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Paediatric asthma management  - from theory to clinical practice Sun rise of River Mississippi, New Orleans, LA  郭和昌 醫師 高雄...
郭和昌 醫師 <ul><li>國立陽明大學醫學士 </li></ul><ul><li>長庚大學臨床醫學研究所博士班進修 </li></ul><ul><li>中華民國小兒科專科醫師 </li></ul><ul><li>中華民國免疫過敏專科醫師 <...
Asthma in children – a global healthcare issue <ul><li>Asthma is a serious global health problem whose  prevalence is incr...
台北地區學童氣喘盛行率
Asthma prevalence is increasing at the highest rate in children Trends in the prevalence of asthma, by age, in the USA (19...
The burden of childhood asthma <ul><li>The high prevalence of childhood asthma is influenced by  genetic and environmental...
<ul><li>The majority of patients consider themselves to have controlled asthma </li></ul>Asthma control in children: Asthm...
Holliday Inn, New Orleans, LA Which is real?
Café Du Monde, more than 100 yrs
Asthma restricts activities in adults and children ( 造成許多的影響 ) Neffen H  et al.   Pan American J Public Health  2005;  17:...
<ul><li>The Global Initiative for Asthma (GINA) defines clinical control of asthma as: 1 </li></ul><ul><li>The GINA treatm...
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Levels of Asthma Control *  Any exacerbation should prompt review of maintenance treatment to ensure that it is adequate. ...
兒童氣喘控制測驗 (C-ACT TM ) <ul><li>分數 : 20 分或  20 分以上表示您小孩的氣喘控制良好。 </li></ul><ul><li>分數 : 19 分或  19 分以下表示您小孩的氣喘並未獲得良好的控制。   </li...
The comparison of GINA Guideline Control Measure and Childhood-ACT in the evaluation of Asthmatic Children  ( 高雄長庚 ) N=63
The GINA guideline-based controlled group had higher C-ACT scores than the partly controlled and uncontrolled groups
 
Conclusions  <ul><li>C-ACT and GINA guideline-based control measure  show significant correlation with each other and are ...
controlled partly controlled uncontrolled exacerbation LEVEL OF CONTROL maintain and find lowest controlling step consider...
* Receptor antagonist or synthesis inhibitors 1. Global Initiative for Asthma (GINA): Global strategy for asthma managemen...
Treating to Maintain Asthma Control Stepping down  treatment when asthma is controlled <ul><li>When controlled on medium- ...
Treating to Maintain Asthma Control Stepping down  treatment when asthma is controlled <ul><li>When controlled on combinat...
Step-down treatment in asthma  N Engl J Med 2007;356:2027-39.
N Engl J Med 2007;356:2027-39. N=500 N=169 N=166 N=165
N Engl J Med 2007;356:2027-39.
Conclusions <ul><li>Patients with asthma that is  </li></ul><ul><li>well controlled with the use of twice-daily inhaled fl...
St. Louis Cathedral and Jackson Square, New Orleans, LA
The red lady, street car, New Orleans 慾望街車
Treating to Maintain Asthma Control Stepping up  treatment in response to loss of control <ul><li>Rapid-onset, short-actin...
Treating to Maintain Asthma Control Stepping up  treatment in response to loss of control <ul><li>Use of a combination  LA...
N Engl J Med. 2010 Mar 3  Step-up tx in childhood asthma with ICS
N Engl J Med. 2010 Mar 3
N Engl J Med. 2010 Mar 3
N Engl J Med. 2010 Mar 3  P = 0.02 P = 0.004 P = 0.004 P = 0.002
N Engl J Med. 2010 Mar 3  Beta-2 adrenergic receptors, position 16  (P = 0.49) (P = 0.009), P = 0.52 (P = 0.37)
N Engl J Med. 2010 Mar 3  no differences P = 0.006
Conclusions <ul><li>Nearly all the children had a  differential response  to each step-up therapy.  </li></ul><ul><li>LABA...
Rothenberg 3.25 公升的葡萄酒
Inhaled therapies vs. oral therapies
GINA guidelines for inhaled vs oral therapy <ul><li>GINA guidelines state that: </li></ul><ul><li>“ Inhaled therapy  is th...
MOSAIC study : FP compared with montelukast in children with asthma <ul><li>MOSAIC study  (Montelukast Study of Asthma in ...
FP compared with MON for treatment of children with asthma Ostrom NK  et al. J Pediatr  2005;  147 : 213–220. Mean change ...
FP compared with MON for treatment of children with asthma Zeiger RS  et al. J Clin Immunol  2006;  117 : 45–52. Asthma co...
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Salmeterol/fluticasone propionate (SFC) gives optimal control of asthma in children
Asthma control: evidence in children <ul><li>The effect of salmeterol/fluticasone propionate (SFC) on asthma control in th...
PEACE study
Rationale for PEACE <ul><li>Despite guideline recommendations on asthma therapy, non-steroidal oral medications are widely...
PEACE study design <ul><li>Changes from baseline in lung function, asthma symptoms and rescue  medication use were assesse...
PEACE study: patient demography and baseline characteristics Maspero J  et al.   Clin Ther. 2008 Aug;30(8):1492-504. Chara...
Primary data: morning PEF over 12 weeks  <ul><li>Over weeks 1–12, the adjusted mean change from baseline in PEF was 45.8 (...
Symptom-free and rescue-free days and nights with no awakenings: SFC compared with MON Maspero J  et al.   Clin Ther. 2008...
Percentage of subjects with controlled asthma: SFC compared with MON Maspero J  et al.   Clin Ther. 2008 Aug;30(8):1492-50...
Mean exacerbation rate  over 12 weeks: SFC compared with MON 0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4 SFC MON Weeks 1–12 Mean...
Most common adverse events  experienced during treatment in the PEACE study Maspero J  et al.   Clin Ther. 2008 Aug;30(8):...
Serious adverse events reported in the PEACE study: SFC compared with MON <ul><li>No serious adverse events  reported with...
<ul><li>SFC was clinically more efficacious and as well tolerated as MON </li></ul>Study summary SFC Maspero J  et al.   C...
A new trend of souvenirs collection
 
Compliance
Patient compliance with asthma medication 1. Horne R.  Chest  2006;  130 : 65–72. Poor Compliance Concern about side effec...
Compliance in children and adolescents <ul><li>In children and adolescents, there is almost  100% self-management  of thei...
Improving patient compliance <ul><li>Simple, regular dosing </li></ul><ul><ul><li>Simple dose regimens are generally easie...
The challenges of children using inhalers <ul><li>Both children and parents overestimate the child’s ability to use their ...
Summary <ul><li>Compliance with asthma medication in children and adolescents is generally poor </li></ul><ul><li>Both par...
Regular, twice-daily SFC gives control of asthma : what does this mean for the patient? <ul><li>Optimal asthma control can...
Mississippi River, New Orleans, LA
Jambalaya, New Orleans, LA
J Allergy Clin Immunol 2009;123:411-6.
J Allergy Clin Immunol 2009;123:411-6.
Physicians treating children with a  Parental history of asthma,  increased eNO levels,  low PC20 values, or  a history of...
Eur J Pediatr (2008) 167:731–736 Inhaled corticosteroids or montelukast as the preferred primary long-term treatment for p...
 
<ul><li>Although there is no cure for asthma,  </li></ul><ul><li>appropriate management that includes a partnership betwee...
Allergy Asthma Immunol Res. 2010 January;2(1):1-13.
