Asthma is a chronic disease characterized by episodic airway obstruction, airway hyperresponsiveness, and airway inflammation. It commonly presents with shortness of breath, wheezing, and cough. The pathophysiology involves type 2 inflammation driven by T helper 2 cells and cytokines like IL-4, IL-5, and IL-13. Management involves avoiding triggers, using reliever medications like bronchodilators for acute symptoms and controller medications like inhaled corticosteroids to reduce inflammation. Other treatments target specific inflammatory pathways through monoclonal antibodies that inhibit IgE, IL-5, IL-4, and IL-13.

1. ASTHMA
BY HIZKIELA, R1

2. Disease characterized by:
Episodic airway obstruction.
Airway hyperresponsiveness.
Airway inflammation.
▪ Most frequently presents as episodic shortness of breath, wheezing and
cough.
▪ Other symptoms like chest tightness and mucus production.
▪ Episodes of acute bronchospasm known as exacerbation.

3. Most common chronic disease associated with significant morbidity
and mortality.
The pathway of development of asthma is interplay b/n
Genetic susceptibility.
Environmental exposure and
Endogenous developmental factors.

5. Pathophysiology
Airway inflammation
Type 2 and non type 2 inflammation.
Most asthma accompanied by airway inflammation.

6. Type 2 inflammation
Immune response.
Involves innate and adaptive arms.
It is called type 2 because associated with type 2 subset of CD4+ T-
helper cells, which produces IL-4, IL-5 & IL-13.
IL-4 induces B cell isotype switching to production of IgE.

7. IgE binds to basophils and mast cells results in environmental
sensitivity to allergens.
The products released from those cells include 2 cytokines as well as
direct activator of smooth muscle constriction and edema
IL-13 induces airway hyperresponsiveness, mucus production and
Goblet metaplasia.
Airway hyperresponsiveness is the hall mark of asthma.
Defined as acute narrowing response to inhaled agents as compared to
that which would occur in non affected.

8. Excess narrowing response to inhaled agents as compared to that
which would occur in non affected individuals.
Hyperresponsiveness occur at the level of airway smooth muscle it
self.
Stimulation of inflammatory cells which release direct
bronchoconstrictor and mediators that cause airway edema and/or
mucus secretion.

9. The major therapeutic objective in asthma is to reduce the degree of
airway hyperresponsiveness.
Cytokines IL-4, IL-5 and IL-13 are associated with type 2
inflammation.
Fatty acid mediates leukotrienes and prostaglandins.

11. Etiologic mechanism, risk factors, triggers and complicating
Comorbidities.
Heritable predisposition.
Strong genetic predisposition.
Atopy is genetic tendency toward specific IgE production in response
to allergen exposure.
Serum level of IgE correlates with development of asthma.

12. Allergens most associated with risk includes:
House dust mites
Indoor fungi.
Cockroaches.
Indoor animals.
Exposure and sensitization
Risk factors
Smoking increases risk 4x
Air pollution causes oxidative stress and inflammation.

13. Infections: clearly precipitate asthma.
Occupational exposure: 10-25% occupational asthma.
Nursing and cleaning.
Fungi and allergic airway mycosis
1-2% of asthma.
IgE mediated.
Aspergillus fumigatus commonest etiology.
Allergic bronchopulmonary aspergillosis- ABPA.

14. Characterized by
IgE >1000IU/ml
Eosinophils >500/ul
Positive skin test to aspergillus.
Specific IgE and IgG antibodies to aspergillus.
2/3 grow aspergillus from sputum.
Treatment by systemic antifungal with itraconazole or
voriconazole and oral corticosteroids.

15. Triggers of airway narrowing
Almost all asthmaticus can identify triggers that worsen their asthma.
In some cases elimination of triggers may dramatically reduce
impairment caused by asthma.

18. Primary assessment tools for establishing diagnosis.
History: patient most commonly complains of
Wheezing, SOB, chest tightness.
Mucus production.
Cough up on exposure to triggers.
Worse symptoms in the morning.
Symptoms with rapid change in temperature or humidity.
2/3 Atopic.

