bluuebunny/crossref_metadata_2025 huggingface dataset:
Current surgical treatment of nonsmall cell lung cancer 2001
Authors: Deslauriers J.
Published: October 2002

Recognizing that surgical treatment is still the best option for controlling lung cancer, surgeons want an operation to be performed when the benefits clearly outweigh the possible risks, and when it has been determined that cancer resection is the most appropriate course of management. The necessity for a compulsive attitude toward preoperative assessment is therefore to be emphasized.

Approximately 45% of all lung cancers are limited to the chest, where surgical resection is the most effective method of controlling the disease. Patients with tumour (T) 1, node (N) 0 and T2N0 tumours have early lung cancer, and most are curable by resection, with 5‐yr survival rates in the range 75–80% for patients with T1N0 status. The “gold standard” of surgery remains lobectomy. Stage T1N1 and T2N1 carcinomas represent a group of patients in whom the disease involves hilar and bronchopulmonary nodes. This group is best treated by complete resection and mediastinal lymphadenectomy.

Survival data following surgical resection of T3 tumours clearly show better survival in patients with T3N0 disease than in those with T3N1–2 disease. Five-year survival rates for completely resected T3N0 lesions are in the range 30–50%. Once N1 disease is present, survival decreases to 15–20%. Incomplete resections fail to cure and surgery is not indicated if N2 disease is documented preoperatively. On occasion, T4 tumours involving the carina or vertebral body can be completely resected but T4N1–2 lesions are virtually incurable by surgery.

The presence of mediastinal lymph node metastasis (N2/N3 disease) is an ominous prognostic sign and stage III‐b disease, by virtue of metastatic contralateral nodes, is an absolute contraindication to surgical resection. Induction treatments with chemoradiation have shown prolongation of survival and three randomized trials have demonstrated a survival advantage over surgery alone.
Exacerbation of sleep-apnoea related nocturnal blood-pressure fluctuations in hypertensive subjects
Authors: Planès C. , Leroy M. , Fayet G. , Aegerter P. , Foucher A. , Raffestin B.
Published: October 2002

Obstructive sleep apnoea syndrome (OSAS) induces marked haemodynamic fluctuations during sleep that might be deleterious to the cardiovascular system. The influence of daytime blood pressure (BP) levels and aging on short-term BP variability during sleep in OSAS patients was investigated.

Twenty-nine subjects with newly-diagnosed untreated OSAS were categorised into three groups: normotensive subjects aged <50 yrs (n=10); subjects aged <50 yrs with untreated hypertension (n=8); and normotensive subjects aged >50 yrs (n=11). Beat-by-beat BP was recorded with a Finapres device during polysomnography. The average values±sd of apnoea-related BP elevations and the values of the frequency distribution of all BP variations during sleep were assessed to estimate short-term BP variability.

Apnoea-related systolic (or diastolic) BP elevations were significantly greater in hypertensives than in normotensives aged <50 yrs (50.3±4.88versus30.7±2.14 mmHg, p<0.001), as was the sd of systolic (or diastolic) BP variations during sleep (I9.6±2.22versus11.1±0.73, p<0.001). Short-term BP variability was not significantly increased in normotensive elderly patients.

To conclude, the results suggested that systemic hypertension is associated with a greater exacerbation of short-term variability during sleep in obstructive sleep apnoea syndrome patients.
Acute adrenal crisis in asthmatics treated with high-dose fluticasone propionate: Table 1—
Authors: Todd G.R.G. , Acerini C.L. , Buck J.J. , Murphy N.P. , Ross-Russell R. , Warner J.T. , McCance D.R.
Published: October 2002

Four cases of asthma (one adult, three children) developing acute adrenal crisis after introduction of high-dose inhaled fluticasone proprionate are presented. The three children, aged 7–9 yrs, had been prescribed inhaled fluticasone, dosage 500–2,000 µg·day−1and duration 5 months–5 yrs. All presented with convulsions due to hypoglycaemia (blood glucose 1.3–1.8 mM). The fourth case was a male of 33 yrs with difficult-to-control asthma and had been taking fluticasone propionate 1,000–2,000 µg·day−1for 3 yrs. He presented with fatigue, lethargy, nausea and postural hypotension.

Acute adrenal crisis in each case was confirmed by investigations which included measurement of acute phase cortisol levels, short and long Synacthen stimulation tests and glucagon stimulation tests. Other cases of hypthoalamic-pituitary-adrenal axis suppression were excluded.
Distribution and degranulation of airway mast cells in normal and asthmatic subjects
Authors: Carroll N.G. , Mutavdzic S. , James A.L.
Published: October 2002

It was hypothesized that the distribution and activation of mast cells across the airway wall may reflect their function in asthma.

