Cost-minimization analysis of treprostinil vs. epoprostenol as an alternate to oral therapy non-responders for the treatment of pulmonary arterial hypertension.

INTRODUCTION: Idiopathic pulmonary arterial hypertension (IPAH) is associated with substantial morbidity and mortality. Treprostinil was compared to epoprostenol for the economic impact of treating IPAH patients who failed or were not candidates for bosentan. METHODS: The model was a cost-minimization analysis, assuming clinical equivalence was achieved by proper dosing of both drugs, in terms of survival and surrogate measures. Two theoretical cohorts of 270 patients were treated with subcutaneous treprostinil and intravenous epoprostenol, and were evaluated over 3 years using a spreadsheet model. Annual survival rates were estimated for the cohorts so that at endpoint 114 (42%) patients survived in both groups. The model utilized resource valuation data for medication and supply costs from Medicare; hospital, consultation, surgical, and diagnostic procedural fees from North Carolina hospitals; and costs to treat adverse events from published sources. Costs were obtained from standard lists and were presented as 2003 US dollars, discounted at 3%. Sensitivity analyses were performed testing all model uncertainties. RESULTS: In the base case analysis, treprostinil demonstrated savings of 22,701 US dollars and 37,433 US dollars per patient over 1- and 3-year time horizons, respectively. The greatest savings came from reduced or minimal hospitalizations attributed to the dose titration and treatment of adverse events, such as sepsis, associated with epoprostenol and its delivery system. Probabilistic sensitivity analyses resulted in average 3-year cost-savings of 41,051 US dollars (Standard Deviation = 13,902 US dollars) per patient. CONCLUSIONS: By initiating and continuing treatment with treprostinil over a 3-year period, the economic burden associated with IPAH may be reduced compared to treatment with epoprostenol. The greatest saving with treprostinil was attributed to decreased sepsis.

Nocturnal hypoxemia is common in primary pulmonary hypertension.

STUDY OBJECTIVE: Unsuspected sleep-related respiratory events are common in patients with severe pulmonary disease. Sleep in patients with primary pulmonary hypertension (PPH) has not been studied (to our knowledge). The purpose of this study was to measure the prevalence of respiratory disturbances and nocturnal hypoxemia during the sleep of patients with PPH. SETTING: Tertiary-care referral hospital. DESIGN: Retrospective review. PATIENTS: Thirteen patients with PPH. MEASUREMENTS: All patients underwent a single-night comprehensive polysomnogram study. Patients who spent > 10% of the total sleep time with oxygen saturation by pulse oximetry (SpO(2)) at < 90% or who needed oxygen to maintain their SpO(2) level at > 90% were classified as nocturnal desaturators. Analysis was performed to determine which clinical variables (ie, demographics, body mass index, spirometry, diffusion capacity, right heart catheterization pressures, 6-min walk test, arterial blood gas levels, resting and walking SpO(2) levels, and polysomnogram variables) would predict nocturnal desaturation. Statistical significance was considered when p values were < 0.05. RESULTS: Of the 13 patients in the study, 10 (77%) were nocturnal desaturators. All patients had normal apnea indexes, but two had mild elevations of the hypopnea index (< 15 episodes per hour). Nocturnal desaturations occurred independently of apneas or hypopneas. Six patients who did not have O(2) titration during sleep spent > 25% of sleep time with SpO(2) < 90%. The mean (+/- SD) variables that were significantly different between desaturators (10 patients) and nondesaturators (3 patients) were FEV(1) (70.1 +/- 9.1% predicted vs 98.1 +/- 15.1% predicted, respectively; p = 0.002), resting PaO(2) (61.8 +/- 16.1 vs 90.3 +/- 2.3 mm Hg, respectively; p = 0.001), alveolar-arterial oxygen pressure difference (P[A-a]O(2)) (40.5 +/- 20.5 vs 12.2 +/- 7.2 mm Hg, respectively; p = 0.048), resting SpO(2) (91.6 +/- 5.4% vs 98.7 +/- 2.3%, respectively; p = 0.038), and walking SpO(2) (83.8 +/- 9.3% vs 95.3 +/- 1.2%, respectively; p = 0.002). The mean hemoglobin level was higher in the group of nocturnal desaturators than in the group of nondesaturators (10.43 +/- 0.31 vs 13.95 +/- 0.98 g/dL, respectively; p < 0.0001). CONCLUSION: Seventy-seven percent of patients with PPH have significant nocturnal hypoxemia that is unrelated to apneas and hypopneas. Nocturnal desaturation occurs more frequently in patients with higher P(A-a)O(2) values and lower FEV(1) values, resting arterial PaO(2) and SpO(2) values, and walking SpO(2) values.

Hypogammaglobulinemia in lung transplant recipients.

