Mary Ellen Kleinhenz

Airway Microbiota and Pathogen Abundance in Age- Stratified Cystic Fibrosis Patients

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.

Antireflux surgery for patients with end-stage lung disease before and after lung transplantation

BackgroundGastroesophageal reflux disease (GERD) is prevalent among patients with end-stage lung disease (ESLD). This disease can lead to microaspiration and may be a risk factor for lung damage before and after transplantation. A fundoplication is the best way to stop reflux, but little is known about the safety of elective antireflux surgery for patients with ESLD. This study aimed to report the safety of laparoscopic fundoplication for patients with ESLD and GERD before or after lung transplantation.MethodsBetween January 1997 and January 2007, 305 patients were listed for lung transplantation, and 189 patients underwent the procedure. In 2003, routine esophageal studies were added to the pretransplantation evaluation. After the authors’ initial experience, gastric emptying studies were added as well.ResultsA total of 35 patients with GERD or delayed gastric emptying were referred for surgical intervention. A laparoscopic fundoplication was performed for 32 patients (27 total and 5 partial). For three patients, a pyloroplasty also was performed. Two patients had a pyloroplasty without fundoplication. Of the 35 operations, 15 were performed before and 20 after transplantation. Gastric emptying of solids or liquids was delayed in 12 (92%) of 13 posttransplantation studies and 3 (60%) of 5 pretransplantation studies. All operations were completed laparoscopically, and 33 patients recovered uneventfully (94%). The median hospital length of stay was 2 days (range, 1–34 days) for the patients admitted to undergo elective operations. Hospitalization was not prolonged for the three patients who had fundoplications immediately after transplantation.ConclusionsThe results of this study show that laparoscopic antireflux surgery can be performed safely by an experienced multidisciplinary team for selected patients with ESLD before or after lung transplantation, and that gastric emptying is frequently abnormal and should be objectively measured in ESLD patients.

Lung transplantation in patients with connective tissue disorders and esophageal dysmotility.

Lung and esophageal dysfunction are common in patients with connective tissue disease (CTD). Recent reports have suggested a link between pathologic gastroesophageal reflux and bronchiolitis obliterans syndrome (BOS) after lung transplant. Because patients with CTD have a high incidence of esophageal dysmotility and reflux, this group may be at increased risk of allograft dysfunction after lung transplantation. Little is known about antireflux surgery in these patients. Our aims were to describe: (i) the esophageal motility and reflux profile of patients with CTD referred for lung transplantation; and (ii) the safety and outcomes of laparoscopic fundoplication in this group. A retrospective review of 26 patients with CTD referred for lung transplantation between July 2003 and June 2007 at a single center. Esophageal studies included manometry and ambulatory 24-h pH monitoring. Twenty-three patients had esophageal manometry and ambulatory 24-h pH monitoring. Nineteen patients (83%) had pathologic distal reflux and 7 (30%) also had pathologic proximal reflux. Eighteen patients (78%) had impaired or absent peristalsis. Eleven of 26 patients underwent lung transplantation. Ten patients are alive at a median follow-up of 26 months (range 3-45) and one has bronchiolitis obliterans syndrome-1. Six patients had a laparoscopic fundoplication, 1 before transplantation and 5 after. All fundoplication patients are alive at median follow-up of 25 months (range 19-45). In conclusion, esophageal dysmotility and reflux are common in CTD patients referred for lung transplant. For this group, laparoscopic fundoplication is safe in experienced hands.

Improving transition from paediatric to adult cystic fibrosis care: programme implementation and evaluation

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.

The Feasibility of Lung Transplantation in HIV-Seropositive Patients

RATIONALE HIV seropositivity has long been considered a contraindication to lung transplantation, primarily because of the potential risks of added immunosuppression. In the past decade, however, experience with kidney and liver transplantation in the setting of HIV infection, with achievement of satisfactory outcomes, has grown considerably. This promising development has created a need to reconsider this contraindication to lung transplantation. OBJECTIVES There is presently limited evidence upon which to base medical decision-making regarding lung transplantation in individuals with HIV infection. In our present study, we wished to extend the existing literature by reporting the outcomes of three individuals with HIV infection who underwent lung transplantation at two centers. METHODS We compiled data for a case series of three HIV-infected subjects undergoing lung transplantation at two centers. MEASUREMENTS AND MAIN RESULTS We reviewed medical records to investigate the effects of lung transplantation on the course of HIV infection, the development of HIV-related opportunistic infections or malignancies, the occurrence of lung transplant and HIV drug interactions, and the extent of acute rejection. Subject 1, who underwent transplantation for HIV-associated pulmonary arterial hypertension, experienced recalcitrant acute rejection requiring a lymphocyte-depleting agent with subsequent rapid development of bronchiolitis obliterans syndrome. Subjects 2 and 3, who underwent transplantation for idiopathic pulmonary fibrosis, experienced mild acute rejection but remain free from chronic rejection at 4 and 2 years after transplant, respectively. CONCLUSIONS Lung transplantation may be feasible for carefully selected patients in the setting of controlled HIV infection. On the basis of our experience with three patients, we caution that acute graft rejection may be more common in such patients.

