This document provides an overview of bronchial asthma, including its pathogenesis, diagnosis, and phenotypes. Some key points: - Asthma is a chronic inflammatory airway disease characterized by variable respiratory symptoms and reversible airflow limitation. It can be triggered by allergens, irritants, and viruses. - Diagnosis is based on symptoms and lung function tests showing variable expiratory airflow limitation that improves with bronchodilators. Spirometry and peak flow monitoring are used to confirm diagnosis. - Asthma has different phenotypes including allergic, non-allergic, obesity-related, and those with persistent airflow limitation. Treatment is tailored based on phenotype and control of symptoms.

1. Bronchial Asthma
Dr. Sanghavi B
Post Graduate

2. INTRODUCTION
 Asthma is a chronic inflammatory disorder of the airways that causes
recurrent episodes of wheezing,
breathlessness,
chest tightness, and
cough
 Particularly at night and/or early in the morning.
 The hallmarks of asthma are intermittent, reversible airway obstruction;
chronic bronchial inflammation with eosinophils; bronchial smooth
muscle cell hypertrophy and hyper reactivity; and increased mucus
secretion.

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. Pathogenesis
 Major factors contributing to the development of asthma include
Genetic predisposition to type I hypersensitivity (atopy),
Acute and chronic airway inflammation, and
Bronchial hyper responsiveness to a variety of stimuli.
Asthma may be sub classified as
Atopic (evidence of allergen sensitization) or
Non-atopic.

5.  In both types, episodes of bronchospasm may be triggered by
diverse exposures, such as
Respiratory infections (especially viral),
Airborne irritants (e.g., smoke, fumes),
Cold air,
Stress and
Exercise.
There also are varying patterns of inflammation—eosinophilic
(most common), neutrophilic, mixed inflammatory, and pauci-
granulocytic.

6.  The classic Atopic form is associated with excessive type 2 helper T (TH2) cell
activation.
 Cytokines produced by TH2 cells account for most of the features of atopic asthma
 IL-4 and IL-13 stimulate IgE production, IL-5 activates eosinophils, and IL-13 also
stimulates mucus production.
 IgE coats submucosal mast cells, which on exposure to allergen release their granule
contents and secrete cytokines and other mediators.
 Mast cell–derived mediators produce two waves of reaction:
• Early (immediate) phase and
• Late phase

7.  The Early-phase reaction
• bronchoconstriction,
• increased mucus production,
• vasodilation.
Bronchoconstriction is triggered by mediators released from mast cells, including
histamine, prostaglandin D2, and leukotrienes LTC4, D4, and E4, and also by reflex
neural pathways.
 The late-phase reaction is inflammatory in nature.
• Inflammatory mediators stimulate epithelial cells to produce chemokines (including
eotaxin, a potent chemoattractant and activator of eosinophils) that promote the
recruitment of TH2 cells, eosinophils, and other leukocytes, thus amplifying an
inflammatory reaction that is initiated by resident immune cells

8. AIRWAY REMODELING
 Repeated bouts of inflammation lead to structural changes in the
bronchial wall that are collectively referred to as airway
remodeling.
 These changes include hypertrophy of bronchial smooth muscle and
mucus glands and increased vascularity and deposition of
subepithelial collagen, which may occur as early as several years
before initiation of symptoms.

9. Ref: Robbins Pathology

10. Drug-Induced Asthma:
 Several pharmacologic agents provoke asthma, aspirin being the most striking
example.
 Patients with aspirin sensitivity present with recurrent rhinitis, nasal polyps,
urticaria, and bronchospasm.
 The precise pathogenesis is unknown but is likely to involve some abnormality in
prostaglandin metabolism stemming from inhibition of cyclooxygenase by aspirin.

