6Determining the cause of chronic cough (non-smoker) Post-nasal drip in up to 30%Cough-variant asthma in up to 20%Gastro-esophageal reflux diseaseLess common causes:bronchiectasis, diffuse parenchyma disease, ACE inhibitors, psychogenic cough
7Parental reports of the allergy symptoms Meltzer EO et al. J Allergy Clin Immunol 2009.
8Disease management and treatment Chronic disease management-AsthmadiagnosissymptomsassessmentcontrolDisease management and treatmentcontrolcomorbiditiesPROQoLAdherence
9Long-term management of asthma Controller medicationsStep up and down regimensEducation
10ยาที่ใช้ในการรักษาโรคหืด Step 1Step 2Step 3Step 4Step 5Low-dose ICS plus sustained-release theophylineSustained release theophylineLow-dose ICS plus leukotriene modifierAnti-IgE treatmentLeukotriene modifierMedium- or high-dose ICSOral glucocorticosteroid (lowest dose)Medium- or high-dose ICS plus long-acting ß2-agonistLow-dose ICS plus long-acting ß2-agonistLow-dose inhaled ICSAdd one or moreSelect oneController optionsAs needed rapid-acting ß2-agonistAsthma educationEnvironmental control1-5%GINA and Thai Guideline 2011.
11Controllers Options for Asthma AgentEffect on AROral administrationAnti-inflammatory effectsSide effectsICSXICS+LABAsTheophyllineLTRAs
12Treatment options in uncontrolled asthma Mild asthmaAS with ARViral induced wheezeEIA in young childrenLTRAICS+LABATheophyllineAnti-IgEICS+LTRAPoor complianceSteroids phobia
13Treatment options in uncontrolled asthma ICSLTRATheophyllineAnti-IgEICS+LABASevere asthmaAtopic asthma
16OSA in children Prevalent of OSA in children is 2-3% The most common treatment is adenotonsillectomyCys LT receptor was elevated in the tonsillar tissues of children with OSAMontelukast may provide an intervention alternative to adenotonsillectomy
17Adenoid size significantly decreased with montelukast
18Montelukast treatment resulted in a significant improvement in the obstructive apnea index A 12 week treatment with daily oral montelukast effectively reduced the severity of OSA and the magnitude of the underlying adenoidal hypertrophy in children with nonsevere OSA
19ผู้ป่วยหญิงไทยอาย ุ30 ปี มีการไอมา 3 เดือนไอแห้งๆตลอดทั้งวัน บางครั้งไอจนปัสสาวะราด นอนไม่หลับ ไม่ค่อยหอบแต่แน่นหน้าอกบ่อย CXR, PEFR, Film PNS-normal2 weeks after LTRA
25การป้องกันผลข้างเคียงของ systemic steroid ผู้ป่วยที่ได้รับสเตียรอยด์กินเกิน3เดือน (> 5MKD)ผู้ป่วยที่ได้รับสเตียรอยด์กิน/ฉีดเกิน3ครั้งต่อปีข้อแนะนำในผู้ป่วยที่ได้รับ systemic steroid บ่อย-วัดความดันทุก 6 เดือน-ตรวจภาวะเบาหวาน-ตรวจ bone mineral density-ให้ calcium (1,200-1,500 mg/day)and vitamin D (800-1,000 unit/day)
26Risk factors for Glucocorticoids-induced osteoporosis Advance ageLow BMI (<24)Underlying disease: RA, chronic pulmonary diseaseSmoking, excessive alcohol consumption,frequent falls, family history of hip fracturehigh glucocorticoid dose (high current or cumulativedose, long duration of therapy)Low bone mineral densityHere is our asthma care team, include with doctor specialist in allergist, chest medicine and emergency medicine, nurse, pharmacist, rehabtherapist. You can see the woman in the middle, she is the president of thammasat asthma club cause she is the founder.N Engl J Med 2011;365:62-70.
