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  • 1.
    Abdalla Omer, Hemn
    et al.
    University of Sulaimani.
    Amin, Kawa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    TGFβ1, SMAD2, CTNNβ1, and Wnt3a gene mutational status and serum concentrations in individuals with non-small cell lung cancer2023In: Cellular and Molecular Biology, ISSN 0145-5680, E-ISSN 1165-158X, Vol. 69, no 11, p. 81-91Article in journal (Refereed)
    Abstract [en]

    The objective of the current investigation was to investigate the diagnostic utility of the serum concentrations and mutational status of TGFβ1, SMAD2, CTNNβ1, and Wnt3a. and the expression levels of human-rela-ted genes in patients with non-small cell lung cancer (NSCLC). The serum concentrations were determined using the ELISA technique, and PCR for genotype variations of TGFβ1, SMAD2, CTNNβ1, and Wnt3a were examined using Sanger sequencing in tissue samples obtained from 93 patients with NSCLC and 84 healthy individuals for blood, and 20 Formalin Fixed Paraffin Embedded (FFPE) from normal samples dissected adja-cent to the tumour. The findings of the current investigation indicate that individuals diagnosed with NSCLC exhibited significant elevation in the serum levels of CEA and CYFRA21-1, as well as TGFβ1, SMAD2, CTNNβ1, and Wnt3a. In total, 325 mutations in four trialled genes (243 mutations in TGFβ1, 24 mutations in SMAD2,47 mutation Wnt3a and 11 mutations in CTNNβ1) were identified in patients with NSCLC. Fur-thermore, all mutations were recorded in adenocarcinoma, not squamous and normal adjacent tumour cells. CYFRA21-1 and CEA are more significant between NSCLC and HC, gender, and NSCLC types (p<0.001). In detail, TGFβ1 exhibited the highest rate of mutations among other genes and three types of genomic mutations. Elevated levels and genetic polymorphisms of TGFβ1, SMAD2, CTNNβ1, and Wnt3a may play crucial func-tions in the pathogenesis and angiogenesis of non-small cell lung cancer (NSCLC). These biomarkers might play a role in future immunologic response and pharmacologically targeted NSCLC therapy.

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  • 2. Abdel-Aal, Arwa
    et al.
    Lisspers, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Williams, Siân
    Adab, Peymané
    Agarwal, Dhiraj
    Barnard, Amanda
    Bouloukaki, Izolde
    van Boven, Job F. M.
    Chavannes, Niels
    Dickens, Andrew P.
    van Gemert, Frederik
    Escarrer, Mercedes
    Haroon, Shamil
    Kayongo, Alex
    Kirenga, Bruce
    Kocks, Janwillem W. H.
    Kotz, Daniel
    Newby, Chris
    McNulty, Cliodna
    Metting, Esther
    Moral, Luis
    Papadakis, Sophia
    Pinnock, Hilary
    Price, David
    Ryan, Dermot
    Singh, Sally J.
    Correia de Sousa, Jaime
    Ställberg, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Szefler, Stanley J.
    Taylor, Stephanie J. C.
    Tsiligianni, Ioanna
    Turner, Alice
    Weller, David
    Yusuf, Osman
    Tabyshova, Aizhamal K.
    Jordan, Rachel E.
    Prioritising primary care respiratory research needs: results from the 2020 International Primary Care Respiratory Group (IPCRG) global e-Delphi exercise2022In: npj Primary Care Respiratory Medicine, E-ISSN 2055-1010, Vol. 32, no 1, article id 6Article in journal (Refereed)
    Abstract [en]

    Respiratory diseases remain a significant cause of global morbidity and mortality and primary care plays a central role in their prevention, diagnosis and management. An e-Delphi process was employed to identify and prioritise the current respiratory research needs of primary care health professionals worldwide. One hundred and twelve community-based physicians, nurses and other healthcare professionals from 27 high-, middle- and low-income countries suggested 608 initial research questions, reduced after evidence review by 27 academic experts to 176 questions covering diagnosis, management, monitoring, self-management and prognosis of asthma, COPD and other respiratory conditions (including infections, lung cancer, tobacco control, sleep apnoea). Forty-nine questions reached 80% consensus for importance. Cross-cutting themes identified were: a need for more effective training of primary care clinicians; evidence and guidelines specifically relevant to primary care, adaption for local and low-resource settings; empowerment of patients to improve self-management; and the role of the multidisciplinary healthcare team.

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  • 3.
    Abdel-Aziz, Mahmoud I.
    et al.
    Dept of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands; Dept of Clinical Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
    Vijverberg, Susanne J.H.
    Dept of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
    Neerincx, Anne H.
    Dept of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
    Brinkman, Paul
    Dept of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
    Wagener, Ariane H.
    Dept of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
    Riley, John H.
    Respiratory Therapeutic Unit, GlaxoSmithKline, Stockley Park, United Kingdom.
    Sousa, Ana R.
    Respiratory Therapeutic Unit, GlaxoSmithKline, Stockley Park, United Kingdom.
    Bates, Stewart
    Respiratory Therapeutic Unit, GlaxoSmithKline, Stockley Park, United Kingdom.
    Wagers, Scott S.
    BioSci Consulting, Maasmechelen, Belgium.
    De Meulder, Bertrand
    European Institute for Systems Biology and Medicine, CIRI UMR5308, CNRS-ENS-UCBLINSERM, Lyon, France.
    Auffray, Charles
    European Institute for Systems Biology and Medicine, CIRI UMR5308, CNRS-ENS-UCBLINSERM, Lyon, France.
    Wheelock, Åsa M.
    Respiratory Medicine Unit, Dept of Medicine and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Dept of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden.
    Bansal, Aruna T.
    Acclarogen Ltd, St John’s Innovation Centre, Cambridge, United Kingdom.
    Caruso, Massimo
    Dept of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
    Chanez, Pascal
    Département des Maladies Respiratoires APHM, U1067 INSERM, Aix Marseille Université Marseille, Marseille, France.
    Uddin, Mohib
    AstraZeneca BioPharmaceuticals R&D, Gothenburg, Sweden.
    Corfield, Julie
    AstraZeneca R&D, Molndal, Sweden; Areteva R&D, Nottingham, United Kingdom.
    Horvath, Ildiko
    Dept of Public Health, Semmelweis University, National Koranyi Institute for Pulmonology, Budapest, Hungary.
    Krug, Norbert
    Fraunhofer Institute for Toxicology and Experimental Medicine Hannover, Hannover, Germany.
    Musial, Jacek
    Dept of Medicine, Jagiellonian University Medical College, Krakow, Poland.
    Sun, Kai
    Data Science Institute, South Kensington Campus, Imperial College London, London, United Kingdom.
    Shaw, Dominick E.
    Respiratory Research Unit, University of Nottingham, Nottingham, United Kingdom.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Montuschi, Paolo
    Pharmacology, Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
    Fowler, Stephen J.
    Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre and NIHR Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom.
    Lutter, René
    Dept of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands; Dept of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
    Djukanovic, Ratko
    NIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences, and Human Development and Health, University of Southampton, Southampton, United Kingdom.
    Howarth, Peter
    NIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences, and Human Development and Health, University of Southampton, Southampton, United Kingdom.
    Skipp, Paul
    Centre for Proteomic Research, Biological Sciences, University of Southampton, Southampton, United Kingdom.
    Sanak, Marek
    Dept of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
    Adcock, Ian M.
    National Heart and Lung Institute, Imperial College London, Royal Brompton and Harefield NHS Trust, London, United Kingdom.
    Chung, Kian Fan
    National Heart and Lung Institute, Imperial College London, Royal Brompton and Harefield NHS Trust, London, United Kingdom.
    Sterk, Peter J.
    Dept of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
    Kraneveld, Aletta D.
    Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands.
    Maitland-Van der Zee, Anke H.
    Dept of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands; Dept of Pediatric Respiratory Medicine, Emma Children’s Hospital, Amsterdam UMC, Amsterdam, Netherlands.
    A multi-omics approach to delineate sputum microbiome-associated asthma inflammatory phenotypes2022In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 59, no 1, article id 2102603Article in journal (Refereed)
    Abstract [en]

    A multi-omics approach revealed the underlying biological pathways in the microbiome-driven severe asthma phenotypes. This may help to elucidate new leads for treatment development, particularly for the therapeutically challenging neutrophilic asthma.

  • 4.
    AbdulWahab, Atqah
    et al.
    Department of Pediatrics, Hamad Medical Corporation, Doha, Qatar; Weill Cornell Medicine‑Qatar, Doha, Qatar.
    Zahraldin, Khalid
    Department of Pediatrics, Hamad Medical Corporation, Doha, Qatar.
    Sid Ahmed, Mazen
    Örebro University, School of Science and Technology. Department of Laboratory Medicine and Pathology, Microbiology Division, Hamad Medical Corporation, Doha, Qatar.
    Abu Jarir, Sulieman
    Departments of Internal Medicine, Hamad Medical Corporation, Doha, Qatar.
    Muneer, Mohammed
    Plastic Surgery, Hamad Medical Corporation, Doha, Qatar.
    Mohamed, Shehab F.
    Departments of Internal Medicine, Hamad Medical Corporation, Doha, Qatar.
    Hamid, Jemal M.
    Department of Laboratory Medicine and Pathology, Microbiology Division, Hamad Medical Corporation, Doha, Qatar.
    Hassan, Abubaker A. I.
    Departments of Internal Medicine, Hamad Medical Corporation, Doha, Qatar.
    Ibrahim, Emad Bashir
    Weill Cornell Medicine‑Qatar, Doha, Qatar; Department of Laboratory Medicine and Pathology, Microbiology Division, Hamad Medical Corporation, Doha, Qatar.
    The emergence of multidrug-resistant Pseudomonas aeruginosa in cystic fibrosis patients on inhaled antibiotics2017In: Lung India, ISSN 0970-2113, E-ISSN 0974-598X, Vol. 34, no 6, p. 527-531Article in journal (Refereed)
    Abstract [en]

    Introduction: Multidrug-resistant Pseudomonas aeruginosa (MDR-PA) is an important and growing issue in the care of patients with cystic fibrosis (CF), and a major cause of morbidity and mortality.

    Objective: The objective of the study was to describe the frequency of MDR-PA recovered from the lower respiratory samples of pediatric and adult CF patients, and its antibiotic resistance pattern to commonly used antimicrobial agents including beta-lactams, aminoglycosides, and fluoroquinolones.

    Materials and Methods: The lower respiratory isolates of P. aeruginosa were obtained from inpatients and outpatients CF clinics from a tertiary care teaching hospital for the period from October 2014 to September 2015. The identification and antimicrobial susceptibility for all the isolates were performed by using the BD Phoenix (TM) and E-test in compliance with Clinical and Laboratory Standards Institute (CLSI) guidelines.

    Results: A total of 61 P. aeruginosa samples were isolated from thirty CF patients from twenty families. Twelve sputum samples were positive for MDR-PA (seven nonmucoid and five mucoid isolates) from five CF patients (five families) with moderate-to-very severe lung disease given MDR-PA frequency of 19.7%. The median age of the study group was 20 (range 10-30) years. Three CF patients were on chronic inhaled tobramycin and two on nebulized colistin. The antimicrobial patterns of isolates MDR-PA showed the highest rate of resistance toward each gentamycin, amikacin, and cefepime (100%), followed by 91.7% to ciprofloxacin, 75% to tobramycin, 58.3% to meropenem, and 50% to piperacillin-tazobactam. None of the isolates were resistant to colistin during the study period.

    Conclusion: The study results emphasize that the emergence of a significant problem in the clinical isolates of P. aeruginosa in CF patients that dictate appropriate attention to the antibiotic management after proper surveillance.

  • 5.
    Abelius, Martina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Jedenfalk, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Janefjord, Camilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Matthiesen, Leif
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Helsingborg Hospital, Sweden.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Pregnancy modulates the allergen-induced cytokine production differently in allergic and non-allergic women2017In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 28, no 8, p. 818-824Article in journal (Refereed)
    Abstract [en]

    Background: The immunological environment during pregnancy may differ between allergic and non-allergic women. This study investigates the effect of maternal allergy on the allergen-induced cytokine and chemokine levels and whether pregnancy modulates these immune responses differently in allergic and non-allergic women. Methods: The birch-, cat-, phytohemagglutinin- and tetanus toxoid-induced interferon-gamma(IFN-gamma), interleukin (IL)-4, IL-5, IL-10, IL-13, the T-helper 1 (Th1)-associated chemokine CXCL10 and the Th2-associated chemokine CCL17 levels were quantified in 20 women with allergic symptoms (sensitized, n=13) and 36 women without allergic symptoms (non-sensitized, n=30) at gestational weeks 10-12, 15-16, 25, 35 and 2 and 12months post-partum. Results: Birch-, but not cat-induced, IL-5, IL-13 and CCL17 levels were increased during pregnancy as compared to post-partum in the sensitized women with allergic symptoms. In contrast, cat-, but not birch-induced, IL-5 and IL-13 levels were increased during pregnancy as compared to post-partum in the non-sensitized women without allergic symptoms. Furthermore, IFN-gamma secretion was increased in the first and decreased in the second and third trimesters in response to birch and decreased in the third trimester in response to cat as compared to post-partum in the non-sensitized women without allergic symptoms. Increased allergen-induced IL-4, IL-5 and IL-13 levels were associated with allergic symptoms and sensitization. Conclusions: Pregnancy had a clear effect on the allergen-induced IL-5, IL-13, CCL17, IFN-gamma and CXCL10 production, with distinct enhanced Th2-responses to birch in the allergic group and to cat in the non-allergic group.

