bluuebunny/crossref_metadata_2025 huggingface dataset:
Review: Prevention of coronary heart disease in women
Authors: Rohit Seth Loomba  , Arora Rohit
Published: September 2008

Objective Coronary heart disease (CHD) mortality is higher in women than in men and misdiagnosis of CHD in women is one of the reasons for this, with differences in the presentation of CHD between men and women being a cause for the misdiagnosis. This review discusses the need for evidence-based guidelines to diagnose and treat CHD in women.

Methods Reviews, randomized controlled trials, and other studies pertinent to the topic were obtained using electronic search strategies, such as MEDLINE and Cochran Library, as well as manual selection. Sources selected were limited to those that discussed CHD, with specific emphasis placed on sources that focused on CHD in women. Selected studies were then assessed for quality of data and relevance via analysis of the study's methodology, results, and data. Results of selected studies were then stratified using a rating system devised to determine the quality of results using the scientific evidence provided for them. The references of the selected studies were then used to obtain and analyze additional studies in the same manner.

Results Control of lifestyle factors such as smoking, physical activity, diet, and weight are all necessary in women to control CHD, as is the maintenance of healthy lipid levels and blood pressure. Angiotensin-converting enzyme inhibitors and antiplatelets can help aid lifestyle changes in CHD management for women while hormone therapy and vitamin E have no proven benefits in CHD management.

Conclusions New gender- and evidence-based guidelines for the prevention of CHD in women need to be developed and adopted by physicians so that prevention, diagnosis, and treatment of CHD is made more effective.
Anti-inflammatory effects of an inflammatory chemokine: CCL2 inhibits lymphocyte homing by modulation of CCL21-triggered integrin-mediated adhesions
Authors: Flaishon Liat , Hart Gili , Zelman Einat , Moussion Christine , Grabovsky Valentin , Lapidot Tal Guy , Feigelson Sara , Margalit Raanan , Harmelin Alon , Avin-Wittenberg Tamar , Shoseyov David , Alon Ronen , Girard Jean-Philippe , Shachar Idit
Published: September 2008

Our studies focus on the pathways that restrict homing of specific subsets of immune cells, and thereby fine-tune the immune response at specific lymphoid and peripheral tissues. Here, we report that CCL2 (at picomolar [pM] levels) renders both murine and human T cells defective in their ability to develop CCR7-triggered activation of LFA-1– and LFA-1–mediated adhesion strengthening to endothelial ICAM-1 both in vitro and in vivo. CCL2 also attenuated lymphocyte chemotaxis toward lymph node chemokines. Consequently, low-dose CCL2 inhibited lymphocyte homing to peripheral lymph nodes but did not affect lymphocyte trafficking through the spleen. Impaired homing of lymphocytes to peripheral lymph nodes resulted in attenuated progression of both asthma and adjuvant arthritis. Thus, pM levels of circulating CCL2 can exert global suppressive effects on T-cell trafficking and differentiation within peripheral lymph nodes, and may be clinically beneficial as an anti-inflammatory agent.
Induction of CD4+ T-cell anergy and apoptosis by activated human B cells
Authors: Tretter Theresa , Venigalla Ram K. C. , Eckstein Volker , Saffrich Rainer , Sertel Serkan , Ho Anthony D. , Lorenz Hanns-Martin
Published: September 2008

B cells are well-known mediators of humoral immunity and serve as costimulators in the generation of T cell–mediated responses. In several mouse models, however, it was observed that B cells can also down-regulate immune reactions, suggesting a dual role for B cells. Due to this discrepancy and so far limited data, we directly tested the effects of primary human B cells on activated CD4+ T helper cells in vitro. We found that under optimal costimulation large, activated CD25+ B cells but not small CD25− B cells induced temporary T-cell anergy, determined by cell division arrest and down-regulation of cytokine production. In addition, large CD25+ B cells directly induced CD95-independent apoptosis in a subpopulation of activated T cells. Suppression required direct B-T-cell contact and was not transferable from T to T cell, excluding potential involvement of regulatory T cells. Moreover, inhibitory effects involved an IL-2–dependent mechanism, since decreasing concentrations of IL-2 led to a shift from inhibitory toward costimulatory effects triggered by B cells. We conclude that activated CD25+ B cells are able to costimulate or down-regulate T-cell responses, depending on activation status and environmental conditions that might also influence their pathophysiological impact.
SWAP-70 regulates RhoA/RhoB-dependent MHCII surface localization in dendritic cells
Authors: Ocana-Morgner Carlos , Wahren Christine , Jessberger Rolf
Published: September 2008

Stimulated dendritic cells (DCs) mature and migrate to lymphoid organs to prime naive T cells. DC maturation augments antigen-presentation capacity of DCs by increasing peptide loading, half-life, and cell surface localization of MHC molecules. Activated SWAP-70−/− DCs fail to properly localize MHCII molecules in the plasma membrane, are strongly impaired in T-cell activation, and are altered in F-actin rearrangement. MHCII synthesis, invariant chain removal, and MHCII internalization, however, are unaffected. MHCII surface localization is known to require RhoGTPases. Surprisingly, SWAP70, hitherto known to bind F-actin and Rac, also binds RhoA-GTP. In SWAP-70−/− DCs, RhoA and RhoB are stimulus-independent and constitutively active. Surface localization of MHCII molecules and T-cell activation can be restored by blocking RhoA and RhoB before but not during DC activation. Thus, contrasting positive regulation of Rac, SWAP-70 negatively regulates RhoA and—indirectly—RhoB, preventing premature RhoA/RhoB activation. Through RhoA/RhoB regulation, SWAP-70 defines a new pathway to control surface localization of MHCII, a critical element in DC-dependent immune responses.
Megakaryocyte-derived microparticles: direct visualization and distinction from platelet-derived microparticles
Authors: Flaumenhaft Robert , Dilks James R. , Richardson Jennifer , Alden Eva , Patel-Hett Sunita R. , Battinelli Elisabeth , Klement Giannoula L. , Sola-Visner Martha , Italiano Joseph E.
Published: September 2008