27Long term asthma management Consider inhalerchangeFix nestappointmentStep-down therapyIncorrectTherapy step upCheck:Minimal symptomsLeading a normal lifeTaking usual exerciseLow inhaled β-agonist useNo additional treatmentCheck inhalertechniqueCorrectNoYesAssess complianceAnd aggravatingfactors
28Median inhaled corticosteroid use (%) Issues with Current Therapies Reported Compliance vs. Actual Use of Inhaled Corticosteroids1/Milgrom, p 1052, Table 1, L1-395.410080Median inhaled corticosteroid use (%)58.4Slide B.8Although ICS are widely used in the treatment of childhood asthma, compliance may be less than optimal. A prospective study specifically assessed compliance in 24 asthmatic children 8 to 12 years of age who required ICS and beta2 agonists for control and who were thought to be compliant. Although patient diaries reported a compliance rate of 95.4% with ICS (i.e., that 95.4% of prescribed doses were taken), electronic monitoring of MDIs revealed that fewer than 60% of doses were actually taken. Moreover, only 31.8% of prescribed doses were taken at the correct time of day. Overall, 92% of patients exaggerated their corticosteroid use. It was concluded that not only did these children fail to comply with therapy, but they misrepresented their use and did so with the tacit approval of their parents.1601/Milgrom, p 1052, Table 1, L1-3; p 1054, C2, ¶1, L2-12; p 1056,C2, ¶2, L1-54031.820(n=24)ReporteduseActualuseActual use at correct timeReported compliance is not always a reflection of actual useAdapted from Milgrom H et al J Allergy Clin Immunol 1996;98(6, pt 1):1051–1057.Reference1. Milgrom H, Bender B, Ackerson L et al. Noncompliance and treatment failure in children with asthma. J Allergy Clin Immunol 1996;98(6, pt 1):1051–1057.
29B.9 Poor compliance can lead to poor outcomes Issues with Current Therapies Adherence/Compliance Issues Can Affect Outcomes1/Milgrom,p 1053, Fig 2 (n’s);p 1055, C1, L4-9Poor compliance can lead to poor outcomes100p=0.008Slide B.9Poor compliance has been strongly correlated with loss of asthma control.1Of 8 children who required oral corticosteroid rescue in a 13-week study of 24 asthmatic children 8 to 12 years of age who required inhaled corticosteroids and beta agonists for control, only 13.7% of their prescribed doses of inhaled corticosteroid were taken, compared with a compliance rate of 68.2% for children with stable asthma, that is, children who did not require corticosteroid rescue (p=0.008). Five of eight children who required courses of oral corticosteroid during the study were among the least compliant, including two who were hospitalized.1These findings suggest that inadequate control of asthma may reflect noncompliance, a problem that is widespread and that may not be confined to obviously uncooperative patients.18068.21/Milgrom,p 1056, C2, ¶3, L1-8p 1052, C2, ¶1, L1-6; p 1053,C2, ¶1, L9-10;p 1054, C2, ¶2, L1-4; p 1055,C1, L4-9; p 1056,C2, L8-11p 1056, C2, ¶2, L10-1460Compliance(%)402013.7Children with stable asthma* (n=16)Children requiring oral corticosteroid rescue (n=8)*Did not require oral corticosteroidsAdapted from Milgrom H et al J Allergy Clin Immunol 1996;98(6, pt 1):1051–1057.B.9ReferenceMilgrom H, Bender B, Ackerson L et al. Noncompliance and treatment failure in children with asthma. J Allergy Clin Immunol 1996;98(6, pt 1):1051–1057.
30Days fully compliant (%) Issues with Current Therapies Preference/Compliance Issues: Montelukast vs. ICS1/Maspero,p 97, C2, ¶3, L1-6 (dosages);p 99, Table 1 (n’s);p 100, C1, ¶1, L7,C2, L1-46-month extension study in 124 children 6–14 years of agep<0.00110098Slide B.11The children in the study were more compliant with montelukast than with beclomethasone. The mean percentage of days during which patients were fully compliant was 98% for montelukast and 83% for beclomethasone, representing a statistically significant difference of 15% (p<0.001).1951/Maspero,p 100, C1, ¶1, L7,C2, L1-4Days fully compliant (%)9085838075Montelukast 5 mg* (n=83)Beclomethasone 300 µg** (n=40)*One chewable tablet once daily at bedtime**Two 50 µg puffs three times dailyAdapted from Maspero JF et al Curr Med Res Opin 2001;17:96–104.Reference1. Maspero JF, Dueñas-Meza E, Volovitz B et al. Oral montelukast versus inhaled beclomethasone in 6- to 11-year-old children with asthma: Results of an open-label extension study evaluating long-term safety, satisfaction, and adherence with therapy. Curr Med Res Opin 2001;17:96–104.
