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1.	Pan, E., et al. (author) Low rate of reoperations after acute type A aortic dissection repair from The Nordic Consortium Registry 2018 In: Journal of Thoracic and Cardiovascular Surgery. - : Elsevier BV. - 0022-5223 .- 1097-685X. ; 156:3, s. 939-948 Journal article (peer-reviewed)abstract Objectives: To describe the relationship between the extent of primary aortic repair and the incidence of reoperations after surgery for type A aortic dissection. Methods: A retrospective cohort of 1159 patients treated for type A aortic dissection at eight Nordic low-to medium-sized cardiothoracic centers from 2005 to 2014. Data were gathered from patient records and national registries. Patients were separately divided into 3 groups according to the distal anastomoses technique (ascending aorta [n = 791], hemiarch [n = 247], and total arch [n = 66]), and into 2 groups for proximal repair (aortic root replacement [n = 285] and supracoronary repair [n = 832]). Freedom from reoperation was estimated with cumulative incidence survival and Fine-Gray competing risk regression model was used to identify independent risk factors for reoperation. Results: The median follow-up was 2.7 years (range, 0-10 years). Altogether 51 out of 911 patients underwent reoperation. Freedom from distal reoperation at 5 years was 96.9%, with no significant difference between the groups (P = .22). Freedom from proximal reoperation at 5 years was 97.8%, with no difference between the groups (P = .84). Neither DeBakey classification nor the extent of proximal or distal repair predicted freedom from a later reoperation. The only independent risk factor associated with a later proximal reoperation was a history of connective tissue disease. Conclusions: Type A aortic dissection repair in low-to medium-volume centers was associated with a low reoperation rate and satisfactory midterm survival. The extent of the primary repair had no significant influence on reoperation rate or midterm survival.
2.	Willadsen, E., et al. (author) Inter-rater reliability in classification of canonical babbling status based on canonical babbling ratio in infants with isolated cleft palate randomised to Timing of Primary Surgery for Cleft Palate (TOPS) 2023 In: Clinical Linguistics & Phonetics. - : Informa UK Limited. - 0269-9206 .- 1464-5076. ; 37:1, s. 77-98 Journal article (peer-reviewed)abstract Canonical babbling (CB) is commonly defined as present when at least 15% of all syllables produced are canonical, in other words a canonical babbling ratio (CBR) >= 0.15. However, there is limited knowledge about inter-rater reliability in classification of CB status based on CBR and inter-rater differences in assessment of CBR. We investigated inter-rater reliability of experienced Speech Language Therapists (SLTs) on: classification of CB status based on CBR >= 0.15, CBRs and the total number of syllables per infant used to calculate CBR. Each infant (n = 484) was video-recorded at a clinical site in play interaction with their parent as part of the randomised controlled trial Timing of Primary Surgery for Cleft Palate. Each recording was subsequently assessed by three independent SLTs, from a pool of 29 SLTs. They assessed the recordings in real time. The three assessing SLTs agreed in classification of CB status in 423 (87.4%) infants, with higher complete agreement for canonical (91%; 326/358) than non-canonical (77%; 97/126). The average difference in CBR and total number of syllables identified between the SLT assessments of each infant was 0.12 and 95, respectively. This study provided new evidence that one trained SLT can reliably classify CB status (CBR >= 0.15) in real time when there is clear distinction between the observed CBR and the boundary (0.15); however, when the observed CBR approaches the boundary multiple SLT assessments are beneficial. Thus, we recommend to include assessment of inter-rater reliability, if the purpose is to compare CBR and total syllable count across infants or studies.
3.	Lindqvist, A, et al. (author) Artery blood pressure oscillation after active standing up: an indicator of sympathetic function in diabetic patients 1997 In: Clinical Physiology. - : Wiley. - 1365-2281 .- 0144-5979. ; 17:2, s. 159-169 Journal article (peer-reviewed)abstract Dynamic artery blood pressure (Finapres) response to active standing up, normally consisting of initial rise, fall and recovery above the baseline (overshoot), was compared with the early steady-state artery blood pressure level to measure sympathetic vasomotor function in healthy subjects (n = 23, age 35 +/- 9 years; mean +/-SD) and in type I diabetic patients without autonomic neuropathy (AN) (group 1: n = 18, 38 +/- 13 years), with AN but no cardiovascular drugs (group 2a: n = 7, 44 +/- 11 years) and with both AN and cardiovascular drugs (group 2b: n = 10, 47 +/- 7 years). Systolic and diastolic overshoot were similar in the control (15 +/- 13/15 +/- 11 mmHg) and group 1 subjects. Systolic overshoot disappeared in 57% of patients in group 2a (-1 +/- 9 mmHg; P < 0.03), whereas artery blood pressure still overshot in diastole (8 +/- 7 mmHg; NS). Systolic overshoot disappeared in all patients in group 2b (-22 +/- 22 mmHg; P < 0.0006) and diastolic overshoot disappeared in 60% of these patients (-6 +/- 16 mmHg; P = 0.0006). Systolic early steady-state level was not lower in group 2a than in group 1 (NS), but it was impaired in group 2b (P < 0.006), in which six diabetic patients had a pathological response beyond the age-related reference values. There was a strong association between the overshoot and steady-state levels (P for chi 2 < 0.001, n = 58). Overshoot of the control subjects and patients in group 2b correlated to their respective steady-state blood pressure levels (r > or = 0.76; P < or = 0.001). In conclusion, baroreceptor reflex-dependent overshoot of the artery blood pressure after active standing up diminishes with the development of AN and it is associated with the early steady-state level of the artery blood pressure.
4.	Torffvit, Ole, et al. (author) The association between diabetic nephropathy and autonomic nerve function in type 1 diabetic patients 1997 In: Scandinavian Journal of Clinical & Laboratory Investigation. - 1502-7686. ; 57:2, s. 183-191 Journal article (peer-reviewed)abstract Diabetic cardiovascular autonomic neuropathy increases the risk of deterioration in renal function and is associated with increased mortality in patients with renal failure. Type 1 diabetic patients with long diabetes duration, matched for age (38 +/- 9 years) and diabetes duration (28 +/- 8 years) were studied regarding the association between cardiovascular autonomic nerve function and different degrees of diabetic nephropathy. Eighteen patients were normo- (< 30 mg/l), six micro- (30-300 mg/l), and 13 macroalbuminuric (> 300 mg/l) based on urinary albumin concentrations in three separate morning samples. They were compared with 33 control subjects with similar age. Autonomic nerve function was evaluated by measuring the response of heart rate to deep breathing and active standing. Beat-to-beat finger artery blood pressure (Finapres) was tested during active standing. During deep breathing both change in heart rate (17 +/- 11, 9 +/- 7 and 4 +/- 3 beats/min) and ratio between expiratory and inspiratory R-R intervals (1.32 +/- 0.24, 1.14 +/- 0.15 and 1.05 +/- 0.04) decreased from normo- over micro- to macroalbuminuria (p < 0.05 vs normoalbuminuric and control subjects [17 +/- 5 beats/min and 1.28 +/- 0.10, respectively]). Similar results were obtained during active standing with respect to change in systolic arterial blood pressure (3 +/- 8, 2 +/- 13 and -6 +/- 11 mmHg; p < 0.05 vs control subjects [8 +/- 11 mmHg]). However, the response of diastolic arterial blood pressure or mean heart rate to standing up did not differ between any of the groups. The ratio of maximum to minimum R-R interval during the dynamic response of heart rate to active standing decreased with the degree of nephropathy (1.27 +/- 0.17, 1.11 +/- 0.11 and 1.05 +/- 0.06) with significantly higher values in patients with normo- compared with patients with macroalbuminuria (p < 0.05). All patients groups had significantly lower values than control subjects (1.46 +/- 0.22, p < 0.05). The overshoot of the blood pressure after an initial fall during active standing decreased with the degree of diabetic nephropathy. In conclusion, type 1 diabetic patients with long duration of diabetes have signs of cardiovascular autonomic neuropathy, the severity of which is related to the degree of nephropathy.