The density of mast cells (intact and degranulated) within airway compartments in cartilaginous and membranous airways, obtained from autopsies on patients with fatal asthma, nonfatal asthma, and nonasthmatic control cases have been examined.

In cartilaginous airways, the mean±se density of mast cells in control cases was 27±9 cells·mm−2. It was similar in nonfatal asthma (24±2 cells·mm−2) but reduced (p<0.05) in fatal asthma cases (16±2 cells·mm−2). In membranous airways, the density of mast cells in control cases was 155±21 cells·mm−2and was higher (p<0.05) in cases of nonfatal (270±51 cells·mm−2) and fatal asthma (219±26 cells·mm−2). Mast-cell density was greatest on the smooth muscle and mucous glands in cartilaginous airways and on the smooth muscle and outer airway wall in membranous airways. The percentage of degranulated mast cells was higher (p<0.05) in cases of asthma, related to disease severity, and was higher in cartilaginous than membranous airways. Degranulation was greatest on the smooth muscle in fatal asthma cases.

Mast-cell distribution and degranulation varies between cartilaginous and membranous airways and across the airway wall. Degranulation of mast cells is related to asthma severity. The increased degranulation in proximal airways may reflect stimulationviathe inhaled route.
New imaging techniques in the treatment guidelines for lung cancer
Authors: Schaefer-Prokop C. , Prokop M.
Published: October 2002

Computed tomography (CT) remains the main imaging technique for the preoperative staging and post-therapeutic evaluation of bronchogenic carcinoma. Spiral CT has already overcome some of the problems encountered with central or more extensive tumours. Multislice CT offers further improvement and allows for scanning of the whole chest within a single breath-hold using a thin-section high-resolution technique. Problem-adapted sections in arbitrary directions become available and provide an excellent spatial resolution. One can expect improved accuracy for the evaluation of transfissural tumour growth, chest wall involvement, mediastinal infiltration and lymph node staging.

Despite recent advances in magnetic resonance (MR) techniques for imaging the chest, the role of MR for staging of bronchogenic carcinoma remains limited. It offers advantages such as the assessment of chest-wall involvement or mediastinal involvement in patients in whom CT remains equivocal. Lymph-node-specific MR contrast agents offer new diagnostic potential for the assessment of metastatic disease.

New techniques for the display of three-dimensional data sets include volume rendering and virtual bronchoscopy. These techniques represent new tools for the evaluation and demonstration of pathology within the central tracheobronchial tree. Their most important application is the guidance of bronchoscopic biopsies.

The assessment of an indeterminate pulmonary nodule is frequently based on positron emission tomography imaging. As an alternative, nodule vascularization (contrast enhancement patterns on CT or magnetic resonance imaging (MRI)), calcifications (absorption characteristics at various X‐ray energies on CT or dual energy radiography), and morphological features (high resolution imaging at CT) can be used as the basis for nodule differentiation. The dynamics of contrast enhancement in CT or MRI can also be used for the assessment of tumour viability after chemotherapy.

Lung cancer screening programmes are still controversial. Low-dose computed tomography scanning and computed assisted detection algorithms based on chest radiographs or computed tomography scans form the technical basis for such projects.
The rapamycin analogue SDZ RAD attenuates bleomycin-induced pulmonary fibrosis in rats: Fig. 1.—
Authors: Simler N.R. , Howell D.C.J. , Marshall R.P. , Goldsack N.R. , Hasleton P.S. , Laurent G.J. , Chambers R.C. , Egan J.J.
Published: October 2002

Pulmonary fibrosis is characterized by excessive deposition of extracellular matrix proteins within the pulmonary interstitium. The new macrolide immunosuppressant SDZ RAD, a rapamycin analogue, inhibits growth-factor dependent proliferation of mesenchymal cells and might therefore be of therapeutic interest for the treatment of fibrotic lung disease.

In this study the effect of SDZ RAD on lung-collagen accumulation in the bleomycin model of pulmonary fibrosis in rats was investigated. SDZ RAD (2.5 mg·kg−1·day−1) or drug vehicle were administered orally by daily gavage. Successful dosing was confirmed by measuring splenic weight. Total lung-collagen content was measured by high-performance liquid chromatographic quantitation of hydroxyproline.

In animals given bleomycin and drug vehicle, total lung collagen was increased by 182±11% (mean±sem) compared with saline controls at 14 days (p<0.001). The increase in lung-collagen accumulation was reduced by 75±12% (p<0.01) in animals given SDZ RAD and was accompanied by a concomitant 56±6% (p<0.001) reduction in lung weight.

