Aims-To compare the respiratory health and function at 8 to 9 years of age of a total population based cohort of 300 very low birthweight (VLBW) children with that of two classroom controls (n=590) matched for age and sex. Study design-Cohort study with controls. Setting-Schools throughout Scotland. Results-The VLBW children were more likely than their peers to use an inhaler, to be absent from school, and to be admitted to hospital because of respiratory illness. They were significantly shorter than their classroom controls, but even after adjusting for differences in height, the VLBW children had reduced forced vital capacity (FVC); this was associated with a history of prolonged ventilation (>28 days) and pneumothorax in the neonatal period. There were no significant differences between the groups in forced expiratory volume in one second (FEV,)/FVC but twice as many (7.9% v 3.7%) of the VLBW children had ratios <700/0, denoting obstructive airways disease. Poor expiratory function was associated with neonatal respiratory distress syndrome, prolonged ventilation, and the need for >40Gb oxygen. Exercise induced airway narrowing was increased in VLBW children (odds ratio=2-0; 95% confidence interval 1*2 to 3.4) and was very little changed by adjustment for inhaler use and exposure to cigarette smoke.Conclusions-As in other low birthweight cohorts, respiratory morbidity was increased. Unlike previous studies, FVC was more affected than expiratory function in this VLBW population. Our findings support the hypothesis that poorer lung function is associated with very low birth weight, but not with intrauterine growth retardation.

This is the first report on the EQ-5D utility values of patients with PSS. These patients have significantly impaired utility values compared with the UK general population. EQ-5D utility values are significantly related to pain and depression scores in PSS.

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. MethodsWe did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. FindingsIn the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo.Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases.

No abstract

ObjectivesThis article reports relationships between serum cytokine levels and patient-reported levels of fatigue, in the chronic immunological condition primary Sjögren's syndrome (pSS).MethodsBlood levels of 24 cytokines were measured in 159 patients with pSS from the United Kingdom Primary Sjögren's Syndrome Registry and 28 healthy non-fatigued controls. Differences between cytokines in cases and controls were evaluated using Wilcoxon test. Patient-reported scores for fatigue were evaluated, classified according to severity and compared with cytokine levels using analysis of variance. Logistic regression was used to determine the most important predictors of fatigue levels.Results14 cytokines were significantly higher in patients with pSS (n=159) compared to non-fatigued healthy controls (n=28). While serum levels were elevated in patients with pSS compared to healthy controls, unexpectedly, the levels of 4 proinflammatory cytokines—interferon-γ-induced protein-10 (IP-10) (p=0.019), tumour necrosis factor-α (p=0.046), lymphotoxin-α (p=0.034) and interferon-γ (IFN-γ) (p=0.022)—were inversely related to patient-reported levels of fatigue. A regression model predicting fatigue levels in pSS based on cytokine levels, disease-specific and clinical parameters, as well as anxiety, pain and depression, revealed IP-10, IFN-γ (both inversely), pain and depression (both positively) as the most important predictors of fatigue. This model correctly predicts fatigue levels with reasonable (67%) accuracy.ConclusionsCytokines, pain and depression appear to be the most powerful predictors of fatigue in pSS. Our data challenge the notion that proinflammatory cytokines directly mediate fatigue in chronic immunological conditions. Instead, we hypothesise that mechanisms regulating inflammatory responses may be important.

