Phenotypes of asthma

Elisabeth Bel

Dept. Respiratory Medicine Academic Medical Centre University of Amsterdam

Heterogeneity of asthma
Childhood onset eosinophilic psychogenic fixed obstruction occupational severe Adult onset intrinsic allergic exacerbation prone brittle neutrophilic aspirin-induced

pre-menstrual steroid resistant

3 patients with uncontrolled asthma

• • • • •

female 50 yr Diagnosis of asthma since 4 years Last 2 years increasingly symptomatic High dose ICS plus LABA plus SABA Oral corticosteroids > 50% of the time

Additional information
1. 2. 3. 4. 5. 6. 7. 8. Never smoker Profession: secretary Recently divorced, 4 children Allergic rhinitis (grass pollen ++) BMI 35 FEV1 65 %pred. 12% reversibility induced sputum: few inflammatory cells R/ metformin, HRT, paracetamol

How many contributing factors? .

7. Never smoker Profession: secretary Recently divorced.Additional information 1. 2. 4. HRT. 12% reversibility induced sputum: few inflammatory cells R/ metformin. paracetamol . 3. 5. 8. 4 children Allergic rhinitis (grass pollen ++) BMI 35 FEV1 65 %predicted. 6.

6 contributing factors! 1. Never smoker Profession: secretary Recently divorced. 12% reversibility induced sputum: few inflammatory cells R/ metformin. 4. 8. 7. 4 children Allergic rhinitis (grass pollen ++) BMI 35 FEV1 65 %predicted. 3. 5. paracetamol . HRT. 2. 6.

Atopic and nonatopic rhinitis Shabaan et al Lancet 2008. 372: 1049–57 .

36:609-13. Thorax 2010. pill and hormone replacement therapy Romieu et al. 65: 292-297 Jenkins MA et al Clin Exp Allergy 2006. .Pregnancies.

Obesity Beuther et al AJRCCM 2007.175:661–666 Von Behren J et al. 64: 889-93 . Thorax 2009.

32:1231–1236 .frequent use of acetaminophen Barr et al AJRCCM 2004. 836–841 Shaheen et al Eur Respir J 2008. 169.

64:630-5 .Stressfull life events Wright RJ et al J Epidemiol Community Health 2010.

Ageing Res Rev 2008.114-25 .Multiple endocrine hits Atwood & Bowen.

Best treatment option? .

5. 4. 7. 2. 6.Best treatment option 1. Extrafine ICS Anti leukotrienes Continuous low dose oral corticosteroids Omalizumab Macrolides Thermoplasty Weight control Þ reduce oral corticosteroids . 3.

Down-titrating oral corticosteroids by use of NO-guided internet strategy Hashimoto et al. Thorax in press .

Effect of bariatric surgery on asthma severity Reddy et al Obes Surg 2011:21:200-6. .

• • • • • male 40 yr Diagnosis of asthma since 4 years 4-6 severe exacerbations / yr High dose ICS plus LABA plus SABA Oral corticosteroids > 50% of the time .

Additional information 1. 5. 15% reversibility R/ furosemide. 6. 2. 2 dogs Single skin prick test: house dust mite ++ BMI 26 induced sputum: 70% neutrophils FEV1 65 %pred. ex smoker (stopped 5 years ago) Profession: policeman. 7. sotalol . 8. 4. 3.

How many contributing factors? .

2 dogs Single skin prick test: house dust mite ++ BMI 26 induced sputum: 70% neutrophils FEV1 65 %pred. 5. 8. 2. 6. 3. 4. sotalol . 7. 15% reversibility R/ furosemide.Additional information 1. ex smoker (stopped 5 years ago) Profession: policeman.

2 dogs Single skin prick test: house dust mite ++ BMI 26 induced sputum: 70% neutrophils !! FEV1 65 %pred. 4. 6. ex smoker (stopped 5 years ago) Profession: policeman. 7. 5. 2.4 contributing factors 1. 15% reversibility R/ furosemide. 8. 3. sotalol .

24:734-739 .smoking and ex-smoking increases asthma risk Piipari et al Eur Respir J 2004.

Traffic related air pollution Künzli et al Thorax 2009.64.664-670 .

.117:642-8.Allergic sensitization to house dust mites and molds Jaakkola et al J Allergy Clin Immunol 2006.

Best treatment option? .

