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INHALED

CORTICOSTEROIDS

VERSUS

MONTELUKAST

IN

REDUCING ASTHMA EXACERBATIONS IN CHILDREN 6 MONTHS TO


5 YEARS OF AGE

ABSTRACT:
Asthma is a leading cause of chronic disease in children globally. According to the 2011 report of
GINA guidelines, asthma is a problem worldwide with an estimated 300 million individuals
affected The diagnosis and management of asthma in young children is difficult, since there are
many different wheezy phenotypes with varying underlying etiologies and outcomes,. provided
the clinical symptoms of asthma are variable and non-specific . Therefore, many infants and
young children do not receive adequate therapy. On the other hand, not all wheeze and cough are
caused by asthma, and caution is needed to avoid giving infants and young children
inappropriate prolonged asthma therapy. In this study comparing the effectiveness of ICS versus
Montelukast, in reducing asthmatic exacerbation in uncontrolled asthma,ICS was found to be
superior

than montelukast in nearly all measured outcomes (97) Montelukast is a valid

alternative to ICS especially in poorly compliant preschool children, or in subjects who show
adverse effects related to long-term steroid therapy (98) . The enormous prevalence of asthma
and the reluctance to prescribing the adequate controller therapy was the basic aim behind this
study. We lack a consensus protocol for the choice of adequate controller therapy. Currently there
are different guidelines which address the management of asthma in young children. This review
discusses the approach to manage young children with asthma based on the recommendations of
the GINA guidelines.

(KEY WORDS: asthma, GINA, ICS, montelukast)

OBJECTIVES:
Inhaled corticosteroids are more effective than Montelukast in reducing exacerbations in
uncontrolled bronchial asthma in children 6 months to 5 years of age.

STUDY DESIGN:
Randomized controlled trial study.

SETTING:
Pediatric Unit 1 Bolan Medical Complex Hospital Quetta from March 2011 to august 2011.

METHODS:
Children 6 months to 5 years of age were admitted to the ward via OPD and emergency. The
patients parents were informed about the study duration and informed consent was taken.
Baseline tests including CBC, Chest X-ray and blood sugar were done. The patients who fulfilled
the inclusion criteria were included in the study. The patients were classified into uncontrolled
asthma according to the GINA guidelines. Patient comfort and temperature maintenance were
kept in consideration. Patients were given ICS and tab Montelukast by lottery method to remove
the bias. Those receiving ICS were named as group A and those receiving Montelukast were
labeled as B .The doses for ICS was 200 microgram per day for uncontrolled asthma.
Leukotriene modifiers were given in a dose of 4 mg once a day below 1 year and 5 mg once a
day above 1 year. They were followed up monthly for up to 6 months. Patients who were
admitted to emergency department in exacerbation or status were considered as treatment failure.
The results of the study were analyzed after six months.

RESULTS:
Various synonymous terms are given in the data, so those terms are assembled and so their
percentages. Those synonymous terms are as follows:

ICS improved/ICS stepped down/ICS recovered/ICS controlled/ ICS exacerbation

These terms were collectively labeled as ICS stepped down

ICS stepped up/ICS treatment stepped up as ICS stepped up

Mont improved/mont stepped down/montelukast improved/mont

controlled as

montelukast stepped down

Mont stepped up/mont exacerbation/montelukast exacerbation as montelukast stepped


up.

Mont admitted in status/mont give status asthmaticus as montelukast in exacerbation.

Mont not improved/mont static

In 6 months duration of study, out of 2400 participants,1200 were prescribed an inhaled


glucocorticosteroids and 1200 were put on montelukast. The results of the treatment response
seen after 6 months of study trial were as follows:
GENDER
As shown in the table 8 majority of the patients enrolled for the study were boys making up
about 1383 out of 2400 i.e.,57.625% remaining 1017(42%) were females with the mean value
of 1.4238 and standard deviation 0.49425.the P value for the sex is significant i.e., ,<0.5

DIAGNOSIS

As shown in table 9 ,the mean for the diagnosis was 4.3742 and standard deviation
5.06794.The P value for diagnosis was found to be significant i.e.,<0.5

Among the 1200 patients who were prescribed an ICS (termed as group A), 51.58% of
patients(n=1238) were stepped down after treatment with an ICS while 6.375%(n=153)
were stepped up.

1 patient was admitted in status when the one was treated with in ICS.

The other group which was put on montelukast,being labeled as group B,16.75%
(n=402)of patients were stepped down when they were treated with montelukast whereas
stepping up of the treatment was considered in 32.125% (n=771) who were put on
montelukast.

2 patients were admitted in status while 7 patients were showed static response to
treatment with montelukast.

AGE
The age range of the patients selected for this study was from 6 months to 5 years. The age
distribution in shown in the table 10 .The mean age of the patients was 2.420 with standard
deviation of 1.2558.As shown in the table, majority of the patients were 3 years of age with a

percentage of 11.8%(n=282)., minimum age range was 39 months making up.0%(n=1).the P


value for age is significant i.e.,<0.5

INTRODUCTION:
Uncontrolled asthma continues to pose a substantial health care and financial burden. The
prevalence of asthma is increasing in most countries, especially among children. The burden of
asthma is experienced not only in terms of healthcare costs but also as lost productivity and
reduced participation in family life. Asthma is characterized physiologically by variable airflow
obstruction and airway hyper responsiveness. Coughing,,shortness of breath and chest tightness
are the cardinal symptom of asthma. These episodes are usually associated with widespread, but
variable, airflow obstruction within the lung that is often reversible either spontaneously or with
treatment..
The higher prevalence of asthma in developed than in developing nations, and in affluent
compared with poor populations in developing nations, is likely to reflect lifestyle differences,
such as exposure to allergens, access to healthcare, etc .
An estimated 300 million people are affected by asthma worldwide and the burden is likely to
rise substantially in the next few decades. The global prevalence of asthma ranges 118% of the
population in different countries.

Worldwide, approximately 180,000 deaths annually are

attributable to asthma .The WHO has estimated that 15 million disability-adjusted life-y ears
are lost annually due to asthma, representing 1% of the total global disease burden .

A study

conducted at National Institute of Child Health showed that up to 4 % of children attending the
outpatient department suffers from bronchial asthma. (12)
The chronic inflammation of asthma is associated with airway hyper responsiveness that leads to
recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at
night or in the early morning . Because of the variety of asthma triggers, such as exercise,

exposure to smoke, weather changes, and allergies, asthma is now considered to be a syndrome
consisting of bronchospasm, airway hyperirritability, and inflammation . This narrowing is
almost always reversible in children with treatment. The airways of children with asthma react
to a variety of stimuli, which may include viral illnesses (e.g., the common cold), pollen, foods,
or environmental conditions . Irritants like paint odors, sprays, perfumes, chemicals, smoke, cold
air, cold water and cough; Weather changes; Infection(viral, fungal (aspergillosis), bacterial (B.
Pertussis), and parasitic (Toxocara, ascariasis); Exercise (70 % of all asthmatics); Emotional
factors; GERD - (Nocturnal Symptoms); Allergic rhinitis; Endocrine - menstrual cycles, oral
contraceptive pills and hyperthyroidism; Sinusitis (Nocturnal symptoms).
In susceptible individuals, inflammation causes:

Increased bronchial hyper responsiveness to various stimuli

Recurrent episodes of wheezing, breathlessness, chest tightness, and cough

Widespread, variable airflow obstruction that is often reversible with


treatment

Airway responsiveness can be defined 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 exercise. Interactions between
environmental and genetic factors result in airway inflammation leading to airway obstruction in
the form of bronchospasm, mucosal edema, and mucus plug. Airway obstruction causes
increased resistance to airflow and decreased expiratory flow rates. These changes lead to a
decreased ability to expel air and may result in hyperinflation. The resulting over distention helps
maintain airway patency, thereby improving expiratory flow; however, it also alters pulmonary

mechanics and increases the work of breathing. Childhood asthma is a major concern for the
patient and the care given. The morbidity leads to greater number of school days off affecting
daily activities and simultaneously the impact on childs psyche. The studies previously done has
shed more light on the age group five and above. The beneficial results of the study will affect
the outcome of asthma morbidity and mortality and will lessen its consequent effects. The
fostering of children is one of the most important sections of society which is being overlooked
and therefore requires

due attention and prudent care. Their growth and development have

strong reflection on the future of a country. Early attention to the morbid events leads to less
harm to children, less costly interventions. Any ignorance at this stage, would ultimately lead to
gross social harm, so treating asthma with appropriate drugs before it gets worse is more wise
and according to GINA guidelines inhaled corticosteroids are the most effective controller
medications available.
Evidence suggests that appropriate treatment of asthma leads to less morbidity with less number
of school absteeinism in children(5) In general, the term control may indicate disease prevention
or even cure. However, in asthma, where neither of these are realistic options at present, it refers
to control of the manifestations of disease. Complete control of asthma is commonly achieved
with treatment, the aim of which should be to achieve and maintain control for prolonged periods
with due regard for the safety of treatment, potential for adverse effects, and the cost of treatment
required to achieve this goal.. Asthma education is an essential part of the treatment of this
disease. The effective management of asthma effective partnership between the patient and the
health care provider. Asthma self-management education improves patient -outcomes and can be
cost effective. Reducing a patients exposure to risk factors (e.g., smoking cessation, reducing
exposure to second hand smoke, reducing or eliminating exposure to occupational agents known

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to cause symptoms, and avoiding foods/additives/drugs known to cause symptoms) improves the
control of asthma and reduces medication needs.

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REVIEW OF LITERATURE
Asthma can be defined as a diffuse obstructive lung disease caused by inflammation of the
airways, increased mucus production, contraction of bronchial smooth muscles, with
hyperactivity of airways to a variety of stimuli, a high degree of reversibility of obstructive
processes which may occur spontaneously or as a result of treatment.

EPIDEMIOLOGY
Asthma has presented itself as a huge burden throughout the world. Asthma is a public problem
with an estimated 300 million individuals affected worldwide. WHO has estimated that 15
million DALYS are lost annually due to asthma representing 1% of the total global disease
burden . Annually, worldwide deaths from asthma have been estimated at 250,000 and mortality
does not appear to correlate well with prevalence.

FACTORS PRECIPATATING EXPRESSION OF ASTHMA


Can be classified as precipitating factors and Host factors.

Precipitating factors includes,

Allergens like food, animal, mold, spores, pollens, insects, infective agents and drugs; Irritants
like paint odors, sprays, perfumes, chemicals, smoke, cold air, cold water and cough; Weather
changes; Infection like viral, fungal (aspergillosis), bacterial (B. Pertussis), and parasitic
(Toxocara, ascariasis); Exercise (70 % of all asthmatics); Emotional factors; GER- (Nocturnal

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Symptoms); Allergic rhinitis; Endocrine - menstrual cycles, oral contraceptive pills and
hyperthyroidism; Sinusitis (Nocturnal symptoms). While Host factors includes,

GenesRecent studies including genome-wide association studies implicate variants in other genes
contribute to bronchodilator response heterogeneity and fail to replicate asthma worsening
associated with continuous -agonist use. Genetic determinants of the safety of long-acting agonist require further study. Variants in CRHR1, TBX21, and FCER2 contribute to variability in
response for lung function, airways responsiveness, and exacerbations in patients taking inhaled
corticosteroids..Similarly, Patient response to the asthma drug classes, bronchodilators, inhaled
corticosteroids and leukotriene modifiers, are characterized by a large degree of heterogeneity,
which is attributable in part to genetic variation . : A recent post hoc analysis showed that the
17q21 locus is specifically associated with early-onset asthma (onset before the age of 4 years).
Obesity: Epidemiological data indicate that obesity increases the prevalence and incidence of
asthma. 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.. Prevalence 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. The increase of adipose tissue in obese subjects leads to a systemic
inflammatory state, which produces a rise in the serum concentrations of several proinflammatory cytokines, chemokines and adipokines .

