Information on Allergy - Asthma in perspective

1. ALLERGY &
HYPERSENSITIVITY
Deurali-Janta
Pharmaceuticals Pvt. Ltd.
Asthma
Phr. Asad Kamran

2. Allergy
Hypersensitivity
“An important undesirable side effect of immunity is the
development, under some conditions, of allergy or other
types of immune hypersensitivity.”

3. Delayed-Reaction Allergy
Delayed-reaction allergy is caused by activated T cells and not by
antibodies.
In the case of poison ivy, the toxin of poison ivy in itself does not
cause much harm to the tissues. However, on repeated exposure, it
does cause the formation of activated helper and cytotoxic T cells.
Then, after subsequent exposure to the poison ivy toxin, within a
day or so, the activated T cells diffuse from the circulating blood in
large numbers into the skin to respond to the poison ivy toxin.
The damage normally occurs in the tissue area where the instigating
antigen is present, such as in the skin in the case of poison ivy, or in
the lungs to cause lung edema or asthmatic attacks in the case of
some airborne antigens.

4. Allergic PersonThe allergic tendency is genetically passed from parent to child
and is characterized by the presence of large quantities of IgE
antibodies in the blood.
These antibodies are called reagins or sensitizing antibodies to
distinguish them from the more common IgG antibodies.
When an allergen (defined as an antigen that reacts
specifically with a specific type of IgE reagin antibody) enters
the body, an allergen-reagin reaction takes place and a
subsequent allergic reaction occurs.
A special characteristic of the IgE antibodies (the reagins) is a
strong propensity to attach to mast cells and basophils.

5. Allergic PersonAt any rate, many of the mast cells and basophils rupture;
others release special agents immediately or shortly
thereafter, including histamine, protease, slowreacting
substance of anaphylaxis (which is a mixture of toxic
leukotrienes), eosinophil chemotactic substance, neutrophil
chemotactic substance, heparin, and platelet activating
factors.
These substances cause such effects as dilation of the local
blood vessels; attraction of eosinophils and neutrophils to the
reactive site; increased permeability of the capillaries with loss
of fluid into the tissues; and contraction of local smooth
muscle cells.

6. Allergic ReactionsAnaphylaxis
Urticaria
Hay Fever
Asthma

7. Asthma

8. The Global BurdenAsthma is now one of the world’s most common long-term
conditions, according to the Global Burden of Asthma Report,
a comprehensive survey of the prevalence and impact of
asthma around the world, based on standardized data
collected in epidemiology studies in more than 80 countries.
The disease is estimated to affect as many as 300 million
people worldwide-a number that could increase by further
100 million by 2025.
Asthma has become more common in both children & adults
around the world in recent decades.
Asthma

9. Central & Sothern AsiaOver 50 million people in Central & Southern Asia have
asthma, and many do not have access to the medications that
can control the disease.
Due to rapid industrialization and urbanization throughout the
region, the prevalence of asthma is predicted to increase
rapidly in the coming years.
Asthma

10. Age of onset:
1 year in more than 26% of the cases; 1-5 year in 52% of the
cases; >5 year in 22% of the cases.
Role of Family history:
The incidence of asthma was 18.79% if one of the parents had
asthma, 1.65% if one of the siblings had asthma, and 4.12% if
the grandparents had the disease.
Asthma

11. Causes:
Viral upper respiratory tract infections: Identified as the
triggering factor for asthma among 40% of children.
Seasonal variation: More than one third of the children had
attacks of asthma during a specific season. Asthma incidences
are more common during winter and rainy season. Only 3% of
these episodes occurred during the summer months.
Food items as causal factor: About one fifth of the children
seem to suffer from food-related asthma. The most blamed
offenders are grapes (57%), bananas (53%) guavas (51%),
Citrus fruits (28%), Ice cream (21.5%), fried foods (19%) and
tomatoes (12.5%). Peanuts are also a major contributing factor
for triggering asthma.
Asthma

12. Asthma is a clinical syndrome rather than a single disease.
Therefore, grouping asthma into distinctive entities is helpful
in developing appropriate management plans.
Although different mechanisms are involved in the
pathogenesis of the different types of asthma, all have chronic
airway inflammation as the underlying abnormality.
Extrinsic or allergic asthma forms a major portion of adult
asthma, & most of the cases are of childhood onset.
Late onset asthma is often caused by sensitization to
occupational agents and drugs.
Asthma
Asthma-A Clinical Syndrome

