bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrophil PRV-1 expression across the chronic myeloproliferative disorders and in secondary or spurious polycythemia
Authors: Tefferi Ayalew , Lasho Terra L. , Wolanskyj Alexandra P. , Mesa Ruben A. 
Published: January 2004

Abstract
Recent studies have demonstrated neutrophil overexpression of the polycythemia rubra vera-1 (PRV-1) gene in polycythemia vera (PV) but not in secondary or spurious polycythemia (SP). To validate as well as expand upon this novel observation, we conducted a prospective study of 88 subjects: 30 with PV, 22 with SP, 14 with essential thrombocythemia (ET), 12 with myelofibrosis with myeloid metaplasia (MMM), and 10 controls. To minimize interstudy methodologic differences, we used a published real-time polymerase chain reaction (PCR)-based assay. The proportion of patients with increased neutrophil PRV-1 expression was 83% in PV, 21% in ET, 42% in MMM, 18% in SP, and 0% in controls. All 5 MMM patients with PRV-1 up-regulation had an antecedent history of PV. We conclude that neutrophil PRV-1 up-regulation is a characteristic feature of PV that may not be affected by fibrotic transformation. However, quantifying neutrophil PRV-1 mRNA, while complementary to other tests, is not in itself sufficient for the diagnosis of PV. (Blood. 2004;103:3547-3548)
Different airway inflammatory responses in asthmatic and healthy humans exposed to diesel
Authors: Stenfors N. , Nordenhäll C. , Salvi S.S. , Mudway I. , Söderberg M. , Blomberg A. , Helleday R. , Levin J-O. , Holgate S.T. , Kelly F.J. , Frew A.J. , Sandström T. 
Published: January 2004

Particulate matter (PM) pollution adversely affects the airways, with asthmatic subjects thought to be especially sensitive. The authors hypothesised that exposure to diesel exhaust (DE), a major source of PM, would induce airway neutrophilia in healthy subjects, and that either these responses would be exaggerated in subjects with mild allergic asthma, or DE would exacerbate pre-existent allergic airways.Healthy and mild asthmatic subjects were exposed for 2 h to ambient levels of DE (particles with a 50% cut-off aerodynamic diameter of 10 µm (PM10) 108 µg·m−3) and lung function and airway inflammation were assessed.Both groups showed an increase in airway resistance of similar magnitude after DE exposure. Healthy subjects developed airway inflammation 6 h after DE exposure, with airways neutrophilia and lymphocytosis together with an increase in interleukin‐8 (IL‐8) protein in lavage fluid, increased IL‐8 messenger ribonucleic acid expression in the bronchial mucosa and upregulation of the endothelial adhesion molecules. In asthmatic subjects, DE exposure did not induce a neutrophilic response or exacerbate their pre-existing eosinophilic airway inflammation. Epithelial staining for the cytokine IL‐10 was increased after DE in the asthmatic group.Differential effects on the airways of healthy subjects and asthmatics of particles with a 50% cut-off aerodynamic diameter of 10 µm at concentrations below current World Health Organisation air quality standards have been observed in this study. Further work is required to elucidate the significance of these differential responses.
Progressive damage on high resolution computed tomography despite stable lung function in cystic fibrosis
Authors: de Jong P.A. , Nakano Y. , Lequin M.H. , Mayo J.R , Woods R. , Paré P.D. , Tiddens H.A.W.M. 
Published: January 2004

For effective clinical management of cystic fibrosis (CF) lung disease it is important to closely monitor the start and progression of lung damage. The aim of this study was to investigate the ability of high-resolution computed tomography (HRCT) scoring systems and pulmonary function tests (PFT) to detect changes in lung disease.CF children (n=48) had two HRCT scans in combination with two PFT 2 yrs apart. Their scans were scored using five scoring systems (Castile, Brody, Helbich, Santamaria and Bhalla). “Sensitivity” was defined as the ability to detect disease progression.In this group of children, HRCT scores worsened. PFT remained unchanged or improved. Of the HRCT parameters, mucous plugging and the severity, extent and peripheral extension of bronchiectasis worsened significantly. Relationships between changes in HRCT scores and PFT were weak. Substantial structural lung damage was evident in some children who had normal lung function.These data show that high-resolution computed tomography is more sensitive than pulmonary function tests in the detection of early and progressive lung disease, and suggest that high-resolution computed tomography may be useful in the follow up of cystic fibrosis children and as an outcome measure in studies that aim to reduce lung damage.
Acute effects of inspiratory pressure support during exercise in patients with COPD
Authors: van 't Hul A. , Gosselink R. , Hollander P. , Postmus P. , Kwakkel G. 
Published: January 2004

