• Clinical science

Asthma

Summary

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.

Epidemiology

  • Prevalence
    • 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. [1]
  • Sex: differs depending on age at onset
    • > in patients < 18 years
    • > in patients > 18 years
  • Age of onset

References:[2][3]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

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:

References:[5][2]

Pathophysiology

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:

  1. Bronchial hyperresponsiveness
  2. Bronchial inflammation
  3. Endobronchial obstruction caused by:

Some forms of asthma have specific pathophysiologies:

References: [2]

Clinical features

Chronic/persistent signs and symptoms

  • Mild to moderate signs and symptoms
    • Persistent, dry cough that worsens at night, with exercise, or on exposure to triggers/irritants (e.g., cold air, allergens, smoke)
    • End-expiratory wheezes
    • Dyspnea
    • Chest tightness
    • Chronic allergic rhinitis with nasal congestion
  • Severe signs and symptoms
    • Severe dyspnea
    • Pulsus paradoxus
    • Hypoxemia
    • Accessory muscle use
    • Increased risk of pulmonary infection (in chronic asthma)
  • Cough variant asthma
    • A form of asthma in which the predominant symptom is chronic, dry cough
    • Other characteristic symptoms of asthma (e.g., wheezes, congestion, dyspnea) are absent.

Acute asthma attack

  • Definition: acute, reversible episode of lower airway obstruction that may be life-threatening
Clinical features Mild Moderate Severe
Symptoms
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
Signs
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%

Clinical examination

  • Auscultation (characteristic findings are usually only present during acute attacks)
  • Percussion
    • 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!

References: [5][8][2][9]

Diagnostics

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

Laboratory studies and further workup

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.

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
Intermittent Mild Moderate Severe
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%

References: [2][4][11]

Differential diagnoses

Comparison of asthma and COPD

Asthma COPD
Age at diagnosis
  • Often childhood or adolescence, although nonallergic asthma can manifest after the age of 40
  • Typically > 40 years old
Etiology
  • Allergic and nonallergic (see “Etiology” above)
  • Cigarette consumption (90% of cases)
Clinical presentation
  • Episodic: symptom-free phases, sudden attacks
  • Insidious onset and chronic progression over years
Obstruction
  • Reversible
  • Persistent airflow limitation

Medication

  • Good response to treatment with long-term inhaled corticosteroids

References:[2]

The differential diagnoses listed here are not exhaustive.

Treatment

Causal

Symptomatic

Overview of asthma medication
Class Examples Mechanism Primary use
Beta-2 agonists
  • SABA: acute exacerbations
  • LABA: long-term maintenance treatment

Inhaled corticosteroids (ICS)

  • Long-term maintenance treatment (first-line)
Leukotriene pathway modifiers
  • ↓ Bronchoconstriction and inflammation
  • Inhibits 5-lipoxygenase↓ production of leukotrienes
Muscarinic antagonists
  • Option for long-term maintenance treatment
Biological agents
  • Monoclonal antibody against IL-5: potent chemoattractant for eosinophils
  • Additional medication for severe eosinophilic asthma that is not sufficiently controlled with other measures
Methylxanthines
  • Limited use (cardiotoxic, neurotoxic)
Mast-cell stabilizers
  • Prevents release of inflammatory mediators from mast cells.
  • Preventive treatment prior to exercise or unavoidable exposure to known allergens in patients ≥ 5 years old
Oral corticosteroids
  • Similar to inhaled corticosteroids
  • Used in severe and refractory cases

Acute management

The following drugs are not effective during an acute asthma attack: LABA, leukotriene pathway modifiers, theophylline, mast-cell stabilizers, biological agents!

To remember the meds for asthma exacerbations, think ASTHMA: Albuterol, Steroids, Theophylline (rare), Humidified O2, Magnesium (severe exacerbations), Anticholinergics.

Long-term management

  • General principles
    • 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.
  • Pharmaceutical management
    • 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 [13]
      • 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)
Severity
Treatment Intermittent Mild Moderate Severe
Preferred reliever
Preferred controller
  • Daily low-dose ICS
  • OR as-needed low dose ICS-formoterol
  • Daily low-dose ICS-LABA
  • Daily medium/high-dose ICS-LABA
Alternative and add-on controllers
  • OR low-dose ICS whenever SABA is taken
  • OR LTRA
  • OR low-dose ICS whenever SABA is taken
  • OR low-dose ICS + LTRA
  • OR medium dose ICS

Inhaled corticosteroids do not take full effect until they have been used for approx. 1 week!

  • Monitoring
    • 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?
  • Patient answers “No” to all questions
  • Patient answers “Yes” to 1–2 questions
  • Patient answers “Yes” to 3–4 questions
Reliever inhaler use more than twice weekly?
Daytime asthma symptoms more than twice weekly?
Awakening at night due to asthma symptoms?

