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  • 1.
    Green, Henrik
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Division of Gene Technology, Royal Institute of Technology, Solna, Sweden/ Royal Institute Technology, Sweden; National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Hasmats, Johanna
    Royal Institute Technology, Sweden.
    Kupershmidt, Ilya
    Royal Institute Technology, Sweden; NextBio, CA USA.
    Edsgard, Daniel
    Royal Institute Technology, Sweden.
    de Petris, Luigi
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Lewensohn, Rolf
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Blackhall, Fiona
    Christie Hospital, England; University of Manchester, England.
    Vikingsson, Svante
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Besse, Benjamin
    University of Paris 11, France.
    Lindgren, Andrea
    Linköping University, Department of Medical and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Branden, Eva
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Koyi, Hirsh
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Peterson, Curt
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Lundeberg, Joakim
    Royal Institute Technology, Sweden.
    Using Whole-Exome Sequencing to Identify Genetic Markers for Carboplatin and Gemcitabine-Induced Toxicities2016In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 22, no 2, p. 366-373Article in journal (Refereed)
    Abstract [en]

    Purpose: Chemotherapies are associated with significant interindividual variability in therapeutic effect and adverse drug reactions. In lung cancer, the use of gemcitabine and carboplatin induces grade 3 or 4 myelosuppression in about a quarter of the patients, while an equal fraction of patients is basically unaffected in terms of myelosuppressive side effects. We therefore set out to identify genetic markers for gemcitabine/carboplatin-induced myelosuppression. Experimental Design: We exome sequenced 32 patients that suffered extremely high neutropenia and thrombocytopenia (grade 3 or 4 after first chemotherapy cycle) or were virtually unaffected (grade 0 or 1). The genetic differences/polymorphism between the groups were compared using six different bioinformatics strategies: (i) whole-exome nonsynonymous single-nucleotide variants association analysis, (ii) deviation from Hardy-Weinberg equilibrium, (iii) analysis of genes selected by a priori biologic knowledge, (iv) analysis of genes selected from gene expression meta-analysis of toxicity datasets, (v) Ingenuity Pathway Analysis, and (vi) FunCoup network enrichment analysis. Results: A total of 53 genetic variants that differed among these groups were validated in an additional 291 patients and were correlated to the patients myelosuppression. In the validation, we identified rs1453542 in OR4D6 (P = 0.0008; OR, 5.2; 95% CI, 1.8-18) as a marker for gemcitabine/carboplatin-induced neutropenia and rs5925720 in DDX53 (P = 0.0015; OR, 0.36; 95% CI, 0.17-0.71) as a marker for thrombocytopenia. Patients homozygous for the minor allele of rs1453542 had a higher risk of neutropenia, and for rs5925720 the minor allele was associated with a lower risk for thrombocytopenia. Conclusions: We have identified two new genetic markers with the potential to predict myelosuppression induced by gemcitabine/ carboplatin chemotherapy. (C)2015 AACR.

  • 2.
    Kentson, Magnus
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Leandersson, Per
    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.
    Jacobson, Petra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Persson, Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    The influence of disease severity and lifestyle factors on the peak annual 25(OH)D value of COPD patients2018In: The International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, E-ISSN 1178-2005, Vol. 13, p. 1389-1398Article in journal (Refereed)
    Abstract [en]

    Background: The prevalence of individuals deficient in vitamin D (defined as a serum level of the stable metabolite 25(OH)D amp;lt; 50 nmol/L) is increasing in countries with low annual ultraviolet (UV) radiation and among individuals unable to perform outdoor activities, for example, COPD patients. Objective: To assess the role of vitamin D deficiency, independently of seasonal variation, the peak annual value of 25(OH)D was measured in subjects with advanced COPD +/- long-term oxygen therapy (LTOT) and lung healthy control subjects. A method to grade the individual annual UV light exposure was designed and tested. Subjects and methods: Sixty-six Caucasians with advanced COPD (28 with LTOT) and 47 control subjects were included, and the levels of 25(OH)D were determined in late summer/ early fall when the annual peak was assumed. Questionnaires about COPD symptoms, general health, lifestyle, dietary habits and QoL were used to collect data. Lung function tests and blood sampling were performed. Results: The peak annual 25(OH)D of COPD subjects was significantly lower than in the control subjects, but there was no significant difference between COPD patients with and without LTOT. Ongoing vitamin D supplementation was the single most important intervention to maintain 25(OH)D levels amp;gt;= 50 nmol/L. Among vitamin D-deficient COPD subjects, 25(OH)D correlated positively with forced expiratory volume in 1 second as % predicted, Modified British Medical Research Council score, blood oxygenation, food portion size, Mediterranean Diet Score and Ultraviolet Score. Conclusion: Vitamin D deficiency was common among healthy individuals and COPD subjects. Peak annual 25(OH)D levels of COPD subjects correlated with clinically important outcomes. The present study emphasizes the need to routinely monitor vitamin D status among patients with advanced COPD and to consider to medicate those with vitamin D deficiency with vitamin D supplementation.