Allergy Asthma Immunol Res. 2010 January;2(1):1-13.
Allergy Asthma Immunol Res. 2010 January;2(1):1-13.
Effect of beta2-adrenergic receptor polymorphism on response to longacting beta2 agonist in asthma (LARGE trial) <ul><li>I...
Associations of β2-adrenergic receptor genotypes and haplotypes with wheezing illness in Taiwanese schoolchildren  <ul><li...
Beta-2 adrenergic receptors in asthma (UpToDate summary) <ul><li>The expression and coupling of beta-2 adrenergic receptor...
PEACE study objectives <ul><li>Primary </li></ul><ul><ul><li>To demonstrate superior efficacy of SFC compared with MON on ...
PEACE study: patient population <ul><li>Male or female, aged 6–14 years </li></ul><ul><li>Diagnosis of asthma in previous ...
PEACE study: patient population randomised to treatment <ul><li>FEV 1  within 15% of the value at visit 1 </li></ul><ul><l...
PEACE study endpoints <ul><li>Primary endpoint </li></ul><ul><ul><li>Change from baseline in the mean morning PEF over wee...
MON chronic asthma study (6–14 years): patient baseline characteristics  <ul><li>MON Placebo </li></ul><ul><li>Characteris...
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Treatment of Pediatric asthma-(Ho-Chang Kuo, MD)郭和昌醫師

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2010 An update of treatment on Pediatric asthma based on the GINA guideline and literature review.

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  • Notes Asthma is a serious global health problem whose prevalence is increasing in most countries, especially among children 1 The global prevalence of asthma ranges from 1% to 18% of the population in different countries 1 The lack of a precise and universally accepted definition of asthma makes reliable comparison of reported prevalence from different parts of the world problematic 1 Childhood asthma has more than doubled in the last 20 years 2 Over the past 40 years, there has been a sharp increase in the prevalence, morbidity, mortality and economic burden associated with asthma, particularly in children 3 Among patients seen in clinical practice up to 60% of paediatric and 30% of adult patients have asthma 3 References Global Initiative for Asthma (GINA): Global strategy for asthma management and prevention. Revised Edition 2007 . European lung white book. Brussels, Belgium: European Respiratory Society and the European Lung Foundation, 2003. 3. Braman SS. Chest 2006; 130 : 4S–12S.
  • Notes The rate of asthma increases as communities adopt Western lifestyles and become urbanised 1 The most striking increases in asthma are seen in children 2 As the proportion of the world&apos;s population that is urban is projected to increase to 59% in 2025, there is likely to be a marked increase in the global prevalence of asthma over the next two decades 1 References 1. Partridge MR. Eur Respir Rev 2007; 16 : 67–72. 2. Braman SS. Chest 2006; 130 : 4S–12S.
  • Notes The most striking increases in asthma prevalence are seen among children with rates &gt; 30% in some areas 1 The increase in asthma prevalence has been associated with a rise in atopic sensitization and a parallel increase in other allergic conditions (eg ezcema, rhinitis). Allergic sensitization appears to begin in utero 1 Environmental influences such as exposure to microorganisms, pollutants, indoor and outdoor allergens, and diet exert a strong influence on the development of the disease in susceptible individuals 1 In France, traffic related particulate air pollution contributes to 243,000 attacks of asthma in children alone 2 Two thirds of asthmatic children still have symptoms at age 21, and 5 to 10% of those with “trivial” asthma as children will have severe disease as adults 1 Children account for a high proportion of indirect costs (39%) reflecting the importance of time spent by others to care for them 3 69% of parents of asthmatic children reported having to take time off work and 13% of parents lost their jobs caring for their child’s asthma 1 During infancy, a number of viruses have been associated with the inception of the asthmatic phenotype 4 Infants fed formulas of intact cow’s milk or soy protein have a higher incidence of wheezing illnesses in early childhood compared with those fed breast milk 4 Children consume a high proportion of resources devoted to emergency treatment (45%) 3 School days lost in Australia and USA were 50 x 10 4 and &gt; 1000 x 10 4 respectively 3 References Braman S. Chest 2006; 130 : 4S–12S. European lung white book. Brussels, Belgium: European Respiratory Society and the European Lung Foundation, 2003. Barnes PJ. Eur Respir J 1996; 9 : 636–42. GINA Global Strategy for Asthma Management and Prevention. Revised 2006.
  • Notes The Asthma Insights and Reality in Europe study (AIRE) assessed the current levels of asthma control as reported by patients and the extent to which guideline recommendations were being implemented 1 It showed that although the majority of patients considered themselves to have controlled asthma, yet symptom levels showed control failing to reach the levels expected by management guidelines 1 Overall, only 5.3% of all patients (5.1% of adults and 5.8% of children) met all the criteria for asthma control 1 In the AIRLA study, only 2.4% of asthma patients (2.3% of adults and 2.6% of children) surveyed in South America achieved GINA-defined levels of control 2 References 1. Rabe KF et al. Eur Resp J 2000; 16 : 802–807. 2. Neffen H et al. Pan American J Public Health 2005; 17 : 191–197.
  • Notes The GINA definition for control of asthma includes no limitation on activities, including exercise However, results from the American Insights and Reality in Latin America (AIRLA) survey showed that activity limitation caused by asthma was considerable in adults and children in Latin American countries In children, symptoms of asthma had the biggest impact on activities such as: Sleeping: 43% Sports and recreation: 42% Normal physical activity: 33% Lifestyle: 33% In addition, 58% of the children with asthma in this study reported that their asthma had caused them to miss school in the last year Reference Neffen H et al. Pan American J Public Health 2005; 17 : 191–197.
  • Notes Improved asthma control is reflected by fewer symptoms, less need for reliever medications, and fewer exacerbations 1 It is recommended that treatment be aimed at controlling the clinical features of disease, including lung function abnormalities 1 Overuse of rescue medication is an indication of poor asthma control. GINA defines &gt;2/week use of rescue medication or 2 rescue medication prescriptions per year as suggestive of poor control 1 Studies have shown that as few as 5% of patients meet all of the criteria for guideline-defined control 2 In the AIRLA study, only 2.4% of asthma patients surveyed in South America achieved guideline-defined levels of control 3 References 1. Global Initiative for Asthma (GINA): Global strategy for asthma management and prevention. Revised Edition 2007 . 2. Rabe KF et al. Eur Resp J 2000; 16 : 802–807. 3. Neffen H et al. Pan American J Public Health 2005; 17 : 191–197.
  • Notes The suggested reliever medication to be taken at each step is also outlined in the updated GINA guidelines, with the preferred controller option show in the shaded box Treatment Steps 2 through 5, combine an as-needed reliever treatment with regular controller treatment At Step 2, a low-dose inhaled glucocorticosteroid (ICS) is recommended as the initial controller treatment for asthma patients of all ages Other options are available but not recommended for routine use as initial or first-line controllers in Step 2. Sustained-release theophylline has only weak anti-inflammatory and controller efficacy and is commonly associated with a wide range of side effects At Step 3, the recommended option for adolescents and adults is to combine a low dose of ICS with an inhaled long-acting  2-agonist, either in a combination inhaler device or as separate components. However, for all children, but particularly those 5 years and younger, combination therapy has been less well studied and the addition of a long-acting  2 -agonist may not be as effective as increasing the dose of ICS in reducing exacerbations. However, the interpretation of some studies is problematic as not all children received concurrent ICSs The preferred treatment at Step 4 is to combine a medium or high dose of ICS with a long-acting inhaled  2 -agonist. However, in most patients, the increase from a medium to a high dose of ICS provides relatively little additional benefit, and the high dose is recommended only on a trial basis for 3 to 6 months when control cannot be achieved with medium-dose ICS combined with a long-acting  2 -agonist and/or a third controller (e.g. leukotriene modifiers or sustained-release theophylline) Reference Global Initiative for Asthma (GINA): Global strategy for asthma management and prevention. Revised Edition 2007.
