Prós e contras: o asmático leve controlado deve usar corticóide inalado para sempre? Não.

Apresentação em tema: "Prós e contras: o asmático leve controlado deve usar corticóide inalado para sempre? Não."— Transcrição da apresentação:

1 Prós e contras: o asmático leve controlado deve usar corticóide inalado para sempre?
Não

2 Em asma CE inalatórios são o padrão ouro
Não para sempre, nem para todos os pacientes....

3 Por que? Alguns pacientes não se beneficiam  aderência
Remissão espontânea Não modificam história natural Não curam Potencial de efeitos colaterais ICSs remain the “gold standard” for asthma therapy Concerns about the long-term detrimental effects of high-dose inhaled corticosteroids therapy include cataracts, osteoporosis in elderly patients, and stunting of growth in children Compliance with inhaled corticosteroids is poor inhaled corticosteroids may not modify the progression of asthma and are not curative, because asthma symptoms and inflammation recur on discontinuation of treatment ver 1.4

4 CEinal são excelentes para a asma
SF 500 F 500 SF 250 F 250 SF 100 F 100 20 80 40 60 % Sem CEinal  500 µg beclo > < 1000 µg beclo Bateman. Am J Respir Crit Care Med 2004; 170: 836–844 ver 1.4 ver 1.4 4 4

5 Bateman. Am J Respir Crit Care Med 2004; 170: 836–844
… mas nem sempre Sem CEinal  500 µg beclo > < 1000 µg beclo 20 80 40 60 % Bateman. Am J Respir Crit Care Med 2004; 170: 836–844 100 ver 1.4 ver 1.4 5 5

6 Uma vez com diagnóstico de asma, você já trocou de uma para outra medicação para asma ou descontinuou o uso porque ….? Brasil Geral Canonica. Allergy 2007; 62: Dados de arquivo Nycomed

7 Sintomas desapareceram
Uma vez com diagnóstico de asma, você já trocou de uma para outra medicação para asma ou descontinuou o uso porque ….? Brasil Geral Sintomas desapareceram ou diminuíram Canonica. Allergy 2007; 62: Dados de arquivo Nycomed

8 Brasil Geral Teve efeitos adversos
Uma vez com diagnóstico de asma, você já trocou de uma para outra medicação para asma ou descontinuou o uso porque ….? Brasil Geral Teve efeitos adversos Canonica. Allergy 2007; 62: Dados de arquivo Nycomed

9 Preocupação com potenciais efeitos adversos
Uma vez com diagnóstico de asma, você já trocou de uma para outra medicação para asma ou descontinuou o uso porque ….? Brasil Geral Preocupação com potenciais efeitos adversos

10 Medicação era muito cara
Uma vez com diagnóstico de asma, você já trocou de uma para outra medicação para asma ou descontinuou o uso porque ….? Brasil Geral Medicação era muito cara

11 Brasil Geral Medicação difícil ou inconveniente de usar
Uma vez com diagnóstico de asma, você já trocou de uma para outra medicação para asma ou descontinuou o uso porque ….? Brasil Geral Medicação difícil ou inconveniente de usar

12 História natural da asma
50% crianças remissão espontânea Adultos remissão espontânea, completa, de longa duração 16 a 29% Muitos pacientes, particularmente com asma discreta têm ciclos de remissão prolongada

13 Bebê “chiador” não é = bebê asmático
 3 anos 6 anos n % Não Não ,5 Sim Não ,9 Não Sim Sim Sim ,7 Interpretação Current - Although asthma is the most common chronic disease in childhood, not every child who wheezes will develop asthma. At least half of preschool wheezers will stop wheezing by the time they start school. Martinez FD, Wright AL, Taussig LM, et al. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med 1995; 332:133–138. Therefore studies trying to prevent asthma in very young children will inevitably unnecessarily treat some who would have grown out of their symptoms regardless. In all, three studies have been published aimed at the preschooler with wheeze, attempting to reduce the future prevalence of wheeze and asthma in these children with the use of inhaled corticosteroids. All have different designs and are aimed at slightly different subjects but reached similar conclusions. Abstract Background. Many young children wheeze during viral respiratory infections, but the pathogenesis of these episodes and their relation to the development of asthma later in life are not well understood. Methods. In a prospective study, we investigated the factors affecting wheezing before the age of three years and their relation to wheezing at six years of age. Of 1246 newborns in the Tucson, Arizona, area enrolled between May 1980 and October 1984, follow-up data at both three and six years of age were available for 826. For these children, assessments in infancy included measurement of cord-serum IgE levels (measured in 750 children), pulmonary-function testing before any lower respiratory tract illness had occurred (125), measurement of serum IgE levels at nine months of age (672), and questionnaires completed by the children’s parents when the children were one year old (800). Assessments at six years of age included measurement of serum IgE levels (in 460), pulmonary-function testing (526), and skin allergy testing (629). Results. At the age of six years, 425 children (51.5 percent) had never wheezed, 164 (19.9 percent) had had at least one lower respiratory tract illness with wheezing during the first three years of life but had no wheezing at six years of age, 124 (15.0 percent) had no wheezing before the age of three years but had wheezing at the age of six years, and 113 (13.7 percent) had wheezing both before three years of age and at six years of age. The children who had wheezing before three years of age but not at the age of six had diminished airway function (length-adjusted maximal expiratory flow at functional residual capacity [V.maxFRC] ) both before the age of one year and at the age of six years, were more likely than the other children to have mothers who smoked but not mothers with asthma, and did not have elevated serum IgE levels or skin-test reactivity. Children who started wheezing in early life and continued to wheeze at the age of six were more likely than the children who never wheezed to have mothers with a history of asthma (P,0.001), to have elevated serum IgE levels (P, 0.01) and normal lung function in the first year of life, and to have elevated serum IgE levels (P,0.001) and diminished values for V.maxFRC (P,0.01) at six years of age. Conclusions.The majority of infants with wheezing have transient conditions associated with diminished airway function at birth and do not have increased risks of asthma or allergies later in life. In a substantial minority of infants, however, wheezing episodes are probably related to a predisposition to asthma. Martinez. N Engl J Med 1995; 332:133–138 ver 1.4

14 Bebê “chiador” não é = bebê asmático
 3 anos 6 anos n % Não Não ,5 Sim Não ,9 Não Sim Sim Sim ,7 Interpretação Current - Although asthma is the most common chronic disease in childhood, not every child who wheezes will develop asthma. At least half of preschool wheezers will stop wheezing by the time they start school. Martinez FD, Wright AL, Taussig LM, et al. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med 1995; 332:133–138. Therefore studies trying to prevent asthma in very young children will inevitably unnecessarily treat some who would have grown out of their symptoms regardless. In all, three studies have been published aimed at the preschooler with wheeze, attempting to reduce the future prevalence of wheeze and asthma in these children with the use of inhaled corticosteroids. All have different designs and are aimed at slightly different subjects but reached similar conclusions. Abstract Background. Many young children wheeze during viral respiratory infections, but the pathogenesis of these episodes and their relation to the development of asthma later in life are not well understood. Methods. In a prospective study, we investigated the factors affecting wheezing before the age of three years and their relation to wheezing at six years of age. Of 1246 newborns in the Tucson, Arizona, area enrolled between May 1980 and October 1984, follow-up data at both three and six years of age were available for 826. For these children, assessments in infancy included measurement of cord-serum IgE levels (measured in 750 children), pulmonary-function testing before any lower respiratory tract illness had occurred (125), measurement of serum IgE levels at nine months of age (672), and questionnaires completed by the children’s parents when the children were one year old (800). Assessments at six years of age included measurement of serum IgE levels (in 460), pulmonary-function testing (526), and skin allergy testing (629). Results. At the age of six years, 425 children (51.5 percent) had never wheezed, 164 (19.9 percent) had had at least one lower respiratory tract illness with wheezing during the first three years of life but had no wheezing at six years of age, 124 (15.0 percent) had no wheezing before the age of three years but had wheezing at the age of six years, and 113 (13.7 percent) had wheezing both before three years of age and at six years of age. The children who had wheezing before three years of age but not at the age of six had diminished airway function (length-adjusted maximal expiratory flow at functional residual capacity [V.maxFRC] ) both before the age of one year and at the age of six years, were more likely than the other children to have mothers who smoked but not mothers with asthma, and did not have elevated serum IgE levels or skin-test reactivity. Children who started wheezing in early life and continued to wheeze at the age of six were more likely than the children who never wheezed to have mothers with a history of asthma (P,0.001), to have elevated serum IgE levels (P, 0.01) and normal lung function in the first year of life, and to have elevated serum IgE levels (P,0.001) and diminished values for V.maxFRC (P,0.01) at six years of age. Conclusions.The majority of infants with wheezing have transient conditions associated with diminished airway function at birth and do not have increased risks of asthma or allergies later in life. In a substantial minority of infants, however, wheezing episodes are probably related to a predisposition to asthma. Martinez. N Engl J Med 1995; 332:133–138 ver 1.4