11. Ref: Robbins Pathology

12. Asthma phenotypes
 Asthma is a heterogeneous disease, with different underlying
disease processes.
 Recognizable clusters of demographic, clinical and/or
pathophysiological characteristics are often called ‘asthma
phenotypes’
 In patients with more severe asthma, some phenotype-guided
treatments are available.
 Many clinical phenotypes of asthma have been identified.
 Some of the most common are:

13.  Allergic asthma:
• this is the most easily recognized asthma phenotype,
• childhood
• associated with a past and/or family history of allergic disease such as eczema, allergic
rhinitis, or food or drug allergy.
• Examination of the induced sputum of these patients before treatment often reveals
eosinophilic airway inflammation.
• respond well to inhaled corticosteroid (ICS) treatment.
 Non-allergic asthma: some patients have asthma that is not associated with allergy. The
cellular profile of the sputum of these patients may be neutrophilic, eosinophilic or
contain only a few inflammatory cells (paucigranulocytic). Patients with non-allergic
asthma often demonstrate a lesser short-term response to ICS.

14.  Adult-onset (late-onset) asthma: some adults, particularly women,
present with asthma for the first time in adult life. These patients tend to
be non-allergic, and often require higher doses of ICS or are relatively
refractory to corticosteroid treatment. Occupational asthma (i.e. asthma
due to exposures at work) should be ruled out in patients presenting
with adult-onset asthma.
 Asthma with persistent airflow limitation: some patients with long-
standing asthma develop airflow limitation that is persistent or
incompletely reversible. This is thought to be due to airway wall
remodeling.
 Asthma with obesity: some obese patients with asthma have prominent
respiratory symptoms and little eosinophilic airway inflammation.

15. Making the Initial Diagnosis
 Based on identifying both a characteristic pattern of respiratory
symptoms such as wheezing, shortness of breath (dyspnea), chest
tightness or cough, and variable expiratory airflow limitation.

16. Confirm the diagnosis
Clinical Evaluation in pediatricians office
 Ask for…
 Cough: Mainly nocturnal and early morning dry/wet//relation
with exercise/ recurrent or persistent/Seasonal or year-round
symptoms
 Breathlessness/chest tightness/whistling sound in the chest
 Personal or family history of atopy? (Eczema, allergic rhinitis)
 Response to medicines? (Bronchodilators, inhaled/oral steroids)
 Emergency room visits for difficult breathing?/Previous
hospitalizations for asthma (PICU or ward)

17. Clinical Diagnosis
• More than 3 episodes of wheeze/year
• Wheezing reversed spontaneously or with broncho dialator
• Rule out other cause of wheezing
Look for:
• Bilateral polyphonic wheeze/widespread Rhonchi
• Unilateral or signs localized to one area/side—unlikely asthma
• Failure to thrive, poor weight gain, chronic diarrhea, draining ears and
sinusitis, clubbing—unlikely asthma ;
• Chronic wet cough productive of sputum—unlikely asthma
• High fever—unusual association
• Involvement of multiple systems—gastrointestinal, hematological, cardiac,
neurological manifestations—unlikely asthma

18. Rule out Mimics
• Onset in early infancy—congenital airway/cardiac/vascular anomaly
• Unilateral wheeze—foreign body/congenital anomaly
• Infection—Recurrent viral infection/PBB/endobronchial
TB/immunodeficiency
• Rare diseases—CF/PCD/hypersensitivity pneumonia Caution–Asthma
unlikely
Caution–Asthma unlikely
 < 6 months of age
 Localizing signs
 Wet productive cough
 Fever and poor weight gain
 Poor response to bronchodilators

19. Co-morbid conditions
 Allergic rhino sinusitis (associated in 75–80% cases of bronchial
asthma)
 Obesity: It is an inflammatory condition of the body, reduction of
even 5–10% of weight helps in better control of asthma
 GERD
 Adenoidal hypertrophy
• Obstructive sleep Apnea syndrome
• Anxiety, depression

20. Identify Triggers
 Aeroallergens:
 Dust mite,
 Pollens,
 Pet animals - dog, cat,
 Cockroaches and molds
 Irritants:
 Cigarette smoke,
 Mosquito repellants,
 Agarbati,
 Automobile exhaust,
 Smoke from firewood.

