Benjamin D. Fox

High prevalence of occult left heart disease in scleroderma-pulmonary hypertension

Our study aimed to determine the prevalence of occult left-heart disease in patients with scleroderma and pulmonary hypertension. In patients with pulmonary hypertension (mean pulmonary artery pressure (mean PAP) ≥25 mmHg), differentiation between pre- and post-capillary pulmonary hypertension has been made according to pulmonary artery wedge pressure (PAWP) less than or more than 15 mmHg, respectively. We performed a retrospective chart review of 107 scleroderma patients. All patients with suspected pulmonary hypertension had routine right or left heart catheterisation with left ventricular end-diastolic pressure (LVEDP) measurement pre-/post-fluid challenge. We extracted demographic, haemodynamic and echocardiographic data. Patients were classified into one of four groups: haemodynamically normal (mean PAP<25 mmHg); pulmonary venous hypertension (PVH) (mean PAP≥25 mmHg, PAWP>15 mmHg); occult PVH (mean PAP≥25 mmHg, PAWP≤15 mmHg, LVEDP>15 mmHg before or after fluid challenge); and pulmonary arterial hypertension (PAH) (mean PAP≥25 mmHg, PAWP≤15 mmHg and LVEDP≤15 mmHg before or after fluid challenge). 53 out of 107 patients had pulmonary hypertension. Based on the PAWP-based definition, 29 out of 53 had PAH and 24 out of 53 had PVH. After considering the resting and post-fluid-challenge LVEDP, 11 PAH patients were reclassified as occult PVH. The occult PVH group was haemodynamically, echocardiographically and demographically closer to the PVH group than the PAH group. PVH had high prevalence in our scleroderma-pulmonary hypertension population. Distinguishing PAH from PVH with only PAWP may result in some PVH patients being misclassified as having PAH. Left heart catheterisation with saline infusion helps in the diagnosis of suspected PH in scleroderma http://ow.ly/mxuXE

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.

Exercise Training-Based Pulmonary Rehabilitation Program Is Clinically Beneficial for Idiopathic Pulmonary Fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, devastating, interstitial lung disease, with few therapeutic options. IPF is characterized by pulmonary restriction, dyspnea, hypoxemia, exercise intolerance and poor quality of life (QOL). Objectives: We aimed to examine the effect of exercise training (ET) on clinical outcomes in IPF patients. Methods: A randomized controlled study included thirty-two IPF patients (aged 68 ± 8 years) who were allocated either to the ET group (n = 15), participating in a 12-week, twice-weekly 60-min supervised ET-based pulmonary rehabilitation program, or to a control group (n = 17) continuing with regular medical treatment alone. Cardiopulmonary exercise test, 6-min walking distance (6MWD) test, 30-second chair-stand test, pulmonary function tests, dyspnea and QOL were assessed at baseline and at the end of the 12-week intervention. Results: Significant differences were observed between the ET and the control groups in raw mean deltas (Δ = post- - pre-intervention): Δ6MWD, 81 m, p < 0.001; ΔVO2 peak, 2.6 ml/kg/min, p = 0.002; Δwork rate, 22 W, p < 0.001; Δanaerobic threshold, 3.1 ml/kg/min, p < 0.001, and ΔFVC % predicted, 6%, p = 0.038. Dyspnea, QOL and 30-second chair-stand were also improved significantly following the program. Conclusions: ET improves exercise tolerance, functional capacity, pulmonary function, dyspnea and QOL in patients with IPF, suggesting a short-term treatment efficacy for clinical improvement, and should be considered the standard care for IPF.

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.

