bluuebunny/crossref_metadata_2025 huggingface dataset:
Home hospitalisation of exacerbated chronic obstructive pulmonary disease patients
Authors: Hernandez C. , Casas A. , Escarrabill J. , Alonso J. , Puig-Junoy J. , Farrero E. , Vilagut G. , Collvinent B. , Rodriguez-Roisin R. , Roca J. ,   and partners of the CHRONIC project
Published: January 2003

It was postulated that home hospitalisation (HH) of selected chronic obstructive pulmonary disease (COPD) exacerbations admitted at the emergency room (ER) could facilitate a better outcome than conventional hospitalisation.

To this end, 222 COPD patients (3.2% female; 71±10 yrs (mean±sd)) were randomly assigned to HH (n=121) or conventional care (n=101). During HH, integrated care was delivered by a specialised nurse with the patient's free-phone access to the nurse ensured for an 8‐week follow-up period.

Mortality (HH: 4.1%; controls: 6.9%) and hospital readmissions (HH: 0.24±0.57; controls: 0.38±0.70) were similar in both groups. However, at the end of the follow-up period, HH patients showed: 1) a lower rate of ER visits (0.13±0.43versus0.31±0.62); and 2) a noticeable improvement of quality of life (Δ St George's Respiratory Questionnaire (SGRQ), −6.9versus−2.4). Furthermore, a higher percentage of patients had a better knowledge of the disease (58%versus27%), a better self-management of their condition (81%versus48%), and the patient's satisfaction was greater. The average overall direct cost per HH patient was 62% of the costs of conventional care, essentially due to fewer days of inpatient hospitalisation (1.7±2.3versus4.2±4.1 days).

A comprehensive home care intervention in selected chronic obstructive pulmonary disease exacerbations appears as cost effective. The home hospitalisation intervention generates better outcomes at lower costs than conventional care.
Systematic assessment of difficult-to-treat asthma
Authors: Robinson D.S. , Campbell D.A. , Durham S.R. , Pfeffer J. , Barnes P.J. , Chung K.F.
Published: January 2003

Five per cent of asthmatics remain symptomatic despite high-dose treatment. The aim of the study was to investigate how often such difficult-to-treat asthma is due to intractable asthma, misdiagnosis, non-adherence with therapy, or psychiatric problems.

Difficult asthma was defined as persistence of symptoms despite treatment at step 4 of British guidelines or requirement for long-term oral glucocorticoids (step 5). One-hundred patients with a respiratory physician diagnosis of asthma were investigated in a single tertiary respiratory unit in an open and descriptive study.

Twelve of the patients studied did not have asthma and a further seven had additional diagnoses. Of the remainder, 55 had an asthma diagnosis confirmed by demonstration of reversible airflow narrowing or peak flow variability, whilst 20 did not. Noncompliance with prednisolone therapy was more frequent in the 55 with confirmed asthma (nine of 18 prescribed oral prednisolone at a dose of ≥15 mg·day−1) and was not detected in the “unconfirmed asthma” group. There were no other significant differences between these groups. A major psychiatric component was detected in 10 patients.

Systematic evaluation of difficult asthma is useful as it can identify alternative or additional diagnoses, psychiatric illness or nonconcordance with therapy in a substantial proportion of cases (32% in the present series).
The role of concomitant respiratory diseases on the rate of decline in FEV1among adult asthmatics
Authors: Sherrill D. , Guerra S. , Bobadilla A. , Barbee R.
Published: January 2003

Several recent reports have presented evidence suggesting that adults with asthma have an accelerated rate of decline in pulmonary function compared with nonasthmatics. However, most of these studies have not taken into account the possible effect of comorbid lung disease in addition to asthma. This study was designed to determine if comorbid respiratory diseases modify or otherwise change the estimates of decline in forced expiratory volume in one second (FEV1).

Study subjects were White, non-Mexican, American participants, who were ≥20 yrs of age at the initial survey and had at least one pulmonary function testing. Respiratory disease status, based on self-reported questionnaires and pulmonary function tests, were assessed during 12 surveys spanning a period of up to 20 yrs.

There were 2,926 subjects who met the inclusion criteria, 214 (7.3%) had physician-confirmed asthma, 325 (11.1%) chronic obstructive pulmonary disease (COPD), and 125 (4.3%) both physician-confirmed asthma and COPD. Longitudinal analysis revealed that among those with longstanding asthma, FEV1values were low but did not decline at a more rapid rate than normal. Likewise, subjects with both asthma and COPD had the lowest levels of FEV1, but also a rate of decline that was not significantly increased. Only those with COPD in the absence of asthma experienced both a low initial FEV1level and a significantly steeper rate of decline.

Based on these findings, the authors conclude that forced expiratory volume in one second does not decline more rapidly in asthmatics or in those with asthma and chronic obstructive pulmonary disease, compared with nonasthmatics.
Cost of illness of atopic asthma and seasonal allergic rhinitis in Germany: 1‐yr retrospective study
Authors: Schramm B. , Ehlken B. , Smala A. , Quednau K. , Berger K. , Nowak D.
Published: January 2003

The purpose of this study was to evaluate the cost of illness of moderate-to-severe atopic asthma and/or seasonal allergic rhinitis (SAR) in Germany from the perspective of third-party payers (TPP) and patients.

Five-hundred patients (276 children/adolescents) with moderate-to-severe asthma and/or SAR were included in this cross-sectional study. Information was collected using a specific patient questionnaire and the abstraction of patient records.