5.	Fagevik Olsén, Monika, 1964, et al. (author) Evaluation of Pressure Generated by Resistors From Different Positive Expiratory Pressure Devices 2015 In: Respiratory Care. - : Daedalus Enterprises. - 0020-1324 .- 1943-3654. ; 60:10, s. 1418-1423 Journal article (peer-reviewed)abstract BACKGROUND: Breathing exercises with positive expiratory pressure (PEP) are used to improve pulmonary function and airway clearance. Different PEP devices are available, but there have been no studies that describe the pressure generated by different resistors. The purpose of this study was to compare pressures generated from the proprietary resistor components of 4 commercial flow-dependent PEP valves with all other parameters kept constant. METHODS: Resistors from 4 flow-regulated PEP devices (Pep/Rmt system, Wellspect HealthCare; Pipe P breathing exerciser, Koo Medical Equipment; Mini-PEP, Philips Respironics [including resistors by Rusch]; and 15-mm endo-adapter, VBM Medizintechnik) were tested randomly by a blinded tester at constant flows of 10 and 18 L/min from an external gas system. All resistors were tested 3 times. RESULTS: Resistors with a similar diameter produced statistically significant different pressures at the same flow. The differences were smaller when the flow was 10 L/min compared with 18 L/min. The differences were also smaller when the diameter of the resistor was increased. The pressures produced by the 4 resistors of the same size were all significantly different when measuring 1.5- and 2.0-mm resistors at a flow of 10 L/min and 2.0-mm resistors at a flow of 18 L/min (P < .001). There were no significant differences between any of the resistors when testing sizes of 4.5 and 5.0 mm at either flow. The Mini-PEP and adapter resistors gave the highest pressures. CONCLUSIONS: Pressures generated by the different proprietary resistor components of 4 commercial PEP devices were not comparable, even though the diameter of the resistors is reported to be the same. The pressures generated were significantly different, particularly when using small-diameter resistors at a high flow. Therefore, the resistors may not be interchangeable. This is important information for clinicians, particularly when considering PEP for patients who do not tolerate higher pressures. (C) 2015 Daedalus Enterprises
6.	Gulyas, Miklos, et al. (author) COX-2 expression and effects of celecoxib in addition to standard chemotherapy in advanced non-small cell lung cancer. 2018 In: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 57:2, s. 244-250 Journal article (peer-reviewed)abstract Aim: Inhibition of cyclooxygenase-2 (COX-2) is proposed as a treatment option in several cancer types. However, in non-small cell lung cancer (NSCLC), phase III trials have failed to demonstrate a benefit of adding COX-2 inhibitors to standard chemotherapy. The aim of this study was to analyze COX-2 expression in tumor and stromal cells as predictive biomarker for COX-2 inhibition.Methods: In a multicenter phase III trial, 316 patients with advanced NSCLC were randomized to receive celecoxib (400 mg b.i.d.) or placebo up to one year in addition to a two-drug platinum-based chemotherapy combination. In a subset of 122 patients, archived tumor tissue was available for immunohistochemical analysis of COX-2 expression in tumor and stromal cells. For each compartment, COX-2 expression was graded as high or low, based on a product score of extension and intensity of positively stained cells.Results: An updated analysis of all 316 patients included in the original trial, and of the 122 patients with available tumor tissue, showed no survival differences between the celecoxib and placebo arms (HR 1.01; 95% CI 0.81–1.27 and HR 1.12; 95% CI 0.78–1.61, respectively). High COX-2 scores in tumor (n = 71) or stromal cells (n = 55) was not associated with a superior survival outcome with celecoxib vs. placebo (HR =0.96, 95% CI 0.60–1.54; and HR =1.51; 95% CI 0.86–2.66), and no significant interaction effect between COX-2 score in tumor or stromal cells and celecoxib effect on survival was detected (p = .48 and .25, respectively).Conclusions: In this subgroup analysis of patients with advanced NSCLC treated within the context of a randomized trial, we could not detect any interaction effect of COX-2 expression in tumor or stromal cells and the outcome of celecoxib treatment in addition to standard chemotherapy.
7.	Hansmann, Georg, et al. (author) 2019 updated consensus statement on the diagnosis and treatment of pediatric pulmonary hypertension: The European Pediatric Pulmonary Vascular Disease Network (EPPVDN), endorsed by AEPC, ESPR and ISHLT 2019 In: The Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1053-2498. ; 38:9, s. 879-901 Research review (peer-reviewed)abstract © 2019 The European Pediatric Pulmonary Vascular Disease Network is a registered, non-profit organization that strives to define and develop effective, innovative diagnostic methods and treatment options in all forms of pediatric pulmonary hypertensive vascular disease, including pulmonary hypertension (PH) associated with bronchopulmonary dysplasia, PH associated with congenital heart disease (CHD), persistent PH of the newborn, and related cardiac dysfunction. The executive writing group members conducted searches of the PubMed/MEDLINE bibliographic database (1990–2018) and held face-to-face and web-based meetings. Ten section task forces voted on the updated recommendations, based on the 2016 executive summary. Clinical trials, meta-analyses, guidelines, and other articles that include pediatric data were searched using the term “pulmonary hypertension” and other keywords. Class of recommendation (COR) and level of evidence (LOE) were assigned based on European Society of Cardiology/American Heart Association definitions and on pediatric data only, or on adult studies that included >10% children or studies that enrolled adults with CHD. New definitions by the World Symposium on Pulmonary Hypertension 2018 were included. We generated 10 tables with graded recommendations (COR/LOE). The topics include diagnosis/monitoring, genetics/biomarkers, cardiac catheterization, echocardiography, cardiac magnetic resonance/chest computed tomography, associated forms of PH, intensive care unit/lung transplantation, and treatment of pediatric PH. For the first time, a set of specific recommendations on the management of PH in middle- and low-income regions was developed. Taken together, these executive, up-to-date guidelines provide a specific, comprehensive, detailed but practical framework for the optimal clinical care of children and young adults with PH.
8.	Johansson, Inger, 1953, et al. (author) Lower incidence of CMV infection and acute rejections with valganciclovir 2013 In: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 13 Journal article (peer-reviewed)abstract Background Cytomegalovirus (CMV) is the most common opportunistic infection following lung transplantation. CMV replication in the lung allograft is described as accelerating the development of bronchiolitis obliterans syndrome (BOS).Finding a strategy to prevent CMV infection is an important issue. Methods We performed a retrospective, single-centre study of 114 lung transplant recipients (LTRs) who underwent lung transplantation from January 2001 to December 2006. In a smaller cohort of 88 CMV seropositive (R+) LTRs, three months of valganciclovir prophylaxis (2004-2006) was compared to three months of oral ganciclovir (2001-2003) with respect to the incidence of CMV infection/disease, the severity of CMV disease, acute rejection, BOS-free 4 year survival and 4 year survival. In the whole group of 114 LTRs the impact of CMV infection on long-term survival (BOS free 4 year survival and 6 year survival) was assessed. Results For the cohort of 88 CMV seropositive LTRs, the incidence of CMV infection/disease at one year was lower in the valganciclovir group compared to the ganciclovir group (24% vs. 54%, p = 0.003). There was a tendency towards reduced CMV disease, from 33% to 20% and a significant lower incidence of asymptomatic CMV infection (22% vs. 4%, p = 0.005). A lower incidence of acute rejection was observed in the valganciclovir group. However, there was no significant difference between the two groups in BOS free 4 year survival and 4 year survival. For the entire group of 114 LTRs, BOS-free 4 year survival for recipients with CMV disease was (32%, p = 0.005) and among those with asymptomatic CMV infection (36%, p = 0.061) as compared with patients without CMV infection (69%). Six year survival was lower among patients with CMV disease, (64%, p = 0.042) and asymptomatic CMV infection (55%, p = 0.018) than patients without CMV infection (84%). Conclusions A lower incidence of CMV infection/disease and acute rejections was observed with valganciclovir (3 months) when compared to oral ganciclovir (3 months). The long-term impact of CMV infection/disease was significant for BOS-free survival and survival.
9.	Elmståhl, Sölve, et al. (author) No association between inhaled corticosteroids and whole body DXA in postmenopausal women 2006 In: Pharmacoepidemiol Drug Saf. - : Wiley. - 1053-8569 .- 1099-1557. ; 15:7, s. 527-35 Journal article (peer-reviewed)abstract PURPOSE: Postmenopausal women treated with corticosteroids are regarded as a high-risk group due to the effect of both natural bone loss and possible adverse effects of treatment with inhaled corticosteroids (IC). OBJECTIVE: To compare bone mineral density (BMD) in postmenopausal women exposed only to IC (IC group, n = 106) with that of BMD in women not exposed to corticosteroids (n = 124) and women exposed to oral and/or intra-articular injections in addition to inhaled corticosteroids (OC group, n = 31). The women were recruited from a population-based prospective cohort study. METHODS: Dual X-ray absorptiometry (DXA) technique was used to measure BMD in whole body, spine, pelvis and lower extremities. A health questionnaire and an interview about past and present medication use were used. RESULTS: The mean duration and dose of IC were 9.5 +/- 4.5 years and 615 microg daily. Whole body BMD did not significantly differ between the IC group (1.103 g/cm(2)) and the unexposed group (1.087 g/cm(2)). Within the IC group, BMD stratified for cumulative dose of IC, duration or current dose above or below 800 microg did not differ. Z-score BMD for tertiles did not differ when comparing the IC and OC groups. CONCLUSION: No difference in BMD was noted between postmenopausal women exposed to inhaled corticosteroids and unexposed controls nor was there any dose response relationship between inhaled corticosteroid therapy and BMD.
