bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary pulmonary lymphangiectasia in infancy and childhood
Authors: Barker P.M. , Esther C.R. , Fordham L.A. , Maygarden S.J. , Funkhouser W.K. 
Published: September 2004

Primary pulmonary lymphangiectasia (PPL) is a rare disorder of unknown aetiology characterised by dilatation of the pulmonary lymphatics. PPL is widely reported to have a poor prognosis in the neonatal period and little is known about the clinical features of patients who survive the newborn period.The current authors report the outcome in nine patients diagnosed in infancy with PPL over a 15-yr period at a single university-based hospital clinic and followed for a median of 6 yrs.Although all of the patients initially experienced respiratory distress, respiratory symptoms improved in most patients after infancy and were notably better by the age of 6 yrs. Many patients had poor weight gain in the first years of life, which eventually improved. Radiological scans showed progressive resolution of neonatal infiltrates, but were characterised by hyperinflation and increased interstitial markings in older children. Most patients had evidence of bronchitis and grew pathogenic organisms from quantitative bronchoalveolar lavage culture. Pulmonary function tests showed predominantly obstructive disease that did not deteriorate over time.In conclusion, these results suggest that primary pulmonary lymphangiectasia does not have as dismal a prognosis as previously described and symptoms and clinical findings improve after the first year of life.
BMPR2 mutations in pulmonary arterial hypertension with congenital heart disease
Authors: Roberts K.E. , McElroy J.J. , Wong W.P.K. , Yen E. , Widlitz A. , Barst R.J. , Knowles J.A. , Morse J.H. 
Published: September 2004

The aim of the present study was to determine if patients with both pulmonary arterial hypertension (PAH), due to pulmonary vascular obstructive disease, and congenital heart defects (CHD), have mutations in the gene encoding bone morphogenetic protein receptor (BMPR)-2.The BMPR2 gene was screened in two cohorts: 40 adults and 66 children with PAH/CHD. CHDs were patent ductus arteriosus, atrial and ventricular septal defects, partial anomalous pulmonary venous return, transposition of the great arteries, atrioventicular canal, and rare lesions with systemic-to-pulmonary shunts.Six novel missense BMPR2 mutations were found in three out of four adults with complete type C atrioventricular canals and in three children. One child had an atrial septal defect and patent ductus arteriosus; one had an atrial septal defect, patent ductus arteriosus and partial anomalous pulmonary venous return; and one had an aortopulmonary window and a ventricular septal defect.Bone morphogenetic protein receptor 2 mutations were found in 6% of a mixed cohort of adults and children with pulmonary arterial hypertension/congenital heart defects. The current findings compliment recent reports in mouse models implicating members of the bone morphogenetic protein/transforming growth factor-β pathway inducing cardiac anomalies analogous to human atrioventricular canals, septal defects and conotruncal congenital heart defects. The small number of patients studied and the ascertainment bias inherent in selecting for pulmonary arterial hypertension require further investigation.
Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2
Authors: Humbert M. , Barst R.J. , Robbins I.M. , Channick R.N. , Galiè N. , Boonstra A. , Rubin L.J. , Horn E.M. , Manes A. , Simonneau G. 
Published: September 2004

The efficacy and safety of combining bosentan, an orally active dual endothelin receptor antagonist and epoprostenol, a continuously infused prostaglandin, in the treatment of pulmonary arterial hypertension (PAH) was investigated.In this double-blind, placebo-controlled prospective study, 33 patients with PAH started epoprostenol treatment (2 ng·kg−1min−1starting dose, up to 14±2 ng·kg−1min−1at week 16) and were randomised for 16 weeks in a 2:1 ratio to bosentan (62.5 mgb.i.dfor 4 weeks then 125 mgb.i.d) or placebo.Haemodynamics, exercise capacity and functional class improved in both groups at week 16. In the combination treatment group, there was a trend for a greater (although nonsignificant) improvement in all measured haemodynamic parameters. There were four withdrawals in the bosentan/epoprostenol group (two deaths due to cardiopulmonary failure, one clinical worsening, and one adverse event) and one withdrawal in the placebo/epoprostenol group (adverse event).This study showed a trend but no statistical significance towards haemodynamics or clinical improvement due to the combination of bosentan and epoprostenol therapy in patients with pulmonary arterial hypertension. Several cases of early and late major complications were reported. Additional information is needed to evaluate the risk/benefit ratio of combined bosentan-epoprostenol therapy in pulmonary arterial hypertension.
Inhaled IFN-γ for persistent nontuberculous mycobacterial pulmonary disease due to functional IFN-γ deficiency
Authors: Hallstrand T.S. , Ochs H.D. , Zhu Q. , Liles W.C. 
Published: September 2004

