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Comparison between Inhaled Corticosteroid and Montelukast in
Uncontrolled Asthma among the Children below 5 Years Age.
INTRODUCTION:
Asthma in childhood is a heterogeneous disease with diferent phenotypes
and variable clinical maniestations, which depend on the age, gender,
genetic background, and environmental inuences o the patient (1-3!
Asthma is the most common chronic disease in children("! #he burden o
asthma is e$perienced not only in terms o healthcare costs but also as lost
productivity and reduced participation in amily lie(%. Asthma is characterized
physiologically by variable airlow obstruction and airway hyperresponsiveness !"#. &or
patients with symptoms consistent with asthma, but normal lung unction,
measurements o airway responsiveness to methacholine, histamine,
mannitol, adenosine monophosphate or e$ercise challenge may help to
establish a diagnosis o asthma('-! Asthma is a condition characteri)ed by
variable airow obstruction, airway hyper-responsiveness (A*+ and airway
inammation which is usually, but not invariably, eosinophilic (1, 11! Clinical
diagnosis o asthma is oten based on the presence o symptoms$ such as cough$ wheeze$
breathlessness$ and chest tightness and other diagnostic testing is essential!%&$ %'#.
Asthma is the most common chronic disease in children in many low( and middle(income
countries !%)#. In these settings$ the burden o childhood asthma is increasing and is associated
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with severe disease because o many actors. *hese include under(diagnosis o childhood
asthma$ access to care$ ability o healthcare workers to manage asthma$ availability and
aordability o inhaled therapy$ environmental control o potential triggers$ education o
healthcare providers and o the public$ and cultural or language issues!%)#.
*he global prevalence o asthma ranges %+%,- o the population although it varies widely in
dierent countries !%5#. *he /0 has estimated that %5 million disability(ad1usted lie(years
are lost annually due to asthma$ representing %- o the total global disease burden! %"#. Annual
worldwide deaths rom asthma have been estimated at &52$222 and mortality does not appear to
correlate well with prevalence !%3#. *here has been a sharp increase in the global prevalence$
morbidity$ mortality$ and economic burden associated with asthma over the last )2 years$
particularly in children !%,(&2#. *he increasing number o hospital admissions or asthma$ which
are most pronounced in young children$ relect an increase in severe asthma$ poor disease
management$ and poverty!&%(&'#. ith an increase in prevalence comes an increased burden o
disease in terms o morbidity$ mortality and compromised 4uality o lie. *he economic burden
in terms o utilization o healthcare resources and limitation o the earning capacity o the
individuals and amilies is an added problem !&)$ &5#. *he data rom Asian countries regarding
these parameters is scarce$ underlining the need or systematic studies in these countries$
especially those that are resource poor !&"#.
*he chronic inlammation o asthma is associated with airway hyperresponsiveness that leads to
recurrent episodes o wheezing$ breathlessness$ chest tightness$ and coughing$ particularly at
night or in the early morning!&3# . Most asthmatics have hyperresponsive airways!"#. *his
makes them more sensitive than non(asthmatics to bronchoconstricting environmental eposures
which$ in their turn$ may enhance responsiveness!&,#. *he main inducers o airway inlammation
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are viral inections$ antigens$ occupational stimuli and pollutants!&6#. Although eercise$ airway
cooling and hyper( or hypotonic aerosols are potent stimuli o bronchoconstriction$ it is
4uestionable i airway inlammation is involved in their mode o action! '2#.*his narrowing is
almost always reversible in children with treatment. *he symptoms occur or worsen in the
presence o Aeroallergens like house dust mites$ pets$ cockroach$ pollens and ungi$ eercise$
respiratory inections$ tobacco smoke and strong emotional epressions like laugh$ cry$ shouting
etc !'%#.7amily history o atopy$ maternal history o asthma$ and the presence o smokers in the
house were risk actors or the maniestation o asthma!'&(')#. 8arly rhino viral wheezing is the
predictor o subse4uent asthma development in high(risk children !'5#.
A clinical diagnosis o asthma is suggested by symptoms such as episodic breathlessness$
wheezing$ cough and chest tightness !'"#. 8pisodic symptoms ater an incidental allergen
eposure$ seasonal variability o symptoms and a positive amily history o asthma and atopic
disease are also helpul diagnostic guides!'3#.
Airway responsiveness can be deined as the ease with which airways narrow in response to
various no allergic and no sensitizing stimuli$ including inhaled pharmacologic agents$ such as
histamine and methacholine$ and physical stimuli$ such as eercise!',#. Interactions between
environmental and genetic actors result in airway inlammation leading to airway obstruction in
the orm o bronchospasm$ mucosal edema$ and mucus plug !'6#. Airway obstruction causes
increased resistance to airlow and decreased epiratory low rates. *hese changes lead to a
decreased ability to epel air and may result in hyperinlation!)2#. *he resulting over distention
helps maintain airway patency$ thereby improving epiratory low9 however$ it also alters
pulmonary mechanics and increases the work o breathing!)%#. Childhood asthma is a ma1or
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concern or the patient and the care given. *he morbidity leads to greater number o school days
o aecting daily activities and simultaneously the impact on child:s psyche !)&())#.
8vidence suggests that appropriate treatment o asthma leads to less morbidity with less number
o school absteeinism in children!5#. *he goals o asthma treatment are to limit the re4uency$
severity and costliness o asthmatic episodes through etensive education o physicians$ children
and caregivers. *he our components o asthma management include regular assessment and
monitoring$ control o actors that contribute to or aggravate symptoms$ pharmacologic therapy
and education o children and their care givers. Asthma education is an essential part o the
treatment o this disease. *he eective management o asthma implies eective partnership
between the patient and the health care providers !)5#. Asthma sel(management education
improves patient (outcomes and can be cost eective!)"#. ;educing a patient:s eposure to risk
actors !e.g.$ smoking cessation$ reducing eposure to second hand smoke$ reducing or
eliminating eposure to occupational agents known to cause symptoms$ and avoiding
oods
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REVIEW OF LITERATURE
EPIDEMIOLOGY
Asthma is a common chronic disease o childhood which causes considerable morbidity. Asthma
aects % in %' school(age children and is a leading cause o oice and emergency department
visits$ hospitalizations$ and school absenteeism. 8stimating the prevalence o asthma in the
community is important in assessing the impact o asthma at the level o population! '#. *he
prevalence o Asthma varies widely.
Asthma is now one o the most important diseases o childhood in developed countries. In the
International =tudy o Asthma and Allergies in Childhood !I=AAC# study$ the highest asthma
prevalence was observed in westernized 8nglish(speaking countries !e.g.$ the United >ingdom$
Australia$ and ?ew @ealand#$ with much lower prevalence rates in 8astern 8urope$ India$ China$
other countries in Asia$ and Arica!5%#. Although there are considerable geographical dierences
in its presentation$ bronchial asthma is an illness in constant increase in the entire world! . *he
prevalence o asthma has gradually increased over the past &2 years in developed countries.
esternization o way o lie is associated with increased prevalence o atopy$ allergic rhinitis
and asthma !5. In a landmark study signiying the eect o geography and lie style conducted
in Chine showed Asthma symptoms in Chinese adolescents were lowest among residents o
mainland China$ were greater or those in /ong >ong and those who had immigrated to Canada$
and were highest among those born in Canada. *hese indings suggest that environmental actors
and duration o eposure inluence asthma prevalence !5'#. =imilarly colleagues rom 8cuador
have shown that the prevalence o asthma increases with increasing levels o urbanization in
transitional communities$ and actors associated with greater socioeconomic level and changes
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towards a more urban liestyle may be particularly important!5)#. In ?etherlands a estern
diet was ound to increase the risk o re4uent respiratory symptoms at ' and ) years o age !55#.
Malmstorm rom 7inland showed that while the prevalence o mild and moderate asthma has
increased$ the occurrence o severe asthma has remained essentially unchanged !5"#. In a
multicenter study noted the prevalence o childhood asthma and availability o indoor swimming
pools in 8urope are linked to pool chlorine in the rise o childhood asthma in industrialized
countries!53#.
In India the prevalence o Asthma was reported to be &.)-!5,#. In another study conducted in
*amil ?adu it was ound that though the prevalence o diagnosed childhood asthma was about
5- in both urban and rural areas$ the prevalence o Bbreathing diicultyB and nocturnal cough was
signiicantly higher among urban children in the age group o "(%& year! 56#. In another study
rom rural India the prevalence o %2.3- in children o grade 3 and ,!"2#.
A study rom /ong >ong 4uoted the prevalence o Asthma to be %%-! "%#. In apan *anaka and
other workers noted a prevalence o 3."-!". *he highest prevalence o asthma was also
reported rom apan which was &5."- in children aged %'(%) years. ! "'#. In *aiwan Diao and
others ound the prevalence o asthma was 3.2-!")#. Another epidemiological study rom
*aipei$ *aiwan showed the prevalence o asthma to have risen rom %.'2- in %63) to 5.23- in
%6,5$ with boys dominating in both studies!"5#. oreover some studies have suggested
that a diet with a high intake o at and simple sugars and low intake o ruit$ vegetables and rice
is associated with an increased risk o asthma in *aiwanese children!""#.orkers rom *urkey
reported the prevalence o Asthma to be %.6- !"3#. A *hai study showed the prevalence o
asthma to be ,.,!",#. orkers rom =iri Danka showed the prevalence o asthma to be %3-! "6#.
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/owever$ recent studies have shown that the prevalence in Asia is increasing$ although the rate
o increase has slowed in the more developed Asian cities!%#.
