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  • 1.
    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.

  • 2.
    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)
  • 3.
    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.

  • 4.
    Al-Shamkhi, Nasrin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Dahlen, S. E.
    Karolinska Inst, Inst Environm Med, Expt Asthma & Allergy Res Unit, Stockholm, Sweden..
    Hedlin, G.
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Middelveld, R.
    Karolinska Inst, Inst Environm Med, Expt Asthma & Allergy Res Unit, Stockholm, Sweden..
    Bjerg, A.
    Univ Gothenburg, Krefting Res Ctr, Dept Internal Med & Clin Nutr, Gothenburg, Sweden..
    Ekerljung, L.
    Univ Gothenburg, Krefting Res Ctr, Dept Internal Med & Clin Nutr, Gothenburg, Sweden..
    Olin, A. C.
    Univ Gothenburg, Sect Occupat & Environm Med, Dept Publ Hlth & Community Med, Inst Med,Sahlgrenska Acad, Gothenburg, Sweden..
    Sommar, J.
    Umea Univ, Dept Publ Hlth & Clin Med Occupat & Environm Med, Umea, Sweden..
    Forsberg, B.
    Umea Univ, Dept Publ Hlth & Clin Med Occupat & Environm Med, Umea, Sweden..
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Important non-disease-related determinants of exhaled nitric oxide levels in mild asthma - results from the Swedish GA(2)LEN study2016In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, no 9, p. 1185-1193Article in journal (Refereed)
    Abstract [en]

    Background Fractional exhaled nitric oxide (FeNO) has a potential clinical role in asthma management. Constitutive factors such as age, height and gender, as well as individual characteristics, such as IgE sensitization and smoking, affect the levels of FeNO in population-based studies. However, their effect on FeNO in subjects with asthma has been scarcely studied. Objective To study the effects on FeNO of these commonly regarded determinants, as demonstrated in healthy subjects, as well as menarche age and parental smoking, in a population of asthmatics. Material and Methods Fractional exhaled nitric oxide was measured in 557 subjects with asthma from the Swedish GA(2)LEN study. Allergic sensitization was assessed by skin prick tests to most common aeroallergens. Upper airway comorbidities, smoking habits, smoking exposure during childhood and hormonal status (for women) were questionnaire-assessed. Results Male gender (P < 0.001), greater height (P < 0.001) and sensitization to both perennial allergens and pollen (P < 0.001) are related to higher FeNO levels. Current smoking (P < 0.001) and having both parents smoking during childhood, vs. having neither (P < 0.001) or only one parent smoking (P = 0.002), are related to lower FeNO. Women with menarche between 9 and 11 years of age had lower FeNO than those with menarche between 12 and 14 years of age (P = 0.03) or 15 and 17 years of age (P = 0.003). Conclusions and Clinical relevance Interpreting FeNO levels in clinical practice is complex, and constitutional determinants, as well as smoking and IgE sensitisation, are of importance in asthmatic subjects and should be accounted for when interpreting FeNO levels. Furthermore, menarche age and parental smoking during childhood and their effects on lowering FeNO deserve further studies.

  • 5.
    Alving, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Basic aspects of exhaled nitric oxide2010In: European Respiratory Monograph, ISSN 1025-448X, E-ISSN 2075-6674, Vol. 49, p. 1-31Article, review/survey (Refereed)
    Abstract [en]

    Nitric oxide (NO) in orally exhaled air mainly originates fromthe respiratory epithelium. NO is produced by inducible NOsynthase (iNOS), which is regulated by signal transducer andactivator of transcription (STAT)-1 under the influence ofhomeostatic interferon-c. In patients with asthma, iNOSexpression is upregulated by interleukin (IL)-4 and IL-13 viathe activation of STAT-6 in the bronchial epithelium. Thus,exhaled NO primarily signals local T-helper cell type 2-driveninflammation in the bronchial mucosa. With these character-istics, exhaled NO will be a suitable marker for predicting theresponse to inhaled corticosteroids, and to monitor the anti-inflammatory effect.The methodology for measuring exhaled NO has beenstandardised based on international consensus. The determi-nants of exhaled NO levels are fairly well characterised, withthe most important being cigarette smoking, nitrate intake, airpollution, allergen sensitisation and exposure, along withheight, sex and age. A future development may be the estima-tion of peripheral airway inflammation by measuring exhaledNO at multiple exhalation flow rates.

  • 6.
    Amaral, Rita
    et al.
    Univ Porto, Fac Med, CINTESIS Ctr Hlth Technol & Serv Res, Edificio Nascente,Piso 2,Rua Dr Placido Costa S-N, P-4200450 Porto, Portugal;Porto Hlth Sch, Dept Cardiovasc & Resp Sci, Porto, Portugal.
    Fonseca, Joao A.
    Univ Porto, Fac Med, CINTESIS Ctr Hlth Technol & Serv Res, Edificio Nascente,Piso 2,Rua Dr Placido Costa S-N, P-4200450 Porto, Portugal;Univ Porto, Fac Med, MEDCIDS Dept Community Med Informat & Hlth Sci, Porto, Portugal;Inst & Hosp CUF, Dept Allergy, Porto, Portugal.
    Jacinto, Tiago
    Univ Porto, Fac Med, CINTESIS Ctr Hlth Technol & Serv Res, Edificio Nascente,Piso 2,Rua Dr Placido Costa S-N, P-4200450 Porto, Portugal;Porto Hlth Sch, Dept Cardiovasc & Resp Sci, Porto, Portugal;Inst & Hosp CUF, Dept Allergy, Porto, Portugal.
    Pereira, Ana M.
    Univ Porto, Fac Med, CINTESIS Ctr Hlth Technol & Serv Res, Edificio Nascente,Piso 2,Rua Dr Placido Costa S-N, P-4200450 Porto, Portugal;Inst & Hosp CUF, Dept Allergy, Porto, Portugal.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Alving, Kjell
    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.
    Having concomitant asthma phenotypes is common and independently relates to poor lung function in NHANES 2007-20122018In: Clinical and Translational Allergy, ISSN 2045-7022, E-ISSN 2045-7022, Vol. 8, article id 13Article in journal (Refereed)
    Abstract [en]

    Background: Evidence for distinct asthma phenotypes and their overlap is becoming increasingly relevant to identify personalized and targeted therapeutic strategies. In this study, we aimed to describe the overlap of five commonly reported asthma phenotypes in US adults with current asthma and assess its association with asthma outcomes. Methods: Data from the National Health and Nutrition Examination Surveys (NHANES) 2007-2012 were used (n =30,442). Adults with current asthma were selected. Asthma phenotypes were: B-Eos-high [if blood eosinophils (B-Eos) >= 300/mm(3)]; FeNO-high (FeNO >= 35 ppb); B-Eos&FeNO-low (B-Eos < 150/mm(3) and FeNO < 20 ppb); asthma with obesity (AwObesity) (BMI >= 30 kg/m(2)); and asthma with concurrent COPD. Data were weighted for the US population and analyses were stratified by age (< 40 and >= 40 years old). Results: Of the 18,619 adults included, 1059 (5.6% [95% CI 5.1-5.9]) had current asthma. A substantial overlap was observed both in subjects aged < 40 years (44%) and >= 40 years (54%). The more prevalent specific overlaps in both age groups were AwObesity associated with either B-Eos-high (15 and 12%, respectively) or B-Eos&FeNO-low asthma (13 and 11%, respectively). About 14% of the current asthma patients were"non-classified". Regardless of phenotype classification, having concomitant phenotypes was significantly associated with (adjusted OR, 95% CI) >= 2 controller medications (2.03, 1.16-3.57), and FEV1 < LLN (3.21, 1.74-5.94), adjusted for confounding variables. Conclusions: A prevalent overlap of commonly reported asthma phenotypes was observed among asthma patients from the general population, with implications for objective asthma outcomes. A broader approach may be required to better characterize asthma patients and prevent poor asthma outcomes.

  • 7.
    Amaral, Rita
    et al.
    Univ Porto, CINTESIS Ctr Hlth Technol & Serv Res, Fac Med, Edificio Nascente,Piso 2, P-4200450 Porto, Portugal;Porto Hlth Sch, Dept Cardiovasc & Resp Sci, Porto, Portugal.
    Pereira, Ana M.
    Univ Porto, CINTESIS Ctr Hlth Technol & Serv Res, Fac Med, Edificio Nascente,Piso 2, P-4200450 Porto, Portugal;Inst & Hosp CUF, Dept Allergy, Porto, Portugal.
    Jacinto, Tiago
    Univ Porto, CINTESIS Ctr Hlth Technol & Serv Res, Fac Med, Edificio Nascente,Piso 2, P-4200450 Porto, Portugal;Porto Hlth Sch, Dept Cardiovasc & Resp Sci, Porto, Portugal.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Alving, Kjell
    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.
    Fonseca, Joao A.
    Univ Porto, CINTESIS Ctr Hlth Technol & Serv Res, Fac Med, Edificio Nascente,Piso 2, P-4200450 Porto, Portugal;Inst & Hosp CUF, Dept Allergy, Porto, Portugal;Univ Porto, MEDCIDS Dept Community Med Informat & Hlth Sci, Fac Med, Porto, Portugal.
    Comparison of hypothesis- and data-driven asthma phenotypes in NHANES 2007-2012: the importance of comprehensive data availability2019In: Clinical and Translational Allergy, ISSN 2045-7022, E-ISSN 2045-7022, Vol. 9, article id 17Article in journal (Refereed)
    Abstract [en]

    Background

    Half of the adults with current asthma among the US National Health and Nutrition Examination Survey (NHANES) participants could be classified in more than one hypothesis-driven phenotype. A data-driven approach applied to the same subjects may allow a more useful classification compared to the hypothesis-driven one.

