Qualidade de vida e inflamação das vias aéreas em diferentes níveis de controle da asma

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Ciências Médicas, Florianópolis, 2013.Introdução: A asma é uma doença inflamatória crônica das vias aéreas cujo objetivo principal do tratamento é atingir e manter o controle. Diversos estudos demonstram que a qualidade de vida dos asmáticos é diminuída pela doença e que esta redução pode estar relacionada ao seu controle. No entanto, até o presente, nenhum estudo avaliou o impacto do controle aferido pela GINA 2012 na qualidade de vida. Objetivos: O presente estudo visa, determinar, nos diferentes níveis de controle da asma propostos pela GINA 2012: (1) o impacto do controle da asma na qualidade de vida dos asmáticos; (2) a inflamação das vias aéreas (eosinofílica e neutrofílica) por meio da análise do escarro induzido; (3) o escore de qualidade de vida medido pelo questionário padronizado de qualidade de vida em asma [AQLQ(S)]. Métodos: Estudo transversal, com 86 participantes, com asma persistente e todos em uso de um corticoide associado com um broncodilatador de ação prolongada, com asma controlada (AC), parcialmente controlada (APC) ou não controlada (ANC) pela escala GINA 2012, avaliados em uma única visita realizada no Núcleo de Pesquisa em Asma e Inflamação das Vias Aéreas, do Hospital Universitário, da Universidade Federal de Santa Catarina (NUPAIVA/HU/UFSC). A qualidade de vida foi estabelecida pelo questionário doença-específico AQLQ(S). O componente inflamatório foi avaliado por meio do escarro induzido. Resultados: Os resultados demonstraram que a qualidade de vida diminuiu com a piora do controle da asma e que o impacto da falta de controle sobre a qualidade de vida foi estatisticamente significante e clinicamente importante mesmo nos pacientes com APC. Na maioria (75%) dos pacientes com AC, a influência da doença na qualidade de vida foi mínima ou ausente. Em contraste, em apenas uma minoria dos pacientes com APC (28%) e com ANC (6%) o comprometimento da asma na qualidade de vida foi mínimo ou ausente (p Abstract : Introduction: Asthma is a chronic inflammatory respiratory disease whose main goal of treatment is to achieve and maintain control. Several studies have shown that quality of life is diminished by asthma and that this reduction may be related to its control. However, to date, no study has evaluated the impact of control measured by GINA 2012 on quality of life. Objectives: This study aims to determine, in the different levels of asthma control proposed by GINA 2012: (1) the impact of asthma control in the quality of life of asthmatics; (2) airway inflammation and eosinophilic and neutrophilic inflammation through analysis of induced sputum; (3) the score of quality of life measured by the asthma quality of life standardized questionnaire [AQLQ(S)]. Methods: Cross-sectional study with 86 participants, all in a corticosteroid use associated with a long-acting bronchodilator with controlled (CA), partly controlled (PCA) or uncontrolled asthma (UA), by GINA 2012 scale, evaluated at a single visit held at the Asthma and Airway Inflammation Center Research, University Hospital, Federal University of Santa Catarina (NUPAIVA/HU/UFSC). The quality of life was established by the AQLQ(S). The inflammation component was assessed by induced sputum. Results: The results showed that quality of life decreased with worsening of asthma control and the impact of the lack of control over the quality of life was statistically significant and clinically important even in patients with PCA. Most (75%) of patients with CA, the influence of disease on quality of life was minimal or none. In contrast, in only a minority of patients with PCA (28%) and UA (6%) the impact of asthma on quality of life was minimal or none (p < 0.001). The greatest mean differences (CA vs. PCA) was observed in the environmental stimulus domain, while the lowest average difference (CA vs PCA) was observed in the symptoms domain. Eosinophilic airway inflammation was found in all three levels of asthma control. Neutrophilic sputum was found in almost half of patients with PCA and UC and in only one patient with CA (p = 0.001). Conclusions: The impact of asthma on quality of life is significant and clinically important even in patients with PCA. The lack of concordance of airway inflammation with the different levels of the GINA 2012 scale and AQLQ(S) score indicates that the airway inflammation measures a different component of asthma control

