Alberto Cukier Divisão de Pneumologia InCor/Hospital das Clínicas Faculdade de Medicina - USP ver 1.4

Devo aumentar a medicação visando a uma espirometria normal?

Devo aumentar a medicação visando a uma espirometria normal? Por que a espirometria é essencial para o controle?

Asma Correlação entre as variáveis de desfecho é pobre Em parte dos pacientes a função não normaliza Controle total nem sempre é possível Avaliar função? Por quê?

Desfechos na asma persistente Madrid 2003 10/04/2017 04:50 Medicação de resgate Despertar noturno PFE matinal VEF1 M e l h o r a HR Dias Semanas Meses Anos Woolcock. Clin Exp Allergy Rev 2001. F01 SHOW

É possível atingir o controle total da asma? SF 500 F 500 SF 250 F 250 SF 100 F 100 20 80 40 60 % Sem CEinal  500 µg beclo > 500 - < 1000 µg beclo Bateman. Am J Respir Crit Care Med 2004; 170: 836–844 ver 1.4 7 7

Consenso Brasileiro de Asma 2012 This classification system, which is largely based around symptom frequency, also forms the basis of current global asthma management guidelines Consenso Brasileiro de Asma 2012 ver 1.4

Consenso Brasileiro de Asma 2012 Future risk has been identified to include the risk of severe asthma exacerbations, loss of lung function, as well as long-term side effects of therapies. Whereas these recent developments represent maturation of the asthma control concept, an improved approach to asthma control that addresses these findings and incorporates current evidence and leads to improved asthma management is lacking. Consenso Brasileiro de Asma 2012 ver 1.4

Desfechos no estudo GOAL Refere Ward (6) = Função pulmonar atinge o pico após 3 meses. Ref (3) – Asma ocupacional por caranguejo. Retirada da ocupação a função pulmonar estabilizou após 1 ano, mas HR ainda melhorou após 2 anos. Ref (7) – retirada de CE inal – primeiro sinal de perda de controle é sintomas, depois PFE. Análise do estudo – tempo para atingir uma semana completa sem o desfecho. Bateman. J Asthma 2007, 44:667. ver 1.4

Desfechos no estudo GOAL Bateman. J Asthma 2007, 44:667.

Desfechos no estudo GOAL

Desfechos no estudo GOAL

Desfechos no estudo GOAL

Desfechos no estudo GOAL

Desfechos no estudo GOAL

ACQ 7 (última semana) Despertar noturno Sintomas ao despertar Limitação das atividades Dispneia Chiado Medicação de alívio VEF1 predito pré BD

ACQ 6 (última semana) Despertar noturno Sintomas ao despertar Limitação das atividades Dispneia Chiado Medicação de alívio VEF1 predito pré BD

ACQ 5 (última semana) Despertar noturno Sintomas ao despertar Limitação das atividades Dispneia Chiado Medicação de alívio VEF1 predito pré BD

Respiratory Medicine 2005

Em estudos clínicos – comparáveis ACQ 5 Juniper. Resp Med 2005

ACT (últimas 4 semanas) Limitação das atividades Dispneia Despertar noturno Medicação de alívio Percepção de controle

ACT não correlaciona com VEF1 Melosini et al. [28] also found that pulmonary function and airway inflammation as assessed by sputum eosinophil count or fractional exhaled nitric oxide (FeNO) were not related to the ACT score in adults with asthma. Similarly in children with asthma, airway inflammation measured by FeNO showed poor accuracy in the differentiation of not well controlled asthma [29]. Furthermore, airway inflammation, either eosinophilic or neutrophilic predominant, persists in a large proportion of patients with well controlled asthma [28,30]. The significance of this is unclear. The finding that airway inflammation is not well correlated with clinical control of asthma may suggest that the measurement of a pathogenic process, particularly airway inflammation, beyond an assessment of clinical control, provides additional information of inherent disease activity (Fig. 1). Melosini. J Asthma 2012; 49:317. ver 1.4

VEF1 (%) 55 ± 17 Miscelânea Carvalho Pinto, RM. Resp Med 2012; 106:47

VEF1 (%) 55 ± 17 Atópico Precoce Eosinofílico Obstrução fixa Carvalho Pinto, RM. Resp Med 2012; 106:47

VEF1 (%) 55 ± 17 Não atópico Tardio Eosinofílico Obstrução fixa Carvalho Pinto, RM. Resp Med 2012; 106:47

VEF1 (%) 55 ± 17 Atópico Tardio Eosinofílico Obstrução fixa Carvalho Pinto, RM. Resp Med 2012; 106:47