SDZ RAD is currently in clinical trials for the prevention of solid organ graft rejection, another condition characterized by excessive extracellular matrix production. The authors propose that SDZ RAD warrants evaluation as a novel therapeutic agent for fibrotic lung disease.
Resistanceversusendurance training in patients with COPD and peripheral muscle weakness
Authors: Spruit M.A. , Gosselink R. , Troosters T. , De Paepe K. , Decramer M.
Published: October 2002

The effects of endurance training on exercise capacity and health-related quality of life (HRQL) in chronic obstructive pulmonary disease (COPD) patients have been studied thoroughly, while resistance training has been rarely evaluated. This study investigated the effects of resistance training in comparison with endurance training in patients with moderate to severe COPD and peripheral muscle weakness (isometric knee extension peak torque <75% predicted).

Forty-eight patients (age 64±8 yrs, forced expiratory volume in one second 38±17% pred) were randomly assigned to resistance training (RT, n=24) or endurance training (ET, n=24). The former consisted of dynamic strengthening exercises. The latter consisted of walking, cycling and arm cranking. Respiratory and peripheral muscle force, exercise capacity, and HRQL were re-evaluated in all patients who completed the 12-week rehabilitation (RT n=14, ET n=16).

Statistically significant increases in knee extension peak torque (RT 20±21%, ET 42±21%), maximal knee flexion force (RT 31±39%, ET 28±37%), elbow flexion force (RT 24±19%, ET 33±25%), 6-min walking distance (6MWD) (RT 79±74 m, ET 95±57 m), maximum workload (RT 15±16 Watt, ET 14±13 Watt) and HRQL (RT 16±25 points, ET 16±15 points) were observed. No significant differences in changes in HRQL and 6MWD were seen between the two treatments.

Resistance training and endurance training have similar effects on peripheral muscle force, exercise capacity and health-related quality of life in chronic obstructive pulmonary disease patients with peripheral muscle weakness.
Spiral computed tomography of pulmonary embolism
Authors: Herold C.J.
Published: October 2002

Within the last several years, spiral computed tomography angiography (SCTA) of the pulmonary arteries has emerged as a noninvasive angiographic modality for the evaluation of patients with suspected pulmonary embolism (PE). SCTA is based on continuous computed tomography (CT) data acquisition during patient transport through the rotating X‐ray tube and detector system, where scanning is performed in the time period in which the injected contrast material passes through the pulmonary arteries. Single detector spiral CT has a sensitivity of ∼85–90% and a specificity between 88–95%. Sensitivity and specificity are very likely to increase with the use of multidetector spiral CT scanners that allow scanning of large lung volumes with a scan collimation as narrow as 1 mm.

Currently, SCTA is most commonly used as a primary imaging method in patients with suspected PE, and as a second-line method in cases with inconclusive ventilation/perfusion scintigraphy results. SCTA has proven to be cost-effective, especially in combination with ultrasound of the lower extremities.

Limitations of the method include a decreased sensitivity for the detection of small isolated clots in the peripheral pulmonary arterial bed, and a potentially reduced image quality in patients with coexistent cardiopulmonary disorders.

Despite these limitations, several studies have now documented that, in patients with suspected pulmonary embolism, it is safe to withhold anticoagulation therapy if a spiral computed tomography exam of the pulmonary arteries is negative and no lower extremity venous thrombosis is present. In the future, multislice computed tomography scanning of the pulmonary arteries with multiplanar reformation and one-stop shopping,i.e.scanning of the pulmonary arteries and the lower extremity veins in a single session, will further enhance the role of computed tomography angiography in the examination of patients with suspected pulmonary embolism.
Acute exacerbation of chronic obstructive pulmonary disease and antibiotics: what studies are still needed?
Authors: Sohy C. , Pilette C. , Niederman M.S. , Sibille Y.
Published: October 2002

The use of antibiotics in acute exacerbations of chronic bronchitis (AECBs) remains the subject of controversy despite considerable medical and socioeconomic implications.

First, the contribution of bacterial infection to AECBs is difficult to assess in patients with chronic obstructive pulmonary disease (COPD) who are chronically colonized with respiratory pathogens. In addition, several studies suggest a major role of viral infections in AECBs.

Secondly, it is unlikely that all COPD patients will benefit from antibiotics during AECBs. In particular, the benefit in mild COPD remains uncertain. Unfortunately, the number of studies complying with evidence-based medicine requirements is too small for definite recommendations in AECBs to be drawn up.

