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8/7/2019 06 Paediatric and Child Health June2009 Pulmonology
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Egyptian_Pediatric yahoo group
http://health.groups.yahoo.com/group/
egyptian_pediatric/
Egyptian_
http://health
eg
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Paediaric appliedrespiraory pysiology e esseials
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Keywords lg vl ss; x; s; lhs-
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Bearing in mind the diversity and prevalence o respiratory ill-
nesses in children, paediatricians should understand the basics
o respiratory physiology and how to monitor respiratory unc-
tion. This discussion will review normal respiratory physiology
and explore non-invasive orms o respiratory monitoring. With
this oundation, the paediatrician can accurately diagnose and
assess the severity o illness.
Kevin Madden MD is at the Department of Anesthesia and Critical Care
Medicine, Childrens Hospital Los Angeles, Los Angeles, USA.
Robinder G KhemaniMD MSCI is Assistant Professor of Pediatrics,
University of Southern California, Keck School of Medicine, Childrens
Hospital Los Angeles, Department of Anesthesia and Critical Care
Medicine, Los Angeles, USA.
Christopher JL Newth MD FRCPC FRACP is Professor of Pediatrics, University
of Southern California, Keck School of Medicine, Childrens Hospital
Los Angeles, Department of Anesthesia and Critical Care Medicine, Los
Angeles, USA.
Brief overview of ormal respiraory pysiology
Mscles of respiraio
The most important and powerul muscle during the inspiratory
phase o respiration is the diaphragm, a dome-shaped musculo-
brous septum that separates the thorax rom the abdominal cav-
ity. When the diaphragm contracts, abdominal contents move
downward and the lung expands in the vertical and horizon-tal planes. During normal tidal breathing the diaphragm moves
approximately 1 cm, but with orced inspiration and exhalation,
it can move up to 10 cm.
During inspiration, external intercostal muscles elevate and
move the ribs orward. This increases the lateral and anteropos-
terior diameters o the thoracic cavity. The two most common
accessory muscles o inspiration are the sternocleidomastoid and
scalenes. The sternocleidomastoid raises the sternum while sca-
lenes elevate the rst two ribs. During normal respiration these
muscles do not participate in inspiration, but during exercise
or in pathological processes they can play an important role in
maintaining normal alveolar ventilation.
While expiration is normally passive due to the elastic proper-ties o the lungs and chest wall, both exercise and certain patho-
physiological conditions invoke both the internal intercostal and
abdominal muscles including the internal and external obliques,
the transversus abdominis and the rectus abdominis. These mus-
cles work to decrease the thoracic volume and assist in orcing
air rom the lungs.
Both the lungs and chest wall are elastic, and each compo-
nent has a natural propensity; the lung to collapse inward and
the chest wall to spring outward. The equilibrium point o lung
volume where these orces are balanced is the unctional residual
capacity (FRC).
Lg volmes ad capaciiesThe various lung volumes and capacities can be measured during
dierent phases o the respiratory cycle and change under dier-
ent pathophysiological conditions. Spirometry is used to record
the volume o air moved during respiration.
The are our lung volumes which, when added together, equal
the total lung capacity (TLC) (Figure 1):
tidal volume (VT) volume o air inspired or expired during anormal breath
inspiratory reserve volume (IRV) the additional volume oair that can be inspired in addition to a tidal breath
expiratory reserve volume (ERV) the additional volume oair that can be expired ater the end o a tidal breath
residual volume (RV) volume o air remaining ater the mostorceul expiration.
In evaluating a patients clinical status and understanding patho-
physiology, it is sometimes advantageous to consider two or
more lung volumes together as capacities. The our lung capaci-
ties (Figure 1) are:
inspiratory capacity (IC) equals tidal volume plus inspira-tory reserve volume
unctional residual capacity (FRC) equals expiratory reservevolume plus residual volume, or the volume o air remaining
at the end o a normal expiratory breath
vital capacity (VC) equals inspiratory reserve volume plustidal volume plus expiratory reserve volume
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total lung capacity (TLC) equals vital capacity plus residualvolume.
Note that since by denition residual volume cannot be exhaled
rom the lungs, it cannot be measured by spirometry. FRC and
TLC also cannot be measured by spirometry alone but instead
are measured by gas-dilution techniques or plethysmography.
Gas excage
The primary purpose o the respiratory system is gas exchange
to maintain cellular homeostasis. The two principal componentsare delivery o oxygen and removal o carbon dioxide.
Oxygeaio
The respiratory system helps to extract oxygen rom the atmo-
sphere and deliver it to mitochondria. The partial pressure o
oxygen in the alveolus (PAO2) is a primary determinant o arterial
oxygen tension (PaO2).
P O (P P FO P CO RQA 2 b H O i 2 A 22= [ ) ] /
where Pb is barometric pressure, PH O2 is the partial pressure o
water vapour and FiO2 is the raction o inspired oxygen. PACO2
is the partial pressure o carbon dioxide in the alveolus and RQis the respiratory quotient. For most purposes RQ is assumed to
be 0.8.
Substituting normal values or an individual breathing room
air at sea level, the PAO2 is approximately 100 mmHg. As oxygen
crosses the alveolar membrane into the pulmonary capillary net-
work a negligible amount o oxygen tension is lost (around 10
mmHg). Thus, the PaO2 o a normal individual is approximately
90 mmHg. By examining the alveolar gas equation closely, one
can see that three conditions can cause a decrease in P AO2:
altitude (low Pb), hypoxic gas mixture (low F iO2) and hypoven-
tilation (high PACO2). The most common aetiology o hypox-
aemia is neither altitude nor hypoventilation, however, but a
disturbance in the number o alveoli participating in matched
ventilation/perusion (V/Q). With either compromised ventila-
tion with adequate perusion (shunt) or adequate ventilation
with compromised perusion (dead space), oxygen residing in
the alveolus cannot move into the pulmonary capillary network
and hypoxaemia will ensue. A wide variety o clinical condi-
tions can cause derangements in V/Q, and interventions such
as continuous positive airway pressure (CPAP), biphasic posi-tive airway pressure (BiPAP) or endotracheal intubation with
mechanical ventilation correct hypoxaemia by restoring normal
lung volumes, assisting cardiac unction and improving the
V/ Q relationship.
Veilaio
The respiratory system also eliminates carbon dioxide rom
the blood through the alveolus. Arterial carbon dioxide ten-
sion (PaCO2) is directly proportional to minute ventilation (VE)
where:
V respiratory rate tidal volumeE =
V fVE T=
It is worth noting that VT comprises dead-space volume (VD)
and alveolar volume (VA).
Dead-space volume is the portion o the tidal breath that does
not participate in gas exchange with pulmonary capillaries. Dead
space comprises anatomical dead space and non-anatomical
dead space. Anatomical dead space is ound within the conduct-
ing airways nose, mouth, oropharynx, trachea, bronchi and
bronchioles and accounts or approximately 2030% o a tidal
breath, although it is relatively larger in inants. Non-anatomi-
cal dead space approaches zero in healthy individuals, as most
lung units are equivalently ventilated and perused. In inantsand children with respiratory disease, however, total dead space
may approach 6070% o a tidal breath.
In contrast, alveolar volume is the portion o inspired breath
that arrives at the alveoli and participates in gas exchange with
pulmonary capillaries. Thereore, it is more accurate to state that
PaCO2 is proportional to alveolar minute ventilation (MVA):
MV f V VA T D= ( )
Hence, an elevated PaCO2 can arise rom a decrease in respiratory
rate, a decrease in tidal volume, or an increase in dead space.
Meods of assessig respiraory fcio i o-ibaed paies
Plse oximery
Cyanosis is the hallmark clinical sign o hypoxaemia, but it can
only be recognized condently when the oxygen saturation is
below 75% and cannot be recognized i the haematocrit is less
than 15%. Pulse oximetry allows or non-invasive and continu-
ous monitoring o arterial oxygen saturation (SaO2). The basic
principles o pulse oximetry are that oxygenated haemoglobin
(HbO2) absorbs mostly inrared light while deoxygenated hae-
moglobin (Hb) absorbs mostly red light. Pulse oximeters exploit
the pulsatile nature o arterial blood and successully ignore the
FRC
VT
RV
ERV
IRV
IC
VC
TLC
Figre 1 th vs lg vls s b b
s. ic, s ; Vc, vl ; Vt, l vl;
tLc, l lg ; rV, sl vl; irV, s sv
vl; erV, x sv vl; Frc, l sl
.
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contributions o the skin, tissues and venous blood. Each stroke
volume ejected rom the heart corresponds to an increase in arte-
rial blood volume across the measuring site. During systole light
absorption peaks, while during diastole it nadirs. The amplitude
o the waveorm generated is proportional to the amplitude o
arterial blood volume. Pulse oximeters, thereore, can detect
pulsus paradoxus, an important nding in certain pulmonary
dysunctions.Pulse oximeters can produce spuriously high or low readings
when a patient has a dyshaemoglobinaemia. In carbon monox-
ide intoxication, carboxyhaemoglobin (HbCO) absorbs light in
the red wavelength and is interpreted by the pulse oximeter as
oxygenated haemoglobin, alsely elevating the SpO2. Methae-
moglobin (Hbmet) is absorbed at a wavelength between red and
inrared light, leading to a alsely lowered SpO2 that generally
plateaus between 85 and 88%. The partial pressure o oxygen,
however, is not changed by the various dyshaemoglobinaemias.
