tbuckley/cabot-search huggingface dataset:
Symptoms and comorbidities associated with restrictive spirometry
Authors: Berne Eriksson, Anne Lindberg, Eva Rönmark, Bo Lundbäck
Journal: European Respiratory Journal (2014)

Introduction The diagnosis of restrictive lung diseases requires static spirometry. However, dynamic spirometry can identify subjects with a restrictive pattern. Few studies have investigated comorbidity and risk-factor pattern for subjects with a restrictive spirometric pattern.

Aim To investigate the risk-factors and comorbidities associated with a restrictive spirometric pattern.

Method A random sample of middle aged and elderly from the general population, n=1,563, mean age 61 y (34-85) participated in pulmonary function tests and structured interviews. A restrictive spirometric pattern was defined as a FEV1/(F)VC≥0.70 and the highest value of FVC or SVC (slow vital capacity)<80% of pred. The group with a restrictive spirometric pattern was compared those with normal spirometry. All analyses were adjusted for sex and age.

Results The prevalence of restrictive spirometric pattern was 9.7% (men 10.0%; women 9.4%). Characteristics for restriction included higher BMI, previous tuberculosis and rheumatic disease, all possible causative associations. The restrictive group had a significantly increased risk of having respiratory symptoms, such as cough, chronic bronchitis and dyspnoea. Heart disease, myocardial infarction and claudication were significantly more common in the restrictive group, OR 1.5 (CI 1.1-2.3); OR 2.5(CI 1.4-4.7); OR 3.1 (CI 1.4-6.4). Non-significantly higher OR:s were found for hypertension, angina and diabetes. Smoking habits did not differ from the normal group.

Conclusion Restrictive spirometric pattern is common in middle age and elderly and is associated with respiratory symptoms and cardiovascular comorbidities, but not with smoking, when compared to subjects with normal lung function.
Obstructive ventilatory defect with normal forced expiratory volume in one second/vital capacity ratio
Authors: D. Stanescu
Journal: European Respiratory Journal (2006)

To the Editors: 

Pellegrino et al . 1 now define obstructive ventilatory defect not only on the basis of a low forced expiratory volume in one second (FEV1)/vital capacity (VC) ratio but also as a particular pattern with a normal FEV1/VC ratio. Although they write that “the definition of an obstructive pulmonary defect given in the present document is consistent with the 1991 American Thoracic Society 2 statement of interpretation,” a definition of an obstructive defect characterised by a normal FEV1/VC ratio cannot be found in this latter document.

Incidentally, this pattern was described several years ago and called “small airways obstructive syndrome”. It is characterised by a normal total lung capacity (TLC) and …
Acceptance of the 2006 Kober Medal
Authors: David G. Nathan
Journal: Journal of Clinical Investigation (2007)

Thank you so much Ed. You have successfully appropriated my Good Citizenship Award. In all fairness, you and this tolerant assemblage should know that I lost the election for that award by a vote of twenty-two to two. My best friend voted for me and I voted for myself. The class was outraged when the teacher decided to “give it to the boy who came in second.” This was their first exposure to a fixed election (Florida in 2000 was their second). I can only hope that the proceedings that led to the Kober Medal were more wholesome.
Does lung transplantation improve chronotropic incompetence
Authors: Matthew Bartels, Hilary Armstrong, Selim Arcasoy
Journal: European Respiratory Journal (2011)

Introduction:  Chronotropic Incompetence (CI), or an attenuated heart rate (HR) response to exercise, has been widely established as a predictor of mortality but has not been studied in patients undergoing lung transplantation.   Objectives:  We aimed to see whether CI in maximal exercise testing exists in patients with advanced lung disease before lung transplantation and improves after surgery.   Methods:  A retrospective review of 153 patients who underwent lung transplantation at Columbia University Lung Transplant Program between 6/2002 and 4/2009. Patients had cardiopulmonary exercise testing (CPET) within 30 months before or after transplant with concurrent with pulmonary function tests (PFT). Exclusion criteria included the use of beta-blockers. Comparisons were made with paired samples t-test.   Results:  The mean PFT and CPET variables for the 71 patients (age 50±15 years) analyzed are shown in table 1.   Conclusions:  Marked CI was observed before lung transplantation and improved afterwards but did not normalize. CI likely improved due to the normalization of pulmonary function post transplant. This was seen through a lower resting HR and a higher maximal HR. The implications of CI are not clear and warrant further investigation, including evaluation of the association of CI and morality after transplant.
Predictors of poor outcome in severe hospitalised COPD exacerbations
Authors: Zinka Matkovic, Marc Miravitlles, Nestor Soler, Arturo Huerta, Rebeca Domingo, Albert Gabarrus, Antoni Torres
Journal: European Respiratory Journal (2011)

Background: The aim of study was to determine predictors of poor outcome in patients hospitalised for exacerbation of chronic obstructive pulmonary disease (ECOPD).

