bluuebunny/crossref_metadata_2025 huggingface dataset:
T-cell receptor excision circle and T-cell dynamics after allogeneic stem cell transplantation are related to clinical events
Authors: Hazenberg Mette D. , Otto Sigrid A. , de Pauw Elmar S. , Roelofs Helene , Fibbe Willem E. , Hamann Dörte , Miedema Frank
Published: October 2002

It is generally believed that homeostatic responses regulate T-cell recovery after peripheral stem cell transplantation (PSCT). We studied in detail immune recovery in relation to T-cell depletion and clinical events in a group of adult patients who underwent PSCT because of hematologic malignancies. Initially, significantly increased proportions of dividing naive, memory, and effector CD4+and CD8+ T cells were found that readily declined, despite still very low numbers of CD4+ and CD8+ T cells. After PSCT, increased T-cell division rates reflected immune activation because they were associated with episodes of infectious disease and graft-versus-host disease (GVHD). T-cell receptor excision circles (TRECs) were measured to monitor thymic output of naive T cells. Mean TREC content normalized rapidly after PSCT, long before naive T-cell numbers had significantly recovered. This is compatible with the continuous thymic production of TREC+ naive T cells and does not reflect homeostatic increases of thymic output. TREC content was decreased in patients with GVHD and infectious complications, which may be explained by the dilution of TRECs resulting from increased proliferation. Combining TREC and Ki67 analysis with repopulation kinetics led to the novel insight that recovery of TREC content and increased T-cell division during immune reconstitution after transplantation are related to clinical events rather than to homeostatic adaptation to T-cell depletion.
High frequency of point mutations clustered within the adenosine triphosphate–binding region of BCR/ABL in patients with chronic myeloid leukemia or Ph-positive acute lymphoblastic leukemia who develop imatinib (STI571) resistance
Authors: Branford Susan , Rudzki Zbigniew , Walsh Sonya , Grigg Andrew , Arthur Chris , Taylor Kerry , Herrmann Richard , Lynch Kevin P. , Hughes Timothy P.
Published: October 2002

Point mutations were found in the adenosine triphosphate (ATP) binding region of BCR/ABL in 12 of 18 patients with chronic myeloid leukemia (CML) or Ph-positive acute lymphoblastic leukemia (Ph+ ALL) and imatinib resistance (defined as loss of established hematologic response), but they were found in only 1 of 10 patients with CML with imatinib refractoriness (failure to achieve cytogenetic response). In 10 of 10 patients for whom samples were available, the mutation was not detected before the initiation of imatinib therapy. Three mutations (T315I, Y253H, and F317L present in 3, 1, and 1 patients, respectively) have a predicted role in abrogating imatinib binding to BCR/ABL, whereas 3 other mutations (E255K, G250E, and M351T, present in 4, 2, and 2 patients, respectively) do not. Thus we confirm a high frequency of mutations clustered within the ATP-binding region of BCR/ABL in resistant patients. Screening may allow intervention before relapse by identifying emerging mutations with defined impacts on imatinib binding. Certain mutations may respond to higher doses of imatinib, whereas other mutations may mandate switching to another therapeutic strategy.
Monitoring of nonlinear respiratory elastance using a multiple linear regression analysis
Authors: Muramatsu K. , Yukitake K. , Nakamura M. , Matsumoto I. , Motohiro Y.
Published: October 2002

The elastic pressure/volume (P/V) curve obtained by the multiple linear regression (MLR) technique using a new model, was compared with the quasi-staticP/Vpoints obtained by the rapid airway occlusion technique.

Seven infants were studied during mechanical ventilation using a pressure controlled mode. The resistive pressure was subtracted from airway opening pressure, thus determining the elastance related pressure, which was then plotted against the volume to make an MLR-elastance curve. Quasi-staticP/Vcurves of the rapid occlusion technique were constructed by plotting the different inspiratory and expiratory volumes against the corresponding values of the quasi-static airway pressure.

The calculated MLR-elastance curves closely fit the experimental quasi-staticP/Vpoints obtained by the occlusion technique. There were, however, some discrepancies due to the viscoelastic behaviour of the respiratory system.

Although slightly altered by these discrepancies, the multiple linear regression-elastance curves did fit the observed quasi-static pressure/volume characteristics for use in clinical practice. The multiple linear regression technique may prove to be clinically useful by continuous monitoring of respiratory system mechanics during mechanical ventilation.
Fewer allergic respiratory disorders among farmers' children in a closed birth cohort from Sweden
Authors: Klintberg B. , Berglund N. , Lilja G. , Wickman M. , van Hage-Hamsten M.
Published: October 2002

The aim of this study was to investigate the prevalence of respiratory allergy, eczema and atopic sensitization in a closed birth cohort of Swedish schoolchildren, 7–8 yrs of age (n=707), of farmers and nonfarmers on the island of Gotland, in the Baltic Sea. All children were born and raised on the island.

The survey comprised a questionnaire on atopic diseases and lifestyle factors. Atopic sensitization was assessed by the skin-prick test (SPT) with 15 standardized allergens.

The risk ratio (RR) for ever having asthma and/or allergic rhinoconjunctivitis was significantly lower among children of farmers compared to children of nonfarmers (RR=0.38, confidence interval (CI) 95% 0.19–0.77). SPTs (test rate 92%) showed that 32% of the children had at least one positive test. Although the number of positive SPTs did not differ between the groups, there was a reduced risk among children of farmers for having both respiratory symptoms and sensitization to any International Study on Asthma and Allergy in Childhood allergen (RR=0.28, CI 95% 0.09–0.88).