Co-oximetry perormed on arterial blood samples will accurately
measure SaO2 as this technique can measure the proportion o
other orms o haemoglobin. Under normal conditions, however,
pulse oximetry measurements correlate well with co-oximetrywhen the saturation is between 70 and 100%.
Veilaio
The ability to monitor the eciency o ventilation by non-
invasive methods provides the clinician with critical inormation.
Oten the underlying disease masks signs o CO2 retention and
clinical diagnosis can be extremely dicult. The eatures only
appear when the PaCO2 is above 100 mmHg and can occur only
when the inspired air is enriched with oxygen, as the highest
PCO2 possible while breathing room air is about 90 mmHg. This
degree o hypercapnia by itsel does not appear to be dangerous,
and death usually results rom the associated hypoxia.
Transcutaneous CO2 monitors (TCOMs) oer a reliable, non-
invasive method or estimating arterial carbon dioxide. A small
adhesive patch, usually placed on the abdomen, warms the skin
and allows CO2 to diuse readily where it is read by the TCOM.
In general, TCOM monitoring correlates well with PaCO2,
although overestimations can occur due to heat and local CO2
production. While the accuracy o TCOMs has been historically
poor in obese patients, newer-generation TCOMs have improved
reliability.
Nasal cannula end-tidal CO2 detection: an easy and non-inva-
sive way o measuring end-tidal CO2 in spontaneously breathing,
non-intubated patients is by using divided nasal cannulas thatsimultaneously deliver oxygen via one prong and sample exhaled
gas through the other. Studies have shown that the end-tidal CO2
correlates highly with PaCO2. Such monitoring is useul or pro-
cedural sedation or to monitor children at risk or impending
respiratory ailure. It is physiologically impossible or end-tidal
CO2 monitors to read greater than PaCO2, so any elevated value
should be taken seriously and urther investigated by obtaining
an arterial blood gas.
Plmoary fcio ess
In addition to measuring lung volumes and capacities, spirom-
etry can be utilized with a orced expiratory manoeuvre that
can help clinicians determine mechanical disorders o the respi-
ratory tract, quantiy the degree o disorder and classiy it as
obstructive, restrictive or mixed in aetiology. Using a variety o
techniques, these can be done on even uncooperative (albeit
sometimes sedated) inants and young children.
Forced expiratory volume: as discussed earlier, vital capacity
(VC) is the lung volume that can be exhaled ater a ull inspira-tion. In contrast, orced vital capacity (FVC) is the lung volume
that can be exhaled ater a ull inspiration as quickly and orc-
ibly as possible, and is highly reproducible. When compared to
orced expiratory volume (FEV1), which by convention is the
amount o gas orcibly exhaled in one second, one can quickly
classiy the nature o respiratory disease. In cooperative children
over the age o 5 years the FEV1/FVC ratio is normally 0.8; values
less than 0.8 represent obstructive lung disease, whereas restric-
tive diseases have proportional decreases in FEV1 and FVC, pre-
serving the ratio o 0.8. Forced expiratory volumes provide an
objective standard to monitor response to treatment or clinical
improvement.
Flowvolume curves: by plotting expiratory and inspiratory
fows against lung volume instead o time, the clinician can
obtain more inormation about underlying lung or airway dys-
unction. Unortunately, orced expiratory spirometry provides
inormation solely about expiratory dysunction. Flowvolume
curves, on the other hand, can reveal both inspiratory and expi-
ratory dysunction and aid in the classication o the disease as
obstructive or restrictive.
Respiraory idcace pleysmograpy
The inspiratory cycle begins as the diaphragm moves downward.
The abdomen and rib cage then expand in concert, known as
thoraco-abdominal synchrony. However, various respiratory con-ditions will alter the timing o these events, resulting in thoraco-
abdominal asynchrony (TAA). The asynchrony can be quantied
using respiratory inductance plethysmography, and the degree
o asynchrony correlates well with the amount o respiratory
dysunction.
Two elastic belts into which a wire is sewn are worn around
the chest and abdomen. A current is passed through the belts,
generating a magnetic eld. The act o breathing changes the
cross-sectional area o the abdomen (ABD) and the rib cage
(RC), altering the shape o the magnetic eld generated by the
belts and inducing a measurable opposing current. A computer
analyses the current produced and generates (1) the phase angle,
which is the degree o synchrony o the ABD and RC and (2) thedirectional loop.
In a normal child, the phase angle is typically less than 22 and
the directional loop is anticlockwise. As the asynchrony worsens,
the phase angle gets larger, although maintaining the anticlock-
wise direction. When there is complete asynchrony the phase
angle is 180. In the case o bilateral diaphragmatic paralysis,
the directional loop becomes clockwise (Figure 2). In unilateral
paralysis, a gure 8 is created, and no phase angle can be mea-
sured. The clinical correlate is known as Hoovers sign, which is
the paradoxical inward movement o the lower lateral rib cage
during inspiration or in the neonate an abnormal movement
o the umbilicus to the contralateral side.
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Pressrerae prodc
A small water- or air-lled catheter o similar size to a nasogastriceeding tube can be inserted with its tip in the mid-oesophagus
to measure, relatively non-invasively, both the peak-to-trough
swings in oesophageal pressure with respiration, and the respi-
ratory rate. The product o the two is called the pressurerate
product and is an excellent surrogate or work o breathing
measurements.
Case sdies
Obsrcive airways disease
The primary pathological deect in obstructive airways disease
is airfow limitation. This limitation can occur during expira-
tion, inspiration or both. Both large airways obstruction (croup,epiglottitis, oreign-body aspiration, laryngomalacia, tracheoma-
lacia) and medium (asthma) and small (bronchiolitis) airways
obstruction have hallmark ndings on physical examination and
in the tests discussed above. Knowledge o these patterns assists
the physician to localize the obstruction, determine disease sever-
ity, monitor disease progression and determine treatment.
Extrathoracic obstructions can be clearly dierentiated rom
intrathoracic obstructions based on characteristic patterns in
fowvolume curves. The primary abnormality o an extratho-
racic obstruction is with inspiratory fow. There is a fatten-
ing o the inspiratory fow limb with a airly normal expiratory
fow pattern. Intrathoracic obstructions can be subdivided into
variable or xed lesions. A variable lesion such as intrathoracic
tracheomalacia will have abnormalities with expiratory fow andproduce a fattening o the expiratory limb, while the inspira-
tory limb will appear normal. Fixed lesions such as oreign-body
aspiration, external compression rom extratracheal masses or
tracheal stenosis have inspiratory and expiratory fow limitation
maniested as a fattening o both the inspiratory and expiratory
limbs o the fowvolume curve (Figure 3).
Croup
Physical examination the major abnormality in croup (an
extrathoracic obstruction) is inspiratory airfow limitation. Air-
fow is generated by lowering intrathoracic and intratracheal
pressures below extrathoracic atmospheric pressure. According
to Poiseuilles law, the change in pressure is inversely propor-tional to the ourth power o the radius o the airway. Thereore,
decreasing a childs airway radius rom 5 mm to 2.5 mm leads to
a 16-old increase in the pressure or airfow. To accomplish this,
children will increase their work o breathing by using accessory
muscles (i.e. supraclavicular retractions). Moreover, childrens
subglottic submucosa is non-brous, and the mucous membrane
is attached more loosely than in adults, allowing or oedema to
accumulate more easily. The sot supporting cartilage o the lar-
ynx and the narrow radius o the childs airway also allow or
dynamic collapse o airways during inspiration. This maniests
clinically with the classic inspiratory stridor that oten accompanies
viral croup.
Rib cage
Synchronous
ABD
m/s = 0
= 0RC
Abdomen
Rib cage
Asynchronous
ABD
m/s = 0.71
= 45
m
s
RC
Abdomen
Phase shift
Rib cage
Paradoxical
ABD
m/s = 0
= 180RC
Abdomen
Figre 2 rs lhsgh wh
h rs. o h l-h s, b
g (rc) b (aBd) vs
l s , h
gh-h s ghll ss hhs gls h l. n
h sl s wh h hg
ls s. as bhg vs
shs shs, h sz
h hs-gl l ws, lhgh
svg lkws . Hwv,
wh hg lss (xl), h rc
aBd xl 180 hs, wh
lkws v.
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Pulsus paradoxus as intrathoracic pressure becomes more
negative, aterload on the let ventricle increases and cardiac
output decreases. Since the pulse oximeter waveorm ampli-
tude is proportional to arterial blood volume, there is a decrease
in amplitude during inspiration known as pulsus paradoxus
(Figure 4). The magnitude o depression during inspiration has
been consistently correlated with the severity o extrathoracic
airway obstruction and can be used to monitor disease progres-
sion or resolution.
Flow and pressure curve against time the limitation o
inspiratory airfow can be visualized when fow and pressure are
simultaneously plotted against time (Figure 5). Respiratory inductance plethysmography phase angles
increase signicantly in viral croup and continuous phase-angle
monitoring can demonstrate clinical improvement as resolution
o the obstruction correlates with decreasing phase angles and
improving pulmonary unction.
Pressurerate product this value increases signicantly
in croup and can be used continuously to ollow response to
therapy.
