Approach to asthma

1. Approach To Asthma
And
Newer Modalities In Treatment
-By
Dr. Praman Kushwah , Dr. Pradeep Pazare

2. Objectives
To know the definition of asthma
To understand the risk factors and triggers of
asthma
To know the pathophysiology of bronchial asthma
To know how to diagnose asthma
To understand the management of chronic stable
asthma
Newer modalities in Treatment

3. Definition
• Asthma is a heterogeneous disease, usually
characterized by chronic airway inflammation. It is
defined by the history of respiratory symptoms such
as wheeze, shortness of breath, chest tightness and
cough that vary over time and in intensity, together
with variable expiratory airflow limitation

4. Triggers

5. Patho-physiology of Asthma

6. When pollens, for instance, are inhaled by an allergic individual  the allergenic protein is
taken up by antigen presenting cells (dendritic cells) in the airway  presented to naïve T-
helper (Th) cells that develop into Th2 cell phenotype These cells respond by secreting Th2
cytokines like IL-4 and IL-13 that cause allergen specific B-cells to switch from IgM producing
to IgE producing cells These cytokines also contribute to epithelial cell damage, increased
mucus secretion and airway hyper responsiveness. Th2 cells also secrete IL-5 that stimulates
eosinophil development, release from the bone marrow and their recruitment to the site of
inflammation. IgE antibodies bind to their receptors on the surface of mast cells. Cross linking
of adjacent IgE molecules leads to degranulation and release of mediators like histamine and
tryptase that are key to features of immediate hypersensitivity reaction. Activation of
mastcells and eosinophils will also stimulate the synthesis and release of lipid derived
mediators like prostaglandins and cysteinyl leukotrienes that are very potent
bronchoconstrictors. Moreover, activation of eosinophils leads to the release of mediators
like eosinophil cataionic protein and major basic protein, which can cause airway epithelial
cell damage and submucosal fibrosis. New evidence suggests that Th1 cells contribute to
chronic changes in the airways including epithelial cells damage and smooth muscle cells
activation. Regulatory T cells (Treg) inhibit Th2 cells by secreting IL-10 and tansforming
growth factor (TGF ). Also, antigen specific Th17 cells were found to play an important role
in neutrophilic airway inflammation and the process of airway remodeling (fixed changes to
the airway) through the secretion of IL-17A and IL-17F .

7. Asthma
Pathophysiology
Early-Phase Response
■ Peaks 30-60 minutes post exposure, subsides 30-90
minutes later
■ Characterized primarily by bronchospasm
■ Increased mucous secretion, edema formation, and
increased amounts of tenacious sputum
■ Patient experiences wheezing, cough, chest tightness,
and
dyspnea

8. Late-Phase Response
• Characterized primarily by inflammation
• Histamine and other mediators set up a selfsustaining
cycle increasing airway reactivity causing
hyperresponsiveness to allergens and other stimuli
• Increased airway resistance leads to air trapping in
alveoli and hyperinflation of the lungs
• If airway inflammation is not treated or does not
resolve, may lead to irreversible lung damage

9. Case scenario
A 4 year old male child patient
presented to the casualty with acute
dyspnea, dry cough
and wheezes, parents gave a history of
recurrent similar attacks in the past,
Parents also admitted increasing
symptoms while playing and dust
exposure, how would you approach
this case?

10. Diagnostic approach
1. Clinical suspicion
2. History with focus on symptom patterns
3. Physical examination for signs of asthma &
allergies
4. Confirm diagnosis with objective measurement
of pulmonary function (Spirometry)
5. Allergy testing
6. Other possibly useful tests
7. Clinical response to treatment

11. 1 Clinical suspicion
 Suspect asthma in patients who have repeated diagnoses of
respiratory illnesses as
1. Reactive airway disease
2. Bronchitis
3. Croup
4. Pneumonia
5. Bronchiolitis
 Previous health records are important!
 Always maintain a high index of suspicion for asthma

12. 2 History
 All that wheezes is not asthma & many asthmatics do not
wheeze!
 Key history points
1. Symptoms
2. Pattern of Symptoms
3. Precipitating Factors (Triggers)
4. Development of Disease
5. Living Situation
6. Disease Impact
7. Patient’s Perception Family & Medical History
 Wheezing with URIs is very common in small children but
1. Many of these children will not develop asthma.
2. Asthma medications may benefit patients who wheeze whether or not
they have asthma.

