Exercise-based rehabilitation programmes for pulmonary hypertension.

BACKGROUND: Individuals with pulmonary hypertension (PH) have reduced exercise capacity and quality of life. Despite initial concerns that exercise training may worsen symptoms in this group, several studies have reported improvements in functional capacity and well-being following exercise-based rehabilitation. OBJECTIVES: To evaluate the benefits and harms of exercise-based rehabilitation for people with PH compared with usual care or no exercise-based rehabilitation. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 28 June 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in people with PH comparing supervised exercise-based rehabilitation programmes with usual care or no exercise-based rehabilitation. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. exercise capacity, 2. serious adverse events during the intervention period and 3. health-related quality of life (HRQoL). Our secondary outcomes were 4. cardiopulmonary haemodynamics, 5. Functional Class, 6. clinical worsening during follow-up, 7. mortality and 8. changes in B-type natriuretic peptide. We used GRADE to assess certainty of evidence. MAIN RESULTS: We included eight new studies in the current review, which now includes 14 RCTs. We extracted data from 11 studies. The studies had low- to moderate-certainty evidence with evidence downgraded due to inconsistencies in the data and performance bias. The total number of participants in meta-analyses comparing exercise-based rehabilitation to control groups was 462. The mean age of the participants in the 14 RCTs ranged from 35 to 68 years. Most participants were women and classified as Group I pulmonary arterial hypertension (PAH). Study durations ranged from 3 to 25 weeks. Exercise-based programmes included both inpatient- and outpatient-based rehabilitation that incorporated both upper and lower limb exercise. The mean six-minute walk distance following exercise-based rehabilitation was 48.52 metres higher than control (95% confidence interval (CI) 33.42 to 63.62; I² = 72%; 11 studies, 418 participants; low-certainty evidence), the mean peak oxygen uptake was 2.07 mL/kg/min higher than control (95% CI 1.57 to 2.57; I² = 67%; 7 studies, 314 participants; low-certainty evidence) and the mean peak power was 9.69 W higher than control (95% CI 5.52 to 13.85; I² = 71%; 5 studies, 226 participants; low-certainty evidence). Three studies reported five serious adverse events; however, exercise-based rehabilitation was not associated with an increased risk of serious adverse event (risk difference 0, 95% CI -0.03 to 0.03; I² = 0%; 11 studies, 439 participants; moderate-certainty evidence). The mean change in HRQoL for the 36-item Short Form (SF-36) Physical Component Score was 3.98 points higher (95% CI 1.89 to 6.07; I² = 38%; 5 studies, 187 participants; moderate-certainty evidence) and for the SF-36 Mental Component Score was 3.60 points higher (95% CI 1.21 to 5.98 points; I² = 0%; 5 RCTs, 186 participants; moderate-certainty evidence). There were similar effects in the subgroup analyses for participants with Group 1 PH versus studies of groups with mixed PH. Two studies reported mean reduction in mean pulmonary arterial pressure following exercise-based rehabilitation (mean reduction: 9.29 mmHg, 95% CI -12.96 to -5.61; I² = 0%; 2 studies, 133 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: In people with PH, supervised exercise-based rehabilitation may result in a large increase in exercise capacity. Changes in exercise capacity remain heterogeneous and cannot be explained by subgroup analysis. It is likely that exercise-based rehabilitation increases HRQoL and is probably not associated with an increased risk of a serious adverse events. Exercise training may result in a large reduction in mean pulmonary arterial pressure. Overall, we assessed the certainty of the evidence to be low for exercise capacity and mean pulmonary arterial pressure, and moderate for HRQoL and adverse events. Future RCTs are needed to inform the application of exercise-based rehabilitation across the spectrum of people with PH, including those with chronic thromboembolic PH, PH with left-sided heart disease and those with more severe disease.

Survival of Idiopathic Pulmonary Arterial Hypertension Patients in the Modern Era in Australia and New Zealand.