15 Crianças “chiadoras” perdem função
Fluxo ajustado à idade Idade (anos) Nunca Interpretação do Current - Cohort studies suggest that of children who wheeze early in life, around half become asymptomatic by school age. These children tend to have diminished lung function in infancy but improved (although still lower than normal) by age six years. Healthy children will usually have increasing lung function during childhood, which levels off during early adulthood (25–35 years) and then slowly declines. In contrast, children with persistent wheeze at age six (probable asthmatics) have normal early life lung function that decreases by age six [2]. Morgan WJ, Stern DA, Sherrill DL, et al. Outcome of asthma and wheezing in the first 6 years of life: follow-up through adolescence. Am J Respir Crit Care Med 2005; 172:1253–1258. Rationale: The effect of early life wheezing on respiratory function and continued symptoms through adolescence has not been fully described. Using data from a population-based birthcohort in Tucson, Arizona, we previously described four phenotypes based on the occurrence of wheezing lower respiratory illnesses before age 3 yr and active wheeze at age 6 yr: never wheezers (n 425), transient early wheezers (n 164), persistent wheezers (n 113), and late onset wheezers (n 124). Objective: We sought to determine the prognosis for these phenotypes, with reference to lung function and symptoms, through adolescence. Methods: Current wheeze was assessed by questionnaire, lung function was measured by conventional spirometry, and atopy was determined by skin prick tests. Results: The prevalence of atopy and wheeze by age 16 yr was similar for never and transient wheezers and for persistent and late-onset wheezers. Both transient early, and persistent wheezers had significantly lower FEF25–75 (–259 ml/s, p , and –260 ml/s, p 0.001, respectively), FEV1 (–75 ml, p 0.02, and –87 ml, p 0.03, respectively), and FEV1:FVC ratio (–1.9%, p , and –2.5%, p , respectively) through age 16 yr compared with never wheezers. Late-onset wheezers had levels of lung function similar to those of never wheezers through age 16 yr. There was no significant change in lung function among subjects with any of the four phenotypes, relative to their peers, from age 6 to 16 yr. Conclusion: Patterns of wheezing prevalence and levels of lung function are established by age 6 yr and do not appear to change significantly by age 16 yr in children who start having asthmalike symptoms during the preschool years. Morgan. Am J Respir Crit Care Med 2005; 172:1253–1258 ver 1.4

16 Crianças “chiadoras” perdem função
Fluxo ajustado à idade Idade (anos) Nunca Transitório precoce Interpretação do Current - Cohort studies suggest that of children who wheeze early in life, around half become asymptomatic by school age. These children tend to have diminished lung function in infancy but improved (although still lower than normal) by age six years. Healthy children will usually have increasing lung function during childhood, which levels off during early adulthood (25–35 years) and then slowly declines. In contrast, children with persistent wheeze at age six (probable asthmatics) have normal early life lung function that decreases by age six [2]. Morgan WJ, Stern DA, Sherrill DL, et al. Outcome of asthma and wheezing in the first 6 years of life: follow-up through adolescence. Am J Respir Crit Care Med 2005; 172:1253–1258. Rationale: The effect of early life wheezing on respiratory function and continued symptoms through adolescence has not been fully described. Using data from a population-based birthcohort in Tucson, Arizona, we previously described four phenotypes based on the occurrence of wheezing lower respiratory illnesses before age 3 yr and active wheeze at age 6 yr: never wheezers (n 425), transient early wheezers (n 164), persistent wheezers (n 113), and late onset wheezers (n 124). Objective: We sought to determine the prognosis for these phenotypes, with reference to lung function and symptoms, through adolescence. Methods: Current wheeze was assessed by questionnaire, lung function was measured by conventional spirometry, and atopy was determined by skin prick tests. Results: The prevalence of atopy and wheeze by age 16 yr was similar for never and transient wheezers and for persistent and late-onset wheezers. Both transient early, and persistent wheezers had significantly lower FEF25–75 (–259 ml/s, p , and –260 ml/s, p 0.001, respectively), FEV1 (–75 ml, p 0.02, and –87 ml, p 0.03, respectively), and FEV1:FVC ratio (–1.9%, p , and –2.5%, p , respectively) through age 16 yr compared with never wheezers. Late-onset wheezers had levels of lung function similar to those of never wheezers through age 16 yr. There was no significant change in lung function among subjects with any of the four phenotypes, relative to their peers, from age 6 to 16 yr. Conclusion: Patterns of wheezing prevalence and levels of lung function are established by age 6 yr and do not appear to change significantly by age 16 yr in children who start having asthmalike symptoms during the preschool years. Morgan. Am J Respir Crit Care Med 2005; 172:1253–1258 ver 1.4

17 Crianças “chiadoras” perdem função
Fluxo ajustado à idade Idade (anos) Nunca Transitório precoce Início tardio Interpretação do Current - Cohort studies suggest that of children who wheeze early in life, around half become asymptomatic by school age. These children tend to have diminished lung function in infancy but improved (although still lower than normal) by age six years. Healthy children will usually have increasing lung function during childhood, which levels off during early adulthood (25–35 years) and then slowly declines. In contrast, children with persistent wheeze at age six (probable asthmatics) have normal early life lung function that decreases by age six [2]. Morgan WJ, Stern DA, Sherrill DL, et al. Outcome of asthma and wheezing in the first 6 years of life: follow-up through adolescence. Am J Respir Crit Care Med 2005; 172:1253–1258. Rationale: The effect of early life wheezing on respiratory function and continued symptoms through adolescence has not been fully described. Using data from a population-based birthcohort in Tucson, Arizona, we previously described four phenotypes based on the occurrence of wheezing lower respiratory illnesses before age 3 yr and active wheeze at age 6 yr: never wheezers (n 425), transient early wheezers (n 164), persistent wheezers (n 113), and late onset wheezers (n 124). Objective: We sought to determine the prognosis for these phenotypes, with reference to lung function and symptoms, through adolescence. Methods: Current wheeze was assessed by questionnaire, lung function was measured by conventional spirometry, and atopy was determined by skin prick tests. Results: The prevalence of atopy and wheeze by age 16 yr was similar for never and transient wheezers and for persistent and late-onset wheezers. Both transient early, and persistent wheezers had significantly lower FEF25–75 (–259 ml/s, p , and –260 ml/s, p 0.001, respectively), FEV1 (–75 ml, p 0.02, and –87 ml, p 0.03, respectively), and FEV1:FVC ratio (–1.9%, p , and –2.5%, p , respectively) through age 16 yr compared with never wheezers. Late-onset wheezers had levels of lung function similar to those of never wheezers through age 16 yr. There was no significant change in lung function among subjects with any of the four phenotypes, relative to their peers, from age 6 to 16 yr. Conclusion: Patterns of wheezing prevalence and levels of lung function are established by age 6 yr and do not appear to change significantly by age 16 yr in children who start having asthmalike symptoms during the preschool years. Morgan. Am J Respir Crit Care Med 2005; 172:1253–1258 ver 1.4

