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  • Olofson, Jan, 1947, et al. (författare)
  • The single breath nitrogen test and mortality - A 38 years follow up
  • 2016
  • Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 112, s. 75-80
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Spirometry data predict mortality, but are less sensitive to detect dysfunction in small airways as compared to the slope of phase III (the N-2 slope) of the single breath nitrogen test. The association between the N-2 slope and mortality has been studied with conflicting results. In the present study the prognostic importance of the N-2 slope was tested taking spirometry variables into account. Methods: A systematic general population sample of 595 middle-aged men had a baseline investigation with lung function tests including spirometry and the N-2 slope. Age, smoking, and anthropometry variables were registered. The cohort was followed up regarding survival for 38 years. Results: The sample was subdivided by tertiles of the N-2 slope. A proportional hazards regression analysis was performed for each group of covariates: anthropometric, smoking variables, and spirometry variables, after accounting for age. Covariates with significant impact on mortality and the highest chi-square levels were smoking habit score and forced expired volume in 1 s corrected for height. These variables, in addition to age and the N-2 tertiles were entered into a final proportional hazards regression analysis. In this multivariate model, mortality was significantly related to age (p < .0001), smoking habit score (p < .0001) and the N-2 tertiles (p = .0004), but not to FEV1 when N-2 slope was allowed for in the model. Conclusions: Dysfunction in small airways as measured by the N-2 slope is significantly associated with overall mortality in middle-aged men, and outrivals spirometry as a predictor in multivariate analysis.
  • Palm, Andreas, 1971-, et al. (författare)
  • Course of DISease in patients reported to the Swedish CPAP Oxygen and VEntilator RegistrY (DISCOVERY) with population-based controls
  • 2020
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 10:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Chronic hypoxic and hypercapnic respiratory failure and obstructive sleep apnoea (OSA) are chronic diseases associated with decreased quality of life and increased mortality. The rationale behind the set up the retrospective nationwide DISCOVERY cohort was to study several questions including disease course and risk factors for incident disease, impaired quality of life, hospitalisation risk and mortality in patients with chronic respiratory failure with long-term oxygen therapy (LTOT), long-term mechanical ventilation (LTMV) and obstructive sleep apnoea (OSA) on treatment with continuous positive airway pressure (CPAP). Participants and settings Data from the national quality registry for respiratory insufficiency and sleep apnoea (Swedevox) and a population-based control group from Statistics Sweden were merged with governmental registries, the Swedish Cancer Registry, the Swedish Cause of Death Registry, the Swedish Drug registry, the Swedish National Patient Registry and the Swedish Dental Health Registry and with national quality registries for diabetes, rheumatic diseases (Swedish Rheumatology Quality Registry), stroke (RiksStroke), heart failure (RiksSvikt), acute heart infarction care (SwedeHeart) and intensive care (SIR) and with socioeconomic data from Statistics Sweden (SCB). Findings to date The cohort comprises 25 804 unique patients with LTOT since 1987 (54.1% females, age 73.3±9.8 years, body mass index (BMI) 26.6±6.5 kg/m 2), 8111 with LTMV since 1996 (48.6% women, age 60.6±16.9 years, BMI 32.9±10.8 kg/m 2), 65 809 with OSA on CPAP since 2010 (29.5% women, age 57.2±12.5 years, BMI 31.9±6.2 kg/m 2) and 145 224 persons in a population-based control group from same time span up to March 2018 (51.7% women, age 49.9±20.4 year, BMI 24.9±4.0 years). Future plans In patients with chronic respiratory failure and sleep apnoea important questions regarding comorbidity burden, hospitalisation rate, mortality and treatment outcomes are still unexplored to a large extent. The DISCOVERY cohort will provide unique opportunities by its size and comprehensiveness to fill this clinically relevant gap of knowledge. © 2020 Author(s). Published by BMJ.