Asma grave: características clínicas e inflamatórias

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Ciências Médicas, Florianópolis, 2019.Introdução: A asma grave é uma doença complexa, multifatorial e heterogênea que constitui um importante problema mundial de saúde por estar associada à elevada morbidade e ser responsável por grande parte dos custos do sistema de saúde relacionados à asma. Objetivo: Caracterizar asma grave de pacientes adultos sob a perspectiva clínica e inflamatória local e sistêmica comparando-os com portadores de asma moderada. Métodos: Estudo transversal consistindo de uma única visita realizada no Núcleo de Pesquisa em Asma e Inflamação das Vias Aéreas, Hospital Universitário, Universidade Federal de Santa Catarina (NUPAIVA/HU/UFSC). Foram incluídos consecutivamente asmáticos adultos em tratamento ambulatorial. Foram considerados como portadores de asma grave os pacientes recebendo tratamento das etapas IV e V da GINA e que atenderam aos critérios diagnósticos de asma grave da força tarefa da ERS/ATS. Também foram incluídos pacientes com asma moderada (em tratamento na etapa III da GINA). Os marcadores inflamatórios foram avaliados no escarro (eosinófilos e neutrófilos) e no sangue (eosinófilos, fibrinogênio e PCRas). A qualidade de vida foi estabelecida pelo questionário doença-específico AQLQ(S) e o nível de controle da asma foi definido pelo ACQ6. Resultados: Cento e seis pacientes com asma moderada (n=55) ou grave (n=51) participaram do presente estudo. Comparados com portadores de asma moderada, uma proporção significativamente maior de participantes com asma grave relatou internação hospitalar anterior (78,4 vs. 25,5%, pAbstract : Introduction: Severe asthma is a complex, multifactorial and heterogeneous disease. It is an important global health problem and it is associated with high morbidity and responds for a large part of the costs of the health system related to asthma. Objective: To characterize severe asthma in adult patients from a clinical and local and systemic inflammatory perspective, comparing them with patients with moderate asthma. Methods: A cross-sectional study consisting of a single visit to the Asthma and Respiratory Tract Inflammation Research Center, University Hospital, Federal University at Santa Catarina (NUPAIVA/HU/UFSC). Asthmatic adults were consecutively included in outpatient treatment. Patients receiving treatment for GINA stage IV and V and with the diagnostic criteria for severe asthma by the ERS/ATS task force were considered as having severe asthma. Also were included patients with moderate asthma (receiving GINA treatment stage III). Inflammatory markers were measured in the sputum (eosinophils and neutrophils) and in the blood (eosinophils, fibrinogen and hsCPR). Quality of life was determinated by the disease-specific questionnaire AQLQ(S) and the level of asthma control was defined by ACQ6. Results: One hundred six patients with moderate (n=55) or severe (n=51) asthma participated in the present study. A significantly higher proportion of participants with severe asthma reported previous hospital admission (78.4 vs. 25.5%, p<0.001) and at ICU (25.5 vs. 7.3%, p=0.01). Participants with severe asthma presented greater impairment of lung function [mean and 95% CI of FEV1% pre-BD 70.4 (65.5-75.3) vs. 54.6 (48.4-60.7), p<0.001 and FEV1/FVC% pre-BD 0.67 (0.64-0.70) vs. 0.59 (0.55-0.62), p<0.001], had higher BMI [mean and CI 95% of BMI kg/m2 27.1 (25.7-28.5) vs. 30.2 (28.2-32.1), p=0.01) and worse control of asthma [mean and CI 95%: 1.9 (1.6-2.3) vs. 1.2 (1.5-2.3), p=0.001, respectively]. Additionally, participants with severe asthma had a higher prevalence of comorbidities related to asthma treatment including osteoporosis (13.7 vs. 1.8%, p=0.02) and cataracts (17.3 vs. 5.5%, p=0.05). The proportion of eosinophilic asthma (43.5 vs. 44.9%, p=0.1) and neutrophilic asthma (45.7 vs. 30.6% p=0.1) was similar between the two study groups (severe asthma and moderate asthma, respectively). The levels of hsCRP [mean and 95% CI: 4.2 (2.5- 6.0)mg/L vs. 13.0 (0.4-26.0)mg/L, p=0.06] were similar between the two study groups insted to plasma fibrinogen levels [mean and 95% CI: 261 (247-276)mg/dl vs. 304 (282-326)mg/dl, p=0.001]. There was a significant correlation between sputum eosinophils and blood eosinophils (rs=751, p<0.001). However, logistic regression analysis showed that sputum eosinophilia explained only 35% of blood eosinophil variability (r2=0.35, p<0.001). There was no association between fibrinogen and eosinophils or neutrophils in the induced sputum, both in the total asthmatic group and in the subgroups moderate asthma and severe asthma. Serum fibrinogen levels were also not associated with BMI and functional parameters. Same situation was observed about the hsCRP. However, there was a weak but significant correlation of fibrinogen with the age of the participant (rs=0.222, p=0.02). In contrast, the correlation between hsCRP and age was stronger and significant (rs=0.459, p<0.001). Quality of life analysis showed that patients with severe asthma had a greater impact at the disease [total score AQLQ(S)=4.5; p=0.02] and that this was predominantly associated with asthma control (r2=0.628, p<0.001). Conclusions: Patients with severe asthma have significantly higher levels of plasma fibrinogen than those with moderate asthma. In general and among the groups of patients with severe asthma and moderate asthma, there was no association between the markers of systemic inflammation and sputum cellularity. Patients with severe asthma have a greater impact of asthma on quality of life than those with moderate asthma, which can largely be explained by the lack of asthma control. The clinical and functional characteristics of patients with severe asthma differ significantly from those with moderate asthma; however, this difference was not found at the inflammatory pattern in the induced sputum and in the blood