Overall, annual costs per patient increased with the severity of atopic asthma and if it was associated with SAR. The average annual cost of SAR was 1,089 per child/adolescent and 1,543 per adult. Annual costs of severe asthma plus SAR increased to 7,928 per child/adolescent and to 9,287 per adult. For TPPs, the main cost drivers were medication, hospitalisation, and rehabilitation. The most significant costs for patients were household modifications. For children/adolescents, 60–78% of the expenditures were direct costs, while in adults, 58% of expenditures were indirect costs. It was also observed that patients with moderate and severe asthma used inhaled corticosteroids less frequently than recommended by treatment guidelines.

In summary, the total cost for patients increases with the severity of atopic asthma and/or seasonal allergic rhinitis and indirect costs represent a large proportion of the total cost.
Effect of inhaled bronchodilators on inspiratory capacity and dyspnoea at rest in COPD
Authors: Di Marco F. , Milic-Emili J. , Boveri B. , Carlucci P. , Santus P. , Casanova F. , Cazzola M. , Centanni S.
Published: January 2003

It has been shown that patients with chronic obstructive pulmonary disease (COPD) develop dynamic hyperinflation (DH), which contributes to dyspnoea and exercise intolerance. Formoterol, salmeterol and oxitropium have been recommended for maintenance therapy in COPD patients, but their effect on DH has only been assessed for salmeterol.

The aim of the present study was to compare the acute effect of four inhaled bronchodilators (salbutamol, formoterol, salmeterol and oxitropium) and placebo on forced expiratory volume in one second, inspiratory capacity, forced vital capacity and dyspnoea in COPD patients. A cross-over, randomised, double-blind, placebo-controlled study was carried out on 20 COPD patients.

Patients underwent pulmonary function testing and dyspnoea evaluation, in basal condition and 5, 15, 30, 60 and 120 min after bronchodilator or placebo administration.

The results indicate that in chronic obstructive pulmonary disease patients with decreased baseline inspiratory capacity, there was a much greater increase of inspiratory capacity after bronchodilator administration, which correlated closely with the improvement of dyspnoea sensation at rest. For all bronchodilators used, inspiratory capacity reversibility should be tested at 30 min following the bronchodilator. On average, formoterol elicited the greatest increase in inspiratory capacity than the other bronchodilators used, though the difference was significant only with salmeterol and oxitropium. The potential advantage of formoterol needs to be tested in a larger patient population.
Epoprostenol therapy for primary pulmonary hypertension after rejection of a single donor lung
Authors: Roeleveld R.J. , Vonk Noordegraaf A. , van der Bij W. , Postmus P.E. , Boonstra A.
Published: January 2003

Before prostacyclins became available, lung or heart/lung transplantation was the only effective treatment for patients with primary pulmonary hypertension (PPH) who deteriorated under supportive medical treatment. Unfortunately, acute and chronic rejections occur in a large number of cases, limiting the average survival to 4.5 yrs.

A female patient, age 35 yrs, was diagnosed with PPH and underwent single lung transplantation. Despite aggressive immunosuppressive therapy, the patient had several episodes of acute rejection. Eventually, chronic rejection with bronchiolitis obliterans developed. After 5 yrs, the donor lung was no longer functional. The patient was in New York Heart Association (NYHA) class 4, had a 6‐min walking distance of 50 m and a resting arterial oxygen tension (Pa,O2) of 9.8 kPa (74 mmHg) when using 3 L·min−1of oxygen.

Epoprostenol treatment was started and the patient showed remarkable improvement. After 17 months the patient was NYHA class 2, walked 503 m in 6 min and had a restingPa,O2of 10.9 kPa (82 mmHg) without supplemental oxygen.

In this patient, treatment with epoprostenol was effective after rejection of a single donor lung transplanted for primary pulmonary hypertension.
Stretch-induced changes in constricted lung parenchymal strips: role of extracellular matrix
Authors: Salerno F.G. , Fust A. , Ludwig M.S.
Published: January 2003

Large amplitude oscillations of contracted airway smooth muscle cause relative relaxation of the preparation. However, little is known about the effect of mechanical stretch on distal lung behaviour.

Rat parenchymal strips were suspended in an organ bath and attached at one end to a force transducer and at the other end to a servo-controlled lever arm that effected length changes. Mechanical impedance of the strip was measured by applying a complex signal consisting of pseudorandom length oscillations of varying frequencies (0.5–19.75 Hz). A constant phase model was fit to changes in length and tension to calculate tissue damping (G) and elastance (H). Hysteresivity was calculated as G/H. Impedance was measured before and after sinusoidal length oscillation at different amplitudes (1, 3, 10 and 25% of resting length) at a frequency of 1 Hz under baseline conditions and after acetylcholine-induced constriction.

Oscillations of 10 and 25% amplitudes significantly decreased the G and H of the lung strip. The effect of length oscillations was no different in controlversusconstricted strips.

These data suggest that in the distal lung, large stretches affect the structural components of the extracellular matrix rather than the contractile elements.
Airway surface pH in subjects with cystic fibrosis
Authors: McShane D. , Davies J.C. , Davies M.G. , Bush A. , Geddes D.M. , Alton E.W.F.W.
Published: January 2003

The cystic fibrosis (CF) transmembrane conductance regulator protein can transport bicarbonate and may therefore regulate airway surface (AS) pH. Disturbances of AS pH could contribute to the pathophysiology of CF lung disease.