13. Airway
Inflammation
Drugs:
NSAIDS
Beta blockers
Respiratory
Infections
Irritants
Environment
Additives Emotion
Pets
Weather changes
Cold air
Endocrine
Exercise
Clinical history : Asthma triggers

14. 3 Physical examination
Respiratory examination
1. Evidence for obstructive respiratory disease
2. R.R , Resp. distress , Chest deformity, Cough , Wheeze
3. May be normal in patients with asthma
 General examination
1. Evidence for atopic disease :
• A.rhinitis , A.dermatitis , Siusitis , Adenoids
2. Absence of clubbing

15. - Chronic Severe Asthma

17. Allergic Rhinitis

18. Allergic Dermatitis - Eczema

19. 4 Confirm diagnosis
 Pulmonary Function Tests
1. Peak flowmetry
2. Spirometry
3. Exhaled nitric oxide
4. Bronchoprovocation test
• Bronchial hyperreactivity
• Reversal of obstruction

20. Peak flowmetry

21. Peak Flowmetry
 Daily peak flow or FEV1 monitoring: day to day
and/or A.M.-to-P.M. variation ≥20%
 More useful for monitoring

22. Spirometry

23. Spirometry

24. Spirometry
 Abnormality
1. Airflow limitation
2. Low FEV1 (relative to percentage of predicted norms)
3. FEV1:FVC ratio <0.80
 Spirometry may be normal in mild or well- controlled
asthma

25. Thomas Kurian

26. Exhaled nitric oxide
• The fractional concentration of exhaled nitric oxide (FENO)
can be measured in some centers.
• FENO is increased in eosinophilic asthma but also in non-
asthma conditions (e.g. eosinophilic bronchitis, atopy and
allergic rhinitis), and has not been established as being useful
for making a diagnosis of asthma
• In patients (mainly non-smokers) with non-specific respiratory
symptoms, a finding of FENO >50 parts per billion (ppb) was
associated with a good short-term response to ICS

27. Bronchoprovocation
Bronchial Hyperreactivity
 Exercise Challenge Test :
 15% or greater decrease in FEV1
 Methacholine challenge Test :
 20% or greater decrease in FEV1
 A negative result does not exclude the Diagnosis of asthma

28. Reversibility of obstruction
• Findings consistent with asthma include
– Bronchodilator response (to inhaled β-agonist) with
Improvement in FEV1 ≥12% and ≥200 mL
– Inhaled or oral corticosteroids may be required to
demonstrate reversibility
• Absence of response does not exclude asthma

29. 5 Allergy testing
 Evidence for allergy common in pediatric
patients with asthma.
 May help guide environmental control
 Skin testing (prick &/or intradermal) the “gold
standard.”
 In vitro (RAST –Radioallergosorbent test)
testing an alternative in some situtions.
 Eosinophils in blood & nasal secretions

30. Allergy Skin testing (prick)

31. 6 Other possibly useful tests
• Chest x-ray (not in every exacerbation!)
• Sinus x-ray
• Sweat chloride (polyp)
• pH probe , Barium swallow , Sonography
• Rhinolaryngoscopy
• Bronchoscopy

32. Chest Xrays
Can Help Identify
• Abnormalities that are hallmarks of asthma
masqueraders
– aspiration pneumonitis
– hyperlucent lung fields in bronchiolitis obliterans
• complications during asthma exacerbations
– Atelectasis
– Pneumomediastinum
– pneumothorax
• Chest xray in asthma
– Increased AP Lateral diameter
– Flat diaphragm

33. Chest Xrays

34. CT Scans (HRCT)
• Bronchiectasis, which is sometimes difficult to
appreciate on chest radiograph but is clearly
seen on CT scan, implicates an asthma
masquerader such as cystic fibrosis, allergic
bronchopulmonary mycoses (aspergillosis),
ciliary dyskinesias, or immunedeficiencies

35. Clinical response to treatment
 Therapeutic trial of :
 SABA (eg salbutamol)
 Inhaled Corticosteroids (beclomethasone) or
Oral Corticosteroids (prednisone)
And then assessment of the response to
treatment.

