bluuebunny/crossref_metadata_2025_split huggingface dataset:
Airway inflammation in patients with symptoms suggesting asthma but with normal lung function
Authors: Rytilä P. , Metso T. , Heikkinen K. , Saarelainen P. , Helenius I.J. , Haahtela T. 
Published: July 2002

The hypothesis that eosinophilic airway inflammation is present in many patients presenting with respiratory symptoms suggestive of asthma but with normal lung function was tested.Thirty-six consecutive patients presenting with these features were studied. Twenty-five asthmatics and 43 healthy volunteers served as control groups. Signs of eosinophilic inflammation in blood and induced sputum were studied. Patients with respiratory symptoms were single-blindly treated with inhaled beclomethasone dipropionate (BDP), 800 μg daily, or placebo for 3 months, and re-examined at 3 months and 1 yr.Patients with respiratory symptoms had higher numbers of blood and sputum eosinophils than healthy persons (p<0.0001), but the degree of eosinophilic inflammation was less pronounced than in asthmatics (p<0.01). Three-month's treatment with BDP significantly reduced total symptom score (p<0.001), cough score (p<0.0001), and the number of blood eosinophils (p<0.01). For cough alone, the improvement was significant compared with placebo (p<0.05). The patients were followed-up for 1 yr, and 17 (55%) still had symptoms but retained normal lung function. Four (13%) patients had developed asthma and another 10 (32%) had become free of symptoms.Using lung function measurements and induced sputum analyses, a group of patients with symptoms suggestive of asthma and signs of eosinophilic airway inflammation but without enough airflow variability to be diagnosed as asthmatics were detected. They seemed to respond favourably to inhaled beclomethasone dipropionate treatment.
Improved asthma control with budesonide/formoterol in a single inhaler, compared with budesonide alone
Authors: Zetterström O. , Buhl R. , Mellem H. , Perpiñá M. , Hedman J. , O'Neill S. , Ekström T. 
Published: July 2002

Budesonide/formoterol in a single inhaler was compared with budesonide alone, and with concurrent administration of budesonide and formoterol from separate inhalers, in patients with asthma, not controlled with inhaled glucocorticosteroids alone.In this 12-week, double-blind, randomized, double-dummy study, 362 adult asthmatics (forced expiratory volume in one second 73.8% of predicted, inhaled glucocorticosteroid dose 960 µg·day−1) received single inhaler budesonide/formoterol (Symbicort® Turbuhaler®) 160/4.5 µg, two inhalationsb.i.d., or corresponding treatment with budesonide, or budesonide plus formoterolviaseparate inhalers.There was a greater increase in morning peak expiratory flow (PEF) with single-inhaler (35.7 L·min−1) and separate-inhaler (32.0 L·min−1) budesonide and formoterol, compared with budesonide alone (0.2 L·min−1; p<0.001, both comparisons); the effect was apparent after 1 day (p<0.001versusbudesonide, both comparisons). Similarly, evening PEF, use of rescue medication, total asthma symptom scores and percentage of symptom-free days improved more with both single inhaler and separate inhaler therapy than with budesonide alone, as did asthma control days (∼15% more, p<0.001versusbudesonide, both comparisons, with a marked increase in the first week). All treatments were well tolerated and the adverse event profile was similar in all three treatment groups.It is concluded that single inhaler therapy with budesonide and formoterol is a clinically effective and well-tolerated treatment for patients with asthma that is not fully controlled by inhaled glucocorticosteroids alone.
Changes in smoking habits and risk of asthma: a longitudinal population based study
Authors: Godtfredsen N.S. , Lange P. , Prescott E. , Osler M. , Vestbo J. 
Published: July 2002

