bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leptin and ghrelin levels in patients with obstructive sleep apnoea: effect of CPAP treatment
Authors: Harsch I.A. , Konturek P.C. , Koebnick C. , Kuehnlein P.P. , Fuchs F.S. , Pour Schahin S. , Wiest G.H. , Hahn E.G. , Lohmann T. , Ficker J.H. 
Published: July 2003

Serum leptin and ghrelin levels were investigated in patients with obstructive sleep apnoea (OSA) syndrome before and during continuous positive airways pressure (CPAP) treatment and compared with body mass index (BMI)-matched controls without OSA.Male patients (n=30) with OSA (apnoea/hypopnoea index=58±16, BMI=32.6±5.3 kg·m−2) underwent CPAP treatment. Fasting leptin and ghrelin were measured atbaseline and 2 days, and in the case of leptin 2 months after initiation of treatment.Baseline plasma ghrelin levels were significantly higher in OSA patients than in controls. After 2 days of CPAP treatment, plasma ghrelin decreased in almost all OSA patients (n=9) to levels that were only slightly higher than those of controls (n=9). Leptin levels did not change significantly from baseline after 2 days of CPAP treatment, but were higher than in the control group. After 8 weeks, leptin levels decreased significantly, although the BMI of the patients showed no change. The decrease in leptin levels was more pronounced in patients with a BMI <30 kg·m−2.These data indicate that the elevated leptin and ghrelin levels are not determined by obesity alone, since they rapidly decreased during continuous positive airways pressure therapy.
Myopathological features in skeletal muscle of patients with chronic obstructive pulmonary disease
Authors: Gosker H.R. , Kubat B. , Schaart G. , van der Vusse G.J. , Wouters E.F.M. , Schols A.M.W.J. 
Published: July 2003

Despite the fact that muscle weakness is a major problem in chronic obstructive pulmonary disease (COPD), detailed information on myopathological changes at the microscopic level in these patients is scarce, if indeed available at all.Vastus lateralis biopsies of 15 COPD weight-stable patients (body mass index (BMI) 23.9±1.0 kg·m−2; fat-free mass index (FFMI) 17.2±1.7 kg·m−2) and 16 healthy age-matched controls (BMI 26.3±0.8 kg·m−2; FFMI 19.6±2.2 kg·m−2) were evaluated. Histochemistry was used to evaluate myopathological features. Immunohistochemistry was used for the detection of macrophages and leukocytes, and active caspase 3 and terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick-end labelling (TUNEL) as markers of apoptosis.Fatty cell replacement and fibrosis were observed in both groups, the latter being slightly, but significantly, more pronounced in COPD. No differences between COPD and controls were found with respect to central nuclei, necrosis, regeneration, or fibre splitting. Signs of mitochondrial abnormalities were absent and normal numbers of inflammatory cells were found. Active caspase 3 positive myocytes were not observed and no difference was found in the number of TUNEL-positive myonuclei between controls and COPD patients (1.1%versus1.0%, respectively). The cross-sectional area of type-IIX muscle fibres was smaller in COPD than in controls (2,566versus4,248 µm2).Except for the I to IIX shift in fibre types, the selective type-IIX atrophy and a slight accompanying increase in fibrosis and fat cell replacement in chronic obstructive pulmonary disease relative to age-matched controls, no other morphological abnormalities were observed in the muscle biopsies of chronic obstructive pulmonary disease patients. Also, in this group of clinically and weight stable chronic obstructive pulmonary disease patients, apoptosis appeared not to be involved in muscle pathology.
Assessment of nasal and sinus nitric oxide output using single-breath humming exhalations
Authors: Maniscalco M. , Weitzberg E. , Sundberg J. , Sofia M. , Lundberg J.O. 
Published: July 2003

