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  • 1. Brandström, Josef
    et al.
    Vetander, Mirja
    Sundqvist, Ann-Charlotte
    Lilja, Gunnar
    Johansson, S. G. O.
    Melén, Erik
    Sverremark-Ekström, Eva
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Nopp, Anna
    Nilsson, Caroline
    Individually dosed omalizumab facilitates peanut oral immunotherapy in peanut allergic adolescents2019Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, nr 10, s. 1328-1341Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Peanut oral immunotherapy (pOIT) has showed good short-term outcomes, but allergic reactions may prevent effective up-dosing and is a major cause of stopping OIT. In placebo-controlled trials, omalizumab has been shown to facilitate allergen immunotherapy and increase tolerance to peanut.

    Objective: We hypothesized that by combining omalizumab with pOIT, and monitor treatment effects with basophil allergen threshold sensitivity tests (CD-sens), peanut allergic patients could safely initiate pOIT and thereafter slowly withdraw omalizumab.

    Methods: This is the 2nd part of a one-armed open phase-2 study where peanut allergic adolescents (n = 23) started pOIT after an individualized omalizumab treatment. The pOIT dose was increased from 280 to 2800 mg peanut protein in 8 weeks followed by an individualized step-wise withdrawal of omalizumab, based on clinical symptoms and CD-sens levels. pOIT continued for 12 weeks followed by an open peanut challenge. Peanut CD-sens and allergen-binding activity (ABA) and IgE-ab, IgG-ab and IgG4-ab to peanut and its components were measured during the study.

    Results: All 23 patients successfully reached the 2800 mg maintenance dose. Moderate/systemic allergic reactions were rare while receiving full-dose omalizumab. Eleven of 23 (48%) successfully continued with pOIT after omalizumab was stopped. Compared to treatment failures, median baseline IgE-ab to peanut components Ara h 1-3 and CD-sens to peanut were significantly lower among successfully treated patients and IgG4-ab to peanut, Ara h 2 and 6 increased significantly more during treatment.

    Conclusions and clinical relevance: This study indicates that omalizumab is an effective adjunctive therapy for initiation and rapid up-dosing of pOIT; however, adverse events from pOIT become more frequent as omalizumab doses are decreased.

  • 2. Bråbäck, Lennart
    et al.
    Ekéus, Cecilia
    Lowe, Adrian J
    Hjern, Anders
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om ojämlikhet i hälsa (CHESS).
    Confounding with familial determinants affects the association between mode of delivery and childhood asthma medication - a national cohort study2013Ingår i: Allergy, Asthma & Clinical Immunology, ISSN 1710-1484, E-ISSN 1710-1492, Vol. 9, nr 14Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Mode of delivery may affect the risk of asthma but the findings have not been consistent and factors shared by siblings may confound the associations in previous studies.

    Methods: The association between mode of delivery and dispensed inhaled corticosteroid (ICS) (a marker of asthma) was examined in a register based national cohort (n=199 837). A cohort analysis of all first born children aged 2-5 and 6-9 years was performed. An age-matched sibling-pair analysis was also performed to account for shared genetic and environmental risk factors.

    Results: Analyses of first-borns demonstrated that elective caesarean section was associated with an increased risk of dispensed ICS in both 2-5 (adjusted odds ratio (aOR)=1.19, 95% confidence interval (CI) 1.09-1.29) and 6-9 (aOR=1.21, 1.09-1.34) age groups. In the sibling-pair analysis, the increased risk associated with elective caesarean section was confirmed in 2-5 year olds (aOR=1.22, 1.05-1.43) but not in 6-9 year olds (aOR=1.06, 0.78-1.44). Emergency caesarean section and vacuum extraction had some association with dispensed ICS in the analyses of first-borns but these associations were not confirmed in the sibling-pair analyses.

    Conclusions: Confounding by familial factors affects the association between mode of delivery and dispensed ICS. Despite this confounding, there was some evidence that elective caesarean section contributed to a modestly increased risk of dispensed ICS but only up to five years of age.

