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Can we predict development of COPD?
Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Clinical Physiology . Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Primary Health Care Centres.
Karolinska Institutet.
Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Clinical Physiology . Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
2008 (English)Article in journal (Refereed) Submitted
Abstract [en]

Background: Cigarette smoking is one of the main causes of chronic obstructive pulmonarydisease (COPD). Chronic inflammation of airways may start years before manifestation ofclinical symptoms, thus early identification of smokers at risk to develop COPD is crucial.Objectives: To evaluate if a single breath test for diffusion capacity (DLCO) or concentrationsof certain biomarkers in exhaled breath condensate (EBC), saliva or serum could identifysubjects with COPD or non-COPD smokers and ex-smokers supposed to be at risk to developCOPD, as suggested by rapid decline of forced expiratory volume in one second (FEV1) during afive year period.

Methods: Twenty-nine symptom free smokers/ex-smokers, 16 smokers/ex-smokers with COPDand 19 matched healthy non-smoking volunteers were studied by means of spirometry, DLCO,and analyses of EBC, saliva and serum [chlorine, lysozyme, eosinophil cationic protein (ECP)and myeloperoxidase (MPO)]. Area under a receiver operated curve (AUCROC) was used toassess sensitivity and specificity of measurements to identify manifest or risk to get COPD.

Results: Only DLCO could identify subjects with COPD or risk to develop COPD, as judged byAUCROC (0.85 or 0.75, respectively). Lower DLCO (p=0.003) and higher serum concentrationsof lysozyme (p=0.011) were recorded in those with COPD than non-COPD subjects.Furthermore, concentration of chlorine was higher in EBC from COPD subjects than fromhealthy volunteers (p<0.05). Except for chlorine, none of the remaining biomarkers weredetected in EBC and there was a vast variability of concentrations of biomarkers in saliva.

Conclusion: DLCO was the most effective discriminator of COPD and rapid decline of lungfunction. Serum concentration of lysozyme was the second strongest discriminator, confirmingprevious findings on involvement of neutrophils in the disease process. The use of EBC as a toolto measure exhaled biomarkers involved in COPD is dubious due to large variability and lowconcentrations of markers in EBC.

Place, publisher, year, edition, pages
2008.
Keyword [en]
Exhaled Breath Condensate, serum, DLCO, COPD, lysozyme and chlorine
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-16293OAI: oai:DiVA.org:liu-16293DiVA: diva2:133635
Available from: 2009-01-13 Created: 2009-01-13 Last updated: 2009-09-18Bibliographically approved
In thesis
1. Exhaled Breath Condensate in Obstructive Lung Diseases: A Methodological study
Open this publication in new window or tab >>Exhaled Breath Condensate in Obstructive Lung Diseases: A Methodological study
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Asthma and chronic obstructive pulmonary disease (COPD) are two common inflammatory airway diseases characterized by airway inflammation and mucus hypersecretion. Prediction of the outcome of these diseases may not be performed and the need for non-invasive diagnostic tools capable of identifying inflammation in asthma and COPD becomes therefore obvious. Validation, sensitivity and specificity of most non-invasive methods to detect and monitor inflammatory responses in airways are poor and there is a great need to identify and standardize less invasive, or non-invasive methods for investigation of airway inflammation.

Epithelial lining fluid (ELF) covers the airway surface and contains soluble and insoluble inflammatory cell products and plasma proteins originating and passively transferred from the underlying tissue. Airborne aerosol particles containing ELF saturated with water may be recovered in exhaled air by allowing the air to pass a cold surface, creating exhaled breath condensate (EBC). EBC may then be analysed for various components of interest.

The aims of this thesis were (1) to explore whether a certain profile of inflammatory cell markers in EBC, saliva or serum may be identified in patients with allergic asthma or COPD, (2) to evaluate the efficacy and reproducibility of a measurable marker in EBC using either of the two condensers ECoScreen or RTube and (3) to evaluate the value of chlorine concentrations in EBC as well as reproducibility of assessments of certain compounds in EBC.

Material and methods: Thirty-six patients with asthma, 49 smokers or ex-smokers and 25 healthy volunteers participated in three clinical studies. In addition, efficacy, reproducibility and comparison of the two condensers were studied in an ex vivo set up using aerosols of solutions of saline, myeloperoxidase (MPO) or human neutrophil lipocalin (HNL). Aerosol boluses were transferred by means of a servo ventilator to either of the two condensers. Concentrations of chlorine (presumed to be a marker of mucous secretion) in EBC or saliva were analyzed by means of a sensitive coulometric technique (AOX). The inflammatory cell markers histamine, MPO, HNL, lysozyme, cysteinyl-leukotrienes (CysLT) and eosinophil cationic protein (ECP) were analysed in EBC, saliva and/or serum by means of ELISA, RIA, EIA or immunochemical fluorescence methods, respectively. Lung function tests, including diffusion capacity were measured by standard techniques according to clinical routines.