  • Notes GINA guidelines recommend i nhaled therapy as the cornerstone of asthma treatment for children of all ages Furthermore, inhaled glucocorticosteroids (ICSs) are the recommended treatment since they are the most effective controller therapy Guidelines are further supported by evidence that oral or systemic glucocorticosteroid use increases the risk of fracture: The risk of fracture increases along with the number of treatments, with a 32% increase at four courses Use of ICSs reduces the need for systemic courses Reference Global Initiative for Asthma (GINA): Global strategy for asthma management and prevention. Revised Edition 2007 .
  • Notes The MOSAIC study (Montelukast Study of Asthma in Children) was a 12-month, randomised, non-inferiority study comparing montelukast (MON) 5 mg od with FP 100 µg bd in children aged 6–14 years In this study, patients receiving MON had more exacerbations that those receiving FP (32.2% vs 25.6%), and required more systemic corticosteroids during the treatment period (17.8% vs 10.5%, p≤0.001) Reference Garcia Garcia ML et al . Paediatrics 2005; 116 : 360–369.
  • Notes Results from a 12-week, randomised, double-blind study comparing MON 5 mg od with fluticasone propionate (FP) 50 µg bd in children aged 6–12 years demonstrated that at week 12, significantly more patients stated that they were satisfied with treatment in the FP group than in the MON group (58% vs 46%; p=0.006) Compared with MON, FP significantly increased mean percent change from baseline FEV1 (p=0.02), morning PEF (p=0.004), evening PEF (p=0.02) and percentage rescue-free days (p=0.002) In addition, the mean daily total asthma-related cost per patient in the FP group was one-third that of the MON group ($1.25 vs $3.49) Reference Ostrom NK et al. J Pediatr 2005; 147 : 213–220.
  • Notes A further study of MON vs FP in children aged 6–14 years compared MON 5–10 mg once a day with FP 100 µg bd showed that asthma control improves consistently and significantly more with FP than with MON: Average asthma control (MON vs FP, adjusted mean values): 5 vs 4.3; p&lt;0.0001 Overall asthma control questionnaire score (MON vs FP, adjusted mean values): 0.59 vs 0.76; p=0.0009 FEV1/FVC (%; MON vs FP, adjusted mean values): 82.2 vs 79.0; p&lt;0.0001 Reference Zeiger RS et al. J Clin Immunol 2006; 117 : 45–52.
  • Notes Despite guideline recommendations on asthma therapy, non-steroidal oral medications are widely used first-line for many children regardless of severity or level of control In Latin America, of the 37% of patients who reported taking a prescribed asthma medication to reduce airway inflammation, only 6% were using ICS Prescription data from the USA indicates that many children are prescribed either MON, ICS or SFC first line, the prescription is given regardless of severity or control Reference Maspero J et al. Poster presented at American Thoracic Society International Conference , Toronto, Canada, 16–21 May 2008.
  • Notes Asthma morbidity in children remains high, with levels of asthma control falling short of guideline recommendations The PEACE Study compared the efficacy and safety of inhaled SFC with oral MON for the control of persistent asthma in children aged 6–14 years Symptomatic patients (FEV 1 55%–80% predicted normal) were randomised to double-blind, double dummy treatment with SFC 50/100 µg twice daily (N=281) or MON 5 mg once daily (N=267) for 12 weeks Changes from baseline in lung function, asthma symptoms and rescue medication use were assessed Reference Maspero J et al. Poster presented at American Thoracic Society International Conference , Toronto, Canada, 16–21 May 2008.
  • Notes A total of 548 patients were randomised to treatment, of which 281 received SFC and 267 recevied MON. The number of patients completing the study was: SFC: 263 (94%) MON 244 (91%) As can be seen from the table, demography and baseline characteristics were similar for the two groups. Reference Maspero J et al. Poster presented at American Thoracic Society International Conference , Toronto, Canada, 16–21 May 2008.
  • Notes Over weeks 1–12, the adjusted mean change from baseline in PEF was 45.8 (2.82) L/min in the SFC group and 28.7 (2.86) L/min in the MON group, giving a statistically significant treatment difference in favour of SFC: 17.6 L/min (95% CI: 9.23, 25.08, p&lt;0.001) Reference Maspero J et al. Poster presented at American Thoracic Society International Conference , Toronto, Canada, 16–21 May 2008.
  • Notes The SFC group had statistically significant greater improvements in percentage symptom-free and rescue-free 24-hour periods compared with MON: % symptom-free 24-hour periods: p=0.025 % rescue-free 24-hour periods: p &lt;0.001 % nights with no awakenings: p=0.0154 Reference Maspero J et al. Poster presented at American Thoracic Society International Conference , Toronto, Canada, 16–21 May 2008.
  • Notes More patients in the SFC group achieved “well controlled” asthma compared with the MON group A week of asthma control was defined as: No night-time awakenings No exacerbations No emergency visits No treatment-related adverse events Having 2 out of 3 of: Symptoms on &lt;3 days Rescue  2 -agonist use on &lt;3 days Daily morning PEF ≥80% predicted Over the whole treatment period, the median percentage of controlled asthma weeks was 83.3% in the SFC group and 66.7% in the MON group (SFC:MON difference 16.7%; 95% CI: 8.3, 16.7; p&lt;0.001 in favour of SFC) Reference Maspero J et al. Poster presented at American Thoracic Society International Conference , Toronto, Canada, 16–21 May 2008.
  • Notes In this study, an exacerbation was defined as worsening asthma requiring: Emergency room visit Hospitalisation Unscheduled clinic visit requiring treatment with systemic corticosteroids or nebulised salbutamol &gt;12 puffs per day of salbutamol or &gt;10 puffs per 2 consecutive days of salbutamol Mean exacerbation rates over 12 weeks was 0.12 in the SFC group and 0.30 in the MON group (SFC/MON ratio 0.40; 95% CI: 0.29, 0.57; p&lt;0.001) Significantly fewer patients had at least one exacerbation during treatment with SFC (29; 10.3%) compared with MON (62; 23.2%), giving a significantly lower exacerbation rate This shows that in children with uncontrolled asthma, treatment with SFC is significantly more effective in decreasing exacerbation rates than treatment with MON Reference Maspero J et al. Poster presented at American Thoracic Society International Conference , Toronto, Canada, 16–21 May 2008.
  • Notes The most commonly reported adverse event in both groups was headache: SFC: 66/281 (23%) MON: 72/267 (27%) Reference Maspero J et al. Poster presented at American Thoracic Society International Conference , Toronto, Canada, 16–21 May 2008.
  • Notes There were four, non drug-related, serious adverse events (SAEs) reported during the study, all in the MON group One SAE, dengue fever, started during the run-in phase The other three were asthma exacerbations, all resulting in hospitalisation Seven patients were withdrawn due to worsening asthma in the MON group, and none in the SFC group No deaths were recorded during the study Reference Maspero J et al. Poster presented at American Thoracic Society International Conference , Toronto, Canada, 16–21 May 2008.