BACKGROUND: Epidemiology and treatment strategies continue to evolve in pulmonary arterial hypertension (PAH). We sought to define the characteristics and survival of patients with idiopathic, heritable and drug-induced PAH in the current management era. METHODS: Consecutive cases of idiopathic, heritable and drug-induced PAH were prospectively enrolled into an Australian and New Zealand Registry. RESULTS: Between January 2012 and December 2016, a total of 220 incident cases were enrolled (mean age 57.2±18.7years, female 69.5%) and followed for a median duration of 26 months (IQR17-39). Co-morbidities were common such as obesity (34.1%), systemic hypertension (30.5%), coronary artery disease (16.4%) and diabetes mellitus (19.5%). Initial combination therapy was used in 54 patients (dual, n=50; triple, n=4). Estimated survival rates at 1-year, 2-years and 3-years were 95.6% (CI 92.8-98.5%), 87.3% (CI 82.5-92.4%) and 77.0% (CI 70.3-84.3%), respectively. Multivariate analysis showed that male sex and lower 6-minute distance at diagnosis independently predicted worse survival, whereas obesity was associated with improved survival. Co-morbidities other than obesity did not impact survival. Initial dual oral combination therapy was associated with a trend towards better survival compared with initial oral monotherapy (adjusted HR=0.27, CI 0.06-1.18, p=0.082) CONCLUSIONS: The epidemiology and survival of patients with idiopathic PAH in Australia and New Zealand are similar to contemporary registries reported in Europe and North America. Male sex and poorer exercise capacity are predictive of mortality whereas obesity appears to exert a protective effect. Despite current therapies, PAH remains a life-threatening disease associated with significant early mortality.

Gas exchange responses during 6-min walk test in patients with pulmonary arterial hypertension.

BACKGROUND AND OBJECTIVE: The 6-min walk test (6MWT) is the most widely utilized method of assessing exercise capacity in pulmonary arterial hypertension (PAH). Cardiopulmonary exercise testing has the advantage of providing additional physiological information over 6MWT. The goals of our study were to describe the addition of gas exchange measurements to 6MWT and to determine how these parameters were related to the severity of PAH in three major subgroups of PAH (idiopathic (IPAH), connective tissue disease-related (CTPAH) and congenital heart disease-related (CHPAH)). METHODS: Seventy-six PAH patients (IPAH, n = 28; CTPAH, n = 24; CHPAH, n = 24) completed the 6MWT with simultaneous gas exchange measurements. The 6-min walk distance (6MWD), oxygen uptake ( V ˙ O2 ), carbon dioxide production ( V ˙ CO2 ), oxygen saturation, minute ventilation to carbon dioxide output ( V ˙ E / V ˙ CO2 ) and end-tidal partial pressure for carbon dioxide (PET CO2 ) were compared between subgroups, different functional classes (FCs) and pharmacotherapy. RESULTS: Whilst no significant difference in 6MWT was observed, absolute V ˙ O2 and V ˙ CO2 were higher for IPAH (P < 0.05). Differences were removed when V ˙ O2 and V ˙ CO2 were expressed relative to body mass (i.e. mL/kg/min). CHPAH had the most significant desaturation during 6MWT (CPAH: 73 ± 15%; CTPAH: 90 ± 8%, IPAH: 92 ± 8%, P < 0.01). There was no difference in V ˙ E / V ˙ CO2 and PET CO2 between groups; however, New York Health Association (NYHA) FC II performed better than FC III subjects in 6MWT with lower V ˙ E / V ˙ CO2 and higher end-exercise PET CO2 . Similarly, individuals on more advanced pharmacotherapy (triple therapy vs monotherapy) had poorer gas exchange during exercise. CONCLUSION: Whilst 6MWT and gas exchange did not differentiate between PAH groups, individuals with more severe disease and on more advanced pharmacotherapy had poorer gas exchange during exercise.

Exercise-based rehabilitation programmes for pulmonary hypertension.

