bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteoporosis in chronic obstructive pulmonary disease
Authors: Ionescu A.A. , Schoon E. 
Published: September 2008

Osteoporosis is one of the systemic effects associated with chronic obstructive pulmonary disease (COPD). Potential risk factors of osteoporosis may be due to the lifestyle, genetics, treatment with corticosteroids, endocrine abnormalities or the impairment of the body composition and peripheral skeletal muscles. Evidence for the possible contribution of such factors is reviewed.The occurrence of fractures, as a consequence of osteoporosis, can contribute to the disability and mortality of patients with COPD and add to the economic burden of the disease. The treatment with corticosteroids for the lung disease is associated with increased prevalence of fractures, but other factors may contribute.There is a remarkable paucity of interventional studies targeting the osteoporosis in patients with COPD. The results of studies on the treatment of osteoporosis in chronic lung diseases, some including small numbers of patients with COPD, are reviewed in the paper.Prospective longitudinal studies on the incidence of osteoporosis in chronic obstructive pulmonary disease need to assess patients with various degrees of disease severity and investigate the possible contribution of etiological factors. Randomised placebo-controlled trials are required to assess the effect of intervention, such as bisphosphonates, hormone replacement, calcium supplementation, on the prevention and treatment of osteoporosis and fractures in chronic obstructive pulmonary disease.
Endocrinological disturbances in chronic obstructive pulmonary disease
Authors: Creutzberg E.C. , Casaburi R. 
Published: September 2008

In this overview, the available literature on endocrinological disturbances in chronic obstructive pulmonary disease (COPD) is reviewed, with stress on growth hormone/insulin-like growth factor I (IGF‐I), thyroid hormone and the anabolic steroids.In COPD, little is known about circulating growth hormone or IGF‐I concentrations. Some authors find a decrease in growth hormone or IGF‐I, others an increase. An increase of growth hormone might reflect a nonspecific response of the body to stress (for instance, hypoxaemia). Until now, only one controlled study on growth hormone supplementation has been published, which however did not reveal any functional benefits. Before growth hormone supplementation can be advised as part of the treatment in COPD, further controlled studies must be performed to investigate its functional efficacy. The prevalence of thyroid dysfunction in COPD and its role in pulmonary cachexia has not been extensively studied. So far, there is no evidence that thyroid function is consistently altered in COPD, except perhaps in a subgroup of patients with severe hypoxaemia. Further research is required to more extensively study the underlying mechanisms and consequences of disturbed thyroid function in this subgroup of COPD patients.A few studies have reported the results of anabolic steroid supplementation in chronic obstructive pulmonary disease. Although some studies have discerned that low circulating levels of testosterone are common in males with chronic obstructive pulmonary disease, little is known about the prevalence, the underlying causes or functional consequences of hypogonadism in these patients. The use of systemic glucocorticosteroids and an influence of the systemic inflammatory response have been suggested as contributing to low testosterone levels. It can be hypothesised that low anabolic hormones will reduce muscle mass and eventually result in a diminished muscle function. Further evidence is required before testosterone replacement can be recommended for males with chronic obstructive pulmonary disease.
Nutritional and metabolic modulation in chronic obstructive pulmonary disease management
Authors: Schols A.M.W.J. 
Published: September 2008

In this paper the perspective for nutritional modulation of systemic impairment in patients with chronic obstructive pulmonary disease (COPD) is discussed. Progressive weight loss is characterised by disease-specific elevated energy requirements unbalanced by dietary intake. Weight gainper secan be achieved by caloric supplementation while future studies may prove efficacy of amino acid modulation to stimulate protein synthesis and enhance muscle anabolism.Disproportionate muscle wasting resembles the cachexia syndrome as described in other chronic wasting diseases (cancer, chronic heart failure, acquired immunodeficiency syndrome (AIDS)). There is yet no adequate nutritional strategy available to treat cachexia in COPD. Muscle substrate metabolism has hardly been investigated, but the few data available point towards a decreased fat oxidative capacity that may show similarities with the “metabolic syndrome” as described in type II diabetes and obesity and could theoretically benefit from polyunsaturated fatty acid modulation.To adequately target the different therapeutic options, clearly more clinical (intervention) studies are needed in chronic obstructive pulmonary disease patients that are adequately characterised by local and systemic impairment and in which molecular and metabolic markers are linked to functional outcome.
Indirect airway challenges
Authors: Joos G.F. , O'Connor B. 
Published: September 2008