18 Crianças “chiadoras” perdem função
Fluxo ajustado à idade Idade (anos) Nunca Transitório precoce Início tardio Persistente Interpretação do Current - Cohort studies suggest that of children who wheeze early in life, around half become asymptomatic by school age. These children tend to have diminished lung function in infancy but improved (although still lower than normal) by age six years. Healthy children will usually have increasing lung function during childhood, which levels off during early adulthood (25–35 years) and then slowly declines. In contrast, children with persistent wheeze at age six (probable asthmatics) have normal early life lung function that decreases by age six [2]. Morgan WJ, Stern DA, Sherrill DL, et al. Outcome of asthma and wheezing in the first 6 years of life: follow-up through adolescence. Am J Respir Crit Care Med 2005; 172:1253–1258. Rationale: The effect of early life wheezing on respiratory function and continued symptoms through adolescence has not been fully described. Using data from a population-based birthcohort in Tucson, Arizona, we previously described four phenotypes based on the occurrence of wheezing lower respiratory illnesses before age 3 yr and active wheeze at age 6 yr: never wheezers (n 425), transient early wheezers (n 164), persistent wheezers (n 113), and late onset wheezers (n 124). Objective: We sought to determine the prognosis for these phenotypes, with reference to lung function and symptoms, through adolescence. Methods: Current wheeze was assessed by questionnaire, lung function was measured by conventional spirometry, and atopy was determined by skin prick tests. Results: The prevalence of atopy and wheeze by age 16 yr was similar for never and transient wheezers and for persistent and late-onset wheezers. Both transient early, and persistent wheezers had significantly lower FEF25–75 (–259 ml/s, p , and –260 ml/s, p 0.001, respectively), FEV1 (–75 ml, p 0.02, and –87 ml, p 0.03, respectively), and FEV1:FVC ratio (–1.9%, p , and –2.5%, p , respectively) through age 16 yr compared with never wheezers. Late-onset wheezers had levels of lung function similar to those of never wheezers through age 16 yr. There was no significant change in lung function among subjects with any of the four phenotypes, relative to their peers, from age 6 to 16 yr. Conclusion: Patterns of wheezing prevalence and levels of lung function are established by age 6 yr and do not appear to change significantly by age 16 yr in children who start having asthmalike symptoms during the preschool years. Morgan. Am J Respir Crit Care Med 2005; 172:1253–1258 ver 1.4

19 Adultos com asma perdem função
Sem asma Com asma Sem asma Com asma VEF1 ajustado à idade Background Although the prevalence of asthma and morbidity related to asthma are increasing, little is known about the natural history of lung function in adults with this disease. Methods We used data from a longitudinal epidemiologic study of the general population in a Danish city, the Copenhagen City Heart Study, to analyze changes over time in the forced expiratory volume in one second (FEV1) in adults with self-reported asthma and adults without asthma. The study was conducted between 1976 and 1994; for each patient, three measurements of lung function were obtained over a 15-year period. The final data set consisted of measurements from 17,506 subjects (8136 men and 9370 women), of whom 1095 had asthma. Results Among subjects who participated in all three evaluations, the unadjusted decline in FEV1 among subjects with asthma was 38 ml per year, as compared with 22 ml per year in those without asthma. The decline in FEV1 normalized for height (FEV1 divided by the square of the height in meters) was greater among the subjects with asthma than among those without the disease (P<0.001). Among both men and women, and among both smokers and nonsmokers, subjects with asthma had greater declines in FEV1 over time than those without asthma (P<0.001). At the age of 60 years, a 175-cm-tall nonsmoking man without asthma had an average FEV1 Of 3.05 liters, as compared with 1.99 liters for a man of similar age and height who smoked and had asthma. Conclusions In a sample of the general population, people who identified themselves as having asthma had substantially greater declines in FEV1 over time than those who did not. (N Engl J Med 1998;339: )   Idade (anos) Lange. NEJM 339:1194, 1998 ver 1.4

20 CEinal não interferem na evolução de bebês com chiado episódico
% dias sem sintomas 2 semanas tratamento % chiado persistente Budesonida Placebo The PAC study aimed at treating infants (from age one month to three years old) of mothers with physician diagnosed asthma with budesonide 400 mg per day or placebo via pressurised metered dose inhaler (MDI) and spacer device. Treatment was initiated only once they had become symptomatic. Treatment was started on day three of any wheezy episode and continued for two weeks. The primary objective was to assess the efficacy of inhaled budesonide relative to that of placebo after the first episode of wheezing in reducing subsequent wheezy symptoms during the first three years of life. The secondary objective was to assess the ability of inhaled budesonide to prevent or delay persistent wheezing. Children discontinued participation in the trial if they had persistent wheezing defined as five episodes each lasting more than three consecutive days within a six month period, or daily symptoms for four weeks. Two hundred and ninety four children were randomised (mean age at randomization 10.7 months). Intermittent ICS therapy had no effect on the progression from episodic to persistent wheeze, with 24% of the budesonide group and 21% of the placebo group being defined as persistent wheezers. In addition, there appeared to be no short-term benefit during episodes of wheezing with no difference between the groups in the proportion of symptom-free days (83% vs. 82% symptom-free days, budesonide vs. placebo). Bisgaard. N Engl J Med 2006; 354:1998 ver 1.4

21 Efeito de CE sobre a  VEF1 é mínimo
Budesonida Placebo Diferença - 1,79 - 2,68 0,88 If ICS are to have an effect on reducing lung function decline in adult asthmatics then the ideal population to be targeted is those with mild persistent asthma, who have normal lung function and more than weekly but less than daily symptoms [21]. Two such studies have recently been published. The first is the START trial [22] Pauwels RA, Pedersen S, Busse WW, et al. Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial. Lancet 2003; 361:1071– This was a randomised double-blind trial of over 7000 patients assessing the effects of budesonide in patients, aged five to 66 years, who had mild persistent asthma for less than two years and who had not had previous regular treatment with ICS. Patients were randomised to either budesonide (400mg if >11 years, 200 mg if <11 years) or placebo once daily. After three years post-bronchodilator FEV1 had declined significantly less in the budesonide group compared with those on placebo, but the difference between the groups was extremely small (mean difference 0.88% predicted). Pauwels. Lancet 2003; 361: 1071–76 ver 1.4

22 CEinal não previnem asma
Aos 5 anos Placebo Fluticasona % % Chiando 47 52 Asma Diagnóstico médico Usando medicação 66 66 The IFWIN study targeted slightly older children, aged six months to five years [16__] and randomised 206 children (median age 1.2 years) after either one prolonged (>one month) or two physician-confirmed wheezy episodes. These children were felt to be at increased risk of asthma compared with the general population because all had one parent who was atopic. Children received fluticasone propionate 100 mg twice daily or placebo via MDI and spacer and the dose was stepped down three monthly to the minimum required to control symptoms. The primary outcomes were the persistence of wheeze and asthma, lung function and airway reactivity at age five years. There was no significant difference between the groups in the proportion of children with current wheeze (47% vs. 52%), physician diagnosed asthma (64% vs. 61%) or use of asthma medication (66% vs. 66%) at age five years, placebo vs. fluticasone propionate respectively. They concluded that use of inhaled fluticasone propionate in young preschool children for early wheezing had no effect on the natural history of asthma or wheeze later in childhood. Murray CS, Woodcock A, Langley SJ, et al. Secondary prevention of asthma by the use of Inhaled Fluticasone propionate in Wheezy INfants (IFWIN): double-blind, randomised, controlled study. Lancet 2006; 368:754–762. RCT of inhaled fluticasone propionate in children aged 6 months to 5 years. ICS had no effect on the natural history of asthma in later childhood, and did not prevent lung function decline or reduce the incidence of airway reactivity. Murray. Lancet 2006; 368:754 ver 1.4

