Asthma phenotypes
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Transcript of Asthma phenotypes
Need for Phenotype DefinitionsAsthma has always been susceptible to phenotypes
1 -according to asthma trigger2 -according to severity
3 -according to response to treatment
Need for phenotypes •Enhance interpretation of studies
•Promote appropriate comparisons among studies
•Facilitate genetics research in which phenotype is correlated with genotype
Asthma genotypesThere is no one gene for asthma.the following genes to be associated with asthma (IL13, IFNGR2, EDN1, and IL4R), atopy (FLG, CHIA, IL18, TBXA2R, TLR10, IL4R, IFNGR2, LTA, and VDR), airway hyperresponsiveness (TLR9, TBXA2R, VDR, and NOD2), and atopic asthma (TLR10, IFNGR2, STAT6, VDR, and C3).
Read More :://http . . / / /10.1513/ .6.3.324www atsjournals org doi full pats a#.VUPoENLtmko
Asthma PhenotypesDefine 9 phenotypes in 3 generalcategories:
-Trigger-induced asthma1 )Allergic
2 )Non-allergic3 )Aspirin-exacerbated respiratory
disease (AERD)4 )Infection
5 )Exercise-induced
Asthma Phenotypes -Clinical presentation of asthma
6 )Pre-asthma wheezing in infants -Episodic (viral) wheeze -Multi-trigger wheezing
7 )Exacerbation-prone asthma
Asthma Phenotypes8 )Asthma associated with apparent
irreversible airflow limitation - Inflammatory markers of asthma
9 )Eosinophilic and neutrophilic asthma
Trigger-induced asthma1 )Allergic
2 )Non-allergic3 )Aspirin-exacerbated respiratory
disease (AERD)4 )Infection
5 )Exercise-induced
Allergic •the most common phenotype.
•Higher prevalence in children. •Defined based on sensitization ±
clinical correlation.
Non-allergicsensitization cannot be demonstratedNegative skin prick or RAST testingNormal or low IgEOnset: Late, adult
Non-allergicNo personal or family history of allergyMore severe than allergic asthmaless responsive to steroidsIncidence: 10-33%
3) Aspirin sensitive asthma PROBABLE CRITERIA, WHENHISTORY OF ASPIRIN SENSITIVITYIS ABSENT IN A SUBJECT WITH ASTHMA:Chronic rhinosinusitis with nasal
polyps •Adult onset (over age 20 years)
•Peripheral blood eosinophilia
���Aspirin sensitive asthma
1 .Prevalence by history is variable (3-5%) but may be present in up to 21% of adults and5% of children.
2 .Aspirinsensitive asthma more in female.3 .Usual age of onset of symptoms is 30-34
years of age.4 .No known racial predisposition.
5 .No known association with lower socioeconomic status.
Aspirin sensitive asthma1 .Familial cases reported but relatively
rare (5.5%).2 .Association with HLA-DQw2 and DPB1.
3 .Genetic polymorphisms found in leukotriene C4 synthase
(LTC4S),prostaglandin E2 receptor genes.
A ��SA1 .Associated with more severe, refractory asthma, representing
A major risk factor for severe asthma in outpatients.2 .ASA may induce severe, lifethreatening asthma attacks.
3 .Rhinorrhea and nasal congestion are usually the first symptoms .of aspirinsensitive
4 .asthma and are commonly poorly responsive to pharmacologicalTreatment.
5 .Symptoms manifest within 1-3 hours of ingestion of aspirin and other NSAD.
1
Asthma PhenotypesTrigger-induced asthma
1 )Allergic2 )Non-allergic
3 )Aspirin-exacerbated respiratorydisease (AERD)
4 )Infection5 )Exercise-induced
respiratory tract infection1 -new onset of disease .
2 -exacerbations of the disease.3 -Co-morbid condition (e.g. sinusitis).
4 -persistence and/or severity of the disease
Exercise-induced (EIB) •No apparent gender disparity
•No known racial predisposition •No known association with socioeconomic
status •No known association with smoking
EIBEIB is generally thought to be due to evaporativeheat and water loss from the airway and variousinflammatory mediators and cells have beenInvolved in its pathogenesis.EIB occurs after the cessation of exercise,usually within 3-5 minutes, with peakbronchoconstriction occurring at 10-15 minutes.
Usually defined as ≥ 10% decrease in FEV1 after exercise.
WheezingPhenotypePre-Asthma Wheezing
(Tucson Children’s Respiratory)
1 -Never wheezed 51.5% 2 -transient early wheezers 19.9%
3 -late-onset wheezers 15%4 -persistent wheezer s 13.7%
7) Exacerbation-prone asthma
Relation to Severe Asthma Factors for Severe Exacerbations
•Low FEV1 •African American Ethnicity
•History of Pneumonia •Early Age of Onset
•NSAID Exacerbated Airway Disease •Worsening Asthma Symptoms with
Menses
8) Asthma associated with apparentirreversible airflow limitationEvidence of both airway obstruction
(reduced FEV1/FVC ratio )and a reducedFEV1 in a patient treated with bothanti-inflammatory agents
(glucocorticosteroids )and bronchodilators(beta-agonists))
9) Eosinophilic and neutrophilic asthma
Eosinophilic asthma
•Eosinophilic inflammation associatedwith poor asthma control, increasedbronchodilator response, lower lungfunction and exacerbations in ICStreated pts
•More common in aspirin-sensitiveasthma, in association with nasal polypsand in later onset disease
>2% eosinophils in sputum
Neutrophilic asthma .Less atopy,Older , Later onset asthma
•Much less well described and defined thaneosinophilic asthma
•Seems to increase with increasingseverity/CS use
“ •Definition”/neutrophil % cut-off unclearand may depend on sputum processingmethod
–Can be seen in association with eosinophilphenotype
IL-5
Eosinophils
ECPMBP
IL-8
Neutrophils
NE
Macrophages and Epithelial Cells
Allergens
Activated TH2 Cells
MMP-9
EosinophilicAsthma
NeutrophilicAsthma
Particulates, Pollutants ,Virus, Endotoxin
Acquired Immunity
InnateImmunityTLRIgE
NF-kB
Oxidativestress
Macrophages and Epithelial Cells
Allergens
Activated TH2 Cells
EosinophilicAsthma
NeutrophilicAsthma
Particulates, Pollutants, Virus,Endotoxin, Bacteria
Acquired Immunity
InnateImmunityTLRIgE
Inflammatory cell activation
hyperresponsiveness
ICS X X LABA
X LABA
Remodelling: ASM, mast cells
Summary: Asthma Phenotypes
•Define 9 phenotypes in 3 general categories: -Trigger-induced asthma
1 )Allergic2 )Non-allergic
3 )Aspirin-exacerbated respiratory disease (AERD)4 )Infection
5 )Exercise-induced -Clinical presentation of asthma
6 )Pre-asthma wheezing in infants -Episodic (viral) wheeze -Multi-trigger wheezing
7 )Exacerbation-prone asthma8 )Asthma associated with apparent irreversible airflow
limitation -Inflammatory markers of asthma
9 )Eosinophilic and neutrophilic asthma
Asthma phenotypes- Asthma is not a single disease.
– A patient can have >1 phenotype – Specific questions for future research to refine
definitions