10.	Nilsson, Jonna, et al. (author) Associations of cardiorespiratory fitness and moderate-to-vigorous physical activity with latent cognitive abilities in older adults 2022 In: Psychology of Sport And Exercise. - : Elsevier. - 1469-0292 .- 1878-5476. ; 60, s. 102171-102171 Journal article (peer-reviewed)abstract It has been demonstrated that physical activity has a small but positive effect on cognition in old age, which suggests that it may be possible to alter the trajectory of age-related cognitive decline. However, our understanding of which aspects of physical activity that are important for modifying cognition remains incomplete. Adopting an exploratory approach in a sample of 115 healthy older adults (65–75 years), the present cross-sectional study used structural equation modelling to investigate the dissociable associations of physical activity (moderate-to-vigorous activity, derived from 7-day accelerometry) and cardiorespiratory fitness (VO2 max, derived from maximal treadmill ergometer test) with multiple latent cognitive abilities (working memory, episodic memory, spatial and verbal reasoning). The results showed a significant positive association between fitness and working memory, when physical activity was statistically controlled for, and a positive association of similar point magnitude between physical activity and episodic memory, when fitness was statistically controlled for, although the latter association did not reach statistical significance. The results add to the foundation for a more careful investigation of the dissociable associations of moderate-to-vigorous physical activity and fitness with cognition in old age, and encourages future research to test the hypothesis that cardiorespiratory fitness benefits working memory via general cerebrovascular effects on grey matter volume, whilst moderate-to-vigorous physical activity benefits episodic memory via effects on neuroplastic processes.
11.	Yilmaz, Aylin, et al. (author) Upper Respiratory Tract Levels of Severe Acute Respiratory Syndrome Coronavirus 2 RNA and Duration of Viral RNA Shedding Do Not Differ Between Patients With Mild and Severe/Critical Coronavirus Disease 2019 2021 In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 223:1, s. 15-18 Journal article (peer-reviewed)abstract This study reports longitudinal viral RNA loads from the nasopharynx/throat in patients with mild and severe/critical coronavirus disease 2019 (COVID-19). We also investigated whether the duration of symptoms correlated with the duration of viral RNA shedding. A total of 56 patients were included. The highest viral loads occurred early after onset of symptoms. Neither the viral RNA loads in the upper respiratory tract nor the time to viral RNA clearance differed between patients with mild or severe/critical disease. There was a moderate correlation between number of days with symptoms and number of days with viral RNA shedding in patients with mild COVID-19.
12.	Humayun, Jhangir, et al. (author) Systematic review of the healthcare cost of bronchopulmonary dysplasia. 2021 In: BMJ open. - : BMJ. - 2044-6055. ; 11:8 Journal article (peer-reviewed)abstract To determine the costs directly or indirectly related to bronchopulmonary dysplasia (BPD) in preterm infants. The secondary objective was to stratify the costs based on gestational age and/or birth weight.Systematic literature review.PubMed and Scopus were searched on 3 February 2020. Studies were selected based on eligibility criteria by two independent reviewers. Included studies were further searched to identify eligible references and citations.Two independent reviewers extracted data with a prespecified data extraction sheet, including items from a published checklist for quality assessment. The costs in the included studies are reported descriptively.Costs of BPD.The 13 included studies reported the total costs or marginal costs of BPD. Most studies reported costs during birth hospitalisation (cost range: Int$21392-Int$1 094509 per child, equivalent to €19103-€977397, in 2019) and/or during the first year of life. One study reported costs during the first 2years; two other studies reported costs later, during the preschool period and one study included a long-term follow-up. The highest mean costs were associated with infants born at extremely low gestational ages. The quality assessment indicated a low risk of bias in the reported findings of included studies.This study was the first systematic review of costs associated with BPD. We confirmed previous reports of high costs and described the long-term follow-up necessary for preterm infants with BPD, particularly infants of very low gestational age. Moreover, we identified a need for studies that estimate costs outside hospitals and after the first year of life.CRD42020173234.
13.	Stråvik, Mia, 1994, et al. (author) Maternal Intake of Cow's Milk during Lactation Is Associated with Lower Prevalence of Food Allergy in Offspring 2020 In: Nutrients. - : MDPI AG. - 2072-6643 .- 2072-6643. ; 12:12, s. 1-19 Journal article (peer-reviewed)abstract Maternal diet during pregnancy and lactation may affect the propensity of the child to develop an allergy. The aim was to assess and compare the dietary intake of pregnant and lactating women, validate it with biomarkers, and to relate these data to physician-diagnosed allergy in the offspring at 12 months of age. Maternal diet during pregnancy and lactation was assessed by repeated semi-quantitative food frequency questionnaires in a prospective Swedish birth cohort (n = 508). Fatty acid proportions were measured in maternal breast milk and erythrocytes. Allergy was diagnosed at 12 months of age by a pediatrician specialized in allergy. An increased maternal intake of cow's milk during lactation, confirmed with biomarkers (fatty acids C15:0 and C17:0) in the maternal blood and breast milk, was associated with a lower prevalence of physician-diagnosed food allergy by 12 months of age. Intake of fruit and berries during lactation was associated with a higher prevalence of atopic eczema at 12 months of age. Our results suggest that maternal diet modulates the infant's immune system, thereby influencing subsequent allergy development.
14.	Möller, Marika, et al. (author) Cognitive dysfunction in post-COVID-19 condition : mechanisms, management, and rehabilitation 2023 In: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 294:5, s. 563-581 Research review (peer-reviewed)abstract The long-term effects of COVID-19 on cognitive function have become an area of increasing concern. This paper provides an overview of characteristics, risk factors, possible mechanisms, and management strategies for cognitive dysfunction in post-COVID-19 condition (PCC). Prolonged cognitive dysfunction is one of the most common impairments in PCC, affecting between 17% and 28% of the individuals more than 12 weeks after the infection and persisting in some cases for several years. Cognitive dysfunctions can be manifested as a wide range of symptoms including memory impairment, attention deficit, executive dysfunction, and reduced processing speed. Risk factors for developing PCC, with or without cognitive impairments, include advanced age, preexisting medical conditions, and the severity of acute illness. The underlying mechanisms remain unclear, but proposed contributors include neuroinflammation, hypoxia, vascular damage, and latent virus reactivation not excluding the possibility of direct viral invasion of the central nervous system, illustrating complex viral pathology. As the individual variation of the cognitive impairments is large, a neuropsychological examination and a person-centered multidimensional approach are required. According to the World Health Organization, limited evidence on COVID-19-related cognitive impairments necessitates implementing rehabilitation interventions from established practices of similar conditions. Psychoeducation and compensatory skills training are recommended. Assistive products and environmental modifications adapted to individual needs might be helpful. In specific attention- and working memory dysfunctions, cognitive training—carefully monitored for intensity—might be effective for people who do not suffer from post-exertional malaise. Further research is crucial for evidence-based interventions specific to COVID-19-related cognitive impairments.
15.	Amid Hägg, Shadi, et al. (author) The negative health effects of having a combination of snoring and insomnia 2022 In: JOURNAL OF CLINICAL SLEEP MEDICINE. - : American Academy of Sleep Medicine (AASM). - 1550-9389 .- 1550-9397. ; 18:4, s. 973-981 Journal article (peer-reviewed)abstract Study Objectives: Insomnia and snoring are common sleep disorders. The aim was to investigate the association of having a combination of insomnia symptoms and snoring with comorbidity and daytime sleepiness. Methods: The study population comprised 25,901 participants (16-75 years, 54.4% women) from 4 Swedish cities, who answered a postal questionnaire that contained questions on snoring, insomnia symptoms (difficulties initiating and/or maintaining sleep and/or early morning awakening), smoking, educational level, and respiratory and nonrespiratory disorders. Results: Snoring was reported by 4,221 (16.2%), while 9,872 (38.1%) reported 1 insomnia symptom. A total of 2,150 (8.3%) participants reported both insomnia symptoms and snoring. The association with hypertension (adjusted odds ratio [OR], 1.4; 95% confidence interval [Cl], 1.2-1.6), chronic obstructive pulmonary disease (adjusted OR, 1.8; 95% CI, 1.3-2.4), asthma (adjusted OR, 1.9; 95% CI, 1.6-2.3), daytime sleepiness (adjusted OR, 7.9; 95% CI, 7.1-8.8), and the use of hypnotics (adjusted OR, 7.5; 95% CI, 6.1-9.1) was highest for the group with both insomnia symptoms and snoring. Conclusions: Participants with both snoring and insomnia run an increased risk of hypertension, chronic obstructive pulmonary disease, asthma, daytime sleepiness, and use of hypnotics. It is important to consider snoring in patients seeking medical assistance for insomnia and, vice versa, in patients with snoring inquiring about insomnia.