21. Test for Diagnosis of Asthma

22.  Spirometry: Recommended for Children >6 Years Age
 Look for: FEV1 (will be reduced in asthma), FVC, and FEV1/FVC ;
 In bronchial asthma FEV1/FVC will be <80%
 Positive bronchodilator reversibility: Increase in FEV1 of >12% (and/or increase by 200 mL)
post bronchodilator, change measured 10–15 minutes after 200–400 µg salbutamol or
equivalent, compared with pre-bronchodilator readings.
 Peak Flowmeter:
 Not a good tool for diagnosis, as it has a low sensitivity
 Good for monitoring in those who experience recurrent exacerbations, particularly “under-
perceivers” of asthma
 Children: average daily diurnal PEF variability >12% indicates asthma.
 After starting ICS, personal best PEF (from twice daily readings) is reached on average within
2 weeks
 Always better to compare the current PEF value with the personal best PEF reading, for
interpretation

23.  FeNO: The fractional concentration of exhaled nitric oxide (FeNO) is
modestly associated with levels of sputum and blood eosinophils. FeNO has
not been established as useful for ruling in or ruling out a diagnosis of asthma.
(GINA 2021)
 Chest X-ray: To rule out alternative conditions, (chest X-ray may be normal or
show hyperinflation due to airways outflow obstruction and air trapping, or
may show atelectasis of a part of a lobe due to mucus plug. However, routine
chest X-ray is not required for diagnosis of asthma.
 Blood tests: Complete blood count: May be normal, or show eosinophilia in
atopy. Serum total IgE: Not useful, does not help in the diagnosis of asthma.

24. Allergy tests:
 Detailed history should guide choice of allergen to be tested and not the fixed
panels
 Recommended in allergic rhinitis, food allergy, difficult to control asthma.
 Allergy tests are of 2 types:
• In vivo test: Skin prick test—gold standard
• In vitro test: Blood test—To find out allergen specific IgE
 Positive skin test or positive sIgE does not mean that it is causative
 The presence of a positive skin test or positive sIgE, however, does not mean that
the allergen is causing symptoms—the relevance of allergen exposure and its
relation to symptoms must be confirmed by the patient’s history
 Allergy testing is not routinely recommended in asthma.

26. Diagnostic flowchart for clinical practice

27. 1. HISTORY OF TYPICAL VARIABLE RESPIRATORY SYMPTOMS
Feature Symptoms or features that support the diagnosis of asthma
Wheeze, shortness of breath,chest
tightness and cough (Descriptors may
vary betweencultures and by age)
 More than one type of respiratory symptom (in adults, isolated cough is seldomdue 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
2. CONFIRMED VARIABLE EXPIRATORY AIRFLOW LIMITATION
Feature Considerations, definitions, criteria
1. Documented* excessive variability in
lung function* (one or more of the
following):
The greater the variations, or the more occasions excess variation is seen, the moreconfident the diagnosis.
If initially negative, tests can be repeated during symptoms or in the early morning.
 Positive bronchodilator (BD)
responsiveness (reversibility)test
Adults: increase in FEV1 of >12% and >200 mL (greater confidence if increase is
>15% and >400 mL). Children: increase in FEV1 from baseline of >12% predicted. Measure change 10–15
minutes after 200–400 mcg salbutamol (albuterol) or equivalent, compared with pre-BD readings. Positive test
more likely if BD withheldbefore test: SABA ≥4 hours, twice-daily LABA 24 hours, once-daily LABA 36 hours
 Excessive variability in twice-daily
PEF over 2 weeks
Adults: average daily diurnal PEF variability >10%*
Children: average daily diurnal PEF variability >13%*
 Increase in lung function after 4weeks
of treatment
Adults: increase in FEV1 by >12% and >200 mL (or PEF† by >20%) from baselineafter 4 weeks of ICS-
containing treatment, outside respiratory infections
 Positive exercise challenge test Adults: fall in FEV1 of >10% and >200 mL from baseline
Children: fall in FEV1 of >12% predicted, or PEF >15% from baseline
 Positive bronchial challenge test
(usually only for adults)
Fall in FEV1 from baseline of ≥20% with standard doses of methacholine, or ≥15%
with standardized hyperventilation, hypertonic saline or mannitol challenge
 Excessive variation in lung function
between visits (good specificity but
poor sensitivity)
Adults: variation in FEV1 of >12% and >200 mL between visits, outside of respiratoryinfections. Children:
variation in FEV1 of >12% in FEV1 or >15% in PEF† between visits (may include respiratory infections)
AND
2 Documented* expiratoryairflow
limitation
At a time when FEV1 is reduced (e.g. during testing above), confirm that FEV1/FVC isalso reduced compared
with the lower limit of normal (it is usually >0.75–0.80 in adults, >0.90 in children

