- Clinical science
Asthma is a chronic inflammatory disease of the respiratory system characterized by bronchial hyperresponsiveness, episodic exacerbations (asthma attacks), and reversible airflow obstruction. Allergic (extrinsic) asthma usually develops in childhood and is triggered by allergens such as pollen, dust mites, and certain foods. Nonallergic (environmental or intrinsic) asthma usually develops in patients over the age of forty and can have various triggers, such as cold air, medication (e.g., aspirin), exercise, and viral infection. The cardinal symptoms of asthma are intermittent dyspnea, coughing, and high-pitched expiratory wheezing. Symptoms remit in response to antiasthmatic medication or resolve spontaneously upon removal of the trigger. Confirmation of the diagnosis involves pulmonary function tests, allergy tests, and chest x-ray. First-line treatment consists of inhaled bronchodilators (e.g., short-acting beta-2 agonists) for acute exacerbations and inhaled corticosteroids (e.g., budesonide) for long-term asthma control. Patients should be taught the correct usage of inhalers for self-medication and measurement of peak expiratory flow (PEF) to self-monitor disease progression and severity. Severe asthma exacerbation can be life-threatening and may require emergency treatment and/or hospitalization.
- 5–10% of the US population
- More common in black than white patients
- For unknown reasons, the prevalence of asthma has been increasing over the past 20 years. 
Sex: differs depending on age at onset
- ♂ > ♀ in patients < 18 years
- ♀ > ♂ in patients > 18 years
- Age of onset
Epidemiological data refers to the US, unless otherwise specified.
The exact etiology of asthma remains unknown. Known risk factors for asthma include the following:
Childhood exposure to second-hand smoke increases the risk of developing asthma!
The following factors can also act as initial triggers of asthma or exacerbate an existing condition:
Allergic asthma (extrinsic asthma)
- Cardinal risk factor:
- Environmental allergens: pollen (seasonal), dust mites, domestic animals; , mold spores
- Allergic occupational asthma: from exposure to allergens in the workplace (e.g., flour dust)
Nonallergic asthma (intrinsic asthma)
- Viral respiratory tract infections (one of the most common stimuli, especially in children) 
- Cold air
- Physical exertion (exercise-induced asthma)
- (GERD): often exists concurrently with asthma
- Chronic sinusitis or rhinitis
- Medication: aspirin/NSAIDS (); , beta-blockers
- Irritant-induced asthma; (e.g., from exposure to solvents, ozone, tobacco or wood smoke, cleaning agents)
Asthma is generally characterized as an inflammatory disease driven by T-helper type 2 (Th2-cell) that manifests in individuals with a genetic predisposition. It consists of the following three pathophysiologic processes:
- Bronchial hyperresponsiveness
- Symptoms are primarily caused by inflammation of the terminal bronchioles, which are lined with smooth muscle but lack the cartilage found in larger airways.
- Overexpression of Th2-cells → inhalation of antigen results in production of cytokines (IL-3, IL-4, IL-5, IL-13) → activation of eosinophils and induction of cellular response (B-cell IgE production) → bronchial submucosal edema and smooth muscle contraction → bronchioles collapse 
- Endobronchial obstruction caused by:
Some forms of asthma have specific pathophysiologies:
- Allergic asthma: IgE-mediated type 1 hypersensitivity to a specific allergen; ; characterized by mast cell degranulation; and release of histamine after a prior phase of sensitization
- Nonallergic asthma
Chronic/persistent signs and symptoms
- Mild to moderate signs and symptoms
- Severe signs and symptoms
- Cough variant asthma
- Definition: acute, reversible episode of lower airway obstruction that may be life-threatening
|Breathlessness||While walking||While at rest||At rest|
|Position||Can lie down||Prefers sitting||Hunched over|
|Ability to speak||Sentences||Phrases||Individual words|
|Alertness||May be agitated||Usually agitated||Agitated|
|Respiratory rate||Increased||Increased||Often > 30/minute|
|Wheezing||Moderate, often only end-expiratory||Loud; throughout exhalation||Throughout inhalation and exhalation; can also be absent|
|Use of accessory muscles||Rarely||Commonly||Usually|
|Pulse/minute||< 100||100–120||> 120|
|Pulsus paradoxus||Absent||May be present||Often present|
|PCO2||< 42 mm Hg||> 42 mm Hg||≥ 42 mm Hg|
|SaO2||> 95%||90–95%||< 90%|
- Auscultation (characteristic findings are usually only present during acute attacks)
- Hyperresonant sound
- Inferior displacement and poor movement of the diaphragm
- In severe attacks
Characteristic examination findings may not be present between episodes of asthma exacerbation!
A combination of clinical findings ; and objective measurement of pulmonary function (for adults and children ≥ 5 years of age) is needed to confirm the diagnosis and assess the severity of asthma.
Evaluation of pulmonary function
- (bronchoprovocation test)
- Chest x-ray
Laboratory studies and further workup
- Pulse oximetry and blood gas analysis (ABG)
Patients with acute asthma exacerbations initially have ↓ PCO2 and respiratory alkalosis (↑ pH) due to tachypnea. Rising PCO2 is a sign of respiratory fatigue and impending respiratory failure! ICU admission and intubation should be considered.