Não atópico Precoce Não eosinofílico Obstrução fixa Carvalho Pinto, RM. Resp Med 2012; 106:47

Efeito do tratamento - VEF1 Carvalho Pinto. ERS (Thematic Poster) 2012 * *# ** VEF1 (%) Pré BD Pré BD Pré BD Basal CE oral 14 d For/Bud 3 m

Efeito do tratamento - VEF1 * ** **# *# # *p<0,05vs. A; **p<0,05vs.C; #p<0,05 vs. Sem Obstrução VEF1 (%) B CE F/B B CE F/B Reversível Obstrução persistente Carvalho Pinto RM. ERS 2012

ΔVR/CPT% grupos, pré-pós tratamento *p<0,05vs. A; **p<0,05vs.C; #p<0,05 vs. Sem Obstrução * ** # *# Carvalho Pinto RM. ERS 2012

Os dois primeiros slides referem-se ao qualitativo Os dois primeiros slides referem-se ao qualitativo. Quem tem impactação mucoide tem melhor melhora no VEF1 apos corticoide.   Os outros dois são dados da análise quantitativa do espessamento brônquico. Não houve diferença de maneira global entre quem reposndeu e quem não respondeu ao coticoide no grau de espessamento bronquico. Mas existe uma correção negativa entre grau de espessamento bronquico e VEf1 basal (grafico que inclui). ver 1.4

Presença de impactação mucóide VEF1 % p < 0,05 Curso de Prednisona 40mg por 14 dias

r = -0,136 p < 0,05

Padrões de obstrução Pré BD Pós BD Pós broncoprovocação Obstrução Gibson. Thorax 2009;64:728-735 Pós BD Pós broncoprovocação %VEF1 Physiological patterns of airflow obstruction, expressed as forced expiratory volume in 1 s (FEV1), percentage predicted. Reversible AO, reversible airflow obstruction with improvement in FEV1 after bronchodilator; irreversible AO, incompletely reversible airflow obstruction, postbronchodilator FEV1 is ,80%; irreversible AO+BDR, incompletely reversible airflow obstruction with significant bronchodilator responsiveness (BDR); irreversible AO+BHR, incompletely significant bronchial hyperresponsiveness with fall in FEV1 after bronchoconstrictor. The label ‘asthma’ can be applied to reversible AO, irreversible AO+BDR and irreversible AO+BHR. Chronic obstructive pulmonary disease (COPD) can be applied to each of the conditions with irreversible AO+BHR. Overlap syndrome is present in AO+BHR Obstrução reversível Obstrução irreversível Obstrução Irreversível com resposta Obstrução Irreversível com HR

DPOC Asma Obstrução irreversível Irreversível com resposta com HR Physiological patterns of airflow obstruction, expressed as forced expiratory volume in 1 s (FEV1), percentage predicted. Reversible AO, reversible airflow obstruction with improvement in FEV1 after bronchodilator; irreversible AO, incompletely reversible airflow obstruction, postbronchodilator FEV1 is ,80%; irreversible AO+BDR, incompletely reversible airflow obstruction with significant bronchodilator responsiveness (BDR); irreversible AO+BHR, incompletely significant bronchial hyperresponsiveness with fall in FEV1 after bronchoconstrictor. The label ‘asthma’ can be applied to reversible AO, irreversible AO+BDR and irreversible AO+BHR. Chronic obstructive pulmonary disease (COPD) can be applied to each of the conditions with irreversible AO+BHR. Overlap syndrome is present in AO+BHR

Overlap Obstrução Irreversível com resposta Obstrução Irreversível Physiological patterns of airflow obstruction, expressed as forced expiratory volume in 1 s (FEV1), percentage predicted. Reversible AO, reversible airflow obstruction with improvement in FEV1 after bronchodilator; irreversible AO, incompletely reversible airflow obstruction, postbronchodilator FEV1 is ,80%; irreversible AO+BDR, incompletely reversible airflow obstruction with significant bronchodilator responsiveness (BDR); irreversible AO+BHR, incompletely significant bronchial hyperresponsiveness with fall in FEV1 after bronchoconstrictor. The label ‘asthma’ can be applied to reversible AO, irreversible AO+BDR and irreversible AO+BHR. Chronic obstructive pulmonary disease (COPD) can be applied to each of the conditions with irreversible AO+BHR. Overlap syndrome is present in AO+BHR Obstrução Irreversível com resposta Obstrução Irreversível com HR

