tbuckley/cabot-search huggingface dataset:
Comparison of the measurement of LCI and FRC by the NDD EasyOne ProLAB and mass spectrometry (MS)
Authors: Emma Raywood, Barbara Bosch, Louis Harpham-Lockyer, Jane Kirkby, Emma Fettes, Janet Stocks, Paul Aurora
Journal: European Respiratory Journal (2013)

Background: Lung Clearance Index (LCI) derived from Multiple Breath Washout (MBW) using MS and SF6 is a sensitive measure of ventilation inhomogeneity[1]. Clinical applications of this test should increase now that ultrasonic flowmeter N2 washout (N2-WO) to measure LCI is commercially available but it is important to establish the relationship between these systems[2].

Aim: To compare LCI and FRC measured by the NDD N2-WO system and a custom-built AMIS 2000 MS SF6 system in healthy adults.

Methods: MBW was performed in healthy adults using the two systems on the same day. The mean of 3 acceptable measures on each were compared.

Results: 18 adults aged 19-64y completed assessments. LCI and FRC were significantly lower on the NDD system compared with MS (mean diff (95%CI): -0.4 (-0.1;-0.8) and -0.5L (-0.3;-0.7). The 95% limits of agreement were relatively wide (Fig 1).

![Figure][1] 



Fig1. Bland-Altman graphs of LCI and FRC

Conclusions: These preliminary results suggest that, as expected, MBW results using MS SF6 and NDD N2-WO are not interchangeable. Further comparative and repeatability data collection is in progress both in healthy subjects and children with lung disease to establish if the NDD N2-WO system can discriminate lung disease from health with as much sensitivity as the MS SF6 system.

References: 

1. Aurora: Thorax 2010

2. Robinson: Eur Resp J 2013.

 [1]: pending:yes
Update in Sepsis and Acute Kidney Injury 2014
Authors: Frédérique Schortgen, Pierre Asfar
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Sepsis and acute kidney injury (AKI) represent an important burden in intensive care unit clinical practices. The Journal published important contributions in sepsis for novel therapeutic approaches suggesting that combined molecular targets (e.g., dual inhibition of IL-1β and IL-18, and coadministration of endothelial progenitor cells and stromal cell–derived factor-1α analog) could perform better. The clinical effectiveness of 1,25-dihydroxyvitamin D was reported in a double-blind, randomized, placebo-controlled trial. Although its experimental properties appeared favorable in the pro- and antiinflammatory cytokine balance, 1,25-dihydroxyvitamin D failed to improve survival. Strategies for decreasing antimicrobial resistances are of particular importance. Effective (aerosolized antibiotics for ventilator-associated pneumonia) and ineffective (procalcitonin algorithm for antibiotic deescalation) approaches were published. In 2014, several publications raised an important point shared by survivors from sepsis and/or AKI. The increased number of survivors over time brought out long-term sequelae, leading to a poor outcome after hospital discharge. Among them, cardiovascular events and chronic kidney disease may explain the significant increase in the risk of death, which can persist up to 10 years and significantly increases the use of health care. Postdischarge survival represents a new target for future research in sepsis and AKI to find how we can prevent and manage long-term sequelae. A milestone of the year was the Ebola outbreak. The Journal contributed to our better understanding of Ebola virus disease with a paper underlying the crucial role of a large implementation of pragmatic supportive care, including fluid infusion and correction of metabolic abnormalities, to save more lives.
The management and follow-up of pulmonary embolism (PE) at a district general hospital: Are we missing CTEPH?
Authors: Amiera Awad, Vallari Shah, Sarah Brewster, Sapna Mawkin, David Morgan
Journal: European Respiratory Journal (2013)