Platelet microparticles are a normal constituent of circulating blood. Several studies have demonstrated positive correlations between thrombotic states and platelet microparticle levels. Yet little is known about the processes by which platelet microparticles are generated in vivo. We now characterize microparticles derived directly from megakaryocytes. Video microscopy of live mouse megakaryocytes demonstrated that microparticles form as submicron beads along the lengths of slender, unbranched micropodia. These microparticles are CD41+, CD42b+, and express surface phosphatidylserine. Megakaryocyte microparticle generation is resistant to inhibition of microtubule assembly, which is critical to platelet formation, and augmented by inhibition of actin polymerization. To determine whether circulating microparticles are derived primarily from activated platelets or megakaryocytes, we identified markers that distinguish between these 2 populations. CD62P and LAMP-1 were found only on mouse microparticles from activated platelets. In contrast, full-length filamin A was found in megakaryocyte-derived microparticles, but not microparticles from activated platelets. Circulating microparticles isolated from mice were CD62P−, LAMP-1− and expressed full-length filamin A, indicating a megakaryocytic origin. Similarly, circulating microparticles isolated from healthy volunteers were CD62P− and expressed full-length filamin A. Cultured human megakaryocytes elaborated microparticles that were CD41+, CD42b+, and express surface phosphatidylserine. These results indicate that direct production by megakaryocytes represents a physiologic means to generate circulating platelet microparticles.
Flexible endoscopy of paediatric airways
Authors: Midulla F. , de Blic J. , Barbato A. , Bush A. , Eber E , Kotecha S , Haxby E , Moretti C , Pohunek P , Ratjen F
Published: September 2008

Paediatric fibreoptic bronchoscopy is used for ever wider indications, and increasingly used in many contexts, including paediatric and neonatal intensive care.

The report of this Task Force contains an overview on the current applications of paediatric bronchoscopy. The report discusses the facilities and equipment needed for the procedure, including the newly developed bronchoscopes which are allowing intervention even in very small children. The indications of both flexible and rigid bronchoscopes in the context of newer and smaller flexible endoscopic equipment are also considered. The care of the instruments, including disinfection and sterilisation, is fully documented. Patient management is described, including the relative merits of conscious sedation and general anaesthesia, as well as special settings for the procedure, including the needs in intensive care.

Special procedures, increasingly performed bronchoscopically are described. These include bronchoalveolar lavage, endobronchial and transbronchial biopsy, laser therapy, bronchography, and endoscopic intubation and drug therapy. Finally, neonatal bronchoscopy is discussed, and the ethics of bronchoscopic procedures, including bronchoscopic research in children.

Advances in instrumentation, and also improved anaesthetic techniques, allow fibreoptic bronchoscopy to be safely performed in even very small, sick infants, provided proper precautions are taken.
Repair mechanisms in embryos: wound healing and learning from how embryos repair perfectly
Authors: Martin P.
Published: September 2008

Embryos heal wounds very rapidly and efficiently without leaving a scar. Studying how they do this can tell a great deal about the natural morphogenetic movements of embryogenesis as well as suggesting ways in which adult tissues could repair more efficiently. Using live confocal imaging of transgenic Drosophila embryos expressing green fluorescent protein­labelled actin in epithelial tissues, the key actin machineries that drive the paradigm morphogenetic process of dorsal closure, which appear to bear striking analogy with re­epithelialisation of a vertebrate skin wound have been revealed. Using embryos expressing mutant forms of the various small guanadine triphosphatases, the function of each of these actin­based elements, the actin cable and dynamic filopodia and lamellipodia, were tested in both dorsal closure and the repair of laser­generated wound holes in the fly embryo. These experiments conducted in embryonic chicks and mice and in the neonatal PU.1 null mouse, which is genetically macrophageless, suggest that an inflammatory response is not essential for healing and may indeed be causal of fibrosis in postembryonic animals. Consequently, a microarray approach was used with this mouse in order to identify a portfolio of candidate inflammation/fibrosis genes. Finally, by taking advantage of the translucency of the zebrafish larval tail, the author's group has begun to make differential interference contrast movies of the inflammatory response and to dissect the genetics of this process by screening for mutants that fail to recruit leukocytes to the wound site and by morpholino knockdown of candidate “inflammation” genes. The hope is that these basic cell and molecular studies in genetically tractable organisms will supply the clues needed to design the new repair and regeneration medicines of the future.
Muscle wasting and changes in muscle protein metabolism in chronic obstructive pulmonary disease
Authors: Jagoe R.T. , Engelen M.P.K.J.
Published: September 2008

Loss of skeletal muscle mass is now recognised as an important feature of chronic obstructive pulmonary disease (COPD) which contributes to symptoms and influences prognosis. The changes in skeletal muscle remain poorly understood, largely because only a few studies have been performed to define the adaptations in whole body and muscle protein metabolism in COPD.