The aim of the present study was to evaluate the acute effects of inspiratory pressure support (IPS) of 5 cmH2O (IPS5) and 10 cmH2O (IPS10) on exercise endurance.Forty-five patients with COPD (mean forced expiratory volume in one second (FEV1)=39±14% pred) performed three constant-load endurance tests on a cycle ergometer at 75% of maximal workload. One test was without IPS, one test with IPS5, and one with IPS10. No statistically significant difference was found in exercise endurance between tests without IPS and IPS5(4.2±2.6versus4.4±2.9 min).In contrast, IPS10resulted in a statistically significant increase in endurance compared with exercise without IPS (6.3±6.7versus4.2±2.6 min), as well as compared with exercise with IPS5(6.3±6.7versus4.4±2.9 min). A wide scatter in individual responses to IPS was found, ranging from a deterioration of 1.6 min (−36%) to an improvement of 16.3 min (+445%). In only 15 patients, the increase in endurance exceeded the upper limit of the 95% confidence interval. Stepwise multiple regression analysis showed that maximal inspiratory pressure was the most important determinant of the increase in exercise endurance due to the application of IPS10.It was concluded that in contrast to inspiratory pressure support of 5 cmH2O, the application of inspiratory pressure support of 10 cmH2O during exercise resulted in a statistically significant improvement in exercise endurance in patients with COPD compared with exercise without inspiratory pressure support. However, on an individual basis, large differences in responses were found. Inspiratory muscle weakness was revealed as a determinant of improvement in exercise endurance due to the application of inspiratory pressure support of 10 cmH2O, explaining only 24% of the variance in outcome.
Nuclear YB‐1 expression as a negative prognostic marker in nonsmall cell lung cancer
Authors: Gessner C. , Woischwill C. , Schumacher A. , Liebers U. , Kuhn H. , Stiehl P. , Jürchott K. , Royer H.D. , Witt C. , Wolff G. 
Published: January 2004

The human Y‐box binding protein, YB‐1, is a multifunctional protein that regulates gene expression. Nuclear expression of YB‐1 has been associated with chemoresistance and poor prognosis of tumour patients.Representative samples from autopsied material of primary tumours from 77 patients with NSCLC were investigated by immunohistochemistry for subcellular distribution of YB‐1 and p53, in order to evaluate the prognostic role of nuclear expression of YB‐1.Cytoplasmic YB‐1 expression was found in all tumour samples, whereas nuclear expression was only observed in 48%. There was no correlation with histological classification, clinical parameters or tumour size, stage and metastasis status. However, patients with positive nuclear YB‐1 expression in tumours showed reduced survival times when compared with patients without nuclear expression. Including information about the histology and mutational status for p53 increased the prognostic value of nuclear YB‐1. Patients with nuclear YB‐1 expression and p53 mutations had the worst prognosis (median survival 3 months), while best outcome was found in patients with no nuclear YB‐1 and wildtype p53 (median survival 15 months).This suggests that the combined analysis of both markers allows a better identification of subgroups with varying prognosis. Nuclear expression of Y‐box binding protien seems to be an independent prognostic marker.
The 6‐min walk distance: change over time and value as a predictor of survival in severe COPD
Authors: Pinto-Plata V.M. , Cote C. , Cabral H. , Taylor J. , Celli B.R. 
Published: January 2004

