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BRONCHIAL ASTHMA
Presenter: Dr P KIREETI
Moderator: Prof T. JEETEN KUMAR SINGH
 Introduction
 Risk factors
 Triggers
 Pathophysiology
 Molecular understanding
 Diagnosis
 Asthma variants
 GINA 2022
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)
 EPIDEMIOLOGY
 Children(8%)>Adults(7%)
 GENDER 
 Children: Boys>Girls(2:1)
 Adults: Females>Males(1.1to1.2: 1)
 RACE:  prevalence in all countries
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
 Allergen exposure- can be a trigger
 Mc House Dust mite(Dermatophagoides)- cause type 2
asthma
 Pollutants
 Tobacco
 Infections- Rhino viruses, RSV, Mycoplasma
 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
 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
 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
 Pre natal and peri natal factors
 Pre eclampsia
 Prematurity
 C section
 Neonatal jaundice
 Breast feeding is a protective factor atleast for initial few
years
TRIGGERS
 Allergen exposure
 Air pollution
 Infection  both URTI& LRTI
 Ambient air temperature- cold and dry-  airway
secretions osmolality- mast cell degranulation- PGD2 and
Histamine
PATHOPHYSIOLOGY
 Airway remodelling
 Thickening of basement membrane
 Airway smooth muscle hypertrophy
 Goblet cell hyperplasia
 Airway inflammation
 Angiogenesis
 Epithelial alteration
BRONCHIAL  ASTHMA.pptx
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
Non type 2 Asthma
viral infections, irritants, pollutants
IL 33 IL6
Th17 Th1
IL 6,8,17 IFN ,留
Neutrophils
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/
 Bronchodilator reversibility test- FEV112% 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
 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 na誰ve patients
 Flow volume loops  limited role
Loop shift to left
PEFR 
Flattening of expiratory limb
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
 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
 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
 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
 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
 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
 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
 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
 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
 GINAs 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
 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
 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
 <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賊
biologicals
 If pt struck at step4 i.e continue to have low lung function or
symptoms doesnt 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
BRONCHIAL  ASTHMA.pptx
 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/袖l = 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
BRONCHIAL  ASTHMA.pptx
BRONCHIAL  ASTHMA.pptx
 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
BRONCHIAL  ASTHMA.pptx
BRONCHIAL  ASTHMA.pptx
 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
 Treatment in specific contexts
 Pregnancy-
 monitor 4-6 weekly
 Dont 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 doesnt control
asthma
 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
 References
 GINA 2022 guidelines
 Harrisons principles of internal medicine 21st edition
THANK YOU

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BRONCHIAL ASTHMA.pptx

  • 1. BRONCHIAL ASTHMA Presenter: Dr P KIREETI Moderator: Prof T. JEETEN KUMAR SINGH
  • 2. Introduction Risk factors Triggers Pathophysiology Molecular understanding Diagnosis Asthma variants GINA 2022
  • 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)
  • 4. EPIDEMIOLOGY Children(8%)>Adults(7%) GENDER Children: Boys>Girls(2:1) Adults: Females>Males(1.1to1.2: 1) RACE: prevalence in all countries
  • 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 secretions osmolality- mast cell degranulation- PGD2 and Histamine
  • 12. PATHOPHYSIOLOGY Airway remodelling Thickening of basement membrane Airway smooth muscle hypertrophy Goblet cell hyperplasia Airway inflammation Angiogenesis Epithelial alteration
  • 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 ,留 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- FEV112% 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 na誰ve 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. GINAs 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賊 biologicals
  • 32. If pt struck at step4 i.e continue to have low lung function or symptoms doesnt 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
  • 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/袖l = 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
  • 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
  • 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 Dont 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 doesnt 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 Harrisons principles of internal medicine 21st edition