Effect of Lung Transplantation on Health-Related Quality of Life in the Era of the Lung Allocation Score: A U.S. Prospective Cohort Study

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 to 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‐min walk test exercise capacity as predictors of HRQL change. Among 211 initial participants (92% of those eligible), LT improved HRQL by all 5 measures (p < 0.05) and all but SF12‐Mental Health improved by threefold 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.

Colonic Wall Redundancy at CT in Patients with Cystic Fibrosis

PURPOSE To describe the appearance, prevalence, and possible associations of colonic wall redundancy in patients with cystic fibrosis (CF). MATERIALS AND METHODS The institutional review board approved this HIPAA-compliant study. Abdominal computed tomographic (CT) images of 38 consecutive patients with CF and a control group of 38 consecutive potential renal donors were retrospectively identified. Three readers independently recorded presence and location of colonic wall redundancy and wall thickness of the ascending, transverse, and descending colon. Interobserver agreement for colonic wall redundancy was determined with the kappa statistic. Colonic wall thicknesses were compared between patient groups with the Student t test. Proportions of adult and pediatric patients with and those without colonic wall redundancy and prevalence of specific gene mutations were compared between groups with the Fisher exact test. CT findings were compared with radiologic reports and clinical records. RESULTS Each reviewer found colonic wall redundancy in 11 of 28 adults with CF but in none of the children with CF (P < .05 for each reviewer). There was excellent interobserver agreement for identification of colonic wall redundancy (kappa = 0.91, P < .001). Mean thickness of the wall of the ascending colon was significantly greater in patients with CF who had colonic wall redundancy (4.0 mm) than in those without this finding (1.8 mm, P < .05) or in control patients (1.2 mm, P < .05). Among adult patients with CF, DeltaF508 mutation was the predominant mutant allele in 10 of 13 patients with normal colons at CT, whereas more uncommon non-DeltaF508 mutations were seen in seven of 10 patients with colonic wall redundancy (P < .05). Asymptomatic colonic wall redundancy at CT was prospectively misinterpreted as acute colonic disease in five adult patients. CONCLUSION Proximal colonic wall redundancy is seen frequently in adults with CF and may be more common in those with non-DeltaF508 CFTR gene mutations. This finding provides a starting point for further investigation of the molecular basis of colonic phenotype in CF.

Improvement in patient-reported outcomes after lung transplantation is not impacted by the use of extracorporeal membrane oxygenation as a bridge to transplantation

Objective: Extracorporeal membrane oxygenation (ECMO) is increasingly used as a bridge to lung transplantation. The impact of preoperative ECMO on health‐related quality of life (HRQL) and depressive symptoms after lung transplantation remains unknown, however. Methods: In a single‐center prospective cohort study, we assessed HRQL and depressive symptoms before and at 3, 6, and 12 months after lung transplantation using the Short Form 12 Physical and Mental Component Scores (SF12‐PCS and SF12‐MCS), Airway Questionnaire 20‐Revised (AQ20R), EuroQol 5D (EQ5D), and Geriatric Depression Scale (GDS). Changes in HRQL were quantified by segmented linear mixed‐effects models controlling for age, sex, diagnosis, preoperative forced expiratory volume in 1 second, 6‐minute walk distance, and Lung Allocation Score. We compared changes in HRQL among subjects bridged with ECMO, subjects hospitalized but not on ECMO, and subjects called in for transplantation as outpatients. Results: Out of 189 subjects, 17 were bridged to transplantation with ECMO. In all groups, improvements in HRQL following lung transplantation exceeded the minimally clinically important difference using the SF12‐PCS, AQ20R, EQ5D, and GDS. HRQL defined by SF12‐MCS did not change after transplantation. Improvements were generally similar among the groups, except for EQ5D, which showed a trend toward less benefit in the outpatients, possibly due to their better HRQL before lung transplantation. Conclusions: Subjects ill enough to require ECMO as a bridge to lung transplantation appear to achieve similar improvements in HRQL and depressive symptoms as those who do not. It is reassuring to both providers and patients that lung transplantation provides substantial improvements in HRQL, even for those patients who are critically ill in the run up to transplantation.

Prolonged Barium-Impaction Ileus in Two Lung Transplant Recipients With Systemic Sclerosis: Case Report

Lung transplantation can be a life-saving measure for people with end-stage lung disease from systemic sclerosis. However, outcomes of lung transplantation may be compromised by gastrointestinal manifestations of systemic sclerosis, which can involve any part of the gastrointestinal tract. Esophageal and gastric disease can be managed by enteral feeding with the use of a gastrojejunal feeding tube. In this report, we describe the clinical courses of 2 lung transplant recipients with systemic sclerosis who experienced severe and prolonged barium-impaction ileus after insertion of a percutaneous gastrojejunal feeding tube.

Understanding the Pediatric and Adult Healthcare System: Adapting to Change

Differences in pediatric and adult healthcare systems often become apparent during the transition and transfer from pediatric- to adult-based care. Lack of disease-specific resources and lack of expertise in the adult healthcare system, along with the differences in approach to chronic disease management between the two systems, are often cited as barriers to successful transfer. This chapter examines the epidemiology of chronic disease in the transition-aged population and the etiologies of the differences seen between pediatrics and adult healthcare systems. Finally we discuss ways to mitigate percieved differences between the health systems to assist pediatric and adult health providers make the transfer process successful.