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  • 6.
    Abrahamsson, Thomas R.
    et al.
    Dept Clin & Expt Med, Div Pediat, Linköping University, Linköping, Sweden.
    Jakobsson, Hedvig E.
    Dept Microbiol Tumor & Cell Biol, Karolinska Institute, Stockholm, Sweden.
    Andersson, Anders F.
    Sch Biotechnol, Sci Life Lab, KTH Royal Inst Technol, Stockholm, Sweden.
    Björksten, Bengt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Inst Environm Med, Karolinska Institute, Stockholm, Sweden.
    Engstrand, Lars
    Sch Biotechnol, Sci Life Lab, KTH Royal Inst Technol, Stockholm, Sweden.
    Jenmalm, Maria C.
    Dept Clin & Expt Med, Div Pediat, Linköping University, Linköping, Sweden.; Unit Autoimmun & Immune Regulat, Dept Clin & Expt Med, Div Clin Immunol, Linköping University, Linköping, Sweden.
    Gut microbiota diversity and atopic disease: Does breast-feeding play a role? Reply2013In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 131, no 1, p. 248-249Article in journal (Refereed)
  • 7. Abrahamsson, Thomas R.
    et al.
    Jakobsson, Ted
    Björkstén, Bengt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Oldaeus, Göran
    Jenmalm, Maria C.
    No effect of probiotics on respiratory allergies: a seven-year follow-up of a randomized controlled trial in infancy2013In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 24, no 6, p. 556-561Article in journal (Refereed)
    Abstract [en]

    Background: Supplementation with the probioticLactobacillus reuteri reduced the incidence of IgE-associated allergic disease in infancy. This treatment might therefore also reduce the risk of asthma and allergic rhinoconjunctivitis in school age.

    Objective: To evaluate whether perinatal and infant supplementation withL.reuteri reduced the prevalence of respiratory allergic disease in school age and to explore whether this supplementation was associated with any long-term side effects.

    Methods: A randomized, placebo-controlled trial with oral supplementation withL.reuteriATCC 55730 (1x10(8)CFU) during the last month of gestation and through the first year of life comprising 232 families with allergic disease, of whom 184 completed a 7-yr follow-up. The primary outcomes at 7yr of age were allergic disease and skin prick test reactivity (ClinicalTrials.govID NCT01285830).

    Results: The prevalence of asthma (15% in the probiotic vs. 16% in placebo group), allergic rhinoconjunctivitis (27% vs. 20%), eczema (21% vs. 19%) and skin prick test reactivity (29% vs. 26%) was similar in the probiotic and placebo group. Growth indices and gastrointestinal symptoms were similar in the two groups. No severe adverse events were reported.

    Conclusion: The effect ofL.reuteri on sensitization andIgE-associated eczema in infancy did not lead to a lower prevalence of respiratory allergic disease in school age. Thus, the effect ofL.reuteri on the immune system seems to be transient. Administration ofL.reuteri during the last weeks of gestation and in infancy was not associated with any long-term side effects.

  • 8.
    Accordini, Simone
    et al.
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy..
    Calciano, Lucia
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy..
    Johannessen, Ane
    Univ Bergen, Ctr Int Hlth, Dept Global Publ Hlth & Primary Care, Bergen, Norway..
    Benediktsdottir, Bryndis
    Univ Iceland, Fac Med, Reykjavik, Iceland..
    Bertelsen, Randi Jacobsen
    Univ Bergen, Dept Clin Sci, Bergen, Norway.;Oral Hlth Ctr Expertise Western Norway Vestland, Bergen, Norway..
    Braback, Lennart
    Umeå Univ, Dept Publ Hlth & Clin Med, Sect Sustainable Hlth, Umeå, Sweden..
    Dharmage, Shyamali C.
    Univ Melbourne, Sch Populat & Global Hlth, Allergy & Lung Hlth Unit, Melbourne, Vic, Australia..
    Forsberg, Bertil
    Umeå Univ, Dept Publ Hlth & Clin Med, Sect Sustainable Hlth, Umeå, Sweden..
    Real, Francisco Gomez
    Univ Bergen, Dept Clin Sci, Bergen, Norway.;Haukeland Hosp, Dept Obstet & Gynecol, Bergen, Norway..
    Holloway, John W.
    Univ Southampton, Fac Med, Human Dev & Hlth, Southampton, Hants, England..
    Holm, Mathias
    Univ Gothenburg, Sahlgrenska Acad, Sch Publ Hlth & Community Med, Occupat & Environm Med, Gothenburg, Sweden..
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Jogi, Nils O.
    Univ Bergen, Dept Clin Sci, Bergen, Norway.;Tartu Univ Hosp, Lung Clin, Tartu, Estonia..
    Jogi, Rain
    Tartu Univ Hosp, Lung Clin, Tartu, Estonia..
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Marcon, Alessandro
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy..
    Rovira, Jesus Martinez-Moratalla
    Complejo Hosp Univ Albacete CHUA, Serv Neurol, Serv Salud Castilla La Mancha SESCAM, Albacete, Spain..
    Sanchez-Ramos, Jose Luis
    Univ Huelva, Dept Nursing, Huelva, Spain..
    Schlunssen, Vivi
    Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark..
    Toren, Kjell
    Univ Gothenburg, Sahlgrenska Acad, Sch Publ Hlth & Community Med, Occupat & Environm Med, Gothenburg, Sweden..
    Jarvis, Deborah
    Imperial Coll London, Fac Med, Natl Heart & Lung Inst, London, England.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England..
    Svanes, Cecilie
    Univ Bergen, Ctr Int Hlth, Dept Global Publ Hlth & Primary Care, Bergen, Norway..
    Prenatal and prepubertal exposures to tobacco smoke in men may cause lower lung function in future offspring: a three-generation study using a causal modelling approach2021In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 58, no 4, article id 2002791Article in journal (Refereed)
    Abstract [en]

    Mechanistic research suggests that lifestyle and environmental factors impact respiratory health across generations by epigenetic changes transmitted through male germ cells. Evidence from studies on humans is very limited. We investigated multigeneration causal associations to estimate the causal effects of tobacco smoking on lung function within the paternal line. We analysed data from 383 adult offspring (age 18-47 years; 52.0% female) and their 274 fathers, who had participated in the European Community Respiratory Health Survey (ECRHS)/Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study and had provided valid measures of pre-bronchodilator lung function. Two counterfactual-based, multilevel mediation models were developed with: paternal grandmothers' smoking in pregnancy and fathers' smoking initiation in prepuberty as exposures; fathers' forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), or FEV1/FVC z-scores as potential mediators (proxies of unobserved biological mechanisms that are true mediators); and offspring's FEV1 and FVC, or FEV1/FVC z-scores as outcomes. All effects were summarised as differences (Delta) in expected z-scores related to fathers' and grandmothers' smoking history. Fathers' smoking initiation in prepuberty had a negative direct effect on both offspring's FEV1 (Delta z-score -0.36, 95% CI -0.63--0.10) and FVC (-0.50, 95% CI -0.80--0.20) compared with fathers' never smoking. Paternal grandmothers' smoking in pregnancy had a negative direct effect on fathers' FEV1/FVC -0.57, 95% CI -1.09--0.05) and a negative indirect effect on offspring's FEV1/FVC (-0.12, 95% CI -0.21--0.03) compared with grandmothers' not smoking before fathers' birth nor during fathers' childhood. Fathers' smoking in prepuberty and paternal grandmothers' smoking in pregnancy may cause lower lung function in offspring. Our results support the concept that lifestyle-related exposures during these susceptibility periods influence the health of future generations.

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    FULLTEXT01
  • 9.
    Accordini, Simone
    et al.
    Unit of Epidemiology and Medical Statistics, Dept of Diagnostics and Public Health, University of Verona, Verona, Italy; Equal contribution as first authors.
    Calciano, Lucia
    Unit of Epidemiology and Medical Statistics, Dept of Diagnostics and Public Health, University of Verona, Verona, Italy; Equal contribution as first authors.
    Johannessen, Ane
    Centre for International Health, Dept of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
    Benediktsdóttir, Bryndis
    Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
    Bertelsen, Randi Jacobsen
    Dept of Clinical Science, University of Bergen, Bergen, Norway.
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Dharmage, Shyamali C.
    Allergy and Lung Health Unit, School of Population and Global Health, University of Melbourne, Melbourne, Australia.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Gómez Real, Francisco
    Dept of Clinical Science, University of Bergen, Bergen, Norway; Dept of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway.
    Holloway, John W.
    Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
    Holm, Mathias
    Occupational and Environmental Medicine, School of Public Health and Community Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Janson, Christer
    Dept of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.
    Jõgi, Nils O.
    Dept of Clinical Science, University of Bergen, Bergen, Norway; Lung Clinic, Tartu University Hospital, Tartu, Estonia.
    Jõgi, Rain
    Lung Clinic, Tartu University Hospital, Tartu, Estonia.
    Malinovschi, Andrei
    Dept of Medical Sciences: Clinical Physiology, Uppsala University, Uppsala, Sweden.
    Marcon, Alessandro
    Unit of Epidemiology and Medical Statistics, Dept of Diagnostics and Public Health, University of Verona, Verona, Italy.
    Martínez-Moratalla Rovira, Jesús
    Servicio de Neumología, Complejo Hospitalario Universitario de Albacete (CHUA), Servicio de Salud de Castilla-La Mancha (SESCAM), Albacete, Spain.
    Sánchez-Ramos, José Luis
    Dept of Nursing, University of Huelva, Huelva, Spain.
    Schlünssen, Vivi
    Dept of Public Health, Aarhus University, Aarhus, Denmark.
    Torén, Kjell
    Occupational and Environmental Medicine, School of Public Health and Community Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Jarvis, Deborah
    Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom; MRC-PHE Centre for Environment and Health, Imperial College London, London, United Kingdom; Equal contribution as last authors.
    Svanes, Cecilie
    Centre for International Health, Dept of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Equal contribution as last authors.
    Prenatal and prepubertal exposures to tobacco smoke in men may cause lower lung function in future offspring: a three-generation study using a causal modelling approach2021In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 58, no 4, article id 2002791Article in journal (Refereed)
    Abstract [en]

    Mechanistic research suggests that lifestyle and environmental factors impact respiratory health across generations by epigenetic changes transmitted through male germ cells. Evidence from studies on humans is very limited.We investigated multigeneration causal associations to estimate the causal effects of tobacco smoking on lung function within the paternal line. We analysed data from 383 adult offspring (age 18-47 years; 52.0% female) and their 274 fathers, who had participated in the European Community Respiratory Health Survey (ECRHS)/Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study and had provided valid measures of pre-bronchodilator lung function. Two counterfactual-based, multilevel mediation models were developed with: paternal grandmothers' smoking in pregnancy and fathers' smoking initiation in prepuberty as exposures; fathers' forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), or FEV1/FVC z-scores as potential mediators (proxies of unobserved biological mechanisms that are true mediators); and offspring's FEV1 and FVC, or FEV1/FVC z-scores as outcomes. All effects were summarised as differences (Δ) in expected z-scores related to fathers' and grandmothers' smoking history.Fathers' smoking initiation in prepuberty had a negative direct effect on both offspring's FEV1 (Δz-score -0.36, 95% CI -0.63- -0.10) and FVC (-0.50, 95% CI -0.80- -0.20) compared with fathers' never smoking. Paternal grandmothers' smoking in pregnancy had a negative direct effect on fathers' FEV1/FVC (-0.57, 95% CI -1.09- -0.05) and a negative indirect effect on offspring's FEV1/FVC (-0.12, 95% CI -0.21- -0.03) compared with grandmothers' not smoking before fathers' birth nor during fathers' childhood.Fathers' smoking in prepuberty and paternal grandmothers' smoking in pregnancy may cause lower lung function in offspring. Our results support the concept that lifestyle-related exposures during these susceptibility periods influence the health of future generations.

