bluuebunny/crossref_metadata_2025_split huggingface dataset:
Substance P‐induced pulmonary vascular remodelling in precision cut lung slices
Authors: Springer J. , Fischer A. 
Published: September 2008

Substance P (SP) levels have been reported to be elevated in animal models of pulmonary hypertension (PH) and chronic administration of SP has been shown to induce PH. In the present study, the role of reactive oxygen species (ROS) as mediators of SP‐induced vascular remodelling and PH was analysed.Vascular remodelling was induced in precision cut lung slices by treatment with [Sar9,Met11(O2)]‐SP and by hypoxia. Functional analyses were used to study the chronic [Sar9,Met11(O2)]‐SP‐mediated effects on proliferation and generation of ROS, which is involved in the pathogenesis of PH. The nonpeptide NK‐1 receptor antagonist CP 96345 was used to block [Sar9,Met11(O2)]‐SP effects. ROS generation and proliferation was assayed by the dichloroflourescein­diacetate method and incorporation of 5‐Bromo‐2′‐Deoxyuridine, respectively.ROS generation was induced by either 1% oxygen (5.8‐fold) or [Sar9,Met11(O2)]‐SP (8‐fold) in normoxia in the alveolar region. [Sar9,Met11(O2)]‐SP did not further elevate ROS levels in hypoxia, suggesting an oxygen­dependent mechanism. High ROS levels stabilised hypoxia inducible factor‐1α and induced proliferation in small vessels (4.3‐fold in hypoxia and [Sar9,Met11(O2)]‐SP). Both ROS generation and proliferation were blocked in the presence of CP 96345, nitroblue­tetrazolium,N‐acetylcysteine‐ and diphenylene­iodonium.The results presented in this study indicate a role of SP in proliferative events associated with vascular remodelling in pulmonary hypertension.
Upregulated response to chemokines in oxidative metabolism of eosinophils in asthma and allergic rhinitis
Authors: Sannohe S. , Adachi T. , Hamada K. , Honda K. , Yamada Y. , Saito N. , Cui C‐H. , Kayaba H. , Ishikawa K. , Chihara J. 
Published: September 2008

Reactive oxygen species (ROS) from eosinophils are known to cause tissue damage in allergic inflammation. CC chemokines, especially eotaxin and regulated on activation, normal T‐cell expressed and secreted (RANTES), are involved not only in chemotaxis but also in eosinophil activation, such as ROS production. It has been shown that eosinophils from allergic patients are not functionally equivalent to those from normal subjects. In the present study, the characteristics of chemokine­primed ROS production in eosinophils from allergic patients and normal controls were compared.After pretreatment with chemokines, eosinophils were stimulated with calcium ionophore A23187. ROS production by eosinophils was measured using luminol­dependent chemiluminescence.Both RANTES and eotaxin exhibited a priming effect on calcium ionophore­induced ROS production from eosinophils. Despite there being no difference in expression of CC chemokine receptor 3, the priming effect of RANTES and eotaxin was significantly enhanced in eosinophils from the patients. Interleukin‐5 further enhanced the priming effect of chemokines in eosinophils from normal subjects, but not those from allergic subjects.The present results suggest an upregulated response to chemokines in eosinophils from allergic patients, and that interleukin‐5 can induce a similar phenotype to that foundin vivoin allergic patients.
Imbalance between vascular endothelial growth factor and endostatin in emphysema
Authors: Kanazawa H. , Hirata K. , Yoshikawa J. 
Published: September 2008

Vascular endothelial growth factor (VEGF) stimulates endothelial cell proliferation, and endostatin directly antagonises the biological effects of VEGF. The maintenance of pulmonary endothelial cells is also thought to depend upon the local balance of VEGF and endostatin in the lung. Therefore, this study was designed to determine whether there is an imbalance between VEGF and endostatin levels in patients with pulmonary emphysema.VEGF and endostatin levels were simultaneously measured from 25 emphysema patients and 12 normal control subjects, and their correlation and balance in induced sputum was evaluated.VEGF levels in induced sputum were significantly lower in emphysema patients (854±307 pg·mL−1) than in normal controls (1,791±1,192 pg·mL−1). In contrast, there was no significant difference in endostatin levels among the two groups. Therefore, the ratio of VEGF to endostatin levels was markedly lower in emphysema patients (4.5±1.8) than in normal controls (8.1±2.6). Moreover, VEGF levels were correlated with endostatin levels in normal controls but not in emphysema patients. In addition, the ratio of VEGF to endostatin levels was correlated with forced expiratory volume in one second (FEV1), FEV1/forced vital capacity and carbon monoxide diffusing capacity of the lung in emphysema patients.The findings in this study suggest that there is an imbalance between vascular endothelial growth factor and endostatin levels in induced sputum from emphysema patients.
Passive smoking and respiratory symptoms in the FinEsS Study
Authors: Larsson M.L. , Loit H-M. , Meren M. , Põlluste J. , Magnusson A. , Larsson K. , Lundbäck B. 
Published: September 2008

