David Shitrit

Lung transplantation in patients with scleroderma: case series, review of the literature, and criteria for transplantation

Abstract:  Backgrounds:  The use of lung transplantation (LTX) to treat respiratory failure because of scleroderma is controversial. We present our experience, review the current literature, and suggest specific criteria for LTX in scleroderma. Of the 174 patients who underwent LTX at our center, seven (4%) had scleroderma‐associated respiratory failure.

Use of Amplatzer device for endobronchial closure of bronchopleural fistulas.

Bronchopulmonary fistula (BPF) is associated with high morbidity and mortality. It occurs as an uncommon but often severe complication of pneumonectomy. BPF may be treated by a range of surgical and medical techniques, including chest drain, Eloesser muscle flap, omental flap, transsternal bronchial closure, thoracoplasty, and prolonged therapy with antibiotic regimens. The use of bronchoscopy has been reported for the delivery of biological glue, coils, covered stents, and sealants. In this work, we describe a novel method of BPF closure using the Amplatzer device, which is commonly used for transcatheter closure of atrial septal defects.

Peripheral Arterial Stiffness and Endothelial Dysfunction in Idiopathic and Scleroderma Associated Pulmonary Arterial Hypertension

Objective. Pulmonary endothelial dysfunction and increased reflection of pulmonary pressure waves have been reported in pulmonary arterial hypertension (PAH). However, the systemic vascular involvement is not fully understood. Our study focused on the systemic arterial stiffness and endothelial involvement in idiopathic and scleroderma associated PAH. Methods. Peripheral arterial stiffness and endothelial function were evaluated in 38 patients with idiopathic (n = 28) and scleroderma associated (n = 10) PAH, and 21 control subjects (13 healthy; 8 with scleroderma and normal pulmonary pressure). All participants underwent clinical and cardiopulmonary evaluation. Arterial stiffness was measured through the fingertip tonometry derived augmentation index (AI), which is the boost increase in the late systolic pressure wave after the initial systolic shoulder. Endothelial function was measured by forearm blood flow dilatation response to brachial artery occlusion by a noninvasive plethysmograph (EndoPAT 2000), which is associated with nitric oxide-dependent vasodilatation and yields a peripheral arterial tone (PAT) ratio. Results. Mean systolic pulmonary pressure was 70.5 ± 21.6 mm Hg (idiopathic-PAH) and 69.3 ± 20 mm Hg (scleroderma-PAH). AI was higher in scleroderma patients (10.5% ± 19.6% in healthy controls, 9.0% ± 21.5% in idiopathic-PAH, 20.1% ± 19.1% in scleroderma-PAH, and 24.4% ± 18.9% in scleroderma-controls; nonsignificant). PAT ratio was significantly lower (p < 0.05) than control values in idiopathic-PAH and scleroderma-PAH (PAT ratio: control 2.20 ± 0.25; idiopathic 1.84 ± 0.51; scleroderma 1.66 ± 0.66). AI was not correlated to endothelial dysfunction. There were no differences between the 2 PAH patient groups in age, body mass index, New York Heart Association classification, or 6-min walk test. Conclusion. Our study shows a trend towards increased arterial stiffness in scleroderma (nonsignificant), and also peripheral endothelial dysfunction in idiopathic-PAH and in scleroderma-PAH. These findings suggest involvement of different vessels in scleroderma-PAH compared to idiopathic-PAH.

Post-transplant diabetes mellitus in lung transplant recipients: incidence and risk factors

OBJECTIVE Post-transplant diabetes mellitus (PTDM) is a common and potentially serious complication after solid organ transplantation. There are only a few data, however, about the incidence of DM in patients undergoing lung transplantation. PATIENTS AND METHODS The medical records of 119 consecutive patients who underwent lung transplantation from 1998 to September 2004 were reviewed. Patients were divided in three groups according to their diabetes status, including pre-transplant DM, the PTDM group and those without DM. Patient records and all laboratory data were reviewed and the clinical course of diabetes was monitored. All recipients were treated with tacrolimus based regimen. RESULTS Mean follow-up for all patients was 25+/-10. Twenty-three patients had DM in the pre-lung transplantation (LTX) DM group. PTDM developed in 34 of the remaining 96 patients (35.4%) with an incidence of 20%, 23% after 6 months and 12 months post-transplant. No significant difference was noted between 12 and 24 months post-LTX. The patients who developed DM were older (57+/-15 vs 53+/-13 years, p=0.009), had increased BMI (26+/-5 vs 24+/-4, p=0.0001), shorter time from diagnosis to LTX (21+/-13 vs 28+/-18 months, p=0.007) more cytomegalovirus infection and more acute rejection and hyperglycemia in the first month after LTX. Four patients died in the PTDM group compared to nine patients in the no-DM group (12% vs 14%; p=0.72). CONCLUSIONS Post-transplant diabetes is a common complication in lung transplant patients receiving tacrolimus-based immunosuppression. The risk for developing PTDM is greatest among older recipients, those obese, and among recipients with more rejections episodes.

