Asthma

Source

GINA Main Report 2024 (ginasthma.org)
Nelson Textbook of pediatrics - 21st edition
An overview of asthma management - UpToDate
Pathogenesis of asthma - UpToDate

#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.

The triad

Variable airflow limitation
Airway hyperresponsiveness
Airway remodelling

Types of Asthma

Type of Asthma	Features
Allergic asthma	- start in childhood - h/o atopy + - sputum reveals eosinophilic airway inflammatin
Non allergic asthma	- sputum can be neutrophilic, eosinophilic or paucigranulocytic - less short term response to ICS
cough variant asthma	- cough may be only symptom - airflow limitation may be absent
adult onset asthma	- present in adulthood - often refractory to ICS
asthma with persistent airflow limitation	- may not be completely reversible with bronchodialators - may be associated with COPD
asthma with obesity	- prominent respiratory inflammation with little eosinophilic inflammation

Pathophysiology

Atopy
Airway inflammation (Mast cell activation model)
- IgE abs to common allergens
- High affinity for mast cells
- Mast cell degranulation
Early phase
- Within minutes
- Mediated by LTC, PG D2, histamine
Late phase reactants
- Several hours later
- Influx of immune cells
- Monocytes, dendric cells, neutrophils
- Partial reversibility with beta agonist
Mast cell
- Secrete histamine, LTC, PGs, TNF
Th2 cells
- Interleukin 3,4, 5, 13, GM CSF
Neutrophil
- Severe asthma
- Non responsive to glucocorticoid therapy
Epithelial mesenchymal tropical unit model
- Bronchial epithelial cells, fibroblast and airway smooth muscle play a role
Both large and small airway close
Mucus plug
Bronchial hyperresponsiveness
- 20% fall in FEV1 by methacholine
Airway remodeling
- Increase in the mucus secreting cells
- Fibrotic thickening in the lamina reticularis

Risk factors

Vitamin D deficiency in maternal diet
Omega 6 fatty acids
Vitamin E deficiency
Refined sugar
Maternal asthma
Maternal exposure to smoking
Acetaminophen
Antacids
Prematurity
Preeclampsia
Neonatal jaundice
Top feed
Male gender
Dust mite
Cockroach
Indoor fungi
Respiratory infections
- HRV
- RSV
Mycoplasma
Air pollution
- NO2
- SO2
Obesity
Early puberty

#Diagnostic_criteria

Test	Variablity
Positive BD test	>12% inc in FEV1 after 10-15 mins of salbutamol therapy
Diurnal variability	>13% over 2 weeks
4 weeks of treatment	>12% increase in FEV1
Positive Exercise challenge test	Fall of >12% FEV1 or 15% PEF
Methacholine challenge	>20% fall of FEV1
Excessive variation in lung function	Variation in FEV1 > 12% or PEF >15%

If PEF is used best of 3 measurements should be used
Responsiveness (Reversibility) - rapid improvement with bronchodilator use

diagnostic #approach

Already on ICS

For children less than 5 years

Other tests

Allergic tests

skin prick test or specific immunoglobulin test
can not confirm allergen is the cause of asthma, but a useful test

Imaging

not routinely used
most used to identify the differential diagnosis

Exhaled Nitric Oxide

not a useful for diagnosis of asthma
Higher FeNO is associated with elevated IL-4, IL-13
elevated in asthma, eosinophilic bronchitis, atopy, allergic rhinitis, eczema

#differential for asthma

older children

Younger children

Treatment

Goal

Remission -
- clinical remission - no asthma symptoms / exacerbations for a specific period of time
- complete (pathophysiological) remission - normal lung function, airway responsiveness, inflammatory markers
Remission on Treatment -goal of GINA

Non Pharmacological strategies

cessation of smoking / avoid passive smoking
Physical activity
avoid medication that can make asthma worse (NSAIDs, aspirin, Beta blockers)
avoid allergens (pollen, dust mite, pets, cockroaches, fungi)
weight reduction
breathing exercises (Buteyko and Papworth)
avoid pollution