Pulmonary infection with nontuberculous mycobacteria (NTM) in previously healthy human immunodeficiency virus-seronegative individuals is difficult to treat. Recently, functional interferon (IFN)-γ deficiency has been identified in individuals susceptible to this disease. Treatment with inhaled IFN-γ for NTM pulmonary disease associated with functional IFN-γ deficiency has not been previously described.In this study, the IFN-γ pathway was characterised in an individual who had progressive NTM pulmonary infection, despite appropriate multidrug antibiotic therapy, and 10 healthy controls. Levels of IFN-γ and tumour necrosis factor-α in whole blood were assessed before and after incubation with lipopolysaccharide, heat-killedEscherichia coli, heat-killedStaphylococcus aureusand phorbol myristate acetate/ionomycin. The coding regions of interleukin (IL)-12, IL-18 and the IL-12 receptor were sequenced using nested primers. IFN-γ1b (100 µg·dose−1) was administered to the affected individual by ultrasonic nebuliser 3 days·week−1for 3 months.In vitrowhole blood production of IFN-γ with and without physiological stimuli was consistent with functional IFN-γ deficiency in the affected individual. There was no evidence of mutation in the coding regions of IL-12p35, IL-12p40, IL-12Rβ1 and IL-18 in the affected individual. Treatment with inhaled IFN-γ resulted in rapid and sustained clearance of the organism from the airways and stabilisation of lung function.In conclusion, inhaled interferon-γ can be effective for the treatment of nontuberculous mycobacteria pulmonary disease associated with functional interferon-γ deficiency.
Safety of research bronchoscopy, biopsy and bronchoalveolar lavage in asthma: Table 1—
Authors: Elston W.J. , Whittaker A.J. , Khan L.N. , Flood-Page P. , Ramsay C. , Jeffery P.K. , Barnes N.C. 
Published: September 2004

Bronchoscopy with endobronchial biopsy (EBB) and/or bronchoalveolar lavage (BAL) has become an important research tool in asthma. A recent report has suggested audit and reporting of the safety of these procedures.A total of 159 asthmatic patients (84 males, 75 females), aged 18–52 (median 27) yrs, forced expiratory volume in one second 53–120 (median 88) % predicted, underwent 273bronchoscopies in six clinical research studies. On 228 occasions, EBB and BAL were performed and, on 45 occasions, EBB was performed alone. On 48 occasions, bronchoscopy was performed 24 h post-allergen challenge.Adverse events occurred on 34 out of 273 occasions, none of which were following allergen challenge. Post-EBB and BAL, four patients developed pleuritic chest pain, shortness of breath and fever. A further two patients experienced pleuritic chest pain alone post-EBB/BAL. Bronchospasm or worsening of asthma symptoms occurred on 14 occasions, 13 post-EBB/BAL and on one occasion post-EBB alone. Fever/flu-like symptoms were reported on nine occasions following EBB and BAL. One subject had haemoptysis post-EBB/BAL, but required no intervention.In conclusion, bronchoscopy, endobronchial biopsy and bronchoalveolar lavage can be performed safely in asthmatic patients. Most of the complications were seen where bronchoalveolar lavage and endobronchial biopsy were both performed, suggesting that bronchoalveolar lavage accounts for most of the adverse events.
European framework to decrease the burden of TB/HIV
Authors: de Colombani P. , Banatvala N. , Zaleskis R. , Maher D. 
Published: September 2004

