Gary Salzman

Oropharyngeal candidiasis in patients treated with beclomethasone dipropionate delivered by metered-dose inhaler alone and with Aerochamber

We compared the incidence of Candida infection, Candida colonization, and reduction in oral prednisone dose in patients with asthma treated with beclomethasone dipropionate delivered by metered-dose inhaler (MDI) alone and MDI plus Aerochamber. Group M contained 18 patients treated with beclomethasone, four actuations four times a day (672 micrograms/day), delivered by MDI alone. Group A contained 18 patients treated with the same dose of beclomethasone delivered by MDI plus Aerochamber. In group M, four of 18 patients had Candida infection, 12 of 18 patients had Candida colonization, and six of 18 patients were completely removed from oral prednisone. In group A, 0 of 18 patients had Candida infection (p = 0.05), six of 18 patients had Candida colonization (p less than 0.05), and 12 of 18 patients were completely removed from oral prednisone (p less than 0.05). We conclude that beclomethasone delivered by MDI plus Aerochamber is more efficacious in reducing oral prednisone dependency and produces less Candida infection and colonization than beclomethasone delivered by MDI alone.

Use of Intrapleural Streptokinase in the Treatment of Thoracic Empyema

The incidence of pleural effusions in bacterial pneumonia may exceed 40%, a factor that may be related to increased morbidity and mortality. Options in the treatment of complicated pleural effusions or empyema, when unresponsive to closed tube drainage, include repositioning of the indwelling tube thoracostomy or insertion of additional chest tubes, instillation of intrapleural streptokinase, and surgical intervention. The authors describe the course of three patients wherein the use of intrapleural streptokinase was efficacious in effecting prompt drainage of previously inadequately evacuated empyema, thus eliminating the necessity for further invasive intervention.

Design, baseline characteristics, and retention of African American light smokers into a randomized trial involving biological data

BackgroundAfrican Americans experience significant tobacco-related health disparities despite the fact that over half of African American smokers are light smokers (use ≤10 cigarettes per day). African Americans have been under-represented in smoking cessation research, and few studies have evaluated treatment for light smokers. This paper describes the study design, measures, and baseline characteristics from Kick It at Swope III (KIS-III), the first treatment study of bupropion for African American light smokers.MethodsFive hundred forty African American light smokers were randomly assigned to receive bupropion (150mg bid) (n = 270) or placebo (n = 270) for 7 weeks. All participants received written materials and health education counseling. Participants responded to survey items and provided blood samples for evaluation of phenotype and genotype of CYP2A6 and CYP2B6 enzymes involved in nicotine and bupropion metabolism. Primary outcome was cotinine-verified 7-day point prevalence smoking abstinence at Week 26 follow-up.ResultsOf 2,628 individuals screened, 540 were eligible, consented, and randomized to treatment. Participants had a mean age of 46.5 years and 66.1% were women. Participants smoked an average of 8.0 cigarettes per day, had a mean exhaled carbon monoxide of 16.4ppm (range 1-55) and a mean serum cotinine of 275.8ng/ml. The mean Fagerström Test for Nicotine Dependence was 3.2, and 72.2% of participants smoked within 30 minutes of waking. The average number of quit attempts in the past year was 3.7 and 24.2% reported using pharmacotherapy in their most recent quit attempt. Motivation and confidence to quit were high.ConclusionKIS-III is the first study designed to examine both nicotine and bupropion metabolism, evaluating CYP2A6 and CYP2B6 phenotype and genotype in conjunction with psychosocial factors, in the context of treatment of African American light smokers. Of 1629 smokers screened for study participation, only 18 (1.1%) were ineligible to participate in the study because they refused blood draws, demonstrating the feasibility of recruiting and enrolling African American light smokers into a clinical treatment trial involving biological data collection and genetic analyses. Future evaluation of individual factors associated with treatment outcome will contribute to advancing tailored tobacco use treatment with the goal of enhancing treatment and reducing health disparities for African American light smokers.Trial RegistrationClinicalTrials.gov: NCT00666978

Flow transport and gas mixing during invasive high frequency oscillatory ventilation.

A large Eddy simulation (LES) based computational fluid dynamics study was performed to investigate gas transport and mixing in patient specific human lung models during high frequency oscillatory ventilation. Different pressure-controlled waveforms (sinusoidal, exponential and square) and ventilator frequencies (15, 10 and 6Hz) were used (tidal volume=50mL). The waveforms were created by solving the equation of motion subjected to constant lung wall compliance and flow resistance. Simulations were conducted with and without endotracheal tube to understand the effect of invasive management device. Variation of pressure-controlled waveform and frequency exhibits significant differences on counter flow pattern, which could lead to a significant impact on the gas mixing efficiency. Pendelluft-like flow was present for the sinusoidal waveform at all frequencies but occurred only at early inspiration for the square waveform at highest frequency. The square waveform was most efficient for gas mixing, resulting in the least wall shear stress on the lung epithelium layer thereby reducing the risk of barotrauma to both airways and the alveoli for patients undergoing therapy.

Pulmonary alveolar proteinosis: an overview for internists and hospital physicians.

