3. DEFINITION
Asthma is characterised by chronic airway
inflammation and increased airway hyper-
responsiveness leading to symptoms of wheeze,
cough, chest tightness and dyspnoea. It is
characterised functionally by the presence of airflow
obstruction which is variable over short periods of
time, or is reversible with treatment. [Davidsons]
The hallmarks of the disease are ; intermittent and
reversible airway obstruction, chronic bronchial
inflammation with eosinophils, bronchial smooth
muscle cell hypertrophy and hyper-reactivity, and
increased mucus secretion. [Robbins]
4. EPIDEMIOLOGY
The prevalence of asthma varies widely in diff.
regions of the world due to distinct genetic,
environmental and occupational risk factors. However,
this disparity appears to be closing as the prevalence
in high income countries is reaching a plateau whereas
the prevalence in low and middle-income countries
continues to rise.
Worldwide it is estimated that approximately
334million currently suffer from asthma, and 250,000
deaths attributed to the disease each year. The
prevalence of the disease is continuing to grow, in the
overall prevalence it is estimated to increase by
100millon by 2025. [Global Burden of Disease Study,
GBD 2014]
5. In the USA, asthma prevalence, especially morbidity
and mortality, is higher in blacks than in whites.
Although genetic factors are of major importance in
determining a predisposition to the development of
asthma, Environmental factors play a greater role than
racial factors in asthma onset. [Medscape]
In sub-Saharan Africa, the prevalence among adults
is less studied or understood. Some prevalence studies
on asthma has been conducted in Africa, but the
reported prevalence varies widely. This may partly be
due to the changing dynamics of asthma and its
determinants and/or the use of disparate definitions
for asthma. Some studies define asthma based on
self-reported wheeze, others on combination
symptoms or doctor diagnoses and a few others have
applied further test like spirometry, PEF or skin allergy
6. Asthma research in Ghana has focused manly on children
between the ages of 5-16yrs with one published study that
included adults. Different markers for the disease has been
used such as clinician diagnosed asthma, exercise-induced
bronchospasm as well as questionnaire-derived symptoms
of asthma. Factors found to be associated with asthma in
Ghana include atopic sensitization to env’tal allergens,
inner-city residence and socio-economic differences.
Other implicated FHx of asthma, sibship position, brest-
feeding and helminths infections.
A survey carried out in 2005 on the prevalence rate of
asthma cases in Ghana revealed that 1 out of 11
pupils(9%), in the country basic schools was asthmatic, as
against 1 out of every 45 in year 2000. [ghanaweb.com,
2nd may 2006]
According to WHO data published in May, 2014 , asthma
deaths in Ghana reached 1,169 or 0.62% of total deaths.
The age adjusted death rate is 7.53 per 100,000 of
population which ranks Ghana at #68.
7. Ghana asthma society(GAS) was established was
established 30yrs ago to create awareness on the need
to help asthmatic patients and the public to manage
and treat asthma patients.
In children, asthma is more common in boys, with
male to female ratio (2:1), until puberty when the ratio
becomes 1:1. But females frequently become affected
after puberty . [Medscape]
GINA estimates that the global prevalence of asthma
ranges from 1-18% of the total population.
The world asthma day is an annual event organized
by GINA to create the awareness among public
worldwide about the precautions and preventions of
asthma. It is celebrated on annual bases of first
Tuesday of May. The theme for this year’s celebration
9. AETIOLOGY
House-dust mites which live in
carpets, mattresses and
upholstered furniture
Spittle, excrements,
hair and fur
of domestic
animals
Plant pollen
Pharmacological agents
(enzymes, antibiotics,
vaccines, serums, drugs)
Food components
(stabilizers, genetically
modified products)Dust of
book
depo-
sitories
10. THE HYGIENE HYPOTHESIS
According WHO, the strongest risk factors for
developing asthma are a combination of genetic
predisposition with env. exposure to inhaled
substances and particles that may provoke allergic rxn
or irritates the airways.
The hygiene hypothesis proposes that decreased
infections in early life bias the immune system towards
an allergic phenotype. T lymphocytes may differentiate
into two distinct subsets: Th1 and Th2. In infancy, a
shift occurs from the in utero Th2 bias towards a
Th1(characterised by IL2 and IFN gamma) response
necessary for fighting viral and bacterial infection. A
reduction in childhood infections favours persistence
of a Th2 (characterised by cytokines such as IL4, 5, 6,
9 and 13), directing the immune system towards an
allergic type of response.