  • 3.
    Lal, R.
    et al.
    Guys and St Thomas NHS Fdn Trust, England.
    Hillerdal, G. N.
    Karolinska University of Jukhuset, Sweden.
    Shah, R. N. H.
    Maidstone and Tunbridge Wells NHS Trust, England.
    Crosse, B.
    Calderdale and Huddersfield NHS Trust, England.
    Thompson, J.
    Birmingham Heartlands Hospital, England.
    Nicolson, M.
    Aberdeen Royal Infirm, Scotland.
    Vikström, Anders
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Potter, V. A.
    Nottingham University Hospital NHS Trust, England.
    Visseren-Grul, C.
    Eli Lilly and Co, IN USA.
    Lorenzo, M.
    Eli Lilly and Co, IN USA.
    Dyachkova, Y.
    Eli Lilly and Co, IN USA.
    Bourayou, N.
    Eli Lilly and Co, IN USA.
    Summers, Y. J.
    Christie Hospital NHS Fdn Trust, England.
    Feasibility of home delivery of pemetrexed in patients with advanced non-squamous non-small cell lung cancer2015In: Lung Cancer, ISSN 0169-5002, E-ISSN 1872-8332, Vol. 89, no 2, p. 154-160Article in journal (Refereed)
    Abstract [en]

    Objectives: To evaluate the feasibility and adherence to home delivery (HD) of pemetrexed maintenance treatment in patients with advanced non-squamous non-small cell lung cancer (nsqNSCLC). Materials and methods: Exploratory, prospective, single-arm, Phase II study in advanced nsqNSCLC patients, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0/1 that did not progress after 4 first-line induction cycles of a platinum doublet. The first cycle of pemetrexed (500 mg/m(2)) was hospital administered, further cycles were HD until progressive disease or discontinuation. Feasibility was assessed by the adherence rate to HD (probability of reversion to hospital administration or treatment discontinuation due to HD) as primary endpoint, and by health-related quality-of-life (HRQoL: EQ-5D, lung cancer symptom scale [LCSS]), satisfaction with HD, overall survival (OS), and safety. Results: 52 patients (UK and Sweden) received a median of 4 (range 1-19) pemetrexed maintenance cycles. Adherence rate up to Cycle 6 was 98.0% (95% confidence interval [CI]: 86.4%, 99.7%). All but 2 patients remained on HD. 1 patient discontinued after Cycle 1 (patient decision), and 1 after Cycle 6 (noncompliance with oral dexamethasone). 87% (33/38) of the patients preferred home to hospital treatment and in 90% (28/31) of cases, physicians were satisfied with distant management of patients. During HD Cycles 2-4 mean change from baseline ranged from 3.0 to 7.7 for EQ-5D visual analog scale. The 6-month OS rate was 73% (95% CI: 58%, 83%). 1 patient had an HD-related adverse event (device-related infection, Grade 2) and 1 patient died after Cycle 1, before HD, due to a possibly drug-related atypical pneumonia. Conclusion: HD of pemetrexed maintenance treatment in patients with advanced nsqNSCLC was feasible, safe, and preferred by patients, while maintaining HRQoL. Physicians were satisfied with distant patient management. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

  • 4.
    Lind, Leili
    et al.
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. SICS East Swedish ICT, Linköping, Sweden.
    Carlgren, Gunnar
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Mudra, Jacqueline
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Synnergren, Henrik
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Hilding, Niclas
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Karlsson, daniel
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering.
    Wiréhn, Ann-Britt
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Persson, Hans Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Preliminary results of a telemonitoring study: COPD and heart failure patients exhibit great difference in their need of health care2015In: European Respiratory Journal: Official Scientific Journal of ERS / [ed] Marc Humbert, European Respiratory Society , 2015, Vol. 46/suppl 59, p. PA2790-PA2790Conference paper (Other academic)
    Abstract [en]

    Background: Growing populations of elderly patients with advanced stages of COPD or heart failure (HF) urge the need for specialized health care in the patients' home. A telemonitoring study has been initiated including patients using digital pens. Health care was provided by the specialized home care unit at a university hospital. Through an IT system the staff checked all daily patient reports. We hypothesized that the two groups of patients, advanced COPD or HF, would exhibit differences regarding exacerbations and the need of health care.