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Sex: Male sex is a risk factor for asthma. Before the age of 4 years the prevalence is twice as
great in boys as in girls but after this the difference narrows and by adulthood the prevalence is
greater in women.
Allergens: Allergens, such as pollen, dust mites and animal fur or feathers, can trigger asthma in
children who are allergic to them. Airborne irritants, such as cigarette smoke, chemical fumes
and atmospheric pollution may trigger asthma. Indoor conditions, such as mold or damp and
occasionally chemicals in carpets and flooring materials, may trigger asthma. However, the
relationship between the allergen exposure and sensitization is not straight forward. It depends
on the allergen, the dose, time of exposure, childs age and possibly genetics. Some children have
allergies to nuts or other foods. A child with a food allergy may have an asthma attack as part of
an allergic reaction to a food. When this is severe, it is known as anaphylaxis. Foods containing
sulphites - sulphites are naturally occurring substances found in some food and drink. They are
also sometimes used as a food preservative. Food and drinks that are high in sulphites include
concentrated fruit juice, jam, prawns and many processed or pre-cooked meals. Most children
with asthma will not have this trigger. Medicines, such as the class of painkillers called nonsteroidal anti-inflammatory drugs (NSAIDs), which includes aspirin and ibuprofen, occasionally
trigger asthma in children.
Viral Infections: RSV infection that is severe enough to warrant hospitalization does not cause
asthma but is an indicator of the genetic predisposition to asthma .Between 50% and 80% of
asthma exacerbations are associated with viral respiratory tract infections (RTIs). In young
children, a variety of viral pathogens accompany wheezing episodes, most notably respiratory
syncytial virus (RSV) A number of long term prospective studies of children admitted to the

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hospital with documented RSV infection have shown that approximately 40% of these continue
to wheeze or have asthma in later childhood.
Exercise: Exercise-induced bronchoconstriction (EIB) has a high prevalence in children with
asthma, and this is a common problem, even in case of controlled asthma, because of the high
levels of physical activity in the childhood . Exercise induced asthma is the conventional term for
transient airway narrowing in a known asthma in association with strenuous exercise usually
lasting 5-10 minutes with a decline in pulmonary function by at least 10%. The kind of physical
activities that can bring on asthma symptoms include not only exercise, but also laughing,
crying, holding one's breath and hyperventilating. The symptoms of exercise-induced asthma
usually go away within a few hours. With proper treatment, a child with exercise-induced asthma
does not need to limit his or her overall physical activity.
Diet: There is evidence that breastfeeding for at least 4 months, compared with feeding formula
made with intact cow milk protein, prevents or delays the occurrence of atopic dermatitis, cow
milk allergy, and wheezing in early childhood.

There is growing evidence that -3

polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties and may modulate
immune responses [1]. Increase in atopy and asthma observed in western countries could be
related to a decreased intake of these nutrients while the intake of n-6 PUFAs from vegetables oil
and prepared food has increased. .

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PATHOPHYSIOLOGY OF ASTHMA
Asthma is a chronic, immunologically mediated condition with a disturbance of the normal
airway repair mechanism, which results in inflammatory changes and airway remodeling. The
airway inflammation and remodeling together likely explain the clinical manifestations of
asthma that is demonstrated by complicated respiratory manifestations in which wheeze
occurring secondary to bronchoconstriction in the setting of airway hyper-responsiveness and
mucous hypersecretion. Clinically, the disease may be divided into allergic and nonallergic
asthma, distinguished by the presence or absence of IgE antibodies to common environmental
allergens. However, in both forms of the disease, the airway is infiltrated by T-helper (Th) cells,
which predominantly secrete characteristic cytokines such as interleukin (IL)-4, IL-5, and IL-13,
the so-called Th2 cytokine milieu. These cytokines stimulate mast cells, cause eosinophilia,
promote leukocytosis, and enhance B-cell IgE production, and may also participate in the
characteristic airway remodeling of asthma. However, for an individual to develop an asthmatic
phenotype appears to require the combination of both exposure to appropriate stimuli and a
genetic predisposition.

EFFECTOR CELLS OF INFLAMMATION AND REMODELLING IN


ASTHMA
In the healthy human airway there is normally a fine balance between immune cells, the
epithelium, and the host immune response. Airway inflammation in asthma reflects a distortion
of this balance and is orchestrated through complex interplay between multiple effector and
target components.

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Airway inflammation:
Airway hyper responsiveness (AHR) and airway inflammation are key pathophysiological
features of asthma . The exact cellular and biochemical processes underlying chronic
inflammation and airway remodelling are poorly understood .Animal models provide an
alternative for investigating disease mechanisms and progression.Asthma is characterized by
reversible airway obstruction, airway hyper responsiveness, and airway inflammation . The first
mechanism identified as important for asthma was bronchial hyper responsiveness. In a second
step, asthma was recognized also as an inflammatory disease, with chronic inflammation
inducing structural changes or remodeling . The acute challenge mouse models reproduce many
key features of clinical asthma, for example elevated levels of IgE, airway inflammation, goblet
cell hyperplasia, epithelial hypertrophy, AHR to specific stimuli and, in some models, early- and
late-phase bronchoconstriction in response to allergen challenge.. One of the features that is
important in chronic inflammation is the dissection of the role of inflammatory cells, resident
cells (e.g., epithelial cells and fibroblasts), and remodeling with fibrosis of the airways.
Angiogenesis is an important event both in the development of allergic inflammation and in the
pathophysiology of tissue remodeling in atopic diseases . Numerous inducers of angiogenesis
have been identified, including members of the fibroblast growth factor (FGF) family, vascular
permeability factor/VEGF, angiogenin, TGF- and TGF-, platelet-derived growth factor, tumor
necrosis factor (TNF-), hepatocyte growth factor, granulocyte-macrophage colony
stimulating factor (GM-CSF), interleukins, chemokines, and angiopoietin 1 and 2 . Among them,
VEGF is the most potent directly acting regulator of angiogenesis , and its expression is often
excessive in chronic inflammation and fibrosis.

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Airflow Obstruction:
Airflow obstruction can be caused by a variety of changes, including acute bronchoconstriction,
airway

edema,

chronic

mucous

plug

formation,

and

airway

remodeling.

Acute

bronchoconstriction is the consequence of Ig E-dependent mediator release upon exposure to


aeroallergens and is the primary component of the early asthmatic response. Airway edema
occurs 6-24 hours following an allergen challenge and is referred to as the late asthmatic
response. Chronic mucous plug formation consists of an exudate of serum proteins and cell
debris that may take weeks to resolve. Airway remodeling is associated with structural changes
due to long-standing inflammation and may profoundly affect the extent of reversibility of
airway obstruction. Airway obstruction causes increased resistance to airflow and decreased
expiratory flow rates. These changes lead to a decreased ability to expel air and may result in
hyperinflation. The resulting over distention helps maintain airway patency, thereby improving
expiratory flow; however, it also alters pulmonary mechanics and increases the work of
breathing.

Airway Hyper responsiveness.


AHRan exaggerated bronchoconstrictor response to a wide variety of stimuliis a major, but
not necessarily unique, feature of asthma. The degree to which airway hyper responsiveness can
be defined by contractile responses to challenges with methacholine correlates with the clinical
severity of asthma. The mechanisms influencing airway hyper responsiveness are multiple and
include inflammation, dysfunctional neuro regulation, and structural changes; inflammation
appears to be a major factor in determining the degree of airway hyper responsiveness.

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Treatment directed toward reducing inflammation can reduce airway hyper responsiveness 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
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma.
National Asthma Education and Prevention Program, Third Expert Panel on the Diagnosis and
Management of Asthma.
Bethesda (MD): National Heart, Lung, and Blood Institute (US); 2007 Aug.

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Figure 2: Factors Limiting Airflow In Acute And Persistent Asthma.


Source: Adapted and reprinted from The Lancet, 368, Holgate ST, Polosa R. The mechanisms,
diagnosis, and management of severe asthma in adults, 78093.

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INDUCTION OF ALLERGIC REACTION:


The development of allergic asthma exists of three phases, namely the induction phase, the earlyphase asthmatic reaction (EAR) and the late-phase asthmatic reaction (LAR). Each phase is
characterized by the production and interplay of various cell-derived mediators

Early-phase asthmatic reaction


Mast cells:
Mast cells are critical in mediating the acute response in asthma. While classically, mast cell
activation occurs following the binding of antigens to FcR1-bound, antigen-specific IgE, they
may also be activated through other mechanisms, including stimulation of complement
receptors, FcR1, and via TLRs TNF- is preformed in mast cells and released as part of the
asthmatic airway response.In murine culture experiments, mast cells induce CD4+ T-cell
migration, but down-regulate FcR1 expression only in Treg cells, while activated Treg cells
suppress mast cell FcR1 expression. This suggests bidirectional communication between mast
cells and Treg cells in modulating IgE-mediated responses. A role for mast cells in antigen
presentation is also suggested by the recent observation that mast cells stimulated by IgEspecific antigen undergo FcR1 cross-linking that enhances apoptosis. These dead mast cells
become ingested by dendritic cells, and this incorporated antigen helps propagate ongoing
CD4+ response.

Whereas mast cells are generally considered proinflammatory and mediators of tissue
destruction, they may conversely help limit airway damage.Mast-cell-derived tryptase can
cleave IgE, thereby preventing further mast cell activation and plausibly helping to contain the

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allergic response.Disappointingly, a recent human study examining a potential role for


therapeutic intervention with the monoclonal antibody to TNF-, golimumab, in severe,
persistent asthma was abandoned because of an unfavorable risk-benefit profile

T Lymphocytes:
A paradigm emerged whereby the fundamental problem in asthma was believed to be
disturbance of the normal Th1/Th2 balance. Th17 cells are a distinct population of CD4+ cells
that produce IL-17A, IL-17F, IL-22, TNF-, and IL-21, and express the transcription factor
RORt. Recently, Th17 cells were isolated from biopsy samples obtained from patients with
asthma.

IL-17 induces the release of a range of proinflammatory cytokines and chemokines from a
variety of cell types. It is linked to the development of airway neutrophilia, and its presence in
the asthmatic airway correlates with increased disease severity. In murine models of asthma, IL23 and Th17 cells enhance antigen-induced airway recruitment of both eosinophils and
neutrophils, while mast-cell-derived TNF has been shown to illicit a Th17-mediated airway
neutrophilic response following antigen challenge.
Regulatory T cells suppresses the immune response through the release of inhibitory cytokines
such as IL-10 and transforming growth factor beta and play an important role in immune
regulation with suppression of TH1 responses.

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Cytokines:
Cytokines can be categorized as pro-inflammatory or anti-inflammatory. Major proinflammatory cytokines are TNF , IL-1, IL-6, IL-8, and IFN. They activate the immune
system and participate in the acute inflammatory response. TNF- and IL-1 are the most
important pro-inflammatory cytokines and stimulate antigen presentation, adhesion molecule
expression on endothelial cells, inflammatory cell activity, and expression of matrix-degrading
enzymes, like collagenase. Major anti-inflammatory cytokines include IL-10, TGF-, and IL-1ra
(a natural IL-1 receptor antagonist)

Late-phase asthmatic reaction


The late-phase of the asthmatic reaction is characterized by excessive inflammation of the
airways resulting in structural changes induced by various mediators derived from
inflammatory cells, like eosinophils, neutrophils, T cells, macrophages, dendritic cells (DCs),
endothelial cells, ASM and BECs.(Bronchial epithelial cells)
Increased numbers of eosinophils exist in the airways of most, but not all, persons who have
asthma. These cells contain inflammatory enzymes, generate leukotrienes, and express a wide
variety of pro-inflammatory cytokines. Increases in eosinophils often correlate with greater
asthma severity. They may release basic proteins that may damage the airway epithelial cells.
They also have a role in release of growth factors and airway remodeling (4) In addition,
numerous studies show that treating asthma with corticosteroids reduces circulating and airway
eosinophils in parallel with clinical improvement.

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Neutrophils:
The regulation of neutrophil recruitment, activation, and alteration in lung function is still under
study, but leukotriene B4 may contribute to these processes.

Macrophages:
Macrophages are the most numerous cells in the airways and also can be activated by allergens
through low-affinity IgE receptors to release inflammatory mediators and cytokines that amplify
the inflammatory response.

Resident cells of the airway:


ASM is not only a target of the asthma response (by undergoing contraction to produce airflow
obstruction) but also contributes to it (via the production of its own family of pro-inflammatory
mediators). As a consequence of airway inflammation and the generation of growth factors, the
airway smooth muscle cell can undergo proliferation, activation, contraction, and hypertrophy
events that can influence airway dysfunction of asthma.

Epithelial Cells:
Airway epithelium forms a continuous, highly regu- lated physical barrier lining of the airway
lumen, which prevents invasion of inhaled environmental agents such as aeroallergens, pollutants
and pathogens
The generation of inflammatory mediators, recruitment and activation of inflammatory cells,
and infection by respiratory viruses can cause epithelial cells to produce more inflammatory

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mediators or to injure the epithelium itself. The repair process, following injury to the
epithelium, may be abnormal in asthma, thus furthering the obstructive lesions that occur in
asthma.

Airway Remodeling:
Ongoing inflammation may result in structural remodeling: wall thickening, sub epithelial
fibrosis, metaplasia, hypertrophy and hyperplasia of airway cells, cartilage breakdown and
angiogenesis.

