Are the enzymatic methods currently being used to measure bronchoalveolar lavage bile salt levels fit for purpose?

Background: Microaspiration after gastroesophageal reflux has been implicated in the chronic loss of allograft function in lung transplant patients. Bronchoalveolar lavage fluid (BALF) assessment for pepsin and bile salts is a common method to document reflux and aspiration. Clinically used methods for bile salt analysis include tandem mass spectrometry and diagnostic enzymatic kits designed to measure bile salts in serum.

The critical role of TAK1 in accentuated epithelial to mesenchymal transition in obliterative bronchiolitis after lung transplantation.

Therapies to limit or reverse fibrosis have proven unsuccessful, highlighting the need for a greater understanding of basic mechanisms that drive fibrosis and, in particular, the link between fibrosis and inflammation. It has been shown that pro-fibrotic transforming growth factor β1 (TGF-β1)-driven epithelial-to-mesenchymal transition (EMT) can be accentuated by tumor necrosis factor α (TNF-α). TGF-β-activated kinase 1 (TAK1) is activated by both TGF-β1 and TNF-α, activating both nuclear factor kappa-light-chain-enhancer of activated B cells and mitogen-activated protein kinase signaling pathways.

Is CFTR-delF508 really absent from the apical membrane of the airway epithelium?

Background: Understanding where mutant CFTR is localised in airway epithelia is essential in guiding the best therapeutic approach to correct the dysfunction of the CFTR protein. The widely held paradigm is that CF patients harbouring the commonest mutation, CFTR-delF508, trap CFTR within the endoplasmic reticulum and target it for degradation. However there are conflicting reports concerning expression and localisation of CFTR-delF508 in lung tissue.

Ceramide is increased in the lower airway epithelium of people with advanced cystic fibrosis lung disease.

Rationale: Ceramide accumulates in the airway epithelium of mice deficient in cystic fibrosis transmembrane conductance regulator, resulting in susceptibility to Pseudomonas aeruginosa infection and inflammation.

Objectives: To investigate quantitatively ceramide levels in the lower airway of people with cystic fibrosis compared with pulmonary hypertension, emphysema, and lung donors.

Methods: Immunohistochemistry was performed on the lower airway epithelium of explanted lungs (eight cystic fibrosis, emphysema, and pulmonary hypertension, respectively) and eight donor lungs using ceramide, neutrophil elastase, and myeloperoxidase antibodies.

Primary bronchial epithelial cell culture from explanted cystic fibrosis lungs.

Lung disease is responsible for more than 95% of morbidity and mortality in cystic fibrosis. The exact pathogenesis of cystic fibrosis lung disease remains poorly understood. Experimental models are therefore vital for use in research.

Azithromycin attenuates effects of lipopolysaccharide on lung allograft bronchial epithelial cells.

Background: The bronchial epithelium is a source of mediators that may play a role in the airway inflammation and remodeling of post-transplant obliterative bronchiolitis (OB). Traditional strategies have failed to have an impact on OB. Recent studies have suggested a role for azithromycin in managing the condition.

Simvastatin attenuates release of neutrophilic and remodeling factors from primary bronchial epithelial cells derived from stable lung transplant recipients.

Obliterative bronchiolitis (OB), the major cause of chronic lung allograft dysfunction, is characterized by airway neutrophilia, inflammation, and remodeling, with progressive fibroproliferation and obliteration of small airways that ultimately leads to patient death. Statins have potential anti-inflammatory effects and have been demonstrated to confer a survival advantage in lung transplant patients. We postulated that the beneficial effects of simvastatin in lung transplantation are in part due to inhibition of the epithelial production of key mediators of neutrophil chemotaxis, inflammation, and airway remodeling.

Pepsin, a biomarker of gastric aspiration in lung allografts: a putative association with rejection.

Rationale: Human lung transplantation is a therapeutic option for selected patients with advanced cardiopulmonary disease, but long-term survival is limited by chronic rejection. Persistent acute rejection and gastric aspiration have been implicated as risk factors but there is little or no evidence to date that they are associated.

Objectives: We have tested the hypothesis that pepsin, a marker of gastric aspiration, is present in lung transplant recipients, and that high levels are associated with biopsy-diagnosed acute rejection and/or bronchiolitis obliterans syndrome.

Anxiety in rheumatoid arthritis.

Objective: To examine the level of anxiety experienced by individuals with rheumatoid arthritis (RA).

Methods: Data from 2 previous studies were used to compare the level of anxiety (measured by the State-Trait Anxiety Inventory) in the following 4 subgroups: a general RA sample, a general osteoarthritis sample, a sample with both RA and major depression, and a normative sample of age-equivalent, working adults. Canonical correlations were used to examine associations between measures of anxiety and measures of both stress and depression.

Management of depression in rheumatoid arthritis: a combined pharmacologic and cognitive-behavioral approach.

Objective: To examine the effectiveness of cognitive-behavioral and pharmacologic treatment of depression in rheumatoid arthritis (RA).

Methods: Subjects (n = 54) with confirmed diagnoses of both major depression and RA were randomly assigned to 1 of 3 groups: 1) cognitive-behavioral/pharmacologic group (CB-PHARM), 2) attention-control/pharmacologic group, or 3) pharmacologic control group. Measures of depression, psychosocial status, health status, pain, and disease activity were collected at baseline, posttreatment (10 weeks), 6-month followup, and 15-month followup.