Longitudinal co-variations between inflammatory cytokines, lung function and patient reported outcomes in patients with asthma

PLoS One. 2017 Sep 15;12(9):e0185019. doi: 10.1371/journal.pone.0185019. eCollection 2017.


Background: Asthma is a chronic inflammatory respiratory disorder associated with reduced lung function and poor quality of life. The condition is also associated with poor self-rated health, a major predictor of objective health trajectories. Of biological correlates to self-rated health, evidence suggests a role for inflammatory cytokines and related sickness behaviours. However, this is mainly based on cross-sectional data, and the relation has not been investigated in patients with chronic inflammatory conditions.

Objective: To investigate inflammatory cytokines, lung function, sickness behaviour and asthma-related quality of life as determinants of self-rated health in patients with asthma, and to investigate if these variables co-vary over time.

Methods: Plasma cytokines (IL-5, IL-6), lung function (FEV1), sickness behaviour, asthma-related quality of life and self-rated health were assessed in 181 patients with allergic asthma aged 18-64 years in a one-year longitudinal study. Mixed effect regression models and Spearman's correlation were performed to analyse the associations between repeated measurements.

Results: More sickness behaviour and poorer asthma-related quality of life were associated with poorer self-rated health (p's<0.001). In men, both low and high levels of interleukin (IL)-6 and poorer lung function were related with poorer self-rated health (p's<0.05). Over the year, improved asthma-related quality of life was associated with better self-rated health (Spearman's rho = -0.34 women,-0.36 men, p's<0.01). Further, if sickness behaviour decreased, self-rated health improved, but only in women (Rho = -0.21, p<0.05). Increased FEV1 in men was associated with an increase in IL-6 (Rho = 0.24, p<0.05) as well as improved self-rated health (Rho = -0.21, p<0.05) and asthma-related quality of life (Rho = 0.29, p<0.01) over the year.

Conclusion: The study highlights the importance of subjectively perceived sickness behaviour and asthma-related quality of life together with lung function as determinants of self-rated health in asthmatic patients. The importance of inflammatory activation for patient reported outcomes in chronic inflammatory conditions need further investigation.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Asthma / blood*
  • Asthma / pathology
  • Asthma / physiopathology*
  • Female
  • Humans
  • Interleukin-5 / blood*
  • Interleukin-6 / blood*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Quality of Life*
  • Respiratory Function Tests


  • IL5 protein, human
  • IL6 protein, human
  • Interleukin-5
  • Interleukin-6

Grant support

The study was funded by the Stockholm County Council (PickUp), Centre for Allergy Research, and Centre for Family Medicine, Karolinska Institutet, and the Swedish Asthma and Allergy Association’s Research Foundation. Support was also received from Aerocrine AB (NIOX MINO instruments). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.