3. INTRODUCTION
• DEFINITION
Asthma is a disease characterized by episodic airway obstruction
and airway hyper responsiveness usually accompanied by airway
inflammation
It is defined by H/O respiratory symptoms – wheeze, sob, chest
tightness ,cough that vary over time and intensity with variable
expiratory airflow limitation(GINA 2022)
5. RISK FACTORS
Epidemiological or exposure factors which ↑ risk of
development of asthma
Genetics-
• 25-85% of monozygotic twins show concordance
– Polymorphisms on chr 5q
– ORMDL3
– GSDM3
– ADAM 33
– IL12
– IL 33- ↑ risk of non type 2 asthma
– HLA DQ 31&DQB2
– Arg-Gly-16 variant of B2 receptors -↓ response to beta
agonists
6. Allergen exposure- can be a trigger
– Mc House Dust mite(Dermatophagoides)- cause type 2
asthma
– Pollutants
– Tobacco
– Infections- Rhino viruses, RSV, Mycoplasma
7. Occupational exposure- mostly in adults
• RADS-Reactive airway dysfunction syndrome
– When exposed to large amounts of particulate
matter/ionising/oxidising substances
– Can develop airway inflammation and
bronchoconstriction
– No sensitization
– Rx- wear mask
8. Diet & Nutrition- relation not well established
– Vit D def- ↑ risk and
– pre existing pts with asthma ↑ severity & frequency
– Zinc and Vit C def in prenatal period - ↑ risk
9. Obesity-
– ↑ adipocytokines= IL6 upregulated
– attacks are severe
Medications –
– no medication identified to cause asthma
– Some studies prenatal exposure to paracetamol have
association
– B blockers etc may precipitate attack
10. Pre natal and peri natal factors
– Pre eclampsia
– Prematurity
– C section
– Neonatal jaundice
– Breast feeding is a protective factor atleast for initial few
years
11. TRIGGERS
– Allergen exposure
– Air pollution
– Infection – both URTI& LRTI
– Ambient air temperature- cold and dry- ↑ airway
secretion’s osmolality- mast cell degranulation- PGD2 and
Histamine
14. MOLECULAR UNDERSTANDING
• Type 2 Asthma
allergen
TSLP
ILC
Th2 cell Lymphocytes
IL4,5,13
stimulate switch of B cells to produce Ig E
stimulate recruitment of mast cells which release PGD2,
histamine-vasodilatation and inflammation
• IL5 recruits eosinophils leading to inflammation
15. Non type 2 Asthma
viral infections, irritants, pollutants
IL 33 IL6
Th17 Th1
IL 6,8,17 IFN Ɣ,α
Neutrophils
16. DIAGNOSIS
• Final diagnosis is based on PFT
• History
• Clinical findings- wheeze, breath sounds =
expiration>inspiration
• As the condition progress wheeze becomes minimal
• PFT- FEV1-↓
• FEV1/FVC –Normal/↑
17. • Bronchodilator reversibility test- FEV1≥12% or ↑ by ≥200ml
• If BDR cant be done oral steroids for 2-3 weeks
• PEFR used for monitoring
• other tests- assessment of airway hyper responsiveness
– PD 20 or PC 20 test – methacholine- dose required to
↓FEV1 by 20%
– PD20 <400mcg or PC16 mg/ ml = air hyper responsiveness
18. • Fraction exhalation of nitric oxide (FeNO)-assessment of
airway eosinophilic inflammation
Role in monitoring
FeNO - >20-25ppb- poor compliance
>35-40ppb - type 2 asthma in treatment naïve patients
• Flow volume loops – limited role
Loop shift to left
PEFR ↓
Flattening of expiratory limb
19. Asthma variants
• Cough variant asthma
– Predominant symptom is cough
– MC in children
– Look for diurnal variation
– Diagnosis is based on PFT and BDR test
– DD-non asthmatic eosinophilic bronchitis
20. • Exercise induced asthma
– Bronchoconstriction due to exercise
– Due to exercise –hyper ventilation-airway dryness-change
in osmolality of secretions-mast cell degranulation
– Symptoms develop 20-30 min after exercise as during
exercise Adr surge cause bronchodilation
21. • Occupational asthma
– Exposure to occupational allergens
– Asthma worse on working days and better on holidays
– If detected <6 months of onset it is reversible
– Recommended to change occupation
22. • Aspirin sensitive asthma
– Previously known as intrinsic asthma
– Samters traid-asthma, nasal polyps and aspirin sensitivity
– Appears after 3rd decade
– Normal IgE levels
– DOC-oral corticosteroids
– LT antagonists , cox inhibitors can used
23. • Refractory asthma
– Poorly controlled despite maximal inhaled therapy
– Mc cause is poor compliance / faulty technique
– Hyperthyroidism / hypothyroidism
– Chronic sinusitis/post nasal drip
– Beta blockers/aspirin/NSAIDS
– Doc is oral corticosteroids
24. • Brittle asthma
o Type 1- chaotic variation-Chaotic lung function despite
appropriate treatment
– Rx –oral corticosteroids
o Type 2- precipitous unpredictable fall in lung function
– Rx- s/c epinephrine
