bluuebunny/crossref_metadata_2025_split huggingface dataset:
Training with inspiratory pressure support in patients with severe COPD
Authors: van 't Hul A. , Gosselink R. , Hollander P. , Postmus P. , Kwakkel G. 
Published: December 2005

This study evaluates the effects of training with noninvasive ventilatory support in patients with chronic obstructive pulmonary disease in a randomised, controlled, observer-blinded trial.Twenty-nine patients with chronic obstructive pulmonary disease and with a ventilatory limited exercise capacity (forced expiratory volume in one second <60% predicted, breathing reserve at maximal exercise <20% of maximally voluntary ventilation, resting arterial oxygen tension ≥8 kPa (60 mmHg), end-exercise arterial oxygen saturation measured by pulse oximetry ≥85%) completed an 8-week supervised outpatient cycle exercise programme. Fourteen patients were randomised to training with inspiratory pressure support of 10 cmH2O and 15 patients to training with control (sham) inspiratory pressure support of 5 cmH2O. Outcome measures were the incremental shuttle walking test and a constant-load cycle endurance test at 75% of peak work rate including the measurement of physiological responses, and health status measured using the St. George's Respiratory Questionnaire.Statistically significant between-group differences were found in favour of the inspiratory pressure support of 10 cmH2O group for improvement in shuttle walking distance (16±17versus3±13%), cycle endurance (164±124versus88±128%), and the reduction in minute ventilation during exercise (-11±10versus-2±9%).It was concluded that exercise training with inspiratory pressure support of 10 cmH2O resulted in statistically significantly larger improvements in exercise performance than training with inspiratory pressure support of 5 cmH2O in patients with chronic obstructive pulmonary disease suffering from a ventilatory limited exercise capacity. Inspiratory pressure support of 10 cmH2O may be considered as adjunct during high-intensity exercise training.
High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis
Authors: Raghu G. , Freudenberger T. D. , Yang S. , Curtis J. R. , Spada C. , Hayes J. , Sillery J. K. , Pope C. E. , Pellegrini C. A. 
Published: December 2005

The aim of this prospective study was to determine the prevalence and characteristics of acid gastro-oesophageal reflux (GER) in patients with idiopathic pulmonary fibrosis (IPF).Sixty-five consecutive patients with well-defined IPF were subjected to 24-h pH monitoring and oesophageal manometry. A total of 133 consecutive patients with intractable asthma and symptoms of GER were used as comparisons.The prevalence of abnormal acid GER in IPF patients was 87%, with 76% and 63% demonstrating abnormal distal and proximal oesophageal acid exposures, respectively. Abnormal acid GER was significantly more common in IPF patients than asthma patients. Only 47% of IPF patients experienced classic GER symptoms. Despite treatment with standard doses of proton pump inhibitors (PPIs), 12 out of 19 patients receiving PPIs during the 24-h pH monitoring had abnormal oesophageal acid exposures by pH probe. There was no correlation between IPF severity and acid GER severity.In conclusion, abnormal acid gastro-oesophageal reflux is highly prevalent, but often clinically occult in patients with idiopathic pulmonary fibrosis. Standard doses of proton pump inhibitors may not suppress the acid gastro-oesophageal reflux in this population. Therefore, further studies are needed to determine if acid abnormal gastro-oesophageal reflux represents an important risk factor for idiopathic pulmonary fibrosis development or progression, and if optimal suppression of acid gastro-oesophageal reflux slows the progression of idiopathic pulmonary fibrosis and/or decreases episodic exacerbations of idiopathic pulmonary fibrosis.
Delayed and persistent suppression of bronchoconstriction by trypsin in the airway lumen
Authors: Sharma A. , Goh H. L. , Asokananthan N. , Bakker A. , Stewart G. A. , Mitchell H. W. 
Published: December 2005