  • Notes The PEACE study concludes that in children with uncontrolled asthma, treatment with SFC is significantly more effective in improving measures of asthma control and in decreasing exacerbation rates than treatment with MON, and the two drugs were both well tolerated Reference Maspero J et al. Poster presented at American Thoracic Society International Conference , Toronto, Canada, 16–21 May 2008.
  • Notes Compliance may be influenced by: Concern about side effects Patient’s negative attitude towards medicines in general Past experience Views of others Cultural influences Practical difficulties Patient’s perceived need Reference 1. Horne R. Chest 2006; 130 : 65–72.
  • Notes In children and adolescents, there is almost 100% self-management of their asthma symptoms 1 The complexity of optimum routine management of asthma results in reduced adherence 1 Adherence to treatment by children and adolescents ranges from 43% to 100%,with an average of 58% in developed countries 2 References 1. Slack MK et al. Am J Health-System Pharmacy 1995; 52 : 1417 – 1421. 2. Burkhart P et al . In: Hayman L, Mahom M,Turner R, eds. Chronic illness in children: An evidence-based approach. New York, Springer, 2002: 199 – 229.
  • Notes It has been shown that simple dose regimens are generally easier for patients to follow 1 Compliance rates are most highly correlated with the number of doses rather than the number of medications or tablets that must be taken daily 1 The core issue for patients is: “How many times a day must I remember to take a dose?” 1 Reference 1. Cramer JA. Heart 2002; 88 : 203–206.
  • Notes Over one third of children with asthma answering the schools questionnaire had been prescribed an inhaler that was almost certainly unsuitable for their use. Most of these had been prescribed a metered dose inhaler alone 1 Both children and parents overestimated the child’s ability to use their inhaler 1 As small children have smaller inspiratory capacities than adults in terms of both flow rate and volume, DPIs are generally not advocated for children under the age of 6 years. However, Diskus™ operates at low flow rates and has been shown to be effective for use in children aged as young as 4 years 2 All patients could generate adequate flow through the Diskus. However, only 57% could generate adequate flow through the Turbuhaler™ and 21% through the Aerolizer ®2 A further study in children highlighted the problems that some may have to generate sufficient inspiratory effort to receive the required dose from a Turbuhaler and recommended that this device should not be prescribed to preschool age children 2 References 1. Childs F et al. Arch Dis Child 2002; 86 : 176–179. 2. Chrystyn H. Int J Clin Pract 2007; 61 : 1022–1036.
  • Notes The aim of this prospective, randomised trial was to directly compare the efficacy and safety of SFC compared with MON in children with persistent uncontrolled asthma, not currently receiving anti-inflammatory treatment Reference Maspero J et al. Poster presented at American Thoracic Society International Conference , Toronto, Canada, 16–21 May 2008.
  • Notes Male or female subjects aged 6–14 years, with a diagnosis of asthma for at least 6 months (ATS definition), a forced expiratory volume in one second (FEV 1 ) between 55% and 80% of predicted normal and  12% FEV 1 reversibility, were eligible for the study Subjects required to be symptomatic on short acting  2 agonists and must not have used ICS over the previous month or LTRAs over the previous 2 weeks Reference Maspero J et al. Poster presented at American Thoracic Society International Conference , Toronto, Canada, 16–21 May 2008.
  • Notes Prior to randomisation, patients were required to show diary card evidence of either salbutamol rescue use or asthma symptoms on at least 4 out of the last 7 days of the run-in period Reference Maspero J et al. Poster presented at American Thoracic Society International Conference , Toronto, Canada, 16–21 May 2008.
  • Notes The primary endpoint was change from baseline in morning peak expiratory flow (PEF) over weeks 1–12, as recorded on daily diary cards. PEF was measured using a Mini Wright Truzone Peak Flow Meter. The highest of three values each morning and evening was recorded, before taking study medication or any as needed salbutamol Secondary efficacy endpoints included pre-dose FEV 1 , evening PEF, level of symptoms and rescue medication use and assessment of asthma control A week of asthma control, as defined in the GOAL study, was defined as no night-time awakenings due to asthma, no exacerbations, no emergency visits, no treatment-related adverse events enforcing a change in asthma therapy, and having 2 out of 3 criteria of: Symptoms (score &gt;1) on less than 3 days Rescue  2 -agonist use on less than 3 days up to a maximum of four occasions per week Morning PEF  80% predicted every day Asthma-specific quality of life was assessed at the start and end of treatment using the Paediatric Asthma Quality of Life Questionnaire (PAQLA) for children and the Paediatric Asthma Caregiver’s Quality of Life Questionnaire (PACQLQ) for the caregivers Questionnaires were only performed in centres where there was a valid translation available. The minimal important difference for both questionnaires is a change in score of  0.5 Reference Maspero J et al. Poster presented at American Thoracic Society International Conference , Toronto, Canada, 16–21 May 2008.
  • Notes An 8-week study had previously been carried out to determine the effect of MON compared with placebo, on asthma control, including measurements of airways obstruction, patient-reported end points, and asthma outcomes, as well as to determine the safety profile in 6- to 14-year-old patients with asthma The treatment groups were well matched with respect to baseline demographic and clinical characteristics The median age of the 336 randomized patients was 11 years, and the mean duration of asthma was 7 years. Approximately two-thirds of patients in each treatment group were male. At baseline, 33% of patients in the placebo group and 39% of patients in the MON group used inhaled corticosteroids. The mean FEV 1 was 72% of predicted in each group 1 Reference Knorr B et al. JAMA 1998; 279 : 1181–1186.
  • Transcript of "Treatment of Pediatric asthma-(Ho-Chang Kuo, MD)郭和昌醫師"

    1. 1. Paediatric asthma management - from theory to clinical practice Sun rise of River Mississippi, New Orleans, LA 郭和昌 醫師 高雄長庚兒童過敏免疫風濕科 Mar 27, 2010, AIR 南區季會
    2. 2. 郭和昌 醫師 <ul><li>國立陽明大學醫學士 </li></ul><ul><li>長庚大學臨床醫學研究所博士班進修 </li></ul><ul><li>中華民國小兒科專科醫師 </li></ul><ul><li>中華民國免疫過敏專科醫師 </li></ul><ul><li>台灣兒童過敏氣喘暨免疫學會專科醫師 </li></ul><ul><li>亞洲兒科醫學研究學會 (ASPR) 會員醫師 </li></ul><ul><li>美國過敏氣喘免疫學會 (AAAAI) 會員醫師 </li></ul><ul><li>歐洲過敏氣喘及臨床免疫學會 (EAACI) 會員醫師 </li></ul><ul><li>高雄長庚講師級主治醫師 (2008~) </li></ul><ul><li>長庚大學兼任講師 (2009~) </li></ul><ul><li>教育部審訂講師 (2009~) </li></ul>Mar, 2010, NOLA
    3. 3. Asthma in children – a global healthcare issue <ul><li>Asthma is a serious global health problem whose prevalence is increasing in most countries , especially among children 1 </li></ul><ul><ul><li>Childhood asthma has more than doubled in the last 20 years 2 </li></ul></ul><ul><ul><li>Represents 60% of all paediatric consultations 3 </li></ul></ul><ul><li>Over the last 40 years there has been a sharp increase in the global prevalence, morbidity, mortality, and economic burden associated with asthma, particularly among children 3 </li></ul><ul><li>Global Initiative for Asthma (GINA): Global strategy for asthma management and prevention. Revised Edition 2007 . </li></ul><ul><li>European Lung White Book </li></ul><ul><li>Braman SS. Chest 2006; 130 : 4S–12S. </li></ul>
    4. 4. 台北地區學童氣喘盛行率
    5. 5. Asthma prevalence is increasing at the highest rate in children Trends in the prevalence of asthma, by age, in the USA (1985–1996) Braman SS. Chest 2006; 130 : 4S–12S. 10 years Age (years) <18 18 - 44 45 - 64 65+ Total (all ages) 80 70 60 50 40 30 20 85 86 87 88 89 90 91 92 93 94 95 96 Rate/1,000 persons Years
    6. 6. The burden of childhood asthma <ul><li>The high prevalence of childhood asthma is influenced by genetic and environmental factors including: </li></ul><ul><ul><li>Rise in atopic sensitization and other allergic conditions 1 </li></ul></ul><ul><ul><li>Diet 1,2 </li></ul></ul><ul><ul><li>Increasing air pollution 3 </li></ul></ul><ul><ul><li>Infections 2 </li></ul></ul><ul><li>Important to identify and treat childhood asthma 1 </li></ul><ul><ul><li>Symptoms persist into adulthood in the majority of cases </li></ul></ul><ul><ul><li>“ trivial” asthma in childhood often progresses to severe disease in adults </li></ul></ul><ul><li>Indirect costs related to family care 1,4 , school days lost 4 , and resources for emergency treatment 4 are a particular economic burden in childhood asthma </li></ul>1. Braman S. Chest 2006; 130 :4S–12S; 2. GINA Global Strategy for Asthma Management and Prevention. Revised 2006. 3. European Lung White Book. Brussels, Belgium: European Respiratory Society and the European Lung Foundation, 2003. 4. Barnes PJ. Eur Respir J 1996; 9 :636–642.