The 6‐min walk distance (6MWD) is used to evaluate the functional capacity of patients with chronic obstructive pulmonary disease (COPD). The change in 6MWD over time and its correlation with changes in spirometry and survival are unclear.Patients (n=198) with severe COPD and 41 age-matched controls were followed for 2 yrs, and anthropometrics, spirometry, 6MWD and comorbidities were measured.The 6MWD decreased in the COPD group from 238±107 m to 218±112 m (−26±37 m·yr−1), and increased in the control group from 532±82 m to 549±86 m (12±25 m·yr−1). In both groups, there was a poor correlation with changes in forced expiratory volume in one second (FEV1). Nonsurvivors in the COPD group (42%) had a more pronounced change in the 6MWD (−40versus−22 m·yr−1) but a similar change in FEV1(118versus102 mL·yr−1). The 6MWD independently predicted survival, after accounting for age, body mass index, FEV1and comorbidities.In severe chronic obstructive pulmonary disease, the 6‐min walk distance predicts mortality better than other traditional markers of disease severity. Its measurement is useful in the comprehensive evaluation of patients with severe disease.
Mechanical ventilation of healthy rats suppresses peripheral immune function
Authors: Vreugdenhil H.A. , Heijnen C.J. , Plötz F.B. , Zijlstra J. , Jansen N.J. , Haitsma J.J. , Lachmann B. , van Vught A.J. 
Published: January 2004

This study was designed to investigate the possible effect of injurious mechanical ventilation on peripheral immune function of healthy rats. Three ventilation strategies were compared: 1) low peak inspiratory pressure (PIP)/positive end-expiratory pressure (PEEP); 2) high PIP/PEEP; and 3) high PIP/zero PEEP (ZEEP). As a reference group, healthy, nonventilated, sham-operated, anaesthetised rats were used.After 4 h, rats were sacrificed and macrophage inflammatory protein (MIP)‐2 levels in lung and plasma were determined. Peripheral immune function was determined by measurement of splenic natural killer (NK) activity, mitogen-induced splenocyte proliferation andin vitrocytokine production. All immune measurements in the low PIP/PEEP group did not differ from the immune measurements in the reference group. High PIP strategies, irrespective of applied PEEP, enhanced MIP‐2 levels in lung and plasma.NK cell activity, mitogen-induced splenocyte proliferation and MIP‐2 and interleukin (IL)‐10 production significantly decreased after high PIP/PEEP ventilation. In the high PIP/ZEEP‐ventilated group, the decrease in splenocyte proliferation, MIP‐2 and IL‐10 production and NK cell activity was more pronounced and interferon‐γ production was also significantly lower than in the low PIP/PEEP group.These data show that high positive inspiratory pressure ventilation induces an inflammatory response in the lung, whereas at the same time the peripheral immune response is downregulated. Ventilator-induced peripheral immune suppression may contribute to poor outcome in acute respiratory distress syndrome patients.
Apoptosis and proliferation in lungs of ventilated and oxygen-treated preterm infants
Authors: May M. , Ströbel P. , Preisshofen T. , Seidenspinner S. , Marx A. , Speer C.P. 
Published: January 2004

Apoptosis and proliferation and the effect of exogenous surfactant on these processes were investigated in the lungs of mechanically ventilated/oxygen-treated preterm infants with respiratory distress syndrome and stillborn foetuses.Apoptotic and proliferation indices were determined in lung tissue sections from 27 ventilated/oxygen-treated preterm infants and 29 stillborn foetuses. The effect of exogenous surfactant on apoptosis and proliferation was studied in 16 ventilated preterm infants; 11 untreated infants served as control. Apoptotic and proliferating cells were identified by double labelling combining terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end-labelling or Ki‐67 with cell marker proteins. Pathways to cell death were explored by immunolabelling of cleaved caspases‐3, ‐8 and ‐9.In the lungs of ventilated/oxygen-treated preterm infants, the numbers of apoptotic and proliferating cells increased significantly compared to the respective numbers in the lungs of stillborn foetuses. Apoptosis was detected in alveolar epithelial cells, whereas epithelial, endothelial and smooth muscle cells proliferated. Surfactant treatment reduced apoptosis induced by ventilation/oxygen-treatment; however, the decrease was not significant. Caspases‐8 and ‐9 do not contribute to ventilation-induced apoptosis, whereas caspase‐3 is involved.In conclusion, ventilation/oxygen-treatment induces epithelial cell apoptosis and proliferation of epithelial, endothelial and smooth muscle cells in the lungs of preterm infants.
Dynamic dead space in face masks used with noninvasive ventilators: a lung model study
Authors: Saatci E. , Miller D.M. , Stell I.M. , Lee K.C. , Moxham J. 
Published: January 2004

