| 11. |
- Barath, Stefan, 1963-, et al.
(författare)
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Short-Term Exposure to Ozone Does Not Impair Vascular Function or Affect Heart Rate Variability in Healthy Young Men
- 2013
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Ingår i: Toxicological Sciences. - : Oxford University Press. - 1096-6080 .- 1096-0929. ; 135:2, s. 292-299
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Tidskriftsartikel (refereegranskat)abstract
- Air pollution exposure is associated with cardiovascular morbidity and mortality, yet the role of individual pollutants remains unclear. In particular, there is uncertainty regarding the acute effect of ozone exposure on cardiovascular disease. In these studies, we aimed to determine the effect of ozone exposure on vascular function, fibrinolysis, and the autonomic regulation of the heart. Thirty-six healthy men were exposed to ozone (300 ppb) and filtered air for 75min on two occasions in randomized double-blind crossover studies. Bilateral forearm blood flow (FBF) was measured using forearm venous occlusion plethysmography before and during intra-arterial infusions of vasodilators 2–4 and 6–8h after each exposure. Heart rhythm and heart rate variability (HRV) were monitored during and 24h after exposure. Compared with filtered air, ozone exposure did not alter heart rate, blood pressure, or resting FBF at either 2 or 6h. There was a dose-dependent increase in FBF with all vasodilators that was similar after both exposures at 2–4h. Ozone exposure did not impair vasomotor or fibrinolytic function at 6–8h but rather increased vasodilatation to acetylcholine (p = .015) and sodium nitroprusside (p = .005). Ozone did not affect measures of HRV during or after the exposure. Our findings do not support a direct rapid effect of ozone on vascular function or cardiac autonomic control although we cannot exclude an effect of chronic exposure or an interaction between ozone and alternative air pollutants that may be responsible for the adverse cardiovascular health effects attributed to ozone.
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| 12. |
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| 13. |
- Brandsma, Joost, et al.
(författare)
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Lipid phenotyping of lung epithelial lining fluid in healthy human volunteers
- 2018
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Ingår i: Metabolomics. - : Springer-Verlag New York. - 1573-3882 .- 1573-3890. ; 14:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lung epithelial lining fluid (ELF)-sampled through sputum induction-is a medium rich in cells, proteins and lipids. However, despite its key role in maintaining lung function, homeostasis and defences, the composition and biology of ELF, especially in respect of lipids, remain incompletely understood. Objectives: To characterise the induced sputum lipidome of healthy adult individuals, and to examine associations between different ELF lipid phenotypes and the demographic characteristics within the study cohort.Methods: Induced sputum samples were obtained from 41 healthy non-smoking adults, and their lipid compositions analysed using a combination of untargeted shotgun and liquid chromatography mass spectrometry methods. Topological data analysis (TDA) was used to group subjects with comparable sputum lipidomes in order to identify distinct ELF phenotypes.Results: The induced sputum lipidome was diverse, comprising a range of different molecular classes, including at least 75 glycerophospholipids, 13 sphingolipids, 5 sterol lipids and 12 neutral glycerolipids. TDA identified two distinct phenotypes differentiated by a higher total lipid content and specific enrichments of diacyl-glycerophosphocholines, -inositols and -glycerols in one group, with enrichments of sterols, glycolipids and sphingolipids in the other. Subjects presenting the lipid-rich ELF phenotype also had significantly higher BMI, but did not differ in respect of other demographic characteristics such as age or gender.Conclusions: We provide the first evidence that the ELF lipidome varies significantly between healthy individuals and propose that such differences are related to weight status, highlighting the potential impact of (over)nutrition on lung lipid metabolism.
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| 14. |
- Brandsma, Joost, et al.