23 Dias livres de sintomas Guilbert. N Engl J Med 2006; 354:1985–1997.
CEinal não curam asma Dias livres de sintomas 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

24 É possível suspender o CE inal quando a asma se controla?
Triancinolona 400 mcg 2x (n = 54) Salmeterol 50 mcg 2x (n = 54) Placebo (n = 56) Semanas 16 Triancinolona 400 mcg 2x - 6 Deykin. JACI 2005; 115:720-6

25 Sim, em vários pacientes
Perda de Até 14 semanas Total controle 2 semanas seguintes Triancinolona (n=54) Placebo (n=56) Deykin. JACI 2005; 115:720-6

26 Sim, em vários pacientes
Perda de Até 14 semanas Total controle 2 semanas seguintes Triancinolona (n=54) Placebo (n=56) Deykin. JACI 2005; 115:720-6

27 Efeitos colaterais são poucos mas não inexistentes
 crescimento Osteoporose Catarata Orofaringe  peso Nunca Raro Ocasional Freqüente Cutâneo BACKGROUND: Inhaled corticosteroids are recognized as the mainstay of prophylactic anti-inflammatory therapy in patients with persistent asthma. In large multiclinic trials, the clinical adverse event profiles have been not significantly different than patients treated with placebo or other medications; however, in small studies evaluating very sensitive in vitro measurements of the hypothalamic pituitary adrenal axis there have been adverse laboratory events noted with moderate and high doses of inhaled steroids. OBJECTIVE: To survey asthma specialists in North America with regard to their personal clinical experience of adverse events with the use of inhaled corticosteroids. METHODS: Two hundred thirteen physicians specializing in the treatment of asthma responded to questionnaires asking their experiences with specific adverse clinical events that have the potential to occur after the use of inhaled corticosteroids (see appendix A for questionnaire). RESULTS: There was a 67% response rate for the questionnaire. Eighty percent of the respondents were allergists/immunologists and 20% were pulmonologists. The average length of time they had been in practice was 16 years. In general, side effects from inhaled steroids were seen very infrequently in the hands of these physicians in spite of the fact that they were primarily secondary or tertiary referral physicians for the treatment of asthma. The local oropharyngeal adverse events were seen 48% of the time on an occasional basis but only 3% of the time on a frequent basis. When spacers were used the oropharyngeal symptoms were reduced significantly. Skin changes such as bruising or thin skin were seen frequently 6% of the time and occasionally 24% of the time only. In general, these skin changes were found in elderly or middle-aged individuals. Weight gain was very unusually seen, as were adverse effects on bone (osteoporosis, fractures, growth problems, etc.). Hypothalamic pituitary axis abnormalities were seen quite infrequently and primarily in patients who had also received oral corticosteroids. CONCLUSIONS: This study shows that inhaled corticosteroids are generally safe in the treatment of asthma and are rarely associated with systemic side effects, as detected in routine clinical practice. Storms. Ann Allergy Asthma Immunol. 1998;80:391 ver 1.4

28 Uma última questão Pacientes com asma leve realmente precisam de corticóide inalatório contínuo?

29 no de cursos de 10 dias de budesonida
8 Zafirlukast BUD intermitente 6 no de pacientes 4 2 1 2 3 no de cursos de 10 dias de budesonida Boushey. NEJM 2005; 352:

30 Corticóide inalatório para sempre, não
Alguns pacientes não se beneficiam  aderência Remissão espontânea Não modificam história natural Não curam Potencial de efeitos colaterais ICSs remain the “gold standard” for asthma therapy Concerns about the long-term detrimental effects of high-dose inhaled corticosteroids therapy include cataracts, osteoporosis in elderly patients, and stunting of growth in children Compliance with inhaled corticosteroids is poor inhaled corticosteroids may not modify the progression of asthma and are not curative, because asthma symptoms and inflammation recur on discontinuation of treatment ver 1.4

31 Você manteria qualquer medicação indefinidamente nestes pacientes?
7 anos Asma totalmente controlada há 1 ano

32 Você manteria qualquer medicação indefinidamente nestes pacientes?
50 anos Asma totalmente controlada há 1 ano

33 Você manteria qualquer medicação indefinidamente nestes pacientes?
70 anos Asma totalmente controlada há 1 ano

34

35 Mulher de 30 anos, administradora de empresas, com asma desde a infância. Quando criança alguns episódios de visitas ao PS, sempre resolvidos apenas com inalação. Ficou assintomática toda a adolescência. Há 5 anos com asma induzida pelo exercício e despertar noturno 1 vez/mês. Medicada com beclometasona 100 mg 2 vezes/dia há 4 anos. Mantém a beclo 2 vezes/dia + salbutamol de demanda (2-3 vezes/semana). Sem despertar noturno. Procura atendimento porque quer reduzir a medicação. Prefere ter algum sintoma a correr o risco de efeitos colaterais de longo prazo. You are consulted by a 30-year-old white woman, who holds an administrative position in an office and has a lifelong history of asthma, about the treatment of her condition. In childhood, the patient visited her local hospital for treatment of acute asthma, but she was never admitted overnight and was discharged from the emergency department after a few “breathing treatments.” Her asthma became quiescent in her late teens and remained so until 5 years ago, when after the birth of her first child, she began to note shortness of breath when recovering from exercise. At that time, she was awakened from sleep about once a month because of her asthma, but she did not need to seek emergency care for her condition. Her physician prescribed inhaled beclomethasone, two puffs (80 μg per puff) twice a day, and gave her an albuterol inhaler to use as an as-needed rescue treatment. With this treatment, the patient’s asthma has been stable for the past 4 years. Her current spirometric data are as follows: forced expiratory volume in 1 second (FEV1), 3.16 liters (82% of the predicted value); forced vital capacity (FVC), 3.85 liters (82% of the predicted value); and the ratio of FEV1 to FVC, The fraction of nitric oxide in the exhaled air is 10 ppb. Skin testing has revealed substantial responses only to ragweed. She uses her albuterol inhaler two or three times a week, usually as premedication before exercise. She has no nocturnal symptoms. She has not had any unscheduled medical visits for her asthma. The patient wonders whether she should receive less asthma treatment. She is willing to tolerate some symptoms if the treatment will be associated with fewer long-term side effects. Which one of the following treatment options will most closely meet the patient’s needs? Base your opinion on the published literature (including the articles by the American Lung Association Asthma Clinical Research Centers1 and Papi et al.2 in this issue of the Journal), your past experience, recent guidelines, and other sources of information, as appropriate. 1. Switch the treatment such that beclomethasone and albuterol inhalers are used only when the patient has symptoms of asthma. 2. Switch the treatment to an oral leukotrienereceptor antagonist, plus as-needed rescue albuterol. 3. Switch the treatment to a corticosteroid and a long-acting β2-agonist, in a single inhaler to be used each morning, plus as-needed rescue albuterol. ver 1.4