28. Current status Steps to confirm the diagnosis of asthma
Variable respiratory symptoms
and variableairflow limitation
Diagnosis of asthma is confirmed. Assess the level of asthma control and reviewICS-containing treatment
Variable respiratory
symptoms but no variable
airflow
limitation
Consider repeating spirometry after withholding bronchodilator (4 hrs for SABA, 24 hrs for twice-daily ICS-LABA, 36 hrs for once-daily ICS-
LABA) or during symptoms. Check between-visit variability of FEV1, and bronchodilator responsiveness. If still normal, consider other
diagnoses
If FEV1 is >70% predicted: consider stepping down ICS-containing treatment and reassess in 2–4 weeks, then consider bronchial
provocation test or repeating bronchodilator
responsiveness.
If FEV1 is <70% predicted: consider stepping up ICS-containing treatment for 3 months, then reassess symptoms and lung function. If no
response, resume previous treatment andrefer patient for diagnosis and investigation.
Few respiratory symptoms,
normal lungfunction, and no
variable airflow limitation
Consider repeating BD responsiveness test again after withholding bronchodilator as above orduring symptoms. If normal, consider
alternative diagnoses
Consider stepping down ICS-containing treatment If symptoms emerge and lung function falls: asthma is confirmed. Step up ICS-
containingtreatment to previous lowest effective dose.
 If no change in symptoms or lung function at lowest controller step: consider ceasing ICS-containing, and monitor patient
closely for at least 12 months
Persistent shortness ofbreath
and persistent airflow limitation
Consider stepping up ICS-containing treatment for 3 months, then reassess symptoms and lung function. If no response, resume
previous treatment and refer patient fordiagnosis and investigation. Consider asthma–COPD overlap
Steps for confirming the diagnosis of asthma in a patient already taking ICS-containing treatment

29. 1. Assess asthma control = symptom control and future risk of adverse outcomes
 Assess symptom control over the last 4 weeks.
 Identify any other risk factors for exacerbations, persistent airflow limitation or side-effects.
 Measure lung function at diagnosis/start of treatment, 3–6 months after starting ICS-containing treatment, then periodically,
e.g., at least once every 1–2 years, but more often in at-risk patients and those with severe asthma.
2. Assess treatment issues
 Document the patient’s current treatment step
 Watch inhaler technique, assess adherence and side-effects.
 Check that the patient has a written asthma action plan.
 Ask about the patient’s attitudes and goals for their asthma and medications.
3. Assess multimorbidity
 Rhinitis, rhinosinusitis, gastroesophageal reflux, obesity, obstructive sleep apnea, depression and anxiety can contribute
to symptoms and poor quality of life, and sometimes to poor asthma control.
Assessment of asthma in adults, adolescents, and children 6–11 years