Composição celular do escarro induzido em adultos saudáveis

OBJETIVO: Estabelecer valores de referência para a celularidade de amostras de escarro induzido coletadas de indivíduos adultos saudáveis. MÉTODOS: O escarro induzido foi obtido de 88 adultos saudáveis que nunca fumaram (39 homens) com média de idade de 36 anos (variação: 18-68 anos) residentes há pelo menos dois anos em Florianópolis, uma cidade brasileira não industrial e de tamanho médio. As amostras foram processadas, e foi realizada a contagem total e diferencial das células. RESULTADOS: A média da contagem celular total foi de 4,8 ± 4,2 × 10(6) células/g. Houve predomínio de macrófagos (média de 77,5 ± 14,7%) e de neutrófilos (média de 23,4 ± 14,3%). Os eosinófilos estiveram virtualmente ausentes (média de 0,1 ± 0,3%). A proporção de linfócitos e de células broncoepiteliais foi pequena. Não houve efeito da idade ou de atopia sobre a contagem celular total ou diferencial. CONCLUSÕES: Nesta população de indivíduos saudáveis, macrófagos e neutrófilos foram as células predominantes no escarro induzido. Contudo, a proporção de neutrófilos foi inferior à previamente relatada, sugerindo que os valores de normalidade podem variar de acordo com o local onde ele é amostrad

