophilic and type 2 asthma phenotypes. METHODS: Post hoc analyses of baseline data were performed in two adult populations: (a) not selected for any asthma subtype (N = 935) and (b) selected for allergic asthma (N = 1049). Degree of overlap was examined using commonly accepted phenotypic definitions to guide treatment for allergic asthma (skin prick-positive and/or positive serum-specific immunoglobulin E > 0.35 kU/L) and eosinophilic asthma (blood eosinophil high count ≥ 300 cells/µL; low cut-off ≥ 150 cells/µL). Consistent with previous studies, fractional exhaled nitric oxide high level of ≥ 35 ppb and low cut-off of ≥ 25 ppb were selected as local markers of type 2 inflammation and to prevent overlap with the systemic eosinophilic asthma definition. RESULTS: In the non-subtype-selected population, 78.0% had allergic asthma; of these, 39.5% had eosinophilic asthma and 29.5% had type 2 asthma. Within patients with eosinophilic asthma (40.6% of total), 75.8% had allergic asthma and 41.3% had type 2 asthma. Within patients with type 2 asthma (28.3% of total), 81.1% had allergic asthma and 59.2% had eosinophilic asthma. In the allergic asthma-selected population, 38.3% had eosinophilic asthma and 29.2% had type 2 asthma. Within patients with eosinophilic asthma, 46.3% had type 2 asthma. Within patients with type 2 asthma, 60.8% had eosinophilic asthma. Overlaps among subtypes increased at low cut-off values. CONCLUSIONS AND CLINICAL RELEVANCE: In this post hoc analysis in adults with moderate-to-severe asthma, allergic asthma was the most prevalent phenotype, followed by eosinophilic and type 2 asthma. Despite observed overlaps, a considerable proportion of patients had only a predominantly allergic subtype. Understanding the degree of overlap across phenotypes will help patient management and guide treatment options.
Assuntos
Asma/imunologia , Eosinofilia/imunologia , Inflamação/imunologia , Adulto , Asma/classificação , Asma/metabolismo , Asma/fisiopatologia , Feminino , Teste da Fração de Óxido Nítrico Exalado , Humanos , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Hipersensibilidade Respiratória/imunologia , Índice de Gravidade de DoençaRESUMO
For a long time asthma was commonly considered as a homogeneous disease. However, recent studies provide increasing evidence of its heterogeneity and existence of different phenotypes of the disease. Currently, classification of asthma into several phenotypes is based on clinical and physiological features, anamnesis, and response to therapy. This review describes five most frequently identified asthma phenotypes. Neutrophilic asthma (NA) deserves special attention, since neutrophilic inflammation of the lungs is closely associated with severity of the disease and with the resistance to conventional corticosteroid therapy. This review focuses on molecular mechanisms of neutrophilic asthma pathogenesis and on the role of Th1- and Th17-cells in the development of this type of asthma. In addition, this review presents current knowledge of neutrophil biology. It has been established that human neutrophils are represented by at least three subpopulations with different biological functions. Therefore, total elimination of neutrophils from the lungs can result in negative consequences. Based on the new knowledge of NA pathogenesis and biology of neutrophils, the review summarizes current approaches for treatment of neutrophilic asthma and suggests new promising ways to treat this type of asthma that could be developed in future.
Assuntos
Antiasmáticos/uso terapêutico , Antibacterianos/uso terapêutico , Asma/tratamento farmacológico , Asma/imunologia , Neutrófilos/imunologia , Fenótipo , Inibidores da Fosfodiesterase 4/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Antiasmáticos/farmacologia , Asma/classificação , Asma/patologia , Citocinas/antagonistas & inibidores , Citocinas/metabolismo , Humanos , Receptores de Citocinas/antagonistas & inibidores , Receptores de Citocinas/metabolismo , Células Th1/imunologia , Células Th17/imunologia , Resultado do TratamentoRESUMO
Asthma is a chronic disease whose main anatomical-functional alterations are grouped into obstruction, nonspecific bronchial hyperreactivity, inflammation and airway remodeling. Currently, the Global Initiative of Asthma 2020 (GINA 2020) suggests classifying it into intermittent cases, slightly persistent, moderately persistent and severely persistent, thus determining the correct guidelines for its therapy. In general, the drugs used for its management are divided into two groups, those with a potential bronchodilator and the controlling agents of inflammation. However, asthmatic treatments continue to evolve, and notable advances have been made possible in biological therapy with monoclonal antibodies and in the relationship between this disease and oxidative stress. This opens a new path to dietary and herbal strategies and the use of antioxidants as a possible therapy that supports conventional pharmacological treatments and reduces their doses and/or adverse effects. This review compiles information from different published research on risk factors, pathophysiology, classification, diagnosis and the main treatments; likewise, it synthesizes the current evidence of herbal medicine for its control. Studies on integrative medicine (IM) therapies for asthmatic control are critically reviewed. An integrative approach to the prevention and management of asthma warrants consideration in clinical practice. The intention is to encourage health professionals and scientists to expand the horizons of basic and clinical research (preclinical, clinical and integrative medicine) on asthma control.
