Lung transplant curriculum in pulmonary/critical care fellowship training.

BACKGROUND: Lung transplantation is an evolving specialty with the number of transplants growing annually. PURPOSE: A structured lung transplant curriculum was developed for Pulmonary/Critical Care (Pulm/CC) fellows. METHODS: Scores on pulmonary in-training examinations (ITE) 2 years prior to and 3 years after implementation were reviewed as well as completion of satisfaction surveys. RESULTS: The mean pulmonary ITE score of 1st-year fellows increased from 54.2 ± 2.5 to 63.6 ± 1.2 (M ± SD), p = .002, whereas mean pulmonary ITE score for 2nd-year fellows increased from 63.0 ± 3.0 to 70.7 ± 1.2, p = .019. The combined mean pulmonary ITE score increased from 58.6 ± 2.3 to 67.1 ± 1.2, p = .001. Satisfaction surveys revealed that fellow perception of the curriculum was that the experience contributed to an overall improvement in their knowledge base and clinical skills while opportunity to perform transbronchial biopsies was available. CONCLUSIONS: A structured educational lung transplant curriculum was associated with improved performance on the pulmonary ITE and was perceived by fellows to be beneficial in their education and training while providing opportunities for fellows to perform transbronchial biopsies.

Lung transplantation in patients with coal workers' pneumoconiosis.

Patients with coal workers' pneumoconiosis (CWP) can develop chronic respiratory failure and require lung transplantation. A retrospective review was performed of the 712 referrals and 143 patients undergoing unilateral or bilateral lung transplantation at the University of Kentucky Medical Center between January 1999 and July 2009. Twenty-one of the 712 referrals (3%) had a diagnosis of CWP with eight patients eventually undergoing lung transplant (six single, two bilateral). The mean age of the cohort was 53 ± 5 (mean ± SD) yr (range 45-59). There was no increased risk of perioperative or postoperative complications. Six patients (75%) remain alive after a mean follow-up of 1013 ± 857 d with the two deaths attributable to sepsis 683 and 145 d after transplant, respectively. There were no pulmonary complications because of the native lung in patients after a single lung transplant, with otherwise good clinical outcomes seen after lung transplantation.

Pre- and post-bronchodilator lung function as predictors of mortality in the Lung Health Study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is supposed to be classified on the basis of post-bronchodilator lung function. Most longitudinal studies of COPD, though, do not have post-bronchodilator lung function available. We used pre-and post bronchodilator lung function data from the Lung Health Study to determine whether these measures differ in their ability to predict mortality. METHODS: We limited our analysis to subjects who were of black or white race, on whom we had complete data, and who participated at either the 1 year or the 5 year follow-up visit. We classified subjects based on their baseline lung function, according to COPD Classification criteria using both pre- and post-bronchodilator lung function. We conducted a survival analysis and logistic regression predicting death and controlling for age, sex, race, treatment group, smoking status, and measures of lung function (either pre- or post-bronchodilator. We calculated hazard ratios (HR) with 95% confidence intervals (CI) and also calculated area under the curve for the logistic regression models. RESULTS: By year 15 of the study, 721 of the original 5,887 study subjects had died. In the year 1 sample survival models, a higher FEV1 % predicted lower mortality in both the pre-bronchodilator (HR 0.87, 95% CI 0.81, 0.94 per 10% increase) and post-bronchodilator (HR 0.84, 95% CI 0.77, 0.90) models. The area under the curve for the respective models was 69.2% and 69.4%. Similarly, using categories, when compared to people with "normal" lung function, subjects with Stage 3 or 4 disease had similar mortality in both the pre- (HR 1.51, 95% CI 0.75, 3.03) and post-bronchodilator (HR 1.45, 95% CI 0.41, 5.15) models. In the year 5 sample, when a larger proportion of subjects had Stage 3 or 4 disease (6.4% in the pre-bronchodilator group), mortality was significantly increased in both the pre- (HR 2.68, 95% CI 1.51, 4.75) and post-bronchodilator (HR 2.46, 95% CI 1.63, 3.73) models. CONCLUSIONS: Both pre- and post-bronchodilator lung function predicted mortality in this analysis with a similar degree of accuracy. Post-bronchodilator lung function may not be needed in population studies that predict long-term outcomes.

