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- Damato, V, et al.
(författare)
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Rituximab abrogates aquaporin-4-specific germinal center activity in patients with neuromyelitis optica spectrum disorders
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 119:24, s. e2121804119-
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Tidskriftsartikel (refereegranskat)abstract
- By studying paired blood and deep cervical lymph node samples from patients with neuromyelitis optica spectrum disorders, our data provide evidence for a germinal center–based generation of aquaporin-4 antibodies. Frequent serum aquaporin-4 immunoglobulin Ms (IgMs) and shifts in IgG subclasses were observed alongside preferential synthesis of aquaporin-4 IgGs and aquaporin-4–reactive B cells within lymph nodes. Both intranodal synthesis of aquaporin-4 antibodies and intranodal aquaporin-4–reactive B cells were robustly eliminated with rituximab administration. This study systematically explores lymph nodes that drain the central nervous system (CNS) in patients with CNS autoimmunity and offers a potential explanation as to why rituximab is clinically highly efficacious in autoantibody-mediated diseases despite no accompanying reduction in serum autoantibody levels.
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- Palm, A., et al.
(författare)
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Cancer prevalence is increased in obstructive sleep apnea - the population-based DISCOVERY study
- 2022
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 60:Suppl. 66
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Nocturnal hypoxia in obstructive sleep apnea (OSA) is a potential risk factor for cancer disease but data are conflicting. We aimed to investigate the association between OSA measures and cancer prevalence in a large national OSA patient cohort.Methods: Population-based, cross-sectional study on patients initiating CPAP therapy between July 2010 and March 2018 in Sweden (n=62,811), with crosslinked data from the National Cancer Registry and socio-economic data from Statistics Sweden. After propensity score matching for anthropometric data, comorbidities, socio-economic status, smoking prevalence, the association between all-cause and subtype cancer diagnosis 5 years prior to start of PAP treatment and sleep apnea severity, measured as apnea hypopnea index (AHI) or oxygen desaturation index (ODI), was analyzed using chi2-tests.Results: 2,093 OSA patients with cancer (age 65.3±10.1 years, BMI 30 (IQR 27-34) kg/m2, 29.8% females) had higher AHI (32 (IQR 20-50) versus 30 (19-45), event/hour, p=0.002) and ODI (28 (17-46) versus 26 (16-41) events/hour, p<0.001) when compared with matched OSA patients without cancer. Subgroup analysis confirmed that ODI was significantly higher in OSA patients with lung cancer (38 (21-61) versus 27 (16-43), p=0.012, N=57), prostate cancer (28 (17-46) versus 24 (16-39), p=0.005, N=617), and malignant melanoma (32 (17-46) versus 25 (14-41), p=0.015, N=170).Conclusion: OSA mediated intermittent hypoxia was independently associated with cancer in this large, national cohort. Future longitudinal studies are warranted to study the potential influence of OSA treatment on cancer incidence.
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- Åkerstedt, T, et al.
(författare)
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Total sleep time, sleep efficiency, and next day subjective sleepiness in a large group of women
- 2022
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Ingår i: Sleep advances : a journal of the Sleep Research Society. - : Oxford University Press (OUP). - 2632-5012. ; 3:1, s. zpac028-
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Tidskriftsartikel (refereegranskat)abstract
- The relationship between sleep duration and sleepiness has seen much research, but no data are available on the association between polysomnographically (PSG) determined total sleep time (TST) (or other PSG variables) and subjective sleepiness during the subsequent day in individuals in their habitual life situation. The purpose of the present study was to study the association between TST and sleep efficiency (SE) (and other PSG variables) and next-day sleepiness at 7 times of the day. A large population-based group of women (N = 400) participated. Daytime sleepiness was measured with the Karolinska Sleepiness Scale (KSS). The association was studied through analysis of variance (ANOVA), as well as regression analyses. For SE there was a significant difference in sleepiness across groups with >90%, 80%–89.99%, and <80% SE (F = 7.2, p < .001, eta2 = 0.04), with lowest sleepiness in the first group. In contrast, TST groups of <6 h, 6–6.99 h, and ≥7 h did not differ significantly. In addition, a pronounced U-shape (eta2 > 0.45) was seen for both analyses, with maximum sleepiness at bedtime (≈ 7.5 KSS units). A multiple regression analysis, including all PSG variables (adjusted for age and BMI), showed that SE was a significant predictor (β = 0.16, p < .05) of mean sleepiness, even after depression, anxiety, and subjective sleep duration were entered, but this was eliminated by subjective sleep quality. It was concluded that high SE is modestly associated with lower next-day sleepiness in women in a real-life context, but that TST is not.
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- Baldanzi, Gabriel, et al.