Five studies were carried out including the following: study 1) nasal pH measurements were made in 25 CF and 10 non-CF adults using an antimony pH probe. Mean nasal pH was significantly lower in the CF group. Nasal potential difference may have been a confounding factor; study 2) in a fresh cohort of CF and non-CF subjects, no significant difference was found between the two groups using a gold pH probe; study 3) simultaneous nasal pH measurements were made in 15 CF and 15 non-CF adults using both probes. In the CF group, there was a trend for the antimony probe to read lower than the gold probe. In the non-CF group, the antimony probe read higher. The pH difference noted in study 1 related to technical factors; study 4) the effect of acute changes in serum acid/base balance on nasal pH was assessed in five non-CF adults. Nasal pH was not altered by either acute respiratory acidosis or alkalosis; study 5) nasal and lower airway pH was measured in five CF and six non-CF children. No difference was found between the groups. There was a correlation between nasal and lower airway pH.

The authors conclude that airway surface pH does not differ between cystic fibrosis and noncystic fibrosis subjects and therefore, cystic fibrosis transmembrane conductance regulator may not play a major role in airway surface pHin vivo.
Distribution of therapeutic response in asthma control between oral montelukast and inhaled beclomethasone
Authors: Baumgartner R.A. , Martinez G. , Edelman J.M. , Rodriguez Gomez G.G. , Bernstein M. , Bird S. , Angner R. , Polis A. , Dass S.B. , Lu S. , Reiss T.F.
Published: January 2003

The distribution of responses in study populations provides a novel method of comparing the benefit of two treatments. This 6‐week, randomised, placebo-controlled, double-blind study compared the effectiveness of oral montelukast with inhaled beclomethasone in chronic asthma by assessing the distribution and overlap of patient responses to therapy, as measured by a clinical outcome (asthma control days).

A total of 730 adult patients with asthma, age 15–65 yrs, with a forced expiratory volume in one second (FEV1) at baseline of 50–85% of predicted and ≥15% improvement in FEV1after inhaled β‐agonist were enrolled. After a 2–week placebo run-in period, patients were randomly allocated to receive montelukast (10 mg once daily), inhaled beclomethasone (200 µg twice daily) or placebo. The primary end-point (per cent of asthma control days) was compared between treatments as the overlap in the response distributions.

The overlap of the distribution of responses between the montelukast and beclomethasone groups was 89% for per cent asthma control days and 96% for change from baseline in FEV1. The mean (±sd) per cent asthma control days in the montelukast and beclomethasone groups was significantly higher than that in the placebo group (placebo 40.0±35.8, montelukast 50.7±37.1, beclomethasone 57.9±36.1). The mean differences between montelukast and placebo, beclomethasone and placebo, and montelukast and beclomethasone were significant. The mean per cent change (±sd) from baseline in FEV1was 12.1±18.7 and 13.9±20.8 in the montelukast and beclomethasone groups, respectively, and significantly greater than that in the placebo group (6.4±20.1); there was no significant difference between the montelukast and beclomethasone groups in mean values or response distribution. There was also no difference among treatment groups in the frequency of adverse experiences.

A comparison of the response distribution is an important approach to comparing therapies; montelukast and beclomethasone provided similar response distributions for the end-point of per cent asthma control days over a 6‐week treatment period.
Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease
Authors: Szafranski W. , Cukier A. , Ramirez A. , Menga G. , Sansores R. , Nahabedian S. , Peterson S. , Olsson H.
Published: January 2003

The efficacy and safety of budesonide/formoterol in a single inhaler compared with placebo, budesonide and formoterol were evaluated in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).

In a 12-month, randomised, double-blind, placebo-controlled, parallel-group study in 812 adults (mean age 64 yrs, mean forced expiratory volume in one second (FEV1) 36% predicted normal), patients received two inhalations twice daily of either budesonide/formoterol (Symbicort®) 160/4.5 µg (delivered dose), budesonide 200 µg (metered dose), formoterol 4.5 µg or placebo. Severe exacerbations and FEV1(primary variables), peak expiratory flow (PEF), COPD symptoms, health-related quality of life (HRQL), mild exacerbations, use of reliever β2‐agonist and safety variables were recorded.

Budesonide/formoterol reduced the mean number of severe exacerbations per patient per year by 24%versusplacebo and 23%versusformoterol. FEV1increased by 15%versusplacebo and 9%versusbudesonide. Morning PEF improved significantly on day 1versusplacebo and budesonide; after 1 week, morning PEF was improvedversusplacebo, budesonide and formoterol. Improvements in morning and evening PEFversuscomparators were maintained over 12 months. Budesonide/formoterol decreased all symptom scores and use of reliever β2‐agonists significantlyversusplacebo and budesonide, and improved HRQLversusplacebo. All treatments were well tolerated.

These results suggest a role for budesonide/formoterol in the long-term management of moderate-to-severe chronic obstructive pulmonary disease.
Genetic polymorphisms associated with acute pulmonary embolism and deep venous thrombosis
Authors: Nizankowska-Mogilnicka E. , Adamek L. , Grzanka P. , Domagala T.B. , Sanak M. , Krzanowski M. , Szczeklik A.
Published: January 2003

Frequently an inherited predisposition to thrombosis remains clinically silent until an additional environmental factor intervenes. The present study aimed to assess distribution of inherited risk factors of venous thrombosis in patients with venous thromboembolism (VTE).

The prevalences of factor V Leiden (FV Leiden), prothrombin factor II G20210A (FII G20210A), C677T and A1298C of methylenetetrahydrofolate reductase (MTHFR) mutations were studied in 149 VTE patients and 100 controls.