Nasal nitric oxide (NO) levels increase greatly during humming compared to silent exhalation. In this study, the physiological and anatomical factors that regulate NO release during humming have been characterised in 10 healthy subjects and in a model of the sinus and the nose.Single-breath humming caused a large initial peak in nasal NO output, followed by a progressive decline. The NO peak decreased in a step-wise manner during repeated consecutive humming manoeuvres but recovered completely after a silent period of 3 min. Topical nasal application of an NO synthase inhibitor reduced nasal NO by >50% but had no effect on the increase evoked by humming. Silently exhaled nasal NO measured immediately after repeated humming manoeuvres was between 5–50% lower than basal silent NO exhalation, suggesting variable continuous contribution from the sinuses to nasal NO. Among the factors known to influence normal sinus ventilation, ostium size was the most critical during humming, but humming frequency was also of importance.In conclusion, humming results in a large increase in nasal nitric oxide, which is caused by a rapid gas exchange in the paranasal sinuses. Combined nasal nitric oxide measurement with and without humming could be of use to estimate sinus ventilation and to better separate nasal mucosal nitric oxide output from sinus nitric oxide in health and disease.
A cyclosporin A/maltosyl‐α‐cyclodextrin complex for inhalation therapy of asthma
Authors: Fukaya H. , Iimura A. , Hoshiko K. , Fuyumuro T. , Noji S. , Nabeshima T. 
Published: July 2003

The inhalation of cyclosporin (Cs)A to the lung is limited by its hydrophobic properties. In order to improve the poor solubility of CsA, cyclodextrin (CD) was evaluated for its suitability for dry powder inhaler formation, and the benefit of an inhaled CsA/CD complexin vivowas demonstrated.The solubilising effect of CDs on CsA was measured by high-performance liquid chromatography. Ciliostatic activity and haemolysis were determined to assess some safety profiles of CDs. The efficacy of an inhaled CsA/CD complex was evaluated by eosinophil infiltration into the bronchoalveolar lavage fluid in actively sensitised mice.CDs markedly improved the poor solubility of CsA. The ciliostatic and haemolytic activities of maltosyl‐α‐CD were the weakest of all the tested CDs. CsA inhaled alone showed inhibitory effects on allergen-induced eosinophilia. Inhalation of the complex of CsA with maltosyl‐α‐CD, where the dose of CsA was approximately nine-times less than that of CsA inhaled alone, also inhibited eosinophil accumulation significantly, with a longer duration of action in comparison with the response to CsA alone.Thus the effective dose of cyclosporin A could be reduced by formation of a complex with maltosyl‐α‐cyclodextrin, and a wider therapeutic safety margin by inhalation of cyclosporin A as a complex with maltosyl‐α‐cyclodextrin could be expected.
Interstitial lung disease in amyopathic dermatomyositis, dermatomyositis and polymyositis
Authors: Cottin V. , Thivolet-Béjui F. , Reynaud-Gaubert M. , Cadranel J. , Delaval P. , Ternamian P-J. , Cordier J-F. ,   and the Groupe d'Etudes et de Recherche sur les Maladies “Orphelines” Pulmonaires (GERM“O”P)
Published: July 2003

This study investigated interstitial pneumonia associated with amyopathic dermatomyositis, dermatomyositis and polymyositis, paying particular attention to muscular and/or cutaneous manifestations and their chronology relative to lung involvement. Patients included four males and 13 females, aged 51.7±10.8 yrs, who had surgical lung biopsy.Diagnoses included dermatomyositis (10 patients), polymyositis (four patients) and amyopathic dermatomyositis (three patients). Solitary respiratory manifestations preceded the onset of any skin or muscle disease in four cases (24%). Reticular and ground glass opacities were the most frequent computed tomography (CT) findings. Pathological review showed nonspecific interstitial pneumonia (eleven, 65%; cellular, two; cellular and fibrotic, five; fibrotic, four), usual interstitial pneumonia (two), organising pneumonia (two), lymphocytic interstitial pneumonia (one), and unclassifiable interstitial pneumonia (one). Nonspecific interstitial pneumonia was the most common histological pattern of interstitial pneumonia in patients with amyopathic dermatomyositis (three of three) and in patients with respiratory symptoms as the initial clinical manifestation of the connective tissue disease (three of four). Survival at 5 yrs was 50%.This study shows the clinician should remain alert to potential muscular or cutaneous manifestations whenever a pathological diagnosis of nonspecific interstitial pneumonia is made.
Humidified nasal continuous positive airway pressure in obstructive sleep apnoea
Authors: Neill A.M. , Wai H.S. , Bannan S.P.T. , Beasley C.R. , Weatherall M. , Campbell A.J. 
Published: July 2003

