Patient-Centered Specialty Practice: Defining the Role of Specialists in Value-Based Health Care.

Health care is at a crossroads and under pressure to add value by improving patient experience and health outcomes and reducing costs to the system. Efforts to improve the care model in primary care, such as the patient-centered medical home, have enjoyed some success. However, primary care accounts for only a small portion of total health-care spending, and there is a need for policies and frameworks to support high-quality, cost-efficient care in specialty practices of the medical neighborhood.

A Comparison of Usage and Outcomes Between Nurse Practitioner and Resident-Staffed Medical ICUs.

Objective: To compare usage patterns and outcomes of a nurse practitioner-staffed medical ICU and a resident-staffed physician medical ICU.

Design: Retrospective chart review of 1,157 medical ICU admissions from March 2012 to February 2013.

Setting: Large urban academic university hospital.

Eosinophil Peroxidase Catalyzed Protein Carbamylation Participates in Asthma.

The biochemical mechanisms through which eosinophils contribute to asthma pathogenesis are unclear. Here we show eosinophil peroxidase (EPO), an abundant granule protein released by activated eosinophils, contributes to characteristic asthma-related phenotypes through oxidative posttranslational modification (PTM) of proteins in asthmatic airways through a process called carbamylation. Using a combination of studies we now show EPO uses plasma levels of the pseudohalide thiocyanate (SCN) as substrate to catalyze protein carbamylation, as monitored by PTM of protein lysine residues into N-carbamyllysine (homocitrulline), and contributes to the pathophysiological sequelae of eosinophil activation.

Sarcoidosis activates diverse transcriptional programs in bronchoalveolar lavage cells.

Background: Sarcoidosis is a multisystem immuno-inflammatory disorder of unknown etiology that most commonly involves the lungs. We hypothesized that an unbiased approach to identify pathways activated in bronchoalveolar lavage (BAL) cells can shed light on the pathogenesis of this complex disease.

Methods: We recruited 15 patients with various stages of sarcoidosis and 12 healthy controls.

Early recognition of obstructive sleep apnea in patients hospitalized with COPD exacerbation is associated with reduced readmission.

Objectives: The combination of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease is known as the "overlap syndrome", and results in frequent hospitalizations and worse prognosis. We hypothesized that early detection and treatment of this condition in hospitalized patients may reduce clinical events (hospital admissions and emergency room visits) Methods: Between April 2013 and January 2014 all patients consulted for COPD exacerbation and having a BMI of > 30 kg/m(2) were screened for OSA. If high risk, patients underwent a polysomnography on discharge.

A pneumocyte-macrophage paracrine lipid axis drives the lung toward fibrosis.

Lipid-laden macrophages, or "foam cells," are observed in the lungs of patients with fibrotic lung disease, but their contribution to disease pathogenesis remains unexplored. Here, we demonstrate that fibrosis induced by bleomycin, silica dust, or thoracic radiation promotes early and sustained accumulation of foam cells in the lung. In the bleomycin model, we show that foam cells arise from neighboring alveolar epithelial type II cells, which respond to injury by dumping lipids into the distal airspaces of the lungs.

Lung cancer screening beyond low-dose computed tomography: the role of novel biomarkers.

Lung cancer is the most common and lethal malignancy in the world. The landmark National lung screening trial (NLST) showed a 20% relative reduction in mortality in high-risk individuals with screening low-dose computed tomography. However, the poor specificity and low prevalence of lung cancer in the NLST provide major limitations to its widespread use.

Readmissions after hospital discharge with acute exacerbation of COPD: are we missing something?

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an important part of the disease's morbidity, mortality, and progression, and is associated with increasing utilization of health care resources. The concept of integrated care based on a chronic care model is relatively new to chronic obstructive pulmonary disease, but has proved successful in improving clinical outcomes and probably in decreasing health care utilization in other chronic conditions. A comprehensive approach is needed to target a change in behavioral patterns in patients, increase physician's awareness and adherence to evidence-based recommendations, and address system related issues.

Carbon nanotube-induced pulmonary granulomatous disease: Twist1 and alveolar macrophage M1 activation.