Results and Conclusions: Chlorine measurements served as the main tool in our tests and intra-assay variability <10% was recorded. However, flow dependency, temperature dependency, substance dependency and concentration dependency characterized yields of EBC. Despite acceptable analytical precision, low concentration levels of inflammation markers, biological variability and occasionally contamination with saliva mean that the feasibility of the EBC method is limited. Despite biological variability, concentrations of chlorine in EBC were significantly higher during than after a mild pollen season, suggesting that chlorine concentrations in EBC are a sensitive marker of allergic airway inflammation. A vast number of confounding factors made interpretations of EBC data obtained from COPD and non-COPD patients difficult and traditional diagnostic tools, such as diffusion capacity (DLCO) and serum lysozyme appeared to best discriminate between COPD and non-COPD.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2009. 72 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1091
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-16294 (URN)9789173937269 (ISBN)
Public defence
2009-02-06, Elsa Brännströmssalen, Campus US, Linköpings Universitet, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2009-01-13 Created: 2009-01-13 Last updated: 2017-12-15Bibliographically approved
2. Chronic Obstructive PulmonaryDisease: Early detection and prevention in primary care
Open this publication in new window or tab >>Chronic Obstructive PulmonaryDisease: Early detection and prevention in primary care
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background and aims. Early detection of Chronic Obstructive Pulmonary Disease (COPD) and secondary prevention by means of smoking cessation are the only available methods of stopping the progression of the disease. The overall aim was to examine the possibilities of early detection and prevention of COPD in General Practice. The specific aims were to evaluate a method of detecting COPD at its early stages, to investigate the rate of emphysema in smokers with normal lung function and smokers defined as preclinical COPD, to investigate the effects of performed spirometries and brief smoking cessation advice on smoking habits and to test if concentrations of certain biomarkers in blood, saliva and exhaled breath condensate (EBC) could identify subjects with COPD or non-COPD subjects supposed to be at risk of developing COPD.

Methods. The first study evaluated an invitational method, which offered voluntary screening spirometry to a targeted population of smokers 40-55 years old. In the second follow-up study, all smokers with COPD and half of the smokers with normal lung function (NLF) were annually invited for spirometry and brief smoking cessation advice for a duration of 3 years, with half of the smokers with NLF being tested only last year. In the third study, 54 smokers with NLF were examined with High Resolution Computed Tomography (HRCT), with blood samples also being collected from each subject. In study four, 19 subjects categorised as having COPD, 30 non-COPD subjects and 15 healthy non-smoking volunteers were studied by means of spirometry, DLCO, and analysis of biomarkers in EBC, saliva and serum.

Results. A total of 512 smokers responded. The prevalence of COPD was 27.5% and was classified as mild in 85% of the sufferers, moderate in 13% and severe in 2%. At year 1, 10% of the smokers with COPD had been continuously abstinent from smoking, compared to 2% of smokers with NLF. The prolonged abstinence rate increased yearly, and at year 3 the smoking cessation rates in smokers with COPD was 25% compared to 7% in smokers with NLF. By visual analysis, HRCT showed signs of emphysema in 43% of the subjects. Emphysema was also associated with low BMI. Higher serum concentrations of lysozyme and lower DLCO were recorded in those with COPD compared to non-COPD subjects. With the exception of chlorine, none of the remaining biomarkers were detected in EBC.

Conclusions. By invitational targeted screening, COPD can be easily detected in its mild stages by using spirometry. By becoming diagnosed with COPD, smokers seem to be more motivated to stop smoking, and COPD patients should repeatedly be offered spirometry and smoking cessation advice which may prevent the progression of the disease to a severe disabling form. HRCT may detect smoke related parenchymal lung damage (i.e. emphysema) in symptom-free smokers with normal spirometry. Serum lysozyme and DLCO appeared to be the strongest discriminator between COPD and non-COPD subjects. The use of EBC as a tool to measure exhaled inflammatory biomarkers involved in COPD is as yet uncertain.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2009. 102 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1093
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-20736 (URN)978-91-7393-721-4 (ISBN)
Public defence
2009-06-01, Elsa Brändströmsalen, Hälsouniversitetet, Campus US, Linköpings Universitet, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2009-09-18 Created: 2009-09-18 Last updated: 2009-09-18Bibliographically approved

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Davidsson, AnetteStratelis, GeorgiosSchmekel, Birgitta

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