(författare)
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Stratification of asthma by lipidomic profiling of induced sputum supernatant
- 2023
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 152:1, s. 117-125
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Tidskriftsartikel (refereegranskat)abstract
- Background: Asthma is a chronic respiratory disease with significant heterogeneity in its clinical presentation and pathobiology. There is need for improved understanding of respiratory lipid metabolism in asthma patients and its relation to observable clinical features.Objective: We performed a comprehensive, prospective, cross-sectional analysis of the lipid composition of induced sputum supernatant obtained from asthma patients with a range of disease severities, as well as from healthy controls.Methods: Induced sputum supernatant was collected from 211 adults with asthma and 41 healthy individuals enrolled onto the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) study. Sputum lipidomes were characterized by semiquantitative shotgun mass spectrometry and clustered using topologic data analysis to identify lipid phenotypes.Results: Shotgun lipidomics of induced sputum supernatant revealed a spectrum of 9 molecular phenotypes, highlighting not just significant differences between the sputum lipidomes of asthma patients and healthy controls, but also within the asthma patient population. Matching clinical, pathobiologic, proteomic, and transcriptomic data helped inform the underlying disease processes. Sputum lipid phenotypes with higher levels of nonendogenous, cell-derived lipids were associated with significantly worse asthma severity, worse lung function, and elevated granulocyte counts.Conclusion: We propose a novel mechanism of increased lipid loading in the epithelial lining fluid of asthma patients resulting from the secretion of extracellular vesicles by granulocytic inflammatory cells, which could reduce the ability of pulmonary surfactant to lower surface tension in asthmatic small airways, as well as compromise its role as an immune regulator.
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| 15. |
- Burg, Dominic, et al.
(författare)
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Large-Scale Label-Free Quantitative Mapping of the Sputum Proteome
- 2018
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 17:6, s. 2072-2091
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of induced sputum supematant is a minimally invasive approach to study the epithelial lining fluid and, thereby, provide insight into normal lung biology and the pathobiology of lung diseases. We present here a novel proteomics approach to sputum analysis developed within the U-BIOPRED (unbiased biomarkers predictive of respiratory disease outcomes) international project. We present practical and analytical techniques to optimize the detection of robust biomarkers in proteomic studies. The normal sputum proteome was derived using data-independent HDMSE applied to 40 healthy nonsmoking participants, which provides an essential baseline from which to compare modulation of protein expression in respiratory diseases. The "core" sputum proteome (proteins detected in >= 40% of participants) was composed of 284 proteins, and the extended proteome (proteins detected in >= 3 participants) contained 1666 proteins. Quality control procedures were developed to optimize the accuracy and consistency of measurement of sputum proteins and analyze the distribution of sputum proteins in the healthy population. The analysis showed that quantitation of proteins by HDMSE is influenced by several factors, with some proteins being measured in all participants' samples and with low measurement variance between samples from the same patient. The measurement of some proteins is highly variable between repeat analyses, susceptible to sample processing effects, or difficult to accurately quantify by mass spectrometry. Other proteins show high interindividual variance. We also highlight that the sputum proteome of healthy individuals is related to sputum neutrophil levels, but not gender or allergic sensitization. We illustrate the importance of design and interpretation of disease biomarker studies considering such protein population and technical measurement variance.
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| 16. |
- Eklund, Linda, et al.
(författare)
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An experimental exposure study revealing composite airway effects of physical exercise in a subzero environment
- 2021
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Ingår i: International Journal of Circumpolar Health. - : Taylor & Francis. - 1239-9736 .- 2242-3982. ; 80:1
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to a cold climate is associated with an increased morbidity and mortality, but the specific mechanisms are largely unknown. People with cardiopulmonary disease and winter endurance athletes are particularly vulnerable. This study aimed to map multiple domains of airway responses to exercise in subzero temperature in healthy individuals.Thirty-one healthy subjects underwent whole-body exposures for 50 minutes on two occasions in an environmental chamber with intermittent moderate-intensity exercise in +10 °C and -10 °C. Lung function, plasma/urine CC16 , and symptoms were investigated before and after exposures.Compared to baseline, exercise in -10 °C decreased FEV1 (p=0.002), FEV1/FVC (p<0.001), and increased R20Hz (p=0.016), with no differences between exposures. Reactance increased after +10 °C (p=0.005), which differed (p=0.042) from a blunted response after exercise in -10 °C. Plasma CC16 increased significantly within exposures, without differences between exposures. Exercise in -10 °C elicited more intense symptoms from the upper airways, compared to +10 °C. Symptoms from the lower airways were few and mild. Short-duration moderate-intensity exercise in -10 °C induces mild symptoms from the lower airways, no lung function decrements or enhanced leakage of biomarkers of airway epithelial injury, and no peripheral bronchodilatation, compared to exercise in +10 °C.
