BRONCHIAL ASTHMABRONCHIAL 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%

CLASSIFICATIONCLASSIFICATION

A) ALLERGIC OR EXTRINSIC ASTHMA

POLLENSFOODSDUST MITES IgE MEDIATEDANIMAL DANDERSRSV

B) INTRINSIC OR NONALLERGIC ASTHMATEMPERATURE CHANGESCOLD AIRODORIRRITANSMENSESSMOKEVIRUS

C) EXERCISE INDUCED ASTHMA

D) ASPIRIN INDUCED ASTHMA

RISK FACTORS FOR CHILDHOOD ASTHMARISK FACTORS FOR CHILDHOOD ASTHMA

• FAMILIAL AND GENETIC FACTORS

• ATOPY

• ENVIRONMENTAL FACTORS VIRAL

• RESPIRATORY TRACT INFECTION BACTERIAL?

• AMBIENT AIR POLLUTION (NO2, SO2, O3)

• PASSIVE EXPOSURE TO CIGARETTE SMOKE

• PSYHOLOGIC FACTORS

• COLD AIR

• EXERCISE

RISK FACTORS FOR CHILDHOOD ASTHMARISK FACTORS FOR CHILDHOOD ASTHMA

NASAL POLYPS• ASPIRIN REACT ALSO TO TARTARAZINE YELLOW

URTICARIA

(INHIBITS CYCLOOXYGENASE PATWAY)

• PRESERVATIVE (SULFIDES) LETTUCE

FRESH SALADDRIED FRUITSDRIED POTATOESWINESOFT DRINKS

MECHANISM OF ASTHMAMECHANISM 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 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

MEDIATORS WITH ACTIONS THAT CAUSE AIRWAY OBSTRUCTIONMEDIATORS WITH ACTIONS THAT CAUSE AIRWAY OBSTRUCTION

BRONCHOCONSTRICTIONBRONCHOCONSTRICTION

HISTAMINE

BRADYKININ

LEUKOTRIENES C.D.E

PGD2, PGF2

THROMBOXANE A2 AND B2

INCREASED CAPİLLARY PERMEABILITYINCREASED CAPİLLARY PERMEABILITY

HISTAMINE

BRADYKININ

LEUKOTRIENES C.D.E

PGE

SECRETION OF MUCUSSECRETION OF MUCUS

HISTAMINE

LEUKOTRIENES C.D

HETEs

PGD2, PGF2, PGI2, PGE

PATHOLOGY OF ASTHMAPATHOLOGY 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 HYPERINFLATION

VENTILATION

↓ ↓ MISMATCHING DECREASED OF VENTILATION COMPLIANCE AND PERFUSION

↓ ↓ALVEOLAR INCREASED

DECRAESED HYPOVENTI WORK OF BREATHING LATIONASIDOSIS

PULMONARY VASOCONSTRICTION

THE PATHOPHYSIOLOGY OF ASTHMA

PCO2PO2

CLINICAL FINDINGSCLINICAL 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

DIAGNOSISDIAGNOSIS

• HISTORY

• ATOPY

• CLINICAL FINDINGS

• LABROTORY FINDINGS

PHYSICAL EXAMINATIONPROLONGATION OF EXSPIRATIONHIGH-PIYCHED MUSICAL WHEEZING LOUDER ON EXSPIRATIONCOARSE RHONCHIELEVATION OF THE RIBS (INSPECTION)

USE OF THE ACCESSORY MUSCLESPULSUS PARADOXICUS INDICATESPULSE RATE 120-130 SEVERE RESPIRATION RATE RISES TO 20-30 OBSTRUCTION CYANOSIS

MILD MILD INTERMITENT – PRESİSTENT INTERMITENT – PRESİSTENT ASTHMAASTHMA

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 BETWEENOR FUNCTIONAL IMPAIRMENT EPISODES

NORMAL LUNG FUNCTION BETWEEN EPISODESPROPHYLACTIC THERAPY IS USUALLY NOT REQUIRED

MODERATE ASTHMA FREQUENT EPISODIC MODERATE ASTHMA FREQUENT EPISODIC ASTHMAASTHMA

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 ASTHMASEVERE 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 TESTSBLOOD COUNTEOSINOPHILISNASAL EOSINOPHIL COUNT 10% (+)IMMUNGLOBULINS(G. A. M) (G1. G2. G3. G4)IgESKIN TESTSCHEST X-RAY PPDX-RAY FILMS OF PARANASAL SINUSIS1 ANTITRYPSINMEASUREMENT OF SWEAT ELECTROLYTESPULMONARY FUNCTION TESTPO2PCO2BICARBONATE LEVELS

PULMONARY FUNCTION TESTPULMONARY 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 TESTPULMONARY 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 DIAGNOSISDIFFERENTIAL DIAGNOSIS