19. Physical examination:
On b/n attacks physical findings may be normal.
Many patients will have evidence of allergic rhinitis with pale nasal
polyps.
Aspirin exacerbated respiratory disease.
During attacks
Tachypnea and tachycardia.
Use of accessory muscles.
Wheezing with prolonged expiratory phase.

20. 2/3 grow aspergillus from sputum.
Treatment by systemic antifungal with Itraconazole/voriconazole and
oral corticosteroid.
Triggers of airway narrowing.
Almost all asthmaticus can identify triggers that will make their asthma
worse.
In some cases elimination the trigger may dramatically reduce
impairment caused by asthma.

21. Diagnosis and evaluation
Presumptive diagnosis
Wheezing, SOB, chest tightness or cough related to
common bronchoconstrictor and
When other DDx excluded.
Severity progresses the chest may become “silent” with
loss of breath sounds.
Confirmed by PFT and demonstration hyperresponsiveness.

22. Pulmonary function test
PEFR
FEV1
FEV1/FVC ratio.
Reduced below lower limit of normal.
Reversibility: >12% increase in the FEV1 and absolute increase of
>200ml at 15 minute after administration of B2 agonist.
Assessment of airway responsiveness
Methacholine- drop in FEV1 by 20%.
Exercise or cold, dry air change with FEV drop >10%.

23. Adjunct assessment tool
Eosinophil count >300cells/ul in those who never treated with
corticosteroid.
Correlates with severity of the disease.
IgE skin tests and radio sorbent tests.
Total serum IgE for considering anti IgE therapy in patient with sever
asthma.
>1000iu/ml consider ABPA.
Radioallergosorbent test-RAST to confirm atopy.

24. Exhaled nitric oxide FeNo- approximate indicator of eosinophilic
inflammation in the airways.
Elevated levels in untreated patients 35-40 ppb indicates eosinophilic
inflammation.
>20-25ppb poor adherence or persistent T2 inflammation.

25. Evaluation of sever/poorly responding asthma
Evaluation for comorbidities.
Esophageal study for those who have symptoms of reflux.
Chest CT scan- asses for presence of bronchiectasis and other
structural lung disease.
Sputum-induced sputum to detect whether its eosinophilic or
neutrophilic in T2 or non T2 inflammation.

26. Management

27. Avoiding and reducing asthma triggers.
Medication divided in to two
Those that relax smooth muscle called reliver
Those that target inflammation called controller.
Allergen immunotherapy
Asthma under control.
Mild to moderate asthma.
Reduces symptom of allergic rhinitis.
Vaccination –pneumococcal vaccines, yearly influenza vaccine and
COVID-19 vaccine.

28. MEDICATION
Bronchodilator
ß2 agonist.
Anticholinergics.
Theophylline
Activate ß2 receptors in airway smooth muscle.
Relieve bronchospasm.
Inhaled form.
Regular use associated with tachyphylaxis of bronchial protective effect and
possible increased airway reactivity.

29. Frequent use associated with increased asthma mortality for short
acting.
Short acting ß2 agonist
Albuterol/salbutamol
Bronchodilation begins 3-5 minutes, lasts 4-6 hours.
Oral forms available, but less frequently used.

30. Long acting ß2 agonist
Salmeterol and Formoterol
12 hour duration of action.
Formoterol has quick onset of action compared to short
acting ß2 agonist.
Salmeterol has slower onset of action.
Used for prophylaxis of exercise induced asthma.
Not for monotherapy.
Restricted to use with combination of ICS.

31. Ultralong acting ß2 agonists
Indacaterol
Olondaterol
Vilanterol
Have 24 hour effect.
Only used with combination of ICS.

32. Safety of ß2 agonists
High doses produce tremor, tachycardia, palpitation and
Hypertension.
Promote K reentry –hypokalemia
Type B-non hypoxic lactic acidosis.
Increased use of ß2 agonist for symptom control is clear
marker of poor control.

33. Anticholinergics
Cholinergic nerve induced smooth muscle constriction play role in
asthmatic bronchospasm.
Anticholinergic produce smooth muscle relaxation by antagonizing
that effect.
Long acting agents- long acting anti muscarinic(LAMA).
Use :short acting can be used alone, less effective than ß2 agonist.
S/E: dry mouth. Elderly- acute glaucoma and urinary retention.
Theophylline rarely used due to low therapeutic index.