33. Term Definition Notes
Maintenancetreatment Asthma treatment that isprescribed for
use everyday (or on a regularly
scheduled basis)
Medications intended to be used continuously, even when the persondoes not have asthma
symptoms. Examples include ICS-containing medications (ICS, ICS-LABA, ICS-LABA-LAMA), as
well as LTRA and biologic therapy.
The term ‘maintenance’ describes the prescribed frequency ofadministration, not a particular
class of asthma medicine.
Controller Medication targeting both domains of
asthma control(symptom control and
future risk)
In the past, ‘controller’ was largely used for ICS-containing medications prescribed for regular
daily treatment, so ‘controller’ and‘maintenance’ became almost synonymous. However, this
became confusing after the introduction of combination ICS-containing relievers for as-needed
use.
To avoid confusion, ‘ICS-containing treatment’ and ‘maintenance treatment’ have been
substituted as appropriate where the intendedmeaning was unclear.
Reliever Asthma inhaler taken as needed, for
quick relief ofasthma symptoms
Sometimes called rescue inhalers. As well as being used for symptom relief, reliever inhalers can
also be used before exercise, toprevent exercise-induced asthma symptoms.
Includes SABAs (e.g., salbutamol [albuterol], terbutaline, ICS- salbutamol), as-needed ICS-
formoterol, and as-needed ICS-SABA.
SABA-containing relievers are not intended for regular maintenanceuse, or to be taken when the
person does not have asthma symptoms (except before exercise).
Anti-inflammatoryreliever
(AIR)
Reliever inhaler that contains both a
low-doseICS and a rapid-acting
bronchodilator
Includes budesonide-formoterol, beclometasone-formoterol and
ICS-salbutamol combinations. Patients can also use them as neededbefore exercise or allergen
exposure to prevent asthma symptoms and bronchoconstriction. Non-formoterol LABAs in
combination with ICS cannot be used as relievers.
Some anti-inflammatory relievers can be used as-needed at Steps 1–2 as the person’s sole
asthma treatment, without a maintenance treatment (‘AIR-only’ treatment). Almost all evidence
for this is with ICS-formoterol. Some ICS-formoterol combinations can be used as both
maintenance treatment and reliever treatment at Steps 3–5 (seeMART, below). For medications
and doses.
Maintenance-and-reliever
therapy (MART)
Treatment regimen in which the
patient uses an ICS-formoterol inhaler
every day (maintenance dose), and
also uses the same medication as
needed for relief of asthmasymptoms
(reliever doses)
MART (Maintenance And Reliever Therapy) can be used only with combination ICS-formoterol
inhalers such as budesonide-formoterol and beclometasone-formoterol. Other ICS-formoterol
inhalers can also potentially be used, but combinations of ICS with non-formoterolLABAs, or
ICS-SABA, cannot be used for MART. MART is also sometimes called SMART (single-inhaler
maintenance and reliever therapy); the meaning is the same.

34. Selecting initial treatment in adults and adolescents with a diagnosis of asthma

35. Flowchart for selecting initial treatment in adults and adolescents with a diagnosis of asthma

36. Selecting initial treatment in children aged 6–11 years with a diagnosis of asthma

37. Flowchart for selecting initial treatment in children aged 6–11 years with a diagnosis of asthma

38. Long term Management of Asthma
To initiate treatment we must assess the level of control:
 Asthma control has two domains: Symptom control and future risk of adverse
outcomes
 Both should always be assessed.
 If the child’s asthma is partly or well controlled then the child can be placed in the step 1 or
step 2 of treatment, provided there is no other serious risk for future exacerbation.
 If the child’s asthma is uncontrolled then the child will be in the step 3–5 of treatment.

44. Inhaled
corticosteroid
Total daily dose (mcg)
Low Medium High
SCHOOL AGED CHILDREN
Beclometasone
dipropionate
100–200 200–400 >400
Budesonide 100–200 200–400 >400
Ciclesonide 80 80–160 >160
Fluticasone
propionate
100–200 200–400 >400
Mometasone
furoate
110 220–440 >440
Triamcinolone
acetonide
400–800 800–1,200 >1,200
ADOLESCENTS
Beclometasone
dipropionate
200–500 500–1,000 >1,000
Budesonide 400–200 400–800 >800
Ciclesonide 80–160 160–320 >320
Fluticasone
propionate
100–250 250–500 >500
Mometasone
furoate
110–220 220–440 >440
Triamcinolone
acetonide
400–1,000 1,000–2,000 >2,000
Tesse R, Borrelli G, Mongelli G, Mastrorilli V, Cardinale F. Treating Pediatric Asthma According Guidelines.
Front Pediatr. 2018 Aug 23;6:234. doi: 10.3389/fped.2018.00234. PMID: 30191146; PMCID: PMC6115494.

45. Selection of appropriate inhalation device:
 Drugs for maintenance treatment can be administered by inhalation or by oral route.
Inhalation route is more effective with rapid onset of action and less side effects.
 Commonly available inhalation devices include:
 (i) metered dose inhaler (MDI),
 (ii) MDI with spacer,
 (iii) MDI with spacer and face mask,
 (iv) dry powder inhaler,
 (v) nebulizer.