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  • 10.
    Accordini, Simone
    et al.
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy.
    Calciano, Lucia
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy.
    Johannessen, Ane
    Univ Bergen, Dept Global Publ Hlth & Primary Care, Ctr Int Hlth, Bergen, Norway.
    Portas, Laura
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy.
    Benediktsdottir, Bryndis
    Univ Iceland, Fac Med, Reykjavik, Iceland.
    Bertelsen, Randi Jacobsen
    Univ Bergen, Dept Clin Sci, Bergen, Norway;Haukeland Hosp, Dept Occupat Med, Bergen, Norway.
    Braback, Lennart
    Umea Univ, Dept Publ Hlth & Clin Med, Div Occupat & Environm Med, Umea, Sweden.
    Carsin, Anne-Elie
    Ctr Res Environm Epidemiol CREAL, ISGlobal, Barcelona, Spain;UPF, Barcelona, Spain;CIBER Epidemiol & Salud PUbl CIBERESP, Barcelona, Spain.
    Dharmage, Shyamali C.
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy;Univ Melbourne, Sch Populat & Global Hlth, Melbourne, Vic, Australia.
    Dratva, Julia
    ZHAW Sch Hlth Profess, Inst Hlth Sci, Winterthur, Switzerland;Basel Univ, Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland.
    Forsberg, Bertil
    Umea Univ, Dept Publ Hlth & Clin Med, Div Occupat & Environm Med, Umea, Sweden.
    Real, Francisco Gomez
    Univ Bergen, Dept Clin Sci, Bergen, Norway.
    Heinrich, Joachim
    Ludwig Maximilians Univ Munchen, Univ Hosp Munich, Inner City Clin, Inst & Outpatient Clin Occupat,Social & Environm, Munich, Germany.
    Holloway, John W.
    Univ Southampton, Fac Med, Human Dev & Hlth, Southampton, Hants, England.
    Holm, Mathias
    Univ Gothenburg, Sahlgrenska Acad, Dept Occupat & Environm Med, Gothenburg, Sweden.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Jogi, Rain
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research. Tartu Univ Hosp, Lung Clin, Tartu, Estonia.
    Leynaert, Benedicte
    INSERM, Pathophysiol & Epidemiol Resp Dis, UMR 1152, Paris, France.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Marcon, Alessandro
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy.
    Martinez-Moratalla Rovira, Jesus
    CHUA, Hlth Serv Castilla La Mancha SESCAM, Pneumol Serv, Albacete, Spain;Univ Castilla La Mancha, Sch Med, Albacete, Spain.
    Raherison, Chantal
    Bordeaux Univ, INSERM, U1219, Bordeaux, France.
    Luis Sanchez-Ramos, Jose
    Univ Huelva, Dept Nursing, Huelva, Spain.
    Schlunssen, Vivi
    Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark;Natl Res Ctr Working Environm, Copenhagen, Denmark.
    Bono, Roberto
    Univ Turin, Dept Publ Hlth & Pediat, Turin, Italy.
    Corsico, Angelo G.
    Univ Pavia, IRCCS San Matteo Hosp Fdn, Div Resp Dis, Pavia, Italy.
    Demoly, Pascal
    Univ Montpellier, Hop Arnaud Villeneuve, Dept Pneumol & Addictol, Montpellier, France;Sorbonne Univ, INSERM, IPLESP, Paris, France.
    Dorado Arenas, Sandra
    Galdakao Usansolo Hosp, Pulmonol Dept, Biscay, Spain.
    Nowak, Dennis
    Ludwig Maximilians Univ Munchen, Univ Hosp Munich, Inner City Clin, Inst & Outpatient Clin Occupat,Social & Environm, Munich, Germany;Comprehens Pneumol Ctr Munich, German Ctr Lung Res, Munich, Germany.
    Pin, Isabelle
    CHU Grenoble Alpes, Pediat, Grenoble, France;Inst Adv Biosci, INSERM 1209, Grenoble, France;Univ Grenoble Alpes, Grenoble, France.
    Weyler, Joost
    Univ Antwerp, Dept Epidemiol & Social Med, Antwerp, Belgium;Univ Antwerp, StatUA Stat Ctr, Antwerp, Belgium.
    Jarvis, Deborah
    Imperial Coll, Natl Heart & Lung Inst, Populat Hlth & Occupat Dis, London, England;Imperial Coll, MRC PHE Ctr Environm & Hlth, London, England.
    Svanes, Cecilie
    Univ Bergen, Dept Global Publ Hlth & Primary Care, Ctr Int Hlth, Bergen, Norway;Haukeland Hosp, Dept Occupat Med, Bergen, Norway.
    Ageing, Lungs European Cohorts A. L. E. C. Study
    A three-generation study on the association of tobacco smoking with asthma2018In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 47, no 4, p. 1106-1117Article in journal (Refereed)
    Abstract [en]

    Background: Mothers' smoking during pregnancy increases asthma risk in their offspring. There is some evidence that grandmothers' smoking may have a similar effect, and biological plausibility that fathers' smoking during adolescence may influence offspring's health through transmittable epigenetic changes in sperm precursor cells. We evaluated the three-generation associations of tobacco smoking with asthma. Methods: Between 2010 and 2013, at the European Community Respiratory Health Survey III clinical interview, 2233 mothers and 1964 fathers from 26 centres reported whether their offspring (aged <= 51 years) had ever had asthma and whether it had coexisted with nasal allergies or not. Mothers and fathers also provided information on their parents' (grandparents) and their own asthma, education and smoking history. Multilevel mediation models within a multicentre three-generation framework were fitted separately within the maternal (4666 offspring) and paternal (4192 offspring) lines. Results: Fathers' smoking before they were 15 [relative risk ratio (RRR) = 1.43, 95% confidence interval (CI): 1.01-2.01] and mothers' smoking during pregnancy (RRR = 1.27, 95% CI: 1.01-1.59) were associated with asthma without nasal allergies in their offspring. Grandmothers' smoking during pregnancy was associated with asthma in their daughters [odds ratio (OR) = 1.55, 95% CI: 1.17-2.06] and with asthma with nasal allergies in their grandchildren within the maternal line (RRR = 1.25, 95% CI: 1.02-1.55). Conclusions: Fathers' smoking during early adolescence and grandmothers' and mothers' smoking during pregnancy may independently increase asthma risk in offspring. Thus, risk factors for asthma should be sought in both parents and before conception.

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  • 11.
    Accordini, Simone
    et al.
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy..
    Calciano, Lucia
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy..
    Marcon, Alessandro
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy..
    Pesce, Giancarlo
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy.;Sorbonne Univ, INSERM, UMR S 1136, IPLESP,Team EPAR, F-75012 Paris, France..
    Ant, Josep M.
    Ctr Res Environm Epidemiol CREAL, ISGlobal, Barcelona, Spain.;Hosp del Mar Med Res Inst IMIM, Barcelona, Spain.;CIBER Epidemiol & Salud Publ CIBERESP, Barcelona, Spain.;Univ Pompeu Fabra UPF, Barcelona, Spain..
    Beckmeyer-Borowko, Anna B.
    Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland.;Univ Basel, Basel, Switzerland..
    Carsin, Anne-Elie
    Ctr Res Environm Epidemiol CREAL, ISGlobal, Barcelona, Spain.;CIBER Epidemiol & Salud Publ CIBERESP, Barcelona, Spain.;Univ Pompeu Fabra UPF, Barcelona, Spain..
    Corsico, Angelo G.
    Univ Pavia, San Matteo Hosp Fdn, IRCCS, Div Resp Dis, Pavia, Italy..
    Imboden, Medea
    Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland.;Univ Basel, Basel, Switzerland..
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Keidel, Dirk
    Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland.;Univ Basel, Basel, Switzerland..
    Locatelli, Francesca
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy..
    Svanes, Cecilie
    Univ Bergen, Dept Global Publ Hlth & Primary Care, Ctr Int Hlth, Bergen, Norway.;Haukeland Hosp, Dept Occupat Med, Bergen, Norway..
    Burney, Peter G. J.
    Imperial Coll London, Natl Heart & Lung Inst, Populat Hlth & Occupat Dis, London, England.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England..
    Jarvis, Deborah
    Imperial Coll London, Natl Heart & Lung Inst, Populat Hlth & Occupat Dis, London, England.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England..
    Probst-Hensch, Nicole M.
    Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland.;Univ Basel, Basel, Switzerland..
    Minelli, Cosetta
    Imperial Coll London, Natl Heart & Lung Inst, Populat Hlth & Occupat Dis, London, England..
    Incidence trends of airflow obstruction among European adults without asthma: a 20-year cohort study2020In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 3452Article in journal (Refereed)
    Abstract [en]

    Investigating COPD trends may help healthcare providers to forecast future disease burden. We estimated sex- and smoking-specific incidence trends of pre-bronchodilator airflow obstruction (AO) among adults without asthma from 11 European countries within a 20-year follow-up (ECRHS and SAPALDIA cohorts). We also quantified the extent of misclassification in the definition based on pre-bronchodilator spirometry (using post-bronchodilator measurements from a subsample of subjects) and we used this information to estimate the incidence of post-bronchodilator AO (AO(post-BD)), which is the primary characteristic of COPD. AO incidence was 4.4 (95% CI: 3.5-5.3) male and 3.8 (3.1-4.6) female cases/1,000/year. Among ever smokers (median pack-years: 20, males; 12, females), AO incidence significantly increased with ageing in men only [incidence rate ratio (IRR), 1-year increase: 1.05 (1.03-1.07)]. A strong exposure-response relationship with smoking was found both in males [IRR, 1-pack-year increase: 1.03 (1.02-1.04)] and females [1.03 (1.02-1.05)]. The positive predictive value of AO for AO(post-BD) was 59.1% (52.0-66.2%) in men and 42.6% (35.1-50.1%) in women. AO(post-BD) incidence was 2.6 (1.7-3.4) male and 1.6 (1.0-2.2) female cases/1,000/year. AO incidence was considerable in Europe and the sex-specific ageing-related increase among ever smokers was strongly related to cumulative tobacco exposure. AO(post-BD) incidence is expected to be half of AO incidence.

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  • 12.
    Accordini, Simone
    et al.
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy.
    Calciano, Lucia
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy.
    Marcon, Alessandro
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy.
    Pesce, Giancarlo
    INSERM, UMR 1152, Pathophysiol & Epidemiol Resp Dis, Paris, France.
    Anto, Josep
    Inst Global Hlth, Barcelona, Spain.
    Beckmeyer-Borowko, Anna
    Swiss Trop & Publ Hlth Inst, Basel, Switzerland.
    Corsico, Angelo
    Univ Pavia, IRCCS San Matteo Hosp Fdn, Div Resp Dis, Pavia, Italy.
    Imboden, Medea
    Swiss Trop & Publ Hlth Inst, Basel, Switzerland.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Keidel, Dirk
    Swiss Trop & Publ Hlth Inst, Basel, Switzerland.
    Locatelli, Francesca
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy.
    Svanes, Cecilie
    Univ Bergen, Ctr Int Hlth, Bergen, Norway.
    Jarvis, Deborah
    Imperial Coll, Natl Heart & Lung Inst, Fac Med, London, England.
    Probst-Hensch, Nicole
    Swiss Trop & Publ Hlth Inst, Basel, Switzerland.
    Minelli, Cosetta
    Imperial Coll, Natl Heart & Lung Inst, Fac Med, London, England.
    Incidence of airflow obstruction over 20 years in Europe2018In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Article in journal (Other academic)
  • 13.
    Accordini, Simone
    et al.
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy.
    Cazzoletti, Lucia
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy.
    Anto, Josep
    Inst Global Hlth, Barcelona, Spain.
    Cerveri, Isa
    Univ Pavia, IRCCS San Matteo Hosp Fdn, Div Resp Dis, Pavia, Italy.
    Corsico, Angelo
    Univ Pavia, IRCCS San Matteo Hosp Fdn, Div Resp Dis, Pavia, Italy.
    Garcia-Aymerich, Judith
    Inst Global Hlth, Barcelona, Spain.
    Heinrich, Joachim
    Ludwig Maximilians Univ Munchen, Univ Hosp Munich, Inner City Clin, Inst & Outpatient Clin Occupat Social & Environm, Munich, Germany.
    Gislason, David
    Landspitali Univ Hosp, Dept Allergy Resp Med & Sleep, Reykjavik, Iceland.
    Jogi, Rain
    Tartu Univ Hosp, Lung Clin, Tartu, Estonia.
    Johannessen, Ane
    Univ Bergen, Ctr Int Hlth, Bergen, Norway.
    Leynaert, Benedicte
    INSERM, UMR 1152, Pathophysiol & Epidemiol Resp Dis, Paris, France.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Pin, Isabelle
    CHU Grenoble Alpes, Pediat, Grenoble, France.
    Portas, Laura
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy.
    Weyler, Joost
    Univ Antwerp, Epidemiol & Social Med, Antwerp, France;Univ Antwerp, StatUA Stat Ctr, Antwerp, France.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Marcon, Alessandro
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy.
    Jarvis, Deborah
    Imperial Coll, Natl Heart & Lung Inst, Fac Med, London, England.
    Asthma control and decline in FEV1/FVC ratio over 10 years in adults2018In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Article in journal (Other academic)
  • 14. Acevedo, Nathalie
    et al.
    Scala, Giovanni
    Kebede Merid, Simon
    Frumento, Paolo
    Bruhn, Sören
    Andersson, Anna
    Ogris, Christoph
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab). Helmholtz Center Munich, Germany.
    Bottai, Matteo
    Pershagen, Göran
    Koppelman, Gerard H.
    Melén, Erik
    Sonnhammer, Erik
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Alm, Johan
    Söderhäll, Cilla
    Kere, Juha
    Greco, Dario
    Scheynius, Annika
    DNA Methylation Levels in Mononuclear Leukocytes from the Mother and Her Child Are Associated with IgE Sensitization to Allergens in Early Life2021In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, no 2, article id 801Article in journal (Refereed)
    Abstract [en]

    DNA methylation changes may predispose becoming IgE-sensitized to allergens. We analyzed whether DNA methylation in peripheral blood mononuclear cells (PBMC) is associated with IgE sensitization at 5 years of age (5Y). DNA methylation was measured in 288 PBMC samples from 74 mother/child pairs from the birth cohort ALADDIN (Assessment of Lifestyle and Allergic Disease During INfancy) using the HumanMethylation450BeadChip (Illumina). PBMCs were obtained from the mothers during pregnancy and from their children in cord blood, at 2 years and 5Y. DNA methylation levels at each time point were compared between children with and without IgE sensitization to allergens at 5Y. For replication, CpG sites associated with IgE sensitization in ALADDIN were evaluated in whole blood DNA of 256 children, 4 years old, from the BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology) cohort. We found 34 differentially methylated regions (DMRs) associated with IgE sensitization to airborne allergens and 38 DMRs associated with sensitization to food allergens in children at 5Y (Sidak p <= 0.05). Genes associated with airborne sensitization were enriched in the pathway of endocytosis, while genes associated with food sensitization were enriched in focal adhesion, the bacterial invasion of epithelial cells, and leukocyte migration. Furthermore, 25 DMRs in maternal PBMCs were associated with IgE sensitization to airborne allergens in their children at 5Y, which were functionally annotated to the mTOR (mammalian Target of Rapamycin) signaling pathway. This study supports that DNA methylation is associated with IgE sensitization early in life and revealed new candidate genes for atopy. Moreover, our study provides evidence that maternal DNA methylation levels are associated with IgE sensitization in the child supporting early in utero effects on atopy predisposition.