Pharmacological management

Category of medications

controller medication - to control symptoms, reduce airway inflammation
Reliever medication - for as-needed relief (SABA - salbutamol, terbutaline)
Maintenance - used for daily use even when symptoms are not there (ICS, ICS-LABA, ICS_LAMA)
Anti-inflammatory medication (AIR) - reliever that has both low dose ICS and rapid acting bronchodilator
Maintenance and reliever therapy - both maintenance and reliever (ICS-formoterol)

GINA recommendations

start with ICS containing treatment as soon as possible - preferably AIR
SABA alone is not recommended
oral SABA and theophylline are not recommended

Initial treatments

6 to 11 yrs

Symptom	Preferred initial treatment
infrequent asthma 1-2 days a week	[low dose ICS + SABA] sos
asthma on some days 3-5 days/week with normal or mildly reduced lung function	low dose ICS daily + SABA sos
Asthma on most days 4-5 days/week	[low dose ICS + LABA] daily + SABA sos (or) medium dose ICS daily + SABA sos
daily asthma/ night asthma 1 per week	[medium dose ICS + LABA] + SABA sos (or) [low dose ICS + formoterol] as MART
exarcerabation	treat as exarcerbation

Step Up / Step Down

Assess

assess risk factors and control for at least 4 weeks or longer
measure lung function at the start of treatment, 3-6 months after starting ICS and 1-2 yearly thereafter.
chose a suitable time to change treatment
written asthma action plan

Adjust

adjust ICS dose by 25-50%
stop other maintenance medication
schedule revisit after 2-4 weeks

Review response

if symptoms recur, return to lowest previous effective dose
follow up for at least 12 months

Other treatment modalities

Allergen immunotherapy
- subcutaneous immunotherapy - administration of extracts in progressively increasing quantity over 3-5 yrs
- Sublingual immunotherapy
Vaccination
- influenza
- RSV
- PCV
- Pertussis
Bronchial thermoplasty
- localized radiofrequency pulse in airway
vitamin D

Management of acute exacerbation / ER management

In ER

older children

Young children

In Acute Care facility

Investigations
- measure lung function
- oxygen saturation
- ABG - not routinely done
- CXR - not routinely done
Treatment
- O2 - 100% to maintain saturation of more than 93%
- SABA through Spacer
- epinephrine for anaphylaxis
- systemic corticosteroids (oral = IV)
  - prednisolone 1-2 mg/kg upto 40 mg/day
  - 3-5 day course
- inhaled corticosteroids
  - high dose corticosteroids
- other treatments
  - Ipratropium bromide
  - Magnesium
  - Helium oxygen therapy
  - LTRAs
  - NIV
  - aminophylline and theophylline (not recommended)
  - Antibiotics (not recommended)
  - Sedatives (avoided)

Asthma control

symptom control
future risk of adverse outcomes
Asthma Control Questionnaire (ACQ)
Asthma Control test (ACT)
Specific Questionnaire for asthma in children aged 6-11 yrs
- asthma symptom control
  - day symptoms
  - night symptoms
  - reliever use
  - level of activity
- Risk factor for adverse outcomes
  - exacerbations
    - more than 1 exacerbation in the previous year
    - more than 3 200 metered dose inhaler
  - lung function
  - side-effects
- treatment factors
  - inhaler technique
  - adherence
  - goals/concern
- Comorbidities
  - Allergic rhinitis
  - Eczema
  - Food allergy
  - obesity
- other investigation
  - 2-week diary
  - formal exercise challenge

Severity of asthma

Uncontrolled asthma - lack of control due to incorrect inhaler technique, poor adherence, over use of SABA, comorbidities, persistent environmental exposures
different meaning in different setting
GINA - Retrospective diagnosis based on difficulty to treat in older children