Methods: Hospitalised patients with ECOPD were included in a prospective study and followed for 1 month. Clinical and epidemiological parameters were evaluated including COPD Severity Score (COPD-SS) and Charlson Index. Poor outcome was: death, intensive care unit (ICU) admission, need for mechanical ventilation (MV), prolonged hospital stay (>11 days) and emergency room (ER) visit/readmission during follow-up.

Results: 155 patients: mean age±standard deviation 70±9.5yrs; 84% men; 96% smokers/ex-smokers; 76% GOLD stage III or IV; mean hospital stay 8.8±5.5days. 69 patients (45%) had poor outcome: 4 (3%) died; 16 (10%) had ICU admission; 33 (21%) had MV, 32 (21%) had prolonged hospital stay and 24 (16%) had ER visit/readmission during follow-up. Univariate analysis identified variables associated with poor outcome: exacerbations and hospitalisation for ECOPD in the last year (p=0.033 and 0.039 respectively); lower FEV1 (p=0.004); GOLD stage (p=0.049); lower pH (p<0.001); lower PaO2/FIO2 (p=0.006); higher PaCO2 (p<0.001); higher COPD-SS (p=0.016); long-term O2 therapy (p=0.042). Independent predictors of poor outcome determined by multivariate analysis: number of exacerbations in the previous year (1 ECOPD: p=0.012, odds ratio [OR] 4.1, 95% confidence interval [CI] 1.4 to 12.3; ≥2 ECOPD: p=0.005, OR 4.4, 95% CI 1.6 to 12.5); pH (p=0.006, OR 0.2, 95% CI 0.1 to 0.7); PaCO22 (p=0.015, OR 1.3, 95% CI 1.1 to 1.7).

Conclusion: Previous exacerbations, hypercapnia and respiratory acidosis were identified as predictors of poor outcome in patients with severe ECOPD.
Mechanical response to electrical- and neuro-stimulation of the genioglossus (GG) in propofol-sedated OSA patients
Authors: Yaniv Dotan, Louis Gaitini, Arie Oliven
Journal: European Respiratory Journal (2011)

Pharyngeal collapsibility during sleep is believed to increase primarily due to decline in dilator muscle activity. However, it is well documented that GG-EMG increases during apneas and hypopneas. The magnitude of increase is limited, however, as arousal terminates the respiratory disturbance. In the present study we prevented arousal by “drug-induced sleep” with propofol. We induced prolonged hypopneas in 17 patients with OSA by lowering CPAP after discontinuation of propofol, and monitored GG-EMG, flow and the area (CSA) at the site of collapse (pharyngoscopy) until arousal. Prolonged hypopnea triggered a dramatic increase in GG-EMG. The mechanical response to this physiological drive to the GG was compared to baseline condition (after lowering CPAP from holding pressure), electrical stimulation (ES) of the GG, and after arousal.  Before arousal from sedation, flow remained unchanged despite the large increase in GG-EMG activity, while inspiratory CSA decreased. ES of GG, however, increased CSA and flow. Arousal resulted in fast enlargement of CSA and restoration of unobstructed flow, associated with marked reduction in GG EMG. We conclude that during propofol-induced sedation (and presumably also during sleep), pharyngeal collapse is due to inadequate mechanical response to activation of the GG, which occurs despite the well preserved mechanical response of this muscle to ES.
Cells from a cavitronic ultrasonic aspirator (CUSA) astrocytoma specimen formed pseudopodia and exhibited neuroectodermal features.
Authors: Marie E. Beckner, Esther P. Jane, Daniel R. Premkumar, Brian Jankowitz, Naomi R. Agostino, Kevin A. Walter, Ronald L. Hamilton, Ian F. Pollack
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5145 

