Advance in asthma Advance in asthma 20092009

Advance in asthma Advance in asthma 20092009

w.pongsak,MD

introductionintroduction

• Recent studies in 2009• Asthma and obesity• Genetics• Biomarkers• Environment• Therapeutics

• Recent studies in 2009• Asthma and obesity• Genetics• Biomarkers• Environment• Therapeutics

Obesity and asthmaObesity and asthma• Obesity and lung physiology - reduction in pulmonary compliance,lung volume,diameter of small airway, circulation,perfusion - How about effect on spirometry ? decrease FVC,FEV1 but FEV1/FVC

unchange decrease FRC esp. ERV - decrease diameter of small airway due to alteration of actin myosin cross bridge

cycle => increase obstruction and BHR

• Obesity and lung physiology - reduction in pulmonary compliance,lung volume,diameter of small airway, circulation,perfusion - How about effect on spirometry ? decrease FVC,FEV1 but FEV1/FVC

unchange decrease FRC esp. ERV - decrease diameter of small airway due to alteration of actin myosin cross bridge

cycle => increase obstruction and BHR

• Obesity and inflammatory mediators - increase TNF-α (present in adipocyte)=>link to Th2 cytokine - increase IL-6 increase in both obesity and asthma - increase leptin from adipocyte => in animal model increase lung inflammation and BHR - decrease adipokines => anti-inflam. property

• Obesity and inflammatory mediators - increase TNF-α (present in adipocyte)=>link to Th2 cytokine - increase IL-6 increase in both obesity and asthma - increase leptin from adipocyte => in animal model increase lung inflammation and BHR - decrease adipokines => anti-inflam. property

N0 ASSOCIATION

POSITIVE CORRELATION

INCREASE RISK

ONLY IN FEMALE

ONLY IN FEMALE

INCREASE RISK

INCREASE RISK

INCREASE RISK

• Prospective studies - Ford et al. N= 317/9,456 f/u 9 yrs obesity increase risk of asthma

Eur Resp J. 2004;24:740-4. - Nystad et al N = 4218/135405 8 yrs increase BMI increase risk of asthma both male and female Am J Epidemiol. 2004;160:969-76.

- McLachan et al N= 925 increase BMI associate with asthma in female J Allergy ClinImm

-unol. 2 0 0 7 Mar;1 1 9 (3 ):6 3 4 9 .

• Prospective studies - Ford et al. N= 317/9,456 f/u 9 yrs obesity increase risk of asthma

Eur Resp J. 2004;24:740-4. - Nystad et al N = 4218/135405 8 yrs increase BMI increase risk of asthma both male and female Am J Epidemiol. 2004;160:969-76.

- McLachan et al N= 925 increase BMI associate with asthma in female J Allergy ClinImm

-2 007 119 3634 9

1.56

Conclusion = Conclusion = failed to find an association failed to find an association between obesity and asthma control in a between obesity and asthma control in a

n n urban population with asthma urban population with asthma.

1.57

Conclusion = weight gain decrease in Conclusion = weight gain decrease in lung function in asthmatic patientslung function in asthmatic patients

N=638

1.58

Conclusion = Conclusion = positive association b positive association b etween BMI and asthma risk that etween BMI and asthma risk that

was similar in magnitude to those o was similar in magnitude to those o bserved in longitudinal studies bserved in longitudinal studies

of white women of white women

2J Allergy Clin Immunol0091231328; :

-34.1.59

N= 1,265

2J Allergy Clin Immunol0091231328; :

-34.1.59

Conclusions: Increased BMI is not ass Conclusions: Increased BMI is not ass ociated with clinically ociated with clinically

significant worsening of impairment significant worsening of impairment in subjects with mild to moderate per in subjects with mild to moderate per

sistent asthma. sistent asthma.

Asthma and genetic

Genetics

Asthma and genetic

GeneticsGenetics

• Several genetic studies suggest possible therapeutic application

• TSLP varients associate with asthma and bronchial hyperresponsiveness

• Urokinase plasminogen activator receptor gene (PLAUR)

• Varient of IL-4 gene• Arg 16 phenotype of β2-adrenergic receptor

agonist gene (ADRB2) associate with asthma exacerbation

• Several genetic studies suggest possible therapeutic application

• TSLP varients associate with asthma and bronchial hyperresponsiveness

• Urokinase plasminogen activator receptor gene (PLAUR)

• Varient of IL-4 gene• Arg 16 phenotype of β2-adrenergic receptor

agonist gene (ADRB2) associate with asthma exacerbation

1.14 J AllergyClin Immunol 20 0 9 ;1 2 4 :1 1 8

-8 9 4

N= 1,182

J AllergyClin Immunol 20 0 9 ;1 2 4 :1 1 8

-8 9 4

1.14

Conclusion: The Arg1 6 genotype of ADRB2 is Conclusion: The Arg1 6 genotype of ADRB2 is associated with exacerbations in asthmatic chil associated with exacerbations in asthmatic chil

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Biomarker for asthmaBiomarker for asthma

• Exhaled nitric oxide level : absolute level or personal best ?