    Objective: To study exacerbations of COPD or HF, and patient health care consumption.

    Methods: A tele-monitoring system, the Health diary, which is based on digital pen technology, was employed. Exacerbations were identified using information provided through the telemonitoring system. Consumed health care was assessed as the number of patient contacts (home visits or telephone consultations).

    Results: Presently, 33 patients with advanced disease are enrolled (13 COPD and 20 HF patients) of which 11 patients (6 COPD and 5 HF patients) have completed the 1-yr study period or have died during the study period (2 COPD and 4 HF patients). Exacerbations were 2.8 and 0.8 and patient contacts were 96 and 42 per COPD and HF patient, respectively. While HF patients were significantly older than COPD patients, the two groups demonstrated no difference regarding gender distribution and comorbidity.

    Conclusions: COPD patients exhibit exacerbations more frequently and demand much more home health care than patients with HF do. It seems that this difference of health care consumption is mainly due to disease characteristics.

  • 5.
    Lind, Leili
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. RISE SICS East.
    Wiréhn, Ann-Britt
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Region Östergötland.
    Carlgren, Gunnar
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Mudra, Jacqueline
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Synnergren, Henrik
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Hilding, Niclas
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Lyth, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Region Östergötland.
    Karlsson, Daniel
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Persson, Hans Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Re-organising care of elderly, multi-morbid COPD and heartfailure patients with low digital literacy: —a 4 year Swedishtelehealth intervention study2016In: Health—exploring complexity: an interdisciplinary systems approach HEC2016 / [ed] Grill, E., Müller, M. & Mansmann, U., Munich, Germany, 2016, Vol. 31, p. 118-118Conference paper (Refereed)
  • 6.
    Sioutas, Apostolos
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Vainikka, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Kentson, Magnus
    Division of Medicine, Ryhov Hospital, Jönköping, Sweden.
    Dam-Larsen, Sören
    Division of Medicine, Hospital of Eksjö, Eksjö, Sweden.
    Wennerström, Urban
    Division of Medicine, Hospital of Västervik, Västervik, Sweden.
    Jacobson, Petra
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Persson, Hans Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Oxidant-induced autophagy and ferritin degradation contribute to epithelial-mesenchymal transition through lysosomal iron2017In: Journal of Inflammation Research, ISSN 1178-7031, E-ISSN 1178-7031, Vol. 10, p. 29-39Article in journal (Refereed)
    Abstract [en]

    Transforming growth factor (TGF)-ß1 triggers epithelial-mesenchymal transition (EMT) through autophagy, which is partly driven by reactive oxygen species (ROS). The aim of this study was to determine whether leaking lysosomes and enhanced degradation of H-ferritin could be involved in EMT and whether it could be possible to prevent EMT by iron chelation targeting of the lysosome.

  • 7.
    Sköld, Carl Magnus
    et al.
    Department of Medicine Solna, Karolinska Institutet, Lung-Allergy Clinic, Karolinska University Hospital Solna, Stockholm, Sweden.
    Janson, Christer
    Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.
    Klackenberg Elf, Åsa
    InterMune Nordics AB, Stockholm, Sweden; Roche AB, Stockholm, Sweden.
    Fiaschi, Marie
    Roche AB, Stockholm, Sweden.
    Wiklund, Kerstin
    PCG Clinical Services, Uppsala, Sweden.
    Persson, Hans Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    A retrospective chart review of pirfenidone-treated patients in Sweden: the REPRIS study2016In: European Clinical Respiratory Journal, E-ISSN 2001-8525, Vol. 3, no 1, article id 32035Article in journal (Refereed)
    Abstract [en]

    Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that usually results in respiratory failure and death. Pirfenidone was approved as the first licensed therapy for IPF in Europe based on phase III trials where patients with a forced vital capacity (FVC) greater than50% of predicted were included. The aim of this study was to characterise patients treated with pirfenidone in Swedish clinical practice and to describe the adherence to the reimbursement restriction since reimbursement was only applied for patients with FVC below 80% of predicted.less thanbr /greater thanMethods: This was a retrospective, observational chart review of IPF patients treated with pirfenidone from three Swedish university clinics. Patients initiated on treatment during the period 28 June 2012 to 20 November 2014 were included. Data on patient characteristics, basis of diagnosis, treatment duration, quality of life, and adverse drug reactions (ADRs) were collected from medical charts.less thanbr /greater thanResults: Forty-four patients were screened and 33 were included in the study. The mean treatment duration from start of pirfenidone until discontinuation or end of study was 38 weeks. At the initiation of pirfenidone treatment, FVC was 62.7% (12.1) [mean (SD)], diffusion capacity (DLco) was 45.1% (13.8) of predicted, and the ratio of forced expiratory volume on 1 sec (FEV1) to FVC was 0.78 (0.1). The percentage of patients with an FVC between 50 and 80% was 87%. Ten of the patients had ADRs including gastrointestinal and skin-related events, cough and signs of impaired hepatic function, but this led to treatment discontinuation in only two patients.less thanbr /greater thanConclusion: Data from this chart review showed that adherence to the Swedish reimbursement restriction was followed in the majority of patients during the study period. At the start of pirfenidone treatment, lung function, measured as FVC, was lower in the present cohort of Swedish IPF patients compared with other registry and real-life data. About a third of the patients had ADRs, but discontinuation of the treatment because of ADRs was relatively uncommon.