36 1. Beclo de demanda 2. Antagonistas de leucotrieno 3. LABA/CEinal cedo

37 CE demanda Antileucotrieno LABA/CEinal
Figure 1. Percentage of Participants Choosing Each Treatment Option for Mild Persistent Asthma. The total number of participants who voted is shown for each continent or region. Option 1 was the as-needed use of inhaled beclomethasone and albuterol. Option 2 was an oral leukotriene-receptor antagonist plus as-needed rescue albuterol. Option 3 was a once-daily corticosteroid plus long-acting beta2-agonist in a single inhaler. Within each continent or region, countries from which votes were cast are shaded. An interactive graphic that includes country-specific data is available at Fredenburgh. N Engl J Med 2007;357: ver 1.4

38

39 CEinal na asma Padrão ouro Resposta não uniforme
Potencial de efeitos colaterais  aderência Não modificam história natural Não curam ICSs remain the “gold standard” for asthma therapy Concerns about the long-term detrimental effects of high-dose inhaled corticosteroids therapy include cataracts, osteoporosis in elderly patients, and stunting of growth in children Compliance with inhaled corticosteroids is poor inhaled corticosteroids may not modify the progression of asthma and are not curative, because asthma symptoms and inflammation recur on discontinuation of treatment ver 1.4

40 Conceito de “Risco Futuro”
Estabilidade da asma Exacerbações graves Prevenção da perda de função Efeitos colaterais das drogas This busy diagram shows the complete management of Symbicort with a single inhaler in orange. The daily base dose is constant and additional inhalations (shown as the orange shaded area) are taken as-needed to respond to the need for relief of symptoms. Severe symptoms may prompt the use of several inhalations, while mild, transient symptoms may require only 1 extra inhalation. Most days patients require NO additional inhalations. While the number of inhalations varies from day to day – control of asthma does not. ver 1.4

41 Você manteria qualquer medicação indefinidamente nestes pacientes?
7 anos Asma totalmente controlada há 1 ano

42 Você manteria qualquer medicação indefinidamente nestes pacientes?
50 anos Asma totalmente controlada há 1 ano

43 Você manteria qualquer medicação indefinidamente nestes pacientes?
70 anos Asma totalmente controlada há 1 ano

44 Asma tem cura? 50% crianças remissão espontânea
50% sintomatologia volta Adultos remissão espontânea, completa, de longa duração 16 a 29% Muitos pacientes, particularmente com asma discreta têm ciclos de remissão prolongada. Uma parcela dos asmáticos deixam de ter manifestação clínica após a retirada de fator desencadeante.

45 Sintomas Exacerbação VEF1 Tempo Remodelamento
ver 1.4

46 Bebê “chiador” não é = bebê asmático
 3 anos 6 anos n % Não Não ,5 Sim Não ,9 Não Sim Sim Sim ,7 Interpretação Current - Although asthma is the most common chronic disease in childhood, not every child who wheezes will develop asthma. At least half of preschool wheezers will stop wheezing by the time they start school. Martinez FD, Wright AL, Taussig LM, et al. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med 1995; 332:133–138. Therefore studies trying to prevent asthma in very young children will inevitably unnecessarily treat some who would have grown out of their symptoms regardless. In all, three studies have been published aimed at the preschooler with wheeze, attempting to reduce the future prevalence of wheeze and asthma in these children with the use of inhaled corticosteroids. All have different designs and are aimed at slightly different subjects but reached similar conclusions. Abstract Background. Many young children wheeze during viral respiratory infections, but the pathogenesis of these episodes and their relation to the development of asthma later in life are not well understood. Methods. In a prospective study, we investigated the factors affecting wheezing before the age of three years and their relation to wheezing at six years of age. Of 1246 newborns in the Tucson, Arizona, area enrolled between May 1980 and October 1984, follow-up data at both three and six years of age were available for 826. For these children, assessments in infancy included measurement of cord-serum IgE levels (measured in 750 children), pulmonary-function testing before any lower respiratory tract illness had occurred (125), measurement of serum IgE levels at nine months of age (672), and questionnaires completed by the children’s parents when the children were one year old (800). Assessments at six years of age included measurement of serum IgE levels (in 460), pulmonary-function testing (526), and skin allergy testing (629). Results. At the age of six years, 425 children (51.5 percent) had never wheezed, 164 (19.9 percent) had had at least one lower respiratory tract illness with wheezing during the first three years of life but had no wheezing at six years of age, 124 (15.0 percent) had no wheezing before the age of three years but had wheezing at the age of six years, and 113 (13.7 percent) had wheezing both before three years of age and at six years of age. The children who had wheezing before three years of age but not at the age of six had diminished airway function (length-adjusted maximal expiratory flow at functional residual capacity [V.maxFRC] ) both before the age of one year and at the age of six years, were more likely than the other children to have mothers who smoked but not mothers with asthma, and did not have elevated serum IgE levels or skin-test reactivity. Children who started wheezing in early life and continued to wheeze at the age of six were more likely than the children who never wheezed to have mothers with a history of asthma (P,0.001), to have elevated serum IgE levels (P, 0.01) and normal lung function in the first year of life, and to have elevated serum IgE levels (P,0.001) and diminished values for V.maxFRC (P,0.01) at six years of age. Conclusions.The majority of infants with wheezing have transient conditions associated with diminished airway function at birth and do not have increased risks of asthma or allergies later in life. In a substantial minority of infants, however, wheezing episodes are probably related to a predisposition to asthma. Martinez. N Engl J Med 1995; 332:133–138 ver 1.4

47 Crianças “chiadoras” perdem função
Fluxo ajustado à idade Idade (anos) Nunca Transitório precoce Início tardio Persistente Interpretação do Current - Cohort studies suggest that of children who wheeze early in life, around half become asymptomatic by school age. These children tend to have diminished lung function in infancy but improved (although still lower than normal) by age six years. Healthy children will usually have increasing lung function during childhood, which levels off during early adulthood (25–35 years) and then slowly declines. In contrast, children with persistent wheeze at age six (probable asthmatics) have normal early life lung function that decreases by age six [2]. Morgan WJ, Stern DA, Sherrill DL, et al. Outcome of asthma and wheezing in the first 6 years of life: follow-up through adolescence. Am J Respir Crit Care Med 2005; 172:1253–1258. Rationale: The effect of early life wheezing on respiratory function and continued symptoms through adolescence has not been fully described. Using data from a population-based birthcohort in Tucson, Arizona, we previously described four phenotypes based on the occurrence of wheezing lower respiratory illnesses before age 3 yr and active wheeze at age 6 yr: never wheezers (n 425), transient early wheezers (n 164), persistent wheezers (n 113), and late onset wheezers (n 124). Objective: We sought to determine the prognosis for these phenotypes, with reference to lung function and symptoms, through adolescence. Methods: Current wheeze was assessed by questionnaire, lung function was measured by conventional spirometry, and atopy was determined by skin prick tests. Results: The prevalence of atopy and wheeze by age 16 yr was similar for never and transient wheezers and for persistent and late-onset wheezers. Both transient early, and persistent wheezers had significantly lower FEF25–75 (–259 ml/s, p , and –260 ml/s, p 0.001, respectively), FEV1 (–75 ml, p 0.02, and –87 ml, p 0.03, respectively), and FEV1:FVC ratio (–1.9%, p , and –2.5%, p , respectively) through age 16 yr compared with never wheezers. Late-onset wheezers had levels of lung function similar to those of never wheezers through age 16 yr. There was no significant change in lung function among subjects with any of the four phenotypes, relative to their peers, from age 6 to 16 yr. Conclusion: Patterns of wheezing prevalence and levels of lung function are established by age 6 yr and do not appear to change significantly by age 16 yr in children who start having asthmalike symptoms during the preschool years. Morgan. Am J Respir Crit Care Med 2005; 172:1253–1258 ver 1.4

