bluuebunny/crossref_metadata_2025 huggingface dataset:
Demethylation of a hypermethylated P15/INK4B gene in patients with myelodysplastic syndrome by 5-Aza-2′-deoxycytidine (decitabine) treatment
Authors: Daskalakis Michael , Nguyen Tudung T. , Nguyen Carvell , Guldberg Per , Köhler Gabriele , Wijermans Pierre , Jones Peter A. , Lübbert Michael
Published: September 2002

p16 and p15, 2 inhibitors of cyclin-dependent kinases, are frequently hypermethylated in hematologic neoplasias. Decitabine, or 5-Aza-2′-deoxycytidine, reverts hypermethylation of these genes in vitro, and low-dose decitabine treatment improves cytopenias and blast excess in ∼50% of patients with high-risk myelodysplastic syndrome (MDS). We examined p15and p16 methylation status in bone marrow mononuclear cells from patients with high-risk MDS during treatment with decitabine, using a methylation-sensitive primer extension assay (Ms-SNuPE) to quantitate methylation, and denaturing gradient gel electrophoresis (DGGE) and bisulfite-DNA sequencing to distinguish individually methylated alleles. p15 expression was serially examined in bone marrow biopsies by immunohistochemistry. Hypermethylation in the 5′ p15 gene region was detected in 15 of 23 patients (65%), whereas the 5′ p16 region was unmethylated in all patients. Among 12 patients with hypermethylation sequentially analyzed after at least one course of decitabine treatment, a decrease in p15 methylation occurred in 9 and was associated with clinical response. DGGE and sequence analyses were indicative of hypomethylation induction at individual alleles. Immunohistochemical staining for p15 protein in bone marrow biopsies from 8 patients with p15 hypermethylation revealed low or absent expression in 4 patients, which was induced to normal levels during decitabine treatment. In conclusion, frequent, selectivep15 hypermethylation was reversed in responding MDS patients following treatment with a methylation inhibitor. The emergence of partially demethylated epigenotypes and re-establishment of normal p15 protein expression following the initial decitabine courses implicate pharmacologic demethylation as a possible mechanism resulting in hematologic response in MDS.
Waldenström macroglobulinemia neoplastic cells lack immunoglobulin heavy chain locus translocations but have frequent 6q deletions
Authors: Schop Roelandt F. J. , Kuehl W. Michael , Van Wier Scott A. , Ahmann Gregory J. , Price-Troska Tammy , Bailey Richard J. , Jalal Syed M. , Qi Ying , Kyle Robert A. , Greipp Philip R. , Fonseca Rafael
Published: September 2002

Lymphoplasmacytic lymphoma (LPL) is characterized by t(9;14)(p13;q32) in 50% of patients who lack paraproteinemia. Waldenström macroglobulinemia (WM), which has an immunoglobulin M (IgM) paraproteinemia, is classified as an LPL. Rare reports have suggested that WM sometimes is associated with 14q23 translocations, deletions of 6q, and t(11;18)(q21;q21). We tested for these abnormalities in the clonal cells of WM patients. We selected patients with clinicopathologic diagnosis of WM (all had IgM levels greater than 1.5 g/dL). Southern blot assay was used to detect legitimate and illegitimate IgH switch rearrangements. In addition to conventional cytogenetic (CC) and multicolor metaphase fluorescence in situ hybridization (M-FISH) analyses, we used interphase FISH to screen for t(9;14)(p13;q32) and other IgH translocations, t(11;18)(q21;q21), and 6q21 deletions. Genomic stability was also assessed using chromosome enumeration probes for chromosomes 7, 9, 11, 12, 15, and 17 in 15 patients. There was no evidence of either legitimate or illegitimate IgH rearrangements by Southern blot assay (n = 12). CC (n = 37), M-FISH (n = 5), and interphase FISH (n = 42) failed to identify IgH or t(11;18) translocations. Although tumor cells from most patients were diploid for the chromosomes studied, deletions of 6q21 were observed in 42% of patients. In contrast to LPL tumors that are not associated with paraproteinemia and that have frequent t(9;14)(p13;q32) translocations, IgH translocations are not found in WM, a form of LPL tumor distinguished by IgM paraproteinemia. However, WM tumor cells, which appear to be diploid or near diploid, often have deletions of 6q21.
Effect of pattern and severity of respiratory muscle weakness on carbon monoxide gas transfer and lung volumes
Authors: Hart N. , Cramer D. , Ward S.P. , Nickol A.H. , Moxham J. , Polkey M.I. , Pride N.B.
Published: September 2002

In clinical practice, an elevated carbon monoxide (CO) transfer coefficient (KCO) and restrictive ventilatory defect are taken as features of respiratory muscle weakness (RMW). However, the authors hypothesised that both pattern and severity of RMW effect gas transfer and lung volumes.

Measurements of CO transfer and lung volumes were performed in patients with isolated diaphragm weakness (n=10), inspiratory muscle weakness (n=12), combined inspiratory and expiratory muscle weakness (n=5) and healthy controls (n=6).

Patients with diaphragm weakness and inspiratory muscle weakness had reduced total lung capacity (TLC) (83.6% predicted and 68.9% pred, respectively), functional residual capacity (FRC) (83.9% pred and 83.6% pred) and transfer factor of the lung for CO (TL,CO) (86.2% pred and 66.2% pred) with increasedKCO(114.1% pred and 130.2% pred). Patients with combined inspiratory and expiratory muscle weakness had reduced TLC (80.9% pred) but increased FRC (109.9% pred) and RV (157.4% pred) with decreasedTL,CO(58.0% pred) andKCO(85.5% pred).