Background  : Chronic thromboembolic pulmonary hypertension (CTEPH) is a recognised complication of acute PE with a reported annual incidence of between 2-4%. ERS guidelines recommend a follow up echocardiogram at 3-6 months in any patient demonstrating signs of pulmonary hypertension (PH) or right ventricular dysfunction. The aim of this audit was to assess our current practise.   Methods  : Retrospective analysis of all new diagnoses of PE from September 2011 to December 2011. Eligible patients were identified using hospital coding databases.   Results  : 67 patients were identified (35 male, 32 female). Mean age was 73 years (range 27-97). 23.8% (16/67) had an echocardiogram during admission. 68.7% (11/16) demonstrated raised pulmonary pressures (>25mmHg). 45% (5/11) survived to discharge: of these, 40% (2/5) had repeat echocardiograms at follow up. 50% (28/56) of those that survived to discharge were followed up in a medical clinic, 54% (15/28) in a Respiratory clinic.   Conclusion  : This audit demonstrates that both early and late assessment of PH in patients with acute PE is suboptimal. Furthermore, only a quarter diagnosed with PE are followed up in a Respiratory Clinic. Patients with significant PH, may therefore be missed and potentially denied further invasive treatment, such as pulmonary endarterectomy.  Setting up a dedicated PE service would ensure that all patients with PE undergo appropriate and timely investigations. Our trust is seeking approval in order to do this.  Our experience is likely to reflect that in other hospitals and by sharing our findings, we hope to encourage other teams to reflect on their local practise.
Abstract 12757: HDAC 7 Couples LPA Signaling to Endothelial Cell CD36 Gene Regulation to Switch off TSP-1 Mediated Antiangiogenic Responses
Authors: Bin Ren, James Hale, Devi P Ramakrishnan, Roy L Silverstein
Journal: Circulation (2010)

CD36 is a microvascular endothelial cell (MVEC) receptor mediating the angiostatic activity of TSP-1 related proteins. We previously reported that lysophosphatidic acid (LPA), a biologically active...
Bronchodilator responsiveness following methacholine-induced bronchoconstriction in children with clinically highly suspected asthma
Authors: Tae Won Song
Journal: European Respiratory Journal (2012)

Rationale: Patients who were clinically highly suspected asthma occasionally showed negative results in methacholine challenge test (MCT), but showed higher bronchodilator responsiveness (BDR) after methacholine induced bronchoconstriction. The aim of this study was to assess the usefulness of BDR following methacholine-induced bronchoconstriction as a tool for the therapeutic plan in clinically suspected asthmatic patients with negative results in MCT. Methods: MCT was performed in 530 children for evaluation of asthma. Immediately after MCT, patients were asked to inhale short-acting beta2 agonists to evaluate BDR. BDR was measured as the percent increase in FEV1 after treatment. Total serum IgE levels, total eosinophil counts, and specific IgE levels were measured in most children. Schedule visits at 1-month to 6-month intervals were done for 3months to 4 years. Results: Among 530 children, 219 patients showed negative results (PC20 >25mg/mL) in MCT. Out of children with negative MCT, 37 patients expressed over 12% increase (high BDR) and 182 patients expressed under 12% increase (low BDR) in FEV1 after bronchodilator following methacholine induced bronchoconstriction. Among patients with high BDR and negative MCT, 37.8% patients were required inhaled corticosteroid therapy for control of their symptoms. But, among patients with low BDR and negative MCT, only 10.8% patients were required inhaled corticosteroid. Conclusion: In clinically highly suspected asthmatic children with negative MCT, BDR following methacholine-induced bronchoconstriction seems to play a considerable role for the decision of treatment with inhaled corticosteroid.
Phase 1 study of RG7155, a novel anti-CSF1R antibody, in patients with locally advanced pigmented villonodular synovitis (PVNS).
Authors: Philippe Alexandre Cassier, Carlos Alberto Gomez-Roca, Antoine Italiano, Michael Cannarile, Carola Ries, Anne Brillouet, Claudia Mueller, Georgina Meneses-Lorente, Monika Baehner, Jayantha Ratnayake, Ross Harding, Keelara Abiraj, Nathalie Gass, Karen Noh, Randolph D. Christen, Mario Campone, Christophe Le Tourneau, Jean-Pierre Delord, Dominik Ruettinger, Jean-Yves Blay
Journal: Journal of Clinical Oncology (2014)