Asthma
Physical examination the major abnormality in asthma is
expiratory airfow limitation. Underlying airway hypersensitivity
causes reversible narrowing and an increase in airways resis-tance up to 500% o normal values. This increased resistance
causes distal air trapping, ultimately leading to elevated end-
expiratory lung volumes and a prolonged expiratory phase with
wheezing. On visual inspection, patients with poorly controlled
asthma oten have a barrel-chest deormity due to the chronically
Expiration
Inspiration
50
40
30
20
10
0500
10
20
30
40
50
Flow
(litres/minute)
Tidal volume (mL)
400 300 200 100
Figre 3 Flwvl v x h w bs.
(nl vs , ss vs sl.) th s fw
l g s x s s fg
bh lbs h fwvl v.
B
A
F
E
CD
Plethysmographic wave
Blood pressure (mm Hg)
100
0
Inhale
Exhale
Breathing cycle
Figre 4 plss xs hl wh . psA B s ssl bl ss, whl s C D s sl bl
ss. ps E F s h k l h ls-x wv. n h h k s (b l) h s
s bh ssl sl ss (l l, s D B) g h ls x wv (
l, F); hs s kw s lss xs.
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elevated end-expiratory lung volumes. During an acute asthma
exacerbation, children will breathe at a lower respiratory rate
than normal to minimize work o breathing and will commonlyhave pursed lip breathing. The increased resistance prevents the
dynamic collapse o the airways on expiration. As the airway
resistance increases urther and initial compensatory mechanisms
ail, patients will become tachypnoeic and use accessory muscles
to generate more negative inspiratory pressure to overcome the
increased elastic recoil o the lungs and chest wall rom hyperin-
fation and increased lung volumes. Eventually, lie-threatening
respiratory muscle atigue leads to hypoventilation, hypercarbia
and hypoxaemia.
Pulsus paradoxus the elevated airways resistance raises
intrathoracic pressure and, much as in croup, causes a transient
decrease in cardiac output during inspiration. The consequential
pulsus paradoxus correlates with the severity o the asthma
exacerbation.
Forced expiratory spirometry and fow-volume curves
spirometry represents the most accessible way to gauge the
severity o obstruction and monitor the eects o therapy. The
measured FEV1/FVC is less than 0.8 since the reduction in air-
fow (FEV1) is greater than the reduction in lung volume (FVC),
with the degree o reduction correlating with disease severity.The expiratory limitation is readily visible on fowvolume curves
as reduced peak expiratory fow and a characteristic concave
appearance on the expiratory limb. Note the change in shape in
the expiratory limb ater bronchodilator therapy rom concave to
straight, the increase in peak expired fow and FEV1 (Figure 6).
Resricive lg disease
Whereas obstructive airways diseases are rooted in airfow limi-
tation, the hallmark o restrictive lung disease is decreased TLC.
The aetiologies are diverse increased elastic recoil (interstitial
infammation/brosis), decreased outward recoil o the chest wall
(scoliosis), respiratory muscle weakness (spinal muscular atro-
phy), alveolar destruction (pneumonia), thoracic space-occupyinglesions (tumour, blood, air, eusion, cysts), signicant abdominal
distension (acute abdomen, intra-abdominal masses) but the
consequences are the same: decreased TLC with preservation o
normal airfow.
Scoliosis
Physical examination deormities o the thoracic cage in
scoliosis lead to decreased lung capacities. In act, the degree o
restrictive pulmonary disease is clearly correlated with the sever-
ity o scoliosis, and those with severe thoracic cage deormities
are prone to more rapid decompensation when aficted with
respiratory inections. Initial attempts at compensation prompt
patients to breathe with aster respiratory rates and deeper than
Pre-epinephrine nebulization
Time (seconds)
100
80
60
40
20
0
20
40
60
80
0.0
8
0.
2
0.3
2
0.4
4
0.5
6
0.6
8
0.8
0
0.9
2
1.0
2
1.1
4
1.2
6
1.3
8
1.5
0
1.6
2
1.7
4
1.8
6
1.9
8
Post-epinephrine nebulization
Time (seconds)
Flow (ml/s) Pressure (cmH2O)
100
80
60
40
20
0
20
40
60
80
0.
06
0.
20
0.
34
0.
48
0.
62
0.76
0.
90
1.
02
1.
16
1.
30
1.
44
1.58
1.72
1.
86
2.
00
2.
14
Figre 5 Flwss v hl wh . Flw ss
vs l gs . t l: b h s
sg s fw l. dg l s
h s sv s s fw ss wh hg
shgl ss (left of solid arrow). t h right of the solid
arrow, l s ss (open arrow), h s vll
h s s fw s lg s
gv ss. dg x, h s ls v fwl, wh shgl ss hgh fws lw h
hs s h h hl. Lw l:
h. F h bgg s, fw ss
kl h k b hsolid arrows ss
ss. th, h s h sll l shgl
ss s b s gv vl (open arrow).
dg x, v s ss ss ss
wh lvl hgh fws.
Expiration
Inspiration
50
40
30
20
10
0500
10
Diseased After response
to bronchodilator
Normal
20
30
40
50
Flow(litres/minute)
Tidal volume (mL)
400 300 200 100
Figre 6 Flwvl v hl wh sh. th x
l s s s k x fw h
hs v h x lb. n h
hg sh h x lb bhl h
v sgh h s k x fw.
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their normal tidal volume. As they begin to atigue, baseline end-
expiratory lung volumes decrease. Alveolar collapse, worsening
V/Q mismatch and hypoxia soon ollow.
Forced expiratory spirometry and fow-volume curves given
the insidious nature o scoliotic deormities, measurement o lung
volumes and capacities is an eective way to gauge the result-
ing decline in pulmonary unction over time. It has been shown
that postoperative pulmonary complications increase with dete-rioration in pulmonary unction tests. Since restrictive diseases
produce a proportional reduction in airfow and lung volume,
the FEV1/FVC remains unchanged or even slightly greater than
normal. However, the lung volumes obtained will be lower than
predicted.
Neuromuscular disorder (e.g. spinal muscular atrophy, infant
botulism)
Physical examination most children with neuromuscular
disorders do not exhibit prominent respiratory symptoms. Simi-
larly to patients with scoliosis, their respiratory abnormalities
usually become apparent when they are aficted by an inection
o the respiratory tract. Unlike patients with scoliosis, however,their restrictive lung disease is urther complicated by underlying
muscular weakness. I disease progression is severe enough, they
will maniest other signs on physical exam unique to neuromus-
cular disorders. The diaphragm is initially seemingly spared
compared with the weaker intercostal muscles and children will
use their accessory muscles to breathe at higher respiratory rates
than normal individuals to minimize work o breathing. Eventu-
ally this will progress to paradoxical breathing, usually apparent
clinically and on respiratory inductance plethysmography.
Respiratory inductance plethysmography patients with spi-
nal muscular atrophy will oten progress to complete thoraco-
abdominal asynchrony. The rib cage is neither stabilized nor
expanded during inspiration and the resulting negative intratho-racic pressure causes the rib cage to collapse. The phase angle
will be above normal or up to 180 and the directional loop
anticlockwise (Figure 2).
Coclsio
There is a wide array o non-invasive tools available to the pae-
diatrician or diagnosis and management o various respiratory
diseases. With a basic knowledge o respiratory physiology and
how pathophysiological states can be monitored, the clinician
can optimize therapeutic interventions and readily track disease
progression.
FuRthER READInG
ag ac, Hhll m, nwh cJ, Kl m. th h
b blz ss w bs s wh
sv . Intensive Care Med2008; 34: 13847.
Bk SJ, t KK. th b x hl
ls x ss po2.Anesthesiology1987; 66:
6779.
Bk SJ, t KK, H J. es hglb ls
x x vs x.Anesthesiology1989; 70:
1127.
ck cW, Bk Ga, es JF, l. rgh hl
ss s : bjv
sg ss. Crit Care Med1981; 9: 58790.
F B, B W. pls x ssss lss xs:
ll s hl. Intensive Care Med1998; 24: 2426.
Gg S, J a, m r. pl s s b
sl s g h slss. Spine 1989; 14:
48690.H J, nwh cJ. i lg sg h sv
. Intensive Care Med1995; 21: 74452.
H J, eb e. p l sg. Bsl: Kg,
2005.
Hs u. Vl, gs xhg, hs bhg
s wk bhl sh.Acta Soc Med Ups
1971; 76: 24870.
Hv cF. th s h sl sls.JAMA 1919; 73:
1720.
K yJ, Lk LG, Bwll KH, l. pl ls
h slss lv h sgl .J Bone Joint
Surg Am 2005; 87: 153441.
Lk LG, Bwll KH, Blk K, Bls c. alss l hs g s hgs hls
h slss. Spine 1995; 20: 134350.
msl m, Z a, F S, l. evl
ss b x sv bs. Intensive
Care Med2008; 34: 13404.
mh Jc, Bss oG, thbl dW, m Gd. th ll
s lvl vl.Am Rev Respir Dis 1968; 98:
86871.
nwh cJL, H J. mss h-bl sh
wk bhg hl. i: H J, eb e, s.
p l sg. Bsl: Kg, 2005.
nhls mm. Shg bls l h ls (h bll
s sg). Clin Pediatr1976; 15: 3423.nhls dG. rs sl s hl.
