2. Astmul:
Afectiune cronica inflamatorie a bronsiilor caracterizata prin bronhospasm episodic, reversibil rezultind dintr-un raspuns bronhoconstrictor exagerat la diversi stimuli
Afecteaza 10% din copii & 5%-7% adulti
Rata crescuta in NZ, Scazuta in Fiji ~ 1% 

3. DEFINITIE
Stare patologica tradusa prin ingustarea difuza a bronsiilor, reversibila spontan sau sub tratament bronhodilatator
Clinic: Crize de dispnee cu bradipnee expiratorie si wheezing

5. Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998
Proportion of 1965 Rate
3.0
Coronary
Heart
Disease
Stroke
Other CVD
COPD
All Other
Causes
2.5
2.0
1.5
1.0
0.5
–59%
–64%
–35%
+163%
–7%

6. Epidemiologie TERENUL ATOPIC (personal si familial)
Virsta de debut este precoce: inainte de 40 de ani in 75-90% din cazuri si frecv. inainte de 5 ani.
Predominenta masculina la copil (3:1) si feminina la adult
Pubertatea este o perioada critica (o parte din cazuri evol. favorabil, altele se cronicizeaza);
Morbiditatea: 1-24% (copil), 1-10% (adult);
Mortalitate scazuta (Franta: 0.5-1/ sau decese/an)

7. Fiziopatologie HIPERREACTIVITATEA BRONSICA
cvasiconstanta, responsabila de spasmul muschilor netezi si de bronhospasm;
T de provocare (reprod efectele sist. parasimpatic, H, ag. chimici); pacientii astmatici sint de x mai sensibili la Ach si de 1000 x mai sensibili la frig si infectii fata de cei normali
Hiperreactivitatea este variabila in timp si maxima noaptea (cresterea tonusului parasimpatic bronhoconstrictor, hiperreactivitatea alfa adrenergica si hiporeactivitate beta adrenergica)

8. Patogeneza: INFLAMMATION Airflow Limitation INDUCERS
Allergens,Chemical sensitisers,
Air pollutants, Virus infections
Airway
Hyperresponsiveness
Genetic*
INFLAMMATION
Airflow Limitation
SYMPTOMS
Cough Wheeze
Dyspnoea
TRIGGERS
Allergens, Exercise,
Cold Air, SO2 Particulates
Inflammation of the airways not only causes symptoms associated with widespread but variable airflow obstruction, it also results in an increase in airway hyperresponsiveness to a variety of stimuli (triggers)
Environmental and genetic influences in asthma (inducers) act mainly by provoking airway inflammation, rather than directly stimulating airway hyperresponsiveness
Triggers of bronchoconstriction, which are factors that provoke contraction of the sensitised airway wall, include a wide range of stimuli, such as exercise, cold air and pollen
Allergens can act as both inducers and triggers

9. Tipuri de Astm : Extrinsec (Alergic/Imun) Intrinsic (Non immune)
Atopic - IgE
Ocupational - IgG
A. Bronchopulomonary Aspergillosis - IgE
Intrinsic (Non immune)
Aspirin induced
Infection induced

10. ATOPIA
- Capacitatea de a sintetiza o cantitate anormala de IgE, in urma contactului cu antigen(e) din mediu, fenomen mediat de limfocitele B
TRIGGER
Mastocitele (intraluminale, epiteliale si submucoase) posedind pe suprafata lor R pentru IgE
Inhalarea alergenului ce se fixeaza pe mastocitele superficiale antreneaza eliberarea mediatorilor (Histamina, PAF, Leukotriene, SRSA, PGF2 alfa, tromboxani, factori chimiotactici pentru PMN)
Infectiile traheobronsice- altereaza epiteliul
Efortul fizic – determina eliberarea acuta de mediatori
Agravarea nocturna se datoreaza hipertoniei parasimpatice si scaderii tonusului catecolaminelor circuante

11. Agentii Responsabili de Criza de Astm
1. ANTIGENE Hipersensibilit imediata de tip I (IgE) + atopie + tinar
Pneumalergeni: polen, praf de casa, acarieni, fanere animale domestice
Alergeni microbieni sau micotici: streptococul, Candida albicans, Aspergillus (maladia Hinson – Pepys);
Alergeni alimentari: crustacee, zmeura, coloranti (tartrazina: E102)
Medicamente: Aspirina, etc
2. IRITANTI: vapori, fum, parfumuri, tutun
3. AGRESIUNE INFECTIOASA: rinite, sinuzite, bronsite
4. FACTORI PSIHOLOGICI: emotii, griji, conflicte
5. INFLUENTE HORMONALE: ciclul, menopauza
6. INFLUENTE METEOROLOGICE: umiditatea, ceata
7. EXERCITIUL FIZIC SI HIPERVENTILATIA

13. Patologia astmului Allergen Leukotrienes C4, D4 & E4 Mucus
hypersecretion
Hyperplasia
Vasodilatation
New vessels
Plasma leak
Oedema
Bronchoconstriction
Hypertrophy/hyperplasia
Cholinergic
reflex
Subepithelial
fibrosis
Sensory nerve
activation
Eosinophil
Mast cell
Th2 cell
Neutrophil
Macrophage/
dendritic cell
Mucus plug
Epithelial shedding
Nerve activation
Leukotrienes
C4, D4 & E4
Asthma is a complex disease involving many different cells
Current thinking on the pathophysiology of asthma regards it as a specific type of inflammatory condition, involving, in particular, mast cells, eosinophils and T lymphocytes, which release a wide range of inflammatory mediators
These mediators act on cells in the airway, leading to contraction of smooth muscle, oedema due to plasma leakage and mucus plugging
Barnes PJ