In patients with diaphragm weakness, the increase in carbon monoxide transfer coefficient was similar to that of normal subjects when alveolar volume was reduced. However, the increase in carbon monoxide transfer coefficient in inspiratory muscle weakness was often less than expected, while in combined inspiratory and expiratory muscle weakness, the carbon monoxide transfer coefficient was normal/reduced despite further reductions in alveolar volume, which may indicate subtle abnormalities of the lung parenchyma or pulmonary vasculature. Thus, this study demonstrates the limitations of using carbon monoxide transfer coefficient in the diagnosis of respiratory muscle weakness, particularly if no account is taken of the alveolar volume at which the carbon monoxide transfer coefficient is made.
Assisted ventilation for heart failure patients with Cheyne-Stokes respiration
Authors: Köhnlein T. , Welte T. , Tan L.B. , Elliott M.W.
Published: September 2002

Patients with chronic congestive cardiac failure (CCF) frequently suffer from central sleep apnoea syndrome (CSAS). Continuous positive airway pressure (CPAP) has been suggested as a treatment. The authors hypothesised that bilevel ventilation might be easier to initiate and superior to CPAP at correcting the sleep-related abnormality of breathing in patients with CCF.

After excluding those with a history suggestive of obstructive sleep apnoea, 35 patients with CCF (left ventricular ejection fraction <35%) were screened with overnight oximetry and the diagnosis of CSAS was established with polysomnography in 18. Two 14-day cycles of CPAP (0.85 kPa (8.5 mbar)) or bilevel ventilation (0.85/0.3 kPa (8.5/3 mbar)) in random order, were compared in a crossover study.

Sixteen patients (13 males), mean age 62.0±7.4 yrs completed the study. The pretreatment apnoea/hypopnoea index of 26.7±10.7 was significantly reduced by CPAP and bilevel ventilation to 7.7±5.6 and 6.5±6.6, respectively. The arousal index fell from 31.1±10.0 per hour of sleep to 15.7±5.4 and 16.4±6.9, respectively. Significant and equal improvements with CPAP and bilevel ventilation were found for sleep quality, daytime fatigue, circulation time and New York Heart Association class.

The authors conclude that continuous positive airway pressure and bilevel ventilation equally and effectively improve Cheyne-Stokes respiration in patients with congestive cardiac failure.
Endobronchial ultrasound-guided transbronchial lung biopsy in solitary pulmonary nodules and peripheral lesions
Authors: Herth F.J.F. , Ernst A. , Becker H.D.
Published: September 2002

Transbronchial biopsy (TBBX) for peripheral lung lesions is usually performed with the help of fluoroscopy, but the yield varies widely. This feasibility study aimed to assess the ability of endobronchial ultrasound (EBUS) to provide imaging guidance for TBBX.

In a prospective study, 50 consecutive patients referred for TBBX for peripheral lesions underwent fluoroscopy-guided and EBUS-guided TBBX in random order. Diagnostic yields were compared for both modalities and feasibility was assessed for EBUS.

Diagnostic material was obtained in 80% of patients with EBUS and 76% of patients with fluoroscopy. There was a nonsignificant trend for EBUS to be better than fluoroscopy for lesions <3 cm in diameter. Four lesions could not be visualised with EBUS. There were no significant complications associated with the use of EBUS.

Endobronchial ultrasound-guided transbronchial biopsy is feasible. It appears to be at least equivalent to fluoroscopy without the accompanying radiation exposure. Further large-scale studies are indicated to assess the possible role of endobronchial ultrasound as a potential imaging method of choice for the biopsy of peripheral lung lesions.
Chronic bronchitis among French adults: high prevalence and underdiagnosis
Authors: Huchon G.J. , Vergnenègre A. , Neukirch F. , Brami G. , Roche N. , Preux P-M.
Published: September 2002

The aims of this survey were to determine the prevalence of symptoms indicative of chronic bronchitis (CB) in the French adult population, to identify the role of risk factors for CB, and to assess rates of CB diagnosis and pulmonary function testing (PFT) in the presence of CB.

A representative sample of 14,076 individuals aged ≥25 yrs completed a self-administered questionnaire on symptoms, comorbidities, smoking history, sociodemographical data, and diagnosis and care by physicians.

The prevalence of CB was 4.1% and the prevalence of chronic cough and/or expectoration was 11.7%. In individuals with comorbidity, these figures were 10.4% and 24.4%, respectively. Smoking was associated with an increased frequency of CB. In subjects with CB, 44.6% had PFT (spirometry or peak expiratory flow measurement), 24% were diagnosed as having CB, and 7.2% received care. Rates of diagnosis, PFT, and follow-up were lower in young individuals and in those without comorbidity. PFT and follow-up were less common in current smokers.

Prevalence of chronic bronchitis in French adults is high and similar in magnitude to that of other industrialised countries. Comorbidities and tobacco smoking increase the frequency of chronic bronchitis symptoms. Chronic bronchitis is too infrequently diagnosed, investigated and cared for.
Efficacy of acupuncture in asthma: systematic review and meta-analysis of published data from 11 randomised controlled trials
Authors: Martin J. , Donaldson A.N.A. , Villarroel R. , Parmar M.K.B. , Ernst E. , Higginson I.J.
Published: September 2002

Contradictory results from randomised controlled trials of acupuncture in asthma suggest both a beneficial and detrimental effect. The authors conducted a formal systematic review and meta-analysis of all randomised clinical trials in the published literature that have compared acupuncture at real and placebo points in asthma patients.

The authors searched for trials published in the period 1970–2000. Trials had to measure at least one of the following objective outcomes: peak expiratory flow rate, forced expiratory volume in one second (FEV1) and forced vital capacity. Estimates of the standarised mean difference, between acupuncture and placebo were computed for each trial and combined to estimate the overall effect. Hetereogeneity was investigated in terms of the characteristics of the individual studies.