36. Remember…!
The diagnosis of asthma in children is a
clinical one.
Based on recognizing a characteristic pattern
of episodic symptoms in the absence of an
alternative explanation

37. Clinical Features that Increase
the Probability of Asthma
• More than one of the following symptoms:
– wheeze, cough, difficulty breathing, Chest - tightness,
• particularly if these symptoms:
– Are frequent and recurrent
– Are worse at night and in the early morning
– Are worse with triggers: exercise ,exposure to pets, cold or damp air,
emotions or laughter
– Occur apart from colds
 Personal history of atopic disorder
 Family history of atopic disorder and /or asthma
 Widespread wheeze heard on auscultation
 History of improvement in symptoms or lung function in response to
adequate therapy

38. Clinical Features that Decrease
the Probability of Asthma
1. Isolated cough in the absence of wheeze or difficulty
breathing
2. History of moist cough
3. Prominent dizziness, light-headedness, peripheral
tingling
4. Repeatedly normal PE of chest when symptomatic
5. Normal spirometry or PFM when symptomatic
6. No response to a trial of asthma therapy
7. Clinical features pointing to alternative diagnosis

41. DIAGNOSTIC FEATURE CRITERIA FOR MAKING THE DIAGNOSIS OF
ASTHMA
History of variable respiratory
symptoms
Wheeze, shortness of breath, chest
tightness and cough
Descriptors may vary between
cultures and by age, e.g. children
may be described as having heavy
breathing
• Generally more than one type of respiratory
symptom (in adults, isolated cough is seldom due
to asthma)
• Symptoms occur variably over time and vary in
intensity
• Symptoms are often worse at night or on
waking
• Symptoms are often triggered by exercise,
laughter, allergens, cold air
• Symptoms often appear or worsen with viral
infections

42. Confirmed variable expiratory airflow limitation
DIAGNOSTIC FEATURE CRITERIA FOR MAKING THE DIAGNOSIS OF
ASTHMA
• Documented excessive variability in lung
function* (one or more of the tests below)
AND documented airflow limitation
The greater the variations, or the more occasions
excess variation is seen, the more confident the
diagnosis
• Positive bronchodilator (BD) reversibility test* -
withheld before test: SABA ≥4 hours, LABA ≥15
hours)
Children: increase in FEV1 of >12% predicted
• Excessive variability in twice-daily PEF over 2
weeks*
Children: average daily diurnal PEF variability
>13%**
• Significant increase in lung function after 4
weeks of anti-inflammatory treatment
increase in FEV1 by >12% and >200 mL (or PEF† by
>20%) from baseline after 4 weeks of treatment,
outside respiratory infections
• Positive exercise challenge test* Children: fall in FEV1 of >12% predicted, or PEF
>15%
• Positive bronchial challenge test (usually only
performed in adults)
Fall in FEV1 from baseline of ≥20% with standard
doses of methacholine or histamine, or ≥15% with
standardized hyperventilation, hypertonic saline or
mannitol challenge
• Excessive variation in lung function between
visits* (less reliable)
Children: variation in FEV1 of >12% in FEV1 or
>15% in PEF† between visits (may include
respiratory infections)

46. The stepwise approach to drugs
Step 1 : occasional use of
relief bronchodilators
Short-acting B2-bronchodilator for relief of symptoms
Step 2 : regular inhaled
preventer therapy
Short-acting B2-bronchodilator as required + low-dose
inhaled steroid (200–400micrograms/day)
Step 3 : add-on therapy • Short-acting B2-bronchodilator as required + high-dose
inhaled steroid or
• Low-dose inhaled steroid +/– long-acting bronchodilator
Step 4 : persistent poor control • Short-acting B2-bronchodilator as required + high-dose
inhaled steroid (up to 800micrograms/day) + long-acting
bronchodilator or
• Theophyllines or ipratropium +/– alternate day steroid
Step 5 : continuous or frequent
use of oral steroid
• Use daily steroid tablet in lowest dose
• Maintain high-dose inhaled steroid at
800micrograms/day
• Refer to respiratory specialist