In Iran a study ound that the pooled prevalence or girls$ boys$ and the two genders was
obtained as '.&- !CI9 &.5 to '.6-#$ ).'- !CI9 '.5 to 5.%-# and '.6- !CI9 '.& to ).3-#$
respectively!'#.In *urkish Cyprus the prevalence o physician diagnosed asthma was %%.)-! 32#.
In the *urkish study conducted in Ankara the prevalence o asthma was ,.%-!3%#. In 8dirine $
*urkey prior physician diagnoses o asthma was ).%- or preschool children!3. In ordan the
prevalence o physician diagnosed asthma was ).%-!3'#.Moreover it was ound that the
prevalence among Eedouin children was more than city children!6.5- versus ,.,-#!3)#. *he
prevalence o asthma in school age children age %'(%) years old was %'.3- in the state o Israel
!35#. In a Debanese study by Musharaae the prevalence o asthma was ,.%- !3"#. Eehbehani
rom >uwait showed the prevalence o asthma to be %".,- !33#. In a Malaysian study the
prevalence o asthma was ,.'-!3,#. 8ven in a particular country$ the prevalence o asthma
varies by race e.g. an 8nglish study showed that %,.&- o Elack Caribbean children and 5.2- o
Eangladeshi children reported ever asthma compared with %%."- o hite children!36#.
Colleagues rom ?orway concluded that lietime prevalence o asthma was &2.&-9 current
asthma %%.%-$ doctor diagnosis o asthma %".%- and wheezes ever '2.'-!,2#. *he prevalence
o physician(diagnosed asthma was 6.5-$ while 6."- reported the use o asthma medicine !,%#.
.everal large =wiss epidemiologic studies conirmed both$ the high prevalence o
asthma!6.%-#$ and the health impact o moderate air pollution levels and o actors associated
with the Bwestern liestyleB!,.
*here are also gender dierences in the prevalence o asthma. A study conducted in *aiwan
ound that boys had signiicantly higher prevalence o wheezing and rhinitis than girls while
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younger children tend to have higher prevalence o the disorders than those that are older in age
!,'#.
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RISK FACTORS FOR DEVELOPING ASTHMA
7actors inluencing Fevelopment and 8pression 0 Asthma can be classiied as precipitating
actors and /ost actors.
Precipitatin !act"r#
a$ Allergens like ood$ animal$ mold$ spores$ pollens$ insects!,)#
%$ Frugs!,5#
c$ Irritants!)3# like paint odors$ sprays$ perumes$ chemicals$ smoke!,"#$ cold air$ cold
water and cough
&$ eather changes
e$ Inection like viral$ ungal !aspergillosis#$ bacterial !E. Gertussis#$ and parasitic
!*oocara$ ascariasis#!,)#
!$ 8ercise !32 - o all asthmatics#!,3#
$ 8motional actors!,,#
'$ Hastro esophageal relu!,6# ( !?octurnal =ymptoms#
i$ Allergic rhinitis!62#
($ 8ndocrine!6%# ( menstrual cycles$ oral contraceptive pills and hyperthyroidism
)$ =inusitis!6 !?octurnal symptoms#
H"#t !act"r#
Gene#: Henetic studies indicate that multiple genes are involved in the pathogenesis o this
disease$ and chromosomal regions likely to harbor asthma currently susceptibility genes have
been replicated in several studies !6'#. 7urthermore$ interaction between susceptibility genes and
environmental actors is probable and is a challenge being pursued by investigators worldwide
!6)$ 65#. 7amily studies have identiied a number o chromosomal regions associated with
asthma susceptibility. *he most consistently replicated regions are on chromosomes &4$ 54$ "p$
%&4 and %'4 !6"#. =imilarly$ Gatient response to the asthma drug classes$ bronchodilators$ inhaled
corticosteroids and leukotriene modiiers$ are characterized by a large degree o heterogeneity$
which is attributable in part to genetic variation!63$ 6,#.
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O%e#it*: Epidemiological data indicate that obesity increases the prevalence and incidence
of asthma (99). Obesity results in important changes to the mechanical properties of the
respiratory system, and these obesity-related factors appear to exert an additive effect to the
asthma-related changes seen in the airways(!!). "revalence of asthma and overweight has
increased simultaneously during the past decades .Obesity is capable of reducing pulmonary
compliance, lung volumes, and the diameter of peripheral respiratory airways, and may
influence on airway hyperresponsiveness(!). #he increase of adipose tissue in obese
sub$ects leads to a systemic inflammatory state, which produces a rise in the serum
concentrations of several pro-inflammatory cyto%ines, chemo%ines and adipo%ines (!&).
Se+: Male se is a risk actor or asthma. Eeore the age o ) years the prevalence is twice as
great in boys as in girls but ater this the dierence narrows and by adulthood the prevalence is
greater in women !%2'#.
A,,eren#: Allergens$ such as pollen$ dust mites and animal ur or eathers$ can trigger asthma in
children who are allergic to them!%2)#. Airborne irritants$ such as cigarette smoke$ chemical
umes and atmospheric pollution may trigger asthma. Indoor conditions$ such as mold or damp
and occasionally chemicals in carpets and looring materials$ may trigger asthma!%25#. /owever$
the relationship between the allergen eposure and sensitization is not straight orward. It
depends on the allergen$ the dose$ time o eposure$ child:s age and possibly genetics. =ome
children have allergies to nuts or other oods. A child with a ood allergy may have an asthma
attack as part o an allergic reaction to a ood!%2"#. hen this is severe$ it is known as
anaphylais. 7oods containing sulphites ( sulphites are naturally occurring substances ound in
some ood and drink. *hey are also sometimes used as a ood preservative. 7ood and drinks that
are high in sulphites include concentrated ruit 1uice$ 1am$ prawns and many processed or pre(
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cooked meals. Most children with asthma will not have this trigger. Medicines$ such as the class
o painkillers called non(steroidal anti(inlammatory drugs !?=AIFs#$ which includes aspirin
and ibuproen$ occasionally trigger asthma in children!%23#.
Vira, In!ecti"n#: ;=$ ollowed by the Gara inluenza viruses$ is the chie cause o
hospitalization or respiratory tract illness in young children!%2,#. =ome types o viral inections
can also trigger asthma. Gara inluenza virus aects the respiratory tract in children$ sometimes
causing bronchitis !inlammation o the bronchi# or pneumonia. A number o long term
prospective studies o children admitted to the hospital with documented ;= inection have
shown that approimately )2- o these continue to wheeze or have asthma in later
childhood!%26#.
E+erci#e: 8ercise(induced bronchoconstriction !8IE# has a high prevalence in children with
asthma$ and this is a common problem$ even in case o controlled asthma$ because o the high
levels o physical activity in the childhood !%%2#. 8ercise induced asthma is the conventional
term or transient airway narrowing in a known asthma in association with strenuous eercise
usually lasting 5(%2 minutes with a decline in pulmonary unction by at least %2- ! %%%# ./eat
loss$ water loss$ post(eertional airway rewarming$ and the role o several mediators have been
proposed as possible mechanisms responsible or the airway obstruction induced by eercise!'2#
. *he kind o physical activities that can bring on asthma symptoms include not only eercise$
but also laughing$ crying$ holding oneBs breath and hyperventilating. *he symptoms o eercise(
induced asthma usually go away within a ew hours. ith proper treatment$ a child with
eercise(induced asthma does not need to limit his or her overall physical activity !%%.
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Diet: Studies reveal that inants ed ormulas o intact cowBs milk or soy protein compared with
breast milk have a higher incidence o atopic dermatitis and wheezing illnesses in early
childhood!%%'#. Increased consumption o linoleic acid$ ound in polyunsaturated atty acids
!GU7As#$ is thought to be linked to asthma$ eczema and allergic rhinitis through increase in the
synthesis o prostaglandin(8& !GH8$ resulting in allergic sensitization!%%)#.
PATHOPHYSIOLOGY
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*he pathophysiology o asthma is comple and involves interlinked connection o airway
inlammation$ intermittent airlow obstruction and bronchial hyper responsiveness.
Air-a* in!,a..ati"n: Airway hyperresponsiveness !A/;# and airway inlammation are key
pathophysiological eatures o asthma. Asthma is characterized by reversible airway obstruction$
airway hyperresponsiveness$ and airway inlammation!%%5#. *he irst mechanism identiied as
important or asthma was bronchial hyperresponsiveness. In a second step$ asthma was
recognized also as an inlammatory disease$ with chronic inlammation inducing structural
changes or remodeling!%%"#. Asthma is a comple chronic inlammatory disease o the airways
that involves the activation o many inlammatory and structural cells$ all o which release
inlammatory mediators that result in the typical pathophysiological changes o asthma. *hese
include mast cells$ macrophages$ eosinophils$ * lymphocytes$ dendritic cells$ basophils$
neutrophils$ and platelets!%%3#. Airway epithelial cells$ smooth muscle cells$ endothelial cells$
and ibroblasts are all capable o synthesizing and releasing inlammatory mediators acute
conse4uences o asthma are bronchoconstriction$ plasma eudation$ and mucus
hypersecretion!%%,#. Inlammatory cells$ such as activated eosinophils and neutrophils identiied
in sputum and bronchial lavages !ED# in severe acute asthma rom children and adults are
associated with increased levels o ID(5$ ID(,$ and o proinlammatory mediators. iruses$ but
also endotoin or allergen eposure$ are able to recruit neutrophils$ via an ID(, production by
activated macrophages or epithelial cells. *ogether$ these inlammatory mediators are responsible
or the diuse bronchial inlammation$ which involve large and small airways!%%,# . *his
chronic inlammation may result in structural changes in the airway$ such as ibrosis !particularly
under the epithelium#$ increased thickness o the airway smooth muscle layer !hyperplasia and
hypertrophy#$ hyperplasia o mucus(secreting cells$ and new vessel ormation !angiogenesis#
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.*he initial physiopathological event o inlammatory response in the production o primary
cytokines$ *?7(alpha$ ID(% and ID(" by macrophages!%%6#. *hese and other cytokines trigger
the progress and ampliication o inlammatory process involving secondary mediators and
inlammatory cells !*h%
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mechanisms in response to inection. *h&$ in contrast$ generates a amily o cytokines !ID()$ ID(
5$ ID("$ ID(6$ and ID(%'# that can mediate allergic inlammation.