Twelve trials met the inclusion criteria but data from one could not be obtained. Individual patient data were available in only three. Standardised differences between means ranging from 0.071 to 0.133, in favour of acupuncture, were obtained. The overall effect was not conventionally significant and it corresponds to an approximate difference in FEV1means of 1.7. After exploring hetereogenenity, it was found that studies where bronchoconstriction was induced during the experiment showed a conventionally significant effect.

This meta-analysis did not find evidence of an effect of acupuncture in reducing asthma. However, the meta-analysis was limited by shortcomings of the individual trials, in terms of sample size, missing information, adjustment of baseline characteristics and a possible bias against acupuncture introduced by the use of placebo points that may not be completely inactive. There was a suggestion of preferential publication of trials in favour of acupuncture. There is an obvious need to conduct a full-scale randomised clinical trial addressing these limitations and the prognostic value of the aetiology of the disease.
Broncholithiasis and lithoptysis associated with silicosis
Authors: Antão V.C.S. , Pinheiro G.A. , Jansen J.M.
Published: September 2002

A case of broncholithiasis associated with massive silicosis is reported, showing a rare aspect of parenchymal lesions generating broncholiths as well as the presence of recurrent lithoptysis, with subsequent regression of radiological lesions.

Aetiological, clinical, physiopathological, and radiological aspects of the disease are discussed, demonstrating the importance of the use of computed tomography in diagnosis. The mineralogical analysis of expectorated fragments is also shown.
Chlamydia pneumoniaeimmunoglobulin A reactivation and airway inflammation in acute asthma
Authors: Wark P.A.B. , Johnston S.L. , Simpson J.L. , Hensley M.J. , Gibson P.G.
Published: September 2002

Infection withChlamydia pneumoniaecan trigger acute asthma and is associated with severe chronic asthma. The aim of the present study was to examine the relationship between airway inflammation and serological response toC. pneumoniaein acute severe asthma.

Subjects (n=54) were recruited within 4 h of presentation to the emergency department with an acute exacerbation of asthma. Clinical history taking, sputum induction (0.9% saline), spirometry and acute and convalescent serology forC. pneumoniaeimmunoglobulins A and G were performed.

At presentation, 47% of subjects had antibodies directed againstC. pneumoniae, and 38% (20) demonstrated an increase inC. pneumoniaeantibody levels, with 15 demonstrating a rise in immunoglobulin A concentration.C. pneumoniaeresponders exhibited significantly higher sputum neutrophil levels (4.6×106cells·mL−1) compared to nonresponders (1.2×106cells·mL−1, p=0.02) and elevated sputum eosinophil cationic protein concentration (3,981versus1,122 ng·mL−1, p=0.02).

An acute antibody response toChlamydia pneumoniaeis common in exacerbations of asthma. The serological features suggest thatChlamydia pneumoniaereactivation may trigger neutrophilic airway inflammation in acute asthma.
Increased alveolar nitric oxide concentration in asthmatic patients with nocturnal symptoms
Authors: Lehtimäki L. , Kankaanranta H. , Saarelainen S. , Turjanmaa V. , Moilanen E.
Published: September 2002

Nocturnal asthma symptoms and impaired lung function at night are related to inflammatory activity in the peripheral lung compartment. Exhaled nitric oxide (NO) measurement at multiple exhalation flow rates can be used to separately assess alveolar and bronchial NO production and inflammation. The authors hypothesised that asthmatic patients with nocturnal symptoms have a higher alveolar NO concentration than those with only daytime symptoms.

The authors asked 40 patients with newly-diagnosed steroid-naïve asthma about their nocturnal asthma symptoms through the use of a written questionnaire. Alveolar NO concentration and bronchial NO flux were assessed in the 40 asthmatics and 40 healthy controls.

Nineteen of the 40 patients reported nocturnal symptoms. Patients with nocturnal symptoms had a higher alveolar NO concentration (1.7±0.3 (mean±sem) parts per billion (ppb)) than patients without nocturnal symptoms (0.8±0.3 ppb, p=0.012) or healthy controls (1.0±0.1 ppb, p=0.032). Bronchial NO flux was higher both in patients with (2.4±0.4 nL·s−1, p<0.001) and without (2.6±0.4 nL·s−1, p<0.001) nocturnal symptoms, compared to controls (0.7±0.1 nL·s−1).

Nocturnal symptoms in asthmatic patients are related to a higher alveolar nitric oxide concentration. The results suggest that assessment of alveolar nitric oxide concentration can be used to detect the parenchymal inflammation in asthmatic patients with nocturnal symptoms.
Measurement of lung volume and ventilation distribution with an ultrasonic flow meter in healthy infants
Authors: Schibler A. , Hall G.L. , Businger F. , Reinmann B. , Wildhaber J.H. , Cernelc M. , Frey U.
Published: September 2002

Small airway disease in infants is characterised by abnormal lung volume and uneven ventilation distribution. An inert tracer gas washin/washout technique using a pulsed ultrasonic flow meter is presented to measure functional residual capacity (FRC) and ventilation distribution in spontaneously breathing and unsedated infants.

With a pulsed ultrasound sent through the main stream of the flow meter, flow, volume and MM of the breathing gas can be calculated. Sulphur hexafluoride was used as a tracer gas. In a mechanical lung model (volume range 53–188 mL) and in 12 healthy infants (aged 38.3±9.2 days; mean±sd) accuracy and reproducibility of the technique was assessed. Indices of ventilation distribution such as alveolar-based mean dilution number (AMDN) and pulmonary clearance delay (PCD) were calculated.

