Docosatetraenoyl LPA is elevated in exhaled breath condensate in idiopathic pulmonary fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease with no effective medical therapies. Recent research has focused on identifying the biological processes essential to the development and progression of fibrosis, and on the mediators driving these processes. Lysophosphatidic acid (LPA), a biologically active lysophospholipid, is one such mediator. LPA has been found to be elevated in bronchoalveolar lavage (BAL) fluid of IPF patients, and through interaction with its cell surface receptors, it has been shown to drive multiple biological processes implicated in the development of IPF. Accordingly, the first clinical trial of an LPA receptor antagonist in IPF has recently been initiated. In addition to being a therapeutic target, LPA also has potential to be a biomarker for IPF. There is increasing interest in exhaled breath condensate (EBC) analysis as a non-invasive method for biomarker detection in lung diseases, but to what extent LPA is present in EBC is not known. Methods: In this study, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess for the presence of LPA in the EBC and plasma from 11 IPF subjects and 11 controls. Results: A total of 9 different LPA species were detectable in EBC. Of these, docosatetraenoyl (22:4) LPA was significantly elevated in the EBC of IPF subjects when compared to controls (9.18 pM vs. 0.34 pM; p = 0.001). A total of 13 different LPA species were detectable in the plasma, but in contrast to the EBC, there were no statistically significant differences in plasma LPA species between IPF subjects and controls. Conclusions: These results demonstrate that multiple LPA species are detectable in EBC, and that 22:4 LPA levels are elevated in the EBC of IPF patients. Further research is needed to determine the significance of this elevation of 22:4 LPA in IPF EBC, as well as its potential to serve as a biomarker for disease severity and/or progression

Prone positioning reduces mortality from acute respiratory distress syndrome in the low tidal volume era: a meta-analysis.

PurposeProne positioning for ARDS has been performed for decades without definitive evidence of clinical benefit. A recent multicenter trial demonstrated for the first time significantly reduced mortality with prone positioning. This meta-analysis was performed to integrate these findings with existing literature and test whether differences in tidal volume explain conflicting results among randomized trials.MethodsStudies were identified using MEDLINE, EMBASE, Cochrane Register of Controlled Trials, LILACS, and citation review. Included were randomized trials evaluating the effect on mortality of prone versus supine positioning during conventional ventilation for ARDS. The primary outcome was risk ratio of death at 60 days meta-analyzed using random effects models. Analysis stratified by high (>8 ml/kg predicted body weight) or low (≤ 8 ml/kg PBW) mean baseline tidal volume was planned a priori.ResultsSeven trials were identified including 2,119 patients, of whom 1,088 received prone positioning. Overall, prone positioning was not significantly associated with the risk ratio of death (RR 0.83; 95% CI 0.68-1.02; p = 0.073; I (2) = 64%). When stratified by high or low tidal volume, prone positioning was associated with a significant decrease in RR of death only among studies with low baseline tidal volume (RR 0.66; 95% CI 0.50-0.86; p = 0.002; I (2) = 25%). Stratification by tidal volume explained over half the between-study heterogeneity observed in the unstratified analysis.ConclusionsProne positioning is associated with significantly reduced mortality from ARDS in the low tidal volume era. Substantial heterogeneity across studies can be explained by differences in tidal volume

Air leak during CPAP titration as a risk factor for central apnea.