    Aim

    To compare previously defined hypothesis-driven with newly derived data-driven asthma phenotypes, identified by latent class analysis (LCA), in adults with current asthma from NHANES 2007-2012.

    Methods

    Adults (18years) with current asthma from the NHANES were included (n=1059). LCA included variables commonly used to subdivide asthma. LCA models were derived independently according to age groups: <40 and 40years old.

    Results

    Two data-driven phenotypes were identified among adults with current asthma, for both age groups. The proportions of the hypothesis-driven phenotypes were similar among the two data-driven phenotypes (p>0.05). Class A <40years (n=285; 75%) and Class A 40years (n=462; 73%), respectively, were characterized by a predominance of highly symptomatic asthma subjects with poor lung function, compared to Class B <40years (n=94; 25%) and Class B 40years (n=170; 27%). Inflammatory biomarkers, smoking status, presence of obesity and hay fever did not markedly differ between the phenotypes.

    Conclusion

    Both data- and hypothesis-driven approaches using clinical and physiological variables commonly used to characterize asthma are suboptimal to identify asthma phenotypes among adults from the general population. Further studies based on more comprehensive disease features are required to identify asthma phenotypes in population-based studies.

  • 8.
    Andersson Kallin, Sandra
    et al.
    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.
    Sommar, Johan Nilsson
    Umeå Univ, Dept Publ Hlth & Clin Med, Occupat & Environm Med, Umeå, Sweden.
    Bossios, Apostolos
    Univ Gothenburg, Sahlgrenska Acad, Krefting Res Ctr, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
    Ekerljung, Linda
    Univ Gothenburg, Sahlgrenska Acad, Krefting Res Ctr, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Middelveld, Roelinde
    Karolinska Inst, Ctr Allergy Res, Stockholm, Sweden; Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Excessive daytime sleepiness in asthma: what are the risk factors?2018In: Journal of Asthma, ISSN 0277-0903, E-ISSN 1532-4303, Vol. 55, no 8, p. 844-850Article in journal (Refereed)
    Abstract [en]

    Objective: Previous studies have found that excessive daytime sleepiness (EDS) is a more common problem in asthmatic subjects than in the general population. The aim of this study was to investigate whether the prevalence of EDS is increased in asthmatic subjects and, if so, to analyse the occurrence of potential risk factors for EDS in asthmatics.

    Methods: Cross-sectional epidemiological study. In 2008, a postal questionnaire was sent out to a random sample of 45,000 individuals aged 16–75 years in four Swedish cities.

    Results: Of the 25,160 persons who participated, 7.3% were defined as having asthma. The prevalence of EDS was significantly higher in asthmatic subjects (42.1% vs. 28.5%, p < 0.001) compared with non-asthmatic subjects. Asthma was an independent risk factor for EDS (adjusted OR 1.29) and the risk of having EDS increased with asthma severity. Risk factors for EDS in subjects with asthma included insomnia (OR, 3.87; 95% CI, 3.10–4.84); chronic rhinosinusitis (OR, 2.00; 95% CI, 1.53–2.62); current smoking (OR, 1.60; 95% CI, 1.15–2.22) and obesity (OR, 1.53; 95% CI, 1.09–2.13).

    Conclusions: EDS is a common problem among subjects with asthma. Asthma is an independent risk factor for having EDS. Furthermore, subjects with asthma often have other risk factors for EDS, many of them potentially modifiable.

  • 9.
    Bengtsson, Caroline
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Jonsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Holmström, Mats
    Karolinska Univ Hosp, Dept Clin Sci Intervent & Technol, Div Ear Nose & Throat Dis, Huddinge, Sweden.
    Sundbom, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Hedner, Jan
    Sahlgrens Univ Hosp, Dept Sleep Med Resp Med & Allergol, Gothenburg, Sweden.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Middelveld, Roelinde
    Karolinska Inst, Ctr Allergy Res, Stockholm, Sweden.; Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Forsberg, Bertil
    Umea Univ, Dept Publ Hlth & Clin Med, Occupat & Environm Med, Umea, Sweden.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Chronic rhinosinusitis impairs sleep quality: Results of the GA(2)LEN study2017In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 40, no 1, article id zsw021Article in journal (Refereed)
    Abstract [en]

    STUDY OBJECTIVES: To analyse the prevalence of sleep problems in subjects with CRS and to determine whether the disease severity of CRS affects sleep quality.

    METHODS: Questionnaires were sent to a random sample of 45 000 adults in four Swedish cities. Questions on CRS, asthma, allergic rhinitis, co-morbidities, tobacco use, educational level and physical activity were included. CRS was defined according to the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) epidemiological criteria. The disease severity of CRS was defined by the number of reported CRS symptoms. Sleep quality was assessed using the Basic Nordic Sleep Questionnaire.

    RESULTS: Of the 26 647 subjects, 2249 (8.4%) had CRS. Reported sleep problems were 50-90% more common among subjects with CRS compared with those without or the total population. The prevalence of reported sleep problems increased in conjunction with the severity of CRS. After adjusting for gender, BMI, age, tobacco use, asthma, somatic diseases, physical activity level and educational level, participants with four symptoms of CRS (compared with subjects without CRS symptoms) displayed a higher risk of snoring (adj. OR (95% CI): 3.13 (2.22-4.41)), difficulties inducing sleep (3.98 (2.94-5.40)), difficulties maintaining sleep (3.44 (2.55-4.64)), early morning awakening (4.71 (3.47-6.38)) and excessive daytime sleepiness (4.56 (3.36-6.18)). The addition of persistent allergic rhinitis to CRS further increased the risk of sleep problems.

    CONCLUSIONS: Sleep problems are highly prevalent among subjects with CRS. The disease severity of CRS negatively affects sleep quality.

  • 10.
    Dahlin, Joakim S
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Öhrvik, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hallgren, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Lineage- CD34hi CD117int/hi FcϵRI+ cells in human blood constitute a rare population of mast cell progenitors2016In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 127, no 4, p. 383-391Article in journal (Refereed)
    Abstract [en]

    Mast cells are rare tissue-resident immune cells that are involved in allergic reactions, and their numbers are increased in the lungs of asthmatics. Murine lung mast cells arise from committed bone marrow-derived progenitors that enter the blood circulation, migrate through the pulmonary endothelium, and mature in the tissue. In humans, mast cells can be cultured from multipotent CD34(+) progenitor cells. However, a population of distinct precursor cells that give rise to mast cells has remained undiscovered. To our knowledge, this is the first report of human lineage(-) CD34(hi) CD117(int/hi) FcϵRI(+) progenitor cells, which represented only 0.0053% of the isolated blood cells in healthy individuals. These cells expressed integrin β7 and developed a mast cell-like phenotype, although with a slow cell division capacity in vitro. Isolated lineage(-) CD34(hi) CD117(int/hi) FcϵRI(+) blood cells had an immature mast cell-like appearance and expressed high levels of many mast cell-related genes as compared with human blood basophils in whole-transcriptome microarray analyses. Furthermore, serglycin, tryptase, and carboxypeptidase A mRNA transcripts were detected by quantitative RT-PCR. Altogether, we propose that the lineage(-) CD34(hi) CD117(int/hi) FcϵRI(+) blood cells are closely related to human tissue mast cells and likely constitute an immediate precursor population, which can give rise to predominantly mast cells. Furthermore, asthmatics with reduced lung function had a higher frequency of lineage(-) CD34(hi) CD117(int/hi) FcϵRI(+) blood mast cell progenitors than asthmatics with normal lung function.

  • 11. Ek, A.
    et al.
    Middelveld, R. J. M.
    Bertilsson, H.
    Bjerg, A.
    Ekerljung, L.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Stjarne, P.
    Larsson, K.
    Dahlen, S. -E
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Chronic rhinosinusitis in asthma is a negative predictor of quality of life: results from the Swedish GA(2)LEN survey2013In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 68, no 10, p. 1314-1321Article in journal (Refereed)
    Abstract [en]

    Background

    Asthma and chronic rhinosinusitis (CRS) both impair quality of life, but the quality-of-life impact of comorbid asthma and CRS is poorly known. The aim of this study was to evaluate the impact of CRS and other relevant factors on quality of life in asthmatic subjects.

    Methods

    This Swedish cohort (age 17-76years) consists of 605 well-characterized asthmatics with and without CRS, 110 individuals with CRS only, and 226 controls and is part of the Global Allergy and Asthma European Network (GA(2)LEN) survey. The Mini Asthma Quality of Life Questionnaire (mAQLQ), the Euro Quality of Life (EQ-5D) health questionnaire, spirometry, skin prick test (SPT), exhaled nitric oxide (FeNO), smell test, and peak nasal inspiratory flow were used.

    Results

    Subjects having both asthma and CRS have lower mAQLQ scores in all domains (P<0.001) and a lower EQ-5D index value and EQ-5D VAS value (P<0.001) compared to those with asthma only. Asthmatics with CRS have significantly lower FEV1%pred and FVC%pred (88.4 [85.1-91.7] and 99.9 [96.7-103.0], respectively) compared with asthma only (91.9 [90.3-93.4] and 104.0 [102.5-105.5], respectively P<0.05). Multiple regression analysis shows that low asthma quality of life is associated with having CRS (P<0.0001), lower lung function (P=0.008), current smoking (P=0.01), BMI>30kg/m(2) (P=0.04), high age (P=0.03), and a negative SPT (P=0.04).