Rhodococcus equi infection after lung transplantation.

Rhodococcus equi is an emerging opportunistic pathogen in immunocompromised patients. A lung-transplant recipient developed weight loss, nonproductive cough, dyspnea, and somnolence. Computed tomogram showed a pulmonary nodule and pleural changes in the right allograft that was due to R. equi infection. Alteration of cell-mediated immunity is a predisposing risk factor for R. equi infection in humans. Our patient developed R. equi infection soon after a course of high-dose corticosteroids for acute allograft infection and animal exposure. A course of intravenous vancomycin followed by single-agent long-term therapy with oral ciprofloxacin was successful.

Asthma, chronic obstructive pulmonary disease, and mortality in the U.S. population.

BACKGROUND: COPD and asthma are common diseases in the U.S. population and can coexist. Our goal was to determine the prevalence of self-reported, physician-diagnosed asthma and COPD in a sample of the U.S. population and their association with lung function impairment and mortality. METHODS: We used baseline data from NHANES III and the follow-up mortality data. We used logistic regression and Cox Proportional Hazards models, adjusting for age, sex, race/ethnicity, education level, smoking status, and disease stage. RESULTS: The sample consisted of 15,203 subjects, of whom 4,542 died during the follow-up period. Coexisting COPD and asthma was reported by 357 (2.7%), COPD by 815 (5.3%), and asthma by 709 (5.3%). Subjects with both conditions had a higher proportion of obstruction (30.9%) than those with COPD (24.3%), asthma (13.3%), or no lung disease (5.4%). In survival models adjusting for all factors except baseline lung function, coexisting COPD and asthma had the highest risk for mortality (Hazard Ratio [HR] 1.83, 95% confidence interval [CI] 1.34, 2.49), followed by COPD only (HR 1.44, 95% CI 1.28, 1.62), and asthma only (HR 1.16, 95% CI 0.94, 1.42). These affects were attenuated after controlling for baseline lung function: coexisting asthma and COPD (HR 1.45, 95% CI 1.06, 1.98), COPD only (1.28, 95% CI 1.13, 1.45), and asthma only (HR 1.04, 95% CI 0.85, 1.27). CONCLUSION: In this analysis, subjects who report coexisting asthma and COPD have a higher risk of obstruction on spirometry and a higher risk of death during follow-up.

Airway obstructive diseases in older adults: from detection to treatment.

Asthma and chronic obstructive pulmonary disease occur commonly and may overlap among older adults. Smoking, air pollution, and bronchial hyperresponsiveness are the main risk factors. The treatment of these diseases in older adults does not differ from the available guidelines but may be complicated by the presence of comorbidities. Smoking cessation is essential for smokers, and pulmonary rehabilitation must be considered regardless of the age of the patient.

Frequency and causes of combined obstruction and restriction identified in pulmonary function tests in adults.