Heated humidification of nasal continuous positive airway pressure (nCPAP) reduces upper airway symptoms and improves initial use in obstructive sleep apnoea syndrome (OSAS). The present study aimed to assess the effect of heated humidification of nCPAP on upper airway symptoms and initial use in obstructive sleep apnoea.This study was of a randomised, crossover design. Subjects with polysomnographically confirmed OSAS were randomised to 3 weeks nCPAP treatment with heated humidification (nCPAP-humid) or placebo humidification (nCPAP pl-humid). Objective and subjective nCPAP use, upper airway symptoms, and treatment satisfaction were compared.Thirty seven of 42 patients completed the protocol. nCPAP-humid reduced the frequency of adverse upper airway symptoms. nCPAP use over 3 weeks was greater with nCPAP-humid compared with nCPAP pl-humid. No difference was found between the treatment arms in terms of subjective treatment satisfaction or alertness.Heated humidification of nasal continuous positive airway pressure reduces upper airway symptoms and is associated with a small increase in initial use but not subjective sleepiness or treatment satisfaction. The results support the use of heated humidification as a strategy to reduce side-effects related to continuous positive airway pressure but not routine initial use.
Inflammation in pulmonary arterial hypertension
Authors: Dorfmüller P. , Perros F. , Balabanian K. , Humbert M. 
Published: July 2003

Inflammatory mechanisms appear to play a significant role in some types of pulmonary hypertension (PH), including monocrotaline-induced PH in rats and pulmonary arterial hypertension of various origins in humans, such as connective tissue diseases (scleroderma, systemic lupus erythematosus, mixed connective disease), human immunodeficiency virus infection, or plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal (M) protein and skin changes (POEMS) syndrome.Interestingly, some patients with severe pulmonary arterial hypertension associated with systemic lupus erythematosus have experienced significant improvements with immunosuppressive therapy, emphasising the relevance of inflammation in a subset of patients presenting with PH. Patients with primary PH (PPH) also have some immunological disturbances, suggesting a possible role for inflammation in the pathophysiology of this disease. A subset of PPH patients have been shown to have circulating autoantibodies, including antinuclear antibodies, as well as elevated circulating levels of the pro-infammatory cytokines, interleukins ‐1 and ‐6. Lung histology has also revealed inflammatory infiltrates in the range of plexiform lesions in patients displaying severe PPH, as well as an increased expression of the chemokines regulated upon activation, normal T‐cell expressed and secreted (RANTES) and fractalkine.Further analysis of the role of inflammatory mechanisms is necessary to understand whether this component of the disease is relevant to its pathophysiology.
Pathogenesis of occupational asthma: Table 1
Authors: Sastre J. , Vandenplas O. , Park H-S. 
Published: July 2003

The development of occupational asthma (OA) is likely to result from the complex interaction of environmental and host factors. This article addresses a series of issues relating to the multiple environmental factors that could affect the initiation of OA, including the intrinsic characteristics of causative agents, as well as the influence of the level, mode and route of exposure.Although the clinical and pathological features of OA caused by low molecular weight agents resemble those of immunoglobulin (Ig)E-mediated asthma, the failure to detect specific IgE antibodies against most of these agents and/or poor association with disease status have resulted in intense speculation about alternative or complementary physiopathological mechanisms leading to airway sensitisation.In this contribution, the roles of specific immunoglobulin E and G antibodies, cell-mediated immunity and inflammatory effector cells are critically reviewed. Recent advances in the characterisation of the molecular interactions between chemical sensitisers and human airway proteins provide promising avenues for elucidating the immunological basis of occupational asthma caused by low molecular weight agents.
Gastro-oesophageal reflux in mechanically ventilated patients: effects of an oesophageal balloon
Authors: Orozco-Levi M. , Félez M. , Martínez-Miralles E. , Solsona J.F. , Blanco M.L. , Broquetas J.M. , Torres A. 
Published: July 2003

