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.

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.

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

BACKGROUND: Gastroesophageal 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. METHODS: Between 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. RESULTS: A 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. CONCLUSIONS: The 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.

The diffusing capacity in adult cystic fibrosis.

The value of adjusting the diffusing capacity for the lung volume has been demonstrated in a large number of patients with other lung diseases but has not been validated in patients with cystic fibrosis (CF). Pulmonary function test results on a cohort of 52 adult CF patients were analyzed to determine whether the diffusing capacity of carbon monoxide by single breath method (DLCO(SB)) when adjusted for alveolar volume (V(A)%), correlated with the severity of pulmonary dysfunction. The DLCO(SB) remained within the reference range except in those with severe lung impairment (61.88 +/- 15.48%). DLCO(SB) has a significant (P < 0.05) positive correlation (0.70, 0.67, 048, 0.69 and 0.31, respectively) with measures of airflow limitation (FVC%, FEV1%, FEV1/FVC%, MVV%, and sGaw) and negative correlation (-0.36 and -0.21, respectively) with measures of air trapping (RV% and RV/TLC%). DLCO(SB)/V(A) remained above 100% of predicted despite worsening lung disease and did not correlate with other measures of lung function. On the other hand, the DLCO(SB) and DLCO(SB)/V(A), when adjusted for V(A)%, decreased and were significantly correlated with worsening airflow limitation and, to a lesser extent, air trapping. The relatively preserved adjusted DLCO(SB) and DLCO(SB)/V(A) values in CF patients up until late in its course may be explained the predominant airway involvement, minimal loss of alveolar-capillary units, and enhanced V/Q relationship due to claustration in CF.

Paradoxical embolization in an adult patient with cystic fibrosis.

To our knowledge, we describe the first reported case of paradoxical embolization via a patent foramen ovale (PFO) in an adult with moderately severe cystic fibrosis (CF) and advanced lung disease. Fluctuating neurologic symptoms and signs suggestive of cerebrovascular disease in an adult patient with advanced CF may be due to paradoxical embolization via a PFO. The possibility of a PFO should be considered before placement of a totally implantable venous access device to avert unnecessary risk of stroke in CF patients. Further study is needed to determine whether the use of a totally implantable venous access device increases the risk of paradoxical embolization in adult CF patients with a PFO.

Chronic ventilator dependence in elderly patients.

Long-term ventilator dependence is the need for mechanical ventilation for more than 6 h/d for more than 21 days. Long-term ventilator dependence complicates 9% to 20% of the episodes of mechanical ventilation treated in the intensive care units of acute care hospitals; it is associated with an average mortality rate of 40%. Unlike acute respiratory failure, the risk for which does not increase with age, long-term ventilator dependence falls disproportionately to patients aged 70 years or older. During the past 2 decades, a profusion of care sites for patients with long-term ventilator dependence has evolved, largely as the product of the prospective payment system for health services introduced by the Health Care Financing Administration in 1983. The outcome of long-term ventilator dependence in elderly patients across this health care continuum is addressed.

Deformation-induced ATP release from red blood cells requires CFTR activity.

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 microM) or niflumic acid (20 microM), 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.

Validity of three clinical performance assessments of internal medicine clerks.

PURPOSE: To analyze the construct validity of three methods to assess the clinical performances of internal medicine clerks. METHOD: A multitrait-multimethod (MTMM) study was conducted at the Case Western Reserve University School of Medicine to determine the convergent and divergent validity of a clinical evaluation form (CEF) completed by faculty and residents, an objective structured clinical examination (OSCE), and the medicine subject test of the National Board of Medical Examiners. Three traits were involved in the analysis: clinical skills, knowledge, and personal characteristics. A correlation matrix was computed for 410 third-year students who completed the clerkship between August 1988 and July 1991. RESULTS: There was a significant (p < .01) convergence of the four correlations that assessed the same traits by using different methods. However, the four convergent correlations were of moderate magnitude (ranging from .29 to .47). Divergent validity was assessed by comparing the magnitudes of the convergence correlations with the magnitudes of correlations among unrelated assessments (i.e., different traits by different methods). Seven of nine possible coefficients were smaller than the convergent coefficients, suggesting evidence of divergent validity. A significant CEF method effect was identified. CONCLUSION: 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.

Informed consent for blood transfusion as a transfusion medicine educational intervention.