BACKGROUND: The frequency of combined obstruction and restriction identified in pulmonary function tests has not been well described. Moreover, although the causes of combined-obstruction-and-restriction patterns are known, the frequency of the various etiologies has received little attention. METHODS: We retrospectively reviewed medical records and surveyed pulmonologists. RESULTS: 43,212 PFT sessions were evaluated, which yielded 130 patients who satisfied our criteria for spirometry evidence of combined obstruction and restriction. Their demographic features were: mean +/- SD age 54 +/- 14 y, 51% male, mean +/- SD body mass index 28.8 +/- 6.7 kg/m(2), mean +/- SD height 174 +/- 9 cm (men) and 162 +/- 7 cm (women). The causes of combined obstruction and restriction were classified as either a pulmonary parenchymal disorder (Group A, n = 49, 38%) or a combination of pulmonary parenchymal and non-pulmonary diseases (Group B, n = 63, 48%). In 18 patients (14%) no clear etiology of combined obstruction and restriction could be determined. The most common pulmonary disease was chronic obstructive pulmonary disease (45/130, 35%), and the most common non-parenchymal disease was congestive heart failure (27/130, 21%). We electronically sent a survey to 55 pulmonary physicians, of whom 30 (55%) responded. The respondents estimated that combined obstruction and restriction occurs in approximately 20% of all the pulmonary function tests performed in their practices and that pulmonary parenchymal diseases were responsible for 35% of all instances of combined obstruction and restriction. CONCLUSIONS: Combined obstruction and restriction occurs infrequently and is more commonly caused by a combination of pulmonary parenchymal and non-pulmonary disorders. Pulmonologists' impressions regarding the frequency and causes are generally discordant with the observed frequencies.

Safety of diagnostic bronchoscopy in patients with pulmonary hypertension.

BACKGROUND: Patients with pulmonary hypertension (PH) are considered to be at risk for complications associated with flexible bronchoscopy (FB). Although previous reports suggest that transbronchial biopsies increase the risk for hemorrhage in this population, data are limited to survey analyses and isolated reports. OBJECTIVES: It was the aim of this study to describe our experience with FB and to determine if bronchoscopic procedures are associated with adverse events in this population. METHODS: We conducted a retrospective review of patients with diagnosis of PH who underwent FB at the Cleveland Clinic between 2002 and 2005. Patients without PH who underwent FB by the same pulmonary physician were used as controls. RESULTS: A total of 90 patients, PH (n = 45) versus controls (n = 45), were included. The mean systolic pulmonary artery pressure in patients with PH was 58 +/- 7 mm Hg. Patients with PH had higher oxygen requirements at baseline (FiO(2) 0.42 vs. 0.3%; p = 0.01). The total number of procedures was similar between the groups (95 vs. 102). Procedures performed were bronchoalveolar lavage (21 vs. 13), transbronchial biopsies (24 vs. 32) and transbronchial needle aspiration (7 vs. 6). There were no hemodynamic complications or episodes of respiratory failure associated with the procedures. None of the patients had significant hemorrhage and only 2 developed mild bleeding which resolved spontaneously. Similarly, none required hospitalization or transfer to an intensive care unit. CONCLUSIONS: FB can be performed safely in patients with mild to moderate PH. Transbronchial biopsies are not associated with worsening hypoxemia or an increased risk of hemorrhage. Prospective studies with hemodynamic measurements are necessary to confirm these findings.

Pulmonary hypertension caused by sarcoidosis.

Pulmonary hypertension is an uncommon complication of sarcoidosis, but in severe pulmonary disease it occurs frequently. It is an important cause of cryptogenic dyspnea in sarcoidosis patients and can occur despite the absence of pulmonary fibrosis. The true prevalence is unknown. With the advent of specific therapies for pulmonary hypertension, there has been a resurgence of interest in the pathophysiology, diagnosis, and treatment of sarcoidosis-associated pulmonary hypertension. This article reviews the status of the current epidemiologic, pathophysiologic, and therapeutic knowledge regarding this entity.

Long-term experience after transition from parenteral prostanoids to oral agents in patients with pulmonary hypertension.