31Randomized Controlled Trials RCTs and Real-World Studies Provide Complementary Information to Help Improve Asthma Care1/Price,p 4, C1, ¶2, L1-32/Holgate,p 1438, C1, ¶2, L1-5p 3, C2, ¶3, L5-9p 1438, C1, ¶1, L1-83/Herland,p 17, C1, ¶3, L1-44/Travers,p 219, C1, ¶1, L13-23p 1438, C1, ¶1, L22-255/Naqvi,p 646, C1, ¶3, L7-116/Hawkins,p 1107, C2, L15-18p 1438, C1, ¶1, L /Tomlinson,p 282, C1, ¶1, L6-8;p 285, C1, ¶1, L1-3;p 286, C2, ¶2, L12-178/Thomson,p 749, C1, ¶1, L6-13,C2, ¶2, L13-169/Zwarenstein,p 1, Table 110/Wells, p 8, C1, ¶2, L1-4,7-101/Price, p 4, C1, ¶2, L1-311/Silverman,p 117, Table 2RCTs:Information provided/Setting/Patient population:Real-World Studies:2/Zwarenstein,Footnote:3/Silverman,Randomized Controlled TrialsReal-World StudiesaInformation providedEfficacy1Effectiveness2SettingControlled environment1Real-world practice2Patient populationPatients meeting strict inclusion and exclusion criteria“Everyday” patients2The findings of real-world trials and RCTs provide complementary information to help formulate strategies that can help to improve asthma care.1,2RCTs study a narrowly defined patient population in a controlled setting, thereby establishing the relative efficacy of treatment, that is, the benefit of the treatment under ideal conditions.1 Patients enrolled in RCTs to evaluate interventions for asthma typically have asthma according to American Thoracic Society criteria, have forced expiratory volume in 1 second (FEV1) of >50% and <85% of predicted, have reversibility of >12% in the last 12 months, and are nonsmokers with no significant comorbidities.2 Therefore, these studies generally exclude many of the types of patients who are seen in everyday practice,2–4 such as patients with β-agonist reversibility of <12% (which may vary in different patient populations)2,5,6 and smokers.2,7,8Real-world or pragmatic studies evaluate the effects of treatments on health outcomes under conditions approximating those used in normal clinical practice, thereby evaluating the effectiveness of an intervention when used in the real-world setting.9 Patients enrolled in these trials typically are selected on the basis of the clinical indication of interest, without further inclusion or exclusion criteria.9 Thus, real-world studies are more likely than RCTs to include patients representative of those encountered in daily clinical practice.2,9In general, the results of RCTs are true to the study population and setting, whereas those of real-world studies can be generalized to other populations and settings.10 Therefore, the findings of pragmatic trials can be a valuable complement to the findings from RCTs.1,2 However, observational studies are not randomized and do not have control groups, which can lead to the possibility for selection bias, and may show correlations without directly proving causation.11RCTs=randomized controlled trials.aNote that observational studies are not randomized and do not have control groups, which can lead to the possibility for selection bias and may show correlations without directly proving causation.31. Price D et al. BMC Pulm Med. 2006;6(suppl 1):S6. 2. Zwarenstein M et al. BMJ. 2008;337:a Silverman SL. Am J Med. 2009; 122(2):114–120.Slide 311. Price D et al. BMC Pulm Med. 2006;6(suppl 1):S6. 2. Holgate S et al. Eur Respir J. 2008;32:1433– Herland K et al. Respir Med. 2005;99(1):11– Travers J et al. Thorax. 2007;62(3):219– Naqvi M et al. J Asthma. 2007;44(8):639–648.6. Hawkins GA et al. Am J Respir Crit Care Med. 2006;174(10):1101– Tomlinson JEM et al. Thorax. 2005;60(4):282–287.8. Thomson NC. Am J Respir Crit Care Med. 2007;175(8):749– Zwarenstein M et al. BMJ. 2008;337:a Wells KB. Am J Psychiatry. 1999;156:5– Silverman SL. Am J Med. 2009;122(2):114–120.