J Pediatr1991; 118: 493502.
n aH, nwh cJ. a s s hl.
J Appl Physiol 1996; 80: 14859.
pz a, ml r, V G, l. thbl
bhg sl ss. Chest1996; 110: 45461.
p S. S hslgl ss sh: bhsl
ws lb. Ciba Found Study Group 1971; 38:
6385.
r J, tsls F, mh J, l. cs vsv
s lss xs ls l s
kg ssss sh sv. Chest2006; 130:
75465.
Sv y, dks tW, nwh cJ. thbl sh
w bs sll hl.Am Rev Respir Dis 1990;
142: 5404.
Sv y, elh mK, chh te, nwh cJ. es l
b x b -l ss pco2
ss vl hl. Pediatr Pulmonol 1992;
12(3): 1537.
Sl Sa, mlls rB. mhl s g l
sh. N Engl J Med1977; 297: 5926.
Sl dW, S Ka, Wgh ro, l. d. plss xs:
bjv s sv .Am J Respir Crit Care Med
1998; 157: 3314.
8/7/2019 06 Paediatric and Child Health June2009 Pulmonology
9/51
SympoSium: reSpiratory medicine
paediatricS and cHiLd HeaLtH 19:6 256 2009 elsv L. all ghs sv.
tbs Jd, Flg JF, Whl tJ, l. nvsv g
-l co2 v sl ls ssl bhg hl
g h v . Crit Care Med1994; 22: 18058.
Ws JB. mhs bhg. i: rs hslg:
h ssls. Bl: L, Wlls Wlks,
2003. yl m, nw W J. evl ls x.
Anesthesiology1983; 59: 349352.
Zhg JG, Wg W, Q GX, l. th l v l ss h sgl slss. Spine 2005; 30:
21821.
Pracice pois
pls x, tcoms sl l -l co2vs s lbl ws gs xhg
chs hgs l sss lssg lg s s
ogg s l ss llw g ss gss
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T atiology o cilooastmaW L
Abstact
ash s hs ss ll s b h
chs h Gks. i vl s h vl hl-
s v hgh, b h vl hs b sg l h vl-
g s v h ls 30 s. th lg s ll
s b g vl s. Gll,
h h ls g h h h, b sgl g
lhs ss xbs sl-
. i s bg v h s vl s l s vl, l hvl s, ,
s, xs, ssl, ll, l skg, bs.
rsh hls s s s h hss vlv, b
hs hss wll v hgl /l h.
usg hs v s k sl g h
vl sh l hs v glbl ss.
Kywos lg; hlh sh; llg; gs; bs;
s; lls; b sk; vs sItoctioChildren with asthma demonstrate episodic symptoms and
variable airow obstructions which occur spontaneously or in
response to various environmental trigger actors. There is also a
strong genetic inuence which is determined more by the childs
mother than by the ather. The Oxord English Dictionary defnes
aetiology as the assignment o a cause and that part o medi-
cal science which investigates the causes o disease. The latter
defnition dates back to 1684, but there has been a consider-
able increase in our understanding o the causations o asthma
since then. In 1860, Henry Hyde Salter published his Treatise
on Asthma. Allergy and atopy had not been propounded at that
time, but he was clearly aware o the hereditary nature o the
disease and o the association with contact and emanationsrom cats and dogs. In 1892, Sir William Osler drew attention
to the wide variety o pathological changes occurring in asthma,
such as mucosal oedema, inammation, and the production
o gelatinous mucus. He also noted the relationship between
these changes and their corresponding symptoms demonstrated
during exposure to dust, cats, oods, inections, and emotional
extremes. He was well inormed that asthma usually commenced
Warren LenneyMBChB DCH MRCP MD FRCP FRCPCH is Professor of Respiratory
Child Health, Keele University and Academic Department of Child
Health, University Hospital of North Staffordshire, Stoke-on-Trent, UK.
in childhood and that it appeared to run in amilies. Today this
exaggerated response to various stimuli is accepted as one o the
key characteristics seen in both children and adults with asthma,
namely bronchial hyper-responsiveness (BHR). The main thrust
o this review is to highlight the main genetic and environmental
inuences which result in the production o symptoms and exac-
erbations in children with asthma: in other words, the relevant
actors to consider in the aetiology o the disease.
Gtic ifcs
Although asthma has been known to run in amilies or centu-
ries, twin studies have shown that BHR is inherited indepen-
dently. It is the BHR mechanisms which are critical to asthma
aetiology, as these are what truly determine the symptoms, the
expression o the disease. The pathological expression has been
shown as mucosal oedema, inammation, hypertrophy o the air-
way smooth muscles, smooth-muscle shortening, and increased
muscle contractions.
The complexity o the above processes suggests there may
be hundreds o potentially attractive candidate genes associatedwith asthma, and this has been confrmed by the large num-
bers o genetic mapping studies which have been published over
recent years.
Some areas o the human genome have more consistently
been associated with many o the recognized asthma pheno-
types. These are 6p21-24 (the major histocompatibility complex),
11q13-21 (clara cell secretory protein, IgE high-afnity receptor
and glutathione S-transerase genes) and 20p13 (ADAM 33). It
was particularly exciting in relation to the identifcation o ADAM
33 that two subsequent candidate gene studies confrmed an
association between BHR and ADAM 33 polymorphism.
Groups o candidate genes which have been shown to be
relevant to asthma are those encoding cytokines and chemo-kines, those encoding receptors associated with the T Helper cell
2 (TH2) response, and those genes related to oxidative stress.
These associations are complex, however, and can be inuenced
by many simple actors such as the size and age o the child. I
BHR is not corrected or such parameters, the associations can
change dramatically and even disappear completely. The risk o
transmission o asthma is greater through the childs mother, and
this has been recently confrmed in relation to polymorphism
in glutathione S-transerase (GSTP1), one o the genes respon-
sible or the detoxifcation o drugs and products o oxidative
stress. Some studies have ound correlations with the athers
genetic make-up in relation to BHR, and one requires an in-depth
knowledge o asthma genetics to ully interpret all the publishedfndings.
One o the issues in attributing specifc genetic relationships
to asthma in children can best be summarized by Figure 1. These
relationships depend on the many and complex interactions
between in-utero, neonatal and external environmental actors,
all o which vary depending on the specifc asthma phenotype,
and even in a single patient these do not remain constant but
vary over time. The phenotype may well vary between the sea-
sons, some worsening in the spring and early summer, others
worsening in the winter. Asthma symptoms in children are more
variable than those in their adult counterparts, and they may
well change signifcantly rom one year to the next. Long-term
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symptomatology and severity are very hard to predict clinically
in the individual young patient.
The above clearly shows that the genetic associations are
complex, asthma aetiology is multiactorial, and despite the
insistence o the media that one day we will fnd the gene or
asthma, there is no such thing.
Foo allgy a it
In surveys o patients attending asthma clinics, over two-thirds
think their asthma is triggered by specifc oods. When ood
allergy challenge studies are undertaken, however, the fgure is
much lower, usually less than 25%. The reason or the high fg-ure in epidemiological surveys is probably the inclusion o oods
such as ice-cream and fzzy drinks, where the causation o the
bronchospasm is more likely to be related to very low tempera-
tures or a low/acidic pH. Foods implicated most commonly in
causing asthma symptoms, ollowing challenge studies, are pea-
nut, milk, egg, and tree nuts.
Both ood allergy and asthma are considered to have an
important allergic component mediated through immunoglobulin
E (IgE), but as with genetics, the relationships are not straight-
orward. When dierent countries are surveyed to establish the
prevalence fgures or atopy and asthma, even i the prevalence
o atopy is similar in each country the prevalence o asthma can
vary enormously. Conversely, over a number o years, the preva-lence o asthma can rise steadily with no similar change in atopy
prevalence.
The role o diet has been investigated extensively in relation
to asthma prevalence over recent years. Anti-oxidants such as
vitamin C and E, atty acids, and magnesium and potassium have
been studied, as have avourings, colouring agents, and addi-
tives such as monosodium glutamate, tartrazine and sulphites.
A Cochrane review o fsh-oil 3 atty acid supplementation
could not fnd any consistent benefcial eect when compared
to placebo. The evidence or the eect o the other compounds
(colouring agents and additives etc) is also not clear, although
some patients can be adversely aected by them. As with other
actors related to the development o asthma in children, the role
o our diet has to be considered as a trigger which may inu-
ence prevalence and/or severity, but which needs careul assess-
ment in each patient or in each patient group, depending on the
asthma phenotype.
