bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of tiotropium on exacerbations and airflow in patients with COPD
Authors: Dusser D. , Bravo M-L. , Iacono P. 
Published: February 2006

This randomised, double-blind, parallel-group, 1-yr study compared the effect of tiotropium 18 µg once daily (n = 500) and placebo (n = 510) on exacerbations, associated health resource use (HRU) and airflow limitation in chronic obstructive pulmonary disease (COPD) patients.The mean±sdnumber of exacerbations during the past year was 2.14±1.40, the mean weekly morning peak expiratory flow (PEF) was 259.6±96.1 L·min−1and the mean forced expiratory volume in one second (FEV1) was 1.37±0.45 L. Tiotropium significantly delayed the time to first exacerbation by ∼100 days, reduced the proportion of patients experiencing more than one exacerbation by 17%, and decreased the number of exacerbations by 35% and exacerbation days by 37%versusplacebo. Tiotropium also decreased HRUversusplacebo, as indicated by the significant reductions in the use of concomitant respiratory medications, antibiotics and oral steroids, and the number of unscheduled physician contacts. Mean weekly morning PEF improved significantly with tiotropiumversusplacebo from week 1 until the end of the study. At the end of the study, tiotropium significantly improved trough (pre-dose) FEV1, forced vital capacity, slow vital capacity and inspiratory capacityversusplacebo.In conclusion, tiotropium reduced exacerbations and associated health resource use, and improved airflow over 1 yr in chronic obstructive pulmonary disease patients.
Reduced Th1 response in the lungs of HLA-DRB1*0301 patients with pulmonary sarcoidosis
Authors: Idali F. , Wikén M. , Wahlström J. , Mellstedt H. , Eklund A. , Rabbani H. , Grunewald J. 
Published: February 2006

To investigate why human leukocyte-associated antigen-DRB1*0301 (HLA-DRB1*0301) positive Scandinavian patients have a better prognosis than HLA-DRB1*0301 negative patients, the present authors examined patterns of cytokine expression in bronchoalveolar lavage (BAL) cells and BAL fluid (BALF) from patients with pulmonary sarcoidosis and controls.Using real-time PCR, the mRNA expression of selected cytokines in BAL cells from newly diagnosed, untreated nonsmoking patients (n = 25) and controls (n = 11) was quantified. Cytokine protein levels in BALF from patients (n = 34) and controls (n = 11) were assessed using cytometric bead array. The patients were evaluated and stratified into two subgroups: HLA-DRB1*0301 positive (all with an acute onset) and HLA-DRB1*0301 negative (all with an insidious onset).When comparing patients and controls, BAL cells of the patients expressed significantly higher levels of interferon (IFN)-γ and interleukin (IL)-10 mRNA. There were significantly decreased IFN-γ and tumour necrosis factor (TNF)-α mRNA levels, and a tendency toward higher levels of transforming growth factor-β1 mRNA in HLA-DRB1*0301 positive compared with HLA-DRB1*0301 negative patients. Protein levels of IL-1β, IL-2, IL-6, IL-12p70 and TNF-α in BALF were significantly higher in patients. HLA-DRB1*0301 positive patients exhibited tendencies to lower levels of most cytokines in BALF.In conclusion, the present data show a reduced expression of T-helper cell type-1 cytokines in human leukocyte-associated antigen-DRB1*0301 positive patients, which may relate to their good prognosis.
Use of tacrolimus, a potent antifibrotic agent, in bleomycin-induced lung fibrosis
Authors: Nagano J. , Iyonaga K. , Kawamura K. , Yamashita A. , Ichiyasu H. , Okamoto T. , Suga M. , Sasaki Y. , Kohrogi H. 
Published: February 2006