The aim of this study was to determine what the influence of different designs of face masks and different noninvasive ventilator modes would be upon total dynamic dead space.Using a spontaneous breathing model, total dynamic dead space was measured when using 19 commercially available face masks and a range of ventilators in various ventilation modes.Total dynamic dead space during spontaneous ventilation was increased above physiological dead space from 32% to 42% of tidal volume by using face masks. The use of noninvasive ventilation modes such as bilevel and continuous positive airway pressure, with continuous pressure throughout the expiratory phase, reduced total dynamic dead space to approach physiological dead space with most face masks. Pressure assist and pressure support ventilation decreased total dynamic dead space to a lesser degree, from 42% to 39% of tidal volume. Face masks with expiratory ports over the nasal bridge resulted in beneficial flow characteristics within the face mask and nasal cavity, so as to decrease total dynamic dead space to less than physiological dead space from 42% to 28.5% of tidal volume.Exhaust ports over the nasal bridge in face masks effect important decreases in dynamic dead space provided positive pressure throughout the expiratory phase is used.
Prevalence of asthma and exhaled nitric oxide are increased in bleachery workers exposed to ozone
Authors: Olin A-C. , Andersson E. , Andersson M. , Granung G. , Hagberg S. , Torén K. 
Published: January 2004

The aims of the present study were to determine whether exposure to high peaks of ozone resulted in an increased prevalence of asthma or respiratory symptoms among bleachery workers and whether nitric oxide (NO) was elevated in the exhaled air of these workers.Bleachery workers (n=228) from three Swedish pulp mills who had been exposed to ozone, together with 63 unexposed control subjects, were investigated by means of spirometry, Phadiatop®, exhaled and nasal NO and answers to a questionnaire concerning respiratory symptoms and exposure. Exposure to an ozone peak that gave rise to respiratory symptoms was defined as a “gassing”.Bleachery workers reporting four or more gassings involving ozone had an increased prevalence of adult-onset asthma, wheeze, and current asthma symptoms. They also had a higher median concentration of exhaled NO in comparison with those who reported no such gassings (19.2versus15.7 parts per billion). No such associations were found in respect of nasal NO.The results from this study show that bleachery workers who have been repeatedly exposed to ozone gassings have an increased prevalence of adult-onset asthma. The results also indicate exhaled nitric oxide may be a marker of airway inflammation in bleachery workers who have been exposed to high peaks of ozone.
Childhood factors that predict asthma in young adulthood
Authors: Toelle B.G. , Xuan W. , Peat J.K. , Marks G.B. 
Published: January 2004

Predicting adult asthma, using childhood characteristics, is important for advising on prognosis and, potentially, for secondary prevention. A novel use of multivariate likelihood ratios (LRs) to quantify prognosis is described here.Of 718 subjects of a community-based cohort, 575 (80%) members were recruited at age 8–10 yrs and were re-assessed 15–17 yrs later. At baseline, information about symptoms, spirometry, histamine challenge and skin-prick tests were collected. At follow-up “asthma symptoms” were defined as wheeze, sleep disturbance from asthma or inhaled steroid use within the previous year. LRs were calculated for significant predictors of this outcome. Shinkage factors were applied to yield multivariate LRs.Childhood characteristics that independently predicted asthma symptoms in adulthood were obstructive spirometry (adjusted (adj)LR 2.9, 95% confidence interval (CI) 1.3–6.5), airway hyperresponsiveness (adjLR 2.6, 95% CI 1.8–3.7), atopy (adjLR 2.0, 95% CI 1.5–2.7), recent wheeze (adjLR 1.9, 95% CI 1.5–2.5) and being female (adjLR 1.29, 95% CI 0.8–2.1). Children with all five characteristics had a cumulative LR of 36.9 for asthma symptoms in adulthood.Most adults who had asthma symptoms did not have manifestations of asthma as children. However, the presence of obstructive spirometry, airway hyperresponsiveness and atopy in childhood identifies individuals with increased likelihood of having asthma in adulthood. Cumulative likelihood ratios are more valuable than odds ratios for quantifying risk in individuals and for identifying people with most to gain from preventive interventions.
New concepts of the pathogenesis of cystic fibrosis lung disease
Authors: Boucher R.C. 
Published: January 2004