BACKGROUND: Long-term follow-up after transition to oral agents from parenteral prostanoid therapy has not been well characterized. METHODS: We reviewed our long-term experience after oral transitioning in patients with pulmonary hypertension. Patients were weaned off parenteral therapy based on a pre-determined outpatient protocol. Data were collected retrospectively after transition had taken place. RESULTS: Twenty-one transitioned patients were identified. Fifteen patients (71.4%) were successfully transitioned (ST): 7 to bosentan, 5 to bosentan and sildenafil, and 3 to sildenafil. Six patients failed transition (FT). None of the patients in the FT group received sildenafil. Prior to transition attempt, patients in the ST group were treated with parenteral agents for a mean of 26 months vs. 16 months in the FT group (p=0.12). Maximal epoprostenol dose was low in both groups (ST 17.8 ng/kg/min vs. FT 14.5 ng/kg/min). Mean duration of oral therapy prior to transition was 11 months. After a mean follow-up of 24 months, most patients on both groups were able to maintain stable 6 min walk distance and hemodynamics. FT was not associated with short- or long-term adverse events. CONCLUSIONS: Oral transition from parenteral prostanoid agents can be safely done in a selected group of patients. Most patients are able to maintain stable functional class and hemodynamics at long follow up regardless of success of transition attempt. Combination therapy with sildenafil appears to be associated with higher likelihood of successful transitioning.

Accuracy of the physical examination in evaluating pleural effusion.

A careful physical examination is a valuable and noninvasive means of assessing pleural effusion and should be routinely performed in every patient in whom this condition is suspected. Although physical examination is less accurate than ultrasonography or computed tomography in detecting a pleural effusion, the sensitivity and specificity of the different physical signs of pleural effusion may be comparable to those of conventional chest radiography.

Diagnosis and management of pleural effusions: a practical approach.

Pleural effusion is defined as an abnormal amount of pleural fluid accumulation in the pleural space and is the result of an imbalance between excessive pleural fluid formation and pleural fluid absorption. Although the list of causes of pleural effusions is extensive, the great majority of the cases are caused by pneumonia, congestive heart failure, and malignancy. In this article, we provide an overview of the most common causes of pleural effusions likely to be encountered by the general practitioner, and a practical approach to the diagnosis and management of this common condition.

Distal airway microbiome is associated with immunoregulatory myeloid cell responses in lung transplant recipients.

BACKGROUND: Long-term survival of lung transplant recipients (LTRs) is limited by the occurrence of bronchiolitis obliterans syndrome (BOS). Recent evidence suggests a role for microbiome alterations in the occurrence of BOS, although the precise mechanisms are unclear. In this study we evaluated the relationship between the airway microbiome and distinct subsets of immunoregulatory myeloid-derived suppressor cells (MDSCs) in LTRs. METHODS: Bronchoalveolar lavage (BAL) and simultaneous oral wash and nasal swab samples were collected from adult LTRs. Microbial genomic DNA was isolated, 16S rRNA genes amplified using V4 primers, and polymerase chain reaction (PCR) products sequenced and analyzed. BAL MDSC subsets were enumerated using flow cytometry. RESULTS: The oral microbiome signature differs from that of the nasal, proximal and distal airway microbiomes, whereas the nasal microbiome is closer to the airway microbiome. Proximal and distal airway microbiome signatures of individual subjects are distinct. We identified phenotypic subsets of MDSCs in BAL, with a higher proportion of immunosuppressive MDSCs in the proximal airways, in contrast to a preponderance of pro-inflammatory MDSCs in distal airways. Relative abundance of distinct bacterial phyla in proximal and distal airways correlated with particular airway MDSCs. Expression of CCAAT/enhancer binding protein (C/EBP)-homologous protein (CHOP), an endoplasmic (ER) stress sensor, was increased in immunosuppressive MDSCs when compared with pro-inflammatory MDSCs. CONCLUSIONS: The nasal microbiome closely resembles the microbiome of the proximal and distal airways in LTRs. The association of distinct microbial communities with airway MDSCs suggests a functional relationship between the local microbiome and MDSC phenotype, which may contribute to the pathogenesis of BOS.

Extracorporeal membrane oxygenation in adults: A practical guide for internists.

