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Wheezy Child: Diagnostic and Therapeutic Approach. Remziye Tanaç, M.D. Ege University Faculty of Medicine Department of Pediatric Pulmonology and Allergy, Izmir, Turkiye. - PowerPoint PPT Presentation
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Wheezy Child: Diagnostic and Therapeutic
Approach
Remziye Tanaç, M.D.Ege University Faculty of Medicine
Department of Pediatric Pulmonology and Allergy, Izmir, Turkiye.
Wheezing; Generally a pathological sound ( sometimes can be heard normally during forced expiratory maneuver) which shows pathological obstruction of lower respiratory tracts.
Wheezy Child; A child whose wheezing persists more than one month and/or has had 3 or more wheezing attacks.
Atypical WheezingGERHCystic fibrosisPrimary ciliary dyskinesiaImmune deficienciesBPDHeart diseasesFBATbcCongenital anomalies
Typical Wheezing Transient wheezingNonatopic (viral)Atopic (persistent)Severe intermittent(PRACTALL)
Tucson Children’s Respiratory Study
n= 1246Beginning in 1980, birth-cohort-11 years49 % wheezing in 0-6 years.
Martinez FD. et all. N. Eng. J. Med. 1995, 332: 133-138
Taussig LM et al JACITaussig LM et al JACI 2003;111:661-752003;111:661-75
Tucson Children’s Respiratory Study
Transient Early Wheezing• Exists in 0-3 years. • Disappears in third year.
Responsible for80 % in first year 60 % in second year 40 % in third year of all.
• Similar frequency history in family.• No asthma or atopy history in family.• No atopy, eosinophilia or
inflammation in infant. • Wheezing after viral infections.
Transient Early Wheezing (Lung Function Tests)
• Lung functions are decreased at birth.• Improves as the infant gets older.• Can’t exactly catch his/her coequals.• PEF variability in 11 years old and
response to metacholine are similar to normal children.
• Becomes COPD if smokes in adulthood.
Transient Early Wheezing Risc Factors
• Prematurity, low birth weight• Maternal smoking during pregnancy or in
postnatal period• Going to day-care center early• Siblings at home• Lower maternal age
Non-atopic Wheezing• 40 % of persistent wheezy
infants• They are non atopic.• Change in control of airway
tonus Congenital, infection relation?Congenital, infection relation?• Attacks are related with viral
infections (most commonly RSV)
• RSV increases the risk until 10th year, ineffective after 13rd year.
Tucson Children’s Respiratory StudyTucson Children’s Respiratory Study 472 LRTI;207 43.9 % RSV68 14.4 % Parainfluenza68 14.4 % Adenovirus, influenza, CMV, Chlamydia, rhinovirus, bacteria, mix infec.129 27.3 % non-infective pathogen
Non-Atopic Wheezing (Lung function tests)
• 0-3 years, RSV (+) Lung function test < RSV(-)
• Bronchodilatator responseRSV (+) Lung fxn test > RSV (-)
The difference persists during 11st year.
Atopic Wheezing (Asthma)• 60 % of persistent
wheezers.• 50 % : before 3rd year, 80
% : before 6th year• Family asthma history• Allergic rhinitis or atopic
dermatitis in patient• Eosinophilia, high serum
IgE level, BHR(+)• Early aeroallergen
sensitization
Early and Late Atopic WheezingEarly atopic wheezing
If atopic wheezing of children has been detected before 3 years old and if it persists during 6th yearHave worse lung function tests, more severe bronchial reactivity, higher serum IgE levels.
Late atopic wheezing If atopic wheezing of children has been detected after 3rd year and if it persists during 6th yearHave better lung function tests, milder bronchial reactivity, less high serum IgE levels.