  • 3. Cohen, Joachim
    et al.
    Beernaert, Kim
    Van den Block, Lieve
    Morin, Lucas
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). National Observatory of End of Life Care, France.
    Hunt, Katherine
    Miccinesi, Guido
    Cardenas-Turanzas, Marylou
    Onwuteaka-Philipsen, Bregje
    MacLeod, Rod
    Ruiz-Ramos, Miguel
    Wilson, Donna M.
    Loucka, Martin
    Csikos, Agnes
    Rhee, Yong-Joo
    Teno, Joan
    Ko, Winne
    Deliens, Luc
    Houttekier, Dirk
    Differences in place of death between lung cancer and COPD patients: a 14-country study using death certificate data2017Ingår i: NPD Bulletin, ISSN 1892-8110, E-ISSN 2055-1010, Vol. 27, artikel-id 14Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Chronic obstructive pulmonary disease and lung cancer are leading causes of death with comparable symptoms at the end of life. Cross-national comparisons of place of death, as an important outcome of terminal care, between people dying from chronic obstructive pulmonary disease and lung cancer have not been studied before. We collected population death certificate data from 14 countries (year: 2008), covering place of death, underlying cause of death, and demographic information. We included patients dying from lung cancer or chronic obstructive pulmonary disease and used descriptive statistics and multivariable logistic regressions to describe patterns in place of death. Of 5,568,827 deaths, 5.8% were from lung cancer and 4.4% from chronic obstructive pulmonary disease. Among lung cancer decedents, home deaths ranged from 12.5% in South Korea to 57.1% in Mexico, while hospital deaths ranged from 27.5% in New Zealand to 77.4% in France. In chronic obstructive pulmonary disease patients, the proportion dying at home ranged from 10.4% in Canada to 55.4% in Mexico, while hospital deaths ranged from 41.8% in Mexico to 78.9% in South Korea. Controlling for age, sex, and marital status, patients with chronic obstructive pulmonary disease were significantly less likely die at home rather than in hospital in nine countries. Our study found in almost all countries that those dying from chronic obstructive pulmonary disease as compared with those from lung cancer are less likely to die at home and at a palliative care institution and more likely to die in a hospital or a nursing home. This might be due to less predictable disease trajectories and prognosis of death in chronic obstructive pulmonary disease.

  • 4.
    Gabrielsson, Susanne
    Stockholms universitet.
    Allergen-induced cytokine production in IgE-mediated allergy1999Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
  • 5. Hales, B. J.
    et al.
    Hizawa, N.
    Jenmalm, M.
    Sverremark-Ekström, Eva
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Wardlaw, A. J.
    Developments in the field of allergy in 2014 through the eyes of Clinical and Experimental Allergy2015Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 45, nr 12, s. 1723-1745Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    The pathogenesis of asthma continues to be a major topic of interest to our authors with reviews and original papers on the role of viruses, mechanisms of inflammation, biomarkers, and phenotypes of asthma being major topics. A number of papers described new treatments for asthma focusing on blocking the Th2 response reflecting the fact that two decades of work in this area is finally bearing fruit. The pathogenesis of chronic rhinosinusitis is a growing area of interest, but there has been less on the genetics of airways disease than in previous years possibly reflecting the degree of rigour (and therefore a smaller body of work), with which these sorts of studies are now being undertaken. There continues to be a wide range of papers dealing with mechanisms of allergic disease ranging from clinical-based studies to basic research and the use of in vivo animal models especially mice. As before, mechanisms and new approaches to immunotherapy are common themes. Several were published in the allergens section investigating modification of allergens to increase their effectiveness and reduce the risk of adverse events. Risk factors for allergic disease was a common theme in the epidemiology section and food allergy a common theme in clinical allergy with papers on the development of protocols to induce tolerance and attempts to find biomarkers to distinguish sensitization from allergic disease. This was another exciting year for the editors, and we hope the readers of the journal.

  • 6. Heikkila, K.
    et al.
    Madsen, I. E. H.
    Nyberg, S. T.
    Fransson, E. I.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet.
    Westerlund, Hugo
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet.
    Westerholm, P. J. M.
    Virtanen, M.
    Vahtera, J.
    Vaananen, A.
    Theorell, Töres
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet.
    Suominen, S. B.
    Shipley, M. J.
    Salo, P.
    Rugulies, R.
    Pentti, J.
    Pejtersen, J. H.
    Oksanen, T.
    Nordin, M.
    Nielsen, M. L.
    Kouvonen, A.
    Koskinen, A.
    Koskenvuo, M.
    Knutsson, A.
    Ferrie, J. E.
    Dragano, N.
    Burr, H.
    Borritz, M.
    Bjorner, J. B.
    Alfredsson, L.
    Batty, G. D.
    Singh-Manoux, A.
    Kivimaki, M.
    Job strain and the risk of severe asthma exacerbations: a meta-analysis of individual-participant data from 100 000 European men and women2014Ingår i: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 69, nr 6, s. 775-783Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BackgroundMany patients and healthcare professionals believe that work-related psychosocial stress, such as job strain, can make asthma worse, but this is not corroborated by empirical evidence. We investigated the associations between job strain and the incidence of severe asthma exacerbations in working-age European men and women. MethodsWe analysed individual-level data, collected between 1985 and 2010, from 102 175 working-age men and women in 11 prospective European studies. Job strain (a combination of high demands and low control at work) was self-reported at baseline. Incident severe asthma exacerbations were ascertained from national hospitalization and death registries. Associations between job strain and asthma exacerbations were modelled using Cox regression and the study-specific findings combined using random-effects meta-analyses. ResultsDuring a median follow-up of 10years, 1 109 individuals experienced a severe asthma exacerbation (430 with asthma as the primary diagnostic code). In the age- and sex-adjusted analyses, job strain was associated with an increased risk of severe asthma exacerbations defined using the primary diagnostic code (hazard ratio, HR: 1.27, 95% confidence interval, CI: 1.00, 1.61). This association attenuated towards the null after adjustment for potential confounders (HR: 1.22, 95% CI: 0.96, 1.55). No association was observed in the analyses with asthma defined using any diagnostic code (HR: 1.01, 95% CI: 0.86, 1.19). ConclusionsOur findings suggest that job strain is probably not an important risk factor for severe asthma exacerbations leading to hospitalization or death.