    Conclusions

    Comorbid CRS was a significant and independent negative predictor of quality of life in asthmatics. Other negative factors were lower lung function, current smoking, obesity, advanced age, and having nonatopic asthma.

  • 12.
    Ellingsen, Jens
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Bröms, Kriistina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    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.
    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.
    Högman, Marieann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Longitudinal measurements of blood eosinophils in relation to COPD outcomes2018In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Article in journal (Other academic)
  • 13.
    Farkhooy, Amir
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Bodegård, Johan
    Erikssen, Jan-Erik
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Hedenström, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Stavem, Knut
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Cross-sectional and longitudinal analyses of the association between lung function and exercise capacity in healthy Norwegian men2018In: BMC Pulmonary Medicine, ISSN 1471-2466, E-ISSN 1471-2466, Vol. 18, no 118Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    It is widely accepted that exercise capacity in healthy individuals is limited by the cardiac function, while the respiratory system is considered oversized. Although there is physiological, age-related decline in both lung function and physical capacity, the association between decline in lung function and decline in exercise capacity is little studied. Therefore, we examined the longitudinal association between lung function indices and exercise capacity, assessed by the total amount of work performed on a standardized incremental test, in a cohort of middle-aged men.

    METHODS:

    A total of 745 men between 40 and 59 years were examined using spirometry and standardized bicycle exercise ECG test within "The Oslo Ischemia Study," at two time points: once during 1972-1975, and again, approximately 16 years later, during 1989-1990. The subjects exercise capacity was assessed as physical fitness i.e. the total bicycle work (in Joules) at all workloads divided by bodyweight (in kg).

    RESULTS:

    Higher FEV1, FVC and PEF values related to higher physical fitness at both baseline and follow-up (all p values < 0.05). Higher explanatory values were found at follow-up than baseline for FEV1 (r2 = 0.16 vs. r2 = 0.03), FVC (r2 = 0.14 vs. r2 = 0.03) and PEF (r2 = 0.13 vs. r2 = 0.02). No significant correlations were found between decline in physical fitness and declines in FEV1, FVC or PEF.

    CONCLUSIONS:

    A weak association between lung function indices and exercise capacity, assessed through physical fitness, was found in middle-aged, healthy men. This association was strengthened with increasing age, suggesting a larger role for lung function in limiting exercise capacity among elderly subjects. However, decline in physical fitness over time was not related to decline in lung function.

  • 14.
    Farkhooy, Amir
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Arnardottir, Rangheidur Harpa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Emtner, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Hedenström, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Impaired Carbon Monoxide Diffusing Capacity is the Strongest Predictor of Exercise Intolerance in COPD2013In: COPD: Journal of Chronic Obstructive Pulmonary Disease, ISSN 1541-2555, E-ISSN 1541-2563, Vol. 10, no 2, p. 180-185Article in journal (Refereed)
    Abstract [en]

    Background: Exercise intolerance is a hallmark of chronic obstructive pulmonary disease (COPD) and forced expiratory volume in one second (FEV1) is the traditional metric used to define the severity of COPD. However, there is dissociation between FEV1 and exercise capacity in a large proportion of subjects with COPD. The aim of this study was to investigate whether other lung function parameters have an additive, predictive value for exercise capacity and whether this differs according to the COPD stage. Methods: Spirometry, body plethysmography and diffusing capacity for carbon monoxide (DLCO) were performed on 88 patients with COPD GOLD stages II-IV. Exercise capacity (EC) was determined in all subjects by symptom-limited, incremental cycle ergometer testing. Results: Significant relationships were found between EC and the majority of lung function parameters. DLCO, FEV1 and inspiratory capacity (IC) were found to be the best predictors of EC in a stepwise regression analysis explaining 72% of EC. These lung function parameters explained 76% of EC in GOLD II, 72% in GOLD III and 40% in GOLD IV. DLCO alone was the best predictor of exercise capacity in all GOLD stages. Conclusions: Diffusing capacity was the strongest predictor of exercise capacity in all subjects. In addition to FEV1, DLCO and IC provided a significantly higher predictive value regarding exercise capacity in COPD patients. This suggests that it is beneficial to add measurements of diffusing capacity and inspiratory capacity when clinically monitoring COPD patients.

  • 15.
    Farkhooy, Amir
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Arnardóttir, Ragnheidur Harpa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Emtner, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy.
    Hedenström, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Impaired Carbon Monoxide Diffusing Capacity is the strongest lung function predictor of decline in 12 minute-walking distance in COPD: a 5-year follow-up study2015In: COPD: Journal of Chronic Obstructive Pulmonary Disease, ISSN 1541-2555, E-ISSN 1541-2563, Vol. 12, no 3, p. 240-248Article in journal (Refereed)
    Abstract [en]

    Background:

    The purpose of this study was to evaluate the longitudinal relationship between functional exercise capacity, assessed through standardized 12-minute walk test (12 MWT), and various lung function parameters obtained using spirometry, body plethysmography and diffusing capacity (DLco) measurements in patients with COPD.

    Methods:

    Spirometry, body plethysmography and DLco-measurements were performed at baseline in 84 subjects with moderate to very severe COPD and at follow-up visit (n = 34) after 5 years. Functional exercise capacity was determined using standardized 12MWT.

    Results:

    Patients were characterized at baseline by FEV1 of 1.2 ± 0.4 L (41 ± 13% predicted), RV of 3.4 ± 1.0 L (187 ± 58% predicted) and DLco of 3.8 ± 1.2 mmol/min/kPa (51 ± 16% predicted). A decrease of 12MWD was found between baseline and follow-up (928 ± 193 m vs. 789 ± 273 m, p < 0.001). DLco and 12MWD at baseline were the only independent predictors of 12MWD at follow-up in a multiple logistic regression model that also included all other lung function parameters, gender, age and BMI. Decline in 12MWD was mainly explained by deterioration in DLco. Furthermore, DLco value at baseline had the highest explanatory value for the loss in 12MWD after 5 years (R2 = 0.18, p = 0.009).

    Conclusions:

    In a 5-year longitudinal study, DLco-measurements at baseline were the most important predictors of declining exercise capacity in COPD patients. These results suggest that integration of DLco in the clinical workup provides a more comprehensive assessment in patients with COPD.

  • 16.
    Genberg, Margareta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Andrén, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hedenström, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Commonly used reference values underestimate oxygen uptake in healthy, 50-year-old Swedish women.2018In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 38, no 1, p. 25-33Article in journal (Refereed)
    Abstract [en]

    Cardiopulmonary exercise testing (CPET) is the gold standard among clinical exercise tests. It combines a conventional stress test with measurement of oxygen uptake (VO2 ) and CO2 production. No validated Swedish reference values exist, and reference values in women are generally understudied. Moreover, the importance of achieved respiratory exchange ratio (RER) and the significance of breathing reserve (BR) at peak exercise in healthy individuals are poorly understood. We compared VO2 at maximal load (peakVO2 ) and anaerobic threshold (VO2@AT ) in healthy Swedish individuals with commonly used reference values, taking gender into account. Further, we analysed maximal workload and peakVO2 with regard to peak RER and BR. In all, 181 healthy, 50-year-old individuals (91 women) performed CPET. PeakVO2 was best predicted using Jones et al. (100·5%), while SHIP reference values underestimated peakVO2 most: 112·5%. Furthermore, underestimation of peakVO2 in women was found for all studied reference values (P<0·001) and was largest for SHIP: women had 128% of predicted peakVO2 , while men had 104%. PeakVO2 was similar in subjects with peak RER of 1-1·1 and RER > 1·1 (2 328·7 versus 2 176·7 ml min(-1) , P = 0·11). Lower BR (≤30%) related to significantly higher peakVO2 (P<0·001). In conclusion, peakVO2 was best predicted by Jones. All studied reference values underestimated oxygen uptake in women. No evidence for demanding RER > 1·1 in healthy individuals was found. A lowered BR is probably a normal response to higher workloads in healthy individuals.

  • 17.
    Gonzalez Lindh, Margareta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Logopedi. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Koyi, Hirsh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Blom Johansson, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Research in Disability and Habilitation. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Logopedi.
    Högman, Marieann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Bendrik, Regina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. 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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Ställberg, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Prevalence of subjective swallowing dysfunction in patients with stable COPD: Results from the TIE-study2017Conference paper (Other academic)
  • 18.
    Gonzalez Lindh, Margareta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Logopedi. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Koyi, Hirsh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Blom Johansson, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Research in Disability and Habilitation. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Logopedi.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Högman, Marieann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. 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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Bröms, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Swallowing dysfunction in COPD: Is it more related to burden of disease than lung function: Results from the TIE-study2017Conference paper (Other academic)
  • 19. Haccuria, Amaryllis
    et al.
    Van Muylem, Alain
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Doan, Vi
    Michils, Alain
    Small airways dysfunction: the link between allergic rhinitis and allergic asthma2018In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 51, no 2, article id 1701749Article in journal (Refereed)
    Abstract [en]

    Abnormal airway reactivity and overproduction of nitric oxide (NO) occurring in smallairways have been found in asthma. If the“one airway, one disease”concept is consistent, suchdysfunctions should also be detected in the peripheral airways of patients suffering from allergicrhinitis.We investigated whether peripheral airway reactivity and NO overproduction could bedocumented in distal airways in patients with allergic rhinitis. Exhaled NO fraction (FeNO)andtheslope (S) of phase III of the single-breath washout test (SBWT) of helium (He) and sulfurhexafluoride (SF6)weremeasuredin31patientswithallergicasthma,23allergicrhinitispatientsand 24 controls, before and after sputum induction. SBWT is sensitive to airway calibre changeoccurring in the lung periphery.TheFeNOdecrease was more significant in asthma and rhinitis than in controls (−55.1% and−50.0%,respectively,versus−40.8%) (p=0.007 and p=0.029, respectively). SSF6and SHeincreased in all groups.Change in SHe(ΔSHe)>ΔSSF6was observed in rhinitis (p=0.004) and asthma (p<0.001), whereasΔSSF6=ΔSHein controls (p=0.431).This study provides evidence of peripheral airway dysfunction in patients with allergic rhinitis quitesimilar to that described in asthma. Furthermore, a large proportion of the increased NO productionreported in allergic rhinitis appears to originate in the peripheral airways.