13. Aspirin & other NSAIDs are the most common causes of drug
induced asthma. App. 10%-20% of adult asthmatic patients are
sensitive to aspirin. In subjects with asthma, sinusitis, and
nasal polyps, aspirin sensitivity increases to 40%.
Patients with brittle asthma are at high risk of dying from
asthma.
Those in whom no environmental cause for asthma can be
identified are considered to have intrinsic (cryptogenic)
asthma. A higher prevalence of intrinsic asthma is noted in
female patients.
Asthma
Asthma-A Clinical Syndrome

14. Different factors trigger asthma exacerbations (attacks) by
inducing inflammation or provoking acute bronchoconstriction
or both.
Inhaled allergens such as house dust mite, pollen, animal
dander, cockroaches and spores of fungi are the most common
trigger factors, but ingested or injected allergens can also
precipitate acute episodes.
Pollens tend to cause seasonal attacks: tree pollen in spring,
grass pollen in summer, & weed pollen in autumn.
Cats & dogs are among the common pets known to trigger the
asthma attacks due to allergy to their dander, saliva, urine &
feces.
Asthma
Precipitating Factors

15. Important fungus associated with asthma is Aspergillus
fumigates, which causes episodes mainly in late autumn &
winter.
Among the respiratory infections, rhinovirus is the common
culprit.
Exercise & associated hyperventilation can exacerbate
symptoms through changes in temperature of airway mucosa
& changes in osmolarity of fluid lining the airway mucosa.
Drugs such as aspirin & other NSAIDs, which induce asthma
development, also cause exacerbation.
Asthma
Precipitating Factors

16. Beta adrenergic blockers provoke bronchoconstriction in
asthma patients by blocking Beta receptors to endogenous
catecholamines.
Although asthma is not a psychosomatic disorder, emotional
stress can cause exacerbation indirectly through
hyperventilation.
Factors causing Asthma:Allergen, Viruses, Exercise, Air
Pollution, Cold Air, Foods/Additives, Emotional Stress, Drugs,
Occupational factors.
Asthma
Precipitating Factors

17. Mothers’ anxiety during pregnancy is associated with asthma
in their children:
Of particular interest is the possibility that parents’
psychological state could influence the risk of asthma in their
children, i.e. the possibility that pregnant women who are
stressed, particularly late in the pregnancy, have an increased
risk of their child developing asthma.
Although the mechanisms behind the relationship are not
understood, it is speculated that increases in a woman’s stress
hormone, cortisol, during pregnancy may affect programming
of the baby’s adrenal functions or immune development.
Asthma
Asthma in Children

18. Obese mothers up babies’ asthma attack:
Babies born to overweight mothers are at a greater risk of
developing asthma.
Obesity is not a neutral state; adipose tissue is an active
producer of pro-inflammatory cytokines, while it also
suppresses the action of anti-inflammatory cytokines.
Therefore, obesity is not just a problem of excess fat, but a
problem of systemic inflammation.
This may affect the immunological and pulmonary
development in the fetus and possibly result in a higher risk of
asthma symptoms after birth.
Asthma
Asthma in Children

19. Researchers found that in children who had at least one
asthmatic parent, maternal obesity increased their risk of
having asthma at age eight by 65% over children of asthmatic
parents whose mothers were not overweight.
Asthma
Asthma in Children

20. Frequent episodes of wheezing-more than once a month.
Activity-induced cough or wheeze.
Cough particularly at night during periods without viral
infections.
Absence of seasonal variation in wheeze.
Symptoms that persist after age 3.
Symptoms occur or worsen in the presence of:
Aeroallergens (house dust mites, companion animals,
cockroach, fungi)
Exercise
Pollen
Asthma
Signs & Symptoms

21. Respiratory (Viral) Infections
Strong emotional expression
Tobacco smoke
The child’s cold repeatedly “goes to the chest” or take more
than 10 days to clear up.
Symptoms improve when asthma medication is given.
Asthma
Signs & Symptoms

