Burden of Asthma

Asthma is one of the most common chronic diseases worldwide with an estimated 300 million affected individuals Prevalence increasing in many countries, especially in children A major cause of school/work absence

Alergia: Enfermedad Sistmica

Epidemiolgicos
ALBANIA
Asma 2.6 RA 4.0 EA 0.8

GEORGIA
Asma 3.6 RA 4.5 EA 2.8

CANADA
Asma 28.1 RA 21.5 EA 11.2

UK

MXICO
Asma 6.6 RA 9.4 EA 4.4

Asma 32.1 RA 18.9 EA 14.7

NZ PER
Asma 26.0 RA 19.4 EA 8.2

INDONESIA
Asma 2.1 RA 5.3 EA 1.2

Asma 30.2 RA 19.1 EA 12.9

AUSTRALIA
Asma 29.4 RA 19.8 EA 12.2

ISAAC

The Lancet 1998; Vol 351:1225-32

Definition of Asthma

A chronic inflammatory disorder of the airways

Many cells and cellular elements play a role Chronic inflammation is associated with airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing

Widespread, variable, and often reversible airflow limitation

Risk Factors for Asthma

Host factors: predispose individuals to, or protect them from, developing asthma
Environmental factors: influence susceptibility to development of asthma in predisposed individuals, precipitate asthma exacerbations, and/or cause symptoms to persist

Factors that Exacerbate Asthma

Allergens Respiratory infections Exercise and hyperventilation Weather changes Sulfur dioxide Food, additives, drugs

Factors that Influence Asthma Development and Expression

Host Factors Genetic - Atopy - Airway hyperresponsiveness Gender Obesity

Environmental Factors Indoor allergens Outdoor allergens Occupational sensitizers Tobacco smoke Air Pollution Respiratory Infections Diet

Is it Asthma?

Recurrent episodes of wheezing Troublesome cough at night Cough or wheeze after exercise Cough, wheeze or chest tightness after exposure to airborne allergens or pollutants Colds go to the chest or take more than 10 days to clear

Asthma Diagnosis

History and patterns of symptoms

Measurements of lung function - Spirometry - Peak expiratory flow Measurement of airway responsiveness Measurements of allergic status to identify risk factors Extra measures may be required to diagnose asthma in children 5 years and younger and the elderly

FISIOPATOLOGA DEL ASMA BRONQUIAL

Justo R. Padilla Ygreda

Pediatra Instituto de Salud del Nio

ASMA: COMPONENTES

Barnes PJ

ASMA : FISIOPATOLOGA
GENES

MEDIO AMBIENTE MEDIO AMBIENTE

ALERGENOS

Th1

Th2

NO ASMA

ASMA

Maddox L.

Annu. Rev. Med. 2002 53:477-98

ASMA : GENES

Genes Candidatos:
Cromosoma
5q 6q 11q 12q 14q 16q 20q

Genes
Citoquinas Th2 (Interleuquinas 4,5,9,13) Factor de Necrosis Tumoral , CHM Receptor de Alta Afinidad Ig E (FcRI) Interfern Receptores de clulas T complejo / Interleuquina-4R ADAM 33

Tattersfield AE.

Lancet 2002; 360:1313-22

ASMA : GENES
Gen ADAM 33:
Locus en el brazo corto del cromosoma 20. ADAM: A Desintegrina A Metaloproteinasa Expresada por fibroblastos pulmonares y clulas musculares lisas bronquiales. Inclinara el equilibrio hacia la respuesta inmune mediada por las clulas Th2. Hiperreactividad Bronquial, y Remodelacin de las Vas Areas Pequeas.

Van Eerdewegh P. Shapiro SD.

Nature 2002; 418:426-30 N Engl J Med 2002; 347:936:38

ASMA Y GEN ADAM 33

Shapiro SD.

N Engl J Med. 2002; 347: 936-38

ASMA Y FENOTIPOS

Martinez FD.

Pediatrics 2002; 109:361-66

ASMA Y ATOPIA

Kay AB N Engl J Med 2001; 344:30-7

ASMA: TEORA DE LA HIGIENE

Busse WW. N Engl J Med 2001; 344:300-62

ASMA: TEORA DE LA HIGIENE

Astra Zeneca

ASMA: INFLAMACIN ALRGICA

Astra Zeneca

ASMA :

INFLAMACIN POR DESREGULACIN EPITELIAL (UTEM)

Astra Zeneca

ASMA: MASTOCITO

Astra Zeneca

ASMA: INFLAMACIN ALRGICA

Astra Zeneca

ASMA: INFLAMACIN ALRGICA

Busse WW.