  • 20.
    Heffler, Enrico
    et al.
    IRCCS, Humanitas Clin & Res Ctr, Personalized Med Asthma & Allergy, Rozzano, MI, Italy;Humanitas Univ, Dept Biomed Sci, Pieve Emanuele, MI, Italy.
    Canonica, Giorgio Walter
    IRCCS, Humanitas Clin & Res Ctr, Personalized Med Asthma & Allergy, Rozzano, MI, Italy;Humanitas Univ, Dept Biomed Sci, Pieve Emanuele, MI, Italy.
    Diamant, Zuzana
    Skane Univ Hosp, Inst Clin Sci, Deptartment Resp Med & Allergol, Lund, Sweden;Univ Med Ctr Groningen, Dept Clin Pharm & Pharmacol, Groningen, Netherlands;Univ Med Ctr Groningen, Deptartment Gen Practice, Groningen, Netherlands;QPS NL, Groningen, Netherlands.
    Fonseca, Joao
    Univ Porto, Fac Med, Dept Community Med Informat & Decis Sci, Porto, Portugal;Univ Porto, Fac Med, CINTESIS, Porto, Portugal;MEDIDA Lda, Porto, Portugal.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Personalized Approach to Severe Asthma2018In: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, article id 2465172Article in journal (Other academic)
  • 21.
    Heijkenskjold-Rentzhog, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Nordvall, Lennart
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Jansson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Borres, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Airway inflammation and obstruction in relation to systemic eosinophilic inflammation in asthma2014In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 69, p. 221-221Article in journal (Other academic)
  • 22.
    Heijkenskjöld Rentzhog, Charlotte
    et al.
    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.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Berglund, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    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.
    Nordvall, Lennart
    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.
    Alving, Kjell
    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.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Overall and peripheral lung function assessment by spirometry and forced oscillation technique in relation to asthma diagnosis and control.2017In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 47, no 12, p. 1546-1554Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Classic spirometry is effort dependent and of limited value in assessing small airways. Peripheral airway involvement, and relation to poor control, in asthma, has been highlighted recently. Forced oscillation technique (FOT) offers an effort-independent assessment of overall and peripheral lung mechanics. We studied the association between lung function variables, obtained either by spirometry or multifrequency (5, 11 and 19 Hz) FOT, and asthma diagnosis and control.

    METHODS: ), resistance difference between 5-19 Hz (R5-R19) and Asthma Control Test scores were determined in 234 asthmatic and 60 healthy subjects (aged 13-39 years). We used standardized lung function variables in logistic regression analyses, unadjusted and adjusted for age, height, gender and weight.

    RESULTS: and R5-R19) were associated with uncontrolled asthma (P-values < .05).

    CONCLUSIONS: /FVC, supporting a complementary role for FOT. Asthma control was related to FOT measures of peripheral airways, suggesting a potential use in identifying such involvement. Further studies are needed to determine a clinical value and relevant reference values in children, for the multifrequency FOT measurements.

  • 23.
    Heijkenskjöld-Rentzhog, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Kalm-Stephens, Pia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Lundberg, Jon O
    Nordvall, Lennart
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    The fraction of NO in exhaled air and estimates of alveolar NO in adolescents with asthma: methodological aspects2012In: Pediatric Pulmonology, ISSN 8755-6863, E-ISSN 1099-0496, Vol. 47, no 10, p. 941-949Article in journal (Refereed)
    Abstract [en]

    Rationale

    This study investigated the oral contribution to exhaled NO in young people with asthma and its potential effects on estimated alveolar NO (CalvNO), a proposed marker of inflammation in peripheral airways. Secondary aims were to investigate the effects of various exhalation flow-rates and the feasibility of different proposed adjustments of (CalvNO) for trumpet model and axial diffusion (TMAD).

    Methods

    Exhaled NO at flow rates of 50–300 ml/sec, and salivary nitrite was measured before and after antibacterial mouthwash in 29 healthy young people (10–20 years) and 29 with asthma (10–19 years). CalvNO was calculated using the slope–intercept model with and without TMAD adjustment.

    Results

    Exhaled NO at 50 ml/sec decreased significantly after mouthwash, to a similar degree in asthmatic and healthy subjects (8.8% vs. 9.8%, P = 0.49). The two groups had similar salivary nitrite levels (56.4 vs. 78.4 µM, P = 0.25). CalvNO was not significantly decreased by mouthwash. CalvNO levels were similar when flow-rates between 50–200 or 100–300 ml/sec were used (P = 0.34 in asthmatics and P = 0.90 in healthy subjects). A positive association was found between bronchial and alveolar NO in asthmatic subjects and this disappeared after the TMAD-adjustment. Negative TMAD-adjusted CalvNO values were found in a minority of the subjects.

    Conclusions

    Young people with and without asthma have similar salivary nitrite levels and oral contributions to exhaled NO and therefore no antibacterial mouthwash is necessary in routine use. TMAD corrections of alveolar NO could be successfully applied in young people with asthma and yielded negative results only in a minority of subjects.

  • 24.
    Heijkenskjöld-Rentzhog, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Kalm-Stephens, Pia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Nordvall, Lennart
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    New method for single-breath fraction of exhaled nitric oxide measurement with improved feasibility in preschool children with asthma2015In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 26, no 7, p. 662-667Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Respiratory societies recommend use of standardized methodologies for fraction of exhaled nitric oxide (FeNO) measurements in adults and children, but in preschoolers, feasibility remains a problem. The exhalation time needed to obtain steady-state FeNO is unclear. Our primary aim was to study the feasibility of an adapted single-breath FeNO method with age-adjusted exhalation times. We also studied the association between time to steady-state NO level and height, as well as FeNO in relation to asthma and current treatment with inhaled corticosteroids (ICS).

    METHODS: Sixty-three children aged 3-10 years performed FeNO measurements with a hand-held electrochemical device with a newly developed flow-control unit. Exhalation times were pre-adapted to age. Exhaled air was simultaneously sampled to a chemiluminescence analyzer to measure time to steady-state NO level.

    RESULTS: Eighty-one percent of the children achieved at least one approved measurement. From 4 years upwards, success rate was high (96%). Time to steady-state [NO] (median and interquartile range) was 2.5 s (2.4-3.5) at the age of 3-4 years and 3.5 s (2.7-3.8) at the age of 5-6 years. Height was associated with time to steady state (r(2)  = 0.13, p = 0.02). FeNO (geometric mean [95% CI]) was higher in ICS-naïve asthmatic children (n = 19): 15.9 p.p.b. (12.2-20.9), than in both healthy controls (n = 8) 9.1 p.p.b. (6.6-12.4) and asthmatic subjects on treatment (n = 24) 11.5 p.p.b. (9.7-13.6).

    CONCLUSION: We found this adapted single-breath method with age-adjusted exhalation times highly feasible for children aged 4-10 years. ICS-naïve asthmatic children had FeNO levels under the current guideline cutoff level (20 p.p.b.), highlighting the importance of taking age into account when setting reference values.

  • 25.
    Heijkenskjöld-Rentzhog, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Nordvall, Lennart
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Borres, Magnus P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Alveolar and exhaled NO in relation to asthma characteristics: effects of correction for axial diffusion2014In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 69, no 8, p. 1102-1111Article in journal (Refereed)
    Abstract [en]

    Background: Inflammation in the small airways might contribute to incomplete asthma disease control despite intensive treatment in some subgroups of patients. Exhaled NO (FeNO) is a marker of inflammation in asthma and the estimated NO contribution from small airways (Calv(NO)) is believed to reflect distal inflammation. Recent studies recommend adjustments of Calv(NO) for trumpet model and axial diffusion (TMAD-adj). This study aimed to investigate the clinical correlates of Calv(NO), both TMAD-adjusted and unadjusted. Methods: Asthma symptoms, asthma control, lung function, bronchial responsiveness, blood eosinophils, atopy and treatment level were assessed in 410 subjects, aged 10-35 years. Exhaled NO was measured at different flow-rates and Calv(NO) calculated, with TMAD-adjustment according to Condorelli. Results: Trumpet model and axial diffusion-adjusted Calv(NO) was not related to daytime wheeze (P = 0.27), FEF50 (P = 0.23) or bronchial responsiveness (P = 0.52). On the other hand, unadjusted Calv(NO) was increased in subjects with daytime wheeze (P < 0.001), decreased FEF50 (P = 0.02) and with moderate-to-severe compared to normal bronchial responsiveness (P < 0.001). All these characteristics correlated with increased FeNO (all P < 0.05). Unadjusted Calv(NO) was positively related to bronchial NO flux (J'aw(NO)) (r = 0.22, P < 0.001) while TMAD-adjCalv(NO) was negatively related to J'awNO (r = -0.38, P < 0.001). Conclusions: Adjusted Calv(NO) was not associated with any asthma characteristics studied in this large asthma cohort. However, both FeNO and unadjusted Calv(NO) related to asthma symptoms, lung function and bronchial responsiveness. We suggest a potential overadjustment by current TMAD-corrections, validated in healthy or unobstructed asthmatics. Further studies assessing axial diffusion in asthmatics with different degrees of airway obstruction and the validity of proposed TMAD-corrections are warranted.