A common statement from exsmokers is that symptoms of asthma develop shortly after smoking cessation. This study, therefore, investigated the relationship between smoking cessation and development of asthma in a large cohort from the Copenhagen City Heart Study (CCHS).The CCHS is a longitudinal, epidemiological study of the general population from the capital of Denmark, conducted between 1976 and 1994. The study population involved the 10,200 subjects who provided information on self-reported asthma and smoking habits from the first two examinations (baseline and 5-yr follow-up), and the 6,814 subjects who also attended the third and last examination (10-yr follow-up). The point-prevalence of smoking cessation as well as the asthma incidence between examinations was estimated, and a multivariate logistic regression model was used to examine the relationship between changes in smoking habits and development of asthma.During the study period, asthma incidence increased from 1.2–4.2%. Between examinations 1,316 subjects quit smoking. Smoking cessation between examinations was significantly related to reported asthma at follow-up. With never-smokers as the reference group and following adjustment for sex, age, chronic bronchitis, level of forced expiratory volume in one second and pack-yrs of smoking, the odds ratio (OR) for developing asthma when quitting smoking between examinations was 3.9 (95% confidence interval (CI) 1.8–8.2) from baseline to first follow-up and 3.1 (95% CI 1.9–5.1) from first to second follow-up. Continuing smoking also increased the risk of asthma significantly (OR 2.6 and 2.0, respectively).The results indicate that exsmokers have a higher incidence of self-reported asthma than never-smokers. It is likely that subjects perceive chronic obstructive pulmonary disease as asthma, hence the relationship between smoking cessation and asthma might be due to misclassification rather than causality.
Guidelinesversusclinical practice in the treatment of chronic obstructive pulmonary disease
Authors: Roche N. , Lepage T. , Bourcereau J. , Terrioux P. 
Published: July 2002

The main purpose of this study was to assess whether pharmacological treatments prescribed by respiratory physicians to patients with chronic obstructive pulmonary disease (COPD) were consistent with the guidelines.The treatments prescribed by respiratory physicians to 631 consecutive patients with COPD, compared to 879 asthmatics were prospectively recorded. All subjects underwent peak expiratory flow rate measurement, spirometry and assessment of recent evolution and dyspnoea (visual analogue and Medical Research Council scales). Patients with COPD received more treatments than asthmatics (mean±sd: 2.6±0.5versus2.2±0.4, p<0.0001). Treatments administered to patients with COPD were β2-agonists in 78% (versus94% in asthmatics), anticholinergic agents (AC) in 56% (versus16% in asthma), methylxanthines in 31% (versus15% in asthma) and inhaled corticosteroids in 76% (versus85% in asthma). Intensity of treatment was influenced by disease severity for all treatments except AC.In conclusion, pharmacological treatment of chronic obstructive pulmonary disease by respiratory physicians is only partially consistent with current guidelines, with a high proportion of inhaled corticosteroid prescriptions and a relative under-use of anticholinergic agents; this most likely reflects the persistent uncertainties of physicians, and emphasizes that more efforts are required to improve implementation of chronic obstructive pulmonary disease guidelines and assess the efficacy and cost-effectiveness of recommended strategies.
Statistics for theEuropean Respiratory Journal
Authors: Chinn S. 
Published: July 2002

This review summarizes statistical methods likely to be needed by researchers. It is not a replacement for a statistics book, and almost no symbols or mathematics are used. It seeks to guide researchers to the appropriate methods and to make them aware of some common pitfalls.Sections deal with methods for quantitative outcomes, both basic and more advanced, and parallel methods for qualitative or categorical outcomes. Reference is made to papers using the more advanced methods in theEuropean Respiratory Journalin order that their relevance may be appreciated.The paper seeks to improve the quality of papers submitted to theEuropean Respiratory Journal, to reduce the revisions to papers required of authors, and to enable readers of the journal to gain more insight into the interpretation of results.
Role of NO pathway, calcium and potassium channels in the peripheral pulmonary vascular tone in dogs
Authors: Chabot F. , Schrijen F. , Saunier C. 
Published: July 2002

Because hypoxic pulmonary vasoconstriction occurs mainly in the small pulmonary arteries, the authors investigated the effects of drugs acting on the nitric oxide (NO) pathway and the calcium and potassium channels in the peripheral pulmonary circulation, without interference with the overall pulmonary or systemic circulation.Mixed venous blood was infused in wedged areas to study the pressure/flow relationship and to compute peripheral pulmonary vascular resistance (PPVR). The authors studied the effects ofNω-nitro-l-arginine methyl ester (l‐NAME), an NO synthase inhibitor, sodium nitroprusside (SNP, an NO donor), the calcium channel blockers verapamil, nifedipine and nicardipine, and the potassium channel opener levcromakalim, during normoxia and acute mild normocapnic hypoxia.In the peripheral pulmonary circulation, l‐NAME caused an increase in PPVR during normoxia (+95%; p<0.001) and hypoxia (+60%; p<0.01). Following the increase by l‐NAME, SNP decreased PPVR during normoxia (−24%; p<0.05) and hypoxia (−23%; p<0.05). Verapamil, nifedipine and nicardipine did not modify PPVR during normoxia but during hypoxia they decreased PPVR (−28%, nonsignificant; −27%, p<0.01 and −33%, p<0.05, respectively). Levcromakalim did not modify PPVR during normoxia or hypoxia.In conclusion, the nitric oxide pathway and voltage-dependent calcium channels, and not adenosine triphosphate sensitive potassium channels, play an important role in the control of peripheral pulmonary circulation in dogs.
Inflammation in cystic fibrosis airways: relationship to increased bacterial adherence
Authors: Scheid P. , Kempster L. , Griesenbach U. , Davies J.C. , Dewar A. , Weber P.P. , Colledge W.H. , Evans M.J. , Geddes D.M. , Alton E.W.F.W. 
Published: July 2002

