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Sökning: hsv:(MEDICIN OCH HÄLSOVETENSKAP) hsv:(Klinisk medicin) hsv:(Lungmedicin och allergi) > Karolinska Institutet

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1.
  • Engström, Gunnar, et al. (författare)
  • Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications
  • 2024
  • Ingår i: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284.
  • Tidskriftsartikel (refereegranskat)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.
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3.
  • Brew, Bronwyn K., et al. (författare)
  • Paediatric asthma and non-allergic comorbidities : A review of current risk and proposed mechanisms
  • 2022
  • Ingår i: Clinical and Experimental Allergy. - Stockholm : Wiley-Blackwell Publishing Inc.. - 0954-7894 .- 1365-2222. ; 15:9, s. 1035-1047
  • Forskningsöversikt (refereegranskat)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.
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4.
  • Geirsson, Arnar, et al. (författare)
  • Differential outcomes of open and clamp-on distal anastomosis techniques in acute type A aortic dissection
  • 2019
  • Ingår i: Journal of Thoracic and Cardiovascular Surgery. - : Elsevier. - 0022-5223 .- 1097-685X. ; 157:5, s. 1750-1758
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Open-distal anastomosis is the preferred technique over clamp-on technique for surgical repair of acute type A aortic dissection (ATAAD). The aim of this study was to define how outcomes of ATAAD were affected by the use of either technique.Methods: Nordic Consortium for Acute Type A Aortic Dissection includes 8 academic cardiothoracic hospitals in 4 Nordic countries. The cohort consisted of 1134 patients, 153 clamp-on and 981 open-distal, from 2005 to 2014.Results: Patients who underwent operation with the clamp-on were younger, more frequently had coronary artery disease, bicuspid aortic valve, hypotension/shock or syncope, and a greater PennClass than open-distal patients. Postoperative cerebral vascular accident occurred less frequently in clamp-on (14/153, 10%) compared with the open-distal group (190/981, 20%). Clamp-on had greater 30-day mortality (39/153, 25%) than the open-distal group (158/981, 16%), and 5-year survival was also worse in clamp-on (61.8% +/- 4.4%) compared with the open-distal group (73.0% +/- 1.6%). The open-distal technique was used more frequently in greater-volume hospitals but was not independently associated with 30-day mortality. Preoperative condition was an independent risk factor whereas hospital volume and later year of operation were beneficial in regard to short-term outcome. Open-distal was independently associated with improved mid-term survival.Conclusions: Patients who underwent operation with the clamp-on were sicker on presentation and had worse short-and mid-term survival compared with the open-distal group. Patients in the open-distal group had greater rates of cerebrovascular complications. The results support the routine use of open-distal anastomosis as the primary operative strategy for ATAAD, although clamp-on can be performed successfully in select cases.
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5.
  • Inghammar, Malin, et al. (författare)
  • COPD and the risk of tuberculosis--a population-based cohort study.
  • 2010
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:4
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Both chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) primarily affect the lungs and are major causes of morbidity and mortality worldwide. COPD and TB have common risk factors such as smoking, low socioeconomic status and dysregulation of host defence functions. COPD is a prevalent co-morbid condition, especially in elderly with TB but in contrast to other diseases known to increase the risk of TB, relatively little is known about the specific relationship and impact from COPD on TB-incidence and mortality. METHODS AND FINDINGS: All individuals > or = 40 years of age, discharged with a diagnosis of COPD from Swedish hospitals 1987-2003 were identified in the Swedish Inpatient Register (n = 115,867). Records were linked to the Swedish Tuberculosis Register 1989-2007 and the relative risk of active TB in patients with COPD compared to control subjects randomly selected from the general population (matched for sex, year of birth and county of residence) was estimated using Cox regression. The analyses were stratified by year of birth, sex and county of residence and adjusted for immigration status, socioeconomic status (SES) and inpatient co-morbidities previously known to increase the risk of TB. COPD patients had a three-fold increased hazard ratio (HR) of developing active TB (HR 3.0 (95% confidence interval 2.4 to 4.0)) that was mainly dependent on an increased risk of pulmonary TB. In addition, logistic regression estimates showed that COPD patients who developed active TB had a two-fold increased risk of death from all causes within first year after the TB diagnosis compared to the general population control subjects with TB (OR 2.2, 95% confidence interval 1.2 to 4.1). CONCLUSIONS: This population-based study comprised of a large number of COPD patients shows that these patients have an increased risk of developing active TB compared to the general population. The results raise concerns that the increasing global burden of COPD will increase the incidence of active TB. The underlying contributory factors need to be disentangled in further studies.
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6.