  • 26.
    Heijkenskjöld-Rentzhog, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Nordvall, Lennart
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Jansson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    The fraction of exhaled nitric oxide but not alveolar nitric oxide correlates to asthma symptoms and bronchial hyperreactivity - results from the MIDAS study2013In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 68, no Suppl. s97, p. 163-163Article in journal (Other academic)
  • 27.
    Henrohn, Dan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Björkstrand, Kristoffer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lundberg, Jon O
    Granstam, Sven-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Baron, Tomasz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ingimarsdóttir, Inga J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hedenström, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Jansson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hedeland, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Science.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Effects of Oral Supplementation With Nitrate-Rich Beetroot Juice in Patients With Pulmonary Arterial Hypertension-Results From BEET-PAH, an Exploratory Randomized, Double-Blind, Placebo-Controlled, Crossover Study.2018In: Journal of Cardiac Failure, ISSN 1071-9164, E-ISSN 1532-8414, Vol. 24, no 10, p. 640-653Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The nitrate-nitrite-nitric oxide (NO) pathway may represent a potential therapeutic target in patients with pulmonary arterial hypertension (PAH). We explored the effects of dietary nitrate supplementation, with the use of nitrate-rich beetroot juice (BRJ), in patients with PAH.

    METHODS AND RESULTS: We prospectively studied 15 patients with PAH in an exploratory randomized, double-blind, placebo-controlled, crossover trial. The patients received nitrate-rich beetroot juice (∼16 mmol nitrate per day) and placebo in 2 treatment periods of 7 days each. The assessments included; exhaled NO and NO flow-independent parameters (alveolar NO and bronchial NO flux), plasma and salivary nitrate and nitrite, biomarkers and metabolites of the NO-system, N-terminal pro-B-type natriuretic peptide, echocardiography, ergospirometry, diffusing capacity of the lung for carbon monoxide, and the 6-minute walk test. Compared with placebo ingestion of BRJ resulted in increases in; fractional exhaled NO at all flow-rates, alveolar NO concentrations and bronchial NO flux, and plasma and salivary levels of nitrate and nitrite. Plasma ornithine levels decreased and indices of relative arginine availability increased after BRJ compared to placebo. A decrease in breathing frequency was observed during ergospirometry after BRJ. A tendency for an improvement in right ventricular function was observed after ingestion of BRJ. In addition a tendency for an increase in the peak power output to peak oxygen consumption ratio (W peak/VO2 peak) was observed, which became significant in patients reaching an increase of plasma nitrite >30% (responders).

    CONCLUSIONS: BRJ administered for 1 week increases pulmonary NO production and the relative arginine bioavailability in patients with PAH, compared with placebo. An increase in the W peak/VO2 peak ratio was observed after BRJ ingestion in plasma nitrite responders. These findings indicate that supplementation with inorganic nitrate increase NO synthase-independent NO production from the nitrate-nitrite-NO pathway.

  • 28.
    Högman, Marieann
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    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.
    Bröms, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    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.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Determinants of FENO in COPD with regard to current smoking2018In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Article in journal (Other academic)
  • 29.
    Högman, Marieann
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Research and Development, Gävleborg.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    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, Respiratory Medicine and Allergology.
    Added value with extended NO analysis in atopy and asthma2011In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 31, no 4, p. 294-299Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    Assessments of the usefulness of exhaled nitric oxide (NO) in the treatment of asthma have given conflicting results. It is not always obvious if atopic status has been tested in these evaluations.

    OBJECTIVES:

    The aim of the study is to use extended NO analysis to characterize subjects from a random sample populations with focus on rhinitis and asthma.

    METHODS:

    Data were extracted from the European Community Respiratory Health Survey II. A subgroup from the Uppsala site that had had their NO measured at multiple flow rates was included (n = 284). The nonlinear model for NO parameters was used. Atopy was defined as having a titre against at least one of the tested allergens ≥0·35 kU l(-1) . Bronchial responsiveness was assessed by methacholine challenge.

    RESULTS:

    Subjects with non-atopic rhinitis or non-atopic asthma could not be separated from healthy subjects regarding NO parameters. There was a gradual increase with atopy in airway diffusion rate (D(aw) NO); healthy subject 8·0 (7·3, 8·8), healthy atopic 8·8 (6·7, 11·5), atopic rhinitis 10·6 (9·0, 12·4) and atopic asthma 11·2 (9·9, 28·3) ml s(-1) [geometrical mean (CI(95%) )]. There was a correlation between bronchial responsiveness and D(aw) NO in atopic rhinitis (r = -0·41, P<0·01), and bronchial responsiveness and airway wall content of NO (C(aw) NO) in atopic asthma (r = -0·56, P<0·001).

    CONCLUSION:

    It is of importance to characterize atopic status when evaluating the association between NO and asthma. Our results indicate that the use of extended NO analysis, with particular attention to D(aw) NO and C(aw) NO, may be useful in monitoring treatment for rhinitis and asthma.

  • 30.
    Högman, Marieann
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Sulku, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Bröms, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Hedenström, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    2017 Global Initiative for Chronic Obstructive Lung Disease reclassifies half of COPD subjects to lower risk group2018In: The International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, E-ISSN 1178-2005, Vol. 13, no `, p. 165-173Article in journal (Refereed)
    Abstract [en]

    Background: Unlike the 2014 guidelines, the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines have removed lung function from the risk assessment algorithm of patients with COPD. The aim of this investigation was to analyze the proportion of subjects who would change to a lower risk group when applying GOLD(2017) and determine if they exhibit different characteristics in terms of inflammation, symptoms and comorbidity compared to the subjects who would remain in a high-risk group.

    Subjects and methods: A total of 571 subjects with physician-diagnosed and spirometry-verified COPD were included in the present study. The data consisted of measurements of lung function, inflammatory markers, together with questionnaires that covered comorbidities, COPD symptoms and medication.

    Results: From group C, 53% of the subjects would be reclassified to the lower risk group A, and from group D, 47% of the subjects would be reclassified to the lower risk group B when using GOLD(2017) instead of GOLD(2014). Compared to the subjects who would remain in group D, those who would change to group B were more often men (56% vs 72%); of an older age, mean (SD), 71 (8) years vs 68 (7) years; had more primary care contact (54% vs 33%); had lower levels of blood neutrophils, geometrical mean (95% CI), 5.3 (5.0, 5.7) vs 4.6 (4.3, 4.9); reported less anxiety/depression (20% vs 34%); experienced less asthma (29% vs 46%) and had fewer symptoms according to the COPD assessment test, 16 (5) vs 21 (7). All p-values were <0.05.

    Conclusion: The removal of spirometry from risk assessment in GOLD(2017) would lead to the reclassification of approximately half of the subjects in the risk groups C and D to the lower risk groups A and B. There are differences in age, gender, health care contacts, inflammation, comorbidity and symptom burden among those changing from group D to group B. The effects of reclassification and changes in eventual treatment for disease control and symptom burden need further investigation.

  • 31.
    Jacinto, Tiago
    et al.
    Univ Porto, Fac Med, Ctr Hlth Technol & Serv Res, Edificio Nascente,Piso 2, P-4200450 Porto, Portugal;Porto Hlth Sch, Dept Cardiovasc & Resp Sci, Porto, Portugal.
    Amaral, Rita
    Univ Porto, Fac Med, Ctr Hlth Technol & Serv Res, Edificio Nascente,Piso 2, P-4200450 Porto, Portugal.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Fonseca, Joao
    Univ Porto, Fac Med, Ctr Hlth Technol & Serv Res, Edificio Nascente,Piso 2, P-4200450 Porto, Portugal;Univ Porto, Fac Med, Dept Community Med Informat & Hlth Sci, Porto, Portugal.
    Alving, Kjell
    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.
    Exhaled NO reference limits in a large population-based sample using the Lambda-Mu-Sigma method2018In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 125, no 5, p. 1620-1626Article in journal (Refereed)
    Abstract [en]

    Absolute values are used in the interpretation of the fraction of exhaled nitric oxide (FeNO), but it has been suggested that equations to calculate reference values may be a practical and clinically useful approach. We hypothesize that the application of the Lambda-Mu-Sigma (LMS) method may improve FeNO reference equations and their interpretation. Our aims were to develop FeNO reference equations with the LMS method and to describe the difference between this method and the absolute fixed cut-offs of the current recommendations. We utilized the United States National Health and Nutrition Examination Surveys 2007-2012 and included healthy individuals with no respiratory diseases and blood eosinophils <300/mm(3) (n = 8,340). Natural log-transformed FeNO was modeled using the LMS method, imbedded in the generalized additive models for location, scale, and shape models. A set of FeNO reference equations was developed. The explanatory variables were sex, age, height, smoking habits, and race/ethnicity. A significant proportion of individuals with normal FeNO given by the equations were classified as having intermediate levels by the current recommendations. Further lower predicted FeNO compared with previous linear models was seen. In conclusion, we suggest a novel model for the prediction of reference FeNO values that can contribute to the interpretation of FeNO in clinical practice. This approach should be further validated in large samples with an objective measurement of atopy and a medical diagnosis of asthma and rhinitis. NEW & NOTEWORTHY Novel reference equations and fraction of exhaled nitric oxide (FeNO)-predicted values to improve interpretation of FeNO in clinical practice are presented. These may increase the accuracy of ruling out airway inflammation in patients with asthma or suspected asthma.