Air!,"- O%#tr/cti"n: Airlow obstruction can be caused by a variety o changes$ including
acute bronchoconstriction$ airway edema$ chronic mucous plug ormation$ and airway
remodeling. Acute bronchoconstriction is the conse4uence o Ig 8(dependent mediator release
upon eposure to aeroallergens and is the primary component o the early asthmatic
response!%&5#. Airway edema occurs "(&) hours ollowing an allergen challenge and is reerred
to as the late asthmatic response. Chronic mucous plug ormation consists o an eudate o serum
proteins and cell debris that may take weeks to resolve. Airway remodeling is associated with
structural changes due to long(standing inlammation and may prooundly aect the etent o
reversibility o airway obstruction!%&"#. Airway obstruction causes increased resistance to
airlow and decreased epiratory low rates. *hese changes lead to a decreased ability to epel
air and may result in hyperinlation!%&3#. *he resulting over distention helps maintain airway
patency$ thereby improving epiratory low9 however$ it also alters pulmonary mechanics and
increases the work o breathing.
Air-a* H*perre#p"n#i0ene##: Airway hyperresponsivenessan eaggerated
bronchoconstrictor response to a wide variety o stimuliis a ma1or$ but not necessarily uni4ue$
eature o asthma. *he degree to which airway hyperresponsiveness can be deined by contractile
responses to challenges with methacholine correlates with the clinical severity o asthma!%&,#.
*he mechanisms inluencing airway hyperresponsiveness are multiple and include inlammation$
dysunctional neuro(regulation$ and structural changes9 inlammation appears to be a ma1or
actor in determining the degree o airway hyper responsiveness !%&6#. *reatment directed
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toward reducing inlammation can reduce airway hyperresponsiveness and improve asthma
control.
Figure 1: The Interplay and Interaction Between Airway Inflammation And The Clinical Symptoms And
Pathophysiology Of Asthma
From: Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma
Epert Panel !eport ": #uidelines for the Diagnosis and $anagement of Asthma.
National Asthma Education and Pre%ention Program, &hird Epert Panel on the Diagnosis and $anagement of Asthma.
'ethesda ($D): National Heart, *ung, and 'lood +nstitute (S)- 2/ Aug.
Steps at 0ellular *e%el K Ig8 antibodies are synthesized by the plasma cells$ which are present on
the surace o the respiratory tract. *hese Ig8 antibodies have become reversibly ied to the
surace receptors o mast cells and basophils !%'2#. Antigens attaches to surace Ig8 on
sensitized mast cells resulting in activation o mast cells and a cascade o biochemical reactions.
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*his results in degranulation and release o preormed mediators !early phase mediators(
histamine$ 8C7$ ?C7$ heparin$ GA7# within '2 minutes !'6#. Arachidonic acid is ormed through
the activation o phospholipase. 7rom arachidonic acid$ leukotrienes are ormed via the
lipoygenase pathway and prostaglandins via the cyclooygenase pathway !%'%#. *hese late
phase mediators are responsible or the late reaction$ which develops " to , hours ater the
eposure to allergen.!D8U>0*;I8?8= C)$F)$8) collectively called slow releasing substances
o anaphylais#
*he development o allergic asthma eists o three phases$ namely the induction phase$ the
early(phase asthmatic reaction !8A;# and the late(phase asthmatic reaction !DA;#. 8ach phase
is characterized by the production and interplay o various cell(derived mediators. Crucial in
the development o airway inlammation in allergic asthma is the allergic cascade!%'. Inhaled
allergens that escape the mucociliary clearance are taken up and processed by antigen presenting
cells !AGCs#$ which are distributed throughout the respiratory tract$ rom the nasal mucosa to the
lung pleura!%''#. *hese AGCs then migrate to the draining lymph nodes where the processed
allergen is presented to allergen( speciic * and E cells. Interactions between those cells elicit
responses that are characterized and inluenced by secreted cytokines and the presence or absence
o cell(bound costimulatory molecules. Activation o * helper !*h# cells by AGCs leads to the
production o cytokines that regulate the iso( type switch o E cells in their production o
Ig8!%')#. 0nce synthesized$ Ig8 antibodies circulate in the blood binding to the high(ainity
Ig8 receptor 7c ;I that is present on mast cells in tissue or on peripheral blood basophils. Ater
re(eposure$ allergens cross(link to mast cell( bound speciic Ig8$ thus causing the activation o
membrane and cytosolic pathways$ which subse4uently trigger the release o preormed
mediators$ such as histamine$ the synthesis o prostaglandins !GHs# and leukotrienes !D*s#$ and
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the transcription o cytokines by mast cells. *hese mediators cause the so(called 8A;$ which is
characterized by constriction o A=M cells$ vascular leakage$ mucus production$ enhanced
A/; and recruitment o inlammatory cells. *his 8A; is immediate$ lasting '2+"2 min and )+"
h later ollowed by the DA;. *he late(phase is characterized by ecessive inlammation o the
airways$ resulting in structural changes$ including airway wall thickening$ subepithelial ibrosis$
goblet cell hyperplasia$ myoi( broblast hyperplasia$ A=M cell hyperplasia and hypertrophy$ and
epithelial hypertrophy. *his is collectively known as airway remodeling!%'5#.
Figure 2: Factors *imiting Airflo1 +n Acute And Persistent Asthma.
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Source: Adapted and reprinted from &he *ancet, "3, Holgate S&, Polosa !. &he mechanisms, diagnosis, and management of
se%ere asthma in adults, /345". 0opyright (2), 1ith permission from Else%ier.
From: Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma
Epert Panel !eport ": #uidelines for the Diagnosis and $anagement of Asthma.
National Asthma Education and Pre%ention Program, &hird Epert Panel on the Diagnosis and $anagement of Asthma.
'ethesda ($D): National Heart, *ung, and 'lood +nstitute (S)- 2/ Aug.
+nduction of the allergic reaction:
Furing the induction phase$ allergens enter the airways$ are processed by AGCs$ and are brought
to the lymph nodes. /ere$ they are presented to * and E cells. Activation o *h cells leads to
the production o various cytokines$ such as interleukin !ID#(&$ ID('$ ID()$ ID(5$ ID("$ ID(6$ ID(
%2$ ID(%&$ ID(%'$ ID(%,$ intereron !I7?#( $ tumor necrosis actor !*?7#( $ *?7( and HM(
C=7!%'"#. 0 these$ ID()$ ID(5$ ID(6 and ID(%' are the most important in the development o
asthma. ID() and ID(%' play a role in isotope switching to Ig8 production. *ogether with ID(6$
they are also important in mast cell development$ mucus overproduction and A/;!%'.
Early6phase asthmatic reaction
$ast cells: *he most crucial cell types in the 8A; are mast cells. Mast cells are involved in the
pathophysiology o asthma through their capacity to secrete a wide variety o mediators ater
activation by allergens!%'3#. ;e(eposure to a previously met allergen leads to its binding on
Ig8 antibodies that are attached to mast cell 7c ;I receptors. *his causes cross(linking o 7c
;I receptors$ where( upon mast cells degranulate and synthesize pro(inlammatory molecules.
Mediators produced by mast cells can be divided into preormed mediators !e.g. histamine#$
newly synthesized lipid mediators !e.g. GHs and D*s#$ and cytokines and growth actors !e.g.
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*?7$ 8H7!%'2#. Greormed mediators are packaged within secretory granules in the mast
cell and$ on activation$ are released into the etracellular environment within minutes. Grincipal
granule constituents include histamine$ proteases !tryptase$ chymase$ and carboypeptidase#
and proteoglycans !heparin and chondroitin sulphate 8#. /istamine eerts eects on smooth
muscle cells !contraction#$ endothelial cells$ venule permeability$ nerve end( dings$ and mucus
secretion. *he unction o tryptase in %i%o is unknown$ but in %itro it can cleave complement
C' and C'a$ activate ibroblasts$ promote accumulation o inlammatory cells and potentiate
histamine(induced smooth muscle contraction!%',#. *ryptase is used as a marker o mast cell
degranulation. Chymase has a procollagen proteinase activity and is probably directly toic to
the airway cells!%',#. 0ther mast cell proteases likely contribute to activation o protein
cascades and inlict local tissue damage
*ipid $ediators include GHs and D*s$ inlammatory metabolites derived rom the peroidation
o arachidonic acid!%'6#. *hese molecules have various eects in the asthmatic airway$ e.g.
recruitment o inlammatory cells$ bronchoconstriction and mucus secretion.
& *ymphocytesK * lymphocytes play a very important role in coordinating the inlammatory
response in asthma through the release o speciic pattern o cytokines resulting in the
recruitment and survival o eosinophils and maintenance o mast cells in airway .*he
programming o * lymphocytes is due to antigen presenting cells such as dendritic cells which
may migrate rom epithelium to regional lymph nodes or which interact with lymphocytes
resident in airway musosa. Children with atopy are more likely to retain */& type
phenotype!%)2#.
;egulatory * cells suppresses the immune response through the release o inhibitory cytokines
such as ID(%2 and transorming growth actor beta and play an important role in immune
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regulation with suppression o */% responses!%)%#. /owever$ their role in allergic diseases has
not been well deined.
