bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of polymorphisms in the promoter and the 3′ region of the TAFI gene: evidence that plasma TAFI antigen levels are strongly genetically controlled
Authors: Henry Mireille , Aubert Hélène , Morange Pierre E. , Nanni Isabelle , Alessi Marie-Christine , Tiret Laurence , Juhan-Vague Irène
Published: July 2002

Thrombin-activable fibrinolysis inhibitor (TAFI) is a recently described carboxypeptidase that is potentially involved in the regulation of fibrinolysis by decreasing plasminogen binding to the fibrin surface. This role makes the TAFI gene a good candidate in atherothrombotic diseases. The great interindividual variability of plasma TAFI antigen levels is poorly explained by lifestyle characteristics, thus suggesting its genetic determination. To test this hypothesis, the promoter and the 3′-untranslated region of the TAFI gene were screened for polymorphisms, and their contribution to the variability of plasma TAFI antigen levels was evaluated. Seven new polymorphisms are described, 5 in the promoter (C-2599G, −2345 2G/1G, A-1690G, G-1102T, and G-438A) and 2 in the 3′UTR (C+1542G and T+1583A). All these polymorphisms were in strong linkage disequilibrium with each other and with the previously described Ala147Thr polymorphism. They generated 4 main haplotypes, accounting for 80% of all observed haplotypes. In univariate analyses, all polymorphisms were associated with plasma TAFI Ag levels and, individually, contributed to a large fraction of plasma TAFI Ag levels, ranging from 20% to 52%. In a stepwise regression analysis including all polymorphisms, several combinations remained significantly and independently associated with plasma TAFI Ag levels: C+1542G associated with Ala147Thr, T+1583A, or −2345 2G/1G explaining 61.6%, 60.2%, and 58.1% of the variance, respectively. These findings clearly demonstrate that circulating levels of TAFI are strongly determined by polymorphic variations in the promoter and the 3′UTR of theTAFI gene.
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.
Increased levels of surfactant protein A and D in bronchoalveolar lavage fluids in patients with bronchial asthma
Authors: Cheng G , Ueda T , Numao T , Kuroki Y , Nakajima H , Fukushima Y , Motojima S , Fukuda T
Published: July 2002

Surfactant proteins (SP)-A and SP-D are collagen-like glycoproteins belonging to the "collectin" class of C-type lectins, which are primarily synthesized in type II cells. Recent studies reported the possibility of local production of SP-A and SP-D in the airways, but the amounts of surfactant proteins in patients with bronchial asthma have not been studied. The composition of surfactant proteins in mild, stable asthmatics in the first lavage as bronchial lavage (BL) and the second and third lavages consecutively as alveolar lavages (AL) were therefore, analysed separately. The co-relationships in the BL between the amounts of surfactant proteins and those of fucose, which is one of the markers of submucosal secretion were also analysed. Increased amounts of SP-A in BL and AL of in asthmatics were found as compared with those in controls. A high concentration of SP-D in the AL asthma patients was also found. The levels of SP-A correlated with those of fucose in patients with bronchial asthma (r=0.849, p<0.01). The observations in the present study suggested that surfactant protein A may be secreted from the airways with allergic inflammation in a different manner from the alveoli. The increased levels of surfactant proteins A and D may play a protective role in an allergic inflammation in the pathogenesis of bronchial asthma.
Relationships of immunoglobulins E and G sensitization to respiratory function in dairy farmers
Authors: Westeel V , Julien S , De Champs C , Polio JC , Mauny F , Gibey R , Laplante JJ , Aiache JM , Depierre A , Dalphin JC
Published: July 2002