32Heterogeneous, Real-World Population ELEVATE1Heterogeneous, Real-World Population1/Price: p1705A1/Price (suppl): p3A; p4A (by omission)1/Price: p1705A; p1698ABroad inclusion criteria allowed assessment of real-world effectiveness in patients seen in clinical practice.Smokers (1/4 of study population)Patients with COPD due to lack of requirement of bronchodilator reversibility (≈3% of study population)Patients with allergic rhinitisPatients with poor adherencePatients with poor inhaler techniqueThe broad inclusion criteria used in the ELEVATE trials allowed assessment of real-world effectiveness for the heterogeneous group of patients seen in everyday clinical practice. Patients who smoked or had comorbidities, poor adherence, or poor inhaler technique were not excluded from study participation. In fact, smokers comprised almost 25% of the total population of both ELEVATE trials, with smokers older than 45 years of age accounting for 9% of the population in both trials. Further, bronchodilator reversibility was not required for enrollment, allowing the inclusion of patients with a mix of chronic obstructive pulmonary disease and asthma. Adherence and proper inhaler technique were not inclusion criteria although adherence was evaluated during the trial.11. Price D et al. N Engl J Med. 2011;364:1695–1707. Additional Information: Supporting online material is available at doi/suppl/ /NEJMoa /suppl_file/nejmoa _appendix.pdf.COPD=chronic obstructive pulmonary disease.1. Price D et al. N Engl J Med. 2011;364:1695–1707.Slide 32
33First-Controller Trial: Improvements in MiniAQLQ (Primary End Point) 1/Price:p1700A,Bp1697D,E; p1698Ep1698B,E; p1703B; p1704AEquivalence CriteriaMetaNot Metb6Improvement5.525.6355.255.284.754.724MiniAQLQ Score32Intention-to-treat analysis of the primary end point (MiniAQLQ score) at Month 2, the primary time point, showed that LTRA and ICS were equivalent as first controller therapy. Both the upper and lower values of the 95% CI for the mean between-group difference, adjusted for baseline values, fell within the prespecified boundary of 0.3 (that is, from –0.3 to +0.3).1Equivalence was not proven at 2 years: the lower boundary of the 95% CI of the adjusted mean difference between groups was –0.35, which fell outside the predefined equivalence limit of 0.3.11(n=148)(n=158)(n=122)(n=132)(n=145)(n=155)Baseline2 Months2 Years1. Price D et al. N Engl J Med. 2011;364:1695–1707. Additional Information: Supporting online material is available at doi/suppl/ /NEJMoa /suppl_file/nejmoa _appendix.pdf.LTRA ICSMean difference adjusted for baseline value (95% CI):a–0.02 (–0.24 to 0.20); b–0.11 (–0.35 to 0.13).1. Price D et al. N Engl J Med. 2011;364:1695–1707.Slide 33
34Add-On Therapy Trial: Improvements on MiniAQLQ (Primary End Point) ELEVATE1Add-On Therapy Trial: Improvements on MiniAQLQ (Primary End Point)1/Price:p1700Dp1697E; p1698B; p1702Cp1700D; p1702C; p1704BEquivalence CriteriaMetaNot Metb6Improvement5.435.4255.095.044.634.414MinAQLQ Score32The intention-to-treat analysis of the primary end point (MiniAQLQ score) at Month 2, the primary time point, showed that LTRA and LABA were equivalent to each other as add-on therapy to baseline ICS. Both the upper and lower values of the 95% CI for the mean between-group difference adjusted for baseline values, fell entirely within the prespecified limit of 0.3 (that is, from –0.3 to +0.3).1Equivalence was not proven at 2 years: the lower boundary of the 95% CI of the adjusted mean difference between groups was –0.32, which fell outside the predefined equivalence limit of 0.3.11(n=170)(n=182)(n=153)(n=156)(n=169)(n=181)Baseline2 Months2 YearsLTRA + ICS LABA + ICS1. Price D et al. N Engl J Med. 2011;364:1695–1707. Additional Information: Supporting online material is available at doi/suppl/ /NEJMoa /suppl_file/nejmoa _appendix.pdf.Mean difference adjusted for baseline value (95% CI): a–0.10 (–0.29 to 0.10); b–0.11 (–0.32 to 0.11).1. Price D et al. N Engl J Med. 2011;364:1695–1707.Slide 34