Mean error of volume measurement in the lung model was 0.58% (coefficient of variance (CV) 1.3%). FRC was in the low predicted range for normal infants (18.0±2.0 mL·kg−1) and highly reproducible (5.5±1.7% intra-subject CV). AMDN was 1.63±0.15 and PCD was 52.9±11.1%.

Measurement of functional residual capacity and ventilation distribution using a sulphur hexafluoride washin/washout and an ultrasonic flow meter proved to be highly accurate and reproducible in a lung model and in healthy, spontaneously breathing and unsedated infants.
Short-term health effects of particulate and photochemical air pollution in asthmatic children
Authors: Just J. , Ségala C. , Sahraoui F. , Priol G. , Grimfeld A. , Neukirch F.
Published: September 2002

In a previous panel study in Paris, France, detrimental effects of moderately high levels of winter air pollution on the symptoms and lung function of asthmatic children were demonstrated. A new study was conducted, with the aim of assessing the short-term effects of photo-oxidant and particulate air pollution on childhood asthma during spring and early summer in Paris.

Eighty-two medically diagnosed asthmatic children were followed up for 3 months. Outcomes included the incidence and prevalence of asthma attacks, nocturnal cough, supplementary use of β2-agonists, symptoms of airway irritation, and peak expiratory flow (PEF) value and its variability. The statistical methods controlled for the lack of independence between daily health outcomes, temporal trends and pollen and weather conditions.

Black smoke and nitrogen dioxide (NO2) were associated with increases in the occurrence of nocturnal cough and respiratory infections. Ozone (O3) was associated with an increase in the occurrence of asthma attacks and respiratory infections and with changes in lung function, as shown by an increase in PEF variability and a decrease in PEF. Statistically significant interactions were demonstrated between O3and temperature and between O3and pollen count for asthma attacks. O3levels had a greater effect on additional bronchodilator use and on irritations of the eyes, nose and throat on days on which no steroids were used. Particulate matter was associated with eye irritation only.

This study showed that, although within international air quality standards, the prevailing levels of photo-oxidant and particulate pollution in spring and early summer had measurable short-term effects on children with mild-to-moderate asthma.
Montelukastversusfluticasone: effects on lung function, airway responsiveness and inflammation in moderate asthma
Authors: Kanniess F. , Richter K. , Böhme S. , Jörres R.A. , Magnussen H.
Published: September 2002

Whether leukotriene receptor antagonists exhibit adequate anti-inflammatory effects in the treatment of asthma is still a controversial issue. The aim of the present study was to perform a direct comparison of the effects of a 4-week treatment with either montelukast (10 mg, once a day) or low-dose inhaled fluticasone (100 µgb.i.d.) on functional and inflammatory parameters in steroid-naïve patients with moderate asthma.

Forty patients (forced expiratory volume in one second (FEV1), 60–80% predicted) were studied in a double-blind, randomised, crossover design. Treatment periods were separated by 3–8 weeks of washout. At the beginning and end of each period, FEV1, airway responsiveness to inhaled methacholine (provocative concentration causing a 20% fall in FEV1(PC20)), the level of exhaled nitric oxide (NO) and sputum differential cell counts were determined. Only short-acting β2-agonists were allowed for relief of symptoms.

FEV1increased by 0.50±0.07 L (mean±sem) after fluticasone and by 0.37±0.07 L after montelukast (p<0.001, each), and PC20by 1.33±0.13 (p<0.001) and 0.15±0.17 (ns) doubling doses, respectively. Correspondingly, percentages of sputum eosinophils were reduced by factor 2.7 (p<0.01) and 1.4 (nonsignificant (ns)), and the levels of exhaled NO (at 50 mL·s−1) by factor 2.1 (p<0.01) and 1.1 (ns).

These data indicate a comparable bronchodilator action of montelukast and fluticasone in patients with moderate asthma, but additional attenuation of airway inflammation by fluticasone as detectable through noninvasive methods.
The effect of hypertonic saline dextran solutions on hypoxic pulmonary vasoconstriction in anaesthetised piglets
Authors: Bellezza M. , Kerbaul F. , Roussel L. , Imbert M. , Guidon C.
Published: September 2002

Hypoxic pulmonary vasoconstriction (HPV) is a regulatory mechanism by which blood is diverted from poorly ventilated to better ventilated areas of the lung. The aim of the present study was to assess the extent to which hypertonic saline dextran and dextran solutions modify the magnitude of HPV during isovolumic haemodilution in intact acutely instrumented piglets.

Eighteen large white piglets were anesthetised and assigned to two groups. Mean pulmonary arterial pressure (PAP) and cardiac output (Q), systemic arterial pressure and left arterial pressure (LAP) were measured. A decrease in Q was obtained by reducing venous return. This enabled measurement of transpulmonary pressures (mean PAP minus LAP) at four levels of Q in hyperoxia (inspiratory oxygen fraction (Fi,O2)=0.4), then in hypoxia (Fi,O2=0.1) in the two groups before blood soustraction (10 mL·kg−1) and after loading with sodium chloride (NaCl) 7.5% and dextran 6% or with dextran 6% alone. Dextran alone led to a decrease in mean PAP–LAP/Q values, and NaCl with dextran was associated with a significant shift of mean PAP–LAP/Q plots to higher pressures in hypoxia.

Hypertonic saline dextran solution, as replacement fluid in isovolaemic haemodilution increased the magnitude of hypoxic pulmonary vasoconstriction, whereas dextran solution reduced it.
Age-related differences in perceived asthma control in childhood: guidelines and reality
Authors: Kuehni C.E. , Frey U.
Published: September 2002

Current guidelines specify the goals of asthma treatment in children and propose a stepwise approach to achieve them. The authors sought to determine whether these goals were attained in children of different age groups in the community and to assess treatment in those with unsatisfactory asthma control.