Vial ictios
Respiratory viruses are the most common cause o asthma exacer-
bations in children and in adults with asthma. Viruses are respon-
sible or 85% o all childhood exacerbations. The most important
virus is the rhinovirus (RV), which is now known to inect the
lower as well as the upper airway. The innate immune response
to RV inection was postulated as being defcient in asthmatic
patients. Production o intereron (IFN-) was investigated and
shown to be low. Patients with asthma thereore probably have
decreased immunity to RV, resulting in increased cell lysis and
more severe lower-airway symptoms ollowing inection. RV
inection may also act synergistically with allergic inammation,
and the fnding o RV together with high allergen exposure in
children results in increased risk o hospitalization with asthma.Respiratory syncytial virus (RSV) has traditionally been con-
sidered the most important virus or severe wheezing in the frst
2 years o lie, and indeed it is still the commonest pathogen
to produce acute viral bronchiolitis (AVB) in this very young
age group. In the UK alone RSV is responsible or the major-
ity o the 20,000 inants admitted to our paediatric wards with
AVB each winter. However, in elegant prospective studies in the
USA, Lemanske et al ound that RV isolated during wheezing ill-
nesses in inancy were the strongest predictor o wheezing in the
third year o lie. We must be careul to try to separate recurrent
respiratory symptoms o cough and wheezing ollowing AVB
rom wheezing in association with allergic sensitization and the
development o true atopic asthma. In practice, however, in theclinic or surgery in primary or secondary care such dierential
diagnoses are almost impossible to make, and fnal dierentia-
tion can only be confrmed in the ullness o time. The reality or
clinicians is much less obvious than many epidemiological stud-
ies would have us believe.
Clearly, RSV and other respiratory viruses may be ound in
inants with a uture diagnosis o atopic allergic asthma, but the
research evidence at present points to RV as the key virus in
the aetiology o true symptoms o atopic asthma. Whether it is
the genetic make-up o the child which is the real determinant
o asthma status remains an unanswered question, but this may
well be the most important actor in the uture progression o
asthma symptoms. By that I mean that RV or any other virusmay produce symptoms in inants, but those inected who then
develop atopic asthma are those with the susceptible genetic
make-up in the frst place.
There is increasing interest in bacterial inections, such as with
Mycoplasma pneumoniae and Chlamydia pneumoniae, which are
known to cause respiratory inections in all ages. In one study,
20% o 215-year-old children admitted to hospital with asthma
were ound to have mycoplasma present as assessed by culture
through nasopharyngeal aspirates and paired serum titres or
mycoplasma antibodies. We need more inormation on these
organisms as potential inective agents which may be actors in
the development o asthma in both children and adults.
Mothers genes
Neonatal immunophenotype
Asthma phenotype
In-utero environment Fetal genes
External environment Childs genes
Fig 1 ps l gv s
g sh h.
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Psts, pts a otoxis
In the 1970s it was generally believed that the aetiology o asthma
was mainly determined by the house-dust mite and, in particu-
lar, its allergenic aeces. Cats were considered to requently con-
tribute to symptoms, and the answer seemed simple get rid
o the amily cat and take specifc measures to keep levels o
house-dust mite low. Remove carpets, cover the mattress withpolythene, regularly damp-dust the bedroom and living rooms,
and buy non-allergenic bedding and pillows. Studies rom moun-
tainous regions o the world, however, inormed us that at levels
over 8000 eet above sea level, such as in the Andes, house-
dust mites could not survive, but asthma prevalence was high.
In countries where cats were not domesticated the prevalence
o asthma was as high as in other countries where cats were
the commonest household pet. Numerous cohort studies have
now evaluated the relevance o dust, house-dust mites, urry
and eathered pets and endotoxins (inammatory lipopolysac-
charides rom gram-negative bacteria that are ubiquitous in the
indoor environment) in the development o allergic sensitization
and childhood asthma. Some studies, but not others, have showna doseresponse relationship or mite allergen exposure and sen-
sitization. In the study by Simpson et al, the higher the endotoxin
allergen exposure the greater the risk o sensitization, but when
the results were re-analysed by genotype only the children with a
particular genotype o the CD14 gene confrmed the relationship,
emphasizing the complex interaction between environmental
and genetic backgrounds.
Perhaps the most convincing evidence o environmental inu-
ences in relation to asthma prevalence is the consistent fnding
that children reared on arms have a lower incidence o asthma.
The most likely explanation or these fndings is that exposure
to irritant, allergenic and inectious actors in early childhood
somehow encourages tolerance to common aeroallergens, per-haps by promoting T-helper-cell type 1 (TH1) as opposed to TH2-
type immunological responses early in lie. Much research has
taken place over the past 20 years, oten involving large cohort
studies, to assess the importance o aeroallergens in the develop-
ment o asthma in children. We now understand the mechanisms
involved ar better, but in practical terms we are little closer to
knowing whether we can alter/manipulate the indoor and out-
door environments to inuence asthma prevalence.
Obsity
The incidence o asthma and that o obesity have increased in
parallel over the last our decades. There are mechanical, immu-nological, hormonal and inammatory eects o obesity that
may well play a role in the persistence o asthma. Although the
relationship is not completely clear, many prospective studies
suggest that increased body mass index (BMI) is associated with
an increase in asthma. However, ew studies have adjusted or
physical activity, and in some the association is seen only in
males, in others it is seen only in emales. Whilst diet and BMI
are relatively easy to measure, the assessment o physical activ-
ity is more challenging, and it could be that lack o activity is the
primary explanation or the increased levels o asthma symp-
toms, and not the obesity itsel. There is no doubt that obesity
is a major present-day health hazard, but whether it is directly
related to increased levels o asthma in childhood populations
requires urther study.
Tobacco smok
Cigarette smoke contains particulate matter and more than 2000
chemical compounds. Tobacco smoke in the environment is
incompatible with good respiratory health. A systemic review oparental smoking revealed an odds ratio or asthma o 1:21 and
or wheeze o 1:4. Although maternal smoking is not consistently
associated with an increase in asthma prevalence, it is associ-
ated with more severe disease, and childhood asthma symptoms
oten improve when the mother stops smoking. Similarly, BHR is
increased in children whose parents smoke, and increased BHR
at 1 month o age has been shown to predict lower lung unction
at 6 years o age. Wheezing and doctor-diagnosed asthma are
more closely related to passive/environment tobacco smoke in
the preschool age range than in schoolchildren 516 years o age,
but such fndings should not detract rom the statement that the
single most important measure to improve the health o children
would be the exclusion o tobacco smoke rom their indoor andoutdoor environments.
Ot polltats
It is known that nitrogen dioxide, sulphur dioxide, ozone, diesel
exhaust and particulate matter can all increase BHR and inam-
mation. The mechanisms may involve oxidative stress, epithelial
damage, and an increase in pro-inammatory mediators. As with
other triggers, such actors are unlikely to work alone, and an
interesting study o children 811 years old who wore nitrogen
dioxide monitors throughout the study showed that respiratory
symptoms increased and lung unction ell as nitrogen dioxide
levels increased. These changes occurred in the week beore arespiratory inection became clinically obvious, once again dem-
onstrating the complex interactions which may be necessary in
the patients environment i they are to inuence the develop-
ment o asthma symptoms.
Ot isss
Asthma is a syndrome with dierent triggers, dierent outcomes
and dierent responses to medications. Recent studies have iden-
tifed actors such as paracetamol usage and rhinitis in children
as important in progression to adult asthma. Progress in under-
standing mechanisms responsible or asthma symptomatology is
slow and cure is still a pipedream.
Smmay
Asthma is a classical multiactorial disease whose aetiology is
complex, involving both genetic and environmental triggers. The
prevalence has risen steeply over the last 30 years at a rate that
cannot be explained simply on genetic grounds. Clearly there
are important environmental actors which have inuenced this
sharp rise, and I have tried to allude to a number o these. Each
patient is dierent, and trying to assess which environmental
actors are important or that individual may result in improve-
ment in asthma control i identifed triggers can be eliminated
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or reduced. O equal importance is the relationship between
such environment triggers and specifc genetic polymorphisms.
Asthma aetiology typifes the comment one glove does not ft
all. There will not suddenly be a miracle cure or this common
yet very complex disease. Each patient behaves in a dierent
way, making asthma a ascinating disease in which to study the
true meaning o the word aetiology.
Cofict o itst
The author has no conict o interests which may have any inu-
ence on the content o this article.
FurTher reAdInG
Bs Ja, alxs n, Bs c, l. Hlh s ll.
J Allergy Clin Immunol 2004; 114: 111623.
Bs S, L m, m e, l. Mycoplasma pneumoniae
sh hl. Clin Infect Dis 2004; 38: 13416.
chh aJ, isk Hm, Lk cH, l. psl xs g
x (no2) h sv vs- sh hl.Lancet2003; 361: 193944.
chl F, L W, cl S, l. c bhl hllg
g sz h sls g ss
ss hl. Pediatr Allergy Immunol 2003; 14: 193200.
chl F, L W, cl S, l. ml b l v
GStp1 s ss wh sh hs hl. Respir
Med2003; 97: 124756.
dls Se, Bhh S, Js a, l. a g-w sh
qv l lg sh. Nature 1996; 383: 24750.
es p, c y. rlv s sh g l
lss s .Am J Respir Crit Care Med2000; 161:
15636.
erS th L. a s-hg sh. Lancet2008; 372:1009119.
Fl SL, Bss WW. th l hvs sh
xbs.J Allergy Clin Immunol 2005; 116: 26773.
F aa, B a, Hl m, l. plhs glh
S-ss GStp1 ls: w k bhl
hssvss sh.Am J Respir Crit Care Med2000;
161: 143742.
Gvs pe, Kbsh m, Hl m, l. a ls sv ghl
lk lhss h iL-13 g s ss wh l
s ige lvls h ls wh hl.J Allergy
Clin Immunol 2000; 105: 50613.
Hg a, Bjk t, Shz po, l. ash l
g s sh ssbl gs.Allergy2002; 57:
6806.
