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Pape, K., Svanes, C., Malinovschi, A., Benediktsdottir, B., Lodge, C., Janson, C., . . . Schlunssen, V. (2019). Agreement of offspring-reported parental smoking status: the RHINESSA generation study. BMC Public Health, 19, Article ID 94.
Open this publication in new window or tab >>Agreement of offspring-reported parental smoking status: the RHINESSA generation study
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2019 (English)In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 19, article id 94Article in journal (Refereed) Published
Abstract [en]

Background:

With increasing interest in exposure effects across generations, it is crucial to assess the validity of information given on behalf of others.

Aims:

To compare adult's report of their parent's smoking status against parent's own report and examine predictors for discrepant answers.

Methods:

We studied 7185 offspring (18-51 years) and one of their parents, n = 5307 (27-67 years) participating in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study. Information about parent's smoking status during offspring's childhood and mother's smoking status during pregnancy was obtained by questionnaires from parents and their offspring. We calculated sensitivity, specificity and Cohen's Kappa [kappa] for agreement using parent's own report as the gold standard. We performed logistic regression to examine if offspring's sex, age, educational level, asthma status, own smoking status or parental status, as well as the parent's sex and amount of smoking during childhood predicted disagreement.

Results:

The sensitivity for offspring's correct report of parent's smoking status during childhood (0-10 years) was 0.82 (95% CI 0.81-0.84), specificity was 0.95 (95% CI 0.95-0.96) and a good agreement was observed, kappa = 0.79 (95% CI 0.78-0.80). Offspring's report of mothers' smoking status during pregnancy showed a lower sensitivity, 0.66 (95% CI 0.60-0.71), a slightly lower specificity, 0.92 (95% CI 0.90-0.95) and a good agreement, kappa = 0.61 (95% CI 0.55-0.67). In multivariate logistic regression analysis, offspring not having children was a predictor for discrepant answers (odds ratio [OR] 2.11 [95% CI 1.21-3.69]). Low amount of parents' tobacco consumption, < 10 cigarettes/day (OR 2.72 [95% CI 1.71-4.31]) also predicted disagreement compared to >= 10 cigarettes per day, and so did offspring's reports of fathers' smoking status (OR 1.73 [95% CI 1.09-2.74]) compared to mothers' smoking status. Offspring's sex, asthma status, educational level, smoking status or age was not related to discrepant answers.

Conclusions:

Adults report their parent's smoking status during their childhood, as well as their mother' smoking status when pregnant with them, quite accurately. In the absence of parents' direct report, offspring's reports could be valuable.

Keywords
Generation study, Validation study, Tobacco smoking, Self-report, Smoking during pregnancy, Parental smoking, Agreement, Sensitivity, Specificity
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-379236 (URN)10.1186/s12889-019-6414-0 (DOI)000459898400003 ()30665381 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and WelfareEU, Horizon 2020, 633212
Available from: 2019-03-19 Created: 2019-03-19 Last updated: 2019-03-19Bibliographically approved
Tsolakis, N., Nordvall, L., Janson, C., Rydell, N., Malinovschi, A. & Alving, K. (2019). Characterization of a subgroup of non-type 2 asthma with cow's milk hypersensitivity in young subjects. Clinical and Translational Allergy, 9, Article ID 12.
Open this publication in new window or tab >>Characterization of a subgroup of non-type 2 asthma with cow's milk hypersensitivity in young subjects
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2019 (English)In: Clinical and Translational Allergy, ISSN 2045-7022, E-ISSN 2045-7022, Vol. 9, article id 12Article in journal (Refereed) Published
Abstract [en]

