---

creation date: 2025-07-12 04:09
tags: Pathologies

---

Asthma

Background

Definitions

Asthma is a chronic inflammatory respiratory condition characterized by inflammation of airways causing intermittent airflow obstruction and bronchial hyperresponsiveness.

This condition is highly prevalent and often presents in childhood. It is associated with other atopic conditions:

• Eczema
• Asthma
• Allergic rhinitis

Etiology and Pathogenesis

There are a number of mechanisms and pathways which results in asthma.

Airway inflammation
Following allergen inhalation, patients produce specific IgE antibodies due to over expressed T-helper 2 lymphocytes relative to T-helper 1 resulting in sensitization. In subsequent exposures, the specific IgE antibodies bind to mast cell receptors and basophils resulting in degranulation and release of histamine, prostaglandin D2 (PGD2), and cysteinyl leukotrienes (LTC4, LTC4, LTE4).

This triggers airway smooth muscle contraction and further inflammatory cell influx may lead to delayed bronchoconstriction.

Airflow obstruction
Narrowing of tracheobronchial tree is due to the following:

• Contraction of airway smooth muscle
• Thickening of airway wall due to edema
• Mucus plugging
• Airway remodelling

Airway remodelling occurs in a progressive and possibly irreversible manner. It involves thickening of the basement membrane, deposition of collagen, and shedding of epithelial cells.

Occupational-induced or aspirin-exacerbated
In cases of occupational-induced asthma, the response may be immunological or not. In cases of nonimmunological asthma, bronchoconstriction may occur from mechanisms such as direct beta-2 antagonism.

In aspirin-exacerbated respiratory disease, COX-1 and COX-2 metabolism generates prostaglandins and thromboxanes which causes dysregulation of leukotriene production.

Clinical Presentation

Signs & Symptoms

Respiratory symptoms:

• Wheezing
• Cough (often worse at night)
• Shortness of breath or difficulty breathing
• Chest tightness

History & Physical Exam

History should evaluate for patterns of symptom occurrence:

• Asthma can develop at any age but common in childhood; remission may occur around puberty
• Symptoms occur after exposures/triggers

Episodes are also often episodic with courses of hours-days and resolving spontaneously with removal of allergen. Common triggers are:

• Exercise
• Cold air
• Dust mites
• Molds
• Furry animals
• Cockroaches
• Pollens
• Viral infections

History may elicit a family history of atopy.

Physical exams may find respiratory symptoms and signs on auscultation. In severe cases, there may be signs of severe airflow obstruction (eg. tachypnea, tachycardia, prolonged expiratory phase)

Factors that support a diagnosis may also be found on exam:

• Pale, boggy nasal mucous membranes
• Posterior pharyngeal cobblestoning
• Nasal polyps
• Atopic dermatitis

Risk factors

The primary risk factor is atopy, characterized by the tendency to produce specific immunoglobulin E (IgE) antibodies in response to common allergens.

Other risk factors include:

• Preterm birth before 36 weeks
• Exposure to maternal smoking during pregnancy
• Wheezing due to viral infections
• Early-life exposure to air pollution

Risk factors for adult-onset asthma include:

• Tobacco smoke
• Occupational exposures
• Medical history of rhinitis or atopy

A number of factors can contribute to asthma and hyperreactivity:

• Environmental allergens such as house dust mites, animal allergens, cockroach allergens, and fungi
• Exercise
• Conditions such as GERD, chonic sinusitis, and hyperventilation
• Hypersensitivity to aspirin, NSAIDs, or sulfite
• Use of beta antagonists
• Emotional factors or stress
• Irritants and certain other compounds

Diagnosis

Criteria

Diagnosis is made with pulmonary function testing (spirometry) and exclusion of alternative diagnoses.

Spirometry is done prior and following bronchodilator administration to evaluate for airflow limitations and reversibility.

Relevant spirometry measurements are:

• Forced expiratory volume in one second (FEV1)
• Forced vital capacity (FVC)

An obstructive pattern is identified by a reduced FEV1/FVC ratio or by observing a concave expiratory flow-volume curve. Note that this ratio may be falsely normal due to inability to fully exhale so having flow-time curves is recommended.

Following bronchodilator use (2-4 puffs of a short-acting bronchodilator), spirometry is done again and bronchodilator response calculated with:

• Bronchodilator response = ((Postbronchodilator value - Prebronchodilator value) $\times$ 100) / Predicted value
  where value is either FEV1 or FVC.

An increase in >10% is considered significant response but some use a cutoff of 15% as a large response is more likely to be asthma rather than other conditions.

Bronchoprovocation testing can be used to diagnose in cases of normal baseline airflow. This involves using a provocative stimulus to cause bronchoconstriction and monitor for improvement following bronchodilator use.