46. Metered dose inhaler :
 An MDI is a device, which delivers a fixed amount of medication in aerosol
form each time it is activated.
 It is used for exacerbation and maintenance therapy.
 It is effective but requires considerable coordination, which might not be
possible in young children. After actuation, the drug comes out at a
pressure and a significant amount of the drug gets deposited in the
oropharynx.
 MDis continue to work past the labeled number of doses because of excess
propellant.

47. Metered dose Inhaler

48.  MDI with spacer :
 Use of spacer inhalation device with an MDI should be encouraged as it results in
a larger proportion of the medication being delivered in the lung, with less
impaction in the oropharynx.
 They also overcome the problems of poor technique and coordination of actuation
and inspiration, which occur with MDI alone.
 Furthermore, use of spacer allows MDI to be used for the young patient.
 MDI used with spacer has been found to be comparable to nebulizer in delivering
salbutamol in acute exacerbation of asthma in children.
 Spacers have the limitation of being bulky, relatively costly and cannot be used in
young infants and toddlers.
 A homemade spacer (prepared from mineral water bottle) can effectively deliver
salbutamol in acute exacerbation.

49. Metered dose Inhaler with spacer

50.  MDI with spacer and face mask : Attaching a face mask to the spacer facilitates
their use in young infants.
Metered dose inhaler with spacer and face mask

51.  Dry powder inhaler (DPI) :
 These are breath· activated devices (Rotahaler; Diskhaler, Spinhaler, Turbohaler,
Acuhaler) that can be used in children above 4-5 years old.
 They are portable and do not require coordination of actuation with breathing.
 The effect of these inhalers depends on a certain inspiratory flow rate, with risk of
reduced effect during acute exacerbations or in children with low pulmonary
function.
Rotahaler

52.  Nebulizers :
 Nebulizers with air compressors are bulky and inconvenient to use. With advent of
efficient spacer systems, the need for nebulizers has greately diminished.
However, there is role for nebulized β-agonist.
 Inhalation method should be chosen on individual basis, but a guideline is as
follows:
 Children < 4yr old : MDI with spacer with face mask
 Children > 4 yr old : : MDI with spacer preferred
 Children >12 year old : MDI used directly. Use of spacer improves drug deposition
Nebulizer

53. IV Salbutamol infusion
 IV salbutamol can be used in patients with severe asthma who fail to respond to
other treatments, mainly to prevent intubation
 In patients with severe attacks, there is very limited evidence that IV beta 2-
agonists reduce recovery time or improve pulmonary function
 The rationale to support IV salbutamol is that inhaled drugs may have a limited
effect in patients with nearly complete airway obstruction and have practical
limitations in ventilated patients
 Cardiac responses, such as arrhythmia and tachycardia, increased lactate and
anxiety are significant side effects, which may increase respiratory workload and
exacerbate respiratory failure
 Patients receiving IV salbutamol should be in a PICU setting

54. IV Aminophylline
 Most guidelines do not recommend use of IV aminophylline because of its low
efficacy and safety profiles.
 It improves diaphragmatic contractility.
 If used, this bronchodilator should be reserved solely for children with a severe
asthma exacerbation, who have failed to improve despite maximal therapy
(continuous inhaled beta 2-agonists, IV corticosteroids, IV magnesium sulfate) and
generally in a PICU setting.
 The risk-benefit balance of IV aminophylline is unfavorable

55. Intubation & Mechanical Ventilation
 Intubation and mechanical ventilation can be life-saving interventions but
their use in pediatric patients with asthma has been associated with
significant adverse effects.
 Up to 45% of patients intubated due to asthma have complications,
including pneumonia, pneumothorax, pneumo-mediastinum, and
cardiovascular collapse.
 This risk highlights the importance of adequate, rapid, and aggressive
initial management of acute exacerbations
 In these situations, ketamine is generally considered the agent of choice
for induction and ongoing sedation.
 Only 0.55% children admitted with acute severe asthma may require
ventilation.