A Randomized Controlled Trial on Optimal Sampling Sequence in Radial Guide Sheath Endobronchial Ultrasound Lung Biopsy.

BACKGROUND: An optimal sampling sequence in radial guide sheath endobronchial ultrasound lung biopsy (R-EBUS) is unclear. This prospective single-center pilot randomized controlled trial aimed to determine if the initial method and sequence of sampling affect the diagnostic accuracy of the procedure. METHODS: Consecutive patients undergoing R-EBUS for lesions >15 mm with a bronchus sign were randomly assigned (1:1:1) to biopsy first (group A), brushings first (group B) or combination (group C). The primary outcome was a positive diagnosis from any sampling method. RESULTS: Fifty-four patients were randomized. The overall diagnostic yield of the procedure was 77.8% (95% confidence interval: 66%-89%), with no difference between groups. A higher rate of positive cytology from brushings was seen if the biopsies were performed before brushings (77.8% in group A vs. 44.4% in group B, P=0.03). The rate of positive cytology from washings was higher if the washings were obtained just after the brushings (61.1% in group A vs. 11.1% in group B, P=0.02). There was no difference in the rate of positive biopsy histology in the groups (P=0.27). All 3 sampling modalities were more likely to be positive in group A (50.0% vs. 11.1% in group B and 22.2% in group C, P=0.04). Complications rate was low and not significantly different between groups. CONCLUSION: The overall rate of a positive R-EBUS procedure was not affected by the initial sampling method or sequence. However, all 3 sampling modalities were more likely to be positive if biopsies were performed first, followed by brushings and washings.

Artificial stone-associated silicosis: a rapidly emerging occupational lung disease.

INTRODUCTION: Artificial stone is an increasingly popular material used to fabricate kitchen and bathroom benchtops. Cutting and grinding artificial stone is associated with generation of very high levels of respirable crystalline silica, and the frequency of cases of severe silicosis associated with this exposure is rapidly increasing. AIM: To report the characteristics of a clinical series of Australian workers with artificial stone-associated silicosis. METHODS: Respiratory physicians voluntarily reported cases of artificial stone-associated silicosis identified in their clinical practices. Physicians provided information including occupational histories, respiratory function tests, chest radiology and histopathology reports, when available. RESULTS: Seven male patients were identified with a median age of 44 years (range 26-61). All were employed in small kitchen and bathroom benchtop fabrication businesses with an average of eight employees (range 2-20). All workplaces primarily used artificial stone, and dust control measures were poor. All patients were involved in dry cutting artificial stone. The median duration of exposure prior to symptoms was 7 years (range 4-10). Six patients demonstrated radiological features of progressive massive fibrosis. These individuals followed up over a median follow-up period of 16 months (IQR 21 months) demonstrated rapid decline in prebronchodilator forced expiratory volume in 1 s of 386 mL/year (SD 204 mL) and forced vital capacity of 448 mL/year (SD 312 mL). CONCLUSIONS: This series of silicosis in Australian workers further demonstrates the risk-associated high-silica content artificial stone. Effective dust control and health surveillance measures need to be stringently implemented and enforced in this industry.

A stonemason with accelerated silicosis in the setting of tumour necrosis factor alpha inhibitor therapy.

We present the case of a 26-year-old stonemason with accelerated silicosis in the setting of treatment for psoriasis with the tumour necrosis factor alpha (TNF-alpha) inhibitor adalimumab. Accelerated silicosis is an important occupational lung disease with a poor prognosis and limited treatment options [1]. Although the exact pathogenesis remains unknown, it is suggested that secretion of cytokines, including TNF-alpha, plays a central role in disease progression [1,2]. Importantly, however, TNF-alpha inhibitors, in addition to resulting in an increased risk of infection, are also now being seen to cause interstitial lung disease [3,4]. To our knowledge, this is the first documented patient to develop silicosis whilst on TNF-alpha inhibitor therapy. This case challenges the theory behind TNF-alpha's exact role in the pathogenesis of silicosis and lung fibrosis, highlights the importance of monitoring individuals with both occupational and drug exposures, and illustrates the increasing difficulties physicians face in investigating patients with pulmonary infiltrates and multiple possible aetiologies.

ARC--augmented renal clearance.

In-hospital and intensive care unit mortality rates for sepsis remain un-acceptably high, and have prompted the publication of international guidelines on best practice. Crucial to this is the application of early appropriate antibacterial therapy, in the correct dose. However, antibacterial regimes in this setting have largely been extrapolated from those in healthy volunteers, and fail to consider the unique pathophysiology and treatment provided to this population. As such, augmented renal clearance (ARC) - the enhanced renal elimination of circulating solute - is likely to be one of the more common physiological changes encountered in this setting, although to date remains largely under-appreciated. Significantly this may alter the pharmacokinetics of many routinely prescribed agents in this setting, pre-disposing to subtherapeutic levels or treatment failure. This review paper examines this phenomenon in detail, providing a summary of the likely underlying mechanisms, those patients at greatest risk, and the implications for antibacterial dosing in the critically ill.

Augmented renal clearance in the Intensive Care Unit: an illustrative case series.

The substantial underlying disease burden, in combination with the therapeutic interventions provided, can result in significantly altered end-organ function in the critically ill. These changes can in turn affect key pharmacokinetic (PK) indices for many antibiotics, including drug clearance, promoting potentially subtherapeutic concentrations for lengthy periods of the dosing interval, therapeutic failure or the selection of resistant organisms. This paper presents three instructional cases from our tertiary-level Intensive Care Unit, where established antibiotic dosing regimens failed to achieve predefined PK targets for optimal bacterial killing. Using therapeutic drug monitoring (TDM), significant dose modification was subsequently undertaken. We propose augmented renal clearance as a possible mechanism underlying this phenomenon, particularly in young post-operative, burns or head-injured patients with normal serum creatinine concentrations. TDM, or at least a measured creatinine clearance, should be considered early in this setting to allow the optimisation of antibiotic exposure.

Muscle stretching technique increases vital capacity and range of motion in patients with chronic obstructive pulmonary disease.

OBJECTIVES: To determine if a specific hold and relax stretching technique was capable of (1) reversing the effect of tight chest wall muscles by increasing chest expansion, vital capacity, and shoulder range of motion and (2) decreasing perceived dyspnea and respiratory rate in persons with chronic obstructive pulmonary disease (COPD). DESIGN: Double-blind crossover trial. SETTING: A physiotherapy department at a major metropolitan hospital. PARTICIPANTS: Fourteen stable patients with COPD who had recently completed a pulmonary rehabilitation program were enrolled, with 10 patients completing the study. INTERVENTION: A hold and relax stretching technique of the pectoralis major and a sham technique each for 2 days. MAIN OUTCOME MEASURES: The primary outcome measure was vital capacity (VC), with secondary outcome measures being perceived dyspnea, axillary (ACE) and xiphisternal chest expansion (XCE), right and left shoulder horizontal extension, and respiratory rate. RESULTS: The hold and relax technique to the pectoralis major compared with the sham technique produced significant effects on VC (P<.01), and right (P<.01) and left (P<.05) upper-limb range of motion. There was no significant effect on ACE, XCE, perceived dyspnea, or respiratory rate. There was no order effect for either technique. CONCLUSIONS: The hold and relax technique produces short-term benefits in patients with COPD and should be investigated further.