An impairment of respiratory function has been demonstrated in dairy farmers. The objective of this study was to evaluate the relationship of allergy to respiratory function in dairy farmers in a longitudinal study conducted in the Doubs (France). A cohort of male dairy farmers constituted in 1990 was re-evalued in 1995. Subjects completed a medical and occupational questionnaire, and a spirometry test in both 1990 and 1995, in 1995 they were also subjected to immunological tests. Relationships between immunological variables and respiratory function were studied by a multiple linear regression model adjusted for age, smoking status, respiratory symptoms, altitude and occupational exposure. Amongst the 394 subjects of the initial cohort, 330 were included in the longitudinal study and 320 had immunological tests. Log immunoglobulin (Ig) E was negatively correlated with the 1995 respiratory function parameters (p<0.05 for forced expiratory volume in one second (FEV1) and FEV1/vital capacity (VC). Immunoglobulin (Ig) G response to Aspergillus fumigatus detected by enzyme-linked immunosorbent assay (ELISA) was negatively correlated to 1995 respiratory function parameters (VC: p<0.01; FEV1: p<0.001; FEV1/VC: p<0.01). There was a positive relationship between IgG antibodies against Aspergillus fumigatus and the mean annual decline in FEV1 (p<0.01) and FEV1/VC (p<0.01). To conclude, allergy may play a role in the impairment of respiratory function in dairy farmers of the Doubs and sensitization to Aspergillus fumigatus seems to constitute an independent risk factor for the development of airflow obstruction in this occupational setting.
Therapy with nCPAP: incomplete elimination of Sleep Related Breathing Disorder
Authors: Grote L , Hedner J , Grunstein R , Kraiczi H
Published: July 2002

Correct assessment of the overall treatment effectiveness requires knowledge about therapy compliance and efficacy. This study aimed to determine overall long-term apnoea alleviation after continuous positive airway pressure (CPAP) in a complete sleep laboratory cohort. Out of 209 consecutive CPAP candidates (mean age 57+/-12 yrs, body mass index (BMI) 30.0+/-5.1 kg x m2, respiratory disturbance index (RDI) 32.9+/-29 h), follow-up treatment was performed in 149 of them at 9, 18 and 30 months after CPAP prescription. Compliance with CPAP (machine run time/days CPAP available) was adjusted for the individual subjective sleep-time. Apnoea alleviation was defined as adjusted compliance multiplied by the CPAP effect (RDI with CPAP applied), remaining RDI was calculated. The baseline RDI, age or BMI in 75 patients, who did not tolerate nasal continuous positive airway pressure (nCPAP), did not differ from those accepting CPAP (acceptors, n=74). In acceptors at 9 months follow-up RDI with CPAP applied was 1.4+/-2.6 (CPAP effect, n=66), mean CPAP use was 3.6+/-2.5 x 24 h(-1) (n=68), mean apnoea alleviation was 52.4+/-32.0% (range 1-100%, n=47), the average remaining whole-night RDI was 17.8+/-26. At 9, 18 and 30 months (n=47), the mean daily CPAP use increased from 3.6+/-2.5 h to 4.1+/-2.5 h and 4.4+/-2.4 h (p<0.01). Effectiveness of continuous positive airway pressure is potentially high but acceptance was low. When accounting for sleep-time, its actual effect and use, only 50% adjusted continuous positive airway pressure effectiveness was observed.
Effects of mandibular advancement on respiratory resistance
Authors: Lorino AM , Maza M , d'Ortho MP , Coste A , Harf A , Lorino H
Published: July 2002

Mandibular advancing devices are proposed as nonsurgical treatment for certain patients with an obstructive sleep apnoea syndrome. Since they act by increasing the upper airway calibre, the aim of the present study was to investigate the changes in respiratory resistance (Rrs) resulting from mandibular advancement. Rrs was measured at the nose by the forced oscillation technique (4-32 Hz). Ten normal subjects were studied under three conditions: resting mandibular position, passive mandibular advancement steadied by a wax bite, and voluntary advancement, in random order. Respiratory resistance was extrapolated to 0 Hz (R0) and estimated at 16 Hz (R16) by linear regression analysis of respiratory resistive impedance versus frequency. R0 (mean+/-SEM=3.5+/-0.2 cmH2O x L(-1) x s in the resting position) decreased significantly with passive advancement (2.9+/-0.2 cmH2O x L(-1) x s, p<0.001), but remained unchanged with voluntary mandibular advancement (3.6+/-0.2 cmH2O x L(-1) s). Similar results were obtained for R16. The results of this study demonstrate that the effects of mandibular advancement on upper airway resistance differ, depending on whether advancement is passive or active, and suggest that in order to simulate the actual effects of therapeutic devices, mandibular advancement should be passive.
Stimulation of eosinophil IgE low-affinity receptor leads to increased adhesion molecule expression and cell migration
Authors: Lantero S , Alessandri G , Spallarossa D , Scarso L , Rossi GA
Published: July 2002