Jhs SL, p pK, Ss G, l. c s
l vl s xbs sh 911 l
hl. BMJ1995; 310: 12259.
Ls Sr, pl-mlls tae. p sh bs. Paediatr
Respir Rev2006; 7: 2338.
Lsk J rF, Jks dJ, Gg re, l. rhvs llsss
g sbsq hlh whzg.J Allergy
Clin Immunol 2005; 116: 5717.
m cS, pl G, Kbz t, l. S fbl sk s
sh xbs: vs llg xs
s h sk sh hslz hl. Thorax2006;
61: 37682.
o J, ml n, tl c, l. plb-ll bl-bl hllg sh.J Allergy Clin Immunol 1986; 78:
113946.
osl W. Bhl sh. ls .
nw yk: d al, 1892.
pl LJ, r p, Gbs n, l. aw ssvss l
s sh, lg s ss b
shl g.Am J Respir Crit Care Med2001; 163: 3742.
pj a, Sh d, B m, l. ash llg alb
h uK. Lancet2001; 358: 14267.
Sl HH. o sh: s hlg . L: Jh
chhll, 1860.
Ss a, Jh SL, J F, l. ex xs, cd14
llg ss: bw gs h v.Am J Respir Crit Care Med2006; 174: 38692.
Sh dp, ck dG. pl skg hlh sh;
lgl s l ss. Thorax1998; 53: 20412.
V ewgh p, Ll rd, ds J, l. ass h adam33
g wh sh bhl hssvss. Nature 2002;
418: 42630.
Ws rK, th Fc, abs mJ. d s (fsh l)
sh ls hl. Cochrane Database Syst Rev
2002 (3): cd001283.
Pactic poits
th ss s hl wh sh sl xgg ss vs sl
.. bhl h-v (BHr)
th lg sh s ll, vlvg bhg vl s
th hvs s h sgl s gg g xb sh
ivl hl b vsl b h ls, b vl sss lx
sg
chl bgh s wh h ls hv lw vl sh, s shw v
s wlw
ds h h vl b sk llws sh ss, ls s bl
ls s skg
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Avacs i tmaagmt of astmaaw Bsh
c Bssl
Ls Flg
nl Wls
Abstract
exg w sg h v bs h g
sh. t h shl whz, h
bs lss s s (vl) lgg whz,
h h g lgl (s vss -
ss) h s bs . es (vl) whz s
l, wh h hl bhls l -
lks h vl ls. i hs h ls, hgh-s hl ss b . ol sl s v
h ll b h svs ks shl s
(vl) whz, s - hs x. i
l hl h l lg-g 2 gss hs b xl. th
s s-l hl h. i hl wh
sv ss, sgl-hl sg sg bs/l
shl b s. i hl wh s vl
sh h, h gss h w whh h sb -
s bg s shl b vw h h bg
bll gv. ms ss wll v wh vl g
whh s l k, wll q vl hs.
Kywors h; ; b gs; hl s; l-k gs; l; sl; vl ;
whzItroctio
The aim o this review is to highlight recent important clinical
trials, particularly those which should lead to a change in clinical
Andrew Bush MD FRCP FRCPCH is Professor of Paediatric Respirology at the
Imperial School of Medicine at the National Heart and Lung Institute,
and Royal Brompton Hospital, London, UK.
Cara BossleyMRCPCH is a Clinical Research Fellow at the Imperial
School of Medicine at the National Heart and Lung Institute, and Royal
Brompton Hospital, London, UK.
Louise Fleming MRCPCH is a Clinical Research Fellow at the Imperial
School of Medicine at the National Heart and Lung Institute, and Royal
Brompton Hospital, London, UK.
Nicola Wilson MD is an Honorary Consultant Paediatrician at the
Imperial School of Medicine at the National Heart and Lung Institute,
and Royal Brompton Hospital, London, UK.
practice in the treatment o wheezing disorders throughout child-
hood. Familiarity with the updated version o the British Thoracic
Society/Scottish Intercollegiate Guidelines Network (BTS/SIGN)
Asthma guidelines is assumed. We aim to produce an update
o treatment or children seen in primary and secondary care in
particular, based on new evidence; space precludes a review o
the recent advances in the basic science o asthma.
Prscool wz
Potypig prscool wzig syroms
There are at least three ways in which wheeze phenotypes have
been characterized: by epidemiological descriptions o the change
in wheeze over time, by the presence or absence o atopy, and by
current symptom pattern, i.e. episodic (viral) versus multitrigger.
Epidemiology: the classic epidemiological phenotypes are
transient wheeze (rst 3 years o lie only); persistent wheeze
(throughout the rst 6 years o lie), and late-onset wheeze (start-
ing ater the rst 3 years o lie), as described in the Tucson
study. These patterns are to some extent orced in that the chil-dren were only seen three times in the rst 6 years o lie, so
no other phenotype could have been detected. The Avon lon-
gitudinal study obtained questionnaires annually, and used a
more objective mathematical technique latent class analysis
to determine rom the data whether there were dierent phe-
notypes, a more sophisticated approach. They determined
phenotypes o (1) never or inrequent (59%); (2) transient (16%)
and (3) prolonged early wheeze (9%); (4) intermediate (3%),
(5) late (6%) and (6) persistent wheeze (7%). Although these
epidemiological phenotypes have value or the epidemiologist
probing mechanisms o disease, they are useless or the clinician,
because they can only be allocated retrospectively, and thereore
cannot guide contemporaneous therapeutic decisions. The basicmessage, amiliar rom clinical practice, is that some wheezy pre-
school children will outgrow their symptoms, and some will not.
A number o predictive indices have been developed which gen-
erally have a good negative predictive value (will tell you who
will not have persistent symptoms) but a poor positive predictive
value (little better than fipping a coin at telling you who will
have persistent symptoms). So it is very dicult or the clinician
to determine whether a wheezy 2-year-old will still be wheezing
at the age o 6. The epidemiological studies have certainly taught
us a great deal about the natural history o wheezing disorders in
childhood, but are not useul in clinical practice.
Atopy: the second way o classiying wheeze is by the presenceor absence o atopy, determined either by skin-prick tests or by
the report o eczema or allergic rhinitis. This too is imperect.
Firstly, just because the child is atopic does not mean that atopy
and wheeze are connected, any more than an ingrowing toenail
in such a child could rationally be described as an atopic digi-
topathy. Indeed, in very young children with wheeze, whether
atopic or not, airway wall histology is normal. In older children
with wheezing in response to viruses and many other triggers,
airway wall histology shows typical eosinophilic infammation
and structural airway wall changes irrespective o the presence
o atopy. Atopy is also a dynamic process, with children mani-
esting it over time; so when assessing the current non-atopic
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wheezer, it is impossible to know whether atopy will appear
subsequently.
Symptom pattern: the third approach, adopted by the recent
guidelines o the European Respiratory Society (ERS), switches
the ocus to symptom pattern at the time o presentation as the
way to guide treatment. The history should determine whether
the child has episodic (viral) wheeze, characterized by wheezein association with usually clinically diagnosed viral inections
only, or multitrigger wheeze, characterized by wheezing with
viral inections, but also with wheeze to typical triggers such
as exercise, allergen and smoke exposure. The implications or
treatment are discussed below; in summary, episodic problems
should be treated with intermittent therapy, whereas children
with multitrigger symptoms should be considered or continu-
ous treatment, usually with low-dose inhaled corticosteroids
(ICS), using a three-stage protocol. It should be noted that this
classication accepts that phenotypes may be modied by time
or treatment; thus an inant with episodic (viral) wheeze may
evolve into a multitrigger picture, and the inant with multitrig-
ger wheeze, when treated with ICS, may be let with episodic(viral) exacerbations, which are much more dicult to control
with prophylactic therapy. Also, although the tacit assumption
is sometimes made that the terms episodic (viral) and transient,
and also multitrigger and persistent are synonymous, there is
no evidence that this is the case. Episodic (viral) wheeze can
certainly persist even into adult lie, and multitrigger wheeze can
remit in mid-childhood.
Implicatios for tratmt of prscool wz
The ERS guidelines attempted an evidence-based approach to
treatment (hampered by the lack o much evidence!) o preschool
wheeze; subsequent to the publication o these guidelines, two
urther papers on the acute management o preschool wheezehave been published. The stimulus or the guidelines was to try
to rectiy the disconnection between the epidemiological data
and the recommendations o many previous guidelines, and also
to be o practical value or the clinician. There might be two
reasons or treating preschool wheeze: (a) to modiy the disease
and prevent persistence o symptoms and the development o
ull-blown asthma in mid-childhood, and (b) or current relie
o symptoms.
Can treatment alter the outcome of preschool wheeze?: the
short answer is, no. Although parents want to know the prog-
nosis o the child, in practice it actually makes no dierence
to therapy because we have no medication which prevents thedevelopment o persistent asthma. Studies have shown that
early use o continuous or intermittent (at the time o symp-
toms) ICS have all shown that they have no eect on outcome.
A trial o cetirizine given to inants with atopic dermatitis to try
to prevent the development o wheeze showed no dierence
or the treatment group as a whole, but some benet, based
on airly small numbers, in subgroups with radioallergosorbent
test (RAST) positivity to house-dust mite, pollen or both. This
hypothesis-generating trial was not conrmed by a repeat study
o l-cetirizine, in which no benet was shown. So treatment or
preschool wheeze should be directed by present symptoms, not
uture prognosis. It cannot be overstressed that, whatever the
evidence in adults, the early use o inhaled corticosteroids in
preschool wheeze to optimize uture outcome is not indicated.