A cross-sectional postal questionnaire survey was performed in 1998 in all members of the major Swiss parents organisation for childhood asthma.

With a response rate of 85%, data from 572 Swiss-German children aged 4–16 yrs with wheeze were analysed. Asthma control was excellent in 18% of the children, satisfactory (only episodic symptoms) in 33%, and unsatisfactory in 49% with disturbed sleep, restricted activities and school absences. When stratified by age, excellent or satisfactory control was attained by 66% of children aged 13–16 yrs, but only by 56%, 44%, and 38% of those aged 10–12, 7–9 and 4–6 yrs, respectively. Although the majority were followed-up by a doctor (95%) and were receiving β2-agonists (82%) and inhaled corticosteroids (68%), intensity and duration of treatment were not sufficiently matched to asthma severity. In virtually all children there was scope to improve medical treatment, preventive measures and knowledge of asthma management, with very few if any children with therapy-resistant asthma. Even in children with poor asthma control, 89% of parents were satisfied with the results of treatment.

The goals of asthma treatment were attained in one-half of the children, particularly in younger age groups. Although inhaler use was common, detailed assessment showed evidence for undertreatment, especially in the youngest age group, and insufficient adherence to preventive measures. Parental expectations of asthma control, which were lower than those outlined in guidelines, might be an important but underestimated factor in paediatric asthma management.
Respiratory symptoms, bronchitis and asthma in children of Central and Eastern Europe
Authors: Leonardi G.S. , Houthuijs D. , Nikiforov B. , Volf J. , Rudnai P. , Zejda J. , Gurzau E. , Fabianova E. , Fletcher T. , Brunekreef B.
Published: September 2002

The multicentre Central European Study of Air Pollution and Respiratory Health (CESAR) aimed to measure the respiratory health of schoolchildren using a standardised questionnaire in six countries of Central and Eastern Europe (CEE), allowing comparisons within this region and with other European countries.

A cross-sectional study was conducted in 25 urban areas of Bulgaria, Czech Republic, Hungary, Poland, Romania, and Slovakia in 1996. Parents of 21,743 schoolchildren of age 7–11 yrs completed a questionnaire based on items from the World Health Organization and International Study of Asthma and Allergies in Childhood questions on cough and wheeze symptoms, as well as on diagnoses by doctors.

Life-time prevalence of bronchitis was 55.9%, asthma 3.9%, and asthmatic, spastic or obstructive bronchitis 12.3%. In CEE countries the prevalence of bronchitis is higher and prevalence of asthma appears lower than in Western Europe. However, if asthma is defined as a diagnosis of either asthma or asthmatic, spastic or obstructive bronchitis, then its prevalence is comparable to Western Europe, or higher.

In this region, within-country variation for most respiratory parameters is less than between-country variation. Between-country comparisons in doctors' diagnoses appear dependent on the choice of definition of asthma. Europe-wide comparisons in prevalence of respiratory symptoms and diagnosis are reported in this study. Some of the East-West difference in asthma prevalence may be attributable to differences in diagnostic practice.
Histopathological studies on the effects of peroxynitrite on the lungs and trachea of rabbits: Fig. 1.—
Authors: Farshid A.A. , Sadeghi-Hashjin G. , Ferdowsi H.R.
Published: September 2002

Peroxynitrite (ONOO−) is the reaction product between nitric oxide and the superoxide anion. It is a biological oxidant and cytotoxic anion, producedin vivo, which might cause inflammation and damage to the lungs. This study was designed to investigate whether direct contact with peroxynitrite could cause pathological changes in the airways.

Twenty New Zealand rabbits were divided into four experimental groups. They were anesthetised by intravascular injection of thiopental sodium, and peroxynitrite (0.5 mL of a 10 mM solution) was inoculated intratracheally. At 2 h, 24 h, 48 h, and 72 h postinoculation trachea and lungs were isolated for histopathology.

The histopathological observations in the lungs were congestion, serous exudation, infiltration of leukocytes and degeneration, which were found to be time-dependent. Changes were similar at 48 and 72 h. Degenerative changes were not progressive. The changes in the trachea were congestion, oedema, leukocyte infiltration, and degeneration of tracheal epithelium.

This study shows that peroxynitrite formation in the respiratory tract induces lung inflammation and degenerative changes.
Talcage by medical thoracoscopy for primary spontaneous pneumothorax is more cost-effective than drainage: a randomised study
Authors: Tschopp J-M. , Boutin C. , Astoul P. , Janssen J-P. , Grandin S. , Bolliger C-T. , Delaunois L. , Driesen P. , Tassi G. , Perruchoud A-P. ,   and the ESMEVAT team
Published: September 2002

Simple thoracoscopic talcage (TT) is a safe and effective treatment of primary spontaneous pneumothorax (PSP). However, its efficacy has not previously been estimated in comparison with standard conservative therapy (pleural drainage (PD)).

In this prospective randomised comparison of two well-established procedures of treating PSP requiring at least a chest tube, cost-effectiveness, safety and pain control was evaluated in 108 patients with PSP (61 TT and 47 PD).