11. GENETICS OF ASTHMA
One of the susceptible loci is on the long arm of chromosome
5 (5q), where several genes involved in regulation of IgE
synthesis and mast cell, and eosinophil growth and
differentiation map. The genes at this locus include;
1. IL13 (linked with susceptibility to the development of atopic
asthma)
2. CD14 (associated with occupational asthma),
3. class II HLA alleles (tendency to produce IgE antibodies)
4. β2-adrenergic receptor gene
5. IL-4 receptor gene (atopy, total serum IgE level, and asthma)
Another important locus is on 20q where ADAM-33 that
regulates
proliferation of bronchial smooth muscle and fbroblasts is
located
13. PATHOPHYSIOLOGY
The pathophysiology is complex and involves the ff
components;
1. Airway inflammation
2. Intermittent airway obstruction
3. Bronchial hyper-responsiveness
14. The classic atopic form of asthma is associated with
an excessive TH2 reaction against environmental
antigens. Cytokines produced by TH2 cells account
for most of the features of asthma—IL-4 stimulates
IgE production, IL-5 activates eosinophils, and IL-13
stimulates mucus production and also promotes IgE
production by B cells. IgE coats submucosal mast
cells, which, on exposure to allergen, release granule
contents. This induces two waves of reaction: an early
(immediate) phase and a late phase. The early
reaction is dominated by bronchoconstriction,
increased mucus production and variable vasodilation.
Bronchoconstriction is triggered by direct stimulation
of subepithelial vagal receptors.
15. The late-phase reaction consists of inflammation, with
activation of eosinophils, neutrophils, and T cells. In
addition, epithelial cells are activated to produce
chemokines that promote recruitment of more TH2
cells and eosinophils (including eotaxin, a potent
chemoattractant and activator of eosinophils), as well
as other leukocytes, thus amplifying the inflammatory
reaction. Repeated bouts of inflammation lead to
structural changes in the bronchial wall, collectively
referred to as airway remodeling.
[Robbins]
16. TYPES OF ASTHMA
1) ATOPIC ASTHMA : This is the most common type of asthma,
usually beginning in childhood, and is a classic example of
type I IgE–mediated hypersensitivity reaction. The disease is
triggered by environmental antigens, such as dusts, pollen,
animal dander, and foods. Infections can also trigger atopic
asthma. A skin test with the offending antigen results in an
immediate wheal-and flare reaction.
2) NON ATOPIC : Patients with nonatopic forms of asthma do
not have evidence of allergen sensitization, and skin test
results usually are negative. Respiratory infections due to
viruses (e.g., rhinovirus, parainfluenza virus) and inhaled air
pollutants (e.g. sulfur dioxide, ozone, nitrogen dioxide) are
common triggers.
17. 3. DRUG-INDUCED : Several pharmacologic agents
provoke asthma, aspirin being the most striking
example. Patients with aspirin sensitivity present
with recurrent rhinitis and nasal polyps, urticaria,
and bronchospasm. The precise mechanism remains
unknown, but it is presumed that aspirin inhibits
the cyclooxygenase pathway of arachidonic acid
metabolism without affecting the lipoxygenase
route, thereby shifting the balance of production
toward leukotrienes that cause bronchial spasm.
4. OCCUPATIONAL ASTHMA : This form of asthma is
stimulated by fumes (epoxy resins, plastics), organic
and chemical dusts (wood, cotton, platinum), gases
(toluene), and other chemicals. Asthma attacks
usually develop after repeated exposure to the
inciting antigen(s).
19. SEVERE ATTACKS
Inability to complete sentence
Pulse >110bpm
RR >25cpm
PEF of 30-35%
LIFE THREATENING ATTACKS
Cynosis
Bradycardia
PEF <33%
Silent chest
Confusion
20. INVESTIGATIONS
DIAGNOSTIC
Pulmonary function test
PEF : reading recorded in the morning and before
retiring to bed. A diurnal variation in PEF (the lowest
values typically being recorded in the morning) of
more than 20% is considered diagnostic and the
magnitude of variability provides some indication of
disease severity .
The measurement of FEV1 and VC by spirometry
allows the demonstration of airflow obstruction, and
following the administration of a bronchodilator,
confirms the diagnosis when a 15% (and 200 ml)
improvement in FEV1 is noted.
21. Methacholine test : Commonly used in adults. Used
if your symptoms and screening spirometry do not
clearly or convincingly establish a diagnosis of asthma.
Methacholine causes spasm and narrowing of airways
if asthma is present. During this test patient inhales
increasingly amount of methacholine mist, and
spirometry reading taken b4 and after the inhalation.
Positive test……if lung fxn drops by at least 20% .