Tuberculosis (TB) in Europe is declining in countries in western and central Europe, but the burden is still high and increasing in eastern Europe. HIV/AIDS is increasing dramatically in eastern Europe. HIV-related tuberculosis (TB/HIV) morbidity and mortality are expected to accelerate significantly in the future.This framework aims to guide European countries in developing their national plan for reducing TB/HIV morbidity and mortality. It results from an extensive consultation process undertaken by the World Health Organization Regional Office for Europe and by those responsible for HIV/AIDS and TB programmes and their partners. It builds on strategies developed globally and in Europe for TB control and for HIV/AIDS prevention and care.This framework sets out the rationale for effective collaboration between HIV/AIDS and tuberculosis national programmes. It identifies five strategic components (political commitment, collaborative prevention, intensified case-finding, coordinated treatment and strengthened surveillance) and eight key operations (central coordination, policy development, surveillance, training, supply management, service delivery, health promotion and research).
Post-genome respiratory epidemiology: a multidisciplinary challenge
Authors: Kauffmann F. ,   the Post Genome Respiratory Epidemiology group
Published: September 2004

The introduction of genetic approaches in respiratory epidemiology is novel for most epidemiologists, and the post-genome phase poses new challenges. After describing specific questions pertinent to the field of asthma and chronic obstructive pulmonary disease, two main methodological aspects regarding technological and scientific advances are presented in this review. The first one concerns biological aspects in the genome and post-genome phases,i.e.how to study the genome, the transcriptome and the proteome. The second area concerns genetic epidemiology, considering design (case control and family based) and statistical analytical issues. Key aspects are large sample size, good phenotyping and the consideration of environment-by-gene interaction according to windows of opportunity.Needs that have been identified include the following. 1) Networking for setting standards in the field and access to sufficiently large samples. 2) Multidisciplinarity; the collaboration of epidemiologists, clinicians, geneticists and specialists in bioinformatics, in addition to specialists in disciplines less familiar to epidemiologists, to be prepared for new phenotypic characterisations based on transcriptome and proteome. 3) Training in genetic analytical techniques for some respiratory epidemiologists, as well as in respiratory epidemiology for some genetic epidemiologists.Implications for research, considering ethical aspects, public health aspects and organisational aspects in the field of genetic and environmental respiratory epidemiology also need to be addressed.
Spirometric reference equations for European females and males aged 65–85 yrs
Authors: García-Río F. , Pino J.M. , Dorgham A. , Alonso A. , Villamor J. 
Published: September 2004

The aim of this study was to describe spirometric reference equations for healthy never-smoking European adults aged 65–85 yrs and to compare the predicted values of this sample with those from other studies including middle-aged and/or older adults.Reference equations and normal ranges for forced expiratory volume in one second (FEV1), forced vital capacity (FVC), forced expiratory volume in six seconds (FEV6), FEV1/FVC ratio and FEV1/FEV6ratio were derived from a healthy subgroup of 458 subjects aged 65–85 yrs. Spirometry examinations followed the 1994 American Thoracic Society recommendations and the quality of the data was continuously monitored and maintained. Reference values and lower limits of normal were derived using a piecewise polynomial model with age and height as predictors.The reference values of FEV1and FVC from the present study were higher than those given by prediction equations from the European Community for Coal and Steel. By contrast, use of prediction equations from Caucasian-American elderly subjects (Cardiovascular Health Study) consistently overpredicted FVC and FEV1in females by 8.5 and 2.1%, respectively. In males, equations from the Cardiovascular Health Study overpredicted FVC by 2.8%, whilst underpredicting FEV1by 2.5%.In conclusion, these results underscore the importance of using prediction equations appropriate to the origin, age and height characteristics of the subjects being studied.
Regulation of interleukin-1β and interleukin-1β inhibitor release by human airway epithelial cells
Authors: Yang Y. , Bin W. , Aksoy M.O. , Kelsen S.G. 
Published: September 2004