Allergic sensitivity and asthmaAllergic sensitivity and asthmaFactors which alter asthma riscFactors which alter asthma risc
IncreasesIncreases• Early allergic
sensitization• Sensitization with
some aeoroallergens (perennial)
• Eosinophilia
DecreasesDecreasesIn young ages • Contact with other
children• Contact with cats• Contact with some
farm animals
Taussig LM et al JACITaussig LM et al JACI 2003;111:661-752003;111:661-75
AsthmaViral inf. wheezing
Transient wheezing
Tucson Children’s Respiratory Study
Major criteria Minor criteria
Parental asthma Allergic rhinitis
Eczema Wheezing without common cold
Eosinophilia > 4 %
Castro Rodriguez JA et al. AJRCCM 2000;162: 1403-6
CLINICAL INDEX FOR ASTHMA RISC
CLINICAL INDEX FOR ASTHMA RISC
Loose index Stringent index
Early wheezing Early frequent wheezing ≥ 3
+ +
1 major or two minor 1 major or two minor
Castro Rodriguez JA et al. AJRCCM 2000;162: 1403-6
Performance of Indexes
OR Sensitivity Specifity PPV NPV
Loose index 4 42 % 85 % 59 % 87-94 %
Stringent index
7 16 % 97 % 77 % 84-92 %
Cystic Fibrosis
• Recurrent RTI • Prolonged jaundice• Meconium ileus• Rectal prolapse• Extreme sweating• Steatorrhea• Growth retardness
• Sweat test• Cl > 60 mEq/l• Mutation analysis
Aspiration Syndromes
• H type TEF• Swallowing malfunction
Familial disautonomiaCleft palateCerebral palsyMusculary dystrophia
• GERH
• Scintigraphy• pH monitorization
Airway Compression
• Airway wall insufficiencyLaryngomalaciaTracheomalaciaSubglottic hemangioma
• Vasculary ring• Perihilar adenopathy
• Bronchoscopy• HRCT• MRI
Congenital Anomalies
• Congenital heart diseaseVSD, ASD, MS, hypoplastic
left heart• Tracheal bronchus• Diaphragmatic hernia
• ECG• ECHO• CT• Bronchoscopy
Immune Deficiencies
• IgG and subgroup deficiencies• Selective IgA deficiency• X linked infantile agammaglobulinemia -
Bruton• Common variable
hypogammaglobulinemia
IgAIgGIgG subgroup
Nonspecific Airway Irritation
• Child nursery centers• Tobacco smoke
ActivePassive
• Air pollutionSO2NONO2Particles
Infections
• RSV, Adenovirus....• Mycoplasma• Chlamydia• Tbc
Agents in Respiratory Tract Infections with Wheezing
0-12 months
1-5 years 6-15 years
RSV RSV Rhinovirus
P.Influenza P.Influenza Influenza
Adenovirus Influenza Mycoplasma
RSV Complications
• Acute ComplicationsApnea 0-6 ay 20 % SIDS
• Long-term complicationsAirway hyperreactivity
Wheezing-Asthma
Long term prognosis of bronchial hyperreactivity seen in these patients
Symptom %2 years 82 %
3.5 years 69 %
4-5 years 55 %
6-8 years 31 %
0,820,69
0,55
0,31
00,10,20,30,40,50,60,70,80,9
2years
3,5years
4-5years
6-8years
RESULT
RSV-LRTI Reactive airway 20-30 %
EUTF Department Of Pediatric Pulmonology & Allergy
1994 - 1998
Acute Bronchiolitis 161
More than 3 attacks 14.1 %
Family atopy history (+) 25 %
EUTF Department Of Pediatric Pulmonology & Allergy
Retrospective
314 patients 0-5 years oldGERH 18 % CF .006%Tracheal Br .006%Asthma 32 %FBA 1 %Bronchiolitis Ob. .025%Viral Inf.? 33 %
If the diagnosis of patient is asthma with a high probability according to all criteria
TREATMENT
CONTROLLED PARTLY CONTROLLED
UNCONTROLLED
Daytime symptoms None
(twice or less/ week)
More than twice /week
Three or more features of partly controlled asthma
present in any week
Nocturnal symtoms/ awakening
None Any
Limitation of activities None Any
Need for releiver/rescue treatment
None (twice or less/
week)
More than twice /week
PEF or FEV1 Normal < 80% predicted or personal best
Exacerbations None One or more /year One in any week
GINA 2006
Step 2 Step 3 Step 4 Step 5Step 1
Asthma EducationEnviromental Control
As needed rapid acting 2
agonists As needed rapid acting 2 agonists
Controller options
Select one Select one Add one or more
Add one or both
Low-dose ICS Low-dose ICS + LABA
Medium or high dose ICS+
LABA
Oral steroid
LTRA Medium or high dose ICS
LTRA Anti-IgE
Low-dose ICS+ LTRA
Theophylline
Low-dose ICS+ Theophylline
INCREASEREDUCE TREATMENT STEPS
GINA 2006
GINA 2006
• Antiinflammatory• LTRA effective?• Bronchodilatators
Efficacy of Bronchodilatator Usage
Bronchodilatators• Double-blind, randomized, placebo, cross overAtopic, n=48, 3 months - 1 year2 months 3x200 g SalbutamolClinical symptoms, Lung fxn tests
Result;Partial recovery.No statistical difference.