34. Controller –anti inflammatory/antimediator Therapies
Reduce asthma exacerbation.
Improve long term control.
Decrease the need for intermittent use of bronchodialator.
None of the medications prevent progression of airway remodeling or
rapid decline in lung function.

35. Corticosteroids:
Effective in reducing type 2 inflammation and airway
hyperresponsiveness.
ICS and ICS/LABA
ICS- cornerstone of asthma therapy.
Decreases asthma mortality.
Twice daily for all forms of asthma.

36. Safety
Chronic administration of systemic corticosteroids associated with
Diabetes
Osteoporosis
Cataracts
Glaucoma
Bruising, weight gain, truncal obesity, HTN, ulcers,
depression and accelerated cardiac risk.

37. Appropriate monitoring.
CPT for those >20mg/d of prednisolone.
Bone health prophylaxis.
Intermittent burst to treat exacerbation are associated with reduced side
effects.
Overtime associated with deleterious side effects.

38. ICS
Dramatically reduced side effects compared to OCS.
At higher doses-bruising can occur and osteoporosis may accelerate.
Small increase in glaucoma and cataracts.
Local effects include thrush. Can be reduced by spacer and gurgling.

39. Doses can be increased and combined with LABA when there is
increasing asthma severity.
European guideline recommend their use in intermittent asthma.
Effects noticeable several day latter.
Not all patients respond to ICS.
Most responders are those with T2 mediated asthma.

40. Oral corticosteroid
Chronic oral corticosteroid at lowest possible doses for those who cant
achieve acceptable asthma control with out them.
Alternate dosing preferred.
CPT for those who took >20mg/d.
Prednisolone 40-60mg/d or equivalent for exacerbation for 1-2 weeks.
Intravenous for hospitalized and rapidly transitioned to OCS.

41. Intramuscular corticosteroid
For high risk poorly adherent patients.
IM triamcinolone acetonide
S/E of ICS
Hoarseness result from direct myopathic effect on vocal cord.

42. Leukotriene modifiers
Agents that inhibit production of leukotriene-
zileuton an inhibitor of 5-lipoxygenase.
Montelukast/zafirlukast- action on leukotriene at CysLT1 receptors.
They are moderately effective in asthma.
They can improve function, but not the same degree to bronchodilator
or ICS.
Effective in reducing symptoms of Allergic rhinitis.

43. They reduce exercise induced bronchoconstriction with out causing
tachyphylaxis.
They are particularly effective in aspirin exacerbated respiratory
disease.
Modest effect as add on therapy in patient poorly controlled with high
dose ICS/LABA.

44. Montelukast and Zafirlukast are administered orally once and twice /d
respectively.
Onset of effect rapid –hours
Chronic effect seen after 1 month.
Zileuton extended for administration twice a day.
Montelukast associated with suicidal ideation.
Zileuton raises Liver function in 3%.

45. Cromlyn Sodium-inhaled agent stabilizes mast cell.
Only available by nebulization.
Must be administered 2-4x/day.
Mild-modestly effective.
Helpful for exercise induced bronchospasm.

46. Anti IgE
Omalizumab
Prevents binding of IgE to mast cell and basophils.
Increase production of interferon in rhinovirus infection so
decreases viral induced asthma exacerbation.
Generally used in patient not responsive to moderate to
high dose of ICs/LABA.
Reduces exacerbation by 25-50%.
Reduce asthma symptom, minimal effect on lung
function.

47. Dose based on circulating IgE level and Wt, every 2 weeks SC
injection.
Most effect seen 3-6 month.
Patient with exhaled NO >20ppb or circulating eosinophils >260/μl
have greatest response.
Low side effects , anaphylaxis in 0.2%.

48. IL-5 active drugs:
Mepolizumab, Reslizumab and Benralizumab.
Rapidly reduces circulating eosinophils
Used in patients with symptomatic on moderate to high
dose ICS/LABA.
Generally two or more exacerbation that require OCs/year
and eosinophil count >300/ul

49. Reduces exacerbation by half or more.
FEV1 and symptoms improve moderately as well.
Less effective in those who are not on OCS and
eosinophils <300.
FeNO and IgE not affected.
Clinical effects seen with in 3-6 month.
Safety: minimal side effects.