BACKGROUND: Individuals with pulmonary hypertension (PH) have reduced exercise capacity and quality of life. Despite initial concerns that exercise training may worsen symptoms in this group, several studies have reported improvements in functional capacity and well-being following exercise-based rehabilitation in PH. OBJECTIVES: To assess the efficacy and safety of exercise-based rehabilitation for people with PH. Primary outcomes were exercise capacity, adverse events during the intervention period and health-related quality of life (HRQoL). Secondary outcomes included cardiopulmonary haemodynamics, functional class, clinical worsening during follow-up, mortality and changes in B-type natriuretic peptide. SEARCH METHODS: We searched the Cochrane Airways Specialised Register of Trials up to August 2016, which is based on regular searches of CINAHL, AMED, Embase, PubMed, MEDLINE, PsycINFO and registries of clinical trials. In addition we searched CENTRAL and the PEDro database up to August 2016 and handsearched relevant journals. SELECTION CRITERIA: All randomised controlled trials (RCTs) focusing on exercise-based rehabilitation programmes for PH. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data independently. For binary outcomes, we calculated odds ratios and their 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a random-effects model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. MAIN RESULTS: We included six RCTs and were able to extract data from five studies. The majority of participants were Group I pulmonary artery hypertension (PAH). Study duration ranged from three to 15 weeks. Exercise programmes included both inpatient- and outpatient-based rehabilitation that incorporated both upper and lower limb exercise. The mean six-minute walk distance following exercise training was 60.12 metres higher than control (30.17 to 90.07 metres, n = 165, 5 RCTs, low-quality evidence; minimal important difference was 30 metres), the mean peak oxygen uptake was 2.4 ml/kg/minute higher (1.4 to 3.4 ml/kg/min, n = 145, 4 RCTs, low-quality evidence) and the mean peak power in the intervention groups was 16.4 W higher (10.9 to 22.0 higher, n = 145, 4 RCTs, low-quality evidence). The mean change in HRQoL for the SF-36 physical component score was 4.63 points higher (0.80 to 8.47 points, n = 33, 2 RCTs, low-quality evidence) and for the SF-36 mental component score was 4.17 points higher (0.01 to 8.34 points; n = 33; 2 RCTs, low-quality evidence). One study reported a single adverse event, where a participant stopped exercise training due to lightheadedness. AUTHORS' CONCLUSIONS: In people with PH, exercise-based rehabilitation results in clinically relevant improvements in exercise capacity. Exercise training was not associated with any serious adverse events. Whilst most studies reported improvements in HRQoL, these may not be clinically important. Overall, we assessed the quality of the evidence to be low. The small number of studies and lack of information on participant selection makes it difficult to generalise these results across the spectrum of people with PH.

Successful use of pre and post-operative ECMO for pulmonary endarterectomy, mitral valve replacement and myomectomy in a patient with chronic thromboembolic pulmonary hypertension and hypertrophic cardiomyopathy.

As a salvage strategy, extracorporeal membrane oxygenation (ECMO) permits the recovery of end-organ perfusion, whilst allowing the surgeon time for patient reassessment and surgical planning. We report upon the first known case in which VA ECMO was instituted as peri-operative supportive therapy for a young patient, in-extremis, with surgically correctable Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Hypertrophic Cardiomyopathy (HOCM).

Retrospective Validation of the REVEAL 2.0 Risk Score With the Australian and New Zealand Pulmonary Hypertension Registry Cohort.