Chavasse R.:Arch.Dis.child. 2000, 2-5, 370-75
Bronchodilatators
2 agonists (short acting)Atopic n=43 < 2 years
Clinical Score +SD 3.75+1.25-2.80+1.65 p<0.0102 saturation 94.8 + 2.84 %– 95.2+ 2.54Effective (in acute period)
Bentur L.:Pediatrics 1992:89,133-37
ICS + Bronchodilatator effective
Teper A.M.: Am.J.Crit.Car.Med., 2005:171, 587
Bronchodilatators
Metaanalysis– <2 years agonist (short acting)• Randomized placebo controlled
8 study3 at home2 in hospital3 in Lung Function Test lab.
• Symptom scoresNo obvious benefit under 2 years
Bronchomotor tonus?Chavasse R.:Cochrane Database Sys.Rev. 2002: (3) CD 002873
Result: The studies are not sufficient to make a certain comment (bronchomotor tonus?). But it can be used according to guidelines in patients who are thought to be asthma with a high probability.
Efficacy of LTRA Usage
LTRA (Asthma)
• Double-blind, placebo controlled• n=689 n=228(placebo) n=461(LTRA)• 2-5 Years intermittent asthma• Duration 12 weeks• Symptom score• Drug usage
Knorr B.:Pediatrics 2001: 108:3, 1-3
Montelukast 4 mg*Montelukast 4 mg*(n=461)(n=461)
00 22WeeksWeeks
PhasePhase I I PreparationPreparation Mono-blindMono-blind
PhasePhase II IIAActive Treatmentctive Treatment (12 (12
wweekseeks))Double-blindDouble-blind
1414
PlaPlaccebo (n=228)ebo (n=228)
PlaPlacceboebo
Marked relief in symptoms.
0 2 4 6 8 10 12Weeks in study (postrandomization)
Placebo (n=227)Montelukast 4 mg* (n=458)
Knorr B et al. Pediatrics 2001;108:e48.
0.00
–0.10
–0.20
–0.30
–0.40
–0.50
–0.60
0.05
Chan
ge in
Sco
re (M
ean
± SE
)
LTRA (Asthma)• Placebo controlled study• n = 30 atopic asthma 2-5 years• Duration 4 weeks (montelukast 4 mg)• eNO, airway resistance (Rint)• Statistically significant difference in
antiinflammatory effect and resistanceStraub D.A.:Chest 2005 ; 127:509-14
Viral Infection – WheezingLTRA
RSV Inflammation
RSV
Cysteinyl Leukotrienes
(CysLTs)
TNF RANTES
IL-1IL-6
T-cell activation
IFNTh1
IL-4, IL-5Th2
MacrophagesNK cells
Neutrophils
van Schaik SM et al. Pediatr Pulmonol 2000;30:131-138
BasophilsMast cells
Eosinophils
Inflammatorymediators
Wheezing
48
cysLT concentration in secretion (log
pg/ml)
500
50Acute URI
(n=17)Bronchiolitis
(n=35)Recurrent wheeze (n=10)
p=0.009p=0.006
van Schaik SM et al. J Allergy Clin Immunol 1999;103:630-636
Montelukast - RSV Post-Bronchiolitis
• Randomized, double-blind, parallel• Hospitalized bronchiolitis• Proved RSV• 130 children • 3-36 months (mean 9 months)• Beginning of treatment: In 7 days• Duration of treatment: 28 days• Symptom score
Bisgaard H. Am J Respir Crit Care Med 2003;167:379-383
Symptom-free day and nights
(%)
Bisgaard H. Am J Respir Crit Care Med 2003;167:379-383
Days
30
20
10
00 7 14 21 28
Montelukast (n=61) mean number %22Placebo (n=55) mean number % 4
p=0.015
Weeks 48
Visits 7
8
Placeborun-in
Placebo
Montelukast 4 or 5 mg
36
1 2 3 4 5 6
241680-2-3
Bisgaard H et al. PREVIA Am J of Resp Crit Care Med 2005; 171, 315-22
Age: 2-5 years (mean 44 months)Mild asthma≥3 attacks in 12 months after URTIs
2.34
1.60
0
1
2
3
Montelukast 4 mg (n=265)
Placebo (n=257)
Exacerbations / years
32%
p0.001
Bisgaard H et al. Am J of Resp Crit Care Med 2005; 171, 315-22
As a result; in patients who has asthma with a high probability, LTRA can be used due to the guidelines.
But in patients whose asthma diagnosis is uncertain, good evaluation of the patient and more studies on this issue are needed for definite indication.
According to GINA 2006, LTRA is effective in postinfectious asthma exacerbations.
