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Severe Asthma: Steroids

Hypothesis

  • Would asthma exacerbations (AE) contribute to progressive lung function decline?​

  • Would AE cause lung functions to decline faster in short-term or long-term?

  • Would different patient profile (e.g. smoker vs non-smoker) have a different effect of lung function decline caused by AE?

Knowledge gap

  • Current evidence on the relationship between asthma exacerbations and progressive lung function decline is mixed and limited to a few mainly small, post-hoc studies of specific asthma subgroups with relatively short follow-up time.

  • World leading experts, including Singapore’s own healthcare professionals, have supported this topic study as a novel finding. It is the first study to ever explore up to 50 years’ worth of lung function data collected on patients with asthma and to explore potential patient profiles of interest for future experimental studies.

Knowledge Generated

Only six previous studies have used FEV1 to assess lung function and exacerbations in asthma, and these have shown considerable variation in the association between accelerated lung function decline and exacerbations.

 

These studies showed:

  • The greatest association of exacerbation rate and lung function may be seen in older patients whose lung function is in the decline phase

  • use of ICS diminishes the association of exacerbations on lung function decline

  • lung function decline is demonstrated by FEV1 measurements

Findings

Our findings in a larger and broader population, suggest that these conclusions may be incorrect, our study showed:

  • Year-on-year loss of lung function with increasing exacerbation burden for the average adult patient with asthma

  • Speed of lung function decline was in fact stronger in younger patients aged 18–39 years, experiencing exacerbations

  • Lung function decline persisted even in patients on higher average daily inhaled corticosteroid doses

  • Trajectories are consistent based on either PEF or FEV

 

The results of earlier small-scale studies on how AER contributes to lung function decline in severe asthma patients is found to be less meaningful/ less significant than previously thought and could be potentially overthrown. Hence, with the new knowledge from the R&D study, OPRI will focus on other important plausible approaches instead of simply AER to find ways to prevent/ reduce lung function decline, as the probability that lung function decline is most modifiable in earlier years is now possible.

 

Real-world application of new knowledge:

  • Identified the existence of a persistent lung function deteriorating phenotype (previously unknown). The phenotype, which can develop to severe asthma in adulthood, was found to be identifiable in younger years (i.e. before 40 years of age).

  • A new experimental trial was designed by OPRI to examine the effectiveness of precision medicine biologics in the ‘’early declining’’ phenotype on preventing future lung function decline and disease severity

  • Discovered a previously unknown understanding that the overall rate of decline in non-exacerbating patients were 2.93 L/year PEF or 20.2mL/year FEV 1 (irrespective of age or ICS dosage) making this group comparable with patients without asthma who are estimated to experience an average decline of 22.4mL FEV 1 /year

  • Research by biomedical companies and consideration of newer classes of biologic therapy

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