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Inflammatory Markers, Respiratory Diseases, Lung Function and Associated Gender Differences
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Systemic inflammation is associated with impaired lung function. Inflammation is part of asthma and chronic obstructive pulmonary disease (COPD), but the local and systemic inflammatory pattern differs.

The overall aim was to evaluate systemic inflammatory markers in obstructive lung diseases and more specifically: To determine if CRP is related to respiratory symptoms, asthma, atopy and bronchial responsiveness (paper I), in a population sample from three countries (paper I and II); to evaluate if CRP is related to COPD, lung function and rate of lung function decline (paper II); to investigate the association of serum MMP-9 and TIMP-1 with lung function in a cross-sectional population based study (paper III); and finally, to study possible gender differences in the longitudinal association between CRP and lung function in a prospective population based study (paper IV).

In the first study we reported that CRP was related to non-allergic asthma but not allergic asthma, and that CRP was related to respiratory symptoms such as wheeze, nocturnal cough and breathlessness after effort, but not associated with atopy or bronchial responsiveness.

In the second study we found that COPD was more common in subjects in the highest CRP quartiles and higher CRP levels were associated with lower FEV1 values in both men and women, but the negative association between CRP and FEV1 was larger in men than women. The FEV1 decline was larger in men with high CRP levels, whereas no such association was found for women.

In the third study we reported that lower FEV1 was associated with higher levels of MMP-9, TIMP-1 and their ratio MMP-9/TIMP-1. After stratification for gender this association was significant in men but not women.

In the fourth study we found that CRP levels were associated with change in both FEV1 and FVC in men but not women. This association was found for both baseline CRP and change in CRP, confirming a stronger association between systemic inflammation and lung function decline in men than women.

In conclusion, systemic inflammation is associated with non-allergic asthma but not allergic asthma. Our findings of a stronger association between the systemic inflammation and lung function impairment in men, but not women, may indicate a gender difference in the mechanisms of lung function decline.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2011. , 64 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 714
Keyword [en]
C-reactive protein, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, COPD, FEV1, FVC, lung function, systemic inflammation, gender differences
National Category
Respiratory Medicine and Allergy
Research subject
Lung Medicine
Identifiers
URN: urn:nbn:se:uu:diva-160226ISBN: 978-91-554-8194-0 (print)OAI: oai:DiVA.org:uu-160226DiVA: diva2:448752
Public defence
2011-11-25, Enghoffssalen, 50 huset, Akademiska University Hospital, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2011-11-02 Created: 2011-10-18 Last updated: 2011-11-10Bibliographically approved
List of papers
1. C-reactive protein is elevated in non-allergic but not allergic asthma.: a multicentre epidemiological study.
Open this publication in new window or tab >>C-reactive protein is elevated in non-allergic but not allergic asthma.: a multicentre epidemiological study.
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2005 (English)In: Thorax, ISSN 0040-6376, Vol. 60, no 6, 451-4 p.Article in journal (Other scientific) Published
Keyword
Adult, Asthma/*blood/physiopathology, Body Mass Index, Bronchial Hyperreactivity/blood, C-Reactive Protein/*metabolism, Dyspnea/etiology, Female, Humans, Male, Research Support; Non-U.S. Gov't, Respiration Disorders/blood, Smoking/adverse effects
Identifiers
urn:nbn:se:uu:diva-80508 (URN)15923243 (PubMedID)
Available from: 2006-05-22 Created: 2006-05-22 Last updated: 2011-11-10
2. CRP is associated with lung function decline in men but not women: a prospective study
Open this publication in new window or tab >>CRP is associated with lung function decline in men but not women: a prospective study
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2013 (English)In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 107, no 1, 91-97 p.Article in journal (Refereed) Published
Abstract [en]

Systemic inflammation is associated with impaired lung function. Studies, most cross-sectional, report a stronger association between systemic inflammation and lung function impairment in men than women. The aim was to evaluate gender differences in the longitudinal association between systemic inflammation and lung function.

We used data from randomly chosen residents of Reykjavík, born 1940–54, who were investigated in three stages: Baseline (1973–75; 1983–85) and follow-up (2001–03). The participants (n = 1049, 574 women) had a mean age of 28 ± 6 years at baseline and mean follow-up time of 27 ± 4 years. At each stage lung function (FEV1 and FVC) and C-reactive protein (CRP) were evaluated.

Change in FEV1 (p = 0.04) and FVC (p = 0.01) was associated with baseline CRP in men but not in women. In the multiple variable analysis, CRP at baseline was associated with a decline in FEV1 (−3.1 mL/year, 95% CI: −5.1, −0.99) and FVC (−2.5 mL/year, 95% CI: −4.4, −0.65) in men but not in women. Similarly during follow-up, change in CRP, standardised to 1SD, was associated with a decline in FEV1 (−0.19 mL/year, 95% CI: −0.30, −0.07) and FVC (−0.11 mL/year, 95% CI: −0.22, −0.01)) in men but not in women.