Assuntos
Asma/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antioxidantes/uso terapêutico , Asma/classificação , Asma/diagnóstico , Asma/fisiopatologia , Broncodilatadores/uso terapêutico , Humanos , Estresse Oxidativo , Preparações de Plantas/uso terapêutico , Fatores de RiscoRESUMO
El asma bronquial es la enfermedad crónica más frecuente en la infancia. Sin embargo, en Chile existe un importante subdiagnóstico. Es fundamental estar atentos a los síntomas y signos que nos hacen sospechar el diagnóstico para iniciar un tratamiento oportuno, que asegure un buen control de la enfermedad. Debemos sospechar asma en todo escolar que presente cuadros repetidos de obstrucción bronquial. El diagnóstico debe confirmarse con pruebas de función pulmonar que demuestren obstrucción variable al flujo aéreo y respuesta broncodilatadora positiva. El tratamiento se basa en dos pilares fundamentales: la educación y el tratamiento farmacológico. Las actividades educativas deben incluir contenidos acerca de la enfermedad y su tratamiento, se debe monitorizar constantemente la adherencia al tratamiento de mantención, enseñar la técnica inhalatoria correcta y revisar en cada control, entregar un plan de acción escrito personalizado frente al inicio de una crisis y realizar controles médicos periódicos. Con respecto al tratamiento farmacológico, el estándar de oro es el uso de corticoides inhalados permanentes, en la mínima dosis posible que logre el control de la enfermedad. El objetivo del tratamiento es la supresión de los síntomas diarios y de las crisis. El tratamiento se irá incrementando en la medida que no haya una respuesta adecuada, pero antes de aquello se debe evaluar la adherencia al tratamiento de mantención, la técnica inhalatoria, presencia de comorbilidades asociadas y exposición ambiental. En el paciente leve, que esté sin tratamiento permanente, el rescate debe realizarse con broncodilatadores asociados siempre a un corticoide inhalado. Este consenso es una guía de apoyo para mejorar el diagnóstico oportuno, tratamiento y control del asma en el escolar.
Bronchial asthma is the most prevalent chronic condition among children, however, in Chile, it is underdiagnosed. This may be due to medical professionals failing to recognize the disease. It is essential to be aware of the symptoms and signs that are suggestive of the disease in order to begin an appropriate treatment to achieve disease control. Asthma must be suspected in school age children who present repeated episodes of bronchial obstruction. The diagnosis should be confirmed with lung function tests that demonstrate variable airflow obstruction with a positive bronchodilator response. Treatment is based on two fundamental pillars: education and pharmacological treatment. Educational activities must include: information about the disease and its treatment, regular monitoring of treatment adherence, teaching and reviewing the correct inhalation technique at every checkup, developing a personalized written action plan and scheduling regular follow-up appointments. The gold standard for treatment is maintenance inhaled corticosteroids, in the lowest possible dose that enables disease control. The goal of the treatment is to eliminate daily symptoms and asthma crisis. Therapy should be increased if control is not achieved, but before starting it, adherence to maintenance treatment, inhalation technique, presence of associated comorbidities and environmental exposure should be evaluated. In the mild patient, who is not receiving maintenance therapy, rescue treatment should be done with bronchodilators, always associated with inhaled corticosteroids. This consensus is a guide to improve the diagnosis, treatment and control of asthma in schoolchildren
Assuntos
Humanos , Criança , Asma/diagnóstico , Asma/terapia , Oxigenoterapia , Testes de Função Respiratória , Asma/classificação , Asma/tratamento farmacológico , Vitamina D/sangue , Índice de Gravidade de Doença , Nebulizadores e Vaporizadores , Radiografia Torácica , Fatores Desencadeantes , Chile , Consenso , Diagnóstico DiferencialRESUMO
Bronchial asthma is the most prevalent chronic condition among children, however, in Chile, it is underdiagnosed. This may be due to medical professionals failing to recognize the disease. It is essential to be aware of the symptoms and signs that are suggestive of the disease in order to begin an appropriate treatment to achieve disease control. Asthma must be suspected in school age children who present repeated episodes of bronchial obstruction. The diagnosis should be confirmed with lung function tests that demonstrate variable airflow obstruction with a positive bronchodilator response. Treatment is based on two fundamental pillars: education and pharmacological treatment. Educational activities must include: information about the disease and its treatment, regular monitoring of treatment adherence, teaching and reviewing the correct inhalation technique at every checkup, developing a personalized written action plan and scheduling regular follow-up appointments. The gold standard for treatment is maintenance inhaled corticosteroids, in the lowest possible dose that enables disease control. The goal of the treatment is to eliminate daily symptoms and asthma crisis. Therapy should be increased if control is not achieved, but before starting it, adherence to maintenance treatment, inhalation technique, presence of associated comorbidities and environmental exposure should be evaluated. In the mild patient, who is not receiving maintenance therapy, rescue treatment should be done with bronchodilators, always associated with inhaled corticosteroids. This consensus is a guide to improve the diagnosis, treatment and control of asthma in schoolchildren.