22. Severity of asthma is classified into four groups according to
symptoms and lung function measurements.
Generally patients have poor perception of the severity of
their asthma because they tend to adapt their lifestyle to
accommodate their Symptoms.
This in turn leads to poor control of the disease as well as poor
quality of life.
Classifying the disease in this stepwise fashion allows the
targeting of therapy according to the severity of the disease.
Asthma
Classification of Asthma Severity

23. Asthma
Classification of Asthma Severity
Step 1
Intermittent
Step 2
Mild Persistent
Step 3
Moderate Persistent
Step 4
Severe Persistent
Intermittent symptoms 
once per week
Brief exacerbation (from a
few hours to a few days)
Night-time asthma
Symptoms  twice a
month
Asymptomatic & normal
lung function between
exacerbations
PEFR or FEV1: >80%
predicted; variability
20%
Symptoms > once per
week but  once per day
Exacerbations may affect
activity and sleep
Night-time asthma
symptoms ≥ twice per
month
PEFR or FEV1: ≥80%
predicted; 20%-30%
variability
Symptoms daily
exacerbations affect
activity and sleep
Night-time asthma
symptoms > once per
week
Daily use of inhaled short
acting Beta 2 agonist
PEFR or FEV1: >60% to
80% predicted: >30%
variability
Continuous symptoms
and frequent
exacerbations
Frequent night-time
asthma symptoms
Physical activities limited
by asthma symptoms
PEFR or FEV1: ≤60%
predicted; >30%
variability.
FEV1: Forced Expiratory Volume
PEFR: Peak Expiratory Flow Rate

24. Asthma is best described as a chronic disease that involves
inflammation of the pulmonary airways and bronchial
hyperresponsiveness that results in the clinical expression of a
lower airway obstruction that usually is reversible.
Bronchial provocation with allergen induces a prompt early
phase immunoglobulin E (IgE)-mediated decrease in bronchial
airflow (FEV1) followed in many patients by a late phase IgE-
mediated reaction with a decrease in bronchial airflow for 4-8
hours.
Microscopically, asthma is characterized by the presence of
increased numbers of eosinophils, neutrophils, lymphocytes, &
plasma cells in the bronchial tissues, bronchial secretions, and
mucus.
Asthma
Pathophysiology

25. Initially, there is recruitment of leukocytes from the
bloodstream to the airway by activated CD4 T-Lymphocytes.
The activated T-Lymphocytes also direct the release of
inflammatory mediators from eosinophils, mast cells, &
lymphocytes.
In addition, the subclass 2 helper T-lymphocytes subset of
activated T-lymphocytes produces interleukin IL-4, IL-5, & IL-
13.
IL-4 in conjunction with IL-13 signals the switch from IgM to
IgE antibodies.
Asthma
Pathophysiology

26. The cross-linkage of two IgE molecules by allergen causes mast
cells to degranulate, releasing histamine, leukotrienes, & other
mediators that perpetuate the airway inflammation.
IL-5 activates the recruitment and activation of eosinophils.
The activated mast cells are eosinophils also generate their
cytokines that help to perpetuate the inflammation.
Regardless of the triggers of asthma, the repeated cycles of
inflammation in the lungs with injury to the pulmonary tissues
followed by repair may produce long-term structural changes
(“remodeling”) of the airways.
Asthma
Pathophysiology

27. Asthma is associated with increased expression of
inflammatory proteins including cytokines, enzymes, &
adhesion molecules.
Induction of many of the genes for these proteins is regulated
by the transcription factor, nuclear factor-Kappa B (NF-Kappa
B).
Activation of NF-Kappa B may be the basis for increased
expression of many inflammatory genes and for the
perpetuation of chronic airway inflammation in asthma.
Asthma
Pathophysiology

28. Serum Folate Level:
higher folate levels were associated with lower total IgE levels,
allergic sensitization & wheeze, and lower odds for doctor-
diagnosed asthma, despite age, sex, race/ethnicity & economic
status.
Vitamin D:
Low levels of vitamin D could increase the severity of asthma.
members with lower Vitamin D levels also tended to have
several markers of allergy, such as dust-mite sensitivity.
Asthma
Nutrition & Asthma

29. Vitamin C:
Vitamin C showed significant improvements in respiratory
measures and asthma symptoms, including positive effects on
pulmonary function tests, bronchoprovocation challenges with
methacholine or histamine or allergens, improvement in white
blood cell function and motility, and a decrease in respiratory
infections.
High dose Vitamin C therapy may also help asthmatics by
lowering histamine levels.
Asthma
Nutrition & Asthma