Background: Asthma with atopy is often characterized by type 2 inflammation but less progress has been made in defining non-type 2 asthma. We have previously identified a subgroup of young non-atopic asthmatics with perceived food hypersensitivity and poor asthma control. Objective: Our aim was to further characterize this subgroup of non-type 2 asthmatics, including the use of a broad panel of inflammation-related proteins. Methods: Sex-and age-matched subjects (10-35 years old) were divided into three groups with regard to history of asthma and atopy: non-atopic asthmatics with perceived cow's milk hypersensitivity but with IgE antibodies < 0.35 kU(A)/L (NAA; n = 24), non-atopic controls with IgE < 0.35 kU(A)/L (NAC; n = 24), and atopic asthmatics with IgE >= 0.35 kU(A)/L (AA; n = 29). Serum or plasma were analysed using the multi-allergen tests Phadiatop and fx5 (Immuno-CAP), a multiplex immunoassay comprising 92 inflammation-related proteins (Proseek Inflammation), and an ELISA for human neutrophil lipocalin (S-HNL). Fraction of exhaled nitric oxide (FeNO), blood eosinophil (B-Eos) count, C-reactive protein (CRP), airway responsiveness to methacholine - (PD20), and asthma-related quality of life (mAQLQ) were also measured. Results: NAA had lower FeNO (p < 0.001) and B-Eos count (p < 0.001), but scored worse on mAQLQ (p = 0.045) compared with AA. NAA displayed higher levels of matrix metalloproteinase-1 (MMP-1) compared with both NAC (p = 0.011) and AA (p = 0.001), and lower - PD20 compared with NAC (p < 0.001). In NAA, S-HNL correlated negatively with -PD20 (rho = -0.048, p < 0.05) and CRP correlated negatively with mAQLQ (rho = -0.439, p < 0.05). Conclusion: In a subgroup of non-atopic young asthmatics with perceived cow's milk hypersensitivity we observed poor asthma-related quality of life, airway hyperresponsiveness, and clinically relevant non-type 2 inflammation. MMP-1 was elevated in this group, which deserves further studies.

Place, publisher, year, edition, pages
BMC, 2019
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-380493 (URN)10.1186/s13601-019-0250-2 (DOI)000460910600001 ()30834110 (PubMedID)
Funder
Swedish Foundation for Strategic Research Swedish Heart Lung FoundationSwedish Asthma and Allergy Association
Available from: 2019-03-28 Created: 2019-03-28 Last updated: 2019-03-28Bibliographically approved
Amaral, R., Pereira, A. M., Jacinto, T., Malinovschi, A., Janson, C., Alving, K. & Fonseca, J. A. (2019). Comparison of hypothesis- and data-driven asthma phenotypes in NHANES 2007-2012: the importance of comprehensive data availability. Clinical and Translational Allergy, 9, Article ID 17.
Open this publication in new window or tab >>Comparison of hypothesis- and data-driven asthma phenotypes in NHANES 2007-2012: the importance of comprehensive data availability
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2019 (English)In: Clinical and Translational Allergy, ISSN 2045-7022, E-ISSN 2045-7022, Vol. 9, article id 17Article in journal (Refereed) Published
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.

Keywords
Asthma, Phenotypes, Population-based study, Unsupervised analysis
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-380449 (URN)10.1186/s13601-019-0258-7 (DOI)000461351800001 ()
Available from: 2019-03-28 Created: 2019-03-28 Last updated: 2019-03-28Bibliographically approved
Heddini, A., Sundh, J., Ekström, M. & Janson, C. (2019). Effectiveness trials: critical data to help understand how respiratory medicines really work?. European Clinical Respiratory Journal, 6(1), Article ID 1565804.
Open this publication in new window or tab >>Effectiveness trials: critical data to help understand how respiratory medicines really work?
2019 (English)In: European Clinical Respiratory Journal, ISSN 2001-8525, Vol. 6, no 1, article id 1565804Article, review/survey (Refereed) Published
Abstract [en]

Most of the information about the benefits, safety aspects, and cost effectiveness of pharmacological treatment in the respiratory field has been obtained from traditional efficacy studies, such as randomised controlled trials (RCT). The highly controlled environment of an RCT does not always reflect everyday practice. The collection, analysis, and application of effectiveness data to generate Real World Evidence (RWE) through pragmatic trials or observational studies therefore has the potential to improve decision making by regulators, payers, and clinicians. Despite calls for more RWE, effectiveness data are not widely used in decision making in the respiratory field. Recent advances in data capture, curation, and storage combined with new analytical tools have now made it feasible for effectiveness data to become routine sources of evidence to supplement traditional efficacy data. In this paper, we will examine some of the current data gaps, diverse types of effectiveness data, look at proposed frameworks for the positioning of effectiveness data, as well as provide examples from therapeutic areas. We will give examples of both previous effectiveness studies and studies that are ongoing within the respiratory field. Effectiveness data hold the potential to address several evidentiary gaps related to the effectiveness, safety, and value of treatments in patients with respiratory diseases.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2019
Keywords
Effectiveness, real-world evidence, pragmatic trials, evidence-base, efficacy RCT, levels of evidence, respiratory disease, asthma, COPD, co-morbidity
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-377497 (URN)10.1080/20018525.2019.1565804 (DOI)000457088000001 ()30728925 (PubMedID)
Available from: 2019-02-22 Created: 2019-02-22 Last updated: 2019-02-22Bibliographically approved
Mogensen, I., Alving, K., Dahlen, S.-E., James, A., Forsberg, B., Ono, J., . . . Malinovschi, A. (2019). Fixed airflow obstruction relates to eosinophil activation in asthmatics. Clinical and Experimental Allergy, 49(2), 155-162
Open this publication in new window or tab >>Fixed airflow obstruction relates to eosinophil activation in asthmatics
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2019 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, no 2, p. 155-162Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Some asthmatics develop irreversible chronic airflow obstruction, for example, fixed airflow obstruction (fixed-AO). This is probably a consequence of airway remodelling, but neither its relation to inflammation nor which asthma biomarkers can be clinically useful are elucidated. We hypothesized that the presence of type 2 inflammation relates to fixed-AO.