47. *Notes:
• The stepwise approach is meant to assist, not replace, the clinical decision
making required to meet individual patient needs.
• If alternative treatment is used and response is inadequate, discontinue it
and use the preferred treatment before stepping up.
• If clear benefit is not observed within 4-6 wk and patient/family medication
technique and adherence are satisfactory, consider adjusting therapy or
alternative diagnosis.
• Studies on children age 0-4 yr are limited. The stepwise approach is meant
to assist, not replace, the clinical decision-making required to meet
individual patient needs.
• Clinicians who administer immunotherapy or omalizumab should be
prepared and equipped to identify and treat anaphylaxis that may occur.
• Theophylline is a less desirable alternative because of the need to monitor
serum concentration levels.
• Zileuton is less desirable alternative because of limited studies as adjunctive
therapy and the need to monitor liver function

48. For treatment purposes, patients who had ≥2 exacerbations requiring oral systemic
corticosteroids in the past 6 mo, or ≥4 wheezing episodes in the past year, and who
have risk factors for persistent asthma may be considered the same as patients who
have persistent asthma, even in the absence of impairment levels consistent with
persistent asthma .

50. Treating modifiable risk factors to
reduce exacerbations

52. Newer Modalities
1. Allergen Immunotherapy
2. Subcutaneous Immunotherapy
3. Sublingual Immunotherapy
4. Anti-IgE Therapy : Omalizumab
5. Anti-interleukin-13 Therapy
6. Airway Hyper-responsiveness
7. Thromboxane A2 Receptor Antagonist
8. Long-acting Beta-2 Adrenoceptor Agonist
9. Phosphodiesterase-4 Inhibitors
10. Bronchial thermoplasty
11. Vaccinations

53. Allergen Immunotherapy
• Treated by hypo-sensitisation

54. Subcutaneous Immunotherapy(SCIT)
• Takes about three years and involves the
injection of increasing doses of allergen
extracts to induce both immunological and
clinical tolerance
• production of antibodies belonging to the IgE
class will compete with IgG as blocking
antibodies, and bind the allergen and
eliminate it without causing any symptoms of
allergy.

55. Sublingual Immunotherapy(SLIT)
• Has a better safety profile and greater
convenience. It is self-administered at home.
• effective in the treatment of grass pollen
allergy .

56. Anti-IgE Therapy : Omalizumab
• Omalizumab is a recombinant, DNA derived, humanised monoclonal anti
IgE antibody , binds to the portion of IgE that recognises its high affinity
receptors on the surface of mast cells, basophils, monocytes and dendritic
cells considered as immune modulating cells.
• Omalizumab is recommended in the treatment of moderate and severe
persistent asthma, especially allergic (IgE-mediated) variety that is non-
responsive to inhaled corticosteroids, long-acting beta-agonists and
leukotriene modifiers
• Administered subcutaneously over 30 seconds in the deltoid region or in
the thigh every 2 or 4 weeks
• Omalizumab has been included in Global Initiative for Asthma (GINA) 2007
guidelines at step 5 as an add-on therapy to high doses of ICS plus LABA.

57. Anti-Interleukin-13 Therapy
• Interleukin-13 ,a cytokine , induces bronchial epithelial cells
to secrete periostin ,secreted in large amounts by the
activated airway epithelial and exhibits autocrine effects on
epithelial cell function and paracrine effects on fibroblasts.
• lebrikizumab, an IgG4 humanised monoclonal antibody to
interleukin-13
• Administration of Lebrikizumab in uncontrolled asthma
shows an improvement in lung function at a dose of 250 mg
subcutaneously once a month for a total of 6 months

58. Airway Hyper-Responsiveness
• In asthma airway smooth muscle involved in
the pathogenesis of airway inflammation by
secreting cytokines, modifying tissue matrix,
binding migrating inflammatory cells in the
bronchial tree, and remodelling, and interact
with bronchial epithelium and nerves .