The present indicate that living in a farming population seems to protect against development of respiratory allergic disorders but not against allergic sensitization.
High morbidity and mortality in cystic fibrosis patients compound heterozygous for 3905insT and ΔF508
Authors: Schibler A. , Bolt I. , Gallati S. , Schöni M.H. , Kraemer R.
Published: October 2002

Genotype-phenotype association in cystic fibrosis (CF) is difficult because of heterogeneous disease expression. The genotype-phenotype correlation for the 3905insT mutation in comparison to ΔF508 was studied here.

Thirty CF patients compound heterozygous for 3905insT were compared to clinical presentation of matched patients homozygous for ΔF508 (1960–1997). Sweat tests, age at diagnosis, at death and at onset ofPseudomonas aeruginosacolonization were analysed. Chrispin-Norman scores and pulmonary function forced expiratory volume in one second (FEV1) determined severity of lung disease. Twenty-five of the patients with 3905insT had ΔF508 as a second mutation and five had another rare mutation.

At the age of 15 yrs, 60% of patients with 3905insT had an FEV1<60% predicted in comparison to 25% of patients with ΔF508 (p<0.05). Age at death and cumulative survival rate was significantly lower (p<0.05) in the 3905insT than in the ΔF508 group (20.3 and 24.0 yrs, respectively). Age at onset ofP. aeruginosacolonization was not different in the study groups. Sweat chloride concentrations were lower in patients homozygous for ΔF508 (105.63±15.3 mmol·L−1) than in patients with 3905insT (119.9±22.1 mmol·L−1) (p<0.05).

Patients compound heterozygous for 3905insT have similar high morbidity and mortality to patients homozygous for ΔF508.
Health-related quality of life in COPD: why both disease-specific and generic measures should be used
Authors: Engström C.P. , Persson L.O. , Larsson S. , Sullivan M.
Published: October 2002

Although research has consistently demonstrated that chronic obstructive pulmonary disease (COPD) impairs health-related quality of life (HRQL), little agreement has been evidenced regarding the factors identified as contributing to impaired HRQL. The aim was to study such factors using well established generic and specific HRQL instruments.

The patients (n=68) were stratified by forced expiratory volume in one second (FEV1) to represent a wide range of disease severity. Pulmonary function, blood gases and 6-min walking distance test (6MWD) were assessed. HRQL instruments included: St George's Respiratory Questionnaire (SGRQ), Sickness Impact Profile (SIP), Hospital Anxiety and Depression Scale and Mood Adjective Check List.

The strength of the impact of COPD on HRQL was represented along a continuum ranging from lung function, functional status (physical and psychosocial) to wellbeing. Although correlations between FEV1versusSGRQ total and SIP overall scores (r=−0.42 and −0.32) were stronger than previously reported, multiple regression analyses showed that lung function contributed little to the variance when dyspnoea-related limitation, depression scores and 6MWD were included in the models. These three factors were important to varying degrees along the whole range of HRQL.

Physiological, functional and psychosocial consequences of chronic obstructive pulmonary disease are only poorly to moderately related to each other. The present study concludes that a comprehensive assessment of the effects of chronic obstructive pulmonary disease requires a battery of instruments that not only tap the disease-specific effects, but also the overall burden of the disease on everyday functioning and emotional wellbeing.
Expression of members of the phospholipase A2family of enzymes in human nasal mucosa
Authors: Lindbom J. , Ljungman A.G. , Lindahl M. , Tagesson C.
Published: October 2002

Phospholipase A2(PLA2) is a family of enzymes thought to play a key role in inflammation by releasing arachidonic acid for the synthesis of eicosanoids and lysophospholipid for the synthesis of platelet-activating factor. However, the precise contribution of different PLA2types to the formation of inflammatory lipid mediators in the upper airways is not known and the expression of different PLA2genes in the human nasal mucosa has not been examined.

This study therefore investigated the occurrence of messenger ribonucleic acids (mRNAs) for different PLA2forms (IB, IIA, IID, IIE, III, IVA, IVB, IVC, V, VI, VII, X, acid calcium-independent (aiPLA2), and calcium-independent membrane bound PLA2, (iPLA2-2)) in the nasal mucosa of five healthy human subjects.

Using reversed transcription-polymerase chain reaction (RT-PCR) techniques it was found that all these PLA2types except PLA2V were expressed in all subjects, whereas PLA2V was detected in only one individual on one single occasion. The relative abundance of the different PLA2transcripts were aiPLA2>X≈IVA>IIA≈IIE≈IVB≈VI>IB≈IID≈III≈IVC≈VII≈iPLA2-2. To further quantify the mRNA-expression of PLA2X, IVA and IIA, the samples were reanalysed with a quantitative PCR-technique utilizing competitive deoxyribonucleic acid (DNA) mimics as references. The amounts of PLA2X, IVA and IIA mRNA were then estimated to 0.9±0.2, 1.1±0.7, and 0.0025±0.0021 amol (mean±se), respectively, confirming the relative abundance of these PLA2transcripts and indicating that the recently described PLA2X form is relatively strongly expressed.

These findings demonstrate that a large number of PLA2types are expressed in the normal human nasal mucosa. Moreover, this investigation demonstrates, for the first time, the presence of the newly discovered phospholipase A2forms IID, IIE, III, IVB, IVC, X and calcium-independent membrane bound phospholipase A2in the human nasal mucosa and raises the possibility that one or several of these may be involved in inflammatory reactions in the nose.
High-resolution computed tomography scanning in α1-antitrypsin deficiency: relationship to lung function and health status
Authors: Dowson L.J. , Guest P.J. , Hill S.L. , Holder R.L. , Stockley R.A.
Published: October 2002

The development of computed tomography (CT) has enabled emphysema to be assessed noninvasively. Objective quantification of lung density correlates well with lung function in patients with chronic obstructive pulmonary disease and has been shown to be a sensitive tool for monitoring disease progression.