' *ymphocytes: In allergic diseases$ E lymphocytes secrete Ig8. ID() is responsible or
switching E cells to Ig8!%).
0yto7ines: Mast cells play a role in more persistent or chronic inlammatory responses through
the release o multiunctional cytokines. *?7( is a ma1or cytokine produced by mast cells9 it
up regulates endothelial and epithelial adhesion molecules$ increases A/;$ and has antitumor
eects !%)'#. 0ther cytokines produced by mast cells include ID()$ which is associated with *h&
cell dierentiation and Ig8 synthesis$ ID('$ HM(C=7$ and ID(5$ which are critical or
eosinophil development and survival$ and ID("$ CNC(chemokine ligand !CNCD# , !ID(,#$ and
ID(%".
*ate6phase asthmatic reaction
*he late(phase o the asthmatic reaction is characterized by ecessive inlammation o the
airways resulting in structural changes induced by various mediators derived rom
inlammatory cells$ like eosinophils$ neutrophils$ * cells$ macrophages$ dendritic cells !FCs#$
endothelial cells$ A=M and E8Cs.
Increased numbers o eosinophils eist in the airways o most$ but not all$ persons who have
asthma !%))#. *hese cells contain inlammatory enzymes$ generate leukotrienes$ and epress a
wide variety o pro(inlammatory cytokines. Increases in eosinophils oten correlate with greater
asthma severity. *hey may release basic proteins that may damage the airway epithelial cells.
*hey also have a role in release o growth actors and airway remodeling . In addition$ numerous
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studies show that treating asthma with corticosteroids reduces circulating and airway eosinophils
in parallel with clinical improvement!%)5#.
Neutrophils: ?eutrophils are increased in the airways and sputum o persons who have severe
asthma$ during acute eacerbations$ and in the presence o smoking!%)"#. *heir
pathophysiological role remains uncertain9 they may be a determinant o a lack o response to
corticosteroid treatment !%)3#. *he regulation o neutrophil recruitment$ activation$ and
alteration in lung unction is still under study$ but leukotriene E) may contribute to these
processes.
$acrophages: Macrophages are the most numerous cells in the airways and also can be activated
by allergens through low(ainity Ig8 receptors to release inlammatory mediators and cytokines
that ampliy the inlammatory response !%%6#.
!esident cells of the air1ay: A=M is not only a target o the asthma response !by undergoing
contraction to produce airlow obstruction# but also contributes to it !via the production o its
own amily o pro(inlammatory mediators#. As a conse4uence o airway inlammation and the
generation o growth actors$ the airway smooth muscle cell can undergo prolieration$
activation$ contraction$ and hypertrophyevents that can inluence airway dysunction o
asthma!%&"#.
Epithelial 0ellsK Airway epithelium is another airway lining cell critically involved in asthma.
*he generation o inlammatory mediators$ recruitment and activation o inlammatory cells$ and
inection by respiratory viruses can cause epithelial cells to produce more inlammatory
mediators or to in1ure the epithelium itsel. *he repair process$ ollowing in1ury to the
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epithelium$ may be abnormal in asthma$ thus urthering the obstructive lesions that occur in
asthma!'2#.
Air1ay !emodeling: 0ngoing inlammation may result in structural remodelingK wall
thickening$ subepithelial ibrosis$ metaplasia$ hypertrophy and hyperplasia o airway cells$
cartilage breakdown and angiogenesis. *he most prominent mediators o airway remodeling are
$atri metalloproteinases, 0yto7ines, 0hemo7ines, .Endothelin68, 9ascular endothelial gro1th
factor, *ipid mediators (Prostaglandin D2, Prostaglandin E2, 36+soprostane), 0ysteinyl
leu7otrienes, *eu7otriene ' and ADA$""( 83 ).
$atri metalloproteinasesK Connective tissue cells produce and secrete an array o macro(
molecules orming a comple network illing the etracellular space o the submucosa$ called
the 8CM. *he 8CM is a dynamic structure$ and e4uilibrium between synthesis and degradation
o 8CM components is re4uired or the maintenance o its homeostasis. MMG:= are responsible
or the development$ morphogenesis$ reproduction$ and tissue resorption and remodeling !%)6#.
*he balance MMGs are thought to play a central role in between MMGs and *IMGs$ which
is critical in tissue repair and remodeling$ and its homeostasis plays an important role in the
breakdown and deposition o 8CM in the airway wall!%52#. MMGs are also implicated in
alteration o angiogenesis and smooth muscle hyperplasia processes.
0yto7ines: Firect and modiy the inlammatory response in asthma and likely determine its
severity. *h&(derived cytokines include ID(5$ which is needed or eosinophil dierentiation and
survival$ and ID() which is important or *h& cell dierentiation and with ID(%' is important or
Ig8 ormation!%5%#. >ey cytokines include ID(%O and *?7(L$ which ampliy the inlammatory
response$ and HM(C=7$ which prolongs eosinophil survival in airways. ;ecent studies o
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treatments directed toward single cytokines !e.g.$ monoclonal antibodies against ID(5 or soluble
ID() receptor# have not shown beneits in improving asthma outcomes.
0hemo7inesK Among them$ CCD& is increased in asthma$ and is a well(established
proibrogenic mediator in %itro and in %i%o by inducing *H7( release and collagen deposition
rom lung ibroblasts$ and by recruiting *h& cells in the lung!%&)#. 0ther CC(chemokines$ such
as CCD3 and CCD&& also contribute to the development o pulmonary ibrosis.
Endothelin 8: 8ndothelin !8*#(% may be involved in airway remodelingK it is mitogenic or A=M
cells and ibroblasts$ and also stimulates collagen synthesis !%5.
9ascular Endothelial #ro1th Factor: vascular endothelial growth actors !8H7# induce epression o
connective tissue growth actor and collagen !%5'#. Macrophages$ eosinophils and CF')P cells
are the ma1or source o 8H7. *he epression o 8H7 is up regulated in the bronchial mucosa
o mild to moderate asthmatic patients$ compared with that o control sub1ects$ and is related to
the number o vessels and mast cells$ as well as to the basement membrane thickness!%),#.
*ipid $ediators: Prostaglandin D26 Grostaglandins appear to have several eects on the
airways$ including bronchoconstriction$ plasma eudation$ sensitization o nerve endings$ and
eects on inlammatory cells. GHF& is involved in the recruitment o inlammatory cells because
it stimulates the chemotais o *h& cells$ eosinophils$ neutrophils and basophils$ GHF& and
GH7& cause bronchoconstriction in asthmatic patients$ but not in healthy sub1ects!%5)#.
Prostaglandin E2 is also an important GH produced in inlammatory processes!%55#. It is the
most important bronchoprotective metabolite yet identiied in the airways!%5"#. GH8& inhibits
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the release o mediators rom mast cells$ monocytes$ neutrophils and eosinophils. GH8& and
GHI& are vasodilators and thereore should theoretically increase leakage in asthmatic.
36+soprostane: Isoprostanes are inlammatory metabolites derived rom arachidonic acid. It
plays a role in non(speciic smooth muscle hyperresponsiveness$ bronchoconstriction and
edema!%53#.
0ysteinyl *eu7otrienes: *here is substantial evidence that cys(D*s !D*C)$ D*F) and D*8)#
play an important role in asthma!%'%#. Cys(D*s mediate several steps in airway inlammation$
including inlammatory cell recruitment$ vascular leakage and possibly also airway
remodeling!%5,#. *hey decrease mucociliary clearance and are potent mediators o
bronchoconstriction9 plasma eudation and mucus secretion also increase eosinophilic
inlammation.
*eu7otriene ': Deukotriene E) is a potent neutrophil chemoattractant that enhances neutrophil(
endothelial interactions and stimulates neutrophil activation. *his leads to degranulation and the
release o mediators$ enzymes and superoides.
ADA$"": A disintegrin and metalloproteinase !AFAM# '' has been a ocus o interest in the last
ew years!%56#. AFAM'' has been linked to asthma in a study o )"2 white amilies. Abnormal
activity o this gene can lead to altered airway unction$ inlammation$ and remodeling!%"2#.
Alterations in AFAM'' activity may underlie abnormalities in the unction o A=M cells and
ibroblasts linked to airway remodeling and A/;.