  • 7. Huan, Ping-I
    et al.
    Shu, Huan
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi. Karlstad University, Sweden.
    Mersha, Tesfaye B.
    Comparing DNA methylation profiles across different tissues associated with the diagnosis of pediatric asthma2020Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 10, nr 1, artikel-id 151Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    DNA methylation (DNAm) profiles in central airway epithelial cells (AECs) may play a key role in pathological processes in asthma. The goal of the current study is to compare the diagnostic performance of DNAm markers across three tissues: AECs, nasal epithelial cells (NECs), and peripheral blood mononuclear cells (PBMCs). Additionally, we focused on the results using the machine learning algorithm in the context of multi-locus effects to evaluate the diagnostic performance of the optimal subset of CpG sites. We obtained 74 subjects with asthma and 41 controls from AECs, 15 subjects with asthma and 14 controls from NECs, 697 subjects with asthma and 97 controls from PBMCs. Epigenome-wide DNA methylation levels in AECs, NECs and PBMCs were measured using the Infinium Human Methylation 450K BeadChip. Overlap analysis across the three different sample sources at the locus and pathway levels were studied to investigate shared or unique pathophysiological processes of asthma across tissues. Using the top 100 asthma-associated methylation markers as classifiers from each dataset, we found that both AEC- and NEC-based DNAm signatures exerted a lower classification error than the PBMC-based DNAm markers (p-value = 0.0002). The area-under-the-curve (AUC) analysis based on out-of-bag errors using the random forest classification algorithm revealed that PBMC-, NEC-, and AEC-based methylation data yielded 31 loci (AUC: 0.87), 8 loci (AUC: 0.99), and 4 loci (AUC: 0.97) from each optimal subset of tissue-specific markers, respectively. We also discovered the locus-locus interaction of DNAm levels of the CDH6 gene and RAPGEF3 gene might interact with each other to jointly predict the risk of asthma - which suggests the pivotal role of cell-cell junction in the pathological changes of asthma. Both AECs and NECs might provide better diagnostic accuracy and efficacy levels than PBMCs. Further research is warranted to evaluate how these tissue-specific DNAm markers classify and predict asthma risk.

  • 8. Jernelov, S.
    et al.
    Lekander, Mats
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet. Karolinska Institutet, Sweden.
    Almqvist, C.
    Axelsson, John
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet. Karolinska Institutet, Sweden.
    Larsson, H.
    Development of atopic disease and disturbed sleep in childhood and adolescence a longitudinal population-based study2013Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 43, nr 5, s. 552-559Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Both atopic diseases and sleep disturbances have increased during recent decades, especially in children. Sleep is important for many aspects of immune regulation relevant in allergic diseases, and sleep disturbances are common in patients with such diseases. A connection between sleep disturbances and fatigue, and atopic disease is well established. However, the time course and putative causal relationships between these factors are obscure.

    Objective We aimed at investigating the developmental relationships between subjectively reported sleep disturbances and symptoms of atopic disease, from childhood to adolescence.

    Methods This longitudinal study used parent-report questionnaire data on symptoms of atopic disease, and sleep disturbances, from the Twin Study of Child and Adolescent Development (TCHAD). Overall, 1480 twin pairs born in Sweden were approached first when children were 89years old, and again later at 1314years old. Response rates were 75% and 72%. Data from the TCHAD questionnaires were linked to the Swedish Medical Birth Register based on personal identification numbers.

    Results Being overtired at age 8 increased the risk [OR; 95% CI (2.59; 1.315.11)] to develop rhinitis symptoms at age 13, even when controlling for gender, previous rhinitis, Socio-economic status, birth weight and other sleep disturbances at age 8. Likewise, symptoms of asthma at age 8 was an independent risk factor for being overtired at age 13 [OR; 95% CI (2.64; 1.444.84)], controlling for similar confounders.