The

most

prominent

mediators

of

airway

remodeling

are

Matrix

metalloproteinase, Cytokines, Chemokines, .Endothelin-1, Vascular endothelial growth factor,


Lipid mediators (Prostaglandin D2, Prostaglandin E2, 8-Isoprostane), Cysteinyl leukotrienes,
Leukotriene B and ADAM33.

Cytokines:
Direct and modify the inflammatory response in asthma and likely determine its severity. Th2derived cytokines include IL-5, which is needed for eosinophil differentiation and survival, and
IL-4 which is important for Th2 cell differentiation and with IL-13 is important for IgE
formation. Key cytokines include IL-1 and TNF-, which amplify the inflammatory response,
and GM-CSF, which prolongs eosinophil survival in airways. Recent studies of treatments
directed toward single cytokines (e.g., monoclonal antibodies against IL-5 or soluble IL-4
receptor) have not shown benefits in improving asthma outcomes.

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Chemokines:
By inducing TGF- release and collagen deposition from lung fibroblasts, and by recruiting Th2
cells in the lung. Other CC-chemokines, such as CCL7 and CCL22 also contribute to the
development of pulmonary fibrosis.

Endothelin 1:
Endothelin (ET)-1 may be involved in airway remodeling: it is mitogenic for ASM cells and
fibroblasts, and also stimulates collagen synthesis.

Vascular Endothelial Growth Factor:


The submucosa of the airways of subjects with asthma has higher VEGF, FGF-2, and angiogenin
immunoreactivity than that of healthy individuals. VEGF induces proliferation, migration, and
tube formation of endothelial cells. It promotes secretion of interstitial collagenase (matrix
metalloproteinase [MMP]-1) and the expression of chemokines, as well as leukocyte adhesion
molecules, such as intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and Eselectin. Macrophages, neutrophils, epithelial cells, fibr EGF is a potent chemoattractant for
leukocytes in experimental asthma and induces migration of mononuclear cells across an
endothelial cell monolayer in vitro.

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LIPID MEDIATORS
Prostaglandin D2- Prostaglandins appear to have several effects on the airways, including
bronchoconstriction, plasma exudation, sensitization of nerve endings, and effects on
inflammatory cells. PGD2 is involved in the recruitment of inflammatory cells because it
stimulates the chemotaxis of Th2 cells, eosinophils, neutrophils and basophils, PGD2 and PGF2
cause bronchoconstriction in asthmatic patients, but not in healthy subjects
Prostaglandin E2 is also an important PG produced in inflammatory processes. It is the most
important bronchoprotective metabolite yet identified in the airways. PGE2 inhibits the release
of mediators from mast cells, monocytes, neutrophils and eosinophils. PGE2 and PGI2 are
vasodilators and therefore should theoretically increase leakage in asthmatic.
8-Isoprostane: Isoprostanes are inflammatory metabolites derived from arachidonic acid. It
plays a role in non-specific smooth muscle hyperresponsiveness, bronchoconstriction and
edema.
Cysteinyl Leukotrienes: Cysteinyl-leukotrienes are potent bronchoconstrictors derived mainly
from mast cells. They are the only mediator whose inhibition has been specifically associated
with an improvement in lung function and asthma symptoms Recent studies have also shown
leukotriene B4 can contribute to the inflammatory process by recruitment of neutrophils
Leukotriene B4: Leukotriene B4 is a potent neutrophil chemoattractant that enhances
neutrophil-endothelial interactions and stimulates neutrophil activation. This leads to
degranulation and the release of mediators, enzymes and superoxides.

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ADAM33:. Abnormal activity of this gene can lead to altered airway function, inflammation, and
remodeling. Alterations in ADAM33 activity may underlie abnormalities in the function of ASM
cells and fibroblasts linked to airway remodeling and AHR.

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CLASSIFICATION OF ASTHMA.
A clinical diagnosis of asthma is suggested by symptoms such as episodic breathlessness,
wheezing, cough and chest tightness. Intermittent dry coughing and expiratory wheezing are the
most common chronic symptoms of asthma. younger children are more likely to report
intermittent, non-focal chest pain. Episodic symptoms after an incidental allergen exposure,
seasonal variability of symptoms and a positive family history of asthma and atopic diseases are
helpful diagnostic studies. The patterns of these symptoms that strongly suggest an asthma
diagnosis are: variability; precipitation by nonspecific irritants, such as smoke, fumes, strong
smells or exercise; worsening at night; and responding to appropriate asthma therapy . A
clinician should consider asthma if the child has physical activity induced cough or wheeze . A
useful method for confirming the diagnosis of asthma in children aged 5years is a trial of
treatment with short-acting bronchodilators and inhaled glucocorticosteroids. Marked clinical
improvement during the treatment, and deterioration when treatment is stopped, supports a
diagnosis of asthma . Three categories of wheezing have been described in children 5 years and
younger .
Transient Early Wheezing outgrows in the first three years. This is often associated with
prematurity and parental smoking .
Persistent Early Onset Wheeze (before the age of 3) these children have recurrent episode of
wheeze associated with acute viral upper respiratory tract infections, have neither evidence nor
family history or atopy. The symptoms normally persist through school age and sometimes till
the age of 12 . The cause of episode is usually respiratory syncytial virus in those under the age

29

of 2 and other viruses in older children. Asthma increased the risk of RSV hospitalization by 3fold, and the risk was not time-dependent..
Late Onset Wheeze/Asthma these children have asthma which often persists throughout
childhood and into adult life. These patients have atopic background often with eczema and
airway pathology which is characteristic of asthma.

Cough Variant Asthma: Patients 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.(47)

Exercise Induced Bronchoconstriction: typically develops within 5 to 10 min after


completing exercise(it rarely occurs during exercise).Patients experience typical asthma
symptoms which resolves spontaneously within 30 to 45 min. Exercise induced
bronchoconstriction can develop in any climatic condition but is more when patient is breathing
dry ,cold air and less common in hot, humid climate.(47) Rapid improvement of symptoms after
inhaled beta 2 agonist use supports the diagnosis of asthma.(47)

DIFFERENTIAL DIAGNOSIS

Airway Foreign Body

Allergic and Environmental Asthma

Alpha1-Antitrypsin Deficiency

Aspergillosis

30

Bronchiectasis

Bronchiolitis

Chronic Obstructive Pulmonary Disease

Churg-Strauss Syndrome

Cystic Fibrosis

Foreign Body Aspiration

Gastro esophageal Reflux Disease

Heart Failure

Pulmonary Embolism

Pulmonary Eosinophilia

Airway Foreign Body : Often, the child presents after a sudden episode of coughing or choking
while eating with subsequent wheezing, coughing, or stridor. However, in numerous cases, the
choking episode is not witnessed, and, in many cases, the choking episode is not recalled at the
time the history is taken.
Aspiration Syndromes: Acute aspiration may manifest as coughing, wheezing, fever, and chest
discomfort. In the setting of massive aspiration, the patient may present with cyanosis and/or
pulmonary edema, which may progress to severe respiratory distress syndrome
Bronchiolitis: Infants may become increasingly fussy and have difficulty feeding during the 2 to 5day incubation period. A low-grade fever, usually less than 101.5F, and increasing coryza and
congestion usually follow the incubation period. Over a period of 2-5 days, RSV infection
progresses from the upper to the lower respiratory tract, and this progression leads to the
development of cough, dyspnea, wheezing, and feeding difficulties. Severe cases progress to
respiratory distress with tachypnea, nasal flaring, retractions, irritability and possibly cyanosis.

31

Gastroesophageal Reflux: The symptoms of GER are most often directly related to the
consequences of emesis (egg, poor weight gain) or result from exposure of the typically cry and
report sleep disturbance and decreased appetite.

Table 1.Differential diagnosis


Upper respiratory tract conditions

Allergic rhinitis
Chronic rhinitis
Sinusitis
Adenoidal or tonsillar hypertrophy
Nasal foreign body
Middle respiratory tract conditions

Laryngotracheobronchomalacia
Larayngotracheobronchitis (e.g. pertusis)
Laryngeal web, cyst or stenosis
Vocal cord dysfunction
Vocal cord paralysis
Tracheoesphageal fistula
Vascular ring, sling or external mass compressing the airway(tumor)
Foreign body aspiration

32

Chronic bronchitis from tobacco smoke exposure


Toxic inhalations

Lower Respiratory Tract Conditions

Bronchopulmonary dysplasia(chronic lung disease of preterm infants)


Viral bronchiolitis
Gastroesophageal reflux
Bronchiectasis
Bronchiolitis obliterans
Interstitial lung disease
Hypersensitivity pneumonitis
Pulmonary eosinophilia,churg strauss syndrome
Pulmonary hemosidrosis
Tuberculosis
Pneumonia
Pulmonary edema(congestive heart failure)
Medications associated with chronic cough
Acetylcholinesterase inhibitors
Beta adrenergic antagonists

33

Angiotensin converting enzyme inhibitors

LABORATORY FINDINGS:
Lung function tests help to confirm the diagnosis of asthma and to determine disease severity.

Pulmonary function testing: Use of spirometry and other lung function measures are

34

difficult to perform in young children below the age of 5 years old and are not suitable for
routine use.

A trial of treatment with short-acting bronchodilators and inhaled

glucocorticosteroids with marked clinical improvement supports the diagnosis of asthma


Peak Expiratory Flow Rate(PEFR), Forced Expiratory Volume in one second (FEV1) and
FEV1/FVC Reversibility test with bronchodilator shown by improvement of at least 12% and
above within 10 -20minutes of 2 agonist aerosol inhalation in FEV1 .
1. Spirometry is helpful as an objective measure of airflow limitation. Valid spirometric
measures depends on a patients ability to properly perform a full, forceful and prolonged
expiratory maneuver ,feasible in children >6 years of age. If the FEV 1 (forced expiratory volume
in 1 sec) is within 5 % on 3 attempts, then the highest FEV 1 effort of the three is used. Generally
an FEV1/FVC ratio < 0.80 indicates significant airflow obstruction . Use of spirometry and other
lung function measures are difficult to perform in young children below the age of 5 years old
and are not suitable for routine use
2. Bronchodilator response to inhaled beta agonist (albuterol) is greater in asthmatic
patients than non-asthmatic: an improvement in FEV1 of more than or equal to 12% or >200 ml
is consistent with asthma .
3. Bronchoprovocation challenges:patients with symptoms consistent with asthma, but
normal lung function, measurements of airway responsiveness to methacholine, histamine,
mannitol, adenosine monophosphate or exercise challenge may help to establish a diagnosis of
asthma can be helpful in diagnosing asthma and optimizing asthma management ..

35

4.

Exercise challenges

(aerobic exercise or running for 6 to 8 min) can help identify

children with an exercise induced bronchospasm. In asthmatic patients,FEV1 typically decreases


during or after exercise by >15%.The onset of exercise induced bronchospasm in usually within
15 minutes after a vigorous exercise challenge and can spontaneously resolve within 30 to 60
min. Studies of exercise challenges in school aged children typically identify an additional 5-10
% with exercise induced bronchospasm and previously unrecognized asthma.
5. Measuring exhaled nitric oxide (FE NO)Exaled nitric oxide (FeNO) is considered a
good noninvasive marker to assess airway inflammation in asthma and allergic rhinitis. In
asthma, exhaled NO is very useful to verify adherence to therapy, and to predict upcoming
asthma exacerbations. It has been also proposed that adjusting anti-inflammatory drugs guided
by the monitoring of exhaled NO, could improve overall asthma control .
No tests diagnose asthma in this age group. The therapeutic trial of treatment with quick relievers
and inhaled steroids for 8 12 weeks showing improvement during therapy and relapse after
stopping therapy is diagnostic of asthma .

36

PHYSICAL EXAMINATION:
The most usual abnormal physical finding is wheezing on auscultation During asthma
exacerbations, expiratory wheezing and a prolonged expiratory phase is heard on auscultation.
Decreased breath sounds in some of the lung fields, indicate areas of hypoventilation due to
obstruction. Crackles indicate excess mucus production and inflammatory exudate in airways in
severe exacerbations, the greater extent of airways obstruction causes labored breathing and
respiratory distress, poor air entry, suprasternal and intercostal recessions, nasal flaring and
accessory respiratory muscle use. In extreme cases, airflow may be so limited that wheezing
cannot be heard.

37

RADIOLOGY
Th findings of chest radiographs (poster anterior and lateral view) in children with asthma often
appear to be normal except of nonspecific findings of hyperinflation (flattening of diaphragm)
and per bronchial thickening. Chest radiographs can be helpful in identifying abnormalities that
are hallmarks of asthma masqueraders(aspiration pneumonitis, hyper-lucent lung fields in
bronchiolitis obliterans) and complications during asthma exacerbations.