Indirect challenges act by causing the release of endogenous mediators that cause the airway smooth muscle to contract. This is in contrast to the direct challenges where agonists such as methacholine or histamine cause airflow limitation predominantlyviaa direct effect on airway smooth muscle.Direct airway challenges have been used widely and are well standardised. They are highly sensitive, but not specific to asthma and can be used to exclude current asthma in a clinic population. Indirect bronchial stimuli, in particular exercise, hyperventilation, hypertonic aerosols, as well as adenosine, may reflect more directly the ongoing airway inflammation and are therefore more specific to identify active asthma. They are increasingly used to evaluate the prevalence of bronchial hyperresponsiveness and to assess specific problems in patients with known asthma,e.g.exercise-induced bronchoconstriction, evaluation before scuba diving.Direct bronchial responsiveness is only slowly and to a modest extent, influenced by repeated administration of inhaled steroids. Indirect challenges may reflect more closely acute changes in airway inflammation and a change in responsiveness to an indirect stimulus may be a clinically relevant marker to assess the clinical course of asthma. Moreover, some of the indirect challenges,e.g.hypertonic saline and mannitol, can be combined with the assessment of inflammatory cells by induction of sputum.
Unsupervised self-testing of airway obstruction by forced oscillation at the patient's home
Authors: Rigau J. , Burgos F. , Hernández C. , Roca J. , Navajas D. , Farré R. 
Published: September 2008

As active patient cooperation is not required, the forced oscillation technique (FOT) could be suitable for measuring airway obstruction in routine home applications. Nevertheless, FOT has never been used at the patient's home to date. The aim of this study was to assess the feasibility of FOT and the reproducibility of measured respiratory resistance (Rrs) in routine patient self-testing at home.Altogether, nine asthmatic patients self-measured theirRrswith a portable FOT device and spirometry for 10–14 days, in the morning and evening, and before and after bronchodilator inhalation. During each measurement session, the patients carried out four consecutive FOT measurements. Grubbs' discordancy test for detecting outliers was used to evaluate intermeasure reliability.Only 4.9% ofRrsdata reported by patients were rejected as artefacts. The coefficient of variation ofRrswas 7.9±6.3% (mean±sd). When compared with spirometry, the per cent change inRrsfor detecting a positive bronchodilator response showed an 83% sensitivity and 72% specificity.Unsupervised self-measurement of respiratory resistance at the patient's home provided results similar to those obtained by a technician in a lung function lab. Forced oscillation technique could be a useful tool for the routine follow-up of asthmatic patients at home.
Biomarkers of lipid peroxidation, airway inflammation and asthma
Authors: Wood L.G. , Gibson P.G. , Garg M.L. 
Published: September 2008

Oxidative stress, specifically lipid peroxidation, is believed to contribute to the pathophysiology of asthma. This review highlights the pathways through which reactive oxygen species (ROS) may lead to lipid peroxidation. The potential of both the innate and acquired immune systems to activate inflammatory cells and release ROS that may overwhelm the host antioxidant defences and cause lipid peroxidation, accompanied by detrimental pathophysiological effects, are discussed.Despite the evidence demonstrating the importance of lipid peroxidation, systematic characterisation of oxidative stress and antioxidant defences has not been undertaken, largely due to the lack of appropriate biomarkers. This review discusses the emergence of isoprostanes (specifically 8‐iso­prostaglandin F2α) as reliable,in vivomarkers of lipid peroxidation, which provides an appropriate tool for studying oxidative stress. Furthermore, the development of techniques to study induced sputum and breath condensate, derived directly from the airway surface, enables the site of oxidative damage to be closely assessed.Evidence suggests that dietary changes that have occurred over recent years have increased susceptibility to lipid peroxidation, due to reduced antioxidant defences. To date, the limited number of long­term (>1 week) supplementation trials have been promising. However, the development of techniques to study isoprostanes in airway­lining fluid pave the way for further studies investigating the potential for antioxidant supplements to be used as routine therapy in asthma.
OralN‐acetylcysteine reduces bleomycin-induced lung damage and mucin Muc5ac expression in rats
Authors: Mata M. , Ruíz A. , Cerdá M. , Martinez-Losa M. , Cortijo J. , Santangelo F. , Serrano-Mollar A. , Llombart-Bosch A. , Morcillo E.J. 
Published: September 2008