OBJECTIVES: To evaluate the presence of four markers for type 2 inflammation in fixed airflow obstruction among asthmatics.

METHODS: This was a cross-sectional study of 403 participants with asthma, aged 17-75 years, from three Swedish centres. Fixed airflow obstruction was defined as forced expiratory volume during the first second (FEV1 ) over forced vital capacity (FVC) being below the lower limit of normal (LLN). The following type 2 inflammation markers were assessed: exhaled nitric oxide (FeNO), serum periostin, serum eosinophil cationic protein (S-ECP), and urinary eosinophil-derived neurotoxin (U-EDN).

RESULTS: Elevated U-EDN (values in the highest tertile, ≥65.95 mg/mol creatinine) was more common in subjects with fixed-AO vs. subjects without fixed-AO: 55% vs. 29%, P < 0.001. Elevated U-EDN related to increased likelihood of having fixed-AO in both all subjects and never-smoking subjects, with adjusted (adjusted for sex, age group, use of inhaled corticosteroids last week, atopy, early-onset asthma, smoking history, and packyears) odds ratios (aOR) of 2.38 (1.28-4.41) and 2.51 (1.04-6.07), respectively. In a separate analysis, having both elevated S-ECP (>20 μg/L) and U-EDN was related to having the highest likelihood of fixed-AO (aOR (95% CI) 6.06 (2.32-15.75)). Elevated serum periostin or FeNO did not relate to fixed-AO.

CONCLUSIONS AND CLINICAL RELEVANCE: These findings support that type 2 inflammation, and in particular eosinophil inflammation, is found in asthma with fixed-AO. This could indicate a benefit from eosinophil-directed therapies. Further longitudinal studies are warranted to investigate causality and relation to lung function decline.

National Category
Medical and Health Sciences Immunology in the medical area
Research subject
Clinical Physiology
Identifiers
urn:nbn:se:uu:diva-372784 (URN)10.1111/cea.13302 (DOI)000457469600003 ()30365193 (PubMedID)
Funder
Swedish Heart Lung FoundationSwedish Research CouncilVårdal FoundationStockholm County CouncilSwedish Asthma and Allergy AssociationSwedish Foundation for Strategic Research
Available from: 2019-01-09 Created: 2019-01-09 Last updated: 2019-03-08Bibliographically approved
Amid Hägg, S., Emilsson, Ö. I., Franklin, K., Janson, C. & Lindberg, E. (2019). Nocturnal gastroesophageal reflux increases the risk of daytime sleepiness in women. Sleep Medicine, 53, 94-100
Open this publication in new window or tab >>Nocturnal gastroesophageal reflux increases the risk of daytime sleepiness in women
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2019 (English)In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 53, p. 94-100Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Daytime sleepiness is common in women and has negative health effects. Nocturnal gastroesophageal reflux (nGER) and snoring are risk factors for daytime sleepiness, but the effect of their interaction remains unknown. The aim of this study was to examine how nGER and snoring combined affected daytime sleepiness and involuntary falling asleep in women.

METHODS: A questionnaire was sent to randomly selected women in 2000 and 2010. Participants who answered questions regarding both nGER and snoring in both questionnaires were included (N = 4882). Daytime sleepiness was defined as severe or very severe problems with daytime sleepiness. Involuntary falling asleep was defined as sometimes, often or very often falling asleep involuntarily during the day. Respondents snoring loudly and disturbingly sometimes, often or very often were defined as snorers. Having nocturnal heartburn or acid reflux sometimes, often or very often was defined as having nGER.

