Sintomas VEF1 Função normal  função

Apresentação em tema: "Sintomas VEF1 Função normal  função"— Transcrição da apresentação:

1

2 Sintomas VEF1 Função normal  função 100 50 20
Sutherland. NEJM 2004: 350:2689

3 Potencial de conflito de interesse
Verba para pesquisas Consultor Palestrante Investigador principal ou co-investigador Patrocínio - eventos nacionais e internacionais Pharmaceutical companies - have served on the Advisory Board and speaker´s bureau, and as a Principal Investigator or co-investigator in clinical trials sponsored by Astra Zeneca, GlaxoSmithKline, Boehringer Ingelheim, Novartis, Altana Pharma and Pfizer Astra Zeneca, Bayer, Boehringer Ingelheim, Farmalab Chiesi, GlaxoSmithKline, Novartis, Nycomed, Pfizer, Schering Plough

4 Potencial de conflito de interesse
Comissão de Farmácia HCFMUSP Protocolo tratamento DPOC - Estado de São Paulo Pharmaceutical companies - have served on the Advisory Board and speaker´s bureau, and as a Principal Investigator or co-investigator in clinical trials sponsored by Astra Zeneca, GlaxoSmithKline, Boehringer Ingelheim, Novartis, Altana Pharma and Pfizer

5 Diagnóstico e tratamento precoces interferem na evolucão da DPOC?

6 Diagnóstico e tratamento precoces interferem na evolucão da DPOC?

7 Diagnóstico e tratamento precoces interferem na evolucão da DPOC?

8 Diagnóstico e tratamento precoces interferem na evolucão da DPOC?
Iniciar BD Tratamento precoce

9 Cessação de tabagismo muda a história natural
Basal 82 80 78 76 74 72 VEF1 (%) Anos Fumante Cessou Lung function improved during Year 1 among quitters, but declined among continuing smokers. The subsequent rate of decline is twice as great among continuing smokers as among sustained quitters. Those who relapsed lost function and those who delayed quitting benefited regardless of when they quit. Study participants in the SI-P and UC groups who stopped smoking in Year 1 had an average increase in FEV1 of 47 ml or 1.98%pred at the Year 1 visit. Between Year 1 and Year 5, the sustained quitters had a rate of decline in FEV1 of 31 ml/yr or 0.27% pred/yr. In contrast, continuing smokers showed a more rapid rate of decline in FEV1 , both during the first year and between Year 1 and Year 5. At the Year 1 visit, FEV1 had decreased by 49 ml or 0.74% pred. Between Year 1 and Year 5, FEV1 decreased by 62 ml/yr, twice the rate observed in sustained quitters (p, 0.001, Table 2). Participants who quit during the first year and then relapsed after Year 1 showed a 1.59% decline in FEV1% pred after relapsing (p , 0.001). Those participants who quit smoking after the first year showed a 1.61% improvement in FEV1 %pred after quitting (p ,0.001), which was also comparable to the benefit observed in SI-P quitters at Year 1 The Lung Health Study. Am J Respir Crit Care Med 2000;161:381

10 Espirometria em massa para fumantes?

11 ? On current evidence, screening to detect mild COPD is not warranted and will waste resources that would be better employed to promote smoking cessation in general. Thorax 2006;61:869 Thorax 2007;62:742

12 ? On current evidence, screening to detect mild COPD is not warranted and will waste resources that would be better employed to promote smoking cessation in general. Thorax 2006;61:869 Thorax 2007;62:742

13 VEF1/CVF subdiagnostica obstrução nos mais jovens e superdiagnostica nos mais velhos
If we define the Lower Limit of Normal (LLN) as SD below the predicted in effect we are accepting a false positive rate of 5% in identifying subjects as abnormal. If we chose the LLN as 1.96 SD below predicted we would accept a false positive rate of 2.5%. The ATS and ERS endorse using the LLN as SD below predicted GOLD applies a value of 70% for the value of FEV1 as a percent of FVC to define airflow limitation. All major prediction equations find that FEV1% falls with age and so the LLN for this index also drops with age. The Figure opposite shows a theoretical sample population of men whose data fit the NHANES III [ 12 ] equation for FEV1%. All subjects plotted as green dots are truly within the normal range. Those plotted in red are below the LLN and represent the expected 5% of the total population (vide supra). The dark blue dots are those subjects where GOLD falsely says they are normal (>70%) but are in fact below the LLN (false negatives) and the mid blue dots are those where GOLD says they are abnormal when in fact they are above the LLN (false positives). When considering a similar plot for females in the Figure opposite it can be seen that the age at which the 70% cutoff changes from giving false negatives (dark blue) to false positives (mid blue) in women is about 50 yrs and is older than that found in men, approx 40 yrs. Thus not only does the GOLD criterion of <70% for FEV1% falsely categorise subjects it also introduces a sex bias. To the right is the same plot as above but for females, and it can be seen that the age where false positives start is again older in the females, and now there are some subjects that GOLD says are normal (dark blue dots) but who are in fact below the LLN and so are false negatives. This will lead to more older subjects being diagnosed with COPD than is justified, since the inclusion criteria as shown above will include a significant number of normal subjects who do not have disease, as well as lead to false negative findings in younger subjects [ 6-11 ]. These false positives will then possibly receive treatment and unnecessary tests they do not require and bear the burden of the label of disease they do not warrant.