10504^ Background: PVNS, also known as tenosynovial giant cell tumor (TGCT), is a rare disease mainly affecting young adults. This neoplastic disease is driven in most cases by a t(1;2) translocation resulting in fusion of COL6A3 and M-CSF genes encoding for colony-stimulating factor 1 (CSF1). The bulk tumor mass consists of CSF1 receptor (CSF1R) positive cells. RG7155 is a monoclonal antibody that potently inhibits the dimerization of CSF1R. Methods: In this dose-escalation and –extension phase I study, we treated patients with locally advanced PVNS, who were not amenable to surgical treatment. Primary objectives were to assess safety, tolerability, pharmaco-kinetics and -dynamics. Clinical activity was evaluated using FDG-PET (at 4 weeks after treatment start; EORTC criteria) and MRI (at 6 weeks; RECIST 1.1). Pre- and on-treatment biopsies of tumor and surrogate skin tissue as well as peripheral blood PD markers were analyzed. Results: Between September 2012 and October 2013, 11 PVNS patients (median age 38 (range 18-64)) were treated at three French institutions at four different dose levels (q2w). Three patients had previously been treated with nilotinib and imatinib, respectively. Seven patients had undergone previous surgeries. RG7155 induced a sustained increase of CSF1 associated with a decrease of CD14+CD16+ monocytes in peripheral blood in all 10 evaluable patients. RG7155 led to striking reductions of CSF1R+ and CD163+ macrophages in tumor tissue associated with rapid onset of objective clinical responses in 7/9 patients (78%; partial metabolic response at 4 weeks; FDG-PET) and 7/10 patients (70%; PR at 6 weeks; MRI). All patients showed tumor shrinkage associated with symptomatic improvement. 9/10 patients remained clinically progression-free with a longest follow-up of 17 months. RG7155 was well tolerated with only two patients experiencing grade 3 adverse events (periorbital edema; mucositis). Conclusions: RG7155 treatment induced rapid clinical responses in the vast majority of PVNS patients associated with profound reduction of CSF1R+ and CD163+ macrophages in tumor tissue. Clinical trial information: NCT01494688. Clinical trial information: NCT01494688.
Short-term physiological effects of the e-cigarette compared to regular cigarette
Authors: Marco Ferrari, Alessandro Zanasi, Piero Ceriana, Antonella Balestrino, Stefano Nava
Journal: European Respiratory Journal (2014)

Electronic cigarettes (E-cigarettes), are battery-operated products designed to deliver nicotine, flavor and other chemicals. Few studies have assessed the short term effects of low dose nicotine e-cigarettes, while data about flavor e-cigarettes are scanty. This study was aimed to assess whether using a flavour e-cigarette for 5 min has an impact on the pulmonary function tests, fraction of exhaled nitric oxide (FeNO) and fractional concentration of carbon monoxide in exhaled breath (FeCO) of healthy adult smokers and not smokers. Twenty healthy subjects (10 smokers and 10 non-smokers) participated in this laboratory-based randomised experimental study. Ab lib use of a flavor e-cigarette (NaturSmoke, l9Angelica Istituto Erboristico, Italy) for 5 min or a regular cigarette(r-cigarette) was assessed. R-cigarettes resulted in a statistically significant increased in FeCO (7,9 +/-7,5, vs 12.1 +/-9.9, p=0,0001)(marker of effective inhalation), while no significant changes were observed in FeNO. In the non-smokers group, r-cigarette also induced a significant decrease from baseline in FEV1 and FEF75% (FEV1%:98,9 +/-10,5 vs 95,9 +/-9,0, p=0,01; FEF75%:80,8 +/-34,9, vs 70,5 +/-27,7, p=0,03) while e-cigarette was associated with a reduction of FEF75% in the smokers (61,6 +/-18,7, vs 55.4 +/-17,7, p=0,04). Flavor e-cigarettes without nicotine assessed in the context of this study were found to have no immediate adverse physiologic effects after short-term use in the non-smokers and a small effect on FEF75% in the smokers group. The long-term health effects of e-cigarette use are unknown but worthy of further investigation.
Nine cases of interstitial lung disease associated with anti-CADM140 antibody positive dermatomyositis
Authors: Yuko Waseda, Hazuki Takato, Satoshi Watanabe, Ryo Matsunuma, Kanako Inuzuka, Yukari Ichikawa, Nobuyuki Katayama, Masahide Yasui, Kazuo Kasahara, Masaki Fujimura
Journal: European Respiratory Journal (2012)