25. • Corticosteroid resistant asthma
– Failure to respond to high dose oral corticosteroids given
for 2 weeks- prednisolone 40mg/day
– Persistent symptoms/exacerbations
Can be due to
• Genetic variance on
glucocorticoid receptors GRB
polymorphic variance coding for HDAC2
– Rx monoclonal antibodies
26. • GINA 2022
– Global initiative for asthma
– Provides asthma guidelines for public health officials and
health care professionals globally to reduce asthma
prevalence, morbidity and mortality
– Main drugs
– Bronchodilators-SABA,LABA,LAMA
– Steroids-ICS,OCS
– Biologicals –IL 4 antagonists, IL 5 antagonists, TSLP
inhibitors
27. • Problem statement
• Attacks – treat by SABA as LABA takes time to act except
FORMOTEROL long acting but acts almost immediately
• Airway remodelling-
– ICS
– OCS-can consider late as side effects are more with oral steroids
– MAb`s
• Diurnal variation of symptoms- LABA,LAMA
– LAMA not recommended as monotherapy
28. • GINA’s stand on
– Diagnosis – clinical assessment and PFT
• FEV1 ↓ , FEV1/FVC ratio < 70%
• BDR - >12% / >200 ml
• In resource limited setting PEFR can be used
– ↑ by ≥ 20% 15 min after 2 puffs of salbutamol
– Or improvement of symptoms and PEFR after 4 wks
of ICS
29. • Two tracks- based on reliever
– Track 1= reliever and maintenance is a combination of
same medications- ICS+ Formoterol
– Track 2= for maintenance -ICS+ Formoterol
for reliever SABA +ICS
• Track 1 is preferred as it improves compliance
• Track 2 is used when you are sure pt is compliant
• Low lung function = FEV1< 30% needs aggressive Rx
• Never give SABA alone increases mortality
• Approved anti TSLP inhibitors
30. • 5 steps
• Start @ step based on where the patient belong by seeing the
symptoms
• Day symptoms >5 /wk or < 5 /wk
• Night symptoms ≥ 1/ wk
• ≥5 day day or ≥1 night symptoms start at step 3 / 4
• If FEV1
<30% >30%
start @ step 4 start @ step 3
31. • <4 day symptoms or no night symptoms start at step 1 /2
• No pt should be directly started at step 5
• Track 1
• Step 1 /2 – as needed low dose ICS+Formoterol
• Step 3 –maintenance is introduced =low dose ICS+ Formoterol
maintenance = reliever
• Step 4- maintenance+ reliever = medium dose
ICS+Formoterol
• Step 5- add on LAMA or high dose ICS+Formoterol±
biologicals
32. • If pt struck at step4 i.e continue to have low lung function or
symptoms doesn’t improve escalate to step 5
• Track 2
• Reliever is SABA+ICS
• Step 1= ICS sos+SABA sos
• Step 2 = low dose ICS alone as maintenance
• Step 3,4,5 = same as track 1
33.
34. • Key changes in GINA 2022
• Assessment of asthma by inflammatory phenotype i.e. type 2
or non type 2
– Useful to start biologicals in step 5
• Use FeNO
– If FeNO >35 ppb /blood eosinophils>300/µl = type 2
– Repeat tests upto 3 times atleast 1-2 wks after stopping
OCS or lowest possible OCS dose
• Consider for LAMA or low dose azithromycin in non type 2
phenotype
35.
36.
37. • Asthma exacerbations
– Acute or sub worsening of symptoms and lung function from patients
usual status
– It may be the first presentation
Common triggers are
viral respiratory infections
Allergen exposure
Food allergy
Outdoor air pollution
Seasonal changes
Poor adherence to medications
38.
39.
40. • Points to consider in acute exacerbations
– Ipratropium can be used but less effective than SABA+ICS
– Aminophylline and theophylline not recommended
– MgS04 i.v / nebulized – a single shot 2g iv infusion over 20
min can be tried if no response after 1 hr of starting
SABA+ ICS
– He +O2 therapy – no role but may be considered if not
responding to standard therapy
– Antibiotics not recommended unless there is evidence of
infection
– Sedatives must be avoided
– NIV has limited role
41. • Treatment in specific contexts
Pregnancy-
– monitor 4-6 weekly
– Don’t stop treatment
– Down titration is low priority
Rhinitis and sinusitis-
– Often coexist with asthma
– Treatment of it reduces nasal symptoms
Obesity -5-10% wt loss can improve asthma control
GERD -common in asthma but treating it doesn’t control
asthma
42. Anxiety and depression- can coexist with asthma, pts should
be assisted in distinguishing anxiety and asthma
Surgery –
– ensure good control pre operatively
– Controller therapy is maintained throughout the peri
operative period
– Pts on long term high dose ICS and oral OCS for >2 wks in
past 6 months should receive intra operative hydrocortisone
to reduce risk of adrenal crisis
43. • References
• GINA 2022 guidelines
• Harrison’s principles of internal medicine 21st edition