The aim here was to determine the effectiveness of a transfusion medicine educational intervention in a medicine core clerkship program. Third-year medical students enrolled in their medicine core clerkship rotations at tertiary care hospitals affiliated with our institution underwent a two-part educational intervention that incorporated a transfusion medicine curriculum within the context of the medicolegal, ethical and educational elements of informed consent. Part one was a 1-h didactic session on standards of practice for red blood cell transfusion. Part two was a 90-min multidisciplinary workshop on informed consent. The effectiveness of the educational intervention was analysed by an objective structured clinical evaluation. The student group receiving the educational intervention scored significantly higher than in the comparison group (65.8 +/- 9.2 vs. 54.1 +/- 10.56, P < 0.001). When student scores were used to determine changes in student response patterns over time, the largest change occurred in identifying possible other options to allogeneic blood transfusion. These results suggest that a transfusion medicine curriculum using an informed consent model can be used effectively as an educational intervention in a medicine core clerkship programme.

Psychological factors in sarcoidosis: the relationship between life stress and pulmonary function.

Seventeen patients with diagnosed sarcoidosis were administered a number of psychological instruments to assess anxiety, depression, life stress, and symptoms of agoraphobia and/or panic. These patients were then followed medically for a period of nine months. Scores on the various psychological tests were then compared with results obtained from repeated pulmonary function tests. Results showed a consistent relationship between increased life stress at time one and impairment in lung function throughout the study period. In addition, no consistent set of psychiatric symptoms were associated with the disease. Sarcoid patients did, however, report many symptoms similar to patients with agoraphobia. These results are discussed in terms of the potential benefits of stress reduction treatment as an adjunctive therapy for patients with sarcoidosis.

Antigen responsiveness during tuberculosis: regulatory interactions of T cell subpopulations and adherent cells.

Previous studies from this laboratory demonstrated that adherent mononuclear cells selectively decreased in vitro tuberculin responses in some anergic patients with tuberculosis; subsequently this adherent suppressor cell was characterized as a monocyte. The current study of 41 patients with active pulmonary tuberculosis examined whether T cell subpopulations also acquired antigen-specific suppressor function during Mycobacterium tuberculosis infection, contributed to monocyte-mediated suppression of tuberculin responses, or both. Alteration in the numbers of circulating T-helper (Leu 3a) and T-suppressor (Leu 2a) cells was not observed in patients with tuberculosis, nor did Leu 2a cells selectively modulate in vitro tuberculin responses. The numbers of circulating T gamma cells, a subset of T cells identified by surface receptors for the Fc portion of IgG (Fc gamma R), was increased twofold in patients with active pulmonary tuberculosis. Depletion of T gamma cells from in vitro cell culture consistently and selectively increased tuberculin responsiveness of T cells from patients with tuberculosis. In addition, in the absence of T gamma cells, monocyte-mediated suppression of tuberculin responses was demonstrated in each patient observed. These studies demonstrate that during M. tuberculosis infection T gamma cells acquire antigen-specific suppressor cell activity and suggest that T gamma cells also contribution to immunoregulation modulating the expression of tuberculin-specific suppression by monocytes.

Immunohistologic identification of antigen-presenting cells in cutaneous sarcoidosis.

Considerable evidence exists to show that activated T lymphocytes preferentially accumulate at sites of disease activity in sarcoidosis. Langerhans cells, which can be recognized by reactivity with an antibody to the T6 antigen are thought to play a primary role in T-lymphocyte activation by the skin, a tissue frequently involved in sarcoidosis. This immunohistologic study examined the distribution of OKT6-positive cells and surface expression of HLA-DR antigen in cutaneous sarcoid lesions. Skin specimens stained with an anti-HLA-DR antibody demonstrated diffuse staining of the granulomas. In addition, keratinocytes, which do not normally express HLA-DR antigens, were found to stain with monoclonal antibody to HLA-DR in an intercellular pattern. Examination of specimens for OKT6-reactive Langerhans cells revealed significantly greater concentrations in the epidermis overlying sarcoidal granulomas (33 +/- 7 cells/mm) than in the epidermis of age-, sex-, and race-matched controls (11 +/- 3 cells/mm, p less than 0.001). Of greater importance was the demonstration that significant numbers of OKT6-positive cells were present within the dermal sarcoid granulomas (19-208/mm2) in a distribution that paralleled that of Leu-3a-positive T lymphocytes. These data suggest that the epidermis may participate in activation of lymphocytes in cutaneous sarcoidosis, and implicate OKT6-positive cells in granuloma formation.