[Background] Anti-CADM140 antibody (CADM) was found in some amyopathic dermatomyositis (DM) patients (pts) in 2005. It was reported that about 50% of CADM positive pts died from acute exacerbation (AE) of DM-related interstitial lung disease (DM-ILD) despite treatment. As compared with CADM negative pts (about 6%), the rate of AE of ILD is clearly high in CADM positive pts. [Objective] To elucidate the clinical characteristics of ILD associated with CADM positive DM. [Methods] Blood examination, arterial blood gas analysis, pulmonary function testing, bronchoalveolar lavage (BAL) analysis and pattern of chest CT were examined in 9 pts who were diagnosed with CADM positive DM in our hospital. [Results] Since the average value of WBC and CRP at the time of the first medical examination was 6629 /μl and 0.56 mg/dl, we thought that inflammation was slight. The value of CK was in the normal range in 7 pts, slightly high (217 IU/l) in 1, and significantly high (26300 IU/l) in 1. The value of KL-6 was in the nearly cut-off range in 8 pts, and significantly high in 1 (3764). Alveolar-arterial oxygen difference was increased in 3 pts. In 4 pts in which BAL was performed, the lymphocyte differentiation was all high. Concerning chest CT image, patchy shadow or patchy shadow and trabecular shadow in outside layer of the lung field were seen in 7 pts, GGO around broncho-vascular bundle in 1, and no abnormal shadow in 1. All of the shade were slight. Although one pt died of AE, 8 pts survive as of February, 2012. [Conclusion] In DM-ILD, even if the CT image and data are slight, whenever the CT image is not typical NSIP pattern, we have to take the possibility of CADM into consideration.
FATE OF PREFORMED IMMUNE COMPLEXES IN RABBITS AND RHESUS MONKEYS
Authors: Mart Mannik, William P. Arend
Journal: The Journal of Experimental Medicine (1971)

Preformed soluble immune complexes injected into rabbits or rhesus monkeys showed similar characteristics of disappearance from circulation. Complexes made with intact gammaG-antibodies and exceeding the Ag(2)Ab(2) lattice formation were rapidly removed by the hepatic RES. These complexes fixed complement effectively in vitro. Their hepatic uptake was not dependent upon circulating complement components, since their accumulation in the liver was unchanged in complement depleted rabbits. Similar antigen-antibody complexes made with reduced and alkylated gammaG-antibodies fixed complement ineffectively in vitro. These complexes possessed different disappearance characteristics and were not rapidly taken up by the liver, regardless of their degree of lattice formation. Both in vitro and in vivo studies failed to suggest any role for the immune adherence receptor on primate erythrocytes in the handling of circulating soluble immune complexes composed of BSA and gammaG-antibodies to this antigen.
Association between airway inflammation, airway remodelling and physiological changes in asthma
Authors: Rachid Berair, Sherif Gonem, Vijay Mistry, Amisha Singapuri, Nisha Rana, Richard Kay, Salman Siddiqui, Christopher Brightling
Journal: European Respiratory Journal (2014)

Background 

In asthma the association between airway inflammation, airway remodelling, determined in bronchial biopsies; and lung physiology is unclear.