  • 15.
    Adermark, Louise
    et al.
    Dept of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Dept of Pharmacology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Galanti, Maria Rosaria
    Dept of Global Public Health, Karolinska Institutet, Stockholm, Sweden; Centre of Epidemiology and Community Medicine, Stockholm, Sweden.
    Ryk, Charlotta
    Swedish Agency for Health Technology Assessment and Assessment of Social Services (SBU), Stockholm, Sweden.
    Gilljam, Hans
    Dept of Global Public Health, Karolinska Institutet, Stockholm, Sweden.
    Hedman, Linnea
    Luleå University of Technology, Department of Health, Learning and Technology, Nursing and Medical Technology. Dept of Public Health and Clinical Medicine, Division Sustainable health, The OLIN Unit, Umeå University, Umeå, Sweden.
    Prospective association between use of electronic cigarettes and use of conventional cigarettes: a systematic review and meta-analysis2021In: ERJ Open Research, E-ISSN 2312-0541, Vol. 7, no 3, p. 00976-2020Article in journal (Refereed)
    Abstract [en]

    Objective The aim of this systematic review and meta-analysis was to assess the association between e-cigarette use and subsequent initiation or recurrence of cigarette smoking.Data sources A systematic literature search was finalised on 11 November 2019 using PubMed (including MEDLINE), EMBASE, Cochrane Library, Scopus, PubMed Health, NICE Evidence Search, PROSPERO, CRD and PsycInfo.Study selection Studies were included if meeting the following criteria: reporting empirical results; longitudinal observational design with a minimum of 3 months of follow-up; including general population samples; allowing for the comparison between users and nonusers of e-cigarettes. Studies rated as having high risk of bias were excluded. Studies were independently assessed by at least two authors. The procedures described by PRISMA were followed, and the quality of evidence was rated using GRADE.Data synthesis 30 longitudinal studies from 22 different cohorts assessing e-cigarette use among nonsmokers or never-smokers at baseline, and subsequent use of cigarette smoking at follow-up, were included in this review. A random-effects meta-analysis based on 89 076 participants showed a pooled unadjusted odds ratio (OR) of cigarette smoking among baseline nonsmoker e-cigarette users compared with nonusers of 4.68 (CI 3.64–6.02), while the adjusted OR was 3.37 (CI 2.68–4.24). These results were consistent irrespective of whether the outcome was measured as ever-smoking or as past 30-day smoking. The evidence was graded as moderate.Conclusions Use of e-cigarettes may predict the initiation or recurrence of cigarette smoking.

  • 16.
    Adhikari, Tara Ballav
    et al.
    Nepal Dev Soc, COBIN Project, Bharatpur, Chitwan, Nepal.;Aarhus Univ, Ctr Global Hlth, Dept Publ Hlth, DK-8000 Aarhus, Denmark..
    Acharya, Pawan
    Nepal Dev Soc, COBIN Project, Bharatpur, Chitwan, Nepal.;Univ Oklahoma, Hlth Sci Ctr, Hudson Coll Publ Hlth, Oklahoma City, OK USA..
    Högman, Marieann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Neupane, Dinesh
    Nepal Dev Soc, COBIN Project, Bharatpur, Chitwan, Nepal.;Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA..
    Karki, Arjun
    HAMS Hosp, Dept Pulm Crit Care & Sleep Med, Kathmandu, Nepal..
    Drews, Arne
    Nepalmed, Leipzig, Germany..
    Cooper, Brendan G.
    Univ Hosp Birmingham, Lung Funct & Sleep, Birmingham, W Midlands, England..
    Sigsgaard, Torben
    Aarhus Univ, Sect Environm Occupat & Hlth, Dept Publ Hlth, Aarhus, Denmark..
    Kallestrup, Per
    Aarhus Univ, Ctr Global Hlth, Dept Publ Hlth, DK-8000 Aarhus, Denmark..
    Prevalence of Chronic Obstructive Pulmonary Disease and its Associated Factors in Nepal: Findings from a Community-based Household Survey2020In: The International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, E-ISSN 1178-2005, Vol. 15, p. 2319-2331Article in journal (Refereed)
    Abstract [en]

    Background: Despite chronic obstructive pulmonary disease (COPD) being the commonest non-communicable disease in Nepal, there is limited research evidence estimating the spirometry-based burden of COPD. This study aims to estimate the prevalence of COPD and its correlates through a community-based survey in Pokhara Metropolitan City, a semiurban area of Western Nepal. Methods: A cross-sectional household survey was conducted among 1459 adults >= 40 years. COPD was defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria as a post-bronchodilator ratio of forced expiratory volume in 1st second (FEV1) to forced vital capacity (FVC) <0.70 with the presence of symptoms. COPD was also defined by the lower limit of normal (LLN) threshold - FEV1/FVC < LLN cut-off values with the presence of symptoms. Study participants were interviewed about sociodemographic and behavioural characteristics and respiratory symptoms. Descriptive statistics and logistic regression analysis were applied. Results: Spirometry reports were acceptable in 1438 participants. The mean age of the participants was 55 (+/- 10) years, and, 54% were female. The prevalence of GOLD-defined COPD was 8.5% (95% CI: 7.1-10.0) and based on the LLN threshold of 5.4% (95% CI: 4.2-6.6). The multivariate logistic regression showed that increasing age, low body mass index, illiterate, current or former smoker, and biomass fuel smoke increased the odds of COPD in both the definitions. Conclusion: COPD is highly prevalent at community level and often underdiagnosed. Strategies aiming at early diagnosis and treatment of COPD, especially for the elderly, illiterate, and reducing exposure to smoking and biomass fuel smoke and childhood lung infection could be effective.

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  • 17.
    Adman, M. A.
    et al.
    Univ Selangor, Dept Hlth Sci, Shah Alam 40000, Selangor, Malaysia.;United Nat Univ Kuala Lumpur, Int Inst Global Hlth, Kuala Lumpur, Malaysia..
    Hashim, J. H.
    Univ Selangor, Dept Hlth Sci, Shah Alam 40000, Selangor, Malaysia.;United Nat Univ Kuala Lumpur, Int Inst Global Hlth, Kuala Lumpur, Malaysia..
    Manaf, M. R. A.
    Natl Univ Malaysia, Dept Community Hlth, Kuala Lumpur, Malaysia..
    Norbäck, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Associations between air pollutants and peak expiratory flow and fractional exhaled nitric oxide in students2020In: The International Journal of Tuberculosis and Lung Disease, ISSN 1027-3719, E-ISSN 1815-7920, Vol. 24, no 2, p. 189-+Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Studies on the effects of outdoor air pollution on the respiratory health of students in tropical countries such as Malaysia are limited. OBJECTIVE: To assess associations between outdoor air pollutants and peak expiratory flow (PEF) and fractional exhaled nitric oxide (FeNO). METHOD: PEF and FeNO levels of 487 students recruited in Melaka and Putrajaya, Malaysia, were measured in April and June 2014. Multiple linear regression with mutual adjustment was used to analyse the associations between exposure to air pollution and health. RESULTS: PEF was significantly associated with ozone for 1-day exposure (beta = -13.3 l/min, 95% CI -22.7 to -3.8), carbon monoxide for 2-day exposure (beta =-57.2 l/min, 95% CI -90.7 to -23.7) and particulate matter <= 10 mu m in diameter for 3-day exposure (beta =-6.0 l/min, 95% CI -9.2 to -2.8) and 7-day exposure (beta = -8.6 l/min, 95% CI -13.0 to -4.1). Stratified analysis showed that associations between PEF and outdoor air pollutant exposures were similar in students with and without elevated FeNO levels. CONCLUSION: Outdoor air pollution in Malaysia may cause airway obstruction unrelated to eosinophilic airway inflammation among students as measured using FeNO.

  • 18. Adrian, L.
    et al.
    Svanes, C.
    Johannessen, A.
    Lodge, C.
    Bertelsen, R.
    Dratva, J.
    Forsberg, B.
    Gislason, T.
    Benedikstdottir, B.
    Holm, M.
    Jogi, R.
    Modig, L.
    Norbäck, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Omenaas, E.
    Real, F.
    Schlunssen, V
    Sigsgaard, T.
    Skorge, T.
    Timm, S.
    Wieslander, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Dharmage, S.
    Early life parental exposure to cats and dogs reduces the risk of allergic disease in their children: possible intergenerational effect2014In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 69, p. 577-578Article in journal (Other academic)
  • 19.
    Agyemang, Amanda
    et al.
    Kravis Childrens Hosp, Icahn Sch Med Mt Sinai, Jaffe Food Allergy Inst, Div Allergy & Immunol,Dept Pediat, New York, NY USA.
    Saf, Sarah
    Kravis Childrens Hosp, Icahn Sch Med Mt Sinai, Jaffe Food Allergy Inst, Div Allergy & Immunol,Dept Pediat, New York, NY USA;Hop Enfants Armand Trousseau, Ctr Asthme & Allergies, Dept Allergol, Paris, France.
    Sifers, Travis
    Kravis Childrens Hosp, Icahn Sch Med Mt Sinai, Jaffe Food Allergy Inst, Div Allergy & Immunol,Dept Pediat, New York, NY USA.
    Mishoe, Michelle
    Kravis Childrens Hosp, Icahn Sch Med Mt Sinai, Jaffe Food Allergy Inst, Div Allergy & Immunol,Dept Pediat, New York, NY USA.
    Borres, Magnus P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research. Thermo Fisher Sci, Uppsala, Sweden.
    Sampson, Hugh A.
    Kravis Childrens Hosp, Icahn Sch Med Mt Sinai, Jaffe Food Allergy Inst, Div Allergy & Immunol,Dept Pediat, New York, NY USA.
    Nowak-Wegrzyn, Anna
    Kravis Childrens Hosp, Icahn Sch Med Mt Sinai, Jaffe Food Allergy Inst, Div Allergy & Immunol,Dept Pediat, New York, NY USA.
    Utilizing boiled milk sIgE as a predictor of baked milk tolerance in cow's milk allergic children2019In: Journal of Allergy and Clinical Immunology: In Practice, ISSN 2213-2198, E-ISSN 2213-2201, Vol. 7, no 6, p. 2049-2051Article in journal (Refereed)
  • 20.
    Ahlbeck, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Astma lathund: Astma hos vuxna2018Other (Other academic)
    Abstract [sv]

    Åtta till tio procent av den vuxna befolkningen har astma. Av dessa har 65 procent lindrig, 25 procent medelsvår och 10 procent svår astma. Astma är en heterogen sjukdom, där en kronisk luftvägsinflammation oftast föreligger.

    Sjukdomen kännetecknas av återkommande luftvägssymtom såsom pip i bröstet, andnöd, trånghetskänsla i bröstet och hosta som varierar över tiden tillsammans med en variabel luftvägsobstruktion.

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    Astma lathund: Astma hos vuxna
  • 21.
    Ahlbeck, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Astmainhalator med återkopplingssystem gav bättre vård och sänkta kostnader [Asthma inhaler with feedback system provided better care and lower costs].2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 5, p. 160-160Article in journal (Other academic)
  • 22.
    Ahlbeck, Lars
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Allergy Center.
    Intralymphatic Immunotherapy: A Novel Route to Ameliorate Allergic Rhinitis Due to Pollen2024Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Allergy to pollen and animal dander is a major public health problem. Close to 30% of the population have symptoms from the upper and/or lower respiratory tract when they meet fur animals or pollen. Whereas symptom-relieving medications have a good to sufficient effect on about 80% of those affected, a large group of 10–20% have severe symptoms, despite medication, with an impact on well-being and ability to work. In Sweden, the annual cost of allergy was calculated at €1.3 billion in 2014.

    Immunotherapy is effective in treating and preventing pollen allergy and allergic asthma, but is expensive, complicated, requiring 40 injections, and takes more than three years to complete if subcutaneous injections are used. Tablets placed under the tongue are another method, with one tablet taken every day for three years. Only 1.5‰ receive such treatment, yet just over 3% would need it.

    With intralymphatic immunotherapy, a small dose of allergen is given in a lymph node in the groin on 3 occasions, one month apart. As this method takes only eight weeks, it is a much faster and less costly treatment. However, although several studies have shown that the treatment is safe, its efficacy remains the subject of doubt.

    Our pilot study in 2012, with a 3-year follow-up to 2015, showed encouraging results, and was followed by a double-blind randomised study with 72 participants from 2014 to 2018. The research subjects then received treatment with birch and grass pollen extract or one extract and a placebo. Regardless of treatment, symptoms, quality of life and medication consumption improved during the birch and grass pollen seasons in the 3 years after treatment. Increased frequencies of T-regulatory lymphocytes may explain the non-specific effects.

    In 2017 to 2018, we conducted a double-blind study with 38 participants, half of whom received placebo and half, active treatment. In this study, we saw no difference between the treatment groups in the first year after treatment. However, after discontinuation and unblinding in 2019, i.e., two years after treatment, the actively treated group improved in terms of symptoms, and quality of life was improved compared with the placebo group despite less need for medication. T-regulatory lymphocytes increased one year after treatment only in the actively treated group.

    A long-term follow-up of the research subjects from our two larger studies in 2022, i.e., five to eight years after treatment, showed in the double-blind study without a pure placebo that the scores for symptoms, medication use, and quality of life remained as low as after the first three years. In the placebo-controlled study, a statistically significant improvement in symptoms remained during the grass pollen season. Analysing the two studies together, symptom improvement was significant even during the birch pollen season. Thus, although the effect does not seem to diminish, those who did not receive birch, but only grass, needed to use more medication during the birch pollen season in 2022, seven to eight years after treatment. Moreover, those who did not receive grass but only birch needed more medication during the grass pollen season. This may suggest that the non-specific effect begins to wane after seven to eight years.

    Allergy to pollen is a major problem for individuals and society, where symptom-relieving treatment with drugs is not enough for many. They can be helped with immunotherapy, which takes at least three years, is expensive and fraught with side effects. In contrast, intralymphatic immunotherapy involves three injections over eight weeks. Our three studies show that the treatment is safe and indicate that it has a clinical effect up to eight years after treatment. T-regulatory cells appear to be important to the immunological mechanism, leading to tolerance to pollen.

