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Showing papers in "European Respiratory Journal in 2005"


Journal ArticleDOI
TL;DR: This research presents a novel and scalable approach called “Standardation of LUNG FUNCTION TESTing” that combines “situational awareness” and “machine learning” to solve the challenge of integrating nanofiltration into the energy system.
Abstract: [⇓][1] SERIES “ATS/ERS TASK FORCE: STANDARDISATION OF LUNG FUNCTION TESTING” Edited by V. Brusasco, R. Crapo and G. Viegi Number 2 in this Series [1]: #F13

13,426 citations


Journal ArticleDOI
TL;DR: This section is written to provide guidance in interpreting pulmonary function tests (PFTs) to medical directors of hospital-based laboratories that perform PFTs, and physicians who are responsible for interpreting the results of PFTS most commonly ordered for clinical purposes.
Abstract: SERIES “ATS/ERS TASK FORCE: STANDARDISATION OF LUNG FUNCTION TESTING” Edited by V. Brusasco, R. Crapo and G. Viegi Number 5 in this Series This section is written to provide guidance in interpreting pulmonary function tests (PFTs) to medical directors of hospital-based laboratories that perform PFTs, and physicians who are responsible for interpreting the results of PFTs most commonly ordered for clinical purposes. Specifically, this section addresses the interpretation of spirometry, bronchodilator response, carbon monoxide diffusing capacity ( D L,CO) and lung volumes. The sources of variation in lung function testing and technical aspects of spirometry, lung volume measurements and D L,CO measurement have been considered in other documents published in this series of Task Force reports 1–4 and in the American Thoracic Society (ATS) interpretative strategies document 5. An interpretation begins with a review and comment on test quality. Tests that are less than optimal may still contain useful information, but interpreters should identify the problems and the direction and magnitude of the potential errors. Omitting the quality review and relying only on numerical results for clinical decision making is a common mistake, which is more easily made by those who are dependent upon computer interpretations. Once quality has been assured, the next steps involve a series of comparisons 6 that include comparisons of test results with reference values based on healthy subjects 5, comparisons with known disease or abnormal physiological patterns ( i.e. obstruction and restriction), and comparisons with self, a rather formal term for evaluating change in an individual patient. A final step in the lung function report is to answer the clinical question that prompted the test. Poor choices made during these preparatory steps increase the risk of misclassification, i.e. a falsely negative or falsely positive interpretation for a lung function abnormality or a change …

5,078 citations


Journal ArticleDOI
TL;DR: Findings, i.e. that as-needed AO provided for a period of 3 months had no effect on quality of life and walked distance, are against the stream of current guidelines.
Abstract: I. Garcia-Talavera's reaction to the results of our trial of ambulatory oxygen (AO) in oxygen-dependent chronic obstructive pulmonary disease (COPD) is of no surprise to us. We realise that our findings, i.e. that as-needed AO provided for a period of 3 months had no effect on quality of life and walked distance 1, are against the stream of current guidelines ( i.e. that active patients receiving long-term oxygen therapy should have both stationary and mobile systems of oxygen delivery) 2 …

3,097 citations


Journal ArticleDOI
TL;DR: This research presents a novel and scalable approach called “Standardation of LUNG FUNCTION TESTing” that combines “situational awareness” and “machine learning” to solve the challenge of integrating nanofiltration into the energy system.
Abstract: [⇓][1] SERIES “ATS/ERS TASK FORCE: STANDARDISATION OF LUNG FUNCTION TESTING” Edited by V. Brusasco, R. Crapo and G. Viegi Number 3 in this Series [1]: #F7

2,414 citations


Journal ArticleDOI
TL;DR: This research presents a novel and scalable approach called “Standardation of LUNG FUNCTION TESTing” that combines “situational awareness” and “machine learning” to solve the challenge of integrating nanofiltration into the energy system.
Abstract: [⇓][1] SERIES “ATS/ERS TASK FORCE: STANDARDISATION OF LUNG FUNCTION TESTING” Edited by V. Brusasco, R. Crapo and G. Viegi Number 4 in this Series [1]: #F4

2,013 citations


Journal ArticleDOI
TL;DR: This statement contains details about procedures that are common for many methods of lung function testing and, hence, are presented on their own and represent a change towards bringing this document in line with the ISO.
Abstract: SERIES “ATS/ERS TASK FORCE: STANDARDISATION OF LUNG FUNCTION TESTING” Edited by V. Brusasco, R. Crapo and G. Viegi Number 1 in this Series ⇓In preparing the joint statements on lung function testing for the American Thoracic Society (ATS) and the European Respiratory Society (ERS), it was agreed by the working party that the format of the statements should be modified so that they were easier to use by both technical and clinical staff. This statement contains details about procedures that are common for many methods of lung function testing and, hence, are presented on their own. A list of abbreviations used in all the documents is also included as part of this statement. All terms and abbreviations used here are based on a report of the American College of Chest Physicians/ATS Joint Committee on Pulmonary Nomenclature 1. The metrology definitions agreed by the International Standards Organization (ISO) are recommended 2 and some important terms are defined as follows. Accuracy is the closeness of agreement between the result of a measurement and the conventional true value. Repeatability is the closeness of agreement between the results of successive measurements of the same item carried out, subject to all of the following conditions: same method, same observer, same instrument, same location, same condition of use, and repeated over a short space of time. In previous documents, the term reproducibility was used in this context, and this represents a change towards bringing this document in line with the ISO. Reproducibility is the closeness of agreement of the results of successive measurements of the same item where the individual measurements are carried out with changed conditions, such as: method of measurement, observer, instrument, location, conditions of use, and time. Thus, if a technician tests a subject several times, this is looking at the …

