IntroductionChronic inflammatory diseases (CIDs) are frequently treated with biological medications, specifically tumour necrosis factor inhibitors (TNFi)). These medications inhibit the pro-inflammatory molecule TNF alpha, which has been strongly implicated in the aetiology of these diseases. Up to one-third of patients do not, however, respond to biologics, and lifestyle factors are assumed to affect treatment outcomes. Little is known about the effects of dietary lifestyle as a prognostic factor that may enable personalised medicine. The primary outcome of this multidisciplinary collaborative study will be to identify dietary lifestyle factors that support optimal treatment outcomes.Methods and analysisThis prospective cohort study will enrol 320 patients with CID who are prescribed a TNFi between June 2017 and March 2019. Included among the patients with CID will be patients with inflammatory bowel disease (Crohn’s disease and ulcerative colitis), rheumatic disorders (rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis), inflammatory skin diseases (psoriasis, hidradenitis suppurativa) and non-infectious uveitis. At baseline (pretreatment), patient characteristics will be assessed using patient-reported outcome measures, clinical assessments of disease activity, quality of life and lifestyle, in addition to registry data on comorbidity and concomitant medication(s). In accordance with current Danish standards, follow-up will be conducted 14–16 weeks after treatment initiation. For each disease, evaluation of successful treatment response will be based on established primary and secondary endpoints, including disease-specific core outcome sets. The major outcome of the analyses will be to detect variability in treatment effectiveness between patients with different lifestyle characteristics.Ethics and disseminationThe principle goal of this project is to improve the quality of life of patients suffering from CID by providing evidence to support dietary and other lifestyle recommendations that may improve clinical outcomes. The study is approved by the Ethics Committee (S-20160124) and the Danish Data Protecting Agency (2008-58-035). Study findings will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences.Trial registration numberNCT03173144; Pre-results.

Cardiovascular disease (CVD) is responsible for 31% of all global deaths. Atherosclerosis is the major cause of cardiovascular disease and is a chronic inflammatory disorder in the arteries. Atherosclerosis is characterized by the accumulation of cholesterol, extracellular matrix, and immune cells in the vascular wall. Recently, the collectin surfactant protein-D (SP-D), an important regulator of the pulmonary immune response, was found to be expressed in the vasculature. Several in vitro studies have examined the role of SP-D in the vascular inflammation leading to atherosclerosis. These studies show that SP-D plays a dual role in the development of atherosclerosis. In general, SP-D shows anti-inflammatory properties, and dampens local inflammation in the vessel, as well as systemic inflammation. However, SP-D can also exert a pro-inflammatory role, as it stimulates C-C chemokine receptor 2 inflammatory blood monocytes to secrete tumor necrosis-factor α and increases secretion of interferon-γ from natural killer cells. In vivo studies examining the role of SP-D in the development of atherosclerosis agree that SP-D plays a proatherogenic role, with SP-D knockout mice having smaller atherosclerotic plaque areas, which might be caused by a decreased systemic inflammation. Clinical studies examining the association between SP-D and cardiovascular disease have reported a positive association between circulatory SP-D level, carotid intima-media thickness, and coronary artery calcification. Other studies have found that circulatory SP-D is correlated with increased risk of both total and cardiovascular disease mortality. Both in vitro, in vivo, and clinical studies examining the relationship between SP-D and CVDs will be discussed in this review.

Cigarette smoke (CS) is the main cause of chronic obstructive pulmonary disease. Surfactant protein D (SP-D) is an important anti-inflammatory protein that regulates host immune defense in the lungs. Here, we investigated the role of SP-D in a murine model of CS-induced inflammation. Pulmonary SP-D localization and abundance was compared between smoker and non-smoker individuals. For in vivo studies, wildtype, and SP-D-deficient mice were exposed to CS for either 12 weeks or 3 days. Moreover, the effect of therapeutic administration of recombinant fragment of human SP-D on the acute CS-induced changes was evaluated. Pulmonary SP-D appeared with heterogenous expression in human smokers, while mouse lung SP-D was uniformly upregulated after CS exposure. We found that SP-D-deficient mice were more susceptible to CS-induced macrophage-rich airway inflammation. SP-D deficiency influenced local pro-inflammatory cytokine levels, with increased CCL3 and interleukin-6 but decreased CXCL1. Furthermore, CS exposure caused significant upregulation of pro-inflammatory ceramides and related ceramide synthase gene transcripts in SP-D-deficient mice compared to wildtype littermates. Administration of recombinant fragment of human SP-D (rfhSP-D) alleviated CS-induced macrophage infiltration and prevented induction of ceramide synthase gene expression. Finally, rfhSP-D treatment attenuated CS-induced human epithelial cell apoptosis in vitro. Our results indicate that SP-D deficiency aggravates CS-induced lung inflammation partly through regulation of ceramide synthesis and that local SP-D enrichment rescues CS-induced inflammation.

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