Mucosal trypsin, a protease-activated receptor (PAR) stimulant, may have an endogenous bronchoprotective role on airway smooth muscle. To test this possibility the effects of lumenal trypsin on airway tone in segments of pig bronchus were tested.Bronchial segments from pigs were mounted in an organ chamber containing Kreb's solution. Contractions were assessed from isovolumetric lumen pressure induced by acetylcholine (ACh) or carbachol added to the adventitia.Trypsin, added to the airway lumen (300 µg·mL−1), had no immediate effect on smooth muscle tone but suppressed ACh-induced contractions after 60 min, for at least 3 h. Synthetic activating peptides (AP) for PAR1, PAR2or PAR3were without effect, but PAR4AP caused rapid, weak suppression of contractions. Lumenal thrombin was without effect and did not prevent the effects of trypsin. Effects of trypsin were reduced byNω-nitro-l-arginine methyl ester but not indomethacin. Trypsin, thrombin and PAR4AP released prostaglandin E2. Adventitially, trypsin, thrombin and PAR4AP (but not PAR2AP) relaxed carbachol-toned airways after <3 min.The findings of this study show that trypsin causes delayed and persistent bronchoprotection by interacting with airway cells accessible from the lumen. The signalling mechanism may involve nitric oxide synthase but not prostanoids or protease-activated receptors.
Heart rate responses during the 6-minute walk test in pulmonary arterial hypertension
Authors: Provencher S. , Chemla D. , Hervé P. , Sitbon O. , Humbert M. , Simonneau G. 
Published: December 2005

Patients with pulmonary arterial hypertension (PAH) exhibit a limited increase in stroke volume on exercise, and the heart rate (HR) increases may reflect the main mechanism that allows cardiac output to increase. The current prospective study documented the contribution of HR to the 6-min walking distance (6MWD) in idiopathic (IPAH) and nonidiopathic PAH.Eighty-three patients (46 IPAH and 37 nonidiopathic PAH) underwent haemodynamic evaluation and a 6MWD test. Chronotropic response (peak walking HR minus resting HR) and peripheral oxygen saturation were monitored. Fifty-seven patients were also assessed after 5±2 months of treatment (bosentan n = 38, epoprostenol n = 14, bosentan-epoprostenol n = 3, iloprost n = 2).Before treatment, the 6MWD was related to numerous demographic, haemodynamic and walking test characteristics. Stepwise regression analysis indicated that the only factors significantly associated with the 6MWD were stroke volume and chronotropic response in both IPAH and nonidiopathic PAH patients. Following treatment, changes in 6MWD were significantly related to changes in chronotropic response in both IPAH and nonidiopathic PAH.In conclusion, baseline stroke volume and chronotropic response were independently associated with the 6-min walking distance in pulmonary arterial hypertension. The lack of chronotropic response may reflect the loss in normal physiological reserve in more unwell patients.
Baroreflex control of heart rate during sleep in severe obstructive sleep apnoea: effects of acute CPAP
Authors: Bonsignore M. R. , Parati G. , Insalaco G. , Castiglioni P. , Marrone O. , Romano S. , Salvaggio A. , Mancia G. , Bonsignore G. , Di Rienzo M. 
Published: December 2005

Baroreflex control of heart rate during sleep (baroreflex sensitivity; BRS) has been shown to be depressed in obstructive sleep apnoea (OSA), and improved after treatment with continuous positive airway pressure (CPAP). Whether CPAP also acutely affects BRS during sleep in uncomplicated severe OSA is still debatable.Blood pressure was monitored during nocturnal polysomnography in 18 patients at baseline and during first-time CPAP application. Spontaneous BRS was analysed by the sequence method, and estimated as the mean sequence slope.CPAP did not acutely affect mean blood pressure or heart rate but decreased cardiovascular variability during sleep. Mean BRS increased slightly during CPAP application (from 6.5±2.4 to 7.5±2.9 ms·mmHg−1), mostly in response to decreasing blood pressure. The change in BRS did not correlate with changes in arterial oxygen saturation or apnoea/hypopnoea index.The small change in baroreflex control of heart rate during sleep at first application of continuous positive airway pressure in severe obstructive sleep apnoea was unrelated to the acute resolution of nocturnal hypoxaemia, and might reflect autonomic adjustments to positive intrathoracic pressure, and/or improved sleep architecture. The small increase in baroreflex control of heart rate during sleep may be of clinical relevance as it was accompanied by reduced cardiovascular variability, which is acknowledged as an independent cardiovascular risk factor.
Inhaled corticosteroids: effects on the airway vasculature in bronchial asthma
Authors: Horvath G. , Wanner A. 
Published: December 2005

