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After asthma: redefining airways diseases

The Lancet Commissions - After asthma: redefining airways diseases

I.D. Pavord, R. Beasley, A. Agusti, G. Brusselle et al. Lancet 2018; 391: 350–400

Introduction:
  • Progress in reducing hospital admissions and mortality in people with asthma have stalled in the past 10 years.
  • This Lancet Commission examines where we are in the understanding of this heterogeneous syndrome and why we need to kickstart a new era of examining, monitoring, treating, and ultimately preventing airways diseases.
  • The Commissioners call for action all clinicians involved in this field to deconstruct airway disease into component parts before planning treatment with a focus on traits that are identifiable and treatable. 
  • This new approach will require a complete change in how we think about airways diseases with the goal of achieving real precision treatment with better patient outcomes. It is unacceptable that people still die from asthma attacks in 2017.
Summary of seven recommendations

1) Change the way we think about asthma, generalisable to all airways diseases, and deliver precision medicine.

  • Use a new approach to the management and monitoring of patients with airway disease whereby the two dominant treatable traits (risk of attacks associated with eosinophilic airway inflammation and symptoms as a result of airflow limitation) are assessed and managed individually, resulting in a precision medicine approach that is applicable in non-specialist care.

2) Move beyond a disease control-based approach for asthma treatment and rethink fundamentally the current guidelines with greater emphasis on traits that can be measured and treated and less emphasis on arbitrary disease labels. 


3) Emerge from our age-associated and discipline-associated silos by considering airway disease in the context of the developmental trajectory from birth to old age.

4) Test before treatment and move away from the current no-test culture in clinical practice.

5) Have zero tolerance for asthma attacks.

  • The pragmatic solution is to use as-required combination low-dose inhaled corticosteroid and rapid onset β₂-agonist inhalers as the default reliever option so that patients with episodic symptoms and airway inflammation are more likely to receive inhaled corticosteroids at a crucial time.

6) Make the most of new treatment opportunities in severe disease by identifying the best biological for the correct responsive subgroup.


7) Push for better research by working in collaboration with the pharmaceutical industry to ensure that future clinical trials establish not only treatment efficacy and safety but identify definable subgroups who derive particular benefit from treatment.

Rationale behind ICS/LABA fast acting as the default reliever option

The Lancet Commission proposes that as-required combination of low-dose inhaled corticosteroid and rapid onset β₂-agonist inhalers becomes the default reliever option with the following rationale:

  • Patients with episodic symptoms and airway inflammation are more likely to receive inhaled corticosteroids at a crucial time, when eosinophilic inflammation increases (eosinophilia can be variable through time).
  • Effective solution for patients with episodic, but high-risk disease, who feature consistently in asthma mortality statistics.
  • Pragmatic approach for milder patients who have to take daily ICS regardless of whether they have symptoms and resulting in adherence as low as 20% for patients potentially at risk of asthma attack (risk of exacerbation ≠ symptoms).
  • Potential alternative for very mild patients who at present only use short-acting β₂-agonists as required, which is only logical if symptoms are exclusively due to intermittent constriction of airway smooth muscle but is not logical for patients with concomitant low-grade eosinophilic inflammation.
  • Proof of concept already exist for moderate to severe patients for which combination inhaled corticosteroid and fast-onset long-acting β₂-agonist therapy prescribed according to the maintenance and reliever regimen reduces the risk of severe attacks by about 40–50% compared with prescribed combination inhaled corticosteroid and long-acting β₂-agonist maintenance and short-acting β₂-agonist reliever therapy, despite similar efficacy for other outcome measures such as lung function and asthma control.


Reference:
I.D. Pavord, R. Beasley, A. Agusti, G. Brusselle et al. Lancet 2018; 391: 350–400

NS ID XL-0368-RD06/2018-LB