In order to determine the clinical impact of changes seen on high-resolution computed tomography (HRCT), the relationship between the objective quantification of emphysema on HRCT, lung function and health status in 111 patients with α1-antitrypsin deficiency was examined (PiZ).

The degree of HRCT scan abnormality correlated well (p<0.001 for all comparisons) with forced expiratory volume in one second (r=−0.60–−0.75), specific airway conductance (r=−0.67–0.76), residual volume/total lung capacity (r=0.46–0.58) and transfer factor of the lung for carbon monoxide (r=−0.64–−0.81). In addition, the CT scans correlated (p<0.001) with health status as assessed by the St. George's Respiratory Questionnaire (SGRQ total: r=−0.38–0.50) and the Short-Form health survey (e.g.physical functioning: r=−0.39–0.54).

In summary, other workers have shown high-resolution computed tomography to be a sensitive indicator of disease progression. This study confirms the relationship between high-resolution computed tomography and lung physiology, and suggests the relationship is even stronger in patients with predominantly lower zone pan-lobular emphysema than in usual chronic obstructive pulmonary disease. High-resolution computed tomography also relates to patients disability and impairment as defined by health status questionnaires and, therefore, should be considered as an alternative outcome measure particularly in a1-antitrypsin deficiency.
Intron-8 polythymidine sequence in Australasian individuals with CF mutations R117H and R117C
Authors: Massie R.J.H. , Poplawski N. , Wilcken B. , Goldblatt J. , Byrnes C. , Robertson C.
Published: October 2002

Compound heterozygotes for a severe cystic fibrosis transmembrane conductance regulator (CFTR) mutation and the R117H or R117C mutation (R117H/C) have clinical presentations that vary from classic cystic fibrosis (CF) to an incidental genetic finding.

The aim of this study was to assess the influence of the intron-8 polythymidine sequence (IVS8) on the relationship between genotype and phenotype of individuals with R117H/C.

All individuals with R117H/C known to CF clinics in Australia and New Zealand were retrospectively studied by collecting information on genotype, age, pancreatic status, sweat electrolytes, sputum microbiology and pulmonary function.

Forty-one individuals (39 with R117H and two with R117C), 16 on an IVS8-5T background and 25 on an IVS8-7T background were identified. Twelve individuals presented clinically, four were siblings of known R117H/C compound heterozygotes and 25 were detected by newborn screening. Eleven of 14 of the IVS8-5T group (78%) with sweat chloride results available had sweat Cl>60 mmol·L−1compared to 5 (20%) of the R117H/7T group (Chi-squared=10.4, p=0.001). Two were pancreatic insufficient, both IVS8-5T. Two IVS8-5T individuals have recently died (aged 43 and 19) and of the 14 surviving IVS8-5T group, 11 (79%) are symptomatic compared to eight (32%) of the IVS8-7T individuals (Chi-squared=6.1, p=0.01).

In conclusion, most individuals with R117H/C on a IVS8-5T background have an elevated sweat chloride and clinical cystic fibrosis, which in some cases is severe. Most individuals with R117H/C on an IVS8-7T background do not have clinical cystic fibrosis but should be followed for the development of clinical disease.
Breathing pattern and gas exchange at peak exercise in COPD patients with and without tidal flow limitation at rest
Authors: Díaz O. , Villafranca C. , Ghezzo H. , Borzone G. , Leiva A. , Milic-Emili J. , Lisboa C.
Published: October 2002

Expiratory flow limitation (FL) at rest is frequently present in chronic obstructive pulmonary disease (COPD) patients. It promotes dynamic hyperinflation with a consequent decrease in inspiratory capacity (IC). Since in COPD resting IC is strongly correlated with exercise tolerance, this study hypothesized that this is due to limitation of the maximal tidal volume (VT,max) during exercise by the reduced IC. The present study investigated the role of tidal FL at rest on: 1) the relationship of resting IC toVT,max; and 2) on gas exchange during peak exercise in COPD patients.

Fifty-two stable COPD patients were studied at rest, using the negative expiratory pressure technique to assess the presence of FL, and during incremental symptom-limited cycling exercise to evaluate exercise performance.

At rest, FL was present in 29 patients. In the 52 patients, a close relationship ofVT,maxto IC was found using non-normalized values (r=0.77; p<0.0001), and stepwise regression analysis selected IC as the only significant predictor ofVT,max. Subgroup analysis showed that this was also the case for patients both with and without FL (r=0.70 and 0.76, respectively). In addition, in FL patients there was an increase (p<0.002) in arterial carbon dioxide partial pressure at peak exercise, mainly due to a relatively lowVT,maxand consequent increase in the physiological dead space (VD)/VTratio. The arterial oxygen partial pressure also decreased at peak exercise in the FL patients (p<0.05).

In conclusion, in chronic obstructive pulmonary disease patients the maximal tidal volume, and hence maximal oxygen consumption, are closely related to the reduced inspiratory capacity. The flow limited patients also exhibit a significant increase in arterial carbon dioxide partial pressure and a decrease in arterial oxygen partial pressure during peak exercise.
Increased circulating levels of α1-antitrypsin and calprotectin are associated with reduced gas diffusion in the lungs
Authors: Welle I. , Bakke P.S. , Eide G.E. , Fagerhol M.K. , Omenaas E. , Gulsvik A.
Published: October 2002

The aim was to examine the relationship of serum inflammatory markers to the level of single-breath diffusing capacity of carbon monoxide (TL,CO).