References: [5][8][4][14][13]

Complications

Status asthmaticus

  • Definition: extreme asthma exacerbation that does not respond to initial treatment with bronchodilators
  • Clinical features
    • Initially: orthopnea, tachypnea, tachycardia, hypoxemia and cyanosis, hypercarbia
    • Signs of imminent respiratory arrest
  • Diagnosis
  • Management
    • Hospitalization
      • PEF or FEV1: 50–70% of the predicted value
      • PEF or FEV1 < 50% of the predicted value → admitted in the ICU
    • Medications
    • Oxygenation and ventilation
      • Supplemental oxygen and/or helium-oxygen mixture (heliox)
      • Noninvasive ventilation (NIV)
        • Bilevel positive airway pressure (BiPAP) provides greater support.
          • Maintains airways open → decreases airways resistance → reduces auto-PEEP → reduces work of breathing
        • Use for 1–2 hours in cooperative patients not responding to medical therapy.
        • Do not delay intubation when it is indicated.
      • Indications for intubation
        • Use of accessory muscles
        • Decreased oxygen saturation
        • Inability to speak in full sentences
        • Inadequate response to initial therapy
        • Normalizing PCO2 or pH (see “Laboratory Studies” under “Diagnostics” above)

Status asthmaticus is a medical emergency, as it can be a life-threatening!

References: [15][16]

We list the most important complications. The selection is not exhaustive.

Special patient groups

  • Pregnant women
    • 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.
  • Children
    • 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. [4]

References: [2][17]

  • 1. Akinbami et al. Trends in asthma prevalence, health care use, and mortality in the United States, 2001–2010. https://www.cdc.gov/nchs/data/databriefs/db94.pdf. Updated May 1, 2012. Accessed April 30, 2019.
  • 2. Morris MJ. Asthma. In: Mosenifar Z. Asthma. New York, NY: WebMD. http://emedicine.medscape.com/article/296301. Updated June 16, 2016. Accessed February 24, 2017.
  • 3. Centers for Disease Control and Prevention. Most Recent Asthma Data. https://www.cdc.gov/asthma/most_recent_data.htm. Updated February 27, 2017. Accessed April 19, 2017.
  • 4. National Heart, Lung, and Blood Institute . Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma, Full Report 2007 . url: https://www.nhlbi.nih.gov/files/docs/guidelines/asthgdln.pdf Accessed April 19, 2017.
  • 5. Agabegi SS, Agabegi ED. Step-Up To Medicine. Baltimore, MD, USA: Lippincott Williams & Wilkins; 2013.
  • 6. Gauvreau et al. Effects of Interleukin-13 Blockade on Allergen-induced Airway Responses in Mild Atopic Asthma. Am J Respir Crit Care Med. 2011; 183(8): pp. 1007–1014. doi: 10.1164/rccm.201008-1210oc.
  • 7. Lloyd CM, Hessel EM. Functions of T cells in asthma: more than just T(H)2 cells. Nat Rev Immunol. 2010; 10(12): pp. 838–48. doi: 10.1038/nri2870.
  • 8. Le T, Bhushan V, Bagga HS. First Aid for the USMLE Step 2 CK. McGraw-Hill Medical; 2009.
  • 9. Niimi A. Cough and asthma. Curr Respir Med Rev. 2011; 7(1): pp. 47–54. doi: 10.2174/157339811794109327.
  • 10. Sakula A. Charcot-Leyden crystals and Curschmann spirals in asthmatic sputum. Thorax. 1986; 41(7): pp. 503–7. pmid: 3538483.
  • 11. Harward MP. Medical Secrets. Elsevier.
  • 12. Fala L. Nucala (Mepolizumab): First IL-5 Antagonist Monoclonal Antibody FDA Approved for Maintenance Treatment of Patients with Severe Asthma. American health & drug benefits. 2016; 9(Spec Feature): pp. 106–10. pmid: 27668056.
  • 13. Global Initiative for Asthma – GINA. Global Initiative for Asthma (GINA) GUIDE FOR ASTHMA MANAGEMENT AND PREVENTION. https://ginasthma.org/wp-content/uploads/2019/04/GINA-2019-main-Pocket-Guide-wms.pdf. Updated January 1, 2019. Accessed May 1, 2019.
  • 14. Fanta CH. Management of Acute Exacerbations of Asthma in Adults. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/management-of-acute-exacerbations-of-asthma-in-adults. Last updated February 16, 2017. Accessed April 19, 2017.
  • 15. Saadeh CK. Status Asthmaticus. In: Oppenheimer JJ. Status Asthmaticus. New York, NY: WebMD. http://emedicine.medscape.com/article/2129484. Updated March 3, 2017. Accessed April 19, 2017.
  • 16. David R Stather, Thomas E Stewart. Clinical review: mechanical ventilation in severe asthma. Crit Care. 2005; 9(6): pp. 581–587. doi: 10.1186/cc3733.
  • 17. Little M. Asthma in Pregnancy. In: Pritchard Taylor J. Asthma in Pregnancy. New York, NY: WebMD. http://emedicine.medscape.com/article/796274. Updated June 6, 2016. Accessed April 19, 2017.
  • Herold G. Internal Medicine. Cologne, Germany: Herold G; 2014.
last updated 10/11/2019
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