38

DIAGNOSIS OF ASTHMA:
Cough, wheeze and breathlessness are classical features of asthma syndrome

Episodic

symptoms after an incidental allergen exposure, seasonal variability of symptoms and a positive
family history of asthma and atopic disease are also helpful diagnostic guides. The patterns of
these symptoms that strongly suggest an asthma diagnosis are: variability; precipitation by
nonspecific irritants, such as smoke, fumes, strong smells or exercise; worsening at night; and
responding to appropriate asthma therapy .
Asthma with onset in early adulthood has its origins in early childhood.
Cough-variant asthma (patients have chronic cough as their principal, if not only, symptom) is
particularly common in children and is often more problematic at night; evaluations during the
day can be normal Cough-variant asthma (patients have chronic cough as their principal, if not
only, symptom) is particularly common in children and is often more problematic at night;
evaluations during the day can be normal. .
A simple clinical index based on the presence of a wheeze before the age of 3 and the presence
of one major risk factor (parental history of asthma or eczema) or two of three minor risk
factors(eosinophilia, wheezing without colds and allergic rhinitis) has been shown to predict the
presence of asthma in later childhood .

39

GOALS AND PRINCIPLES OF MANAGEMENT


The goal of asthma therapy is asthma control. Control implies that the asthmatic child is able to
lead a normal and physically active life. The criteria for normal life are to:
be completely free from any symptoms, i.e. cough, wheeze and breathlessness
attend school regularly and participate fully in all school activities, including sport
sleep restfully, free from night-time cough and/or wheeze
grow and develop normally
minimize the number of attacks of acute asthma and avoid hospitalization
avoid or minimize medication-related side-effects.

40

MANAGEMENT OPTIONS
Clinical studies have shown that asthma can be effectively controlled by intervening to suppress
and reverse the inflammation, as well as treating the bronchoconstriction and related symptoms.
Furthermore, early intervention to stop exposure to the risk factors that sensitized the airway may
help improve the control of asthma and reduce medication needs
The goal of asthma treatment is to achieve and maintain clinical control. Medications to treat
asthma can be classified as controllers or relievers. Controllers are medications taken daily on a
long term basis to keep asthma under clinical control chiefly through their anti-inflammatory
effects. They include:
Inhaled glucocorticosteroids, leukotriene receptor antagonists, and combination therapies with
long-acting beta agonists and glucocorticosteroids, anti-IgE and other steroid-sparing therapies.
Relievers are used on an as needed basis to quickly reverse bronchoconstriction and relieve
symptoms. The most commonly used relievers are inhaled short-acting beta agonists ..Inhaled
anticholinergics, short acting theophyllines and short acting oral beta 2 agonistsB

, 2008 #5335}

ROUTES OF ADMINSTRATION:

41

Asthma treatment can be administered in a variety of ways: inhaled, orally or parenterally (by
subcutaneous, intravenous and intramuscular routes) .The major advantage of inhaled therapy is
that the drug is directly delivered to the airways producing higher local concentrations and less
systemic side effects .
Multiple types of aerosol devices are commonly used for the administration of medical aerosol
therapy to patients with pulmonary diseases. All of these devices have been shown to be effective
in trials where they are used correctly. However, failure to operate any of these devices properly
has been associated with poor clinical response and limited patient adherence to therapy..Inhaled
therapy via an MDI with spacer is preferable to nebulised therapy because of the convenience,
more effective lung deposition, fewer side-effects and lower cost . For children >5 years old, a
dry powder inhaler (DPI) or breath-actuated pressurised MDI may be alternatives to an MDI
with spacer .Spacers retain large drug particles that would be deposited in the oropharynx, so
reducing oropharyngeal side-effects and systemic absorption and availability of inhaled drug.
This consideration is especially important for ICS with poor first-pass metabolism such as
beclomethasone dipropionate (BDP) and budesonide . A metered dose inhaler (MDI) with spacer
is preferable to nebulised therapy because of convenience, more effective lung deposition,
fewerside-effects and lower cost Nebulizers have imprecise dosing, are expensive, waste large
amounts of drug into the surrounding air, are time-consuming to use and care for, and require
maintenance .

42

CONTROLLER MEDICATIONS
Controller medications for children include inhaled and systemic glucocorticosteroids,
leukotriene modifiers, long acting inhaled 2-agonists, theophylline, cromones, and long-acting
oral 2-agonists.

Inhaled glucocorticosteroids.
Role in Therapy
Inhaled glucocorticosteroids are the most effective controller therapy for asthma in children with
rapid improvement in symptoms and lung function, even at low doses of inhaled
glucocorticosteroids .Duration of treatment should continue till bronchial hyper-responsiveness
improves . In children of all ages, maintenance treatment with inhaled glucocorticosteroids
controls asthma symptoms, reduces the frequency of acute exacerbations and the number of
hospital

admissions,

improves

quality

of

life,

lung

function,

and

bronchial

hyperresponsiveness.Most of the benefit from inhaled glucocorticosteroids is achieved in adults


at relatively low doses, equivalent to 400g of budesonide per day .Early intervention with
inhaled budesonide is associated with improved asthma control and less additional asthma
medication use . Most of the benefit from inhaled glucocorticosteroids is achieved in adults at
relatively low doses, equivalent to 400g of budesonide per day. Increasing to higher doses
provides little further benefit in terms of asthma control but increases the risk of side-effects.
However,

there

is

marked

individual

variability

of

responsiveness

to

inhaled

glucocorticosteroids, and because of this and the recognized poor adherence to treatment with
inhaled glucocorticosteroids, many patients will require higher doses to achieve full therapeutic
benefit . Symptom control and improvements in lung function occur rapidly (after 1 to 2 weeks),

43

although longer treatment (over the course of months) and sometimes higher doses may be
required to achieve maximum improvements in airway hyperresponsiveness (10). When
glucocorticosteroid treatment is discontinued, asthma control deteriorates within weeks to
months

44

TABLE 2
DOSES OF ICS
Estimated equipotent daily dosage of ICS for children
DRUG

LOW
DOSE(g)

Budesonide
Beclomethasone

100 - 200
100 - 200

MEDIUM

HIGH
DOSE(g)

DOSE(g)

200 - 400

>400

200 - 400

>400

Dipropionate
Ciclesonide

80 - 160

160 - 320

>320

Fluticasone
100 - 200

Side effects-

200 - 500

>500

45

The majority of studies evaluating the systemic effects of inhaled glucocorticosteroids have been
undertaken in children older than 5 years.

Growth: Of greater concern has been the potential effect of ICSs on linear growth.
Again, the available data for low- to medium-dose ICS show a minimal effect on growth
velocity: a reduction of 1 cm in the first year of treatment in some children. This 2

decrease, when observed, usually does not progress over time, and long-term studies have
indicated that these children attain their full adult height Continuous administration of
ICSs in low to medium dose over many years is well tolerated. . Low doses do not have
clinically deleterious side effects on the bones, growth, eye, or hypothalamic-pituitaryadrenal-axis. Effect of ICS on growth depends on dose and duration of intake as well as
the susceptibility of the growth phase during which the child inhales steroids . With all
inhaled corticosteroids given at high dosage, there is likely to be a dual effect due to
topical bioactivity from the airway dose as well as prednisone like activity from the
systemic bioavailable dos.

Hypothalamic-pituitary-adrenal (HPA) axis. . With sensitive techniques, dosedependent adrenal suppression has been documented in children treated with inhaled
steroids but generally this effect has no clinical relevance . Most children develop
biochemical evidence of adrenal suppression after treatment with medium to high doses
of ICs .

46

Bones and Glucocorticosteroids in Children: One of the greatest concerns of

long-term corticosteroid therapy for asthma is its potential for adverse effects on bone
turnover, resulting in an increased risk for osteoporosis and fracture No studies have
reported any statistically significant increase of risk of fractures in children taking inhaled
glucocorticosteroids. In 157 asthmatic children receiving inhaled budesonide for 3 to 6
years, bone density measurement was not significantly different compared with that in
asthmatic controls who had not received steroids . Low doses do not have clinically
deleterious side effects on the bones, growth, eye, or hypothalamic-pituitary-adrenal-axis.
However, they do not normalize lung function and prevent structural changes in the
airway wall in all asthmatic patients .No studies have reported any statistically significant
increased risk of fractures in children taking inhaled glucocorticosteroids. Oral or
systemic glucocorticosteroid use increases the risk of fracture. The risk of fracture
increases along with the number of treatments, with a 32% increase at four courses ever.
Use of inhaled glucocorticosteroids reduces the need for systemic courses. Controlled
longitudinal studies of 25years duration and several cross-sectional studies found no
adverse effects of inhaled glucocorticosteroid treatment on bone mineral density. No
prospective studies have followed children on inhaled glucocorticosteroid treatment until
peak bone mineral density has been reached .

Cataracts. Inhaled glucocorticosteroids have not been associated with an increased

occurrence of cataract development in children.

Central nervous system effects: no increase in hyperactive behavior,


aggressiveness, insomnia, uninhibited behavior, and impaired concentration such effects

47

has been found in two long-term controlled trials of inhaled budesonide involving more
than 10,000 treatment years.

Oral candidiasis, hoarseness, and bruising. Clinical thrush is seldom a problem


in children treated with inhaled or systemic glucocorticosteroids. This side effect seems
to be related to concomitant use of antibiotics, high daily doses, dose frequency, and
inhaler device. Spacers reduce the incidence of oral candidiasis. Mouth rinsing is
beneficial.

Dental side effects. Inhaled glucocorticosteroid treatment is not associated with


increased incidence of caries. However, the increased level of dental erosion reported in
children with asthma may be due to a reduction in oral pH that may result from inhalation
of 2-agonists.

Other local side effects. The long-term use of inhaled glucocorticosteroids is not
associated with an increased incidence of lower respiratory tract infections, including
tuberculosis.

LEUKOTRIENE MODIFIERS.

48

Leukotriene receptor antagonists (LTRAs) are an accepted treatment option for childhood
asthma. They have a rapid onset of action (within 1 - 3 hours),48 are administered orally, treat
asthma via a different pathway to other currently available medications (specific cysteinyl
leukotriene receptor antagonists), and have been shown to be effective for aspirin-sensitive
asthma. However, when used alone as controller, the effects of leukotriene modifiers are less
than those of low doses of inhaled glucocorticosteroids and, in patients already on inhaled
glucocorticosteroids, leukotriene modifiers cannot substitute for this treatment without risking
the loss of asthma control . Leukotriene modifiers used as add-on therapy may reduce the dose of
inhaled glucocorticosteroids required by patients with moderate to severe asthma , and may
improve asthma control in patients whose asthma is not controlled with low or high doses of
inhaled glucocorticosteroidsLeukotriene modifiers provide partial protection against exercise
induced bronchoconstriction.

Side effects
No significant safety concerns have been demonstrated for leukotriene modifiers in children.
Headache and gastrointestinal upset are the most commonly encountered side-effects; skin
rashes or flu-like symptoms are much less common

49

LONG ACTING INHALED BETA 2 AGONISTS


Role in therapy
A Cochrane review of 25 trials of 572 children reported that addition of LABAs did not
significantly reduce the risk of asthma exacerbations requiring rescue systemic steroids,
hospitalisation or duration of symptoms, but improved lung function compared with ongoing
treatment with a similar dose of inhaled corticosteroids. There was no evidence of increased
serious side-effects or withdrawals with the addition of LABAs.Long-acting inhaled 2-agonists,
including formoterol and salmeterol, should never be used as monotherapy for asthma as these
medications do not appear to influence the airway inflammation in asthma. They are most
effective when combined with inhaled glucocorticosteroids, and this combination therapy is the
preferred treatment when a medium dose of inhaled glucocorticosteroid alone fails to achieve
control of asthma. Addition of long-acting inhaled 2-agonists to a daily regimen of inhaled
glucocorticosteroids improves symptom scores, decreases nocturnal asthma, improves lung
function, decreases the use of rapid-acting inhaled 2-agonists , reduces the number of
exacerbations and achieves clinical control of asthma in more patients, more rapidly, and at a
lower dose of inhaled glucocorticosteroids than inhaled glucocorticosteroids given alone

Side effects: LABAs are generally well tolerated in children. Side effects are similar in type
and frequency to those of SABAs, and include muscle tremor, headache and palpitations.An
increased risk of severe asthma exacerbations and mortality has been reported, particularly when
used as monotherapy; therefore, LABAs should never be used without an ICS

50

THEOPHYLLINE:
Role in therapy
Theophylline has been used in the treatment of asthma mainly as a bronchodilator (10 - 20
mg/kg/day), though it may also have anti-inflammatory effects at lower doses (5 - 10
mg/kg/day).71-74 However, the anti-inflammatory effects of theophylline are small (less than
that of low dose ICSs) and side-effects are common. Theophylline may be used as alternative,
adjunctive therapy with ICSs in children >5 years old . Monitoring of serum theophylline
concentration is essential. Long term treatment with theophylline is not generally recommended
in young children because of its adverse effects. Sustained-release theophylline has little effect as
a first-line controller 112 but may provide benefit, although less than that provided by longacting inhaled 2-agonists , as add-on therapy in patients who do not achieve control on inhaled
glucocorticosteroids alone

Side effects
The most common side effects of theophylline are anorexia, nausea, vomiting, and headache.
Mild central nervous stimulation, palpitations, tachycardia, arrhythmias, abdominal pain,
diarrhea, and, rarely, gastric bleeding may also occur. These side effects are mainly seen at doses
higher than 10 mg/kg/day.