N Engl J Med 2001; 344:300-62

ASMA: MASTOCITO

Astra Zeneca

ASMA: BRONCOCONSTRICCIN
Receptor Adrenrgico Receptor Adrenrgico

Receptor Histamina

AMPc
Receptor PGE

GMPc

Receptor Leucotrienos

Receptor Colinrgico Receptor PGF2

Broncodilatacin

Broncoconstriccin

ASMA: MASTOCITO

Astra Zeneca

ASMA: CIDO ARAQUIDNICO

Fosfolipidos (Membrana Celular)
Fosfolipasa A2

Acido Araquidnico

Prostaglandinas Tromboxanos Prostaciclinas

Leucotrienos C,D,E

ASMA Y LEUCOTRIENOS
LEUCOTRIENOS C4, D4, E4

Producen potente broncoconstriccin L/H 1000:1 Hipertrofian el musculo liso. Inducen hipersecrecin de la mucosa bronquial. Producen edema de mucosa. Reducen la actividad ciliar. Incrementan la permeabilidad microvascular. Estimulan la llegada de eosinfilos a las vas areas. Aumentan la hiperreactividad bronquial.

LEUCOTRIENO B4

Potente agente quimiotctico y activador de neutrfilos.

ASMA: BRONCOCONSTRICCIN
Receptor Adrenrgico Receptor Adrenrgico

Receptor Histamina

AMPc
Receptor PGE

GMPc

Receptor Leucotrienos

Receptor Colinrgico Receptor PGF2

Broncodilatacin

Broncoconstriccin

ASMA: CITOQUINAS
CITOQUINAS
Protenas producidas por diversas clulas como el linfocito Th y los macrfagos. Mensajeros celulares que regulan la maduracin y la amplificacin de la respuesta inmune. Se clasifican en cinco grupos: * INF *FNT * FECC *Interleuquinas * Quimiquinas o citoquinas quimioatrayentes.

ASMA: QUIMIOQUINAS

Luster AD. N Eng J Med 1998; 338:426-451

ASMA: EOSINFILO

Astra Zeneca

ASMA: INFLAMACIN Y EOSINFILO

Busse WW. N Engl J Med 2001; 344:300-62

ASMA: CONTROL NEURAL

DEL MUSCULO BRONQUIAL

Hiatt PW

New York Thoracic Society 1998; 17-20

ASMA: CONTROL VIAS AEREAS

Barnes PJ

ASMA:

RITMO CIRCADIANO BRONCOMOTOR

Astra Zeneca

ASMA: INFLAMACIN Temprana

Broncoconstricin

Tarda
Broncoconstriccin, Edema, Secrecin Inflamacin

FEV1

1 2 3 4

5 6 7 8 9 10

Horas despus del evento

ASMA: COMPONENTES

Barnes PJ

ASMA: PROCESO INFLAMATORIO

Barnes PJ

ASMA: ANATOMA PATOLGICA

Astra Zeneca

ASMA: PATOLOGA

NORMAL
Jeffery P. Asthma, Academic Press 1998

ASMA

ASMA: BRONCOFIBROSCOPA

ASMA: EVOLUCIN DINMICA

Inflamacin Aguda

Inflamacin Crnica

Remodelacin De las Vas Areas

Vignola M.

1999

ASMA : REMODELACIN

PARED BRONQUIAL
NORMAL
Badiola C

PARED REMODELADA

ASMA : REMODELACIN
CAMBIOS EPITELIALES

DESCAMACIN EPITELIAL

INFILTRADO CLULAS INFLAMATORIAS

DEPSITO SUBEPITELIAL PROTEINAS MATRIZ EXTRACELULAR

HIPERPLASIA CLULAS CALICIFORMES

Badiola C

ASMA : REMODELACIN

ESTRUCTURA SUBEPITELIAL NORMAL

MEMBRANA BASAL LMINA RETICULAR MIOFIBROBLASTOS

Badiola C

ASMA : REMODELACIN

ENGROSAMIENTO SUBEPITELIAL

MEMBRANA BASAL LMINA RETICULAR

MIOFIBROBLASTOS

Badiola C

ASMA: REMODELACIN
MEMBRANA BASAL

Jeffery P. Asthma, Academic Press 1998

ASMA: VISIN GLOBAL

Holgate ST J Allergy Clin Inmunol 2000; 105:193-04

TEORA DE LA HIGIENE !!!