1,797 citations


Journal ArticleDOI
TL;DR: The aim of the American Thoracic Society/European Respiratory Society Task Force on EBC was to identify the important methodological issues surrounding EBC collection and assay, to provide recommendations for the measurements and to highlight areas where further research is required.
Abstract: Collection of exhaled breath condensate (EBC) is a noninvasive method for obtaining samples from the lungs. EBC contains large number of mediators including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, nitrogen oxides, peptides and cytokines. Concentrations of these mediators are influenced by lung diseases and modulated by therapeutic interventions. Similarly EBC pH also changes in respiratory diseases. The aim of the American Thoracic Society/European Respiratory Society Task Force on EBC was to identify the important methodological issues surrounding EBC collection and assay, to provide recommendations for the measurements and to highlight areas where further research is required. Based on the currently available evidence and the consensus of the expert panel for EBC collection, the following general recommendations were put together for oral sample collection: collect during tidal breathing using a noseclip and a saliva trap; define cooling temperature and collection time (10 min is generally sufficient to obtain 1-2 mL of sample and well tolerated by patients); use inert material for condenser; do not use resistor and do not use filter between the subject and the condenser. These are only general recommendations and certain circumstances may dictate variation from them. Important areas for future research involve: ascertaining mechanisms and site of exhaled breath condensate particle formation; determination of dilution markers; improving reproducibility; employment of EBC in longitudinal studies; and determining the utility of exhaled breath condensate measures for the management of individual patients. These studies are required before recommending this technique for use in clinical practice.

1,202 citations


Journal ArticleDOI
TL;DR: The guidelines cover the breadth of adult community-acquired respiratory infection, including prevention (both vaccine- and nonvaccine-related), infections in the community and infections in those admitted to hospital, including pneumonia, exacerbations of chronic obstructive pulmonary disease (COPD) and exacerbation of bronchiectasis.
Abstract: Guidelines for the management of adult lower respiratory tract infections (LRTIs) were first published by a Task Force of the European Respiratory Society (ERS) in 1998 [1]. In 2005, a completely revised version was produced, this time by a joint Task Force of the ERS and the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) [2]. They used up-to-date methodology for guideline development, including a transparent and objective systematic literature search strategy, and evidence and recommendation grading [2]. Now, 6 yrs later, a joint Task Force of the two Societies, using the same methodology as in 2005, has produced a further update of these guidelines incorporating publications through to May 2010. The Task Force included an epidemiologist with expertise in guideline methodology and experts in the specialty areas relevant to LRTI management, including general practice, microbiology, infectious diseases, respiratory medicine, intensive care and public health. A short version of the guidelines containing only the recommendations has now been published in Clinical Microbiology and Infection [3], with more detailed versions available on each Society’s website. The guidelines cover the breadth of adult community-acquired respiratory infection, including prevention (both vaccine- and nonvaccine-related), infections in the community and infections in those admitted to hospital, including pneumonia, exacerbations of chronic obstructive pulmonary disease (COPD) and exacerbations of bronchiectasis. The …

904 citations


Journal ArticleDOI
TL;DR: The authors individualise the computer tomography-defined syndrome of combined pulmonary fibrosis and emphysema characterised by subnormal spirometry, severe impairment of gas exchange, high prevalence of pulmonary hypertension, and poor survival.
Abstract: The syndrome resulting from combined pulmonary fibrosis and emphysema has not been comprehensively described. The current authors conducted a retrospective study of 61 patients with both emphysema of the upper zones and diffuse parenchymal lung disease with fibrosis of the lower zones of the lungs on chest computed tomography. Patients (all smokers) included 60 males and one female, with a mean age of 65 yrs. Dyspnoea on exertion was present in all patients. Basal crackles were found in 87% and finger clubbing in 43%. Pulmonary function tests were as follows (meaniSD): total lung capacity 88%i17, forced vital capacity (FVC) 88%i18, forced expiratory volume in one second (FEV1) 80%i21 (% predicted), FEV1/FVC 69%i13, carbon monoxide diffusion capacity of the lung 37%i16 (% predicted), carbon monoxide transfer coefficient 46%i19. Pulmonary hypertension was present in 47% of patients at diagnosis, and 55% during follow-up. Patients were followed for a mean of 2.1i2.8 yrs from diagnosis. Survival was 87.5% at 2 yrs and 54.6% at 5 yrs, with a median of 6.1 yrs. The presence of pulmonary hypertension at diagnosis was a critical determinant of prognosis. The authors hereby individualise the computer tomography-defined syndrome of combined pulmonary fibrosis and emphysema characterised by subnormal spirometry, severe impairment of gas exchange, high prevalence of pulmonary hypertension, and poor survival.