    Conclusion & Clinical Relevance The findings from this study are consonant with the proposition that atopic disease and disturbed sleep are more than passively interrelated. Future research needs to delineate whether causal relationships between these problems are at hand and, if so, at what periods in development this applies. These results point to a need for clinicians to investigate sleep difficulties and treat impaired sleep in paediatric patients with atopic disease.

  • 9. Khatab, Khaled
    et al.
    Felten, Michael K.
    Kandala, Nagianga B.
    Ghilagaber, Gebrenegus
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Statistiska institutionen.
    Gumber, Anil
    Kraus, Thomas
    Risk Factors Associated with Asbestos-related Diseases: Results of the Asbestos Surveillance Programme Aachen2014Ingår i: European medical journal. Respiratory, ISSN 2054-3166, s. 1-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to examine the association between workplace exposure to asbestos and risk factors for developing related chronic respiratory diseases, using the analysis of a cohort of 8,582 formerly asbestos-exposed workers, as well as to assess the grade value of three risk categories used for a focused surveillance procedure. The results showed that the participants who were aged over 65 (OR and 95% CI: 11.47 [5.48-23.99]) and active smokers (OR and 95% CI: 9.48 [4.07-22.09]), were at a significantly high risk for developing lung cancer. The risk of developing benign lesions of the lung or pleura (BLLP) was almost 6-times higher (OR and 95% CI: 5.76 [4.7-7]) for the age group over 65. The risk of developing mesothelioma was influenced by exposure duration (OR and 95% CI: 4.36 [1-19.01]); and for the age group over 65 (OR and 95% CI: 4.58 [1.86-11.27]). The study has demonstrated that the use of risk categories based on a combination of risk factors (age, smoking status, and duration of exposure) could be advantageous for planning the target health surveillance programmes.

  • 10. Lodin, Karin
    et al.
    Lekander, Mats
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet. Karolinska Institutet, Sweden.
    Syk, Jörgen
    Alving, Kjell
    Andreasson, Anna
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet. Karolinska Institutet, Sweden; Macquarie University, Australia.
    Associations between self-rated health, sickness behaviour and inflammatory markers in primary care patients with allergic asthma: a longitudinal study2017Ingår i: NPD Bulletin, ISSN 1892-8110, E-ISSN 2055-1010, Vol. 27, artikel-id 67Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Allergic asthma is a chronic inflammatory disorder associated with elevated levels of immunoglobulin E (IgE), serum eosinophilic cationic protein (S-ECP), plasma eosinophil-derived neurotoxin (P-EDN) and fraction of exhaled nitric oxide (FENO). Poor self-rated health and sickness behaviour has repeatedly been associated with inflammatory markers, but the nature of this relationship in chronic inflammatory disease is not known. Likewise, such findings largely rely on cross-sectional investigations. Self-rated health (How would you rate your general state of health?), sickness behaviour (mean rating of satisfaction with energy, sleep, fitness, appetite and memory), IgE, S-ECP, P-EDN, and FENO were assessed in 181 non-smoking primary care patients with asthma in a 1-year longitudinal study. Associations between repeated measurements were calculated using mixed regression models and Spearman's correlations for change scores. Poor self-rated health was associated with high levels of seasonal IgE (p = 0.05) and food IgE (p = 0.04), but not total IgE or inflammatory markers. An increase over 1 year in perennial IgE was associated with a worsening of self-rated health (rho = 0.16, p = 0.04). Poor self-rated health was associated with more pronounced sickness behaviour (p < 0.001), and a worsening in sickness behaviour was associated with a worsening of self-rated health over time (rho = 0.21, p = 0.007). The study corroborates the importance of sickness behaviour as a determinant of self-rated health by showing that these factors co-vary over a 1-year period in a group of patients with allergic asthma. The importance of specific IgE for perceived health in primary care patients with mild to moderate asthma needs further investigation.

  • 11. Marengoni, Alessandra
    et al.
    Vetrano, Davide L.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Università Cattolica del Sacro Cuore, Italy.
    Manes-Gravina, Ester
    Bernabei, Roberto
    Onder, Graziano
    Palmer, Katie
    The Relationship Between COPD and Frailty: A Systematic Review and Meta-Analysis of Observational Studies2018Ingår i: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 154, nr 1, s. 21-40Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Frailty is common in seniors and is characterized by diminished physiological reserves and increased vulnerability to stressors. Frailty can change the prognosis and treatment approach of several chronic diseases, including COPD. The association between frailty and COPD has never been systematically reviewed.

    OBJECTIVES: The goal of this study was to conduct a systematic review and meta-analysis assessing the association of COPD with frailty and pre-frailty.

    METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used when reporting this review. We searched PubMed, Web of Science, and Embase from January 1, 2002, to October 6, 2017. The quality of the studies was evaluated by using the Newcastle Ottawa Scale. Two assessors independently rated each study: scores > 7 were considered a low risk of bias; 5 to 7, a moderate risk of bias; and < 5, a high risk of bias. Pooled estimates were obtained through random effect models and Mantel-Haenszel weighting. Homogeneity (I-2) and publication bias were assessed.

    RESULTS: Atotal of 27 studies were selected: 23 cross-sectional, three longitudinal, and one both. The pooled prevalence of pre-frailty in individuals with COPD was 56% (95% CI, 52-60; I-2 = 80.8%); it was 19% (95% CI, 14-24; I-2 = 94.4%) for frailty. Patients with COPD had a two-fold increased odds of frailty (pooled OR, 1.97 [95% CI, 1.53-2.53]; I-2 = 0.0%). Three longitudinal studies, presenting heterogeneous aims and methods, suggested a bidirectional association between COPD and frailty.

    CONCLUSIONS: Frailty and pre-frailty are common in individuals with COPD. Older subjects with COPD have a two-fold increased odds of frailty. These results may have clinical implications, as they identify the need to assess frailty in individuals with COPD and to further investigate any potential negative effects associated with the co-occurrence of these conditions. Longitudinal research that examines temporal associations between COPD and frailty are needed to further clarify this relationship and to assess if treatment of COPD may prevent the onset of frailty.

  • 12. Muala, Ala
    et al.
    Rankin, Gregory
    Sehlstedt, Maria
    Unosson, Jon
    Bosson, Jenny A.
    Behndig, Annelie
    Pourazar, Jamshid
    Nyström, Robin
    Pettersson, Esbjörn
    Bergvall, Christoffer
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Westerholm, Roger
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Jalava, Pasi I.
    Happo, Mikko S.
    Uski, Oskari
    Hirvonen, Maija-Riitta
    Kelly, Frank J.
    Mudway, Ian S.
    Blomberg, Anders
    Boman, Christoffer
    Sandström, Thomas
    Acute exposure to wood smoke from incomplete combustion - indications of cytotoxicity2015Ingår i: Particle and Fibre Toxicology, ISSN 1743-8977, E-ISSN 1743-8977, Vol. 12, artikel-id 33Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Smoke from combustion of biomass fuels is a major risk factor for respiratory disease, but the underlying mechanisms are poorly understood. The aim of this study was to determine whether exposure to wood smoke from incomplete combustion would elicit airway inflammation in humans. Methods: Fourteen healthy subjects underwent controlled exposures on two separate occasions to filtered air and wood smoke from incomplete combustion with PM1 concentration at 314 mu g/m(3) for 3 h in a chamber. Bronchoscopy with bronchial wash (BW), bronchoalveolar lavage (BAL) and endobronchial mucosal biopsies was performed after 24 h. Differential cell counts and soluble components were analyzed, with biopsies stained for inflammatory markers using immunohistochemistry. In parallel experiments, the toxicity of the particulate matter (PM) generated during the chamber exposures was investigated in vitro using the RAW264.7 macrophage cell line. Results: Significant reductions in macrophage, neutrophil and lymphocyte numbers were observed in BW (p < 0.01, < 0.05, < 0.05, respectively) following the wood smoke exposure, with a reduction in lymphocytes numbers in BAL fluid (< 0.01. This unexpected cellular response was accompanied by decreased levels of sICAM-1, MPO and MMP-9 (p < 0.05, < 0.05 and < 0.01). In contrast, significant increases in submucosal and epithelial CD3+ cells, epithelial CD8+ cells and submucosal mast cells (p < 0.01, < 0.05, < 0.05 and < 0.05, respectively), were observed after wood smoke exposure. The in vitro data demonstrated that wood smoke particles generated under these incomplete combustion conditions induced cell death and DNA damage, with only minor inflammatory responses. Conclusions: Short-term exposure to sooty PAH rich wood smoke did not induce an acute neutrophilic inflammation, a classic hallmark of air pollution exposure in humans. While minor proinflammatory lymphocytic and mast cells effects were observed in the bronchial biopsies, significant reductions in BW and BAL cells and soluble components were noted. This unexpected observation, combined with the in vitro data, suggests that wood smoke particles from incomplete combustion could be potentially cytotoxic. Additional research is required to establish the mechanism of this dramatic reduction in airway leukocytes and to clarify how this acute response contributes to the adverse health effects attributed to wood smoke exposure.

