The mediating role of cytokine IL-6 on the relationship of FEV1 upon 6-minute walk distancein chronic obstructive pulmonary disease

Simonetta Baldi, Paul E. Jose, Claudio Bruschi, Gian Domenico Pinna, Roberto Maestri, Antonella Rezzani, Ezio Bellinzona, Claudio Fracchia, Elena Dacosto, Paola Crotti, Silvia Montemartini

Research output: Contribution to journalArticlepeer-review


Measurements: At run-in phase of the protocol, clinical and functional screening included BMI, fasting plasma levels of protein (IL-6), spirometry, and standardized 6-minute walking test, measured at the start of the respiratory rehabilitation program.

Objectives: To explore the mediating role of protein interleukin-6 (IL-6) on the relationship between forced expiratory volume in 1 second (FEV1) and 6-minute walk distance (6MWD) and, further, to determine whether status variables (such as age, sex, and body mass index [BMI]) operate as moderators of this mediation relationship.

Design: Moderated mediation model.

Setting: An inpatient pulmonary rehabilitation center in Italy.

Participants: All 153 patients involved in the screening of a randomized controlled clinical trial ( identifier: NCT01253941) were included in this study. All patients were Global initiative for chronic Obstructive Lung Disease (GOLD) stages I–IV and were aged 70.1±9.1 years.

Methods: The size of the indirect effect of the initial variable (FEV1) upon the outcome variable (6MWD) through the intervening variable (IL-6) was computed and tested for statistical significance. Moderated mediation analyses were subsequently conducted with age, sex, and BMI.

Results: FEV1 averaged 53.4%±21.2%, and 6MWD 66.4%±41.3% of predicted. Median protein IL-6 was 6.68 pg/mL (interquartile range: 5.96). A bootstrapped mediation test supported the predicted indirect pathway (P=0.003). The indirect effect through IL-6 log units accounted for 17% of the total effect between FEV1 and 6MWD. Age functioned as a significant moderator of the mediational pattern. For individuals aged70 years it was not significant (0.04, 95% CI: –0.010 to 0.142, P=0.10).

Conclusion: This moderated mediation result based on concurrent data suggests, but does not prove, a causal role of systemic inflammatory syndrome on progression from functional impairment to “frailty” status and substantial disability in aging chronic obstructive pulmonary disease.

Original languageEnglish
Pages (from-to)1091-1099
Number of pages9
JournalInternational Journal of COPD
Publication statusPublished - Oct 7 2014


  • Aging
  • Chronic airflow obstruction
  • COPD
  • Mediation analysis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Public Health, Environmental and Occupational Health
  • Health Policy
  • Medicine(all)


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