ObjectivesEmergence of central sleep apnea has been described in the setting of continuous positive airway pressure (CPAP) initiation. The underlying mechanism is unclear; however, we postulate that air leak washing out anatomical dead space is a contributing factor.DesignData were obtained from 310 patients with obstructive sleep apnea (OSA) who underwent either split-night or full-night CPAP titration during January to July of 2009. The majority (n = 245) underwent titration with a nasal mask. Average total leak and maximum total leak were measured at therapeutic CPAP level. Unintentional leak was calculated by subtracting manufacturer-defined intentional leak from maximum leak.ResultsSUBJECTS WERE DIVIDED INTO TWO GROUPS: central apnea index (CAI) during titration < 5/hour and ≥ 5/hour. The groups were similar in terms of gender, age, BMI, and AHI. The CAI < 5 group had a median average leak of 45.5 L/min (IQR 20.8 L/min) versus 51.0 L/min (IQR 21.0 L/min) with CAI ≥ 5 (p = 0.056). Maximum leak was 59.5 L/min (IQR 27.0 L/min) with CAI < 5 and 75.0 L/min (IQR 27.8 L/min) with CAI ≥ 5 (p = 0.003). In the subset of subjects titrated using a nasal mask, median average leak was 42.0 L/min (IQR 17.0) in the CAI < 5 group and 50.0 L/min (IQR 16.8) in the CAI ≥ 5 group (p = 0.001). In the CAI < 5 group, median maximum leak was 57.0 L/min (IQR 23.0) versus 74.5 L/min (IQR 24.3) in the CAI ≥ 5 group (p < 0.001).ConclusionsLeak during CPAP titration is associated with the development of acute central apnea; these data may have mechanistic and therapeutic implications for complex apnea.CommentaryA commentary on this article appears in this issue on page 1193

Clinical role, safety and diagnostic accuracy of percutaneous transthoracic needle biopsy in the evaluation of pulmonary consolidation

Abstract Background To determine the clinical role, safety, and diagnostic accuracy of percutaneous transthoracic needle biopsy in the evaluation of pulmonary consolidation. Methods A retrospective review of all computed tomography (CT)-guided percutaneous transthoracic needle biopsies (PTNB) at a tertiary care hospital over a 4-year period was performed to identify all cases of PTNB performed for pulmonary consolidation. For each case, CT Chest images were reviewed by two thoracic radiologists. Histopathologic and microbiologic results were obtained and clinical follow-up was performed. Results Thirty of 1090 (M:F 17:30, mean age 67 years) patients underwent PTNB for pulmonary consolidation (2.8% of all biopsies). A final diagnosis was confirmed in 29 patients through surgical resection, microbiology, or clinicoradiologic follow-up for at least 18 months after biopsy. PTNB had an overall diagnostic accuracy of 83%. A final diagnosis of malignancy was made in 20/29 patients, of which 19 were correctly diagnosed by PTNB, resulting in a sensitivity of 95% and specificity of 100% for malignancy. In all cases of primary lung cancer, adequate tissue for molecular testing was obtained. A benign final diagnosis was made in 9 patients, infection in 5 cases and non-infectious benign etiology in 4 cases. PTNB correctly diagnosed all cases of infection. Minor complications occurred in 13% (4/30) of patients. Conclusions Pulmonary consolidation can be safely evaluated with CT-guided percutaneous needle biopsy. Diagnostic yield is high, especially for malignancy. PTNB of pulmonary consolidation should be considered following non-diagnostic bronchoscopy

A pilot study investigating the effects of continuous positive airway pressure treatment and weight-loss surgery on autonomic activity in obese obstructive sleep apnea patients.

BackgroundWe have previously demonstrated that severity of obstructive sleep apnea (OSA) as measured by the apnea-hypopnea index (AHI) is a significant independent predictor of readily-computed time-domain metrics of short-term heart rate variability (HRV).MethodsWe aimed to assess time-domain HRV measured over 5-min while awake in a trial of obese subjects undergoing one of two OSA therapies: weight-loss surgery (n=12, 2 males, median and interquartile range (IQR) for BMI 43.7 [42.0, 51.4] kg/m2, and AHI 18.1 [16.3, 67.5] events/h) or continuous positive airway pressure (CPAP) (n=15, 11 males, median BMI 33.8 [31.3, 37.9] kg/m2, and AHI 36.5 [24.7, 77.3] events/h). Polysomnography was followed by electrocardiography during wakefulness; measurements were repeated at 6 and 12-18 months post-intervention.ResultsDespite similar measurements at baseline, subjects who underwent surgery exhibited greater improvement in short-term HRV than those who underwent CPAP (p=0.04).ConclusionsOur data suggest a possible divergence in autonomic function between the effects of weight loss resulting from bariatric surgery, and the amelioration of obstructive respiratory events resulting from CPAP treatment. Randomized studies are necessary before clinical recommendations can be made