The study of malignant astrocytomas in primary cell cultures is limited by the small size of surgically resected specimens that must be saved for diagnostic purposes as a priority. However, abundant numbers of brain tumor cells are routinely removed with the Cavitronic Ultrasonic Aspiration (CUSA) technique and discarded as medical waste. Although these tumor cells are exposed to the trauma of ultrasonic aspiration, saline and blood, and elevated temperatures, their viability has been documented in many previous studies. In this study, CUSA cells from a malignant astrocytoma demonstrated unstained morphology and immunoperoxidase staining results that were comparable to cells cultured from surgically dissected tissue from the same tumor. Almost all cells in both types of specimens stained positive for nestin indicating that they were of neuroectodermal lineage. A few cells with morphology resembling neurons demonstrated intense nestin staining. Some cells stained intensely for beta-III tubulin. Although each nucleus had 3-5 bright spots of Oct 3/4 staining, no homogenous staining of entire nuclei that would be characteristic of undifferentiated stem cells was identified in either type of specimen. Our recently described method for obtaining pseudopodia from tumor cells (Beckner et al., Lab Invest 85:316-27, 2005) was applied to the same fresh CUSA specimen. The procedure yielded numerous rounded pseudopodia that extended through 3 μm diameter pores of gelatin-coated filters in response to hepatocyte growth factor/scatter factor (HGF) and fetal bovine serum as chemoattractants at six hours. The CUSA pseudopodia retained their morphology following filter removal with homogeneous Diff Quik staining seen except for condensation of cytoplasm at the sites of pores. No nuclear material was identified. In separate chambers, entire cells (nuclei and cytoplasm) from the fresh CUSA specimen migrated through 8 μm pores during the same time span. Filtered conditioned media from several astrocytoma cell lines maintained the CUSA cells in culture for several weeks with consistent morphology and without overgrowth by fibroblasts. This study indicates that CUSA specimens are a source of primary tumor cells for functional studies, such as investigations of HGF’s downstream signaling effects. Studies of HGF’s targets in the pseudopodia of responsive cultured cell lines can now be applied to pseudopodia formed by fresh primary human tumor cells. We gratefully acknowledge funding from the Nick Eric Wichman Foundation, Ellicott City, MD.
Electrocardiographic abnormalities in patients with low or moderate risk pulmonary embolism: Prevalence and association with PO2 /FiO2 ratio
Authors: Christos Kampolis, Angeliki Loukeri, Anna Aiginitou, Dimosthenis Papapetrou, Aikaterini Tzagkaraki, Prokopis Kythreotis, Pinelopi Loukeri, Dimitrios Veldekis
Journal: European Respiratory Journal (2014)

Introduction:Pulmonary embolism (PE) is a relatively common and potentially life-threatening condition. Previous studies have documented that approximately 70% of patients with mild to massive PE have an abnormal electrocardiogram (ECG).  Aims and Objectives: To determine the prevalence of initial ECG findings in patients admitted for low and moderate risk PE and the possible association of those findings with the oxygenation index (PO 2 /FiO 2  ratio).  Methods: Seventy two outpatients [age (mean ± SD): 60.4±18.5 years] admitted for low or moderate risk PE were retrospectively studied. The diagnosis was established on the basis of computed tomography pulmonary angiography in 73.6% (n=53), lung perfusion scintigraphy in 23.6% (n=17), or other methods in 2.8% (n=2) of total cases of PE.  Results: Twenty three patients (31.9%) had normal ECG on admission. Sinus tachycardia was the most frequent ECG abnormality [37.5% (n=27)]. Other abnormalities observed were as follows: atrial fibrillation or flutter [8.3% (n=6)], right bundle branch block [12.5% (n=9)], “P pulmonale” [11.1% (n=8)], ST segment depression [1.4% (n=1)], T-wave inversion [18.1% (n=13)], T-wave flattening [12.5% (n=9)], and S1Q3T3 pattern [11.1% (n=8)]. The combined presence of supraventricular tachycardias (SVTs) and QRS abnormalities was associated with a significantly lower PO 2 /FiO 2  ratio, compared to patients with either SVTs, QRS abnormalities or normal ECG [one-way ANOVA: F(3,68)=3.77, p=0.014].  Conclusions:Approximately 2/3 of patients with PE have ECG abnormalities on admission. The combined presence of SVTs and QRS abnormalities is associated with lower PO 2 /FiO 2  ratio.
History of tuberculosis in Australia, New Zealand and Papua New Guinea
Journal: Thorax (1992)