=ummary o mediators released by the various cell types that are involved in the early and late
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asthmatic reaction
Cell source ;eleased mediators
+nduction phase
* cells Cytokines !ID()$ ID(5$ ID(6$ and ID(%'#
Early asthmatic reaction
Mast cells /istamine9 proteases !tryptase$ chymase$ and
carboypeptidase#9 proteoglycans !heparin$
chondroitin sulphate 8#9 prostaglandins !GHF
leukotrienes !D*C)#9 cytokines !*?7( $ ID('$ ID()$
ID(5$ ID("$ ID(,$ ID(%"$ and HM(C=7#9 chemokines
!CCD&$ CCD'$ CCD%%#
Easophils /istamine9 leukotrienes !cys(D*sK D*C)$ D*F)$
D*8)#9 cytokines !ID()$ ID(%'#
*ate asthmatic reaction
8osinophils MEG9 8CG9 8F?9 8G9 leukotrienes !cys(D*sK D*C)$
D*F)$ D*8)#9 cytokines !ID(%$ ID(&$ ID('$ ID()$ ID(5$
ID("$ ID(%2$ ID(%%$ ID(%&$ *?7( $ *H7( $ *H7( $ HM(
C=7#9 chemokines !CNCD,$ CCD'$ CCD5#
?eutrophils Deukotrienes !D*A)$ D*E)#9 GA79 *NA&9 cytokines
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!ID(% $ ID("$ *?7( $ *H7( #9 chemokine !CNCD,#9
proteases !elastase$ collagenase$ gelatinase E#9
microbicidal products !lactoerrin$ myeloperoidase$
lysozyme#9 reactive oygen intermediates !superoide$
hydrogen peroide#9 ?0
* cells Cytokines !ID('$ ID()$ ID(5$ ID("$ ID(6$
ID(%2$ ID(%'$ HM(C=7#9 chemokines
!CCD%$ CCD&
Macrophages Cytokines !ID(%$ ID("$ I7?( $ *?7( #9
chemokines !CNCD,#9 lipids9 GA79
;0=9 ?0 Fendritic cells
Chemokines !CCD&$ CCD'$ CCD)$
CCD%3$ CCD&&$ CNCD,#
8ndothelial cells ICAM(%$ ICAM(&9 G8CAM(%9 CAM(%9 selectins !8(
selectin$ G(selectin#
Airway smooth muscle cells Chemokines !CCD5$ CCD3$ CCD%%$ CCD%'$ CNCD,#9
cytokines !HM(C=7$ ID("#9 prostaglandins !GH8 8CM
proteins
Eronchial epithelial cells Cytokines !ID("$ HM(C=7#9 chemokines !CCD%%$ CCD%3$
CCD&&$ CNCD%$ CNCD"$ CNCD,#9 ICAM(%
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CLASSIFICATION AND DIAGNOSIS OF ASTHMA1
A clinical diagnosis o asthma is suggested by symptoms such as episodic breathlessness$
wheezing$ cough and chest tightness!'"#. Intermittent dry coughing and epiratory wheezing are
the most common chronic symptoms o asthma!%"%#. Younger children are more likely to report
intermittent$ non(ocal chest pain!%". 8pisodic symptoms ater an incidental allergen eposure$
seasonal variability o symptoms and a positive amily history o asthma and atopic diseases are
helpul diagnostic studies. *he patterns o these symptoms that strongly suggest an asthma
diagnosis areK variability9 precipitation by nonspeciic irritants$ such as smoke$ umes$ strong
smells or eercise9 worsening at night9 and responding to appropriate asthma therapy!%"'# . A
clinician should consider asthma i the child has physical activity induced cough or
wheeze!%")# . A useul method or conirming the diagnosis o asthma in children aged Q5 years
is a trial o treatment with short(acting bronchodilators and inhaled glucocorticosteroids. Marked
clinical improvement during the treatment$ and deterioration when treatment is stopped$ supports
a diagnosis o asthma!%"5#.
;espiratory symptoms that begin at or persist through ages ' to ) years are highly diagnostic o
asthma. Cough(variant asthma !patients have chronic cough as their principal$ i not only$
symptom# is particularly common in children and is oten more problematic at night9 evaluations
during the day can be normal!%""# . Children with cough variant asthma do not wheeze .A
simple clinical inde based on the presence o a wheeze beore the age o ' and the presence o
one ma1or risk actor !parental history o asthma or eczema# or two o three minor risk
actors!eosinophilia$ wheezing without colds and allergic rhinitis# has been shown to predict the
presence o asthma in later childhood !%"3#.
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*hree categories o wheezing have been described in children 5 years and younger.
Tran#ient Ear,* W'ee2in outgrows in the irst three years. *his is oten associated with
prematurity and parental smoking!%",#.
Per#i#tent Ear,* On#et W'ee2e !beore the age o '# these children have recurrent episode o
wheeze associated with acute viral upper respiratory tract inections$ have neither evidence nor
amily history or atopy !%"6$ %32#. *he symptoms normally persist through school age and
sometimes till the age o %&. *he cause o episode is usually respiratory syncytial virus in those
under the age o & and other viruses in older children. . *here is now convincing evidence that
children who develop lower respiratory symptoms during inection with respiratory syncytial
virus !;=# in early lie are at increased risk o developing asthma(like symptoms during the
school years!%3%#.
Late On#et W'ee2e3A#t'.a *hese children have asthma which oten persists throughout
childhood and into adult lie. *hese patients have atopic background oten with eczema and
airway pathology which is characteristic o asthma !%32#.
Cough Variant AsthmaK Gatients with cough variant asthma have chronic cough as their
principal symptom. It is more problematic at night$ evaluations during the day time can be
normal.
E+erci#e In&/ce& 4r"nc'"c"n#tricti"nK *ypically develops within 5 to %2 min ater completing
eercise!it rarely occurs during eercise#.Gatients eperience typical asthma symptoms which
resolves spontaneously within '2 to )5 min. 8ercise induced bronchoconstriction can develop
in any climatic condition but is more when patient is breathing dry $cold air and less common in
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hot$ humid climate. ;apid improvement o symptoms ater inhaled beta & agonist use supports
the diagnosis o asthma!%%2#.
Di!!erentia, Dian"#e#
*able %.Fierential diagnosis
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Upper respiratory tract conditions
Allergic rhinitis
Chronic rhinitis
=inusitis
Adenoidal or tonsillar hypertrophy
?asal oreign body
Middle respiratory tract conditions
Daryngotracheobronchomalacia
Darayngotracheobronchitis !e.g. pertusis#
Daryngeal web$ cyst or stenosis
ocal cord dysunction
ocal cord paralysis
*racheoesphageal istula
ascular ring$ sling or eternal mass compressing the airway!tumor#
7oreign body aspiration
Chronic bronchitis rom tobacco smoke eposure
*oic inhalations
Dower ;espiratory *ract Conditions
Eronchopulmonary dysplasia!chronic lung disease o preterm inants#
iral bronchiolitis
Hastroesophageal relu
Eronchiectasis
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La%"rat"r* Fin&in#:
Dung unction tests help to conirm the diagnosis o asthma and to determine disease severity.
P/,."nar* !/ncti"n te#tinK Use o spirometry and other lung unction measures are
diicult to perorm in young children below the age o 5 years old and are not suitable or
routine use!%3. A trial o treatment with short(acting bronchodilators and inhaled
glucocorticosteroids with marked clinical improvement supports the diagnosis o asthma
7or patients R5 yrs o age$ measurements o lung unction to conirm airlow limitation$ and
particularly the demonstration o reversibility o lung unction abnormalities$ greatly enhance
diagnostic conidence!%3'#. *he degree o reversibility in orced epiratory volume in one
second !78%# that indicates a diagnosis o asthma is generally accepted as %&- and &22 mD
rom the pre(bronchodilator value .
51 Spir".etr* is helpul as an ob1ective measure o airlow limitation. alid spirometric
measures depends on a patient:s ability to properly perorm a ull$ orceul and prolonged
epiratory maneuver$ easible in children R" years o age. I the 78 % !orced epiratory volume
in % sec# is within 5 - on ' attempts$ then the highest 78 % eort o the three is used!%3)#.
Henerally an 78%
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&. 4r"nc'"&i,at"r re#p"n#e to inhaled beta agonist !albuterol# is greater in asthmatic patients
than non(asthmaticK an improvement in 78% o more than or e4ual to %&- or R&22 ml is
consistent with asthma !%3)#.
'. 4r"nc'"pr"0"cati"n c'a,,ene#K Gatients with symptoms consistent with asthma$ but normal
lung unction$ measurements o airway responsiveness to methacholine$ histamine$ mannitol$
adenosine monophosphate or eercise challenge may help to establish a diagnosis o asthma can
be helpul in diagnosing asthma and optimizing asthma management!%3"#.
). E+erci#e c'a,,ene# !aerobic eercise or running or " to , min# can help identiy children
with an eercise induced bronchospasm. In asthmatic patients$78% typically decreases during
or ater eercise by R%5-.*he onset o eercise induced bronchospasm in usually within %5
minutes ater a vigorous eercise challenge and can spontaneously resolve within '2 to "2 min.
=tudies o eercise challenges in school aged children typically identiy an additional 5(%2 -
with eercise induced bronchospasm and previously unrecognized asthma!%33#.
5. Mea#/rin e+'a,e& nitric "+i&e 6FENO$
8aled nitric oide !7e?0# is considered a good noninvasive marker to assess airway
inlammation in asthma and allergic rhinitis. In asthma$ ehaled ?0 is very useul to veriy
adherence to therapy$ and to predict upcoming asthma eacerbations !%3,#. It has been also
proposed that ad1usting anti(inlammatory drugs guided by the monitoring o ehaled ?0$ could
improve overall asthma control!%36#.
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?o tests diagnose asthma in this age group. *he therapeutic trial o treatment with 4uick relievers
and inhaled steroids or , + %& weeks showing improvement during therapy and relapse ater
stopping therapy is diagnostic o asthma!%,2#.
P'*#ica, E+a.inati"nK
*he most usual abnormal physical inding is wheezing on auscultation! %,%#. Furing asthma
eacerbations$ epiratory wheezing and a prolonged epiratory phase is heard on auscultation
!%,. Fecreased breath sounds in some o the lung ields$ indicate areas o hypoventilation due
to obstruction!%,2#. Crackles indicate ecess mucus production and inlammatory eudate in
airways in severe eacerbations$ the greater etent o airways obstruction causes labored
breathing and respiratory distress$ poor air entry$ suprasternal and intercostal recessions$ nasal
laring and accessory respiratory muscle use!%,'#. In etreme cases$ airlow may be so limited
that wheezing cannot be heard.
Ra&i","*K
*he indings o chest radiographs !poster anterior and lateral view# in children with asthma oten
appear to be normal ecept o nonspeciic indings o hyperinlation !lattening o diaphragm#
and per bronchial thickening !%,)#. Chest radiographs can be helpul in identiying abnormalities
that are hallmarks o asthma mas4ueraders !aspiration pneumonitis$ hyper(lucent lung ields in
bronchiolitis obliterans# and complications during asthma eacerbations !%26#.
