| 1. |
- Abdel-Aziz, Mahmoud I., et al.
(författare)
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A multi-omics approach to delineate sputum microbiome-associated asthma inflammatory phenotypes
- 2022
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 59:1
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Tidskriftsartikel (refereegranskat)abstract
- A multi-omics approach revealed the underlying biological pathways in the microbiome-driven severe asthma phenotypes. This may help to elucidate new leads for treatment development, particularly for the therapeutically challenging neutrophilic asthma.
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| 2. |
- Brinkman, Paul, et al.
(författare)
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Identification and prospective stability of electronic nose (eNose)-derived inflammatory phenotypes in patients with severe asthma
- 2019
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:5, s. 1811-1820.e7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Severe asthma is a heterogeneous condition, as shown by independent cluster analyses based on demographic, clinical, and inflammatory characteristics. A next step is to identify molecularly driven phenotypes using “omics” technologies. Molecular fingerprints of exhaled breath are associated with inflammation and can qualify as noninvasive assessment of severe asthma phenotypes.Objectives: We aimed (1) to identify severe asthma phenotypes using exhaled metabolomic fingerprints obtained from a composite of electronic noses (eNoses) and (2) to assess the stability of eNose-derived phenotypes in relation to withinpatient clinical and inflammatory changes.Methods: In this longitudinal multicenter study exhaled breath samples were taken from an unselected subset of adults with severe asthma from the U-BIOPRED cohort. Exhaled metabolites were analyzed centrally by using an assembly of eNoses. Unsupervised Ward clustering enhanced by similarity profile analysis together with K-means clustering was performed. For internal validation, partitioning around medoids and topological data analysis were applied. Samples at 12 to 18 months of prospective follow-up were used to assess longitudinal within-patient stability.Results: Data were available for 78 subjects (age, 55 years [interquartile range, 45-64 years]; 41% male). Three eNosedriven clusters (n = 26/33/19) were revealed, showing differences in circulating eosinophil (P = .045) and neutrophil (P = .017) percentages and ratios of patients using oral corticosteroids (P = .035). Longitudinal within-patient cluster stability was associated with changes in sputum eosinophil percentages (P = .045).Conclusions: We have identified and followed up exhaled molecular phenotypes of severe asthma, which were associated with changing inflammatory profile and oral steroid use. This suggests that breath analysis can contribute to the management of severe asthma.
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| 3. |
- Gisslander, Karl, et al.
(författare)
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Data quality and patient characteristics in European ANCA-associated vasculitis registries : data retrieval by federated querying
- 2023
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Ingår i: Annals of the Rheumatic Diseases. - 0003-4967. ; 83:1, s. 112-120
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Tidskriftsartikel (refereegranskat)abstract
- Objectives This study aims to describe the data structure and harmonisation process, explore data quality and define characteristics, treatment, and outcomes of patients across six federated antineutrophil cytoplasmic antibody-associated vasculitis (AAV) registries. Methods Through creation of the vasculitis-specific Findable, Accessible, Interoperable, Reusable, VASCulitis ontology, we harmonised the registries and enabled semantic interoperability. We assessed data quality across the domains of uniqueness, consistency, completeness and correctness. Aggregated data were retrieved using the semantic query language SPARQL Protocol and Resource Description Framework Query Language (SPARQL) and outcome rates were assessed through random effects meta-analysis. Results A total of 5282 cases of AAV were identified. Uniqueness and data-type consistency were 100% across all assessed variables. Completeness and correctness varied from 49%-100% to 60%-100%, respectively. There were 2754 (52.1%) cases classified as granulomatosis with polyangiitis (GPA), 1580 (29.9%) as microscopic polyangiitis and 937 (17.7%) as eosinophilic GPA. The pattern of organ involvement included: lung in 3281 (65.1%), ear-nose-throat in 2860 (56.7%) and kidney in 2534 (50.2%). Intravenous cyclophosphamide was used as remission induction therapy in 982 (50.7%), rituximab in 505 (17.7%) and pulsed intravenous glucocorticoid use was highly variable (11%-91%). Overall mortality and incidence rates of end-stage kidney disease were 28.8 (95% CI 19.7 to 42.2) and 24.8 (95% CI 19.7 to 31.1) per 1000 patient-years, respectively. Conclusions In the largest reported AAV cohort-study, we federated patient registries using semantic web technologies and highlighted concerns about data quality. The comparison of patient characteristics, treatment and outcomes was hampered by heterogeneous recruitment settings.