Patients in both groups had comparable clinical characteristics. Drainage and hospitalisation duration were similar in TT and PD patients. There were no complications in either group. The immediate success rate was different: after prolonged drainage (>7 days), 10 out of 47 PD patients, but only 1 out of 61 TT patients required a TT as a second procedure. Total costs of hospitalisation including any treatment procedure were not significantly different between TT and PD patients. Pain, measured daily by visual analogue scales, was statistically higher during the first 3 days in TT patients but not in those patients receiving opiates. One month after leaving hospital, there was no significant difference in residual pain or full working ability: 20 out of 58 (34%)versus10 out of 47 (21%) and 36 out of 61 (59%)versus26 out of 39 (67%) in TTversusPD groups, respectively. After 5 yrs of follow-up, there had been only three out of 59 (5%) recurrences of pneumothorax after TT, but 16 out of 47 (34%) after conservative treatment by PD. Cost calculation favoured TT pleurodesis especially with regard to recurrences.

In conclusion, thoracoscopic talc pleurodesis under local anaesthesia is superior to conservative treatment by chest tube drainage in cases of primary spontaneous pneumothorax that fail simple aspiration, provided there is efficient control of pain by opioids.
Safety of formoterol by Turbuhaler® as reliever medication compared with terbutaline in moderate asthma
Authors: Ind P.W. , Villasante C. , Shiner R.J. , Pietinalho A. , Böszörményi N.G. , Soliman S. , Selroos O.
Published: September 2002

The present study compared the safety of 4.5 µg formoterol with 0.5 mg terbutaline, both by Turbuhaler® and used as needed, in addition to regular formoterol in moderate asthma.

In this double-blind parallel-group study, 357 patients taking a moderate-to-high dose of inhaled corticosteroids and additional terbutaline (2–5 inhalations·day−1during run-in) were randomised to either formoterol or terbutaline as needed in addition to formoterol 9 µgb.i.d.over 12 weeks. Adverse events, serum potassium levels, electrocardiogram, vital signs and lung function were assessed monthly; peak expiratory flow and severe asthma exacerbations were recorded daily.

Patients used 2.16 (range 0.0–6.3) formoterol and 2.34 (range 0.1–7.5) terbutaline relief inhalations·day−1. No clinically significant differences in safety variables were found between treatments. Statistically greater increases in cardiac frequency (2.6 beats·min−1, p=0.03) were found on terbutaline. There were 44 and 52 severe asthma exacerbations with formoterol and terbutaline, respectively, with no significant difference in time to first exacerbation. There was also no difference between treatments for other efficacy measures (peak expiratory flow, forced expiratory volume in one second and morning/evening symptom scores).

Formoterol 4.5 µg as needed was at least as safe, well tolerated and effective as terbutaline 0.5 mg in stable patients (requiring up to 6 relief inhalations·day−1) taking formoterol plus inhaled corticosteroids regularly over 12 weeks.
Vaccination of COPD patients with a pneumococcus type 6B tetanus toxoid conjugate vaccine
Authors: Jonsson S. , Vidarsson G. , Valdimarsson H. , Schiffman G. , Schneerson R. , Jonsdottir I.
Published: September 2002

This paper examines how pneumococcal type 6B polysaccharide conjugated to tetanus toxoid (Pn6B-TT) compares to a 23 valent pneumococcal vaccine (pneumococcal polysaccharide (PPS)-23) with respect to immunogenicity and serum opsonic activity in patients with chronic obstructive pulmonary disease (COPD).

Patients with COPD aged 55–75 yrs were vaccinated with Pn6B-TT (n=10) or with PPS-23 (n=9). Healthy young adults (HA) were vaccinated with Pn6B-TT as controls. Total antibodies to serotype 6B polysaccharide were measured by radioimmunoassay and immunoglobulin (Ig)G antibodies by enzyme-linked immunosorbent assay. Opsonic activity was measured by a phagocytosis assay using human neutrophils as effector cells.

The patient groups were comparable by age, smoking history, lung function and use of steroids. COPD patients vaccinated with Pn6B-TT or PPS-23 showed an increase in IgG antibodies and a nonsignificant increase in opsonic activity. This was similar to the increase in IgG and opsonic activity seen in HA. There was a significant correlation between antibody levels and opsonic activity in COPD patients vaccinated both with Pn6B-TT and PPS-23.

Pneumococcal antibodies have been shown to confer protection from infection. The results of the present study indicate that protective immunity can be expected in elderly chronic obstructive pulmonary disease patients vaccinated with conjugate vaccines.
Systemic cytokine levels in community-acquired pneumonia and their association with disease severity
Authors: Antunes G. , Evans S.A. , Lordan J.L. , Frew A.J.
Published: September 2002

Pro-inflammatory and anti-inflammatory cytokines are important mediators in the host response to infection. In contrast to the pro-inflammatory cytokines little is known about anti-inflammatory cytokines in community-acquired pneumonia (CAP) and their relation to disease severity.

Circulating levels of three pro-inflammatory cytokines (interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α) and two anti-inflammatory cytokines (IL-10, IL-1 receptor antagonist (IL-1ra)) were measured using an enzyme immunoassay on admission, day 3 and day 5 in 24 patients with CAP. The modified British Thoracic Society (BTS) prognostic rule and Acute Physiology and Chronic Health Evaluation (APACHE) II score were used to assess disease severity.

IL-6, TNF-α, IL-10 and IL-1ra concentrations were detected in most patients on admission and decreased significantly on day 3 and day 5 in all survivors. A significant difference between the BTS high-risk and low-risk groups was only found for IL-6 (median (range) 477 pg·mL−1(7.6–1402 pg·mL−1)versus81.6 pg·mL−1(0–943 pg·mL−1); p<0.05). IL-6 also correlated with the APACHE II scores on admission.