  • Rydell, Andreas, et al. (författare)
  • Endothelial dysfunction is associated with impaired lung function in two independent community cohorts
  • 2018
  • Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 143, s. 123-128
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundPrior studies investigating the association between endothelial dysfunction and impaired lung function have been small and inconsistent. The primary aim was to investigate the association between endothelial function and lung function in two community-based cohorts.MethodsWe used a discovery/replication approach to study the association between endothelial function and lung function in the Prospective investigation of Obesity, Energy and Metabolism (POEM, discovery cohort, n = 490, mean age 50.3 ± 0.2 years) and the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, replication cohort, n = 892, mean age 70.2 ± 0.15 years). Spirometry and three different measures of endothelial function were performed including both the invasive forearm technique (endothelium-dependent and endothelium-independent vasodilation [EDV and EIDV, respectively] and noninvasive flow mediated dilation [FMD]).ResultsAn age and sex adjusted association between lower EDV and lower FEV1 was found in POEM and replicated in PIVUS. After merging the two cohorts, 1 standard deviation decrease in EDV was associated with 1.57% lower FEV1 after additional adjustment for smoking status, body mass index, exercise level, and C-reactive protein (95% confidence intervals 0.63–2.51, p = 0.001). The association was slightly lower albeit still statistically significant after excluding participants without cardiovascular disease and chronic respiratory disease and appeared stronger among previous/current smokers vs. non-smokers and in men vs. women (p for interaction = 0.2 and 0.02 respectively).ConclusionsOur findings suggest that even individuals with sub-clinical impairments of lung function in the community have concomitant endothelial dysfunction.
  • Rydell, Andreas, et al. (författare)
  • Plasma proteomics and lung function in four community-based cohorts
  • 2021
  • Ingår i: Respiratory Medicine. - : Elsevier. - 0954-6111 .- 1532-3064. ; 176
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Underlying mechanism leading to impaired lung function are incompletely understood.OBJECTIVES: To investigate whether protein profiling can provide novel insights into mechanisms leading to impaired lung function.METHODS: We used four community-based studies (n = 2552) to investigate associations between 79 cardiovascular/inflammatory proteins and forced expiratory volume in 1 s percent predicted (FEV1%) assessed by spirometry. We divided the cohorts into discovery and replication samples and used risk factor-adjusted linear regression corrected for multiple comparison (false discovery rate of 5%). We performed Mendelian randomization analyses using genetic and spirometry data from the UK Biobank (n = 421,986) to assess causality.MEASUREMENTS AND MAIN RESULTS: In cross-sectional analysis, 22 proteins were associated with lower FEV1% in both the discovery and replication sample, regardless of stratification by smoking status. The combined proteomic data cumulatively explained 5% of the variation in FEV1%. In longitudinal analyses (n = 681), higher plasma levels of growth differentiation factor 15 (GDF-15) and interleukin 6 (IL-6) predicted a more rapid 5-year decline in lung function (change in FEV1% per standard deviation of protein level -1.4, (95% CI, -2.5 to -0.3) for GDF-15, and -0.8, (95% CI, -1.5 to -0.2) for IL-6. Mendelian randomization analysis in UK-biobank provided support for a causal effect of increased GDF-15 levels and reduced FEV1%.CONCLUSIONS: Our combined approach identified GDF-15 as a potential causal factor in the development of impaired lung function in the general population. These findings encourage additional studies evaluating the role of GDF-15 as a causal factor for impaired lung function.