Letters to the,Editor tions (60 3 (10 4, range min; n = 19; p < 0 001).The CD4 counts on the patients before the first 99"Tc DTPA transfer were 120, 130, and 170 respectively.All three were smokers, as were nine of 19 with various non-pneumo- cystis pneumonia chest conditions, and all three took nebulised pentamidine, 300 mg monthly, as primary prophylaxis for pneu- mocystis pneumonia, as did eight of 19 patients without pneumocystis pneumonia.Bronchopulmonary lavage (all three) and transbronchial biopsy (two patients) had negative results.Open lung biopsy in the first two patients did not show any opportunist infection.Both patients died-10 and 12 months after the initial "Tc DTPA transfer.Postmortem examination in the first patient showed cytomegalovirus and toxoplasma brain disease.The third is symptom free 10 months after the first test.It is concluded that a rapid biphasic "mTc DTPA transfer may be seen in advanced HIV infection in the absence of pneumocystis pneumonia.
Characterization of amoxicillin‐ and clavulanic acid‐specific T cells in patients with amoxicillin‐clavulanate–induced liver injury
Authors: Seung‐Hyun Kim, Katy Saide, John Farrell, Lee Faulkner, Arun Tailor, Monday Ogese, Ann K. Daly, Munir Pirmohamed, B. Kevin Park, Dean J. Naisbitt
Journal: Hepatology (2015)

Drug-induced liver injury (DILI) frequently has a delayed onset with several human leukocyte antigen (HLA) genotypes affecting susceptibility, indicating a potential role for the adaptive immune system in the disease. The aim of this study was to investigate whether drug-responsive T lymphocytes are detectable in patients who developed DILI with the combination, antimicrobial amoxicillin-clavulanate. Lymphocytes from 6 of 7 patients were found to proliferate and/or secrete interferon-gamma (IFN-γ) when cultured with amoxicillin and/or clavulanic acid. Amoxicillin (n = 105) and clavulanic acid (n = 16) responsive CD4(+) and CD8(+) T-cell clones expressing CCR, chemokine (C-C motif) receptor 4, CCR9, and chemokine (C-X-C motif) receptor 3 were generated from patients with and without HLA risk alleles; no cross-reactivity was observed between the two drug antigens. Amoxicillin clones were found to secrete a heterogeneous panel of mediators, including IFN-γ, interleukin-22 and cytolytic molecules. In contrast, cytokine secretion by the clavulanic acid clones was more restricted. CD4(+) and CD8(+) clones were major histocompatability complex class II and I restricted, respectively, with the drug antigen being presented to CD4(+) clones in the context of HLA-DR molecules. Several pieces of evidence indicate that the clones were activated by a hapten mechanism: First, professional antigen-presenting cells (APCs) were required for optimal activation; second, pulsing APCs for 4-16 hours activated the clones; and third, inhibition of processing abrogated the proliferative response and cytokine release.Both amoxicillin- and clavulanic acid-specific T cells participate in the liver injury that develops in certain patients exposed to amoxicillin-clavulanate.
Biomarkers as complication predictors in community-acquired pneumonia
Authors: Sergio Fandos, Elisa Mincholé, Ana Lasierra, Ana Lilian Simon, Elisabeth Vera, Maria Angeles Ruiz, Salvador Bello
Journal: European Respiratory Journal (2011)

In order to determine if some marker that can help us to predict complications in patients admitted with community-acquired pneumonia (CAP), we prospectively included 228 patients and studied leukocyte count (WBC), C-reactive protein (CRP), procalcitonin (PCT) and midregional proadrenomedullin (MR-proADM) in the first 24 hours of their arrival.  One hundred and forty six (64%) patients suffered 310 significant complications within first 30 days after hospital admittance. Most frequent complications were: respiratory failure, pleural effusion, left cardiac failure, tachyarritmias, septic shock and mechanical ventilation. We found significant raised levels of MR-proADM (p  In ROC analysis the best AUCs were PSI 0.729 and MR-proADM 0.706. The optimal cut-off to predict complications for MR-proADM was 0.833 nmol/L, (sensitivity 67.35%, specificity 66.23%, positive likelihood ratio (LHR+) 1.99 and negative likelihood ratio (LHR-) 0.49. Findings for PSI class 4 and 5, were sensitivity 72.3%, specificity 62.34%, LHR+ 1.92 and LHR- 0.44. Similar results were obtained when we compared patients with and without only respiratory complications.  PCT and CRP, and especially MR-proADM and PSI score, appear to be useful in early identification of patients at risk for complications during hospitalization
Asthma in pregnancy and risk of preterm delivery
Authors: David Olsson, Lennart Bråbäck, Bertil Forsberg
Journal: European Respiratory Journal (2012)