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| 17. |
- Eklund, Linda, 1982-
(författare)
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Cold air, physical activity, and the airways : epidemiological and experimental studies
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Cold exposure is associated with increased morbidity and mortality. Elite cross-country skiers are regularly exposed to cold, dry air and have a high prevalence of asthma compared to the Swedish population. However, evidence is limited regarding how a combination of sub-zero temperatures and physical activity affects the airways of healthy individuals.Aims: The aims of this thesis were to study the prevalence of self-reported asthma, age at asthma onset, and predictors of asthma in Swedish endurance athletes, with a focus on cross-country skiers. This thesis also aimed to assess the effects of subzero temperature and physical activity on healthy human airways.Methods: Study 1 (papers I-II) consisted of an annual postal questionnaire investigating asthma prevalence and predictors of asthma that was sent to invited athletes in 2011–2015. Invited athletes were Swedish elite cross-country skiers, biathletes, ski orienteers, and orienteers from Swedish National Elite Sport Schools, national teams, and Swedish Ski Universities, or top orienteers according to national ranking. Former Swedish Olympic skiers and an adolescent reference group were invited in 2013. Paper I included cross-sectional data from 2011 for adolescents/adults and from 2013 for former skiers (n=491). Paper II included adolescent elite skiers (n=253) from the Swedish National Elite Sport Schools invited during 2011-2013, as well as a reference group (n=500) aged 16-20 years that was matched for school municipalities and invited in 2013. Study 2 (papers III-IV) comprised whole-body experimental exposure of healthy adults to sub-zero temperatures and exercise in an environmental chamber. Lung function and biochemical markers in plasma and urine were measured before and after exposure. Symptoms were investigated before, during, and after exposure. In both trials, study subjects were exposed for 50 min on two separate occasions in randomized order. Paper III comprised 31 subjects and moderate-intensity exercise (30 min running at 62-78% of VO2max), at 10°C vs. -10°C. Paper IV included 29 subjects and hard-intensity exercise (30 min of running at 85% of VO2max) vs. rest, both at a temperature of -15°C.Results: In paper I, the overall response rate was 82%. Athletes reporting asthma in the different age categories were: 29% of skiers (38% of the female skiers) and 17% of orienteers (p=0.071) among 15 to 19-year-olds; 35% of skiers and 16% of orienteers (p=0.029) among 20 to 34-year-olds; and 22% of the skiers aged 40–94 years. Asthma onset occurred in adolescence among the active athletes. Increasing age, female sex, allergy, family history of allergy/asthma, and being a skier were predictors of self-reported physician-diagnosed asthma. In paper II, the response rate was 96% for skiers and 48% for the reference group. Skiers reported a higher prevalence of self-reported physician-diagnosed asthma than the reference population (27% vs. 19%, p=0.046). Physician-diagnosed asthma was more frequently reported by female skiers than male skiers (34% vs. 20%, p=0.021). Median age at asthma onset was higher among skiers than in the reference population (12.0 vs. 8.0 years; p<0.001). Female sex, family history of asthma, nasal allergy, and being a skier were risk factors associated with self-reported physician-diagnosed asthma. In paper III, exercise at -10°C decreased FEV1 (p=0.002) and FEV1/FVC (p<0.001) and increased resistance at 20 Hz (p=0.016) to similar magnitudes as exercise at 10°C. Exercise at 10°C increased reactance (p=0.005), which differed (p=0.042) from a less pronounced response after exercise at -10°C. Plasma CC16 increased similarly after both exposures, without significant differences. More intense symptoms from the upper airways were reported after exercise at -10°C than at 10°C. Symptoms from the lower airways were few and mild. In paper IV, FEV1 decreased from baseline after both rest (p<0.001) and exercise (p=0.012) at -15°C, with no differences between exposures. Compared to rest, exercise at -15°C induced greater increases in reactance (p=0.023), plasma CC16 (p<0.001), and plasma IL-8 (p<0.001). Exercise gave rise to more intense symptoms from the lower airways, whereas rest induced more general symptoms.Conclusions: In the 1990s, a high prevalence of physician-diagnosed asthma was reported among Swedish elite cross-country skiers, and our studies show that this has not changed. Asthma onset commonly occurs in early adolescence among skiers, in the beginning of their career. Being an elite skier is an independent risk factor associated with asthma. Targeted preventive measures should be introduced at an early age to avoid the development of asthma in endurance athletes. Healthy individuals performing short-duration moderate- and hard-intensity exercise in sub-zero temperatures responded with lung function changes and an increased airway permeability. These findings warrant further research on airway responses to sub-zero temperatures in vulnerable individuals such as elite endurance athletes.