14 40% dos DPOC fumantes atendidos no HCFMUSP negam o hábito
eCO (ppm) Cotinina Urinária (ng/mL) 5 10 15 20 25 1 100 1000 10000

15 Eliminar fatores de risco Vacinação anti-influenza
0-Sob risco Leve Moderada Grave Muito grave Eliminar fatores de risco Vacinação anti-influenza + BD de curta ação de demanda + um ou mais BD de ação prolongada (se necessário) + reabilitação + CE inalatório se exacerbações freqüentes +O2 Cirurgia GOLD Workshop Report Update 2001

16 Eliminar fatores de risco Vacinação anti-influenza
Leve Moderada Grave Muito grave Eliminar fatores de risco Vacinação anti-influenza + BD de curta ação de demanda + um ou mais BD de ação prolongada (se necessário) + reabilitação + CE inalatório se exacerbações freqüentes +O2 Cirurgia GOLD Workshop Report Update 2007

17 Recomendação ACP Espirometria deve ser utilizada para avaliar obstrução somente em indivíduos sintomáticos. (Grau da recomendação - forte, qualidade da evidência - moderada.) American College of Physicians. Ann Intern Med. 2007;147:633.

18 Medicar assintomáticos?
Iniciar BD Tratamento precoce

19 Fármacos melhoram prognóstico?

20 TORCH - Análise primária: mortalidade por todas as causas em 3 anos
17,5% redução de risco Probabilidade de óbito (%) 18 16 Placebo 15,2% 14 SFC ,6% 12 10 2,6% Redução absoluta 8 6 4 The survival status of 6111/6112 patients was established. One subject in the SFC arm with survival status unknown at 3 years was treated as censored at 2 years (113 weeks) (the last time point at which survival status was known). The difference in all-cause mortality between SFC and placebo was analysed by the log-rank test (stratified by smoking status) and presented as a Kaplan-Meier plot and calculated hazard ratios. The log-rank test is a popular method for comparing the survival of groups that takes into account the whole follow-up period. It was used to test the null hypothesis that there was no difference between treatment groups in the probability of an event (death) at any time point. The unadjusted hazard ratio for time to all-cause mortality at 3 years between SFC versus placebo was 0.820, p= This p value must be compared to a significance level of p=0.04 because of the interim analyses. The adjusted Hazard Ratio for time to all-cause mortality at 3 years between SFC versus placebo was 0.825, indicating a 17.5% reduction in the risk of death from any cause (p=0.052). The absolute risk reduction with SFC was 2.6% compared with placebo. Although the difference between SFC and placebo was on the edge of the pre-specified p-value of 0.05, it is debatable whether this modest reduction in confidence about the significance of the mortality data invalidates the conclusions. The number of deaths in this 4-limb trial was substantial (875 in the ITT population in total, 193 on SFC and 231 on placebo), although still less than anticipated (the study was powered assuming 440 deaths for SFC and placebo in total, whereas we actually had 424). We powered the study assuming a 17% placebo mortality rate over 3 years whereas our placebo rate was only 15.2%). This, together with the impact of the interim analyses, may explain the observed significance level for the primary outcome. Reference Calverley PMA, Anderson JA, Celli B. for the TORCH investigators. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. NEJM 2007; 356(8): Dizer da pneumonia e outros efeitos colaterais sem fazer slide específico 2 12 24 36 48 60 72 84 96 108 120 132 144 156 Tempo até o óbito (semanas) Calverley et al. NEJM 2007