It is unclear whether inflammation in the cystic fibrosis (CF) lung relates predominantly to bacterial infection, or occurs as a direct consequence of mutant cystic fibrosis transmembrane conductance regulator (CFTR) protein.Interleukin (IL)-8 secretion from CF and non-CF cell lines, and from CF and non-CF human primary nasal epithelial cells incubated with or withoutPseudomonas aeruginosa, was measured. Activation of nuclear factor-κB (NF-κB) in unstimulated CF and non-CF nasal epithelial cells, cell lines and murine tissues was measured by gel-shift assays.No significant difference in basal IL-8 production or NF-κB activation was observed between CF and non-CF primary nasal cells. However, CF cells exhibited a significantly (p<0.01) increased IL-8 secretion followingP. aeruginosastimulation. Equalization of the increasedP. aeruginosaadherence observed in CF cells, to non-CF levels, resulted in comparable IL-8 secretion. Further, IL-8 production did not differ with mutations which result in either correctly localized CFTR, or in partial/total mislocalization of this protein. Similar levels of NF-κB activation were observed in a number of organs of wild-type and CF mice. Finally, IL-8 secretion and NF-κB activity were not consistently increased in CF cell lines. Cos-7 cell transfection with plasmids expressing ΔF508 or G551D mutant CFTR protein resulted in increased activation of a p50-containing NF-κB complex, but IL-8 secretion was similar to wild-type cells.The authors conclude that the stimulus produced byPseudomonas aeruginosais the predominant inflammatory trigger in their models.
Nedocromil sodiumversussodium cromoglycate in treatment of exercise-induced bronchoconstriction: a systematic review
Authors: Kelly K.D. , Spooner C.H. , Rowe B.H. 
Published: July 2002

The objective of this review was to compare the effects of prophylactic doses of nedocromil sodium (NCS) and sodium cromoglycate (SCG) on postexercise lung function, in persons diagnosed with exercise-induced bronchoconstriction.Randomized controlled trials were identified from the Cochrane Airways Review Group Asthma Register, plus hand searching for trials in journals, bibliographies of relevant studies and review articles. Randomized controlled trials comparing NCS to SCG in prophylactic treatment of exercise-induced bronchoconstriction were eligible. Studies were pooled using odds ratios (OR) for dichotomous outcomes or weighted mean differences (WMD) with 95% confidence intervals (95% CI) for continuous outcomes.No significant differences were noted between NCS and SCG with respect to the maximum per cent decrease in forced expiratory volume in one second (WMD=−0.88; 95% CI −4.50–2.74), complete protection (OR=0.95; 95% CI 0.50–1.81), clinical protection (OR=0.71; 95% CI 0.36–1.39), unpleasant taste (OR=6.85; 95% CI 0.77–60.73), or sore throat (OR=3.46; 95% CI 0.32–37.48). Subgroup analyses based on age, dosages of medications and timing of exercise postinhalation were consistent with the overall pooled analyses.No significant differences were evident between the effects of nedocromil sodium and sodium cromoglycate during the immediate postexercise period in adults and children with exercise-induced bronchoconstriction, with regards to maximum per cent decrease in forced expiratory volume in one second, complete protection, or clinical protection. Side-effect profiles were similar.
Respiratory impedance response to continuous negative airway pressure in awake controls and OSAS
Authors: Lorino A.M. , Lofaso F. , Dahan E. , Harf A. , Lorino H. 
Published: July 2002