A stratified sample (n=1,121) of a Norwegian general population aged 18–73 yrs was examined. The inflammatory markers measured were calprotectin, a prominent protein in the cytosol fraction of neutrophil granulocytes, and α1-antitrypsin (α1-AT), the major inhibitor of neutrophil elastase in the lower respiratory system. Both markers have increased circulating levels in the course of an acute inflammatory reaction.

Subjects with a TL,CO<80% of predicted value had a higher level of both α1-AT (p=0.003) and calprotectin (p<0.03) than those with a TL,CO>100%. In multiple linear regression analyses, α1-AT was still significantly associated withTL,COafter adjusting for sex, age, smoking habits, haemoglobin, carboxyhaemoglobin, forced expiratory volume in one second and alveolar volume. In a similar analysis, no significant overall association was found between calprotectin and TL,CO, but in a stratified analysis, calprotectin was significantly related to TL,COin females. However, no significant sex interaction in the relationship between the inflammatory markers and TL,COwas found.

The findings suggest that increased levels of α1-antitrypsin and of calprotectin are risk factors for decreased diffusing capacity of carbon monoxide.
Supported discharge shortens hospital stay in patients hospitalized because of an exacerbation of COPD
Authors: Sala E. , Alegre L. , Carrera M. , Ibars M. , Orriols F.J. , Blanco M.L. , Cárceles F. , Bertran S. , Mata F. , Font I. , Agustí A.G.N.
Published: October 2002

This prospective, controlled, but not formally randomized study investigates the feasibility and efficiency of an alternative to standard hospitalization for patients with exacerbated chronic obstructive pulmonary disease (COPD), based upon supported discharge with nurse supervision at home.

Over a 12-month period, emergency physicians, not directly involved in the study, admitted 205 patients with exacerbated COPD to the authors' respiratory unit. Patients were included in the supported discharge group (n=105) if they voluntarily chose to participate in the programme and lived in the city of Palma de Mallorca (where adequate home support could be provided). Patients not fulfilling these criteria (mainly residents outside the city) served as controls (n=100). Inpatient treatment was standardized in all patients and included oxygen therapy, bronchodilators, antibiotics and steroids.

Both groups were comparable in terms of age (mean±sd: 70±10versus65±11 yr for supported discharge and control group, respectively), severity of airflow obstruction (forced expiratory volume in one second 45±18% referenceversus46±19% ref.), comorbidity and socioeconomic status. Length of hospital stay (LOS) in the supported discharge group was shorter (5.9±2.8versus8.0±5.1 days, p<0.001). After discharge, a respiratory nurse visited supported discharge patients at home during 7.3±3.8 days. Only one patient (1%) required hospital readmission during this period of time. The reduced LOS resulted in a lower utilization of hospital beds at any given point in time throughout the study period.

Within the framework and potential limitations of this study, the results indicate that the supported discharge programme in Spain: 1) allows a significant reduction in the length of hospital stay of patients hospitalized because of an exacerbation of chronic obstructive pulmonary disease; 2) does not result in an inappropriately increased rate of hospital readmissions; and 3) reduces the utilization of hospital resources.
A bibliometric evaluation of European Union research of the respiratory system from 1987–1998
Authors: García-Río F. , Serrano S. , Dorgham A. , Alvarez-Sala R. , Ruiz Peña A. , Pino J.M. , Alvarez-Sala J.L. , Villamor J.
Published: October 2002

This study analyses the evolution of the bibliometric indicators of productivity and repercussion of European Union (EU) research into the respiratory system during the period from 1987–1998, describing the geographical distribution.

Using MedLine, a selection was made of those articles by EU authors published between 1987–1998 in 38 respiratory system journals (classification from the Institute for Scientific Information). The journals, country of origin, number of articles and the relation to socioeconomic data, productivity index, visibility index, expected impact factor (EIF) and relative impact factor (RIF) were all analysed.

The number of EU publications in respiratory system journals experienced an exponential increase, going from 606 articles (14.3% of world production) in 1987, to 2,325 (33.2%) in 1998. During this same period, the EIF increased from 1,258 to 2,111. The greatest gross productivities were those of the UK, France, Italy and Germany, although when corrected for number of inhabitants, Sweden, the Netherlands, Belgium and Denmark headed the list. The countries with the greatest mean EIF were the Netherlands, the UK, Spain and Belgium.

In conclusion, productivity and repercussions of European Union research of the respiratory system experienced an important increase during this period.
A model of viral wheeze in nonasthmatic adults: symptoms and physiology
Authors: Mckean M.C. , Leech M. , Lambert P.C. , Hewitt C. , Myint S. , Silverman M.
Published: October 2002

Episodic wheezing associated with viral infections of the upper respiratory tract (URT) is a common problem in young children but also occurs in adults. It is hypothesized that an experimental infection with human coronavirus (HCoV), the second most prevalent common cold virus, would cause lower respiratory tract (LRT) changes in adults with a history of viral wheeze.