Methods 

Patients with moderate-to-severe persistent asthma and sputum eosinophilia (>2%) underwent endobronchial sampling, spirometry, lung plethysmography and impulse oscillometry. Airway biopsies were examined for airway smooth muscle (ASM) content (ASM%), reticular basement membrane (RBM) thickness and inflammatory cells counts (cells/mm2 of submucosa) for eosinophils, T-lymphocytes, neutrophils and mast cells.

Results 

34 patients were recruited. ASM% was negatively correlated with both pre-bronchodilator ( rs = -0.446, p=0.008) and post-bronchodilator FEV1/FVC and ( r s= -0.445, p=0.008); but no correlation with oscillometry indices or inflammatory cell counts. RBM thickness did not correlate with submucosal inflammatory cell counts or physiological indices. Submucosal eosinophils were positively correlated with CO transfer coefficient (KCO) ( r s= 0.381, p=0.026), and R5 ( r s= 0.441, p=0.009).

![Figure][1] 



Conclusion 

Increased ASM% and submucosal eosinophils were associated with airflow obstruction and resistance respectively. Whether resistance measures are a sensitive measure of response to anti-eosinophilic therapies requires further study.

Acknowledgements : Work funded by Novartis Pharmaceuticals.

 [1]: pending:yes
Epigenome‐Wide Scan Identifies a Treatment‐Responsive Pattern of Altered DNA Methylation Among Cytoskeletal Remodeling Genes in Monocytes and CD4+ T Cells From Patients With Behçet's Disease
Authors: Travis Hughes, Filiz Ture‐Ozdemir, Fatma Alibaz‐Oner, Patrick Coit, Haner Direskeneli, Amr H. Sawalha
Journal: Arthritis & Rheumatology (2014)

The pathogenesis of Behçet's disease (BD), an inflammatory disease with multisystem involvement, remains poorly understood. This study was undertaken to investigate whether there are DNA methylation abnormalities in BD that might contribute to the pathogenesis of the disease.We examined genome-wide DNA methylation patterns in monocytes and CD4+ T cells from 16 male patients with untreated BD and age, sex, and ethnicity-matched healthy controls. Additional samples were collected from 12 of the same BD patients after treatment and achievement of disease remission. Genome-wide DNA methylation patterns were assessed using the Infinium HumanMethylation450 BeadChip array, which includes >485,000 individual methylation sites across the genome.We identified 383 CpG sites in monocytes, and 125 in CD4+ T cells, that were differentially methylated between BD patients and controls. Bioinformatic analysis revealed a pattern of aberrant DNA methylation among genes that regulate cytoskeletal dynamics, suggesting that aberrant DNA methylation of multiple classes of structural and regulatory proteins of the cytoskeleton might contribute to the pathogenesis of BD. Further, treatment of BD modified the differences in DNA methylation observed in patients compared to controls; indeed, among CpG sites that were differentially methylated after disease remission versus before treatment, there was widespread reversal of the direction of aberrant DNA methylation observed between the patient and control groups.The results of this epigenome-wide study-the first such study in BD-provide strong evidence that epigenetic modification of cytoskeletal dynamics underlies the pathogenesis of BD and its response to treatment.
Respiratory effects of air pollutants: experimental studies in humans
Authors: T Sandstrom
Journal: European Respiratory Journal (1995)

Epidemiological and environmental chamber studies in man, and toxicological studies in animals, have provided valuable insights into the biological effects, the mechanisms of action, and the dose-response characteristics of some major air pollutants. This review describes the information currently available on air pollutant effects in man, as the result of experimental studies. There are certain advantages, as well as some limitations, in human chamber exposure studies, but if carefully designed and based upon relevant background data they may give information that is valuable for understanding the effects of air pollutants in man. Reversible effects on the airway mechanics, the responsiveness of the airways to methacholine and allergen have been shown to be caused by air pollutants. Furthermore, significant changes have been demonstrated in airway permeability, bronchoalveolar lavage, nasal lavage, and peripheral blood cells and inflammatory markers. Currently, human toxicology to air pollutants is a progressive research area.
Evaluation of incidental findings other than PE on CT pulmonary angiogram
Authors: Urvi Shah, Freya Shah, Kabali Nandakumar
Journal: European Respiratory Journal (2012)

