The Role of TGF‐β in the Association Between Primary Graft Dysfunction and Bronchiolitis Obliterans Syndrome

Primary graft dysfunction (PGD) is a possible risk factor for bronchiolitis obliterans syndrome (BOS) following lung transplantation; however, the mechanism for any such association is poorly understood. Based on the association of TGF‐β with acute and chronic inflammatory disorders, we hypothesized that it might play a role in the continuum between PGD and BOS. Thus, the association between PGD and BOS was assessed in a single‐center cohort of lung transplant recipients. Bronchoalveolar lavage fluid concentrations of TGF‐β and procollagen collected within 24 h of transplantation were compared across the spectrum of PGD, and incorporated into Cox models of BOS. Immunohistochemistry localized expression of TGF‐β and its receptor in early lung biopsies posttransplant. We found an association between PGD and BOS in both bilateral and single lung recipients with a hazard ratio of 3.07 (95% CI 1.76–5.38) for the most severe form of PGD. TGF‐β and procollagen concentrations were elevated during PGD (p < 0.01), and associated with increased rates of BOS. Expression of TGF‐β and its receptor localized to allograft infiltrating mononuclear and stromal cells, and the airway epithelium. These findings validate the association between PGD and the subsequent development of BOS, and suggest that this association may be mediated by receptor/TGF‐β biology.     

Developing a protocol to identify and prioritize research questions for psoriasis: a James Lind Alliance Priority Setting Partnership

Psoriasis is a common condition that affects over two million people in the UK and causes red, flaky patches of skin which can sometimes feel sore or itchy. People with psoriasis can be affected by their disease physically, emotionally and socially. There are many unanswered questions about psoriasis. To find out what the most important questions are, a Psoriasis Priority Setting Partnership PSP is being carried out now. The PSP involves patients, families, carers and healthcare professionals working together to follow a process outlined by the James Lind Alliance. The first step is for all groups with an interest in psoriasis to complete a survey about what they think the important research questions are. Survey responses are then checked against existing evidence. Questions raised in the surveys, but which have already previously been answered, will be shared with relevant organisations who may consider how this information can be better shared with clinicians, patients and their families. Questions raised in the surveys, which have not already been answered will be compiled into a list. This list will be sent round to stakeholders in a second survey where they will be ordered by importance. At a final workshop, a ‘top ten’ list of unanswered questions will be agreed by patients, their carers and health professionals. This ‘top ten’ list will be shared widely with psoriasis researchers and funders, to encourage research that focuses on tackling the key issues which really matter to patients, families, carers and healthcare professionals.     

Asymmetrical knowledge claims in general practice consultations with frequently attending patients: Limitations and opportunities for patient participation

Asymmetry of knowledge does not simply relate to knowing or not knowing. Participants in consultations also display normative entitlements to knowledge which are related to their identities in the interaction. Claims of entitlement to knowledge are oriented to by the other participant as either straightforwardly acceptable or problematic. Thus research has shown that asymmetry in doctor-patient interactions is collaboratively achieved.Whilst the asymmetry of medical consultations has long been recognised, understanding asymmetry in the context of patient participation is becoming an increasingly important priority. This paper is not concerned with potential benefits or the feasibility of increasing patient participation in general practice (GP) consultations. Rather it seeks to describe specific limitations and opportunities for the participation of patients regarding the discussion of their problems, treatments and management of illness.Using Conversation Analysis this paper investigates GP consultations with frequently attending patients in the UK. It describes how the moral dimensions of epistemic authority constrain the different conversational resources available to GPs and patients. Findings suggest that in maintaining asymmetrical claims to knowledge debate is foregone in favour of efficient progression through the phases of the interaction. Thus interactions militate against the discussion of areas where alignment of perspectives might be lacking and participants do not pursue actions which might lead towards claiming a greater understanding of each others' point of view. However, there are aspects of consultations with frequently attending patients which display reduced asymmetry with regard to participants' claims to epistemic authority.     

Voriconazole increases the risk for cutaneous squamous cell carcinoma after lung transplantation

Lung transplant recipients (LTR) are at high risk of cutaneous squamous cell carcinoma (SCC). Voriconazole exposure after lung transplant has recently been reported as a risk factor for SCC. We sought to study the relationship between fungal prophylaxis with voriconazole and the risk of SCC in sequential cohorts from a single center. We evaluated 400 adult LTR at UCLA between 7/1/2005 and 12/22/2012. On 7/1/2009, our center instituted a protocol switch from targeted to universal antifungal prophylaxis for at least 6 months post‐transplant. Using Cox proportional hazards models, time to SCC was compared between targeted (N = 199) and universal (N = 201) prophylaxis cohorts. Cox models were also used to assess SCC risk as a function of time‐dependent cumulative exposure to voriconazole and other antifungal agents. The risk of SCC was greater in the universal prophylaxis cohort (HR 2.02, P < 0.01). Voriconazole exposure was greater in the universal prophylaxis cohort, and the cumulative exposure to voriconazole was associated with SCC (HR 1.75, P < 0.01), even after adjustment for other important SCC risk factors. Voriconazole did not increase the risk of advanced tumors. Exposure to other antifungal agents was not associated with SCC. Voriconazole should be used cautiously in this population.