Nocturnal periodic breathing in primary pulmonary hypertension.

Cheyne-Stokes respiration is frequently observed in congestive heart failure. Among other factors, prolongation of circulation time, hypocapnia and hypoxia are thought to underlie this sleep-related breathing disorder. Primary pulmonary hypertension (PPH) is also characterized by reduced cardiac output and blood gas alterations. Therefore, the aim of the present study was to determine whether a nocturnal periodic breathing (PB) occurs in PPH. A total of 20 consecutive patients with PPH who had been admitted for pharmacological investigation of pulmonary vasoreactivity were investigated by lung function testing, right heart catheterization and full-night attended polysomnography. PB was detected in six patients (30%) (mean +/- SEM: apnoea/hypopnoea index 37 +/- 5 h(-1); arterial oxygen saturation was <90% during 56 +/- 6.5% of total sleep time). The patients with PB had more severe haemodynamic impairment than those without. They also had a more marked reduction in the pulmonary diffusion capacity and greater arterial hypoxia. PB was markedly improved or even eradicated by nasal oxygen during the night. Periodic breathing occurs in patients with advanced primary pulmonary hypertension and can be reversed by nocturnal nasal oxygen. The clinical and prognostic significance of periodic breathing in primary pulmonary hypertension needs to be determined by further studies.     

Reversal of idiopathic pulmonary arterial hypertension and allograft pneumonectomy after single lung transplantation

Prior to the advent of effective medical therapies, the only treatment option for patients with idiopathic pulmonary arterial hypertension (IPAH) was lung transplantation. We present the case of a woman who underwent single-lung transplantation for the treatment of IPAH > 10 years ago in whom chronic rejection developed. Despite complete obliteration of the allograft, it was noted that her PA pressure levels had almost normalized. Therefore, an allograft pneumonectomy was performed. To our knowledge, this is the first reported case of the regression of pulmonary vascular disease following lung transplantation with subsequent successful removal of the allograft.     

Single lung transplantation for primary pulmonary hypertension

Single lung transplantation has become a therapeutic option for end-stage interstitial lung disease and obstructive lung disease. Our group recently extended this treatment to three patients with primary pulmonary hypertension. All patients had marked decreases in pulmonary artery pressures and pulmonary vascular resistance and increases in cardiac output following single lung transplantation. Spirometry, lung volumes, and diffusion capacity were not different in comparison to preoperative studies. Quantitative ventilation-perfusion scans revealed the majority of perfusion distributed to the transplanted lung, with ventilation approximately equally divided between the native and the transplanted lung. Despite ventilation-perfusion imbalance, there was no resting hypoxemia and there was no arterial oxygen desaturation with exercise. One patient expired on the 30th postoperative day due to cytomegalovirus infection of the lungs. In the remaining two patients, maximum exercise capacity following transplantation was near normal in one recipient and reduced in the second recipient. Of note, there was no evidence of ventilatory limitation or impaired oxygenation during exercise in these two recipients. Although an exaggerated exercise ventilatory response was present, this did not limit exercise performance. This report supports the use of single lung transplantation for the treatment of primary pulmonary hypertension.     

Anastomotic pulmonary hypertension after lung transplantation for primary pulmonary hypertension: report of surgical correction.

This report describes a patient who developed pulmonary hypertension 6 years after lung transplantation for primary pulmonary hypertension (PPH). Evaluation with right heart catheterization followed by pulmonary angiography, however, demonstrated that the pulmonary hypertension was secondary to an anastomotic narrowing of the pulmonary artery, rather than a recurrence of her PPH. Vascular complications of lung transplantation should be considered in patients who experience exertional dyspnea after lung transplantation. The suggestion of pulmonary hypertension on echocardiography should prompt further evaluation, including meticulous hemodynamic measurements.     

Recovery of cardiac function after living-donor lung transplantation in a patient with primary pulmonary hypertension.

Legislation for brain death and organ transplantation was passed in Japan in 1997, but there is still a great shortage of brain-death donors. Primary pulmonary hypertension (PPH) is a progressive disease that is usually followed by death within 5 years of diagnosis. Continuous infusion of prostacyclin is effective, but some patients will ultimately require heart-lung or lung transplantation. The first case of bilateral living-donor lobar lung transplantation (LDLLT) for PPH in Japan is reported. The recipient was a 19-year-old woman who was diagnosed as PPH at the age of 14 years and began intravenous prostacyclin therapy. Initially her symptoms improved, but she returned to New York Heart Association class IV in 2000. In January 2001, she underwent bilateral LDLLT. Postoperative echocardiography showed that the right ventricular diameter had decreased and septal wall motion had normalized, resulting in a round-shaped left ventricle. Right heart catheterization demonstrated that cardiac output and pulmonary arterial pressure had normalized. The right ventricular ejection fraction improved from 15% to 77%. The patient was discharged from hospital after 60 days postoperatively. LDLLT will become one of the options in Japan for end-stage PPH.     