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| 18. |
- Eklund, Linda M., et al.
(författare)
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Cold air exposure at -15 °C induces more airway symptoms and epithelial stress during heavy exercise than rest without aggravated airway constriction
- 2022
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Ingår i: European Journal of Applied Physiology. - : Springer. - 1439-6319 .- 1439-6327. ; 122:12, s. 2533-2544
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Exposure to cold air may harm the airways. It is unclear to what extent heavy exercise adds to the cold-induced effects on peripheral airways, airway epithelium, and systemic immunity among healthy individuals. We investigated acute effects of heavy exercise in sub-zero temperatures on the healthy airways.Methods: Twenty-nine healthy individuals underwent whole body exposures to cold air in an environmental chamber at − 15 °C for 50 min on two occasions; a 35-min exercise protocol consisting of a 5-min warm-up followed by 2 × 15 min of running at 85% of VO2max vs. 50 min at rest. Lung function was measured by impulse oscillometry (IOS) and spirometry before and immediately after exposures. CC16 in plasma and urine, and cytokines in plasma were measured before and 60 min after exposures. Symptoms were surveyed pre-, during and post-trials.Results: FEV1 decreased after rest (− 0.10 ± 0.03 L, p < 0.001) and after exercise (− 0.06 ± 0.02 L, p = 0.012), with no difference between trials. Exercise in − 15 °C induced greater increases in lung reactance (X5; p = 0.023), plasma CC16 (p < 0.001) as well as plasma IL-8 (p < 0.001), compared to rest. Exercise induced more intense symptoms from the lower airways, whereas rest gave rise to more general symptoms.Conclusion: Heavy exercise during cold air exposure at − 15 °C induced signs of an airway constriction to a similar extent as rest in the same environment. However, biochemical signs of airway epithelial stress, cytokine responses, and symptoms from the lower airways were more pronounced after the exercise trial.
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| 19. |
- Eliasson, Gabriella, et al.
(författare)
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Comorbid conditions as predictors of mortality in severe COPD - an eight-year follow-up cohort study
- 2023
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Ingår i: European Clinical Respiratory Journal. - : Taylor & Francis. - 2001-8525. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Co-morbidities are common in chronic obstructive pulmonary disease (COPD) and are associated with increased morbidity and mortality. The aim of the present study was to explore the prevalence of several comorbid conditions in severe COPD, and to investigate and compare their associations with long-term mortality.Methods: In May 2011 to March 2012, 241 patients with COPD stage 3 or 4 were included in the study. Information was collected on sex, age, smoking history, weight and height, current pharmacological treatment, number of exacerbations the recent year and comorbid conditions. At December 31st, 2019, mortality data (all-cause and cause specific) were collected from the National Cause of Death Register. Data were analyzed using Cox-regression analysis with gender, age, previously established predictors of mortality and comorbid conditions as independent variables, and all-cause mortality and cardiac and respiratory mortality, respectively, as dependent variables.Results: Out of 241 patients, 155 (64%) were deceased at the end of the study period; 103 patients (66%) died of respiratory disease and 25 (16%) of cardiovascular disease. Impaired kidney function was the only comorbid condition independently associated with increased all-cause mortality (HR (95% CI) 3.41 (1.47-7.93) p=0.004) and respiratory mortality (HR (95%CI) 4.63 (1.61 to 13.4), p = 0.005). In addition, age >= 70, BMI <22 and lower FEV1 expressed as %predicted were significantly associated with increased all-cause and respiratory mortality.Conclusion: In addition to the risk factors high age, low BMI and poor lung function; impaired kidney function appears to be an important risk factor for mortality in the long term, which should be taken into account in the medical care of patients with severe COPD.