The aim of the present study was to examine the relationship between reported environmental tobacco smoke (ETS) exposure and respiratory symptoms.In 1996, a postal questionnaire was randomly distributed in three areas of Estonia to a population-based sample, of which 4,995 females and 1,822 males had never smoked. The main outcome measures were current respiratory symptoms and the amount of reported ETS exposure outside the home.ETS exposure at home was more common in females (31%versus19%), while exposure outside of the home was more common in males (53%versus7%). Females reported more symptoms from tobacco smoke than males (37.7%versus21.6%). If ETS exposure outside of the home exceeded 5 h daily, the risk for wheeze (odds ratio (OR) 2.67, 95% confidence interval (CI) 1.98–3.61) and physician-diagnosed asthma (OR 1.79, 1.02–3.16) were increased. ETS exposure outside of the home was shown to be strongly related to almost all respiratory symptoms in a dose/response manner. ETS exposure at home did not show significantly elevated ORs for any respiratory symptoms.This study shows that females seem to be more troubled by environmental smoke exposure than males and provides further evidence of the serious health hazards associated with environmental smoke exposure. Indeed, the findings of this study support a ban on smoking in the workplace and public areas.
A method to preserve sputum for delayed examination
Authors: Kelly M.M. , Hargreave F.E. , Cox G. 
Published: September 2008

Examination of sputum cell counts is limited by the need to process samples within hours of expectoration. The validity and repeatability of a method to preserve sputum for delayed processing and examination were investigated in this study.Portions of selected sputum from 39 subjects were dispersed with dithiothreitol (routine method), or were fixed in a dithiothreitol-formaldehyde mixture for 48–72 h before dispersal with trypsin (preservation method). Total and differential cell counts using the two methods were compared; within-method repeatability of the preservation method was also examined.The intraclass correlation coefficient (ICC) for total cell counts and percentage of eosinophils, neutrophils and macrophages in sputum processed by the two methods was 0.89, 0.86, 0.91 and 0.90, respectively. Within-method repeatability (ICC) of the preservation method for the same cellular indices was 0.99, 0.94, 0.97 and 0.97, respectively. The interobserver repeatability for eosinophils, neutrophils and macrophages was 0.96, 0.97 and 0.97 using the preservation method, and 0.96, 0.99 and 0.99 using the routine method, respectively.This method of sputum preservation and dispersal is valid, reliable and convenient, and may be used for delayed processing and examination.
Bronchoalveolar lavage alterations during prolonged ventilation of patients without acute lung injury
Authors: Tsangaris I. , Lekka M.E. , Kitsiouli E. , Constantopoulos S. , Nakos G. 
Published: September 2008

Mechanical ventilation deteriorates previously injured lung, but little is known about its effect on healthy human lung. This work was designed to assess the effect of prolonged mechanical ventilation on bronchoalveolar lavage (BAL) fluid composition of patients without acute lung injury.Twenty-two ventilated patients (tidal volume 8–10 mL·kg−1, positive end-expiratory pressure 3–5 cmH2O) without lung injury, who did not develop any complication from the respiratory system during the 2‐week study period, were studied. They were subjected to three consecutive BALs, the first during 36 h from intubation, the second at the end of the first week of mechanical ventilation and the third at the end of the second week of mechanical ventilation.Total BAL protein increased during mechanical ventilation (148±62, 381±288, 353±215 µg·mL−1BAL for the first, second and third BAL, respectively). In contrast, BAL phospholipids decreased (2.7±1.1, 1.4±0.6, 1.2±0.7 µg·mL−1BAL, respectively). Large surfactant aggregates were reduced and inflammatory markers, such as platelet activating factor (PAF), PAF-acetylhydrolase and neutrophils, significantly increased after 1 week, but partially remitted after 2 weeks of mechanical ventilation.In summary, this study demonstrates that prolonged mechanical ventilation even of patients without acute lung injury is associated with the presence of inflammatory markers and surfactant alterations.
Exhaled breath condensate pH is a robust and reproducible assay of airway acidity
Authors: Vaughan J. , Ngamtrakulpanit L. , Pajewski T.N. , Turner R. , Nguyen T-A. , Smith A. , Urban P. , Hom S. , Gaston B. , Hunt J. 
Published: September 2008

