Specific Inhibition of the NLRP3 Inflammasome as an Anti-Inflammatory Strategy in Cystic Fibrosis.

Specific Inhibition of the NLRP3 Inflammasome as an Anti-Inflammatory Strategy in Cystic Fibrosis. Am J Respir Crit Care Med. 2019 Aug 27;: Authors: McElvaney OJ, Zaslona Z, Becker-Flegler K, Palsson-McDermott EM, Boland F, Gunaratnam C, Gulbins E, O'Neill LA, Reeves EP, McElvaney NG Abstract RATIONALE: Cystic fibrosis (CF) pulmonary disease is characterized by chronic infection with Pseudomonas aeruginosa and sustained neutrophil-dominant inflammation. The lack of effective anti-inflammatory therapies for people with CF (PWCF) represents a significant challenge. OBJECTIVES: To identify altered immunometabolism in the CF neutrophil, and investigate the feasibility of specific inhibition of the NLR family, pyrin domain-containing protein 3 (NLRP3) inflammasome as a CF anti-inflammatory strategy in vivo. METHODS: Key markers of increased aerobic glycolysis, known as a Warburg effect, including cytosolic pyruvate kinase M2 (PKM2), phosphorylated PKM2, succinate, HIF-1α, lactate and the interleukin (IL)-1β precursor pro-IL-1β, as well as caspase-1 activity and processing of pro-IL-1β to IL-1β by the NLRP3 inflammasome, were measured in neutrophils from blood and airway secretions from healthy controls (n=12), PWCF (n=16) and PWCF post-double-lung transplant (n=6). The effects of specific inhibition of NLRP3 on airway inflammation and bacterial clearance in a murine CF model were subsequently assessed in vivo. MAIN RES...
Source: American Journal of Respiratory and Critical Care Medicine - Category: Respiratory Medicine Authors: Tags: Am J Respir Crit Care Med Source Type: research

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AbstractThe contribution of T-cells after lung transplant (LTx) remains controversial with no current consensus of their role concerning chronic lung allograft dysfunction. Using flow cytometry to assess T-cell subsets of bronchoalveolar lavage fluid (BALF) in 16 cystic fibrosis (CF) LTx recipients, we identified a decline in CD4+ T-cell frequency and an increase in CD8+ T-cell frequency in patients who developed severe bronchiolitis obliterans syndrome (BOS) (N = 10) when comparing baseline (6 months post-LTx) and follow-up (most recent bronchoscopy—clinical or surveillance per protocol). Comparin...
Source: Lung - Category: Respiratory Medicine Source Type: research
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Source: OnMedica Latest News - Category: UK Health Source Type: news
Conclusion: BE accounts for 11,2% of all LTx done in our center, a distribution that is superior to ISHLT registry. Comparing to all LTx pts we recognize a good BE post-transplant outcome, with a similar survival rate at 1-year and even superior at 5-years. These results reinforce the need to referral pts with severe and end stage BE and supports the role of LTx as valuable treatment for this disease.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Transplantation Source Type: research
MUC5B polymorphism has been associated with an increased risk of IPF. Compared to the 9% found in controls, the minor allele was found in 34% of patients with familial IPF, in 38% of sporadic IPF. Recently, MUC5B has also been associated with chronic hypersensitivity pneumonitis (24.4-and 32.2 vs. 10.7%) and rheumatoid arthritis with interstitial lung disease (32.6 vs 10.9%).We retrospectively assessed MUC5B SNP (rs35705950) in all patients that underwent lung transplant between 1991 and 2015 in our hospital (n=746). We associated the incidence of the MUC5B minor allele with the underlying lung disease and post transplant ...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Idiopathic interstitial pneumonias Source Type: research
Conclusions: Of those patients deemed suitable for therapy, TLI was well tolerated with the majority of complications being minor and not leading to cessation of treatment. Therapy is associated with a significant slowing in the rate of decline in lung function impacting overall survival.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Transplantation Source Type: research
Introduction: Identification of risk factors that predict poor survival can aid clinical decision making and allow optimization of any potentially modifiable factors (Stephenson, A.L. et al. J Heart Lung Transplant 2015;34:1139–1145). This may facilitate improved patient selection and ultimately improve overall outcomes.Aims: To describe the Irish experience of co-morbidity post-transplant for cystic fibrosis and to investigate potential non-pulmonary pre-transplant risk factors that could impact on long term survival.Methods: We performed a retrospective review of all 61 patients who received a lung transplant for c...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Transplantation Source Type: research
Conclusions: The survival rate of CF patients after LTx in Norway is similar to internationally published data. LTx increases survival significantly compared to the observed survival on the waitlist and patients of intermediary risk seem to have the greatest survival benefit.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Transplantation Source Type: research
Conclusion: Not performing quality control of clinical MBW data may result in overestimation of LCI. We recommend prospective MBW quality control in the clinical setting.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Paediatric respiratory physiology and sleep Source Type: research
We report our 10-year experience in the use of NIV with regards to indications and outcomes.Methods: A retrospective analysis of data captured prospectively was performed. All patients started on NIV between 2008 and 2018 were included; lung transplant (LTX) recipients and those who received NIV for
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Cystic fibrosis Source Type: research
We report outcomes at 6 months after NIV initiation in adult patients attending a large CF centre.Methods: A retrospective analysis of data captured prospectively was performed. All episodes of NIV between 2008 and 2018 were included. Exclusion criteria were: use in lung transplant (LTx) recipients, use for
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Cystic fibrosis Source Type: research
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