Twenty-four viral wheezers (15 atopic) and 19 controls (seven atopic) were inoculated with HCoV 229E and monitored for the development of symptoms, changes in airway physiology and provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20). At baseline, viral wheezers were similar to controls in PC20(mean±sd log2PC20: 5.1±1.9 and 5.8±1.4 g·L−1, respectively) but had a lower FEV1than controls (mean±sd 85.8±11.4 and 95.6±13.2% predicted, respectively p<0.05). Nineteen viral wheezers and 11 controls developed colds. Viral wheezers with colds reported significantly more URT symptoms than controls (median scores (interquartile range): 24 (10–37) and 6 (4–15), respectively p=0.014). Sixteen viral wheezers and no controls reported LRT symptoms (wheeze, chest tightness and shortness of breath). The viral wheezers with colds had small (3–4%) reductions in FEV1and peak expiratory flow on days with LRT symptoms (days 3–6), but a progressive reduction in PC20from baseline on days 2, 4 and 17 after inoculation (by 0.82, 1.35 and 1.82 doubling concentrations, respectively). The fall in PC20affected both atopic and nonatopic subjects equally. There were no changes in FEV1or PC20in controls.

An adult model of viral wheeze that is independent of atopy and therefore, of classical atopic asthma was established.
Type II alveolar epithelial cells and interstitial fibroblasts express connective tissue growth factor in IPF
Authors: Pan L-H. , Yamauchi K. , Uzuki M. , Nakanishi T. , Takigawa M. , Inoue H. , Sawai T.
Published: October 2002

Connective tissue growth factor (CTGF) is a growth and chemotactic factor for fibroblasts encoded by an immediate early gene that is transcriptionally activated by transforming growth factor-β. Previous studies have shown that both CTGF messenger ribonuclear acid (mRNA) and protein are expressed in renal fibrosis and bleomycin-induced pulmonary fibrosis in mice. The aim of the present study was to investigate the localization of CTGF protein and its mRNA expression in the fibrotic lung tissue of patients with idiopathic pulmonary fibrosis (IPF).

Using human fibrotic lung tissue obtained from eight autopsy cases and four biopsy cases with IPF, immunohistochemical staining,in situhybridization, and reverse transcription-polymerase chain reaction (RT-PCR) were performed.

The cellular immunoreactivity for CTGF was markedly increased in the lung tissue of patients with IPF, compared to normal lungs. The immunolocalization of CTGF was confined predominantly to proliferating type II alveolar epithelial cells and activated fibroblasts. In the normal lung, type II alveolar epithelial cells stained for CTGF were sparsely distributed. CTGF mRNA was localized in proliferating type II alveolar epithelial cells and activated fibroblasts in the interstitium of fibrotic lung tissues. RT-PCR analysis showed that CTGF mRNA was expressed at a higher level in fibrotic lungs than in normal lungs.

In both an autocrine and a paracrine manner, type II alveolar epithelial cells and activated fibroblasts may play a critical role in pulmonary fibrosis by producing connective tissue growth factor which modulates fibroblast proliferation and extracellular matrix production.
Vascular endothelial growth factor synthesis in the acute phase of experimental and clinical lung injury
Authors: Maitre B. , Boussat S. , Jean D. , Gouge M. , Brochard L. , Housset B. , Adnot S. , Delclaux C.
Published: October 2002

Vascular endothelial growth factor (VEGF) is a potent angiogenic and endothelial survival factor, which is abundantly expressed in the normal lung. Conceivably, VEGF may be released by numerous cell types found around the airspaces, including alveolar type 2 cells, alveolar macrophages, and polymorphonuclear neutrophils.

Using a bacteria-induced lung injury model in rats, VEGF expression in lung was investigated. Both VEGF protein and VEGF messenger ribonucleic acid (mRNA), 4 and 24 h after bacterial challenge (Pseudomonas aeruginosa), were decreased compared with sham rats.

VEGF protein was also investigated in bronchoalveolar lavage (BAL) from patients studied within 7 days of acute respiratory distress syndrome (ARDS) onset and in patients without ARDS. VEGF protein levels in BAL were decreased in patients with ARDSversusthose without (14.3±11.1 pg·mL−1versus76.8±51.1 pg·mL−1, p=0.03).

In aggregate, these findings show that the initial phase of acute lung injury is associated with a decrease in vascular endothelial growth factor in the lung. This downregulation may represent a protective mechanism aimed at limiting endothelial permeability, and may participate in the decrease in capillary number that is observed during early acute respiratory distress syndrome.
Discrepant distribution of big endothelin (ET)-1 and ET receptors in the pulmonary artery
Authors: Takahashi H. , Soma S. , Muramatsu M. , Oka M. , Ienaga H. , Fukuchi Y.
Published: October 2002

Since pulmonary vasculature is complex in terms of regional difference in structure and function, it is important to understand the site of endothelin (ET) synthesis and the distribution of the ET system along the axial pathways of pulmonary artery.

The expression of big ET-1, ET converting enzyme (ECE) and ETAreceptors were examined in rat pulmonary arteries under normal and hypoxic conditions using an immunohistochemical method and Northern blot analysis.

In normal conditions, big ET-1 was expressed in the intima and media of pulmonary arteries with a predominant distribution in the distal segments and a preferential localization in the media, while ETAreceptors were dominantly expressed in the proximal segments. ECE was constitutively expressed in the intima and media. Following exposure to hypoxia, messenger ribonucleic acid (mRNA) expression of ET-1 and ETAreceptors were up-regulated by two-fold and immunoreactivities for big ET-1, ECE, and ETAreceptors significantly increased by two to five-fold in the distal segments.

Smooth muscle cells are an important source of endothelin-1 in the pulmonary artery. The distribution of big endothelin-1 and endothelin A receptors in pulmonary arteries was discrepant in normal conditions while their expression concomitantly increased in the distal segments in hypoxic conditions. This heterogeneity may play an important role in the regulation of pulmonary vascular tone.
Dose-response effect of oxygen on hyperinflation and exercise endurance in nonhypoxaemic COPD patients
Authors: Somfay A. , Porszasz J. , Lee S.M. , Casaburi R.
Published: October 2002

Dynamic hyperinflation contributes to exertional breathlessness and reduced exercise tolerance in chronic obstructive pulmonary disease (COPD) patients. This study examined whether oxygen supplementation results in a dose-dependent decrease in hyperinflation associated with functional and symptomatic improvement.