Asma na infância está associada a DPOC no adulto Sem asma Remissão da asma Asma atual DPOC The original groups were classified as follows: control or nonasthmatics—105 children who had never wheezed; MWB—74 children with fewer than five episodes of wheezing associated with bronchitis; WB—104 children with five or more episodes of wheezing associated with bronchitis; asthma—113 children with wheezing not associated with respiratory tract infection; and SA—83 children with onset of symptoms before 3 years of age, persistent symptoms at 10 years of age, barrel-chest deformity and or FEV1 to FVC ratio to 50% or less (of which only three had a FEV1 to FVC ratio under 50%). The group of children with MWB and WB would now be regarded as children with intermittent asthma. Non-asthmatics: Those who were originally in the nonasthmatic childhood group and remained wheeze-free throughout the study period. Asthma remission: Those who were originally in one of the four symptomatic groups at recruitment who had been wheezefree and not taken asthma medication in the preceding 3 years. Current asthma: Those who were originally in one of the four symptomatic groups or non-asthmatic group at recruitment and who had asthma symptoms or had taken asthma medication for the preceding 3 years. COPD: Postbronchodilator FEV1 to FVC ratio <0.7 group who were defined at the age of 50. The reduced lung function seen in those with COPD and current asthma at 50 years was clearly established in the childhood years (figure 1). In the COPD group, there is a lack of increase in %predicted FEV1 when compared with the nonasthmatic, asthma remission and current asthma groups during the age of 14–21. Tai S. Thorax 2014 ver 1.4

Tai S. Thorax 2014

Risco de DPOC, asma, ICC, diabete, Ca próstata, Ca mama However, an ominous pattern is apparent in the data for asthma in fi gure 3 of Gershon and co-workers’ Article. Cross-sectional studies12 of adults with COPD suggest that asthma is a risk factor for the development of COPD later in life, and future rates of COPD (caused by increased asthma rates) might be higher than they are now, even if smoking rates continue to fall. However, better interventions for asthma, such as the use of inhaled steroids to treat infl ammation, could result in less airway remodelling and, subsequently, less COPD. The analysis by Gershon and colleagues did not follow up the population across the lifetime but only 14 years, which is a little more than the interval between two risk estimates in the fi gure. Thus, whether the increased cases of asthma recorded in childhood and young adulthood will result in more COPD in the future is unclear. Gershon. Lancet 2011; 378: 991–96

Guilbert. N Engl J Med 2006; 354:1985–1997. CEinal não curam asma The PEAK study recruited 285 two to four year old wheezy children (mean age 3.0 years) with a positive asthma predictive index and randomly assigned them to fluticasone propionate 88mg twice daily or placebo via MDI and spacer for two years. They were then followed for a further observational year. The primary outcome was the proportion of episode-free days during the observational year. During the observational year no significant differences were seen between the two groups in the proportion of episode free days (85.9% vs. 86.8%) or the number of exacerbations/100 child-years (82.5 vs. 85.5), placebo vs. fluticasone propionate respectively. They concluded that in preschool children at high risk of asthma, two years of ICS treatment did not change the development of asthma symptoms during a third treatment free year Guilbert. N Engl J Med 2006; 354:1985–1997. ver 1.4

Fu, McDonald, Wang, Gibson. Curr Opin Pulm Med 2014; 20:1 KEY POINTS The agreement between some assessment instruments of asthma control is poor. The identification of uncontrolled asthma using composite scores with current established cut-off points is problematic due to the low sensitivity. An assessment of overall asthma control involves the evaluation of clinical control, disease activity/control and the consideration of asthma-related comorbidities. Current status of clinical control and exacerbation risk are different components of overall asthma control that are not necessarily related. Fu, McDonald, Wang, Gibson. Curr Opin Pulm Med 2014; 20:1 ver 1.4

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Efeito do tratamento de rinite no controle da asma Nasal Inalado Nasal+ inalado Stelmach R. Chest 2005; 128:3140 ver 1.4

Efeito do tratamento de rinite no controle da asma PS n Nasal Inalado Nasal+ inalado Stelmach R. Chest 2005; 128:3140 ver 1.4

Efeito do tratamento de rinite no controle da asma Despertar Nasal Inalado Nasal+ inalado Stelmach R. Chest 2005; 128:3140 ver 1.4

Efeito do tratamento de rinite no controle da asma Falta Nasal Inalado Nasal+ inalado Stelmach R. Chest 2005; 128:3140 ver 1.4

Impacto do emagrecimento no controle da asma Dias-Júnior, S. ERJ 2014 (no prelo)

Fazer espirometria? Por quê? Instrumento de trabalho do pneumologista Cardiologista faz consulta sem ECG? Em fase aguda Avaliar gravidade e resposta ao tratamento Em fase estável Função máxima possível Step down Reversibilidade = manter broncodilatador ver 1.4