The aim of the study was to determine whether the response of respiratory impedance (Zrs) to decreasing levels of continuous negative airway pressure (CNAP) during wakefulness, differs in controls and subjects with obstructive sleep apnoea syndrome (OSAS).Zrswas measured by the forced oscillation technique (4–32 Hz) in 15 controls and 21 patients with OSAS (apnoea/hypopnoea index >20 per sleep hour) with normal lung function, in the basal state and with application of decreasing CNAP of −5, −10, and −15 hPa. Respiratory resistance was extrapolated to 0 Hz (R0) and estimated at 16 Hz (R16) by linear regression analysis of respiratory resistive impedanceversusfrequency. Respiratory elastance (Ers) and inertance (Irs) were estimated by multilinear regression analysis of respiratory reactanceversusfrequency, and resonance frequency (RF) was determined as RF=(1/2π)(Ers/Irs)0.5.In both groups,R0,R16,Ersand RF significantly increased as the CNAP level decreased (p<0.0001 for all).R0,Ers, and RF increased significantly more in OSAS than in controls (p<0.01, 0.001, and 0.0001, respectively), independently of the severity of obesity. Receiver operator characteristic curves showed that the parameter which best detected OSAS was RF, with a sensitivity of 81% and 93% specificity for the 13.6 Hz cut-off point.The results of the present study suggest that the response of respiratory impedance to decreasing continuous negative airway pressure levels, might allow detection of obstructive sleep apnoea syndrome in subjects with normal lung function.
Cost-effectiveness of self-management in asthmatics: a 1-yr follow-up randomized, controlled trial
Authors: Gallefoss F. , Bakke P.S. 
Published: July 2002

Patient education in asthma can improve outcome but cost-effectiveness has not been widely assessed. The aim of the present study was to carry out a cost-effectiveness analysis of patient education in asthmatics in a 12-month follow-up.The authors randomly allocated 78 asthmatics to a control or intervention group after they had received ordinary outpatient consultation care. Intervention consisted of two 2-h group sessions followed by 1–2 individual sessions administered by a nurse and a physiotherapist. Self-management was emphasized. Effectiveness was expressed in terms of quality of life and forced expiratory volume in one second (FEV1). Doctor visits, days off work, dispensed pharmaceuticals, hospital admissions, travel costs, time costs and educational costs were recorded.The control and intervention groups induced mean total costs of Norwegian Krone (NOK) 16,000 and 10,500 per patient, respectively. A 10-unit improvement in St. George's Respiratory Questionnaire total score and a 5% improvement in FEV1in the intervention group were associated with a saving of NOK 3,400 and 4,500, respectively, compared to the control group. The number needed to educate (NNE) to make one person symptom free was associated with a saving of NOK 12,200. The results were robust to realistic changes in the assumptions upon which they were based.It could be concluded from this study that patient education in asthmatics in a 12-month follow-up improved patient outcomes and reduced costs.
Histamine challenges discriminate between symptomatic and asymptomatic children
Authors: Niggemann B. , Illi S. , Madloch C. , Völkel K. , Lau S. , Bergmann R. , von Mutius E. , Wahn U. ,   MAS-Study Group
Published: July 2002

The aims of this study were to investigate a threshold value for bronchial responsiveness in children aged 7 yrs, which discriminates between symptomatic and asymptomatic children, and to identify determinants of this responsiveness.Titrated bronchial histamine challenges using the reservoir method were performed in 645 children aged 7 yrs, from the birth cohort Multicentre Allergy Study (MAS).When defining a reference population of healthy children within the MAS cohort, the 95th percentile of the provocative concentration causing a 20% fall in forced expired volume in one second PC20among these asymptomatic study subjects amounted to 0.60 mg·mL−1. This resulted in a specificity of 93.0% and a sensitivity of 45.9%, for discriminating between “current wheezers” and “non-current wheezers”. Determinants of airway responsiveness at this age were pulmonary function, sensitization to indoor allergens, total immunoglobulin E and current wheeze.The results indicate that a very low cut-off provocative concentration causing a 20% fall in forced expired volume in one second (<1.0 mg·mL−1) defines airway hyperresponsiveness in children aged 7 yrs using the reservoir method. Provocation protocols for histamine challenges in this age group should therefore start with concentrations markedly below 1.0 mg·mL−1.
Systemic inflammatory response after bronchoalveolar lavage in critically ill patients
Authors: Bauer T.T. , Arosio C. , Montón C. , Filella X. , Xaubet A. , Torres A. 
Published: July 2002