Oxidative stress is involved in the pathogenesis of pulmonary fibrosis, therefore antioxidants may be of therapeutic value. Clinical work indicates thatN‐acetylcysteine (NAC) may be beneficial in this disease. The activity of this antioxidant was examined on bleomycin-induced lung damage, mucus secretory cells hyperplasia and mucin Muc5ac gene expression in rats.NAC (3 mmol·kg−1·day−1) or saline was given orally to Sprague-Dawley rats for 1 week prior to a single intratracheal instillation of bleomycin (2.5 U·kg−1) and for 14 days postinstillation.NAC decreased collagen deposition in bleomycin-exposed rats (hydroxyproline content was 4,257±323 and 3,200±192 µg·lung−1in vehicle- and NAC‐treated rats, respectively) and lessened the fibrotic area assessed by morphometric analysis. The bleomycin-induced increases in lung tumour necrosis factor‐α and myeloperoxidase activity were reduced by NAC treatment. The numbers of mucus secretory cells in airway epithelium, and the Muc5ac messenger ribonucleic acid and protein expression, were markedly augmented in rats exposed to bleomycin. These changes were significantly reduced in NAC‐treated rats.These results indicate that bleomycin increases the number of airway secretory cells and their mucin production, and that oralN‐acetylcysteine improved pulmonary lesions and reduced the mucus hypersecretion in the bleomycin rat model.
Fatal primary pulmonary hypertension in a 30‐yr-old female with APECED syndrome
Authors: Korniszewski L. , Kurzyna M. , Stolarski B. , Torbicki A. , Smerdel A. , Ploski R. 
Published: September 2008

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by mutations in the autoimmune regulator (AIRE) gene, which has a central function in maintaining immunological tolerance. A number of conditions with proven or likely autoimmune pathogenesis occur in APECED: hypoparathyroidism, adrenocortical insufficency, candidiasis, hypogonadism, type 1 diabetes, hypothyroidism, hypophysitis, hepatitis, malabsorption, nail dystrophy, enamel hypoplasia and keratopathy. It is not clear which factors are responsible for variation in clinical picture of APECED, but human leukocyte antigen (HLA) genotype may be important.The authors report the first description of a case of primary pulmonary hypertension (PPH) in patient with APECED, caused by R257X mutation in AIRE. The HLA genotype of the patient (DRB1*01/DRB1*11, DQB1*0301/DQB1*0501) has been previously reported as a predisposing factor to PPH.The findings from this study, provided that other similar cases are reported, suggest that immune deregulation plays a role in the pathogenesis of primary pulmonary hypertension.
Increased inflammatory markers in the exhaled breath condensate of cigarette smokers
Authors: Carpagnano G.E. , Kharitonov S.A. , Foschino-Barbaro M.P. , Resta O. , Gramiccioni E. , Barnes P.J. 
Published: September 2008

Cigarette smoking induces an inflammatory response in the airways that may play a key role in the pathogenesis of chronic obstructive pulmonary disease. Noninvasive markers of inflammation may, therefore, be useful in monitoring the airways of smokers as well as in the screening of subjects at high risk of developing airway obstruction.The aim of the present study was to determine whether the concentrations of the pro-inflammatory cytokine, interleukin (IL)-6, is increased in the exhaled breath condensate of smokers and whether the number of cigarettes smoked has any influence on the exhaled concentrations. The possibility that exhaled IL-6 levels are related to exhaled carbon monoxide (CO) and lung function has also been explored. Another inflammatory marker, leukotriene (LT), was also measured.Twenty-one smokers (39±7 yrs, 13 male) and 14 nonsmokers (45±6 yrs, eight male) were recruited. IL-6 and LTB4levels in the breath condensate were measured with an immunoassay kit and exhaled CO examined by means of a modified electrochemical sensor. Higher IL-6 and exhaled CO concentrations were found in current smokers (5.6±1.4 pg·mL−1and 16.7±5.5 parts per million (ppm)) than in nonsmokers (2.6±0.2 pg·mL−1and 2.1±0.6 ppm). Elevated concentrations of LTB4were also observed in smokers compared to nonsmokers (9.4±0.4 pg·mL−1versus6.1±0.3 pg·mL−1). In addition, there was a correlation between IL-6 concentrations, the number of cigarettes smoked per day, exhaled CO, LTB4and lung function.Exhaled interleukin-6 and leukotriene B4levels may be useful noninvasive markers of airway inflammation in cigarette smokers.
N‐terminal pro-brain natriuretic peptide in patients with acute pulmonary embolism
Authors: Pruszczyk P. , Kostrubiec M. , Bochowicz A. , Styczyński G. , Szulc M. , Kurzyna M. , Fijałkowska A. , Kuch-Wocial A. , Chlewicka I. , Torbicki A. 
Published: September 2008