The use of extracorporeal membrane oxygenation (ECMO) in adults has rapidly increased as the technology has evolved, although there is little definitive evidence that it is beneficial in this group. ECMO is now being used in acute respiratory distress syndrome (and was used extensively for this indication during the influenza H1N1 pandemic), as a bridge to lung or heart transplant, and in postcardiac arrest patients. We review the current evidence and indications for ECMO, focusing on its principles and practical aspects in adult patients with respiratory or cardiac failure.

Automated Rotational Percussion Bed and Bronchoscopy Improves Respiratory Mechanics and Oxygenation in ARDS Patients Supported with Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) has been used to provide "lung rest" through the use of low tidal volume (6 ml/kg) and ultralow tidal volume (<6 ml/kg) ventilation in acute respiratory distress syndrome (ARDS). Low and ultralow tidal volume ventilation can result in low dynamic respiratory compliance and potentially increased retention of airway secretions. We present our experience using automated rotational percussion beds (ARPBs) and bronchoscopy in four ARDS patients to manage increased pulmonary secretions. These beds performed automated side-to-side tilt maneuver and intermittent chest wall percussion. Their use resulted in substantial reduction in peak and plateau pressures in two patients on volume control ventilation, while the driving pressures (inspiratory pressure) to attain the desired tidal volumes in patients on pressure control ventilation also decreased. In addition, mean partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FiO2) ratio (109 pre-ARPB vs. 157 post-ARPB), positive end-expiratory pressure (10 cm H2O vs. 8 cm H2O), and FiO2 (0.88 vs. 0.52) improved after initiation of ARPB. The improvements in the respiratory mechanics and oxygenation helped us to initiate early ECMO weaning. Based on our experience, the use of chest physiotherapy, frequent body repositioning, and bronchoscopy may be helpful in the management of pulmonary secretions in patients supported with ECMO.

Flexible Bronchoscopy Is Safe and Effective in Adult Subjects Supported With Extracorporeal Membrane Oxygenation.

BACKGROUND: Previous studies have demonstrated the safety of flexible bronchoscopy (FB) in mechanically ventilated subjects. However, the safety of FB in adult subjects receiving extracorporeal membrane oxygenation (ECMO) has not been described previously. METHODS: A retrospective review was conducted of all adult subjects who underwent FB while receiving ECMO support at the University of Alabama at Birmingham Hospital from January 1, 2013, to December 31, 2014. Physiologic variables, pre- and post-FB ECMO, and ventilator settings were recorded. RESULTS: 79 adult subjects underwent FB receiving ECMO with a total of 223 bronchoscopies. The most common indications for bronchoscopy included diagnostic evaluation of infection in subjects with pneumonia (29%) and clearance of excessive secretions (22%). In 70% of subjects, moderate or greater amounts of secretions were noted. FB yielded positive culture data in 37 subjects (47%), which resulted in a change to the antibiotic regimen in 14 subjects (38%) with positive culture data. No significant differences in mean PaO2 /FIO2 , mean ECMO flow, mean sweep gas, ventilator settings, or hemodynamic parameters (heart rate, oxygen saturation, and mean blood pressure) were noted before and after FB. Complications were mild and transient: blood-tinged secretions after FB in 21% cases, which resolved spontaneously, intraprocedural hypoxemia in 2.2% of cases, and dysrhythmia in <1% of cases. There were no episodes of ECMO cannula dislodgement or inadvertent extubation. CONCLUSIONS: FB can be used safely in adult subjects supported with ECMO and is not associated with significant hemodynamics changes, bleeding, or mechanical complications during ECMO support.

Early initiation of extracorporeal membrane oxygenation improves survival in adult trauma patients with severe adult respiratory distress syndrome.

