Research Article The Association of Olfactory Dysfunction, Frailty, and Mortality Is Mediated by Inflammation: Results from the InCHIANTI Study Alice Laudisio , 1 Luca Navarini , 2 Domenico Paolo Emanuele Margiotta , 2 Davide Onofrio Fontana, 1 Irene Chiarella, 1 Daniele Spitaleri, 1 Stefania Bandinelli, 3 Antonella Gemma, 4 Luigi Ferrucci, 5 and Raffaele Antonelli Incalzi 1 1 Unit of Geriatrics, Department of Medicine, Università Campus Bio-Medico, Rome, Italy 2 Unit of Allergology, Immunology, Rheumatology, Department of Medicine, Università Campus Bio-Medico, Rome, Italy 3 Geriatric Rehabilitation Unit, Azienda Sanitaria di Firenze, Florence, Italy 4 Department of Homecare Service, Azienda Sanitaria Locale Roma E, Rome, Italy 5 Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, USA Correspondence should be addressed to Alice Laudisio; lavoralice@gmail.com Received 25 May 2018; Accepted 29 November 2018; Published 20 February 2019 Academic Editor: Ilaria Roato Copyright © 2019 Alice Laudisio et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Olfactory dysfunction might unveil the association between ageing and frailty, as it is associated with declining cognitive function, depression, reduced physical performance, reduced dietary intake, and mortality; all these conditions are characterized by increased levels of inflammatory parameters. The present study is aimed at evaluating the association between olfactory dysfunction, frailty, and mortality and whether such association might be mediated by inflammation. Methods. We analysed data of 1035 participants aged 65+ enrolled in the “InCHIANTI” study. Olfactory function was tested by the recognition of the smells of coffee, mint, and air. Olfactory dysfunction was defined as lack of recognition of at least two smells. Considering the items “shrinking,”“exhaustion,”“sedentariness,”“slowness,” and “weakness” included in the Fried definition, frailty was defined as the presence of at least three criteria, prefrailty of one or two, and robustness of none. Serum interleukin-6 (IL-6) was measured in duplicate by high-sensitivity enzyme-linked immunosorbent assays. Logistic regression was adopted to assess the association of frailty with olfactory function, as well as with the increasing number of olfactory deficits. Cox regression was used to test the association between olfactory dysfunction and 9-year survival. Results. Olfactory dysfunction was associated with frailty, after adjusting (OR 1.94, 95% CI = 1 07-3.51; P = 028); analysis of the interaction term indicated that the association varied according to interleukin-6 levels (P for interaction = 005). Increasing levels of olfactory dysfunction were associated with increasing probability of being frail. Also, olfactory dysfunction was associated with reduced survival (HR 1.52, 95% CI = 1 16-1.98; P = 002); this association varied according to the presence of frailty (P for interaction = 017) and prefrailty status (P for interaction = 046), as well as increased interleukin-6 levels (P for interaction = .011). Conclusions. Impairment of olfactory function might represent a marker of frailty, prefrailty, and consequently reduced survival in an advanced age. Inflammation might represent the possible link between these conditions. 1. Introduction Due to its prevalence rates exceeding 50% among individ- uals aged 65-80 years and reaching 80% above the age of 80, olfaction dysfunction is considered a very common problem in older populations [1]. This sensory deficit has important implications for safety, nutrition, quality of life, and social relationships [2]. Olfactory impairment is partially age-related and reflects either central neurodegenerative mechanisms or peripheral cumulative damage of olfactory receptors [1]. In fact, the olfactory system is the only sense which depends upon stem cell turnover, and the olfactory nerve is the only cranial nerve directly exposed to the environment [1]. Frailty is an age-related condition of increased vulnerabil- ity, associated with higher risk of several adverse outcomes, Hindawi Journal of Immunology Research Volume 2019, Article ID 3128231, 8 pages https://doi.org/10.1155/2019/3128231