51

Anti-IgE.
Role in therapy
Anti-IgE (omalizumab) has proven efficacy in children age 6 to 12 years with moderate-tosevere and severe persistent allergic (IgE-mediated) asthma. A one-year study evaluated the
efficacy and safety of anti- IgE in 627 children with IgE-mediated asthma
controlled on doses of inhaled glucocorticosteroid equivalent to 200 g/day

inadequately
fluticasone

propionate or higher (mean dose 500 g/day) A substantial number of children with difficult
asthma will have higher IgE levels than the upper limit of IgE recommended for therapy 1,300
IU). It is unknown if these patients will still benefit from omalizumab therapy. There are no tests
which can currently be recommended in order to predict who will respond. Anti-IgE therapy is
expensive.

Side effects:
Drug-related adverse events in anti-IgE treated patients are mild to moderate in severity and
include urticaria, rash, flushing, and pruritus.

CROMONES:SODIUM CROMOGLYCATE AND NEDOCROMIL SODIUM


Sodium cromoglycate and nedocromil sodium have limited role in the long term treatment of
asthma in children. One meta-analysis has concluded that long-term treatment with sodium
cromoglycate is not significantly better than placebo for management of asthma in children.
Studies of the use of these medications in children 5 years and younger are sparse and results are
conflicting.

52

Side effects
Cough, throat irritation, and bronchoconstriction occur in a small proportion of patients treated
with sodium cromoglycate. A bad taste, headache, and nausea are the most common side effects
of nedocromil.

LONC ACTING ORAL 2-AGONISTS.


Treatment with long-acting oral 2-agonist such as slow release formulations of salbutamol,
terbutaline, and bambuterol reduces nocturnal symptoms of asthma Due to their potential side
effects of cardiovascular stimulation, anxiety, and skeletal muscle tremor, their use is not
encouraged. If used, dosing should be individualized, and the therapeutic response monitored to
limit side effects.

SYSTEMIC GLUCOCORTICOSTEROIDS:
Because of the side effects of prolonged use, oral glucocorticosteroids in children with asthma
should be restricted to the treatment of acute severe exacerbations, whether viral-induced or
otherwise. Oral preparations are preferred over parenteral (intramuscular or intravenous) for
long-term therapy because of their lower mineralocorticoid effect, relatively short half-life and
lesser effects on striated muscle, as well as the greater flexibility of dosing that permits titration

53

SIDE EFFECTS
The systemic side-effects of long-term oral or parenteral glucocorticosteroid treatment include
osteoporosis, arterial hypertension, diabetes, hypothalamic-pituitary-adrenal (HPA) axis
suppression, obesity, cataracts, glaucoma, skin thinning leading to cutaneous striae and easy
bruising, and muscle weakness.the lowest acceptable dose that maintains control. Caution and
close medical supervision are recommended when considering the use of systemic
glucocorticosteroids in patients with asthma who also have tuberculosis, parasitic infections,
osteoporosis, glaucoma, diabetes, severe depression or peptic ulcers.

RELIEVER MEDICATIONS
RAPID ACTING INHALED 2-AGONISTS AND SHORT ACTING ORAL
2- AGONISTS
Role in therapy
Rapid-acting inhaled 2-agonists are the medications of choice for quick relief of bronchospasm
during acute exacerbations of asthma and for the pretreatment of exercise-induced
bronchoconstriction. They should be used only on an as-needed basis at the lowest dose and
frequency required. Increased use, especially daily use, is a warning of deterioration of asthma
control and indicates the need to reassess treatment. Similarly, failure to achieve a quick and
sustained response to 2-agonist treatment during an exacerbation mandates medical attention
and may indicate the need for short-term treatment with oral glucocorticosteroids.

54

SIDE EFFECTS
Tremor and tachycardia occur with higher doses.

. ANTICHOLINERGICS

Role in therapy
Inhaled ipratropium bromide is a less effective reliever medication in asthma than rapid-acting
inhaled 2-agonists and it is not recommended for the long-term management of asthma, except
as an alternative bronchodilator for patients who experience tachycardia, arrhythmia and tremor
from rapid-acting 2-agonists.

SIDE EFFECTS
These include dryness of the mouth and a bitter taste, but there is no evidence of a drying effect
on airway mucus

55

ASTHMA MANAGEMENT AND PREVENTION:


The responsibility for patient education rests with the doctor, and should be shared with trained
health care professionals. Patients and parents must be encouraged to participate actively in their
own management. Patient education significantly improves asthma control and decreases
hospitalisation rates. The influence of education is greater in moderate-severe, compared with
mild-moderate, asthma. Intensive education is of greater benefit than limited education, and
written plans are superior to oral instructions. Education given at follow-up visits is more
effective than education during emergency visits. Culture-specific programmes for adults and
children from minority groups with asthma are more effective than generic programmes in
improving quality of life, asthma knowledge, asthma exacerbations and asthma control
The recommendations for asthma management are described in following interrelated
components of therapy and have the following major goals:
1) to achieve and maintain control of symptoms;
2) to maintain normal activity levels, including exercise;
3) to maintain pulmonary function as close to normal as possible;
4) to prevent asthma exacerbations;
5) to avoid adverse effects from asthma medications
6) to prevent asthma mortality.
7) Avoid known allergens and nonspecific triggers, particularly tobacco smoke

56

8) Educate patients and parents about asthma and its treatment, e.g. difference between controller
and reliever treatment, correct use of inhalers, use of
a spacer where necessary, and correct use of peak flow meter where appropriate.
9) Provide patients and parents with an asthma adherence and symptom diary as a tool for
monitoring asthma control.
10) Provide all patients with a written action plan that includes instructions for both daily
management (long-term control medication, if appropriate, and environmental control measures)
and actions to manage worsening asthma (what signs, symptoms and PEF measurements (if
used) indicate worsening asthma; what medications to take in response; what signs and
symptoms indicate the need for immediate medical care). Written action plans are particularly
recommended for patients who have moderate or severe persistent asthma, or a history of severe
exacerbations, or poorly controlled asthma
The effective management of asthma requires the development of a partnership between the
person with asthma and his or her health care professional(s) (and parents/caregivers in the case
of children with asthma). The aim of this partnership is to enable patients with asthma to gain the
knowledge, confidence, and skills to assume a major role in the management of their asthma.

57

ASTHMA EDUCATION
Education should be an integral part of all interactions between health care professionals and
patients, and is relevant to asthma patients of all ages. Although the focus of education for small
children will be on the parents and caregivers, children as young as 3 years of age can be taught
simple asthma management skills but regional issues and the developmental stage of the children
may affect the outcomes of such programs.

EDUCATION AND PATIENT DOCTOR PARTNERSHIP:


Goal is to provide the person with asthma, their family, and other caregivers with suitable
information and training so that they can keep well and adjust treatment according to a
medication plan developed with the health care professional

Key Components:

Focus on the development of the partnership

Acceptance that this is a continuing process

A sharing of information

Full discussion of expectations

Expression of fears and concerns

Difference between relievers and controllers

Potential side effects of medications

Use of inhaler devices


Prevention of symptoms and attacks
Signs that suggest asthma is worsening and actions to take

58

Monitoring control of asthma

How and when to seek medical attention

The person then requires:

A written asthma action plan

Regular supervision, revision, reward, and reinforcement

Good communication is essential as the basis for subsequent good compliance/adherence


At the Initial Consultation
Early in the consultation the person with asthma needs information about the diagnosis and
simple information about the types of treatment available, the rationale for the specific
therapeutic interventions being recommended, and strategies for avoiding factors that cause
asthma symptoms. Different inhaler devices can be demonstrated, and the person with asthma
encouraged to participate in the decision as to which is most suitable for them. At the initial
consultation, verbal information should be supplemented by the provision of written or pictorial
information about asthma and its treatment.

59

ASTHMA CONTROL:
Control refers to the degree to which the manifestations of asthma are minimised by therapeutic
intervention and the goals of therapy are met. After therapy is initiated, the emphasis for clinical
management changes to the assessment of asthma control. The level of asthma control will guide
decisions either to maintain or to adjust therapy, i.e. step up if necessary, or step down if
possible. Asthma control may be assessed clinically (symptoms, physical findings, reliever use),
and by measurement of lung function and fractional exhaled nitric oxide (FENO) in certain
situations.

CLINCAL ASSESSMENT
Clinical assessment includes the frequency of daytime and nocturnal symptoms, the extent of
limitation of activities, and the need for reliever treatment. This can be achieved with various
tools such as a symptom assessment questionnaire or Asthma Control Test (ACT). As a screening
tool, ACT scores have demonstrated an overall agreement with specialist ratings ranging from
71% to 78%. (5) Drug therapy can then be adjusted according to the patients level of control.
Children who are very well controlled on low doses of inhaled corticosteroids may be able to
come off treatment (49). Complete control of asthma is commonly achieved with treatment, the
aim of which should be to achieve and maintain control for prolonged periods with due regard
for the safety of treatment, potential for adverse effects, and the cost of treatment required to
achieve this goal (6).Its assessment should incorporate the dual components of current clinical
control (e.g. symptoms, reliever use and lung function) and future risk (e.g. exacerbations and
lung function decline) (56).It should be noted that inhaled glucocorticoid improve clinical
control and reduce future risk(6)

60

Table 3
Levels Of Asthma Control.(47)
Assessment of current clinical control (preferably over 4 weeks)
CHARACTERISTIC CONTROLLED(All PARTLY
of the following)

UNCONTROLLED

CONTROLLED(any

(3 in a week)

1 in a week)
DAY

TIME NONE(2/week

SYMPTOMS

2/WEEK(lasting

lasting for minutes for

minute

2/WEEK(lasting

for

and hours or recur or partly

and reieved by short rapidly relieved by relieved by short acting


acting

short

acting bronchodilators)

bronchodilators)

bronchodialtors)

NOCTURNAL

NONE(no nocturnal ANY(may

SYMPTOMS

cough during sleep)

during

cough ANY(may cough during

sleep

or sleep

or

wakes

with

wakes with cough or cough or wheeze)


wheeze)
LIMITATIONS
ACTIVITIES

OF NONE(active
child,play and runs
without symptoms)

ANY(cough,wheeze, ANY(cough,wheeze,diffi
Difficult

breathing Cult

breathing

during

during

vigorous vigorous play,laughing)

play,laughing)
NEED

FOR 2 days/week

More than 2 days More than 2 days per

61

RELIEVER

per week

week

MEDICATIONS
ASSESSMENT OF FUTURE RISK(risk of exacerbations,instability,rapid decline in lung
function,side effects)
Features associated with increased risk of adverse events in the future include:
Poor clinical control,frequent exacerbations in the past year,ever admission to critical care for
asthma,low FEV1,exposure t cigarette smoke,high dose medications.

62

TABLE 4
Definition of Well-Controlled Asthma
Asthma symptoms twice a week or less
Rescue bronchodilator use twice a week or less.
No nighttime or early morning awakenings
No limitation of exercise ,work or school.
Well controlled asthma by patient and physician assessment.
Normal or personal best PEF or FEV1

63

FOLLOW UP AND REVIEW


Re-evaluate treatment within 2 - 6 weeks and adjust therapy as appropriate. The main objective
of follow-up visits is to determine whether asthma is controlled or
not . In addition, the following points should be assessed/monitored at each visit:
inhaler technique
adherence
written action plan
patient concerns
side-effects of medication
growth (weight, height).

Non Adherence
Studies of adults and children have shown that approximately 50% of those on long-term therapy
fail to take medications as directed at least part of the time. Nonadherence may be defined in a
non-judgemental way as failing to take treatment as agreed upon by the patient and the health
care professional. Non-adherence may be identified by prescription monitoring, pill counting or
drug assay, but at a clinical level it is best detected by asking about therapy in a way that
acknowledges the likelihood of incomplete adherence .