(författare)
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OSA Is Associated With the Human Gut Microbiota Composition and Functional Potential in the Population-Based Swedish CardioPulmonary bioImage Study
- 2023
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Ingår i: Chest. - : Elsevier. - 0012-3692 .- 1931-3543. ; 164:2, s. 503-516
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Obstructive sleep apnea (OSA) is a common sleep-breathing disorder linked to increased risk of cardiovascular disease. Intermittent hypoxia and intermittent airway obstruction, hallmarks of OSA, have been shown in animal models to induce substantial changes to the gut microbiota composition and subsequent transplantation of fecal matter to other animals induced changes in blood pressure and glucose metabolism.RESEARCH QUESTION: Does obstructive sleep apnea in adults associate with the composition and metabolic potential of the human gut microbiota?STUDY DESIGN AND METHODS: We used respiratory polygraphy data from up to 3,570 individuals aged 50-64 from the population-based Swedish CardioPulmonary bioImage Study combined with deep shotgun metagenomics of fecal samples to identify cross-sectional associations between three OSA parameters covering apneas and hypopneas, cumulative sleep time in hypoxia and number of oxygen desaturation events with gut microbiota composition. Data collection about potential confounders was based on questionnaires, on-site anthropometric measurements, plasma metabolomics, and linkage with the Swedish Prescribed Drug Register.RESULTS: We found that all three OSA parameters were associated with lower diversity of species in the gut. Further, the OSA-related hypoxia parameters were in multivariable-adjusted analysis associated with the relative abundance of 128 gut bacterial species, including higher abundance of Blautia obeum and Collinsela aerofaciens. The latter species was also independently associated with increased systolic blood pressure. Further, the cumulative time in hypoxia during sleep was associated with the abundance of genes involved in nine gut microbiota metabolic pathways, including propionate production from lactate. Lastly, we observed two heterogeneous sets of plasma metabolites with opposite association with species positively and negatively associated with hypoxia parameters, respectively.INTERPRETATION: OSA-related hypoxia, but not the number of apneas/hypopneas, is associated with specific gut microbiota species and functions. Our findings lay the foundation for future research on the gut microbiota-mediated health effects of OSA.
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- Ekstrom, M., et al.
(författare)
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Validation of the Swedevox registry of continuous positive airway pressure, long-term mechanical ventilator and long-term oxygen therapy
- 2021
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Ingår i: Erj Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Swedish Registry of Respiratory Failure (Swedevox) collects nationwide data on patients starting continuous positive airway pressure (CPAP) treatment, long-term mechanical ventilator (LTMV) and long-term oxygen therapy (LTOT). We validated key information in Swedevox against source data from medical records. Methods: This was a retrospective validation study of patients starting CPAP (n=175), LTMV (n=177) or LTOT (n=175) across seven centres 2013-2017. Agreement with medical record data was analysed using differences in means (SD) and proportion (%) of a selection of clinically relevant variables. Variables of interest included for CPAP: apnoea-hypopnoea index (AHI), height, weight, body mass index (BMI) and Epworth Sleepiness Scale (ESS) score; for LTMV: date of blood gas, arterial carbon dioxide tension (P-aCO2) (breathing air), weight and diagnosis group; and for LTOT: blood gases breathing air and oxygen, spirometry and main diagnosis. Results: Data on CPAP and LTOT had very high validity across all evaluated variables (all <5% discrepancy). For LTMV, variability was higher against source information for P-aCO2 (>0.5 kPa in 25.9%), weight (>5 kg in 47.5%) and diagnosis group. Inconsistency was higher for patients starting LTMV acutely versus electively (P-aCO2 difference >0.5 kPa in 36% versus 21%, p<0.05, respectively). However, there were no signs of systematic bias (mean differences close to zero) across the evaluated variables. Conclusion: Validity of Swedevox data, compared with medical records, was very high for CPAP, LTMV and LTOT. The large sample size and lack of systematic differences support that Swedevox data are valid for healthcare quality assessment and research.
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- Ervasti, Jenni, et al.
(författare)
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Long working hours and risk of 50 health conditions and mortality outcomes : a multicohort study in four European countries
- 2021
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Ingår i: The Lancet Regional Health. - : Elsevier BV. - 2666-7762. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies on the association between long working hours and health have captured only a narrow range of outcomes (mainly cardiometabolic diseases and depression) and no outcome-wide studies on this topic are available. To achieve wider scope of potential harm, we examined long working hours as a risk factor for a wide range of disease and mortality endpoints.Methods: The data of this multicohort study were from two population cohorts from Finland (primary analysis, n=59 599) and nine cohorts (replication analysis, n=44 262) from Sweden, Denmark, and the UK, all part of the Individual-participant Meta-analysis in Working Populations (IPD-Work) consortium. Baseline-assessed long working hours (≥55 hours per week) were compared to standard working hours (35-40 h). Outcome measures with follow-up until age 65 years were 46 diseases that required hospital treatment or continuous pharmacotherapy, all-cause, and three cause-specific mortality endpoints, ascertained via linkage to national health and mortality registers.Findings: 2747 (4·6%) participants in the primary cohorts and 3027 (6·8%) in the replication cohorts worked long hours. After adjustment for age, sex, and socioeconomic status, working long hours was associated with increased risk of cardiovascular death (hazard ratio 1·68; 95% confidence interval 1·08-2·61 in primary analysis and 1·52; 0·90-2·58 in replication analysis), infections (1·37; 1·13-1·67 and 1·45; 1·13-1·87), diabetes (1·18; 1·01-1·38 and 1·41; 0·98-2·02), injuries (1·22; 1·00-1·50 and 1·18; 0·98-1·18) and musculoskeletal disorders (1·15; 1·06-1·26 and 1·13; 1·00-1·27). Working long hours was not associated with all-cause mortality.Interpretation: Follow-up of 50 health outcomes in four European countries suggests that working long hours is associated with an elevated risk of early cardiovascular death and hospital-treated infections before age 65. Associations, albeit weak, were also observed with diabetes, musculoskeletal disorders and injuries. In these data working long hours was not related to elevated overall mortality.
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