The first sections of this review summarise background information about skeletal muscle wasting in COPD, and focuses on the studies concerned with amino acid profiles and protein synthesis and degradation rates. To aid interpretation some discussion of the techniques commonly used is included.

A variety of different catabolic factors may determine whether chronic obstructive pulmonary disease patients become cachectic. The precise role for each one of these factors as well as the intracellular pathways activated in muscle as a result of chronic obstructive pulmonary disease are unknown and remain to be defined. Details of the actions of a range of different catabolic factors and potential mechanisms will be discussed.
Exhaled NO and plasma cGMP increase after endotoxin infusion in healthy volunteers
Authors: Soop A. , Sollevi A. , Weitzberg E. , Lundberg J.O.N. , Palm J. , Albert J.
Published: September 2008

Nitric oxide (NO) is believed to be involved in the pathophysiology of sepsis. This study evaluated the activity of the NO pathway in a human endotoxin model.

At baseline and after endotoxin, on-line measurements of exhaled NO (eNO) were made using a chemiluminescence technique with a single-breath method. NO-free air was inhaled prior to exhalation against a resistance. NO in orally and nasally exhaled air and in rectal gas was investigated. Plasma nitrite, nitrate, and guanosine 3′, 5′-monophosphate (cGMP) and the events after diclophenac administration were also studied.

Endotoxin infusion resulted in tachycardia and fever. An early increase in oral eNO concentration was observed and oral eNO decreased after diclophenac administration. NO exhaled nasally, NO in rectum gas and nitrite/nitrate levels remained unchanged over the study period. cGMP increased after 4 h.

These findings suggest an early increase in nitric oxide production from the lungs, probably due to increased activity of the constitutive nitric oxide synthase upon endotoxin stimulation. In contrast, nitric oxide production in the upper airways, measured as nasally exhaled nitric oxide and nitric oxide in rectal gas, remained unchanged. Further studies will elucidate if exhaled nitric oxide is a valuable marker of sepsis-induced lung injury and if monitoring of treatment is possible.
Microsatellite DNA instability and loss of heterozygosity in bronchial asthma
Authors: Paraskakis E. , Sourvinos G. , Passam F. , Tzanakis N. , Tzortzaki E.G. , Zervou M. , Spandidos D. , Siafakas N.M.
Published: September 2008

Genetic alterations, such as loss of heterozygosity (LOH) or microsatellite instability (MI), have been reported in both malignant and benign disorders. In order to identify loci of deoxyribonucleic acid (DNA) mutation in asthma, MI and LOH were studied in sputum cells.

DNA was extracted from cells in the sputum and blood cells of 22 patients with moderate asthma. Cells were analysed for MI and LOH using 18 polymorphic markers on chromosome 5q, 6p, 11q, 14q. Microsatellite analysis was also performed in six healthy subjects.

None of the healthy individuals exhibited any genetic alteration. Genetic alterations were found in 16 of 22 asthmatic patients (73%). In total, 12 (54.5%) patients exhibited LOH only, one (4.5%) MI only, while three showed both MI and LOH. The highest incidence of LOH and MI was found on chromosome 14q. Mean immunoglobulin E and blood eosinophil levels were significantly higher in asthmatics with three or more genetic alterations.

A high incidence of genetic alterations in the deoxyribonucleic acid of the sputum cells was found in asthmatic patients. Further studies are needed to identify the role of loss of heterozygosity and microsatellite instability in the investigation of genetic susceptibility of asthma and thus, in its pathogenesis.
Assessment of thoracoabdominal bands to detect respiratory effort-related arousal
Authors: Masa J.F. , Corral J. , Martín M.J. , Riesco J.A. , Sojo A. , Hernández M. , Douglas N.J.
Published: September 2008

It would be helpful to be able to identify respiratory effort-related arousal (RERA) without needing to measure oesophageal pressure. Thoracoabdominal movements yield an indirect flow measurement from which reduction of amplitude and alteration of the inspiratory flow curve can be detected. The aim of this study was to evaluate the accuracy of using the shape and amplitude of signals from thoracoabdominal bands (inductance plethysmography) to detect RERAs.

Altogether, 94 subjects suspected of having sleep apnoea but with an apnoea/hypopnoea index ≤10 in full polysomnography with oesophageal pressure were studied. A routine polysomnographical analysis was carried out. The polysomnographies were then reanalysed at random to determine which of the identified arousals were due to RERA, as determined either by oesophageal pressure or by induction bands without an oesophageal pressure signal. Altogether, 14,617 arousals were analysed.

The sensitivity and specificity to find RERA (arousal by arousal) from bandsversusoesophageal pressure were both 94%. The average difference of RERA index between oesophageal pressure and bands was −0.6. The correlation between RERA index determined by oesophageal pressure and bands was 0.98. To evaluate the intra and interobserver agreement, 1183 arousals were additionally analysed. The intraobserver agreement was 91% for RERAs by oesophageal pressure and 80% by bands. The interobserver agreement was 89% by oesophageal pressure and 85% by bands.