50. Anti IL-4/13
Dupilumab
Use: poorly controlled asthma in moderate to high dose of ICS/LABA
when FeNO of 20-25ppb.
They respond even if eosinophils are not elevated.
Reduces exacerbation by >50%.
Decreases symptoms.

51. May produce an effect on FEV1 then anti IL-5 days.
Paradoxically eosinophils raises.
Most effect seen by 3-6 month.
Safety: minimal side effects.
Serious systemic eosinophils associated with reduction of oral
corticosteroids.
Approved for home administration and atopic dermatitis.

52. Bronchial Thermoplasty
Radiofrequency ablation of airway smooth muscle in major airways.
Most guidelines do not recommended.
Alternative therapies
Acupuncture and yoga- have not shown to improve asthma.
Therapies in development:
Therapies target TSLP, IL-13 and CRTH2.

53. PATIENT APPROACH
GINAAdvise a symptomatic approach
Poor adherence and poor inhaler technique cause for poor
control in up to 50%.
Stepwise approach to intensify and reducing.
Address comorbidities.
Evaluate adherence.
Avoid triggers.
Verify inhaler technique.
Cornerstone of therapy is intensification of ICS therapy in conjunction
with use of LABA.

55. Formoterol-LABA can be used ICS/Formoterol combination as
needed with out background therapy in mild asthma.
As needed in addition to twice daily dosing in sever asthma.
ICS/Formoterol should be used in all steps including intermittent
asthma.
Leukotriene receptor antagonist-LTRA alternative in step 2.
LTRA and long acting anticholinergics for those requiring step 4 or 5
therapies.
Biologics in step 5 therapy or beyond.

56. Asthma attacks
Mild to moderate severity deterioration should be treated with ß2
Increasing the dose of ICS by 4-5x.
If patient fails to achieve adequate control and continue to require ß2
agonists, PEFR or FEV1 should be assessed and treated with nebulized
ß2 agonist up to Q20 minutes.
Those with PEFR >60% responds to ß2 agonist only, if fail to responds
in 1-2hr then IV corticosteroid should be administered.
Supplemental oxygen to correct hypoxemia.

57. NIPPV to assists with respiratory exhaustion used to prevent a need for
intubation.
Antibiotics should be administered only if there are signs of infection.
Mechanical ventilation may be difficult due to high positive pressure.
Most patients present with hypocapnia due to high respiratory rate.
Normal or near normal PCO2 should raise concerns of impending
respiratory failure.

58. Mechanical ventilation aim low RR and/or ventilation volumes to
decrease peak airway pressure.
Achieved by permissive hypercapnia.
Neuromuscular blocks can some times may be beneficial.

59. Special consideration
High risk asthma patients

60. Exercise induced asthma.
Degree of exercise intolerance may reflect poor asthma control.
For occasional exercise ICS/LABA can be used.
For regular Execise LTRA.
SABA or ICS/Formoterol should only be available for quick relief.
Warming-up.
Using mask in colder weather.

61. Pregnancy
May improve, deteriorate or unchanged.
Poor asthma control specially exacerbation associated with poor fetal
outcomes.
General principle and goals unchanged.
Salbutamol, formoterol, salmeterol, beclomethasone, budesonide and
fluticasone are generally safe during pregnancy.
Animal study suggest no risk with zafirlukast, montelukast and
ipratropium.

62. Chronic use of OCS has been associated with neonatal adrenal
insufficiency, preeclampsia, low birth weight and slight increase in
cleft palate.
Poorly controlled asthma carries greater risk than those S/e.
No hesitancy to administer in acute exacerbation.
Allergen immunotherapy with Omalizumab is not recommended
during pregnancy.

63. Aspirin exacerbated respiratory disease
Those patients should avoid aspirin and NSAID.
Should be treated leukotriene modifier.
Aspirin desensitization.
Dupilumab and IL-5 active agents superseded aspirin desensitization.

64. Sever asthma
Sever and difficult to treat asthma is 5-10%.
Requires step 5 therapy.
Macrolides are of use in a subset.
Elderly patients with asthma
Can present or persist to older age
Mortality 5x in age >65.
Eosinophil tends to be sever.