Development of malignancy following lung transplantation

Background. A substantial excess risk of certain malignancies has been demonstrated after organ transplantation. Immunosupressive treatment to prevent allograft rejection is probably the main cause. Methods. We reviewed retrospectively all medical records of the 121 patients that underwent lung and heart-lung transplantation from 1992 until December 2004. We compared our results to the International Society for Heart and Lung Transplantation (ISHLT) registry data and previous reports concerning lung transplantation. Results. 102 of the 121 patients survived for 3 months to 12 years. Malignancies developed in 16 patients, as follows: lymphoproliferative disorder in 3, Kaposis sarcoma in 3, other nonmelanoma skin cancers in 7, urinary bladder transitional cel carcinoma in 3, and colon cancer in 1. Patients with malignancy were older at transplantation than those without (mean ± SD, 54.1±7.8 vs. 49.5±14.2 years; P=0.03). Fourteen had smoked in the past. Four died of bronchiolitis obliterans. In comparison with the ISHLT, we observed more skin cancer and transitional cell carcinoma (12.8% vs. 0.7% and 3.8% vs. 0.03%, respectively) and a similar frequency of posttransplant lymphoproliferative disease. Conclusions. We conclude that malignancy is a common complication after lung transplantation. In Israel, which is sunny most of the year, skin cancers and transitional cell carcinoma of bladder are more common. Modification of the immunosuppression late posttransplantation may reduce the risk of cancer. Patients should also be counseled to avoid sun exposure and ensure adequate hydration.

Peripheral endothelial dysfunction in patients with pulmonary arterial hypertension

BACKGROUND Pulmonary endothelium plays an important role in the mechanism of pulmonary arterial hypertension (PAH). However, there is only a few data regarding the systemic endothelium in this syndrome. This study focused on the systemic endothelial involvement in PAH. METHODS Endothelial function was evaluated in 54 patients with idiopathic (n=28), scleroderma-associated (n=10), chronic thromboembolic (n=7), or Eisenmenger (n=9) PAH and 21 controls (13 healthy; eight scleroderma and normal pulmonary pressure). All underwent clinical evaluation, pulmonary assessment, echocardiography, and pulmonary cardiac stress test. Endothelial function was evaluated by measuring the forearm blood flow dilatation response to brachial arterial occlusion by a non-invasive plethysmograph, yielding a peripheral arterial tone (PAT) ratio. RESULTS The PAT ratio was significantly lower (p<0.05) than healthy controls in all patients except the Eisenmenger group (control: 2.20+/-0.25; idiopathic 1.84+/-0.51; scleroderma 1.66+/-0.66; thromboembolic 1.89+/-0.32; Eisenmenger 2.17+/-0.62). The impaired hyperemic response significantly correlated with disease severity, as measured by NYHA classification (r=-0.210, p=0.035), pulmonary pressure (r=-0.228, p=0.035), 6 min walking distance (r=0.215, p=0.047), and oxygen desaturation on effort (r=0.207, p=0.038). Mean systolic pulmonary pressure among patients was 54-99 mmHg. CONCLUSION A systemic component of endothelial dysfunction might be involved in idiopathic, scleroderma-associated and chronic thromboembolic PAH that is correlated with disease severity.

An association between oxygen desaturation and D-dimer in patients with obstructive sleep apnea syndrome

D-dimer, a degradation product of fibrin, is being increasingly used as a marker and prognostic factor in various thrombotic diseases. Previous reports have shown that obstructive sleep apnea is associated with platelet activation and hypercoagulability. The aim of the study was to assess the potential role of the plasma D-dimer test in patients with obstructive sleep apnea. We designed a prospective group comparison study in a tertiary-care, university-affiliated medical center. One hundred and three patients of mean age 57 years (range 50-76 years) with symptoms suggestive of obstructive sleep apnea were included. Polysomnography was performed in all cases, and blood was collected for plasma D-dimer measurement by MiniQuant turbidmetric assay. The demographic and polysomnograph data were compared between patients with normal and high (> 250 ng/ml) D-dimer levels. The group with higher D-dimer values had lower mean minimal oxygen saturation (72.1 +/- 16.4 vs. 81.7 +/- 11.6%, p = 0.008) and a longer mean period of oxygen saturation below 90% (84.1 +/- 86.2 vs. 38.5 +/- 70.8 minutes, p = 0.032). There was no correlation of respiratory disturbance index and sleep architecture with D-dimer values. We concluded that sleep apnea syndrome is associated with fibrinolytic activity. Oxygen desaturation seems to be one of the mediatory factors in the putative connection between obstructive sleep apnea and hypercoagulability state.