16.	Barman, Malin, 1983, et al. (author) Single Nucleotide Polymorphisms in the FADS Gene Cluster but not the ELOVL2 Gene are Associated with Serum Polyunsaturated Fatty Acid Composition and Development of Allergy (in a Swedish Birth Cohort). 2015 In: Nutrients. - : MDPI AG. - 2072-6643. ; 7:12, s. 10100-10115 Journal article (peer-reviewed)abstract Exposure to polyunsaturated fatty acids (PUFA) influences immune function and may affect the risk of allergy development. Long chain PUFAs are produced from dietary precursors catalyzed by desaturases and elongases encoded by FADS and ELOVL genes. In 211 subjects, we investigated whether polymorphisms in the FADS gene cluster and the ELOVL2 gene were associated with allergy or PUFA composition in serum phospholipids in a Swedish birth-cohort sampled at birth and at 13 years of age; allergy was diagnosed at 13 years of age. Minor allele carriers of rs102275 and rs174448 (FADS gene cluster) had decreased proportions of 20:4 n-6 in cord and adolescent serum and increased proportions of 20:3 n-6 in cord serum as well as a nominally reduced risk of developing atopic eczema, but not respiratory allergy, at 13 years of age. Minor allele carriers of rs17606561 in the ELOVL2 gene had nominally decreased proportions of 20:4 n-6 in cord serum but ELOVL polymorphisms (rs2236212 and rs17606561) were not associated with allergy development. Thus, reduced capacity to desaturase n-6 PUFAs due to FADS polymorphisms was nominally associated with reduced risk for eczema development, which could indicate a pathogenic role for long-chain PUFAs in allergy development.
17.	Bengtsson, Caroline, et al. (author) Sinonasal outcome test-22 and peak nasal inspiratory flow : valuable tools in obstructive sleep apnoea 2020 In: Rhinology. - 0300-0729 .- 1996-8604. ; 58:4, s. 341-348 Journal article (peer-reviewed)abstract Background: Sinonasal complaints contribute to low adherence to continuous positive airway pressure (CPAP) treatment. We aimed to investigate sinonasal health in obstructive sleep apnoea (OSA) patients, using the sinonasal outcome test-22 (SNOT-22), and to analyse whether SNOT-22 is affected by CPAP adherence. We also aimed to investigate whether peak nasal inspiratory flow (PNIF) was able to predict adherence to CPAP. Methods:The study population comprised 197 OSA patients (60 females) initiating CPAP treatment The SNOT-22, PNIF and the Epworth Sleepiness Scale were assessed at baseline and follow-up. One-night polygraphy, the Hospital Anxiety and Depression Scale, peak expiratory flow and health-related issues were assessed at baseline. At follow-up, the patients were categorised into adherent (>4 hours/night) and non-adherent (<4 hours/night) to CPAP treatment. Results: The average time for following up CPAP treatment was (mean +/- SD) 24.0 +/- 23.9 days and it did not differ significantly between the groups.The SNOT-22 score was elevated among all OSA patients, 36.1 +/- 19.4.There was a larger improvement in the SNOT-22 score at follow-up among adherent CPAP users compared with non-adherent users (-10.4 +/- 13.9 vs. -3.2 +/- 15.4). A PNIF value of < 100 litres/min increased the risk of non-adherence to CPAP with an adjusted odds ratio (OR) of 2.40 ((95% CI 1.16-5.00)). Conclusions: The SNOT-22 was elevated in patients with OSA, indicating a considerable sinonasal disease burden.The SNOT-22 improved with good CPAP adherence. A low PNIF value was able to predict poor CPAP adherence. Both the SNOT-22 and PNIF can be valuable tools in the evaluation of OSA patients and in the management of CPAP treatment.
18.	Bjerg, Anders, 1982, et al. (author) A population-based study of animal component sensitization, asthma, and rhinitis in schoolchildren 2015 In: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 26:6, s. 557-563 Journal article (peer-reviewed)abstract BackgroundAnimal sensitization is a major determinant of asthma in children. Component-resolved studies of unselected pediatric populations are lacking. The aim was to describe sensitization to animal components and the association with asthma and rhinitis in animal-sensitized schoolchildren. MethodsA random sample of 696 children (11-12years) from a Swedish population-based cohort was tested for sensitization to cat, dog, and horse dander using ImmunoCAP. Sera from animal-sensitized children were further analyzed by microarray including three allergen components from cat, four from dog, and two from horse. The parents completed an expanded ISAAC questionnaire. ResultsOf 259 animal-sensitized children (0.1 kU(A)/l), 51% were sensitized to all three, 23% to two, and 25% to one species. Current asthma and asthma symptoms following contact with cats were associated with co-sensitization to Fel d 1 and Fel d 4. This association was seen already at moderate-level sensitization (1-15 ISU) to Fel d 4, at which level most children were sensitized to Fel d 1, as well. In dog-sensitized children, the majority was sensitized to more than one dog component, and co-sensitization to Can f 5 and Can f 1/f 2 conferred the greatest risk for asthma. Sensitization to the highly cross-reactive serum albumins was uncommon and not associated with asthma. ConclusionsAmong schoolchildren in northern Sweden, where mite allergy is uncommon, furry animals were the primary perennial sensitizers. Asthma was associated with higher levels of component sensitization, and sensitization to more than one component from the same animal conferred the greatest risk.
19.	Bjornsdottir, E., et al. (author) Are symptoms of insomnia related to respiratory symptoms? Cross-sectional results from 10 European countries and Australia 2020 In: BMJ Open. - : BMJ. - 2044-6055. ; 10:4 Journal article (peer-reviewed)abstract Objectives To compare the prevalence of different insomnia subtypes among middle-aged adults from Europe and Australia and to explore the cross-sectional relationship between insomnia subtypes, respiratory symptoms and lung function. Design Cross-sectional population-based, multicentre cohort study. Setting 23 centres in 10 European countries and Australia. Methods We included 5800 participants in the third follow-up of the European Community Respiratory Health Survey III (ECRHS III) who answered three questions on insomnia symptoms: difficulties falling asleep (initial insomnia), waking up often during the night (middle insomnia) and waking up early in the morning and not being able to fall back asleep (late insomnia). They also answered questions on smoking, general health and chronic diseases and had the following lung function measurements: forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and the FEV1/FVC ratio. Changes in lung function since ECRHS I about 20 years earlier were also analysed. Main outcome measures Prevalence of insomnia subtypes and relationship to respiratory symptoms and function. Results Overall, middle insomnia (31.2%) was the most common subtype followed by late insomnia (14.2%) and initial insomnia (11.2%). The highest reported prevalence of middle insomnia was found in Iceland (37.2%) and the lowest in Australia (22.7%), while the prevalence of initial and late insomnia was highest in Spain (16.0% and 19.7%, respectively) and lowest in Denmark (4.6% and 9.2%, respectively). All subtypes of insomnia were associated with significantly higher reported prevalence of respiratory symptoms. Only isolated initial insomnia was associated with lower FEV1, whereas no association was found between insomnia and low FEV1/FVC ratio or decline in lung function. Conclusion There is considerable geographical variation in the prevalence of insomnia symptoms. Middle insomnia is most common especially in Iceland. Initial and late insomnia are most common in Spain. All insomnia subtypes are associated with respiratory symptoms, and initial insomnia is also associated with lower FEV1.
20.	Hagman, Cecilia, et al. (author) Club cell secretory protein (CC16) in gastric fluid at birth and subsequent lung disease in preterm infants 2018 In: Pediatric Pulmonology. - : Wiley. - 8755-6863. ; 53:10, s. 1399-1406 Journal article (peer-reviewed)abstract BackgroundClub cell secretory protein (CC16) probably has a role in protecting the lung from inflammation. AimTo evaluate if low levels of CC16 in gastric fluid at birth, reflecting low levels of CC16 in the lung, would be associated with lung inflammation and respiratory morbidity. MethodsA study of 64 infants with mean gestational age 26.1 weeks. CC16 was analyzed in gastric fluid at birth. CC16, pro-inflammatory cytokines, and MMP-9 were analyzed in tracheal aspirate within 24h from birth. ResultsCC16 in gastric fluid increased with gestational age (P=0.033). Lower concentrations of CC16 in gastric fluid at birth were associated with higher concentrations of IL-1 (P=0.028), TNF- (P=0.034), and MMP-9 (P=0.015) in tracheal aspirate. Infants who needed mechanical ventilation at 24 and 72h of age had lower CC16 in gastric fluid than those not ventilated at these ages (P=0.011 and P=0.024, respectively). Lower CC16 in gastric fluid was associated with higher FiO(2) at 6h (P=0.009), higher PaCO2 at 24h (P=0.03), more ventilator days (P=0.012) and more days with supplemental oxygen (P=0.03). Infants who had either died or were still treated with supplemental oxygen at 36 weeks postmenstrual age had lower CC16 in gastric fluid than infants with none of these outcomes (P=0.049). ConclusionA low CC16 concentration in gastric fluid at birth was associated with increased inflammation in the trachea within the first 24h of life and with more need for respiratory support in the neonatal period.