48 Repercute na idade adulta
Sem asma Com asma Sem asma Com asma VEF1 ajustado à idade Background Although the prevalence of asthma and morbidity related to asthma are increasing, little is known about the natural history of lung function in adults with this disease. Methods We used data from a longitudinal epidemiologic study of the general population in a Danish city, the Copenhagen City Heart Study, to analyze changes over time in the forced expiratory volume in one second (FEV1) in adults with self-reported asthma and adults without asthma. The study was conducted between 1976 and 1994; for each patient, three measurements of lung function were obtained over a 15-year period. The final data set consisted of measurements from 17,506 subjects (8136 men and 9370 women), of whom 1095 had asthma. Results Among subjects who participated in all three evaluations, the unadjusted decline in FEV1 among subjects with asthma was 38 ml per year, as compared with 22 ml per year in those without asthma. The decline in FEV1 normalized for height (FEV1 divided by the square of the height in meters) was greater among the subjects with asthma than among those without the disease (P<0.001). Among both men and women, and among both smokers and nonsmokers, subjects with asthma had greater declines in FEV1 over time than those without asthma (P<0.001). At the age of 60 years, a 175-cm-tall nonsmoking man without asthma had an average FEV1 Of 3.05 liters, as compared with 1.99 liters for a man of similar age and height who smoked and had asthma. Conclusions In a sample of the general population, people who identified themselves as having asthma had substantially greater declines in FEV1 over time than those who did not. (N Engl J Med 1998;339: )   Idade (anos) Lange. NEJM 339:1194, 1998 ver 1.4

49 CEinal não interferem na evolução de bebês com chiado episódico
% dias sem sintomas 2 semanas tratamento % chiado persistente Budesonida Placebo The PAC study aimed at treating infants (from age one month to three years old) of mothers with physician diagnosed asthma with budesonide 400 mg per day or placebo via pressurised metered dose inhaler (MDI) and spacer device. Treatment was initiated only once they had become symptomatic. Treatment was started on day three of any wheezy episode and continued for two weeks. The primary objective was to assess the efficacy of inhaled budesonide relative to that of placebo after the first episode of wheezing in reducing subsequent wheezy symptoms during the first three years of life. The secondary objective was to assess the ability of inhaled budesonide to prevent or delay persistent wheezing. Children discontinued participation in the trial if they had persistent wheezing defined as five episodes each lasting more than three consecutive days within a six month period, or daily symptoms for four weeks. Two hundred and ninety four children were randomised (mean age at randomization 10.7 months). Intermittent ICS therapy had no effect on the progression from episodic to persistent wheeze, with 24% of the budesonide group and 21% of the placebo group being defined as persistent wheezers. In addition, there appeared to be no short-term benefit during episodes of wheezing with no difference between the groups in the proportion of symptom-free days (83% vs. 82% symptom-free days, budesonide vs. placebo). Bisgaard. N Engl J Med 2006; 354:1998 ver 1.4

50 CEinal não previnem asma
Aos 5 anos Placebo Fluticasona % % Chiando 47 52 Asma Diagnóstico médico Usando medicação 66 66 The IFWIN study targeted slightly older children, aged six months to five years [16__] and randomised 206 children (median age 1.2 years) after either one prolonged (>one month) or two physician-confirmed wheezy episodes. These children were felt to be at increased risk of asthma compared with the general population because all had one parent who was atopic. Children received fluticasone propionate 100 mg twice daily or placebo via MDI and spacer and the dose was stepped down three monthly to the minimum required to control symptoms. The primary outcomes were the persistence of wheeze and asthma, lung function and airway reactivity at age five years. There was no significant difference between the groups in the proportion of children with current wheeze (47% vs. 52%), physician diagnosed asthma (64% vs. 61%) or use of asthma medication (66% vs. 66%) at age five years, placebo vs. fluticasone propionate respectively. They concluded that use of inhaled fluticasone propionate in young preschool children for early wheezing had no effect on the natural history of asthma or wheeze later in childhood. Murray CS, Woodcock A, Langley SJ, et al. Secondary prevention of asthma by the use of Inhaled Fluticasone propionate in Wheezy INfants (IFWIN): double-blind, randomised, controlled study. Lancet 2006; 368:754–762. RCT of inhaled fluticasone propionate in children aged 6 months to 5 years. ICS had no effect on the natural history of asthma in later childhood, and did not prevent lung function decline or reduce the incidence of airway reactivity. Murray. Lancet 2006; 368:754 ver 1.4

51 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

52 START Pauwels RA, Pedersen S, Busse WW, et al. Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial. Lancet 2003; 361:1071–1076 ver 1.4

53 Probabilidade de exacerbação grave
10 6 4 2 8 1 3 BUD Placebo Anos If ICS are to have an effect on reducing lung function decline in adult asthmatics then the ideal population to be targeted is those with mild persistent asthma, who have normal lung function and more than weekly but less than daily symptoms [21]. Two such studies have recently been published. The first is the START trial [22] Pauwels RA, Pedersen S, Busse WW, et al. Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial. Lancet 2003; 361:1071– This was a randomised double-blind trial of over 7000 patients assessing the effects of budesonide in patients, aged five to 66 years, who had mild persistent asthma for less than two years and who had not had previous regular treatment with ICS. Patients were randomised to either budesonide (400mg if >11 years, 200 mg if <11 years) or placebo once daily. After three years post-bronchodilator FEV1 had declined significantly less in the budesonide group compared with those on placebo, but the difference between the groups was extremely small (mean difference 0.88% predicted). Pauwels. Lancet 2003; 361: 1071–76 ver 1.4

54 Por que não usar CEinal de demanda?
Boushey

55 Opções de redução de medicação
Fluticasona 100 2x (n = 168) Montelucaste (n = 165) Salm50/Flut 100 1x (n = 162) Semanas 16 Fluticasona 100 mcg 2x - 6 NEJM 2007; 356:

56 Opções de redução de medicação
% falhas de tratamento Semanas Montelucaste Fluticasona Salmeterol/Fluticasona NEJM 2007; 356:

57 Budesonida intermitente (n = 70) Budesonide 800 mcg 2 x + zafirlukast
Tratamento intermitente com CE inalatório em asma persistente leve pode ser suficiente Budesonida 200 mcg 2x (n = 67) Zafirlukast 200 mg 2x (n = 62) Budesonida intermitente (n = 70) Semanas 52 Prednisona + Budesonide 800 mcg 2 x + zafirlukast - 2 In a further study of 225 adults with mild persistent asthma, the IMPACT study randomised patients to twice-daily budesonide (200mg), zafirlukast (20mg) or placebo [23]. After 12 months of treatment no significant difference in post-bronchodilator FEV1 was found between the groups. Boushey HA, Sorkness CA, King TS, et al. Daily versus as-needed corticosteroids for mild persistent asthma. N Engl J Med 2005; 352:1519–1528. Procurar o artigo para colocar o VEF1 Boushey. NEJM 2005; 352: ver 1.4

58 no de cursos de 10 dias de budesonida
8 Zafirlukast BUD intermitente 6 no de pacientes 4 2 1 2 3 no de cursos de 10 dias de budesonida Boushey. NEJM 2005; 352:

59 Exacerbações foram semelhantes
% sem exacerbações Budesonida Zafirlukast BUD intermitente Dias desde a randomização Boushey. NEJM 2005; 352:

60 Opções de redução de medicação
Salbut 100/Beclo 250 s/n (n = 102) Salbutamol s/n (n = 101) Beclo 250 2x (n = 93) Semanas 24 Beclometasona 250 mcg 2x - 4 Salbut 100/Beclo 250 2x (n = 97) Papi. NEJM 2007; 356:

61 Opções de redução de medicação
Dias % sem exacerbações Salb/Beclo s/n Beclo 2 x Salb/Beclo 2x Salbutamol s/n Papi. NEJM 2007; 356:

62 Apresentar o caso do NEJM exatamente como ele era

63 %de médicos que escolheram diferentes opções de tratamento para asma persistente leve
Figure 1. Percentage of Participants Choosing Each Treatment Option for Mild Persistent Asthma. The total number of participants who voted is shown for each continent or region. Option 1 was the as-needed use of inhaled beclomethasone and albuterol. Option 2 was an oral leukotriene-receptor antagonist plus as-needed rescue albuterol. Option 3 was a once-daily corticosteroid plus long-acting beta2-agonist in a single inhaler. Within each continent or region, countries from which votes were cast are shaded. An interactive graphic that includes country-specific data is available at Fredenburgh. N Engl J Med 2007;357: ver 1.4

64 X% assintomáticos longo prazo
Procurar slides de estudo de redução e suspensão

65 É possível suspender o CE inal quando a asma se controla?
Triancinolona 400 mcg 2x (n = 54) Salmeterol 50 mcg 2x (n = 54) Placebo (n = 56) Semanas 16 Triancinolona 400 mcg 2x - 6 Deykin. JACI 2005; 115:720-6

66 Sim, em alguns pacientes
Perda de Até 14 semanas Total controle 2 semanas seguintes Triancinolona (n=54) Salmeterol Placebo (n=56) Deykin. JACI 2005; 115:720-6

67 OPTIMA - Critérios de inclusão
b2 demanda  2 vezes/semana Reversibilidade a BD Grupo A Sem CEinal  3 meses VEF1 pós BD  80% Grupo B Em uso dose baixa CEinal

68 Perfil de pacientes com asma persistente leve
VEF1 (% predito) 90 Dias com sintomas/semana 3 Despertar noturno/semana < 1 b2 demanda/semana 7 % de dias não controlados/ano 15% O’Byrne. Am J Respir Crit Care Med 2001; 164:1392–1397

69 OPTIMA - Tempo para a primeira exacerbação grave
1 Exacerbações graves/ano 0,77 0,9 0,8 0,7 0,7 0,6 Dias O’Byrne. Am J Respir Crit Care Med 2001; 164:1392–1397

70 OPTIMA - Tempo para a primeira exacerbação grave
Placebo BUD200 + F 1 BUD 200 0,9 0,8 0,7 0,7 0,6 Dias O’Byrne. Am J Respir Crit Care Med 2001; 164:1392–1397

71 Time to first severe exacerbation
34/226 B200 Proportion 44/227 B200+F 79/237 PLA This plot shows the proportion of patients in the three treatment groups who at the time recorded on the horizontal axis have not experienced a severe exacerbation. In the P200 group there is no recorded event between day 126 and day 277, which explains the curve being parallel with time-axis in that segment. The numbers in the plot are Number of patients with at least one SEVEX /Total number of patients with data. Both P200 and P200+O are statistically significant from PLA. There is no difference between P200 and P200+O Days O’Byrne et al. Am. J. Respir. Crit. Care Med. 2001; ver 1.4

72 Rate for poorly controlled days
0.144 0.15 0.10 0.083 0.073 Rate 0.05 This plot shows the rate (or proportion) of poorly controlled days for the three treatment groups. The calculations are based on the diary data recorded after visits 3-8. The estimates are based on the “group approach” that is intrinsic in the Poisson model and has been used for analysis: all poorly controlled days are summed for a treatment group and divided by the total number of days for that group. Both P200 and P200+O are significantly better than PLA. No difference between P200 and P200+O can be found. 0.00 PLA B200 B200 + F O’Byrne et al. Am. J. Respir. Crit. Care Med. 2001; ver 1.4

73 START – Criterios de inclusão
Sintomas ≥ 1 vez/semana mas não diário Reversibilidade VEF1 pós BD > 80%

74 O’Byrne. Am J Respir Crit Care Med 2001; 164:1392–1397
START VEF1 (% predito) 86 Dias com sintomas/semana 4 O’Byrne. Am J Respir Crit Care Med 2001; 164:1392–1397

75 Probabilidade de exacerbação grave
10 8 Placebo 6 BUD 4 2 1 2 3 Anos Pauwels. Lancet 2003; 361: 1071–76

76 Cursos de budesonida por 10 dias
no de pacientes Cursos de budesonida por 10 dias Boushey. NEJM 2005;352:

77 Paciente tomaria a decisão por você
Altana

78 Por que manter um medicamento quando ele não funciona?
GOAL

79 Por que manter um medicamento quando ele não funciona?
Nossos dados

80 NO exalado em vez de escarro induzido?
(ppb) Pred CE inal ver 1.4

81 NO exalado em vez de escarro induzido?
(ppb) Pred CE inal ver 1.4

82 Uma vez com diagnóstico de asma, você já trocou de uma para outra medicação para asma ou descontinuou o uso porque ….? Brasil Geral Canonica. Allergy 2007; 62: Dados de arquivo Nycomed

83 Sintomas desapareceram
Uma vez com diagnóstico de asma, você já trocou de uma para outra medicação para asma ou descontinuou o uso porque ….? Brasil Geral Sintomas desapareceram ou diminuíram Canonica. Allergy 2007; 62: Dados de arquivo Nycomed

84 Brasil Geral Teve efeitos adversos
Uma vez com diagnóstico de asma, você já trocou de uma para outra medicação para asma ou descontinuou o uso porque ….? Brasil Geral Teve efeitos adversos Canonica. Allergy 2007; 62: Dados de arquivo Nycomed

85 Preocupação com potenciais efeitos adversos
Uma vez com diagnóstico de asma, você já trocou de uma para outra medicação para asma ou descontinuou o uso porque ….? Brasil Geral Preocupação com potenciais efeitos adversos

86 Medicação era muito cara
Uma vez com diagnóstico de asma, você já trocou de uma para outra medicação para asma ou descontinuou o uso porque ….? Brasil Geral Medicação era muito cara

87 Brasil Geral Medicação difícil ou inconveniente de usar
Uma vez com diagnóstico de asma, você já trocou de uma para outra medicação para asma ou descontinuou o uso porque ….? Brasil Geral Medicação difícil ou inconveniente de usar

88 Controle da asma é possível …
SF 500 F 500 SF 250 F 250 SF 100 F 100 20 80 40 60 % Sem CEinal  500 µg beclo > < 1000 µg beclo Bateman. Am J Respir Crit Care Med 2004; 170: 836–844 ver 1.4 ver 1.4 88 88

89 Bateman. Am J Respir Crit Care Med 2004; 170: 836–844
… mas nem sempre Sem CEinal  500 µg beclo > < 1000 µg beclo 20 80 40 60 % Bateman. Am J Respir Crit Care Med 2004; 170: 836–844 100 ver 1.4 ver 1.4 89 89

90 Controller treatment may be stopped if the patientʼs asthma remains controlled on the lowest dose of controller and no recurrence of symptoms occurs for one year (Evidence D).