Inhaled corticosteroids suppress airway inflammation and components of airway remodelling in bronchial asthma. In the tracheobronchial (airway) vasculature, these include the inhibition of inflammatory hyperperfusion, microvascular hyperpermeability, mucosal oedema formation, and the formation of new blood vessels (angiogenesis).Corticosteroids are now known to exert their effects on the airway vasculature through genomic and nongenomic mechanisms. Genomic actions involve the regulation of target genes, and suppress most of the vascular elements of inflammation and angiogenesis in the airway. In contrast, nongenomic actions are mediated by rapid cellular mechanisms, and induce transient vasoconstriction in the airway, thereby reversing inflammatory hyperperfusion.The vascular actions of corticosteroids contribute to controlling clinical symptoms of asthma primarily by influencing airway calibre in the lung periphery and airway hyperreactivity.In this review article, recent advances into the understanding of cellular mechanisms and the clinical implications of the interaction of inhaled corticosteroids and the airway vasculature in asthma are reviewed.
Appropriateness and delay to initiate therapy in ventilator-associated pneumonia
Authors: Luna C. M. , Aruj P. , Niederman M. S. , Garzón J. , Violi D. , Prignoni A. , Ríos F. , Baquero S. , Gando S. 
Published: December 2005

Inappropriate therapy (IT) and delayed initiation of appropriate therapy (DIAT) result in inadequate therapy in patients with ventilator-associated pneumonia (VAP). The aim of the current study was to assess the impact of DIAT in VAP. A total of 76 mechanically ventilated patients with bacteriologically confirmed VAP were prospectively evaluated in the intensive care unit of six hospitals in Buenos Aires, Argentina.Appropriate therapy was defined as coverage of all the identified pathogens by the antimicrobial therapy administered at the time of VAP clinical diagnosis. The clinical pulmonary infection score was measured during the 3 days before, at the onset and during the days which followed the onset of VAP. A total of 24 patients received adequate therapy; mortality was 29.2%. The remaining 52 patients received either IT (n = 16) or DIAT (n = 36); the mortality was 63.5% combined, and 75.0 and 58.3% for IT and DIAT, respectively (statistically significant compared with adequate therapy).Inappropriate therapy and delayed initiation of appropriate therapy increased the mortality of ventilator-associated pneumonia. Patients with inappropriate therapy and/or delayed initiation of appropriate therapy had a more gradual increase in clinical pulmonary infection score than those receiving adequate therapy, and this increase was found to occur prior to the time of the clinical diagnosis.In conclusion, these findings might provide the rationale for a trial of earlier initiation of therapy, based on clinical grounds in an effort to improve the outcome of patients with ventilator-associated pneumonia.
Occult alveolar haemorrhage in pulmonary veno-occlusive disease
Authors: Rabiller A. , Jaïs X. , Hamid A. , Resten A. , Parent F. , Haque R. , Capron F. , Sitbon O. , Simonneau G. , Humbert M. 
Published: December 2005

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary arterial hypertension that affects predominantly post-capillary pulmonary vessels. A major concern with PVOD is the poor response to available therapies and the risk of pulmonary oedema with continuous intravenous epoprostenol.The present authors hypothesised that alveolar haemorrhage may be a characteristic feature of pulmonary veno-occlusive disease, as compared with other forms of pulmonary arterial hypertension that predominantly involve pre-capillary pulmonary arteries.This paper reports a series of 19 patients with either PVOD (n = 8) or idiopathic pulmonary arterial hypertension (IPAH; n = 11) who underwent bronchoalveolar lavage. Cytological analyses were performed and differential counts were made on Perls-stained preparations. The Golde score was used to assess alveolar haemorrhage. As compared with IPAH, PVOD was characterised by a higher percentage of haemosiderin-laden macrophages (40±37versus3±6%), resulting in elevated Golde scores (81±88versus4±10).It was concluded that occult alveolar haemorrhage is a common feature of pulmonary veno-occlusive disease. Detecting occult alveolar haemorrhage may be of interest in the diagnostic approach of pulmonary veno-occlusive disease.
Area-level socio-economic status and health status among adults with asthma and rhinitis
Authors: Blanc P. D. , Yen I. H. , Chen H. , Katz P. P. , Earnest G. , Balmes J. R. , Trupin L. , Friedling N. , Yelin E. H. , Eisner M. D. 
Published: December 2005

Socio-economic status (SES) may affect health status in airway disease at the individual and area level.In a cohort of adults with asthma, rhinitis or both conditions, questionnaire-derived individual-level SES and principal components analysis (PCA) of census data for area-level SES factors were used. Regression analysis was utilised to study the associations among individual- and area-level SES for the following four health status measures: severity of asthma scores and the Short Form-12 Physical Component Scale (SF-12 PCS) (n = 404); asthma-specific quality of life (QoL) scores (n = 340); and forced expiratory volume in one second (FEV1) per cent predicted (n = 218).PCA yielded a two-factor solution for area-level SES. Factor 1 (lower area-level SES) was significantly associated with poorer SF-12 PCS and worse asthma QoL. These associations remained significant after adding individual-level SES. Factor 1 was also significantly associated with severity of asthma scores, but not after addition of the individual-level SES. Factor 2 (suburban area-level SES) was associated with lower FEV1per cent predicted in combined area-level and individual SES models.In conclusion, area-level socio-economic status is linked to some, but not all, of the studied health status measures after taking into account individual-level socio-economic status.
Estimated numbers and prevalence of PI*S and PI*Z alleles of α1-antitrypsin deficiency in European countries
Authors: Blanco I. , de Serres F. J. , Fernandez-Bustillo E. , Lara B. , Miravitlles M. 
Published: December 2005