    7. 7. <ul><li>The majority of patients consider themselves to have controlled asthma </li></ul>Asthma control in children: Asthma Insights and Reality in Europe (AIRE) study Rabe KF et al. Eur Resp J 2000; 16 : 802–807. SP: severe persistent; MOP: moderate persistent; MP: mild persistent; MI: mild intermittent; Well/completely controlled Somewhat controlled Poorly/not controlled <ul><li>However, overall, only 5.3% of all patients (5.1% of adults and 5.8% of children) met all the criteria for asthma control </li></ul>虛實 100 75 50 25 0 Patients % SP MOP MP MI Children SP MOP MP MI Adults
    8. 8. Holliday Inn, New Orleans, LA Which is real?
    9. 9. Café Du Monde, more than 100 yrs
    10. 10. Asthma restricts activities in adults and children ( 造成許多的影響 ) Neffen H et al. Pan American J Public Health 2005; 17: 191–197 .
    11. 11. <ul><li>The Global Initiative for Asthma (GINA) defines clinical control of asthma as: 1 </li></ul><ul><li>The GINA treatment guidelines for children > 5 years are identical to the adult recommendation 1 </li></ul>Goal of asthma management: Guideline-defined control ( 控制良好 ) Global Initiative for Asthma (GINA): Global strategy for asthma management and prevention. Revised Edition 2007 . <ul><li>No (twice or less/week) daytime symptoms </li></ul><ul><li>No limitations of daily activities, including exercise </li></ul><ul><li>No nocturnal symptoms or awakening because of asthma </li></ul><ul><li>No (twice or less/week) need for reliever treatment </li></ul><ul><li>Normal or near-normal lung function </li></ul><ul><li>No exacerbations </li></ul>
    12. 12. Heidelberg, Germany
    13. 13. Levels of Asthma Control * Any exacerbation should prompt review of maintenance treatment to ensure that it is adequate. † By definition, an exacerbation in any week makes that an uncontrolled asthma week. One in any week† One or more/year* None Exacerbations < 80% predicted or personal best (if known) Normal Lung function (PEF or FEV 1 ) More than twice/week None (twice or less/week) Need for reliever/ rescue treatment Any None Nocturnal symptoms/awakening Any None Limitations of activities Three or more features of partly controlled asthma present in any week More than twice/week None (twice or less/week) Daytime symptoms Uncontrolled Partly Controlled (Any measure present in any week) Controlled (All of the following) Characteristic
    14. 14. 兒童氣喘控制測驗 (C-ACT TM ) <ul><li>分數 : 20 分或 20 分以上表示您小孩的氣喘控制良好。 </li></ul><ul><li>分數 : 19 分或 19 分以下表示您小孩的氣喘並未獲得良好的控制。 </li></ul>白天 晚上 運動
    15. 15. The comparison of GINA Guideline Control Measure and Childhood-ACT in the evaluation of Asthmatic Children ( 高雄長庚 ) N=63
    16. 16. The GINA guideline-based controlled group had higher C-ACT scores than the partly controlled and uncontrolled groups
    17. 18. Conclusions <ul><li>C-ACT and GINA guideline-based control measure show significant correlation with each other and are reliable tools to monitor childhood asthma control </li></ul><ul><li>only the GINA guideline-based control measure correlates with spirometry parameters </li></ul><ul><li>C-ACT may overestimate asthma control </li></ul><ul><li>For children with poorly controlled asthma or poor symptom perception , more closely timed visits and serial pulmonary function tests are preferable. </li></ul>
    18. 19. controlled partly controlled uncontrolled exacerbation LEVEL OF CONTROL maintain and find lowest controlling step consider stepping up to gain control step up until controlled treat as exacerbation TREATMENT OF ACTION TREATMENT STEPS REDUCE INCREASE STEP 1 STEP 2 STEP 3 STEP 4 STEP 5 REDUCE INCREASE
    19. 20. * Receptor antagonist or synthesis inhibitors 1. Global Initiative for Asthma (GINA): Global strategy for asthma management and prevention. Revised Edition 2007 . GINA stepwise management of asthma in adults and children >5 years Step 1 Step 2 Step 3 Step 4 Step 5 Asthma education Environmental control As needed rapid-acting  2-agonist As-needed rapid-acting  2-agonist Controller options Select one Select one Add one or more Add one or more Low-dose inhaled ICS Low-dose ICS plus long-acting  2 -agonist Medium- or high-dose ICS plus long-acting  2 -agonist Oral glucocorticosteroid (lowest dose) Leukotriene modifier* Medium- or high-dose ICS Leukotriene modifier Anti-IgE treatment Low-dose ICS plus leukotriene modifier Sustained-release theophylline Low-dose ICS plus sustained-release theophylline Preferred option
    20. 21. Treating to Maintain Asthma Control Stepping down treatment when asthma is controlled <ul><li>When controlled on medium- to high-dose ICS: 50% dose reduction at 3 month intervals ( Evidence B ) </li></ul><ul><li>中高劑量 3 個月降 50 % ICS </li></ul><ul><li>When controlled on low-dose ICS: switch to once-daily dosing ( Evidence A ) </li></ul><ul><li>低劑量則改一次使用 ICS </li></ul>
    21. 22. Treating to Maintain Asthma Control Stepping down treatment when asthma is controlled <ul><li>When controlled on combination inhaled glucocorticosteroids and long-acting inhaled β 2 -agonist, reduce dose of ICS by 50% while continuing the LABA ( Evidence B ) </li></ul><ul><li>先降 ICS 續用 LABA </li></ul><ul><li>If control is maintained, reduce to low-dose ICS and stop LABA ( Evidence D ) </li></ul><ul><li>後停 LABA </li></ul>
    22. 23. Step-down treatment in asthma N Engl J Med 2007;356:2027-39.