30. Fish Oil supplementation:
A possible contributing factor to the increased incidence of
asthma may be the consumption of a pro-inflammatory diet.
In the typical modern diet, 20-fold to 25-fold more omega (n)-
6 polyunsaturated fatty acids (PUFAs) than n-3 PUFAs are
consumed, which results in the release of pro-inflammatory
AA metabolites.
Eicosapentaenoic acid (EPA) & decosahexaenoic acid (DHA) are
n-3 PUFAs derived from fish oil that competitively inhibit n-6
PUFA metabolism & thus reduce the generation of pro-
inflammatory four-series leukotrienes & two-series
prostaglandins & production of cytokines from inflammatory
cells.
Asthma
Nutrition & Asthma

31. Quercetin-The anti-inflammatory bioflavonoid:
Quercetin has long been used as a potent natural anti-allergen
as it helps to stabilize the histamine-containing mast cells.
Quercetin acts by modifying inflammatory signals at the gene
level.
Inflammatory signals such as TNF alpha, IL-6 and NF-Kappa B
were all reduced by Quercetin.
Quercetin is high in apples, & to a lesser amount in many fresh
fruits.
Mothers who ate apples during pregnancy had children with
fewer symptoms of asthma.
Asthma
Nutrition & Asthma

32. Yoga:
Yoga is an ancient Hindu discipline that uses postures and
breathing techniques (pranayama) to increase the lung airflow,
air capacity, stamina & reduces stress.
Simple relaxation techniques also help to reduce stress,
regulate breathing patterns & also improve lung function.
Asthma
Nutrition & Asthma

33. Asthma
Management of Asthma
CurrentTherapiesUsedin Asthma
Bronchodilators Anti-Inflammatory Therapies
Inhaled short acting Beta 2 agonists: Salbutamol &
Terbutaline
Inhaled Corticosteroids: Budesonide, Fluticasone
propionate, Beclomethasone dipropionate & Mometasone
Inhaled long acting Beta 2 agonists: Salmeterol &
Formoterol
Antileukotrienes: Montelukast, Pranlukast
Inhaled Anti-cholinergics: Ipratropium bromide &
Tiotropium bromide
Cromones: Sodium crmoglycate & Nedocromil sodium
Slow release Theophylline, Aminophyline, Doxofylline Anti - Immunoglobin E: Omalizumab

34. Drugs currently used to treat asthma include Beta 2 agonist,
Glucocorticoids, methylxanthines (Theophylline, Doxofylline),
cromones & Anticholinergic agents.
For acute, severe asthma, the inhaled Beta 2 agonists are the
most effective bronchodilators.
Short-acting forms give rapid relief, long acting agents provide
sustained relief and help nocturnal asthma, & serious side
effects are rare when these drugs are used properly.
First line therapy for chronic asthma is inhaled Glucocorticoids
(ICS), the most potent among currently available agents that
reduces airway inflammation.
Asthma
Management of Asthma

35. Their side effects can be reduced by rinsing the mouth or by
using large (volume spacers).
Methylxanthines are used both for their anti-inflammatory as
well as bronchodilatory actions. Although Theophylline is
inexpensive, monitoring its plasma concentrations is both
expensive & inconvenient.
Doxofylline is a safer alternative to theophylline. Doxofylline is
a novel bronchodilator with similar efficacy as theophylline.
Doxofylline is preferred in patients with GI intolerance.
Doxofylline produces stable serum concentration, hence
plasma monitoring is required only in patients with hepatic
insufficiency & intolerance to xanthine drugs.
Asthma
Management of Asthma

36. Cromones work best for patients who have mild asthma; they
have few adverse effects, but their activity is brief, so they
must be given four times daily.
The Anticholinergic bronchodilators are more useful for
treating COPD than for chronic asthma. These drugs have
virtually no side effects, & their onset is slower & their actions
longer than inhaled Beta 2 agonists.
The new direction in treating asthma will be medications that
have few side effects and is targeted specifically to the
pathogenesis of asthma.
Asthma
Management of Asthma

37. Asad Kamran
Technical Consultant, MPD
Deurali-Janta Pharmaceuticals Pvt. Ltd.