BACKGROUND: Pulmonary arterial hypertension (PAH) prognosis has improved with targeted therapies; however, the long-term outlook remains poor. Objective multiparametric risk assessment is recommended to identify patients at risk of early morbidity and mortality, and for optimization of treatment. The US Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) 2.0 risk score is a new model proposed for the follow-up of patients with PAH but has not been externally validated. METHODS: The REVEAL 2.0 risk score was applied to a mixed prevalent and incident cohort of patients with PAH (n = 1,011) from the Pulmonary Hypertension Society of Australia and New Zealand (PHSANZ) Registry. Kaplan-Meier survival was estimated for each REVEAL 2.0 risk score strata and for a simplified three-category (low, intermediate, and high risk) model. Sensitivity analysis was performed on an incident-only cohort. RESULTS: The REVEAL 2.0 model effectively discriminated risk in the large external PHSANZ Registry cohort, with a C statistic of 0.74 (both for full eight-tier and three-category models). When applied to incident cases only, the C statistic was 0.73. The three-category REVEAL 2.0 model demonstrated robust separation of 12- and 60-month survival estimates (all risk category comparisons P < .001). Although the full eight-tier REVEAL 2.0 model separated patients at low, intermediate, and high risk, survival estimates overlapped within some of the intermediate- and high-risk strata. CONCLUSIONS: The REVEAL 2.0 risk score was validated in a large external cohort from the PHSANZ Registry. The REVEAL 2.0 model can be applied for risk assessment of patients with PAH at follow-up. The simplified three-category model may be preferred for clinical use and for future comparison with other prognostic models.

Human metapneumovirus in lung transplant recipients and comparison to respiratory syncytial virus.

RATIONALE: Human metapneumovirus is a newly described virus isolated in 2001 from children with acute respiratory viral infection. It has subsequently been reported globally, although there are limited data in lung transplant recipients. OBJECTIVES: To prospectively analyze whether human metapneumovirus was circulating in our adult lung transplant community and assess the morbidity of this infection and to compare the clinical presentation and outcome after intravenous ribavirin of human metapneumovirus with that of respiratory syncytial virus (RSV). METHODS: Lung transplant patients with clinical features of respiratory viral infection underwent nasopharyngeal aspirates. Patients with a positive specimen for RSV or human metapneumovirus by reverse transcriptase-polymerase chain reaction analysis and graft dysfunction received intravenous ribavirin and pulse steroid therapy. MEASUREMENTS AND MAIN RESULTS: Eighty-nine patients had 199 visits for aspirate studies. A viral cause was determined for 62 visits in 47 patients (19 human metapneumovirus, 18 RSV, 13 parainfluenza, 9 influenza A, 2 adenovirus, and 1 influenza B). A significant percentage of patients with metapneumovirus (63%) and RSV (72%) developed graft dysfunction, with average declines in FEV(1) of 30 +/- 12.4% and 25.9 +/- 11.2%, respectively. In these patients, bronchiolitis obliterans syndrome onset or progression occurred in no patients with human metapneumovirus compared with 5 of 13 (38%) patients with RSV at 6 months. CONCLUSIONS: Human metapneumovirus is a leading cause of acute respiratory tract illness in lung transplant recipients. The incidence and clinical spectrum at presentation are similar to RSV, although the latter seems to be associated with a higher risk of chronic rejection. We recommend testing of nasopharyngeal aspirates for human metapneumovirus with polymerase chain reaction to assess local epidemiologic patterns.

Prognostic value of right ventricular free wall strain in pulmonary hypertension patients with pseudo-normalized tricuspid annular plane systolic excursion values.

Pulmonary hypertension (PH) is a progressively fatal disease having a significant impact on right ventricular (RV) function, a major determinant of long-term outcome in PH patients. In our clinic we frequently noticed the combination of PH and reduced RV function, but with discordant Tricuspid Annular Plane Systolic Excursion (TAPSE) values. The present study focuses on whether RV free wall strain measured using 2-dimensional speckle-tracking echocardiography is able to predict mortality in this subgroup of PH patients. 57 patients with PH and RV dysfunction (visual echocardiographic assessment of ≥2) and pseudo-normalized TAPSE values (defined as ≥16 mm) were retrospectively evaluated. Patients were divided by RV free -20 % as cut-off value. Follow-up data on all-cause mortality were registered after a median follow-up time of 27.9 ± 1.7 months. RV free of ≥-20 % was predictive of all-cause mortality after a median follow-up time of 27.9 ± 1.7 months (HR 3.76, 95 % CI 1.02-13.92, p = 0.05). RV free ≥-20 % remained a significant predictor of all-cause mortality (HR 4.30, 95 % CI 1.11-16.61, p = 0.04) after adjusting for PH-specific treatment. On the contrary, TAPSE was not a significant predictor of all-cause mortality. RV free wall strain provides prognostic information in patients with PH and RV dysfunction, but with normal TAPSE values. Future studies with larger cohorts, longer follow-up periods and inclusion of more echocardiographic parameters measuring LV and RV function could confirm the strength of RV free ≥-20 % as a predictor of mortality for this subgroup of patients with PH.