3. Extrafine ICS Anti leukotrienes Continuous low dose oral corticosteroids Omalizumab Macrolides ?? Thermoplasty Weight control . 6.Best treatment option 1. 5. 4. 2. 7.

177:148-55. .Clarithromycin in neutrophilic asthma Simpson et al AJRCCM 2008:15.

177:148-55. .Clarithromycin in neutrophilic asthma Simpson et al AJRCCM 2008:15.

.macrolides in chronic stable asthma Kraft M et al Chest 2002:121:1782-8.

39: 1324–1329 .Persistent infections implicated in the development of “intrinsic” asthma Dahlberg & Busse Clin Exp Allergy 2009.

• • • • • female 45 yr Diagnosis of asthma since 10 years High dose ICS plus LABA plus SABA Oral corticosteroids > 50% of the time Poor quality of life .

7. 2 children chronic sinusitis with nasal polyps skin prick test: negative BMI 27 induced sputum: 20% eo.Additional information 1. 2. 50% neutro FEV1 65 %pred. 3% reversibility . never smoker Profession: cleaning lady Married. 4. 6. 5. 8. 3.

How many contributing factors? .

4. never smoker Profession: cleaning lady Married.Additional information 1. 6. 7. 3% reversibility . 8. 3. 2. 2 children chronic sinusitis with nasal polyps skin prick test: negative BMI 27 induced sputum: 20% eo. 5. 50% neutro FEV1 65 %pred.

2. 3. never smoker Profession: cleaning lady Married. 4. 7. 3% reversibility . 1 child chronic sinusitis with nasal polyps skin prick test: negative BMI 27 induced sputum: 20% eo !!.2 aggravating factors 1. 6. 5. 50% neutro FEV1 65 %pred. 8.

176:735–741 .Houshold cleaning products use increases asthma risk Zock et al Am J Respir Crit Care Med 2007.

ERJ 2005.Sinus disease is associated with frequent exacerbations ten Brinke A et al.26:812–818 ..

Patients with CRS have higher eosinophils in peripheral blood Steinke et al.111:342-9 . J Allergy Clin Immunol 2003.

109:621-6 .CT-sinus score is associated with sputum eosinophils and exhaled NO ten Brinke et al . 2002. J Allergy Clin Immunol.

CT-sinus score is associated with degree of air trapping ten Brinke ten etBrinke.109:621 .109:621 -6 -6 . 2002 . J Allergy J Allergy Clin Clin Immunol Immunol . al . 2002 .

J Allergy Clin Immunol 2007.Inflammation in distal airways in severe asthma Mauad et al.2:333-339 .

Best treatment option? .

Extrafine ICS + nasal corticosteroids Anti leukotrienes Continuous low dose oral corticosteroids Omalizumab Macrolides Thermoplasty Weight control . 2.Best treatment option 1. 5. 7. 6. 4. 3.

Eur Respir J 2006.Effect of CRS treatment on asthma (% change compared to baseline) Ragab et al. 28: 68–74 .

Effect of extrafine ICS on large and small airways inflammation Small airways Large airways Hauber HP et al. J Allergy Clin Immunol 2003.112:58-63 .

et al. Pulm Pharm Ther 2008.Effect of extra-fine ICS on asthma exacerbations Bateman E. 21: 489-498 .

001 placebo triamcinolone median 50 25 0 0 pre post pre post 3 Ten Brinke et al.170:601–605 . AJRCCM 2004.49 Sputum eosinophils (%) 75 p<0.001 p<0.Systemic steroids in 'refractory' eosinophilia p<0..

3 clinical phenotypes of asthma .

SARP Severe Asthma Cluster Analysis COPD ? Early onset Atopic mild Normal pb FEV1 < 2 Controllers Early onset Atopic moderate Normal pb FEV1 More medications Late onset 71% female Obese postmenopauzal Lower pb FEV1 High symptom level Early onset severe severe Long duration Very low FEV1 Reversible Late Onset severe non atopic Oral steroids Fixed obstruction 63% female 1 2 3 4 5 Moore et al.181:315-323 . Am J Respir Crit Care Med 2010.

COPD? Haldar et al AJRCCM 2008.178:218-224 .

Future of phenotyping: ‘Systems Medicine’ Patient reported Clinical Functional Cellular Molecular Auffray et al. Genome Med 2009.1:2 .