Immunoglobulin binding on eosinophil surface receptors results in activation of these cells. Evaluating blood eosinophils from atopic subjects, it was investigated whether ligation of immunoglobulin E low-affinity receptor (FcepsilonRII/ CD23) with specific monoclonal antibodies (Mabs) resulted in enhanced eosinophil migration and adhesion molecule expression. Eosinophils from 20 subjects with allergic asthma (atopic individuals) and nine nonatopic normal individuals (controls) were purified using Percoll gradients. The effect of antihuman CD23 Mabs on: 1) eosinophil migration through human umbilical vein endothelial cells (HUVECs); and 2) eosinophil expression of the adhesion molecules leukocyte function-associated antigen-1 (LFA-1, CD11a/CD18), macrophage antigen-1 (Mac-1, CD11b/CD18) and very late activation antigen-1 (VLA-4, CD49d/CD29) was evaluated by specific Mab staining and flow cytometric analysis. As compared to controls, freshly isolated eosinophils from atopic individuals showed enhanced migration through HUVECs (p<0.05) and increased LFA-1 expression (p<0.01), but similar Mac-1 and VLA-4 expression (p>0.1 for both). In both controls and atopic individuals, eosinophil incubation with antihuman CD23 Mabs induced a dose-dependent increase in cell migration through HUVECs, significant at antihuman CD23 Mab concentrations of 5 microg x mL(-1) (p>0.05 for all). Similarly, incubation of the cells with antihuman CD23 Mabs induced dose-dependent upregulation of LFA-1 and Mac-1 expression, whereas no changes in VLA-4 expression were observed (p>0.1). Finally, the enhanced eosinophil migration induced by antihuman CD23 Mab stimulation was significantly inhibited by antihuman LFA-1 (84+/-14% (mean+/-SEM); p<0.01) and VLA-4 Mabs (47+/-15%; p<0.05) but not by antihuman Mac-1 Mabs (p>0.1). In both atopic and control subjects, immunoglobulin E, low-affinity receptor stimulation induces functional changes in eosinophils characterized by increased eosinophil migration associated with enhanced late function antigen-1 and Mac-1 expression.
Interleukin 5 and granulocyte-macrophage colony-stimulating factor levels in bronchoalveolar lavage fluid in interstitial lung disease
Authors: Taniguchi H , Katoh S , Kadota J , Matsubara Y , Fukushima K , Mukae H , Matsukura S , Kohno S
Published: July 2002

The purpose of this study was to evaluate the role of several eosinophil growth factors including interleukin (IL)-5, interleukin (IL)-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the pathogenesis of interstitial lung disease with eosinophilia. IL-5, IL-3 and GM-CSF in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA) in patients with eosinophilic pneumonia (EP), bronchiolitis obliterans organizing pneumonia (BOOP), idiopathic pulmonary fibrosis (IPF), sarcoidosis and healthy volunteers. IL-5 in BALF was high only in patients with EP. IL-3 in BALF was undetectable in the majority of patients with these diseases. GM-CSF in BALF was detectable in 30-67% of each group of patients. In patients with BOOP and IPF, the number of eosinophils in BALF was higher in patients with detectable GM-CSF than in patients in whom GM-CSF was below the detection limit. Eosinophil cationic protein (ECP) was detected in all patients with EP and some with BOOP and IPF. There was a significant correlation between ECP levels and percentage or number of eosinophils in BALF. The results suggest the possibility that interleukin 5 in eosinophilic pneumonia, and granulocyte-macrophage colony-stimulating factor in bronchiolitis obliterans organizing pneumonia and idiopathic pulmonary fibrosis may play important roles in eosinophil recruitment in the lung. Activation of eosinophils in the lung is likely to be induced by both interleukin 5 and granulocyte-macrophage colony-stimulating factor.
Peak expiratory flow changes during experimental rhinovirus infection
Authors: Bardin PG , Fraenkel DJ , Sanderson G , van Schalkwyk EM , Holgate ST , Johnston SL
Published: July 2002

