Download Wheezy Child: Diagnostic and Therapeutic Approach

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.
Typical Wheezing
Transient wheezing
Nonatopic (viral)
Atopic (persistent)
Severe intermittent
(PRACTALL)
Atypical Wheezing
GERH
Cystic fibrosis
Primary ciliary dyskinesia
Immune deficiencies
BPD
Heart diseases
FBA
Tbc
Congenital anomalies
Tucson Children’s Respiratory
Study
n= 1246
Beginning in 1980, birth-cohort-11 years
49 % wheezing in 0-6 years.
Martinez FD. et all. N. Eng. J. Med. 1995, 332: 133-138
Tucson Children’s Respiratory
Study
Taussig LM et al JACI 2003;111:661-75
Transient Early Wheezing
• Exists in 0-3 years.
• Disappears in third year.
Responsible for
80 % 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?
• Attacks are related with viral
infections (most commonly
RSV)
• RSV increases the risk until
10th year, ineffective after 13rd
year.
Tucson
Children’s Respiratory Study
472 LRTI;
207 43.9 % RSV
14.4 % Parainfluenza
68 14.4 % Adenovirus, influenza, CMV,
Chlamydia, rhinovirus, bacteria,
mix infec.
129 27.3 % non-infective pathogen
68
Non-Atopic Wheezing
(Lung function tests)
• 0-3 years, RSV (+) Lung function test <
RSV(-)
• Bronchodilatator response
RSV (+) 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 Wheezing
Early atopic wheezing
If atopic wheezing of children has been
detected before 3 years old and if it persists
during 6th year
Have 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 year
Have better lung function tests, milder bronchial
reactivity, less high serum IgE levels.
Allergic sensitivity and asthma
Factors which alter asthma risc
Increases
• Early allergic
sensitization
• Sensitization with
some
aeoroallergens
(perennial)
• Eosinophilia
Decreases
In young ages
• Contact with other
children
• Contact with cats
• Contact with some
farm animals
Tucson Children’s Respiratory
Study
Transient
wheezing
Viral inf.
wheezing
Asthma
Taussig LM et al JACI 2003;111:661-75
CLINICAL INDEX FOR ASTHMA RISC
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
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 disautonomia
Cleft palate
Cerebral palsy
Musculary dystrophia
• GERH
• Scintigraphy
• pH monitorization
Airway Compression
• Airway wall
insufficiency
Laryngomalacia
Tracheomalacia
Subglottic
hemangioma
• Vasculary ring
• Perihilar adenopathy
• Bronchoscopy
• HRCT
• MRI
Congenital Anomalies
•
• Congenital heart
•
disease
•
VSD, 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
IgA
IgG
IgG subgroup
Nonspecific Airway Irritation
• Child nursery centers
• Tobacco smoke
Active
Passive
• Air pollution
SO2
NO
NO2
Particles
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 Complications
Apnea
0-6 ay
20 %
SIDS
• Long-term complications
Airway hyperreactivity
Wheezing-Asthma
Long term prognosis of bronchial hyperreactivity
seen in these patients
Symptom
2 years
%
82 %
0,9
0,8
0,82
0,69
0,7
0,6
3.5 years
4-5 years
6-8 years
69 %
55 %
31 %
0,55
0,5
0,4
0,31
0,3
0,2
0,1
0
2
3,5
4-5
6-8
years years years years
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 old
GERH
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
GINA 2006
Daytime
symptoms
CONTROLLED
PARTLY
CONTROLLED
None
More than twice
/week
(twice or less/
week)
Nocturnal
symtoms/
awakening
None
Limitation of
activities
None
Any
Need for
releiver/rescue
treatment
None
More than twice
/week
PEF or FEV1
Exacerbations
(twice or less/
week)
UNCONTROLLED
Any
Normal
< 80% predicted or
personal best
None
One or more /year
Three or more
features of partly
controlled asthma
present in any
week
One in any week
GINA 2006
REDUCE
Step 1
TREATMENT STEPS
Step 2
Step 3
INCREASE
Step 4
Step 5
Asthma Education
Enviromental Control
As needed
rapid acting
2 agonists
As needed rapid acting 2 agonists
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
Controller
options
Low-dose ICS
+ Theophylline
GINA 2006
• Antiinflammatory
• LTRA
• Bronchodilatators
effective?
Efficacy of Bronchodilatator Usage
Bronchodilatators
• Double-blind, randomized, placebo, cross over
Atopic, n=48, 3 months - 1 year
2 months 3x200 mg Salbutamol
Clinical 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<0.01
02 saturation 94.8 + 2.84 %– 95.2+ 2.54
Effective (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
2 agonist (short acting)
• Randomized placebo controlled
8 study
3 at home
2 in hospital
3 in Lung Function Test lab.