Considering the impact of acute exacerbations of chronic bronchitis on chronic obstructive pulmonary disease patients, as well as the community, and the impact of antibiotic therapy on the development of bacterial resistance, there is an urgent need for the design of appropriate multicentric studies to define the usefulness of this type of treatment in acute exacerbations of chronic bronchitis.
Particulate matter and lung function growth in children: a 3-yr follow-up study in Austrian schoolchildren
Authors: Horak F. , Studnicka M. , Gartner C. , Spengler J.D. , Tauber E. , Urbanek R. , Veiter A. , Frischer T.
Published: October 2002

The effects of particulate matter <10 µm in diameter (PM10) and other air pollutants on lung function were assessed in 975 schoolchildren, from eight communities in Lower Austria between 1994–1997. In each community, air pollution data were collected. Spirometry was performed twice a year. PM10concentration (mean concentration between two subsequent lung-function measures in spring and autumn (summer interval) or between autumn and spring (winter interval)) showed a mean value of 17.36 µg·m−3in the summer interval and 21.03 µg·m−3in the winter interval. A slower increase in the forced expiratory volume in one second (FEV1) and midexpiratory flow between 25 and 75% of the forced vital capacity (MEF25–75) with age in children exposed to higher summer PM10was observed in the 3-yr study period. After adjusting for potential confounders (sex, atopy, passive smoking, initial height, height difference, site, initial lung function) an increase of summer PM10by 10 µg·m−3was associated with a decrease in FEV1growth of 84 mL·yr−1and 329 mL·s−1·yr−1for MEF25–75. Nitrogen dioxide and ozone also showed a negative effect on lung-function growth, confirming previous work.

The authors concluded that long-term exposure to particulate matter <10 µm in diameter had a significant negative effect on lung-function proxy for the development of large (forced expiratory volume in one second) and small (midexpiratory flow between 25 and 75% of the forced vital capacity) airways, respectively, with strong evidence for a further effect of ozone and nitrogen dioxide on the development of forced vital capacity and forced expiratory volume in one second.
Supramaximal flow in asthmatic patients
Authors: Sala H. , Fernández A. , Guardia S. , González A. , Rodenstein D.
Published: October 2002

In normal subjects supramaximal flows (SF) are known to be correlated with flow limitation. To further understand the mechanisms involved in SF this correlation and the influence of salbutamol and methacholine administration on SF have been investigated in asthmatic subjects.

Protocol A involved obtaining basal maximal expiratory flow/volume curves and interrupted curves through a fast valve from 36 asthmatic patients. Maximal flow at 50% of forced vital capacity (V′max50) increase (ΔV′max50) was compared between basal curves and envelope curves passing through SF peaks obtained after each interruption.

Protocol B involved the study of 33 asthmatic patients after salbutamol administration and 12 asthmatic patients after methacholine challenge. ΔV′max50between basalversusinterrupted curves were analysed (ΔV′max50B). Similar procedures were performed after salbutamol (ΔV′max50S) and after methacholine administration (ΔV′max50M). A significant negative correlation between forced expiratory volume in one second and ΔV′max50was observed. SF decreased significantly after salbutamol administration and increased significantly after methacholine.

The results of this study suggest that in asthmatic patients participation of “pendelluft” in SF increases as airflow limitation increases.
Respiratory impedance response to a deep inhalation in asthmatic children with spontaneous airway obstruction
Authors: Schweitzer C. , Moreau-Colson C. , Marchal F.
Published: October 2002

The aim of the study was to determine whether the bronchomotor effect of a deep inhalation (DI) may be detected during tidal breathing in asthmatic children with spontaneous airway obstruction (AO).

Two groups of children aged 5–15 yrs were studied. AO was mild in group 1 (n=12, forced expiratory volume in one second (FEV1) ≥75% predicted) and moderate-to-severe in group 2 (n=9, FEV1≤70% pred). The forced oscillation technique at 12 Hz using a head generator allowed the determination of respiratory resistance in inspiration (Rrsi) and expiration (Rrse) before and after DI, at baseline and after salbutamol.

At baseline,Rrsibut notRrsewas found to decrease significantly after DI in group 1 but not in group 2. The change induced by DI was significantly different in group 1 (−1.5±0.5 hPa·s·L−1) compared to group 2 (0.5±0.5 hPa·s·L−1) and exhibited significant negative correlation to FEV1% pred. After salbutamol, DI had no effect.