  • 13.
    Nordin, Maria
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet. Umeå University, Sweden.
    Nordin, Steven
    Sleep and sleepiness in environmental intolerances: a population based study2016Ingår i: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 24, s. 1-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: About one fourth of the general population report environmental intolerance (El) to odorous/pungent chemicals, certain buildings, electromagnetic fields (EMFs), and/or sounds. EI sufferers show various clinical features, of which sleep disturbance is one. Sleep disturbance is common also in the general population, but it is not known whether the disturbance is more prominent in EI sufferers than in individuals who do not experience EI. Therefore, El was compared on various sleep aspects with referents without El.

    Methods: A population-based sample of 3406 individuals, aged 18-79 years, was recruited from Northern Sweden. Sleep quality, non-restorative sleep, daytime sleepiness, obstructive breathing, and nocturnal insomnia were assessed with the Karolinska Sleep Questionnaire. Single questions assessed time slept, amount of hours of needed sleep, and extent of enough time slept.

    Results: All four EI groups, compared to the referents, reported significantly poorer sleep quality, more non-restorative sleep, more daytime sleepiness, more obstructive breathing and higher prevalence of nocturnal insomnia than the referents. Nocturnal insomnia was an important factor for El groups attributing their most prevalent symptoms to chemicals and sounds, irrespective of distress and certain syndromes. None of the EI groups differed significantly from the referents on time slept, but reported needing more sleep time (the EMF-intolerance group showing only a tendency), and all four groups reported to perceive enough sleep to a significantly lesser extent.

    Conclusion: Sleep disturbance and daytime sleepiness are more common in individuals reporting El compared to normal referents. Moreover, nocturnal insomnia is an important symptom in its own right in various types of EI. This evokes the question of whether or not sleep therapy may attenuate the severity of the El.

  • 14.
    Sverremark-Ekström, Eva
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Hultgren, E. H.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Borres, M. P.
    Nilsson, C.
    Peanut sensitization during the first five years of life is associated with elevated levels of peanut-specific IgG2012Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 23, nr 3, s. 224-229Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Allergen-specific IgE antibodies are implicated in allergic diseases while allergen-specific IgG antibodies have been proposed to prevent allergic reactions. The objective for this study was to study if the immune response (IgG and IgG4) to peanut differs in IgE sensitized and non-sensitized young children.

    Methods: A total of 239 children have been followed prospectively from birth to 5 years of age. Levels of IgG and IgG4 to peanut, Ara h 2 and Ara h 8 were analyzed at 2 and 5 years of age and related to IgE-sensitization and peanut consumption.

    Results:  Levels of peanut-specific IgG and IgG4 were significantly higher in peanut-sensitized children at 2 and 5 years of age when compared to non-sensitized children and children sensitized to other food/inhalant allergens. A strong correlation was seen between levels of peanut-specific IgG/IgG4-ratios and peanut-specific IgE at 5 years of age. Children avoiding peanuts, a subgroup of the peanut sensitized, had statistically significant higher levels of IgE to peanut and a tendency of higher IgG and IgG4 levels to peanut. In the avoidance-group significant correlations between IgE and IgG/IgG4 to peanut was found compared to children eating peanuts. 

    Conclusion: Peanut-specific IgG or IgG4 levels were elevated in peanut-sensitized children especially those avoiding peanuts. In our study, IgG and IgG4 do not seem to indicate tolerance or protection from sensitization.

  • 15. Syk, Jörgen
    et al.
    Malinovschi, Andrei
    Johansson, Gunnar
    Undén, Anna-Lena
    Andreasson, Anna
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet. Karolinska Institutet, Sweden.
    Lekander, Mats
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet. Karolinska Institutet, Sweden.
    Alving, Kjell
    Anti-inflammatory Treatment of Atopic Asthma Guided by Exhaled Nitric Oxide: A Randomized, Controlled Trial2013Ingår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 1, nr 6, s. 639-648Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Atopic asthma is characterized by Th2 cytokine–driven inflammation of the airway mucosa, which is signaled by the fraction of exhaled nitric oxide (FENO).

    Objective

    We tested whether an FENO-guided anti-inflammatory treatment algorithm could improve asthma-related quality of life and asthma symptom control, and reduce exacerbations in atopic asthmatics within primary care.

    Methods

    Altogether, 187 patients with asthma and who were nonsmokers (age range, 18-64 years) with perennial allergy and who were on regular inhaled corticosteroid treatment were recruited at 17 primary health care centers, randomly assigned to 2 groups and followed up for 1 year. For the controls (n = 88), FENO measurement was blinded to both operator and patient, and anti-inflammatory treatment was adjusted according to usual care. In the active group (n = 93), treatment was adjusted according to FENO. Questionnaires on asthma-related quality of life (Mini Asthma Quality of Life Questionnaire) and asthma control (Asthma Control Questionnaire) were completed, and asthma events were noted.