Single lung transplantation for primary pulmonary hypertension without cardiopulmonary bypass.

We report the first case, to our knowledge, of single lung transplantation for primary pulmonary hypertension carried out without cardiopulmonary bypass. This operation seems to be possible even if the right ventricular ejection fraction is low (0.17) and the pulmonary vascular resistance very high (1,096 dynes.s.cm5). Since 1981, heart-lung transplantation has been successfully performed in patients with primary pulmonary hypertension. If heart-lung transplantation results in resolution of pulmonary hypertension, the incidence of obliterative bronchiolitis is significant in heart-lung transplantation recipients. Single lung transplantation has been performed for end-stage interstitial and obstructive lung disease but has not been considered a good option for primary pulmonary hypertension due to concerns that a single transplanted lung would be unable to cope with the entire blood flow. However, recently single lung transplantation has been performed for primary pulmonary hypertension, the risk of obliterative bronchiolitis remaining unknown. The purpose of this communication is to report one case of single lung transplantation for primary pulmonary hypertension and the feasibility of this operation without the use of cardiopulmonary bypass, if cardiopulmonary bypass is thought to be dangerous.     

Lung transplantation for primary pulmonary hypertension

Recent progress in medical therapies has diminished the role of transplantation in the management of PPH during the past decade. Drug therapy is not effective in some patients, responses to therapy are not sustained over time in others, and drug side effects eventually limit the benefits of treatment in a few more. Lung transplantation therefore ultimately is the only alternative for patients whose PPH is severe and cannot be managed medically. Choosing the right patient as a transplant candidate and the right time to make the initial referral to a transplant center are the crucial initial steps in the transplantation process, and the long waiting time before transplantation must be integrated into this decision. The outcome of lung and heart-lung transplantation for PHH has been good but sobering. Functional recovery has been excellent, but long-term survival results have been limited by the high prevalence of chronic allograft rejection.     

Lung transplantation for primary pulmonary hypertension

Significant advances in the treatment of primary pulmonary hypertension (PPH) have been achieved in the past decade. Continuous intravenous prostacyclin and lung transplantation are complex and effective approaches in the therapy of PPH. Indication, technique, postoperative care and results of lung transplantation for PPH are discussed.     

Noninfectious pulmonary complications after lung transplantation

This article reviews several important noninfectious pulmonary complications that threaten survival, pulmonary function, and quality of life after lung transplantation. Topics reviewed include primary graft dysfunction (PGD), native lung hyperinflation, anastomotic complications, phrenic nerve injury, pleural complications, lung cancer, pulmonary toxicity associated with immunosuppressive medications, and exercise limitation.     

Reversal of high altitude pulmonary hypertension

Significant pulmonary hypertension is present in most normal residents of the high altitude community of Leadville, Colorado, elevation 10,200 feet. One 15 year old girl with unusually severe pulmonary hypertension in Leadville was studied again after she had lived near sea level for 11 months. Marked regression of her pulmonary hypertension had occurred. This is the first demonstration of reversibility of high altitude pulmonary hypertension in a girl of European ancestry.     

Ventilation-perfusion inequalities during graft rejection in patients undergoing single lung transplantation for primary pulmonary hypertension.

We report herein data on single lung transplant (SLT) recipients with primary pulmonary hypertension (PPH). One patient did well following surgery but died on the 30th postoperative day due to cytomegalovirus pneumonia. The remaining two patients initially did well with unlimited exercise tolerance following transplantation, but then developed marked dyspnea on exertion and hypoxemia on postoperative days 144 and 120, respectively. Pulmonary function testing showed marked deterioration of function and transbronchial lung biopsy specimens revealed acute graft rejection in one patient and evidence of chronic graft rejection in the second patient. Quantitative ventilation-perfusion lung scanning demonstrated a marked decrease in ventilation to the transplanted lung in both cases associated with only a mild decrease in perfusion. This V/Q mismatch resulted in markedly decreased arterial oxygen saturations, widened alveolar-arterial oxygen gradients, and clinically debilitating dyspnea. We conclude that rejection may result in significant V/Q mismatch and hypoxemia in PPH patients undergoing SLT, which may limit the use of this specific type of surgery for PPH.     

Living-donor lobar lung transplantation for pulmonary arterial hypertension after failure of epoprostenol therapy.