  • Sawalha, Sami, et al. (författare)
  • The impact of comorbidities on mortality among men and women with COPD: report from the OLIN COPD study
  • 2019
  • Ingår i: Therapeutic Advances in Respiratory Disease. - : SAGE Publications. - 1753-4658 .- 1753-4666. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Comorbidities probably contribute to the increased mortality observed among subjects with chronic obstructive pulmonary disease (COPD), but sex differences in the prognostic impact of comorbidities have rarely been evaluated in population-based studies. The aim of this study was to evaluate the impact of common comorbidities, cardiovascular disease (CVD), diabetes mellitus (DM), and anxiety/depression (A/D), on mortality among men and women with and without airway obstruction in a population-based study. Methods: All subjects with airway obstruction [forced expiratory volume in 1 second (FEV1)/(forced) vital capacity ((F)VC) <0.70, n = 993] were, together with age- and sex-matched referents, identified after examinations of population-based cohorts in 2002-2004. Spirometric groups: normal lung function (NLF) and COPD (post-bronchodilator FEV1/(F)VC <0.70) and additionally, LLN-COPD (FEV1/(F)VC
  • Sigurðardóttir, E. S., et al. (författare)
  • Female sex hormones and symptoms of obstructive sleep apnea in European women of a population-based cohort
  • 2022
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The prevalence of obstructive sleep apnea is higher in women after menopause. This is suggested to be a result of an altered sex hormone balance but has so far not been confirmed in a population-based study. Objective To investigate whether serum concentration of estrogens and progesterone are associated with the prevalence of sleep apnea symptoms in middle-aged women of the general population. Methods We analyzed data from 774 women (40–67 years) from 15 study centers in seven countries participating in the second follow-up of the European Community Respiratory Health Survey (2010–2012). Multiple logistic regression models were fitted with self-reported symptoms of sleep apnea as outcomes and serum concentrations of various estrogens and progesterone as predictors. All analyses were adjusted for relevant covariates including age, BMI, education, study center, smoking habits, and reproductive age. Results Among all included women, a doubling of serum concentrations of estrone and progesterone was associated with 19% respectively 9% decreased odds of snoring. Among snorers, a doubling of the concentrations of 17β-estradiol, estrone and estrone 3-sulfate was associated with 18%, 23% and 17% decreased odds of breathing irregularly, and a doubling of the progesterone concentration was further associated with 12% decreased odds of waking up suddenly with a chocking sensation. Other evaluated associations were not statistically significant. Conclusions Middle-aged women with low serum estrogen and progesterone levels are more likely to snore and report symptoms of obstructive sleep apnea.
  • Voss, Erica A, et al. (författare)
  • Contextualising adverse events of special interest to characterise the baseline incidence rates in 24 million patients with COVID-19 across 26 databases: a multinational retrospective cohort study.
  • 2023
  • Ingår i: EClinicalMedicine. - 2589-5370. ; 58
  • Tidskriftsartikel (refereegranskat)abstract
    • Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population.A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases.Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism.Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term.None.
  • Wackernagel, Dirk, et al. (författare)
  • Enteral supplementation with arachidonic and docosahexaenoic acid and pulmonary outcome in extremely preterm infants
  • 2024
  • Ingår i: Prostaglandins Leukotrienes and Essential Fatty Acids. - 0952-3278 .- 1532-2823. ; 201
  • Tidskriftsartikel (refereegranskat)abstract
    • Enteral supplementation with arachidonic acid (AA) and docosahexaenoic acid (DHA) in extremely preterm infants has shown beneficial effects on retinopathy of prematurity and pulmonary outcome whereas exclusive DHA supplementation has been associated with increased pulmonary morbidity. This secondary analysis evaluates pulmonary outcome in 204 extremely preterm infants, randomized to receive AA (100 mg/kg/day) and DHA (50 mg/kg/day) enterally from birth until term age or standard care. Pulmonary morbidity was primarily assessed based on severity of bronchopulmonary dysplasia (BPD). Serum levels of AA and DHA during the first 28 days were analysed in relation to BPD. Supplementation with AA:DHA was not associated with increased BPD severity, adjusted OR 1.48 (95 % CI 0.85–2.61), nor with increased need for respiratory support at post menstrual age 36 weeks or duration of oxygen supplementation. Every 1 % increase in AA was associated with a reduction of BPD severity, adjusted OR 0.73 (95 % CI 0.58–0.92). In conclusion, in this study, with limited statistical power, enteral supplementation with AA:DHA was not associated with an increased risk of pulmonary morbidity, but higher levels of AA were associated with less severe BPD. Whether AA or the combination of AA and DHA have beneficial roles in the immature lung needs further research.