The following key risks were established: previous deep venous thrombosis or pulmonary embolism (23.5%), bed rest (34.2%), immobilisation of lower limb (10.1%), hospitalisation (30.9%) and obesity (28.9%). In 29 (19%) patients and in three (3%) controls FV Leiden was found. A significant association between VTE and FV Leiden was established. There were six (4%) carriers of the FII G20210A among VTE patients and one in the controls. No associations between VTE and MTHFR polymorphisms (C677T, A1298C) were found. In three of 149 patients both FV Leiden and FII G20210A polymorphisms were observed. The mean protein C activity was slightly, though nonsignificantly, smaller in VTE patients.

In conclusion, there was a positive association between venous thromboembolism and factor V Leiden. Only a weak trend favouring a relationship between prothrombin factor II G20210A and venous thrombolism was present. No associations between common polymorphisms of methylenetetrahydrofolate reductase and venous thromboembolism were found.
Effectiveness of oral moxifloxacin in standard first-line therapy in community-acquired pneumonia
Authors: Torres A. , Muir J-F. , Corris P. , Kubin R. , Duprat-Lomon I. , Sagnier P-P. , Höffken G.
Published: January 2003

Based on recent guidelines for the management of community-acquired pneumonia, this study was designed to evaluate the effectiveness of a new fluoroquinolone compared with standard antimicrobial regimens, in conditions relating as closely as possible to the real world setting.

In this study, 564 patients were randomised to either oral moxifloxacin (400 mgo.d.) or to standard oral therapy (amoxicillin 1 gt.i.d.or clarithromycin 500 mgb.i.d.alone or in combination) for up to 14 days using a double-blind procedure. The choice between the three standard regimens was made by the clinician prior to randomisation. Clinical response, quality of life, symptoms, healthcare resources and safety were assessed.

In the per-protocol population, clinical success was reported for 201 of 215 (93.5%) and 217 of 231 (93.9%) in the moxifloxacin and standard groups, respectively, at 7–10 days post-therapy. At 28–35 days follow-up, continued clinical cure was observed in 183 of 192 (95.3%) moxifloxacin and 207 of 221 (93.7%) standard groups. Drug-related adverse events were reported in 55 of 274 (20%) moxifloxacin and 86 of 279 (31%) standard patients with diarrhoea >5%.

Oral moxifloxacin monotherapy was as effective as, and better tolerated than, optimal antibiotic strategy represented either by mono- or combination therapy (amoxicillin and/or clarithromycin) in community-acquired pneumonia management.
Monitoring the quality of laboratories and the prevalence of resistance to antituberculosis drugs: Italy, 1998–2000
Authors: Migliori G.B. , Centis R. , Fattorini L. , Besozzi G. , Saltini C. , Orefici G. , Piersimoni C. , Gori A. , Cassone A. ,   the Italian Multicentre Study on Resistance to Antituberculosis drugs (SMIRA) Study Group
Published: January 2003

In 1998 a network of 20 regional tuberculosis (TB) laboratories (the Italian Multicentre Study on Resistance to Antituberculosis drugs (SMIRA) network) was established in Italy to implement proficiency testing and to monitor the prevalence of drug resistance nationwide. The network managed 30% of all TB cases reported in Italy each year.

The aim of the present report is to describe: 1) the accuracy of drug-susceptibility testing in the network; 2) the prevalence of drug resistance for the period 1998–2000.

Data were collected from the network laboratories. Sensitivity to streptomycin and ethambutol increased from the first survey (1998–1999) to the second survey (2000) from 87.7 to 91.9%. Specificity, predictive values for resistance and susceptibility, efficiency and reproducibility were consistent in both surveys. In previously untreated cases, the prevalence of multidrug-resistance was the same in both surveys (1.2%), while a slight decrease from the first to the second survey was observed for monoresistance to rifampicin (from 0.8 to 0.4%) and isoniazid (from 2.9 to 2%).

The significant association found between isoniazid resistance and immigration is a useful indicator for both clinicians managing individual tuberculosis cases and public health services planning control strategies.
Impact of nurse-led outpatient management of children with asthma on healthcare resource utilisation and costs
Authors: Kamps A.W.A. , Roorda R.J. , Kimpen J.L.L. , Overgoor-van de Groes A.W. , van Helsdingen-Peek L.C.J.A.M. , Brand P.L.P.
Published: January 2003

The high burden of asthma on healthcare utilisation and costs warrants economic appraisal of management approaches. The authors previously demonstrated that the efficacy of nurse-led outpatient management of childhood asthma was comparable to management by a paediatrician and now report on the healthcare utilisation and costs of both management approaches.

A total of 74 newly referred children with asthma were randomly assigned to a 1‐yr follow-up by paediatricians or asthma nurse. Healthcare utilisation was recorded and associated costs calculated for both management approaches.

There were no significant differences in healthcare utilisation except for the total time spent on patient contact (136(n=14)versus187(n=41) min, for patients followed-up by paediatrician and an asthma nurse repectively). Costs within the healthcare sector were reduced by 7.2% in favour of nurse-led care. The reduction in costs was solely attributable to a 17.5% reduction in the costs of outpatient visits. Nurse-led care appeared to be cost-saving even if the duration of follow-up visits would be twice that of doctor's visits. Overall healthcare costs (within and outside the healthcare sector) were 4.1% lower for nurse-led outpatient management compared to traditional medical care.