OBJECTIVES: The aim of this study was to evaluate the long-term effects of living-donor lobar lung transplantation (LDLLT) for critically ill patients with pulmonary arterial hypertension (PAH) who failed in epoprostenol treatment. BACKGROUND: Although continuous epoprostenol infusion has markedly improved survival in patients with PAH, some patients do not benefit from this therapy. METHODS: From July 1998 to December 2003, 28 consecutive PAH patients who were treated with epoprostenol and accepted as candidates for lung transplantation were enrolled. All data were prospectively collected. As of July 2006, LDLLT was performed in 11 of those patients whose condition was deteriorating. Cadaveric lung transplantation (CLT) was performed in 2 patients. Medical treatment was continued in 15 patients. RESULTS: There was no mortality in patients receiving LDLLT during a follow-up period of 11 to 66 months (average 48 months), and all patients returned to World Health Organization functional class I. Mean pulmonary artery pressure decreased from 62 +/- 4 mm Hg to 15 +/- 2 mm Hg (p < 0.001) at discharge and remained normal at 3 years. One CLT patient died of primary graft failure. Among medically treated patients, 6 patients died of disease progression. The survival rate was 100% at 5 years for patients receiving LDLLT, and 80% at 1 year, 67% at 3 years, and 53% at 5 years for patients medically treated (p = 0.028). All living donors have returned to their previous lifestyles. CONCLUSIONS: These follow-up data support the option of LDLLT in patients with PAH who would die soon otherwise.     

Improvement of pulmonary hypertension after liver transplantation.

Pulmonary hypertension at the end stage of chronic liver disease is not an uncommon situation. This association termed portopulmonary hypertension raises the question of the feasibility of performing orthotopic liver transplantation (OLT). In the case reported herein, there was a favorable outcome after OLT, even though the mean pulmonary artery pressure (MPAP) before transplantation was increased to 45 mm Hg. Before OLT, the cardiac index (CI) was considerably elevated (7.69 L/min/m2), giving evidence of a marked hyperdynamic circulatory state. The CI decreased significantly after OLT (3.38 L/min/m2), and this produced a significant decrease in the MPAP. Our observation suggests that portopulmonary hypertension due to a marked increase in the CI can be managed successfully by OLT.     

Reversibility of primary pulmonary hypertension with vasodilator, anticoagulant and nocturnal oxygen therapy

Successful vasodilator therapy of a 19 year old woman with primary pulmonary hypertension is described. Long-term home oxygen therapy during sleep (2 1/min, 8 hours) in combination with vasodilator drugs (prazosin 2 mg and long-acting ISDN 20 mg bid) and an anticoagulant (ticlopidine 100 mg bid) brought significant reduction of pulmonary artery pressure and a rise of cardiac output 3 years later. This combination therapy may be effective in selected patients with primary pulmonary hypertension.     

Epoprostenol therapy for primary pulmonary hypertension after rejection of a single donor lung.

Before prostacyclins became available, lung or heart/lung transplantation was the only effective treatment for patients with primary pulmonary hypertension (PPH) who deteriorated under supportive medical treatment. Unfortunately, acute and chronic rejections occur in a large number of cases, limiting the average survival to 4.5 yrs. A female patient, age 35 yrs, was diagnosed with PPH and underwent single lung transplantation. Despite aggressive immunosuppressive therapy, the patient had several episodes of acute rejection. Eventually, chronic rejection with bronchiolitis obliterans developed. After 5 yrs, the donor lung was no longer functional. The patient was in New York Heart Association (NYHA) class 4, had a 6-min walking distance of 50 m and a resting arterial oxygen tension (Pa,O2) of 9.8 kPa (74 mmHg) when using 3 L x min(-1) of oxygen. Epoprostenol treatment was started and the patient showed remarkable improvement. After 17 months the patient was NYHA class 2, walked 503 m in 6 min and had a resting Pa,O2 of 10.9 kPa (82 mmHg) without supplemental oxygen. In this patient, treatment with epoprostenol was effective after rejection of a single donor lung transplanted for primary pulmonary hypertension.     

Management of end-stage sarcoidosis: pulmonary hypertension and lung transplantation

Sarcoidosis is not only a multisystem, but also a multinational disease that is prevalent throughout the world, including Europe, the USA and Japan. Lung involvement in sarcoidosis is seemingly invariable, with up to 95% of patients manifesting some form of pulmonary disease during the course of their lifetime. The natural history of sarcoidosis in the lung is quite variable and spans the spectrum from spontaneous resolution to advanced fibrocystic disease in ~5% of cases. Advanced sarcoidosis will be the subject of this review with a special focus on pulmonary hypertension and lung transplantation as a last-resort treatment option for some patients with end-stage disease.