91 May be considered for use only during periods of previously documented risk for a
child (Evidence D). If daily long-term control therapy is discontinued after the season of increased risk, written asthma action plans indicating specific signs of worsening asthma and actions to take should be reviewed with the caregivers, and a clinic contact should be scheduled 2–6 weeks after discontinuation of therapy to ascertain whether adequate control is maintained satisfactorily (Evidence D). Because of seasonal variations in exacerbations among children, such as during the seasons of increased upper respiratory infections (Johnston et al. 2006), it is possible, although not yet evaluated systematically, that some of the children described above may require daily therapy only during previously documented periods of increased risk of exacerbations for that individual. NHBLI

92 underlying disease process.
With respect to the potential role of ICSs in changing the natural course of asthma, the relevant clinical question is: Are ICSs associated with less disease burden after discontinuation of therapy? The best available evidence in children 5–12 years of age (CAMP 2000) and 2–3 years of age (Guilbert et al. 2006) demonstrated that, although ICSs provide superior control and prevention of symptoms and exacerbations during treatment, symptoms and airway hyperresponsiveness worsen when treatment is withdrawn (EPR⎯Update 2002; Guilbert et al. 2006). This evidence suggests that currently available therapy controls but does not modify the underlying disease process. NHBLI

93 Etapa 5 Etapa 4 Etapa 3 Etapa 2 Etapa 1

94 Etapa 5 Etapa 4 Etapa 3 Etapa 2 Etapa 1

95 ver 1.4

96 Alberto Cukier Divisão de Doenças Respiratórias
InCor/Hospital das Clínicas Faculdade de Medicina - USP ver 1.4

97 Em asma persistente o uso de corticóides inalatórios:
ver 1.4

98 ¯ sintomas, melhora função
Semanas Escore de sintomas Salbutamol - puffs/dia % de variação do PFE Djukanovic. Am Rev Respir Dis 145: 669, 1992 ver 1.4

99 Reduz exacerbações Beclometasona % sem exacerbações Placebo Dias
Salmeron. Am Rev Respir Dis 140: 167, 1989 ver 1.4

100 Reduz o risco de internações
20 40 60 80 12 Meses No de internações Com corticóide inalatório Sem corticóide inalatório Blais. Am J Respir Crit Care Med 158: 126, 1998 ver 1.4

101 Reduz a mortalidade “Rate ratio” No bombinhas de CI/ano 3 6 9 12 1,0
3 6 9 12 1,0 1,5 2,0 “Rate ratio” Suissa. NEJM 343: 332, 2000 Reduz a mortalidade ver 1.4

102 Inflamação aguda crônica Remodela/o das vias aéreas
Bousquet, Jeffery, Busse, Johnson, Vignola. Am J Respir Crit Care Med 161:1720, 2000

103 Inflamação aguda crônica Remodela/o das vias aéreas Sintomas
(Broncoconstrição) Exacerbações  responsividade Obstrução persistente Bousquet, Jeffery, Busse, Johnson, Vignola. Am J Respir Crit Care Med 161:1720, 2000

104 Corticóide inalatório diminui a velocidade de declínio do VEF1
Budesonide 800 mg/dia Dompeling. Ann Intern Med,118:770, 93 1.2 1.6 2 2.4 2.8 6 12 18 24 30 36 42 48 Tempo (meses) VEF 1 (l) Pré BD Pós BD 28 adultos com asma 28 com DPOC Corticóide inalatório diminui a velocidade de declínio do VEF1 ver 1.4

105 Sintomas > 1 vez/semana mas < 1 vez/ dia
Asma persistente leve Dados clínicos pré-tratamento Sintomas > 1 vez/semana mas < 1 vez/ dia Exacerbações podem afetar atividades e sono Asma noturna > 2 vezes/mês PFE ou VEF1 > 80% predito variabilidade 20-30% Slide 3 As all of you are aware patients with mild persistent asthma do not have daily symptoms, usually do not wake at night because of asthma and have nearly normal lung function. GINA ver 1.4

106 CE inalatório - quanto antes melhor?
105 adultos Asma persistente leve a moderada sem tratamento prévio com corticóide Início dos sintomas - 6 meses a 10 anos Budesonida Selroos, Chest 108: 1228, 1995 ver 1.4

107 CE inalatório - quanto antes melhor?
Selroos, Chest 108: 1228, 1995 D VEF1 Tempo de sintomas - meses 105 adultos Asma persistente leve a moderada sem tratamento prévio com corticóide Início dos sintomas - 6 meses a 10 anos Budesonida – 2 anos ver 1.4

108 103 adultos com asma < 1 ano VEF1 86,7%
Terbutalina vs budesonida 1200 mg/dia 2 anos Haahtela. NEJM 325:388, 91 ver 1.4

109 103 adultos com asma < 1 ano VEF1 86,7%
Terbutalina vs budesonida 1200 mg/dia 2 anos Budesonida  sintomas  função  hiperresponsividade Haahtela. NEJM 325:388, 91 ver 1.4

110 Budesonida Terbutalina Sintomas b2 de demanda Meses 3 2 1 24
Haahtela. NEJM 325:388, 91 1 2 3 24 Meses Sintomas Budesonida Terbutalina b2 de demanda ver 1.4

111 D PFE Budesonida – 33 L/min Terbutalina – 5 L/min Budesonida
Haahtela. NEJM 325:388, 91 1 2 3 24 Meses Sintomas b2 de demanda D PFE Budesonida – 33 L/min Terbutalina – 5 L/min Budesonida Terbutalina ver 1.4

112 PC15 Budesonida Terbutalina
Haahtela. NEJM 325:388, 91 1 2 3 4 5 24 PC15 Meses Budesonida Terbutalina

113 Budesonida Terbutalina Estudo 1
1 2 3 4 5 6 24 36 PC15 Meses Budesonida Terbutalina Estudo 1 Haahtela. NEJM 325:388, 91 NEJM 331:700, 94

114 Budesonida Placebo Budes. Terbutalina Estudo 1 Estudo 2
1 2 3 4 5 6 24 36 PC15 Meses Budesonida Placebo Budes. Terbutalina Estudo 1 Estudo 2 Haahtela. NEJM 325:388, 91 NEJM 331:700, 94

115 Céls. Espessura Espessura inflamatórias do epitélio da MB
Controles (6) , , ,8 Asma (6) Pré CE inal ,46* , ,0 Pós CE inal ,41** , ,8 (10 anos) *pré vs controles; **pré vs pós Lundgren, Eur Resp J, 88 ver 1.4

116 Desvantagens dos CE inalatórios
Rouquidão Candidíase oral

117 Desvantagens dos CE inalatórios
Rouquidão Candidíase oral  crescimento Equimoses Pele “fina” Glaucoma Catarata Insuficiência adrenal Osteoporose

118 Desvantagens dos CE inalatórios
Rouquidão Candidíase oral  crescimento Equimoses Pele “fina” Glaucoma Catarata Insuficiência adrenal Osteoporose Uso inalatório “Medo” de corticóides

119 Aderência ao tratamento de longa duração é baixa
Mais freqüente – suspensão voluntária Raramente – manutenção de doses altas Ocasionalmente – seguem as orientações

120 Conclusões A resposta clínica aos CE inalatórios em asma persistente é evidente ver 1.4

121 Conclusões A resposta clínica aos CE inalatórios em asma persistente é evidente As doses de CE inalatórios devem ser reduzidas progressivamente, se a asma estiver controlada ver 1.4

122 Conclusões A resposta clínica aos CE inalatórios em asma persistente é evidente As doses de CE inalatórios devem ser reduzidas progressivamente, se a asma estiver controlada Duração mínima do tratamento - 1 ano? ver 1.4

123 Conclusões A resposta clínica aos CE inalatórios em asma persistente é evidente As doses de CE inalatórios devem ser reduzidas progressivamente, se a asma estiver controlada Duração mínima do tratamento - 1 ano? A suspensão depende de resposta individualizada, imprevisível ver 1.4

124 Conclusões A resposta clínica aos CE inalatórios em asma persistente é evidente As doses de CE inalatórios devem ser reduzidas progressivamente, se a asma estiver controlada Duração mínima do tratamento - 1 ano? A suspensão depende de resposta individualizada, imprevisível Asma persistente sazonal - tratamento cíclico? ver 1.4