ASTHMA

1. ASTHMA

2. BRONCHIAL ASTHMA ASTHMA IS DEFINED AS REVERSIBLE OBSTRUCTION OF LARGE AND SMALL AIRWAYS DUE TO HYPERRESPONSIVENESS TO VARIOUS IMMUNOLOGIC AND NONIMMUNOLOGIC STIMULI “ASTHMA IS AN EOZINOPHYLIC INFLAMMATION OF THE AIRWAYS” PREVALANCE 7-12%

3. CLASSIFICATION A) ALLERGIC OR EXTRINSIC ASTHMA POLLENS FOODS DUST MITES IgE MEDIATED ANIMAL DANDERS RSV

4. B) INTRINSIC OR NONALLERGIC ASTHMA TEMPERATURE CHANGES COLD AIR ODOR IRRITANS MENSES SMOKE VIRUS C) EXERCISE INDUCED ASTHMA D) ASPIRIN INDUCED ASTHMA

5. RISK FACTORS FOR CHILDHOOD ASTHMA • FAMILIAL AND GENETIC FACTORS • ATOPY • ENVIRONMENTAL FACTORS • VIRAL • RESPIRATORY TRACT INFECTIONBACTERIAL? • AMBIENT AIR POLLUTION (NO2, SO2, O3) • PASSIVE EXPOSURE TO CIGARETTE SMOKE • PSYHOLOGIC FACTORS • COLD AIR • EXERCISE

6. RISK FACTORS FOR CHILDHOOD ASTHMA • NASAL POLYPS • ASPIRINREACT ALSO TO TARTARAZINEYELLOW • URTICARIA • (INHIBITS CYCLOOXYGENASE PATWAY) • PRESERVATIVE (SULFIDES) • LETTUCE • FRESH SALAD • DRIED FRUITS • DRIED POTATOES • WINE • SOFT DRINKS

7. MECHANISM OF ASTHMA ALLERGIC MECHANISM (IgE MEDIATED) AUTONOMIC REGULATION  ADRENERGIC  ADRENERGIC ? CHOLINERGIC

8. İnhale allerjen  antijen sunan hücre Karşılıklı etkileşim THO → IL4 → TH2 IL4 IL3 plasma hücresi IgE yapımı mast hücresinden Kanda IgE doku mast hücresi FcεR1 bozofil (yüksek afiniteli) histamin önceden serotinin mevcut lenfosit eo FcεR2 lokotrienler sonra trombosit (düşük afiniteli) prostoglandin yapılanlar Makrofaj - Bronş düz kas kasılmaları - Damar geçirgenliğinde artma - Mukus sekresonunda artma Erken Faz Reaksiyonu Tip I Reaksiyonu

9. MEDIATORS WITH ACTIONS THAT CAUSE AIRWAY OBSTRUCTION BRONCHOCONSTRICTION HISTAMINE BRADYKININ LEUKOTRIENES C.D.E PGD2, PGF2 THROMBOXANE A2 AND B2 INCREASED CAPİLLARY PERMEABILITY HISTAMINE BRADYKININ LEUKOTRIENES C.D.E PGE SECRETION OF MUCUS HISTAMINE LEUKOTRIENES C.D HETEs PGD2, PGF2, PGI2, PGE

10. PATHOLOGY OF ASTHMA • ALLERGIC AND NONSPESIFIC STIMULI (COLD AIR EXERCISE, ASA) • ↓ • SMOOTH MUSCLE SPASM • AIRWAYS INFLAMMATION • MUCOUS PLUGGING OF THE AIRWAYS • CELLULAR INFILTRATION OF THE AIRWAYS • CHEMICAL MEDIATORS AND NONSPESIFIC STIMULI • ↓ • BRONCHOCONSTRICTION, MUCOSAL EDEMAEXCESSIVE SECRETIONS • ↓ • AIRWAY OBSTRUCTION • ↓ ↓↓ATELECTASIS NON UNIFORM HYPERINFLATION • VENTILATION • ↓ ↓ MISMATCHING DECREASED • OF VENTILATIONCOMPLIANCE • AND PERFUSION • ↓ ↓ • ALVEOLAR INCREASED • DECRAESED HYPOVENTI WORK OF BREATHING LATION • ASIDOSIS • PULMONARY • VASOCONSTRICTION • THE PATHOPHYSIOLOGY OF ASTHMA PCO2 PO2