Nurse-led outpatient management of childhood asthma can be provided at a lower cost than medical care by paediatricians.
Single arterial occlusion to locate resistance in patients with pulmonary hypertension
Authors: Fesler P. , Pagnamenta A. , Vachiéry J‐L. , Brimioulle S. , Abdel Kafi S. , Boonstra A. , Delcroix M. , Channick R.N. , Rubin L.J. , Naeije R.
Published: January 2003

The purpose of this study was to determine the site of increased resistance using the arterial occlusion technique in patients with severe pulmonary hypertension.

Pulmonary vascular resistance was partitioned in arterial and venous components based on double exponential fitting analysis of the pulmonary artery pressure decay curve: after balloon occlusion in 36 patients with pulmonary arterial hypertension (PAH); at baseline and during the inhalation of 20 parts per million of nitric oxide (NO); in four patients with chronic thromboembolic pulmonary hypertension; and in two patients with pulmonary veno-occlusive disease.

In the patients with PAH, at baseline, mean pulmonary artery pressure was 56±2 mmHg (mean±se), with an arterial component of resistance of 63±1%. Inhaled NO did not change the partition of resistance. The arterial component of resistance amounted on average to 42% and 77% in the patients with veno‐occlusive disease and the patients with thromboembolic pulmonary hypertension, respectively. However, the partitioning of resistance did not discriminate between these three diagnostic categories.

The occlusion technique may help to locate the predominant site of increased resistance in patients with severe pulmonary hypertension, but does not allow for a satisfactory differential diagnosis on an individual basis.
Use of anti-inflammatory therapy and asthma mortality in Japan
Authors: Suissa S. , Ernst P.
Published: January 2003

Asthma treatment guidelines were introduced in Japan in the 1990s, insisting as elsewhere, on the importance of anti-inflammatory therapy. The present study assessed whether use of anti-inflammatory medications was associated with a decrease in asthma mortality in Japan, the first country to use leukotriene receptor antagonists.

A population-based ecological study was conducted, spanning the period 1987–1999, among people aged 5–34 yrs in Japan. The association between the yearly rate of asthma death and sales of inhaled corticosteroids and leukotriene receptor antagonists was estimated using Poisson regression.

The yearly asthma death rate was stable at 6–7 deaths per million before the introduction of leukotriene receptor antagonists in 1995 and decreased by 23% thereafter, reaching 3.5 per million in 1999. The rate of asthma death was found to decrease with increasing use of both leukotriene receptor antagonists and inhaled corticosteroids. The rate ratio of asthma death was 0.96 per 1 million 25-day treatment courses of inhaled corticosteroids and 0.80 for every 1 million 25-day treatment courses of leukotriene receptor antagonists, consumed per year in Japan.

The increasing use of inhaled corticosteroids and leukotriene receptor antagonists may have contributed to the significant reduction in asthma mortality among young asthmatics in Japan.
Markers of activity in clinically recovered human leukocyte antigen-DR17-positive sarcoidosis patients
Authors: Planck A. , Eklund A. , Grunewald J.
Published: January 2003

Scandinavian human leukocyte antigen-DR17-positive (DR17+) sarcoidosis patients are characterised by a good prognosis. They also reveal an accumulation in bronchoalveolar lavage fluid of T‐lymphocytes expressing the T‐cell receptor V gene segment AV2S3 at disease onset. The authors of this study wished to establish whether AV2S3 T‐lymphocyte accumulation changes from disease onset to clinically resolved disease and how this relates to other activity parameters.

Bronchoalveolar lavage fluid and serum from nine DR17+ sarcoidosis patients were examined at disease onset and after spontaneous resolution of clinical and radiographical signs of disease.

Nine DR17+ patients with lung accumulated CD4+ AV2S3+ T‐cells were investigated after clinically recovery. At re-examination the percentage of CD4+ AV2S3+ lymphocytes in bronchoalveolar lavage fluid was normalised (29versus5.4%). A significant reduction in lymphocyte percentage (14versus4.4%) and a decrease in cellular concentration (179×106·L−1versus111×106·L−1) and CD4/CD8 ratio (5.2versus2.4) were also seen. In serum, the activity of angiotensin-converting enzyme (24.9versus14.0 U·mL−1) as well as the levels of neopterin (7.8versus5.3 nmol·L−1) decreased significantly after recovery.

These results indicate that the locally accumulated AV2S3 positive T‐lymphocytes in bronchoalveolar lavage are involved in the pathogenic process of sarcoidosis in this patient group.
Pulmonary arterial hypertension in children
Authors: Widlitz A. , Barst R.J.
Published: January 2003

For physicians to admit that a group of patients remains for whom no cure is available in modern medicine is intellectually unsatisfying. Pulmonary arterial hypertension is a rare condition. Because the symptoms are nonspecific and the physical finding can be subtle, the disease is often diagnosed in its later stages. The natural history of pulmonary arterial hypertension is usually progressive and fatal.

At the 1998 Primary Pulmonary Hypertension World Symposium, clinical scientists from around the world gathered to review and discuss the future of pulmonary arterial hypertension. Bringing together experts from a variety of disciplines provided the opportunity for a better understanding of the pathology, pathobiology, risk factors, genetics, diagnosis and treatment for pulmonary arterial hypertension.