Symptomatic treatment for preschool wheeze: given the
lack o any evidence that the prognosis o preschool wheeze
is aected by treatment, we suggest that a symptom-based
approach, as suggested by the ERS guidelines, is appropriate.
The validity o this approach appears to be borne out by alimited amount o clinical trial data, and in practice we suggest
that in any case mothers dont want to medicate a completely
well toddler.
Treatment of episodic (viral) wheeze: bronchodilators the
rst-line treatment o episodic (viral) wheeze is with inhaled
short-acting 2 agonist and/or inhaled anticholinergics just at
the time o symptoms, depending on the response. A mask and
spacer is used; the mask can be discarded in older children.
Treatment of episodic (viral) wheeze: leukotriene receptor
antagonists i this is insucient, the use o intermittent monte-
lukast, just at the time o viral wheezing, should be considered,
ollowing the publication o the PRE-EMPT study. This group
randomized more than 200 children to receive placebo or mon-telukast at the time o a virus-induced exacerbation o wheez-
ing. The number and duration o episodes was the same in both
groups, but in the montelukast group the children lost one-third
ewer days out o school or child care, and the carers lost one-
third ewer days rom work. This strategy does not work or all
children, but is well worth considering i episodic (viral) wheeze
is seriously disruptive. The approach is more logical than using
montelukast daily or episodic (viral) wheeze, since the eleva-
tion o cysteinyl leukotrienes is present only during viral inec-
tions, and is more likely to be practical since parents are mostly
reluctant to medicate well children. It is o course possible to
use montelukast as a prophylactic medication, but no study has
shown that this approach is superior to low-dose inhaled corti-costeroids at any age.
Treatment of episodic (viral) wheeze: steroids there have
been important new studies addressing the role o inhaled and
oral corticosteroids in preschool episodic (viral) wheeze. A
Cochrane review had previously concluded that prophylactic
low-dose inhaled corticosteroids did not prevent viral exacerba-
tions o wheeze, but that there might be a role or intermittent
high-dose treatment. New evidence has been published on the
treatment o acute exacerbations o episodic wheeze in preschool
children. A Canadian study compared high-dose (1.5 mg daily)
inhaled futicasone against placebo, given at the time o viral
exacerbations o wheeze, and demonstrated benet in terms o
ewer prescribed courses o oral prednisolone. This has to beconsidered a proo-o-concept study; the futicasone-treated chil-
dren had a small reduction in linear growth over the 612-month
study period, and they could not exclude eects on adrenal unc-
tion. It should be recalled that 10% o preschool children have
more than ten viral colds a year, and symptoms may last or at
least 2 weeks, so these high doses may lead cumulatively to a
big total dose o futicasone. Dose-nding studies are needed,
with more detailed saety data, beore this strategy can be
recommended.
Oral prednisolone is the bedrock o treatment or acute exac-
erbations o asthma in older children and adults, and this med-
ication is widely prescribed or acute preschool viral wheeze.
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A previous study recruited preschoolers who had been admit-
ted to hospital or an exacerbation o wheeze, and randomized
them to a parent-initiated course o either prednisolone or pla-
cebo at the time o the next episode. This intervention had no
benet. The group has now reported a randomized double-blind,
placebo-controlled trial in nearly 700 preschool children who
came to hospital with a presumed viral exacerbation o wheeze.
There was no benet o oral prednisolone in this more severegroup either. Thereore one is orced to the conclusion that, in
preschool children with episodic (viral) wheeze, prednisolone
is indicated in secondary care only in children in whom a very
severe or prolonged course is anticipated. Prednisolone should
not be prescribed in primary care or these children. It may
be that prednisolone will benet the highly atopic, multitrig-
ger wheezer who has a viral exacerbation, or children already
admitted to hospital and looking like needing admission to the
intensive care unit, but, in particular in young children, this is
probably the exception.
It may appear to be paradoxical that high-dose inhaled ste-
roids may work whereas oral steroids do not; the (speculative)
explanation may be that the steroid eect is by local vasocon-striction as a topical eect, leading to a reduction in airway cali-
bre by lessening airway oedema.
Treatment of multitrigger wheeze: what works best there
has been a single randomized controlled trial comparing the
addition o either oral montelukast or nebulized budesonide or
placebo to inhaled salbutamol in the setting o episodic (viral)
wheeze. Both budesonide and montelukast treatment led to mod-
est improvements in the severity but not requency o attacks.
Given the side-eect prole, we would recommend intermittent
montelukast as the rst line, with the use o intermittent ICS or
montelukast treatment ailures.
Treatment of multitrigger wheeze i a preschool child
is having symptoms several times per week, and symptomsrespond to inhaled bronchodilators, then a trial o ICS may
be merited. That some preschool children benet rom ICS is
indubitable, in particular those aged 3 years and over, who
are atopic, and who have multitrigger wheeze. However, ben-
et in non-atopics is unlikely, and given the evidence rom
bronchoalveolar lavage and endobronchial biopsy studies that
wheezing at age less than 3 years is usually not an eosinophilic
disease, the use o these medications in such children should
be very limited i they are used at all . I a trial is contemplated,
we recommend a three-stage protocol. The rst step is to intro-
duce ICS or an arbitrary 2-month period in a moderately high
dose (or example, budesonide 400 g twice daily). Symptoms
are assessed at stage two, and the medication discontinued. Ithere has been no response, the symptoms are not steroid-sensi-
tive; i they have disappeared, it is not clear whether this is due
to the medication or the passage o time. I symptoms appear
to respond, but then recur on stopping the medication, then
treatment is restarted, titrating to the lowest dose required to
control symptoms. Only thus will the over-diagnosis o asthma
due to an apparent response to steroid therapy be avoided.
Undoubtedly some preschool children will benet, but equally
without doubt steroids are grossly over-prescribed to young
children.
Treatment of preschool wheeze: summary it is clear that we
need radically to overhaul our current therapeutic practices with
regard to the prescription o oral and inhaled corticosteroids, and
to curtail their use drastically in preschool children.
Astma i t olr cil
Tratmt of mil astma i cilr: missio crp
Current guidelines recommend low-dose inhaled corticosteroids
as rst-line therapy in children with asthma who merit prophy-laxis. Long-acting 2 agonists are introduced at a later step, and
in children, the benets are by no means clear-cut. Data rom
Denmark has shown that, in primary care, more children are
prescribed combination inhalers (Seretide) than inhaled corti-
costeroids. Over a period o less than 10 years the proportion o
school-age asthmatic children prescribed combination therapy
has risen rom 16% to 44%, with no evidence base, and no new
trials and no new evidence-based guideline recommendations to
support such a change. One is orced to the conclusion that this
change is driven by aggressive marketing by the pharmaceutical
industry. This has implications o scal cost, but also, perhaps
more importantly, saety and ecacy. A recent meta-analysis
has highlighted the possible adverse eects o long-acting 2agonists; we accept that the main concern is when they are
used as single agents, without concomitant inhaled corticoste-
roids. Ecacy may be an issue; the Pediatric Asthma Controller
Trial (PACT) was a three-way comparison between montelukast
5 mg at night versus futicasone 100 g twice daily versus futi-
casone 100 g once daily and salmeterol 50 g twice daily. More
than 80 children were completions in each limb o the study.
Montelukast was signicantly inerior to the other regimens
(which were equivalent) in the primary outcome o days when
asthma was controlled. However, the futicasone-only regimen
was better than both the alternatives or some secondary end-
points. The number o children requiring rescue steroid therapy
showed a trend to be smaller in the futicasone group (P< 0.10),and exhaled nitric oxide levels and the improvement in pre-
bronchodilator rst-second orced expired volume (FEV1) were
signicantly better in the futicasone group than either o the
other regimens. Thus, i anything, the evidence avours the
current guideline recommendations, that rst-line prophylaxis
should be with inhaled corticosteroid monotherapy and not
combination treatment. Stand rm against the siren cry o the
marketers!
Tratmt of mor svr paiatric astma: SMART or GOAL?
Two new treatment strategies have been proposed. The data
come largely rom adult studies, but there are enough paediat-
ric data to challenge current dogma. The GOAL (Gaining Opti-mal Asthma ControL) philosophy is that all symptoms can be
abolished by increasing medication (in this case Seretide) to
ever higher levels. The SIGN/BTS target o using short-acting
2 agonist less than three times a week is replaced by the much
more stringent one o requiring no rescue medication at all.