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| 20. |
- Emma, Rosalia, et al.
(författare)
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Enhanced oxidative stress in smoking and ex-smoking severe asthma in the U-BIOPRED cohort
- 2018
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Ingår i: PLOS ONE. - : Public Library Science. - 1932-6203. ; 13:9
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Tidskriftsartikel (refereegranskat)abstract
- Oxidative stress is believed to be a major driver of inflammation in smoking asthmatics. The U-BIOPRED project recruited a cohort of Severe Asthma smokers/ex-smokers (SAs/ex) and non-smokers (SAn) with extensive clinical and biomarker information enabling characterization of these subjects. We investigated oxidative stress in severe asthma subjects by analysing urinary 8-iso-PGF(2 alpha) and the mRNA-expression of the main pro-oxidant (NOX2; NOSs) and anti-oxidant (SODs; CAT; GPX1) enzymes in the airways of SAs/ex and SAn. All the severe asthma U-BIOPRED subjects were further divided into current smokers with severe asthma (CSA), ex-smokers with severe asthma (ESA) and non-smokers with severe asthma (NSA) to deepen the effect of active smoking. Clinical data, urine and sputum were obtained from severe asthma subjects. A bronchoscopy to obtain bronchial biopsy and brushing was performed in a subset of subjects. The main clinical data were analysed for each subset of subjects (urine-8-iso-PGF(2 alpha); IS-transcriptomics; BB-transcriptomics; BBrtranscriptomics). Urinary 8-iso-PGF(2 alpha) was quantified using mass spectrometry. Sputum, bronchial biopsy and bronchial brushing were processed for mRNA expression microarray analysis. Urinary 8-iso-PGF(2 alpha) was increased in SAs/ex, median (IQR) = 31.7 (24.5 +/- 44.7) ng/mmol creatinine, compared to SAn, median (IQR) = 26.6 (19.6 +/- 36.6) ng/mmol creatinine (p< 0.001), and in CSA, median (IQR) = 34.25 (24.4 +/- 47.7), vs. ESA, median (IQR) = 29.4 (22.3 +/- 40.5), and NSA, median (IQR) = 26.5 (19.6 +/- 16.6) ng/mmol creatinine (p = 0.004). Sputum mRNA expression of NOX2 was increased in SAs/ex compared to SAn (probe sets 203922_PM_s_at fold-change = 1.05 p = 0.006; 203923_PM_s_at fold-change = 1.06, p = 0.003; 233538_PM_s_at fold-change = 1.06, p = 0.014). The mRNA expression of antioxidant enzymes were similar between the two severe asthma cohorts in all airway samples. NOS2 mRNA expression was decreased in bronchial brushing of SAs/ex compared to SAn (fold-change = -1.10; p = 0.029). NOS2 mRNA expression in bronchial brushing correlated with FeNO (Kendal's Tau = 0.535; p< 0.001). From clinical and inflammatory analysis, FeNO was lower in CSA than in ESA in all the analysed subject subsets (p< 0.01) indicating an effect of active smoking. Results about FeNO suggest its clinical limitation, as inflammation biomarker, in severe asthma active smokers. These data provide evidence of greater systemic oxidative stress in severe asthma smokers as reflected by a significant changes of NOX2 mRNA expression in the airways, together with elevated urinary 8-iso-PGF(2 alpha) in the smokers/ex-smokers group.
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