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A#t'.a c"ntr",:
As the goal o asthma treatment is to achieve control$ all patients must be continually reviewed
to monitor that control has been achieved and is maintained. *his can be achieved with various
tools such as a symptom assessment 4uestionnaire or Asthma Control *est !AC*# !%,5#or
monitoring o pulmonary unction with peak epiratory low rates$ spirometry$ or ehaled nitric
oide. Frug therapy can then be ad1usted according to the patient:s level o control. Children
who are very well controlled on low doses o inhaled corticosteroids may be able to come o
treatment. Complete control o asthma is commonly achieved with treatment$ the aim o which
should be to achieve and maintain control or prolonged periods with due regard or the saety o
treatment$ potential or adverse eects$ and the cost o treatment re4uired to achieve this
goal!%3%#. Its assessment should incorporate the dual components o current clinical control !e.g.
symptoms$ reliever use and lung unction# and uture risk !e.g. eacerbations and lung unction
decline#
Clinical studies have shown that asthma can be eectively controlled by intervening to suppress
and reverse the inlammation$ as well as treating the bronchoconstriction and related symptoms
!%,"#. 7urthermore$ early intervention to stop eposure to the risk actors that sensitized the
airway may help improve the control o asthma and reduce medication needs
*he goal o asthma treatment is to achieve and maintain clinical control. Medications to treat
asthma can be classiied as controllers or relievers !%,3#. Controllers are medications taken daily
on a long term basis to keep asthma under clinical control chiely through their anti(
inlammatory eects. *hey include inhaled glucocorticosteroids$ leukotriene receptor
antagonists$ and combination therapies with long(acting beta agonists and glucocorticosteroids$
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anti(Ig8 and other steroid(sparing therapies !&&$ %,,#. ;elievers are used on an as needed basis
to 4uickly reverse bronchoconstriction and relieve symptoms. *he most commonly used
relievers are inhaled short(acting beta agonists and short acting oral beta &.!%,6#
Ta%,e 7: Le0e,# "! A#t'.a C"ntr",1
Assessment o current clinical control !preerably over ) weeks#
0HA!A0&E!+S&+0 0;N&!;**ED
(all of the
follo1ing)
PA!&*
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acti%ities active childK plays
and runs without
symptoms#
or diicult breathing
during vigorous play$
laughing#
diicult breathing during
vigorous play$ laughing
Need for relie%er
medication
& d per week More than & days per
week
More than & days per week
A==8==M8?* 07 7U*U;8 ;I=> !risk o eacerbations$ instability$ rapid decline in lung
unction$ side eects#
7eatures that are associated with increased risk o adverse events in the uture includeK
Goor clinical control$ re4uent eacerbations in the past year$ ever admission to critical care or
Asthma$ low 78%$ eposure to cigarette smoke$ high dose medications
ROUTES OF ADMINSTRATION:
Asthma treatment can be administered in a variety o waysK inhaled$ orally or parenterally !by
subcutaneous$ intravenous and intramuscular routes# !%,,$ %62# .*he ma1or advantage o inhaled
therapy is that the drug is directly delivered to the airways producing higher local concentrations
and less systemic side eects.
Fierent age groups re4uire dierent inhalers or eective therapy. *he choice o inhaler device
should include consideration o the eicacy o the drug delivery$ cost$ saety$ ease o use$
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convenience and documentation or it:s in patient:s age group. Although nebulizers have been the
mainstay o inhalation therapy in childhood asthma or many years$ these devices are
cumbersome$ bulky$ time(consuming$ and epensive to use. As a result$ over the past decade the
emphasis o inhalation therapy in children has shited rom nebulizers to metered(dose inhalers
!MFI# in combination with spacer devices!%,6# .=pacers retain large drug particles that would be
deposited in the oropharyn$ so reducing oropharyngeal side(eects and systemic absorption and
availability o inhaled drug. *his consideration is especially important or IC= with poor irst(
pass metabolism such as beclomethasone dipropionate !EFG# and budesonide !%6%#. *he vast
ma1ority o children o all ages with acute severe asthma can be managed eectively and saely
by O& agonists delivered via MFI
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Controller Medications
Controller medications or children include inhaled and systemic glucocorticosteroids$
leukotriene modiiers$ long acting inhaled O&(agonists$ theophylline$ cromones$ and long(acting
oral O&(agonists.
In'a,e& ,/c"c"rtic"#ter"i
Inhaled glucocorticosteroids are the most eective controller therapy or asthma in children with
rapid improvement in symptoms and lung unction$ even at low doses o inhaled
glucocorticosteroids !%6 .Furation o treatment should continue till bronchial hyper(
responsiveness improves !%6'#. In children o all ages$ maintenance treatment with inhaled
glucocorticosteroids controls asthma symptoms$ reduces the re4uency o acute eacerbations
and the number o hospital admissions$ improves 4uality o lie$ lung unction$ and bronchial
hyperresponsiveness$ and reduces eercise(induced bronchoconstriction!%6)#. Fose(response
studies and dose titration studies in children demonstrate marked and rapid clinical
improvements in symptoms and lung unction at low doses o inhaled glucocorticosteroids !e.g.$
%22(&22 Tg budesonide daily#$ and mild disease is well controlled by such doses in the ma1ority
o patients!%6. Inhaled steroids are now used at a much earlier stage in asthma therapy$ and
there is a strong argument or their early introduction in both adults and children to prevent
asthma morbidity and mortality and possibly the structural changes resulting rom uncontrolled
chronic inlammation$ which may lead to irreversible airlow obstruction in some
patients!%65# .8arly intervention with inhaled budesonide is associated with improved asthma
control and less additional asthma medication use . ?ebulized budesonide reduced the need or
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oral glucocorticoid therapy and also improved lung unction in children under the age o three
years !%6"# . Increasing to higher doses provides little urther beneit in terms o asthma control
but increases the risk o side(eects. /owever$ there is marked individual variability o
responsiveness to inhaled glucocorticosteroids$ and because o this and the recognized poor
adherence to treatment with inhaled glucocorticosteroids$ many patients will re4uire higher doses
to achieve ull therapeutic beneit!%63# 1 =ymptom control and improvements in lung unction
occur rapidly !ater % to & weeks#$ although longer treatment !over the course o months# and
sometimes higher doses may be re4uired to achieve maimum improvements in airway
hyperresponsiveness !%2#. hen glucocorticosteroid treatment is discontinued$ asthma control
deteriorates within weeks to months !%6,#.
Fesirable properties in an inhaled glucocorticoid are high topical potency$ low systemic
bioavailability o the portion o the dose swallowed by the patient$ and rapid metabolic clearance
o any glucocorticoid that reaches the systemic circulation. Ater inhalation a large proportion o
the inhaled dose$ ,2 to 62 percent$ is deposited on the oropharyn and swallowed. It is then
available or absorption into the systemic circulation through the liver.! %66# *his raction is
markedly reduced i the glucocorticoid is administered through a large(volume spacer attached to
a metered(dose inhaler.
Corticosteroid *rade
name
Children !" to %% years o age# Adults !%& years o
age and over#
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Eeclomethasone
dipropionate /7A
A;
Q&22 &2%+)22 R)22
Inhaled corticosteroid !IC=# dosing categories in children and adults
Dow Medium /igh Dow Medium /igh
V Q&52 &5%+522 R522
EudesonideW Gulmicort *urbuhalerX Q)22 )2%+,22 R,22 Q)22 )2%+,22
R,22
CiclesonideW Alvesco Q&22 &2%+)22 R)22 Q&22 &2%+)22 R)22
7luticasone 7lovent MFI and spacer9 7lovent FiskusZ Q&22 &2%+522 R522 Q&52
&5%+522 R522
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Si&e e!!ect# (*he ma1ority o studies evaluating the systemic eects o inhaled
glucocorticosteroids have been undertaken in children older than 5 years.
• HrowthK Asthma and its level o control may directly aect growth in the same way as
most chronic diseases o childhood! Continuous administration o IC=s in low to medium
dose over many years is well tolerated. . Dow doses do not have clinically deleterious
side eects on the bones$ growth$ eye$ or hypothalamo(pituitary(adrenal(ais!&22#.
/owever$ they do not normalize lung unction and prevent structural changes in the
airway wall in all asthmatic patients !&2%#. 8ect o IC= on growth depends on dose and
duration o intake as well as the susceptibility o the growth phase during which the child
inhales steroids!&2 . ith all inhaled corticosteroids given at high dosage$ there is
likely to be a dual eect due to topical bioactivity rom the airway dose as well as
prednisone like activity rom the systemic bioavailable dose!&2'#. *he use o a large
spacer device has been shown to reduce the incidence o both topical and systemic
adverse eects rom inhaled steroids !&2. /eight measurements made over a period o
less than % year are liable to error and misinterpretation. *he delay in pubertal growth is$
however$ also associated with a delay in skeletal maturation so that the bone age o the
child corresponds to the height !&2)#. Ultimately$ there is no decrease in attained adult
height$ though it is reached at a later age than normal !&25#. *his dierence in growth
pattern seems to be unrelated to the use o inhaled corticosteroids and is more
pronounced in those children with the most severe asthma!&2"# . In school(age children
asthma should be treated irst with inhaled steroids. It is probable that the best
combination o eicacy and saety can be achieved by using low steroid doses ! &25#.