21 TORCH - Escore total SGRQ
Mudança ajustada média do escore total do SGRQ (unidades) 3 Placebo 2 1 SALM * FP † SFC †† –1 –2 –3 The St George’s Respiratory Questionnaire (SGRQ) was used to record patient health status. The Health Outcomes population comprised 4,951 patients from 28 countries in which a validated SGRQ exists. A transformed score was calculated for each of the SGRQ’s three domains (Symptoms, Impacts and Activity) as well as the overall total score. SGRQ was analysed as change from baseline using repeated measures analysis. This model included treatment, smoking status, age, gender, baseline FEV1, BMI, region, visit (as a categorical variable) and treatment by visit. Baseline SGRQ and visit by baseline SGRQ were also included in the model. Estimated treatment differences at each visit were averaged with equal weights to obtain the overall treatment effect over the study period. Total SGRQ score improved initially from baseline in all groups, the greatest changes occurring with SFC treatment (a decrease in SGRQ score indicates improvement). A statistically significant improvement in SGRQ total score in patients taking SFC compared to placebo was seen at 6 months (p=0.001) and maintained over the course of the study (p < 0.001). The adjusted mean change in SGRQ total score at 3 years was –1.2 for patients taking SFC, –0.2 for patients taking FP, 1.0 for patients taking SALM and 2.1 for patients taking placebo. At 3 years, patients taking SFC had still not returned to baseline SGRQ Although a clinically relevant 4 unit difference from baseline SGRQ total score was not achieved over 3 years, at 1 year, a 4 unit improvement (raw change) in SGRQ total score was observed in patients taking SFC (the only group to show this). It is important to remember that the fitter patients on placebo remain in the study for longer, which is likely to produce a conservative estimate of the treatment effect of SFC (see backup slides) COPD is a progressive disease in which health status declines over time, so these results for patients taking SFC (in whom SGRQ score had still not returned to baseline at 3 years and in which SGRQ score was significantly greater than placebo and components) is very important. Reference Calverley PMA, Anderson JA, Celli B. for the TORCH investigators. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. NEJM 2007; 356(8): & Online Supplement –4 –5 24 48 72 96 120 156 Tempo (semanas) Calverley et al. NEJM 2007

22 TORCH - Taxa de exacerbações moderadas e graves em três anos
Número médio de exacerbações/ano 1.2 1.13 0.97* 1 0.93* 0.85*†‡ 0.8 0.6 0.4 Moderate exacerbations are defined as those which require treatment with systemic corticosteroids and/or antibiotics; severe exacerbations are defined as those which require hospitalisation. The exacerbation rate was calculated as the total number of moderate and/or severe exacerbations experienced by a patient during the treatment period. The number of exacerbations was analysed using a generalised linear model, assuming the Negative Binomial distribution, with time on treatment as an offset variable. The model included adjustments for the effects of smoking status, age, gender, baseline FEV1, number of exacerbations reported in the 12 months prior to screening, and region.1 SFC significantly lowered the rate of moderate/severe exacerbations compared with placebo (25% reduction, p < 0.001), SALM (12% reduction, p = 0.002) and FP (9% reduction, p = 0.024). SALM and FP also had significantly lower exacerbation rates than placebo (15%, p < and 18%, p < 0.001, respectively).1 SFC reduced the rate of moderate-to-severe exacerbations to a much greater extent than placebo or either of the component monotherapies.1 Exacerbations and hospitalisations predict the risk of dying from COPD over 5 years.2 Reference Calverley PMA, Anderson JA, Celli B. for the TORCH investigators. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. NEJM 2007; 356(8): & Online Supplement Soler-Cataluna JJ, Martinez-Garcia MA, Roman Sanchez P, et al. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax 2005;60:925–31. 0.2 Placebo SALM FP SFC Calverley et al. NEJM 2007