    23. 24. N Engl J Med 2007;356:2027-39. N=500 N=169 N=166 N=165
    24. 25. N Engl J Med 2007;356:2027-39.
    25. 26. Conclusions <ul><li>Patients with asthma that is </li></ul><ul><li>well controlled with the use of twice-daily inhaled fluticasone </li></ul><ul><li>can be switched to once-daily fluticasone plus salmeterol without increased rates of treatment failure. </li></ul><ul><li>A switch to montelukast results in an increased rate of treatment failure and decreased asthma control ; </li></ul><ul><li>however, patients taking montelukast remained free of symptoms on 78.7% of treatment days. </li></ul>
    26. 27. St. Louis Cathedral and Jackson Square, New Orleans, LA
    27. 28. The red lady, street car, New Orleans 慾望街車
    28. 29. Treating to Maintain Asthma Control Stepping up treatment in response to loss of control <ul><li>Rapid-onset, short-acting or long-acting inhaled β 2-agonist bronchodilators provide temporary relief. </li></ul><ul><li>Need for repeated dosing over more than one/two days signals need for possible increase in controller therapy </li></ul><ul><li>警訊 </li></ul>
    29. 30. Treating to Maintain Asthma Control Stepping up treatment in response to loss of control <ul><li>Use of a combination LABA ( e.g., formoterol) and an ICS ( e.g., budesonide) in a single inhaler both as a controller and reliever is effecting in maintaining a high level of asthma control and reduces exacerbations ( Evidence A ) </li></ul><ul><li>ICS+LABA 效果好 </li></ul><ul><li>Doubling the dose of inhaled glucocortico-steroids is not effective , and is not recommended ( Evidence A ) </li></ul><ul><li>加ICS不好 </li></ul>
    30. 31. N Engl J Med. 2010 Mar 3 Step-up tx in childhood asthma with ICS
    31. 32. N Engl J Med. 2010 Mar 3
    32. 33. N Engl J Med. 2010 Mar 3
    33. 34. N Engl J Med. 2010 Mar 3 P = 0.02 P = 0.004 P = 0.004 P = 0.002
    34. 35. N Engl J Med. 2010 Mar 3 Beta-2 adrenergic receptors, position 16 (P = 0.49) (P = 0.009), P = 0.52 (P = 0.37)
    35. 36. N Engl J Med. 2010 Mar 3 no differences P = 0.006
    36. 37. Conclusions <ul><li>Nearly all the children had a differential response to each step-up therapy. </li></ul><ul><li>LABA step-up was significantly more likely to provide the best response than either ICS or LTRA step-up. </li></ul><ul><li>However, many children had a best response to ICS or LTRA step-up therapy, </li></ul><ul><li>highlighting the need to regularly monitor and appropriately adjust each child’s asthma therapy. </li></ul><ul><li>各有所需 </li></ul>
    37. 38. Rothenberg 3.25 公升的葡萄酒
    38. 39. Inhaled therapies vs. oral therapies
    39. 40. GINA guidelines for inhaled vs oral therapy <ul><li>GINA guidelines state that: </li></ul><ul><li>“ Inhaled therapy is the cornerstone of asthma treatment for children of all ages” </li></ul><ul><li>“ ICS are currently the most effective anti-inflammatory medications for the treatment of persistent asthma ” </li></ul>1. Global Initiative for Asthma (GINA): Global strategy for asthma management and prevention. Revised Edition 2007 .
    40. 41. MOSAIC study : FP compared with montelukast in children with asthma <ul><li>MOSAIC study (Montelukast Study of Asthma in Children) </li></ul>0.036 1.05 0.92 Overall quality of life 0.003 -25.4 -22.7 Days with β -receptor agonist use, % 0.004 2.7 0.6 FEV 1 , % predicted p-value FP Montelukast Change from baseline Garcia Garcia ML et al . Paediatrics 2005; 116 : 360–369.
    41. 42. FP compared with MON for treatment of children with asthma Ostrom NK et al. J Pediatr 2005; 147 : 213–220. Mean change at endpoint MON FP p-value FEV 1 (%) 4.60 10.6 0.002 AM PEF (L/min) 23.0 39.9 0.004 PM PEF (L/min) 20.4 35.5 0.02 Night-time asthma symptom score -0.19 -0.40 <0.001 Total albuterol use (puffs/day) -1.23 -1.43 0.018 Night-time albuterol use (puffs/day) -0.21 -0.39 <0.001 % rescue-free days 35.0 45.1 0.002
    42. 43. FP compared with MON for treatment of children with asthma Zeiger RS et al. J Clin Immunol 2006; 117 : 45–52. Asthma control responses to FP and MON Baseline mean Adjusted MON mean Adjusted FP mean p-value Average asthma control days per week 2.2 5 4.3 <0.0001 Overall asthma control questionnaire score 0.96 0.59 0.76 0.0009 FEV 1 /FVC (%) 80.1 82.2 79.0 <0.0001 AM PEF (L/min) 307.6 334.2 324.8 0.0002 R5 (kPA/L/s) 0.64 0.60 0.63 0.0027 AX (kPA/L) 1.60 1.25 1.53 0.0003 eNO (ppb) 39.5 20.6 30.9 0.0028
    43. 44. Kapellbrucke, Luzern
    44. 45. Salmeterol/fluticasone propionate (SFC) gives optimal control of asthma in children
    45. 46. Asthma control: evidence in children <ul><li>The effect of salmeterol/fluticasone propionate (SFC) on asthma control in the paediatric population has been investigated in two key studies </li></ul><ul><ul><li>The Pediatric Asthma Control Evaluation (PEACE) study 1 </li></ul></ul><ul><ul><ul><li>SFC vs MON </li></ul></ul></ul><ul><ul><ul><li>Asthma control defined according to GINA guidelines 2 </li></ul></ul></ul><ul><ul><li>SFC vs doubling FP dose in children 3 </li></ul></ul><ul><ul><ul><li>Asthma control defined according to GOAL study 4 </li></ul></ul></ul>1. Maspero et al . Abstract presented at ATS 2008, A709. 2. Bateman ED et al. Eur Respir J 2008; 31 : 143–78. 3. De Blic J et al. Allergy 2007; 62 (Suppl 83): 397. 4. Bateman ED et al. Am J Respir Crit Care Med 2004; 170 : 836–44.
    46. 47. PEACE study
    47. 48. Rationale for PEACE <ul><li>Despite guideline recommendations on asthma therapy, non-steroidal oral medications are widely used first-line for many children regardless of severity or level of control </li></ul><ul><li>In Latin America, of the 37% of patients who reported taking a prescribed asthma medication to reduce airway inflammation, only 6% were using ICS </li></ul><ul><li>Prescription data from the USA indicates that many children are prescribed either MON, ICS or SFC first line, the prescription is given regardless of severity or control </li></ul>Maspero J et al. Clin Ther. 2008 Aug;30(8):1492-504.
    48. 49. PEACE study design <ul><li>Changes from baseline in lung function, asthma symptoms and rescue medication use were assessed </li></ul>SFC 50/100 µg BID plus placebo tablet QD MON 5 mg QD plus placebo Diskus QD Run-in Follow-up Visits (weeks) -2 weeks 0 2 4 8 12 +2 weeks Maspero J et al. Clin Ther. 2008 Aug;30(8):1492-504.