Idiopathic pulmonary fibrosis has a poor prognosis and few efficacious treatments. The immunosuppressant cyclosporin A has been shown to inhibit tumour growth factor (TGF)-β-induced collagen depositionin vitro, and is widely used in Japan as a potent antifibrotic agent. Tacrolimus (FK506) is another attractive immunosuppressant, which may be useful in the treatment of pulmonary fibrosis. The aim of the present study was to elucidate the antifibrotic effect of FK506.The inhibitory effect of FK506 on collagen synthesis in cultured lung fibroblastic cells, TIG-3-20, and its antifibrotic effect on bleomycin (BLM)-induced pulmonary fibrosis in mice was investigated.FK506 inhibited TGF-β-induced collagen synthesis, and suppressed the expression of TGF-β type I receptor (TβR-I) in TIG-3-20 cells. Consistent with thein vitrofindings, FK506 treatment starting on day 6 attenuated BLM-induced pulmonary fibrosis, in part,viareduced TβR-I expression. FK506 treatment in the acute BLM injury phase unexpectedly increased pro-inflammatory cytokine levels in bronchoalveolar lavage fluid and enhanced lung injury, resulting in poor survival.In conclusion, the present results suggest that FK506 has a potent antifibrotic effect and may be useful for the treatment of pulmonary fibrosis, although its use in the acute inflammatory phase may exacerbate lung injury.
Prevalence of oxygen desaturation and use of oxygen at home in adults at sea level and at moderate altitude
Authors: Perez-Padilla R. , Torre-Bouscoulet L. , Muiño A. , Marquez M. N. , Lopez M. V. , de Oca M. M. , Talamo C. , Menezes A. M. B. 
Published: February 2006

The aim of this study was to determine the prevalence of oxygen desaturation in adults aged ≥40 yrs as altitude above sea level increases.A population-based, cross-sectional study with a multistage cluster sampling of 1,063 subjects from metropolitan Mexico City (Mexico; 2,240 m above sea level), 1,357 from Caracas (Venezuela; 950 m) and 943 from Montevideo (Uruguay; 35 m). The mean of six measurements of arterial oxygen saturation (SP,O2) was estimated using a pulse oximeter.MeanSP,O2decreased with altitude. No subject from Montevideo had a meanSP,O2≤88%. Prevalence of subjects withSP,O2≤88%, a common criterion used for oxygen prescription, was 1.0% in Caracas and 6.0% in Mexico City. Additional predicting factors for hypoxaemia in multiple regression models were age, body mass index and a low forced expiratory volume in one second as a percentage of the predicted value. In Mexico City and Caracas, <10% of the hypoxaemic subjects reported use of domiciliary oxygen, whereas at least half of the subjects reporting use of oxygen at home had a restingSP,O2>88%.In conclusion, the prevalence of hypoxaemia was closely related to altitude. Priorities for oxygen prescription must be defined in moderate altitudes because it is unfeasible to provide it to all subjects fulfilling the criteria commonly used.
Telomere shortening in smokers with and without COPD
Authors: Morlá M. , Busquets X. , Pons J. , Sauleda J. , MacNee W. , Agustí A. G. N. 
Published: February 2006

Telomeres are complex DNA–protein structures located at the end of eukaryotic chromosomes. Telomere length shortens with age in all replicating somatic cells. It has been shown that tobacco smoking enhances telomere shortening in circulating lymphocytes. The present study investigated whether this effect was further amplified in smokers who develop chronic obstructive pulmonary disease.Telomere length was determined by fluorescencein situhybridisation in circulating lymphocytes harvested from 26 never-smokers, 24 smokers with normal lung function and 26 smokers with moderate-to-severe airflow obstruction (forced expiratory flow in one second 48±4% predicted).In contrast to never-smokers, telomere length significantly decreased with age in smokers. There was also a dose–effect relationship between the cumulative long-life exposure to tobacco smoking (pack-yrs) and telomere length. The presence and/or severity of chronic airflow obstruction did not modify this relationship.The results of the current study confirm that smoking exposure enhances telomere shortening in circulating lymphocytes. It also demonstrates a dose–effect relationship between exposure to tobacco smoking and telomere length, but failed to show that this effect is amplified in smokers who develop chronic obstructive pulmonary disease.
A study of aspirin and clopidogrel in idiopathic pulmonary arterial hypertension
Authors: Robbins I. M. , Kawut S. M. , Yung D. , Reilly M. P. , Lloyd W. , Cunningham G. , Loscalzo J. , Kimmel S. E. , Christman B. W. , Barst R. J. 
Published: February 2006