11. CLINICAL FINDINGS • RECURRENT EPISODES OF COUGH • DYSPNEA • WHEEZING • - PAROXYSMAL COUGHING AND INDUCES • VOMITING • - SHORTNESS OF BREATH • - A FEELING OF TIGHTNESS IN THE CHEST • - POOR EXERCISE TOLERANCE • - RECURRENT CHEST COLDS OR • PNEUMONIA

12. DIAGNOSIS • HISTORY • ATOPY • CLINICAL FINDINGS • LABROTORY FINDINGS

13. PHYSICAL EXAMINATION PROLONGATION OF EXSPIRATION HIGH-PIYCHED MUSICAL WHEEZING LOUDER ON EXSPIRATION COARSE RHONCHI ELEVATION OF THE RIBS (INSPECTION) USE OF THE ACCESSORY MUSCLES PULSUS PARADOXICUS INDICATES PULSE RATE 120-130 SEVERE RESPIRATION RATE RISES TO 20-30 OBSTRUCTION CYANOSIS

14. MILD INTERMITENT – PRESİSTENT ASTHMA CONSTITUES UP TO 75% OF THE CHILDHOOD ASTHMATIC POPULATION AND IS ASSOCIATED WITH EPISODIC OCCURING LESS THAN ONCE EVERY 4-6 WEEKS MINOR WHEEZING AFTER HEAVY EXERTION NO OBVIOUS SYMPTOMS BETWEEN ORFUNCTIONAL IMPAIRMENT EPISODES NORMAL LUNG FUNCTION BETWEEN EPISODES PROPHYLACTIC THERAPY IS USUALLY NOT REQUIRED

15. MODERATE ASTHMA FREQUENT EPISODIC ASTHMA CONSTITUES ABOUT 20% OF THE ASTHMA POPULATION AND IS ASSOCIATED WITH SOME WHAT MORE FREQUENT ATTACK AND WHEEZE ON MODERATE EXERCISE, BUT IS PREVENT BY PREDOSING WITH A B2 AGONIST . SYMPTOMS OCCUR LESS FREQUENTLY THAN ONCE A WEEK AND THERE IS NORMAL OR NEAR NORMAL LUNG FUNCTION BETWEEN EPISODES. PROPHYLACTIC TREATMENT IS USUALLY NECESSARY

16. SEVERE ASTHMA PERSISTENT ASTHMA AFFECTS ROUGHLY 5% CHILDREN WITH ASTHMA AND IS ASSOCIATED WITH FREQUENT ACUTE EPISODES, WHEEZING WITH MINOR EXERTION, AND INTERVAL SYMPTOMS REQUIRING B2 AGONIST DRUGS MORE THAN 3 TIMES A WEEK BECAUSE OF EITHER NIGHT WAKENING OR CHEST TIGHTNESS IN THE MORNING. THERE IS NEARLY ALWAYS EVIDENCE OF AIRFLOW LIMITATION BETWEEN EPISODES. PROPHYLACTIC TREATMENT IS MANDATORY.

17. LABORATORY TESTS BLOOD COUNT EOSINOPHILIS NASAL EOSINOPHIL COUNT  10% (+) IMMUNGLOBULINS (G. A. M) (G1. G2. G3. G4) IgE SKIN TESTS CHEST X-RAY PPD X-RAY FILMS OF PARANASAL SINUSIS 1 ANTITRYPSIN MEASUREMENT OF SWEAT ELECTROLYTES PULMONARY FUNCTION TEST PO2 PCO2 BICARBONATE LEVELS

19. PULMONARY FUNCTION TEST • IN ASTHMA • TOTAL LUNG CAPACITY • FUNCTIONAL RESUDIAL CAPACITY • RESUDIAL VOLUME ARE INCREASED • VITAL CAPACITY  • FORCED VITAL CAPACITY (FVC)  • FORCED EXPIRATORY VOLUME IN 1 sec (FEV1)  • PEAK FLOW RATE (PFR)  Mild % 80 Modere %60 – 80 Severe  60

20. PULMONARY FUNCTION TEST • IF THE FEV1 VALUE INCREASES BY 15% AFTER THE ADMINISTRATION OF AEOROLIZE BRONCHODILATATOR ASTHMA IS DIAGNOSED. • IN EIA FEV1 VALUE DECREASEMENTS BY 15% AFTER EXERCISES IS A REASON FOR DIAGNOSIS OF EIA ASTHMA