The thoracoabdominal bands can be used to identify respiratory effort-related arousal (obstructive events not detected by thermistor) with similar efficacy to oesophageal pressure measurement. Since bands are routinely used in most polysomnographies, they can be used as the usual method to detect respiratory effort-related arousal, using a thermistor to evaluate apnoeas and hypopnoeas or as a complement to other methods, such as nasal cannula, which can detect apnoeas, hypopnoeas and respiratory effort-related arousal.
Diagnostic tools in tuberculous pleurisy: a direct comparative study
Authors: Diacon A.H. , Van de Wal B.W. , Wyser C. , Smedema J.P. , Bezuidenhout J. , Bolliger C.T. , Walzl G.
Published: September 2008

Thoracoscopy is the most accurate yet most expensive tool for establishing the diagnosis of tuberculous (TB) pleurisy. However, most high TB‐incidence regions have limited financial resources, lack the infrastructure needed for routine thoracoscopy and require an alternative, cost­effective diagnostic approach for pleural effusions.

Altogether, 51 patients with undiagnosed exudative pleural effusions were recruited for a prospective, direct comparison between bronchial wash, pleural fluid microbiology and biochemistry (adenosine deaminase (ADA) and cell count), closed needle biopsy, and medical thoracoscopy.

The final diagnosis was TB in 42 patients (82%), malignancy in five (10%) and idiopathic in four patients (8%). Sensitivity of histology, culture and combined histology/culture was 66, 48 and 79%, respectively for closed needle biopsy and 100, 76 and 100%, respectively for thoracoscopy. Both were 100% specific. Pleural fluid ADA of ≥50 U·L−1was 95% sensitive and 89% specific. Combined ADA, lymphocyte/neutrophil ratio ≥0.75 plus closed needle biopsy reached 93% sensitivity and 100% specificity.

A combination of pleural fluid adenosine deaminase, differential cell count and closed needle biopsy has a high diagnostic accuracy in undiagnosed exudative pleural effusions in areas with high incidences of tuberculosis and might substitute medical thoracoscopy at considerably lower expense in resource­poor countries.
Risk factors for recent transmission ofMycobacterium tuberculosis
Authors: Heldal E. , Dahle U.R. , Sandven P. , Caugant D.A. , Brattaas N. , Waaler H.T. , Enarson D.A. , Tverdal A. , Kongerud J.
Published: September 2008

In recent decades, the decline of tuberculosis has stopped in Western Europe, mainly due to increased immigration from high-prevalence countries. The objective of the current study was to identify risk factors for developing tuberculosis following recent infection, in order to better target interventions.

Strains from 861 culture-positive cases, diagnosed in Norway in 1994–1999, were analysed by use of restriction fragment length polymorphism (RFLP). A cluster was defined as two or more isolates with identical RFLP patterns. Risk factors for being part of a cluster were identified by univariate and multivariate analysis.

A total of 134 patients were part of a cluster. These constituted 5% Asian-born, 18% Norwegian-born, 24% European-born and 29% African-born patients. Four independent risk factors for being part of a cluster were identified: being born in Norway, being of young age, being infected with an isoniazid-resistant strain and being infected with a multidrug-resistant strain.

Transmission of tuberculosis may be further reduced by improving case management, contact tracing, preventive treatment, screening of immigrants and access to health services for the foreign-born population.
Exhaled nitric oxide after lung transplantation: impact of the native lung
Authors: Verleden G.M. , Dupont L.J. , Delcroix M. , Van Raemdonck D. , Vanhaecke J. , Lerut T. , Demedts M.
Published: September 2008

It has already been demonstrated that exhaled nitric oxide (eNO) is increased in lung transplant patients with chronic rejection, although it is not known whether the diseased native lung after single lung transplantation (SLTx) contributes to the increased eNO values. This study aimed to compare the eNO values in stable lung transplant patients (SLTxversussequential (S)SLTx and heart (H)LTx) and in patients with established chronic rejection.

Altogether, 42 LTx patients (25 females, 13 SLTx, 18 SSLTx, 11 HLTx), with a mean follow­up of 1149 days and a mean age of 44.6 yrs at transplantation, were included. Twenty­six patients had no signs of chronic rejection (five SLTx and 21 SSLTx/HLTx). There was no difference in their eNO values (10.2 in SLTxversus12.2 (parts per billion) ppb in SSLTx/HLTx). Sixteen patients (eight SLTx and eight SSLTx/HLTx) had a chronic rejection (eight bronchiolitis obliterans syndrome (BOS) potential stage, four BOS stage 1, three BOS stage 2 and one BOS stage 3). Their eNOs were 18.1 (SLTx) and 17.0 (SSLTx/HLTx) ppb, respectively, which were significantly different to the stable LTx patients and showed a trend towards significance for SSLTx/HLTx. There was no significant difference in eNO between the patients with chronic rejection who underwent SLTx and those who underwent SSLTx/HLTx.

The diseased native lung after single lung transplantation probably does not contribute much to the exhaled nitric oxide values, either in stable lung transplant patients or in lung transplant patients with chronic rejection.
Unaltered respiratory-related evoked potentials after acute diaphragm dysfunction in humans
Authors: Bezzi M. , Donzel-Raynaud C. , Straus C. , Tantucci C. , Zelter M. , Derenne J-P. , Similowski T.
Published: September 2008

Respiratory muscles play an important role in the origin of respiratory sensations. Data dissecting the role of the diaphragm and other inspiratory muscles are scarce. This study aimed to determine the impact of diaphragm dysfunction following inspiratory resistive loading on respiratory-related evoked potentials considered as a neurophysiological substrate of certain types of respiratory sensations.

