Transcript bronchial asthma

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