• INFANTS AND YOUNG CHILDREN

• BRONCHIOLITIS

• FOREIGN BODY

• CROUP

• EPIGLOTTITIS

• CYSTIC FIBROSIS

DIFFERENTIAL DIAGNOSISDIFFERENTIAL DIAGNOSIS

• IMMOTILE CILIA SYNDROME

• HABIT COUGH

• BRONCHOPULMONARY DYSPLASIA

• TRACHEOMALACIA

• TRACHOESOPHAGEAL FISTULA, ANOMALIES OF AORTIC ARCH

• GASTROESOPHAGEAL REFLUX

OLDER CHILDREN AND YOUNG ADULTSOLDER CHILDREN AND YOUNG ADULTS

• TBC• HABIT COUGH

• VOCAL CORD DYSFUNCTION

• HYPERVENTILATION

• 1 ANTITRYPSIN DEFICIENCY

• CYSTIC FIBROSIS

• IMMOTILE CILIA SYNDROME

• CARCINOID SYNDROME

• BRONCHIECTASIS

COMPLICATIONSCOMPLICATIONS I I

• INFECTIONBRONCHITISPNEUMONITISSINUSITISO.MEDIA

• BRONCHIECTASIS• ATELECTASIS• MEDIASTINAL AN SUBCUTANEOUS EMPHYSEMA

COMPLICATIONSCOMPLICATIONS II II

• PNEUMOTHORAX

• COUGH SYNCOPE

• GROWTH COMPLICATIONS

A) INHIBITION OF LINEAR GROWTH AND BONE MATURATIONB) THORACIC DEFORMITIES

• COR PULMONALE

• EMPHYSEMA

• STATUS ASTHMATICUS

• POLIOMYELITIS LIKE ILLNESS

MEDICAL TREATMENTMEDICAL TREATMENT

MEDICAL TREATMENTMEDICAL TREATMENT

BRONCHODILATORS DRUGS

BETA-2 ADRENERGIC AGONISTS

BETA- AGONIST PRODUCE BRONCHODILATATIONBY DIRECTLY STIMULATING BETA-2 RECEPTORSIN AIRWAY SMOOTH MUSCLE, WHICH LEADS TORELAXATION

2 agonist Etken madde

İlaç adı Veriliş yolu

Doz

Short acting Terbutaline Bricanly MDI 200 mcq

Bricanly Susp

Salbutomal Ventolin MDI 100 mcq

Ventolin nebul 2-5 mg

Ventolin susp

Long acting Salmoteral Serevent MDI 25-50 mcq

Astmerol MDI 25-50 mcq

Formoteral Forodil MDI 12 mcq

Antıcholınergıc Ipratropium bromide

Atrovent MDI 20 mcq

ANTICHOLINERGIC: ATROVENT NEBUL

6-12 YEAR 0,25 mg EVERY 6 h

12 YEAR 0,5 mg EVERY 6 h

SIDE EFFECT:SIDE EFFECT:

MUSCLE TREMOR, TACHYCARDIA PALPILATION,

HYPOKALEMIA

ANTI-INFLAMMATORY DRUGSANTI-INFLAMMATORY DRUGS

1-1- CORTICOSTEROID: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 DRUGSANTI-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 50-125 mcq

propinate Flixotide discus 100 mcq

SIDE EFFECT:SIDE EFFECT:

DYSPHONIA, ORAPHARYNGEAL CANDIDIASIS,

COUGH, ADRENAL SUPRESSION, GROWTH

SUPRESSION, CATARACTS, GLOUCOME,

OSTEOPROSIS

2-2- METHYLXANTHINESMETHYLXANTHINES

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

Theo-Dur 100-200-300 mg

Talotren 200-300 mg

Theo-Kap 100-200-300 mg

SLOW-RELEASE PREPARATIONSSLOW-RELEASE PREPARATIONS

SIDE EFFECT:SIDE EFFECT:

NAUSEA, VOMITING, GASTRIC DISCOMFORT, HEADACHES CARDIAC ARRYHYTMIAS, EPILEPTIC SEIZURES

2- CROMOLYN SODIUM2- 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 SODIUM2- 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 HYPERRESPONSIVENESSCROMOLYN IS A PROPHYLACTIC DRUG OF FIRST CHOISE IN CHILDREN BECAUSE IT HAS ALMOST NO SIDE EFFECTS

INTAL 5 mg MDI 4x1

SIDE EFFECTS:SIDE EFFECTS:

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

3- ANTI- LEUCOTRIENES3- 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

5 YEAR↓ 4 mg ONCE A DAY MONTELUKAST 5-14 YEAR 5 mg “ “

(SINGULAIR) 14 YEAR 10 mg “ “

ZAFIRLUKAST 12 YEAR 2x1(ACCOLATE)

SIDE EFFECT:SIDE EFFECT:

MONTELUKAST WELL TOLERATED IN CHILDREN WITH NO SIGNIFICANT ADVERSE EFFECTS.

HIGH DOSES OF ZAFIRLUKAST MAY BE ASSOCIATED WITH ABNORMAL LIVER FUNCTION

4- KETOTIFEN4- 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 2x1TABLET 1 mg 2x1

NEDOCROMIL SODIUM:

NEDOCROMIL SODIUM HAS ANTI INFLAMATORY

EFFECTS. IT IS EFFECTIVE IN EIA

TILADE 4 mg 2-4x4 puff 6 YEAR

SIDE EFFECTS:SIDE EFFECTS:

SAME AS CROMOLYN SODIUM

IMMUNOTHERAPYIMMUNOTHERAPY

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

IMMUNOTHERAPYIMMUNOTHERAPY

• 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 medium-dose 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 ASTHMATREATMENT OF ACUTE EPISODES OF ASTHMA

INHALED 2 AGONISTMDI (with or without a spacer)

MILD 4-6 h FOR 24-36 h

IF THERE IS RAPID IF THERE IS NO IMPROVEMENT ADDED IMPROVEMENT IPRATROPIUM BROMIDE (by nebulizer) SEND TO HOME OR HIGHER DOSES OF 2 AGONIST

IF THERE IS INCOMPLETE RESPONSEOR RELAPS OF SYMPTOMS WITHIN 4 h

MODEREADDED 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