23 Broncodilatadores melhoram a qualidade de vida
INTRODUCTION: Use of maintenance bronchodilator therapy is currently recommended in symptomatic patients with Chronic obstructive pulmonary disease (COPD) and in those with Stage II or greater COPD as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Because no prospective data describe when rescue therapy alone is insufficient or the optimal time to start maintenance therapy, it is unclear whether maintenance therapy has benefits in milder disease. To explore potential benefits we asked: Does once-daily tiotropium improve lung function, health status, and/or symptoms in "undertreated" COPD patients (i.e., those who are not receiving maintenance bronchodilator therapy) or patients considered by their health care providers as having milder disease? METHODS: A post-hoc analysis of data from COPD patients participating in two, 1-year, placebo-controlled trials with tiotropium was performed. Patients were defined as "undertreated" if they received no respiratory medication or only as-needed short-acting beta-agonists prior to enrollment. Measures included serial spirometry, Transition Dyspnea Index (TDI), and St. George's Respiratory Questionnaire (SGRQ). RESULTS: Of 921 patients enrolled, 218 (23.7%) were "undertreated": 130 received tiotropium; 88 received placebo. Demographics for the two treatment groups were comparable. Tiotropium-treated patients had significantly improved forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) compared with patients using placebo on all study days. Additionally, TDI and SGRQ scores significantly improved with tiotropium compared with placebo. CONCLUSIONS: Once-daily tiotropium provides significant improvement in lung function, health status, and dyspnea when used as maintenance therapy in undertreated COPD patients who were not previously receiving maintenance bronchodilator therapy. Adams. Respir Med 2006; 100:1495

24 Broncodilatadores melhoram a qualidade de vida
INTRODUCTION: Use of maintenance bronchodilator therapy is currently recommended in symptomatic patients with Chronic obstructive pulmonary disease (COPD) and in those with Stage II or greater COPD as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Because no prospective data describe when rescue therapy alone is insufficient or the optimal time to start maintenance therapy, it is unclear whether maintenance therapy has benefits in milder disease. To explore potential benefits we asked: Does once-daily tiotropium improve lung function, health status, and/or symptoms in "undertreated" COPD patients (i.e., those who are not receiving maintenance bronchodilator therapy) or patients considered by their health care providers as having milder disease? METHODS: A post-hoc analysis of data from COPD patients participating in two, 1-year, placebo-controlled trials with tiotropium was performed. Patients were defined as "undertreated" if they received no respiratory medication or only as-needed short-acting beta-agonists prior to enrollment. Measures included serial spirometry, Transition Dyspnea Index (TDI), and St. George's Respiratory Questionnaire (SGRQ). RESULTS: Of 921 patients enrolled, 218 (23.7%) were "undertreated": 130 received tiotropium; 88 received placebo. Demographics for the two treatment groups were comparable. Tiotropium-treated patients had significantly improved forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) compared with patients using placebo on all study days. Additionally, TDI and SGRQ scores significantly improved with tiotropium compared with placebo. CONCLUSIONS: Once-daily tiotropium provides significant improvement in lung function, health status, and dyspnea when used as maintenance therapy in undertreated COPD patients who were not previously receiving maintenance bronchodilator therapy. VEF1 (%predito) 40 ± 14 Adams. Respir Med 2006; 100:1495

25 Broncodilatadores podem aumentar morbimortalidade
% sem o evento anos Cessação + ipratrópio Cessação só SI-A smoking intervention plus Atrovent; SI-P smoking intervention plus placebo; UC usual care. This report deals with deaths and hospitalizations during the 5- year Lung Health Study, as documented by examination of appropriate records. There were 149 deaths (2.5%) during the study, caused largely by lung cancer and cardiovascular disease, particularly coronary heart disease. A total of 12.8% of participants were hospitalized, with cancer, cardiovascular disease, and nonmalignant respiratory disease accounting for 75% of hospitalizations. There were no significant differences among the original treatment groups for all-cause mortality, lung cancer, or hospitalizations for respiratory disease. Deaths and hospitalizations for cardiovascular disease and coronary artery disease were more common in the smoking intervention plus Atrovent inhaler (SI-A) group, which received ipratropium bromide, than in the smoking intervention plus placebo inhaler (SI-P) group, which received placebo, and the differences approached statistical significance. However, we were unable to find a dose effect, in that differences were not related to self-reported inhaler compliance. In the SI-A group, nine participants were hospitalized for supraventricular tachycardia as compared with two in the SI-P group, and SI-A participants with this condition were unusually compliant with their inhaled medication. When all participants were considered and smoking status considered as a time-dependent covariate, smoking cessation was associated with significant reductions in fatal or nonfatal cardiovascular disease and coronary artery disease. Anthonisen. Am J Respir Crit Care Med 2002; 166:333

26 Estádio IV (Muito grave)
Estadiamento % Estádio I (Leve) 62,5 Estádio II (Moderado) 29,9 Estádio III (Grave) 6,2 Estádio IV (Muito grave) 1,4

27 Pacientes com DPOC sintomas x diagnóstico prévio
100 * 90 Diagnóstico 88,9 * 80 prévio * 77,8 70 Sem diagnóstico 72,2 60 % pessoas com sintomas 50 * 54,8 40 44,4 30 34,9 34,9 Cotejar estes dados em relação ao resumo do Walker no curso pré de DPOC. Contraponto entre diagnóstico, sintomas, realidade, aumento de medicação. 20 22,2 10 15,1 9,5 Tosse crônica Chiado Dispnéia Qualquer Sintoma Expectoração

28 Recomendação ACP Tratamento para DPOC estável
Pacientes com sintomas respiratórios e VEF1 < 60% do predito (Grau da recomendação - forte, qualidade da evidência - moderada.) American College of Physicians. Ann Intern Med. 2007;147:633.