857 citations


Journal ArticleDOI
TL;DR: It is concluded that special consideration should be given to studying and regulating coarse particles separately from fine particles, suggesting that coarse PM may lead to adverse responses in the lungs triggering processes leading to hospital admissions.
Abstract: Studies on health effects of airborne particulate matter (PM) have traditionally focused on particles ,10 mm in diameter (PM10) or particles ,2.5 mm in diameter (PM2.5). The coarse fraction of PM10, particles .2.5 mm, has only been studied recently. These particles have different sources and composition compared with PM2.5. This paper is based on a systematic review of studies that have analysed fine and coarse PM jointly and examines the epidemiological evidence for effects of coarse particles on health. Time series studies relating ambient PM to mortality have in some places provided evidence of an independent effect of coarse PM on daily mortality, but in most urban areas, the evidence is stronger for fine particles. The few long-term studies of effects of coarse PM on survival do not provide any evidence of association. In studies of chronic obstructive pulmonary disease, asthma and respiratory admissions, coarse PM has a stronger or as strong short-term effect as fine PM, suggesting that coarse PM may lead to adverse responses in the lungs triggering processes leading to hospital admissions. There is also support for an association between coarse PM and cardiovascular admissions. It is concluded that special consideration should be given to studying and regulating coarse particles separately from fine particles.

822 citations


Journal ArticleDOI
TL;DR: First-line bosentan therapy was found to improve survival in patients with advanced primary pulmonary hypertension, and factors that predicted a worse outcome included World Health Organization Functional Class IV and 6-min walk distance below the median at baseline.
Abstract: Primary pulmonary hypertension (PPH) is a progressive disease with high mortality. Administration of i.v. epoprostenol has demonstrated improved exercise tolerance, haemodynamics, and survival. The orally active, dual endothelin receptor antagonist bosentan improves exercise endurance, haemodynamics, and functional class over the short term. To determine the effect of first-line bosentan therapy on survival, this study followed 169 patients with PPH treated with bosentan in two placebo-controlled trials and their extensions. Data on survival and alternative treatments were collected from September 1999 (start of the first placebo-controlled study) to December 31, 2002. Observed survival up to 36 months was reported as Kaplan-Meier estimates and compared with predicted survival as determined for each patient by the National Institutes of Health Registry formula. Kaplan-Meier survival estimates were 96% at 12 months and 89% at 24 months. In contrast, predicted survival was 69% and 57%, respectively. In addition, at the end of 12 and 24 months, 85% and 70% of patients, respectively, remained alive and on bosentan monotherapy. Factors that predicted a worse outcome included World Health Organization Functional Class IV and 6-min walk distance below the median (358 m) at baseline. First-line bosentan therapy was found to improve survival in patients with advanced primary pulmonary hypertension.

Journal ArticleDOI
TL;DR: Wide variations exist in the patterns of home mechanical ventilation provision throughout Europe and further work is needed to monitor its use and ensure equality of provision and access.
Abstract: The study was designed to assess the patterns of use of home mechanical ventilation (HMV) for patients with chronic respiratory failure across Europe. A detailed questionnaire of centre details, HMV user characteristics and equipment choices was sent to carefully identified HMV centres in 16 European countries. A total of 483 centres treating 27,118 HMV users were identified. Of these, 329 centres completed surveys between July 2001 and June 2002, representing up to 21,526 HMV users and a response rate of between 62% and 79%. The estimated prevalence of HMV in Europe was 6.6 per 100,000 people. The variation in prevalence between countries was only partially related to the median year of starting HMV services. In addition, there were marked differences between countries in the relative proportions of lung and neuromuscular patients using HMV, and the use of tracheostomies in lung and neuromuscular HMV users. Lung users were linked to a HMV duration of or =6 yrs. In conclusion, wide variations exist in the patterns of home mechanical ventilation provision throughout Europe. Further work is needed to monitor its use and ensure equality of provision and access.

Journal ArticleDOI
TL;DR: The reduction in histone deacetylase activity can be restored by theophylline, which may be able to reverse steroid resistance in chronic obstructive pulmonary disease and other inflammatory diseases.
Abstract: Inflammatory lung diseases are characterised by increased expression of multiple inflammatory genes that are regulated by proinflammatory transcription factors, such as nuclear factor-kappa B. Gene expression is regulated by acetylation of core histones through the action of coactivators, such as CREB-binding protein, with intrinsic histone acetyltransferase (HAT) activity. Conversely, gene repression is mediated via histone deacetylases (HDACs) and other corepressors. In asthma, there is an increase in HAT activity and some reduction in HDAC activity, which is restored by corticosteroid therapy. Corticosteroids switch off inflammatory genes in asthma through the inhibition of HAT activity and by the recruitment of HDAC2 to the activated inflammatory gene complex. In chronic obstructive pulmonary disease, there is a reduction in HDAC2 activity and expression, which may account for the amplified inflammation and resistance to the actions of corticosteroids. The reduction in HDAC2 may be secondary to oxidative and nitrative stress as a result of cigarette smoking and severe inflammation, and may also occur in severe asthma, smoking asthmatic patients and cystic fibrosis. Similar mechanisms may also account for the steroid resistance seen with latent adenovirus infections. The reduction in histone deacetylase activity can be restored by theophylline, which may be able to reverse steroid resistance in chronic obstructive pulmonary disease and other inflammatory diseases.