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) in the trauma population has been reported to have a mortality benefit in patients with severe refractory hypoxic respiratory failure. This study compares the early initiation of ECMO for the management of severe adult respiratory distress syndrome (ARDS) versus a historical control immediately preceding the use of ECMO for trauma patients. METHODS: A retrospective study was conducted at a single verified Level I trauma center. The study population was limited to trauma patients diagnosed with severe ARDS using the Berlin definition (PaO2/FIO2 ratio < 100). Patients managed with ECMO versus conventional ventilation (CONV) were compared. The primary outcome of interest was mortality; secondary outcomes included hospital length of stay, intensive care unit-free days, and ventilator-free days. RESULTS: Fifteen ECMO patients managed from March 2013 to November 2014 were identified, as were 14 CONV patients managed from March 2012 to February 2013 who met the Berlin definition of severe ARDS. Data related to age, Injury Severity Scores (ISSs), admission lactic acid levels, base deficit, the number of transfused red blood cell units within the first 24 hours, and presence of severe traumatic brain injury were collected and were not statistically different between the groups. Likewise, Murray Lung Injury (MLI), Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores determined at the onset of severe ARDS were not statistically different between the groups. Median hospital stay (CONV, 28.0 days [14.0-47.0]; ECMO, 43.5 days [30.0-93.0]; p = 0.15), intensive care unit-free days (CONV, 0.0 days [0.0-5.0]; ECMO, 5.0 days [0.0-7.0]; p = 0.26), and ventilator-free days (CONV, 0.0 days [0.0-10.0]; ECMO, 8.0 days [0.0-19.0]; p = 0.13) were not statistically different between the groups. Mortality in the ECMO group was significantly reduced compared with the CONV group (ECMO, 13.3%; CONV, 64%; p = 0.01). Timing from the onset of severe ARDS to ECMO intervention occurred at a mean 1.9 ± 1.4 days. CONCLUSION: Patients who were treated with ECMO for severe ARDS had an improved mortality compared with historical controls. ECMO should be considered at the early onset of severe ARDS to improve survival. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Modern use of extracorporeal life support in pregnancy and postpartum.

Extracorporeal membrane oxygenation (ECMO) use during pregnancy and the postpartum period are thought to be associated with an increased risk for maternal or fetal bleeding complications. We present our recent institutional experience in managing pregnant and postpartum patients with ECMO. We also performed a literature review of modern use of ECMO in pregnant and postpartum patients utilizing Pubmed and Embase databases. ECMO was used for severe cardiopulmonary failure due to multiple conditions. Based on published reports, overall maternal and fetal survival on ECMO were 80% and 70%, respectively. Mild-to-moderate vaginal bleeding was reported in a few cases, with rare occurrences of catastrophic postpartum hemorrhage. There was no consensus on an optimal anticoagulation strategy in these patients, though most preferred to keep anticoagulation at lower therapeutic levels. We conclude that ECMO, in well-selected pregnant and postpartum patients, appears to be safe and associated with low risk of maternal and fetal complications.

Successful Treatment of Severe Carbon Monoxide Poisoning and Refractory Shock Using Extracorporeal Membrane Oxygenation.

Carbon monoxide (CO) is the most common cause of poisoning and poisoning-related death in the United States. It is a tasteless and odorless poisonous gas produced from incomplete combustion of hydrocarbons, such as those produced by cars and heating systems. CO rapidly binds to hemoglobin to form carboxyhemoglobin, leading to tissue hypoxia, multiple-organ failure, and cardiovascular collapse. CO also binds to myocardial myoglobin, preventing oxidative phosphorylation in cardiac mitochondria and resulting in cardiac ischemia or stunning and cardiogenic pulmonary edema. Treatment of CO poisoning is mainly supportive, and supplemental oxygen remains the cornerstone of therapy, whereas hyperbaric oxygen therapy is considered for patients with evidence of neurological and myocardial injury. Extracorporeal membrane oxygenation (ECMO) has been utilized effectively in patients with respiratory failure and hemodynamic instability, but its use has rarely been reported in patients with CO poisoning. We report the successful use of venoarterial ECMO in a patient with severe CO poisoning and multiple-organ failure.