  • 8.
    Svedberg, Anna
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. National Board Forens Med, Department Forens Genet and Forens Toxicol, SE-58758 Linkoping, Sweden; KTH Royal Institute Technology, Sweden.
    Vikström, Anders
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Lundeberg, Joakim
    KTH Royal Institute Technology, Sweden.
    Vikingsson, Svante
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    A validated liquid chromatography tandem mass spectrometry method for quantification of erlotinib, OSI-420 and didesmethyl erlotinib and semi-quantification of erlotinib metabolites in human plasma2015In: Journal of Pharmaceutical and Biomedical Analysis, ISSN 0731-7085, E-ISSN 1873-264X, Vol. 107, p. 186-195Article in journal (Refereed)
    Abstract [en]

    A liquid chromatography tandem mass spectrometry method was developed and validated for quantification of erlotinib and its metabolites in human plasma. The method is suitable for therapeutic drug monitoring and pharmacokinetic studies. The substances were extracted using protein precipitation, separated on a BEH XBridge C18 column (100 x 2.1 mm, 1.7 mu m) by gradient elution at 0.7 mL/min of acetonitrile and 5 mM ammonium acetate. The concentration was determined using a Waters Xevo triple quadrupole mass spectrometer in a multi reaction monitoring mode. The total run time was 7 min. Deuterated erlotinib and OSI-597 were used as internal standard for erlotinib and its metabolites, respectively. Erlotinib, OSI-420 and didesmethyl erlotinib were quantified in the concentration range 25-5000 ng/mL, 0.5-500 ng/mL and 0.15-10 ng/mL, respectively. Precision and accuracy was less than14% except for OSI-420 at LLOQ (17%). Extraction recovery was above 89%, 99% and 89% for erlotinib, OSI-420 and didesmethyl erlotinib, respectively. The human liver microsomes generated 14 metabolites, three of them not previously reported. Twelve metabolites were measured semi-quantitatively and validated with respect to selectivity, precision and stability. (C) 2014 Elsevier B.V. All rights reserved.

  • 9.
    Toren, K.
    et al.
    University of Gothenburg, Sweden.
    Bake, B.
    University of Gothenburg, Sweden.
    Olin, A-C
    University of Gothenburg, Sweden.
    Engstrom, G.
    Lund University, Sweden.
    Blomberg, A.
    Umeå University, Sweden.
    Vikgren, J.
    University of Gothenburg, Sweden.
    Hedner, J.
    University of Gothenburg, Sweden.
    Brandberg, J.
    University of Gothenburg, Sweden.
    Persson, Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Sköld, C. M.
    Karolinska Institute, Sweden.
    Rosengren, A.
    University of Gothenburg, Sweden.
    Bergstrom, G.
    University of Gothenburg, Sweden.
    Janson, C.
    Uppsala University, Sweden.
    Measures of bronchodilator response of FEV1, FVC and SVC in a Swedish general population sample aged 50-64 years, the SCAPIS Pilot Study2017In: The International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, E-ISSN 1178-2005, Vol. 12, p. 973-980Article in journal (Refereed)
    Abstract [en]