Journal ArticleDOI
TL;DR: A therapeutic approach utilising combinations of bosentan, sildenafil and inhaled iloprost in conjunction with a goal-oriented treatment strategy provides acceptable long-term results in patients with severe pulmonary arterial hypertension, and reduces the need for intravenous prostaglandin treatment and lung transplantation.
Abstract: Combination therapy may improve outcome in patients with severe pulmonary arterial hypertension (PAH). PAH patients were treated according to a goal-oriented therapeutic strategy. Patients who did not reach the treatment goals with monotherapy received combination treatment according to a predefined strategy, including bosentan, sildenafil and inhaled iloprost. Intravenous iloprost and lung transplantation were reserved for treatment failures. End points were overall survival, transplantation-free survival, and survival free from transplantation and intravenous prostanoid treatment. Between January 2002 and December 2004, 123 consecutive patients with PAH were treated according to the novel approach. Survival at 1, 2 and 3 yrs was 93.0, 83.1 and 79.9%, respectively, which was significantly better than the survival of a historical control group, as well as the expected survival. Compared to the historical control group, the use of combination treatment also significantly improved the combined end point of death, lung transplantation and need for intravenous iloprost treatment. In conclusion, a therapeutic approach utilising combinations of bosentan, sildenafil and inhaled iloprost in conjunction with a goal-oriented treatment strategy provides acceptable long-term results in patients with severe pulmonary arterial hypertension, and reduces the need for intravenous prostaglandin treatment and lung transplantation.

Journal ArticleDOI
TL;DR: The results show that recurrent exacerbations in asthma are associated with specific co-morbid factors that are easy to detect and that are treatable and Therapeutic interventions aimed at correcting these factors are likely to reduce morbidity and medical expenditure in patients with asthma.
Abstract: Recurrent exacerbations are a major cause of morbidity and medical expenditure in patients with asthma. Various exogenous and endogenous factors are thought to influence the level of asthma control, but systematical data on the involvement of these factors in the recurrence of asthma exacerbations are scarce. In this study, 13 clinical and environmental factors potentially associated with recurrent exacerbations were investigated in 136 patients with difficult-to-treat asthma. Patients with more than three severe exacerbations (n = 39) in the previous year were compared with those with only one exacerbation per year (n = 24). A systematic diagnostic protocol was used to assess 13 potential risk factors. Factors significantly associated with frequent exacerbations included: severe nasal sinus disease (adjusted odds ratio (OR) 3.7); gastro-oesophageal reflux (OR 4.9); recurrent respiratory infections (OR 6.9); psychological dysfunctioning (OR 10.8); and obstructive sleep apnoea (OR 3.4). Severe chronic sinus disease and psychological dysfunctioning were the only independently associated factors (adjusted OR 5.5 and 11.7, respectively). All patients with frequent exacerbations exhibited at least one of these five factors, whilst 52% showed three or more factors. In conclusion, the results show that recurrent exacerbations in asthma are associated with specific co-morbid factors that are easy to detect and that are treatable. Therapeutic interventions aimed at correcting these factors are likely to reduce morbidity and medical expenditure in these patients.

Journal ArticleDOI
TL;DR: In chronic obstructive pulmonary disease patients, tiotropium q.i.d. achieved a greater improvement in daytime and comparable improvement in night-time lung function compared with formoterol b.d or both combined, and provided an additive effect throughout the 24-h dosing interval.
Abstract: This study compared the bronchodilator effects of tiotropium, formoterol and both combined in chronic obstructive pulmonary disease (COPD). A total of 71 COPD patients (mean forced expiratory volume in one second (FEV1) 37% predicted) participated in a randomised, double-blind, three-way, crossover study and received tiotropium 18 μg q.d. , formoterol 12 μg b.i.d. or both combined q.d. for three 6-week periods. The end-points were 24-h spirometry (FEV1, forced vital capacity (FVC)) at the end of each treatment, rescue salbutamol and safety. Compared with baseline (FEV1 prior to the first dose in the first period), tiotropium produced a significantly greater improvement in average daytime FEV1 (0–12 h) than formoterol (127 versus 86 mL), while average night-time FEV1 (12–24 h) was not different (tiotropium 43 mL, formoterol 38 mL). The most pronounced effects were provided by combination therapy (daytime 234 mL, night-time 86 mL); both differed significantly from single-agent therapies. Changes in FVC mirrored the FEV1 results. Compared with both single agents, daytime salbutamol use was significantly lower during combination therapy (tiotropium plus formoterol 1.81 puffs·day−1, tiotropium 2.41 puffs·day−1, formoterol 2.37 puffs·day−1). All treatments were well tolerated. In conclusion, in chronic obstructive pulmonary disease patients, tiotropium q.d. achieved a greater improvement in daytime and comparable improvement in night-time lung function compared with formoterol b.i.d. A combination of both drugs q.d. was most effective and provided an additive effect throughout the 24-h dosing interval.