21.	Michelet, Mona, et al. (author) Associations between unmet needs for daytime activities and company and scores on the Neuropsychiatric Inventory-Questionnaire in people with dementia : a longitudinal study 2021 In: Aging & Mental Health. - : Informa UK Limited. - 1360-7863 .- 1364-6915. ; 26:4, s. 725-734 Journal article (peer-reviewed)abstract OBJECTIVES To examine prospectively the association between unmet needs for daytime activities and company and behavioural and psychological symptoms of dementia.METHODS We included 451 people with mild or moderate dementia, from eight European countries, who were assessed three times over 12 months. Unmet needs were measured with the Camberwell Assessment of Need for the Elderly. Three sub-syndromes of the Neuropsychiatric Inventory-Questionnaire were regressed, one-by-one, against unmet needs for daytime activities and company, adjusting for demographic and clinical-functional covariates.RESULTS Unmet needs for daytime activities were associated with more affective symptoms at baseline, six and twelve months, mean 0.74 (p < 0.001), 0.76 (p < 0.001) and 0.78 (p = 0.001) points higher score respectively, and with more psychotic symptoms at baseline (mean 0.39 points, p = 0.007) and at six months follow-up (mean 0.31 points, p = 0.006). Unmet needs for company were associated with more affective symptoms at baseline, six and twelve months, mean 0.44 (p = 0.033), 0.67 (p < 0.001) and 0.91 (p < 0.001) points higher score respectively, and with more psychotic symptoms at baseline (mean 0.40 points, p = 0.005) and at six months (mean 0.35 points, p = 0.002) follow-up.CONCLUSION Interventions to reduce unmet needs for daytime activities and company could reduce affective and psychotic symptoms in people with dementia.
22.	Sigurðardóttir, E. S., et al. (author) Female sex hormones and symptoms of obstructive sleep apnea in European women of a population-based cohort 2022 In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17 Journal article (peer-reviewed)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.
23.	Steen, Stig, et al. (author) Transplantation of lungs from a non-heart-beating donor 2001 In: The Lancet. - 1474-547X. ; 357:9259, s. 825-829 Journal article (peer-reviewed)abstract BACKGROUND: In animals, we have previously done successful lung transplantations using organs from non-heart-beating donors. We have also developed an ex-vivo system of assessing the function of such organs before transplantation. The next stage was to try the technique in human beings. Bearing in mind the sensitive ethical issues involved, our first aim was to find out what procedures would be acceptable, and to use the results to guide a clinical lung transplantation from a non-heart-beating donor. METHODS: The ethical acceptability of the study was gauged from the results of a broad information programme directed at the general public in Sweden, and from discussions with professionals including doctors, nurses, hospital chaplains, and judges. The donor was a patient dying of acute myocardial infarction in a cardiac intensive-care unit after failed cardiopulmonary resuscitation. The next of kin gave permission to cool the lungs within the intact body, and intrapleural cooling was started 65 min after death. Blood samples were sent for virological testing and cross matching. The next of kin then had time to be alone with the deceased. After 3 h, the body was transported to the operating theatre and the heart-lung block removed. The lungs were assessed ex vivo, and the body was transported to the pathology department for necropsy. RESULTS: No contraindications to transplantation were found, and the right lung was transplanted successfully into a 54-year-old woman with chronic obstructive pulmonary disease. The donor lung showed excellent function only 5 min after reperfusion and ventilation, and during the first 5 months of follow-up, the function of the transplanted lung has been good. INTERPRETATION: About half the deaths in Sweden are caused by cardiac and cerebrovascular disease. This group could be a potential source of lung donors. When all hospitals and ambulance personnel in Sweden have received training in non-heart-beating lung donation, we hope that there will be enough donor lungs of good quality for all patients needing a lung transplant.
24.	Wackernagel, Dirk, et al. (author) Enteral supplementation with arachidonic and docosahexaenoic acid and pulmonary outcome in extremely preterm infants 2024 In: Prostaglandins Leukotrienes and Essential Fatty Acids. - 0952-3278 .- 1532-2823. ; 201 Journal article (peer-reviewed)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.
25.	Forsberg, Gustaf, et al. (author) Risk factors for ventilator-associated lower respiratory tract infection in COVID-19, a retrospective multicenter cohort study in Sweden 2024 In: Acta Anaesthesiologica Scandinavica. - : John Wiley & Sons. - 0001-5172 .- 1399-6576. ; 68:2, s. 226-235 Journal article (peer-reviewed)abstract Background: Ventilator-associated lower respiratory tract infections (VA-LRTI) increase morbidity and mortality in intensive care unit (ICU) patients. Higher incidences of VA-LRTI have been reported among COVID-19 patients requiring invasive mechanical ventilation (IMV). The primary objectives of this study were to describe clinical characteristics, incidence, and risk factors comparing patients who developed VA-LRTI to patients who did not, in a cohort of Swedish ICU patients with acute hypoxemic respiratory failure due to COVID-19. Secondary objectives were to decipher changes over the three initial pandemic waves, common microbiology and the effect of VA-LTRI on morbidity and mortality.Methods: We conducted a multicenter, retrospective cohort study of all patients admitted to 10 ICUs in southeast Sweden between March 1, 2020 and May 31, 2021 because of acute hypoxemic respiratory failure due to COVID-19 and were mechanically ventilated for at least 48 h. The primary outcome was culture verified VA-LRTI. Patient characteristics, ICU management, clinical course, treatments, microbiological findings, and mortality were registered. Logistic regression analysis was conducted to determine risk factors for first VA-LRTI.Results: Of a total of 536 included patients, 153 (28.5%) developed VA-LRTI. Incidence rate of first VA-LRTI was 20.8 per 1000 days of IMV. Comparing patients with VA-LRTI to those without, no differences in mortality, age, sex, or number of comorbidities were found. Patients with VA-LRTI had fewer ventilator-free days, longer ICU stay, were more frequently ventilated in prone position, received corticosteroids more often and were more frequently on antibiotics at intubation. Regression analysis revealed increased adjusted odds-ratio (aOR) for first VA-LRTI in patients treated with corticosteroids (aOR 2.64 [95% confidence interval [CI]] [1.31-5.74]), antibiotics at intubation (aOR 2.01 95% CI [1.14-3.66]), and days of IMV (aOR 1.05 per day of IMV, 95% CI [1.03-1.07]). Few multidrug-resistant pathogens were identified. Incidence of VA-LRTI increased from 14.5 per 1000 days of IMV during the first wave to 24.8 per 1000 days of IMV during the subsequent waves.Conclusion: We report a high incidence of culture-verified VA-LRTI in a cohort of critically ill COVID-19 patients from the first three pandemic waves. VA-LRTI was associated with increased morbidity but not 30-, 60-, or 90-day mortality. Corticosteroid treatment, antibiotics at intubation and time on IMV were associated with increased aOR of first VA-LRTI.
26.	Hårdstedt, Maria, 1971-, et al. (author) Swimming-Induced Pulmonary Edema : Diagnostic Criteria Validated by Lung Ultrasound 2020 In: Chest. - : American College of Chest Physicians. - 0012-3692 .- 1931-3543. ; 158:4, s. 1586-1595 Journal article (peer-reviewed)abstract BACKGROUND: Despite the increasing popularity of open water swimming worldwide, swimming-induced pulmonary edema (SIPE) is a poorly recognized condition lacking established diagnostic criteria.RESEARCH QUESTION: The aim of this study was to identify diagnostic criteria of SIPE during a large open water swimming event.STUDY DESIGN AND METHODS: In this cross-sectional study, 17,904 individuals swam 1,000, 1,500, or 3,000 m in cold open water during Sweden's largest open water swimming event in 2018 and 2019. Of 166 swimmers seeking medical attention for acute respiratory symptoms, 160 were included in the study. Medical history, symptoms, and clinical findings were collected. On-site lung ultrasound (LUS) was performed to verify pulmonary edema.RESULTS: Pulmonary edema was confirmed by LUS in 102 patients (64%); findings were unilateral in 11 (7%). Peripheral oxygen saturation was identified as a strong independent diagnostic test for pulmonary edema, with ≤ 95% as the suggested cut off based on receiver-operating characteristic curve analysis (area under the curve, 0.893; P < .0001). Crackles on lung auscultation, predominantly over the anterior chest, identified 88% of patients with edema. Peripheral oxygen saturation ≤ 95% or auscultation findings of crackles identified pulmonary edema with a sensitivity of 97% and a specificity of 86%. A specificity of 98% and a positive predictive value of 99% for LUS-verified pulmonary edema were reached if patients presented with both oxygen saturation ≤ 95% and auscultation of crackles.INTERPRETATION: We suggest a clinical algorithm for diagnosis of SIPE for swimmers with acute respiratory symptoms during swimming in cold open water. Novel features of focally distributed edema in the anterior parts of the lungs, sometimes unilateral, add to this unique dataset of an underreported condition.
27.	Voss, Erica A, et al. (author) 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 In: EClinicalMedicine. - 2589-5370. ; 58 Journal article (peer-reviewed)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.
28.	Ekelund, Ulf, et al. (author) Effects of the combined ETA and ETB receptor antagonist PD145065 on arteries, arterioles, and veins in the cat hindlimb 1995 In: Journal of Cardiovascular Pharmacology. - 1533-4023. ; 26:Suppl. 3, s. 211-213 Journal article (peer-reviewed)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.