Sarcoidosis, a chronic granulomatous disease of unknown cause, has been linked to several environmental risk factors, among which are some that may favor carbon nanotube formation. Using gene array data, we initially observed that bronchoalveolar lavage (BAL) cells from sarcoidosis patients displayed elevated mRNA of the transcription factor, Twist1, among many M1-associated genes compared to healthy controls. Based on this observation we hypothesized that Twist1 mRNA and protein expression might become elevated in alveolar macrophages from animals bearing granulomas induced by carbon nanotube instillation.

Alveolar macrophages of GM-CSF knockout mice exhibit mixed M1 and M2 phenotypes.

Background: Activin A is a pleiotrophic regulatory cytokine, the ablation of which is neonatal lethal. Healthy human alveolar macrophages (AMs) constitutively express activin A, but AMs of patients with pulmonary alveolar proteinosis (PAP) are deficient in activin A. PAP is an autoimmune lung disease characterized by neutralizing autoantibodies to Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF).

Extracorporeal membrane oxygenation to support whole-lung lavage in pulmonary alveolar proteinosis: salvage of the drowned lungs.

Pulmonary alveolar proteinosis is a rare lung disease characterized by accumulation of lipoproteinaceous material within the alveoli. Therapeutic whole-lung lavage (WLL) under general anesthesia is the standard treatment in patients with progressive symptomatic disease. Severe hypoxemic respiratory failure is uncommon, yet when present poses a technical challenge to performing WLL without further compromising respiratory status.

Alveolar macrophage cathelicidin deficiency in severe sarcoidosis.

Background: Dysfunctional immune responses characterize sarcoidosis, but the status of cathelicidin, a potent immunoregulatory and antimicrobial molecule, has not been established in clinical disease activity.

Methods: Alveolar macrophage cathelicidin expression was determined in biopsy-proven sarcoidosis patients classified clinically as 'severe' (requiring systemic treatment) or 'non-severe' (never requiring treatment). Bronchoalveolar lavage (BAL) cells from sarcoidosis patients and healthy controls were analyzed for mRNA expression of cathelicidin, vitamin D receptor (VDR) and the VDR coactivator steroid receptor coactivator-3 (SRC3) by quantitative PCR.

Rituximab therapy in pulmonary alveolar proteinosis improves alveolar macrophage lipid homeostasis.

Rationale: Pulmonary Alveolar Proteinosis (PAP) patients exhibit an acquired deficiency of biologically active granulocyte-macrophage colony stimulating factor (GM-CSF) attributable to GM-CSF specific autoantibodies. PAP alveolar macrophages are foamy, lipid-filled cells with impaired surfactant clearance and markedly reduced expression of the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) and the PPARγ-regulated ATP binding cassette (ABC) lipid transporter, ABCG1. An open label proof of concept Phase II clinical trial was conducted in PAP patients using rituximab, a chimeric murine-human monoclonal antibody directed against B lymphocyte specific antigen CD20.

Alveolar macrophage activation in obese patients with obstructive sleep apnea.

Background: Classically, activated macrophages in adipose tissue, liver, and muscle have been implicated in many conditions associated with obesity, including insulin resistance and the metabolic syndrome. Despite numerous pulmonary comorbidities and the sentinel role alveolar macrophages play in innate immunity and lung homeostasis, their activation status has not been examined in these patients. Peroxisome proliferator-activated receptor-gamma (PPAR-γ) has been shown to be a negative regulator of inflammation in addition to regulating lipid and glucose metabolism.

Inflammatory profile and response to anti-tumor necrosis factor therapy in patients with chronic pulmonary sarcoidosis.

Sarcoidosis is an inflammatory, granulomatous disease of unknown etiology that most commonly afflicts the lungs. Despite aggressive immunosuppressive therapies, many sarcoidosis patients still chronically present significant symptoms. Infliximab, a therapeutic tumor necrosis factor alpha (TNF-α) monoclonal antibody (MAb), produced a small but significant improvement in forced vital capacity (FVC) in sarcoidosis patients in a double-blind, placebo-controlled, phase II clinical trial.

Novel murine model of chronic granulomatous lung inflammation elicited by carbon nanotubes.

Lung granulomas are associated with numerous conditions, including inflammatory disorders, exposure to environmental pollutants, and infection. Osteopontin is a chemotactic cytokine produced by macrophages, and is implicated in extracellular matrix remodeling. Furthermore, osteopontin is up-regulated in granulomatous disease, and osteopontin null mice exhibit reduced granuloma formation.

Restoration of PPARγ reverses lipid accumulation in alveolar macrophages of GM-CSF knockout mice.