Rhinovirus (RV) colds are associated with asthma exacerbations and experimental infections are commonly used to investigate the mechanisms involved. However, a temporal association between experimental RV infections and falls in peak expiratory flow (PEF) have not been demonstrated. PEF was measured in 22 volunteers (11 normal, five atopic, six atopic asthmatic) who developed RV serotype 16 colds after inoculation. PEF was measured twice daily for 2 weeks prior and 6 weeks after RV infection and episodes of respiratory morbidity based on changes in PEF were defined using validated criteria. Six significant reductions in PEF were temporally related to the RV infections (in two (18%) normal, one (20%) atopic, three (50%) atopic asthmatic subjects, p=0.1) and occurred 4-9 days (median 6) after inoculation. Mean+/-SEM PEF at day 6 was 87.8+/-1.8% of the predicted value in the six subjects with reductions versus 99.4+/-1.4% pred in those without (p=0.01). Symptom scores were significantly different at day 6 in the two groups (10.6+/-1.9 versus 6.8+/-1.0, p=0.03), but no differences were noted in the viral culture scores and changes in nasal albumin. In subjects with significant PEF reduction, the decrease in the provocative concentration causing a 20% fall in the forced expiratory volume in one second (FEV1) (PC20) was 1.7+/-1.3 mg x mL(-1) versus 1.2+/-1.1 mg x mL(-1) in the negative group (p=0.06). The degree of seroconversion to RV was significantly higher in the group with reduced PEF (median change dilutions 8 versus 4, p=0.02). The results of the present study suggest that rhinovirus-associated, respiratory morbidity occurs during experimental infection in some but not all normal and asthmatic subjects and also that experimental colds are a valid model for the study of rhinovirus-associated airway symptoms and asthma exacerbations.
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.
Evaluation of a simplified oscillation technique for assessing airway obstruction in sleep apnoea
Authors: Farré R. , Rigau J. , Montserrat J.M. , Ballester E. , Navajas D.
Published: July 2002

The forced oscillation technique (FOT) is a noninvasive method that is useful for assessing airway obstruction and for titrating continuous positive airway pressure (CPAP) in patients with sleep apnoea. The aim was to evaluate the routine applicability of a simplified FOT set-up based on recording pressure and flow at the level of the CPAP device,i.e.obviating the need for connecting the transducers to the nasal mask.

A correction to account for the tubing and the exhaust port was applied. This simplified FOT was evaluated on nine patients with moderate or severe sleep apnoea during routine CPAP titration. Patient impedance measured by the simplified FOT (|Z|) was compared with actual patient impedance (|Zrs|) measured simultaneously with a reference FOT based on recording pressure and flow at the nasal mask.

An excellent agreement was found between |Z| and |Zrs| over the wide range of airway obstruction explored (4.8–72.1 cmH2O·s·L−1): |Z|=|Zrs|×0.86+1.3 cmH2O·s·L−1(r= 0.99). Moreover, the simplified and the conventional FOT settings detected the same respiratory events during sleep.