Altogether, nine subjects aged 25–50 yrs (six females) participated in the study. Transdiaphragmatic pressure output of cervical magnetic stimulation (with subdivision in oesophageal and gastric component), and respiratory-related evoked potentials (C3 and C4 derivations in the international 10–20 system) following mid-inspiratory occlusions were studied before and after an inspiratory-resistive loading challenge.

Predominant diaphragm dysfunction was observed in seven subjects (average 28% reduction in transdiaphragmatic pressure, from 27.25–19.91 cmH20, with increased oesophageal-to-gastric pressure ratio). The latencies and amplitudes of all the components of the respiratory-related evoked potentials were unchanged.

The study concluded that predominant diaphragm fatigue does not affect respiratory-related evoked potentials.
Duration of length of stay in pneumonia: influence of clinical factors and hospital type
Authors: Menéndez R. , Cremades M.J. , Martínez-Moragón E. , Soler J.J. , Reyes S. , Perpiñá M.
Published: September 2008

Length of stay (LOS) in hospital for community-acquired pneumonia depends on the characteristics of the patient and hospital. The present study sought to identify these variables within the first 24 h of hospitalisation.

Patients hospitalised for pneumonia in four hospitals (one teaching and three general hospitals) had their data analysed by univariate and multivariate statististics. The variables entered were LOS, demographical characteristics, referral source, comorbidity, initial severity of illness, laboratory analyses, initial radiograph findings and antibiotic treatment regimens.

The study sample included 425 patients. The overall mortality was 8.2% and the median LOS was 9 days. Using LOS as a dependent variable, three multivariate linear regression analyses were performed with: 1) the whole cohort; 2) the low-risk classes (categories I and II of Fine); and 3) the high-risk classes (categories III, IV and V of Fine). The mathematical model identified hypoxemia, low diastolic pressure, pleural effusion, multi-lobe involvement and hypoalbuminaemia as associated with longer stays in risk classes III–V, while in the low-risk patients (I–II) only hypoxemia and pleural effusion appeared in the equation. Following adjustment for these clinical variables, the LOS remained lower in some hospitals.

Several independent clinical factors increased the pneumonia-associated length of stay with significant differences between hospitals. Hypoxemia and pleural effusions were the predictive variables of length of stay in low-risk patients and, additionally, diastolic blood pressure, multi-lobe involvement and hypoalbuminaemia were significant in the higher-risk classes III–V.
Short­burst oxygen immediately before and after exercise is ineffective in nonhypoxic COPD patients
Authors: Lewis C.A. , Eaton T.E. , Young P. , Kolbe J.
Published: September 2008

Short­burst oxygen therapy (SBOT) remains an unproven treatment for reduction of exertional dyspnoea in chronic obstructive pulmonary disease (COPD). This study aimed to assess whether SBOT before exercise reduces dyspnoea or improves performance, and whether SBOT after exercise reduces dyspnoea during recovery.

Twenty­two clinically stable COPD patients (mean forced expiratory volume in one second 34% predicted, mean resting saturation 94%) attended a respiratory gymnasium and undertook four 6‐min walk (6MW) tests at each of two sessions, 1 week apart. Cylinder air or oxygen was administered single­blind in random order for 5 min prior to the first two 6MW and during recovery following the final two 6MW. Dyspnoea was self­rated by subjects using the modified Borg scale.

There was no significant difference in mean 6MW distance or final Borg score for air and oxygen given before exercise. There was also no significant difference in mean time­to­resting Borg score for air and oxygen given after exercise. Only two subjects demonstrated a clinically significant and consistent reduction in dyspnoea for oxygen compared with air either before or after exercise.

Overall, short­burst oxygen therapy neither reduced dyspnoea nor improved performance. This study does not support the use of short­burst oxygen therapy either immediately before or after exercise.
Face mask spirometry and respiratory pressures in normal subjects
Authors: Wohlgemuth M. , van der Kooi E.L. , Hendriks J.C. , Padberg G.W. , Folgering H.T.
Published: September 2008

Spirometry and maximal respiratory pressures are pulmonary function parameters commonly used to evaluate respiratory function. Prediction values are available for conventional lung function devices using a standard tube or flanged type of mouthpiece connection. This equipment is not suitable for patients with facial or buccal muscle weakness, because of air leakage around the mouthpiece. A face mask was used for the portable lung function devices used in the neuromuscular department.

The aim of this study was to compare the face mask and the conventional mouthpiece for the measurement of spirometry and of respiratory pressures in 22 healthy subjects.

Values obtained with the conventional mouthpiece differed significantly from values obtained with the face mask. With the mask, forced vital capacity and forced expiratory volume in one second were 200 mL lower, and maximal expiratory pressure was 3.2 kPa lower than with the mouthpiece. Subsequently, new prediction values for face mask spirometry and maximal respiratory pressures were obtained from 252 other healthy subjects, from which new prediction equations were derived.

