Biomarkers of asthma relapse and lung function decline in adults with spontaneous asthma remission: A population-based cohort study

Daniel J Tan; Caroline J Lodge; Eugene Haydn Walters; Adrian J Lowe; Dinh S Bui; Gayan Bowatte; Rangi Kandane-Rathnayake; Fahad M Aldakheel; Bircan Erbas; Garun S Hamilton; Paul S Thomas; Mark Hew; Mimi L K Tang; Michael J Abramson; Jennifer L Perret; Shyamali C Dharmage

doi:10.1111/all.15566

Biomarkers of asthma relapse and lung function decline in adults with spontaneous asthma remission: A population-based cohort study

Allergy. 2023 Apr;78(4):957-967. doi: 10.1111/all.15566. Epub 2022 Nov 16.

Authors

Daniel J Tan¹, Caroline J Lodge¹, Eugene Haydn Walters^{1

2}, Adrian J Lowe¹, Dinh S Bui¹, Gayan Bowatte^{1

3}, Rangi Kandane-Rathnayake⁴, Fahad M Aldakheel⁵, Bircan Erbas^{6

7}, Garun S Hamilton^{4

8}, Paul S Thomas⁹, Mark Hew^{10

11}, Mimi L K Tang^{12

13}, Michael J Abramson¹⁰, Jennifer L Perret^{1

14}, Shyamali C Dharmage¹

Affiliations

¹ Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
² School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.
³ Department of Basic Sciences, Faculty of Allied Health Sciences, University of Peradeniya, Peradeniya, Sri Lanka.
⁴ School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia.
⁵ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.
⁶ School of Psychology and Public Health, La Trobe University, Melbourne, Victoria, Australia.
⁷ Violet Vines Marshman Centre for Rural Health Research, La Trobe University, Bendigo, Victoria, Australia.
⁸ Monash Lung, Sleep, Allergy and Immunology, Monash Health, Melbourne, Victoria, Australia.
⁹ Prince of Wales' Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
¹⁰ School of Public Health & Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
¹¹ The Alfred Hospital, Melbourne, Victoria, Australia.
¹² Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
¹³ Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.
¹⁴ Institute for Breathing and Sleep, Melbourne, Victoria, Australia.

Abstract

Background: The extent to which biomarkers of asthma activity persist in spontaneous asthma remission and whether such markers are associated with future respiratory outcomes remained unclear. We investigated the association between sub-clinical inflammation in adults with spontaneous asthma remission and future asthma relapse and lung function decline.

Methods: The Tasmanian Longitudinal Health Study is a population-based cohort (n = 8583). Biomarkers of systemic inflammation were measured on participants at age 45, and latent profile analysis was used to identify cytokine profiles. Bronchial hyperresponsiveness (BHR) and nitric oxide products in exhaled breath condensate (EBC NOx) were measured at age 50. Participants with spontaneous asthma remission at ages 45 (n = 466) and 50 (n = 318) were re-evaluated at age 53, and associations between baseline inflammatory biomarkers and subsequent asthma relapse and lung function decline were assessed.

Results: We identified three cytokine profiles in adults with spontaneous asthma remission: average (34%), Th2-high (42%) and Th2-low (24%). Compared to the average profile, a Th2-high profile was associated with accelerated decline in post-BD FEV₁ /FVC (MD -0.18% predicted per-year; 95% CI -0.33, -0.02), while a Th2-low profile was associated with accelerated decline in both post-BD FEV₁ (-0.41%; -0.75, -0.06) and post-BD FVC (-0.31%; -0.62, 0.01). BHR and high TNF-α during spontaneous remission were associated with an increased risk of asthma relapse. In contrast, we found no evidence of association between EBC NOx and either asthma relapse or lung function decline.

Conclusion: BHR and serum inflammatory cytokines have prognostic value in adults with spontaneous asthma remission. At-risk individuals with BHR, Th2-high or Th2-low cytokine profiles may benefit from closer monitoring and on-going follow-up.

Keywords: asthma; biomarkers; endotypes; precision medicine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Asthma* / diagnosis
Asthma* / epidemiology
Biomarkers
Bronchial Hyperreactivity*
Chronic Disease
Cohort Studies
Humans
Inflammation
Lung
Middle Aged
Nitric Oxide
Remission, Spontaneous

Substances

Biomarkers
Nitric Oxide