Lung cancer in lung transplant recipients: Experience of a tertiary hospital and literature review

BACKGROUND Lung transplantation is a viable therapy for patients with end-stage lung disease and is being increasingly performed worldwide. The incidence of lung cancer after lung transplantation has increased concomitantly, although data are still sparse. METHODS The computerized medical records of the Pulmonary Institute of a tertiary care medical center were searched for patients who underwent lung transplantation from 1997 to 2009 and acquired lung cancer postoperatively. The prevalence, potential contributing factors, and outcome of bronchogenic cancer were determined, and the medical literature was reviewed. RESULTS Bronchogenic cancer developed in 7 of the 290 lung transplant recipients (2.4%). All had received a single lung transplant and in most cases, the cancer developed in the native lung. These findings were similar to reports in the literature. The indication for transplantation was chronic obstructive pulmonary disease or idiopathic pulmonary fibrosis/interstitial lung disease. All had a history of smoking. The average interval from transplantation to development of lung cancer was 5 years (range 1-9). Five patients had stage 4 cancer at diagnosis and 2 had stage 1. Six patients died from 10 days to 1 year after diagnosis. CONCLUSION Lung transplantation is associated with a relatively high prevalence of bronchogenic cancer, particularly in the native lung, in patients with primary chronic obstructive pulmonary disease/idiopathic pulmonary fibrosis, and a history of smoking. The cancer is usually diagnosed at an advanced stage with poor outcome. Efforts to improve screening are recommended, as aggressive management and treatment may be beneficial for earlier stage disease.

Long-term follow-up of flexible bronchoscopic treatment for bronchial carcinoids with curative intent.

Background. Typical pulmonary carcinoids represent less than 5% of primary lung tumors. In patients with typical bronchial carcinoid, formal surgical resection still remains the gold-standard treatment. Data regarding long-term outcome in using flexible bronchoscope-based modalities under conscious sedation is very limited. Objectives. We sought to investigate, over extended follow-up period, the effectiveness of endobronchial resection for carcinoid tumors with curative intent using flexible bronchoscopy. Methods. Nd:YAG laser photoresection using flexible bronchoscope under conscious sedation. Follow-up included repeat bronchoscopy every 6 months and chest CT every year. Results. Ten patients aged 24 to 70 years with endobronchial carcinoid were treated. The tumor location was variable: 2 left Main bronchus, 1 left upper lobe bronchus, 2 right main bronchus, 2 right middle lobe bronchus and 3 right lower lobe bronchus. No major complications were observed. The patients required between 2 and 4 procedures. Patients were followed for a median period of 29 months with no evidence of tumor recurrence. Conclusions. Endobronchial laser photoresection of typical bronchial carcinoids using flexible bronchsocopy under conscious sedation is an effective treatment modality for a subgroup of patients that provides excellent long-term results that are similar to outcome obtained by more invasive procedures.

Herpes zoster after lung transplantation: incidence, timing, and outcome.

BACKGROUND Although herpes zoster is a common complication of lung transplantation, the epidemiologic data are limited. The aims of the present study were to determine the incidence and clinical manifestations of herpes zoster in a large cohort of lung transplant recipients and to identify risk factors associated with its development. METHODS The files of all adult patients who underwent lung transplantation at a major tertiary medical center from January 2001 to December 2007 were reviewed. Data were extracted on background, transplant-related, and posttransplantation factors. The occurrence and clinical characteristics of all episodes of herpes zoster were recorded. RESULTS Of the 198 lung transplant recipients, 23 had a herpes zoster infection, of whom 18 had herpes in a single dermatome. Disseminated cutaneous infection was documented in 4 cases (17%) and visceral involvement in 1. The median duration of follow-up was 34 months (range, 1 to 85 months). There were no recurrent infections. Postherpetic neuralgia was detected in 26% of cases. Antiviral prophylaxis, primarily for cytomegalovirus, was effective (during treatment) against herpes zoster. The incidence of herpes zoster was higher in patients treated with rabbit antithymocyte globulin. CONCLUSIONS The occurrence of herpes zoster peaks between 12 and 36 months after lung transplantation. Additional immunosuppression may increase the risk. Further studies on preventive strategies against herpes zoster in this population are warranted.