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  • 23.
    Ahlbeck, Lars
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Allergy Center.
    Ahlberg, Emelie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Björkander, Janne
    Acad Hlth & Care, Sweden.
    Aldén, Caroline
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Papapavlou, Georgia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Palmberg, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Nyström Kronander, Ulla
    Region Östergötland, Medicine Center, Allergy Center.
    Retsas, Pavlos
    Region Östergötland, Medicine Center, Allergy Center.
    Nordenfelt, Patrik
    Cty Hosp Ryhov, Sweden.
    Togö, Totte
    Region Östergötland, Medicine Center, Allergy Center.
    Johansen, Pål
    Univ Zurich, Switzerland.
    Rolander, Bo
    Acad Hlth & Care, Sweden.
    Duchén, Karel
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Allergy Center. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Jenmalm, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Intralymphatic immunotherapy with one or two allergens renders similar clinical response in patients with allergic rhinitis due to birch and grass pollen2022In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 52, no 6, p. 747-759Article in journal (Refereed)
    Abstract [en]

    Introduction

    There is a need for a fast, efficient and safe way to induce tolerance in patients with severe allergic rhinitis. Intralymphatic immune therapy has been shown to be effective.

    Methods

    Patients with severe birch and timothy allergy were randomized and received three doses of 0.1 ml of birch and 5-grass allergen extracts (10,000 SQ units/ml, ALK-Abello), or birch and placebo or 5-grass and placebo by ultrasound-guided injections into inguinal lymph nodes at monthly intervals. Rhinoconjunctivitis total symptom score, medication score and rhinoconjunctivitis quality of life questionnaire were evaluated before treatment and after each birch and grass pollen season during three subsequent years. Circulating proportions of T helper subsets and allergen-induced cytokine and chemokine production were analysed by flow cytometry and Luminex.

    Results

    The three groups reported fewer symptoms, lower use of medication and improved quality of life during the birch and grass pollen seasons each year after treatment at an almost similar rate independently of treatment with one or two allergens. Mild local pain was the most common adverse event. IgE levels to birch decreased, whereas birch-induced IL-10 secretion increased in all three groups. IgG4 levels to birch and timothy and skin prick test reactivity remained mainly unchanged. Conjunctival challenge tests with timothy extract showed a higher threshold for allergen. In all three groups, regulatory T cell frequencies were increased 3 years after treatment.

    Conclusions

    Intralymphatic immunotherapy with one or two allergens in patients with grass and birch pollen allergy was safe, effective and may be associated with bystander immune modulatory responses.

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  • 24.
    Ahlbeck, Lars
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Allergy Center.
    Ahlberg, Emelie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Stuivers, Linn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Bjorkander, Janne
    Futurum, Sweden.
    Nyström Kronander, Ulla
    Region Östergötland, Medicine Center, Allergy Center.
    Retsas, Pavlos
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Govindaraj, Dhanapal
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Duchén, Karel
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Allergy Center.
    Intralymphatic immunotherapy with birch and grass pollen extracts. A randomized double-blind placebo-controlled clinical trial2023In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 53, no 8, p. 809-820Article in journal (Refereed)
    Abstract [en]

    IntroductionThere is a need to evaluate the safety and efficacy of intralymphatic immunotherapy (ILIT) for inducing tolerance in patients with allergic rhinitis. MethodsThirty-seven patients with seasonal allergic symptoms to birch and grass pollen and skin prick test &gt;3 mm and/or IgE to birch and timothy &gt;0.35 kU/L were randomized to either ILIT, with three doses of 0.1 mL of birch pollen and 5-grass pollen allergen extracts on aluminium hydroxide (10,000 SQ-U/ml; ALK-Abello) or placebo using ultrasound-guided intralymphatic injections at monthly intervals. Daily combined symptom medical score and rhinoconjunctivitis total symptom score were recorded during the peak pollen seasons the year before and after treatment. Rhinoconjunctivitis total symptom score, medication score and rhinoconjunctivitis quality of life questionnaire were recorded annually starting 2 years after treatment. Circulating proportions of T helper cell subsets and allergen-induced cytokine and chemokine production were analysed using flow cytometry and ELISA. ResultsThere were no differences between the groups related to daily combined symptom medical score the year before and after treatment. Two years after ILIT (after unblinding), the actively treated group reported significantly fewer symptoms, lower medication use and improved quality of life than did the placebo group. After the pollen seasons the year after ILIT, T regulatory cell frequencies and grass-induced IFN-gamma levels increased only in the actively treated group. ConclusionIn this randomized controlled trial, ILIT with birch and grass pollen extract was safe and accompanied by immunological changes. Further studies are required to confirm or refute the efficacy of the treatment.

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  • 25.
    Ahlbeck, Lars
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Berggren Rygaard, Helena
    Region Östergötland, Primary Care Center, Primary Health Care Center Ekholmen, Linköping.
    Astma lathund: Astma hos barn2019Other (Other academic)
    Abstract [sv]

    Eftersom få läkemedelsstudier utförs på barn är många av dagens läkemedel som ges till barn ofullständigt dokumenterade vad gäller dosering, effekt och säkerhet. Barn får många läkemedel utanför godkänd produktresumé (off-label), som licensläkemedel eller som apoteksberett läkemedel. I brist på vetenskaplig dokumentation har barnläkarna tvingats att utveckla egna behandlingsrekommendationer som vilar på beprövad erfarenhet. Det gör att det kan föreligga skillnader mellan riktlinjer både på lokal och på nationell nivå. Vidare är diagnostiken svårare eftersom lungfunktionstester inte är möjligt på små- och förskolebarn. Våra rekommendationer vilar på referenserna sist i denna lathund.

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    Astma lathund: Astma hos barn
  • 26. Ahlgrim, C.
    et al.
    Gutermuth, J.
    Onell, A.
    Borres, Magnus P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Schaeffner, I
    Darsow, U.
    Pfab, F.
    Brockow, K.
    Ring, J.
    Behrendt, H.
    Jakob, T.
    Huss-Marp, J.
    Comparison of Molecular Multiplex and Singleplex Analysis of IgE to Grass Pollen Allergens in Untreated German Grass Pollen-Allergic Patients2015In: Journal of investigational allergology & clinical immunology, ISSN 1018-9068, E-ISSN 1698-0808, Vol. 25, no 3, p. 190-195Article in journal (Refereed)
    Abstract [en]

    Background: The ImmunoCAP ISAC 112 platform is the only commercially available molecular allergy IgE multiplex test. Data on the comparison of this rather novel test with the molecular singleplex ImmunoCAP IgE platform are lacking. Objective:To compare the multiplex ISAC 112 platform and the singleplex ImmunoCAP platform in regard to IgE to grass pollen allergens in untreated grass pollen allergic patients in Germany. Methods: Serum samples from 101 adults with grass pollen allergy were analyzed for specific IgE (sIgE) to 8 allergenic molecules from timothy grass pollen and to the 112 allergenic molecules included in the ISAC panel. The results for the multiplex and singleplex tests were subsequently analyzed statistically. Results: Comparison of sIgE to grass pollen allergens detected by ISAC 112 and the singleplex ImmunoCAP assay revealed the following correlation coefficients: 0.88 (rPhl p1), 0.96 (rPhl p2), 0.70 (nPhl p4), 0.94 (rPhl p5b), 0.92 (rPhl p6), 0.85 (rPhl p11), and 0.78 (rPhl p12). Conclusion: Molecular testing with ISAC 112 correlates well with the ImmunoCAP platform for respective molecular timothy grass pollen allergens.

  • 27. Ahlroth Pind, C.
    et al.
    Gunnbjörnsdottír, M.
    Bjerg, A.
    Järvholm, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lundbäck, B.
    Malinovschi, A.
    Middelveld, R.
    Nilsson Sommar, Johan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Norbäck, D.
    Janson, C.
    Patient-reported signs of dampness at home may be a risk factor for chronic rhinosinusitis: a cross-sectional study2017In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 47, no 11, p. 1383-1389Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: An association between dampness at home and respiratory conditions has been convincingly demonstrated in children. Fewer studies have been performed in adults, and data are lacking for chronic rhinosinusitis (CRS). With a prevalence of 10.9% in Europe, CRS imposes a significant burden on quality of life, as well as economy.

    OBJECTIVE: Our aim was to study CRS and other respiratory conditions in relation to dampness at home in a representative sample of adults.

    METHODS: The Swedish GA(2) LEN questionnaire was answered by 26 577 adults (16-75 years) and included questions on respiratory symptoms, smoking, education and environmental exposure. CRS was defined according to the EP(3) OS criteria. Dampness was defined as reporting water damage, floor dampness or visible moulds in the home during the last 12 months. The dampness score was ranked from 0 to 3, counting the number of signs of dampness reported.

    RESULTS: Dampness at home was reported by 11.3% and was independently related to respiratory conditions after adjustment for demographic and socio-economic factors and smoking: CRS odds ratio (OR) 1.71; allergic rhinitis OR 1.24; current asthma OR 1.21; wheeze OR 1.37; nocturnal dyspnoea OR 1.80; nocturnal coughing OR 1.34; and chronic bronchitis OR 1.64. The risk of CRS and most of the other respiratory conditions was further elevated in subjects reporting multiple signs of dampness.

    CONCLUSIONS AND CLINICAL RELEVANCE: This study demonstrated an independent association between dampness at home and CRS in adults. The high burden of this and the other respiratory conditions studied is a strong argument in favour of countering indoor dampness by improving building standards.

  • 28.
    Ahlroth Pind, Caroline
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Gunnbjörnsdottír, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research. National University Hospital of Iceland, Reykjavik, Iceland.
    Bjerg, A
    Karolinska Inst, Stockholm, Sweden.
    Järvholm, B
    Umeå Univ, Umeå, Sweden.
    Lundbäck, B
    Univ Gothenburg, Gothenburg, Sweden.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Middelveld, R
    Karolinska Inst, Stockholm, Sweden.
    Nilsson Sommar, J
    Umeå Univ, Umeå, Sweden.
    Norbäck, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Patient-reported signs of dampness at home may be a risk factor for chronic rhinosinusitis: A cross-sectional study2017In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 47, no 11, p. 1383-1389Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: An association between dampness at home and respiratory conditions has been convincingly demonstrated in children. Fewer studies have been performed in adults, and data are lacking for chronic rhinosinusitis (CRS). With a prevalence of 10.9% in Europe, CRS imposes a significant burden on quality of life, as well as economy.

    OBJECTIVE: Our aim was to study CRS and other respiratory conditions in relation to dampness at home in a representative sample of adults.

    METHODS: The Swedish GA2 LEN questionnaire was answered by 26 577 adults (16-75 years) and included questions on respiratory symptoms, smoking, education and environmental exposure. CRS was defined according to the EP3 OS criteria. Dampness was defined as reporting water damage, floor dampness or visible moulds in the home during the last 12 months. The dampness score was ranked from 0 to 3, counting the number of signs of dampness reported.

    RESULTS: Dampness at home was reported by 11.3% and was independently related to respiratory conditions after adjustment for demographic and socio-economic factors and smoking: CRS odds ratio (OR) 1.71; allergic rhinitis OR 1.24; current asthma OR 1.21; wheeze OR 1.37; nocturnal dyspnoea OR 1.80; nocturnal coughing OR 1.34; and chronic bronchitis OR 1.64. The risk of CRS and most of the other respiratory conditions was further elevated in subjects reporting multiple signs of dampness.

    CONCLUSIONS AND CLINICAL RELEVANCE: This study demonstrated an independent association between dampness at home and CRS in adults. The high burden of this and the other respiratory conditions studied is a strong argument in favour of countering indoor dampness by improving building standards.

  • 29.
    Ahlroth Pind, Caroline
    et al.
    Centre for Clinical Research, Uppsala University, Västmanland County Hospital, Västerås, Sweden; Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.
    Ställberg, Björn
    Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.
    Lisspers, Karin
    Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.
    Sundh, Josefin
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Respiratory Medicine.
    Kisiel, Marta A.
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Sandelowsky, Hanna
    NVS, Section for Family Medicine and Primary Care, Karolinska Institutet, Stockholm, Sweden; Academic Primary Care Centre, Region Stockholm, Sweden; Department of Medicine, Clinical Epidemiology Division, Karolinska Institute, Stockholm, Sweden.
    Nager, Anna
    NVS, Section for Family Medicine and Primary Care, Karolinska Institutet, Stockholm, Sweden.
    Hasselgren, Mikael
    Örebro University, School of Medical Sciences. Centre for Clinical Research and Education, Karlstad, Sweden.
    Montgomery, Scott
    Department of Medicine, Clinical Epidemiology Division, Karolinska Institute, Stockholm, Sweden; Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Epidemiology and Public Health, University College London, London, UK.
    Janson, Christer
    Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.
    Pharmacological treatment of asthma in Sweden from 2005 to 20152023In: Journal of Asthma, ISSN 0277-0903, E-ISSN 1532-4303Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Despite access to effective therapies many asthma patients still do not have well-controlled disease. This is possibly related to underuse of inhaled corticosteroids (ICS) and overuse of short-acting β2-agonists (SABA). Our aim was to investigate longitudinal trends and associated factors in asthma treatment.

    METHODS: Two separate cohorts of adults with physician-diagnosed asthma were randomly selected from 14 hospitals and 56 primary health centers in Sweden in 2005 (n = 1182) and 2015 (n = 1225). Information about symptoms, maintenance treatment, and use of rescue medication was collected by questionnaires. Associations between treatment and sex, age, smoking, education, body mass index (BMI), physical activity, allergic asthma, and symptom control were analyzed using Pearson's chi2-test. Odds ratios (ORs) were calculated using logistic regression.