Defective interleukin 2 production and responsiveness in human pulmonary tuberculosis.

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.

Increased interleukin-1 production and monocyte suppressor cell activity associated with human tuberculosis.

Interleukin-1 (IL-1) production by blood monocytes and blastogenesis produced by tuberculin purified protein derivative (PPD) in blood T lymphocytes were examined in patients with pulmonary tuberculosis. Monocytes were isolated from blood mononuclear cells by plastic adherence, and IL-1 activity was determined in the mouse thymocyte proliferation assay. Monocytes from patients with tuberculosis produced significantly higher activities of IL-1 than did those from healthy tuberculin reactors when stimulated with lipopolysaccharide (LPS) (patients, 56.1 +/- 20.0 U/ml; healthy control subjects, 7.3 +/- 1.7 U/ml; p less than 0.05) or PPD (patients, 28.1 +/- 7.2 U/ml; healthy control subjects, 9.5 +/- 2.9 U/ml; p less than 0.05). In contrast, PPD-induced blastogenic responses in peripheral blood mononuclear cells (PBMC) from the patients were lower than those from healthy subjects (patients, 4,506 +/- 1,145 cpm; healthy control subjects, 14,655 +/- 2,240 cpm; p less than 0.005), and IL-1 production by monocytes showed a positive correlation with monocyte suppressor activity for PPD-induced blastogenesis. Moreover, exogenous IL-1 was capable of suppressing antigen-induced blastogenesis of PBMC from healthy subjects. These data suggest that monocytes from patients with pulmonary tuberculosis are activated to produce or secrete increased levels of IL-1 and that IL-1 may be a mediator of suppressor cell function.

Immunoregulatory adherent cells in human tuberculosis: radiation-sensitive antigen-specific suppression by monocytes.

In human tuberculosis, adherent mononuclear cells (AMC) selectively depress in vitro responses to the mycobacterial antigen tuberculin purified protein derivative (PPD). The phenotype of this antigen-specific adherent suppressor cell was characterized by examining the functional activity of adherent cells after selective depletion of sheep erythrocyte-rosetting T cells or OKM1-reactive monocytes. Adherent cell suppression was studied in the [3H]thymidine-incorporation microculture assay by using T cells rigorously depleted of T cells with surface receptors for the Fc portion of IgG (T gamma cells) as antigen-responsive cells. PPD-induced [3H]thymidine incorporation by these non gamma T cells was uniformly reduced (mean, 42% +/- 10% [SD]) when autologous AMC were added to non gamma T cells at a ratio of 1:2. Antigen-specific suppression by AMC was not altered by depletion of sheep erythrocyte-rosetting T cells or treatment with indomethacin. However, AMC treated with OKM1 and complement or gamma irradiation (1,500 rads) no longer suppressed tuberculin responses in vitro. These studies identify the antigen-specific adherent suppressor cell in tuberculosis as an OKM1-reactive, non-erythrocyte-rosetting monocyte. The radiosensitivity of this monocyte immunoregulatory function may facilitate its further definition.

Bovine aortic endothelial cells elaborate an inhibitor of the generation of lipopolysaccharide-stimulated human blood monocyte procoagulant activity.

We examined the effect of bovine aortic endothelial cell culture supernatants upon the generation of procoagulant activity by human blood monocytes. Confluent endothelial monolayers were cultured for up to 96 h. At timed intervals, culture supernatants were collected and incubated for 5 h with lipopolysaccharide-stimulated human peripheral blood mononuclear cells. The procoagulant activity of mononuclear cell lysates was determined in a one-stage clotting assay. In five experiments, procoagulant activity with culture supernatant (time 0) was 2,294 +/- 761 U/ml (mean +/- SEM). Culture supernatants from endothelial cells incubated for 24-96 h strongly inhibited mononuclear cell generation of procoagulant activity. Indomethacin (10 microM) added to endothelial cells delayed the appearance of procoagulant inhibitor for 72 h. Bovine aortic smooth muscle cell culture supernatants did not inhibit procoagulant activity. The inhibitor was heat stable, effective at 1:50 dilution, soluble, and acid sensitive, with a molecular weight of less than 1,500. Further studies on subpopulations of mononuclear cells demonstrated that endothelial inhibitor selectively decreased the generation of monocyte procoagulant activity and interfered with T lymphocyte amplification of monocyte production of procoagulant activity. Thus, we have demonstrated that endothelial cells elaborate a potent inhibitor of monocyte procoagulant activity.