Delay and inequalities in the treatment of idiopathic pulmonary fibrosis : the case of two Nordic countries

Background: Idiopathic pulmonary fibrosis (IPF) is characterized by progressive loss of lung function with high mortality within the first 5 years from diagnosis. In 2011-2014, two drugs, pirfenidone and nintedanib, have been approved worldwide for prevention of IPF progression. National IPF-registries have been established in both Finland and Sweden. Our study explored potential differences in the care of IPF in these two countries. Methods: Patients included consecutively in the Finnish and Swedish IPF-registries from January 1, 2014 through December 31, 2016 were included in the study. Data on demographics and lung function at the time of inclusion were collected. Access to antifibrotic drugs and data on disease outcomes, mortality and the proportion of patients who underwent lung transplantation, was collected during a 3-year follow up. Results: One-hundred and fifty-two patients from the Finnish and 160 patients from the Swedish IPF-cohorts were included in the study. At inclusion, Finnish patients were significantly older than the Swedish patients (74.6 years vs 72.5 years, p = 0.017). The proportion of non-smokers was significantly higher in the Finnish cohort (41.7% vs 26.9%, p = 0.007). Forced vital capacity (FVC), % of predicted (78.2 vs 71.7 for Finnish and Swedish patients, respectively, p = 0.01) and diffusion capacity for carbon monoxide (DLCO), % of predicted (53.3 vs 48.2 for Finnish and Swedish patients, respectively, p = 0.002) were significantly higher in the Finnish cohort compared to the Swedish cohort at the time of inclusion. During the 3-year follow up period, 45 (29.6%) Finnish and 111 (69.4%) Swedish patients, respectively, were initiated on treatment with an antifibrotic drug (pirfenidone or nintedanib) (p <0.001). When comparing possible determinants of treatment, patients with higher FVC % were less likely to start antifibrotic drugs (OR 0.96, 95% CI 0.93-1.00, p <0.024). To be resident in Sweden was the main determinant for receiving antifibrotic drugs (OR 5.48, 95% CI 2.65-11.33, p <0.0001). No significant difference in number of deaths and lung transplantation during the follow up period was found. Conclusions: This study highlights differences concerning how IPF patients are treated in Finland and Sweden. How these differences will influence the long-term outcome of these patients is unknown.Peer reviewe

Magnetic Susceptibility As a Proxy for Investigating Microbially Mediated Iron Reduction

We investigated magnetic susceptibility (MS) variations in hydrocarbon contaminated sediments. Our objective was to determine if MS can be used as an intrinsic bioremediation indicator due to the activity of iron-reducing bacteria. A contaminated and an uncontaminated core were retrieved from a site contaminated with crude oil near Bemidji, Minnesota and subsampled for MS measurements. The contaminated core revealed enriched MS zones within the hydrocarbon smear zone, which is related to iron-reduction coupled to oxidation of hydrocarbon compounds and the vadose zone, which is coincident with a zone of methane depletion suggesting aerobic or anaerobic oxidation of methane is coupled to iron-reduction. The latter has significant implications for methane cycling. We conclude that MS can serve as a proxy for intrinsic bioremediation due to the activity of iron-reducing bacteria iron-reducing bacteria and for the application of geophysics to iron cycling studies

Cell Recovery in Bronchoalveolar Lavage Fluid in Smokers Is Dependent on Cumulative Smoking History

Background: Smoking is a risk factor for various lung diseases in which BAL may be used as a part of a clinical investigation. Interpretation of BAL fluid cellularity is however difficult due to high variability, in particular among smokers. In this study we aimed to evaluate the effect of smoking on BAL cellular components in asymptomatic smokers. The effects of smoking cessation, age and gender were also investigated in groups of smokers and exsmokers. Methods: We performed a retrospective review of BAL findings, to our knowledge the largest single center investigation, in our department from 1999 to 2009. One hundred thirty two current smokers (48 males and 84 females) and 44 ex-smokers (16 males and 28 females) were included. A group of 295 (132 males and 163 females) never-smokers served as reference. Result: The median [5–95 pctl] total number of cells and cell concentration in current smokers were 63.4 [28.6–132.1]610 6 and 382.1 [189.7–864.3]610 6 /L respectively and correlated positively to the cumulative smoking history. Macrophages were the predominant cell type (96.7 % [90.4–99.0]) followed by lymphocytes (2 % [0.8–7.7]) and neutrophils (0.6 % [0–2.9]). The concentration of all inflammatory cells was increased in smokers compared to never smokers and ex-smokers. BAL fluid recovery was negatively correlated with age (p,0.001). Smoking men had a lower BAL fluid recovery than smoking women. Conclusion: Smoking has a profound effect on BAL fluid cellularity, which is dependent on smoking history. Our results performed on a large group of current smokers and ex-smokers in a well standardized way, can contribute to bette

B7-H1-Deficiency Enhances the Potential of Tolerogenic Dendritic Cells by Activating CD1d-Restricted Type II NKT Cells

Background: Dendritic cells (DC) can act tolerogenic at a semi-mature stage by induction of protective CD4+ T cell and NKT cell responses. Methodology/Principal Findings: Here we studied the role of the co-inhibitory molecule B7-H1 (PD-L1, CD274) on semimature DC that were generated from bone marrow (BM) cells of B7-H12/2 mice and applied to the model of Experimental Autoimmune Encephalomyelitis (EAE). Injections of B7-H1-deficient DC showed increased EAE protection as compared to wild type (WT)-DC. Injections of B7-H12/2 TNF-DC induced higher release of peptide-specific IL-10 and IL-13 after restimulation in vitro together with elevated serum cytokines IL-4 and IL-13 produced by NKT cells, and reduced IL-17 and IFN-c production in the CNS. Experiments in CD1d2/2 and Ja2812/2 mice as well as with type I and II NKT cell lines indicated that only type II NKT cells but not type I NKT cells (invariant NKT cells) could be stimulated by an endogenous CD1d-ligand on DC and were responsible for the increased serum cytokine production in the absence of B7-H1. Conclusions/Significance: Together, our data indicate that BM-DC express an endogenous CD1d ligand and B7-H1 to ihibit type II but not type I NKT cells. In the absence of B7-H1 on these DC their tolerogenic potential to stimulate tolerogenic CD4+ and NKT cell responses is enhanced