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• H*p"t'a,a.ic8pit/itar*8a&rena, 6HPA$ a+i#. Dong(term ollow(up studies in children
concluded that inhaled steroids are well tolerated$ with little or no eect on growth and
hypothalamic(pituitary(adrenal ais unction!&22#. *hus it is a valuable therapeutic
alternative to systemic corticosteroid therapy in inants and young children. ith
sensitive techni4ues$ dose(dependent adrenal suppression has been documented in
children treated with inhaled steroids but generally this eect has no clinical relevance
!&23#. Most children develop biochemical evidence o adrenal suppression ater treatment
with medium to high doses o IC=!&2,#. At higher doses$ small changes in /GA ais
unction can be detected with sensitive methods.
• 4"ne# an& G,/c"c"rtic"#ter"i in C'i,&ren: 0ne o the greatest concerns o long(term
corticosteroid therapy or asthma is its potential or adverse eects on bone turnover$
resulting in an increased risk or osteoporosis and racture. ?o studies have reported any
statistically signiicant increase o risk o ractures in children taking inhaled
glucocorticosteroids !&2)#. Dow doses do not have clinically deleterious side eects on
the bones$ growth$ eye$ or hypothalamo(pituitary(adrenal(ais !&26#. /owever$ they do
not normalize lung unction and prevent structural changes in the airway wall in all
asthmatic patients. Calcium supplementation may be necessary in children with asthma
treated with inhaled steroids since this treatment may cause reduction in osteocalcin$ a
marker o osteoblast activity and bone ormation!&%2# .0ral Corticosteroids!continuous
or intermittent# is associated with an increased risk o racture and cataracts in children
and continuous treatment also with increased risk o adrenal insuiciency and growth
retardation!&%%#. Eone mineral density may be decreased by high doses o inhaled
glucocorticoids$ but their eect is conounded by the act that patients taking these drugs
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also receive intermittent courses o oral glucocorticoids. 0ral glucocorticoid therapy is a
well(known cause o osteoporosis and an increased risk o vertebral and rib ractures 1
Cataract#1 Dong(term administration o medium dose IC=s does not increase the risk o
cataracts or osteopenia in children and young adults !&% .
• Centra, ner0"/# #*#te. e!!ect#K Fespite the propensity o glucocorticoids to cause
psychiatric disturbance including emotional lability$ euphoria$ depression$
aggressiveness$ and insomnia inhaled corticosteroids are not associated with any
adverse eects!&23#.
•Ora, can&i&ia#i#9 '"ar#ene##9 an& %r/i#in. 0ropharyngeal candidiasis and dysphonia
are the most commonly recognized adverse eects o therapy$ but these topical
phenomena cause no signiicant morbidity and are easily managed!&%'#. =pacers reduce
the incidence o oral candidiasis. *he use o spacer devices and mouth rinsing may
reduce local and systemic adverse eects.
• Denta, #i&e e!!ect#. ;ecent studies have provided little evidence or asthma caries
causative relationship ./owever$ Asthma is one o the most common chronic medical
conditions in childhood which is considered high risk or caries. *he most recent reports
have concluded that the individualistic nature o asthmatic condition$ through either its
disease status or its pharmacotherapy !dierent combinations o medicaments#$ carries
several actors or an increased caries risk !&%)# .
E!!ect# "n C"nnecti0e Ti##/e1 *here are reports o increased skin bruising and purpura
in patients receiving high doses o inhaled beclomethasone$ but the amount o
intermittent glucocorticoids they received is not known. 8asy bruising linked to inhaled
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glucocorticoids is more re4uent in elderly patients9 there are no reports o this problem
in children!&%5#.
• Ot'er ,"ca, #i&e e!!ect#. *he long(term use o inhaled glucocorticosteroids is not
associated with an increased incidence o lower respiratory tract inections$ including
tuberculosis.
\
Le/)"triene ."&i!ier#1
*he leukotrienes are potent inlammatory mediators in asthma and contribute to increased mucus
production$ bronchoconstriction and eosinophil iniltration!&%"#. *hese compounds are produced
via the lipoygenase pathway by mast cells$ eosinophils and alveolar macrophages
Clinical studies have demonstrated that leukotriene modiiers have a small and variable
bronchodilator eect$ reduce symptoms !including cough# $ improve lung unction$ and reduce
airway inlammation and asthma eacerbations!&%3#. /owever$ when used alone as controller$
the eects o leukotriene modiiers are less than those o low doses o inhaled
glucocorticosteroids and$ in patients already on inhaled glucocorticosteroids$ leukotriene
modiiers cannot substitute or this treatment without risking the loss o asthma control!&%,#.
Deukotriene modiiers used as add(on therapy may reduce the dose o inhaled
glucocorticosteroids re4uired by patients with moderate to severe asthma$ and may improve
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asthma control in patients whose asthma is not controlled with low or high doses o inhaled
glucocorticosteroids!&%6#.
Deukotriene modiiers provide clinical beneit in children older than 5 years at all levels o
severity$ but generally less than that o low(dose inhaled glucocorticosteroids!&%,#. Deukotriene
modiiers provide partial protection against eercise(induced bronchoconstriction within hours
ater administration with no loss o bronchoprotective eect.
D*;As have been proposed as alternative irst(line therapy to IC=s or episodic or mild
persistent asthma who have diiculty in utilizing inhalation treatment$ with poor compliance$ or
where eercise(induced bronchospasm !8IE# is a dominant component o asthma!&&2$ &&%# .
D*;As are approved or treatment o both allergic rhinitis and asthma !&&.
Side effects: ?o saety concerns have been demonstrated rom the use o leukotriene modiiers in
children .
Long-acting inhaled O2-agonists.
;ole in therapy (Dong(acting inhaled O&(agonists are primarily used as add(on therapy in
children older than 5 years whose asthma is insuiciently controlled by medium doses o inhaled
glucocorticosteroids or as single(dose therapy beore vigorous eercise!&&'#. Monotherapy with
long acting inhaled O&(agonists should be avoided!%"5#. Dong(acting inhaled O&(agonists have
mainly been studied in children older than 5 years as add(on therapy or patients whose asthma is
not controlled on low to high doses o inhaled glucocorticosteroids!). =igniicant
improvements in peak low and other lung unction measurements have been ound in most
studies. /owever$ their eects on other outcomes such as symptoms and need or reliever
medication have been less consistent and have only been observed in about hal o the trials
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conducted. Combination products containing an inhaled glucocorticosteroid and long(acting
inhaled O&(agonists are preerred to long(acting inhaled O&(agonists and inhaled
glucocorticosteroids administered by separate inhalers !&&)#.
In Children 5 years and younger$ the eect o long(acting inhaled O&(agonists has not been
ade4uately studied. Combination therapy with budesonide and ormoterol used both as
maintenance and rescue has been shown to reduce asthma eacerbations in children ages ) years
and older with moderate to severe asthma!&&5#.
=ide eectsK Dong acting inhaled beta & agonists are not the recommended option when more
than one controller is re4uired!). I used$ long(acting O&(agonists should only be used in
combination with an appropriate dose o inhaled glucocorticosteroid as determined by a
physician$ preerably in a ied combination inhaler !&&"#.
THEOPHYLLINE: *heophylline has been shown to be eective as monotherapy and as add(on
treatment to inhaled or oral glucocorticosteroids in children older than 5 years!&&3#.
Maintenance treatment oers a marginal protective eect against eercise(induced
bronchoconstriction. Add(on treatment with theophylline has been ound to improve asthma
control and reduce the maintenance glucocorticosteroid dose necessary in children with severe
asthma treated with inhaled or oral glucocorticosteroids!&&3$ &&,#./owever$ the eicacy o
theophylline is less than that o low(dose inhaled glucocorticosteroids. Glasma theophylline
levels were maintained within the therapeutic range o 5(%%2 Tmol
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used or when drugs that may increase theophylline levels are also used chronically$ plasma
theophylline levels should be measured two hours beore administration o the net dose once
steady state has been !ater ' days#.
Side effects : *he most common side eects o theophylline are anoreia$ nausea$ vomiting$ and
headache!&'%#. Mild central nervous stimulation$ palpitations$ tachycardia$ arrhythmias$
abdominal pain$ diarrhea$ and$ rarely$ gastric bleeding may also occur!&'. *hese side eects
are mainly seen at doses higher than %2 mg
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better than placebo or management o asthma in children!&'3#. =tudies o the use o these
medications in children 5 years and younger are sparse and results are conlicting!&',$ &'6#.
Side effects Cough$ throat irritation$ and bronchoconstriction occur in a small proportion o
patients treated with sodium cromoglycate!&)2#. A bad taste$ headache$ and nausea are the most
common side eects o nedocromil.
Long-acting oral O2-agonists.
*reatment with long(acting oral O&(agonist such as slow release ormulations o salbutamol$
terbutaline$ and bambuterol reduces nocturnal symptoms o asthma!&)%#. Fue to their potential
side eects o cardiovascular stimulation$ aniety$ and skeletal muscle tremor$ their use is not
encouraged. I used$ dosing should be individualized$ and the therapeutic response monitored to
limit side eects.
Systemic glucocorticosteroids.
Eecause o the side eects o prolonged use$ oral glucocorticosteroids in children with asthma
should be restricted to the treatment o acute severe eacerbations$ whether viral(induced or
otherwise !&)&$ &)'#.
;eliever Medications
Rapi&8actin in'a,e& 78a"ni#t# an& #'"rt8actin "ra, 78 a"ni#t#1
;apid(acting inhaled [&(agonistss are the most eective bronchodilators available and thereore
the preerred treatment or acute asthma in children o all ages!&))#. *he inhaled route results in
more rapid bronchodilation at a lower dose and with ewer side eects than oral or intravenous
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administration. 7urthermore$ inhaled therapy oers signiicant protection against eercise(
induced bronchoconstriction and other challenges or 2.5 to & hours !long(acting [&(agonists
oer longer protection#!&)5#. *his is not seen ater systemic administration. 0ral therapy is
rarely needed and reserved mainly or young children who cannot use inhaled therapy.