• Symptom scores
No 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)
Phase I
Phase II
2-5 Years intermittent asthmaPreparation
Active Treatment
Mono-blind
Double-blind
Duration 12 weeks
Symptom score
Drug usage
(12 weeks)
Montelukast 4 mg*
(n=461)
Placebo
Placebo (n=228)
0
2
Knorr B.:Pediatrics 2001: 108:3, 1-3
14
Weeks
Change in Score (Mean ± SE)
0.05
0.00
Placebo (n=227)
Montelukast 4 mg* (n=458)
–0.10
–0.20
–0.30
–0.40
–0.50
–0.60
0
2
4
6
8
10
12
Weeks in study (postrandomization)
Marked relief in symptoms.
Knorr B et al. Pediatrics 2001;108:e48.
•
•
•
•
•
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 resistance
Straub D.A.:Chest 2005 ; 127:509-14
Viral Infection – Wheezing
LTRA
RSV Inflammation
RSV
Th1
T-cell
Th2 activation
Macrophages
NK cells
Neutrophils
TNFa,
RANTES
IL-1
IL-6
Inflammatory
mediators
48
IFNg
IL-4, IL-5
Basophils
Mast cells
Eosinophils
Cysteinyl
Leukotrienes
(CysLTs)
Wheezing
van Schaik SM et al. Pediatr Pulmonol 2000;30:131-138
p=0.006
p=0.009
cysLT
concentration in
secretion (log
pg/ml)
500
50
Acute URI
(n=17)
Bronchiolitis
(n=35)
Recurrent
wheeze
(n=10)
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
30
Montelukast (n=61) mean number %22
Placebo (n=55)
mean number % 4
Symptom-free 20
day and nights
(%)
10
p=0.015
0
0
7
14
Days
21
28
Bisgaard H. Am J Respir Crit Care Med 2003;167:379-383
Age: 2-5 years (mean 44 months)
Mild asthma
≥3 attacks in 12 months after URTIs
Placebo
Placebo
run-in
Montelukast 4 or 5 mg
Weeks
-3
-2
0
8
16
24
36
48
Visits
1
2
3
4
5
6
7
8
Bisgaard H et al. PREVIA Am J of Resp Crit Care Med 2005; 171, 315-22
Exacerbations /
years
3
p0.001
2.34
32%
2
1.60
1
0
Montelukast 4 mg
(n=265)
Placebo
(n=257)
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
hospitalization
Rytila P.:Allrgy 2004;59:839-41
Merkus PJFM.:Eur.resp.J. 2004;23:861-68
Boehmer ALM.:Carr.Op.IPL Pulm.Med. 2006;12:34-41
ICS
Placebo controlled recurrent wheezing
n = 30 age mean 16 (7-24) months
Treatment: FP. 100-250 micrograms/day, duration 6 months
Symptom score – 2 agonist usage
Side effect (development, bone density)
Result: effective, no side effects
Teper A.M.:Ped.Pulmonol.2004;37:111-15
ICS
Placebo controlled recurrent wheezing
n = 26 age: (0-2)
Treatment: FP 250 micrograms/day, duration 6 months
Vmax – FRC
Result: Effective
Teper A.M.:Am.J.Crit.Care.Med. 2005;171: 584-89
ICS
Placebo controlled wheezy child
n = 62 Age: 11.3 (7-20) months
Treatment: FP 200 micrograms/day, duration 3 months
Symptom score, VmaxFRC
Result: Ineffective, duration is short
Hofius 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 study
n = 104 Age: 100 (84-119) months
Treatment: BDP 400 mg/gün
duration 6 months
Number 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 Effective
Doul I.J.:BMJ 1997;315:858-62
ICS – Viral Wheezing
Placebo controlled study
n = 40 Age:1.9 (0.8-6.0)
years
Treatment: 4 months
Score, admission to E.R.
Budesonide
Placebo
Daily score
(med)
0.6
0.6
Symptom-free
days (med)
73
78
30
31
Nocturnal /
daytime cough
7.8/4.0
7.3/4.0
Nocturnal /
daytime whe.
7.5/5.1
7.6/5.0
2.6
2.4
8.0
8.6
Total duration
Acute episode
No difference from placebo.
Willson N.:Arch Dis.Child. 1995;72:317-20
Total score
(mean)
Number of
episode
Episode
duration (d)
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 choice
BDS 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...