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- Albrecht, Eva, et al.
(author)
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Telomere length in circulating leukocytes is associated with lung function and disease
- 2014
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 43:4, s. 983-992
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Journal article (peer-reviewed)abstract
- Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in is (FEV1), forced vital capacity (PVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (beta= -0.0452, p= 0.024) as well as COPD (beta= -0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07 x 10(-7)), FVC (p=2.07 x 10(-5)), and FEV1/FVC (p =5.27 x 10(-3)). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.
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| 2. |
- Almstrand, Ann-Charlotte, et al.
(author)
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TOF-SIMS analysis of exhaled particles from patients with asthma and healthy controls.
- 2012
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In: The European respiratory journal: official journal of the European Society for Clinical Respiratory Physiology. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 39:1, s. 59-66
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Journal article (peer-reviewed)abstract
- Particles in exhaled air (PEx) may reflect the composition of respiratory tract lining fluid (RTLF); thus, there is a need to assess their potential as sources of biomarkers for respiratory diseases. In the present study, we compared PEx from patients with asthma and controls using time-of-flight-secondary ion mass spectrometry (TOF-SIMS) and multivariate analysis. Particles were collected using an instrument developed in-house. 15 nonsmoking subjects with physician-diagnosed asthma and 11 nonsmoking healthy controls performed 10 consecutive forced exhalations into the instrument. Particle concentrations were recorded and samples of particles collected on silicon plates were analysed by TOF-SIMS. Subjects with asthma exhaled significantly lower numbers of particles than controls (p=0.03) and the ratio of unsaturated to saturated phospholipids was significantly lower in samples from subjects with asthma (0.25 versus 0.35; p=0.036). Orthogonal partial least squares-discriminant analysis models showed good separation between both positive and negative spectra. Molecular ions from phosphatidylcholine and phosphatidylglycerol, and protein fragments were found to discriminate the groups. We conclude that analysis of PEx is a promising method to examine the composition of RTLF. In the present explorative study, we could discriminate between subjects with asthma and healthy controls based on TOF-SIMS spectra from PEx.
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| 3. |
- Amin, Reshma, et al.
(author)
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The effect of dornase alfa on ventilation Inhomogeneity in patients with Cystic Fibrosis.
- 2011
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 37:4, s. 806-812
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Journal article (peer-reviewed)abstract
- Outcome measures to assess therapeutic interventions in cystic fibrosis (CF) patients with mild lung disease are lacking. Our aim was to determine if the Lung Clearance Index (LCI) can detect a treatment response to dornase alfa in paediatric CF patients with normal spirometry. CF patients between 6 and 18 years of age with FEV1% ≥80% predicted were eligible. In a crossover design, 17 patients received 4 weeks of dornase alfa and placebo in a randomized sequence separated by a 4-weekwashout period. The primary endpoint was the change in LCI from dornase alfa versus placebo. A mixed model approach incorporating period-dependent baselines was used. This trial was registered with ClinicalTrials.gov, number NCT00557089. The mean age±SD was 10.32±3.35 years. Dornase alfa improved LCI versus placebo (0.90±1.44, p=0.022). Forced expiratory flow at 25-75% expired volume (FEF25-75) measured by percent predicted and z-scores also improved in subjects on dornase alfa (6.1%±10.34, p=0.03; and 0.28 z-score±0.46, p=0.03). Dornase alfa significantly improved LCI. Therefore the LCI may be a suitable tool to assess early intervention strategies in this patient population.
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| 4. |
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| 5. |
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| 6. |
- Bakke, PS, et al.
(author)
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Recommendations for epidemiological studies on COPD
- 2011
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 38:6, s. 1261-1277
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Journal article (peer-reviewed)abstract
- The prevalence of chronic obstructive pulmonary disease (COPD) has been extensively studied, especially in Western Europe and North America. Few of these data are directly comparable because of differences between the surveys regarding composition of study populations, diagnostic criteria of the disease and definitions of the risk factors. Few community studies have examined phenotypes of COPD and included other ways of characterising the disease beyond that of spirometry. The objective of the present Task Force report is to present recommendations for the performance of general population studies in COPD in order to facilitate comparable and valid estimates on COPD prevalence by various risk factors. Diagnostic criteria in epidemiological settings, and standardised methods to examine the disease and its potential risk factors are discussed. The paper also offers practical advice for planning and performing an epidemiological study on COPD. The main message of the paper is that thorough planning is worth half the study. It is crucial to stick to standardised methods and good quality control during sampling. We recommend collecting biological markers, depending on the specific objectives of the study. Finally, studies of COPD in the population at large should assess various phenotypes of the disease
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| 8. |
- Bakolis, I, et al.
(author)
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Respiratory health and endotoxin : associations and modification by CD14/-260 genotype
- 2012
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 39:3, s. 573-581
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Journal article (peer-reviewed)abstract
- Exposure to endotoxin has been associated with increased respiratory symptoms and decrements in lung function in occupational settings but little is known about health effects of domestic exposure in adults. We describe the association of respiratory disease, IgE sensitisation, bronchial reactivity and lung function with mattress endotoxin levels in adults and determine whether these associations are modified by polymorphisms in CD14.Endotoxin levels in mattress dust from a population based sample of 972 adults were measured. Associations were examined using generalized linear mixed models, adjusting for individual and household confounders. Effect modification of these associations by CD14/-260 (rs2569190) was assessed.Mattress endotoxin levels varied from 0.1 to 402.6 EU·mg(-1). Although there was no overall association of lung function with endotoxin exposure, there was evidence that the association of FEV1 and FVC with endotoxin was modified by CD14/-260 genotype (p for interaction 0.005 and 0.013 respectively). There was no evidence that symptoms, IgE sensitisation or bronchial reactivity was associated with mattress endotoxin levels.In this large epidemiological study of adults there was no evidence that mattress endotoxin level was associated with respiratory symptoms or IgE sensitisation but the association of lung function with endotoxin levels may be modified by CD14-genotype.
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