Although there has been impressive progress in the elucidation of the genetic and molecular basis of cystic fibrosis (CF), the pathogenesis of CF lung disease remains obscure. The elucidation of the pathogenesis of CF lung disease requires both a full description of normal innate airway defence and how absent function of the cystic fibrosis transmembrane regulator protein (CFTR) adversely perturbs this activity.Recent data have linked the abnormal ion transport properties of CF airway epithelia to depleted airway surface liquid (ASL) volume, reflecting the combined defects of accelerated Na+transport and the failure to secrete Cl−. Depletion of a specific compartment of the ASL,i.e.the periciliary liquid (PCL), appears to abrogate both cilia-dependent and cough clearance.Subsequent to PCL depletion, mucus adheres to airway surfaces and persistent mucin secretion generates the formation of “thickened” mucus plaques and plugs, which become the nidus for bacterial infection. The paucity of liquid in these plaques/plugs, and the hypoxia in this environment, appear to promote biofilm bacterial infection.Therapeutic agents that restore airway surface liquid volume,i.e.blockers of Na+transport, initiators of Cl−transport and osmolytes, are reviewed, as are strategies that may be required to use volume-restoring agents safely in patients with cystic fibrosis.
Formoterol protects against platelet-activating factor-induced effects in asthma
Authors: Gabrijelcic J. , Casas A. , Rabinovich R.A. , Roca J. , Barberà J.A. , Chung K.F. , Rodríguez-Roisin R. 
Published: January 2004

Platelet-activating factor (PAF) is an inflammatory mediator that provokes neutropaenia, bronchoconstriction and gas exchange defects due to exudation of bulk plasma within the airways. While the inhibitory effects of short-acting β2‐agonists on PAF‐induced disturbances have been consistently shown, those of long-acting β2‐agonists are less convincing.To further explore the mechanisms involved in PAF challenge in asthma, 12 patients (forced expiratory volume in one second, 90±4% predicted) were investigated 2 h after inhaled formoterol (18 µg), in a double-blind, placebo-controlled, crossover design following PAF (18 µg) inhalation.Compared with the placebo, at 5 min, premedication with formoterol reduced PAF-induced cough and dyspnoea, and attenuated increased respiratory system resistance (by 67%) and arterial deoxygenation (by 50%). Likewise, ventilation-perfusion (V′A/Q′) inequality improved, as reflected by the dispersion of pulmonary blood flow (by 63%) and an overall index ofV′A/Q′ heterogeneity (by 71%). In contrast, PAF-induced facial flushing, neutropaenia and subsequent rebound neutrophilia remained unchanged.The improvement in gas exchange abnormalities shown after platelet-activating factor in patients with asthma pretreated with formoterol at the recommended clinical dose may reflect, in addition to its class effects, an anti-exudative effect of formoterol in the airways.
KL‐6 levels are elevated in plasma from patients with acute respiratory distress syndrome
Authors: Sato H. , Callister M.E.J. , Mumby S. , Quinlan G.J. , Welsh K.I. , duBois R.M. , Evans T.W. 
Published: January 2004

The acute respiratory distress syndrome (ARDS) is an extreme form of lung injury characterised by disruption to the alveolar epithelium. KL‐6 is a mucin-like glycoprotein expressed on type II pneumocytes. Circulating levels of KL‐6 have diagnostic and prognostic significance in a number of interstitial lung diseases, and when elevated are thought to indicate disruption of the alveolar epithelial lining. In this study, the authors sought to determine whether plasma KL‐6 levels were elevated in patients with ARDS and whether these were associated with aetiology, disease severity, outcome or ventilatory strategy.Plasma samples were collected from 28 patients with ARDS, nine ventilated controls of matched illness severity and 10 healthy individuals. KL‐6 concentrations were measured by enzyme-linked immunosorbent assay.Patients with ARDS had higher plasma levels of KL‐6 (median 537 U·mL−1, interquartile range (IQR) 383–1,119), as compared to ventilated controls (median 255 U·mL−1, IQR 83–338) and normal individuals (median 215 U·mL−1, IQR 149–307). In patients with ARDS, plasma KL-6 levels were higher in nonsurvivors than survivors, and correlated positively with oxygenation index and negatively with arterial oxygen tension:inspiratory oxygen fraction ratio. There were also significant positive correlations with mean and peak airway pressures.Elevated levels of plasma KL‐6 may provide a useful marker for acute respiratory distress syndrome in ventilated patients and have possible prognostic significance. Alveolar epithelial cell damage may be influenced by the nature of mechanical ventilatory support.