Knowledge Graph (KG) approaches are increasingly being used for data integration processes to combine clinical data with other data sources. Health Data Researchers (HDR) could benefit from these technologies since they require additional types of data outside the health sector, like environmental data, to better understand the extrinsic factors that influence health outcomes in rare disease research. However, using and directly navigating the combined data in the KG can be an obstacle for HDRs. To address this problem, the Semantic Environmental and Rare Disease data Integration Framework (SERDIF) was designed to hide the complexities for these researchers when exploring linked environmental observations with clinical data using a KG approach. The framework was evaluated by HDRs for a case study on Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) in Ireland, and promising usability and effectiveness results were observed. HDRs studying AAV were able to access, explore and export environmental related data to be used as input for their statistical models. SERDIF has the potential to be a solution for HDRs, who require a flexible methodology to integrate environmental data with longitudinal and geospatial diverse clinical data, in their hypothesis validation of environmental factors for rare disease research.

Recent advances on the environmental determinants of Kawasaki Disease have pointed to the important role of the atmospheric transport of a still unknown agent potentially triggering the disease. The hypothesis arose from an innovative methodology combining expertise in climate dynamics, the analysis of ocean and atmosphere data, the use of dispersion models and the search for biological agents in air samples. The approach offered a new perspective to reveal the identity of the potential trigger, but at the same time, it increased the level of complexity, which could potentially lead to the misinterpretation of the mechanisms. Some years after it was originally formulated, we here provide a brief clarification on the approach and limits of the methodology in order to prevent an eventual misuse of our research ideas and theory, so that further research can better focus on the knowledge gaps that still remain open.

Background The aetiology of ANCA-associated vasculitis (AAV) and triggers of relapse are poorly understood. Vitamin D (vitD) is an important immunomodulator, potentially responsible for the observed latitudinal differences between granulomatous and non-granulomatous AAV phenotypes. A narrow ultraviolet B spectrum induces vitD synthesis (vitD-UVB) via the skin. We hypothesised that prolonged periods of low ambient UVB (and by extension vitD deficiency) are associated with the granulomatous form of the disease and an increased risk of AAV relapse. Methods Patients with AAV recruited to the Irish Rare Kidney Disease (RKD) (n = 439) and UKIVAS (n = 1961) registries were studied. Exposure variables comprised latitude and measures of ambient vitD-UVB, including cumulative weighted UVB dose (CW-D-UVB), a well-validated vitD proxy. An n-of-1 study design was used to examine the relapse risk using only the RKD dataset. Multi-level models and logistic regression were used to examine the effect of predictors on AAV relapse risk, phenotype and serotype. Results Residential latitude was positively correlated (OR 1.41, 95% CI 1.14–1.74, p = 0.002) and average vitD-UVB negatively correlated (0.82, 0.70–0.99, p = 0.04) with relapse risk, with a stronger effect when restricting to winter measurements (0.71, 0.57–0.89, p = 0.002). However, these associations were not restricted to granulomatous phenotypes. We observed no clear relationship between latitude, vitD-UVB or CW-D-UVB and AAV phenotype or serotype. Conclusion Our findings suggest that low winter ambient UVB and prolonged vitD status contribute to AAV relapse risk across all phenotypes. However, the development of a granulomatous phenotype does not appear to be directly vitD-mediated. Further research is needed to determine whether sufficient vitD status would reduce relapse propensity in AAV.

Background The etiology of ANCA-associated vasculitis (AAV) and triggers of relapse are poorly understood. Vitamin D (vitD) is an important immunomodulator, potentially responsible for the observed latitudinal differences between granulomatous and non-granulomatous AAV phenotypes. A narrow ultraviolet B spectrum induces vitD synthesis (vitD-UVB) via the skin. We hypothesised that prolonged periods of low ambient UVB (and by extension vitD deficiency) are associated with the granulomatous form of the disease and an increased risk of AAV relapse. Methods Patients with AAV recruited to the Irish Rare Kidney Disease (RKD) (n = 439) and UKIVAS (n = 1961) registries were studied. Exposure variables comprised latitude and measures of ambient vitD-UVB, including cumulative weighted UVB dose (CW-D-UVB), a well-validated vitD proxy. An n-of-1 study design was used to examine relapse risk. Multi-level models and logistic regression were used to examine the effect of predictors on AAV relapse risk, phenotype and serotype. Results Residential latitude was positively correlated (OR:1.41, 95% CI 1.14–1.74, p = 0.002) and average vitD-UVB negatively correlated (0.82, 0.70–0.99, p = 0.04) with relapse risk, with a stronger effect when restricting to winter measurements (0.71, 0.57–0.89, p = 0.002). However, these associations were not restricted to granulomatous phenotypes. We observed no clear relationship between latitude, vitD-UVB or CW-D-UVB and AAV phenotype or serotype. Conclusion Our findings suggest that low winter ambient UVB and prolonged vitD status contribute to AAV relapse risk across all phenotypes. However, development of a granulomatous phenotype does not appear to be directly vitD-mediated. Further research is needed to determine whether sufficient vitD status would reduce relapse propensity in AAV.

Anthropogenic pollution has frequently been linked to myriad human ailments despite clear mechanistic links are yet lacking, a fact that severely downgraded its actual relevance. Now a prominent unnoticed sub-weekly cycle (SWC) of 3.5 days is uncovered in the long-term epidemiological records of Kawasaki disease (KD) in Japan, a mysterious vasculitis of yet unknown origin. After ruling out the effect of reporting biases, the analysis of Light Detection and Ranging (LIDAR) atmospheric profiles further confirms that this variability is linked to atmospheric particles with an aerodynamic diameter less than 1 micron. SWC accounts for 20% of the variance in KD and its contribution is stable throughout the entire epidemiological record dating back to 1970, both at the prefecture level and for entire Japan. KD maxima in 2010-2016 always occur in full synchrony with LIDAR particle arrival in diverse locations such as Tokyo, Toyama and Tsukuba as well as for the entire of Japan. Rapid intrusion of aerosols from heights up to 6km to the surface is observed with KD admissions co-varying with their metal chemical composition. While regional intensity of winds has not changed in the interval 1979-2015, our study instead points for the first time to increased anthropogenic pollution as a necessary co-factor in the occurrence of KD and sets the field to associate other similar human vasculitis.