Allergic test
CT scan : helical scan of the bronchus which will
differentiate asthma from bronchiectasis
MRI scan
23. NOTE : To make a definitive diagnoses of asthma, you
will need a compatible clinical history plus either/or ;
1. FEV >/= 15%* (and 200mL) increase following
administration of a bronchodilator
2. >20% diurnal variation on >/= 3 days in a week for
2 weeks on PEF diary
3. FEV >/= 15% decrease after 6mins of exercise.
*GINA accepts an increase of 12%.
24. MANAGEMENT
The goals of asthma management
1. Achieve and maintain control of symptoms
2. Prevent asthma exacerbations
3. Maintain pulmonary function as close to normal as possible
4. Avoid adverse effects from asthma medications
5. Prevent development of irreversible airflow limitation
6. Prevent asthma mortality
25. Non-Pharmacological treatment
1. Involve patient in his/her management
2. Avoidance of provoking factors where possible
3. Selection of the best treatment available
4. Step up treatment as needed for good control
27. STEPWISE APPROACH TO THE
MANAGEMENT OF ASTHMA
Step 1 : Reliever medication
Use of inhaled short acting beta2 adrenoceptor
agonist bronchodilators.
For patients with mild intermittent asthma (symptoms < once a
week for 3/12 and fewer 2 nocturnal episodes per month), it is
usually sufficient to prescribe an inhaled short-acting beta2
agonist eg. Salbutamol or terbutaline.
Step 2 : Controller medication
Introduction of regular preventer therapy
Regular anti-inflammatory therapy (ICS such as beclometasone,
budesonide or ciclesonide) should be started in addition to
beta2 agonist as required.
28. Step 3 : add-on therapy
If a patient remains poorly controlled, despite regular use of
ICS, a thorough review should be undertaken of adherence,
inhaler technique and ongoing exposure to modifiable
aggravating factors. Long acting beta2 agonist (LABAs) such as
salmeterol and formoterol represent the 1st choice of add-on
therapy
Step 4 : Poor control on moderate dose of inhaled steroid and
add-on therapy: Addition of a fourth drug.
In adults the dose of ICS may be increase to 2000ug daily. Oral
therapy with leukotriene receptor antagonist, theophillines or a
slow-release beta2 agonist may be considered
29. Step 5 : Continuous or frequent use of oral steroids
At this stage prednisolone therapy(usually
administered as single daily dose in the morning)
should be prescribed in the lowest amount necessary
to control symptoms. Patients on long term
corticosteroids tablets (> 3/12) are at risk of systemic
side effects eg osteoporosis, which can be prevented
by bisphosphonates.
Step down:
Once asthma control is established, the dose of
inhaled (or oral) corticosteroid should be titrated to
the lowest dose at which effective control of asthma is
maintained. Decreasing the dose of ICS by around 25-
30. EXACERBATION OF ASTHMA
The course of asthma may be punctuated by
exacerbations characterised by increased symptoms,
deterioration in PEF and an increase in airway
inflammation. Exacerbations may be precipitated by
infections or pollens. Most attacks are characterised
by a gradual deterioration over several hours to days
but some appear to occur with little or no warning:
so-called brittle asthma
31. It has been widely believed that an impending exacerbation may
be avoided by doubling the dose of ICS; however, recent studies
have failed to confirm this. Short courses of 'rescue' oral
corticosteroids (prednisolone 30-60 mg daily) are therefore
often required to regain control of symptoms. Tapering of the
dose to withdraw treatment is not necessary unless given for
more than 3 weeks.Indications for 'rescue' courses include:
• symptoms and PEF progressively worsening day by day
• fall of PEF below 60% of the patient's personal best recording
onset or worsening of sleep disturbance by asthma
• persistence of morning symptoms until midday
• progressively diminishing response to an inhaled
bronchodilator
• symptoms severe enough to require treatment with nebulised
or injected bronchodilators
Management of mild-moderate exacerbations
33. INDICATIONS FOR ASSISTED VENTILATION IN
ACUTE SEVERE ASTHMA
• Coma
•Respiratory arrest
•Deterioration of arterial blood gas tensions despite
optimal therapy
• PaO2 < 8 kPa (60 mmHg) and falling
• PaCO2 > 6 kPa (45 mmHg) and rising
• pH low and falling (H+ high and rising)
•Exhaustion, confusion, drowsiness
36. PROGNOSIS
The outcome from acute severe asthma is generally
good. Death from asthma is fortunately rare but a
considerable number of deaths occur in young people
and many are preventable. Failure to recognise the
severity of an attack, on the part of either the
assessing physician or the patient, contribute to
under-treatment and delay in delivering appropriate
therapy
37. REFERENCE
Davidson’s principle and practice of medicine; 22nd
edition
Oxford handbook of clinical medicine; 9th edition
Standard treatment guide; 6th edition . 2010
Medscape
WHO
www.ghanaweb.com