  • 32.
    Jacinto, Tiago
    et al.
    Inst & Hosp CUF, Dept Allergy, Oporto, Portugal.;Univ Porto, Fac Med, CINTESIS Ctr Hlth Technol & Serv Res, Oporto, Portugal.;Porto Hlth Sch, Dept Cardiovasc & Resp Sci, Oporto, Portugal..
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Fonseca, Joao
    Inst & Hosp CUF, Dept Allergy, Oporto, Portugal.;Univ Porto, Fac Med, CINTESIS Ctr Hlth Technol & Serv Res, Oporto, Portugal.;Univ Porto, Fac Med, MEDCIDS Dept Community Med Informat & Hlth Sci, Oporto, Portugal..
    Alving, Kjell
    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.
    Differential effect of cigarette smoke exposure on exhaled nitric oxide and blood eosinophils in healthy and asthmatic individuals2017In: Journal of Breath Research, ISSN 1752-7155, E-ISSN 1752-7163, Vol. 11, no 3, article id 036006Article in journal (Refereed)
    Abstract [en]

    Background:

    Tobacco smoking affects both the fraction of exhaled nitric oxide (FeNO) and blood eosinophil (B-Eos) count, two clinically useful biomarkers in respiratory disease that represent local and systemic type-2 inflammation, respectively.

    Objective:

    We aimed to study the influence of objectively measured smoke exposure on FeNO and B-Eos in a large population of subjects with and without asthma.

    Methods:

    We utilized the US National Health and Nutrition Examination Surveys 2007-2012 and included 10 669 subjects aged 6-80 years: 9869 controls and 800 asthmatics. Controls were defined as having no respiratory disease, no hay fever in the past year, and B-Eos count ≤0.3 × 109 l−1. Asthma was defined as self-reported current asthma and at least one episode of wheezing or an asthma attack in the past year, but no emphysema or chronic bronchitis. Tobacco use was collected via questionnaires and serum cotinine was measured with mass spectrometry.

    Results:

    Increasing cotinine levels were associated with a progressive reduction in FeNO in both controls and asthmatics. FeNO remained significantly higher in asthmatics than controls except in the highest cotinine decile, equivalent to an average reported consumption of 13 cigarettes/day. B-Eos count increased with cotinine in controls, but was unchanging in asthmatics. Interestingly, B-Eos count was significantly higher in presently non-exposed (cotinine below detection limit) former smokers than never smokers.

    Conclusion:

    Smoke exposure decreases FeNO and increases B-Eos count. These effects should be considered in the development of normalized values and their interpretation in clinical practice. The persistence of elevated B-Eos in former smokers warrants further studies.

  • 33.
    Jacinto, Tiago
    et al.
    Inst & Hosp CUF Porto, Oporto, Portugal.;Univ Porto, Fac Med, CINTESIS, P-4200450 Oporto, Portugal..
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Fonseca, Joao
    Inst & Hosp CUF Porto, Oporto, Portugal.;Univ Porto, Fac Med, CINTESIS, P-4200450 Oporto, Portugal..
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Evolution of exhaled nitric oxide levels throughout development and aging of healthy humans2015In: Journal of Breath Research, ISSN 1752-7155, E-ISSN 1752-7163, Vol. 9, no 3, article id 036005Article in journal (Refereed)
    Abstract [en]

    It is not fully understood how the fraction of exhaled nitric oxide (FeNO) varies with age and gender in healthy individuals. We aim to describe the evolution of FeNO with age, giving special regard to the effect of gender, and to relate this evolution to natural changes in the respiratory tract. We studied 3081 subjects from NHANES 2007-08 and 2009-10, aged 6-80 years, with no self-reported diagnosis of asthma, chronic bronchitis or emphysema, and with normal values of blood eosinophils and C-reactive protein. The relationship of the mean values of FeNO to age, in all participants and divided by gender, was computed, and compared with changes in anatomic dead space volume and forced vital capacity. A change-point analysis technique and subsequent piecewise regression was used to detect breakpoints in the evolution of FeNO with age. Three distinct phases in the evolution of FeNO throughout the age range 6-80 years can be seen. FeNO values increase linearly between 6-14 years of age in girls and between 6-16 years of age in boys, in parallel with somatic growth. After that, FeNO levels plateau in both genders until age 45 years in females and age 59 years in males, when they start to increase linearly again. This increase continues until age 80. Our data clearly show a triphasic evolution of FeNO throughout the human age range in healthy individuals. This should be accounted for in development of reference equations for normal FeNO values.

  • 34.
    James, A.
    et al.
    Karolinska Inst, Expt Asthma & Allergy Res, Natl Inst Environm Med, Stockholm, Sweden..
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Holweg, C.
    Genentech Inc, South San Fransisco, CA USA..
    Alving, Kjell
    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.
    Ono, J.
    Shinotest Corp Ltd, Sagamihara, Kanagawa, Japan..
    Ohta, S.
    Saga Med Sch, Dept Lab Med, Saga, Japan..
    Ek, A.
    Karolinska Inst, Expt Asthma & Allergy Res, Natl Inst Environm Med, Stockholm, Sweden..
    Middelveld, R.
    Karolinska Inst, Expt Asthma & Allergy Res, Natl Inst Environm Med, Stockholm, Sweden..
    Dahlen, B.
    Karolinska Inst, Dept Med, Stockholm, Sweden.;Karolinska Inst, Lung & Allergy Clin, Stockholm, Sweden.;Karolinska Univ, Hosp Huddinge, Stockholm, Sweden..
    Forsberg, B.
    Umea Univ, Div Occupat & Environm Med, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Izuhara, K.
    Saga Med Sch, Div Med Biochem, Dept Biomol Sci, Saga, Japan..
    Dahlen, S. -E
    Serum periostin relates to type-2 inflammation and lung function in asthma: Data from the large population-based cohort Swedish GA(2)LEN2017In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 72, no 11, p. 1753-1760Article in journal (Refereed)
    Abstract [en]

    Background

    Periostin has been suggested as a novel, phenotype-specific biomarker for asthma driven by type 2 inflammation. However, large studies examining relationships between circulating periostin and patient characteristics are lacking and the suitability of periostin as a biomarker in asthma remains unclear.

    Aim

    To examine circulating periostin in healthy controls and subjects with asthma from the general population with different severity and treatment profiles, both with and without chronic rhinosinusitis (CRS), in relation to other biomarkers and clinical characteristics.

    Methods

    Serum periostin was examined by ELISA in 1100 subjects aged 17-76 from the Swedish Global Allergy and Asthma European Network (GA(2)LEN) study, which included 463 asthmatics with/without chronic rhinosinusitis (CRS), 98 individuals with CRS only, and 206 healthy controls. Clinical tests included measurement of lung function, Fraction of exhaled NO (FeNO), IgE, urinary eosinophil-derived neurotoxin (U-EDN), and serum eosinophil cationic protein (S-ECP), as well as completion of questionnaires regarding respiratory symptoms, medication, and quality of life.

    Results

    Although median periostin values showed no differences when comparing disease groups with healthy controls, multiple regression analyses revealed that periostin was positively associated with higher FeNO, U-EDN, and total IgE. In patients with asthma, an inverse relationship with lung function was also observed. Current smoking was associated with decreased periostin levels, whereas increased age and lower body mass index (BMI) related to higher periostin levels in subjects both with and without asthma.

    Conclusion

    We confirm associations between periostin and markers of type 2 inflammation, as well as lung function, and identify novel constitutional factors of importance to the use of periostin as a phenotype-specific biomarker in asthma.

  • 35.
    Janson, Christer
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Johannessen, Ane
    Haukeland Hosp, Ctr Clin Res, Bergen, Norway.
    Franklin, Karl
    Umea Univ, Dept Surg & Perioperat Sci, Surg, Umea, Sweden.
    Svanes, Cecilie
    Univ Bergen, Inst Clin Sci, Bergen, Norway.
    Schioler, Linus
    Sahlgrens Univ Hosp, Dept Occupat & Environm Med, Gothenburg, Sweden.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Gislason, Thorarinn
    Natl Univ Hosp Iceland, Dept Resp Med & Sleep, Reykjavik, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Benediktsdottir, Bryndis
    Natl Univ Hosp Iceland, Dept Resp Med & Sleep, Reykjavik, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Schlunssen, Vivi
    Aarhus Univ, Dept Publ Hlth, Sect Environm Occupat & Hlth, Aarhus, Denmark;Natl Res Ctr Working Environm, Copenhagen, Denmark.
    Jogi, Rain
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research. Tartu Univ Clin, Lung Clin, Tartu, Estonia.
    Jarvis, Deborah
    Imperial Coll, Natl Heart & Lung Inst, Resp Epidemiol Occupat Med & Publ Hlth, London, England.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Change in the prevalence asthma, rhinitis and respiratory symptom over a 20 year period: associations to year of birth, life style and sleep related symptoms2018In: BMC Pulmonary Medicine, ISSN 1471-2466, E-ISSN 1471-2466, Vol. 18, article id 152Article in journal (Refereed)
    Abstract [en]

    Background: The aim of this investigation was to study change in adults over a 20 year period in the prevalence of respiratory symptoms and disorders and its association to year of birth, life style and sleep related variables.