    Results

    The Asthma Control Questionnaire score change over 1 year improved significantly more in the FENO-guided group (–0.17 [interquartile range {IQR}, −0.67 to 0.17] vs 0 [−0.33 to 0.50]; P = .045), whereas the Mini Asthma Quality of Life Questionnaire score did not (0.23 [IQR, 0.07-0.73] vs 0.07 [IQR, −0.20 to 0.80]; P = .197). The change in Asthma Control Questionnaire was clinically important in subpopulations with poor control at baseline (P = .03). Furthermore, the exacerbation rate (exacerbations/patient/y) was reduced by almost 50% in the FENO-guided group (0.22 [CI, 0.14-0.34] vs 0.41 [CI, 0.29-0.58]; P = .024). Mean overall inhaled corticosteroid use was similar in both groups (P = .95).

    Conclusion

    Use of FENO to guide anti-inflammatory treatment within primary care significantly reduced the exacerbation rate and improved asthma symptom control without increasing overall inhaled corticosteroid use.

  • 16.
    Trevisan, Caterina
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). University of Padova, Italy.
    Rizzuto, Debora
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Stockholm Gerontology Research Center, Sweden.
    Maggi, Stefania
    Sergi, Giuseppe
    Welmer, Anna-Karin
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Stockholm Gerontology Research Center, Sweden; Karolinska Institutet, Sweden; Karolinska University Hospital, Sweden.
    Vetrano, Davide Liborio
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). IRCCS Fondazione Policlinico “A. Gemelli”, Italy; Catholic University of Rome, Italy.
    Cross-Sectional and Longitudinal Associations between Peak Expiratory Flow and Frailty in Older Adults2019Ingår i: Journal of Clinical Medicine, ISSN 2077-0383, Vol. 8, nr 11, artikel-id 1901Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Peak expiratory flow (PEF) has been linked to several health-related outcomes in older people, but its association with frailty is still unclear. This study investigates the association between PEF and prevalent and incident frailty in older adults. Data come from 2559 community-dwelling participants (age >= 60 years) of the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K). Baseline PEF was expressed as standardized residual (SR) percentiles. Frailty was assessed at baseline and over six years, according to the Fried criteria. Associations between PEF and frailty were estimated cross-sectionally through logistic regressions, and longitudinally by multinomial logistic regression, considering death as alternative outcome. Obstructive respiratory diseases and smoking habits were treated as potential effect modifiers. Our cross-sectional results showed that the 10th-49th and <10th PEF SR percentile categories were associated with three- and five-fold higher likelihood of being frail than the 80th-100th category. Similar estimates were confirmed longitudinally, i.e., adjusted OR = 3.11 (95% CI: 1.61-6.01) for PEF SR percentiles < 10th, compared with 80th-100th percentiles. Associations were enounced in participants without physical deficits, and tended to be stronger among those with baseline obstructive respiratory diseases, and, longitudinally, also among former/current smokers. These findings suggest that PEF is a marker of general robustness in older adults, and its reduction exceeding that expected by age is associated with frailty development.

  • 17.
    Vetrano, Davide L.
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Catholic University of Rome, Italy; IRCCS Fondazione Policlinico “A. Gemelli”, Italy; University of Brescia, Italy.
    Zucchelli, Alberto
    Bianchini, Elisa
    Cricelli, Claudio
    Piraino, Alessio
    Zibellini, Marco
    Ricci, Alberto
    Onder, Graziano
    Lapi, Francesco
    Triple inhaled therapy in COPD patients: determinants of prescription in primary care2019Ingår i: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 154, s. 12-17Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To assess the incidence and determinants of the triple inhaled therapy in chronic obstructive pulmonary disease (COPD) primary care patients.

    Methods: Data derived from the Health Search Database (HSD) gathering information on 700 Italian general practitioners. A cohort of COPD patients, prescribed for the first time with inhaled treatments, was followed-up between January 2002 and December 2014. The outcome was the first incident prescription of a triple inhaled therapy, namely the combination of inhaled corticosteroids (ICS), long-acting beta agonists (LABA), and long-acting muscarinic antagonists (LAMA). Cox regressions were used to test the association (hazard ratios, HR) between candidate determinants and the outcome.

    Results: Out of 17589 patients (mean age 71.1 +/- 11.3 years; 37.4% females), 3693 (21%) were prescribed with a triple inhaled therapy during follow-up. Older age (HR=1.79 to 2.61), current and former smoking habit (HR=1.72 and 1.66), higher GOLD stage (HR=1.45 to 2.79), the number of moderate and severe COPD exacerbations (HR=1.10 to 2.63), and heart failure (HR=1.17) resulted statistically significantly associated with an increased incident prescription of the triple inhaled therapy. Female sex (HR=0.80) and some co-morbidities (HR=0.21 to 0.87) resulted negatively associated with the outcome. Furthermore, patients initially treated with LAMA (HR=1.5) and LABA/ICS (HR=1.23) were more likely to escalate to the triple therapy, than those on LABA. Conversely, patients initially treated with ICS presented a negative hazard (HR=0.72).