Remarkable progress has been made in the field of pulmonary arterial hypertension over the past several decades. The pathology is now better defined and significant advances have occurred in understanding the pathobiological mechanisms. Risk factors have been identified and the genetics have been characterised. Advances in technology allow earlier diagnosis as well as better assessment of disease severity. Therapeutic modalities such as new drugs,e.g.epoprostenol, treprostinil and bosentan, and surgical interventions,e.g.transplantation and blade septostomy, which were unavailable several decades ago, have had a significant impact on prognosis and outcome. Thus, despite the inability to really cure pulmonary arterial hypertension, therapeutic advances over the past two decades have resulted in significant improvements in the outcome for children with various forms of pulmonary arterial hypertension.

This review of pulmonary arterial hypertension will highlight the key features of pulmonary hypertension in infants and children and the current understanding of pulmonary arterial hypertension with specific recommendations for current practice and future directions.
Evaluation of an individualised asthma programme directed at behavioural change
Authors: Put C. , van den Bergh O. , Lemaigre V. , Demedts M. , Verleden G.
Published: January 2003

An individualised asthma programme directed at behavioural change was evaluated in asthmatic subjects who reported complaints and impairment, despite adequate medical treatment.

Mild-to-moderate asthma patients (n=23) were randomly assigned to a programme or waiting list condition. Outcome measures were: McMaster Asthma Quality of Life Questionnaire, Asthma Symptom Checklist, Negative Emotionality Scale, Knowledge, Attitude and Self-Efficacy Asthma Questionnaire, Adherence Scale, and peak flow measurements. Both groups were evaluated at three consecutive moments, each separated by 3 months; the programme was delivered between the first two evaluations. At onset the patient received a workbook containing information, exercises and homework assignments. Psycho-education, behavioural and cognitive techniques were introduced during six 1‐h individual sessions.

Compared with controls the programme group reported less symptoms (obstruction, fatigue), better quality of life (activity, symptoms, emotions), decreased negative affectivity, and increased adherence, immediately after finishing the programme and at 3 months follow-up. All three cognitive variables (knowledge, attitude towards asthma, self-efficacy) and day and night peak flow ratings improved in the programme group but not in the waiting list group.

Participation in an individualised programme resulted in improvement of asthma morbidity, and asthma-related behaviour and cognitions, in subjects reporting symptoms and impairment despite adequate medical therapy.
T‐helper 1 cells induce alveolitis but do not lead to pulmonary fibrosis in mice
Authors: Irifune K. , Yokoyama A. , Kohno N. , Sakai K. , Hiwada K.
Published: January 2003

T‐helper (Th)1 cells have a pivotal role in the pathogenesis of hypersensitivity pneumonitis. Continued low-level exposure to the antigens may induce chronic hypersensitivity pneumonitis with lung fibrosis. Although such exposure may activate Th1 cells in the lung, it is not known whether activation of Th1 cellsper secan lead to pulmonary fibrosis. To determine this, the lung pathology induced by Th1 clones was investigated.

Mice (BALB/c) were injected intraperitoneally with Th1 clones 1–4 times. Each injection was performed 4 days apart and was followed by repeated exposure to aerosolised ovalbumin (OVA) once a day for 5 days.

The number of macrophages and lymphocytes in bronchoalveolar lavage fluids (BALF) increased as the number of Th1 transfers increased. The number of neutrophils also increased but peaked in the second transfer and then decreased following further transfers. Increased cell infiltration, thickness of alveolar walls and number of type II cells in the lung occurred. However, histological findings showed no evidence of fibrosis and hydroxyproline levels did not increase. Findings of histology and BALF were ameliorated 2 weeks after the discontinuation of OVA exposure, indicating the reversibility of the Th1-induced pathology.

In conclusion, adoptive transfer of T‐helper 1 cells results in reversible alveolitis but does not lead to pulmonary fibrosis.
Acute interstitial pneumonia: report of a series
Authors: Bonaccorsi A. , Cancellieri A. , Chilosi M. , Trisolini R. , Boaron M. , Crimi N. , Poletti V.
Published: January 2003

Four cases of acute interstitial pneumonia (AIP) are described with special emphasis on clinical background, lung imaging and bronchoalveolar lavage findings.

A retrospective chart review of four patients with histologically-proven AIP, diagnosed between 1998 and 2000, was carried out. Clinical data, bronchoalveolar lavage (BAL) findings, high-resolution computed tomography (HRCT) and histological features were analysed.

Three patients died and only one is in follow-up. HRCT showed areas of ground glass attenuation and alveolar consolidation in all patients. Histology, documented by open lung biopsy or autopsy specimens, was consistent with the organising form of diffuse alveolar damage pattern.

BAL findings were characteristic, with a huge neutrophilia associated with scattered atypical type II pneumocytes collected in clusters with extracellular amorphous material (fragments of hyaline membranes) observed in two out of three cases.

In this paper, four cases of acute interstitial pneumonia are reported in detail. The poor prognosis associated with this entity has been confirmed and the possible diagnostic role of the bronchoalveolar lavage is emphasised.
Nasal nitric oxide measurements for the screening of primary ciliary dyskinesia
Authors: Wodehouse T. , Kharitonov S.A. , Mackay I.S. , Barnes P.J. , Wilson R. , Cole P.J.
Published: January 2003

Primary ciliary dyskinesia (PCD) presents to general practitioners with symptoms pertinent to a variety of specialists because of the involvement of ciliated epithelium in the upper/lower respiratory tract, ears, eyes and genital tract. There is no easy, reliable screening test for PCD, and thus, the majority of patients remain undiagnosed. Nitric oxide (NO) is measurable in nasal air of normal subjects and found to be low in cystic fibrosis (CF) and very low in PCD. Recently, it was suggested to play an important role in regulating ciliary motility. The aim of this study was to evaluate whether measurements of nasal NO could be used to screen for PCD.