59. Thromboxane A2 Receptor Antagonist
• Thromboxane A2 (TXA2) a bronchoconstrictor Prostanoid, is a
cyclooxygenase product of arachidonic acid involved in the
pathogenesis of asthma, and takes part in its acute and
chronic inflammatory processes
• Seratrodust, a thromboxane A2 (TXA2) receptor antagonist
inhibits bronchoconstriction induced by TXA2. It causes airway
smooth muscle and vascular dilatation, and decreases airway
hyperresponsiveness
• Administered in a dose of 80 mg once a day orally, and the
dose can be increased up to 320 mg a day

60. Long-acting Beta-2 Adrenoceptor Agonist
• Inhaled beta-2 adrenoceptor agonists are
most effective bronchodilators for
management of bronchial asthma.
• Indacaterol ,an ultra-long acting beta-2
adrenoceptor agonist , with a high intrinsic
efficacy
• Dose of 200-800 microgram, it has a
favourable therapeutic index , provides
sustained 24-hour bronchodilation

61. Phosphodiesterase-4 Inhibitors
• Phosphodiesterases(PDEs) are intracellular
enzymes that inactivate cyclicadenosine
monophosphate (cAMP).
• Roflumilast acts as a selective, long-acting
inhibitor of the enzyme PDE-4 to exhibit anti-
inflammatory effects seen in asthma and COPD .It
improves FEV1 and peak expiratory flow rate.
• Orally administered drug , tablet of 500 mcg of
Roflumilast , administered once daily.

62. Bronchial Thermoplasty
• A novel intervention in which controlled radiofrequency
energy is delivered to the intra-parenchymal airways distal to
the main stem bronchi down to airways 3 mm in diameter
during a series of bronchoscopies resulting in a prolonged
reduction of airway smooth muscle mass to reduce smooth
muscle-mediated broncho-constriction
• Clinical benefit: Bronchial thermoplasty is likely to provide
clinical benefit by reducing the contractile function of airway
smooth muscle and exacerbation of asthma. By modifying the
structure and elements of the airway wall, BT can bring about
changes in airway hyper-responsiveness.

63. Vaccinations
• Patients with moderate-severe asthma are advised to receive
an influenza vaccination every year, or when vaccination of
the general population is advised
• Particularly children and the elderly, are at higher risk of
pneumoccal disease,but there is insufficient evidence to
recommend routine pneumococcal vaccination in people with
asthma

64. Drug Delivery Options
 Metered dose inhalers (MDI)
 Dry powder inhalers (Rota haler)
 Dry powder compressed for Disc haler
 Spacers / Holding chambers
 Nebulizers
Pitfalls in Asthma Treatment
Poor technique!

65. Common Pitfalls
in
Management of Asthma
Late &/or mis-diagnosis
Late &/or mis-therapy
Poor perception of symptoms
Poor adherence
Poor knowledge(patient
& family)
Poor relation between the patient ,
physician & family
Prolonged exposure to triggers
Smoking or exposure to ETS
Poverty
Psycho-social problems
65

66. Asthma Devices
Metered Dose inhaler Turbuhaler
Diskus DPI
MDI DPI

67. Spacer devices / masks

68. Inhalation Devices
Spacer
Space halers
Rotahaler
Dry powder
Inhaler
Metered dose
inhaler or MDI

69. Why use a Spacer with an Inhaler?
When an inhaler is used alone,
medicine ends up in the
mouth, throat, stomach and
lungs.
When an inhaler is used with
a spacer device, more
medicine is delivered to the
lungs.
Inhaler alone
Inhaler used with spacer
device

70. Therapy to avoid!
Sedatives & hypnotics
Cough syrups & Mucolytics
Anti-histamines (routinely!)
Antibiotics (routinely!)
Corticosteroid injections (routinely!)
Combination tablets
Immunosuppressive drugs
Chest physiotherapy
Immunotherapy
Maintenance oral prednisone >10mg/day

71. Conclusions :
• Good asthma control
• Risk factor control
• Compliance
• Inhaler technique
• Step up/down treatment as appropriate
• Suitable treatment for acute exacerbation
• Patient & Family Education:…
• Be always up-to-date!

72. References
• Nelson TEXTBOOK of PEDIATRICS EDITION 20
• Global Strategy for Asthma Management
and Prevention (2016 update)
• Supplement to Journal of the association of
physicians of India • march 2014 • VOL . 62

73. THANK YOU