Usage and Efficacy of Inhaled Steroids
Antiinflammatory Treatment
Effectiveness ICS
School Child, Adolescent, Adult• Reduction in symptoms• Improvement in lung functions• Improvement in airway reactivity• Reduction in admissions to emergency room and
hospitalizationRytila P.:Allrgy 2004;59:839-41Merkus PJFM.:Eur.resp.J. 2004;23:861-68
Boehmer ALM.:Carr.Op.IPL Pulm.Med. 2006;12:34-41
ICS
Placebo controlled recurrent wheezingn = 30 age mean 16 (7-24) monthsTreatment: FP. 100-250 micrograms/day, duration 6 monthsSymptom score – 2 agonist usageSide effect (development, bone density)Result: effective, no side effects
Teper A.M.:Ped.Pulmonol.2004;37:111-15
ICSPlacebo controlled recurrent wheezingn = 26 age: (0-2)Treatment: FP 250 micrograms/day, duration 6 monthsVmax – FRCResult: Effective
Teper A.M.:Am.J.Crit.Care.Med. 2005;171: 584-89
ICSPlacebo controlled wheezy childn = 62 Age: 11.3 (7-20) monthsTreatment: FP 200 micrograms/day, duration 3 monthsSymptom score, VmaxFRCResult: Ineffective, duration is shortHofius W.:Am.J.Crit.Care.Med. 2005;171:328-33
ICS
Boehmer ALM: Cur.Op.Pulm.Med. 2006;12:34-41
ICS – Viral Wheezing
Placebo controlled studyn = 104 Age: 100 (84-119) monthsTreatment: BDP 400 g/gün
duration 6 monthsNumber of attacks, score , FEV1
No difference from placebo
Doul I.J.:BMJ. 1997;315:858-62
Beclomethasone 400 μg/gün
Placebo
Days with RTI sypmtoms %
16 ± 26 26 ± 29
Frequency (day/year)
5.6 ± 4.2 7.0 ± 6.1
Attack max score 3.2 ± 1.7 3.7 ± 1.8
Mean duration (day)
6.8 ± 6.0 6.3 ± 3.6
ICS – Viral Wheezing
FEV1 EffectiveDoul I.J.:BMJ 1997;315:858-62
ICS – Viral Wheezing
Placebo controlled studyn = 40 Age:1.9 (0.8-6.0)
yearsTreatment: 4 monthsScore, admission to E.R.
No difference from placebo.
Willson N.:Arch Dis.Child. 1995;72:317-20
Budesonide Placebo
Total duration
Daily score (med)
0.6 0.6
Symptom-free days (med)
73 78
Acute episode
Total score (mean)
30 31
Nocturnal / daytime cough
7.8/4.0 7.3/4.0
Nocturnal / daytime whe.
7.5/5.1 7.6/5.0
Number of episodeEpisode duration (d)
2.6
8.0
2.4
8.6
Result: Although ICSs are less effective in young ages when compared to school children and adults, it’s still more effective than the other medications in these ages.
Should be used in treatment.
Treatment in 0-2 Years (asthma)
• >3 exacerbations in last 6 months, responsive to bronchodilatators
•In acute attack (intermittent), first choice is β2 agonists.
•LTRA in viral wheezy child for controller effect
•In patients with persistent asthma, first choice is inhaled steroids (100-200 µgr /day)
•In frequently repetitive acute attacks, oral corticosteroids 3-5 days
PRACTA L.L.Allergy 2008; 63;5-34
Treatment in 3-5 Years (asthma)
• ICS first choiceBDS 100-200 µgrx2 days or Flutic 50-125 µgrx2 days
• Short acting β2 agonists, for every 4 hours 1-2 puff when needed• LTRA as a monotherapy in intermittent and mild persistent patients
instead of ICS • If not fully controlled with ICS, add LTRA • If not still well controlled, add LABA according to age. Increase ICS
dosage. Add theophylline.
PRACTALL.ALLERGY 2008:63;5-34
Well-controlled Asthma
• Daytime symptoms twice or less per week (not more than once on each day)
• No limitations of activities due to asthma• Night-time symptoms 0-1 per month • Reliever/rescue medications twice or less per week• Normal lung function (if able to measure)• 0-1 exacerbations in the last year
PRACTALL Allergy. 2008: 63;5-34
Result
• Inhale steroids are the main drugs in the treatment. Should be used.
• LTRA can be used as a monotherapy or with ICSs in post-infectious (viral) wheezings.
• Bronkodilatators can be used in acute period or if needed.PRACTALL 2008-GINA 2006
Treatment of Atypic Wheezing
• The underlying disease should be treated.
Thanks...