21. DIFFERENTIAL DIAGNOSIS • INFANTS AND YOUNG CHILDREN • BRONCHIOLITIS • FOREIGN BODY • CROUP • EPIGLOTTITIS • CYSTIC FIBROSIS

22. DIFFERENTIAL DIAGNOSIS • IMMOTILE CILIA SYNDROME • HABIT COUGH • BRONCHOPULMONARY DYSPLASIA • TRACHEOMALACIA • TRACHOESOPHAGEAL FISTULA, • ANOMALIES OF AORTIC ARCH • GASTROESOPHAGEAL REFLUX

23. OLDER CHILDREN AND YOUNG ADULTS • TBC • HABIT COUGH • VOCAL CORD DYSFUNCTION • HYPERVENTILATION • 1 ANTITRYPSIN DEFICIENCY • CYSTIC FIBROSIS • IMMOTILE CILIA SYNDROME • CARCINOID SYNDROME • BRONCHIECTASIS

24. COMPLICATIONS I • INFECTION • BRONCHITIS • PNEUMONITIS • SINUSITIS • O.MEDIA • BRONCHIECTASIS • ATELECTASIS • MEDIASTINAL AN SUBCUTANEOUS • EMPHYSEMA

25. COMPLICATIONS II • PNEUMOTHORAX • COUGH SYNCOPE • GROWTH COMPLICATIONS • A) INHIBITION OF LINEAR GROWTH AND BONE MATURATION • B) THORACIC DEFORMITIES • COR PULMONALE • EMPHYSEMA • STATUS ASTHMATICUS • POLIOMYELITIS LIKE ILLNESS

26. MEDICAL TREATMENT

32. MEDICAL TREATMENT BRONCHODILATORS DRUGS BETA-2 ADRENERGIC AGONISTS BETA- AGONIST PRODUCE BRONCHODILATATION BY DIRECTLY STIMULATING BETA-2 RECEPTORS IN AIRWAY SMOOTH MUSCLE, WHICH LEADS TO RELAXATION

34. ANTICHOLINERGIC: ATROVENT NEBUL 6-12 YEAR 0,25 mg EVERY 6 h 12 YEAR 0,5 mg EVERY 6 h SIDE EFFECT: MUSCLE TREMOR, TACHYCARDIA PALPILATION, HYPOKALEMIA

35. ANTI-INFLAMMATORY DRUGS • 1-CORTICOSTEROID: • CORTICOSTEROIDS HAS ANTI-INFLAMMATORY EFFECTSCORTICOSTEROIDS • SUPRESSING TRANSCRIPTION OF • INFLAMMATORY GENES • HAVE INHIBITORY EFFECTS ON MANY • INFLAMMATORY AND STRUCTURAL • CELLS, CYTOKINES (IL1, IL5, IL13, TNF, • CMCSF)

36. ANTI-INFLAMMATORY DRUGS IT IS IMPORTANT TO RECOGNISETHAT STEROIDS SUPRESS INFLAMMATION IN THE AIRWAYS BUT DO NOT CURE THE UNDERLYING DISEASE

38. SIDE EFFECT: DYSPHONIA, ORAPHARYNGEAL CANDIDIASIS, COUGH, ADRENAL SUPRESSION, GROWTH SUPRESSION, CATARACTS, GLOUCOME, OSTEOPROSIS

39. 2-METHYLXANTHINES THEOPHYLLINE, ALTHOUGH INEXPENSIVE IS A DRUG THAT IS LESS EFFECTIVE AS BRONCHODILATATORS THAN 2 AGONIST AND THAT HAS LESS ANTI INFLAMATORY EFFECT THAN INHALED STEROIDS. HOWEVER IN PATIENTS WITH SEVERE ASTHMA THEOPHYLLINE STILL REMAINS A VERY USEFUL DRUG “THERE IS EVIDENCE THAT THEOPHYLLINE HAS AN ANTI-INFLAMATORY OR IMMUNOMODULATORY EFFECT”

40. THE INHIBITORY EFFECT OF THEOPHYLLINE ON PHOSPHODIESTERASES MAY RESULT IN BRONCHODILATATION AND INHIBITION ON INFLAMATORY CELLS THERAPEUTIC RANGE IS 10 TO 20 mg/L OPTIMAL DOSES 10 mg/L THERE IS NOT ORAL SHORT ACTING THEOPHYLLINE IN TURKEY I.V AMINOCARDOL 2-4 mg/kg/dose