Benzodiazepine and opioid sedation attenuate the sympathetic response to fiberoptic bronchoscopy. Prophylactic labetalol gave no additional benefit. Results of a randomized double-blind placebo-controlled study.

BACKGROUND Hypertension and tachycardia are common during fiber-optic bronchoscopy (FOB), and this may lead to cardiac ischemia. The prophylactic addition of a beta-adrenergic anatagonist might mask this response and prevent the deleterious cardiovascular effects of FOB. METHODS We performed a randomized double-blind placebo-controlled trial of labetalol 10mg iv given with midazolam-alfentanil sedation. We monitored heart rate (HR) and systolic/diastolic blood pressure (SBP/DBP) throughout the bronchoscopy and calculated the rate-pressure product (RPP=(HRxSBP)/100). One-hundred twenty patients were enrolled. RESULTS In the placebo group, there was no rise in HR, SBP, DBP or RPP, and there was no difference between the placebo and labetalol groups. Adverse events during bronchoscopy were similar in both groups. In a subgroup of patients undergoing interventional bronchoscopy, there was a trend towards lower SBP (p=0.06). CONCLUSIONS Patients undergoing FOB under adequate midazolam-alfentanil sedation do not develop excessive sympathetic drive that may lead to cardiac stress. The addition of labetalol did not confer additional benefit or risk to the patients. (ClinicalTrials.gov number, NCT00394537).

Removal of metallic tracheobronchial stents in lung transplantation with flexible bronchoscopy

BackgroundAirway complications are among the most challenging problems after lung transplantation, and Self-Expandable Metallic Stents (SEMS) are used to treat airway complications such as stenosis or malacia at the bronchial anastomosis sites. Several transplantation centers are reluctant to use SEMS since their removal is sometimes needed and usually requires the use of rigid bronchoscopy under general anesthesia. The objective of the current report is to describe our experience in SEMS retrieval by flexible bronchoscopy under conscious sedation.MethodsA retrospective review was done of patients requiring tracheobronchial stent placement after lung transplantation in which the SEMS had to be removed. The retrieval procedure was done by flexible bronchoscopy on a day-care ambulatory basis.ResultsBetween January 2004 and January 2010, out of 305 lung transplantation patients, 24 (7.8%) underwent SEMS placement. Indications included bronchial stenosis in 20 and bronchomalacia in 4. In six patients (25%) the SEMS had to be removed due to excessive granulation tissue formation and stent obstruction. The average time from SEMS placement to retrieval was 30 months (range 16-48 months). The stent was completely removed in five patients and partially removed in one patient; no major complications were encountered, and all patients were discharged within 3 hours of the procedure. In all procedures, new SEMS was successfully re-inserted thereafter.ConclusionsThe retrieval of SEMS in patients that underwent lung transplantation can be effectively and safely done under conscious sedation using flexible bronchoscopy on a day-care basis, this observation should encourage increasing usage of SEMS in highly selected patients.

Pandemic influenza (H1N1): Impact on lung transplant recipients and candidates

BACKGROUND The year 2009 was notable for the outbreak of a novel strain of influenza A (H1N1). We report the outcomes of H1N1 infection in a large cohort of lung transplant (LTx) recipients and candidates. METHODS This was a retrospective review of 22 suspected cases of H1N1 influenza screened using real-time polymerase chain reaction from nasal secretions. There were 15 confirmed cases (10 LTx recipients, 5 LTx candidates). RESULTS All patients were treated with oseltamivir at the time of the first clinical assessment. In the LTx recipients group, 7 of the 10 confirmed cases were treated at home with oseltamivir alone. Three patients were admitted with complications (2 pneumonia, 1 acute rejection). Two patients required mechanical ventilation. Two patients had prolonged viral shedding. No deaths occurred among the LTx recipients. In the 5 LTx candidates with confirmed H1N1, 2 deaths occurred from pneumonia and acute respiratory distress syndrome. CONCLUSIONS Influenza H1N1 had a significant complication rate amongst LTx recipients and a high mortality rate amongst LTx candidates.