29.	Saetrum Opgaard, Ole, et al. (author) Endocardial expression and functional characterization of endothelin-1 2001 In: Molecular and Cellular Biochemistry. - 0300-8177. ; 224:1-2, s. 151-158 Journal article (peer-reviewed)abstract Endothelin-1 (ET-1), a 21 amino acid peptide exerts a wide range of biological activities including vasoconstriction, mitogenesis and inotropic effects on the heart. In this study, we examined whether endocardial endothelial cells express ET-1 and evaluated its functional properties. Using immunofluorescence localization method, we demonstrated cytoplasmic staining of ET-1 in the human endocardial endothelial cells from the right atrium and left ventricle. Employing reverse transcriptase polymerase chain reaction (RT-PCR) expression of ET-1 mRNA and its receptors ET(A) and ET(B) mRNAs were found in human myocardial as well as in endocardial endothelial cells. Biological activity of endocardial endothelial cells derived ET-1 was established as the conditioned media obtained from cultured porcine endocardial endothelial cells induced a slowly developing, strong and long-lasting contraction of circular rat aortic segments, with similar characteristics to that obtained with exogenous ET-1. Furthermore, the selective endothelin-A receptor antagonist, FR 139317, blocked the conditioned media induced contractions. Our results suggest that endocardial endothelial cells express and release biologically active ET-1 which could play a pivotal role in the regulation of myocardial contractility as well as a circulatory peptide may further act in other peripheral target organs.
30.	Brew, Bronwyn K., et al. (author) Paediatric asthma and non-allergic comorbidities : A review of current risk and proposed mechanisms 2022 In: Clinical and Experimental Allergy. - Stockholm : Wiley-Blackwell Publishing Inc.. - 0954-7894 .- 1365-2222. ; 15:9, s. 1035-1047 Research review (peer-reviewed)abstract It is increasingly recognized that children with asthma are at a higher risk of other non-allergic concurrent diseases than the non-asthma population. A plethora of recent research has reported on these comorbidities and progress has been made in understanding the mechanisms for comorbidity. The goal of this review was to assess the most recent evidence (2016-2021) on the extent of common comorbidities (obesity, depression and anxiety, neurodevelopmental disorders, sleep disorders and autoimmune diseases) and the latest mechanistic research, highlighting knowledge gaps requiring further investigation. We found that the majority of recent studies from around the world demonstrate that children with asthma are at an increased risk of having at least one of the studied comorbidities. A range of potential mechanisms were identified including common early life risk factors, common genetic factors, causal relationships, asthma medication and embryologic origins. Studies varied in their selection of population, asthma definition and outcome definitions. Next, steps in future studies should include using objective measures of asthma, such as lung function and immunological data, as well as investigating asthma phenotypes and endotypes. Larger complex genetic analyses are needed, including genome-wide association studies, gene expression-functional as well as pathway analyses or Mendelian randomization techniques; and identification of gene-environment interactions, such as epi-genetic studies or twin analyses, including omics and early life exposure data. Importantly, research should have relevance to clinical and public health translation including clinical practice, asthma management guidelines and intervention studies aimed at reducing comorbidities.
31.	Rusanen, Minna, et al. (author) Chronic Obstructive Pulmonary Disease and Asthma and the Risk of Mild Cognitive Impairment and Dementia : A Population Based CAIDE Study 2013 In: CURRENT ALZHEIMER RESEARCH. - : Bentham Science Publishers Ltd.. - 1567-2050 .- 1875-5828. ; 10:5, s. 549-555 Journal article (peer-reviewed)abstract Background: Previous research indicates that persons with chronic obstructive pulmonary disease (COPD) and asthma may have more cognitive impairment compared to persons without these diseases. However, there are no previous studies regarding long-term effects of these diseases on the risk of clinically diagnosed mild cognitive impairment (MCI) and dementia. We examined the association between midlife and late-life self-reported COPD and asthma and the lifelong risk of cognitive impairment (MCI/dementia) in a population-based study with a follow-up of over 25 years. Methods: Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study includes 2000 participants who were randomly selected from four separate, population-based samples originally studied in midlife (1972, 1977, 1982 or 1988). Re-examinations were carried out in 1998 and 2005-8 (N=1511, 75.6 %) during which 172 persons were diagnosed with MCI and 117 with dementia. Results: Midlife COPD (HR 1.85, 95% CI 1.05 - 3.28), asthma (HR 1.88, 95% CI 0.77 - 4.63) and both pulmonary diseases combined (HR 1.94, 95% CI 1.16 - 3.27) increased the later risk of cognitive impairment even after full adjustments. However, pulmonary diseases diagnosed later in life seemed to be inversely related to cognitive impairment (fully adjusted model for both pulmonary diseases combined HR 0.42, 95% CI 0.19 - 0.93). Conclusions: In this population-based study, with more than 25 years of follow-up, midlife COPD and asthma were associated with an almost two-fold risk of MCI and dementia later in life. Pulmonary diseases diagnosed later in life seemed to have an inverse relationship with cognitive impairment probably reflecting survival bias.
32.	Vasileiadou, Styliana, et al. (author) Low agreement between Swedish national registers and parental questionnaires on allergic rhinitis 2023 In: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. - 1399-3038. ; 34:11 Journal article (peer-reviewed)abstract Allergic rhinitis (AR) has been well documented using questionnaire-based studies. Here, we examine the agreement between parental-reported data during childhood with the emphasis on 12-year-olds and data from two national Swedish registers to determine whether register data on AR can supplement or replace questionnaire data.Data were collected from a prospective, longitudinal cohort study of children born in western Sweden in 2003. Parental questionnaires were filled out at 6months and one, four, eight, and 12years of age. A total of 3634 children were linked to the Swedish Prescribed Drug Register (SPDR) and the National Patient Register (NPR) using personal identity numbers. The agreement between the register and questionnaire data was estimated using Cohen's kappa with 95% confidence intervals.According to the SPDR, 9.9% (n=360/3634) of the children were dispensed specific AR medication at 11-13years of age compared with the 12years questionnaire where 23% reported AR medication use during the last 12months. The overall agreement between questionnaire and SPDR data on AR medication was slight (kappa 0.05). At 11-12years, 1.8% (n=65/3634) of the children received an outpatient AR diagnosis in the NPR, while 10% reported doctor-diagnosed AR in the questionnaire. The overall agreement between questionnaire and NPR data on AR diagnosis was slight (kappa 0.16).There was poor agreement between questionnaire and register data regarding AR and dispensed medication. Explanations could include over-the-counter drugs and diagnosis in primary care, which are not included in the registers.
33.	Wennergren, Göran, 1947, et al. (author) Luftrörsbesvär hos äldre barn 1991 In: Hyperreaktivitet i hud och luftvägar. - Mölndal : Glaxo AB, Sektionen för Astma/Allergi. Book chapter (other academic/artistic)
34.	Dutta, Nikita, 1992, et al. (author) Combinatory analysis of immune cell subsets and tumor-specific genetic variants predict clinical response to PD-1 blockade in patients with non-small cell lung cancer 2023 In: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 12 Journal article (peer-reviewed)abstract Immunotherapy by blocking programmed death protein-1 (PD-1) or programmed death protein-ligand1 (PD-L1) with antibodies (PD-1 blockade) has revolutionized treatment options for patients with non-small cell lung cancer (NSCLC). However, the benefit of immunotherapy is limited to a subset of patients. This study aimed to investigate the value of combining immune and genetic variables analyzed within 3-4 weeks after the start of PD-1 blockade therapy to predict long-term clinical response.Blood collected from patients with NSCLC were analyzed for changes in the frequency and concentration of immune cells using a clinical flow cytometry assay. Next-generation sequencing (NGS) was performed on DNA extracted from archival tumor biopsies of the same patients. Patients were categorized as clinical responders or non-responders based on the 9 months' assessment after the start of therapy.We report a significant increase in the post-treatment frequency of activated effector memory CD4+ and CD8+ T-cells compared with pre-treatment levels in the blood. Baseline frequencies of B cells but not NK cells, T cells, or regulatory T cells were associated with the clinical response to PD-1 blockade. NGS of tumor tissues identified pathogenic or likely pathogenic mutations in tumor protein P53, Kirsten rat sarcoma virus, Kelch-like ECH-associated protein 1, neurogenic locus notch homolog protein 1, and serine/threonine kinase 11, primarily in the responder group. Finally, multivariate analysis of combined immune and genetic factors but neither alone, could discriminate between responders and non-responders.Combined analyses of select immune cell subsets and genetic mutations could predict early clinical responses to immunotherapy in patients with NSCLC and after validation, can guide clinical precision medicine efforts.
