D. Kyle Hogarth

Management of sedation in mechanically ventilated patients

Purpose of reviewThere are many new and exciting studies in the sedation literature. Recent studies of new scoring systems to monitor sedation, new medications, and new insights into post–intensive care unit (ICU) sequelae have brought about interesting ideas for achieving an adequate level of sedation of our patients while minimizing complications. Recent findingsThe recent literature focuses on monitoring the level of a patient’s sedation with new bedside clinical scoring systems and new technology. Outcomes studies have highlighted problems with both inadequate sedation and excessive sedation in regard to patients’ post-ICU psychological health. More insight into drug withdrawal and addiction as complications of ICU care were examined. A new medication for sedation in the ICU has been approved for use, but its role is not yet defined. SummaryMany patients in the ICU receive mechanical ventilation and will require sedative medications. A frequently overlooked cause of agitation in the ventilated patient is pain, and assessing the adequacy of analgesia is an important part of the continuous assessment of a patient. The goal of sedation is to provide relief while minimizing the development of drug dependency and oversedation. Careful monitoring with bedside scoring systems, the appropriate use of medications, and a strategy of daily interruption can lead to diminished time on the ventilator and in the ICU.

Investigation of the Cause of Death in a Gene-Therapy Trial

We present a case of disseminated histoplasmosis, complicated by retroperitoneal bleeding and leading to death, in a patient who was receiving systemic immunosuppressive therapy for rheumatoid arthritis and who was enrolled in a gene-therapy trial. This trial was designed to evaluate intraarticular delivery of a tumor necrosis factor alpha (TNF-alpha) antagonist, through an adeno-associated virus (AAV) type 2 delivery system, for inflammatory arthritis. The patients receipt of concurrent anti-TNF-alpha therapy and other immunosuppressive therapy while she was living in an area where histoplasmosis was endemic was thought to be the most likely explanation for the infection; the evidence presented suggests that this fatal infection was unlikely to have been related to exposure to the agent administered in the gene-therapy trial. This case reinforces the importance of considering infectious complications, such as those from endemic mycoses, in patients receiving treatment with a TNF-alpha antagonist and the importance of having a well-designed monitoring plan when subjects in a research study become ill. (ClinicalTrials.gov number, NCT00126724.)

Myocardial damage in patients with sarcoidosis and preserved left ventricular systolic function: an observational study

Late gadolinium enhanced cardiovascular magnetic resonance (LGE‐CMR) is a valuable test to detect myocardial damage in patients with sarcoidosis; however, the clinical significance of LGE in sarcoidosis patients with preserved left ventricular ejection fraction (LVEF) is not defined. We aim to characterize the prevalence of LGE, its associated cardiac findings, and its clinical implications in sarcoidosis patients with preserved LVEF.

Prognosis of Myocardial Damage in Sarcoidosis Patients With Preserved Left Ventricular Ejection Fraction: Risk Stratification Using Cardiovascular Magnetic Resonance.

Background—Cardiac sarcoidosis is associated with an increased risk of heart failure and sudden death, but its risk in patients with preserved left ventricular ejection fraction is unknown. Using cardiovascular magnetic resonance in patients with extracardiac sarcoidosis and preserved left ventricular ejection fraction, we sought to (1) determine the prevalence of cardiac sarcoidosis or associated myocardial damage, defined by the presence of late gadolinium enhancement (LGE), (2) quantify their risk of death/ventricular tachycardia (VT), and (3) identify imaging-based covariates that predict who is at greatest risk of death/VT. Methods and Results—Parameters of left and right ventricular function and LGE burden were measured in 205 patients with left ventricular ejection fraction >50% and extracardiac sarcoidosis who underwent cardiovascular magnetic resonance for LGE evaluation. The association between covariates and death/VT in the entire group and within the LGE+ group was determined using Cox proportional hazard models and time-dependent receiver–operator curves analysis. Forty-one of 205 patients (20%) had LGE; 12 of 205 (6%) died or had VT during follow-up; of these, 10 (83%) were in the LGE+ group. In the LGE+ group (1) the rate of death/VT per year was >20× higher than LGE− (4.9 versus 0.2%, P<0.01); (2) death/VT were associated with a greater burden of LGE (14±11 versus 5±5%, P<0.01) and right ventricular dysfunction (right ventricular EF 45±12 versus 53±28%, P=0.04). LGE burden was the best predictor of death/VT (area under the receiver-operating characteristics curve, 0.80); for every 1% increase of LGE burden, the hazard of death/VT increased by 8%. Conclusions—Sarcoidosis patients with LGE are at significant risk for death/VT, even with preserved left ventricular ejection fraction. Increased LGE burden and right ventricular dysfunction can identify LGE+ patients at highest risk of death/VT.