• FeNO and cost effectiveness• IgE level and asthma IgE level correlate with asthmatic symptom only in atopic asthma J Allergy Clin Immunol 2009;124:447-53

• Biomarker of chronic persistant asthma• Bronchial provocation test - mannitol bronchoprovocation test - sensitivity and specificity

• Exhaled nitric oxide level : absolute level or personal best ?

• FeNO and cost effectiveness• IgE level and asthma IgE level correlate with asthmatic symptom only in atopic asthma J Allergy Clin Immunol 2009;124:447-53

• Biomarker of chronic persistant asthma• Bronchial provocation test - mannitol bronchoprovocation test - sensitivity and specificity

1.19 N=73

Conclusion : Conclusion : Targeting FENO on refere Targeting FENO on refere nce values is not justified. nce values is not justified.

1.20

Conclusion : Conventional asthma management resu lted in good control of symptoms in mostparticipants.

aaa aaaaaaaa aa aaaaaaaa aa aaaaaaa a a aa aa aaaaaaaaa a f control ofasthma resulted in higher doses of inhaled

corticosteroids, withoutclinically important improveme nts in symptomatic asthma control.

1.22

1.23 N=34

middleton 6 th edition

J Allergy Clin Immunol200912492; :

-832.

1.25 N=238

J Allergy Clin Immunol200912492; :

-832.

1.25

Area = 0.89 Conclusions : In an unselected sample ofyo Conclusions : In an unselected sample ofyo ung adults, bronchial provocation with inhal ung adults, bronchial provocation with inhal

- ed dry powder mannitol had a high diagnos - ed dry powder mannitol had a high diagnos tic specificity for the diagnosis of asthma tic specificity for the diagnosis of asthma.

EnvironmentEnvironment

• Pollution ,viral infection and social stress are studied in 2009

• Air pollution - positive correlation of FEV1 and distance from roadways - ozone increase risk of asthma• Difference of viral infection in asthma and non

asthma

• Pollution ,viral infection and social stress are studied in 2009

• Air pollution - positive correlation of FEV1 and distance from roadways - ozone increase risk of asthma• Difference of viral infection in asthma and non

asthma

1.31

Conclusions: These findings suggest that Conclusions: These findings suggest that subjects with mild allergic asthma and he subjects with mild allergic asthma and he

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es.es.

TherapeuticsTherapeutics

• Leukotriene modifiers - increase risk of suicide or not - effect on behavior• ICSs - increase dose of ICSs or add LABA - high dose or low dose ICSs/LABA - early or delay ICSs

• Leukotriene modifiers - increase risk of suicide or not - effect on behavior• ICSs - increase dose of ICSs or add LABA - high dose or low dose ICSs/LABA - early or delay ICSs

J Allergy Clin Immunol20091246; :

-99706.

1.34

JAllergyClinImmunol2 0 0 9 ;1 2 4 :6-916.

1.35

J Allergy ClinImmunol20091231; :

-1621

1.41

Conclusion: Although symptomatic control and Conclusion: Although symptomatic control and rescue bronchodilator use may be improved by the rescue bronchodilator use may be improved by the

addition ofa LABAto ICS, there may addition ofa LABAto ICS, there may be a lower riskof severe exacerbations be a lower riskof severe exacerbations

and hospitalizations from ICSdose increase. and hospitalizations from ICSdose increase.

Oral steroid use : lower in ICS group ( 22%vs 27%)

Hospitalization : lower in ICS group ( 1.3% vs 1.7%)

J Allergy ClinImmunol20091231; :

-1621

1.42

ns

ns

ns

Conclusion : low dose fixed combination Conclusion : low dose fixed combination and and reliever therapy is associated with higher eosinoph reliever therapy is associated with higher eosinoph

il counts, but these remain within the range associ il counts, but these remain within the range associ ated with stable clinical control. ated with stable clinical control.

J Allergy Clin Immunol200912411; :

-8 0 5 .

1.43

Conclusions: Conclusions: relative mild asthmatic patients relative mild asthmatic patients with delay ICS Rx had elevate inflammatory with delay ICS Rx had elevate inflammatory markers but no clinical difference compare markers but no clinical difference compare with early ICS Rxwith early ICS Rx

Take home messageTake home message

• Relationship of asthma and asthma• New genetic susceptibility for

asthma• Mannitol challenge test• Early and delayed ICS• Information for monteleukast• FENO

• Relationship of asthma and asthma• New genetic susceptibility for

asthma• Mannitol challenge test• Early and delayed ICS• Information for monteleukast• FENO

Thank you for

your attention

Thank you for

your attention