In asthma, human airway epithelial cells (HAECs) regulate the intensity of mucosal inflammation, in part, by releasing the pro-inflammatory cytokine interleukin (IL)-1β. However, the IL-1β inhibitors, IL-1 receptor antagonist (IL-1RA) and soluble IL-1 receptor type II (sIL-1RII), regulate IL-1β bioactivity. In order to better understand the control of IL-1β activity in the airway mucosa, the role(s) of tumour necrosis factor (TNF)-α, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in the release of IL-1β and its inhibitors by cultured HAECs were examined.HAECs were treated with TNF-α (2–200 ng·mL−1), dibutyryl cAMP (0.01–1 mM), 8-bromo-cGMP (0.01–1 mM) or vehicle for 24 h, and cytokine levels in the HAEC-conditioned medium were measured by enzyme-linked immunosorbent assay.HAECs produced IL-1β, IL-1RA and sIL-1RII constitutively, but the inhibitor concentrations greatly exceeded that of IL-1β (by ∼100- and ∼550-fold, respectively). TNF-α dose-dependently increased the levels of all IL-1β cytokine family members. However, over the range of TNF-α concentrations studied, IL-1β concentration increased more than those of its inhibitors. cAMP increased constitutive and TNF-α-stimulated IL-1β release but reduced that of sIL-1RII. In contrast, cGMP had no effect on IL-1β but reduced IL-1RA and sIL-1RII release.Under basal conditions, the disproportionate release of inhibitors relative to interleukin-1β by human airway epithelial cells probably prevents interleukin-1β-mediated biological effects. Tumour necrosis factor-α, cyclic adenosine monophosphate and cyclic guanosine monophosphate may potentiate mucosal inflammation by increasing interleukin-1β levels relative to those of its inhibitors in the airway mucosa.
Phase II of the International Study of Asthma and Allergies in Childhood (ISAAC II): rationale and methods
Authors: Weiland S.K. , Björkstén B. , Brunekreef B. , Cookson W.O.C. , von Mutius E. , Strachan D.P. ,   the International Study of Asthma and Allergies in Childhood Phase II Study Group
Published: September 2004

International comparative studies, investigating whether disease incidence or prevalence rates differ between populations and, if so, which factors explain the observed differences, have made important contributions to the understanding of disease aetiology in many areas. In Phase I of the International Study of Asthma and Allergies in Childhood (ISAAC), the prevalence rates of symptoms of asthma, allergic rhinitis and atopic eczema in 13–14-yr-olds, assessed by standardised questionnaires, were found to differ >20-fold between the 155 study centres around the world. Phase II of ISAAC aims to identify determinants of these differences by studying informative populations.A detailed study protocol was developed for use in community-based random samples of children aged 9–11 yrs. The study modules include standardised questionnaires with detailed questions on the occurrence and severity of symptoms of asthma, allergic rhinitis and atopic eczema, their clinical management, and a broad range of previous and current exposure conditions. In addition, standardised protocols were applied for examination of flexural dermatitis, skin-prick testing, bronchial challenge with hypertonic saline, blood sampling for immunoglobulin E analyses and genotyping, and dust sampling for assessment of indoor exposures to allergens and endotoxin.To date, ISAAC II field work had been completed or started in 30 study centres in 22 countries.The majority of centres are in countries that participated in International Study of Asthma and Allergies in Childhood Phase I and reflect almost the full range of the observed variability in Phase I prevalence rates.
Exercise-induced flow limitation, dynamic hyperinflation and exercise capacity in patients with bronchial asthma
Authors: Kosmas E.N. , Milic-Emili J. , Polychronaki A. , Dimitroulis I. , Retsou S. , Gaga M. , Koutsoukou A. , Roussos Ch. , Koulouris N.G. 
Published: September 2004

It is known that, in stable asthmatics at rest, tidal expiratory flow limitation (EFL) and dynamic hyperinflation (DH) are seldom present. This study investigated whether stable asthmatics develop tidal EFL and DH during exercise with concurrent limitation of maximal exercise work rate (WRmax).A total of 20 asthmatics in a stable condition and aged 32±13 yrs (mean±sd) with a forced expiratory volume in one second (FEV1) of 101±21% of the predicted value were studied. Only three patients exhibited an FEV1below the normal limits. On a first visit, patients performed a symptom-limited incremental (20 W·min−1) bicycle exercise test. On the second visit, the occurrence of EFL (using the negative expiratory pressure technique) and DH (viareduction in inspiratory capacity) were assessed at rest and when cycling at 33, 66 and 90% of their predetermined WRmax. FEV1was measured to detect exercise-induced asthma, 5 and 15 min after stopping exercise at 90% WRmax.Only one patient showed EFL at rest, whereas 13 showed EFL and DH during exercise. In these 13 asthmatics, exercise capacity was significantly reduced (WRmax75±9% pred) compared to the seven non-EFL patients (WRmax95±13% pred). Moreover, a significant correlation of WRmax(% pred) to the change in inspiratory capacity (percentage of resting value) from rest to 90% WRmaxwas found. Tidal EFL during exercise was not associated with exercise-induced asthma, which was detected in only three patients.In conclusion, tidal expiratory flow limitation and dynamic hyperinflation during exercise are common in stable asthmatics with normal spirometric results and without exercise-induced asthma, and may contribute to reduction in exercise capacity.
Endobronchial brachytherapy in the treatment of malignant lung tumours
Authors: Escobar-Sacristán J.A. , Granda-Orive J.I. , Gutiérrez Jiménez T. , Delgado J.M. , Rodero Baños A. , Saez Valls R. 
Published: September 2004