41. SLOW-RELEASE PREPARATIONS SIDE EFFECT: NAUSEA, VOMITING, GASTRIC DISCOMFORT, HEADACHES CARDIAC ARRYHYTMIAS, EPILEPTIC SEIZURES

42. 2- CROMOLYN SODIUM • IS A MAST CELL STABILIZER • POTENTLY INHIBIT BRONCHOCONSTRICTION INDUCED BY SULFURDIOXIDE, METABISULFITE AND BRADYKININ WHICH ARE BELIEVED TO ACT THROUGH ACTIVATION OF SENSORY NERVES IN THE AIRWAY • HAVE VARIABLE INHIBITORY ACTIONS ON OTHER INFLAMMATORY CELLS THAT MAY PARTICIPATE IN ALLERGIC INFLAMMATION INCLUDING MACRAPHAGES AND EOSINOPHILIS

43. 2- CROMOLYN SODIUM • BLOCKING EARLY BUT ALSO THE LATE RESPONSE • PROTECTS INDIRECT BRONCHOCONSTRICTOR STIMULI SUCH AS EXERCISES AND FOG • LONG-TERM TREATMENT WITH CROMONES REDUCES AIRWAY HYPERRESPONSIVENESS • CROMOLYN IS A PROPHYLACTIC DRUG OF FIRST CHOISE IN CHILDREN BECAUSE IT HAS ALMOST NO SIDE EFFECTS • INTAL 5 mg MDI 4x1

44. SIDE EFFECTS: CROMOLYN IS ONE OF THE SAFEST DRUGS AVAILABLE AND SIDE EFFECTS ARE EXTREMELY RARE. THROAT IRRITATION, COUGHING

45. 3- ANTI- LEUCOTRIENES THESE DRUGS INHIBITS BRONCHOCONSTRICTION INDUCED BY ALLERGEN, EXERCISE, COLD AIR AND MUCUS SECRETIONS AND MAY ALSO AN EOSINOPHILIC INFLAMMATION IN THE AIRWAYS. ALSO IT HAS BENEFOCAL EFFECT IN ALLERGIC RHINITIS AND EIA. ONE OF THE MAJOR ADVANTAGES OF ANTI-LEUCOTRIENES IS THAT THEY ARE ACTIVE IN TABLET FORM. THIS MAY INCREASE THE COMPLIANCE WITH CHRONIC THERAPY AND IT WILL MAKE TREATMENT OF CHILDREN EASIER

46. 5 YEAR↓ 4 mg ONCE ADAY MONTELUKAST 5-14 YEAR 5 mg “ “ (SINGULAIR) 14 YEAR 10 mg “ “ ZAFIRLUKAST12 YEAR 2x1 (ACCOLATE)

47. SIDE EFFECT: MONTELUKAST WELL TOLERATED IN CHILDREN WITH NO SIGNIFICANT ADVERSE EFFECTS. HIGH DOSES OF ZAFIRLUKAST MAY BE ASSOCIATED WITH ABNORMAL LIVER FUNCTION

48. 4- KETOTIFEN KETOTIFEN IS A PROPHYLACTIC ANTIHISTAMINIC DRUG.IT IS CLAIMED THAT KETOTIFEN HAS DISEASE MODIFYING EFFECTS IF STARTED EARLY IN CHILDHOOD ASTHMA AND MAY EVEN PREVENT THE DEVELOPMENT OF ASTHMA IN ATOPIC CHILDREN ZADITEN SUSP 5 ml=1 mg 2x1 TABLET 1 mg 2x1

49. NEDOCROMIL SODIUM: NEDOCROMIL SODIUM HAS ANTI INFLAMATORY EFFECTS. IT IS EFFECTIVE IN EIA TILADE 4 mg 2-4x4 puff 6 YEAR SIDE EFFECTS: SAME AS CROMOLYN SODIUM

50. IMMUNOTHERAPY • HYPOSENSITIZATION: INVOLVES THE INJECTION OF AQUEOUS EXTRACTS OF ALLERGENS GIVEN AT REGULAR INTERVALS • IT SHOULD NOT BE USED UNDER 5 YEARS • IT IS MOST EFFECTIVE IN ALLERGIC • RHINOCONJUNCTIVIS WITH OR WITHOUT ASTHMA