BACKGROUND: Infectious complications continue to represent a significant source of morbidity and mortality in lung transplant recipients. Identifying specific, remediable immune defects is of potential value. After one lung transplant patient with recurrent infections was noted to be severely hypogammaglobulinemic, a screening program for humoral immune defects was instituted. The objectives were to define the prevalence of hypogammaglobulinemia in lung transplant recipients, assess levels of antibody to specific pathogens, and correlate infectious disease outcomes and survival with immunoglobulin levels. METHODS: All lung transplant recipients followed at a single center between October 1996 and June 1999 underwent a posttransplant humoral immune status survey as part of routine posttransplant follow-up. This survey consists of total immunoglobulin levels (IgG, IgM, IgA), IgG subclasses (IgG1-4), and antibody titers to Pneumococcus, diphtheria, and tetanus. Since February 1997, this survey has been incorporated into the pretransplant evaluation as well. Humoral survey results for October 1996 through July 1999 were recorded, and clinical information on major infectious disease outcomes was obtained from chart reviews, discharge summaries, the Cleveland Clinic Unified Transplant Database, and review of all microbiological studies and pathology results for each patient. RESULTS: Of 67 patients with humoral immune surveys drawn posttransplant, 47 (70%) had IgG levels less than 600 mg/dl (normal 717-1410 mg/dl), of which 25 (37%) had IgG levels less than 400 mg/dl ("lowest IgG group") and 22 (33%) had IgG levels between 400 and 600 mg/dl ("moderately low IgG group"). A total of 20 patients (30%) had IgG levels of more than 600 mg/dl ("normal IgG group"). Infections that were significantly more common in the lowest IgG group, and more common in the moderately low IgG group than the normal IgG group, included: number of pneumonias (P=0.0006), bacteremias (P=0.02), total bacterial infections (P=0.002), tissue-invasive cytomegalovirus (P=0.01), invasive aspergillosis (P=0.001), total fungal infections (P=0.001), and total infections (P=0.006). Median hospital days per posttransplant year was significantly different in the three groups (11.0 vs. 7.4 vs. 2.8 days, P=0.0003.) Invasive aspergillosis occurred in 44% of the lowest IgG group, 9% of the moderately low IgG group, and 0% of the normal IgG group (P<0.001). Survival was poorest in the lowest IgG group and intermediate in the moderately low IgG group. IgG subclass deficiencies occurred in a variety of patterns. Hypogammaglobulinemic patients lacked protective responses to Pneumococcus in 14/47 (30%), diphtheria in 15%, and tetanus in 19%. In a group of 48 patients screened pretransplant, 90% had normal immunoglobulin levels. CONCLUSIONS: Hypogammaglobulinemia in lung transplant recipients is more common than has been previously recognized. An IgG level of less than 400 mg/dl identifies a group at extremely high risk of bacterial and fungal infections, tissue-invasive cytomegalovirus, and poorer survival. Immunoglobulin monitoring may offer an opportunity for intensive surveillance, tapering of immunosuppression, and preemptive therapy for infection.

Does the donor-recipient ABO blood group compatibility status predict subsequent lung transplantation outcomes?

BACKGROUND: The study was conducted to compare lung transplantation outcomes between ABO-identical (AI) and ABO-compatible (AC) recipients. METHODS: Charts of lung allograft recipients transplanted between February, 1990 and October, 1995 were reviewed. Standard triple-drug immunosuppression and general antimicrobial prophylaxis were provided. Surveillance spirometry was administered every three months. Flexible bronchoscopy (FB) with transbronchial biopsies (TBBs) were undertaken for clinical indications. Time to event analysis on acute (AR) and chronic (CR) rejection and actuarial survival were determined by Kaplan-Meier analysis. Cumulative curves were compared with a log rank test. Comparisons of age, maximum forced expiratory volume in one second (FEV1) in the single (SLT) and double (DLT) lung recipients, duration of intensive care unit and hospital stay were carried out using the Wilcoxon Rank Sum test. Gender, race, underlying diagnoses, cytomegalovirus (CMV) status and pulmonary reimplantation response (PRR) were compared by Chi-square or Fisher's exact test where appropriate. RESULTS: Of the 100 lung recipients (age = 42.5 +/- 13.4 years; M:F = 50:50), 64 were AI and 36 AC. Median follow-up was 22 (range = 0-78) months. Outcome did not differ significantly between the 2 groups in terms of intensive care unit and hospital stay, PRR incidence and grade, incidence and frequencies of AR, median time and grade of first AR, maximum FEV1 for SLT and DLT recipients, incidence of CR and survival at 12 months. CONCLUSIONS: As the donor supply remains limited, this could considerably simplify the logistics of future transplantation.