    RESULTS: Maintenance treatment with ICS together with long-acting β2-agonists (LABA) and/or montelukast increased from 39.2% to 44.2% (p = 0.012). The use of ICS + LABA as-needed increased (11.1-18.9%, p < 0.001), while SABA use decreased (46.4- 41.8%, p = 0.023). Regular treatment with ICS did not change notably (54.2-57.2%, p = 0.14). Older age, former smoking, and poor symptom control were related to treatment with ICS + LABA/montelukast. In 2015, 22.7% reported daily use of SABA. A higher step of maintenance treatment, older age, obesity, shorter education, current smoking, allergic asthma, low or very high physical activity, and a history of exacerbations were associated with daily SABA use.

    CONCLUSIONS: The use of ICS + LABA both for maintenance treatment and symptom relief has increased over time. Despite this, the problem of low use of ICS and high use of SABA remains.

  • 30.
    Ahlroth Pind, Caroline
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Ställberg, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Lisspers, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Sundh, Josefin
    Kisiel, Marta A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Sandelowsky, Hanna
    Nager, Anna
    Hasselgren, Mikael
    Montgomery, Scott
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Pharmacological treatment of asthma in Sweden from 2005 to 2015.2023In: Journal of Asthma, ISSN 0277-0903, E-ISSN 1532-4303, p. 1-9Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Despite access to effective therapies many asthma patients still do not have well-controlled disease. This is possibly related to underuse of inhaled corticosteroids (ICS) and overuse of short-acting β2-agonists (SABA). Our aim was to investigate longitudinal trends and associated factors in asthma treatment.

    METHODS: Two separate cohorts of adults with physician-diagnosed asthma were randomly selected from 14 hospitals and 56 primary health centers in Sweden in 2005 (n = 1182) and 2015 (n = 1225). Information about symptoms, maintenance treatment, and use of rescue medication was collected by questionnaires. Associations between treatment and sex, age, smoking, education, body mass index (BMI), physical activity, allergic asthma, and symptom control were analyzed using Pearson's chi2-test. Odds ratios (ORs) were calculated using logistic regression.

    RESULTS: Maintenance treatment with ICS together with long-acting β2-agonists (LABA) and/or montelukast increased from 39.2% to 44.2% (p = 0.012). The use of ICS + LABA as-needed increased (11.1-18.9%, p < 0.001), while SABA use decreased (46.4- 41.8%, p = 0.023). Regular treatment with ICS did not change notably (54.2-57.2%, p = 0.14). Older age, former smoking, and poor symptom control were related to treatment with ICS + LABA/montelukast. In 2015, 22.7% reported daily use of SABA. A higher step of maintenance treatment, older age, obesity, shorter education, current smoking, allergic asthma, low or very high physical activity, and a history of exacerbations were associated with daily SABA use.

    CONCLUSIONS: The use of ICS + LABA both for maintenance treatment and symptom relief has increased over time. Despite this, the problem of low use of ICS and high use of SABA remains.

  • 31.
    Ahlström, J. Zebialowicz
    et al.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Massaro, F.
    Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden.
    Mikolka, P.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden;Comenius Univ, Jessenius Fac Med Martin, Biomed Ctr Martin, Martin, TN USA;Comenius Univ, Jessenius Fac Med Martin, Dept Physiol, Martin, TN USA.
    Feinstein, R.
    Swedish Natl Vet Inst, Dept Pathol, Uppsala, Sweden.
    Perchiazzi, Gaetano
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala Univ, Dept Surg Sci, Hedenstierna Lab, Uppsala, Sweden.
    Basabe-Burgos, O.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Curstedt, T.
    Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Stockholm, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Johansson, J.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Rising, A.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden;Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden.
    Synthetic surfactant with a recombinant surfactant protein C analogue improves lung function and attenuates inflammation in a model of acute respiratory distress syndrome in adult rabbits2019In: Respiratory Research, ISSN 1465-9921, E-ISSN 1465-993X, Vol. 20, article id 245Article in journal (Refereed)
    Abstract [en]

    AimIn acute respiratory distress syndrome (ARDS) damaged alveolar epithelium, leakage of plasma proteins into the alveolar space and inactivation of pulmonary surfactant lead to respiratory dysfunction. Lung function could potentially be restored with exogenous surfactant therapy, but clinical trials have so far been disappointing. These negative results may be explained by inactivation and/or too low doses of the administered surfactant. Surfactant based on a recombinant surfactant protein C analogue (rSP-C33Leu) is easy to produce and in this study we compared its effects on lung function and inflammation with a commercial surfactant preparation in an adult rabbit model of ARDS.MethodsARDS was induced in adult New Zealand rabbits by mild lung-lavages followed by injurious ventilation (V-T 20m/kg body weight) until P/F ratio<26.7kPa. The animals were treated with two intratracheal boluses of 2.5mL/kg of 2% rSP-C33Leu in DPPC/egg PC/POPG, 50:40:10 or poractant alfa (Curosurf (R)), both surfactants containing 80mg phospholipids/mL, or air as control. The animals were subsequently ventilated (V-T 8-9m/kg body weight) for an additional 3h and lung function parameters were recorded. Histological appearance of the lungs, degree of lung oedema and levels of the cytokines TNF alpha IL-6 and IL-8 in lung homogenates were evaluated.ResultsBoth surfactant preparations improved lung function vs. the control group and also reduced inflammation scores, production of pro-inflammatory cytokines, and formation of lung oedema to similar degrees. Poractant alfa improved compliance at 1h, P/F ratio and PaO2 at 1.5h compared to rSP-C33Leu surfactant.ConclusionThis study indicates that treatment of experimental ARDS with synthetic lung surfactant based on rSP-C33Leu improves lung function and attenuates inflammation.

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  • 32.
    Ahmadi, Z.
    et al.
    Lund Univ, Lund, Sweden..
    Sundh, J.
    Univ Orebro, Orebro, Sweden..
    Bornefalk Hermansson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ekström, M.
    Lund Univ, Lund, Sweden..
    Does Long-Term Oxygen Therapy 24 H/day Improve Survival Compared To 15 H/day In Hypoxemic Chronic Obstructive Pulmonary Disease?2016In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 193Article in journal (Refereed)
  • 33. Ahmadi, Zainab
    et al.
    Bornefalk-Hermansson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Franklin, Karl A.
    Midgren, Bengt
    Ekstrom, Magnus P.
    Hypo- and hypercapnia predict mortality in oxygen-dependent chronic obstructive pulmonary disease: a population-based prospective study2014In: Respiratory Research, ISSN 1465-9921, E-ISSN 1465-993X, Vol. 15, p. 30-Article in journal (Refereed)
    Abstract [en]

    Background: The prognostic role of the arterial blood gas tension of carbon dioxide (PaCO2) in severe Chronic Obstructive Pulmonary Disease (COPD) remains unknown. The aim of this study was to estimate the association between PaCO2 and mortality in oxygen-dependent COPD. Methods: National prospective study of patients starting long-term oxygen therapy (LTOT) for COPD in Sweden between October 1, 2005 and June 30, 2009, with all-cause mortality as endpoint. The association between PaCO2 while breathing air, PaCO2 (air), and mortality was estimated using Cox regression adjusted for age, sex, arterial blood gas tension of oxygen (PaO2), World Health Organization performance status, body mass index, comorbidity, and medications. Results: Of 2,249 patients included, 1,129 (50%) died during a median 1.1 years (IQR 0.6-2.0 years) of observation. No patient was lost to follow-up. PaCO2 (air) independently predicted adjusted mortality (p < 0.001). The association with mortality was U-shaped, with the lowest mortality at approximately PaCO2 (air) 6.5 kPa and increased mortality at PaCO2 (air) below 5.0 kPa and above 7.0 kPa. Conclusion: In oxygen-dependent COPD, PaCO2 (air) is an independent prognostic factor with a U-shaped association with mortality.

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  • 34.
    Ahmadi, Zainab
    et al.
    Lund Univ, Fac Med, Dept Clin Sci Lund, Resp Med & Allergol, Lund, Sweden..
    Igelström, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Åsenlöf: Physiotheraphy.
    Sandberg, Jacob
    Lund Univ, Fac Med, Dept Clin Sci Lund, Resp Med & Allergol, Lund, Sweden..
    Sundh, Josefin
    Örebro Univ, Sch Med Sci, Dept Resp Med, Örebro, Sweden..
    Sköld, Magnus
    Karolinska Inst, Dept Med Solna, Resp Med Unit, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Dept Resp Med & Allergy, Stockholm, Sweden..
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Blomberg, Anders
    Umeå Univ, Dept Publ Hlth & Clin Med, Sect Med, Umeå, Sweden..
    Bornefalk, Hans
    Hans Bornefalk AB, Vallentuna, Sweden..
    Bornefalk Hermansson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Ekström, Magnus
    Lund Univ, Fac Med, Dept Clin Sci Lund, Resp Med & Allergol, Lund, Sweden..
    Agreement of the modified Medical Research Council and New York Heart Association scales for assessing the impact of self-rated breathlessness in cardiopulmonary disease2022In: ERJ Open Research, E-ISSN 2312-0541, Vol. 8, no 1, article id 00460-2021Article in journal (Refereed)
    Abstract [en]

    Background The functional impact of breathlessness is assessed using the modified Medical Research Council (mMRC) scale for chronic respiratory disease and with the New York Heart Association Functional Classification (NYHA) scale for heart failure. We evaluated agreement between the scales and their concurrent validity with other clinically relevant patient-reported outcomes in cardiorespiratory disease. Methods Outpatients with stable chronic respiratory disease or heart failure were recruited. Agreement between the mMRC and NYHA scales was analysed using Cramer's V and Kendall's tau B tests. Concurrent validity was evaluated using correlations with clinically relevant measures of breathlessness, anxiety, depression, and health-related quality of life. Analyses were conducted for all participants and separately in chronic obstructive pulmonary disease (COPD) and heart failure. Results In a total of 182 participants with cardiorespiratory disease, the agreement between the mMRC and NYHA scales was moderate (Cramer's V: 0.46; Kendall's tau B: 0.57) with similar results for COPD (Cramer's V: 0.46; Kendall's tau B: 0.66) and heart failure (Cramer's V: 0.46; Kendall's tau B: 0.67). In the total population, the scales correlated in similar ways to other patient-reported outcomes. Conclusion In outpatients with cardiorespiratory disease, the mMRC and NYHA scales show moderate to strong correlations and similar associations with other patient-reported outcomes. This supports that the scales are comparable when assessing the impact of breathlessness on function and patient-reported outcomes.

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  • 35.
    Ahmadi, Zainab
    et al.
    Lund University, Faculty of Medicine, Dept of Clinical Sciences Lund, Respiratory Medicine and Allergology, Lund, Sweden.
    Igelström, Helena
    Dept of Neuroscience, Physiotherapy, Uppsala University, Uppsala, Sweden.
    Sandberg, Jacob
    Lund University, Faculty of Medicine, Dept of Clinical Sciences Lund, Respiratory Medicine and Allergology, Lund, Sweden.
    Sundh, Josefin
    Dept of Respiratory Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Sköld, Magnus
    Respiratory Medicine Unit, Dept of Medicine Solna and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Dept of Respiratory Medicine and Allergy, Karolinska University Hospital Solna, Stockholm, Sweden.
    Janson, Christer
    Dept of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Bornefalk, Hans
    Hans Bornefalk AB, Vallentuna, Sweden.
    Bornefalk-Hermansson, Anna
    Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Ekström, Magnus
    Lund University, Faculty of Medicine, Dept of Clinical Sciences Lund, Respiratory Medicine and Allergology, Lund, Sweden.
    Agreement of the modified Medical Research Council and New York Heart Association scales for assessing the impact of self-rated breathlessness in cardiopulmonary disease2022In: ERJ Open Research, E-ISSN 2312-0541, Vol. 8, no 1, article id 00460-2021Article in journal (Refereed)
    Abstract [en]

    Background: The functional impact of breathlessness is assessed using the modified Medical Research Council (mMRC) scale for chronic respiratory disease and with the New York Heart Association Functional Classification (NYHA) scale for heart failure. We evaluated agreement between the scales and their concurrent validity with other clinically relevant patient-reported outcomes in cardiorespiratory disease.

    Methods: Outpatients with stable chronic respiratory disease or heart failure were recruited. Agreement between the mMRC and NYHA scales was analysed using Cramér’s V and Kendall’s tau B tests. Concurrent validity was evaluated using correlations with clinically relevant measures of breathlessness, anxiety, depression, and health-related quality of life. Analyses were conducted for all participants and separately in chronic obstructive pulmonary disease (COPD) and heart failure.

    Results: In a total of 182 participants with cardiorespiratory disease, the agreement between the mMRC and NYHA scales was moderate (Cramér’s V: 0.46; Kendall’s tau B: 0.57) with similar results for COPD (Cramér’s V: 0.46; Kendall’s tau B: 0.66) and heart failure (Cramér’s V: 0.46; Kendall’s tau B: 0.67). In the total population, the scales correlated in similar ways to other patient-reported outcomes.

    Conclusion: In outpatients with cardiorespiratory disease, the mMRC and NYHA scales show moderate to strong correlations and similar associations with other patient-reported outcomes. This supports that the scales are comparable when assessing the impact of breathlessness on function and patient-reported outcomes.