- In allergic asthma
- In asthma triggered by infection: elevated inflammatory markers
- Sputum sample: Curschmann spirals, Charcot-Leyden crystals, and/or Creola bodies 
Classification of asthma severity at initial assessment for children ≥ 12 years and adults
The following table allows for classification of asthma severity in the initial assessment of patients who are not yet taking asthma control medication.
|Classification of asthma severity|
|Mild intermittent||Mild persistent||Moderate persistent||Severe persistent|
|Symptoms (e.g., dyspnea, wheezing, cough)||≤ 2 days/week||> 2 days/week||Daily||Throughout the day|
|Nighttime symptoms (e.g., difficulty falling asleep because of symptoms, nighttime awakenings)||Rare||3–4 times/month||1–2 times/week||Often (most nights)|
|FEV1||> 80%||> 80%||60–80%||< 60%|
- The and the causes of are both addressed in other learning cards.
- The other main COPD, which is compared with asthma in the table below. is
|Age at diagnosis|| || |
|Etiology|| || |
|Clinical presentation|| || |
|Obstruction|| || |
| || |
The differential diagnoses listed here are not exhaustive.
- Avoid triggers (see “Etiology” above).
- Allergen immunotherapy in allergic asthma
- Early treatment of infections in infection-triggered asthma
- If GERD is suspected: proton pump inhibitors
|Overview of asthma medication|
Inhaled corticosteroids (ICS)
| || |
|Leukotriene pathway modifiers|| || |
|Muscarinic antagonists|| |
|Biological agents|| || |
| || |
|Methylxanthines|| || |
|Mast cell stabilizers|| || || |
|Oral corticosteroids|| || |
- For mild symptoms: short-acting beta-2 agonist
- For exercise-induced asthma: short-acting beta-2 agonist prior to exercise
- For severe asthma exacerbations, see “Treatment” in .
To remember the meds for asthma exacerbations, think ASTHMA: Albuterol, Steroids, Theophylline (rare), Humidified O2, Magnesium (severe exacerbations), Anticholinergics.
- Reduce number of asthma attacks → Medical therapy is escalated or de-escalated depending on the patient's individual needs.
Self-monitoring for patients: peak flow meter to measure peak expiratory flow rate (PEFR)
- Patients can avoid exacerbations with frequent PEFR measurements: PEFR decreases before symptoms appear → indicates insufficient medication regimen
- Influenza and pneumococcal vaccines are administered in all patients.
- Reliever medications: provide relief of asthma symptoms and are taken as needed when symptoms are present
- Controller medications: control underlying inflammation of asthma
- Shift in treatment paradigm as of 2019 
- Previously: As-needed SABA reliever inhaler was the mainstay of intermittent asthma treatment.
- New recommendation: ICS-containing controller inhaler for every adult and adolescent with asthma (no more SABA-only treatment)
- Reasoning: ICS addresses the underlying problem of airway inflammation → reduces both frequency of symptoms and risk of severe asthma exacerbations (SABAs only address symptoms)
- Note that many resources still list as-needed SABA reliever treatment as the only therapy necessary in intermittent asthma.
|Pharmaceutical management of chronic asthma (adults and adolescents)|
|Treatment||Mild intermittent||Mild persistent||Moderate persistent||Severe persistent|
|Preferred controller|| || || || |
|Alternative and add-on controllers|| || || |
Inhaled corticosteroids do not take full effect until they have been used for approx. 1 week!
- Routine follow-up every 1–6 months, depending on severity
- Purpose of follow-up: assessment of asthma symptom control
|Asthma symptom control|
|Control questions||Well controlled||Partly controlled||Uncontrolled|
|Limitation of activities due to asthma symptoms?|| || || |
|Reliever inhaler use more than twice weekly?|
|Daytime asthma symptoms more than twice weekly?|
|Awakening at night due to asthma symptoms?|
- Definition: extreme asthma exacerbation that does not respond to initial treatment with bronchodilators
- Clinical features
- PEF or FEV1: 50–70% of the predicted value
- PEF or FEV1 < 50% of the predicted value → admitted in the ICU
Oxygenation and ventilation
- Supplemental oxygen and/or helium-oxygen mixture (heliox)
- Noninvasive ventilation (NIV)
- Indications for intubation
Status asthmaticus is a medical emergency, as it can be a life-threatening!
We list the most important complications. The selection is not exhaustive.
- Asthma symptoms can be worse, better, or unchanged during pregnancy.
- Same stepwise management as with other patients
- Inhalation treatments preferred
- Poorly managed asthma can increase the risk of pregnancy complications (e.g., preeclampsia, premature birth, congenital abnormalities).
- Monthly monitoring of asthma is recommended.
- Asthma in patients under 5 years of age is challenging to diagnose and is often underdiagnosed, as children in this age group are not typically able to adequately perform the spirometric maneuvers.
- Treatment similar to that for adults, with inhaled corticosteroids as the initial drug of choice
- Young children (< 5 years) may require nebulizers because of difficulty using inhalers.