    Background: Data are lacking from general population studies on how to define changes in lung function after bronchodilation. This study aimed to analyze different measures of bronchodilator response of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and slow vital capacity (SVC). Materials and methods: Data were derived from the Swedish Cardiopulmonary Bioimage Study (SCAPIS) Pilot study. This analysis comprised 1,050 participants aged 50-64 years from the general population. Participants were investigated using a questionnaire, and FEV1, FVC and SVC were recorded before and 15 minutes after inhalation of 400 mu g of salbutamol. A bronchodilator response was defined as the relative change from baseline value expressed as the difference in units of percent predicted normal. Predictors of bronchodilator responses were assessed using multiple linear regression models. Airway obstruction was defined as FEV1/FVC ratio below lower limit of normal (LLN) before bronchodilation, and COPD was defined as an FEV1/FVC ratio below LLN after bronchodilation. Physician-diagnosed asthma was defined as an affirmative answer to " Have you ever had asthma diagnosed by a physician?". Asymptomatic never-smokers were defined as those not reporting physician-diagnosed asthma, physician-diagnosed COPD or emphysema, current wheeze or chronic bronchitis and being a lifelong never-smoker. Results: Among all subjects, the greatest bronchodilator responses (FEV1, FVC and SVC) were found in subjects with asthma or COPD. The upper 95th percentile of bronchodilator responses in asymptomatic never-smokers was 8.7% for FEV1, 4.2% for FVC and 5.0% for SVC. The bronchodilator responses were similar between men and women. In a multiple linear regression model comprising all asymptomatic never-smokers, the bronchodilator response of FEV1 was significantly associated with airway obstruction and height. Conclusion: When the bronchodilator response in asymptomatic never-smokers is reported as the difference in units of predicted normal, significant reversibility of FEV1, FVC and SVC to bronchodilators is 9%, 4% and 5%, respectively.

  • 10.
    Toren, Kjell
    et al.
    University of Gothenburg, Sweden.
    Olin, Anna-Carin
    University of Gothenburg, Sweden.
    Lindberg, Anne
    Umeå University, Sweden.
    Vikgren, Jenny
    University of Gothenburg, Sweden.
    Schioler, Linus
    University of Gothenburg, Sweden.
    Brandberg, John
    University of Gothenburg, Sweden.
    Johnsson, Ase
    University of Gothenburg, Sweden.
    Engstrom, Gunnar
    Department Clin Science, Sweden; University of Lund, Sweden.
    Persson, Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Skold, Magnus
    Karolinska Institute, Sweden.
    Hedner, Jan
    University of Gothenburg, Sweden.
    Lindberg, Eva
    Uppsala University, Sweden.
    Malinovschi, Andrei
    Uppsala University, Sweden.
    Piitulainen, Eeva
    University of Lund, Sweden.
    Wollmer, Per
    University of Lund, Sweden.
    Rosengren, Annika
    University of Gothenburg, Sweden.
    Janson, Christer
    Uppsala University, Sweden.
    Blomberg, Anders
    Umeå University, Sweden.
    Bergstrom, Goran
    University of Gothenburg, Sweden.
    Vital capacity and COPD: the Swedish CArdioPulmonary bioImage Study (SCAPIS)2016In: The International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, E-ISSN 1178-2005, Vol. 11, p. 927-933Article in journal (Refereed)
    Abstract [en]

    Background: Spirometric diagnosis of chronic obstructive pulmonary disease (COPD) is based on the ratio of forced expiratory volume in 1 second (FEV1)/vital capacity (VC), either as a fixed value <0.7 or below the lower limit of normal (LLN). Forced vital capacity (FVC) is a proxy for VC. The first aim was to compare the use of FVC and VC, assessed as the highest value of FVC or slow vital capacity (SVC), when assessing the FEV1/VC ratio in a general population setting. The second aim was to evaluate the characteristics of subjects with COPD who obtained a higher SVC than FVC. Methods: Subjects (n=1,050) aged 50-64 years were investigated with FEV1, FVC, and SVC after bronchodilation. Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPDFVC was defined as FEV1/FVC <0.7, GOLDCOPD(VC) as FEV1/VC <0.7 using the maximum value of FVC or SVC, LLNCOPDFVC as FEV1/FVC below the LLN, and LLNCOPDVC as FEV1/VC below the LLN using the maximum value of FVC or SVC. Results: Prevalence of GOLDCOPD(FVC) was 10.0% (95% confidence interval [CI] 8.2-12.0) and the prevalence of LLNCOPDFVC was 9.5% (95% CI 7.8-11.4). When estimates were based on VC, the prevalence became higher; 16.4% (95% CI 14.3-18.9) and 15.6% (95% CI 13.5-17.9) for GOLDCOPD(VC) and LLNCOPDVC, respectively. The group of additional subjects classified as having COPD based on VC, had lower FEV1, more wheeze and higher residual volume compared to subjects without any COPD. Conclusion: The prevalence of COPD was significantly higher when the ratio FEV1/VC was calculated using the highest value of SVC or FVC compared with using FVC only. Subjects classified as having COPD when using the VC concept were more obstructive and with indications of air trapping. Hence, the use of only FVC when assessing airflow limitation may result in a considerable under diagnosis of subjects with mild COPD.

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