| 1. |
|
|
| 2. |
|
|
| 3. |
- Östling, Jörgen, et al.
(författare)
-
IL-17-high asthma with features of a psoriasis immunophenotype
- 2019
-
Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 144:5, s. 1198-1213
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required.Objective: We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity.Methods: Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17–high and IL-13–high asthma phenotypes.Results: Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17–high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and β-defensin.Conclusion: The IL-17–high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.
|
|
| 4. |
|
|
| 5. |
- Shaw, DE, et al.
(författare)
-
Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort
- 2015
-
Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 46:5, s. 1308-1321
-
Tidskriftsartikel (refereegranskat)abstract
- U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach.This cross-sectional assessment of adults with severe asthma, mild/moderate asthma and healthy controls from 11 European countries consisted of analyses of patient-reported outcomes, lung function, blood and airway inflammatory measurements.Patients with severe asthma (nonsmokers, n=311; smokers/ex-smokers, n=110) had more symptoms and exacerbations compared to patients with mild/moderate disease (n=88) (2.5 exacerbations versus 0.4 in the preceding 12 months; p<0.001), with worse quality of life, and higher levels of anxiety and depression. They also had a higher incidence of nasal polyps and gastro-oesophageal reflux with lower lung function. Sputum eosinophil count was higher in severe asthma compared to mild/moderate asthma (median count 2.99% versus 1.05%; p=0.004) despite treatment with higher doses of inhaled and/or oral corticosteroids.Consistent with other severe asthma cohorts, U-BIOPRED is characterised by poor symptom control, increased comorbidity and airway inflammation, despite high levels of treatment. It is well suited to identify asthma phenotypes using the array of “omic” datasets that are at the core of this systems medicine approach.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Kiendler-Scharr, A., et al.
(författare)
-
Ubiquity of organic nitrates from nighttime chemistry in the European submicron aerosol
- 2016
-
Ingår i: Geophysical Research Letters. - 0094-8276. ; 43:14, s. 7735-7744
-
Tidskriftsartikel (refereegranskat)abstract
- In the atmosphere nighttime removal of volatile organic compounds is initiated to a large extent by reaction with the nitrate radical (NO3) forming organic nitrates which partition between gas and particulate phase. Here we show based on particle phase measurements performed at a suburban site in the Netherlands that organic nitrates contribute substantially to particulate nitrate and organic mass. Comparisons with a chemistry transport model indicate that most of the measured particulate organic nitrates are formed by NO3 oxidation. Using aerosol composition data from three intensive observation periods at numerous measurement sites across Europe, we conclude that organic nitrates are a considerable fraction of fine particulate matter (PM1) at the continental scale. Organic nitrates represent 34% to 44% of measured submicron aerosol nitrate and are found at all urban and rural sites, implying a substantial potential of PM reduction by NOx emission control.
|
|
| 9. |
|
|
| 10. |
- Tariq, K., et al.
(författare)
-
Sputum proteomic signature of gastro-oesophageal reflux in patients with severe asthma
- 2019
-
Ingår i: Respiratory Medicine. - : Saunders Elsevier. - 0954-6111 .- 1532-3064. ; 150, s. 66-73
-
Tidskriftsartikel (refereegranskat)abstract
- Gastro-oesophageal reflux disease (GORD) has long been associated with poor asthma control without an established cause-effect relationship. 610 asthmatics (421 severe/88 mild-moderate) and 101 healthy controls were assessed clinically and a subset of 154 severe asthmatics underwent proteomic analysis of induced sputum using untargeted mass spectrometry, LC-IMS-MSE. Univariate and multiple logistic regression analyses (MLR) were conducted to identify proteins associated with GORD in this cohort. When compared to mild/moderate asthmatics and healthy individuals, respectively, GORD was three-and ten-fold more prevalent in severe asthmatics and was associated with increased asthma symptoms and oral corticosteroid use, poorer quality of life, depression/anxiety, obesity and symptoms of sino-nasal disease. Comparison of sputum proteomes in severe asthmatics with and without active GORD showed five differentially abundant proteins with described roles in antimicrobial defences, systemic inflammation and epithelial integrity. Three of these were associated with active GORD by multiple linear regression analysis: Ig lambda variable 1-47 (p = 0.017) and plasma protease C1 inhibitor (p = 0.043), both in lower concentrations, and lipocalin-1 (p = 0.034) in higher concentrations in active GORD. This study provides evidence which suggests that reflux can cause subtle perturbation of proteins detectable in the airways lining fluid and that severe asthmatics with GORD may represent a distinct phenotype of asthma.
|
|
| 11. |
|
|
| 12. |
- Patoulias, D., et al.