64

ADHERENCE
Strategies to promote adherence include:
prescribing a simple dosage regimen (once or twice daily) and as few drugs as possible
selecting treatment that achieves outcomes and addresses preferences that are important to the
patient, and reminding patients that adherence will help to achieve goals of treatment
assessing the patients and familys level of social support, and encourage family involvement
tailoring the self-management approach to the needs and literacy levels of the patient, and
maintaining sensitivity to cultural beliefs and ethno-cultural practices.Individualised selfmanagement of asthma has been shown to improve medication adherence and asthma control.

65

IDENTIFY AND REDUCE EXPOSURE TO RISK FACTORS


ASTHMA PREVENTION:
Measures to prevent asthma may be aimed at the prevention of allergic sensitization (i.e., the
development of atopy, likely to be most relevant prenatally and perinatally), or the prevention of
asthma development in sensitized people. Other than preventing tobacco exposure both in utero
and after birth, there are no proven and widely accepted interventions that can prevent the
development of asthma.
The role of diet particularly breast-feeding, in relation to the development of asthma has been
extensively studied and, in general, infants fed formulas of intact cows milk or soy protein
compared with breast milk have a higher incidence of wheezing illnesses in early childhood.
Exclusive breastfeeding during the first months after birth is associated with lower asthma rates
during childhood.
Exposure to tobacco smoke both prenatally and postnatally is associated with measurable
harmful effects, including effects on lung development and a greater risk of developing wheezing
illnesses in childhood. Passive smoking increases the risk of allergic sensitization in children.
Both prenatal and postnatal maternal smoking is problematic. Pregnant women and parents of
young children should be advised not to smoke.
.

66

TREATMENT.
Pharmacotherapy is the cornerstone of asthma management, with appropriate medication and
delivery devices to meet patients needs and circumstances. When asthma is first diagnosed, it is
convenient for initiation of treatment to classify it as mild intermittent or persistent asthma that
is mild, moderate or severe. Asthma severity assessment is used to initiate therapy, while asthma
control is determined to monitor and adjust therapy

Table 5
Classification of asthma severity based on symptoms and PEF in patients
presenting for the first time
SYMPTOMS

DAILY

MILD

MILD

MODERATE

SEVERE

INTERMITTENT PERSISTENT

PERSISTENT

PERSISTENT

2days/week

2days/week

Daily symptoms

continual

3-4/month

1/week but not

7 days/week

SYMPTOMS
NIGHT

TIME

SYMPTOMS

nightly

PEF

80%predicted

80%predicted

60% but 80%

60%

PEF variability

<20%

20 - 30%

>30%

>30%

The goal of asthma treatment, to achieve and maintain clinical control can be reached with a
pharmacological intervention developed in partnership between the patient, family and the
doctor..

67

Treatment involves steps 1 to 5,provide options of increasing efficacy except for step 5 where
issues of availability and safety influence the selection of treatment. Step 2 is the initial treatment
for most treatment nave patients with persistent asthma symptoms, in case of severely
uncontrolled symptoms, treatment should be commenced at step 3 .
At each treatment step, a reliever medication(rapid onset bronchodilator)should be provided for
quick relief of symptoms. However, regular use of reliever medication is one of the elements
defining uncontrolled asthma and indicates controller treatment should be increased. Thus
reducing the need for reliever medication is the measure of success of treatment. The steps are
described as below:

STEP 1: AS NEEDED RELIEVER MEDICATION


Step 1 is reserved for untreated patients with occasional day time symptoms (cough, wheeze,
dyspnea occurring twice or less per week) of short duration (lasting for few hours).Between
episodes, the patient is asymptomatic with normal lung function and there is no nocturnal
awakening. When symptoms are more frequent or worsen periodically, patients require regular
controller treatment in addition to as needed reliever medication.

TREATMENT IN STEP 1:

68

For the majority of patients in step 1, rapid acting inhaled beta 2 agonist is the recommended
treatment. Alternatives are: An inhaled anticholinergic, short acting oral beta 2 agonist or short
acting theophylline. The alternatives medications have a slower onset of action and higher risk of
side effects.
Physical

activity

is

an

important

cause

of

asthma

symptoms.

Exercise

induced

bronchoconstriction indicates that asthma in uncontrolled and stepping up of treatment is


required which results in reduction of exercise induced symptoms. for those in whom exercise
induced bronchoconstriction is the only manifestation or if patient still experience exercise
induced symptoms in otherwise well controlled asthma, a rapid acting inhaled beta 2 agonists
taken prior to exercise is recommended.
Alternatives are: Leukotriene modifiers, Chromones.

STEP 2:RELIEVER MEDICATION PLUS A SINGLE CONTROLLER


Low dose inhaled steroid is recommended as the initial controller treatment for asthma patients
of all ages. Suitable alternatives are:
Leukotriene modifiers

STEP

3:RELIEVER

MEDICATION

PLUS

ONE

OR

TWO

CONTROLLERS:
The recommended option for all ages of asthma is to combine a low dose inhaled steroid with an
inhaled long acting beta 2 agonist, either in combination or as separate components. The low
dose steroid is usually sufficient and need only to be increased if control is not achieved within 3

69

to 4 months of this regime. The use of a long acting beta 2 agonist as monotherapy reliever
medication is discouraged since it must always be used with an inhaled steroid.
Another option for both adults and children is to increase to a medium dose inhaled steroid. For
patients of all ages on medium or high dose of inhaled steroid, delivered by mdi, use of a spacer
device is recommended to improve delivery to the airways, reduce oropharayngeal side effects
and reduce systemic absorption.
Another option is to combine low dose inhaled steroid with a Leukotriene modifier.
STEP 4:RELIEVER MEDICATION PLUS 2 OR MORE CONTROLLERS:
The preferred treatment for step 4 is to combine medium or high dose inhaled steroid with a long
acting beta 2 agonist, the use of high dose instead of medium dose steroid is of little benefit and
the high dose is recommended on a trial basis for 3 to 6 months when control cannot be achieved
with a medium dose steroid with a LABA or a third controller(Leukotriene modifier or a
sustained release theophylline)
Prolonged use of high dose steroid is associated with increase potential for adverse effects. At
medium and high dose steroid, twice daily dosing is necessary for most but not all inhaled
glucocorticosteroids. With budesonide, efficacy may be increased with more frequent
dosing(four times daily)
Leukotriene modifiers as add on treatment to medium or high dose steroid have been shown to
provide benefit but usually less than that achieved with the addition of LABA.
The addition of low dose sustained release theophylline to medium or high dose steroid and
LABA may also provide benefit..

70

STEP 5: RELIEVER MEDICATION PLUS ADDITIONAL CONTROLLER OPTIONS:


Addition of oral glucocorticosteroids to other controller medications may be effective but its
associated with severe side effects and should only be considered if the patients asthma remains
severely uncontrolled on step 4 medications with daily limitations of activities and frequent
exacerbations. Patients should be counseled about the side effects and all other alternative
treatments must be considered
When control is not achieved with additions of high doses of inhaled or oral
glucocorticosteroids, addition of anti IgE to other controller medications has been shown to
improve control of allergic asthma.
.
DURATIONS AND ADJUSTMENT OF TREATMENT:
For most classes of controller medications, controlled may be achieved within days of treatment
but full benefit may be evident after 3 to 4 months.in severe and chronically untreated cases, this
may take even longer.
The reduced need for medication, once asthma is fully controlled is not understandable but may
represent reversal of some of the consequences of long term inflammation. Higher dose of antiinflammatory medication is required for this and to maintain this for prolonged periods.
Alternatively, reduced need may also represent spontaneous improvement as part of the cyclical
natural history of asthma. Rarely asthma may go into remission in children 5 years and younger
and during puberty.

STEPPING DOWN TREATMENT WHEN ASTHMA IS CONTROLLED:

71

There is little experimental data on optimal timings sequence and magnitude of treatment
reductions in asthma and the approach will differ from patient to patient depending on the
combination and doses of medications that were needed to achieve control. These changes
should ideally be made by agreement between patient and health care professional with full
discussion of potential consequences including the reappearance of symptoms and increased risk
of exacerbations:
When inhaled glucocorticosteroid alone in medium to high doses are being used, a 50%
reduction in dose should be attempted at 3 months interval.
When asthma is controlled with a combination of inhaled glucocorticosteroid and a LABA, the
preferred approach is to begin by reducing the dose on inhaled steroid by approximately 50%
while continuing the LABA. If control is maintained, further reduction in steroid dose should be
attempted until a low dose is reached when the LABA may be stopped. An alternative is to
switch the combination treatment to once daily dosing. A second alternative is to discontinue the
LABA at an earlier stage and substitute the combination treatment with inhaled steroid
monotherapy at the same dose contained in the combination inhaler,However,this is more likely
to lead to loss of control.
When asthma is controlled with inhaled steroid in combination with controllers other than
LABA, the dose of inhaled steroid should be reduced by 50% until a low dose of inhaled steroid
is reached, then the combination treatment stopped as described as above
Controller treatment may be stopped if the patients asthma remains controlled on the lowest
dose of inhaled glucocorticosteroids with no recurrence of symptoms for an year.

STEPPING UP TREATMENT IN RESPONSE TO LOSS OF CONTROL:

72

Treatment has to be adjusted periodically in response to worsening asthma control which may be
recognized by the minor recurrences or worsening of symptoms. Treatment options are as
follows:
Rapid onset, short acting or long acting beta2 agonist bronchodilators. Repeated dosing with
bronchodilators in this class provides temporary relief until the cause of worsening symptoms
passes. The need for repeated doses over more than one or two days signals the need for review
and possible increase of controller therapy. Combination of inhaled glucocorticosteroids and
rapid and long acting beta 2 agonist bronchodilator(e.g.,formeterol) for combined relief and
control. The combination of rapid and long acting beta 2 agonist (formeterol) and an inhaled
glucocorticosteroid(budesonide) in a single inhaler both as an effective controller and reliever is
effective in maintaining a high level of asthma control and reduces exacerbation requiring
systemic steroids and hospitalization.

DIFFICULT TO TREAT ASTHMA:


Although clinical benefit is seen in majority of patients with asthma, some patients will not do so
even with best therapy. Patients who do not reach an acceptable level of control at step 4 of

73

treatment is said to be having difficult to treat asthma. These patients may have an element of
poor steroid responsiveness and may require higher doses of inhaled steroid than is routinely
recommended to treat asthma. There is currently no evidence to support continuing these high
doses of inhaled steroid beyond 6 months. Instead dose optimization should be pursued by
stepping down to a dose that maintains maximal level of control achieved on higher dose.
Because very few patients are completely resistant to steroids, , compliance should be
investigated and confirmed, complete cessation of smoking should be considered weather current
or past, other comorbidities that may aggravate asthma should be investigated e.g., chronic
sinusitis, GER, obesity and obstructive sleep apnea. These comorbidities have been reported in
higher percentages in patients with difficult to treat asthma. When these reasons for the lack of
treatment responses have been considered and addressed, a compromised level of control is
accepted and discussed with the patient to avoid futile over treatment. The objective then is to
minimize exacerbations and need for emergency medical interventions while achieving as high a
level of clinical control with as little disruption of activities and as few daily symptoms as
possible. For these difficult to treat patients, frequent rescue medication is accepted, as is a
degree of chronic functional lung impairment

ASTHMATIC EXACERBATION:

74

Asthma exacerbations are an exaggerated lower airway response to an environmental exposure. .


Airway inflammation is a key part of the lower airway response in asthma exacerbation, and
occurs together with airflow obstruction and increased airway responsiveness. The patterns of
airway inflammation differ according to the trigger factor responsible for the exacerbation. The
reasons for the exaggerated response of asthmatic airways are not completely understood, but
recent studies have identified a deficient epithelial type 1 interferon response as an important
susceptibility mechanism for viral infection.
For children, the American Academy of Pediatrics has defined an asthma exacerbation as an
abrupt and/or progressive worsening of symptoms of shortness of breath, wheezing, chest
tightness, or some combination of these. However, symptoms are often sensitive indicators of the
onset of an exacerbation because they usually precede the deterioration in peak flow rate . Still, a
minority of patients, and particularly males, perceive airflow limitation poorly and are at
increased risk of near-fatal attacks of asthma
Provision of assistance for patients experiencing exacerbations is essential in order to reduce
morbidity and mortality.Patients at high risk of asthma-related death require closer attention and
should be encouraged to seek urgent care early in the course of their exacerbations.
Response to treatment may take time and patients should be closely monitored using clinical as

well as objective measurements. The increased treatment should continue until measurements of
lung function return to their previous best (ideally) or plateau, at which time a decision to admit
or discharge can be made based upon these values. Patients who can be safely discharged will
have responded within the first 2h, at which time decisions regarding patient disposition can be
made.. Respiratory virus infection is the most common environmental exposure to cause a severe
asthma exacerbation.