    Method: Adults 20-44 years of age, 6085 women and 5184 men, were randomly selected from seven centres in Northern Europe and followed for 20 years. The number of participants in the first survey was 21,595 and 11,269 participated in all three surveys. The participants were divided into three birth cohorts: 1944-1955, 1956-1965 and 1966-1975.

    Results: During the 20 year period the prevalence of wheeze decreased (-2%) and the prevalence of asthma (+ 4%) and allergic rhinitis (+ 5%) increased, whereas the prevalence of nocturnal respiratory symptoms was relatively unchanged. The increase in allergic rhinitis was largest in those born 1966 to 1975 except in Estonia. There was large decrease in smoking (-20%), increase in obesity (+ 7%) and snoring (+ 6%) during the study period. Smoking, obesity, snoring and nocturnal gastroesophageal reflux (nGER) were related to a higher risk of all symptoms. Obesity, snoring and nGER were also independently related to asthma.

    Conclusion: We conclude that as our participants got older there was a decrease in wheeze, no change in nocturnal symptoms and an increase in reported asthma and allergic rhinitis. These changes in prevalence are probably related to a decrease in smoking being counteracted by an increase in allergy, obesity and sleep related disorders.

  • 36.
    Jerning, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Martinander, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Bjerg, Anders
    Ekerljung, Linda
    Franklin, Karl A.
    Jarvholm, Bengt
    Larsson, Kjell
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Middelveld, Roelinde
    Emtner, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotheraphy. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Asthma and physical activity - A population based study results from the Swedish GA(2)LEN survey2013In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 107, no 11, p. 1651-1658Article in journal (Refereed)
    Abstract [en]

    Background: Having asthma has in previous reports been related to a lower physical activity level. At the same time the prevalence of asthma among elite athletes is high. The aim of this study was to investigate the association between physical activity level and asthma. Methods: A postal questionnaire was completed by 25,610 individuals in Sweden. Current asthma was defined as having had an asthma attack during the last 12 months or current use of asthma medication. The participants were asked how often and for how many hours a week they were physically active. Results: In the population 1830 subjects (7.1%) had current asthma. There was no significant difference in the proportion of subjects that reported being inactive or slightly physically active between asthmatic and non-asthmatics (57 vs. 58%) while the proportion of subjects that were vigorously physically active (>= 2 times a week and >= 7 h per week) was higher among the subjects with asthma (6.7 vs. 4.8%, p < 0.0001). Being vigorously physically active was independently related to current asthma (OR (95% CI)) 1.40 (1.11-1.77)), wheeze (1.39 (1.17-1.65)), wheeze and breathlessness (1.68 (1.38-2.04)), and wheezing without having a cold (1.39 (1.13-1.71)). The association between being vigorously physically active and wheeze was significantly stronger in women compared to men. Conclusions: There was no difference in the proportion of subjects with a reported low level of physical activity between asthmatics and non-asthmatics. Health care professionals should, however, be aware of the increased prevalence of asthma and asthma-related symptoms in vigorously physically active subjects.

  • 37.
    Johannessen, Ane
    et al.
    Univ Bergen, Dept Global Publ Hlth & Primary Care, Ctr Int Hlth, Bergen, Norway.
    Kuiper, Ingrid Nordeide
    Haukeland Hosp, Dept Occupat Med, Bergen, Norway.
    Accordini, Simone
    Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy.
    Bertelsen, Randi Jacobsen
    Univ Bergen, Dept Clin Sci, Bergen, Norway.
    Forsberg, Bertil
    Umea Univ, Div Occupat & Environm Med, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Gislason, Thorarinn
    Landspitali Univ Hosp Reykjavik, Dept Resp Med & Sleep, Reykjavik, Iceland.
    Heinrich, Joachim
    Ludwig Maximilians Univ Munchen, Inst & Clin Occupat Social & Environm Med, Munich, Germany.
    Holm, Mathias
    Sahlgrens Univ Hosp, Dept Occupat & Environm Med, Gothenburg, Sweden.
    Jogi, Rain
    Tartu Univ Hosp, Lung Clin, Tartu, Estonia.
    Kirkeleit, Jorunn
    Haukeland Hosp, Dept Occupat Med, Bergen, Norway.
    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.
    Markevych, Iana
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 1, Neuherberg, Germany.
    Oudin, Anna
    Umea Univ, Div Occupat & Environm Med, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Schlunssen, Vivi
    Aarhus Univ, Sect Environm Occupat & Hlth, Danish Ramazzini Ctr, Dept Publ Hlth, Aarhus, Denmark.
    Sigsgaard, Torben
    Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark.
    Svanes, Cecilie
    Haukeland Hosp, Dept Occupat Med, Bergen, Norway.
    Toren, Kjell
    Sahlgrens Univ Hosp, 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.
    Long-term air pollution exposure is associated with sick leave 20 years later2018In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Article in journal (Other academic)
  • 38.
    Johansson, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Emtner, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Norlander, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Nordang, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Exercise induced dyspnea among adolescents - prevalence and incidence, a five-year follow-up2018In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Article in journal (Other academic)
  • 39.
    Johansson, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Ersson, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Mallmin, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Norlander, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Nordang, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Prevalence of exercise-induced bronchoconstriction and exercise-induced laryngeal obstruction in adolescents attending national sports high school2018In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Article in journal (Other academic)
  • 40.
    Johansson, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Norlander, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hedenström, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Nordang, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Emtner, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Exercise test using dry air in random adolescents: temporal profile and predictors of bronchoconstriction2016In: Respirology (Carlton South. Print), ISSN 1323-7799, E-ISSN 1440-1843, Vol. 21, no 2, p. 289-296Article in journal (Refereed)
    Abstract [en]

    Background and objective

    Guidelines recommend exercise tests using dry air to diagnose exercise-induced bronchoconstriction (EIB). Lung function changes subsequent to these tests have not been investigated in a general adolescent population, and it remains unknown whether signs of airway inflammation, measured using exhaled nitric oxide (FeNO), can predict a positive response. The aim of this study was to investigate the temporal aspect of decline in forced expiratory volume in 1 s (FEV1) after an exercise test using dry air, and to investigate predictors of EIB.

    Methods

    From a cross-sectional study on adolescents aged 13–15 years (n = 3838), a random subsample of 146 adolescents (99 with and 47 without self-reported exercise-induced dyspnoea) underwent standardized treadmill exercise tests for EIB while breathing dry air.

    Results

    Of the adolescents, 34% had a positive EIB test (decline of ≥10% in FEV1 from baseline) within 30 min. Of the subjects with EIB, 53% showed the greatest decline in FEV1 at 5 to 10 min (mean decline 18.5%), and the remaining 47% of the subjects showed the greatest decline at 15 to 30 min (mean decline 18.9%) after exercise. Increased FeNO (>20 ppb), female gender and self-reported exercise-induced dyspnoea were independently associated with a positive EIB test.

    Conclusion

    When assessing general adolescents for EIB with exercise test using dry air, there is a temporal variation in the greatest FEV1 decline after exercise. Therefore, lung function should be measured for at least 30 min after the exercise. Increased FeNO, female gender and self-reported exercise-induced dyspnoea can be predictors of a positive EIB test.

  • 41.
    Johansson, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy.
    Norlander, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Nordvall, Lennart
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Nordang, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Emtner, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Prevalence of exercise-induced bronchoconstriction and exercise-induced laryngeal obstruction in a general adolescent population2015In: Thorax, ISSN 0040-6376, E-ISSN 1468-3296, Vol. 70, no 1, p. 57-63Article in journal (Refereed)
    Abstract [en]

    Background Exercise-induced respiratory symptoms are common among adolescents. Exercise is a known stimulus for transient narrowing of the airways, such as exercise-induced bronchoconstriction (EIB) and exercise-induced laryngeal obstruction (EILO). Our aim was to investigate the prevalence of EIB and EILO in a general population of adolescents. Methods In this cross-sectional study, a questionnaire on exercise-induced dyspnoea was sent to all adolescents born in 1997 and 1998 in Uppsala, Sweden (n=3838). A random subsample of 146 adolescents (99 with self-reported exercise-induced dyspnoea and 47 without this condition) underwent standardised treadmill exercise tests for EIB and EILO. The exercise test for EIB was performed while breathing dry air; a positive test was defined as a decrease of >= 10% in FEV1 from baseline. EILO was investigated using continuous laryngoscopy during exercise. Results The estimated prevalence of EIB and EILO in the total population was 19.2% and 5.7%, respectively. No gender differences were found. In adolescents with exercise-induced dyspnoea, 39.8% had EIB, 6% had EILO and 4.8% had both conditions. In this group, significantly more boys than girls had neither EIB nor EILO (64.7% vs 38.8%; p=0.026). There were no significant differences in body mass index, lung function, diagnosed asthma or medication between the participants with exercise-induced dyspnoea who had or did not have a positive EIB or EILO test result. Conclusions Both EIB and EILO are common causes of exercise-induced dyspnoea in adolescents. EILO is equally common among girls and boys and can coexist with EIB.