It was concluded that the face mask connection to the lung function device is a valid alternative, is easy to use and is most useful to monitor changes in patients. This study confirms the importance of appropriate prediction equations, depending on subject-instrument interfaces.
Long-term mortality among adults with or without asthma in the PAARC study
Authors: Vandentorren S. , Baldi I. , Annesi Maesano I. , Charpin D. , Neukirch F. , Filleul L. , Cantagrel A. , Tessier J.F.
Published: September 2008

The Pollution Atmosphérique et Affections Respiratoires Chroniques (PAARC; Air Pollution and Chronic Respiratory Diseases) study provided the opportunity to examine the 25-yr mortality of 940 asthmatic adults drawn from a large population-based sample of 14,267 adults investigated during 1974–1976 in seven French cities.

Vital statistics were collected in 2001 for the whole population. Multivariate survival analysis was used to assess exact survival rates in asthmatics and nonasthmatics taking relevant confounders into account.

On average, the mortality rates obtained were 10.4 and 6.9 deaths·1,000 person-yrs−1in asthmatics and nonasthmatics, respectively. On univariate analysis, asthma increased the relative risk (RR) of death by 1.48 (95% confidence interval (CI) 1.29–1.69). The association between asthma and death had an RR of 1.16 (95% CI 0.99–1.37) when age, sex, educational level, smoking habits, occupational exposure and forced expiratory volume in one second (FEV1) were taken into account. FEV1was an important contributive factor causing increased risk of death in both smokers and nonsmokers. For instance, in asthmatics, the numbers of deaths due to respiratory disease and cancer appeared excessive.

The present study suggests that asthmatics exhibit a higher risk of mortality.
Fluticasone reduces IL-6 and IL-8 production of cystic fibrosis bronchial epithelial cellsviaIKK-β kinase pathway
Authors: Escotte S. , Tabary O. , Dusser D. , Majer-Teboul C. , Puchelle E. , Jacquot J.
Published: September 2008

Inhaled fluticasone propionate (FP) is widely used to reduce pulmonary inflammation in chronic obstructive pulmonary disease, but the potential effects of FP on airway epithelial cells from patients with cystic fibrosis (CF) are unknown. In CF disease, a nonregulated inflammatory lung response occurs through exaggerated nuclear factor (NF)-κB activation and elevated pro-inflammatory cytokines production by airway epithelial cells.

To determine whether FP reduces cytokine production in bronchial epithelial cellsviaNF-κB, the authors investigated the nonstimulated and thePseudomonas aeruginosalipopolysaccharide (LPS) stimulated production of NF-κB-dependent interleukin (IL)-6, IL-8 and RANTES (regulated on activation, T-cell expressed and secreted) along with the activation of NF-κB in non-CF and CF human bronchial gland epithelial cells.

It was demonstrated that a relevant concentration of FP (10−8 M) inhibited constitutive andP. aeruginosaLPS-induced IL-6 and IL-8 production of non-CF and CF bronchial epithelial cells. Interestingly, the expression of two IκB kinases (IKK)-α/β, the degradation of cytosolic IκB-β inhibitor and the NF-κB deoxyribonucleic acid binding activity were markedly reduced after FP treatment in both CF and non-CF bronchial epithelial cells.

It was shown by the authors that fluticasone propionate exerts an anti-inflammatory effect by blocking a signal transduction leading to a reduced level of IκB-α/β kinases in bronchial epithelial cells. In particular the strong effect on the IκB-β kinase, which is known to be elevated in bronchial epithelial cells in cystic fibrosis patients, was observed.
Early pulmonary response to allergen is attenuated during acute emotional stress in females with asthma
Authors: Laube B.L. , Curbow B.A. , Fitzgerald S.T. , Spratt K.
Published: September 2008

Some asthma patients and physicians who treat asthma have reported that stress worsens their disease. It has also recently been shown that chronic stressful life events increase airway inflammation 6–24 h after inhalation of antigen in patients with allergic asthma. However, there is no data regarding the effect of an acute stressor on the airway constriction that occurs within minutes of antigen inhalation (early pulmonary response) in this same population. The aim of this study was to examine this effect in eight females with allergic asthma.

Each subject was challenged with increasing concentrations of inhaled allergen on a control visit (no stress) and on a stress visit, when they were asked to verbally recount an emotionally stressful situation between each concentration. Systolic (SP) and diastolic (DP) blood pressure, cardiac frequency (fc) and forced expiratory volume in one second (FEV1) were measured on both visits.

SP, DP andfcwere statistically increased on the stress visit as compared to control. Per cent decrease in FEV1at the same last dose of allergen was significantly less on the stress visit (11.2±7.0%) compared to control (15.0±8.7%).

These findings suggest that the early pulmonary response to inhaled allergen is attenuated while verbally re­experiencing an acute emotional stressor in females with allergic asthma.
Wheeze monitoring in children for assessment of nocturnal asthma and response to therapy
Authors: Bentur L. , Beck R. , Shinawi M. , Naveh T. , Gavriely N.
Published: September 2008

The utilisation of nocturnal wheeze monitoring and quantification for assessment of asthma activity was studied in symptomatic school-aged children before and during treatment.

Twelve children 6–14 yrs of age with mild or moderate untreated asthma were studied at home three times: before, 48 h and 6 weeks into treatment with 5 mg montelukast daily. Lung sounds were recorded overnight by an automatic wheeze detection device (PulmoTrack®). Per cent wheezing within each respiratory cycle was calculated every 30 s throughout the night and a Nocturnal Wheeze Index (NWI) was calculated for the total night. The results were compared with spirometric indices (forced expiratory volume in one second (FEV1), forced vital capacity), bronchial reactivity (provocative concentration causing a 20% fall in FEV1by adenosine 5′-monophosphate (PC20)) and daily symptom scores, performed in parallel at each stage of the study.