Ten severe COPD patients without clinically significant oxygen (O2) desaturation during exercise, and seven healthy subjects, performed five exercise tests at 75% of maximally tolerated work rate. Inspired oxygen fraction (FI,O2) was varied (0.21, 0.3, 0.5, 0.75 and 1.0) among tests in a randomized order. Ventilation (V'E) was measured, and end-inspiratory (EILV) and end-expiratory (EELV) lung volume changes were assessed from inspiratory capacity manoeuvres.

In the patients, compared to room air, endurance time increased withFI,O2=0.3 (mean±sem 92±20%) and increased further withFI,O2=0.5 (157±30%). At isotime, compared to room air, there were significant reductions in dyspnoea score, EELV, EILV,V'Eand respiratory frequency (fR) withFI,O2=0.3. Improved endurance time negatively correlated with change in EELV (r=0.48, p=0.002) and EILV (r=043, p=0.005). The dyspnoea rating decrease correlated withfRdecrease. In healthy subjects, smallerV'EandfRdecreases were observed atFI,O2=0.5, accompanied by more modestly increased endurance.

Oxygen supplementation during exercise induced dose-dependent improvement in endurance and symptom perception in nonhypoxaemic chronic obstructive pulmonary disease patients, which may be partly related to decreased hyperinflation and slower breathing pattern. This effect is maximized at an inspired oxygen fraction of 0.5.
Variations in the prevalence across countries of chronic bronchitis and smoking habits in young adults
Authors: Cerveri I. , Accordini S. , Verlato G. , Corsico A. , Zoia M.C. , Casali L. , Burney P. , de Marco R.
Published: October 2002

The present work aims to assess the international variation in the prevalence of chronic bronchitis and its main risk factor, smoking habits, in young adults of 35 centres from 16 countries.

Respiratory symptoms and pulmonary function were assessed in 17,966 subjects (20–44 yrs), randomly selected from the general population, in the frame of the European Community Respiratory Health Survey.

The median prevalence of chronic bronchitis was 2.6%, with wide variations across countries (p<0.001; 0.7–9.7%). The prevalence of current smokers ranged 20.1–56.9% (p<0.001) with a median value of 40%. Current smoking was the major risk factor for chronic bronchitis, especially in males. Its effect increased according to number of pack-yrs: in males, the odds ratio of chronic bronchitis was 3.51 (95% confidence interval (CI) 2.31–5.32) in 1–14 pack-yrs smokers and increased to 17.32 (9.97–30.11) in ≥45 pack-yrs smokers with respect to nonsmokers. Only 30% of the geographical variability in prevalence could be explained by differences in smoking habits, suggesting that other environmental and/or genetic factors may play an important role.

In conclusion, chronic bronchitis is a substantial health problem even in young adults. The impressive prevalence in current smokers in most countries highlights the need to improve the quality of prevention.
Ventilatory and cerebrovascular responses in normocapnic and hypercapnic COPD patients
Authors: Van de Ven M.J.T. , Colier W.N.J.M. , Van der Sluijs M.C. , Kersten B.T.P. , Oeseburg B. , Folgering H.
Published: October 2002

This study investigated the hypothesis that hypercapnia in some chronic obstructive pulmonary disease (COPD) patients may be related to a high cerebrovascular response to carbon dioxide (CO2).

The relationship between responses of ventilation and of cerebral blood volume (CBV) to acute changes in carbon dioxide tension in arterial blood (Pa,CO2) was measured in 17 chronic hypercapnic (Pa,CO2>6.0 kPa) and 16 normocapnic (Pa,CO2⪕6.0 kPa) COPD patients, who were matched for degree of airway obstruction (forced expiratory volume in one second 27% predicted). Results were compared with 15 age-matched healthy subjects. CBV was measered using near infrared spectroscopy during normo- and hypercapnia and related to inspired minute ventilation (V′I) and mouth occlusion pressure (P0.1). Hypercapnia (end-tidal pressure of carbon dioxide (ΔPET,CO2) >1 kPa) was induced by giving adequate amounts of CO2in the inspired air.

During normocapnia, CBV (mL·100 g−1) was 2.41±0.66 and 2.90±0.60 (mean±sd) in the normocapnic and chronic hypercapnic patients, respectively, which was significantly lower compared to healthy subjects (3.53±0.77). All slopes of CO2responsiveness (ΔCBV/ΔPa,CO2, ΔV′I/ΔPa,CO2, ΔP0.1/ΔPa,CO2) were significantly lower in both COPD groups relative to healthy subjects, but were not significantly different between the COPD groups. A poor but positive correlation between ventilatory and cerebrovascular CO2responsiveness (ΔCBV/ΔPa,CO2and ΔV′I/ΔPa,CO2) was found in COPD patients and healthy subjects.

The findings do not support the hypothesis of abnormal cerebrovascular responses to carbon dioxide in hypercapnic chronic obstructive pulmonary disease patients.
Comparison of the standard gamble, rating scale, AQLQ and SF-36 for measuring quality of life in asthma
Authors: Juniper E.F. , Norman G.R. , Cox F.M. , Roberts J.N.
Published: October 2002

With interest in health economics growing, there is a demand for valid methods for measuring health-related quality of life (HRQL) in asthma using utilities. The aims of this study were to develop disease-specific versions of the standard gamble and rating scale, to compare their measurement properties with those of the Asthma Quality of Life Questionnaire (AQLQ) and the Medical Outcomes Survey Short-Form 36 (SF-36), as well as to determine their validity for assessing asthma-specific quality of life.

