Wheezing in
Children
Prof RJ Green
Department of Paediatrics
Adventitious Airway Sounds
Snoring
Stridor
Wheezing
Crepitations
Airway Diameter
Cause of Wheezing
Not from obstruction of small airways –
Surface area too large
From increased intrathoracic pressure +
decreased large airway pressure =
vibration of airway wall in large airways
(Generations 1-5)
Wheezing
Sign of lower (intra-thoracic) airway
obstruction
Small airways
Air Trapping
Hyperinflated chest
Barrel shaped
Loss of cardiac dullness
Liver pushed down
Hoover sign
Hoover Sign
Normal diagphragm movement
Hyperinflation = diaphragm flattened
Diaphragm contraction = paradoxical
inward movement of lower interrcostal
area during inspiration
Acute Wheezing
Asthma
Bronchiolitis
Foreign body
Bronchiolitis
10
What Is Bronchiolitis?
Bronchiolitis is acute inflammation
of the airways, characterised by
wheeze
Bronchiolitis can result from a viral
infection
Respiratory Syncytial Virus (RSV)
may be responsible for up to 90%
of bronchiolitis cases in young
Hall CB, McCarthy CA. In: Principles and Practice of Infectious Diseases 2000:1782-1801;
11 children Panitch HB et al. Clin Chest Med 1993;14:715-731
RSV Is a Common Virus Causing
Bronchiolitis in Children
In a clinical study in Argentina, RSV was the
most common virus isolated from a sample of
children aged <5 years with acute lower
respiratory infection
6.5% 0.7% RSV
6.8%
7.8% Adenovirus
78.2% Parainfluenza
Influenza A
Influenza B
New viruses (Human
Metapneumovirus,
Bocca, Corona)
Carballal G et al. J Med Virol 2001;64:167-174
12
Chronic Wheezing
Thriving child – Happy wheezer
Child failing to thrive - Causes
Exclude other conditions
Structural problems: bronchoscopy
URTD : Polysomnography,
Esophageal disease: Barium swallow, pH
probes, scopes and gram
Primary ciliary dyskinesia: nasal ciliary motility,
Exhaled NO, EM, saccharine test
TB: mantoux, induced sputum/ gastric lavage/
BAL = Culture, microscopy & PCR
Bronchiectasis: HRCT scan, BAL
CF: sweat test, nasal potentials, genotypes
Systemic immune deficiency: Ig subtypes,
lymphocytes & neutrophil function, HIV
Cardiovascular disease: echo, angiography
WHEEZING PHENOTYPES
12 Longitudinal birth cohorts
Original Tucson Group (Taussig L et al 1985)
Persistent
Atopic
Non Atopic
Transient
TRANSIENT WHEEZERS
Commonest form of wheeze
Decrease lung function at birth
No airway hyper-responsiveness
Non Atopic
No immune responses to viruses
Resolves by 3 years
– Wheeze in first year – better outcome
– Wheeze 2-3 year – worse outcome due to
maturity of immune system
Affected by :
Teenage pregnancy & smoking
Male gender
Day care- infections
STRUCTURAL CONSIDERATIONS
Lung Growth: Fetal 8 years
Affected by:
Temperature & O2 tension
Nutrition & Smoking
Functional disorders eg CDH
Prematurity
Growth factors-Gene repair
Drugs (B2 agonist/ C/S)
Risk factors for COPD
Mx: antioxidant, retinoids,MMPI
PERSISTENT NON
ATOPIC WHEEZER
Lung function abnormal at birth and
reduced in later life
Non Atopic
Airway hyper-responsiveness
Peak flow variability
RSV induced wheeze due to alteration
in airway tone
BETTER OUTCOME THAN ATOPIC
PERSISTENT WHEEZERS
Immunology associated with RSV
Unknown - natural infection # total immunity
Re-infection by same strains by 6 weeks
Recurrent disease- all infected by 3yrs
Infancy-immature immune system
Maternal antibodies
Incomplete protection,worse in premature
Prevalence of RSV Infection
n= 125 children followed from birth to 12m & 92
children followed from age 24-60m, virtually all
were infected with RSV by 24 m
97.1% 100.0%
100
80with
Children 68.0%
RSV infection
60
(%)
40
20
0
0-12 13-24 25-36
Age (months)
Glezen WP et al. Am J Dis Child 1986;140:543-546
20
RSV-Induced Bronchiolitis
May Consist of Several Phases
Phase I Phase II Phase III Long term
Viral Acute Persistent Wheezing
infection phase wheezing and asthma
Days Weeks Months
(Not to scale)(
21
Wheezing Often Persists Post
Bronchiolitis Korppi M et al. Am J Dis