Idiopathic pulmonary arterial hypertension (IPAH) is characterised byin situthrombosis and increased thromboxane (Tx) A2synthesis; however, there are no studies of antiplatelet therapy in IPAH. The aim of the current study was to determine the biochemical effects of aspirin (ASA) and clopidogrel on platelet function and eicosanoid metabolism in patients with IPAH.A randomised, double-blind, placebo-controlled crossover study of ASA 81 mg once daily and clopidogrel 75 mg once daily was performed. Plasma P-selectin levels and aggregometry were measured after exposure to adenosine diphosphate, arachidonic acid and collagen. Serum levels of TxB2and urinary metabolites of TxA2and prostaglandin I2(Tx-M and PGI-M, respectively) were assessed.A total of 19 IPAH patients were enrolled, of whom nine were being treated with continuous intravenous epoprostenol. ASA and clopidogrel significantly reduced platelet aggregation to arachidonic acid and adenosine diphosphate, respectively. ASA significantly decreased serum TxB2, urinary Tx-M levels and the Tx-M/PGI-M ratio, whereas clopidogrel had no effect on eicosanoid levels. Neither drug significantly lowered plasma P-selectin levels. Epoprostenol use did not affect the results.In conclusion, aspirin and clopidogrel inhibited platelet aggregation, and aspirin reduced thromboxane metabolite production without affecting prostaglandin I2metabolite synthesis. Further clinical trials of aspirin in patients with idiopathic pulmonary arterial hypertension should be performed.
Simplified stepwise management of primary spontaneous pneumothorax: a pilot study
Authors: Marquette C-H. , Marx A. , Leroy S. , Vaniet F. , Ramon P. , Caussade S. , Smaiti N. , Bonfils C. 
Published: February 2006

In primary spontaneous pneumothorax (PSP) requiring intervention, removal of air from the pleural space can be achieved by manual needle aspiration or by pleural drainage after insertion of a chest tube. This study aimed to evaluate the efficacy and safety of a serial-steps approach with a single system (small-calibre catheter/Heimlich valve) in a homogeneous population of patients with a first episode of PSP.All patients had an 8.5 F distally multiperforated polyurethane pigtail catheter insertedviathe anterior route, at the bedside without any guidance, using the Seldinger technique. A one-way Heimlich valve was connected to the catheter, allowing the air to flow spontaneously outwards for 24–48 h. Thereafter, if the lung failed to re-expand wall suction was applied. Patients with an air leak persisting for >4 days were referred for surgery. Primary end-points were success rates at 24 h and 1 week, and 1 yr recurrence-free survival.In total, 41 consecutive patients entered the study. They were typically thin, young, smoking males. No procedure-related complications were observed. The need for pain relief medication was minimal. Within the first 24 h, most of the patients were able to walk around and half of them were able to take a shower with their catheter in place. The 24-h and 1-week success rates were 61 and 85%, respectively, and the actuarial 1-yr recurrence rate was 24%. Four patients underwent surgical pleurodesis because of a persistent air leak. The length of stay when excluding the four surgical cases was 2.3±1.3 days.When 24-h and 1-week success rates and recurrence at 12 months were taken as end-points, the method described here is as effective as simple manual needle aspiration or a conventional chest tube thoracotomy. These results support further studies assessing this “one system, serial-steps approach” in an outpatient management algorithm.
Changes in active and passive smoking in the European Community Respiratory Health Survey
Authors: Janson C. , Künzli N. , de Marco R. , Chinn S. , Jarvis D. , Svanes C. , Heinrich J. , Jõgi R. , Gislason T. , Sunyer J. , Ackermann-Liebrich U. , Antó J. M. , Cerveri I. , Kerhof M. , Leynaert B. , Luczynska C. , Neukirch F. , Vermeire P. , Wjst M. , Burney P. 
Published: February 2006

The aim of the present investigation was to study changes and determinants for changes in active and passive smoking.The present study included 9,053 adults from 14 countries that participated in the European Community Respiratory Health Survey II. The mean follow-up period was 8.8 yrs. Change in the prevalence of active and passive smoking was expressed as absolute net change (95% confidence interval) standardised to a 10-yr period. Determinants of change were analysed and the results expressed as adjusted hazard risk ratio (HRR) or odds ratio (OR).The prevalence of active smoking declined by 5.9% (5.1–6.8) and exposure to passive smoking in nonsmokers declined by 18.4% (16.8–20.0). Subjects with a lower educational level (HRR: 0.73 (0.54–0.98) and subjects living with a smoker (HRR: 0.45 (0.34–0.59)) or with workplace smoking (HRR: 0.69 (0.50–0.95)) were less likely to quit. Low socio-economic groups were more likely to become exposed (OR: 2.21 (1.61–3.03)) and less likely to cease being exposed to passive smoking (OR: 0.48 (0.37–0.61)).In conclusion, the quitting rate was lower and the risk of exposure to passive smoking higher among subjects with lower socio-economic status. Exposure to other peoples smoking decreased quitting rates and increased the risk of starting to smoke.
Circulating haemopoietic and endothelial progenitor cells are decreased in COPD
Authors: Palange P. , Testa U. , Huertas A. , Calabrò L. , Antonucci R. , Petrucci E. , Pelosi E. , Pasquini L. , Satta A. , Morici G. , Vignola M. A. , Bonsignore M. R. 
Published: February 2006