Pulmonary alveolar proteinosis (PAP) is a lung disease characterized by a deficiency of functional granulocyte macrophage colony-stimulating factor (GM-CSF) resulting in surfactant accumulation and lipid-engorged alveolar macrophages. GM-CSF is a positive regulator of PPARγ that is constitutively expressed in healthy alveolar macrophages. We previously reported decreased PPARγ and ATP-binding cassette transporter G1 (ABCG1) levels in alveolar macrophages from PAP patients and GM-CSF knockout (KO) mice, suggesting PPARγ and ABCG1 involvement in surfactant catabolism.

Sleep and metabolism: an overview.

Sleep and its disorders are increasingly becoming important in our sleep deprived society. Sleep is intricately connected to various hormonal and metabolic processes in the body and is important in maintaining metabolic homeostasis. Research shows that sleep deprivation and sleep disorders may have profound metabolic and cardiovascular implications.

Montelukast added to fluticasone propionate does not alter inflammation or outcomes.

Background: Airway inflammation is a key pathological feature of asthma which underlies its clinical presentation.

Objectives: To examine whether adding a leukotriene modifier to an inhaled corticosteroid produces further clinical and/or anti-inflammatory benefits in patients symptomatic on short-acting beta(2)-agonists.

Methods: Patients uncontrolled on short-acting beta(2)-agonists were treated for 12 weeks with either fluticasone propionate (100mcg BD) or fluticasone propionate (100mcg BD) and montelukast (10mg QD) in a randomized, double-blind, parallel group study.

PPARgamma regulates the expression of cholesterol metabolism genes in alveolar macrophages.

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear transcription factor involved in lipid metabolism that is constitutively expressed in the alveolar macrophages of healthy individuals. PPARgamma has recently been implicated in the catabolism of surfactant by alveolar macrophages, specifically the cholesterol component of surfactant while the mechanism remains unclear. Studies from other tissue macrophages have shown that PPARgamma regulates cholesterol influx, efflux, and metabolism.

Targeted PPAR{gamma} deficiency in alveolar macrophages disrupts surfactant catabolism.

Surfactant accumulates in alveolar macrophages of granulocyte-macrophage colony-stimulating factor (GM-CSF) knockout (KO) mice and pulmonary alveolar proteinosis (PAP) patients with a functional loss of GM-CSF resulting from neutralizing anti-GM-CSF antibody. Alveolar macrophages from PAP patients and GM-CSF KO mice are de-ficient in peroxisome proliferator-activated receptor-gamma (PPARgamma) and ATP-binding cassette (ABC) lipid transporter ABCG1. Previous studies have demonstrated that GM-CSF induces PPARgamma.

Alveolar proteinosis syndrome: pathogenesis, diagnosis, and management.

Purpose Of Review: This review discusses the most recent clinical and basic research literature on pulmonary alveolar proteinosis (PAP) as it relates to pathogenesis, diagnosis, and management.

Recent Findings: The discovery of Granulocyte macrophage-colony stimulating factor (GM-CSF) and the alveolar macrophage as critical regulators of surfactant protein and lipid homeostasis has led to significant advances in PAP. Adults affected by PAP have circulating neutralizing anti-GM-CSF antibodies.

Changes in chest roentgenogram of sarcoidosis patients during a clinical trial of infliximab therapy: comparison of different methods of evaluation.

Background: The best method to interpret the chest roentgenogram and its sensitivity to detect effect of treatment for sarcoidosis remains unclear. In a double-blind, randomized trial of infliximab for chronic pulmonary sarcoidosis, changes in serial chest roentgenograms were examined by radiologists, blinded to order or treatment.

Methods: Chest roentgenograms were obtained at 0, 6, and 24 weeks of therapy with either placebo, 3 mg/kg infliximab, or 5 mg/kg infliximab.

Deletion of PPAR gamma in alveolar macrophages is associated with a Th-1 pulmonary inflammatory response.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is constitutively expressed at high levels in healthy alveolar macrophages, in contrast to other tissue macrophages and blood monocytes. PPARgamma ligands have been shown to down-regulate IFN-gamma-stimulated inducible NO synthase (iNOS) in macrophages. Because NO is an important inflammatory mediator in the lung, we hypothesized that deletion of alveolar macrophage PPARgamma in vivo would result in up-regulation of iNOS and other inflammatory mediators.