75

BURDEN OF ASTHMA EXACERBATIONS


Asthma exacerbations can be severe and require medical intervention, either as an emergency
department (ED) visit, admission to hospital, or an unscheduled visit to the doctor. Children
experience the majority of ED attendances for asthma (63%)There is a significant seasonal
variation in presentation to ED with severe asthma exacerbations, with a peak occurring in early
summer in school age children, coinciding with a return to school
Severe asthma exacerbations may also result in death The death rates from asthma are higher in
winter months, consistent with the winter rise in influenza infection which is associated with
very severe asthma exacerbations. Wark et al found that influenza infection led to severe and
refractory asthma exacerbation requiring ICU admission..(93).

TRIGGERS OF ASTHMATIC EXACERBATIONS

Virus infection
Allergen
Environmental pollutants
Occupational sensitisers/irritants
Medication: aspirin

76

TABLE 6
MECHANISM OF EXAGERRATED RESPONSE OF TRIGGER IN
ASTHMA EXACERBATION
TRIGGER
Virus

EFFECT
Enhanced

MECHANISM
lower

airway Deficient IFN- response

damage
Allergen

Enhanced

eosinophil Allergic sensitisation

response
Occupational

Increased eosinophilic and/or Sensitisation


neutrophilic bronchitis

Pollution

Neutrophilic bronchitis

Medication: aspirin

Severe bronchospasm

IFN, interferon.

77

PREVENTION OF ASTHMA SYMPTOMS AND EXACERBATIONS


Reducing a patients exposure to some of the triggers (e.g., smoking cessation, reducing
exposure to secondhand smoke, reducing or eliminating exposure to occupational agents known
to cause symptoms, and avoiding foods/additives/drugs known to cause symptoms) improves the
control of asthma and reduces medication needs. In the case of other factors (e.g., allergens, viral
infections and pollutants), measures where possible should be taken to avoid these. Because
many asthma patients react to multiple factors that are ubiquitous in the environment, avoiding
these factors completely is usually impractical and very limiting to the patient. Thus, medications
to maintain asthma control have an important role because patients are often less sensitive to
these risk factors when their asthma is under good control. Patients with well-controlled asthma
are less likely to experience exacerbations than those whose asthma is not well controlled.(5)

ASSESSING THE CHILD IN RESPIRATORY DISTRESS FROM AN


ACUTE ASTHMA ATTACK:
Effective treatment depends on an accurate and rapid assessment of disease severity upon
presentation.

78

TABLE 7
SEVERITY OF ASTHMATIC EXACERBATION
Impending
Clinical
Mild

Moderate

Severe

respiratory

features
failure
Might
Mental status

look

Normal

Drowsy
Usually agitated

agitated

confused

Normal activity Decreased


Activity

and

exertional activity

dyspnea

Decreased
or activity

feeding (infant)
Speaks

Speech

or

Normal

infant, Unable to eat

stops feeding

in
Speaks in words

Unable to speak

phrases
Work
breathing

of Minimal

Intercostal

and Significant

intercostal

substernal

respiratory

retractions

retractions

distress. Usually distress at rest.


all

Marked
respiratory

accessory All

muscles

muscles

involved,
may

accessory

and involved,
display including

nasal flaring and flaring


paradoxical

paradoxical

thoraco-

thoraco-

abdominal

abdominal

nasal
and

79

movement
Loud

pan- Wheezes

movement
might
The

Chest

Moderate

expiratory

and be

auscultation

wheeze

inspiratory

without

wheeze

stethoscope

chest

is

audible
silent

(absence

of wheeze)
SpO2 on room
>94%

9194%

<90%

air

TREATMENT OF ASTHMATIC EXACERBATIONS:


The following treatment is instituted to achieve rapid resolution of exacerbation

OXYGEN:
To achieve arterial oxygen saturation of 95%, oxygen should be administered by nasal cannula,
by mask or rarely by head may box in some infants. PaCO2 worsen in some patients on 100%

80

oxygen, especially with more severe airflow obstruction. Oxygen therapy should be titrated
against pulse oximetry to maintain satisfactory oxygen saturation.

RAPID ACTING INHALED BETA 2 AGONISTS:


Rapid acting inhaled beta 2 agonists should be administered at regular intervals. The closest
effective and efficient delivery is by metered dose inhaler and a spacer device. Although most
rapid acting beta 2 agonists have a short duration of effect .the long acting bronchodilator
formoterol which has both a rapid onset of action and long duration of effect, has been shown to
be equally effective without increasing side effects, although it is considerably more expensive.
A modestly greater bronchodilator effect has been shown with levabuterol compared to racemic
albuterol in both children and adults with an asthma exacerbation.

ADDITIONAL BRONCHODILATORS:
IPRATROPIUM BROMIDE :
The addition of nebulized beta 2 agonist to ipratropium bromide appears may produce better
bronchodilator than with either drug alone and should be administered before methylxanthines
are considered. Combination of beta 2 agonist and ipratropium bromide is associated with lower
hospitalization rates and greater improvement in lung functions. However once children with

81

asthma are hospitalized after intensive emergency department treatment, the addition of
nebulized ipratropium bromide to nebulized beta 2 agonist and systemic glucocorticosteroids
appears to confer no extra benefit.

THEOPHYLLINES:
In view of safety and cost effectiveness of rapid acting beta 2 agonists, theophylline has a
minimal role in the management of acute asthma. Its use is associated with severe and potentially
fatal side effects particularly those on sustained release theophyllines and there bronchodilator
effect is less than that of beta 2 agonist. However in one study of children with near fatal asthma,
IV theophylline provided greater benefit to patients also receiving aggressive regime of inhaled
and IV beta 2 agonist, inhaled ipratropium bromide and IV systemic glucocorticosteroids.

SYSTEMIC GLUCOCORTICOSTEROIDS:
Systemic glucocorticosteroids speed resolution of exacerbations and should be utilized in the all
but the mildest exacerbations especially if, the initial rapid acting beta 2 agonists fail to achieve
lasting improvement, the exacerbation develops even though the patient was already taking oral
glucocorticosteroids. Previous exacerbations require oral glucocorticosteroids.

ORAL STEROIDS:
Should are usually as effective as those administered IV and are preferred because this route of
delivery is less invasive and less expensive. If vomiting gas occurred, then equivalent dose

82

should be re-administered intravenously.in patients being discharged from the emergency


department, IM administration may be helpful especially if there are concerns about compliance
with oral therapy. Oral glucocorticosteroids require at least 4 hours producing clinical
improvement.

Daily

doses

of

system

glucocorticosteroids

equivalent

to

60-80mg

methylprednisolone as a single dose or 300-400 mg hydrocortisone in divided doses are adequate


for hospitalized patients and 40 mg of methylprednisolone or 200 mg hydrocortisone is probably
adequate in most cases. An oral glucocorticosteroid dose of 1 mg/kg daily for 3-5 days is
adequate for treatment of exacerbations in children with mild persistent asthma. Two days of oral
dexamethasone can also be used to treat asthma exacerbations but there are concerns about
metabolic side effects if dexamethasone is continued beyond 2 days. Evidence suggests that there
is no need to taper the dose of oral steroids, either in the short term or over several weeks as long
as the patient is on the maintenance inhaled glucocorticosteroids.

INHALED STEROIDS:
Inhaled steroids are effective as part of therapy for asthma exacerbations.in one study, the
combination of high dose inhaled glucocorticosteroids and salbutamol in acute asthma provided
greater bronchodilation than salbutamol alone and provide greater benefit than the addition of
systemic steroids across all parameters, including hospitalizations, especially patients with more
severe attacks. Inhaled steroids can be as effective as oral steroids in preventing relapses.
Patients discharged from the ED on prednisone and inhaled budesonide have a lower rate of
relapse than those on prednisone alone.

MAGNESIUM:

83

IV magnesium sulphate (usually given as single 2g infusion given over 20 min)is not
recommended for routine use in asthma exacerbations but can reduce hospital admission rates in
certain patients including adults and children who fail to respond to initial treatment and
children whose FEV1 fails to improve above 60%predicted after 1 hour of care. Nebulized
salbutamol administered in isotonic magnesium sulphate provide greater benefit than if its
delivered in normal saline. IV magnesium sulphate has not been studied in young children.

HELIUM OXYGEN THERAPY:


A systematic survey of studies have evaluated that there is no role of helium oxygen compared to
helium alone.it might be considered for patients who do not respond to standard therapy.

LEUKOTRIENE MODIFIERS:
There is little data to suggest a role for leukotriene modifiers in acute asthmatic exacerbation. It
might be considered for patients who do not respond to standard therapy.

SEDATIVES:
Sedation should be strictly avoided during exacerbations because of respiratory depressant effect
of anxiolytic and hypnotic drugs.

84

CRITERIA FOR DISCARGE FROM THE EMERGENCY DEPARTMENT


VERSUS HOSPITALIZATION
The following points refer to patients discharged from the emergency department.
1) At a minimum, a 35 days oral glucocorticosteroids for children should be prescribed, along
with continuation of bronchodilator therapy
2)

The bronchodilator can be used on an as-needed basis, based on both symptomatic and
objective improvement, until the patient returns to his or her pre-exacerbation use of rapidacting inhaled 2-agonists.

3)

Ipratropium bromide is unlikely to provide additional benefit beyond the acute phase and
may be quickly discontinued.

4) Patients should initiate or continue inhaled glucocorticosteroids.


5) The patient's inhaler technique at home should be reviewed.
6)

The factors that precipitated the exacerbation should be identified and strategies for their
future avoidance implemented.

7)

The patient's response to the exacerbation should be evaluated. The action plan should be
reviewed and written guidance provided.

8) Use of controller therapy during the exacerbation should be reviewed: whether this therapy
was increased promptly, by how much and, if appropriate, why oral glucocorticosteroids
were not added. Consideration should be given to providing a short course of oral
glucocorticosteroids to be on hand for subsequent exacerbations

85

9) The patient or family should be instructed to contact the primary healthcare professional or
asthma specialist within 24h of discharge
10) . A follow-up appointment with the patient's usual primary care professional or asthma
specialist should be made within a few days of discharge to assure that treatment is
continued until baseline control parameters, including personal best lung function, are
reached

86

PROGNOSIS
In the infants who had wheezing, regardless of bronchodilator reversibility or atopic status, the
characteristic histopathologic features of thickening of the laminar reticularis and eosinophil
inflammation were absent. Taken together, these data indicate that the airway inflammatory
responses and structural changes that are characteristic of asthma develop during the preschool
years and may follow, and not precede, the physiologic changes associated with asthma. Among
children 5 years of age and younger, the most common cause of asthma symptoms is viral
respiratory infection. At present, the relative contributions of airway inflammation, bronchial
smooth muscle abnormalities, or other structural factors in producing wheeze with acute viral
upper respiratory infections are unknown. Two general patterns of illness appear in infants and
children who have wheezing with acute viral upper respiratory infections: a remission of
symptoms in the preschool years and persistence of asthma throughout childhood. No absolute
markers are available to predict the prognosis of an individual child; however, an asthma
predictive index has been developed that identifies risk factors for developing persistent asthma.
Children under 3 years of age who had four or more episodes of wheezing in the past year that
lasted more than 1 day and affected sleep are significantly likely to have persistent asthma after
the age of 5 years if they also have either one of the following: parental history of asthma, a
physician diagnosis of atopic dermatitis, or evidence of sensitization to aeroallergens, OR two of
the following: evidence of sensitization to foods, 4 percent peripheral blood eosinophilia, or
wheezing apart from colds.

87

RESULTS

Frequency Table
GENDER
TABLE NO:8

NUMBER OF PATIENTS

PERCENTAGE

N=2400
1383
Male

57.6

Female
Total

1017
2400

Mean 1.4238
Std.deviation 0.49425

42.4
100.0

88

TABLE NO:9
DIAGNOSIS.