RETRACTED: Right to left ventricular volume ratio: A novel marker of disease severity in chronic thromboembolic pulmonary hypertension.

[This retracts the article DOI: 10.1016/j.ijchv.2013.10.001.].

Time from symptoms to definitive diagnosis of idiopathic pulmonary arterial hypertension: The delay study.

Survival rates for patients with idiopathic pulmonary arterial hypertension (IPAH) have improved with the introduction of PAH-specific therapies. However, the time between patient-reported onset of symptoms and a definitive diagnosis of IPAH is consistently delayed. We conducted a retrospective, multi-center, descriptive investigation in order to (a) understand what factors contribute to persistent diagnostic delays, and (b) examine the time from initial symptom onset to a definitive diagnosis of IPAH. Between January 2007 and December 2008, we enrolled consecutively diagnosed adults with IPAH from four tertiary referral centers in Australia. Screening of patient records and "one-on-one" interviews were used to determine the time from patient-described initial symptoms to a diagnosis of IPAH, confirmed by right heart catheterization (RHC). Thirty-two participants (69% female) were studied. Mean age at symptom onset was 56 ± 16.4 years and 96% reported exertional dyspnea. Mean time from symptom onset to diagnosis was 47 ± 34 months with patients subsequently aged 60 ± 17.3 years. Patients reported 5.3 ± 3.8 GP visits and 3.0 ± 2.1 specialist reviews before being seen at a pulmonary hypertension (PH) center. Advanced age, number of general practitioner (GP) visits, heart rate, and systolic blood pressure at the time of diagnosis were significantly associated with the observed delay. We found a significant delay of 3.9 years from symptom onset to a diagnosis of IPAH in Australia. Exertional dyspnea is the most common presenting symptom. Current practice within Australia does not appear to have the specific capacity for timely, multi-factorial evaluation of breathlessness and potential IPAH.

An Australian tertiary referral center experience of the management of chronic thromboembolic pulmonary hypertension.

The objective of this study was to report the outcome of pulmonary endarterectomy (PEA) surgery performed for chronic thromboembolic pulmonary hypertension (CTEPH) at a single tertiary center. The prospective study consisted of 35 patients with surgically amenable CTEPH undergoing PEA between September 2004 and September 2010. The main outcome measures were Functional (New York Heart Association [NYHA] class, 6-Minute Walk Distance), hemodynamic (echocardiography, right heart catheterization, and cardiac MRI), and outcome data (morbidity and mortality). Following PEA, there were significant improvements in NYHA class (pre 2.9±0.7 vs. post 1.3±0.5, P < 0.0001), right ventricular systolic pressure (pre 77.4±24.8 mmHg vs. post 45.1±24.9 mmHg, P = 0.0005), 6-Minute Walk Distance (pre 419.6±109.4 m vs. post 521.6±83.5 m, P = 0.0017), mean pulmonary artery pressure (pre 41.8±15.3 mmHg vs. post 24.7±8.8 mmHg, P = 0.0006), and cardiac MRI indices (end diastolic volume pre 213.8±49.2 mL vs. post 148.1±34.5 mL, P < 0.0001; ejection fraction pre 40.7±9.8 mL vs. post 48.1±8.9 mL, P = 0.0069). The mean cardiopulmonary bypass time was 258.77±26.16 min, with a mean circulatory arrest time of 43.83±28.78 min, a mean ventilation time of 4.7±7.93 days (range 0.2-32.7), and a mean intensive care unit stay of 7.22±8.71 days (range 1.1-33.8). Complications included reperfusion lung injury (20%), persistent pulmonary hypertension (17.1%), slow respiratory wean (25.7%), pericardial effusion (11.4%), and cardiac tamponade (5.7%). 1-year mortality post-procedure was 11.4%. Pulmonary endarterectomy can be performed safely with relatively low mortality.