Journal ArticleDOI
TL;DR: In healthy children, the 6-min walk test is a reliable and valid functional test for assessing exercise tolerance and endurance and Bland and Altman plots demonstrated a high degree of repeatability.
Abstract: The aim of this study was to assess the reliability and validity of the 6-min walk test (6MWT) in healthy children. Chinese secondary school students were randomly recruited. They attended the current authors' unit on two occasions, separated by 2 weeks. Physical examination and standardised maximum incremental exercise testing on a treadmill were performed on the first visit. Spirometry and 6MWT were carried out on the second visit. A randomly selected subgroup was invited to return for repeat 6MWT at an interval of 2-4 weeks. Seventy-eight subjects were recruited; however, four failed to achieve maximal effort on exercise test. The final group included 43 young females and the mean+/-sd age of the subjects was 14.2+/-1.2 yrs. Physical examination was unremarkable in all cases. The mean+/-sd per cent predicted forced expiratory volume in one second was 91.4+/-10.2%. Concurrent validity was demonstrated by good correlation between the 6-min walking distance and maximum oxygen uptake determined on the exercise treadmill. Test-retest reliability was undertaken in 52 subjects, and the intraclass correlation coefficient (95% confidence interval) was calculated as 0.94 (0.89-0.96). In addition, Bland and Altman plots demonstrated a high degree of repeatability. In healthy children, the 6-min walk test is a reliable and valid functional test for assessing exercise tolerance and endurance.

Journal ArticleDOI
TL;DR: Pulmonary rehabilitation participation improves BODE and is associated with better outcomes, and the BODE index change after pulmonary rehabilitation provides valuable prognostic information.
Abstract: The BODE index, which integrates body mass index, airflow limitation (forced expiratory volume in one second), dyspnoea and 6-min walk distance, predicts mortality in chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation (PR) improves some components of BODE. It was hypothesised that changes in BODE may reflect the effects of PR. To test this, participation in PR was offered to 246 patients (BODE quartiles 2-4). The patients were divided as follows: no PR (130 who declined rehabilitation or who dropped out from PR), and PR (116 who completed PR). BODE was determined at entry, after PR, and at 1 and 2 yrs. Other outcomes were: length of stay (LOS) for respiratory-related hospitalisations and mortality. At entry, the two groups had similar age and comorbidity but different BODE. After PR, the BODE improved by 19% and returned to baseline after 2 yrs. The BODE worsened in the no PR group by 4% at 12 months and 18% at 2 yrs. Respiratory mortality at 2 yrs for PR was 7%, compared with 39% for no PR. LOS at 1 yr for COPD decreased 20% in PR, while it increased 25% in no PR. In conclusion, pulmonary rehabilitation participation improves BODE and is associated with better outcomes. The BODE index change after pulmonary rehabilitation provides valuable prognostic information.

Journal ArticleDOI
TL;DR: In patients with low health status, anxiety is an important risk factor for rehospitalisation, and the closest relation between the risk of re Hospitalisation and activity scale was seen with the activity scale.
Abstract: The aim of the present study was to analyse the risk of rehospitalisation in patients with chronic obstructive pulmonary disease and associated risk factors. This prospective study included 416 patients from a university hospital in each of the five Nordic countries. Data included demographic information, spirometry, comorbidity and 12 month follow-up for 406 patients. The hospital anxiety and depression scale and St. George's Respiratory Questionnaire (SGRQ) were applied to all patients. The number of patients that had a re-admission within 12 months was 246 (60.6%). Patients that had a re-admission had lower lung function and health status. A low forced expiratory volume in one second (FEV1) and health status were independent predictors for re-admission. Hazard ratio (HR; 95% CI) was 0.82 (0.74-0.90) per 10% increase of the predicted FEV1 and 1.06 (1.02-1.10) per 4 units increase in total SGRQ score. The risk of rehospitalisation was also increased in subjects with anxiety (HR 1.76 (1.16-2.68)) and in subjects with low health status (total SGRQ score >60 units). When comparing the different subscales in the SGRQ, the closest relation between the risk of rehospitalisation was seen with the activity scale (HR 1.07 (1.03-1.11) per 4 unit increase). In patients with low health status, anxiety is an important risk factor for rehospitalisation. This may be important for patient treatment and warrants further studies.

Journal ArticleDOI
TL;DR: The time course of the changes in inflammatory and dendritic cells in both bronchoalveolar lavage and the pulmonary compartment of cigarette smoke-exposed mice was carefully characterised.
Abstract: Inflammation of the airways and lung parenchyma plays a major role in the pathogenesis of chronic obstructive pulmonary disease. In the present study a murine model of tobacco smoke-induced emphysema was used to investigate the time course of airway and pulmonary inflammatory response, with a special emphasis on pulmonary dendritic cell (DC) populations. Groups of mice were exposed to either cigarette smoke or to control air for up to 24 weeks. In response to cigarette smoke, inflammatory cells (i.e. neutrophils, macrophages and lymphocytes) progressively accumulated both in the airways and lung parenchyma of mice. Furthermore, a clear infiltration of DCs was observed in airways (10-fold increase) and lung parenchyma (1.5-fold increase) of cigarette-exposed mice at 24 weeks. Flow cytometric analysis of bronchoalveolar lavage (BAL) DCs of smoke-exposed mice showed upregulation of major histocompatability complex II molecules and costimulatory molecules CD40 and CD86, compared with BAL DCs of air-exposed mice. Morphometric analysis of lung histology demonstrated a significant increase in mean linear intercept and alveolar wall destruction after 24 weeks of smoke exposure. In conclusion, the time course of the changes in inflammatory and dendritic cells in both bronchoalveolar lavage and the pulmonary compartment of cigarette smoke-exposed mice was carefully characterised.