Concentrations of anti-inflammatory cytokines were elevated on admission in community-acquired pneumonia but they did not correlate with disease severity scores.
The role of EGF-R expression on patient survival in lung cancer: a systematic review with meta-analysis
Authors: Meert A-P. , Martin B. , Delmotte P. , Berghmans T. , Lafitte J-J. , Mascaux C. , Paesmans M. , Steels E. , Verdebout J-M. , Sculier J-P.
Published: September 2002

The prognostic value of epidermal growth factor receptor (EGF-R) for survival of patients with lung cancer remains controversial. The authors performed a systematic review of the literature in order to clarify its impact.

Published studies were identified using an electronic search in order to aggregate the available survival results, after a methodological assessment using a scale specifically designed by the European Lung Cancer Working Party (ELCWP). To be eligible, a study had to have dealt with EGF-R assessment in lung cancer patients on the primary site and to have analysed survival according to EGF-R expression.

Among the 16 eligible studies, 14 assessed any nonsmall-cell lung cancer (NSCLC) subtype, one adenocarcinoma only and one squamous-cell carcinoma only. The overall median quality score was 56.3%, with no significant difference either between studies assessable or not assessable for meta-analysis or between studies with significant and nonsignificant results. One individual trial reported a survival benefit for patients with EGF-R expression, three a survival disadvantage and 12 no statistically significant difference. Eleven studies (2,185 patients) provided sufficient data to allow a meta-analysis of the survival results. EGF-R expression positivity was determined according to the cut-off as determined by the authors. The meta-analysis showed that EGF-R expression was not a statistically significant prognostic factor for survival in NSCLC. In the subgroup of studies using immunohistochemistry, statistical tests reached a significant level against EGF-R.

Epidermal growth factor receptor might be a poor prognostic factor for survival in nonsmall-cell lung cancer. The amplitude of the impact is small, however, and may be subject to publication bias.
An overnight comparison of two ventilators used in the treatment of chronic respiratory failure
Authors: Highcock M.P. , Morrish E. , Jamieson S. , Shneerson J.M. , Smith I.E.
Published: September 2002

Differences between bilevel ventilators used for noninvasive intermittent positive pressure ventilation (NIPPV) have been demonstrated during bench testing. However, there are no clinical studies comparing these machines. The authors have previously shown that the Quantum pressure support ventilator and Sullivan variable positive airway pressure II ST differ in performance during bench testing. To examine the clinical significance of this, these two machines were compared in the overnight treatment of subjects with chronic respiratory failure.

Ten clinically-stable subjects with thoracic scoliosis were recruited. The subjects were already established on NIPPV, but none were using either of the ventilators to be tested. After familiarisation, the patients used the two ventilators in random order on consecutive nights. Peripheral oxygen saturation and transcutaneous carbon dioxide tension (Pt,CO2) were measured continuously, and sleep was recorded using polysomnography.

There were no significant differences in arterial oxygen saturation,Pt,CO2or sleep duration and quality between the two nights.

Despite previously illustrated variation in laboratory performance, no differences were seen between the two ventilators when comparing overnight gas exchange and sleepin vivo. Further study is required to evaluate the significance of the differences found during bench testing in the clinical setting.
Survival in COPD patients after regular use of fluticasone propionate and salmeterol in general practice
Authors: Soriano J.B. , Vestbo J. , Pride N.B. , Kiri V. , Maden C. , Maier W.C.
Published: September 2002

Despite substantial evidence regarding the benefits of combined use of inhaled corticosteroids and long-acting β2-agonists in asthma, such evidence remains limited for chronic obstructive pulmonary disease (COPD). Observational data may provide an insight into the expected survival in clinical trials of fluticasone propionate (FP) and salmeterol in COPD.

Newly physician-diagnosed COPD patients identified in primary care during 1990–1999 aged ≥50 yrs, of both sexes and with regular prescriptions of respiratory drugs were identified in the UK General Practice Research Database. Three-year survival in 1,045 COPD patients treated with FP and salmeterol was compared with that in 3,620 COPD patients who regularly used other bronchodilators but not inhaled corticosteroids or long-acting β2-agonists. Standard methods of survival analysis were used, including adjustment for possible confounders.

Survival at year 3 was significantly greater in FP and/or salmeterol users (78.6%) than in the reference group (63.6%). After adjusting for confounders, the survival advantage observed was highest in combined users of FP and salmeterol (hazard ratio (HR) 0.48 (95% confidence interval 0.31–0.73)), followed by users of FP alone (HR 0.62 (0.45–0.85)) and regular users of salmeterol alone (HR 0.79 (0.58–1.07))versusthe reference group. Mortality decreased with increasing number of prescriptions of FP and/or salmeterol.

In conclusion, regular use of fluticasone propionate alone or in combination with salmeterol is associated with increased survival of chronic obstructive pulmonary disease patients managed in primary care.
α1-antitrypsin deficiency: a report from the 2nd meeting of the Alpha One International Registry, Rapallo (Genoa, Italy), 2001
Authors: Luisetti M. , Miravitlles M. , Stockley R.A.
Published: September 2002

The Alpha One International Registry is a scientific foundation established to comply with a World Health Organization recommendation to develop a multinational registry of α1-antitrypsin deficiency, with the aim of creating a common database of subjects recognised in a standardised way.