35.	Johansson, I, et al. (author) PD-1 inhibitor therapy of basal cell carcinoma with pulmonary metastasis. : PD-1 inhibition in basal cell carcinoma 2022 In: Journal of the European Academy of Dermatology and Venereology. - : Wiley. - 1468-3083 .- 0926-9959. ; 36:Suppl 1, s. 70-73 Journal article (peer-reviewed)abstract Basal cell carcinoma (BCC) may be challenging to differentiate from basaloid squamous cell carcinoma (bSCC), both clinically and histologically. BCC constitutes one of the most common tumours and metastatic behaviour is extremely rare. In contrast, bSCC is a rare entity with an increased propensity for distant metastasis. If these conditions develop into inoperable metastatic disease, the therapeutic alternatives are different, but the use of PD-1 inhibitors may be a valid option for both. Here, we report a case with complex histology with a component initially classified as bSCC with lung metastases and treated with the PD-1 inhibitor cemiplimab resulting in radiological and clinical responses. Re-examination of the lung biopsy using routine histomorphology in combination with immunohistochemical staining for cytokeratin 14, cytokeratin17 and BerEp4 has, however, revealed a histopathological pattern of BCC, which is in concordance with a similar analysis of the cutaneous primary tumour in the face that the patient underwent surgery for more than 5years earlier.
36.	Sörenson, Sverre, et al. (author) Predictive role of plasma vascular endothelial growth factor for the effect of celecoxib in advanced non-small cell lung cancer treated with chemotherapy 2013 In: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 49:1, s. 115-120 Journal article (peer-reviewed)abstract Aim of the study: The primary purpose of this study is to investigate if pretreatment plasma levels of vascular endothelial growth factor (VEGF) are predictive of the effect of celecoxib on survival in advanced non-small cell lung cancer (NSCLC) treated with palliative chemotherapy. A secondary objective is to describe the course of plasma VEGF levels during and after treatment with cytotoxic chemotherapy combined with celecoxib or placebo. less thanbrgreater than less thanbrgreater thanMethods: In a previously published double-blind multicenter phase III trial, 316 patients with NSCLC stage IIIB or IV and World Health Organisation (WHO) performance status 0-2 were randomised to receive celecoxib 400 mg b.i.d. or placebo in combination with two-drug platinum-based chemotherapy. Chemotherapy cycle length was three weeks and planned duration of chemotherapy was four cycles. Celecoxib was given for a maximum of one year but was stopped earlier in case of disease progression or prohibitive toxicity. In a subset of patients, plasma VEGF levels were examined at onset of treatment and at 6, 12 and 20 weeks. less thanbrgreater than less thanbrgreater thanResults: VEGF levels at start of treatment were obtained in 107 patients at four study sites. The median value was 70 pg/ml. Mean values declined during the first 12 weeks and then increased at 20 weeks. A subpopulation treatment effect pattern plot (STEPP) analysis showed an inverse relationship between initial plasma VEGF and the impact of celecoxib on survival with zero effect at 200 pg/ml. The effect on survival by celecoxib in the whole subset of patients was positive (hazard ratio (HR)=0.64 [confidence interval (CI) 0.43-0.95], p=0.028). less thanbrgreater than less thanbrgreater thanConclusion: Low pretreatment plasma levels of VEGF appear to be predictive of a positive effect of celecoxib on survival.
37.	Balcan, Baran, et al. (author) Continuous Positive Airway Pressure Treatment and Depression in Adults with Coronary Artery Disease and Nonsleepy Obstructive Sleep Apnea. A Secondary Analysis of the RICCADSA Trial 2019 In: Annals of the American Thoracic Society. - 2325-6621. ; 16:1, s. 62-70 Journal article (peer-reviewed)abstract RATIONALE: Obstructive sleep apnea (OSA) and depression are common among adults with coronary artery disease (CAD). OBJECTIVES: To determine the impact of continuous positive airway pressure (CPAP) treatment on depression in adults with CAD and nonsleepy OSA. METHODS: This was a secondary analysis of the RICCADSA (Randomized Intervention with CPAP in CAD and Sleep Apnea) trial, conducted in Sweden between 2005 and 2013. Adults with CAD and nonsleepy OSA (apnea-hypopnea index ≥15/h, and Epworth Sleepiness Scale <10 at baseline) and complete Zung Self-Rating Depression Scale (SDS) questionnaires at baseline, after 3 and 12 months, were included. Participants analyzed in their randomized arm were CPAP (n = 99) or no-CPAP (n = 104). Depression was defined as a Zung SDS score of 50 or greater. The primary outcome was the between-group difference in the absolute change in the SDS score from baseline. RESULTS: No significant between-group differences were observed in SDS scores during follow-up in the entire study sample. Among the 56 participants with an SDS of 50 or greater at baseline (27.6%), the mean (±SD) baseline SDS was 55.0 (±5.5) in the CPAP group, and 53.9 (±4.0) in the no-CPAP group. In the CPAP group, SDS scores decreased at 3 months (47.2 ± 8.2) and 12 months (45.8 ± 7.6), but remained stable in the no-CPAP group at 3 months (53.1 ± 8.0) and 12 months (52.6 ± 8.1) (P = 0.01). The proportion with depression decreased from 30.3% at baseline to 16.2% after 3 months, and to 13.1% after 12 months in the CPAP group, from 25.0% at baseline to 23.1% after 3 months, and to 24.0% after 12 months in the no-CPAP group (P = 0.001). Moreover, there was an association between the duration of CPAP usage (h/night) and the longitudinal decline in SDS score (r = 0.46; P < 0.001). CPAP usage categories (3, 4, and 5 h/night) were significantly associated with improvement in SDS (odds ratio = 3.92, 4.45, and 4.89, respectively) in multivariate analyses adjusted for age, sex, body mass index, left ventricular ejection fraction, apnea-hypopnea index, and Epworth Sleepiness Scale at baseline. CONCLUSIONS: Among adults with depression, nonsleepy OSA, and CAD, 3 months of CPAP treatment improved depression scores. The improvement in mood persisted up to 12 months. An on-treatment adjusted analysis confirmed these findings. Clinical trial registered with www.clinicaltrials.gov (NCT00519597).
38.	Baldanzi, Gabriel, et al. (author) OSA Is Associated With the Human Gut Microbiota Composition and Functional Potential in the Population-Based Swedish CardioPulmonary bioImage Study 2023 In: Chest. - : Elsevier. - 0012-3692 .- 1931-3543. ; 164:2, s. 503-516 Journal article (peer-reviewed)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.
39.	Carlsson, Axel C, et al. (author) Endostatin predicts mortality in patients with acute dyspnea - a cohort study of patients seeking care in emergency departments. 2019 In: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 75 Journal article (peer-reviewed)abstract BACKGROUND: Increased levels of circulating endostatin predicts cardiovascular morbidity and impaired kidney function in the general population. The utility of endostatin as a risk marker for mortality in the emergency department (ED) has not been reported.AIM: Our main aim was to study the association between plasma endostatin and 90-day mortality in an unselected cohort of patients admitted to the ED for acute dyspnea. Design Circulating endostatin was analyzed in plasma from 1710 adults and related to 90-day mortality in Cox proportional hazard models adjusted for age, sex, body mass index, oxygen saturation, respiratory rate, body temperature, C-reactive protein, lactate, creatinine and medical priority according to the Medical Emergency Triage and Treatment System-Adult score (METTS-A). The predictive value of endostatin for mortality was evaluated with receiver operating characteristic (ROC) analysis and compared with the clinical triage scoring system and age.RESULTS: Each one standard deviation increment of endostatin was associated with a HR of 2.12 (95 % CI 1.31-3.44 p< 0.01) for 90-day mortality after full adjustment. Levels of endostatin were significantly increased in the group of patients with highest METTS-A (p<0.001). When tested for the outcome 90-day mortality, the area under the ROC curve (AUC) was 0.616 for METTS-A, 0.701 for endostatin, 0.708 for METTS -A and age and 0.738 for METTS-A, age and levels of endostatin.CONCLUSIONS: In an unselected cohort of patients admitted to the ED with acute dyspnea, endostatin had a string association to 90-day mortality and improved prediction of 90-day mortality in the ED beyond the clinical triage scoring system and age with 3 %.
40.	Celik, Y., et al. (author) Association of Excessive Daytime Sleepiness with the Zung Self-Rated Depression Subscales in Adults with Coronary Artery Disease and Obstructive Sleep Apnea 2021 In: Diagnostics. - : MDPI AG. - 2075-4418. ; 11:7 Journal article (peer-reviewed)abstract Excessive daytime sleepiness (EDS) is a factor associated with both obstructive sleep apnea (OSA) and depressive symptoms. Continuous positive airway pressure (CPAP) treatment may decrease EDS in adults with OSA; however, the modulatory role of depressive symptoms on the improvement of EDS is not known. We aimed to explore the association between subscales of the Zung Self-rated Depression Scale (SDS) and Epworth Sleepiness Scale (ESS) over a 2-year period in coronary artery disease (CAD) patients with OSA. This was a post-hoc analysis of the RICCADSA cohort, in which 399 adults with CAD (155 sleepy OSA [apnea-hypopnea index >= 15/h] and ESS score >= 10, who were offered CPAP; and 244 nonsleepy OSA [ESS < 10]), randomized to CPAP [n = 122] or no-CPAP [n = 122]) were included. Three factors were extracted from the Zung SDS, based on the principal component analysis: F1, cognitive symptoms and anhedonia; F2, negative mood; and F3, appetite. In a mixed model, the ESS score decreased by 3.4 points (p < 0.001) among the sleepy OSA phenotype, which was predicted by the decline in the F2, but not in the F1 and F3 scores. The fixed effects of time were not significant in the nonsleepy OSA groups, and thus, further analyses were not applicable. Additional within-group analyses showed a significant decrease in all subscales over time both in the sleepy and nonsleepy OSA patients on CPAP whereas there was a significant increase in the nonsleepy OSA group randomized to no-CPAP. We conclude that the improvement in negative mood symptoms of depression, but not changes in cognitive symptoms and anhedonia as well as appetite, was a significant predictor of decline in the ESS scores over a 2-year period in this CAD cohort with sleepy OSA on CPAP treatment.