Journal ArticleDOI
TL;DR: It is suggested that the observed persistent airway inflammation in patients with chronic obstructive pulmonary disease is related to repair of tissue damage in the airways.
Abstract: Smoking cessation is the only treatment in patients with chronic obstructive pulmonary disease (COPD) effective in slowing down disease progression. Its effect on airway inflammation in COPD is unknown, although cross-sectional studies suggest ongoing inflammation in ex-smokers. In order to elucidate the effect of smoking cessation on airway inflammation, 28 smokers with COPD (mean age: 55 yrs; forced expiratory volume in one second: 71% predicted) and 25 asymptomatic smokers with normal lung function (aged 50 yrs) were included in a 1-yr smoking cessation programme. Effects of smoking cessation on airway inflammation were investigated in bronchial biopsies (baseline, 12 months) and sputum samples (baseline, 2, 6 and 12 months). In the 12 candidates with COPD who successfully ceased smoking, airway inflammation persisted in bronchial biopsies, while the number of sputum neutrophils, lymphocytes, interleukin (IL)-8 and eosinophilic-cationic-protein levels significantly increased at 12 months. In the 16 asymptomatic smokers who successfully quitted, inflammation significantly reduced (i.e. number of sputum macrophages, percentage of eosinophils and IL-8 levels) or did not change. The current authors suggest that the observed persistent airway inflammation in patients with chronic obstructive pulmonary disease is related to repair of tissue damage in the airways. It remains to be elucidated whether this reflects a beneficial or detrimental effect.

Journal ArticleDOI
TL;DR: Endobronschial ultrasound with real-time transbronchial needle aspiration offers improved sensitivity and accuracy for staging of the middle mediastinum, and, combined with endoscopic ultrasound, should allow investigation of the majority of the mediastInum.
Abstract: Accurate staging of the mediastinum in lung cancer is essential for optimising treatment strategies. Conventional transbronchial needle aspiration (TBNA) is a blind procedure, reliant upon prior computed tomography (CT) or ultrasound imaging, but has low sensitivity. The current study reports the initial experience of using a prototype endobronchial ultrasound (EBUS) probe that allows TBNA under real-time imaging. In 20 patients selected by CT scanning, a linear-array ultrasound bronchoscope was used to visualise paratracheal and hilar lymph nodes, and TBNA was performed under direct ultrasonic control. In seven cases, sequential endoscopic ultrasound (EUS) was used to assess postero-inferior mediastinal lymph nodes. All procedures were performed under conscious sedation. EBUS-TBNA was undertaken in 18 out of 20 cases and EUS-guided fine-needle aspiration in six out of seven cases. Cytology showed node (N)2/N3 disease in 11 out of 18 EBUS-TBNA cases and provided a primary diagnosis for eight patients. EBUS-TBNA cytology was negative in six cases, which was confirmed by mediastinoscopy or clinical follow-up in four. EUS provided additional information in all cases. There were no procedural complications. Sensitivity, specificity and accuracy for EBUS-TBNA were 85%, 100% and 89%, respectively. In conclusion, endobronchial ultrasound with real-time transbronchial needle aspiration offers improved sensitivity and accuracy for staging of the middle mediastinum, and, combined with endoscopic ultrasound, should allow investigation of the majority of the mediastinum.

Journal ArticleDOI
TL;DR: Moderate and severe levels of sleep apnoea are moderately associated with an increased risk of all-cause mortality, in comparison with the general population, particularly in males aged <50 yrs, although the lack of information about possible confounders and treatment effects should be taken into consideration.
Abstract: The objective of this study was to assess whether an increasing severity of sleep apnoea is associated with increased all-cause mortality hazards and to assess whether the syndrome is associated with excess mortality, in comparison with the general population. Participants included 14,589 adult males, aged 20-93 yrs, referred to the sleep clinics with suspected sleep apnoea or diagnosed with sleep apnoea. Altogether, 372 deaths were recorded after a median follow-up of 4.6 yrs. The crude all-cause mortality rate was 5.55/1,000 patient yrs, increasing with apnoea severity. Cox proportional analysis revealed that both respiratory disturbance index (RDI) and body mass index significantly influenced all-cause mortality hazard but there was no interaction between them. Males with respiratory disturbance index .30 had a significantly higher mortality hazard rate than the reference group of males with RDI f10. Comparing mortality rates of males with moderate/severe sleep apnoea to the general population revealed that only males aged ,50 yrs showed an excess mortality rate. The hazard of mortality in sleep apnoea increases with apnoea severity as indexed by respiratory disturbance index. Moderate and severe levels of sleep apnoea are moderately associated with an increased risk of all-cause mortality, in comparison with the general population, particularly in males aged ,50 yrs. The lack of information about possible confounders and treatment effects should be taken into consideration in the interpretation of these results.

