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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% CLASSIFICATION A) ALLERGIC OR EXTRINSIC ASTHMA POLLENS FOODS DUST MITES ANIMAL DANDERS RSV IgE MEDIATED B) INTRINSIC OR NONALLERGIC ASTHMA TEMPERATURE CHANGES COLD AIR ODOR IRRITANS MENSES SMOKE VIRUS C) EXERCISE INDUCED ASTHMA D) ASPIRIN INDUCED ASTHMA RISK FACTORS FOR CHILDHOOD ASTHMA • FAMILIAL AND GENETIC FACTORS • ATOPY • ENVIRONMENTAL FACTORS • RESPIRATORY TRACT INFECTION VIRAL BACTERIAL? • AMBIENT AIR POLLUTION (NO2, SO2, O3) • PASSIVE EXPOSURE TO CIGARETTE SMOKE • PSYHOLOGIC FACTORS • COLD AIR • EXERCISE RISK FACTORS FOR CHILDHOOD ASTHMA NASAL POLYPS • ASPIRIN REACT ALSO TO TARTARAZINE YELLOW URTICARIA (INHIBITS CYCLOOXYGENASE PATWAY) • PRESERVATIVE (SULFIDES) LETTUCE FRESH SALAD DRIED FRUITS DRIED POTATOES WINE SOFT DRINKS MECHANISM OF ASTHMA ALLERGIC MECHANISM (IgE MEDIATED) AUTONOMIC REGULATION ADRENERGIC ADRENERGIC ? CHOLINERGIC İnhale allerjen antijen sunan hücre Karşılıklı etkileşim THO → IL4 → TH2 IL4 IL3 plasma hücresi IgE yapımı Kanda IgE doku mast hücresi FcεR1 bozofil (yüksek afiniteli) lenfosit eo trombosit Makrofaj FcεR2 (düşük afiniteli) Erken Faz Reaksiyonu Tip I Reaksiyonu mast hücresinden histamin serotinin önceden mevcut lokotrienler sonra prostoglandin yapılanlar - Bronş düz kas kasılmaları - Damar geçirgenliğinde artma - Mukus sekresonunda artma 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 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 EDEMA EXCESSIVE SECRETIONS ↓ AIRWAY OBSTRUCTION ↓ ↓ ATELECTASIS NON UNIFORM VENTILATION ↓ HYPERINFLATION ↓ MISMATCHING OF VENTILATION AND PERFUSION ↓ DECREASED COMPLIANCE ↓ DECRAESED ALVEOLAR HYPOVENTI LATION ASIDOSIS ↓ INCREASED WORK OF BREATHING PCO2 PULMONARY VASOCONSTRICTION PO2 THE PATHOPHYSIOLOGY OF ASTHMA 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 DIAGNOSIS • HISTORY • ATOPY • CLINICAL FINDINGS • LABROTORY FINDINGS 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 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 OR FUNCTIONAL IMPAIRMENT BETWEEN EPISODES NORMAL LUNG FUNCTION BETWEEN EPISODES PROPHYLACTIC THERAPY IS USUALLY NOT REQUIRED 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 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. 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 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 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 DIFFERENTIAL DIAGNOSIS • INFANTS AND YOUNG CHILDREN • BRONCHIOLITIS • FOREIGN BODY • CROUP • EPIGLOTTITIS • CYSTIC FIBROSIS DIFFERENTIAL DIAGNOSIS • IMMOTILE CILIA SYNDROME • HABIT COUGH • BRONCHOPULMONARY DYSPLASIA • TRACHEOMALACIA • TRACHOESOPHAGEAL FISTULA, ANOMALIES OF AORTIC ARCH • GASTROESOPHAGEAL REFLUX OLDER CHILDREN AND YOUNG ADULTS • TBC • HABIT COUGH • VOCAL CORD DYSFUNCTION • HYPERVENTILATION • 1 ANTITRYPSIN DEFICIENCY • CYSTIC FIBROSIS • IMMOTILE CILIA SYNDROME • CARCINOID SYNDROME • BRONCHIECTASIS COMPLICATIONS I • INFECTION BRONCHITIS PNEUMONITIS SINUSITIS O.MEDIA • BRONCHIECTASIS • ATELECTASIS • MEDIASTINAL AN SUBCUTANEOUS EMPHYSEMA 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 MEDICAL TREATMENT 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 2 agonist Etken madde Short acting Long acting Veriliş yolu Doz Terbutaline Bricanly MDI 200 mcq Bricanly Susp Salbutomal Ventolin MDI 100 mcq Ventolin nebul 2-5 mg Ventolin susp Serevent MDI 25-50 mcq Astmerol MDI 25-50 mcq Forodil MDI 12 mcq MDI 20 mcq Salmoteral Formoteral İlaç adı Antıcholınergıc Ipratropium Atrovent bromide ANTICHOLINERGIC: 6-12 YEAR 12 YEAR ATROVENT 0,25 mg 0,5 mg NEBUL EVERY 6 h EVERY 6 h SIDE EFFECT: MUSCLE TREMOR, TACHYCARDIA PALPILATION, HYPOKALEMIA ANTI-INFLAMMATORY DRUGS 1- CORTICOSTEROID: CORTICOSTEROIDS HAS ANTI-INFLAMMATORY EFFECTS CORTICOSTEROIDS • SUPRESSING TRANSCRIPTION OF INFLAMMATORY GENES • HAVE INHIBITORY EFFECTS ON MANY INFLAMMATORY AND STRUCTURAL CELLS, CYTOKIN ES (IL1, IL5, IL13, TNF, CMCSF) ANTI-INFLAMMATORY DRUGS IT IS IMPORTANT TO RECOGNISE THAT STEROIDS SUPRESS INFLAMMATION IN THE AIRWAYS BUT DO NOT CURE THE UNDERLYING DISEASE Etken madde Ilaç adı Veriliş yolu Doz IV Hydrocortisone 2-4 mg/kg Every 6 hr ORAL Prednisone 1-2 mg/kg max 60-80 mg/day prednisolone INHALED Beclamethasone Beclaforte MDI 250 mcq dipropionate Becotide MDI 50 mcq Budesonid Pulmicort turbahaler 100-200 mcq Pulmicort MDI 50-100 mcq Fluticasone Flixotide propinate Flixotide 50-125 mcq discus 100 mcq SIDE EFFECT: DYSPHONIA, ORAPHARYNGEAL CANDIDIASIS, COUGH, ADRENAL SUPRESSION, GROWTH SUPRESSION, OSTEOPROSIS CATARACTS, GLOUCOME, 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” 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 SLOW-RELEASE PREPARATIONS Theo-Dur 100-200-300 mg Talotren 200-300 mg Theo-Kap 100-200-300 mg SIDE EFFECT: NAUSEA, VOMITING, GASTRIC DISCOMFORT, HEADACHES CARDIAC ARRYHYTMIAS, EPILEPTIC SEIZURES 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 2- CROMOLYN SODIUM • BLOCKING RESPONSE EARLY BUT ALSO THE LATE • 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 SIDE EFFECTS: CROMOLYN IS ONE OF THE SAFEST DRUGS AVAILABLE AND SIDE EFFECTS ARE EXTREMELY RARE. THROAT IRRITATION, COUGHING 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 ANTILEUCOTRIENES IS THAT THEY ARE ACTIVE IN TABLET FORM. THIS MAY INCREASE THE COMPLIANCE WITH CHRONIC THERAPY AND IT WILL MAKE TREATMENT OF CHILDREN EASIER MONTELUKAST (SINGULAIR) ZAFIRLUKAST (ACCOLATE) 5 YEAR↓ 4 mg ONCE A DAY 5-14 YEAR 5 mg “ “ 14 YEAR 10 mg “ “ 12 YEAR 2x1 SIDE EFFECT: MONTELUKAST WELL TOLERATED IN CHILDREN WITH NO SIGNIFICANT ADVERSE EFFECTS. HIGH DOSES OF ZAFIRLUKAST MAY BE ASSOCIATED WITH ABNORMAL LIVER FUNCTION 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 TABLET 1 mg 2x1 2x1 NEDOCROMIL SODIUM: NEDOCROMIL SODIUM HAS ANTI INFLAMATORY EFFECTS. IT IS EFFECTIVE IN EIA TILADE 4 mg 2-4x4 puff SIDE EFFECTS: SAME AS CROMOLYN SODIUM 6 YEAR 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 IMMUNOTHERAPY • IT SEEMS TO BE MORE EFFECTIVE IN CHILDREN THAN IN ADULTS • IT IS MORE EFFECTIVE WHEN EMPLOYING HIGH DOSE SINGLE-ALLERGEN THERAPY IT MUST