Forty adults with symptomatic asthma participated in a 9-week observational study. Participants completed the standard gamble, rating scale, AQLQ, SF-36 and other measures of clinical asthma status at baseline and after 1, 5 and 9 weeks.

In patients whose asthma was stable between assessments, reliability was good for the rating scale (intraclass correlation coefficient (ICC)=0.89) and the AQLQ (ICC=0.95) but more modest for the SF-36 mental score (ICC=0.68), SF-36 physical score (ICC= 0.65) and standard gamble (ICC=0.59). The responsiveness index was highest in the AQLQ (1.35), followed by the rating scale (0.74), the physical score of the SF-36 (0.61) and the standard gamble (0.31). Construct validity (correlation with other indices of health status) was strongest for the AQLQ and the rating scale.

In conclusion, both the disease-specific rating scale and the Asthma Quality of Life Questionnaire have strong measurement properties for measuring asthma-specific quality of life; the Short-Form 36 health survey physical summary score has more modest properties. Although the disease-specific standard gamble has acceptable discriminative properties, its evaluative properties are too inadequate for it to be used in cost/utility analyses. Poor correlation between the standard gamble and the rating scale indicates that utilities cannot be derived from rating scale data.
Usefulness of transcutaneous Doppler jugular venous echo to predict pulmonary hypertension in COPD patients
Authors: Matsuyama W. , Ohkubo R. , Michizono K. , Abe M. , Nakamura Y. , Kawabata M. , Osame M.
Published: October 2002

Pulmonary hypertension is an important factor that determines the prognosis of chronic obstructive pulmonary disease (COPD) patients. Echocardiography is a noninvasive and useful bedside method for measurement of pulmonary artery pressure. However, this method is sometimes difficult because of the overinflated lungs in COPD patients. This study attempted to estimate pulmonary hypertension in COPD patients using transcutaneous Doppler jugular vein flow velocity recording.

The mean pulmonary artery pressure (MPAP) of 64 COPD patients was examined using cardiac catheterization. The right jugular vein flow velocity was measured within 24 h using transcutaneous Doppler echo, after which the ratio of diastolic flow (Df) and systemic flow (Sf) velocity was calculated. Subsequently, the statistical correlation of MPAP and the Df/Sf ratio was examined. MPAP was also measured using standard cardiac echo methods and the results were compared.

The Df/Sf velocity ratio showed significant correlation with MPAP in COPD patients (r=0.844, p<0.0001). The sensitivity was 71.4%, and the specificity 95.3% (cut-off ratio=1.0). Jugular venous Doppler echo could be performed in all patients while other cardiac echo methods could not be performed in all patients. The specificity of the methods used was higher than other cardiac echo methods.

Transcutaneous jugular vein flow velocity measurement may be applicable to bedside prediction of pulmonary hypertension in chronic obstructive pulmonary disease patients.
Effectiveness of salmeterolversusipratropium bromide on exertional dyspnoea in COPD
Authors: Ayers M.L. , Mejia R. , Ward J. , Lentine T. , Mahler D.A.
Published: October 2002

The hypothesis of the study was that salmeterol and ipratropium would have similar dyspnoea ratings during steady-state cycle ergometry at 1 h, but that salmeterol would reduce dyspnoea at 6 h after administration in patients with chronic obstructive pulmonary disease (COPD).

The study design was a randomized, double-blind trial in 16 patients (aged 63±11 yrs) with symptomatic COPD. Two days after familiarization with testing procedures, patients were randomly assigned to receive either two puffs (42 µg) of salmeterol and two puffs of placebo inhaler, or two puffs (36 µg) of ipratropium from each of two inhalers (total, 72 µg). Two days later, patients received the alternative medication. During exercise at 60% of peak oxygen consumption patients rated dyspnoea and performed inspiratory capacity manoeuvres each minute.

Forced expiratory volume in one second was 1.13±0.48 L (37±13% predicted). Dyspnoea ratings were similar for salmeterol and ipratropium at 1 and 6 h. Inspiratory capacity was similar for salmeterol and ipratropium at 1 h, but significantly higher for salmeterol at 6 h (Δ=120 mL; p=0.03).

It is concluded that with the doses used, salmeterol and ipratropium provided similar dyspnoea ratings during exercise at 1 and 6 h after administration.
How should airways resistance be measured in young children: mask or mouthpiece?
Authors: Child F. , Clayton S. , Davies S. , Fryer A.A. , Jones P.W. , Lenney W.
Published: October 2002

The reproducibility and acceptability of airways resistance measurements using the interrupter technique (MicroRint) obtained using a mouthpiece were compared with those using a face mask.

Fifty children aged 4–7 yrs performed four sets of sixRintmeasurements; two using a mouthpiece and two using a face mask with integral mouthpiece.

Complete data were obtained from 45 (90%) children using the mouthpiece and 43 (86%) children using the mask. The two methods were equally repeatable with comparable intraclass correlation coefficients (ICC) and coefficients of variation. MeanRintvalues obtained using the mouthpiece were significantly lower than those using the face mask ((mean±sd) mouthpiece=0.81±0.18 kPa·L−1·s, mask=0.88±0.24 kPa·L−1·s p=0.0002). Although the mean paired differences between the two methods were small (0.07 kPa·L−1·s), the ICC and limits of agreement confirmed that the two methods could not be used interchangeably. Sixty-seven per cent of children preferred the face mask but this was more time-consuming (p=0.03). Children did not produce more repeatable results using their preferred method, nor did they improve with practice.