Gastro-oesophageal reflux (GOR) and bronchoaspiration of gastric content are risk factors linked with ventilator-associated pneumonia. This study was aimed at evaluating the effect of a nasogastric tube (NGT) incorporating a low-pressure oesophageal balloon on GOR and bronchoaspiration in patients receiving mechanical ventilation.Fourteen patients were studied in a semi-recumbent position for 2 consecutive days. Inflation or deflation of the oesophageal balloon was randomised. Samples of blood, gastric content, and oropharyngeal and bronchial secretions were taken every 2 h over a period of 8 h. A radioactively labelled nutritional solution was continuously administered through the NGT. The magnitude of both the GOR and bronchoaspiration was measured by radioactivity counting of oropharyngeal and bronchial secretion samples, respectively.Inflation of the oesophageal balloon resulted in a significant decrease of both GOR and bronchoaspiration of gastric content. This protective effect was statistically significant from 4 h following inflation throughout the duration of the study.This study demonstrates that an inflated oesophageal balloon delays and decreases gastro-oesophageal and bronchial aspiration of gastric content in patients carrying a nasogastric tube and receiving enteral nutrition during mechanical ventilation. Although the method was found to be safe when applied for 8 h, longer times should be considered with caution.
Mechanics and crossbridge kinetics of tracheal smooth muscle in two inbred rat strains
Authors: Blanc F-X. , Coirault C. , Salmeron S. , Chemla D. , Lecarpentier Y. 
Published: July 2003

The aim of the study was to determine whether the nonspecificin vivoairway hyperresponsiveness of the inbred Fisher F‐344 rat strain was associated with differences in the intrinsic contractile properties of tracheal smooth muscle (TSM) when compared with Lewis rats.Isotonic and isometric contractile properties of isolated TSM from Fisher and Lewis rats (each n=10) were investigated, and myosin crossbridge (CB) number, force and kinetics in both strains were calculated using Huxley's equations adapted to nonsarcomeric muscles. Maximum unloaded shortening velocity and maximum extent of muscle shortening were higher in Fisher than in Lewis rats (∼46% and ∼42%, respectively), whereas peak isometric tension was similar.The curvature of the hyperbolic force/velocity relationship did not differ between strains. Myosin CB number and unitary force were similar in both strains. The duration of CB detachment and attachment was shorter in Fisher than in Lewis rats (∼−46% and −34%, respectively).In Fisher rats, these results show that inherited, genetically determined factors of airway hyperresponsiveness are associated with changes in crossbridge kinetics, contributing to an increased tracheal smooth muscle shortening capacity and velocity.
Population impact of different definitions of airway obstruction
Authors: Celli B.R. , Halbert R.J. , Isonaka S. , Schau B. 
Published: July 2003

There is currently no consensus on the criteria for diagnosing chronic obstructive pulmonary disease. This study evaluated the impact of different definitions of airway obstruction on the estimated prevalence of obstruction in a population-based sample.Using the Third National Health and Nutrition Examination Survey, obstructive airway disease was defined using the following criteria: 1) self-reported diagnosis of chronic bronchitis or emphysema; 2) forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) <0.70 and FEV1<80% predicted (Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage IIA); 3) FEV1/FVC below the lower limit of normal; 4) FEV1/FVC <88% pred in males and <89% pred in females; 5) FEV1/FVC <0.70 (“fixed ratio”). Spirometry in this dataset did not include reversibility testing, making it impossible to distinguish reversible from irreversible obstruction.Rates in adults varied from 77 per 1,000 (self-report) to 168 per 1,000 (fixed ratio). For persons aged >50 yrs, the fixed ratio criteria produced the highest rate estimates. For all subgroups tested, the GOLD Stage II criteria produced lower estimates than other spirometry-based definitions.Different definitions of obstruction may produce prevalence estimates that vary by >200%. International opinion leaders should agree upon a clear definition of chronic obstructive pulmonary disease that can serve as a population-based measurement criterion as well as a guide to clinicians.
Variable tissue expression of transferrin receptors: relevance to acute respiratory distress syndrome
Authors: Upton R.L. , Chen Y. , Mumby S. , Gutteridge J.M.C. , Anning P.B. , Nicholson A.G. , Evans T.W. , Quinlan G.J. 
Published: July 2003