Bronchoscopic bronchoalveolar lavage (BAL) may be followed by a systemic inflammatory response. Previous reports have suggested pneumonia as a predisposing condition and systemic cytokines as possible mediators.To test this hypothesis, systemic levels of interleukin (IL)-1β, IL-6 and tumour necrosis factor-alpha (TNF-α) were studied before and at 12 h and 24 h after bronchoscopically guided BAL in 30 mechanically ventilated patients (median age 67 (range 54–76) yrs, simplified acute physiology score II (SAPS II) 33 (12–56)), 20 of whom had pneumonia and 10 of whom were control patients without pneumonia. Arterial oxygen partial pressure to inspired oxygen fraction ratio (Pa,O2/FI,O2), body temperature, mean arterial pressure, and cardiac frequency were recorded. The majority of patients (28/30, 93%) received antibiotic treatment prior to the procedure.Pa,O2/FI,O2ratio was lower at 12 h compared to baseline in patients with pneumonia (baseline median 192 (range 65–256); 12 h 160 (66–190) mmHg, p<0.001) and ventilated controls (baseline 293 (205–473); 12 h 226 (153–330) mm Hg p=0.011), but returned to baseline levels at 24 h (pneumonia: 194 (92–312), p=0.991; controls: 309 (173–487) mmHg, p=0.785). No changes in other clinical variables were observed. Systemic TNF-α levels before BAL (pneumonia: 35 (10–88); controls: 17 (0–33) pg·mL−1) did not increase at 12 h (pneumonia: 35 (0–64); p=0.735; controls: 16 (0–21) pg·mL−1, p=0.123 comparison to baseline) or 24 h (pneumonia: 31 (0–36), p=0.464; controls: 19 (0–43) pg·mL−1, p=0.358). No changes of IL-1β (baseline: pneumonia 0 (0–13); controls 1 (0–32) pg·mL−1) or IL-6 (baseline: pneumonia, 226 (9–4300); controls, 53 (0–346) pg·mL−1) were detected.No deterioration of clinical variables and no increase in systemic cytokine release has been observed after bronchoalveolar lavage, in critically ill patients. The potential cytokine increase is probably too small, in relation to the pre-existing inflammatory response, to yield clinical significance in this population otherwise antibiotic therapy may have been protective.
The Bronchitis Randomized On NAC Cost-Utility Study (BRONCUS): hypothesis and design
Authors: Decramer M. , Dekhuijzen P.N.R. , Troosters T. , van Herwaarden C. , Rutten-van Mölken M. , van Schayck C.P.O. , Olivieri D. , Lankhorst I. , Ardia A. 
Published: July 2002

Chronic obstructive pulmonary disease (COPD) is an irreversible disorder characterized by airflow obstruction and a progressive decline in forced expiratory volume in one second (FEV1). At present, no treatment except quitting smoking appears to affect the progression of the disease. Oxidative stress has been implicated in its pathogenesis.The Bronchitis Randomized on NAC Cost-Utility Study (BRONCUS) is a phase III, randomized, double-blind, placebo-controlled, parallel group, multicentre study designed to assess the effectiveness of the antioxidant agent N‐acetylcysteine (NAC) in altering the decline in FEV1, exacerbation rate, and quality of life in patients with moderate to severe COPD. In addition, cost-utility of the treatment will be estimated. Patients will be followed for 3 yrs and evaluated every 3 months. The necessary sample size to demonstrate an effect on the decline in FEV1of 20 mL·yr−1was estimated to be 478 patients.Five hundred and twenty‐three patients with moderate to severe COPD were recruited from 10 European countries from June 1, 1997–December 31, 1999. They were 63±8 yrs old and consisted of 243 (46%) current smokers and 280 (54%) exsmokers. Patients had on the average 4.9±1.6 exacerbations during the last 2 yrs. Postbronchodilator FEV1averaged 57±9% and the reversibility after 400 μg of Salbutamol averaged 4±4% predicted.The final results of the trial will be available in about 2 yrs. The study will provide objective data on the effects of N‐acetylcysteine on outcome variables in chronic obstructive pulmonary disease.
Alpha‐1‐antitrypsin genotyping with mouthwash specimens
Authors: Stockley R.A. , Campbell E.J. 
Published: July 2002

α1‐antitrypsin (α1‐AT) deficiency is diagnosed as a two-stage procedure (concentration and phenotype). However the latter does not provide clues to the presence of null genes without family studies and obtaining blood from patients at a distance often proves difficult. The aim of the study was to assess the feasibility of genotyping α1‐AT using buccal cells.Mouthwash specimens were sent by 84 patients (with a variety of phenotypes of α1‐antitrypsin) through the post. Deoxyribonucleic acid (DNA) was isolated from buccal cells in each sample and subjected to polymerase chain reaction (PCR) using a genotyping kit to detect the S and Z alleles.Eighty-three of 84 samples received were suitable for amplification. The specific primers successfully identified the S and Z alleles in each case. However, five of the 35 samples obtained from patients thought to be Z allele homozygotes were found to be heterozygotes for another severe deficiency allele.These data confirm the feasibility of “at distance” testing for α1‐antitrypsin deficiency alleles using buccal cells from mouthwash samples. The results raise the possibility that other deficiency alleles are more common than has previously been suspected.