  • Niespodziana, K, et al. (författare)
  • Microarray Technology May Reveal the Contribution of Allergen Exposure and Rhinovirus Infections as Possible Triggers for Acute Wheezing Attacks in Preschool Children
  • 2021
  • Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 13:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Allergen exposure and rhinovirus (RV) infections are common triggers of acute wheezing exacerbations in early childhood. The identification of such trigger factors is difficult but may have therapeutic implications. Increases of IgE and IgG in sera, were shown against allergens and the N-terminal portion of the VP1 proteins of RV species, respectively, several weeks after allergen exposure or RV infection. Hence, increases in VP1-specific IgG and in allergen-specific IgE may serve as biomarkers for RV infections or allergen exposure. The MeDALL-allergen chip containing comprehensive panels of allergens and the PreDicta RV chip equipped with VP1-derived peptides, representative of three genetic RV species, were used to measure allergen-specific IgE levels and RV-species-specific IgG levels in sera obtained from 120 preschool children at the time of an acute wheezing attack and convalescence. Nearly 20% of the children (22/120) showed specific IgE sensitizations to at least one of the allergen molecules on the MeDALL chip. For 87% of the children, increases in RV-specific IgG could be detected in the follow-up sera. This percentage of RV-specific IgG increases was equal in IgE-positive and -negative children. In 10% of the children, increases or de novo appearances of IgE sensitizations indicative of allergen exposure could be detected. Our results suggest that, in the majority of preschool children, RV infections trigger wheezing attacks, but, in addition, allergen exposure seems to play a role as a trigger factor. RV-induced wheezing attacks occur in IgE-sensitized and non-IgE-sensitized children, indicating that allergic sensitization is not a prerequisite for RV-induced wheeze.
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7.
  • Rusanen, Minna, et al. (författare)
  • Chronic Obstructive Pulmonary Disease and Asthma and the Risk of Mild Cognitive Impairment and Dementia : A Population Based CAIDE Study
  • 2013
  • Ingår i: CURRENT ALZHEIMER RESEARCH. - : Bentham Science Publishers Ltd.. - 1567-2050 .- 1875-5828. ; 10:5, s. 549-555
  • Tidskriftsartikel (refereegranskat)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.
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8.
  • Bengtsson, Caroline, et al. (författare)
  • Sinonasal outcome test-22 and peak nasal inspiratory flow : valuable tools in obstructive sleep apnoea
  • 2020
  • Ingår i: Rhinology. - 0300-0729 .- 1996-8604. ; 58:4, s. 341-348
  • Tidskriftsartikel (refereegranskat)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.
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9.
  • Kuhlin, Johanna, et al. (författare)
  • Sputuminduktion bör väljas före ventrikelsköljning vid tbc-prov [Is it time to use sputum induction as a complementary specimen collection procedure in adult patients with suspected pulmonary tuberculosis?]
  • 2020
  • Ingår i: Läkartidningen. - Stockholm, Sweden : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 117
  • Tidskriftsartikel (refereegranskat)abstract
    • Gastric aspiration (GA) and sputum induction (SI) are used for diagnosing pulmonary tuberculosis (TB) in patients who cannot spontaneously produce sputum. This meta-analysis compares the sensitivity of GA and SI as alternative strategies for TB specimen collection in adult patients and describes procedure preference across Swedish Departments for Infectious Diseases (DID). We searched PubMed for articles on SI, GA and TB in adults. The meta-analysis included six articles (418 patients) and resulted in a crude OR 3.5 (95% CI 1.6-7.8) for positive culture from SI compared with GA. We asked all DID which procedure they currently used for collecting TB specimens (Sep 2019). Answers were received from 27/29 DID of which 67% (18/27) used SI as the primary diagnostic strategy when a patient could not spontaneously submit sputum. In conclusion, SI seems more effective than GA in detecting culture positive pulmonary TB in adult patients.
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10.
  • Arruda, Lucas C. M., et al. (författare)
  • A novel CD34-specific T-cell engager efficiently depletes acute myeloid leukemia and leukemic stem cells in vitro and in vivo
  • 2022
  • Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 107:8, s. 1786-1795
  • Tidskriftsartikel (refereegranskat)abstract
    • Less than a third of patients with acute myeloid leukemia (AML) are cured by chemotherapy and/or hematopoietic stem cell transplantation, highlighting the need to develop more efficient drugs. The low efficacy of standard treatments is associated with inadequate depletion of CD34(+) blasts and leukemic stem cells, the latter a drug-resistant subpopulation of leukemia cells characterized by the CD34(+)CD38(-) phenotype. To target these drug-resistant primitive leukemic cells better, we have designed a CD34/CD3 bi-specific T-cell engager (BTE) and characterized its anti-leukemia potential in vitro, ex vivo and in vivo. Our results show that this CD34-specific BTE induces CD34-dependent T-cell activation and subsequent leukemia cell killing in a dose-dependent manner, further corroborated by enhanced T-cell-mediated killing at the singlecell level. Additionally, the BTE triggered efficient T-cell-mediated depletion of CD34(+) hematopoietic stem cells from peripheral blood stem cell grafts and CD34(+) blasts from AML patients. Using a humanized AML xenograft model, we confirmed that the CD34-specific BTE had in vivo efficacy by depleting CD34(+) blasts and leukemic stem cells without side effects. Taken together, these data demonstrate that the CD34-specific BTE has robust antitumor effects, supporting development of a novel treatment modality with the aim of improving outcomes of patients with AML and myelodysplastic syndromes.
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