Acute respiratory distress syndrome (ARDS) is associated with altered plasma and lung iron chemistry. Iron can promote microbial virulence and catalyse pro-oxidant reactions, thereby contributing to the oxidative stress that characterises the syndrome.Therefore, the expression of ferritin and transferrin receptors (TfR) were sought in the lungs and hearts of rodents treated with lipopolysaccharide (LPS), and measurements of TfR and ferritin protein expression were taken from lung biopsy specimens from patients with ARDS and appropriate controls.TfR messenger ribonucleic acid (mRNA) was significantly upregulated in the lungs and significantly downregulated in the hearts of rats 4 h after LPS. Ferritin mRNA levels (light and heavy chains) remained unaltered. Protein TfR levels were significantly upregulated in lungs and downregulated in hearts 4 h post-LPS. Ferritin protein levels were significantly downregulated in lungs compared to baseline values but were unaltered in hearts. Nonhaem iron levels were increased in lungs and decreased in hearts, and iron-regulatory-protein activity increased in hearts but not lungs. TfR protein levels were significantly increased in lung biopsies from patients with ARDS compared to controls.Transferrin receptors are upregulated in rodent lungs during inflammation but are downregulated in the heart. Transferrin receptor protein levels were significantly increased in the lungs in clinical acute respiratory distress syndrome. These findings have implications for the pathogenesis of acute respiratory distress syndrome, especially in relation to the role of iron as a mediator of oxidative stress.
Assessment of variations in control of asthma over time
Authors: Combescure C. , Chanez P. , Saint-Pierre P. , Daurès J-P. , Proudhon H. , Godard P. 
Published: July 2003

Control and severity of asthma are two different but complementary concepts. The severity of asthma could influence the control over time. The aim of this study was to demonstrate this relationship.A total 365 patients with persistent asthma (severity) were enrolled and followed-up prospectively. Data were analysed using a continuous time homogeneous Markov model of the natural history of asthma. Control of asthma was defined according to three health states which were qualified: optimal, suboptimal and unacceptable control (states 1, 2 and 3). Transition forces (denoted λijfrom state i to state j) and transition probabilities between control states were assessed and the results stratified by asthma severity were compared.Models were validated by comparing expected and observed numbers of patients in the different states. Transition probabilities stabilised between 100–250 days and more rapidly in patients with mild-to-moderate asthma. Patients with mild-to-moderate asthma in suboptimal or unacceptable control had a high probability of transition directly to optimal control. Patients with severe asthma had a tendency to remain in unacceptable control.A Markov model is a useful tool to model the control of asthma over time. Severity modified clearly the health states. It could be used to compare the performance of different approaches to asthma management.
Role of the chemokines RANTES, monocyte chemotactic proteins‐3 and ‐4, and eotaxins‐1 and ‐2 in childhood asthma
Authors: Rojas-Ramos E. , Avalos A.F. , Pérez-Fernandez L. , Cuevas-Schacht F. , Valencia-Maqueda E. , Terán L.M. 
Published: July 2003

Eosinophil recruitment into the airways is a feature of asthma in children. However, the mechanisms by which these cells migrate into the airways are not fully understood. The present study investigated the presence of the eosinophil-activating chemokines regulated on activation, normal T‐cell expressed and secreted (RANTES), monocyte chemotactic proteins (MCP)‐3 and ‐4, and eotaxins‐1 and ‐2 in the bronchoalveolar lavage (BAL) fluid obtained from both asthmatic (n=10, age 6–10 yrs) and normal children (n=10, age 5–10 yrs).Measurements of chemokines in BAL fluid showed that levels of RANTES, MCPs‐3 and ‐4, and eotaxins‐1 and ‐2 were significantly increased in fluid obtained from asthmatic children when compared with normal children. Among the different chemokines, RANTES was the cytokine released in greatest quantities in BAL fluid from asthmatic children. There was a significant correlation between the concentrations of MCP‐4 and eosinophil numbers in BAL fluid and a trend between both chemokines MCP‐3 and eotaxin‐2 and eosinophils.Interestingly, the levels of most chemokines correlated with one another. These findings suggest that RANTES monocyte chemotactic proteins‐3 and ‐4, and eotaxins‐1 and ‐2 may regulate eosinophil trafficking into the airways of asthmatic children in a coordinated manner.