VII Scandinavian Copd Research Symposium, Holmenkollen, Oslo 18th-19th November 2016

Peer reviewe

Salinity dependence of spectral induced polarization in sands and sandstones

International audienceIn electrolyte-saturated sands, the reversible storage of electrical charges is responsible for a phase lag between the current (injected and retrieved by two current electrodes) and the electrical field recorded by two voltage electrodes. This phenomenon is called 'spectral induced polarization' in geophysics and can potentially be used to monitor salt tracer tests in shallow aquifers to infer their permeability and dispersivity tensors. We demonstrate analytically that the polarization of the inner part of the electrical triple layer coating the surface of the grains (named the Stern layer in electrochemistry) is consistent with available data. We also perform new experiments using silica sands saturated by NaCl and CaCl2 pore water solutions. The salinity dependence of quadrature conductivity can be modelled using an analytical solution of the triple layer model, which offers a simple way to interpret laboratory and field data. This analytical solution depends on the total site density of the mineral surface, the pH value and the sorption coefficient of the cation in the Stern layer. This model shows that both the specific surface conductivity of the Stern layer and the quadrature conductivity of the porous material depend on the conductivity of the pore water. The quadrature conductivity is becoming independent of the salinity above 1 S m−1. The parameters entering the analytical model are consistent with independent estimates from titration data and zeta potential measurements, which are two classical methods to characterize the electrical triple layer at the pore water mineral interface

The pH dependence of spectral induced polarization of silica sands: Experiment and modeling

6p.International audienceIn electrolyte-saturated sands, the storage of electrical charges under an alternating electrical field (called "induced polarization") is responsible for a phase lag between the applied current and the resulting electrical field. Because a variety of polarization mechanisms exists in porous materials, the underlying physics of induced polarization is somehow unclear and the field data difficult to interpret quantitatively. Measurements at various pHs and salinities can be used to discriminate between different competing mechanisms at low frequencies (1 mHz-1 kHz) in porous media in the absence of electronic conductors. New experimental data point out that, in addition to the polarization of the Stern layer (the inner part of the electrical double layer coating the surface of the silica grains), there is another polarization mechanism possibly associated with a hopping process of the protons on the silica surface. We propose that such a process could follow a Grotthuss cooperation mechanism (as in ice) involving the bound water of the silica surface. Our data also rule out a mechanism based on the diffuse layer. The new polarization mechanism may be applied to quantifying induced-polarization data collected over acidic contaminant plumes

Artificial spider silk supports and guides neurite extension in vitro

Surgical intervention with the use of autografts is considered the gold standard to treat peripheral nerve injuries. However, a biomaterial that supports and guides nerve growth would be an attractive alternative to overcome problems with limited availability, morbidity at the site of harvest, and nerve mismatches related to autografts. Native spider silk is a promising material for construction of nerve guidance conduit (NGC), as it enables regeneration of cm-long nerve injuries in sheep, but regulatory requirements for medical devices demand synthetic materials. Here, we use a recombinant spider silk protein (NT2RepCT) and a functionalized variant carrying a peptide derived from vitronectin (VN-NT2RepCT) as substrates for nerve growth support and neurite extension, using a dorsal root ganglion cell line, ND7/23. Two-dimensional coatings were benchmarked against poly-d-lysine and recombinant laminins. Both spider silk coatings performed as the control substrates with regards to proliferation, survival, and neurite growth. Furthermore, NT2RepCT and VN-NT2RepCT spun into continuous fibers in a biomimetic spinning set-up support cell survival, neurite growth, and guidance to an even larger extent than native spider silk. Thus, artificial spider silk is a promising biomaterial for development of NGCs

A common model for the breathlessness experience across cardiorespiratory disease

Chronic breathlessness occurs across many different conditions, often independently of disease severity. Yet, despite being strongly linked to adverse outcomes, the consideration of chronic breathlessness as a stand-alone therapeutic target remains limited. Here we use data-driven techniques to identify and confirm the stability of underlying features (factors) driving breathlessness across different cardiorespiratory diseases. Questionnaire data on 182 participants with main diagnoses of asthma (21.4%), COPD (24.7%), heart failure (19.2%), idiopathic pulmonary fibrosis (18.7%), other interstitial lung disease (2.7%), and "other diagnoses" (13.2%) were entered into an exploratory factor analysis (EFA). Participants were stratified based on their EFA factor scores. We then examined model stability using 6-month follow-up data and established the most compact set of measures describing the breathlessness experience. In this dataset, we have identified four stable factors that underlie the experience of breathlessness. These factors were assigned the following descriptive labels: 1) body burden, 2) affect/mood, 3) breathing burden and 4) anger/frustration. Stratifying patients by their scores across the four factors revealed two groups corresponding to high and low burden. These two groups were not related to the primary disease diagnosis and remained stable after 6 months. In this work, we identified and confirmed the stability of underlying features of breathlessness. Previous work in this domain has been largely limited to single-diagnosis patient groups without subsequent re-testing of model stability. This work provides further evidence supporting disease independent approaches to assess breathlessness