A commitment of the Alpha One International Registry members, belonging to 15 national registries, is to meet every 2 yrs in an open scientific conference to provide a scientific and clinical update on the deficiency. The second Alpha One International Registry meeting was held in Rapallo (Genoa, Italy) on September 27th–28th, 2001, and 26 speakers provided an exhaustive overview of all aspects of α1-antitrypsin deficiency, including epidemiology, genetics, biochemistry, associated conditions, established and novel therapeutic options, and markers of efficacy. In the framework of a rare and often under-recognised condition, this meeting is likely to be central to improving understanding and increasing awareness of α1-antitrypsin deficiency.
Sodium cromoglycate and doxantrazole are oxygen radical scavengers
Authors: Sadeghi-Hashjin G. , Nijkamp F.P. , Henricks P.A.J. , Folkerts G.
Published: September 2002

The effects of two mast cell stabilisers, sodium cromoglycate (SCG) and doxantrazole, on the formation of reactive oxygen species (ROS) were studied. Guinea-pig alveolar macrophages (AMs) generated lucigenin-dependent chemiluminescence (LDCL). This was increased when the cells were stimulated by phorbol myristate acetate (PMA) or zymosan (by 133% and 464%, respectively, in total LDCL over 60 min). SCG decreased PMA-induced LDCL at higher concentrations (10 mM, by 55%) than doxantrazole (1 mM, by 75%). SCG decreased radical production by AMs in response to zymosan in a concentration-dependent manner by ≤72%. Doxantrazole (0.1–1 mM) diminished total LDCL by 30–80%. In addition, glucose oxidase led to LDCL generation when incubated with glucose in a cell-free medium. This was inhibited by 47–83% in the presence of SCG or doxantrazole. SCG and doxantrazole inhibited the hydrogen peroxide- and peroxynitrite-induced LDCL by ≤92%. Moreover, these drugs slightly increased the survival rate of the AMs.

It is concluded that doxantrazole- and sodium cromoglycate-inhibited lucigenin-dependent chemiluminescence production by guinea-pig alveolar macrophages is due to a direct scavenging effect on reactive oxygen species. Doxantrazole is ∼10-times more potent. Mast cell stabilisers may be effective in allergic asthma not only by preventing the allergen-induced mediator release, but also by preventing radical-induced lung damage.
Prone position in acute respiratory distress syndrome
Authors: Pelosi P. , Brazzi L. , Gattinoni L.
Published: September 2002

In the last few years prone positioning has been used increasingly in the treatment of patients with acute respiratory distress syndrome (ARDS) and this manoeuvre is now considered a simple and safe method to improve oxygenation. However, the physiological mechanisms causing respiratory function improvement as well as the real clinical benefit are not yet fully understood. The aim of this review is to discuss the physiological and clinical effects of prone positioning in patients with ARDS.

The main physiological aims of prone positioning are: 1) to improve oxygenation; 2) to improve respiratory mechanics; 3) to homogenise the pleural pressure gradient, the alveolar inflation and the ventilation distribution; 4) to increase lung volume and reduce the amount of atelectatic regions; 5) to facilitate the drainage of secretions; and 6) to reduce ventilator-associated lung injury.

According to the available data, the authors conclude that: 1) oxygenation improves in ∼70–80% of patients with early acute respiratory distress syndrome; 2) the beneficial effects of oxygenation reduce after 1 week of mechanical ventilation; 3) the aetiology of acute respiratory distress syndrome may markedly affect the response to prone positioning; 4) extreme care is necessary when the manoeuvre is performed; 5) pressure sores are frequent and related to the number of pronations; 6) the supports used to prone and during positioning are different and nonstandardised among centres; and 7) intensive care unit and hospital stay and mortality still remain high despite prone positioning.
Equipment needs for noninvasive mechanical ventilation
Authors: Schönhofer B. , Sortor-Leger S.
Published: September 2002

Noninvasive mechanical ventilation (NIV) has a long tradition for the treatment of chronic respiratory failure and more recently has also been applied in acute respiratory failure. Based on this experience both critical care ventilators and portable ventilators are used to perform NIV. The individual choice of ventilator type should depend on the patient's condition and also on the expertise of attending staff, therapeutic requirements and the location of care.

The majority of studies have used pressure-targeted ventilation in the assist mode. Positive qualities of pressure support ventilation (PSV) are leak compensation, good patient/ventilator synchrony and the option of integrated positive end-expiratory pressure to counteract the effect of dynamic hyperinflation. In this article, some crucial issues concerning PSV (i.e.triggering into inspiration, pressurisation, cycling into expiration and carbon dioxide rebreathing) and some corrective measures are discussed.

The parameters which should be monitored during noninvasive ventilation are presented. The interface between patient and ventilator is a crucial issue of noninvasive ventilation. Advantages and disadvantages of face and nasal masks are discussed. Finally, causes and possible remedies of significant air leaks and some technical accessories for noninvasive ventilation are dealt with.
Apparent but not real increase in asthma prevalence during the 1990s
Authors: Barraclough R. , Devereux G. , Hendrick D.J. , Stenton S.C.
Published: September 2002

The authors investigated changes in asthma prevalence and perception of bronchoconstriction over 6 yrs in adults of Newcastle-upon-Tyne.

Postal questionnaires were sent to 6,000 subjects aged 20–44 yrs in 1992–1993 and 1998–1999. Random samples of 600 responders had assessments of atopy, airway responsiveness, and their ability to perceive methacholine-induced bronchoconstriction. The prevalences of asthmatic symptoms, physician-diagnosis, and medication use increased by an average of 4.4%, particularly in subjects aged <30 yrs (8.7versus2.7). Atopy prevalence increased from 25% to 31% but atopics and nonatopics had similar mean changes in questionnaire data (5.2versus3.4). The probability of a positive methacholine test decreased as did the mean methacholine dose/response slope (0.00527 to 0.00379), indicating lower levels of airway responsiveness. This can be largely explained by an increase in use of inhaled corticosteroids (5.0–9.3%). The proportion of subjects perceiving bronchoconstriction during methacholine tests increased from 63 to 77%.

The authors conclude that current changes in asthma epidemiology in adults may result from increased awareness of symptoms (and/or an increased willingness to report them), and from an increased willingness of physicians to make the diagnosis and prescribe treatment, not from increased disease prevalence.