BE APPLILED BY A SPECIALIST Table 1 NAEPP elassification of disease severity* Disease serverity Symptoms/day Symptoms/night Peak flow or FEV1 Peak flow variability Mild İntermittent < 2 days/week < 2 nights/month >80% <20% Mild persistent > 2 week but <1/day >2 nights/month >80% 20-30% Modere persistent Daily >1 night/week >60% - <80% >30% Severe persistent Continual Frequent <60% >30% Table 2 Stepwise approach for managing infants and young children (<5 years Severity class Daily medications Step 4 Severe persistent • Preferred treatment: high-dose ICS + LABA and, • if needed: corticosteroid tablets or syrup long-term Step 3 Moderate persistent • Preferred treatment: low-dose ICS + LABA or medium-dose ICS • Alternative treatment: low-dose ICS + LTRA or theophylline • If needed: medium-dose ICS + LABA • Alternative treatment: medium-dose ICS + LTRA or theophylline Step 2 Mild persistent • Preferred treatment: low-dose ICS • Alternative treatment: cromolyn or LTRA Step 1 Mild intermittent • No daily medication needed Table 3 Stepwise approach for adults and children (>5 years) Severity class Daily medications Step 4 Severe persistent • Preferred treatment: high-dose ICS + LABA and, if needed, corticosteroid tablets or syrup long-term Step 3 Moderate persistent • Preferred treatment: low-to-medium dose ICS + LABA • Alternative treatment: increase ICS dose within mediumdose range OR low-to-medium dose ICS + LTRA OR theophylline If needed: increase medium-dose ICS + LABA • Alternative treatment: increase medium-dose ICS + LTRA or theophylline Step 2 Mild persistent • Preferred treatment: low-dose ICS • Alternative treatment: cromolyn, LTRA, nedocromil or theophylline SR (serum concertration of 5 -15 μ/mL) or LTRA Step 1 Mild intermittent • No daily medication needed TREATMENT OF ACUTE EPISODES OF ASTHMA MILD IS ASSOCIATED WITH COUGH AND AUDIBLE WHEEZING WITHOUT ANY FROM OF DISTRESS, CYANOSIS, INCREASED RESPIRATORY RATE OR IMPAIRMENT OF ACTIVITY, THEY CAN SPEAK IN NORMAL SENTENCES BETWEEN BREATHS. PEF OR FEV, ABOVE 75% OF PREDICTED VALUES MODERATE IS ASSOCIATED AUDIBLE WHEEZE, USE OF ACCESSORY MUSCLES, A SLIGHT INCREASE IN RESPIRATORY RATE, INABILITY TO WALK, THEY CAN SPEAK MORE THAN THREE OR FIVE WORDS BETWEEN BREATHS SEVERE IS ASSOCIATED WITH CYANOSIS SEVERE DISTRESS, LOWER RIB RETRACTION, ONLY ONE TO THREE WORDS OF SPEESH WILL BE POSSIBLE BETWEEN BREATH AND THE PATIENT WILL BE CHAIR OR BED BOUND TREATMENT OF ACUTE EPISODES OF ASTHMA INHALED 2 AGONIST MDI (with or without a spacer) 4-6 h FOR 24-36 h MILD IF THERE IS RAPID IMPROVEMENT SEND TO HOME IF THERE IS NO IMPROVEMENT ADDED IPRATROPIUM BROMIDE (by nebulizer) OR HIGHER DOSES OF 2 AGONIST IF THERE IS INCOMPLETE RESPONSE OR RELAPS OF SYMPTOMS WITHIN 4 h MODERE ADDED ORAL CORTICOSTEROID (1-2 mg) IF THERE IS NO IMPROVEMENT AFTER 3 DOSES OF 2 AGONIST HOSPITALIZED NEBULIZED 2 AGONIST + OXYGEN SEVERE I.V HYDROCORTIZONE (4 mg/kg) EVERY 4-6 h IF THERE IS NOT IMPROVEMENT ADMISSION TO INTENSIVE CARE ADDED I.V AMINOPHYLLINE IF THERE IS NOT IMPRAVEMENT MECHANICAL VENTILATION