Exhaled breath condensate (EBC) pH is low in several lung diseases and it normalises with therapy.The current study examined factors relevant to EBC pH monitoring. Intraday and intraweek variability were studied in 76 subjects. The pH of EBC collected orally and from isolated lower airways was compared in an additional 32 subjects. Effects of ventilatory pattern (hyperventilation/hypoventilation), airway obstruction after methacholine, temperature (−44 to +13°C) and duration of collection (2–7 min), and duration of sample storage (up to 2 yrs) were examined. All samples were collected with a disposable condensing device, and de-aerated with argon until pH measurement stabilised.Mean EBC pH (n=76 subjects, total samples=741) was 7.7±0.49 (mean±sd). Mean intraweek and intraday coefficients of variation were 4.5% and 3.5%. Control of EBC pH appears to be at the level of the lower airway. Temperature of collection, duration of collection and storage, acute airway obstruction, subject age, saliva pH, and profound hyperventilation and hypoventilation had no effect on EBC pH.The current authors conclude that in health, exhaled breath condensate pH is slightly alkaline, held in a narrow range, and is controlled by lower airway source fluid. Measurement of exhaled breath condensate pH is a simple, robust, reproducible and relevant marker of disease.
Ageing does not influence the sleep-related decrease in the hypercapnic ventilatory response
Authors: Browne H.A.K. , Adams L. , Simonds A.K. , Morrell M.J. 
Published: September 2008

In young people, a sleep-related reduction in the gain of the ventilatory chemoreflex feedback loop occurs; in the elderly, it has been reported that no sleep-related reduction occurs. A relatively high loop gain could contribute to periodic breathing and central sleep apnoea in the elderly. This study tested the hypothesis that ageing is associated with a reduction in the magnitude of the sleep-related decrease in the hypercapnic ventilatory response (HCVR).The HCVR was measured using a steady state method, awake and asleep, in groups (n=10) of elderly (66–81 yrs) and young (23–35 yrs) nonapnoeics. Upper airway resistance was maintained close to wakefulness levels using continuous positive airway pressure (mean sleep-related increase in resistance: elderly 1.6±1.2 cmH2O·L·s−1, young 1.2±0.8 cmH2O·L·s−1).The sleep-related decrease in the HCVR was similar in the elderly and young groups (elderly: wake 0.14±0.06 and sleep 0.06±0.02 L·min−1·kPa and young, wake 0.19±0.07 and sleep 0.10±0.04 L·min−1·kPa).Ageingper sewas shown not to change the magnitude of the sleep-related decrease in hypercapnic ventilatory response. The authors speculate that age-related changes in the hypercapnic ventilatory response are unlikely to contribute to the increased prevalence of central sleep apnoea in the elderly.
Post-transplant bronchiolitis obliterans
Authors: Boehler A. , Estenne M. 
Published: September 2008

Over the last decade, improvements in surgical techniques, lung preservation, immunosuppression, and management of ischaemia/reperfusion injury and infections have made intermediate-term survival after lung transplantation an achievable goal. However, chronic allograft dysfunction in the form of bronchiolitis obliterans remains a major hurdle that threatens both the quality of life and long-term survival of the recipients. It affects up to 50–60% of patients who survive 5 yrs after surgery, and it accounts for >30% of all deaths occurring after the third postoperative year.This article discusses the alloimmune-dependent and -independent risk factors for bronchiolitis obliterans, the current understanding of the pathogenesis of bronchiolitis obliterans based on results of animal and human studies, the clinical staging of the complication, strategies that may contribute to the prevention and/or early detection of bronchiolitis obliterans, and suggestions for future research.
Blood pressure responsiveness to obstructive events during sleep after chronic CPAP
Authors: Marrone O. , Salvaggio A. , Bonsignore M.R. , Insalaco G. , Bonsignore G. 
Published: September 2008