A randomised trial of lung sealant versus medical therapy for advanced emphysema

Uncontrolled pilot studies demonstrated promising results of endoscopic lung volume reduction using emphysematous lung sealant (ELS) in patients with advanced, upper lobe predominant emphysema. We aimed to evaluate the safety and efficacy of ELS in a randomised controlled setting. Patients were randomised to ELS plus medical treatment or medical treatment alone. Despite early termination for business reasons and inability to assess the primary 12-month end-point, 95 out of 300 patients were successfully randomised, providing sufficient data for 3- and 6-month analysis. 57 patients (34 treatment and 23 control) had efficacy results at 3 months; 34 (21 treatment and 13 control) at 6 months. In the treatment group, 3-month lung function, dyspnoea, and quality of life improved significantly from baseline when compared to control. Improvements persisted at 6 months with >50% of treated patients experiencing clinically important improvements, including some whose lung function improved by >100%. 44% of treated patients experienced adverse events requiring hospitalisation (2.5-fold more than control, p=0.01), with two deaths in the treated cohort. Treatment responders tended to be those experiencing respiratory adverse events. Despite early termination, results show that minimally invasive ELS may be efficacious, yet significant risks (probably inflammatory) limit its current utility. Emphysematous lung sealant therapy is highly efficacious in some patients, but benefits bring significant risks http://ow.ly/JJ2vg

Screening and Familial Testing of Patients for α1-Antitrypsin Deficiency

alpha(1)-Antitrypsin deficiency (AATD) is an autosomal-codominant genetic disorder that predisposes individuals to the development of liver and lung disease. AATD is greatly underrecognized and underdiagnosed. Early identification allows preventive measures to be taken, the most important of which is the avoidance of smoking (including the inhalation of second-hand smoke) and exposure to environmental pollutants. Early detection also allows careful lung function monitoring and augmentation therapy while the patient still has preserved lung function. Cost factors and controversies have discouraged the initiation of large-scale screening programs of the newborn and adult populations in the United States and Europe (except for Sweden). There are sound medical reasons for targeted screening. Evidence-based recommendations for testing have been published by the American Thoracic Society/European Respiratory Society task force, which take potential social, psychological, and ethical adverse factors into consideration. This review discusses rationales for testing and screening for AATD in asymptomatic individuals, family members, and the general population, weighing benefits against potential psychological, social, and ethical implications of testing. For most, negative issues are outweighed by the benefits of testing. AATD testing should be routine in the management of adults with emphysema, COPD, and asthma with incompletely reversible airflow obstruction.