Reliability of a rapid hematology stain for sputum cytology

Objective: To determine the reliability of a rapid hematology stain for the cytological analysis of induced sputum samples. Methods: This was a cross-sectional study comparing the standard technique (May-Grünwald-Giemsa stain) with a rapid hematology stain (Diff-Quik). Of the 50 subjects included in the study, 21 had asthma, 19 had COPD, and 10 were healthy (controls). From the induced sputum samples collected, we prepared four slides: two were stained with May-Grünwald-Giemsa, and two were stained with Diff-Quik. The slides were read independently by two trained researchers blinded to the identification of the slides. The reliability for cell counting using the two techniques was evaluated by determining the intraclass correlation coefficients (ICCs) for intraobserver and interobserver agreement. Agreement in the identification of neutrophilic and eosinophilic sputum between the observers and between the stains was evaluated with kappa statistics. Results: In our comparison of the two staining techniques, the ICCs indicated almost perfect interobserver agreement for neutrophil, eosinophil, and macrophage counts (ICC: 0.98-1.00), as well as substantial agreement for lymphocyte counts (ICC: 0.76-0.83). Intraobserver agreement was almost perfect for neutrophil, eosinophil, and macrophage counts (ICC: 0.96-0.99), whereas it was moderate to substantial for lymphocyte counts (ICC = 0.65 and 0.75 for the two observers, respectively). Interobserver agreement for the identification of eosinophilic and neutrophilic sputum using the two techniques ranged from substantial to almost perfect (kappa range: 0.91-1.00). Conclusions: The use of Diff-Quik can be considered a reliable alternative for the processing of sputum samples

Reliability of a rapid hematology stain for sputum cytology

Objective: To determine the reliability of a rapid hematology stain for the cytological analysis of induced sputum samples. Methods: This was a cross-sectional study comparing the standard technique (May-Grünwald-Giemsa stain) with a rapid hematology stain (Diff-Quik). Of the 50 subjects included in the study, 21 had asthma, 19 had COPD, and 10 were healthy (controls). From the induced sputum samples collected, we prepared four slides: two were stained with May-Grünwald-Giemsa, and two were stained with Diff-Quik. The slides were read independently by two trained researchers blinded to the identification of the slides. The reliability for cell counting using the two techniques was evaluated by determining the intraclass correlation coefficients (ICCs) for intraobserver and interobserver agreement. Agreement in the identification of neutrophilic and eosinophilic sputum between the observers and between the stains was evaluated with kappa statistics. Results: In our comparison of the two staining techniques, the ICCs indicated almost perfect interobserver agreement for neutrophil, eosinophil, and macrophage counts (ICC: 0.98-1.00), as well as substantial agreement for lymphocyte counts (ICC: 0.76-0.83). Intraobserver agreement was almost perfect for neutrophil, eosinophil, and macrophage counts (ICC: 0.96-0.99), whereas it was moderate to substantial for lymphocyte counts (ICC = 0.65 and 0.75 for the two observers, respectively). Interobserver agreement for the identification of eosinophilic and neutrophilic sputum using the two techniques ranged from substantial to almost perfect (kappa range: 0.91-1.00). Conclusions: The use of Diff-Quik can be considered a reliable alternative for the processing of sputum samples

How does the GINA definition of control correlate with quality of life and sputum cellularity?

Since 2014, the Global Initiative for Asthma (GINA) has stated that asthma control should be measured using four questions concerning diurnal and nocturnal symptoms, activity limitation, and rescue medication use. We assessed how asthma control by this definition correlates with airway inflammation and quality of life. 113 asthmatic subjects consecutively recruited from their routine clinical appointment underwent spirometry, sputum induction and answered the Standardised Asthma Quality of Life Questionnaire (AQLQ(S)) during a single visit. 43 (38.1%), 37 (32.7%) and 33 (29.2%) subjects had controlled asthma, partly controlled asthma and uncontrolled asthma, respectively. The majority of subjects with controlled asthma (67.4%) had paucigranulocytic sputum. Eosinophilic sputum was present in all levels of asthma control. Although most subjects with controlled asthma (58.1%) achieved an AQLQ(S) score ≥6 (minimal or no impairment), the remaining patients (41.9%) had moderate/some impairment (AQLQ(S) score <6 and ≥3) due to activity impairment and environmental exposure. The present GINA definition of current symptom control reflects control of airway inflammation. However, quality of life impairment can be present even in these patients. Measuring quality of life may provide useful information when evaluating asthma control