In children under the age of 6, spirometry may not be possible. In such a case, a presumed diagnosis is typically used. Spirometry should be done whenever possible.

Work-up

Routine bloodwork is typically done to screen for eosinophilia or significant anemia, especially when symptoms are severe.

A chest radiograph may be considered to exclude alternative diagnoses such as mediastinal mass or if atypical respiratory symptoms are present (eg. fever, sputum production).

Allergy tests are not useful for diagnosis but may be used to confirm sensitivity to suspected allergic triggers.

Differential

There are a few respiratory diseases that results in symptoms of asthma.

Wheeze can be caused by any luminal narrowing along the respiratory tract.

• Inspiratory airway sounds such as stridor are generally distinguishable from asthma.
• Expiratory wheezes due to vocal cord dysfunction syndrome are also distinguishable.
• Focal, monophonic wheeze may be due to bronchogenic carcinoma or foreign body

Cough can be caused by a number of condition. A persistent cough with a clear chest x-ray may be:

• Rhinitis
• GERD
• Postviral tussive syndrome
• Eosinophilic bronchitis
• ACEi-induced cough
• Pertussis infection

A chronic cough with sputum in a long-term smoker suggests chronic bronchitis.

Dyspnea has a broad differential including COPD, heart failure, and pulmonary embolism. This is discussed further in the dyspnea workup.

Obstructive spirometry pattern can be presenting complaint for:

• COPD - especially in long-term smokers. Typically, irreversible by bronchodilators but even if so, the effect is less pronounced.
• Bronchiectasis - possibly due to airway wall injury or chronic infection
• Sarcoidosis - although generally restrictive rather than obstructive
• Constrictive bronchiolitis
• Central airway obstruction - by both benign and malignant processes

Red Flags / Complications

Complications related to the disease, adverse effects from the use of glucocorticoids and leukotriene receptor antagonists, and endotracheal intubation.

Briefly:

• Long-term lung damage/decline in function (due to remodelling)
• Sleep disturbances and associated complications
• Medical conditions such as OA, diabetes, and heart disease
• Respiratory failure requiring emergency treatment

Management

Lifestyle / Social

Non-pharmacological component should be done concurrently with pharmacological treatment.

This includes education on:

• Inhaler technique
• Asthma action plan (medication regimen and symptom awareness)

It is also important to identify and avoid asthma triggers. These include common allergens, irritants, and stress. Occupational or school-related factors should mitigated too.

Patients should also stay up to date on immunization to prevent infections.

Pharmacological / Interventional

The mainstay medication of asthma are inhaled bronchodilators. The initiation and adjustment of therapy is done using a stepwise approach to achieve good control. Choice of “step” is based on:

• Frequency of daytime symptoms
• Frequency of nocturnal awakening
• Frequency of reliever therapy used following initiation
• Frequency of exacerbation requiring oral glucocorticoids
• Severity of airway obstruction

The following are preferred therapy regimens. Alternatives are listed below.

Note that anti-inflammatory reliever (AIR) therapy (ICS-formoterol, ICS-SABA, and ICS plus SABA) is preferred over SABA for acute symptoms as they are associated with decreased exacerbation risk.

Patients <4 years old
For all patients in this group, a short-acting beta-agonist (SABA) is used as needed for reliever therapy.

For controller therapy, steps are as follow:

1. Short course of medium dose inhaled corticosteroid (ICS) at start of respiratory tract infection
2. Daily low-dose ICS
3. Daily medium-dose ICS or daily low-dose ICS-LABA
4. Daily high-dose ICS or daily medium-dose ICS-LABA

Patients 4-11 years old
In this group, therapy is as follow:

	Reliever (prn)	Controller
1	SABA	None
2	SABA	Daily low-dose ICS
3	Low-dose ICS-formoterol	Daily low-dose ICS-formoterol
4	Medium-dose ICS-formoterol	Daily medium dose ICS-formoterol
Note, formoterol is a fast-onset LABA which allows for reliever therapy.

Patients >11 years old (adolescents and adults)
Anti-inflammatory reliever therapy is the preferred choice in this group:

1. Low-dose ICS-formoterol prn
2. Low-dose ICS-formoterol as reliever and maintenance
3. Medium-dose ICS-formoterol as reliever and maintenance

Exacerbations
In cases of significant asthma exacerbation, a short course of glucocorticoids should be given.

• Prednisone PO 40-60mg/day for 5-7 days
• Dexamethasone PO 12-16mg for 1-2 doses

References

Tools / Guidelines

Uptodate - Stepwise management table with alternatives:

• <4 years old
• 4-11 years old
• >11 years old

Additional Reading