Airway Inflammation after Bronchial Thermoplasty for Severe Asthma

RATIONALE Bronchial thermoplasty is an alternative treatment for patients with severe, uncontrolled asthma in which the airway smooth muscle is eliminated using radioablation. Although this emerging therapy shows promising outcomes, little is known about its effects on airway inflammation. OBJECTIVES We examined the presence of bronchoalveolar lavage cytokines and expression of smooth muscle actin in patients with severe asthma before and in the weeks after bronchial thermoplasty. METHODS Endobronchial biopsies and bronchoalveolar lavage samples from 11 patients with severe asthma were collected from the right lower lobe before and 3 and 6 weeks after initial bronchial thermoplasty. Samples were analyzed for cell proportions and cytokine concentrations in bronchoalveolar lavage and for the presence of α-SMA in endobronchial biopsies. MEASUREMENTS AND MAIN RESULTS α-SMA expression was decreased in endobronchial biopsies of 7 of 11 subjects by Week 6. In bronchoalveolar lavage fluid, both transforming growth factor-β1 and regulated upon activation, normal T-cell expressed and secreted (RANTES)/CCL5 were substantially decreased 3 and 6 weeks post bronchial thermoplasty in all patients. The cytokine tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL), which induces apoptosis in several cell types, was increased in concentration both 3 and 6 weeks post bronchial thermoplasty. CONCLUSIONS Clinical improvement and reduction in α-SMA after bronchial thermoplasty in severe, uncontrolled asthma is associated with substantial changes in key mediators of inflammation. These data confirm the substantial elimination of airway smooth muscle post thermoplasty in the human asthmatic airway and represent the first characterization of significant changes in airway inflammation in the first weeks after thermoplasty.

Corticosteroid therapy and airflow obstruction influence the bronchial microbiome, which is distinct from that of bronchoalveolar lavage in asthmatic airways

BACKGROUND The lung has a diverse microbiome that is modest in biomass. This microbiome differs in asthmatic patients compared with control subjects, but the effects of clinical characteristics on the microbial community composition and structure are not clear. OBJECTIVES We examined whether the composition and structure of the lower airway microbiome correlated with clinical characteristics of chronic persistent asthma, including airflow obstruction, use of corticosteroid medications, and presence of airway eosinophilia. METHODS DNA was extracted from endobronchial brushings and bronchoalveolar lavage fluid collected from 39 asthmatic patients and 19 control subjects, along with negative control samples. 16S rRNA V4 amplicon sequencing was used to compare the relative abundance of bacterial genera with clinical characteristics. RESULTS Differential feature selection analysis revealed significant differences in microbial diversity between brush and lavage samples from asthmatic patients and control subjects. Lactobacillus, Pseudomonas, and Rickettsia species were significantly enriched in samples from asthmatic patients, whereas Prevotella, Streptococcus, and Veillonella species were enriched in brush samples from control subjects. Generalized linear models on brush samples demonstrated oral corticosteroid use as an important factor affecting the relative abundance of the taxa that were significantly enriched in asthmatic patients. In addition, bacterial α-diversity in brush samples from asthmatic patients was correlated with FEV1 and the proportion of lavage eosinophils. CONCLUSION The diversity and composition of the bronchial airway microbiome of asthmatic patients is distinct from that of nonasthmatic control subjects and influenced by worsening airflow obstruction and corticosteroid use.

Issues in the diagnosis of α1-antitrypsin deficiency

Alpha 1-antitrypsin deficiency is a relatively common genetic disease that is underrecognized and underdiagnosed. Early diagnosis in the asymptomatic patient helps modify lifestyle choices to reduce the risk of emphysema. In 2003, the American Thoracic Society and the European Respiratory Society issued guidelines to improve standards in diagnosing alpha(1)-antitrypsin deficiency. This review highlights key recommendations for diagnosis of alpha(1)-antitrypsin deficiency, including the different types of diagnostic tests recommended in the guidelines. Options for patient treatment will be discussed.

Interventional Pulmonology Fellowship Accreditation Standards: Executive Summary of the Multisociety Interventional Pulmonology Fellowship Accreditation Committee

&NA; Interventional pulmonology (IP) is a rapidly evolving subspecialty of pulmonary medicine. In the last 10 years, formal IP fellowships have increased substantially in number from five to now > 30. The vast majority of IP fellowship trainees are selected through the National Resident Matching Program, and validated in‐service and certification examinations for IP exist. Practice standards and training guidelines for IP fellowship programs have been published; however, considerable variability in the environment, curriculum, and experience offered by the various fellowship programs remains, and there is currently no formal accreditation process in place to standardize IP fellowship training. Recognizing the need for more uniform training across the various fellowship programs, a multisociety accreditation committee was formed with the intent to establish common accreditation standards for all IP fellowship programs in the United States. This article provides a summary of those standards and can serve as an accreditation template for training programs and their offices of graduate medical education as they move through the accreditation process.