The aim of this study was to investigate whether chronic continuous positive airway pressure (CPAP) affects blood pressure (BP) responsiveness to obstructive events occurring on the first night of CPAP withdrawal in obstructive sleep apnoea (OSA) after chronic treatment.Thirteen male subjects with severe OSA underwent nocturnal polysomnography with beat­by­beat BP monitoring before treatment and after 4.9±3.4 months of home CPAP (mean daily use 5.1±1.7 h). Variations in oxyhaemoglobin saturation (ΔSa,O2), systolic (ΔPs), and diastolic (ΔPd) BP within nonrapid eye movement apnoeas and hypopnoeas were measured on a sample of pre­ and post­treatment events. In addition, a pretreatment sample was selected for ΔSa,O2to match post­treatment events.The higher the mean ΔSa,O2was in the full pretreatment sample, the more ΔSa,O2, ΔPsand ΔPdwere attenuated after treatment. Mean ΔPsdecreased from 47.3±8.5 in the full pretreatment sample to 42.2±6.9 in the selected pretreatment sample, to 31.5±5.9 mmHg in the post­treatment sample. The post­treatment value differed significantly from both the pretreatment values. The corresponding values for mean ΔPdwere 27.0±3.5, 24.0±3.1 and 19.6±3.7 mmHg, with all values differing significantly from each other.Chronic continuous positive airway pressure is followed by a decrease in apnoea/hypopnoea­related blood pressure swings, possibly secondary to both reduced severity of event­related hypoxaemia and decreased responsiveness to obstructive events secondary to chronic prevention of nocturnal intermittent hypoxaemia.
Chronic obstructive pulmonary disease: molecular and cellularmechanisms
Authors: Barnes P.J. , Shapiro S.D. , Pauwels R.A. 
Published: September 2008

Chronic obstructive pulmonary disease is a leading cause of death and disability, but has only recently been extensively explored from a cellular and molecular perspective.There is a chronic inflammation that leads to fixed narrowing of small airways and alveolar wall destruction (emphysema). This is characterised by increased numbers of alveolar macrophages, neutrophils and cytotoxic T‐lymphocytes, and the release of multiple inflammatory mediators (lipids, chemokines, cytokines, growth factors). A high level of oxidative stress may amplify this inflammation. There is also increased elastolysis and evidence for involvement of several elastolytic enzymes, including serine proteases, cathepsins and matrix metalloproteinases.The inflammation and proteolysis in chronic obstructive pulmonary disease is an amplification of the normal inflammatory response to cigarette smoke. This inflammation, in marked contrast to asthma, appears to be resistant to corticosteroids, prompting a search for novel anti-inflammatory therapies that may prevent the relentless progression of the disease.
Agreement between written and video questions for comparing asthma symptoms in ISAAC
Authors: Crane J. , Mallol J. , Beasley R. , Stewart A. , Asher M.I. 
Published: September 2008

Phase One of the International Study of Asthma and Allergies in Childhood (ISAAC) has reported the prevalence of asthma, rhinitis and eczema symptoms in children. In 99 centres from 40 countries, a total of just under 317,000 13–14-yr-old children also completed a video questionnaire, showing the symptoms and signs of asthma. This first video sequence has been compared to the ISAAC written question asking about current wheezing to explore variations in agreement and the contribution of each questionnaire to wheezing prevalence between centres, by region and language groups.In general, responses to the video questionnaire gave a lower prevalence than the written questionnaire and responses were closely correlated. The overall proportion of agreement was high, mean 0.89, but unbalanced, with good negative agreement but poor positive agreement. Chance corrected agreement using Cohen's kappa coefficient, was generally low, with only 20 centres with kappa >0.4. The contribution of each questionnaire to wheezing prevalence also varied between centres and suggests that written questions about wheezing are variably understood and interpreted by 13–14 yr olds.International comparisons of wheezing and its audiovisual presentation suggest that adolescents interpret a written question about wheezing differently from its audiovisual presentation and that this interpretation shows variation between centres. This relationship and the interpretation of both written and audiovisual presentation of symptoms requires further study in order to better predict asthma.
Hospital-acquired pneumonia: coverage and treatment adequacy of current guidelines
Authors: Ioanas M. , Cavalcanti M. , Ferrer M. , Valencia M. , Agusti C. , Puig de la Bellacasa J. , Torres A. 
Published: September 2008