NUMBER

OF PERCENTAGE

PATIENTS
N=2400
Valid

ICS Improved

900

37.5

ICS Exacerbation

30

1.3

Mont Improved

318

13.3

Mont Stepped Up

708

29.5

Mont Exacerbation

62

2.6

ICS Stepped Up

121

5.0

ICS Recoved

.1

ICS treatment Stepped Up

.0

Mont Not Improved

.0

Mont Static

.3

.0

.1

Montelukast Exacerbation

.1

Mont Stepped down

.0

ICS Stepped down

.1

ICS Status

.0

Mont

Admitted

in

Status

asthmtas
Mont

Give

status

asthmaticus

89

Montelukast Improved

.0

Mont Controlled

82

3.4

ICS Controlled

157

6.5

Total

2400

100.0

Mean:4.3742
Std.deviation:5.06794

90

TABLE NO 10
PATIENTS AGE
NUMBER

OF PERCENTAGE

PATIENTS
N=2400
Valid

.6

97

4.0

.7

38

1.6

.8

62

2.6

.9

108

4.5

1.0

108

4.5

1.1

30

1.3

1.2

42

1.8

1.3

31

1.3

1.4

88

3.7

1.5

.3

1.6

258

10.8

1.7

34

1.4

1.8

18

.8

1.9

34

1.4

2.0

233

9.7

2.2

79

3.3

2.4

47

2.0

2.5

.1

2.6

189

7.9

91

2.7

.2

2.8

18

.8

2.9

.3

3.0

282

11.8

3.2

.2

3.3

.0

3.6

208

8.7

4.0

139

5.8

4.6

35

1.5

5.0

196

8.2

Total

2400

100.0

Mean: 2.420
Std.deviation:1.2558

92

Crosstabs
Case Processing Summary
Cases
Valid

Sex

of

Patients

diagnosis

and

Missing

Total

Percent

Percent

Percent

2400

100.0%

0.0%

2400

100.0%

TABLE NO 11
11A
Sex of Patients AND Daignosis
Count
Daignosis
ICS Improved

ICS Exacerbation

Mont Improved

Mont
Up

Sex of Patients

Total

Male

536

13

183

423

Female

364

17

135

285

900

30

318

708

Stepped

93

11B

Sex of Patients and Daignosis


Count
Daignosis
Mont Exacerbation ICS Stepped Up

ICS Recoved

ICS

treatment

Stepped Up
Male

37

62

Female

25

59

62

121

Sex of Patients

Total

11C

Sex of Patients and Daignosis


Count
Daignosis
Mont Not Improved

Mont Static

Mont Admitted in Mont


Status asthmtas

asthmaticus

Male

Female

Sex of Patients

Total

Give

status

94
11D
Sex of Patients and Daignosis
Count
Daignosis
Montelukast

Mont

Stepped ICS

Stepped ICS Status

Montelukast

Exacerbation

down

down

Male

Female

Improved

Sex of Patients

Total

11E

Sex of Patients and Daignosis

Count
Daignosis

Total

Mont Controlled

ICS Controlled

Male

35

81

1383

Female

47

76

1017

82

157

2400

Sex of Patients

Total

P value is significant i.e.,<0.5

Case Processing Summary

95

Cases
Valid

Daignosis * Patients Age

Missing

Total

Percent

Percent

Percent

2400

100.0%

0.0%

2400

100.0%

12a
Daignosis and Patients Age
Count
Patients Age

Daignosis

.6

.7

.8

.9

1.0

ICS Improved

20

27

ICS Exacerbation

Mont Improved

51

20

28

27

13

Mont Stepped Up

15

17

32

44

Mont Exacerbation

ICS Stepped Up

ICS Recoved

ICS treatment Stepped Up

Mont Not Improved

Mont Static

status 0

Mont

Admitted

asthmtas
Mont

Give

asthmaticus

in

Status

96

Montelukast Exacerbation

Mont Stepped down

ICS Stepped down

ICS Status

Montelukast Improved

Mont Controlled

15

ICS Controlled

97

38

62

108

108

Total

12b
Daignosis and Patients Age
Count
Patients Age

Daignosis

1.1

1.2

1.3

1.4

1.5

ICS Improved

15

14

28

ICS Exacerbation

Mont Improved

11

Mont Stepped Up

10

30

Mont Exacerbation

ICS Stepped Up

ICS Recoved

ICS treatment Stepped Up

Mont Not Improved

Mont Static

97

Mont

Admitted

in

Status

Mont Give status asthmaticus

Montelukast Exacerbation

Mont Stepped down

ICS Stepped down

ICS Status

Montelukast Improved

Mont Controlled

ICS Controlled

30

42

31

88

1.6

1.7

1.8

1.9

2.0

ICS Improved

97

16

95

ICS Exacerbation

Mont Improved

26

30

Mont Stepped Up

81

14

10

76

Mont Exacerbation

ICS Stepped Up

18

ICS Recoved

asthmtas

Total

12c
Daignosis and Patients Age
Count
Patients Age

Daignosis

98

ICS treatment Stepped Up

Mont Not Improved

Mont Static

Mont Give status asthmaticus

Montelukast Exacerbation

Mont Stepped down

ICS Stepped down

ICS Status

Montelukast Improved

Mont Controlled

ICS Controlled

17

11

258

34

18

34

233

2.2

2.4

2.5

2.6

2.7

ICS Improved

14

18

89

ICS Exacerbation

Mont Improved

14

16

Mont Stepped Up

34

13

64

Mont

Admitted

in

Status

asthmtas

Total

12d
Daignosis and Patients Age
Count
Patients Age

Daignosis

99

Mont Exacerbation

ICS Stepped Up

ICS Recoved

ICS treatment Stepped Up

Mont Not Improved

Mont Static

Mont Give status asthmaticus

Montelukast Exacerbation

Mont Stepped down

ICS Stepped down

ICS Status

Montelukast Improved

Mont Controlled

ICS Controlled

79

47

189

2.9

3.0

3.2

3.3

Mont

Admitted

in

Status

asthmtas

Total

12e
Daignosis and Patients Age
Count
Patients Age
2.8

100

Daignosis

ICS Improved

123

ICS Exacerbation

Mont Improved

23

Mont Stepped Up

89

Mont Exacerbation

10

ICS Stepped Up

ICS Recoved

ICS treatment Stepped Up

Mont Not Improved

Mont Static

Mont Give status asthmaticus

Montelukast Exacerbation

Mont Stepped down

ICS Stepped down

ICS Status

Montelukast Improved

Mont Controlled

ICS Controlled

21

18

282

Mont

Admitted

in

Status

asthmtas

Total

10f
Daignosis and Patients Age

101

Count
Patients Age

Daignosis

3.6

4.0

4.6

5.0

ICS Improved

85

78

14

115

900

ICS Exacerbation

30

Mont Improved

18

318

Mont Stepped Up

65

30

31

708

Mont Exacerbation

62

ICS Stepped Up

10

121

ICS Recoved

ICS treatment Stepped Up

Mont Not Improved

Mont Static

Mont Give status asthmaticus

Montelukast Exacerbation

Mont Stepped down

ICS Stepped down

ICS Status

Montelukast Improved

Mont Controlled

14

82

ICS Controlled

18

19

157

208

139

35

196

2400

Mont

Admitted

in

Status

asthmtas

Total

Total

102

P value is significant i.e.,<0.5

103

DISCUSSION
Asthma is a major public health problem affecting 300 million individual worldwide. . Asthma
prevalence, morbidity and mortality were found to increase in all age groups, but particularly in
children. Asthma was found to affect the social life of the patients , and to be a leading cause of
school and work absenteeism. . Absence from school and days lost from school are reported as
substantial economic and social loss in Asia pacific region, India, Latin America, United
Kingdom and United States. During the 6 month study period comparing the efficacy of inhaled
steroid with Montelukast in the context of uncontrolled bronchial asthma,it was evident that the
patients who were started treatment with inhaled glucocorticosteroids had a significantly lower
risk of experiencing an asthma-related hospitalization or hospitalization/emergency department
visit compared with montelukast, .As shown in a previous study, fluticasone propionate,
administered twice daily, significantly reduced asthma exacerbations, asthma symptoms, and
rescue medication use and was well tolerated, with no clinically relevant systemic effects, as
measured by growth velocity . IC S was found to be superior than montelukast in nearly all
measured outcomes Montelukast is a valid alternative to ICS especially in poorly compliant
preschool children, or in subjects who show adverse effects related to long-term steroid therapy .
However, limited data is available for age group 6 months to 5 years. Among 2400 patients
selected for the study, of which 1200 were prescribed inhaled corticosteroid and 1200 was given
Montelukast.The patients who were put on inhaled steroids suffered less frequent asthmatic
exacerbations,less school days off and less nocturnal cough. Non-atopic asthma and transient
wheezers are more prevalent in the age group till 3 years. Wheeze of transient wheezers being
primarily triggered by respiratory syncytial virus infection. However, their wheeze generally
remit in preschool years if its not accompanied by other risk factors of asthma like history of

104

atopy or parental allergies or history of allergic sensitization in any of the other sibs. These
transient wheezers have reduced airflow at birth, suggestive of narrowed airways which improve
with time. The present study has suggested that asthma is more prevalent in males and the
previous work done revealed no consistent reasons for this sex-related difference. However, lung
size is smaller in males than in females at birth but larger in adulthood. Obesity is more related
to asthmatic episode, Obese people with asthma have lower lung function and more comorbidities compared with normal weight people with asthma. Half of the patients met the
criteria for atopy with typical features of parental allergies and that in the sibs. This was the
group in which comprised of mostly the upper age limit of the study that is above 2 to 3 years.
They had the history of one or the other risk factor for asthma like exposure to smoke or humid
environment favoring the growth of fungus. Few patients had history of contact with pets at their
home. Early exposure to cat seems to increase the risk of sensitization to cat but not of asthma at
4 years of age. Dog ownership, on the other hand, appears to be associated with lowered risk of
sensitization to airborne allergens and asthma. None of the patients had history of prenatal
exposure to smoke. Those who were breast fed had otherwise more protected from diarrheal
illnesses and other infections but in the context of my study, I didnt find a consistent protective
effect of breast feeding in the context of allergies. However, older studies demonstrated that early
breast feeding is associated with reduced asthmatic events, in contrast to recent studies..Many of
the patients had infantile eczema as a manifestation of atopic illness. Eczema was twice as
common in the( PNC) persistent nocturnal cough(19%) as in the asymptomatic children (10%).
GERD treatment may benefit patients who have asthma and complain of frequent heartburn,
particularly those who have frequent nocturnal asthma symptoms. Wheeze is the most common
presenting complaint of every age group of my study, being more common in less than 1 year

105

because of compliant airways. .Various asthmatic phenotypes is a challenge for the physician, for
differentiating it from other common infectious illnesses like tuberculosis. Most the patients
coming to Out Patient Department (OPD) with complaints of cough variant asthma are
misdiagnosed as Gastroesophageal reflux, postnasal drip, chronic sinusitis, and vocal cord
dysfunction. Cough variant asthma is an occult form of asthma of which the only sign or
symptom is chronic cough. It is characterized as a persistent, nonproductive cough with minimal
or no wheezing and dyspnea and so the diagnosis is frequently overlooked . Nocturnal cough is
the most common and important symptom and an important marker of uncontrolled bronchial
asthma, Many of the patients had complaints of nocturnal cough before they get worse to
exacerbation requiring systemic steroids. It is concluded from a study that the clinical features of
children with persistent nocturnal cough resembled those of the asymptomatic population more
closely than those of the polysymptomatic asthmatic population. In this age group persistent
nocturnal cough, in the absence of wheeze, shortness of breath or tightness in the chest, is likely
to be a manifestation of atypical or hidden asthma in only a minority of cases. Activity induced
cough was also used as a marker of uncontrolled asthma.
LTRAs have been proposed as alternative first-line therapy to ICSs for episodic or mild
persistent asthma, particularly in children who have difficulty in utilising inhalation treatment,
with poor compliance, or where exercise-induced bronchospasm (EIB) is a dominant component
of asthma..ICS should be introduced as initial maintenance treatment (200 g BDP equivalent)
when the patient has inadequate asthma control. Atopy and poor lung function predict a
favorable response to ICS ..It was concluded from a study that ICS can be used to control
active disease and to reduce the burden of illness, but should not be used to prevent asthma in
high-risk children In one of a study,it has been shown that early intervention with inhaled

106

budesonide within the first 2 years of asthma diagnosis in patients with persistent asthma
improves both prebronchodilator and postbronchodilator FEV1.

107

CONCLUSIONS:
Based on the variability of presentations, frequent respiratory morbidity, poor or no cooperation
from the child for testing respiratory function, favoring the under diagnosis, delaying treatment
and affecting the proper assessment of severity, level of control, and adequate clinical response
to treatment leading to difficulty in making a prompt diagnosis of asthma. Simultaneously, lack
of studies done on children 6 months to 5 years of age, this study provided reliable information
for choosing an adequate controller therapy. Asthma control is purely clinical,assesed with the
number of more rescue free days, no nocturnal cough and no limitation of daily activities and all
these favorable outcomes were associated with the being adherent to an ICS.So , ICS proved to
be the most effective controller therapy in this age group.

108

REFERENCES