The pretreatment NWI was 814±898 (mean±sd), which declined to 318±199 2 days after onset, and to 137±101 after 6 weeks of treatment. The NWI in seven healthy children was 47±43. The FEV1, PC20and symptom scores improved in parallel.

Wheeze monitoring provides quantitative and noninvasive information about the extent of nocturnal wheezing in children, correlates well with conventional indices of asthma activity and can assist in assessing efficacy of treatment.
Can early infection explain the sibling effect in adult atopy?
Authors: Cullinan P. , Harris J.M. , Newman Taylor A.J. , Jones M. , Taylor P. , Dave J.R. , Mills P. , Moffat S.A. , White C.W. , Figg J.K. , Moon A.M. , Barnes M.C.
Published: September 2008

Atopy is strongly and inversely related to family size, a pattern which is plausibly assumed to reflect a protective effect of early infection. The current study tested this hypothesis by case-referent analysis of an adult cohort in the UK.

The study established that atopy, defined by prick tests to common aeroallergens, was less common among those from larger families after adjustment for potentially confounding factors. In particular, a higher number of brothers appeared to offer protection. The current authors attempted to explain this distribution by examining contemporary family-doctor records of early childhood infections; and by a number of other indirect indices of early-life “hygiene”.

The sibling effect was unexplained by evidence of infection with either hepatitis A orHelicobacter pylori, or by counts of infections or antibiotic prescriptions in early life. There was a significant and independent negative association between the number of gastrointestinal infections before the age of 5 yrs and the odds of atopy. Dog ownership and home moving in early life also displayed potentially protective associations.

Although the current study replicates the finding that atopy is inversely associated with family size this could not be explained by documentary or serological evidence of early infection. The findings support the suggestion that the “sibling effect” in atopy may not simply reflect protection by early infection.
OralN‐acetylcysteine attenuates the rat pulmonary inflammatory response to antigen
Authors: Blesa S. , Cortijo J. , Mata M. , Serrano A. , Closa D. , Santangelo F. , Estrela J.M. , Suchankova J. , Morcillo E.J.
Published: September 2008

Oxidative stress is involved in the pathophysiology of inflammatory airway diseases including asthma; therefore, antioxidants might be of clinical benefit in asthma treatment. In the present study, the effects ofN‐acetylcysteine on sensitised brown Norway rats were examined.

N‐Acetylcysteine (3 mmol·kg body weight−1administered orally) was given daily for 1 week before challenge and various antigen-induced pulmonary responses were studied.

Antigen exposure increased lipid peroxidation in bronchoalveolar lavage fluid (BALF) and oxidised glutathione levels in lung tissue 2 h after challenge. Lung nuclear transcription factor‐κB‐binding activity was increased 2 h after challenge, and BALF tumour necrosis factor‐α and inducible nitric oxide synthase expression in lungs peaked 4 h after challenge. Expression of intercellular adhesion molecule‐1 and mucin MUC5AC was also increased 4 h after challenge. These changes in oxidant status, transcription factor activation, and inflammatory cytokine and gene expression were reduced byN‐acetylcysteine. This thiol did not affect the immediate bronchospasm reaction to antigen in anaesthetised rats but inhibited airways hyperresponsiveness to 5‐hydroxytryptamine and the augmented eosinophil numbers in BALF, which appear 24 h after exposure of conscious rats to antigen aerosol, and abolished antigen-induced extravasation of Evans blue into BALF.

These results indicate that oralN‐acetylcysteine exerts an antioxidant protective effect and attenuates pulmonary inflammation in experimental asthma.
Lower risk of atopic disorders in whole cell pertussis-vaccinated children: Table 1
Authors: Bernsen R.M.D. , de Jongste J.C. , van der Wouden J.C.
Published: September 2008

This study addressed whether whole cell pertussis-vaccinated children have a different risk of atopic disorders compared with children who did not receive this vaccination.

Data on vaccination status, atopic disorders and child and family characteristics of the children of 700 families were collected in this retrospective study. A minority of these 700 families refused vaccinations for religious reasons. The relation between pertussis-vaccination status and atopic disorders was analysed by means of adjusted logistic regression for repeated measurements in order to account for the correlation between sibship members.

The 700 families included 1,961 children. Data on vaccination status and atopic disorders were available for 1,724 children. Vaccinated children had a reduced risk of atopic disorders.

Whole cell pertussis vaccination is associated with a lower risk of atopic disorders, though other vaccine components (diphtheria, tetanus, poliomyelitis) or other vaccinations may also be involved.
Exosomes with major histocompatibility complex class II and co-stimulatory molecules are present in human BAL fluid
Authors: Admyre C. , Grunewald J. , Thyberg J. , Gripenbäck S. , Tornling G. , Eklund A. , Scheynius A. , Gabrielsson S.
Published: September 2008

Exosomes are 30–100 nm diameter vesicles formed by inward budding of endosomal compartments and are produced by several cell types, including T‐cells, B‐cells and dendritic cells (DC)s. Exosomes from DCs express major histocompatibility complexes (MHC) class I and II, and co-stimulatory molecules on their surface, and can induce antigen-specific activation of T‐cells.