Journal ArticleDOI
TL;DR: The prediction chart can function as a simple tool to predict the risk of failure of noninvasive positive pressure ventilation and thus improve clinical management of patients tailoring medical intervention.
Abstract: Knowing the likelihood of failure of noninvasive positive pressure ventilation (NPPV) in patients with exacerbation of chronic obstructive pulmonary disease (COPD) could indicate the best choice between NPPV and endotracheal intubation instituted earlier. For this purpose, two risk charts were designed (at admission and after 2 h of NPPV) that included all relevant measurable clinical prognostic indicators derived from a population representing the patients seen routinely in clinical practice. Risk stratification of NPPV failure was assessed in 1,033 consecutive patients admitted to experienced hospital units, including two intensive care units, six respiratory intermediate care units, and five general wards. NPPV was successful in 797 patients. Patients with a Glasgow Coma Score or =29, respiratory rate > or =30 breaths x min(-1) and pH at admission 70%. A pH 90%). The risk charts were validated on an independent group of 145 consecutive COPD patients treated with NPPV due to an acute ventilatory failure episode. To identify patients with a probability of failure >50%, the sensitivity and specificity were 33% and 96.7% on admission and 52.9% and 94.1% after 2 h of NPPV, respectively. The prediction chart, based on data from the current study, can function as a simple tool to predict the risk of failure of noninvasive positive pressure ventilation and thus improve clinical management of patients tailoring medical intervention.

Journal ArticleDOI
TL;DR: Since pulmonary hypertension is associated with poor outcomes and because simple clinical criteria fail to identify patients with sarcoidosis and pulmonary hypertension, more aggressive screening for this should be considered.
Abstract: Pulmonary hypertension (PH) is a predictor of poor outcome in sarcoidosis. Little is known about the epidemiology of PH in sarcoidosis. The current authors reviewed the records of patients with sarcoidosis listed for lung transplantation in the USA between January 1995 and December 2002. PH was defined as a mean pulmonary artery pressure of >25 mmHg and severe PH as a mean pulmonary artery pressure of > or =40 mmHg. The cohort included 363 patients of whom 73.8% had PH. Neither spirometric testing nor the need for corticosteroids was associated with PH. Subjects with PH required more supplemental oxygen (2.7+/-1.8 L.min(-1) versus 1.6+/-1.4 L.min(-1)). The cardiac index was lower in individuals with PH, whereas the pulmonary capillary wedge pressure was higher. In multivariate analysis, supplemental oxygen remained an independent predictor of PH, whereas the relationship between cardiac index and PH was no longer significant. As a screening test, the need for oxygen had a sensitivity and specificity of 91.8% and 32.6%, respectively. Pulmonary hypertension is common in advanced sarcoidosis. The need for oxygen correlates with pulmonary hypertension. Since pulmonary hypertension is associated with poor outcomes and because simple clinical criteria fail to identify patients with sarcoidosis and pulmonary hypertension, more aggressive screening for this should be considered.

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TL;DR: In vitro criteria of resistance for susceptibility testing should be carefully determined with representative clinical samples of Mycobacterium tuberculosis isolated from patients never treated with any antituberculosis drug, and from patients having failed treatment with a regimen containing the tested drug; DST should then be carefully standardised to obtain reproducible results.
Abstract: The demand for reliable drug-susceptibility testing (DST) increases with the expansion of antituberculosis drug-resistance surveillance, and with the need for an appropriate treatment of multidrug-resistant tuberculosis, whose incidence gradually increases in many parts of the world. However, the reliability of DST results obtained through widely used methods does not meet acceptable levels, except for DST to isoniazid and rifampicin. In general, susceptibility results are highly predictable, while resistance results show low predictive values when the resistance prevalence is <10%. Poor reliability stems from a weak correlation with clinical response and a low reproducibility due to the poor standardisation of the complex and fragile test procedures. Therefore, in vitro criteria of resistance for susceptibility testing should be carefully determined with representative clinical samples of Mycobacterium tuberculosis isolated from patients never treated with any antituberculosis drug, and from patients having failed treatment with a regimen containing the tested drug; DST should then be carefully standardised to obtain reproducible results. The critical concentration of some drugs is close to the minimal inhibitory concentration for wild susceptible strains and, thus, drug-susceptibility testing is prone to yield poorly reproducible results. These issues call for physicians' attention when using the results from drug-susceptibility testing for case management.

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TL;DR: What is known about autoimmune phenomena in pulmonary arterial hypertension patients is focused on to better consider whether an early loss of self-tolerance followed by autoimmune injury could influence the early development of severe angioproliferative pulmonary hypertension.
Abstract: The association between autoimmunity and pulmonary arterial hypertension (PAH) has been appreciated for >40 yrs, but how autoimmune injury might contribute to the pathogenesis of this disease has only been examined in a case-specific manner. It is becoming increasingly clear that a variety of diverse clinical diseases, ranging from viral infections to connective tissue disorders, can culminate in pulmonary vascular pathology that is indistinguishable. Is there a hitherto unappreciated biology that unites these seemingly unrelated conditions? The answer to this question may come from the increasing body of evidence concerned with the central importance of regulatory T-cells in preventing inappropriate B-cell activity. Two striking similarities between conditions associated with severe angioproliferative pulmonary hypertension are a defect in the CD4 T-cell compartment and auto-antibody production. Pathogenic auto-antibodies targeting endothelial cells are capable of inducing vascular endothelial apoptosis and may initiate the development of PAH. The present review will focus on what is known about autoimmune phenomena in pulmonary arterial hypertension patients, in order to better consider whether an early loss of self-tolerance followed by autoimmune injury could influence the early development of severe angioproliferative pulmonary hypertension.