Oral treprostinil for the treatment of pulmonary arterial hypertension in patients on background endothelin receptor antagonist and/or phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C study): a randomized controlled trial.

BACKGROUND: Infused and inhaled treprostinil are effective for treatment of pulmonary arterial hypertension (PAH), although their administration routes have limitations. This study assessed the efficacy and safety of bid oral sustained-release treprostinil in the treatment of PAH with a concomitant endothelin receptor antagonist (ERA) and/or phosphodiesterase type 5 inhibitor. METHODS: A 16-week, multicenter, double-blind, placebo-controlled study was conducted in 350 patients with PAH randomized to placebo or oral treprostinil. All patients were stable on background ERA, PDE-5 inhibitor, or both. Primary end point was Hodges-Lehmann placebo-corrected median difference in change from baseline 6-min walk distance (6MWD) at week 16. Secondary end points included time to clinical worsening, change in World Health Organization functional class, Borg dyspnea score, and dyspnea fatigue index score. RESULTS: Thirty-nine patients (22%) receiving oral treprostinil and 24 patients (14%) receiving placebo discontinued the study. Placebo-corrected median difference in change from baseline 6MWD at week 16 was 11 m (P = .07). Improvements in dyspnea fatigue index score (P = .01) and combined 6MWD and Borg dyspnea score (P = .01) were observed with oral treprostinil vs placebo treatment. Patients who achieved a week-16 bid oral treprostinil dose of 1.25 to 3.25 mg and 3.5 to 16 mg experienced a greater change in 6MWD (18 m and 34 m, respectively) than patients who achieved a bid dose of < 1 mg or discontinued because of adverse events (4 m). CONCLUSIONS: The primary end point of improvement in 6MWD at week 16 did not achieve significance. This study enhanced understanding of oral treprostinil titration and dosing, which has set the stage for additional studies. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00325442; URL: www.clinicaltrials.gov.

A novel approach to the assessment of lymphocytic bronchiolitis after lung transplantation--transbronchial brush.

BACKGROUND: Lymphocytic bronchiolitis (LB) is the strongest risk factor for subsequent allograft loss due to bronchiolitis obliterative syndrome (BOS); however, it is poorly assessed by transbronchial biopsy (TBBx) because of sampling error, interpretation error and the presence of non-alloimmune airway inflammation. We hypothesized that flow cytometric evaluation of bronchiolar brushings (transbronchial brush, TBBr) may be a better approach. METHODS: Transbronchial brushings (2 to 3 cm from the pleural surface under radiologic guidance) were obtained prior to TBBx in 32 patients and analyzed by flow cytometry. We assessed the proportion of nucleated cells that were CD3(+)CD103(+) (epithelial-specific T cells). RESULTS: No adverse events occurred; 0.5% (0.27 to 0.84) of the cells were epithelial-specific T cells and numbers increased with episodes of Grade A1 rejection (p < 0.01) and in patients with BOS (p = 0.02). Viral and invasive fungal infection were associated with marked infiltration with CD103(-) T cells (p < 0.01). CONCLUSION: TBBr is simple to obtain, low risk, quantitative, and can discriminate between infective and alloimmune LB. It may be a valuable addition to current lung allograft assessment.

Oil red O stain of alveolar macrophages is an effective screening test for gastroesophageal reflux disease in lung transplant recipients.

