Raised interferon β, type 3 interferon and interferon stimulated genes - evidence of innate immune activation in neutrophilic asthma.

BACKGROUND: Interferons play an important role in innate immunity. Previous studies report deficiency in virus-induction of interferon (IFN)-α, -β and -λ in bronchial epithelial and bronchial lavage cells in atopic asthmatics. It is now recognized that asthma is a heterogeneous disease comprising different inflammatory phenotypes, some of which may involve innate immune activation in the absence of overt infection. OBJECTIVE: The aim of the study was investigate if the severity of asthma or a specific cellular sputum pattern may be linked to evidence of innate immune activation. METHODS: Here we investigate the expression of IFN-β, IFN-λ1 (IL-29), IFN-λ2/3 (IL-28A/B) and the interferon-stimulated genes (ISGs) myxovirus resistance 1 (Mx1), oligoadenylate synthetase (OAS) and viperin in unstimulated sputum cells in 57 asthmatics (including 16 mild, 19 moderate and 22 severe asthma patients) and compared them with 19 healthy subjects. RESULTS: We observed increased expression of IFN-β, IFN-λ1/IL-29, OAS and viperin in asthmatic compared to healthy subjects while IL-28 was not expressed in any group. The overexpression was restricted to neutrophilic asthmatics (sputum neutrophils ≥ 76%) while eosinophilic asthmatics (sputum eosinophils ≥ 3%) did not differ from healthy subjects or even showed a lower expression of Mx1. No difference in interferon or ISG expression was seen according to clinical asthma severity. CONCLUSION AND CLINICAL RELEVANCE: Neutrophilic, but not eosinophilic, asthmatics display overexpression of IFN-β, IFN-λ1/IL-29 and ISGs in their sputum cells that may reflect ongoing innate immune activation. This article is protected by copyright. All rights reserved

Involuntary treatment in dementia care at home: Results from the Netherlands and Belgium

Aims and objectives: To gain insight into the request, use and associated factors of involuntary treatment in people with dementia (PwD) receiving professional home care in the Netherlands and Belgium. Background: Most of the PwD remain living at home as long as possible. Due to complex care needs, this can result in an increased risk for care provided against the wishes of the client and/or to which the client resists, referred to as involuntary treatment. Design: Secondary data analyses of two cross-sectional surveys. Methods: Dementia case managers and district nurses filled in a questionnaire for each PwD in their caseload. This study included data of 627 PwD receiving professional home care in the Netherlands and 217 in Belgium. The same methodology (questionnaire and variables) was used in both samples. Descriptive statistics and multi-level logistic regression analyses were used to analyse the data. The study adhered to the STROBE checklist. Results: More than half of the PwD (50.7%) living at home received involuntary treatment (Belgium 68.2% and the Netherlands 44.7%). Nonconsensual care (82.7%) was the most common, followed by psychotropic medication (40.7%) and physical restraints (18.5%). Involuntary treatment use was associated with living alone, greater ADL dependency, lower cognitive ability, higher family caregiver burden and receiving home care in Belgium versus the Netherlands. Involuntary treatment was most often requested by family caregivers. Conclusions: Involuntary treatment is often used in PwD, which is in line with previous findings indicating dementia as a risk factor for involuntary treatment use. More research is needed to gain insight into variations in prevalence across other countries, which factors influence these differences and what countries can learn from each other regarding prevention of involuntary treatment Relevance to clinical practice: To provide person-centered care, it is important to study ways to prevent involuntary treatment in PwD and to stimulate dialogue between professional and family caregivers for alternative intervention

Recent Surgical and Medical Advances in the Treatment of Dupuytren’s Disease - A Systematic Review of the Literature

Dupuytren’s disease (DD) is a type of fibromatosis which progressively results in the shortening and thickening of the fibrous tissue of the palmar fascia. This condition which predominantly affects white-northern Europeans has been identified since 1614. DD can affect certain activities of daily living such as face washing, combing hair and putting hand in a glove. The origin of Dupuytren’s contracture is still unknown, but there are a number of treatments that doctors have come across throughout the years. Historically surgery has been the mainstay treatment for DD but not the only one. The objective is to make a structured review of the most recent advances in treatment of DD including the surgical and medical interventions. We have looked at the most relevant published articles regarding the various treatment options for DD. This review has taken 55 articles into consideration which have met the inclusion criteria. The most recent treatments used are multi-needle aponeurotomy, extensive percutaneous aponeurotomy and lipografting, injecting collagenase Clostridium histolyticum, INF-gamma and shockwave therapy as well as radiotherapy. Each of these treatments has certain advantages and drawbacks and cannot be used for every patient. In order to prevent this condition, spending more time and money in the topic is required to reach better and more consistent treatments and ultimately to eradicate this disease

Disturbed Cytokine Production at the Systemic Level in Difficult-to-Control Atopic Asthma: Evidence for Raised Interleukin-4 and Decreased Interferon-gamma Release following Lipopolysaccharide Stimulation.

