Asthma-Pathogenesis

What is the pathogenesis behind asthma? 

  • Three corner stones of asthma pathogenesis are airflow obstruction, bronchial hyperresponsiveness, and an underlying inflammation.
  1. Airflow obstruction
  • Seondary be due to many causes
  • Bronchoconstriction
    • The dominant causative event behind clinical symptoms.
    • Secondary to IgE and non-IgE mediated pathways. 
      • IgE-mediated
        • Bronchial smooth muscle contraction after exposure to allergens or irritants. 
      • Non-IgE-mediated
        • Mediators are released from airway cells in response to aspirin and other NSAIDs that cause bronchoconstriction.
        • Stimuli like exercise, cold air, and irritants can also bronchoconstriction through a non-IgE-mediated pathway.
  • Airway edema
    • Edema, mucus hypersecretion and formation of mucus plugs are secondary to the persistent inflammation.
    • Persistent inflammation can also lead to irreversible structural changes to the airways (airway remodeling) that may not respond to traditional therapy.
  1. Airway hyperresponsiveness
  • Consists of an exaggerated response to stimuli.
  • It is a reversible phenomenon and is the principle behind the methacholine challenge, in which asthma patient show a dramatic decrease in FEV1.
  • Exact mechanism behind the hyperresponsiveness is not known
  • Inflammation, dysfunctional neuroregulation, and structural change are thought to be important.
  1. Inflammation
  • Plays a central role in the pathogenesis of asthma.
  • Consists of an ‘early-phase reaction’ and a ‘late-phase reaction.’

Early-phase reaction:

  1. An individual is exposed to allergens and produces IgE antibodies due to overexpression of Th2 T-cell response.
  • Th2 T-cell response is associated with helminthic responses as well as atopic diseases like asthma.
  • With a combination of genetics and environmental exposure,  susceptible individuals overexpress Th2 T-cells rather than Th1 T-cells.
  1. IgE antibodies produced by plasma cells bind to mast-cells.
  2. Exposure to the same allergen leads to cross-linking of IgE antibodies on the mast cell surface.
  • This leads to rapid degranulation and cytokine release. 
  • Histamine, prostaglandin D2, leukotrienes are released, leading to airway smooth muscle contraction

 

Late-phase reaction

  1. The mediators released during the early-phase reaction lead to recruitment of innate and adaptive inflammatory cells (e.g. neutrophils, monocytes, eosinophils, basophils, memory T-cells, etc.).
  2. These cells release more mediators that lead to smooth muscle contraction
    • Contraction occurs several hours after the exposure to the allergen.
    • The mediators shape other aspects of the inflammatory response.

 

What is wheezing and what do we hear in asthma patients? 

  • Wheezing is a continuous adventitious lung sound that lasts longer than 250 milliseconds heard during auscultation.
  • Produced by oscillation of opposing walls of an airway narrowed almost to the point of closure.
  • Most commonly heard in the expiratory phase of the respiratory cycle.
  • Most commonly is heard bilaterally
    • This is in contrast to a localized obstruction as a cause of wheezing that will be appreciated as radiating from a point of origin.
  • Timing, location, and location help differentiate the various types of wheezes
  • Wheezing in asthma is multitonal (or multiphonic) in contrast to wheezing in localized obstruction that are monotonal.
    • Many different sizes of airways oscillate and superimpose to produce a multiphonic sound
    • in a localized obstruction, an airway of one size will be obstructed to produce a more monotonal sound.
  • The absence of wheezing and breath sounds is a far more ominous finding in asthma than the presence of wheezing. 

 

Example of monophonic wheeze


www.youtube.com/watch?v=JDBPj9A8BJE

 

Example of polyphonic wheeze 


www.youtube.com/watch?v=L8o9JqN-HPg

 

References

  1. National Asthma Education and Prevention Program (NAEPP) Coordinating Committee (CC), National Heart, Lung, and Blood Institute (NHLBI). Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma - Summary Report 2007. http://www.nhlbi.nih.gov/health-pro/guidelines/current/asthma-guidelines/summary-report-2007
  2. National Asthma Education and Prevention Program (NAEPP) Coordinating Committee (CC), National Heart, Lung, and Blood Institute (NHLBI). Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma : Section 2, Definition, Pathophysiology And Pathogenesis Of Asthma, And Natural History Of Asthma. http://www.nhlbi.nih.gov/files/docs/guidelines/03_sec2_def.pdf
  3. Liu, M. Pathogenesis of Asthma. In: Bochner BS, Hollingsworth H. UpToDate. Waltham, MA: UpToDate: 2015. http://www.uptodate.com/contents/pathogenesis-of-asthma

 

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