Bronchoscopic balloon dilatation of tracheobronchial stenosis: long-term follow-up

OBJECTIVES Bronchoscopic balloon dilatation (BBD) has become a valuable tool in the treatment of tracheobronchial stenosis (TBS). The objective of this study was to assess the short- and long-term effects of BBD. METHODS A retrospective study that included all patients with confirmed, symptomatic stenosis, who underwent BBD between 2002 and 2008. A total of 92 BBD procedures were performed in 35 patients at our institute. Lung function studies were recorded for all patients before, immediately after and 1 month following the BBD. Long-term follow-up was for a mean of 33+/-4 months. RESULTS All patients had initial success, including increased airway dimensions and symptom relief. No complications were noted related to BBD. Forced expiratory volume after one second (FEV(1)) was significantly increased after BBD (10.5%, p=0.03). These effects persisted for at least 1 month. Long-term follow-up, however, demonstrated the need for stent placement in 25 of 35 patients (71%), 210+/-91 days after BBD. Ten of 35 patients died 456+/-119 days after BBD due to progression of primary disease; all deaths were unrelated to the BBD procedures. CONCLUSIONS BBD is a safe method that offers immediate symptomatic relief in both tracheal and bronchial stenosis. However, BBD is a temporary measure, as many patients will require definitive or additional treatment with laser or stent placement.

Combination therapy with prostacyclin and tadalafil for severe pulmonary arterial hypertension: a pilot study.

Abstract:  Despite the introduction of new drugs that have changed the course of pulmonary arterial hypertension (PAH), some patients are still refractory to treatment and deteriorate rapidly. Long‐acting phosphodiesterase‐5 inhibitors are a new class of drugs that are effective in PAH. This prospective study assessed the potential of combination therapy with prostacyclin and tadalafil for treatment of severe PAH. We report four cases of severe PAH that deteriorated despite prostacyclin therapy. Two patients had Eisenmenger syndrome, one had pulmonary hypertension associated with scleroderma and one had histiocytosis X. All were treated with tadalafil, 10–20 mg once daily, in addition to prostacyclin. After 3 months of treatment, all patients improved clinically, with an increase in mean 6MWD from 214 to 272 m. In three patients, the New York Heart Association functional class decreased from IV to III. Echocardiograms showed no significant changes in pulmonary arterial pressure. Although this study was limited by the small sample size, it suggests that tadalafil in combination with prostacyclin is an effective treatment for severe PAH. Tadalafil may be beneficial for the treatment of patients with advanced disease.

Flexible bronchoscopic management of benign tracheal stenosis: long term follow-up of 115 patients.

BackgroundManagement of benign tracheal stenosis (BTS) varies with the type and extent of the disease and influenced by the patients age and general health status, hence we sought to investigate the long-term outcome of patients with BTS that underwent minimally invasive bronchoscopic treatment.MethodsPatients with symptomatic BTS were treated with flexible bronchoscopy therapeutic modalities that included the following: balloon dilatation, laser photo-resection, self-expanding metal stent placement, and High-dose rate endobronchial brachytherapy used in cases of refractory stent-related granulation tissue formation.ResultsA total of 115 patients with BTS and various cardiac and respiratory co-morbidities with a mean age of 61 (range 40-88)were treated between January 2001 and January 2009. The underlining etiologies for BTS were post - endotracheal intubation (N = 76) post-tracheostomy (N = 30), Wegeners granulomatosis (N = 2), sarcoidosis (N = 2), amyloidosis (N = 2) and idiopathic BTS (N = 3). The modalities used were: balloon dilatation and laser treatment (N = 98). Stent was placed in 33 patients of whom 28 also underwent brachytherapy. Complications were minor and mostly included granulation tissue formation. The overall success rate was 87%. Over a median follow-up of 51 months (range 10-100 months), 30 patients (26%) died, mostly due to exacerbation of their underlying conditions.ConclusionsBTS in elderly patients with co-morbidities can be safely and effectively treated by flexible bronchoscopic treatment modalities. The use of HDR brachytherapy to treat granulation tissue formation following successful airway restoration is promising.