Background: Disturbed cytokine production is thought to govern inflammation in asthma, which, in its turn, may lead to uncontrolled disease. The aim of this study was to assess the relationship between cytokine production from blood leucocytes and the level of asthma control. Methods: We compared the production of interleukin (IL)-4, IL-6, IL-10, interferon (IFN)-gamma and tumour necrosis factor-alpha from peripheral blood leucocytes in non-atopic healthy subjects (n = 22), atopic non-asthmatics (n = 10), well-controlled asthmatics [Juniper asthma control questionnaire (ACQ) score /=1.5; n = 20). Fifty microlitres of peripheral blood was incubated for 24 h with RPMIc, lipopolysaccharide (LPS; 1 ng/ml) or phytohaemagglutinin (1 mug/ml), and cytokines were measured by immunotrapping (ELISA). Results: Both controlled and uncontrolled asthmatics as well as atopic non-asthmatics spontaneously produced more IL-4 than non-atopic healthy subjects (p < 0.001). IL-4 production induced by LPS was significantly greater (p < 0.05) in both asthma groups compared to atopic non-asthmatics and non-atopic healthy subjects. By contrast, IFN-gamma release induced by LPS was lower in uncontrolled asthmatics than in non-atopic healthy subjects (p < 0.05) and controlled asthmatics (p < 0.05). IL-10 release after LPS was greater in uncontrolled asthmatics than in atopic non-asthmatics (p < 0.05). No difference was observed regarding other cytokines. Conclusion: Blood cells from patients with difficult-to-control atopic asthma display highly skewed Th2 cytokine release following LPS stimulation

Blood Biomarkers in Idiopathic Pulmonary Fibrosis.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease of unknown origin whose incidence has been increasing over the latest decade partly as a consequence of population ageing. New anti-fibrotic therapy including pirfenidone and nintedanib have now proven efficacy in slowing down the disease. Nevertheless, diagnosis and follow-up of IPF remain challenging. METHODS: This review examines the recent literature on potentially useful blood molecular and cellular biomarkers in IPF. Most of the proposed biomarkers belong to chemokines (IL-8, CCL18), proteases (MMP-1 and MMP-7), and growth factors (IGBPs) families. Circulating T cells and fibrocytes have also gained recent interest in that respect. Up to now, though several interesting candidates are profiling there has not been a single biomarker, which proved to be specific of the disease and predictive of the evolution (decline of pulmonary function test values, risk of acute exacerbation or mortality). CONCLUSION: Large scale multicentric studies are eagerly needed to confirm the utility of these biomarkers

Lung function and airway inflammation monitoring after hematopoietic stem cell transplantation

SummaryBackgroundInduced sputum is a non-invasive method to investigate airway inflammation, which has been used to assess pulmonary inflammatory diseases. However, this procedure has not been studied in the context of hematopoietic stem cell transplantation (HSCT).MethodsWe monitored lung function in 182 patients who underwent HSCT and measured airway inflammation by sputum induction in 80 of them. We prospectively measured FEV1, FVC, DLCO, KCO, TLC, RV, exhaled nitric oxide (FeNO) as well as sputum cell counts before and 3, 6, 12, 24 and 36 months after HSCT.ResultsFor the whole cohort there was a progressive decrease in TLC, which was significant after 3 years (p < 0.01). By contrast, there was no change in other lung functions parameters or in FeNO. Baseline sputum analysis revealed increased neutrophil counts in patients {Median (IQR): 63% (38–79)} compared to healthy subjects matched for age {Median (IQR): 49% (17–67), p < 0.001} but there was no significant change in any type of sputum cell counts over the three years. When comparing myeloablative (MA) vs non-myeloablative (NMA) conditioning, falls in FEV1, FVC and DLCO, and rise in RV and sputum neutrophils were more pronounced over the first year of observation in those receiving MA.ConclusionsThere was a progressive loss in lung function after HSCT, featuring a restrictive pattern. Myeloablative conditioning was associated with early rise of sputum neutrophils and greater alteration in lung function over the first year