Circulating CD34+ cells are haemopoietic progenitors that may play a role in tissue repair. No data are available on circulating progenitors in chronic obstructive pulmonary disease (COPD).Circulating CD34+ cells were studied in 18 patients with moderate-to-severe COPD (age: mean±sd68±8 yrs; forced expiratory volume in one second: 48±12% predicted) and 12 controls, at rest and after endurance exercise. Plasma concentrations of haematopoietic growth factors (FMS-like tyrosine kinase 3 (Flt3) ligand, kit ligand), markers of hypoxia (vascular endothelial growth factor (VEGF)) and stimulators of angiogenesis (VEGF, hepatocyte growth factor (HGF)) and markers of systemic inflammation (tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-8) were measured.Compared with the controls, the COPD patients showed a three-fold reduction in CD34+ cell counts (3.3±2.5versus10.3±4.2 cells·µL−1), and a 50% decrease in AC133+ cells. In the COPD patients, progenitor-derived haemopoietic and endothelial cell colonies were reduced by 30–50%. However, four COPD patients showed progenitor counts in the normal range associated with lower TNF-α levels. In the entire sample, CD34+ cell counts correlated with exercise capacity and severity of airflow obstruction. After endurance exercise, progenitor counts were unchanged, while plasma Flt3 ligand and VEGF only increased in the COPD patients. Plasma HGF levels were higher in the COPD patients compared with the controls and correlated inversely with the number of progenitor-derived colonies.In conclusion, circulating CD34+ cells and endothelial progenitors were decreased in chronic obstructive pulmonary disease patients and could be correlated with disease severity.
Can heart rate variation rule out sleep-disordered breathing in heart failure?
Authors: Vazir A. , Dayer M. , Hastings P. C. , McIntyre H. F. , Henein M. Y. , Poole-Wilson P. A. , Cowie M. R. , Morrell M. J. , Simonds A. K. 
Published: February 2006

In patients with obstructive sleep apnoea (OSA), the very low frequency power spectral density index (VLFI) derived from analysis of heart rate correlates with the severity of obstructive apnoeas. VLFI is also associated with Cheyne–Stokes respiration/central sleep apnoea (CSR/CSA) in congestive heart failure (CHF). The present authors have tested the hypothesis that per cent VLFI, derived from a standard Holter ECG recording, can be used to detect the presence of OSA and CSR/CSA in patients with mild-to-moderate CHF.In total, 60 CHF patients underwent polysomnography with monitoring of heart rate. Data from 33 patients were analysed for per cent VLFI. Of the 60 patients, 27 were excluded due to atrial fibrillation, extensive pacing or frequent ventricular extra systoles.Receiver operator characteristic curves were constructed to establish the per cent VLFI that would optimally identify the presence or absence of sleep-disordered breathing. Using an apnoea–hypopnoea index >20 events·h−1and setting the per cent VLFI at 2.23% yielded a sensitivity of 85%, specificity of 65%, positive predictive value of 61% and a negative predictive value of 87%. The latter increased to 100% when using an apnoea–hypopnoea cut-off of 30 events·h−1.In conclusion, these results suggest that spectral analysis of heart rate may be useful as a “rule-out test” for sleep-disordered breathing in patients with mild-to-moderate congestive heart failure.
Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations
Authors: Jayaram L. , Pizzichini M. M. , Cook R. J. , Boulet L-P. , Lemière C. , Pizzichini E. , Cartier A. , Hussack P. , Goldsmith C. H. , Laviolette M. , Parameswaran K. , Hargreave F. E. 
Published: February 2006