Furthermore, in this study, the dosage having been racked up
to high levels, no attempt at reduction was made over the ol-
lowing 12 months. This strategy, seductive as it may be, seems
to us to have signicant faws. Firstly, it conuses control o
interval symptoms with prevention o exacerbations. Loss o
baseline control is not the same as an exacerbation. It is per-
ectly possible to be symptom-ree between viral colds, but
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still have signicant virus-associated exacerbations. Indeed,
increasing the dose o prophylactic medications in an unavail-
ing attempt to prevent viral exacerbations may well have been
a signicant contributor to the epidemic o severe hypoglycae-
mia secondary to adrenal suppression reported in children on
high-dose inhaled steroids. Secondly, given the tendency or
much childhood asthma to improve, and hence guideline rec-
ommendations to try to reduce therapy when asthma is wellcontrolled, the strategy o no dose reduction seems rather dan-
gerous. Finally, we do not have the data to know whether it is
better in terms o long-term respiratory outcome and systemic
side-eects such as growth ailure to have a ew symptoms
requiring short-acting 2 agonists, with a lower dose o inhaled
corticosteroids, or to have a higher steroid dosage and no symp-
toms. In terms o respiratory outcomes, it should be noted that
in the Childrens Asthma Management Program (CAMP) study,
treatment with inhaled corticosteroids did not prevent around
25% o asthmatic children rom having suboptimal increases in
spirometry with growth. At the moment, this approach cannot
be recommended in children.
The alternative approach, SMART (Symbicort Maintenanceand Reliever Therapy), is a one-inhaler strategy which takes
advantage o the rapid onset o action o the long-acting 2 agonist
ormoterol. This is based on a study comparing three regimens:
budesonide 100 g/ormoterol 6 g once daily plus extra doses o
the same inhaler as required (SMART regimen): the same inhaler
twice daily, with rescue terbutaline; or budesonide 400 g twice
daily with rescue terbutaline. The children in the SMART regi-
men had ewer exacerbations. Perhaps surprisingly, there was
no dramatic increase in ICS use in the SMART regimen, with an
average o less than one extra inhalation per day. This regimen
has the advantage o simplicity, and might possibly increase the
adherence o recalcitrant adolescents, although as yet there is no
evidence or this. O course it relies on the adequate perceptiono symptoms, which is a problem in some asthmatics. Nonethe-
less, this is a regimen we have ound to be useul in clinical
practice. There is an urgent need or a well-designed randomized
controlled trial comparing SMART and GOAL in children with
asthma.
Tratmt of mor svr paiatric astma: gt t
basics rigt
Perhaps one o the most worrying trends in asthma therapeu-
tics is the ever-higher doses o medication being prescribed in
primary care beore a reerral to hospital is made. Perhaps this
seems like special pleading by tertiary care, but we already know
o the hypoglycaemia and adrenal ailure caused by high-doseICS prescribed inappropriately. The approach to a child with
asthma not responding to moderate doses o standard therapy is
not slavishly to increase the therapy, but to ask why there is no
response. The two usual reasons are that the diagnosis is wrong,
or that the child is not getting the treatment. This was under-
scored in a trial recruiting children with asthma uncontrolled on
a minimum o budesonide 400 g twice daily plus salmeterol
50 g twice daily, to determine whether adding azithromycin or
montelukast as supplementary therapy was benecial. Neither
was eective. However, the main signicance o the trial was
that o 292 children evaluated, only 55 went into the trial; the
commonest reasons or non-randomization were non-adherence
to treatment and improved control with proper supervision. In
another study o inner-city asthma, attention to detail in the run-in
period led to a marked attrition o symptomatic asthmatics. So
the really important take-home message is that oten therapy-
resistant asthma is no such thing.
The standard denitions o severe asthma incorporate per-
sistent symptoms or severe exacerbations or both, despite high-
dose standard therapy, usually combinations o high-dose ICS,long-acting 2 agonists and leukotriene receptor antagonists. We
suggest that children meeting this denition require systematic
evaluation rather than escalating trials o treatment. A ull work-
up or alternative diagnoses is essential. I the diagnosis is truly
asthma, then we have suggested the term problematic severe
asthma or this group. A ull multidisciplinary assessment,
including a nurse-led home and school visit, is undertaken to
urther categorize these children. Those with dicult asthma
include children who are non-compliant, have adverse environ-
mental actors, or have psychosocial issues. Their asthma may
still be dicult to treat, but they would not be candidates or
novel molecular-based therapies such as anti-IgE (Xolair). The
second group have severe therapy-resistant asthma (sometimescalled reractory asthma in adult practice), and are worked up
with a series o invasive tests, including bronchoscopy. Indeed,
we recommend this sort o detailed specialist evaluation, which
goes beyond even the NICE (National Institute or Clinical Excel-
lence) guidelines, beore Xolair is prescribed. In our experience,
more than 50% o problematic severe asthmatics need attention
to the basics rather than expensive and potentially dangerous
therapies.
FuRTheR ReAdInG
Bh LB, phlls Br, Zg rS, l. care nwk. es s hl s lk gs
shl hl wh --sv whzg.
J Allergy Clin Immunol 2008; 122: 112735.
B ed, Bsh Ha, Bsq J, l. GoaL ivsgs G.
c gl- sh l b hv? th Gg
ol ash cL s.Am J Respir Crit Care Med2004;
170: 83644.
Bsg H, Hs mn, Ll L, l. i hl
ss s wh s whzg. N Engl J Med
2006; 354: 19982005.
Bsg H, L rx p, Bj d, l. Bs/l
ls lv h: w sg
sh. Chest2006; 130: 173343.
B pL, Bl e, Bsg H, l. d, ssss
whzg ss shl hl: v-
bs h. Eur Respir J2008; 32: 1096110.
dh Fm, L c, n FJ, l. pv s hgh-s
fs vs- whzg g hl. N Engl J
Med2009; 360: 33953.
Glb tW, mg WJ, Zg rS, l. Lg- hl
ss shl hl hgh sk sh. N Engl
J Med2006; 354: 198597.
Hs J, Gll r, H J, l. asss whzg
hs h s 6 s l wh , lg
w ssvss -hlh. Thorax2008; 63: 97480.
8/7/2019 06 Paediatric and Child Health June2009 Pulmonology
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SympoSium: reSpiratory medicine
paediatricS and cHiLd HeaLtH 19:6 265 2009 pblsh b elsv L.
m cS, Wk a, Lgl SJ, l. S v
sh b h s hl fs whz
s (iWWin): bl-bl, s ll s. Lancet
2006; 368: 75462.
o a, Lb pc, Ggg J. e sh s
- l sl vl whz hl
g 15 s: s ll l. Lancet2003; 362:
14338.pk J, Lkhl m, Lb pc, l. ol sl
shl hl wh vs- whzg. N Engl J Med
2009; 360: 32938.
rbs cF, p d, H r, l. Sh-s lks
sh hl: z ll l.Am J
Respir Crit Care Med2007; 175: 3239.
Skss ca, Lsk J. rF, mg dt, l. chlh ash
rsh e nwk h nl H, Lg,
Bl is. Lg- s 3 ll
gs l ss hlh sh: h
p ash cll tl.J Allergy Clin Immunol 2007; 119:
6472.
Sk rc, Bh LB, phlls Br, l. care nwk. azh lks s hl s-sg gs
--sv hlh sh s.J Allergy Clin Immunol
2008; 122: 113844.
Szf SJ, mhll H, Skss ca, l. mg sh bs
xhl x gl-bs
- lss g ls: s ll
l. Lancet2008; 372: 106572.
Practic poits
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paediatricS and cHiLd HeaLtH 19:6 266 2009 elsv L. all ghs sv.
Maaemet of brochiolitisml as
il dll
Abstract
Bhls s h s s hsl ss .
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s, h s bg s sl vs (rSV). Sv
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Keywors bhls; bhls; ss; h
sl; rSVItroctioIn 1963 EOR Reynolds concluded that oxygen therapy is vitally
important in bronchiolitis and there is little convincing evidence
that any other therapy is consistently or even occasionally use-
ul. It is arguable that there has been little progress in the sub-
sequent 46 years. Treatments that might be eective include
nebulized 3% hypertonic saline mixed with a bronchodilator,
and ventilatory support or respiratory ailure. For the major-
ity o patients, however, supportive management is the main-
stay, with emphasis on treating insucient fuid intake and
hypoxia.
EpiemioloyBronchiolitis is the commonest cause o hospitalization in
inancy. It usually aects inants aged 16 months, although it
can occur up to 2 years o age, and is usually a mild sel-limiting
illness that does not require medical intervention. It is a clinical
syndrome characterized initially by coryzal symptoms ollowed
Madeleine AdamsMRCPCH is a Specialist Registrar in Paediatrics at the
Cystic Fibrosis/Respiratory Unit, Childrens Hospital for Wales, Cardiff, UK.
Iolo DoullDM FRCPCH is a Consultant Respiratory Paediatrician at the
Cystic Fibrosis/Respiratory Unit, Childrens Hospital for Wales, Cardiff, UK.
by onset o harsh cough, tachypnoea and wheezing. On exami-
nation there may be chest hyperinfation with costal recession,
and ne inspiratory crackles and polyphonic expiratory wheeze
on auscultation.
A signicant contributor to conusion over the management
o bronchiolitis is the absence o an internationally agreed com-
mon denition. In the United Kingdom, Australasia, and parts
o Europe, bronchiolitis is interpreted as the presence o tachy-pnoea, hyperinfation o the chest, and characteristically wide-
spread ne end inspiratory crackles on auscultation. Wheeze is
commonly but not invariably present. The pattern o illness is
virtually always seen in the rst year o lie, most commonly in
the rst 6 months o lie. In contrast, in North America and other
parts o Europe, bronchiolitis is a term or any viral inection o
the lower respiratory tract in the rst 2 years o lie, and may
include children with recurrent wheeze. The conusion over de-
nition is compounded by dierent ty