The current study focuses on developing estimates of the numbers of individuals carrying the two most common deficiency alleles, PI*S and PI*Z, for α1-antitrypsin deficiency (AT-D) in Europe.Criteria for selection of epidemiological studies were: 1) AT phenotyping performed by isoelectrofocusing or antigen–antibody crossed electrophoresis; 2) rejection of “screening studies”; 3) statistical precision factor score of ≥5 for Southwest, Western and Northern Europe, ≥4 for Central Europe, ≥3 for Eastern Europe; and 4) samples representative of the general population.A total of 75,390 individuals were selected from 21 European countries (one each from Austria, Belgium, Latvia, Hungary, Serbia-Montenegro, Sweden and Switzerland; two each from Denmark, Estonia and Lithuania; three each from Portugal and the UK; four each from Finland, the Netherlands, Norway and Spain; five each from Russia and Germany; six from Poland; eight from Italy; and nine from France). The total AT-D populations of a particular phenotype in the countries selected were: 124,594 ZZ; 560,515 SZ; 16,323,226 MZ; 630,401 SS; and 36,716,819 MS. The largest number of ZZ (5,000–15,000) were in Italy, Spain, Germany, France, the UK, Latvia, Sweden and Denmark, followed by Belgium, Portugal, Serbia-Montenegro, Russia, The Netherlands, Norway and Austria (1,000–2,000), with <1,000 in each of the remaining countries.A remarkable lack in number of reliable epidemiological studies and marked differences among these European countries and regions within a given country was also found.
Validation of a predictive rule for the management of community-acquired pneumonia
Authors: Capelastegui A. , España P. P. , Quintana J. M. , Areitio I. , Gorordo I. , Egurrola M. , Bilbao A. 
Published: December 2005

The CURB-65 score (Confusion, Urea >7 mmol·L−1, Respiratory rate ≥30·min−1, low Blood pressure, and age ≥65 yrs) has been proposed as a tool for augmenting clinical judgement for stratifying patients with community-acquired pneumonia (CAP) into different management groups.The six-point CURB-65 score was retrospectively applied in a prospective, consecutive cohort of adult patients with a diagnosis of CAP seen in the emergency department of a 400-bed teaching hospital from March 1, 2000 to February 29, 2004. A total of 1,100 inpatients and 676 outpatients were included.The 30-day mortality rate in the entire cohort increased directly with increasing CURB-65 score: 0, 1.1, 7.6, 21, 41.9 and 60% for CURB-65 scores of 0, 1, 2, 3, 4, and 5, respectively. The score was also significantly associated with the need for mechanical ventilation and rate of hospital admission in the entire cohort, and with duration of hospital stay among inpatients.The CURB-65 score (Confusion, Urea >7 mmol·L−1, Respiratory rate ≥30·min−1, low Blood pressure, and age ≥65 yrs), and a simpler CRB-65 score that omits the blood urea measurement, helps classify patients with community-acquired pneumonia into different groups according to the mortality risk and significantly correlates with community-acquired pneumonia management key points. The new score can also be used as a severity adjustment measure.
Cough and hypereosinophilia due toFIP1L1-PDGFRAfusion gene with tyrosine kinase activity
Authors: Chung K. F. , Hew M. , Score J. , Jones A. V. , Reiter A. , Cross N. C. P. , Bain B. J. 
Published: December 2005