Objective. Several studies have demonstrated that primary Sjö gren's syndrome (SS) is associated with reduced productivity; however, the impact of primary SS on daily function is not fully understood. This study aims to assess the physical function of primary SS patients and determine the relationship between the functional impairment experienced by primary SS patients and disease activity, patient-reported symptoms, and quality of life. Methods. Sixty-nine primary SS patients from a specialist clinical service were assessed for their functional ability (Improved Health Assessment Questionnaire [HAQ]), dryness, pain, and overall primary SS-related symptom burden; systemic disease activity; levels of fatigue, daytime somnolence, anxiety, and depression symptoms; quality of life; and systemic inflammation (erythrocyte sedimentation rate, C-reactive protein [CRP] level). Data were compared to 69 healthy volunteers matched for age and sex. Results. Primary SS patients experienced greater functional impairment than controls (Improved HAQ total scores: mean ؎ SD 24 ؎ 25 for primary SS versus 9 ؎ 19 for controls; P ‫؍‬ 0.0002) across all domains of activity. In primary SS, functional impairment was significantly associated with physical fatigue (P < 0.0001, R 2 ‫؍‬ 0.3), pain (P < 0.0001, R 2 ‫؍‬ 0.3), depression (P < 0.0001, R 2 ‫؍‬ 0.3), total symptom burden (P < 0.0001, R 2 ‫؍‬ 0.3), systemic disease activity (P ‫؍‬ 0.002, R 2 ‫؍‬ 0.15), quality of life (P < 0.0001, R 2 ‫؍‬ 0.3), dryness (P ‫؍‬ 0.002, R 2 ‫؍‬ 0.12), daytime somnolence (P ‫؍‬ 0.02, R 2 ‫؍‬ 0.08), anxiety score (P ‫؍‬ 0.03, R 2 ‫؍‬ 0.07), and CRP level (P ‫؍‬ 0.04, R 2 ‫؍‬ 0.06). Only CRP level is independently associated with functional impairment (␤ ‫؍‬ 0.38, P ‫؍‬ 0.025). Conclusion. Primary SS patients experience significant functional disability compared to age-matched healthy controls. Impaired function is associated with reduced quality of life and symptoms such as pain, fatigue, and depression, as well as disease activity, illustrating the importance of optimal management of all aspects of the disease.

ObjectivesTo determine the prevalence of autonomic dysfunction (dysautonomia) among patients with primary Sjögren's syndrome (PSS) and the relationships between dysautonomia and other clinical features of PSS.MethodsMulticentre, prospective, cross-sectional study of a UK cohort of 317 patients with clinically well-characterised PSS. Symptoms of autonomic dysfunction were assessed using a validated instrument, the Composite Autonomic Symptom Scale (COMPASS). The data were compared with an age- and sex-matched cohort of 317 community controls. The relationships between symptoms of dysautonomia and various clinical features of PSS were analysed using regression analysis.ResultsCOMPASS scores were significantly higher in patients with PSS than in age- and sex-matched community controls (median (IQR) 35.5 (20.9–46.0) vs 14.8 (4.4–30.2), p<0.0001). Nearly 55% of patients (vs 20% of community controls, p<0.0001) had a COMPASS score >32.5, a cut-off value indicative of autonomic dysfunction. Furthermore, the COMPASS total score correlated independently with EULAR Sjögren's Syndrome Patient Reported Index (a composite measure of the overall burden of symptoms experienced by patients with PSS) (β=0.38, p<0.001) and disease activity measured using the EULAR Sjögren's Syndrome Disease Activity Index (β=0.13, p<0.009).ConclusionsAutonomic symptoms are common among patients with PSS and may contribute to the overall burden of symptoms and link with systemic disease activity.

ObjectiveTo determine the prevalence of traditional cardiovascular risk factors using established definitions in a large cohort of clinically well-characterized primary Sjögren's syndrome (SS) patients and to compare them to healthy controls.MethodsData on cardiovascular risk factors in primary SS patients and controls were collected prospectively using a standardized pro forma. Cardiovascular risk factors were defined according to established definitions. The prevalence of cardiovascular risk factors in the primary SS group was determined and compared to that in the control group.ResultsPrimary SS patients had a higher prevalence of hypertension (28–50% versus 15.5–25.6%; P < 0.01) and hypertriglyceridemia (21% versus 9.5%; P = 0.002) than age- and sex-matched healthy controls. Furthermore, a significant percentage (56%) of hypertensive patients expected to be on antihypertensive treatment according to best practice was not receiving it.ConclusionPrimary SS patients are more than 2 times more likely to experience hypertension and hypertriglyceridemia than age- and sex-matched healthy controls. Additionally, hypertension is underdiagnosed and suboptimally treated in primary SS.