Plasma brain natriuretic peptide (BNP), released from myocytes of ventricles upon stretch, has been reported to differentiate pulmonary from cardiac dyspnoea. Limited data have shown elevated plasma BNP levels in acute pulmonary embolism (APE), frequently accompanied by dyspnoea and right ventricular (RV) dysfunction. The aim of this study was to assess plasma N‐terminal proBNP (NT‐proBNP) in APE, and to establish whether it reflects the severity of RV overload and if it can be used to predict adverse clinical outcome.On admission, NT‐proBNP and echocardiography for RV overload were performed in 79 APE patients (29 males), aged 63±16 yrs.Plasma NT‐proBNP was elevated in 66 patients (83.5%) and was higher in patients with (median 4,650 pg·mL−1(range 61–60,958)) than without RV strain (363 pg·mL−1(16–16,329)). RV‐to-left ventricular ratio and inferior vena cava dimension correlated with NT‐proBNP. All 15 in-hospital deaths and 24 serious adverse events occurred in the group with elevated NT‐proBNP, while all 13 (16.5%) patients with normal values had an uncomplicated clinical course. Plasma NT‐proBNP predicted in-hospital mortality.Plasma N‐terminal pro-brain natriuretic peptide is elevated in the majority of cases of pulmonary embolism resulting in right ventricular overload. Plasma levels reflect the degree of right ventricular overload and may help to predict short-term outcome. Acute pulmonary embolism should be considered in the differential diagnosis of patients with dyspnoea and abnormal levels of brain natriuretic peptide.
Lung accumulations of eosinophil granulocytes after exposure to cornstarch glove powder
Authors: Grunewald J. , Eklund A. , Katchar K. , Moshfegh A. , Lidén C. , Lundgren L. , Skare L. , Tornling G. 
Published: September 2008

Starch is a main component of wheat flour, which, besides being an occupational allergen can also induce irritative symptoms in the airways. A purified starch product (cornstarch glove powder) was used to investigate whether starch alone could induce airway inflammation. The aim of the study was to investigate a role for starch in wheat flour-induced airway inflammation.Ten healthy individuals were exposed to cornstarch glove powder in a whole-body exposure chamber. Bronchoscopy with bronchoalveolar lavage (BAL) was performed 2–3 weeks before and 1 day after exposure, and the BAL cells were counted differentially. In addition, the expression of activation, adhesion and subset markers on alveolar macrophages and BAL T-cells were investigated using flow cytometry.A three-fold increase in BAL cell concentrations was found, with a selective accumulation and activation of eosinophilic granulocytes, as well as an influx of nonactivated monocytes and polyclonal CD4+ T-cells into the airways.The results show that inhalation of cornstarch glove powder leads to the development of a subclinical inflammation in the airways, with an accumulation of eosinophilic granulocytes. The authors suggest that such exposure may be an interesting model for studying factors contributing to lung accumulations of eosinophil granulocytes in humans.
Cytokines and dietary energy restriction in stable chronic obstructive pulmonary disease patients
Authors: Godoy I. , Campana Á.O. , Geraldo R.R.C. , Padovani C.R. , Paiva S.A.R 
Published: September 2008