One important goal of asthma treatment is to reduce exacerbations. The current authors investigated if the use of sputum cell counts to guide treatment would achieve this goal.A total of 117 adults with asthma were entered into a multicentre, randomised, parallel group-effectiveness study for two treatment strategies over a 2-yr period. In one strategy (the clinical strategy: CS) treatment was based on symptoms and spirometry. In the other (the sputum strategy: SS) sputum cell counts were used to guide corticosteroid therapy to keep eosinophils ≤2%; symptoms and spirometry were used to identify clinical control, exacerbations and other treatments. Patients were blind to sputum cell counts in both strategies and physicians were blind in the CS, thus removing bias. First, the minimum treatment to maintain control was identified in 107 patients (Phase 1) and then this treatment was continued (Phase 2) for the remaining of the 2 yrs. The primary outcomes were the relative risk reduction for the occurrence of the first exacerbation in Phase 2 and the length of time without exacerbation. The current authors also examined the type and severity of exacerbations and the cumulative dose of inhaled steroid needed.The duration and number of exacerbations in Phase 1 were similar in both groups. In Phase 2 there were a 126 exacerbations of which 79 occurred in the CS (62.7%) and 47 (37.3%) in the SS groups. The majority of the 126 exacerbations (101; 80.1%) were mild. The majority of the 102 exacerbations, where sputum examination was performed before any treatment (n = 70), were noneosinophilic. In the SS patients, the time to the first exacerbation was longer (by 213 days) especially in those considered to need treatment with a long acting β2-agonist (by 490 days), the relative risk ratio was lower (by 49%), and the number of exacerbations needing prednisone was reduced (5versus15). This benefit was seen mainly in patients needing treatment with inhaled steroid in a daily dose equivalent to fluticasone >250 μg, and was due to fewer eosinophilic exacerbations. The cumulative dose of corticosteroid during the trial was similar in both groups.Monitoring sputum cell counts was found to benefit patients with moderate-to-severe asthma by reducing the number of eosinophilic exacerbations and by reducing the severity of both eosinophilic and noneosinophilic exacerbations without increasing the total corticosteroid dose. It had no influence on the frequency of noneosinophilic exacerbations, which were the most common exacerbations.
Implications of COPD in patients admitted to the intensive care unit by community-acquired pneumonia
Authors: Rello J. , Rodriguez A. , Torres A. , Roig J. , Sole-Violan J. , Garnacho-Montero J. , de la Torre M. V. , Sirvent J. M. , Bodi M. 
Published: March 2006

The mortality rate of chronic obstructive pulmonary disease (COPD) patients with community-acquired pneumonia (CAP) is reported to be low. However, studies carried out to date have included <20% of critically ill patients.The current authors performed a secondary analysis of a prospective study evaluating 428 immunocompetent patients admitted to the intensive care unit (ICU) for severe CAP.In total, 176 COPD patients were compared with 252 non-COPD patients. In COPD patients, ICU mortality (odds ratio (OR) 1.58; 95% confidence interval (CI) 1.01–1.43) and mechanical ventilation (OR 2.78; 95% CI 1.63–4.74) rates were higher than in non-COPD patients. The ICU mortality was 39% for COPD patients initially intubated and 50% for those who failed noninvasive ventilation. The proportion of patients who were males, aged ≥70 yrs, smokers and who had chronic heart disease orPseudomonas aeruginosawere higher in COPD patients. Inappropriate empirical antibiotic therapy was associated with higher mortality (OR 3.8; 95% CI 1.19–12.6). ICU mortality in COPD patients with adequate therapy was associated with bilateral pneumonia (OR 2.32; 95% CI 1.18–4.53) and shock (OR 3.53; 95% CI 1.31–9.71).In conclusion, chronic obstructive pulmonary disease patients hospitalised with community-acquired pneumonia in the intensive care unit had higher mortality and need of mechanical ventilation when compared with patients without chronic obstructive pulmonary disease.
La belle indifférencein conversion symptoms and hysteria
Authors: Stone Jon , Smyth Roger , Carson Alan , Warlow Charles 
Published: February 2006

BackgroundLa belle indifférencerefers to an apparent lack of concern shown by some patients towards their symptoms. It is often regarded as typical of conversion symptoms/hysteria.AimsTo determine the frequency ofla belle indifférencein studies of patients with conversion symptoms/hysteria and to determine whether it discriminates between conversion symptoms and symptoms attributable to organic disease.MethodA systematic review of all studies published since 1965 that have reported rates ofla belle indifférencein patients with conversion symptoms and/or patients with organic disease.ResultsAtotal of 11 studies were eligible for inclusion. The median frequency ofla belle indifférencewas 21 % (range 0–54%) in 356 patients with conversion symptoms, and 29% (range 0–60%) in 157 patients with organic disease.ConclusionsThe available evidence does not support the use ofla belle indifférenceto discriminate between conversion symptoms and symptoms of organic disease. The quality of the published studies is poor, with a lack of operational definitions and masked ratings.La belle indifférenceshould be abandoned as a clinical sign until both its definition and its utility have been clarified.