(författare)
-
The role of organic condensation on ultrafine particle growth during nucleation events
- 2015
-
Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 15:11, s. 6337-6350
-
Tidskriftsartikel (refereegranskat)abstract
- A new aerosol dynamics model (DMANx) has been developed that simulates aerosol size/composition distribution and includes the condensation of organic vapors on nanoparticles through the implementation of the recently developed volatility basis set framework. Simulations were performed for Hyytiala (Finland) and Finokalia (Greece), two locations with different organic sources where detailed measurements were available to constrain the new model. We investigate the effect of condensation of organics and chemical aging reactions of secondary organic aerosol (SOA) precursors on ultrafine particle growth and particle number concentration during a typical springtime nucleation event in both locations. This work highlights the importance of the pathways of oxidation of biogenic volatile organic compounds and the production of extremely low volatility organics. At Hyytiala, organic condensation dominates the growth process of new particles. The low-volatility SOA contributes to particle growth during the early growth stage, but after a few hours most of the growth is due to semi-volatile SOA. At Finokalia, simulations show that organics have a complementary role in new particle growth, contributing 45% to the total mass of new particles. Condensation of organics increases the number concentration of particles that can act as CCN (cloud condensation nuclei) (N-100) by 13% at Finokalia and 25% at Hyytiala during a typical spring day with nucleation. The sensitivity of our results to the surface tension used is discussed.
|
|
| 13. |
- Riipinen, Ilona, et al.
(författare)
-
Connecting the solubility and CCN activation of complex organic aerosols : a theoretical study using solubility distributions
- 2015
-
Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 15:11, s. 6305-6322
-
Tidskriftsartikel (refereegranskat)abstract
- We present a theoretical study investigating the cloud activation of multicomponent organic particles. We modeled these complex mixtures using solubility distributions (analogous to volatility distributions in the VBS, i.e., volatility basis set, approach), describing the mixture as a set of surrogate compounds with varying water solubilities in a given range. We conducted Khler theory calculations for 144 different mixtures with varying solubility range, number of components, assumption about the organic mixture thermodynamics and the shape of the solubility distribution, yielding approximately 6000 unique cloud condensation nucleus (CCN)-activation points. The results from these comprehensive calculations were compared to three simplifying assumptions about organic aerosol solubility: (1) complete dissolution at the point of activation; (2) combining the aerosol solubility with the molar mass and density into a single effective hygroscopicity parameter kappa; and (3) assuming a fixed water-soluble fraction eff. The complete dissolution was able to reproduce the activation points with a reasonable accuracy only when the majority (70-80 %) of the material was dissolved at the point of activation. The single-parameter representations of complex mixture solubility were confirmed to be powerful semi-empirical tools for representing the CCN activation of organic aerosol, predicting the activation diameter within 10% in most of the studied supersaturations. Depending mostly on the condensedphase interactions between the organic molecules, material with solubilities larger than about 0.1-100 g L-1 could be treated as soluble in the CCN activation process over atmospherically relevant particle dry diameters and supersaturations. Our results indicate that understanding the details of the solubility distribution in the range of 0.1-100 g L-1 is thus critical for capturing the CCN activation, while resolution outside this solubility range will probably not add much information except in some special cases. The connections of these results to the previous observations of the CCN activation and the molecular properties of complex organic mixture aerosols are discussed. The presented results help unravel the mechanistic reasons behind observations of hygroscopic growth and CCN activation of atmospheric secondary organic aerosol (SOA) particles. The proposed solubility distribution framework is a promising tool for modeling the interlinkages between atmospheric aging, volatility and water uptake of atmospheric organic aerosol.
|
|
| 14. |
- van der Gon, Hacd, et al.
(författare)
-
Particulate emissions from residential wood combustion in Europe revised estimates and an evaluation
- 2015
-
Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 15:11, s. 6503-6519
-
Tidskriftsartikel (refereegranskat)abstract
- Currently residential wood combustion (RWC) is increasing in Europe because of rising fossil fuel prices but also due to climate change mitigation policies. However, especially in small-scale applications, RWC may cause high emissions of particulate matter (PM). Recently we have developed a new high-resolution (7 x 7 km) anthropogenic carbonaceous aerosol emission inventory for Europe. The inventory indicated that about half of the total PM2.5 emission in Europe is carbonaceous aerosol and identified RWC as the largest organic aerosol source in Europe. The inventory was partly based on national reported PM emissions. Use of this organic aerosol inventory as input for two chemical transport models (CTMs), PMCAMx and EMEP MSC-W, revealed major underestimations of organic aerosol in winter time, especially for regions dominated by RWC. Interestingly, this was not universal but appeared to differ by country. In the present study we constructed a revised bottom-up emission inventory for RWC accounting for the semivolatile components of the emissions. The revised RWC emissions are higher than those in the previous inventory by a factor of 2-3 but with substantial inter-country variation. The new emission inventory served as input for the CTMs and a substantially improved agreement between measured and predicted organic aerosol was found. The revised RWC inven-tory improves the model-calculated organic aerosol significantly. Comparisons to Scandinavian source apportionment studies also indicate substantial improvements in the modelled wood-burning component of organic aerosol. This suggests that primary organic aerosol emission inventories need to be revised to include the semivolatile organic aerosol that is formed almost instantaneously due to dilution and cooling of the flue gas or exhaust. Since RWC is a key source of fine PM in Europe, a major revision of the emission estimates as proposed here is likely to influence source-receptor matrices and modelled source apportionment. Since usage of biofuels in small combustion units is a globally significant source, the findings presented here are also relevant for regions outside of Europe.
|
|