35Change in AM PEF Asthma+AR Patients: Using Rhinitis Meds§ Post Hoc Analysis Weeks§ Intranasal steroids or antihistamines or other treatments for rhinitis* Montelukast 10 mg once-daily along with budesonide 400 g twice-daily.** Budesonide 800 g twice-daily
37Dosing in Children Dosing in Children and adults Source A (WPC),p 1, §III, ¶3-5;p 2, ¶1; p 8, § XVIIIb, ¶2, L1-3Children 6 months to 2 years of ageOne 4 mg oral granulepackage mixed withfood taken once dailyin the eveningChildren 2 to 5 years of ageOne 4 mg cherry- flavored chewable tablet in the eveningChildren 6 to 14 years of ageOne 5 mg cherry- flavored chewable tablet in the eveningPatients 15 yearsof age and olderOne 10 mg tabletin the eveningSlide I.2The leukotriene receptor antagonist montelukast provides convenient once-daily administration in the evening and is very well tolerated. Montelukast is available in 4 mg packets of oral granules for pediatric patients 6 months to 2 years of age and cherry-flavored, chewable tablets for pediatric patients 2 to 14 years of age (4 mg for children 2–5 years and 5 mg for children 6–14 years). Montelukast is also available in a 10 mg tablet for adults 15 years of age and older.Easy to administer and very well toleratedSource A (WPC),p 1, §III, ¶1, L1;p 4, §XI, ¶1, L1-3;p 1, §III, ¶3-5;p 2, ¶1; p 8,§ XVIIIb, ¶2, L1-3I.2
38กรณี LTRA ต้อง taper off ยาหรือไม่ เมื่อไหร่หยุดยา การลดยาในผู้ป่วยโรคหืดเมื่อไหร่ต้องลดยาลดตัวไหนก่อน-ICS+LABA, ICS+LTRAกรณี LTRA ต้อง taper off ยาหรือไม่เมื่อไหร่หยุดยา
44Reasons for Non-adherence complexityof treatment, S/Epatient educationdifficult to accesscost/reimbursementPossible avoidancepatients featureschronicityPt/HCW partnershipImpact on adherence
45The potential effect of personality on adherence interventions High effect on adherenceShared decision makingPhone callsaddressingmedicationbeliefsIndividualisedinhalerinstructionsTailored /targeted /individualisededucationalinterventionsDrug presentation styleRepeated inhaler instructionsLow costHigh costPatient/providerinteraction notfocusingexpressedpersonalneedsAsthmaeducationfocusinggeneralmanagementIndividualisedproblem-solvingaddressingadherence barriersSelf-managementillness modelLow effect on adherenceThe potential effect of personality on adherence interventions
46Asthma Education Phenotype of non-adherence patient How to give asthma education
47Asthma self-management topics asthma education-allergen avoidance-chronic but treatableNature of disease-reliever-controllerNature of treatmentUse of treatment-inhaler-peak flow meterSelf-monitoring-action plan-management ofexacerbation
48BTS/GINA guideline for action plan “In primary care, people with asthma should be reviewed regularly by a nurse or doctor with appropriate training in asthma management, written action plan”
49Keys components to asthma action plan Recognizing attackAssessing severityInitial treatmentWhen to get helpAccording to asthma guideline, the goal of asthma treatment is no exacerbation and no loss work. The results of a study in Thailand show that asthma symptom is still uncontrolled in large number of patients as you can see that 15% of patients were admitted, 20% need ER visit and 24% were absent from work due to asthmatic attack.
50Asthma action plan: priority patients Those having frequent exacerbationThose requiring frequent courses of steroid tabletsUsers of high-dose ICSED/hospitalizationRisk of developing severe/fatal asthma
51Asthma Education www.tuasthmaclub.com 1.Asthma action plan 2.Asthma treatment3. Allegen avoidance
52The five R’s for teaching Reach agreement on goals for treatment-keep it simple-set priorities-specific action planRehearse asthma management skills: taking medicine, monitor symptomsRepeat messageReinforce appropriate behaviorReview results