Nasal NO was measured from the nasal cavity by a chemiluminescence analyser in subjects with PCD, healthy controls, CF, idiopathic bronchiectasis, Young's syndrome and lone sinusitis.

Nasal NO was significantly lower in PCD (64.0±36.6) compared with normal controls (759±145.8), idiopathic bronchiectasis (734±163.7), CF (447.5±162.6), lone sinusitis (1487±734) and Young's syndrome (644±129.9). Nasal NO was also significantly lower in PCD than CF patients.

Measurement of nasal nitric oxide may therefore be used clinically in various specialities to screen suspected patients for primary ciliary dyskinesia.
Ion transport in cultured pig tracheal submucosal gland acinar cells studied by X-ray microanalysis
Authors: Zhang AL , Roomans GM
Published: January 2003

The submucosal glands of the airway may contribute more to the airway fluid than the surface epithelium. The cellular mechanisms underlying the regulation of electrolyte and water transport in airway submucosal glands are, however, still poorly understood. Therefore, we attempted to establish a cell culture system to facilitate study of this regulation. Acinar cells were isolated by enzymatic disaggregation from pig tracheal submucosal tissue and cultured on a plastic substrate coated with human placental collagen. The fine structure of the cells in confluent culture was studied by conventional transmission electron microscopy. The elemental content in resting cells and stimulated cells grown on a permeable substrate was studied by X-ray microanalysis. The cultured cells retained structural characteristics (microvilli, secretory granules and desmosomes) of in situ epithelia. The total intracellular Cl and K concentrations significantly decreased after stimulation with the cholinergic agonist acetylcholine, the predominantly alpha-adrenergic agonist norepinephrine, or the beta-adrenergic agonist isoproterenol. Both ionomycin and 8-bromoadenosine 3':5'-cyclic monophosphate (8-bromo-cAMP) caused a marked decrease of the intracellular Cl, K and Na concentrations. Cl- secretion induced by acetylcholine was inhibited by Cl- channel blockers anthracene-9-carboxylic acid and 5-nitro-2-(3-phenylpropyl-amino)-benzoic acid (NPPB), but Cl- efflux induced by 8-bromo-cAMP was blocked only by NPPB. The intracellular Cl and Na content significantly increased and the cellular K content markedly decreased after treatment with ouabain. These results indicate that the cultured acinar cells maintained the structural and functional characteristics of in situ tissue and that this system is suitable for studying aspects of ion and water transport by the airway submucosal gland cells.
Effects of antihistamines in adult asthma: a meta-analysis of clinical trials
Authors: Van Ganse E , Kaufman L , Derde MP , Yernault JC , Delaunois L , Vincken W
Published: January 2003

A meta-analysis of clinical trials of antihistamines was performed to assess the risk-benefit ratio of this therapeutic class in asthma. Double-blind randomized placebo-controlled trials assessing lung function changes under repeated use of antihistamine in adult asthma were selected, and the quality of studies was scored. Morning peak expiratory flow rate (PEFR) was the primary outcome: an effect size was computed for each study, with a 95% confidence interval (95% CI), and a mean effect size was computed, combining all studies. Effect sizes were also determined for secondary outcomes: evening PEFR, forced expiratory volume in one second (FEV1) and daily use of inhaled beta-agonists. Nineteen studies were included in the meta-analysis. Mean quality score of studies was 59.4%; asthma was generally uncontrolled at study inclusion. Altogether, 582 antihistamine-treated and 557 placebo-treated asthma patients were evaluable. Antihistamines had little effect on airway calibre (mean increase in morning PEFR: 13 L x min(-1); 95 CI: 8-18 L x min(-1)) and on use of inhaled beta-agonists (mean reduction in daily use: 0.4 doses; 95% CI: 0-0.8 doses). Sedation occurred more often with antihistamines than with placebo (p<0.001); additional side-effects were mentioned, including weight gain, altered taste, headache and dry mouth. Respiratory and systemic effects observed after repeated use of antihistamines do not support the use of these medications in the treatment of asthma; better designed studies could affect this appraisal.
Nasal eupnoeic inhalation of cold, dry air increases airway resistance in asthmatic patients
Authors: Fontanari P , Zattara-Hartmann MC , Burnet H , Jammes Y
Published: January 2003

The aim of this study was to establish a relationship between bronchial hyperreactivity to carbachol and reflex bronchomotor response to the activation of cold receptors in the nose, and also to examine whether any differences exist between asthmatic patients with or without symptoms of rhinitis. The changes in interrupting resistance (Rint) induced by nasal eupnoeic inhalation of cold (-5 degrees C) dry air were measured in 22 normal subjects and in 18 asthmatic patients (nine of whom had asthma with rhinitis and nine without) with bronchial hyperreactivity to carbachol. In normal individuals, nasal cold air challenge induced a significant increase in Rint (+31%). This was also the case in asthmatic patients (asthma with rhinitis +49%; asthma alone +40%), but the increase was not significantly larger than for normal individuals. The magnitude of Rint increase induced by nasal cold air breathing was correlated with the sensitivity to carbachol (defined as the dose inducing a 50% increase in specific airway conductance (D50)) in asthmatic patients with symptoms of rhinitis. These observations suggest that airway hyperreactivity is associated with enhanced bronchoconstrictor response to the activation of nasal cold receptors, particularly when rhinitis is present.
Does alpha1-antitrypsin augmentation therapy slow the annual decline in FEV1 in patients with severe hereditary alpha1-antitrypsin deficiency? Wissenschaftliche Arbeitsgemeinschaft zur Therapie von Lungenerkrankungen (WATL) alpha1-AT study group
Authors: Seersholm N , Wencker M , Banik N , Viskum K , Dirksen A , Kok-Jensen A , Konietzko N
Published: January 2003