RESULTS: Daytime sleepiness was reported by 14% of the participants, involuntary falling asleep by 11%. After adjustment for age, smoking, physical activity, caffeine intake and alcohol dependency, increased odd ratios (ORs) for both daytime sleepiness (adjusted OR 4.2, 95% confidence interval (CI): 1.9-9.2) and involuntary falling asleep (adjusted OR 3.1, 95% CI: 1.5-6.4) were seen in women with the combination of nGER and snoring at both baseline and follow-up. The association with daytime sleepiness was also strong for those with only persistent nGER but not for those with only persistent snoring.

CONCLUSION: Women with nGER were at increased risk of developing daytime sleepiness and snoring augmented this association. In addition, women with both nGER and snoring were also at increased risk of developing involuntary falling asleep.

Keywords
Daytime sleepiness, Involuntary falling asleep, Nocturnal gastroesophageal reflux, Snoring
National Category
Medical and Health Sciences
Research subject
Lung Medicine
Identifiers
urn:nbn:se:uu:diva-375498 (URN)10.1016/j.sleep.2018.08.036 (DOI)000457169500016000457169500016 ()30504084 (PubMedID)
Funder
Swedish Heart Lung Foundation
Available from: 2019-01-30 Created: 2019-01-30 Last updated: 2019-03-05Bibliographically approved
Wilkinson, A., Hillman, T., Hopkinson, N. S., Janson, C., Smith, J. & Woodcock, A. A. (2019). Our patients and our planet-holistic considerations for inhaler choice [Letter to the editor]. The Lancet Respiratory Medicine, 7(3), E11-E11
Open this publication in new window or tab >>Our patients and our planet-holistic considerations for inhaler choice
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2019 (English)In: The Lancet Respiratory Medicine, ISSN 2213-2600, E-ISSN 2213-2619, Vol. 7, no 3, p. E11-E11Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
Elsevier, 2019
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-379420 (URN)10.1016/S2213-2600(19)30035-9 (DOI)000459820400002 ()30823976 (PubMedID)
Available from: 2019-03-19 Created: 2019-03-19 Last updated: 2019-03-19Bibliographically approved
Sundström, J., Björkelund, C., Giedraitis, V., Hansson, P.-O., Högman, M., Janson, C., . . . Svennblad, B. (2019). Rationale for a Swedish cohort consortium. Upsala Journal of Medical Sciences, 124(1), 21-28
Open this publication in new window or tab >>Rationale for a Swedish cohort consortium
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2019 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 21-28Article in journal (Refereed) Published
Abstract [en]

We herein outline the rationale for a Swedish cohort consortium, aiming to facilitate greater use of Swedish cohorts for world-class research. Coordination of all Swedish prospective population-based cohorts in a common infrastructure would enable more precise research findings and facilitate research on rare exposures and outcomes, leading to better utilization of study participants' data, better return of funders' investments, and higher benefit to patients and populations. We motivate the proposed infrastructure partly by lessons learned from a pilot study encompassing data from 21 cohorts. We envisage a standing Swedish cohort consortium that would drive development of epidemiological research methods and strengthen the Swedish as well as international epidemiological competence, community, and competitiveness.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2019
Keywords
Common infrastructure, epidemiological research, pilot study, rare outcomes, Swedish cohort consortium
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-381205 (URN)10.1080/03009734.2018.1556754 (DOI)000461811100006 ()30618330 (PubMedID)
Available from: 2019-04-10 Created: 2019-04-10 Last updated: 2019-04-10Bibliographically approved
Sundh, J., Bornefalk-Hermansson, A., Ahmadi, Z., Blomberg, A., Janson, C., Currow, D. C., . . . Ekstrom, M. (2019). REgistry-based randomized controlled trial of treatment and Duration and mortality in long-term OXygen therapy (REDOX) study protocol. BMC Pulmonary Medicine, 19, Article ID 50.
Open this publication in new window or tab >>REgistry-based randomized controlled trial of treatment and Duration and mortality in long-term OXygen therapy (REDOX) study protocol
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2019 (English)In: BMC Pulmonary Medicine, ISSN 1471-2466, E-ISSN 1471-2466, Vol. 19, article id 50Article in journal (Refereed) Published
Abstract [en]

Objective:Long-term oxygen therapy (LTOT) during 15 h/day or more prolongs survival in patients with chronicobstructive pulmonary disease (COPD) and severe hypoxemia. No randomized controlled trial has evaluated the neteffects (benefits or harms) from LTOT 24 h/day compared with 15 h/day or the effect in conditions other than COPD.We describe a multicenter, national, phase IV, non-superiority, registry-based, randomized controlled trial (R-RCT) ofLTOT prescribed 24 h/day compared with 15 h/day. The primary endpoint is all-cause-mortality at 1 year. Secondaryendpoints include cause-specific mortality, hospitalizations, health-related quality of life, symptoms, and outcomes ininterstitial lung disease.

