Mechanisms of Disease 1 HC29: Asthma

HC29: Asthma

Symptoms

Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation (not every patient has this). It is defined by the history of symptoms such as:

  • Wheeze
  • Shortness of breath
  • Chest tightness and cough

These symptoms occur together with variable expiratory airflow limitation and vary over the time and in intensity. Eosinophils are prominently present. In case of fatal asthma, the airways are filled with mucus.

Phenotypes

Symptoms of asthma can vary greatly → asthma ≠ asthma. There are many pnenotypes of asthma:

  • Allergic asthma
  • Work related asthma
  • Asthma in obesity
  • Exercise induced asthma
  • Recurrent infectious asthma
  • Severe eosinophilic asthma
  • Et cetera

Patients can have severe disease and absence of eosinophils, or presence of eosinophils but hardly any symptoms → the asthma spectrum is very broad. For this reason, obstructive lung disease may be a better definition for the disease.

Treatment

Asthma has the following characteristics, which can be treated with:

  • Remodeling
    • Hypertrophy of the muscles → thicker wall, narrow lumen
    • Cannot be treated
  • Mucus production
    • Inhaled steroids
    • Antibiotics
      • Azithromycin changes the environment of the airways → removes microorganisms
  • Inflammation
    • Inhaled steroids
      • Have many side effects such as obesity
    • Monoclonal antibodies
      • Reduce the dose of steroids
  • Smooth muscle contraction
    • Bronchodilators
      • b2-agonists → stimulate the sympathetic nervous system
      • Anticholinergics → reduce the parasympathetic nervous system
      • Relieve the muscle contraction, but don’t treat the inflammatory process

Treatment of mild asthma:

There has been a historical change in treatment of “mild” asthma. At first there was only treatment with bronchodilators, but it appears patients with apparently mild asthma are at risk of serious adverse events:

  • 30-37% of adults with acute asthma had symptoms less than weekly in the previous 3 months
  • 16% of patients with near-fatal asthma had symptoms less than weekly in the previous 3 months
  • 15-20% of adults dying of asthma had symptoms less than weekly in the previous 3 months

Exacerbation triggers are variable:

  • Viruses
  • Pollens
  • Pollutions
  • Poor adherence

Inhaled SABA has been first-line treatment for asthma for 50 years:

  • This dates from an era when asthma was thought to be a disease of bronchoconstriction
  • Patient satisfaction with, and reliance on, SABA treatment is reinforced by its rapid relief of symptoms, its prominence in ED and hospital management of exacerbations, and low cost
  • Patients commonly believe that “my reliever gives me control over my asthma” → they often don’t see the need for additional treatment

In 2020, GINA constated that the first line treatment for mild asthma is ICS-formoteral as needed. b2-agonists are no longer the first treatment for mild asthma.

Diagnosis

There are 2 ways to diagnose asthma:

  • History of characteristic symptoms: vary over the time and in intensity
    • Wheeze
    • Shortness of breath
    • Chest tightness and cough
  • Evidence of variable airflow limitation

Allergic asthma

In case of allergic asthma, one needs to be aware of late asthmatic reactions. A while after an asthma attack, patients again can suffer from severe bronchus obstruction → there is an acute and chronic response. This is caused by the following process:

  1. Acute response → smooth muscle contraction
    1. A mucosal mast cell captures an antigen
    2. Inflammatory mediators contract smooth muscle, increase mucus secretion by airway epithelium and increase blood vessel permeability
  2. Chronic response → inflammatory process
    1. Cytokines and eosinophil products mediate a chronic response

Bronchodilators are not enough to suppress the chronic response. For this reason, patients shouldn’t be sent home immediately when their symptoms have vanished.

Severe eosinophilic asthma

Severe eosinophilic asthma has a low symptom expression. There is a risk of undertreatment. Biologicals are available.

Obesity related asthma

All patients with obesity have narrowed (obstructed) airways. They often suffer from shortness of breath and have correlating diseases with asthma. In case of obesity related asthma, there is a risk of overtreatment. First treatment should be encouraging the patient to lose weight. No oral steroids should be given.

Bronchus obstruction

Bronchus obstruction can be divided into:

  • Reversible → asthma
    • Smooth muscle contraction
    • Smooth muscle hypertrophy
    • Inflammation
    • Mucus
  • Irreversible → COPD
    • Loss of interalveolar septa → collaps
    • Chronic bronchitis

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