These results demonstrate that this simplified FOT is applicable for measuring airway obstruction during routine sleep studies in patients with sleep apnoea.
Pleural-fluid myeloperoxidase in complicated and noncomplicated parapneumonic pleural effusions
Authors: Alegre J. , Jufresa J. , Segura R. , Ferrer A. , Armadans L. , Aleman C. , Marti R. , Ruiz E. , Fernández de Sevilla T.
Published: July 2002

The diagnostic accuracy of myeloperoxidase (MPO) in pleural fluid, for differentiating between complicated and noncomplicated parapneumonic pleural effusions (PPE) evaluated prospectively.

Seventy patients aged >18 yrs with PPE (36 complicated and 34 noncomplicated) were studied after admission to a tertiary referral teaching hospital. MPO concentration was measured in plasma and pleural fluid using a double-antibody competitive radioimmunoassay.

The concentrations of MPO in complicated and noncomplicated PPE were compared using a Mann-Whitney U-test and multiple logistic regression models were used to predict the odds that an effusion was complicated. MPO pleural-fluid concentrations were significantly higher in complicated than in noncomplicated PPE. After excluding purulent effusions, pleural-fluid MPO was the marker that best differentiated between the two types of PPE: the area under the receiver operating characteristic curve was 0.912, the sensitivity was 87.5% and the specificity was 85.1% at a cut-point limit of 3.000 µg·L−1.

The authors concluded that the concentration of pleural-fluid myeloperoxidase helps to differentiate between nonpurulent complicated and noncomplicated parapneumonic pleural effusions.
Sleep quality and daytime function in adults with cystic fibrosis and severe lung disease
Authors: Dancey D.R. , Tullis E.D. , Heslegrave R. , Thornley K. , Hanly P.J.
Published: July 2002

It was hypothesized that adult cystic fibrosis (CF) patients with severe lung disease have impaired daytime function related to nocturnal hypoxaemia and sleep disruption.

Nineteen CF patients (forced expiratory volume in one second 28±7% predicted) and 10 healthy subjects completed sleep diaries, overnight polysomnography (PSG), and assessment of daytime sleepiness and neurocognitive function.

CF patients tended to report more awakenings (0.7±0.5versus0.3±0.2·h−1, p=0.08), and PSG revealed reduced sleep efficiency (71±25versus93±4%, p=0.004) and a higher frequency of awakenings (4.2±2.7versus2.4±1.4·h−1, p=0.06). Mean arterial oxygen saturation during sleep was lower in CF patients (84.4±6.8versus94.3±1.5%, p<0.0001) and was associated with reduced sleep efficiency (regression coefficient (r)=0.57, p=0.014). CF patients had short sleep latency on the multiple sleep latency test (6.7±3 min). The CF group reported lower levels of activation and happiness and greater levels of fatigue (p<0.01), which correlated with indices of sleep loss, such as sleep efficiency (r=0.47, p=0.05). Objective neurocognitive performance was also impaired in CF patients, reflected by lower throughput for simple addition/subtraction, serial reaction and colour-word conflict.

The authors concluded that adult cystic fibrosis patients with severe lung disease have impaired neurocognitive function and daytime sleepiness, which is partly related to chronic sleep loss and nocturnal hypoxaemia.
Tidal expiratory flow limitation and chronic dyspnoea in patients with cystic fibrosis
Authors: Goetghebeur D. , Sarni D. , Grossi Y. , Leroyer C. , Ghezzo H. , Milic-Emili J. , Bellet M.
Published: July 2002

Cystic fibrosis (CF) eventually leads to hyperinflation linked to tidal expiratory flow limitation (FL) and ventilatory failure.

Presence of FL was assessed at rest in 22 seated children and adults with CF (forced expiratory volume in one second (FEV1) range: 16–92% predicted), using both the negative expiratory pressure (NEP) technique and the “conventional” method based on comparison of tidal and maximal expiratory flow/volume curves. In addition, chronic dyspnoea was scored with the modified Medical Research Council (MRC) scale. Measurements were made before and 15 min after inhalation of salbutamol.