Repeatable airway resistance measurements using the interrupter technique can be obtained from young children using either a mouthpiece or a face mask, but there are significant clinical and statistical differences between the results obtained.
High prevalence of asthma in five remote indigenous communities in Australia
Authors: Valery P.C. , Chang A.B. , Shibasaki S. , Gibson O. , Purdie D.M. , Shannon C. , Masters I.B.
Published: October 2002

Data on the prevalence of asthma in children residing in remote indigenous communities in Australia are sparse, despite the many reports of high prevalence in nonindigenous children of this country. Two previous Australian studies have had poor participation rates, limiting interpretation of their results.

A study of children in the Torres Strait and Northern Peninsula Area of Australia was conducted to document the prevalence of asthma symptoms. Five indigenous communities were randomly selected and trained interviewers, who were local indigenous health workers, recruited participants using a house-by-house approach. Information was collected by a structured face-to-face interview based on a standardized questionnaire constructed from the protocol International Study of Asthma and Allergy in Childhood; 1,650 children were included in the study with a 98% response rate.

Overall, the prevalence of self-reported ever wheezing was 21%; 12% reported wheezing in the previous year; and 16% reported ever having asthma. There was significant variation in the prevalence of asthma symptoms between communities.

It is concluded that there are significant intercommunity variations in the prevalence of asthma symptoms in remote communities and that the prevalence in these communities is as high as in nonindigenous groups.
EGTA treatment of human airwaysin vitrounmasks M1/MUC5AC mucin in submucosal glands
Authors: Roger P. , Gascard J-P. , Bara J. , Dulmet E. , Brink C.
Published: October 2002

Mucin staining can be used to evaluate secretory activity of human airways. However, mucin epitopes may be masked by physicochemical properties of the secretions. The aim of this investigation was to examine the effects of the calcium chelator, ethyleneglycol-bis-(β-aminoethylether)-N, N, N′, N′-tetraacetic acid (EGTA) on the detection of M1/MUC5AC mucin in isolated human bronchial preparations.

Immunohistochemical investigation and immunoradiometric assays with anti-M1 monoclonal antibodies (Mabs) were used to detect M1/MUC5AC mucin derived from bronchial preparations with an intact surface epithelium, or in tissues where the epithelium had been removed (rubbed preparations).

The Mabs labelled both epithelial goblet cells and submucosal glandular cells in EGTA (4 mM)-exposed bronchial preparations, while only goblet cells were stained in EGTA (0.4 mM)-exposed tissues. The quantities of M1/MUC5AC mucin detected in either the bronchial fluids derived from EGTA (4 mM)-exposed intact and rubbed preparations or in bronchial fluids treated with EGTA (4 mM) were significantly increased by two-fold when compared with untreated control values (p<0.001). In addition, lactate dehydrogenase (LDH) activity and protein measurements were unaltered during exposure of human airways to EGTA (4 mM) suggesting that this treatment did not affect tissue viability.

These results provide evidence that ethyleneglycol-bis-(β-aminoethylether)-N, N, N′, N′-tetraacetic acid (4 mM) facilitates the detection of M1/MUC5AC mucin by altering the physicochemical properties of respiratory mucin, thereby exposing epitopes with which anti-M1 monoclonal antibodies are reactive. This will allow more accurate measurement of secretory activity in human airwaysin vitro.
Small airways diseases: detection and insights with computed tomography
Authors: Hansell D.M.
Published: October 2002

Diseases affecting the small airways are difficult to detect by traditional diagnostic tests. Widespread involvement is needed before symptoms and abnormalities on pulmonary function testing or chest radiography become apparent. Obstruction of the bronchioles may be detected indirectly by computed tomography (CT) because regional under-ventilation results in reduced perfusion which in turn is shown as a mosaic attenuation pattern of the lung parenchyma. When there is inflammation of the bronchioles with accompanying exudate, the airways may become directly visible on CT, for example in cases of diffuse panbronchiolitis.

Quantification of the various morphological features of small airways disease is possible from CT images and this increased precision has aided investigations of structure/function relationships.

An understanding of the pathology and microscopic distribution of disease in relation to the airways allows some prediction of the likely computed tomography appearances in this wide spectrum of conditions, and thus helps to refine the differential diagnosis.
Imaging of pneumonia: trends and algorithms
Authors: Franquet T.
Published: October 2002

Pneumonia is one of the major infectious diseases responsible for significant morbidity and mortality throughout the world. Imaging plays a crucial role in the detection and management of patients with pneumonia.

This review article discusses the different imaging methods used in the diagnosis and management of suspected pulmonary infections. The imaging examination should always begin with conventional radiography. When the results of routine radiography are inconclusive, computed tomography is mandatory. A combination of pattern recognition with knowledge of the clinical setting is the best approach to the pulmonary infectious processes.

A specific pattern of involvement can suggest a likely diagnosis in many instances. In acquired immune deficiency syndrome patients, diffuse ground-glass and interstitial infiltrates are most commonly present inPneumocystis cariniipneumonia whereas in the nonimmunosuppressed patients, a segmental lobar infiltrate is suggestive of a bacterial pneumonia. Round pneumonia is most often encountered in children than adults and is most often caused byStreptococcus pneumoniae. Different combinations of parenchymal and pleural abnormalities may be suggestive for additional diagnoses.

When an infectious pulmonary process is suspected, knowledge of the varied radiographic manifestations will narrow the differential diagnosis, helping to direct additional diagnostic measures, and serving as an ideal tool for follow-up examinations.