Patients with severe hereditary alpha1-antitrypsin deficiency (alpha1-ATD) face a high risk of developing emphysema at a young age. Intravenous augmentation therapy with purified human alpha1-antitrypsin (alpha1-AT) is now available. However, a controlled trial to show its efficacy has never been carried out. The aim of this study was to compare the decline in forced expiratory volume in one second (deltaFEV1) between Danish patients who had never received augmentation therapy and German patients treated with weekly infusion of alpha1-AT. From the files of the Danish alpha1-ATD register, 97 exsmokers, with a PiZ phenotype and for whom results of at least two lung function measurements with an interval of at least 1 yr were available, were identified. From a German group of patients treated with weekly infusions of alpha1-AT, 60 mg x kg(-1) body weight, 198 exsmokers, with biannual lung function measurements were identified. The deltaFEV1 was compared between the two treatment groups by random effects modelling. The deltaFEV1 in the treated group was significantly lower than in the untreated group, with annual declines of 53 mL x yr(-1) (95% confidence interval (95% CI) 48-58 mL x yr(-1)) and 75 mL x yr(-1) (95% CI 63-87 mL x yr(-1)), respectively (p=0.02). The two groups differed with respect to gender and initial FEV1% predicted. Gender did not have any influence on the deltaFEV1. Stratification by initial FEV1% pred showed a significant effect of the treatment only in the group of patients with an initial FEV1% pred of 31-65%, and deltaFEV1 was reduced by 21 mL x yr(-1). This nonrandomized study suggests that weekly infusion of human alpha1-antitrypsin in patients with moderately reduced lung function may slow the annual decline in forced expiratory volume in one second.
Effects of an acute exacerbation on nutritional and metabolic profile of patients with COPD
Authors: Vermeeren MA , Schols AM , Wouters EF
Published: January 2003

In this study, we investigated the influence of an acute disease exacerbation on the nutritional and metabolic status of patients with chronic obstructive pulmonary disease (COPD). The study group consisted of 23 patients acutely admitted to the hospital for standardized medical treatment. Dietary intake (dietary records and diet history), resting energy expenditure (ventilated hood), body composition (bioelectrical impedance spectroscopy) and disease symptoms (visual analogue scale) were assessed on admission, daily throughout the hospitalization period, at discharge and 3 months thereafter in stable clinical condition. Dietary intake, since aggravation of disease symptoms, prior to admission, (5,640+/-2,671 kJ) was significantly lower than habitual intake (7,863+/-2,005 kJ). The balance between dietary intake with measured resting energy expenditure and estimated diet-induced thermogenesis was severely impaired during the first 3 days of hospitalization, stabilizing thereafter to 145+/-24% at discharge. Resting energy expenditure decreased from 6,812+/-900 kJ (123+/-11%) on admission to 6,196+/-795 kJ (113+/-14%) at discharge (p<0.001). During treatment, no significant shift in water compartments, fat-free mass and body weight was seen. Follow-up data were obtained from 10 out of 23 patients. Three months after admission, dietary intake was not significantly different from usual dietary intake (8,512+/-2,290 and 8,415+/-2,600 kJ, respectively), resting energy expenditure was similar to the value at discharge, and a significant body weight gain was seen. We conclude that an acute exacerbation of chronic obstructive pulmonary disease is accompanied by an impaired energy balance due to a decreased dietary intake and an increased resting energy expenditure.
Chest wall motion in preterm infants using respiratory inductive plethysmography
Authors: Warren RH , Horan SM , Robertson PK
Published: January 2003

Preterm infant tidal breathing may be different from that of healthy full-term infants because of various features of the premature thorax. The purpose of this project was to describe chest wall motion in the preterm infant (gestational age <37 weeks) and compare it with chest wall motion data in a group of healthy, full-term infants. We wanted to use an objective bedside method for assessment with minimal disruption to the infant. The study population consisted of 61 preterm human infants whose mean(+/-sD) postconceptional age at time of study was 35.3+/-2.1 weeks. During the study, the infants were quietly awake in a prone position. Preterm infants had initially been admitted to a level III neonatal intensive care unit for acute management and had been transferred to a step-down area, where they were in stable condition for study. Data were collected with a semiquantitatively calibrated, noninvasive respiratory inductive plethysmograph. Mean(+/-SD) phase angle was significantly greater in preterm infants than in full-term infants (60.6+/-39.8 degrees versus 12.5+/-5.0 degrees, respectively, p < or = 0.0001). The laboured breathing index was significantly greater in preterm infants than in full-term infants (1.35+/-0.35 versus 1.01+/-0.01, respectively, p = 0.001). The ribcage contribution to breathing did not differ significantly between preterm and full-term infants (25.5+/-17.7% versus 36.3+/-14.4%, respectively, p = 0.11). These results indicate a significant increase in the degree of ribcage and abdomen asynchrony in the preterm subjects compared to the full-term infants. Plethysmography provided a time-efficient and objective method of assessing chest wall motion in this fragile population.