    49. 50. PEACE study: patient demography and baseline characteristics Maspero J et al. Clin Ther. 2008 Aug;30(8):1492-504. Characteristic SFC (n=281) MON (n=267) Age in years, mean (SD) 9.3 (2.15) 9.3 (2.12) Male, n (%) 156 (56) 179 (67) Diary card data, mean (SD):* – morning PEF (L/min) – % predicted morning PEF – % symptom-free days – % nights with no awakenings – % rescue-free days 216.0 (72.6) 74.4 (17.8) 16.8 (26.5) 69.3 (32.8) 13.4 (21.2) 214.0 (67.1) 74.3 (17.1) 15.3 (22.2) 66.0 (32.8) 11.3 (20.0) Lung function, mean at baseline visit (SD): – FEV 1 (L) – % predicted FEV 1 – % reversibility in FEV 1 1.49 (0.43) 72.9 (6.8) 26.0 (14.0) 1.48 (0.43) 72.9 (6.9) 26.3 (12.2) *Over last 7 days of run-in
    50. 51. Primary data: morning PEF over 12 weeks <ul><li>Over weeks 1–12, the adjusted mean change from baseline in PEF was 45.8 (2.82) L/min in the SFC group and 28.7 (2.86) L/min in the MON group, giving a treatment difference of 17.16 (4.03) L/min, p<0.001 </li></ul>200 220 240 260 280 300 0 1 2 3 4 5 6 7 8 9 10 11 12 Weeks Morning PEF (L/min) MON Maspero J et al. Clin Ther. 2008 Aug;30(8):1492-504. SFC
    51. 52. Symptom-free and rescue-free days and nights with no awakenings: SFC compared with MON Maspero J et al. Clin Ther. 2008 Aug;30(8):1492-504. SFC:MON Odds ratio 95% CI p-value % symptom-free 24-hour periods 1.74 1.07, 2.82 0.025 % rescue-free 24-hour periods 3.24 2.09, 5.02 <0.001 % nights with no awakenings 2.33 0.73, 7.47 .0154
    52. 53. Percentage of subjects with controlled asthma: SFC compared with MON Maspero J et al. Clin Ther. 2008 Aug;30(8):1492-504. 83.3% in the SFC group and 66.7% in the MON group, p<0.001 0 10 20 30 40 50 60 70 80 90 % controlled subjects 1 2 3 4 5 6 7 8 9 10 11 12 Weeks SFC MON
    53. 54. Mean exacerbation rate over 12 weeks: SFC compared with MON 0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4 SFC MON Weeks 1–12 Mean exacerbation rate An exacerbation was defined as worsening asthma requiring: emergency room visit, hospitalisation, unscheduled clinic visit requiring treatment with systemic corticosteroids or nebulised salbutamol, >12 puffs per day of salbutamol or >10 puffs per 2 consecutive days of salbutamol p<0.001 (SFC/MON ratio: 0.40; 95% CI: 0.29, 0.57) Maspero J et al. Clin Ther. 2008 Aug;30(8):1492-504.
    54. 55. Most common adverse events experienced during treatment in the PEACE study Maspero J et al. Clin Ther. 2008 Aug;30(8):1492-504. Adverse events, n (%) SFC (n=281) MON (n=267) Any event 155 (55) 153 (57) Headache 66 (23) 72 (27) Pyrexia 24 (9) 18 (7) Pharyngitis 17(6) 17 (6) Cough 13 (5) 16 (6) Allergic rhinitis 13 (5) 10 (4) Nasopharyngitis 14 (5) 8 (3) Rhinorrhoea 15 (5) 8 (3) Sinusitis 9 (3) 13 (5) Abdominal pain 9 (3) 13 (5)
    55. 56. Serious adverse events reported in the PEACE study: SFC compared with MON <ul><li>No serious adverse events reported with SFC </li></ul><ul><li>4 serious adverse events with MON </li></ul><ul><ul><li>2 during treatment, 1 pre-treatment and 1 post-treatment </li></ul></ul><ul><ul><li>3 events were associated with asthma exacerbations and 1 with dengue fever </li></ul></ul><ul><ul><li>None were assessed as treatment-related by the investigator </li></ul></ul><ul><li>Seven patients were withdrawn due to worsening asthma in the MON group, and none in the SFC group </li></ul><ul><li>No deaths were recorded during the study </li></ul>Maspero J et al. Clin Ther. 2008 Aug;30(8):1492-504.
    56. 57. <ul><li>SFC was clinically more efficacious and as well tolerated as MON </li></ul>Study summary SFC Maspero J et al. Clin Ther. 2008 Aug;30(8):1492-504. <ul><ul><li> Symptoms </li></ul></ul><ul><ul><li> Rescue medication need </li></ul></ul><ul><ul><li> Exacerbations </li></ul></ul> Lung function  Asthma control  Caregiver QoL
    57. 58. A new trend of souvenirs collection
    58. 60. Compliance
    59. 61. Patient compliance with asthma medication 1. Horne R. Chest 2006; 130 : 65–72. Poor Compliance Concern about side effects Patient’s negative attitude towards medicines in general Past experience Views of others Cultural influences Practical difficulties Patient’s perceived need
    60. 62. Compliance in children and adolescents <ul><li>In children and adolescents, there is almost 100% self-management of their asthma symptoms 1 </li></ul><ul><li>The complexity of optimum routine management of asthma results in reduced adherence 1 </li></ul><ul><li>Adherence to treatment by children and adolescents ranges from 43% to 100%,with an average of 58% in developed countries 2 </li></ul>1. Slack MK et al. Am J Health Syst Pharmacy 1995; 52 : 1417–1421. 2. Burkhart P et al. In: Hayman L, Mahom M,Turner R, eds. Chronic illness in children: An evidence-based approach . New York, Springer, 2002; 199–229.
    61. 63. Improving patient compliance <ul><li>Simple, regular dosing </li></ul><ul><ul><li>Simple dose regimens are generally easier for patients to follow </li></ul></ul><ul><ul><li>Compliance rates are most highly correlated with the number of doses rather than the number of medications or tablets that must be taken daily </li></ul></ul><ul><ul><li>The core issue for patients is: “ How many times a day must I remember to take a dose ?” </li></ul></ul>Cramer JA. Heart 2002; 88: 203–206.
    62. 64. The challenges of children using inhalers <ul><li>Both children and parents overestimate the child’s ability to use their inhaler 1 </li></ul><ul><li>Up to a 1/3 of children use an inappropriate inhaler device 1 </li></ul><ul><li>Spacers are underrepresented in children >5 years old 1 </li></ul><ul><li>In general children cannot use a metered dose inhaler appropriately 1 </li></ul><ul><li>DPIs are generally not advocated for children under the age of 6 years due to small inspiratory capacity </li></ul><ul><ul><li>However, Diskus TM operates at low flow rates and has been shown to be effective for use in children aged as young as 4 years 2 </li></ul></ul>Childs F et al. Arch Dis Child 2002; 86 : 176–179. Chrystyn H. Int J Clin Pract 2007; 61 : 1022–1036. Diskus
    63. 65. Summary <ul><li>Compliance with asthma medication in children and adolescents is generally poor </li></ul><ul><li>Both parents and children overestimate the child’s ability to use their inhaler </li></ul><ul><li>Simple, regular dosing improves compliance over time </li></ul><ul><li>Compliance can be improved by tailoring treatment to patient needs </li></ul><ul><li>SFC improves patient compliance, as measured by patient medication refill persistence </li></ul>
    64. 66. Regular, twice-daily SFC gives control of asthma : what does this mean for the patient? <ul><li>Optimal asthma control can be achieved according to both GINA guidelines and the GOAL study definition 1,2 </li></ul><ul><li>S FC leads to more symptom-free days, less rescue medication use and a decrease in night-time awakenings 1,2 </li></ul><ul><li>Regular, twice-daily dosing may facilitate improved patient compliance 3 </li></ul>1. De Blic J et al. Allergy 2007; 62 (Suppl. 83): 397. 2. Maspero J et al. Poster presented at American Thoracic Society International Conference , Toronto, Canada, 16–21 May 2008. 3. Cramer JA. Heart 2002; 88: 203–206.