Methods/design:Patients qualifying for LTOT are randomized to LTOT 24 h/day versus 15 h/day during 12 monthsusing the Swedish Register for Respiratory Failure (Swedevox). Planned sample size in this pragmatic study is 2126randomized patients. Clinical follow-up and concurrent treatments are according to routine clinical practice. Mortality,hospitalizations, and incident diseases are assessed using national Swedish registries with expected complete follow-up. Patient-reported outcomes are assessed using postal questionnaire at 3 and 12 months.

Discussion:The R-RCT approach combines the advantages of a prospective randomized trial and large clinical nationalregistries for enrollment, allocation, and data collection, with the aim of improving the evidence-based use of LTOT.

Trial registration:Clinical Trial registered withwww.clinicaltrials.gov, Title: REgistry-based Treatment Duration andMortality in Long-term OXygen Therapy (REDOX); ID: NCT03441204.

Place, publisher, year, edition, pages
BMC, 2019
Keywords
Register-based randomized controlled trial, Hypoxaemia, Long-term oxygen therapy, Oxygen duration, Chronic obstructive pulmonary disease, Interstitial lung disease, Mortality, Hospitalizations, Health-related quality of life, Symptoms
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-379585 (URN)10.1186/s12890-019-0809-7 (DOI)000459873800001 ()30808321 (PubMedID)
Available from: 2019-03-25 Created: 2019-03-25 Last updated: 2019-03-25Bibliographically approved
Carsin, A.-E., Fuertes, E., Schaffner, E., Jarvis, D., Anto, J. M., Heinrich, J., . . . Garcia-Aymerich, J. (2019). Restrictive spirometry pattern is associated with low physical activity levels. A population based international study. Respiratory Medicine, 146, 116-123
Open this publication in new window or tab >>Restrictive spirometry pattern is associated with low physical activity levels. A population based international study
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2019 (English)In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 146, p. 116-123Article in journal (Refereed) Published
Abstract [en]

Introduction: Restrictive spirometry pattern is an under-recognised disorder with a poor morbidity and mortality prognosis. We compared physical activity levels between adults with a restrictive spirometry pattern and with normal spirometry.

Methods: Restrictive spirometry pattern was defined as a having post-bronchodilator FEV1/FVC >= Lower Limit of Normal and a FVC< 80% predicted in two population-based studies (ECRHS-III and SAPALDIA3). Physical activity was measured using the International Physical Activity Questionnaire. The odds of having low physical activity (< 1st study-specific tertile) was evaluated using adjusted logistic regression models.

Results: Subjects with a restrictive spirometry pattern (n = 280/4721 in ECRHS, n = 143/3570 in SAPALDIA) reported lower levels of physical activity than those with normal spirometry (median of 1770 vs 2253 MET.min/week in ECRHS, and 3519 vs 3945 MET.min/week in SAPALDIA). Subjects with a restrictive spirometry pattern were more likely to report low physical activity (meta-analysis odds ratio: 1.41 [95% CI 1.07-1.86]) than those with a normal spirometry. Obesity, respiratory symptoms, co-morbidities and previous physical activity levels did not fully explain this finding.

Conclusion: Adults with a restrictive spirometry pattern were more likely to report low levels of physical activity than those with normal spirometry. These results highlight the need to identify and act on this understudied but prevalent condition.

Place, publisher, year, edition, pages
W B SAUNDERS CO LTD, 2019
Keywords
Restrictive spirometry pattern, Body mass index, Epidemiology, Lung function, Physical activity
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-376892 (URN)10.1016/j.rmed.2018.11.017 (DOI)000456074000018 ()30665509 (PubMedID)
Funder
EU, Horizon 2020, 633212EU, Horizon 2020, 704268
Available from: 2019-02-13 Created: 2019-02-13 Last updated: 2019-02-13Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-5093-6980

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