BACKGROUND: Gastroesophageal reflux disease (GORD) and microaspiration may be associated with acute graft dysfunction and development of obliterative bronchiolitis (OB) after lung transplantation. The "gold standard" for diagnosis of GORD is the 24-hour esophageal pH-monitoring study, although no simple, non-invasive screening test is routinely employed. Oil red O staining of alveolar macrophages in bronchoalveolar lavage (BAL) fluid identifies exogenous lipid and may be a surrogate marker for microaspiration. In this study we aimed to assess the utility of the lipid index in identifying patients with significant GORD. METHODS: Our investigation was a prospective analysis of 34 lung transplant patients who were transplanted between April 1999 and July 2006 at a single institution. All patients with recurrent respiratory infections, recurrent acute rejection, unexplained graft dysfunction or newly diagnosed OB had Oil red O staining of alveolar macrophages on BAL specimens at bronchoscopy and 24-hour esophageal pH monitoring. A quantitative assessment called the lipid index was performed resulting in a score from 0 to 400. Abnormal 24-hour pH studies were defined as acid exposure >3.4% in the distal and/or >1% in the proximal esophageal site. RESULTS: Thirty-four patients with a mean age 36.1 years and mean post-operative day of 571 +/- 648 had lipid indices of 143 +/- 94 (range 3 to 341). Twenty-four-hour pH studies revealed a distal mean of 16.1 +/- 6.2% and proximal mean of 6.4 +/- 3.7%. A lipid index >150 was 82.3% sensitive and 76.4% specific for an abnormal 24-hour pH result. Foreign material present on cytology of bronchial fluid seen in 28% of patients showed poor correlation with Oil red O stains and pH studies. CONCLUSIONS: The lipid index is an effective, non-invasive screening test that provides direct evidence of esophageal aspiration. Patients with high positive results should proceed to surgical assessment for Nissen fundoplication.

Unexplained chronic anemia and leukopenia in lung transplant recipients secondary to parvovirus B19 infection.

Parvovirus B19 (PVB) is a non-enveloped, single-stranded DNA virus of the Parvoviridae family pathogenic to humans. Despite numerous case reports of pure red cell aplasia in lung transplant (LT) recipients after PVB infection, the epidemiology remains poorly outlined. Over a 3-year period, 3 of 54 LT patients with unexplained anemia tested positive for circulating PVB by a nested polymerase chain reaction (PCR) assay. All of these patients presented with anemia and leukopenia, with a favorable long-term prognosis.

Bosentan for the treatment of pulmonary arterial hypertension associated with congenital cardiac disease.

AIMS: Bosentan is efficacious in idiopathic pulmonary arterial hypertension, and the variants associated with connective tissue disease, but not currently approved for treatment of pulmonary arterial hypertension due to Eisenmenger's syndrome. We sought to evaluate its effect in adults with Eisenmenger's syndrome. METHODS: We administered bosentan on the basis of compassionate use in 23 patients with Eisenmenger's syndrome, aged 37 plus or minus 14 years. Of the patients, 17 had never received specific treatment for pulmonary arterial hypertension, five were transitioned from treprostinil, and one from beraprost to bosentan. We measured functional class, saturation of oxygen, haemoglobin levels and six-minute walk distance at baseline, one, six months and at most recent follow-up. RESULTS: Baseline functional class was IV in three, III in fifteen, and II in five patients. At follow-up, with a mean of 15 plus or minus 10 months, 13 of the 23 patients (57%) had improved by at least one functional class, from a median baseline of III to II (p equal to 0.016), mean saturation of oxygen at rest had increased from 81% to 84% (p equal to 0.001), and levels of haemoglobin had decreased from 178 plus or minus 26 grams per litre to 167 plus or minus 19 grams per litre (p equal to 0.001). Overall, the six-minute walk distance did not change from baseline of 335 metres. The distance walked by those not previously receiving specific therapy, however, improved from 318 plus or minus 129 to 345 plus or minus 123 metres (p equal to 0.03). CONCLUSION: Treatment of adults with Eisenmenger's syndrome using bosentan significantly improved functional class, saturation of oxygen at rest, and decreased levels of haemoglobin. Treatment with bosentan was associated with improvement in six-minute walk distance in those not previously receiving specific therapy. In patients already in receipt of specific therapy, transition to bosentan resulted in no clinical deterioration.