This prospective study confirms a stronger association between systemic inflammation and lung function decline in men than in women. This may indicate a gender difference in the mechanisms of lung function decline.

National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-160224 (URN)10.1016/j.rmed.2012.09.020 (DOI)000314135600011 ()
Available from: 2011-10-18 Created: 2011-10-18 Last updated: 2017-12-08Bibliographically approved
3. Serum levels of matrix metalloproteinase-9, tissue inhibitors of metalloproteinase-1 and their ratio are associated with impaired lung function in the elderly: a population-based study
Open this publication in new window or tab >>Serum levels of matrix metalloproteinase-9, tissue inhibitors of metalloproteinase-1 and their ratio are associated with impaired lung function in the elderly: a population-based study
Show others...
2010 (English)In: Respirology (Carlton South. Print), ISSN 1323-7799, E-ISSN 1440-1843, Vol. 15, no 3, 530-535 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND OBJECTIVE: Matrix metalloproteinases (MMP) and their inhibitors, tissue inhibitors of metalloproteinases (TIMP), regulate homeostasis and turnover of the extra cellular matrix. The aim of this study was to investigate the associations of serum MMP-9 and TIMP-1 with lung function. METHODS: Spirometry was performed in a population-based sample of 888 subjects aged 70 years. Serum MMP-9 and TIMP-1 concentrations were measured by ELISA. RESULTS: Lower FEV(1) values were associated with higher serum levels of MMP-9 (P = 0.001) and TIMP-1 (P < 0.001), and a higher ratio of MMP-9 to TIMP-1 (P = 0.02). These associations were significant after adjustment for gender, weight, height, BMI, current smoking, pack years of smoking and the time for which samples were frozen. After stratification for gender, the associations between FEV(1) and MMP-9, TIMP-1, and their ratio, were significant in men but not in women. CONCLUSIONS: Lower FEV(1) was significantly but weakly associated with higher serum levels of MMP-9, TIMP-1 and a higher MMP-9/TIMP-1 ratio. This association was stronger in men than in women, suggesting a possible role for extracellular matrix remodelling in the development of impaired lung function. These associations may also partly explain the association between low FEV(1) and cardiovascular disease.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-135247 (URN)10.1111/j.1440-1843.2010.01718.x (DOI)000276036400019 ()20337997 (PubMedID)
Available from: 2010-12-06 Created: 2010-12-06 Last updated: 2017-12-11Bibliographically approved
4. Gender differences in the association between C-reactive protein, lung function impairment, and COPD
Open this publication in new window or tab >>Gender differences in the association between C-reactive protein, lung function impairment, and COPD
Show others...
2007 (English)In: International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, Vol. 2, no 4, 635-642 p.Article in journal (Refereed) Published
Abstract [en]

Individuals with COPD have systemic inflammation that can be assessed by measuring C-reactive protein (CRP). In this paper we evaluated whether CRP is related to COPD, lung function and rate of lung function decline. We included 1237 randomly selected subjects (mean age 42, range 28–56 years) from three centers in the European Community Respiratory Health Survey: Reykjavik, Uppsala and Tartu. CRP was measured at the end of the follow-up (mean 8.3 years) and the values were divided into 4 quartiles. Fifty-three non-asthmatic subjects fulfilled spirometric criteria for COPD (FEV1/FVC < 70%). COPD occurred more often in the 4th CRP quartile (OR (95% CI) 3.21 (1.13–9.08)) after adjustment for age, gender, body weight and smoking. High CRP levels were related to lower FEV1 values in both men (−437 (−596, −279) mL) and women (−144 (−243, −44) mL). The negative association between CRP and FEV1 was significantly larger in men than women (p = 0.04). The decline in FEV1 was larger (16 (5, 27) mL) in men with high CRP levels whereas no significant association between CRP and FEV1 decline was found in women. Higher CRP values are significantly associated with COPD and lower lung function in men and women. In men higher CRP values are related to a larger decline in FEV1.

Keyword
Adult, C-Reactive Protein/analysis/immunology/*metabolism, Estonia, Female, Humans, Iceland, Male, Middle Aged, Pulmonary Disease; Chronic Obstructive/*immunology, Questionnaires, Respiratory Function Tests, Respiratory Insufficiency/*immunology, Sex Factors, Smoking/immunology, Spirometry, Sweden
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-16771 (URN)18268938 (PubMedID)
Available from: 2008-06-04 Created: 2008-06-04 Last updated: 2012-02-29Bibliographically approved

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