41.	Engström, Gunnar, et al. (author) Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications 2024 In: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49 Journal article (peer-reviewed)abstract Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
42.	Gunduz, C., et al. (author) Long-term positive airway pressure therapy is associated with reduced total cholesterol levels in patients with obstructive sleep apnea: data from the European Sleep Apnea Database (ESADA) 2020 In: Sleep Medicine. - : Elsevier BV. - 1389-9457. ; 75, s. 201-209 Journal article (peer-reviewed)abstract Background and aim: Obstructive sleep apnea (OSA) is an independent risk factor for dyslipidemia. The current study examined the effects of positive airway pressure (PAP) treatment on lipid status in the European Sleep Apnea Database (ESADA). Methods: The prospective cohort study enrolled 1564 OSA subjects (74% male, mean age 54 ± 11y, body mass index (BMI) 32.7 ± 6.6 kg/m2 and apnea-hypopnea index (AHI) 40.3 ± 24.4 n/h) undergoing PAP therapy for at least three months (mean 377.6 ± 419.5 days). Baseline and follow-up total cholesterol (TC) from nine centers were analyzed. Repeated measures and logistic regression tests (adjusted for age, sex, weight changes, lipid lowering medication, PAP compliance, and treatment duration) were used to compare changes in TC concentration. Incident risk for a coronary heart disease event (CHD) was used to compute a Framingham CHD risk score (estimated from age, BMI, blood pressure, and TC). Results: Adjusted means of TC decreased from 194.2 mg/dl to 189.3 mg/dl during follow-up (p = 0.019). A clinically significant (10%) reduction of TC at PAP follow-up was observed in 422 patients (27%). Duration of PAP therapy was identified as independent predictor for TC reduction, which implies an approximately 10% risk reduction for incident CHD events (from 26.7% to 24.1% in men and from 11.2% to 10.1% in women, p < 0.001 respectively). Conclusion: This observational study demonstrates a reduction of TC after long-term PAP treatment. The close association between TC concentration and cardiovascular (CV) mortality suggests that identification and treatment of OSA may have a beneficial effect on overall CV risk due to this mechanism. This possibility needs to be evaluated in prospective randomized studies. © 2020 Elsevier B.V.
43.	Javaheri, S., et al. (author) Obstructive sleep apnea and stroke: The mechanisms, the randomized trials, and the road ahead 2022 In: Sleep Medicine Reviews. - : Elsevier BV. - 1087-0792. ; 61:February Journal article (peer-reviewed)abstract When considered separately from cardiovascular disease, stroke is the third leading cause of death in the U.S. and is the leading cause of long-term disability in adults. New approaches that can be offered to the majority of ischemic stroke patients, can be continued throughout post-stroke care, can limit stroke severity, and can complement or even enhance rehabilitation, would transform ischemic stroke recovery. The treatment of obstructive sleep apnea (OSA) in patients with acute ischemic stroke may represent one such approach. This manuscript reviews the epidemiologic studies of the bidirectional association between OSA and stroke, and the mechanisms and molecular signatures of OSA leading to transient ischemic attack and stroke as well as the randomized controlled trials and observational cohort studies examining continuous positive airway treatment efficacy on the impact of stroke outcomes. Finally, the insights these studies provide on future research are also discussed. © 2021 Elsevier Ltd
44.	Johansson, Peter, et al. (author) The contribution of hypoxia to the association between sleep apnoea, insomnia, and cardiovascular mortality in community-dwelling elderly with and without cardiovascular disease 2015 In: European Journal of Cardiovascular Nursing. - : Sage Publications. - 1474-5151 .- 1873-1953. ; 14:3, s. 222-231 Journal article (peer-reviewed)abstract Aims:This study explores if nightly hypoxia (i.e. percentage of sleep time with oxygen saturation lower than 90% (SaO2<90%)) contributed to the association between sleep-disordered breathing (SDB) and insomnia in community-dwelling elderly with and without cardiovascular disease (CVD). A second aim was to explore a potential cut-off score for hypoxia to predict insomnia and the association of the cut-off with clinical characteristics and cardiovascular mortality.Method:A total of 331 community-dwelling elderly aged 71–87 years underwent one-night polygraphic recordings. The presence of insomnia was recorded by a self-report questionnaire. The presence of CVD was objectively established and mortality data were collected after three and six years.Results:In both patients with CVD (n=119) or without CVD (n=212) SDB was associated with hypoxia (p<0.005). Only in the patients with CVD was hypoxia associated with insomnia (p<0.001) which mediated an indirect effect (p<0.05) between SDB and insomnia. Hypoxia of more than 1.5% of sleep time with SaO2<90% was found to be a critical level for causing insomnia. According to this criterion 32% (n=39) and 26% (n=55) of those with and without CVD had hypoxia, respectively. These groups did not differ with respect to age, gender, body mass index, diabetes, hypertension, respiratory disease or levels of SDB. However, in the CVD group, hypoxia was associated with cardiovascular mortality at the three-year follow-up (p=0.008) and higher levels of insomnia (p=0.002).Conclusion:In the elderly with CVD, SDB mediated by hypoxia can be associated with more insomnia and a worse prognosis.
45.	Kjellström, Barbro, et al. (author) Adherence to disease-specific drug treatment among patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension 2020 In: European Respiratory Journal Open Research. - Sheffield : European Respiratory Society (ERS). ; 6:4 Journal article (peer-reviewed)abstract Background: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) require lifelong treatment. The aim of the present study was to investigate adherence to disease-specific treatment in patients with PAH or CTEPH. Methods: The study comprised an adult population diagnosed with PAH (n=384) or CTEPH (n=187) alive in 2016-2017. The study utilised three registries: the Swedish PAH registry, the National Board of Health and Welfare, and Statistics Sweden. Withdrawals from pharmacies of disease-specific oral treatments were studied. Adherence was assessed as: 1) Number of days covered defined as the difference between the total number of daily dosages dispensed and the total number of days covered; and 2) Manual assessment by two persons that independently reviewed each patient's prescription fill history to detect anomalies or patterns of deteriorating or improving adherence over time. Results: The mean age was 61±16 years, 61% were female and mean time since diagnosis was 4.6 years. Adherence was 62% using the Number of days covered method and 66% by the Manual assessment method. Drug-specific adherence varied from 91% for riociguat to 60% for sildenafil. Good adherence was associated with shorter time since diagnosis in patients with PAH and with lower number of concomitant other chronic treatments in patients with CTEPH. Age, sex, socioeconomic status or number of pulmonary hypertension (PH) treatments were not associated with adherence. Conclusion: Adherence to oral disease-specific treatment was 60-66% and associated with time since diagnosis and number of concomitant chronic treatments. Sex, age or socioeconomic factors did not affect adherence.
46.	Olofson, Jan, 1947, et al. (author) The single breath nitrogen test and mortality - A 38 years follow up 2016 In: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 112, s. 75-80 Journal article (peer-reviewed)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.
47.	Palm, Andreas, 1971-, et al. (author) Course of DISease in patients reported to the Swedish CPAP Oxygen and VEntilator RegistrY (DISCOVERY) with population-based controls 2020 In: BMJ Open. - : BMJ. - 2044-6055. ; 10:11 Journal article (peer-reviewed)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.
48.	Rydell, Andreas, et al. (author) Endothelial dysfunction is associated with impaired lung function in two independent community cohorts 2018 In: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 143, s. 123-128 Journal article (peer-reviewed)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.
49.	Rydell, Andreas, et al. (author) Plasma proteomics and lung function in four community-based cohorts 2021 In: Respiratory Medicine. - : Elsevier. - 0954-6111 .- 1532-3064. ; 176 Journal article (peer-reviewed)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.
50.	Sawalha, Sami, et al. (author) The impact of comorbidities on mortality among men and women with COPD: report from the OLIN COPD study 2019 In: Therapeutic Advances in Respiratory Disease. - : SAGE Publications. - 1753-4658 .- 1753-4666. ; 13 Journal article (peer-reviewed)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

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