    65. 67. Mississippi River, New Orleans, LA
    66. 68. Jambalaya, New Orleans, LA
    67. 69. J Allergy Clin Immunol 2009;123:411-6.
    68. 70. J Allergy Clin Immunol 2009;123:411-6.
    69. 71. Physicians treating children with a Parental history of asthma, increased eNO levels, low PC20 values, or a history of ICS use can expect the best long-term outcomes with ICS therapy compared with treatment with leukotriene receptor antagonists. J Allergy Clin Immunol 2009;123:411-6.
    70. 72. Eur J Pediatr (2008) 167:731–736 Inhaled corticosteroids or montelukast as the preferred primary long-term treatment for pediatric asthma?
    71. 74. <ul><li>Although there is no cure for asthma, </li></ul><ul><li>appropriate management that includes a partnership between the physician and the patient/family most often results in the achievement of control </li></ul>Thanks a lot! 雅典學院 :Academy
    72. 75. Allergy Asthma Immunol Res. 2010 January;2(1):1-13.
    73. 76. Allergy Asthma Immunol Res. 2010 January;2(1):1-13.
    74. 77. Allergy Asthma Immunol Res. 2010 January;2(1):1-13.
    75. 78. Effect of beta2-adrenergic receptor polymorphism on response to longacting beta2 agonist in asthma (LARGE trial) <ul><li>In asthma patients with B16 Arg/Arg and B16 Gly/Gly genotypes, combination treatment with salmeterol and inhaled corticosteroid improved airway function when compared with inhaled corticosteroid therapy alone. </li></ul><ul><li>These findings suggest that patients should continue to be treated with LABA plus moderate-dose inhaled corticosteroids irrespective of B16 genotype. </li></ul>Lancet. 2009 Nov 21;374(9703):1754-64.
    76. 79. Associations of β2-adrenergic receptor genotypes and haplotypes with wheezing illness in Taiwanese schoolchildren <ul><li>case–control study comprising 215 wheezing children and 183 nonwheezing controls </li></ul><ul><li>selected from 2524 fourth- to ninth-grade schoolchildren in southern Taiwan. </li></ul><ul><li>ADRB2 Glu27 allele and Gly16/Glu27 haplotype were significantly protective factors for wheezing illness in Taiwanese schoolchildren </li></ul>Allergy. 2009 Oct;64(10):1451-7.
    77. 80. Beta-2 adrenergic receptors in asthma (UpToDate summary) <ul><li>The expression and coupling of beta-2 adrenergic receptors are dynamically controlled in airway cells by a variety of mechanisms that may modify the effect of receptor stimulation. </li></ul><ul><li>Tachyphylaxis following chronic beta agonist stimulation is demonstrable in vitro, but the clinical impact of this phenomenon is less well defined. </li></ul><ul><li>Common polymorphisms of the beta adrenergic receptor are found at amino acid positions 16 and 27. Studies examining the influence of these polymorphisms are conflicting; the weight of the evidence is that they do not increase the risk of developing asthma or the severity of asthma, but may be associated with a greater likelihood of asthma persisting from childhood to adulthood. Further study may clarify the precise role of these and other beta receptor polymorphisms in the genesis and course of asthma. </li></ul><ul><li>The Arg/Arg polymorphism at position 16 of the beta-2 adrenergic receptor may be associated with adverse outcomes related to regular use of short acting beta agonists (SABA). However, at least within a clinical trial setting, this polymorphism does not appear to affect the safety or efficacy of currently available long-acting beta agonists (LABAs), when used in combination with inhaled glucocorticoids . </li></ul>反向抗藥性 : tachyphylaxis 'A rapid decrease in the response to a drug after repeated doses over a short period of time'
    78. 81. PEACE study objectives <ul><li>Primary </li></ul><ul><ul><li>To demonstrate superior efficacy of SFC compared with MON on lung function in children aged 6–14 years with persistent asthma </li></ul></ul><ul><li>Secondary </li></ul><ul><ul><li>To assess the effects of each treatment on other lung function measures and symptom-based endpoints </li></ul></ul>Maspero J et al. Clin Ther. 2008 Aug;30(8):1492-504.
    79. 82. PEACE study: patient population <ul><li>Male or female, aged 6–14 years </li></ul><ul><li>Diagnosis of asthma in previous 6 months </li></ul><ul><li>Use of short-acting  2 -agonists in preceding 3 months </li></ul><ul><li>At least 4 prescriptions of any asthma medication in previous 12 months </li></ul><ul><li>FEV 55–80% predicted </li></ul><ul><li>Demonstrated reversibility of ≥12% </li></ul>Maspero J et al. Clin Ther. 2008 Aug;30(8):1492-504.
    80. 83. PEACE study: patient population randomised to treatment <ul><li>FEV 1 within 15% of the value at visit 1 </li></ul><ul><li>AND </li></ul><ul><li>Salbutamol use for the treatment of asthma symptoms on at least 4 of the previous 7 days </li></ul><ul><li>OR </li></ul><ul><li>A symptom score of 2 (indicating at least moderate symptoms) or more on the previous 7 days </li></ul>Maspero J et al. Clin Ther. 2008 Aug;30(8):1492-504.
    81. 84. PEACE study endpoints <ul><li>Primary endpoint </li></ul><ul><ul><li>Change from baseline in the mean morning PEF over weeks 1–12 </li></ul></ul><ul><li>Secondary/other endpoints </li></ul><ul><ul><li>Change from baseline in morning pre-dose FEV 1 at week 12 </li></ul></ul><ul><ul><li>Change in symptom free 24 hour-periods over weeks 1–12 </li></ul></ul><ul><ul><li>Change in % of rescue medication-free 24 hour-periods over weeks 1–12 </li></ul></ul><ul><ul><li>Mean change from baseline in evening PEF over weeks 1–12 </li></ul></ul><ul><ul><li>Level of asthma control over weeks 1–12 </li></ul></ul><ul><ul><li>Quality of life over weeks 1–12 </li></ul></ul>Maspero J et al. Clin Ther. 2008 Aug;30(8):1492-504.
    82. 85. MON chronic asthma study (6–14 years): patient baseline characteristics <ul><li>MON Placebo </li></ul><ul><li>Characteristic (n=201) (n=135) </li></ul><ul><li>Age (years) </li></ul><ul><li>Median (range) 11 (6–15*) 11 (6–15*) </li></ul><ul><li>Gender (% of patients) </li></ul><ul><li>Male 67 62 </li></ul><ul><li>Female 33 38 </li></ul><ul><li>Duration of asthma (years) </li></ul><ul><li>Median (range) 7 (0.5–14) 7 (0.5–15) </li></ul><ul><li>Concomitant ICS (% of patients) 39 33 </li></ul><ul><li>FEV 1 (mean  SD) (% of predicted) 72  10 72  9 </li></ul>*Two patients were 14 years old at the prestudy visit and became 15 years old prior to randomization. 1. Knorr B et al. JAMA 1998; 279 : 1181–1186.

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