A prospective study was made to assess the short-term clinical and endoscopic response to high-dose-rate endobronchial brachytherapy (HDREB) in patients with malignant endobronchial tumours.From July 1995 to May 2000, 288 HDREB sessions were carried out on 81 patients. The mean patient age was 61.57 yrs (range 34–82); males were predominant (87.65%). Tumours were primary in 76 patients (93.82%) and metastatic in five patients (6.18%). The inclusion criteria were malignant endobronchial tumour and either palliative treatment for incurable disease or intent-to-cure treatment for residual malignancy on the bronchial resection surface after surgery or an inoperable tumour. The exclusion criteria were as follows: impediments to catheter placement, expected survival <2 months, Karnofsky index <60, or absence of informed consent. The clinical response of a symptom was categorised as complete (disappearance of the symptom), partial (less than complete) or absent. The endoscopic response was considered to be complete if lesions disappeared and biopsy findings remained negative 1 month after the last radiation session; partial if lesions improved to some extent, but the biopsy findings were positive; and absent if there was no change in relation to baseline. The technique consisted of delivering high-dose irradiation from an Ir192source to a target volume using one or two endobronchial catheters inserted under optical or video bronchoscopic guidance. Four sessions were scheduled at weekly intervals and 500 cGy was applied per session over a length of 1–9 cm, measured 0.5–1 cm from the centre of the source.In total, 85% of the symptoms analysed (haemoptysis, cough, dyspnoea, expectoration, and stridor) disappeared with HDREB, which was categorised as a complete response. The endoscopic response was complete in 56.79% of patients, partial or less than complete in 40.74% and absent in 2.46%. One major complication occurred (bronchial fistula 1.2%), but no lethal haemoptysis. Minor complications (pneumonitis, bronchospasm and bronchial stenosis) each occurred in one patient (1.2%).High-dose-rate endobronchial brachytherapy is a good palliative treatment for endoluminal lung neoplasms, effectively alleviating symptoms and endoscopic evidence in many cases with an acceptable rate of complications. High-dose-rate endobronchial brachytherapy can be carried out as an intent-to-cure procedure in highly selected cases.
Smoking cessation improves both direct and indirect airway hyperresponsiveness in COPD
Authors: Willemse B.W.M. , ten Hacken N.H.T. , Rutgers B. , Lesman-Leegte I.G.A.T. , Timens W. , Postma D.S. 
Published: September 2004

Smoking induces chronic obstructive pulmonary disease (COPD) and is associated with airway inflammation and airway hyperresponsiveness (AHR). It has not been studied in COPD whether direct (methacholine) and indirect (adenosine-5'-monophosphate (AMP)) stimuli are associated with airway inflammation and neither whether smoking cessation improves these features.The current authors cross-sectionally investigated the relationship of AHR to methacholine and AMP with lung function and inflammatory cells in the sputum of 33 smokers with COPD. In addition, changes in these parameters were prospectively assessed in 14 smokers who successfully quit smoking for 1 yr.The presence of AHR to both methacholine and AMP was associated with lower lung function, but not with sputum inflammation. AHR to methacholine and AMP improved significantly after a 1-yr smoking cessation, yet this was unrelated to changes in sputum cell counts. The numbers of neutrophils and epithelial cells significantly increased with smoking cessation.Both direct and indirect airway hyperresponsiveness are associated with lower lung function, but not with sputum inflammation in chronic obstructive pulmonary disease. Interestingly, 1-yr smoking cessation improved both direct and indirect airway hyperresponsiveness, yet without a significant association with changes in lung function or sputum inflammation. Thus, other factors are likely to induce these improvements,e.g.a reduction in stimulation of irritant receptors, airway wall changes or mucus hypersecretion.