Eosinophil-associated conditions, such as asthma and eosinophilic bronchitis, have been associated with chronic persistent cough, usually responding to corticosteroid therapy.This case study reports a case of persistent cough associated with gastro-oesophageal reflux (GOR) and hypereosinophilia. Treatment of GOR with proton pump inhibitors and fundoplication did not control the cough. However, high dose prednisolone, but not inhaled corticosteroids, did.The presence of theFIP1L1-PDGFRAfusion gene in myeloid cells was confirmed by fluorescencein situhybridisation analysis usingCHIC2deletion as a surrogate marker. The cough and other disease features were subsequently suppressed by the tyrosine kinase inhibitor, imatinib.This is the first case of persistent cough caused by hypereosinophilic syndrome characterised byFIP1L1-PDGFRAfusion gene and aberrant tyrosine kinase activity.
Acute exacerbation of idiopathic pulmonary fibrosis: frequency and clinical features
Authors: Kim D. S. , Park J. H. , Park B. K. , Lee J. S. , Nicholson A. G. , Colby T. 
Published: December 2005

Although acute exacerbations of idiopathic pulmonary fibrosis are well recognised, there are no studies documenting their prevalence or identifying pre-existing risk factors.This study analysed the clinical, radiological and pathological data of 11 patients who satisfied the criteria for acute exacerbation among 147 patients with biopsy-proven idiopathic pulmonary fibrosis. There were five additional patients who had similar demographics, radiology and surgical lung biopsy pathology, but had clinically less severe disease, and so were not included. The 2-yr frequency of acute exacerbation was 9.6% after the diagnosis. Most exacerbations were idiopathic, although two cases presented after surgical lung biopsy and one after bronchoalveolar lavage.No significant risk factor was found by univariate proportional hazard analysis. Imaging revealed diffuse bilateral ground-glass opacification superimposed on subpleural reticular and honeycombing densities. The biopsies of four patients taken during acute exacerbation exhibited diffuse alveolar damage superimposed upon usual interstitial pneumonia.The findings of this study demonstrate that acute exacerbation of idiopathic pulmonary fibrosis is rather common and this exacerbation is likely to have a spectrum of severity.
The contribution of transforming growth factor-β and epidermal growth factor signalling to airway remodelling in chronic asthma
Authors: Boxall C. , Holgate S. T. , Davies D. E. 
Published: December 2005

Asthma is increasing in prevalence in the developing world, affecting ∼10% of the world’s population. It is characterised by chronic lung inflammation and airway remodelling associated with wheezing, shortness of breath, acute bronchial hyperresponsiveness to a variety of innocuous stimuli and a more rapid decline in lung function over time.Airway remodelling, involving proliferation and differentiation of mesenchymal cells, particularly myofibroblasts and smooth muscle cells, is generally refractory to corticosteroids and makes a major contribution to disease chronicity. Transforming growth factor-β is a potent profibrogenic factor whose expression is increased in the asthmatic airways and is a prime candidate for the initiation and persistence of airway remodelling in asthma.This review highlights the role of transforming growth factor-β in the asthmatic lung, incorporating biosynthesis, signalling pathways and functional outcome.In vivo, however, it is the balance between transforming growth factor-β and other growth factors, such as epidermal growth factor, which will determine the extent of fibrosis in the airways.A fuller comprehension of the actions of transforming growth factor-β, and its interaction with other signalling pathways, such as the epidermal growth factor receptor signalling cascade, may enable development of therapies that control airway remodelling where there is an unmet clinical need.
Obstructive sleep apnoea and its therapy influence high-density lipoprotein cholesterol serum levels
Authors: Börgel J. , Sanner B. M. , Bittlinsky A. , Keskin F. , Bartels N. K. , Buechner N. , Huesing A. , Rump L. C. , Mügge A. 
Published: December 2005

Recent studies suggest an association of obstructive sleep apnoea (OSA) with cardiovascular risk factors, such as dyslipidaemia.The present study analyses the effects of OSA and its therapy on serum lipid concentrations in 470 OSA patients in a single centre study.Multivariate regression showed a significant association between the apnoea–hypopnoea index and high-density lipoprotein cholesterol (HDL-C) serum levels (n = 366), independent of age, sex, body mass index, diabetes and lipid lowering medication. There were no independent associations with total cholesterol, triglyceride and low-density lipoprotein cholesterol serum levels. During follow-up (6 months) with effective bilevel or continuous positive airway pressure therapy in 127 patients (lipoproteins: n = 86) without change in their lipid lowering therapy, the mean HDL-C serum level increased significantly by 5.8% from 46.9±15.8 to 49.6±15.3 mg·dL−1(mean±SD).An independent relationship was found between the change of apnoea–hypopnoea index and the change of high-density lipoprotein cholesterol or triglycerides, respectively. All patients with abnormal serum lipid/lipoprotein levels improved significantly under bilevel or continuous positive airway pressure therapy. This study demonstrates an influence of obstructive sleep apnoea and its therapy on high-density lipoprotein cholesterol levels.