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| 4. |
- Hellmich, Bernhard, et al.
(författare)
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EULAR recommendations for the management of ANCA-associated vasculitis : 2022 update
- 2024
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 83:1, s. 30-47
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Tidskriftsartikel (refereegranskat)abstract
- Background: Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several randomised clinical trials have been published that have the potential to change clinical care and support the need for an update. Methods: Using EULAR standardised operating procedures, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 16 countries. We modified existing recommendations and created new recommendations. Results: Four overarching principles and 17 recommendations were formulated. We recommend biopsies and ANCA testing to assist in establishing a diagnosis of AAV. For remission induction in life-threatening or organ-threatening AAV, we recommend a combination of high-dose glucocorticoids (GCs) in combination with either rituximab or cyclophosphamide. We recommend tapering of the GC dose to a target of 5 mg prednisolone equivalent/day within 4-5 months. Avacopan may be considered as part of a strategy to reduce exposure to GC in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis. For remission maintenance of GPA/MPA, we recommend rituximab. In patients with relapsing or refractory eosinophilic GPA, we recommend the use of mepolizumab. Azathioprine and methotrexate are alternatives to biologics for remission maintenance in AAV. Conclusions: In the light of recent advancements, these recommendations provide updated guidance on AAV management. As substantial data gaps still exist, informed decision-making between physicians and patients remains of key relevance.
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| 5. |
- Tesi, Michelangelo, et al.
(författare)
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Mortality Rate by Diagnosis in ANCA-Associated Vasculitis Across FAIRVASC Registries
- 2024
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Ingår i: ; , s. 187-187
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background/ Objectives: Research into ANCA-associated vasculitis (AAV) is hampered by the rarity of the disease and thesubsequent small sample sizes of observational cohorts. This is further aggravated by the observational cohorts being containedin fragmented data pools and lacking standardisation to allow for interoperability. FAIRVASC is a Europe-wide research project,which has developed an infrastructure linking 7 existing AAV registries into a single European dataset, to allow high-qualityresearch on natural disease history and clinical outcomes.This analysis highlights the capabilities of the FAIRVASC infrastructure to assess clinical outcome of AAV across the federatedregistries.Methods: Within the FAIRVASC project, 7 national/regional AAV registries were harmonized using a semantic web approach,including the creation of a dedicated AAV ontology, to enable semantic interoperability. For this study, aggregated data regardingmortality rate (/100 person years, with related 95% Confidence Intervals) per diagnosis were retrieved through the FAIRVASC webinterface, a tool that allows federated querying over linked registries. We defined mortality rate in the first and second year postdiagnosis, and in years 3-5 and after 5 years.Results: Mortality queries were posed over the FAIRVASC registries, namely RKD (Republic of Ireland, 677 patients), GFEV(France, 2814 pts), ANCA (Czech Republic, 377 pts), PolVas (Poland, 944 pts), Skane (Sweden, 374 pts), Italivas (Italy, 301pts), GeVas (Germany, 169 pts). Mortality rates, stratified by diagnosis and registry, are reported in Table 1. The lowest mortalitywas reported for eosinophilic granulomatosis with polyangiitis (EGPA), with rates ranging from 0 to 2.5 cases/100 person-yearsdepending on the post-diagnosis interval. Conversely, the highest mortality was found for microscopic polyangiitis (MPA), withmortality rates ranging from 6.7 to 22.3 across registries in the first year after diagnosis, and from 3.9 to 7.4 after >5 years fromdiagnosis. In patients with granulomatosis with polyangiitis (GPA), mortality rates ranged from 3.3 to 8.2 in the first year afterdiagnosis and from 0.7 to 4.5 after >5 years from diagnosis.Conclusions: The FAIRVASC infrastructure is a reliable tool to query multiple AAV registries for assessing long-term clinicaloutcomes of AAV in a large number of patients, in a privacy-compliant manner.Disclosures: None.
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