  • 42.
    Johansson, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Norlander, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Nordang, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Emtner, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    The relationship between exercise induced bronchial obstruction and health related quality of life in female and male adolescents from a general population2016In: BMC Pulmonary Medicine, ISSN 1471-2466, E-ISSN 1471-2466, Vol. 16, article id 63Article in journal (Other academic)
    Abstract [en]

    Background: Previous studies have observed that exercise-induced bronchoconstriction (EIB) is more common and more strongly related to exercise related breathing problems in female adolescents than male adolescents. However, few studies have investigated the association between EIB and health related quality of life (HRQoL) from a gender perspective. The aim of this study was to examine the association between EIB and HRQoL and physical activity level in female and male adolescents with and without EIB. Methods: From a population based study on exercise-induced breathing problems among adolescents (13-15 years, n = 3838) a cross sectional study with prospective data collection was carried out in a random subsample of 140 adolescents. The subjects in the sample were tested for EIB with a standardised exercise test, of which 49 adolescents were tested positive. HRQoL was assessed with the Pediatric Quality of Life Inventory (PedsQL) and the adolescents' physical activity levels were measured objectively with accelerometer. Results: The female subjects with EIB reported a lower HRQoL, both in total score (p = 0.03) and physical functioning score (p = 0.009) and had a lower baseline FEV1 compared to females without EIB (88 vs. 94 % predicted, p = 0.001). No differences were found in HRQoL or baseline lung function between males with or without EIB. There were no differences in minutes of moderate to vigorous physical activity per day between females or males with and without EIB. Conclusion: In a general population, the female adolescents with EIB had lower HRQoL and poorer baseline lung function compared to counterparts without EIB. These differences were not observed in males. EIB does not appear to affect the level of daily physical activity neither in females nor males.

  • 43.
    Johansson, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Åsenlöf: Physiotheraphy.
    Norlander, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Increased prevalence of exercise-induced airway symptoms: A five-year follow-up from adolescence to young adulthood2019In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 154, p. 76-81Article in journal (Refereed)
    Abstract [en]

    Background: Exercise-induced airway symptoms are common in adolescents. Little is known about the development of symptoms from adolescence to early adulthood. Therefore, we studied the prevalence, incidence, and remission of exercise-induced airway symptoms (including wheeze, cough, chest and throat tightness, hoarseness, and stridor) in adolescents, over a five-year period.

    Methods: In 2011, all adolescents aged 12-13 years in Uppsala (n=3 838) were invited to answer a questionnaire on exercise-induced airway symptoms. All responding adolescents (n=2 309) were invited to answer the same questionnaire again after five years. In total, 1 002 adolescents responded (43.4%).

    Results: The prevalence of exercise-induced airway symptoms increased from 25% at baseline to 49% at follow-up (p<0.001). More females than males reported symptoms at both time points. The incidence of airway symptoms was 42.2%, with no sex differences. More males than females reported symptom remission (20.2 vs. 10.7%, p<0.001). Females reported a higher asthma prevalence at follow-up than at baseline (7.6 vs. 15.2%), while males did not (10.9 vs. 8.0%), leading to a sex difference in prevalence at follow-up (p<0.001). Smoking and baseline respiratory symptoms were associated with an increased risk of reporting symptoms at follow-up.

    Conclusions: A twofold increase in the prevalence of exercise-induced airway symptoms over a five-year period was found in this cohort. Females were more likely to report symptoms at both time points. Knowledge of these age-related changes in symptoms and their association to female gender is useful for future studies and healthcare providers.

  • 44.
    Johnson, Jennifer
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Borres, Magnus P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Nordvall, Lennart
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Lidholm, Jonas
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Perceived Food Hypersensitivity Relates to Poor Asthma Control and Quality of Life in Young Non-Atopic Asthmatics2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 4, article id e0124675Article in journal (Refereed)
    Abstract [en]

    Background The relationship between perceived food hypersensitivity in asthmatics, food allergen sensitization, asthma control and asthma-related quality of life has not been studied. Objective Our aim was to study the prevalence of perceived food hypersensitivity in a cohort of young asthmatics, its relation to food allergen sensitization, and any correlation to asthma control and asthma-related quality of life. Methods Perceived food hypersensitivity, as well as IgE sensitization to common food allergens, levels of exhaled nitric oxide (FeNO), and blood eosinophil counts (B-Eos) were assessed in 408 subjects (211 women) with asthma, aged (mean +/- SEM) 20.4 +/- 0.3 years. Subjects filled out the Asthma Control Test (ACT) and the Mini Asthma Quality of Life Questionnaire (Mini-AQLQ). Inflammation was assessed by means of FeNO and B-Eos. Results Fifty-three per cent of subjects reported food hypersensitivity. A corresponding food allergen sensitization was found in 68% of these subjects. Non-atopic subjects with perceived food hypersensitivity (n = 31) had lower ACT (19 (15 - 22) vs. 21 (20 - 23), p < 0.001) and Mini-AQLQ - scores (5.3 (4.3 - 6.1) vs. 6.1 (5.5 - 6.5), p < 0.001) than subjects with no food hypersensitivity (n = 190), despite lower levels of FeNO and B-Eos (p < 0.05). Conclusions and Clinical Relevance Food hypersensitivity was commonly reported among young asthmatics. In a majority of cases, a corresponding food allergen sensitization was found. A novel and clinically important finding was that non-atopic subjects with perceived food hypersensitivity were characterized by poorer asthma control and asthma-related quality of life.

  • 45.
    Johnson, Jennifer
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Lidholm, J.
    Borres, M. P.
    Nordvall, Lennart
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Milk and peanut hypersensitivity in young asthmatics in relation to asthma control and airway inflammation results from the MIDAS study2013In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 68, no Suppl. s97, p. 145-146Article in journal (Other academic)
  • 46.
    Johnson, Jennifer
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Lidholm, Jonas
    Borres, Magnus P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Nordvall, Lennart
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Ten-year review reveals changing trends and severity of allergic reactions to nuts and other foods2014In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, no 8, p. 862-867Article in journal (Refereed)
    Abstract [en]

    Aim:

    Over the past few decades, the incidence of food allergies has risen and Sweden has increased its import of peanuts and exotic nuts, such as cashew nuts, which may cause severe allergic reactions. This study aimed to retrospectively investigate paediatric emergency visits due to food reactions over a 10-year period, focusing on reactions to peanuts and tree nuts.

    Methods:

    Emergency visits to Uppsala University Children's Hospital, Sweden, between September 2001 and December 2010, were reviewed, and cases containing diagnostic codes for anaphylaxis, allergic reactions or allergy and hypersensitivity not caused by drugs or biological substances were retrieved.

    Results:

    We analysed 703 emergency visits made by 578 individuals with food allergies. Peanuts and tree nuts accounted for 50% of the food allergies and were more frequently associated with adrenaline treatment and hospitalisation than other foods. Cashew nut reactions increased over the study period, and together with peanuts, they were responsible for more anaphylactic reactions than hazelnuts.

    Conclusion:

    Peanut and tree nut reactions were more likely to result in adrenaline treatment and hospitalisation than other food reactions. Peanut and cashew nut reactions were more likely to cause anaphylaxis than hazelnuts. Cashew nut reactions increased during the study period.

  • 47.
    Kalm-Stephens, Pia
    et al.
    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.
    Nordvall, Lennart
    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.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Alving, Kjell
    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.
    Airway responsiveness and inflammatory markers in non-asthmatic adolescents with elevated FeNO2018In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Article in journal (Other academic)
  • 48.
    Kalm-Stephens, Pia
    et al.
    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.
    Nordvall, Lennart
    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.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Neuman, Åsa
    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.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Alving, Kjell
    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.
    Elevated exhaled nitric oxide in adolescents relates to incident allergic symptoms: a prospective cohort study2019In: Journal of investigational allergology & clinical immunology, ISSN 1018-9068, E-ISSN 1698-0808, Vol. 29, no 3, p. 231-238Article in journal (Refereed)
    Abstract [en]

    Background: The fraction of exhaled nitric oxide (FeNO) is a marker of type-2 inflammation in the airways and elevated FeNO may precede development of allergic disease. The aim of the present study was to investigate the association between elevated FeNO and the development of allergic symptoms.

    Methods: A total of 959 adolescents from a general population answered, together with their parents, a standardized questionnaire, performed lung function and FeNO measurements at a baseline visit. Four years later, 921 of these subjects (96%) completed a to a great extent same version of the baseline questionnaire.

    Results: Adolescents with self-reported incident allergic symptoms to cat (n = 50) or dog (n = 33) had higher baseline FeNO (p < 0.001) than subjects without allergic symptoms to cat and dog at either time point (n = 776 and n = 838, respectively). Adolescents with incident allergic symptoms to pollen did not have elevated baseline FeNO. The adjusted odds ratio [aOR (95% confidence interval)] for incident allergic symptoms to cat was 4.2 (2.2, 8.0) times higher if FeNO was > 75th percentile (vs. < 75th percentile) at baseline. This was consistent after exclusion of subjects with reported asthma, wheeze or rhinitis at baseline [aOR (95% CI) 8.6 (3.0, 24.1)].

    Conclusion: Elevated FeNO in adolescents related to an increased risk of developing allergic symptoms to cat and dog, but not pollen allergens, within four years.

  • 49.
    Kalm-Stephens, Pia
    et al.
    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.
    Nordvall, Lennart
    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.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research. Uppsala Univ, Uppsala, Sweden..
    Neuman, Åsa
    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.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Alving, Kjell
    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.
    Elevated exhaled nitric oxide levels in adolescents are related to new-onset allergic symptoms to cat within four years2017In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 72, p. 427-428Article in journal (Other academic)
  • 50.
    Kalm-Stephens, Pia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Rentzhog, Heijkenskjöld Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Nordvall, Lennart
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Single-breath FeNO measurement in preschool children using a new method and device2014In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 69, p. 56-56Article in journal (Other academic)
123 1 - 50 of 133
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