BACKGROUND  PE is a common cause of admission to hospital, with CTPA increasingly being used to make this diagnosis. However, incidental findings other than PE are frequently noted. Our objective was to investigate the incidence of these, and the implications in patient management.  METHOD  This is a retrospective study which involved all inpatients who had undergone CTPA from June until November 2009. Data was obtained from PACS and electronic records. Abnormalities other than PE was identified and new lesions were differentiated from old.  RESULTS  A total of 112 patients were identified with the majority being male 67 (60%). The mean age was 61 years (range 23 to 97). SOB was the most prevalent presenting symptom in 62 (55.3%) followed by chest pain 37(33%). Chest radiographs were performed in 110 (98.2%) patients, of 52.7% were normal.  PE was found in 28 (25%) patients. Incidental findings were seen in 56 (50%) patients, 40(71.4%) of these were new of which 28(70%) of them needed further interventions. The most prevalent findings were pneumonia 22 (39%) followed by fibrosis7 (12.5%), effusions 5(8.9%) and lung masses 4(7%). 10 patients had both PE and incidental findings.  The average length of stay was 7.3 days. Patients with additional pathology stayed a day longer (7.8 days) than those without (6.8days).  Conclusion  In patients with suspected PE, CTPA has become a routine investigation with a yield of 25% in our study. Incidental pathology was evident in 50% of scans, which is in keeping with other studies. The addition of these findings on CTPA impacts on the length of stay of patients in hospital by one day, and has important implications for the acute clinical management of these patients.
Exercise capacity as an index of progress of lung disease among children and adolescents with CF
Authors: Elpis Hatziagorou, Vassiliki Georgopoulou, Kalliopi Kontouli, Vasiliki Avramidou, Fotis Kirvassilis, John Tsanakas
Journal: European Respiratory Journal (2011)

Background:  Spirometry, high resolution computed tomography (HRCT) and exercise testing provide addional information about lung disease among children with cystic fibrosis (CF). There is significant correlation between levels of aerobic fitness (VO 2  peak) and survival rate.   Aim:  To compare decline of exercise capacity, HRCT scores and lung function among children with CF over a period of two years.   Method:  Sixteen stable children and adolescents with CF, aged 8–19 years, performed spirometry and maximal incremental cardiopulmonary exercise testing using a cycle ergometer, as part of their annual review. At the same time the patients underwent low dose of radiation chest HRCT scans, with a Bhalla score assessment.   Results:  Sixteen stable children and adolescents with CF were evaluated (mean age 15.64±3.2 years and FEV 1  38-94% predicted). There was evidence of mild exercise limitation during the cardiopulmonary exercise test, with mean Peak Aerobic Capacity (V9Opeak) 71.81±14.07% predicted. Evaluation of the study population two years later, showed that Bhalla total score, Peak Aerobic Capacity (V9Opeak) and Anaerobic Threshold (AT) deteriorated significantly (mean difference ±SD, p): 1.4±1.7, p: 0.029, -6.4±9.1, p: 0.022, -7.8±9.3, p: 0.006, respectively. Ventilatory equivalent for CO 2  (V9E/V9CO 2 ), Dead space/Tidal Volume Ratio (VD/VT) and FEV 1  didn9t deteriorate significantly (p: 0.321, p: 0.165 and p: 0.135, respectively).   Conclusions:  The maximal incremental cardiopulmonary exercise test correlates well with HRCT scans; it is a very sensitive method for measuring progression of lung disease in children with CF.