Tumour necrosis factor (TNF)‐α has been found to be increased in malnourished chronic obstructive pulmonary disease (COPD) patients; however, the main cause of this phenomenon remains undetermined. In normal subjects, TNF‐α production may be induced by dietary energy deprivation. The aim of this study was to investigate if stable COPD patients present alterations of inflammatory mediators after 48 h of dietary energy restriction.Fourteen COPD patients were admitted to the hospital while receiving an experimental diet with an energy content of approximately one-third of their energy needs. Clinical evaluation, nutritional assessment and serum levels of interleukin (IL)‐6, TNF‐α and C‐reactive protein, and secretion of TNF‐α by peripheral blood monocytes were assessed on admission and after the experimental diet. For reference values of the laboratory parameters, blood was collected from 10 healthy, elderly subjects.COPD patients showed significantly higher serum concentrations of IL‐6 than control subjects, however, the experimental diet was not associated with statistically significant changes in the inflammatory mediators.The findings of this study, although preliminary because of the limited degree and duration of the energy restriction, suggest that the elevated levels of tumour necrosis factor‐α, previously described in undernourished or weight-losing chronic obstructive pulmonary disease patients, may not be linked to a decrease of dietary energy intake.
Maintenance therapy with budesonide and formoterol in chronicobstructive pulmonary disease
Authors: Calverley P.M. , Boonsawat W. , Cseke Z. , Zhong N. , Peterson S. , Olsson H. 
Published: September 2008

Lung function in chronic obstructive pulmonary disease (COPD) can be improved acutely by oral corticosteroids and bronchodilators. Whether clinical improvement can be maintained by subsequent inhaled therapy is unknown.COPD patients (n=1,022, mean prebronchodilator forced expiratory volume in one second (FEV1) 36% predicted) initially received formoterol (9 µgb.i.d.) and oral prednisolone (30 mgo.d.) for 2 weeks. After this time, patients were randomised tob.i.d.inhaled budesonide/formoterol 320/9 µg, budesonide 400 µg, formoterol 9 µg or placebo for 12 months.Postmedication FEV1improved by 0.21 L and health-related quality of life using the St George's Respiratory Questionnaire (SGRQ) by 4.5 units after run-in. Fewer patients receiving budesonide/formoterol withdrew from the study than those receiving budesonide, formoterol or placebo. Budesonide/formoterol patients had a prolonged time to first exacerbation (254versus96 days) and maintained higher FEV1(99%versus87% of baseline), both primary variablesversusplacebo. They had fewer exacerbations (1.38versus1.80 exacerbations per patient per year), had higher prebronchodilator peak expiratory flow, and showed clinically relevant improvements in SGRQversusplacebo (−7.5 units). Budesonide/formoterol was more effective than either monocomponent in both primary variables.Budesonide/formoterol in a single inhaler (Symbicort®) maintains the benefit of treatment optimisation, stabilising lung function and delaying exacerbations more effectively than either component drug alone or placebo.
The early allergic response in small airways of human precision-cut lung slices
Authors: Wohlsen A. , Martin C. , Vollmer E. , Branscheid D. , Magnussen H. , Becker W-M. , Lepp U. , Uhlig S. 
Published: September 2008

To study the role of small airways in the early allergic response (EAR), the method of human precision-cut lung slices (PCLS) was developed and used to examine the bronchoconstriction elicited by passive sensitisation and allergen provocation.Viable human PCLS of 250-µm thickness containing airways <1.5 mm in outer diameter were prepared from lung lobes obtained from lung resection and taken into culture. According to the low release of lactate dehydrogenase and the constant ciliary beat frequency, human PCLS were viable for at least 3 days.Following overnight passive sensitisation with serum from allergic individuals, administration of grass-pollen extract or activating immunoglobulin E antibody resulted in immediate airway contraction that was quantified by videomicroscopy. The extent of the EAR increased with decreasing airway size (outer airway diameter), with the strongest response occurring in the terminal bronchioles.Histamine receptor antagonism was ineffective, and leukotriene or thromboxane receptor antagonism attenuated the early allergic response only in some cases. However, simultaneous blockade of leukotriene and thromboxane receptors almost completely prevented the early allergic response in the precision-cut lung slices from all individuals, suggesting such a dual treatment as a potential future asthma therapy.