allergic phenotypes: asthma - eaaci.org - paloma campo.pdf · allergic phenotypes: asthma eaaci...
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Paloma Campo MD, PhD
U.G.C. Allergy
Hospital Regional, Málaga- SPAIN
ALLERGIC PHENOTYPES: ASTHMA
EAACI SUMMER SCHOOL
2-5 JULY
BRINDISI, ITALY
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Chronic inflammatory disease of airways in which multiple mechanisms
and cells are involved
Bronchial hyperresponsiveness causes recurrent episodes of cough,
dyspnea, chest tightness and wheezing, specially at night or early
morning
Episodes associated with variable airflow obstruction, reversible
spontaneously or with treatment
Hipocrates (460-360 BC) defined asthma as “a disease
commonly seen in fishermen, taylors and metal workers”
ASTHMA
Global Initiative for Asthma (GINA Updated 2014)
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• 300 million people worldwide
• Spain: (ISAAC): 1994-1995 y 2002-2003
Garcia-Marcos L et al. Stabilization of asthma prevalence among adolescents and increase among schoolchildren (ISAAC phases
I and III) in Spain. Allergy. 2004 Dec;59(12):1301-7.
o 6-7 yrs:
o Boys: increase from 7% to 10.7 %
o Girls: increase from 5.3% to 8.2 %
o 13-14 yrs: no changes (9 %)
o 80% is IgE mediated (allergic asthma)
o Some countries: stable
ASTHMA
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• More frequent in developed countries, more populated areas and
specially urban environment
• Comorbidities:
• Rhinitis
• Polyposis
• CRS
• Major cause of work and school loss
• High cost in hospitalization & medication
• Allergic asthma most common
Global Initiative for Asthma ( GINA Updated 2014)
ASTHMA
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Global Initiative for Asthma ( GINA Updated 2014)
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ASTHMA
MULTIFACTORIAL DISEASE
GENETIC
FACTORS
ENVIRONMENTAL
FACTORS
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Viral
Infections
Obesity
Others
ExerciseAlergens
Occupational
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50% <10 yrs old
33% < 40 yrs old
NATURAL HISTORY
DIFFERENTPHENOTYPES
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Inflammation Airway
Hyperreactivity
Reversible airflow
obstruction
MAIN CHARACTERISTICS
DIFFERENT TYPESOF INFLAMMATION
NOT ALWAYS REVERSIBLE(FIXED)
NOTEXCLUSIVE
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ASTHMA PHENOTYPES
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ASTHMA PHENOTYPES
Clinicians are already familiar with the phenotyping exerciseconsisting of identifying visible properties associated withasthma. Yet, phenotypic descriptions in clinical notes and medicalpublications are often imprecise and frequently over-lapping
Agache I. Curr Opin Allergy Clin Immunol 2013, 13:249–256
Different approaches (cluster analysis, biomarkers, clinicalpresentation….)
Different underlying disease mechanisms
NO strong relationship between pathological features and clinicalpatterns/treatment response except for some forms of severeasthma
Global Initiative for Asthma (GINA Updated 2014)
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ASTHMA PHENOTYPES
According to GINA 2014, many phenotypes have been identified.
Some of the most common are:
ALLERGIC ASTHMA
NON-ALLERGIC ASTHMA
LATE-ONSET ASTHMA
ASTHMA WITH FIXED AIRFLOW LIMITATION
ASTHMA WITH OBESITY
SEVERE ASTHMA?
NERD?
OVERLAP ASTHMA/COPD?
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ASTHMA PHENOTYPES
ALLERGIC ASTHMA:
-Starts in childhood-Associated with family history of allergic disease (eczema, allergic rhinitis, food/drug allergy)
-Eosinophilic airway inflammation-Respond well to ICS treatment
NON-ALLERGIC ASTHMA:
-Not associated with allergy-Adults-Neutrophilic/eosinophilic/paugranulocytic inflammation-Respond less well to ICS
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ASTHMA PHENOTYPES
LATE-ONSET ASTHMA:
-Adults
-Women
-Non allergic
-Require higher doses of ICS/relatively refractory to ICS
ASTHMA WITH FIXED AIRFLOW LIMITATION:
-Long-standing asthma
-Airway wall remodeling
ASTHMA WITH OBESITY:
-Obese patients
-Prominent respiratory symptoms
-Little eosinophilic airway inflammation
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ALLERGIC ASTHMA
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IN VIVODIAGNOSIS
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“IN VITRO”DIAGNOSIS
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APV
HMW LMW
+ CARRIER
CD4
CD8
IgE
IL4
IL13
Eosinophil Basophilo
Macrophage Neutrophil
IL5
MCP-1
IFN gamma
BRONCHIAL HYPERREACTIVITY
BRONCHIAL OBSTRUCTION
INFLAMMATION
TISULAR DAMAGE
ALARM SIGNAL
OCCUPATIONAL ASTHMA
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SPIROMETRYBRONCHODILATOR TEST
BHR (METACHOLINE)
NITRIC OXIDE
INDUCED SPUTUMPEF VARIABILITY
OCCUPATIONAL ASTHMA
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SPECIFIC INHALATIONCHALLENGE (CHAMBERS)
SPECIFIC INHALATION CHALLENGE(WORKPLACE)
OCCUPATIONAL ASTHMA
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SEVERE ASTHMA PHENOTYPES
Campo P et al JIACI 2013
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SEVERE ASTHMA ENDOTYPES
• Classification where asthma is divided into different entities with specific
biological causal mechanisms (asthma endotypes)
• An asthma endotype can encompass various phenotypes, and an specific
phenotype may be present in several endotypes
• Cluster analysys
Campo P et al JIACI 2013
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TreatmentFollow-up
Triggers
Pharmacotherapy
Inmunotherapy
Education
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DIAGNOSIS
PERSONALIZED MANAGEMENT
ASTHMA
PHENOTYPE MECHANISMS
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• Add-on treatment without phenotyping:
Add controler meds(Teophyline/LTRs)
• Sputum-guided treatment:
Adjust ICS based on sputum results
• Phenotype-guided add-on treatment:– NERD: LTRs (evidence B)
– Severe allergic with high IgE: Omalizumab(evidence A)
– Eosinophilic: monoclonals anti IL5/IL13.
PHENOTYPE-ORIENTED TREATMENT
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Thank you for your attention
EAACI SUMMER SCHOOL2-5 JULY
BRINDISI, ITALY