14. Cell Membrane Phospholipids
Arachidonic Acid
Leukotrienes
LTC4, D4, E4
Cyclooxygenase
5-Lipoxygenase
Prostaglandins
Prostacyclins
Cell Damage
Cell Membrane Phospholipids
Steroids
NSAID
5-LO inhibitors
Antileukotrienes

15. Mastocitele in Patogenia Astmului

16. Degranularea Mastocitului
Normal Seconds 60 Seconds
Asthma is a complex disease involving many different cells
Current thinking on the pathophysiology of asthma regards it as a specific type of inflammatory condition, involving, in particular, mast cells, eosinophils and T lymphocytes, which release a wide range of inflammatory mediators
These mediators act on cells in the airway, leading to contraction of smooth muscle, oedema due to plasma leakage and mucus plugging
Barnes PJ

17. Eozinofilul in Astm

18. Eosinofilele in Astm:

19. CONSECINTELE ANATOMICE: hipertrofia muschilor netezi bronsici, hipertrofia gl. mucoase, ingrosarea mbr. bazale si infiltratie eozinofilica a peretelui bronsic, exsudate intrabronsice, dilatatii capilare cu infiltrate leucocitare.

20. Morfologia Pulmonara in Astm
Bronchial inflammation
Edema, Mucousplugging
Bronchospasm
Obstruction
Over inflation/Atelectasis
COPD

21. Hiperinflatie Pulmonara in Astm

22. Bronsii ingrosate cu dopuri de mucus

23. Dop de mucus in astm:

24. Spiralele Curschmann :

25. Anatomie Patologica
Obstructed
Inflammed
Bronchi

26. Astm – Morfologia Bronsica
inflammation
Eosinophils
Gland hyperplasia
Mucous plug in lumen
Hypertrophy of muscle layer

27. Astm – Limfocitele TH2 - immunostaining

28. Terapia - Patologica:
Asthma is a complex disease involving many different cells
Current thinking on the pathophysiology of asthma regards it as a specific type of inflammatory condition, involving, in particular, mast cells, eosinophils and T lymphocytes, which release a wide range of inflammatory mediators
These mediators act on cells in the airway, leading to contraction of smooth muscle, oedema due to plasma leakage and mucus plugging
Barnes PJ

29. Diagnostic – Criza de Astm
Debut brutal, frecv nocturn ± prodrom (astenie, cefalee, tuse)
Dispnee caracteristica: bradipnee expiratorie, wheezing, inspir scurt ineficient
Obiectiv: torace destins, hipersonor, tiraj suprasternal, raluri sibilante difuze si ronflante
Faza catarala: bradipneea se atenueaza si este inlocuita de o tuse cu expectoratie dificila, densa (sputa perlata a lui Laennec); ralurile sibilante sint inlocuite de ronflante

30. Rx pulmonar: hiperclaritate difuza cu distensie si aplatizarea diaframelor
Explorarea funct: normala intre crize
T de provocare: pozitive
(scadere cu min 20% a VEMS si sub 75% a raportului Tiffeneau: VEMS/CV; VR poate creste dar CPT= n)
T bronhodilatatoare: reversibilitate a obstructiei
Endoscopia bronsica: utila pentru a elimina posibilitatea unei stenoze traheale
HLG: Eozinofilie
Teste alergologice: teste cutanate sau de provocare inhalatorie

31. Diagnostic Diferential
Stenoza acuta traheala
Corpi straini
Astmul cardiac
Embolie pulmonara
Tumori carcinoide

32. Tratamentul in Criza Criza moderata:
Beta 2 mimetice (2-3 puf/zi): Terbutalina (Bricanyl), Fenoterol (Berotec), Salbutamol (Ventoline)
Teofilina retard (Theotard): 200 mg, 350 mg
Criza severa sau moderata ce nu cedeaza intr-o ora:
Beta 2 mimetice s.c: Terbutalina (Bricanyl) ½ - 1 fiola
Cortizon 0.5 mg/kg i.v.- 1g (starea de rau astmatic)
Teofilina retard sau i.v lent 5 mg/Kg in 20 min
Spitalizare
Oxigenoterapie
Administrare de teofilina, corticoizi, beta 2 mimetice
Antibioterapie
Supraveghere in serviciul ATI (ventilatie asistata, etc)

33. Tratamentul de fond Tratamentul etiologic
Evictia alergenului (greu de realizat)
Desensibilizarea specifica (eficace in astmul polinic; dificila in polisensibilizari): presezoniera, anuala, etc
Tratamentul antiinfectios: evictia focarelor ORL si stomatologice, vaccinare IBC
Cromoglicat de Na (Lomudal: 4 puf/zi), Nedocromil (Tilade)
Tratarea componentei psihice: anxiolitice in doze mici, psihoterapie
Antihistaminice: Hismanal, Zyrtec
Ketotifen (Zaditen) –pentru diminuarea frecv. si nr. crizelor
Tratamentul simptomatic
Bronhodilatatoare
Beta 2 mimetice in aerosol (Ventoline, Bricanyl, Berotec), derivati atropinici (bromura de oxitropium – Tersigat, bromura de ipratropium – Atrovent in aerosoli
Theotard mg/zi (teoretic aprox 10 mg/kc/zi – Atentie la Ef sec !)…
Cortizon (aerosoli cu beclometasona – Becotide), dexametazona, dupa inhalarea unui bronhodilatator
La Gravida
Fara desensibilizare;
Evitam pe cit posibil corticoterapia
La Copil
Alergia este adesea pe primul plan
Corticoterapia orala sau parenterala trebuie evitata la maximum
Teofilina trebuie atent monitorizata