29 Eliminar fatores de risco Vacinação anti-influenza
Leve Moderada Grave Muito grave Eliminar fatores de risco Vacinação anti-influenza + BD de curta ação de demanda + um ou mais BD de ação prolongada (se necessário) + reabilitação + CE inalatório se exacerbações freqüentes +O2 Cirurgia GOLD Workshop Report Update 2007

30 Racional UPLIFT: Efeito BD do tiotrópio superior a 24 horas...
1,3 3, 6 e 12 meses Tiotrópio 1,2 VEF1 (L) pré dose 1,1 Placebo 1,0 In several 1-year clinical trials, inhaled tiotropium significantly improved lung function and appeared to reduce the rate of decline of FEV1 Tiotropium treatment significantly increased FEV1 trough (before dosing) values compared with placebo (Figure 2)43 and compared with ipratropium. 0,9 - 1 1 2 3 Horas após administração Casaburi. Eur Respir J 2002; 19:

31 Perdura após 1 ano Tiotrópio (n=518) VEF1 pré dose (L) - 12,4 mL/ano
1.20 Tiotrópio (n=518) 1.15 1.10 - 12,4 mL/ano VEF1 pré dose (L) 1.05 1.00 This beneficial effect of tiotropium treatment on FEV1 was sustained for a year - 58 mL/ano 0.95 Placebo (n=328) 0.90 1 ano This slide shows that trough FEV1* for tiotropium, measured at 23–24 hours after the last dose, remains constant throughout the study year. At Day 344, the difference from the level at Day 8 is only 10mL, whereas for placebo there is a significant decrease of 40mL. The rate of decline in trough FEV1 is significantly reduced with tiotropium compared with placebo. *Trough FEV1 is defined as the mean of the two FEV1 measurements taken at 1 hour and at 5 minutes before the first daily dose. For tiotropium, which is given once daily in the morning, this represents FEV1 approximately 1 day after the previous dose. Casaburi R. Eur Respir J 2002; 19:217

32 Uso outras medicações 99% (incluindo CE inal)
Understanding the Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) Idade (anos) 65 VEF1 (% predito) 39 Tabagismo 30% fumantes 70% ex-fumantes Uso outras medicações 99% (incluindo CE inal) Gravidade da DPOC VEF % (44%) VEF % (45%) VEF1 < 30% (11%) Tashkin. Amer J Med 2006; 119: S63

33 Uso outras medicações 99% (incluindo CE inal)
Understanding the Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) Idade (anos) 65 VEF1 (% predito) 39 Tabagismo 30% fumantes 70% ex-fumantes Uso outras medicações 99% (incluindo CE inal) Gravidade da DPOC VEF % (44%) VEF % (45%) VEF1 < 30% (11%) Tashkin. Amer J Med 2006; 119: S63

34 Uso outras medicações 99% (incluindo CE inal)
Understanding the Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) Idade (anos) 65 VEF1 (% predito) 39 Tabagismo 30% fumantes 70% ex-fumantes Uso outras medicações 99% (incluindo CE inal) Gravidade da DPOC VEF % (44%) VEF % (45%) VEF1 < 30% (11%) Tashkin. Amer J Med 2006; 119: S63

35 Uso outras medicações 99% (incluindo CE inal)
Understanding the Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) Idade (anos) 65 VEF1 (% predito) 39 Tabagismo 30% fumantes 70% ex-fumantes Uso outras medicações 99% (incluindo CE inal) Gravidade da DPOC VEF % (44%) VEF % (45%) VEF1 < 30% (11%) Tashkin. Amer J Med 2006; 119: S63

36

37 External validity of randomised controlled trials: “To whom do the results of this trial apply?”  
Rothwell. Lancet 2005; 365:82-93

38 Em DPOC leve Cessação de tabagismo Para qualquer fumante Medicação
Caso a caso