  • Yakut, T., et al. (författare)
  • Impact of concomitant obstructive sleep apnea on pulmonary involvement and main pulmonary artery diameter in adults with scleroderma
  • 2021
  • Ingår i: Sleep and Breathing. - : Springer Science and Business Media LLC. - 1520-9512 .- 1522-1709. ; 25:1, s. 135-143
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Pulmonary involvement is common in adults with scleroderma. The effect of concomitant obstructive sleep apnea (OSA) on risk for pulmonary hypertension in scleroderma is unknown. An enlarged main pulmonary artery diameter (mPAD) derived from chest computer tomography (CT) is a useful predictor of pulmonary hypertension. We addressed the effect of OSA on pulmonary involvement and enlarged mPAD in adults with scleroderma. Methods All participants underwent pulmonary function testing, carbon monoxide diffusion capacity, chest CT, and overnight sleep recording with home sleep apnea testing. OSA diagnosis was based on an apnea-hypopnea index (AHI) >= 15/h. Oxygen desaturation index (ODI) was also recorded. Scleroderma involvement of the lungs was defined as the Warrick score >= 7 based on the CT findings. Enlarged mPAD was defined as an mPAD >= 29 mm in men and >= 27 mm in women. Results After exclusions, 62 patients (58 women) were included. OSA was found among 20 (32%), 17/42 (38%) in the limited cutaneous type, and 3/20 (15%) in the diffuse cutaneous type (p = 0.08). Scleroderma involvement of the lungs was observed in 40 participants (65% in OSA vs 64% in no-OSA; n.s.). Enlarged mPAD was measured in 16 participants, 10 of 20 (50%) in the OSA group and 6 of 17 (14%) in the no-OSA group (p = 0.003). OSA was associated with enlarged mPAD (odds ratio 4.7, 95% confidence interval 1.1-20.9; p = 0.042) independent of age, body mass index, and pulmonary involvement. There was a linear relationship between mPAD and AHI (r = 0.37; p = 0.003) as well as ODI (r = 0.41; p < 0.001). Conclusions In this cohort, OSA was associated with risk for pulmonary hypertension independent of pulmonary involvement. These findings suggest that assessing the effect of therapy for concomitant OSA in patients with scleroderma is warranted.
  • Ekelund, Ulf, et al. (författare)
  • Effects of the combined ETA and ETB receptor antagonist PD145065 on arteries, arterioles, and veins in the cat hindlimb
  • 1995
  • Ingår i: Journal of Cardiovascular Pharmacology. - 1533-4023. ; 26:Suppl. 3, s. 211-213
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to describe in quantitative terms the effects of ETA and ETB receptor blockade on vascular tone (resistance) in large-bore arterial resistance vessels (> 25 microns), small arterioles (< 25 microns), and veins in the cat gastrocnemius muscle in vivo. In the muscle vascular bed, the combined ETA and ETB receptor antagonist PD145065 (1 mg/kg/min, intra-arterially) abolished the biphasic vascular responses (dilatation followed by constriction) to both ET-1 (0.4 microgram/kg/min, intra-arterially) and to the selective ETB receptor agonist IRL1620 (3.2 micrograms/kg/min, intra-arterially). In the cat femoral artery and vein in vitro, PD145065 competitively inhibited the contractile responses to both ET-1 and IRL1620. The contractile response to the latter agonist could be evoked only after long-term incubation of the vessels (37 degrees C for 5 days). These results indicate that PD145065 is a potent antagonist at both ETA and ETB receptors in vivo and in vitro. Therefore, this antagonist may prove useful for elucidating the possible physiologic and/or pathophysiologic roles of the endothelins. For example, it was shown that PD145065 had no effect on vascular tone in the resting state, indicating no role for the endothelins in the regulation of basal vascular tone in cat skeletal muscle.
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