Side effects. =keletal muscle tremor$ headache$ palpitations$ and some agitation are the most
common complaints associated with high doses o [&(agonists in children. *hese complaints are
more common ater systemic administration and disappear with continued treatment.
Anticholinergics : Inhaled anticholinergics are not recommended or long(term management o
asthma in children!&)"#.
ASTHMA MANAGEMENT AND PREVENTION:
*he goals or successul management o asthma are toK
\ Achieve and maintain control o symptoms
\ Maintain normal activity levels$ including eercise
\ Maintain pulmonary unction as close to normal as possible
\ Grevent asthma eacerbations
\ Avoid adverse eects rom asthma medications
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\ Grevent asthma mortality.
Clinical studies have shown that asthma can be eectively controlled by intervening to suppress
and reverse the inlammation as well as treating the bronchoconstriction and related symptoms
!%3%#. 7urthermore$ early intervention to stop eposure to the risk actors that sensitized the
airway may help improve the control o asthma and reduce medication needs.
*he recommendations or asthma management are laid out in ive interrelated components o
therapy !&)3#K
%. Fevelop Gatient
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most ma1or treatment changes to their physician at the time o planned or unplanned
consultations!&),#.
ASTHMA EDUCATION
8ducation should be an integral part o all interactions between health care proessionals and
patients$ and is relevant to asthma patients o all ages!%)#. Although the ocus o education or
small children will be on the parents and caregivers$ children as young as ' years o age can be
taught simple asthma management skills but regional issues and the developmental stage o the
children may aect the outcomes o such programs.
E&/cati"n an& t'e Patient D"ct"r Partner#'ip
G"a,: *o provide the person with asthma$ their amily$ and other caregivers with suitable
inormation and training so that they can keep well and ad1ust treatment according to a
medication plan developed with the health care proessional!&)6#.
Ke* C".p"nent#:
• 7ocus on the development o the partnership
• Acceptance that this is a continuing process
• A sharing o inormation
• 7ull discussion o epectations
• 8pression o ears and concerns
• Fierence between ]relieversJ and ]controllersJ
• Gotential side eects o medications
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• Use o inhaler devices
• Grevention o symptoms and attacks
• =igns that suggest asthma is worsening and actions to take
• Monitoring control o asthma
• /ow and when to seek medical attention
T'e per#"n t'en re;/ire#:
• A written asthma action plan
• ;egular supervision$ revision$ reward$ and reinorcement.
#ood communication is essential as the basis or subse4uent good compliance
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these action plans$ the eects were also greater when the patients themselves both stepped up
inhaled glucocorticosteroids and added oral glucocorticosteroids$ based on their symptoms or or
peak low(based!&5. Gatients eperience a one(third to two(thirds reduction in hospitalizations$
emergency room visits$ unscheduled visits to the doctor or asthma$ missed days o work$ and
nocturnal wakening!&5'#. *hus$ patients who are unable to undertake guided sel(management
can still achieve beneit rom a structured program o regular medical review.
F",,"-8Up an& Re0ie-
7ollow(up consultations should take place at regular intervals. At these visits$ the patient:s
4uestions are discussed$ and any problems with asthma and its initial treatment are reviewed
!&5)#. Gatients should be asked to demonstrate their inhaler device techni4ue at every visit$ with
correction and re(checking i it is inade4uate. 7ollow(up consultations should also include
checking the person:s adherence
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A##e## *"/r ,e0e, "! A#t'.a C"ntr",
In t'e pa#t -ee) 'a0e *"/ 'a&:
Da*ti.e a#t'.a #*.pt".# ."re t'an 7 ti.e# = N" Ye#
Acti0it* "r e+erci#e ,i.ite& %* a#t'.a= N" Ye#
Wa)in at ni't %eca/#e "! a#t'.a= N" Ye#
T'e nee& t" /#e *"/r >re#c/e .e&icati"n? ."re t'an 7 ti.e#= N" Ye#
I! *"/ are ."nit"rin pea) !,"-9 pea) !,"- ,e## t'an
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EMERGENCY3SEVERE LOSS OF CONTROL
'I! *"/ 'a0e #e0ere #'"rtne## "! %reat'9 an& can "n,* #pea) in #'"rt #entence#9
' I! *"/ are 'a0in a #e0ere attac) "! a#t'.a an& are !ri'tene&9
'I! *"/ nee& *"/r re,ie0er .e&icati"n ."re t'an e0er* '"/r# an& are n"t
I.pr"0in1
51 Ta)e 7 t" p/!!#
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%. Fiiculties with inhaler devices Awkward regimes !e.g.$ our times daily or multiple
drugs#
&. =ide eects
'. Cost o medication
). Fislike o medication
5. Fistant pharmacies
N"n8&r/ !act"r#
%. Misunderstanding or lack o instruction
&. 7ears about side eects
'. Fissatisaction with health care proessionals
). Unepressed
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SELF MANAGEMENT IN CHILDREN
A systematic review ound that educational programs or the sel(management o asthma in
children and adolescents led to improvements in lung unction and eelings o sel(control$ and
reduced absences rom school$ the number o days with restricted activity$ and the number o
emergency department visits!&5'#. 7or children$ symptom(based action plans are more eective
than those based on peak lows!&5"#.
IDENTIFY AND REDUCE EBPOSURE TO RISK FACTORS
A#t'.a Pre0enti"n: Measures to prevent asthma may be aimed at the prevention o allergic
sensitization !i.e.$ the development o atopy$ likely to be most relevant prenatally and
perinatally#$ or the prevention o asthma development in sensitized people. 0ther than preventing
tobacco eposure both in utero and ater birth$ there are no proven and widely accepted
interventions that can prevent the development o asthma !&53#.
*he role o diet particularly breast(eeding$ in relation to the development o asthma has been
etensively studied and$ in general$ inants ed ormulas o intact cow:s milk or soy protein
compared with breast milk have a higher incidence o wheezing illnesses in early
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childhood!&5,#. 8clusive breasteeding during the irst months ater birth is associated with
lower asthma rates during childhood !&56$ &"2#.
8posure to cats has been shown to reduce risk o atopy in some studies!&"%#.
8posure to tobacco smoke both prenatally and postnatally is associated with measurable
harmul eects$ including eects on lung development and a greater risk o developing
wheezing illnesses in childhood!&". Gassive smoking increases the risk o allergic sensitization
in children!&"'#. Eoth prenatal and postnatal maternal smoking is problematic!&")#. Gregnant
women and parents o young children should be advised not to smoke.
Pre0enti"n "! a#t'.a S*.pt".# an& e+acer%ati"n#
Asthma eacerbations may be caused by a variety o actors$ sometimes reerred to as ]triggers$J
including allergens$ viral inections$ pollutants$ and drugs. ;educing a patient:s eposure to some
o these categories o risk actors !e.g.$ smoking cessation$ reducing eposure to secondhand
smoke$ reducing or eliminating eposure to occupational agents known to cause symptoms$ and
avoiding oods
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In&""r A,,eren#
Among the wide variety o allergen sources in human dwellings are domestic mites$ urred
animals$ cockroaches$ and ungi.
D".e#tic .ite#: Fomestic mite allergy is a universal health problem!&",#. =ince mites live and
thrive in many sites throughout the house$ they are diicult to reduce and impossible to
eradicate!&"6#. 0ne study showed some eicacy o mattress encasing at reducing airway
hyperresponsiveness in children.
%urred animals. Complete avoidance o pet allergens is impossible$ as the allergens are
ubi4uitous and can be ound in many environments outside the home$ including schools$ public
transportation$ and cat(ree buildings!&32#. Although removal o such animals rom the home is
encouraged$ even ater permanent removal o the animal it can be many months beore allergen
levels decrease and the clinical eectiveness o this and other interventions remains unproven.
Coc&roaches. Avoidance measures or cockroaches include eliminating suitable environments
restricting access !sealing entry sources such as around paperwork and doors#$ chemical control$
and traps. /owever$ these measures are only partially eective in removing residual allergens
!&3%#.
%ungi: 7ungal eposure has been associated with eacerbations rom asthma and the number o
ungal spores can best be reduced by removing or cleaning mold laden ob1ects !&3. In tropical
and subtropical climates$ ungi may grow on the walls o the house due to water seepage and
humidity. *o avoid this$ the walls could be tiled or leaned as necessary.
O/t&""r A,,eren#
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0utdoor allergens such as pollens and molds are impossible to avoid completely ! &3'#. 8posure
may be reduced by closing windows and doors$ remaining indoors when pollen and mold counts
are highest and using air conditioning i possible.
In&""r Air P",,/tant#
*he most important measure in controlling indoor air pollutants is to avoid passive and active
smoking !&3)#. =econdhand smoke increases the re4uency and severity o symptoms in children
with asthma. Garents< caregivers o children with asthma should be advised not to smoke and not
to allow smoking in rooms their children use. 0ther ma1or indoor air pollutants include nitric
oide$ nitrogen oides$ carbon monoide$ carbon dioide$ sulur dioide$ ormaldehyde$ and
biological !endotoin#!&35#.
O/t&""r Air P",,/tant#
=everal studies have suggested that outdoor pollutants aggravate asthma symptoms$ possibly
having an additive eect with allergen eposure !&3"#. Most epidemiological studies show a
signiicant association between air pollutants+such as ozone$ nitrogen oides$ acidic aerosols$
and particulate matter+and symptoms or eacerbations o asthma!&33#. 0n occasion$ certain
weather and atmospheric conditions$ e.g.