The effects of asthma on pregnancy outcomes differ between studies. A recent review indicates that the conflicting results are related to study design, where larger database studies have reported increased risks, and smaller clinical prospective cohort studies have not found significantly increased risks. We study the effect of asthma within a large study of air pollution and preterm birth; is there an increase in preterm birth and how common are exacerbations in pregnancy resulting in outpatient hospital visits?  Our study cohort from Stockholm, Sweden, is constructed by matching live births 1998-2006 from the Medical Birth Registry with information on the mother from the Patient Registry (1987-2010 for hospital admissions and 2001-2010 for outpatient hospital visits) and information from the drug register (July 2006 -2011). We define all mothers who had at least one hospital visit for asthma or had asthma medication as having asthma. We used logistic regression to assess the relation between asthma and preterm birth. We adjusted the model for education, previous preterm birth, origin, parity, date of conception and maternal age.  The prevalence of preterm birth was 5.4 % among mothers with asthma (n=13 261) and 4.4 % in the rest of the population (n= 111 931). The odds ratio for giving birth preterm was 1.27 (p   Asthma is associated with an increased risk of preterm birth, particularly in women with exacerbations of the asthma during pregnancy.
Copeptin predicts early clinical deterioration and persistent instability in community-acquired pneumonia
Authors: Martin Kolditz, Michael Halank, Bernhard Schulte-Hubbert, Sybille Bergmann, Steffen Albrecht, Gert Höffken
Journal: European Respiratory Journal (2012)

Optimal risk prediction of early clinical deterioration in CAP remains unresolved. We prospectively examined the predictive value of the new biomarkers copeptin and proadrenomedullin (MR-proADM) in comparison to clinical scores and inflammatory markers to predict early high risk prognosis in CAP.

Methods:

51 consecutive hospitalised adult patients were enrolled. We measured CRB-65- and PSI-scores, the ATS/IDSA 2007 minor criteria to predict ICU-admission and the biomarkers CRP, procalcitonin, copeptin and MR-proADM on admission. Predefined outcome parameters were combined mortality or ICU-admission after 7 days and clinical instability after 72 hours.

Results:

Copeptin was the only biomarker significantly elevated in patients with either adverse short term outcome (p=0.003). In ROC-curve analysis copeptin predicted ICU admission or death within 7 days (AUC 0.81, cut-off 35 pmol/l: sensitivity 78%, specificity 79%) and persistent clinical instability after 72 h (AUC 0.74). In Kaplan-Meier-analysis patients with high copeptin showed lower ICU-free survival within 7 days (p=0.001). The diagnostic accuracy of copeptin was superior to the CRB-65 score and comparable to the PSI-score and the ATS/IDSA minor criteria. If copeptin was included as additional minor criterion for combined 7-day mortality / ICU-admission, the diagnostic accuracy of the criteria was significantly improved (AUC 0.85, p=0.045).

Conclusion:

Copeptin predicts early deterioration and persistent clinical instability in hospitalised CAP and improves the predictive properties of existing clinical scores. It should be evaluated within a biomarker guided strategy for early identification of high risk CAP patients.
Recombinant DNase in cystic fibrosis: a protocol for targeted introduction through n-of-1 trials
Authors: F G Böllert, J Y Paton, T G Marshall, J Calvert, A P Greening, J A Innes
Journal: European Respiratory Journal (1999)

Theophylline, a known phosphodiesterase inhibitor, has been widely used as an additional bronchodilator in asthmatic patients who are not adequately controlled on high-doses of inhaled steroids. However, there is growing evidence that theophylline may also have anti-inflammatory or immunomodulatory effects in asthma. This study investigated whether theophylline administration has an impact on serum levels of interleukin (IL)-4 and IL-5 in asthmatic patients. Eight asymptomatic patients aged 30+/-1.5 yrs (mean +/- SEM) with mild atopic asthma were given a single daily dose of theophylline 150 mg or placebo in an on (theophylline)-off (placebo)-on (theophylline)-off (placebo) protocol with a 3-week duration of each on- or off- interval. Determination of serum IL-4 and IL-5 was done at baseline for all subjects and on the last day of each 3-week interval for the patients under study. Serum IL-4 levels were: 35+/-6 (baseline), 19+/-3 (on-1 interval), 29.5+/-4 (off-2), 15+/-2 (on-3) and 26+/-4 pg x mL(-1) (off-4), while IL-5 levels were 27+/-5, 18+/-4, 28+/-5, 17+/-4 and 28+/-5 pg x mL(-1), respectively. Spirometry was unchanged during the study and serum theophylline levels at the end of the two on-periods were 4.5+/-0.05 and 4.2+/-0.07 microg x mL(-1), while all patients remained asymptomatic. In conclusion, the administration of a low, single, daily dose of oral theophylline in asymptomatic patients with mild atopic asthma seems to reduce circulating interleukin-4 and interleukin-5.