The aims of the present study were to investigate for the presence of exosomes in bronchoalveolar lavage fluid (BALF) from healthy individuals, and to establish if these exosomes bear MHC and co-stimulatory molecules.

The authors analysed BALF taken from seven healthy volunteers and used exosomes from monocyte-derived DC (MDDC) cultures as a reference. After ultracentrifugation, exosomes were bound to anti‐MHC class II coated magnetic beads and analysed by flow cytometry and electron microscopy.

The authors report for the first time that exosomes are present in BALF. These exosomes are similar to MDDC derived exosomes as they express MHC class I and II, CD54, CD63 and the co-stimulatory molecule CD86.

The results demonstrate that exosomes are present in the lung, and since they contain both major histocompatibility complex and co-stimulatory molecules it is likely that they are derived from antigen presenting cells and might have a regulatory role in local immune defence.
The pattern and timing of breathing during incremental exercise: a normative study
Authors: Neder J.A. , Dal Corso S. , Malaguti C. , Reis S. , De Fuccio M.B. , Schmidt H. , Fuld J.P. , Nery L.E.
Published: September 2008

Clinical evaluation of the pattern and timing of breathing during submaximal exercise can be valuable for the identification of the mechanical ventilatory consequences of different disease processes and for assessing the efficacy of certain interventions.

Sedentary individuals (60 male/60 female, aged 20–80 yrs) were randomly selected from >8,000 subjects and submitted to ramp incremental cycle ergometry. Tidal volume (VT)/ resting inspiratory capacity, respiratory frequency, total respiratory time (Ttot), inspiratory time (TI), expiratory time (TE), duty cycle (TI/Ttot) and mean inspiratory flow (VT/TI) were analysed at selected submaximal ventilatory intensities.

Senescence and female sex were associated with a more tachypnoeic breathing pattern during isoventilation. The decline inTtotwas proportional to theTIandTEreductions,i.e.TI/Ttotwas remarkably constant across age strata, independent of sex. The pattern, but not timing, of breathing was also influenced by weight and height; a set of demographically and anthropometrically based prediction equations are therefore presented.

These data provide a frame of reference for assessing the normality of some clinically useful indices of the pattern and timing of breathing during incremental cycle ergometry in sedentary males and females aged 20–80 yrs.
Cough augmentation with mechanical insufflation/exsufflation in patients with neuromuscular weakness
Authors: Chatwin M. , Ross E. , Hart N. , Nickol A.H. , Polkey M.I. , Simonds A.K.
Published: September 2008

Adults and children with neuromuscular disease exhibit weak cough and are susceptible to recurrent chest infections, a major cause of morbidity and mortality. Mechanical insufflation/exsufflation may improve cough efficacy by increasing peak cough flow. It was hypothesised that mechanical insufflation/exsufflation would produce a greater increase in peak cough flow than other modes of cough augmentation. The acceptability of these interventions was also compared.

Twenty-two patients aged 10–56 yrs (median 21 yrs) with neuromuscular disease and 19 age-matched controls were studied. Spirometry was performed and respiratory muscle strength measured. Peak cough flow was recorded during maximal unassisted coughs, followed in random order by coughs assisted by physiotherapy, noninvasive ventilation, insufflation and exsufflation, and exsufflation alone. Subjects rated strength of cough, distress and comfort on a visual analogue scale.

In the neuromuscular disease group, mean±sd forced expiratory volume in one second was 0.8±0.6 L·s−1, forced vital capacity 0.9±0.8 L, maximum inspiratory pressure 25±16 cmH2O, maximum expiratory pressure 26±22 cmH2O and unassisted peak cough flow 169±90 L·min−1. The greatest increase in peak cough flow was observed with mechanical insufflation/exsufflation at 235±111 L·min−1(p<0.01). All techniques showed similar patient acceptability.

Mechanical insufflation/exsufflation produces a greater increase in peak cough flow than other standard cough augmentation techniques in adults and children with neuromuscular disease.
Chlorine inhalation produces nasal congestion in allergic rhinitics without mast cell degranulation
Authors: Shusterman D. , Balmes J. , Avila P.C. , Murphy M.A. , Matovinovic E.
Published: September 2008

Seasonal allergic rhinitic (SAR) subjects are more sensitive to nasal irritants than nonrhinitic (NR) subjects; however, the mechanism underlying this difference is unclear. This study sought to determine whether irritant-induced nasal congestion involves mast cell degranulation.

Eight SAR and eight NR subjects were exposed to both 1.0 parts per million chlorine and filtered air in separate visits; exposures werevianasal mask and lasted 15 min. Rhinomanometry was performed before, immediately after and 15 min after exposure. Following ≥2 weeks, exposures and symptom reporting were repeated with nasal lavage, rather than rhinomanometry, pre- and postexposure. A separate substudy using rye grass antigen provided a positive control. Mast cell tryptase was measured in nasal lavage fluid from both substudies using an automated fluoroenzyme immunoassay.

Chlorine provocation significantly increased nasal airway resistance in SAR but not NR subjects. Conversely, tryptase levels in nasal lavage fluid were unaffected. Nasal allergen challenge significantly increased both nasal obstruction and nasal lavage tryptase in SAR subjects.

Irritant-induced nasal congestion is more pronounced among seasonal allergic rhinitic than nonrhinitic subjects. However, unlike nasal allergen challenge, the mechanism of response to chlorine does not appear to involve mast cell degranulation.