Abstract Pulmonary alveolar proteinosis (PAP) is a rare diffuse lung disease characterized by abnormal accumulation of surfactant-associated phospholipoproteinaceous material in the pulmonary alveoli. The clinical findings of slow-onset dyspnea or dyspnea on exertion and persistent dry cough are nonspecific; radiographic findings of “bat-wing configuration” and “crazy paving” appearance in high-resolution computed tomography are suggestive, but not diagnostic of PAP. The current gold standard of PAP diagnosis involves histopathological examination of alveolar specimens obtained from bronchoalveolar lavage and transbronchial lung biopsy. The characteristic histopathological features are intraalveolar periodic acid Schiff (PAS)-positive eosinophilic homogeneous material with well-preserved architecture of alveolar septa. The current standard medical treatment of PAP involves the physical removal of the surfactant-associated phospholipoproteinaceous alveolar deposit by whole lung lavage, which causes clinical and radiological improvement in a majority of patients. Some patients have been successfully treated with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF).

The role of coupled resistance–compliance in upper tracheobronchial airways under high frequency oscillatory ventilation

A large eddy simulation (LES) based computational fluid dynamics (CFD) study was conducted to investigate lung lobar ventilation and gas exchange under high frequency oscillatory ventilation conditions. Time-dependent pressure coupled with the airways resistance and compliance (R&C) were imposed as boundary conditions (BCs) in the upper tracheobronchial tree of patient-specific lung geometry. The flow distribution in the left and right lungs demonstrated significant variations compared to the case in which traditional BCs based on mass flow rate fractions was used and is in agreement with the in vivo data available in the literature. The gas transport due to the pendelluft mechanism was captured in the different lung lobes and units. The computed pendelluft elapsed time was consistent with available physiological data. In contrast to in vivo studies, our simulations were able to predict the volume associated with the pendelluft elapsed time at different frequencies. Significant differences in coaxial counter flow and flow structures were observed between different BCs. The consistency of the results with the physiological in vivo data indicates that computations with coupled R&C BCs provide a suitable alternative tool for understanding the gas transport, diagnosing lung pathway disease severity, and optimizing ventilation management techniques.

Chronic Obstructive Pulmonary Disease: Clinical Review and Update on Consensus Guidelines

Abstract In the last 2 decades, chronic obstructive pulmonary disease (COPD) has been increasingly recognized as a major public health problem. Since the introduction of the Global Initiative for Chronic Obstructive Lung Disease in 1998, growing interest in the pathogenesis and management of patients with COPD has led to notable improvements in patient care and quality of life. Despite greater awareness of this common preventable disease and major therapeutic advances during this period, the global impact of COPD remains strikingly large. We provide an evidence-based clinical review on COPD, with a focus on internists as the target audience.

Continuously Nebulized Albuterol in Severe Exacerbations of Asthma in Adults: A Case-Controlled Study

A retrospective, case-controlled analysis comparing patients admitted to a medical intensive care unit with severe exacerbations of asthma who received continuously nebulized albuterol (CNA) versus intermittent albuterol (INA) treatments is reported. Forty matched pairs of patients with asthma are compared. CNA was administered for a mean of 11 +/- 10 hr. The incidence of cardiac dysrhythmias was similar between groups. Symptomatic hypokalemia did not occur. CNA patients had higher heart rates during treatment, which may reflect severity of illness. The incidence of intubation was similar. We conclude that CNA and INA demonstrated similar profiles with regard to safety, morbidity, and mortality.

Fluid flow and particle transport in mechanically ventilated airways. Part I. Fluid flow structures

A large eddy simulation-based computational study of fluid flow and particle transport in upper tracheobronchial airways is carried out to investigate the effect of ventilation parameters on pulmonary fluid flow. Respiratory waveforms commonly used by commercial mechanical ventilators are used to study the effect of ventilation parameters and ventilation circuit on pulmonary fluid dynamics. A companion paper (Alzahrany et al. in Med Biol Eng Comput, 2014) reports our findings on the effect of the ventilation parameters and circuit on particle transport and aerosolized drug delivery. The endotracheal tube (ETT) was found to be an important geometric feature and resulted in a fluid jet that caused an increase in turbulence and created a recirculation zone with high wall shear stress in the main bronchi. Stronger turbulence was found in lower airways than would be found under normal breathing conditions due to the presence of the jet caused by the ETT. The pressure-controlled sinusoidal waveform induced the lowest wall shear stress on the airways wall.

Hepatic hydrothorax: clinical review and update on consensus guidelines

ABSTRACT Hepatic Hydrothorax (HH) is defined as a pleural effusion greater than 500 ml in association with cirrhosis and portal hypertension. It is an uncommon complication of cirrhosis, most frequently seen in association with decompensated liver disease. The development of HH remains incompletely understood and involves a complex pathophysiological process with the most acceptable explanation being the passage of the ascetic fluid through small diaphragmatic defects. Given the limited capacity of the pleural space, even the modest pleural effusion can result in significant respiratory symptoms. The diagnosis of HH should be suspected in any patient with established cirrhosis and portal hypertension presenting with unilateral pleural effusion especially on the right side. Diagnostic thoracentesis should be performed in all patients with suspected HH to confirm the diagnosis and rule out infection and alternative diagnoses. Spontaneous bacterial empyema and spontaneous bacterial pleuritis can complicate HH and increase morbidity and mortality. HH can be difficult to treat and in our review below we will list the therapeutic modalities awaiting the evaluation for the only definitive therapy, which is liver transplantation