El asma bronquial es la enfermedad crónica más frecuente en la infancia. Sin embargo en Chile existe un importante subdiagnóstico. Es fundamental estar atentos a los síntomas y signos que nos hacen sospechar el diagnóstico para iniciar un tratamiento oportuno, que asegure un buen control de la enfermedad. Debemos sospechar asma en todo escolar que presente cuadros repetidos de obstrucción bronquial. El diagnóstico debe confirmarse con pruebas de función pulmonar que demuestren obstrucción variable al flujo aéreo y respuesta broncodilatadora positiva. El tratamiento se basa en dos pilares fundamentales: la educación y el tratamiento farmacológico. Las actividades educativas deben incluir contenidos acerca de la enfermedad y su tratamiento, se debe monitorizar constantemente la adherencia al tratamiento de mantención, enseñar la técnica inhalatoria correcta y revisar en cada control, entregar un plan de acción escrito personalizado frente al inicio de una crisis y realizar controles médicos periódicos. Con respecto al tratamiento farmacológico, el estándar de oro es el uso de corticoides inhalados permanentes, en la mínima dosis posible que logre el control de la enfermedad. El objetivo del tratamiento es la supresión de los síntomas diarios y de las crisis. El tratamiento se irá incrementando en la medida que no haya una respuesta adecuada, pero antes de aquello se debe evaluar la adherencia al tratamiento de mantención, la técnica inhalatoria, presencia de comorbilidades asociadas y exposición ambiental. En el paciente leve, que esté sin tratamiento permanente, el rescate debe realizarse con broncodilatadores asociados siempre a un corticoide inhalado. Este consenso es una guía de apoyo para mejorar el diagnóstico oportuno, tratamiento y control del asma en el escolar.
Assuntos
Humanos , Criança , Asma/diagnóstico , Asma/terapia , Respiração Artificial , Testes de Função Respiratória , Asma/classificação , Asma/fisiopatologia , Estado Asmático/etiologia , Nebulizadores e Vaporizadores , Chile , Antiasmáticos/uso terapêutico , Consenso , Cooperação e Adesão ao TratamentoRESUMO
BACKGROUND: More than 300 million people carry a diagnosis of asthma, with data to suggest that they are at a higher risk for infection or adverse outcomes from severe acute respiratory syndrome coronavirus 2. Asthma is remarkably heterogeneous, and it is currently unclear how patient-intrinsic factors may relate to coronavirus disease 2019. OBJECTIVE: We sought to identify and characterize subsets of patients with asthma at increased risk for severe acute respiratory syndrome coronavirus 2 infection. METHODS: Participants from 2 large asthma cohorts were stratified using clinically relevant parameters to identify factors related to angiotensin-converting enzyme-2 (ACE2) expression within bronchial epithelium. ACE-2-correlated gene signatures were used to interrogate publicly available databases to identify upstream signaling events and novel therapeutic targets. RESULTS: Stratifying by type 2 inflammatory biomarkers, we identified subjects who demonstrated low peripheral blood eosinophils accompanied by increased expression of the severe acute respiratory syndrome coronavirus 2 receptor ACE2 in bronchial epithelium. Genes highly correlated with ACE2 overlapped with type 1 and 2 IFN signatures, normally induced by viral infections. T-cell recruitment and activation within bronchoalveolar lavage cells of ACE2-high subjects was reciprocally increased. These patients demonstrated characteristics corresponding to risk factors for severe coronavirus disease 2019, including male sex, history of hypertension, low peripheral blood, and elevated bronchoalveolar lavage lymphocytes. CONCLUSIONS: ACE2 expression is linked to upregulation of viral response genes in a subset of type 2-low patients with asthma with characteristics resembling known risk factors for severe coronavirus disease 2019. Therapies targeting the IFN family and T-cell-activating factors may therefore be of benefit in a subset of patients.