Bacterial communities in the airways of cystic fibrosis (CF) patients are, as in other ecological niches, influenced by autogenic and allogenic factors. However, our understanding of microbial colonization in younger versus older CF airways and the association with pulmonary function is rudimentary at best. Using a phylogenetic microarray, we examine the airway microbiota in age stratified CF patients ranging from neonates (9 months) to adults (72 years). From a cohort of clinically stable patients, we demonstrate that older CF patients who exhibit poorer pulmonary function possess more uneven, phylogenetically-clustered airway communities, compared to younger patients. Using longitudinal samples collected form a subset of these patients a pattern of initial bacterial community diversification was observed in younger patients compared with a progressive loss of diversity over time in older patients. We describe in detail the distinct bacterial community profiles associated with young and old CF patients with a particular focus on the differences between respective “early” and “late” colonizing organisms. Finally we assess the influence of Cystic Fibrosis Transmembrane Regulator (CFTR) mutation on bacterial abundance and identify genotype-specific communities involving members of the Pseudomonadaceae, Xanthomonadaceae, Moraxellaceae and Enterobacteriaceae amongst others. Data presented here provides insights into the CF airway microbiota, including initial diversification events in younger patients and establishment of specialized communities of pathogens associated with poor pulmonary function in older patient populations.

Recently, it was reported that rabbit and human red blood cells (RBCs) release ATP in response to mechanical deformation. Here we investigate the hypothesis that the activity of the cystic fibrosis transmembrane conductance regulator (CFTR), a member of the ATP binding cassette, is required for deformation-induced ATP release from RBCs. Incubation of rabbit RBCs with either of two inhibitors of CFTR activity, glibenclamide (10 μM) or niflumic acid (20 μM), resulted in inhibition of deformation-induced ATP release. To demonstrate the contribution of CFTR to deformation-induced ATP release from human RBCs, cells from healthy humans, patients with cystic fibrosis (CF), or patients with chronic obstructive lung disease (COPD) unrelated to CF were studied. RBCs of healthy humans and COPD patients released ATP in response to mechanical deformation. In contrast, deformation of RBCs from patients with CF did not result in ATP release. We conclude that deformation-induced ATP release from rabbit and human RBCs requires CFTR activity, suggesting a previously unrecognized role for CFTR in the regulation of vascular resistance.

Under the U.S. Lung Allocation Score (LAS) system, older and sicker patients are prioritized for lung transplantation (LT). The impact of these changes on health-related quality of life (HRQL) after transplant has not been determined. In a single-center prospective cohort study, from 2010–2016 we assessed HRQL before and repeatedly after LT for up to 3 years using the SF12-Physical and Mental Health, the respiratory-specific Airway Questionnaire 20-Revised, and the Euroqol 5D/Visual Analog Scale utility measures by multivariate linear mixed models jointly modeled with death. We also tested changes in LT-Valued Life Activities disability, BMI, allograft function, and 6-minute walk test exercise capacity as predictors of HRQL change. Amongst 211 initial participants (92% of those eligible), LT improved HRQL by all five measures (p<0.05) and all but SF12-Mental Health improved by three-fold or greater than the minimally clinically important difference. Compared to younger participants, those aged ≥65 improved less in SF12-Physical and Mental Health (p<0.01). Improvements in disability accounted for much of the HRQL improvement. In the LAS era, LT affords meaningful and durable HRQL improvements, mediated by amelioration of disability. Identifying factors limiting HRQL improvement in selected subgroups, especially those aged ≥65, are needed to maximize the net-benefits of LT.

Patients with newly diagnosed, pulmonary tuberculosis had a tuberculin-specific defect in IL-2 production. Mean PPD-induced IL-2 activity was 81.2% lower in patients as compared with healthy tuberculin reactors. PPD-induced expression of T cell IL-2 receptors was 5.9 times less in peripheral blood mononuclear cells of patients with tuberculosis as compared with healthy tuberculin reactors. Furthermore, purified IL-2 failed to correct PPD-induced blastogenesis in patients. Suppression by adherent cells was operative in one group of patients; adherent cell depletion increased their T cell production of IL-2 7.2-fold. A second group of patients with low IL-2 production did not have suppressor adherent cells and were clinically distinct, with more extensive disease on chest x ray. The basis for low IL-2 production in such individuals is unknown. Disordered regulation of IL-2 metabolism may be a key feature in the depressed cellular immune response of tuberculosis.

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Background The paradigm of cystic fibrosis (CF) care has changed as effective therapies extend the lives of patients well into adulthood. Preparing for and maintaining high quality CF care into the adult healthcare setting is critical for prolonged survival. Unfortunately, this transfer process from the paediatric to the adult CF centre is met with a variety of challenges. Objective and methods The objective of this quality improvement (QI) project was to develop, implement and evaluate a theory-based programme for transition from paediatric to adult CF care. In a multi-phase process, the paediatric and adult programmes developed a transition curriculum, addressed care standards and standardised patient transfer protocols. We evaluated the impact of this process through staff surveys, review of field notes from QI meetings, tracking transfers and responses of patients to the Transition Readiness Assessment Questionnaire (TRAQ) at the start of the programme and 18 months after initiation. Results The collaboration between the paediatric and adult teams continued through quarterly meetings over the past 4 years. This has provided a forum that sustained our transition programme, harmonised care across CF centres and addressed other needs of our CF centre. Discussion of transition with families in the paediatric centre increased twofold (35% to 73% p<0.001), and resulted in a trend towards improved patient TRAQ self-advocacy scores and decreased in-hospital transfer. Conclusions We successfully created a curriculum and process for transition from paediatric to adult CF care at our centres. This collaboration shapes the communication between our paediatric and adult CF care teams and enables ongoing feedback among patients, families and providers. The impact of our transition programme on long-term patient morbidity will require future evaluation.

There was convergent validity and some evidence of divergent validity with a significant method effect. The findings were similar for correlations corrected for attenuation. Four conclusions were reached: (1) the reliability of the OSCE must be improved, (2) the CEF ratings must be redesigned to further discriminate among the specific traits assessed, (3) additional methods to assess personal characteristics must be instituted, and (4) several assessment methods should be used to evaluate individual student performances.