Child 1993;146:628-631
100
76%
80
Children 58%
60
with
wheezing
40
(%)
20
0
1-2 Age (years) 2-3
(n=83) (n=76)
83 children <2 years hospitalised with bronchiolitis,
22 a large proportion had subsequent wheezing
RSV-Induced Bronchiolitis:
Association With Asthma
n= 140, the incidence of asthma at 7.5 yrs was
higher in children who had been infected with
RSV compared with controls
35
30%
30
Children
with
25
asthma
at age
20
7.5 years
15
(%)
10
5 3%
0
RSV Control
(n=47) (n=93)
Sigurs N et al. Am J Respir Crit Care Med 2000;161:1501-1507
23
TIME COURSE OF RECURRENT LOWER
RESPIRATORY SYMPTOMS
90
80
% children affected
70
60
50
40
30
20
10
0
1 2 3.5 4 to 5 6 to 8
Years after initial RSV infection
Henry et al. 1985 Arch Dis Child
Webb et al. 1985 Arch Dis Child
Hall et al. 1984 J Pediatr
Therapeutic Options:
viral induced wheeze
25
Options
Humidified oxygen: Beneficial
?? Antibiotics -associated infection
??Efficacy of Bronchodilators
– Inhaled & oral B2 agonists
– Inhaled ipratropium bromide
– theophyllines
??Use of corticosteroids
?Use on leukotriene antagonists
?Efficacy of immunoglobulin
Effect of Montelukast on
RSV-Induced Bronchiolitis
A RDBPC trial studied the effects of the LTRA
montelukast on the post-infectious course of
RSV-induced bronchiolitis
130 infants aged 3-36 months were randomized
to receive montelukast or placebo
Study treatment was montelukast 5 mg chewable
tablets or matching placebo taken in the evening
for 28 days
Symptoms were recorded by the caretakers on
diary cards
27 Bisgaard H. Am J Respir Crit Care Med 2003;167:379-383
Montelukast Improved the Symptoms of
RSV-Induced Bronchiolitis
Montelukast significantly improved symptom-free
days &nights (daily median)
30
Montelukast (n=61)
Placebo (n=55)
20 Median
symptom-
free days p=0.015
10
and nights
(%)
0
0 7 14 21 28
Missing data were considered to be symptomatic days.
Days
Bisgaard H. Am J Respir Crit Care Med 2003;167:379-383
28
Montelukast : Reduced
Exacerbations - Post RSV
Bronchiolitis
25
20
Patients 18.2%
with
15
exacerbations
(%)
10
6.6%
5
0
Montelukast Placebo
* Withdrawal due to symptom severity, or attending emergency department or hospitalisation
due to lung symptoms
Bisgaard H. Am J Respir Crit Care Med 2003;167:379-383
29
PERSISTENT ATOPIC WHEEZER
Lung function normal at birth but
deteriorates with recurrent symptoms
Increased symptoms with increasing
age
Airway liability
Atopic (increase IgE at 6-9m; increase
cytokines)
Abnormal immune responses to
viruses
PREDICTORS + RISK FACTORS
FOR PERSISTENT WHEEZE
Family history of Atopy
Viral infections
Allergens
Environmental factors
Household chemicals (OR 2.3 CI 1.2- 4.39)
Genetics
Multiple factors in combination
RISKS OF FAMILY HISTORY
OF ATOPY
No family history : 16%
Single parent atopy : 22%
Maternal Atopy : 32 %
Both parents atopic : 50%
(Aberdeen Study 1994)
MULTIPLE FACTORS
Triad of interactions
Genetic variability
Infections & environment
Complex receptor interaction
Single factor PPV < 50%
Combination factors PPV 80%
(German MAS
1990)
% OF INFANTS SUBSEQUENTLY
DEVELOPING ASTHMA
100 90%
80
60 50%
40%
40
20%
20
0
Infant wheeze Infant wheeze Infant wheeze + Infant wheeze +
with atopic atopic eczema atopic parent +
parent (s) and/or other positive skin prick
food allergies test + raised sIL-2R
OUTCOME OF INFANT WHEEZING
Low birth weight Affluence
Pregnancy smoking Atopy
Male Sex Low maternal age (first born)
Infant wheeze
With viral infection alone With various precipitants
Remission in 80%
Persistent asthma (with or without
evidence of atopy) in 50-60%
?? COPD in adults
Points on examination
LOW, FTT – systemic disease
UAO: Tonsils, Adenoids, Polyps, Rhinitis
Fixed Monophonic/asymmetric wheeze :
foreign body
Chest deformity- chronic lung disease
Clubbing & Halitosis- chronic suppurative
lung disease -bronchiectasis
Stridor – bronchomalacia, vascular ring
mediastinal syndrome
signs of cardiac or systemic disease