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  • 36.
    Ahmadi, Zainab
    et al.
    Lund University, Faculty of Medicine, Dept of Clinical Sciences Lund, Respiratory Medicine and Allergology, Lund, Sweden.
    Igelström, Helena
    Dept of Neuroscience, Physiotherapy, Uppsala University, Uppsala, Sweden.
    Sandberg, Jacob
    Lund University, Faculty of Medicine, Dept of Clinical Sciences Lund, Respiratory Medicine and Allergology, Lund, Sweden.
    Sundh, Josefin
    Örebro University, School of Medical Sciences. Dept of Respiratory Medicine.
    Sköld, Magnus
    Respiratory Medicine Unit, Dept of Medicine Solna and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Dept of Respiratory Medicine and Allergy, Karolinska University Hospital Solna, Stockholm, Sweden.
    Janson, Christer
    Dept of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.
    Blomberg, Anders
    Dept of Public Health and Clinical Medicine, Section of Medicine, Umeå University, Umeå, Sweden.
    Bornefalk, Hans
    Hans Bornefalk AB, Vallentuna, Sweden.
    Bornefalk-Hermansson, Anna
    Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Ekström, Magnus
    Lund University, Faculty of Medicine, Dept of Clinical Sciences Lund, Respiratory Medicine and Allergology, Lund, Sweden.
    Agreement of the modified Medical Research Council and New York Heart Association scales for assessing the impact of self-rated breathlessness in cardiopulmonary disease2022In: ERJ Open Research, E-ISSN 2312-0541, Vol. 8, no 1, article id 00460Article in journal (Refereed)
    Abstract [en]

    Background: The functional impact of breathlessness is assessed using the modified Medical Research Council (mMRC) scale for chronic respiratory disease and with the New York Heart Association Functional Classification (NYHA) scale for heart failure. We evaluated agreement between the scales and their concurrent validity with other clinically relevant patient-reported outcomes in cardiorespiratory disease.

    Methods: Outpatients with stable chronic respiratory disease or heart failure were recruited. Agreement between the mMRC and NYHA scales was analysed using Cramér's V and Kendall's tau B tests. Concurrent validity was evaluated using correlations with clinically relevant measures of breathlessness, anxiety, depression, and health-related quality of life. Analyses were conducted for all participants and separately in chronic obstructive pulmonary disease (COPD) and heart failure.

    Results: In a total of 182 participants with cardiorespiratory disease, the agreement between the mMRC and NYHA scales was moderate (Cramér's V: 0.46; Kendall's tau B: 0.57) with similar results for COPD (Cramér's V: 0.46; Kendall's tau B: 0.66) and heart failure (Cramér's V: 0.46; Kendall's tau B: 0.67). In the total population, the scales correlated in similar ways to other patient-reported outcomes.

    Conclusion: In outpatients with cardiorespiratory disease, the mMRC and NYHA scales show moderate to strong correlations and similar associations with other patient-reported outcomes. This supports that the scales are comparable when assessing the impact of breathlessness on function and patient-reported outcomes.

  • 37.
    Ahmadi, Zainab
    et al.
    Lund Univ, Div Resp Med & Allergol, Dept Clin Sci, Lund, Sweden.
    Sundh, Josefin
    Univ Orebro, Sch Med Sci, Dept Resp Med, Orebro, Sweden.
    Bornefalk-Hermansson, Anna
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics.
    Ekström, Magnus
    Lund Univ, Div Resp Med & Allergol, Dept Clin Sci, Lund, Sweden.
    Long-Term Oxygen Therapy 24 vs 15 h/day and Mortality in Chronic Obstructive Pulmonary Disease2016In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 9, article id e0163293Article in journal (Refereed)
    Abstract [en]

    Long-term oxygen therapy (LTOT) >= 15 h/day improves survival in hypoxemic chronic obstructive pulmonary disease ( COPD). LTOT 24 h/day is often recommended but may pose an unnecessary burden with no clear survival benefit compared with LTOT 15 h/day. The aim was to test the hypothesis that LTOT 24 h/day decreases all-cause, respiratory, and cardiovascular mortality compared to LTOT 15 h/day in hypoxemic COPD. This was a prospective, observational, population-based study of COPD patients starting LTOT between October 1, 2005 and June 30, 2009 in Sweden. Overall and cause-specific mortality was analyzed using Cox and Fine-Gray regression, controlling for age, sex, prescribed oxygen dose, PaO2 (air), PaCO2 (air), Forced Expiratory Volume in one second (FEV1), WHO performance status, body mass index, comorbidity, and oral glucocorticoids. A total of 2,249 included patients were included with a median follow-up of 1.1 years (interquartile range, 0.6-2.1). 1,129 (50%) patients died and no patient was lost to follow-up. Higher LTOT duration analyzed as a continuous variable was not associated with any change in mortality rate (hazard ratio [HR] 1.00; (95% confidence interval [CI], 0.98 to 1.02) per 1 h/day increase above 15 h/day. LTOT exactly 24 h/day was prescribed in 539 (24%) patients and LTOT 15-16 h/day in 1,231 (55%) patients. Mortality was similar between the groups for all-cause, respiratory and cardiovascular mortality. In hypoxemic COPD, LTOT 24 h/day was not associated with a survival benefit compared with treatment 15-16 h/day. A design for a registry-based randomized trial (R-RCT) is proposed.

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  • 38.
    Ahmadi, Zainab
    et al.
    Lund University, Lund, Sweden.
    Sundh, Josefin
    Örebro University, School of Medical Sciences.
    Hermansson, Anna B.
    Uppsala University Hospital, Uppsala, Sweden.
    Ekström, Magnus
    Lund University, Lund, Sweden.
    Does Long-Term Oxygen Therapy 24 H/day Improve Survival Compared To 15 H/day In Hypoxemic Chronic Obstructive Pulmonary Disease?2016In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 193Article in journal (Refereed)
  • 39.
    Ahmed, Mohamed R.
    et al.
    Otolaryngology Unit, Faculty of Medicine, Suez Canal University, Ismailia, 41611, Egypt.
    Madian, Yasser T.
    Otolaryngology Unit, Faculty of Medicine, Suez Canal University, Ismailia, 41611, Egypt.
    El-Tabbakh, Mohammed T.
    Otolaryngology Unit, Faculty of Medicine, Suez Canal University, Ismailia, 41611, Egypt.
    El-Serafi, Ahmed Taher
    Medical Biochemistry Units, Suez Canal University, Ismailia, Egypt.
    Nasr, Gamela M.
    Cardiology Units, Suez Canal University, Ismailia, Egypt.
    Hessam, Waheed F.
    Departments of Microbiology and Immunology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
    Correlation between dyslipidemia and severity of allergic rhinitis2018In: The Egyptian Journal of Otolaryngology, ISSN 1012-5574, Vol. 34, no 2, p. 111-115Article in journal (Refereed)
    Abstract [en]

    Background

    Allergic rhinitis is a common problem affecting between 20 and 25% of the population lowering the quality of life (QOL) more than any other disease. Dyslipidemia is known to impact potently the development of atopy as it promotes proatopic Th2 immunity and allergic inflammation.

    Objective

    The aim was to test the correlation between severity of allergic rhinitis and dyslipidemia.

    Materials and methods

    A comparative study carried out on 350 allergic rhinitis patients were subjected to full serum lipid assays, visual analog scale assessing their nasal symptoms, and QOL assessment using a seven-point scale.

    Results

    Patients were divided into two groups (according to their lipid profile): abnormal dyslipidemia group (33%) and normal lipid profile group (67%).

    The abnormal dyslipidemia group showed a more intense allergic rhinitis symptoms compared with the normal lipid profile with poor QOL score (1.97).

    Conclusion

    Dyslipidemia might play an important role in increasing the severity of allergic rhinitis symptoms with impaired patients’ QOL; therefore, its control could achieve better treatment outcomes. 

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  • 40. Akerstedt, T.
    et al.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Gruber, G.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Schwarz, J.
    What does good sleep mean in terms of macro and microstructure of sleep in women and how does age affect this relation?2014In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 23, p. 240-240Article in journal (Other academic)
  • 41.
    Akerstedt, T.
    et al.
    Stockholm Univ, Stress Res Inst, Stockholm, Sweden.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Schwarz, J.
    Stockholm Univ, Stress Res Inst, Stockholm, Sweden.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    The change in sleepiness across 10 years of aging and its relation to changes in polysomnographic variables2017In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 40, no Supplement 1, p. E8-E8Article in journal (Other academic)
  • 42.
    Akerstedt, Torbjorn
    et al.
    Karolinska Inst, Dept Clin Neurosci, S-17177 Stockholm, Sweden;Stockholm Univ, Stress Res Inst, Stockholm, Sweden.
    Schwarz, Johanna
    Karolinska Inst, Dept Clin Neurosci, S-17177 Stockholm, Sweden;Stockholm Univ, Stress Res Inst, Stockholm, Sweden.
    Gruber, Georg
    Siesta Grp, Vienna, Austria.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Women with both sleep problems and snoring show objective impairment of sleep2018In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 51, p. 80-84Article in journal (Refereed)
    Abstract [en]

    Objective: Combined insomnia and obstructive sleep apnea has been the focus of considerable research with respect to its health effects. A related issue is whether sleep disturbances in combination with snoring might exert effects on objective sleep variables in the non-clinical general population. The purpose of the present study was to investigate the polysomnographical characteristics of individuals who had sought medical help for both disturbed sleep and for snoring. No previous work of this type has been carried out. Method: For this study we used a representative set of data of 384 women with one night of in-home PSG. We identified those individuals who had sought medical help for sleep problems (SL), individuals that had sought help for snoring (SN), as well as those that had sought help for either both (Combined), or for neither (Control). Results: Our results yielded an N of 46, 16, 21, and 301 individuals, respectively. A one-factor analysis of variance showed significant main effects on N1% (F = 10.2, p < 0.001), N3% (F = 2.7, p < 0.05), AHI/h (F = 5.5, p < 0.001), and a delta power measure (F = 3.8, p < 0.05). The combined group showed significantly higher levels than the other groups for N1% (29% vs < 21%), AHI/h (19/h vs < 10/h) and lower levels for N3%, and a measure of delta power. Reported sleep quality measures did not show the same pattern, since the highest/lowest value were found for either the group presenting snoring alone or sleep problems alone. Conclusion: We concluded that individuals who had sought help for both insomnia and snoring showed impaired sleep in terms of PSG and that this was not reflected in ratings of sleep or health. This suggests that simultaneous sleep disturbances and snoring may potentiate each other to cause impaired sleep, yet the mechanism still needs to be elucidated.

  • 43.
    Akner, Gunnar
    Örebro University, School of Health and Medical Sciences.
    Undernäringstillstånd vid KOL2006In: KOL: kroniskt obstruktiv lungsjukdom / [ed] Kjell Larsson, Stockholm: Studentlitteratur , 2006, 2, p. 227-237Chapter in book (Other academic)
  • 44.
    Akula, Srinivas
    et al.
    Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, POB 7011, SE-75007 Uppsala, Sweden..
    Riihimaki, Miia
    Swedish Univ Agr Sci, Fac Vet Med & Anim Sci, Dept Clin Sci, SE-75007 Uppsala, Sweden..
    Waern, Ida
    Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, POB 7011, SE-75007 Uppsala, Sweden..
    Abrink, Magnus
    Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, SE-75007 Uppsala, Sweden..
    Raine, Amanda
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hellman, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Wernersson, Sara
    Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, POB 7011, SE-75007 Uppsala, Sweden..
    Quantitative Transcriptome Analysis of Purified Equine Mast Cells Identifies a Dominant Mucosal Mast Cell Population with Possible Inflammatory Functions in Airways of Asthmatic Horses2022In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 22, article id 13976Article in journal (Refereed)
    Abstract [en]

    Asthma is a chronic inflammatory airway disease and a serious health problem in horses as well as in humans. In humans and mice, mast cells (MCs) are known to be directly involved in asthma pathology and subtypes of MCs accumulate in different lung and airway compartments. The role and phenotype of MCs in equine asthma has not been well documented, although an accumulation of MCs in bronchoalveolar lavage fluid (BALF) is frequently seen. To characterize the phenotype of airway MCs in equine asthma we here developed a protocol, based on MACS Tyto sorting, resulting in the isolation of 92.9% pure MCs from horse BALF. We then used quantitative transcriptome analyses to determine the gene expression profile of the purified MCs compared with total BALF cells. We found that the MCs exhibited a protease profile typical for the classical mucosal MC subtype, as demonstrated by the expression of tryptase (TPSB2) alone, with no expression of chymase (CMA1) or carboxypeptidase A3 (CPA3). Moreover, the expression of genes involved in antigen presentation and complement activation strongly implicates an inflammatory role for these MCs. This study provides a first insight into the phenotype of equine MCs in BALF and their potential role in the airways of asthmatic horses.

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  • 45.
    Akyurek, Levent M.
    et al.
    Sahlgrens Univ Hosp, Sweden.
    Hussein, Aziz
    Sahlgrens Univ Hosp, Sweden.
    Nicholson, Andrew G.
    Imperial Coll, England; Imperial Coll, England.
    Mauritz, Nils-Johan
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Department of Nephrology, Jönköping, Region Jönköping County, Sweden.
    Molne, Johan
    Sahlgrens Univ Hosp, Sweden.
    Pulmonary manifestations of systemic karyomegaly2020In: RESPIRATORY MEDICINE CASE REPORTS, ISSN 2213-0071, Vol. 29, article id 101032Article in journal (Refereed)
    Abstract [en]

    Over 40 years ago, abnormal enlargement of the nucleus of tubular epithelial cells was reported in a rare distinct hereditary chronic interstitial nephritis, karyomegalic interstitial nephritis (KIN). Here, we report the second case of systemic karyomegaly with pulmonary manifestations and present a detailed characterization of the karyomegalic cells in lung parenchyma. A 59-year-old woman who was diagnosed with KIN developed renal failure and eventually received a renal transplant later evaluated for chronic and progressive restrictive lung disease. The KIN diagnosis prompted us to carefully examine her lung parenchyma. Karyomegalic cells were identified in the alveolar epithelium, interstitium, as well as, in the vascular wall. Viral serological and biochemical blood analyses were negative. We consider that the pulmonary manifestations of karyomegaly expands the differential diagnosis of interstitial lung disease in patients with KIN.