The American Thoracic Society (ATS) guideline for hospital-acquired pneumonia (HAP) released in 1996 and the Trouillet classification published in 1998 supply different rational foundations for the classification of patients with HAP and for the selection of initial antibiotic therapy. The aims of this study were to assess the level of bacterial coverage and to assess and validate the adequacy of antibiotic strategy of each of these classifications.Intensive care unit-admitted patients (n=71) with suspicion of HAP were evaluated. The ATS and Trouillet classifications demonstrated an accuracy to predict the causative microorganism of 91% and 83%, respectively. The ATS and Trouillet antibiotic treatment recommendations were adequate in 79% and 80% of the patients, respectively. The microorganisms implicated in the treatment inadequacy of the ATS guideline werePseudomonas aeruginosa(n=3),Acinetobacter baumanii(n=1),Stenotrophomonas maltophilia(n=1) and methicillin-resistantStaphylococcus aureus(n=1).P. aeruginosawas implicated with Trouillet treatment inadequacy.The current recommendations for empirical antibiotic treatment of hospital-acquired pneumonia (American Thoracic Society and Trouillet) showed a good ability to predict the involved pathogen. However, considering the resistance pattern of the isolated pathogens, both classifications demonstrated a rather lower treatment adequacy; the main reason was the failure to treat highly resistant strains.
Montelukast attenuates the airway response to hypertonic saline in moderate-to-severe COPD
Authors: Zühlke I.E. , Kanniess F. , Richter K. , Nielsen-Gode D. , Böhme S. , Jörres R.A. , Magnussen H. 
Published: September 2008

This study assessed the effect of the leukotriene receptor antagonist montelukast on hypertonic saline-induced airway obstruction.A total of 29 patients with chronic obstructive pulmonary disease (forced expiratory volume in one second (FEV1), 42±4% predicted) received either 10 mg montelukast and 3 h later placeboviametered-dose inhaler (MDI) (M), or placebo and 3h later 200 µg salbutamol (S), or two doses of placebo (P), in a randomised order. Patients inhaled salbutamol 1 h after MDI and the challenge was performed 15 min later (3% saline, 5 min). Data are given as per cent changesversusbaseline.Compared to P, S caused significant bronchodilation in FEV1(7.3%) and forced inspiratory volume in one second (FIV1) (4.5%), and M in FIV1(1.5%). The saline-induced fall in FEV1was lower after M (−5.8%), compared with S (−10.3%) and P (−13.1%). FEV1(11.3%) and FIV1(7.6%) was improved over baseline after recovery by M but not P and S. Recovery times regarding FEV1(8.5 min) and FIV1(15.2 min) were shortest after M, respective values for S being 16.8 and 20.4 min, and for P 15.9 and 21.2 min. Effects were strongest in patients with low baseline FEV1and/or inhaled corticosteroids.Data from this study indicate beneficial effects of montelukast on hypertonic saline-induced airway responses in patients with chronic obstructive pulmonary disease, particularly those with severe disease. The major effect was an accelerated recovery leading to values above baseline.
Interleukin‐13 and ‐4 expression in the central airways of smokers with chronic bronchitis
Authors: Miotto D. , Ruggieri M.P. , Boschetto P. , Cavallesco G. , Papi A. , Bononi I. , Piola C. , Murer B. , Fabbri L.M. , Mapp C.E. 
Published: September 2008

The aim of this study was to determine whether the T‐helper 2‐type cytokines interleukin (IL)‐13 and ‐4 are involved in mucus hypersecretion, the hallmark of chronic bronchitis (CB).Surgical specimens were examined from 33 subjects undergoing lung resection for localised peripheral malignant pulmonary lesions: 21 smokers with symptoms of CB, 10 asymptomatic smokers (AS) and two nonsmokers with normal lung function. The number of IL‐4 and ‐13 positive (+) cells in the central airways was quantified. To better assess the cytokine profile, a count was also made of IL‐5+ and interferon (IFN)‐γ+ cells.Compared to AS, the CB group had an increased number of IL‐13+ and ‐4+ cells in the bronchial submucosa, while the number of IL‐5+ and IFN‐γ+ cells were similar in all the groups. No significant associations were found between the number of cells expressing IL‐13 or ‐4 and the number of inflammatory cells. Double labelling showed that 13.2 and 12.9% of IL‐13+ cells were also CD8+ and CD4+, whereas 7.5 and 5% of IL‐4+ cells were CD8+ and CD4+, respectively.In conclusion, T‐helper‐2 and ‐1 protein expression is present in the central airways of smokers and interleukin‐4 and ‐13 could contribute to mucus hypersecretion in chronic bronchitis.