With NEP, FL was present in only three malnourished patients, who had the lowest FEV1values (16–27% pred) and claimed very severe dyspnoea (MRC score 5). By contrast, an additional seven patients were classified as FL with the conventional method. Six of these patients had little or no dyspnoea (MRC scores 0–1). Salbutamol administration had no effect on the extent of FL, and the concomitant decrease in functional residual capacity (FRC) was too small to play any clinically significant role.

This study concluded that in seated patients with cystic fibrosis, expiratory flow limitation is absent at rest, unless the forced expiratory volume in one second is <30% predicted. If present, expiratory flow limitation is associated with severe chronic dyspnoea. The conventional method for assessing expiratory flow limitation is not reliable and bronchodilator administration has little effect on expiratory flow limitation.
Nocturnal periodic breathing in primary pulmonary hypertension
Authors: Schulz R. , Baseler G. , Ghofrani H.A. , Grimminger F. , Olschewski H. , Seeger W.
Published: July 2002

Cheyne-Stokes respiration is frequently observed in congestive heart failure. Among other factors, prolongation of circulation time, hypocapnia and hypoxia are thought to underlie this sleep-related breathing disorder. Primary pulmonary hypertension (PPH) is also characterized by reduced cardiac output and blood gas alterations. Therefore, the aim of the present study was to determine whether a nocturnal periodic breathing (PB) occurs in PPH.

A total of 20 consecutive patients with PPH who had been admitted for pharmacological investigation of pulmonary vasoreactivity were investigated by lung function testing, right heart catheterization and full-night attended polysomnography.

PB was detected in six patients (30%) (mean±SEM: apnoea/hypopnoea index 37±5 h−1; arterial oxygen saturation was <90% during 56±6.5% of total sleep time). The patients with PB had more severe haemodynamic impairment than those without. They also had a more marked reduction in the pulmonary diffusion capacity and greater arterial hypoxia. PB was markedly improved or even eradicated by nasal oxygen during the night.

Periodic breathing occurs in patients with advanced primary pulmonary hypertension and can be reversed by nocturnal nasal oxygen. The clinical and prognostic significance of periodic breathing in primary pulmonary hypertension needs to be determined by further studies.
Recording flow in the first second of a maximal forced expiratory manoeuvre: influence of frequency content
Authors: Miller M.R. , Lloyd J. , Bright P.
Published: July 2002

The frequency content of the first second of the maximum forced expiratory manoeuvre (MFEM) was measured to determine if the currently accepted frequency limit of 20 Hz for MFEM is adequate for recording peak expiratory flow (PEF).

The frequency response of a Fleisch pneumotachograph (PT) was measured and used to record MFEM from 24 patients attending a lung-function laboratory and 26 normal volunteers. The first 1.024 s of the signal recorded at 1,000 Hz for that blow with maximum PEF, underwent fast Fourier transformation using a triangular window function, applied after 0.75 s to reduce flow linearly to zero. All the frequencies above a set limit were removed, followed by inverse transformation to reconstitute the blow. The limits for this frequency cut-off were progressively varied from 100 Hz down to 15 Hz, with the resulting PEF being compared with the PEF from the reconstituted blow with no frequency reduction.

The average±sd age for the group was 47±18 yrs and the average PEF was 450±187 L·min−1, which, when expressed as a standardized residual, was 0.1±2.1, with a range from −4.5–3.9 indicating a good spread around normal values. Average rise time to PEF was 83±38 ms and dwell time >90% PEF was 45±25 ms. Cut-off >20 Hz reduced the mean PEF of the group by 8.5 L·min−1(95% confidence limit 5.5–11.4 L·min−1), whereas cut-off >30 Hz reduced mean PEF by 4.4 L·min−1(2.6–6.2). In the present study subjects, 30 Hz was on the 95th percentile of frequencies for defining the upper limit for 98% of the power spectrum for the first second of the blow.

It has been shown that there are frequencies >20 Hz that contribute to peak expiratory flow enough to influence readings made using conventional hand-held peak expiratory flow meters, such as the mini-Wright. Devices used for recording flow from a maximum forced expiratory manoeuvre should therefore have an adequate frequency response of up to 30 Hz.