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  • 46. Alahmadi, Fahad
    et al.
    Simpson, Andrew
    Gomez, Christina
    Wheelock, Craig
    Shaw, Dominick
    Fleming, Louise
    Roberts, Graham
    Riley, John
    Bates, Stewart
    Sousa, Ana R.
    Knowles, Richard
    Bansal, Aruna
    Corfield, Julie
    Pandis, Ioannis
    Sun, Kai
    Bakke, Per
    Caruso, Massimo
    Chanez, Pascal
    Dahlen, Babro
    Horvath, Ildiko
    Krug, Norbert
    Montuschi, Paolo
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Singer, Florian
    Wagers, Scott
    Adcock, Ian
    Djukanovic, Ratko
    Chung, Kian
    Sterk, Peter J.
    Dahlen, Sven-Erik
    Fowler, Stephen J.
    Measures of adherence in patients with severe asthma prescribed systemic steroids in the U-BIOPRED cohort2018In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Article in journal (Other academic)
    Abstract [en]

    Introduction: Rates of sub-optimal adherence to medications in asthma range up to 70%; the impact in severe asthma is likely to be particularly high. We measured self-reported adherence in participants in the U-BIOPRED cohort prescribed daily prednisolone using the Medication Adherence Response Scale (MARS), and compared to measured urinary prednisolone and metabolites in order to determine: 1. the prevalence of suboptimal adherence by each method; 2. the ability of MARS to predict urinary steroid detection.

    Methods: Participants completed the MARS, and/or provided urine samples (analysed for prednisolone and metabolites by LCMS). The performance characteristics of the MARS predicting undetected urinary steroid were calculated in the subgroup having both tests.

    Results: 181 participants currently taking regular oral corticosteroids were included, 59% female, mean (SD) age 54(12)yrs, FEV1 64.7(20.4)% predicted. Sub-optimal adherence (MARS score < 4.5) was reported in 62 participants, and 76 did not have detectable urinary prednisolone or metabolites. Good adherence by both methods was detected in only 52 participants (34%, see table). There was no difference in daily prednisolone dose between detectable and undetectable metabolites groups (p=0.848).

    Conclusion: Low levels of adherence to treatment in severe asthma is a common problem, when measured either directly or self-reported. There was very poor agreement (48% concordance) between these two methods, and we suggest that, for now both approaches should be used.

  • 47.
    Alexandre, Luana
    et al.
    Univ Porto, Fac Med, Porto, Portugal..
    Pereira, Ana Margarida
    Univ Porto, Fac Med, Dept Community Med Informat & Hlth Decis Sci MEDCI, Porto, Portugal.;CUF Porto Hosp, Allergy Unit, Porto, Portugal.;Institute, Porto, Portugal..
    Amaral, Rita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Inflammation, Metabolism and Child Health Research. Univ Porto, Fac Med, CINTESISRISE MEDCIDS, Porto, Portugal.;Polytech Inst Porto, Sch Hlth, Dept Cardiovasc & Resp Sci, Porto, Portugal..
    Alves-Correia, Magna
    CUF Porto Hosp, Allergy Unit, Porto, Portugal.;Institute, Porto, Portugal..
    Almeida, Rute
    Univ Porto, Fac Med, CINTESISRISE MEDCIDS, Porto, Portugal..
    Fonseca, Joao Almeida
    CUF Porto Hosp, Allergy Unit, Porto, Portugal.;Institute, Porto, Portugal.;Univ Porto, Fac Med, CINTESISRISE MEDCIDS, Porto, Portugal.;MEDIDA Med Educ Invest Desenvolvimento & Avaliacao, Porto, Portugal..
    Jacome, Cristina
    Univ Porto, Fac Med, CINTESISRISE MEDCIDS, Porto, Portugal.;Univ Porto, Fac Med, Ctr Hlth Technol & Serv Res, Dept Community Med Informat & Hlth Decis Sci, Rua Placido da Costa, P-4200450 Porto, Portugal..
    Patients' Satisfaction with Remote Asthma Medical Follow-Up Before and During the COVID-19 Pandemic2023In: Telemedicine journal and e-health, ISSN 1530-5627, E-ISSN 1556-3669, Vol. 29, no 9, p. 1383-1389Article in journal (Refereed)
    Abstract [en]

    Background: The COVID-19 pandemic forced the change of health care services, favoring the use of remote consultations.

    Objective: To assess the differences in asthma medical follow-up before and during the COVID-19 pandemic and to evaluate patients' satisfaction regarding remote consultations.

    Methods: A cross-sectional, observational, web-based study, including 335 Portuguese patients with self-reported physician-diagnosed asthma, was conducted. The survey was available between February and May 2021 and included questions about patients' sociodemographic and clinical characteristics and follow-up (consultations' type and satisfaction in 2019 and 2020). Satisfaction was assessed using 10 statements on different aspects of patient experience (Likert scale 1-5), with a total score between 10 and 50.

    Results: The 335 patients included had a median [P25-P75] age of 27 [21-43] years and 75% had uncontrolled asthma. Overall, fewer participants had consultations during the pandemic compared to 2019 (161 vs. 185; p < 0.001). Most patients had >= 1 face-to-face consultation both in 2020 and 2019 (131 vs. 184; p < 0.001). In 2020, there was an increase in the proportion of participants reporting >= 1 remote (telephonic plus video) consultation (40% vs. 3%; p < 0.001). This increase was mainly attributed to the use of telephonic consultation (38% vs. video 3%, p < 0.001). Patients' satisfaction was similar in 2020 and 2019 for face-to-face consultations (44 [38-47] and 44 [39-48], p = 0.136). In 2020, satisfaction with remote consultations was slightly lower than with face-to-face (43 [37-46] vs. 44 [38-47], p < 0.001).

    Conclusions: Even though patients were slightly more satisfied with face-to-face consultations, remote consultations can be an alternative in follow-up services for patients with asthma in the near future.

  • 48.
    Alharbi, Khalid Saad
    et al.
    Jouf Univ, Coll Pharm, Dept Pharmacol, Al Jouf, Saudi Arabia..
    Fuloria, Neeraj Kumar
    AIMST Univ, Fac Pharm, Bedong 08100, Kedah, Malaysia..
    Fuloria, Shivkanya
    AIMST Univ, Fac Pharm, Bedong 08100, Kedah, Malaysia..
    Rahman, Sk Batin
    Bengal Sch Technol, Hooghly, W Bengal, India..
    Al-Malki, Waleed Hassan
    Umm Al Qura Univ, Coll Pharm, Dept Pharmacol, Mecca, Saudi Arabia..
    Shaikh, Mohammad Arshad Javed
    Suresh Gyan Vihar Univ, Sch Pharm, Mahal Rd, Jaipur 302017, Rajasthan, India..
    Thangavelu, Lakshmi
    Saveetha Univ, Saveetha Dent Coll, Dept Pharmacol, Chennai, Tamil Nadu, India..
    Singh, Sachin K.
    Lovely Profess Univ, Sch Pharmaceut Sci, Phagwara 144411, Punjab, India..
    Allam, Venkata
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Jha, Niraj Kumar
    Sharda Univ, Sch Engn & Technol SET, Dept Biotechnol, Plot 32-34,Knowledge Pk 3, Greater Noida 201310, Uttar Pradesh, India..
    Chellappan, Dinesh Kumar
    Int Med Univ, Sch Pharm, Dept Life Sci, Kuala Lumpur 57000, Malaysia..
    Dua, Kamal
    Univ Technol Sydney, Grad Sch Hlth, Discipline Pharm, Sydney, NSW 2007, Australia..
    Gupta, Gaurav
    Suresh Gyan Vihar Univ, Sch Pharm, Mahal Rd, Jaipur 302017, Rajasthan, India..
    Nuclear factor-kappa B and its role in inflammatory lung disease2021In: Chemico-Biological Interactions, ISSN 0009-2797, E-ISSN 1872-7786, Vol. 345, article id 109568Article in journal (Refereed)
    Abstract [en]

    Nuclear factor-kappa B, involved in inflammation, host immune response, cell adhesion, growth signals, cell proliferation, cell differentiation, and apoptosis defense, is a dimeric transcription factor. Inflammation is a key component of many common respiratory disorders, including asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, and acute respiratory distress syndrome. Many basic transcription factors are found in NF-xB signaling, which is a member of the Rel protein family. Five members of this family c-REL, NF-xB2 (p100/ p52), RelA (p65), NF-xB1 (p105/p50), RelB, and RelA (p65) produce 5 transcriptionally active molecules. Proinflammatory cytokines, T lymphocyte, and B lymphocyte cell mitogens, lipopolysaccharides, bacteria, viral proteins, viruses, double-stranded RNA, oxidative stress, physical exertion, various chemotherapeutics are the stimulus responsible for NF-xB activation. NF-xB act as a principal component for several common respiratory illnesses, such as asthma, lung cancer, pulmonary fibrosis, COPD as well as infectious diseases like pneumonia, tuberculosis, COVID-19. Inflammatory lung disease, especially COVID-19, can make NF-xB a key target for drug production.

  • 49.
    Ali, Neserin
    et al.
    Lund Univ, Sweden.
    Ljunggren, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Wierzbicka, Aneta
    Lund Univ, Sweden.
    Pagels, Joakim
    Lund Univ, Sweden.
    Isaxon, Christina
    Lund Univ, Sweden.
    Gudmundsson, Anders
    Lund Univ, Sweden.
    Rissler, Jenny
    Lund Univ, Sweden.
    Nielsen, Jorn
    Lund Univ, Sweden.
    Lindh, Christian H.
    Lund Univ, Sweden.
    Karedal, Monica
    Lund Univ, Sweden.
    Comprehensive proteome analysis of nasal lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor, LXR/RXR, activation that influence the status of the extracellular matrix2018In: Clinical Proteomics, ISSN 1542-6416, E-ISSN 1559-0275, Vol. 15, article id 20Article in journal (Refereed)
    Abstract [en]

    Background: Epidemiological studies have shown that many welders experience respiratory symptoms. During the welding process a large number of airborne nanosized particles are generated, which might be inhaled and deposited in the respiratory tract. Knowledge of the underlying mechanisms behind observed symptoms is still partly lacking, although inflammation is suggested to play a central role. The aim of this study was to investigate the effects of welding fume particle exposure on the proteome expression level in welders suffering from respiratory symptoms, and changes in protein mediators in nasal lavage samples were analyzed. Such mediators will be helpful to clarify the pathomechanisms behind welding fume particle-induced effects. Methods: In an exposure chamber, 11 welders with work-related symptoms in the lower airways during the last month were exposed to mild-steel welding fume particles (1 mg/m(3)) and to filtered air, respectively, in a double-blind manner. Nasal lavage samples were collected before, immediately after, and the day after exposure. The proteins in the nasal lavage were analyzed with two different mass spectrometry approaches, label-free discovery shotgun LC-MS/MS and a targeted selected reaction monitoring LC-MS/MS analyzing 130 proteins and four in vivo peptide degradation products. Results: The analysis revealed 30 significantly changed proteins that were associated with two main pathways; activation of acute phase response signaling and activation of LXR/RXR, which is a nuclear receptor family involved in lipid signaling. Connective tissue proteins and proteins controlling the degradation of such tissues, including two different matrix metalloprotease proteins, MMP8 and MMP9, were among the significantly changed enzymes and were identified as important key players in the pathways. Conclusion: Exposure to mild-steel welding fume particles causes measurable changes on the proteome level in nasal lavage matrix in exposed welders, although no clinical symptoms were manifested. The results suggested that the exposure causes an immediate effect on the proteome level involving acute phase proteins and mediators regulating lipid signaling Proteases involved in maintaining the balance between the formation and degradation of extracellular matrix proteins are important key proteins in the induced effects.

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  • 50.
    Ali, Neserin
    et al.
    Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
    Mattsson, Karin
    Center for Molecular Protein Science, Biochemistry and Structural Biology, Lund University, Lund, Sweden.
    Rissler, Jenny
    Department of Design Sciences, Ergonomic and Aerosol Technology, Lund University, Lund, Sweden.
    Karlsson, Helen Marg
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Svensson, Christian R
    Department of Design Sciences, Ergonomic and Aerosol Technology, Lund University, Lund, Sweden.
    Gudmundsson, Anders
    Department of Design Sciences, Ergonomic and Aerosol Technology, Lund University, Lund, Sweden.
    Lindh, Christian H
    Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
    Jönsson, Bo A G
    Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
    Cedervall, Tommy
    Center for Molecular Protein Science, Biochemistry and Structural Biology, Lund University, Lund, Sweden.
    Kåredal, Monica
    Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
    Analysis of nanoparticle-protein coronas formed in vitro between nanosized welding particles and nasal lavage proteins.2016In: Nanotoxicology, ISSN 1743-5390, E-ISSN 1743-5404, Vol. 10, no 2, p. 226-234Article in journal (Refereed)
    Abstract [en]

    Welding fumes include agglomerated particles built up of primary nanoparticles. Particles inhaled through the nose will to some extent be deposited in the protein-rich nasal mucosa, and a protein corona will be formed around the particles. The aim was to identify the protein corona formed between nasal lavage proteins and four types of particles with different parameters. Two of the particles were formed and collected during welding and two were manufactured iron oxides. When nasal lavage proteins were added to the particles, differences were observed in the sizes of the aggregates that were formed. Measurements showed that the amount of protein bound to particles correlated with the relative size increase of the aggregates, suggesting that the surface area was associated with the binding capacity. However, differences in aggregate sizes were detected when nasal proteins were added to UFWF and Fe2O3 particles (having similar agglomerated size) suggesting that yet parameters other than size determine the binding. Relative quantitative mass spectrometric and gel-based analyses showed differences in the protein content of the coronas. High-affinity proteins were further assessed for network interactions. Additional experiments showed that the inhibitory function of secretory leukocyte peptidase inhibitor, a highly abundant nasal protein, was influenced by particle binding suggesting that an understanding of protein function following particle binding is necessary to properly evaluate pathophysiological events. Our results underscore the importance of including particles collected from real working environments when studying the toxic effects of particles because these effects might be mediated by the protein corona.

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