    Conclusions: The knowledge of demographic and clinical determinants of the escalation to the triple inhaled therapy in real-world COPD patients may help clinicians to better personalize respiratory pharmacological treatments of their patients, and inform international societies that issue clinical guidelines.

  • 18. Westerlund, Anna
    et al.
    Brandt, Lena
    Harlid, Richard
    Åkerstedt, Torbjorn
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet. Karolinska Institutet, Sweden.
    Lagerros, Ylva Trolle
    Using the Karolinska Sleep Questionnaire to identify obstructive sleep apnea syndrome in a sleep clinic population2014Ingår i: Clinical Respiratory Journal, ISSN 1752-6981, E-ISSN 1752-699X, Vol. 8, nr 4, s. 444-454Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: In Scandinavia, portable monitoring has virtually replaced standard polysomnography for diagnosis of obstructive sleep apnea syndrome (OSAS). Because waiting times for specialized OSAS care remain long, an accurate screening tool to exclude low-risk patients from diagnostic testing would be valuable. Objectives: To examine the diagnostic accuracy of the Karolinska Sleep Questionnaire (KSQ) for OSAS. Methods: Consecutive patients, 30-66 years old, attending a large sleep clinic in Sweden for OSAS evaluation completed the KSQ and underwent in-home portable monitoring and medical history evaluation. OSAS was defined as apnea-hypopnea index >= 5 with symptoms of disease. We calculated sensitivity and specificity of apnea/snoring and sleepiness indices of the KSQ. Retrospectively, we combined six KSQ items (snoring, breathing cessations, disturbed sleep, etc.) and four clinical variables (age, sex, body mass index, smoking status) predictive of OSAS into a new instrument, which we also evaluated. Instrument score ranged between 0 and 21; a higher score indicated more severe symptoms. Results: Of 103 patients, 62 were diagnosed with OSAS. Sensitivity and specificity of the indices were 0.56 and 0.68 (apnea/snoring), and 0.37 and 0.71 (sleepiness). The new instrument performed optimally at a score of 9. Sensitivity was 0.76 (95% confidence interval 0.63-0.86) and specificity 0.88 (0.74-0.96). Between 19.4% and 50.5% of patients were unaware of having apnea/snoring symptoms. Conclusions: Diagnostic accuracy of the apnea/snoring and sleepiness indices for OSAS was poor but could be improved by combining clinical and KSQ items. The usefulness of the apnea/snoring index and the combined instrument was questionable because of extensive symptom unawareness.

  • 19.
    Åkerstedt, Torbjörn
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet. Karolinska Institutet, Sweden.
    Narusyte, Jurgita
    Alexanderson, Kristina
    Svedberg, Pia
    Sleep Duration, Mortality, and Heredity-A Prospective Twin Study2017Ingår i: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 40, nr 10, artikel-id zsx135Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction

    A number of studies have shown a U-shaped association between sleep duration and mortality. Since sleep duration is partly genetically determined, it seems likely that its association with mortality is also genetically influenced. The purpose of the present study was to investigate the influence on heredity on the association between sleep duration and mortality.

    Methods

    We used a cohort of 14 267 twins from the Swedish Twin Registry.

    Results

    A Cox proportional hazards regression analysis, adjusted for a number of covariates, confirmed a clear U shape with a hazard ratio (HR) = 1.34 and 95% confidence interval (CI) = 1.15-1.57 for a sleep duration of = 6.5 hours and HR = 1.18 (CI = 1.07-1.30) for sleep of = 9.5 hours. Reference value was 7.0 hours. A co-twin analysis of 1942 twins discordant on mortality showed a HR = 2.66 (CI = 1.17-6.04) for long (= 9.5 hours) sleep in monzygotic twins and an HR = 0.66 (CI = 0.20-2.14) for short (< 6.5 hours) sleep. In dizygotic twins, no association was significant. The heritability for mortality was 28% for the whole group, while it was 86% for short sleepers and 42% for long sleepers. Thus, the link with mortality for long sleep appears to be more due to environmental factors than to heredity, while heritability dominates among short sleepers.

    Conclusions

    We found that both long and short sleep were associated with higher total mortality, that the difference in mortality within twin pairs is associated with long sleep, and that short sleep has a higher heritability for mortality, while long sleep is associated with more environmental influences on mortality.

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