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TL;DR: Findings show that patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease have poor short- and long-term survival.
Abstract: Factors determining in-hospital mortality and long-term survival of patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are not precisely understood. The aim of the present study was to assess the parameters related to in-hospital mortality and long-term survival after hospitalisation of patients with AECOPD. Clinical and epidemiological parameters on admission in 205 consecutive patients hospitalised with AECOPD were prospectively assessed. Patients were followed-up for 3 yrs. Factors determining short- and long-term mortality were analysed. In total, 17 patients (8.3%) died in hospital. In-hospital mortality was significantly associated with lower arterial oxygen tension (P(a,O2)), higher carbon dioxide arterial tension, lower arterial oxygen saturation and longer hospital stay. The overall 6-month mortality rate was 24%, with 1-, 2- and 3-yr mortality rates of 33%, 39% and 49%, respectively. Cox regression analysis revealed that long-term mortality was associated with longer disease duration (relative risk (RR) = 1.158), lower albumin (RR = 0.411), lower P(a,O2) (RR = 0.871) and lower body mass index (RR = 0.830). When the model was run for the time elapsed since first hospitalisation, it also appeared as statistically significant (RR = 1.195). These findings show that patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease have poor short- and long-term survival. Prediction of survival status may be enhanced by considering arterial oxygen tension, albumin, body mass index, disease duration and time elapsed since the first hospitalisation.

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TL;DR: A new Task Force on pulmonary function testing, implemented by the Forum of International Respiratory Societies (FIRS), has recently started its work based on the ATS/ERS documents, with the hope that they will be accepted by other respiratory societies.
Abstract: Since 1979, guidelines for standardising pulmonary function tests have been published and updated by both the American Thoracic Society (ATS) 1–6 and the European Respiratory Society (ERS) 7–9. In addition, several joint ATS/ERS workshops on pulmonary function testing have been held and the resulting reports published 10, 11. In 1995, European scientists participated in the ATS updates of standards for spirometry and single-breath carbon monoxide diffusing capacity of the lung ( D L,CO), but no joint statement has been published by the two societies. Although generally concordant, the spirometry and D L,CO guidelines published separately by the ATS and the ERS differed in some aspects that were of appreciable importance. Official guidelines for the measurement of lung volumes were made available by the ERS 7, 10, but not the ATS. In recent years, global initiatives were undertaken for the diagnosis and treatment of pulmonary diseases, and the worldwide market for instruments to test lung function widened considerably. This increased the pressure for more uniform pulmonary function testing across the world, and prompted the ATS and the ERS to appoint a joint Task Force to provide new combined standards for clinical pulmonary function testing, with the hope that they will be accepted by other respiratory societies. A new Task Force on pulmonary function testing, implemented by the Forum of International Respiratory Societies (FIRS), has recently started its work based on the ATS/ERS documents. Our Task Force consisted of 19 scientists with recognised expertise in pulmonary function testing. The group worked on a “one-draft” system, in which each of five sections was assigned to a small subgroup and eventually discussed by the whole committee. There …

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TL;DR: Airway T-lymphocytes and airway epithelial cells (AEC) show an increased likelihood of undergoing apoptosis in COPD and if this was related to smoking and continued excess apoptosis after smoking cessation may offer a new target for therapeutic interventions.
Abstract: There is heterogeneity in the propensity of smokers to develop chronic obstructive pulmonary disease (COPD), and improved treatment strategies are hindered by limited understanding of COPD pathogenesis, especially as distinct from the effects of smoking per se. Although apoptosis is essential for tissue homeostasis, increased apoptosis may cause tissue damage and inflammation. This study addressed whether airway T-lymphocytes and airway epithelial cells (AEC) show an increased likelihood of undergoing apoptosis in COPD and if this was related to smoking. Apoptosis (7-amino-actinomycin D, Annexin, single-stranded DNA and caspase), Bcl-2, Bax and p53 were assessed in cells obtained from bronchial bushing and bronchoalveolar lavage from ex- and continuing smokers with COPD, and nonsmoking controls, using flow cytometry. A mean 87% increase in apoptosis of AEC and a 103% increase in T-lymphocyte apoptosis were found in COPD. There were no significant differences in apoptosis of AEC between current and ex-smokers with COPD. Apoptosis may contribute to chronic obstructive pulmonary disease pathogenesis, and continued excess apoptosis after smoking cessation may offer a new target for therapeutic interventions. Whether the persistence of increased apoptosis after smoking cessation results from changes in the pulmonary milleau after years of noxious insult, or whether some individuals have a natural predisposition toward increased apoptosis and possible development of chronic obstructive pulmonary disease remains to be determined.