In conclusion, asthmatic children show a bronchomotor response to deep inhalation that depends on the degree of airway obstruction. The effect is more readily demonstrated in inspiration than in expiration.
Effect of inhaled fluticasone on bronchial responsiveness to neurokinin A in asthma
Authors: Van Schoor J. , Joos G.F. , Pauwels R.A.
Published: October 2002

Neurokinin (NK) A causes airway narrowing in patients with asthma through direct and indirect mechanisms. The effects of the inhaled glucocorticosteroid fluticasone propionate (FP) on the bronchial responsiveness to NKA and methacholine were studied.

Patients (n=11) with mild asthma participated in a randomized, double-blind, placebo-controlled crossover trial. FP (500 µgb.i.d) or matched placebo was administeredviaDiskhalerTMfor 14 days. Bronchial challenges were performed on days 1 and 13 (methacholine) and 0 and 14 (NKA) for each treatment period.

At the active treatment period, the mean log2provocative concentration causing a 20% fall in the forced expiratory volume in one second (PC20)±sem for NKA was −12.72±0.63 at the beginning and −9.77±0.49 at the end of the period (p<0.0001), while under placebo, it was −12.16±0.82 and −12.19±0.51 respectively (ns). At the active treatment period, the mean log2PC20for methacholine was −5.25±0.40 at the beginning and −4.22±0.31 at the end of the period (p=0.012), while under placebo, it was −5.47±0.47 and −5.24±0.42 respectively (ns). The reduction in response to NKA was significantly larger than that for methacholine.

A 2-week course of an inhaled steroid reduces bronchial responsiveness to neurokinin A, an effect more pronounced than the reduction in bronchial responsiveness to methacholine.
Adaptation to organic dust exposure: a potential role of l-selectin shedding?
Authors: Israël-Assayag E. , Cormier Y.
Published: October 2002

Swine confinement workers, exposed to high levels of organic dust, present a high prevalence of respiratory symptoms but show only mild lung inflammation. This contrasts with the intense inflammatory response observed when naive subjects are exposed to the same environment. Shedding of l-selectin may regulate the recruitment of inflammatory cells and explain this discrepancy.

Soluble l-selectin (sl-selectin) levels were measured in sera of 36 workers, 35 control subjects and eight healthy volunteers briefly and repeatedly exposed to swine confinement buildings. White blood cell counts (WBC) and serum interleukin (IL)-6 levels were measured as markers of systemic inflammation.

Higher concentrations of sl-selectin were found in the sera of workers than in controls (1452±62 ng·mL−1and 872±25 ng·mL−1, respectively) whereas no differences were detected before and after acute repeated exposures of exposed volunteers. WBC were increased after exposure in exposed volunteers but not in workers. Both workers and exposed volunteers had increased IL-6 serum levels, although it was more pronounced for the exposed volunteers.

These results support the hypothesis that shedding of l-selectin may downregulate the inflammatory response to organic dust-contaminated environments and constitute one mechanism of adaptation to the farm environment.
Alterations in gene expression in hamster diaphragm after emphysema and lung volume reduction surgery
Authors: Reynders V. , Marchand E. , Gayan-Ramirez G. , De Leyn P. , Verhoeven G. , Decramer M.
Published: October 2002

The authors have demonstrated previously that emphysema and lung volume reduction surgery (LVRS) resulted in a significant shift of type IIx/b to type IIa fibres in the diaphragm of hamsters with elastase-induced emphysema. To explore the mechanisms leading to this fibre switching, the mRNA expression of the myogenic regulatory factors, the inhibitors of DNA binding proteins (Id-proteins) and insulin-like growth factor-I were examined.

Ribonucleic acid was extracted from the diaphragm of control, emphysematous, emphysematous and sham operated and LVRS hamsters and subjected to reverse transcriptase polymerase chain reaction.

Compared to control, the ratio MyoD to myogenin declined with emphysema, sham and even more after LVRS, due to a decrease in MyoD mRNA and an increase in myogenin mRNA. Similarly, compared to control, Id-1 protein mRNA levels decreased significantly in sham and even more in LVRS. Id-2 protein mRNA levels decreased in all groups, but reached statistical significance in LVRS only, compared to control.

In conclusion: 1) the reduced MyoD/myogenin ratio may be the mechanism of the shift to a slower fibre type, 2) the decreased MyoD/myogenin ratio in lung volume reduction surgery animals suggests that lung volume reduction surgery enhances rather than decreases the load placed on the diaphragm and 3) the observed down-regulation of the inhibiting factors may facilitate the diaphragm adaptation to overload.
Severe lung involvement in systemic scleromyxoedema: a highly unusual finding
Authors: Morales P. , Martinez M.Á. , Vera F. , Romero G.
Published: October 2002

Scleromyxoedema is a rare systemic disorder characterized by a lichenoid papular rash.

Although scleromyxoedema can involve any organ, very few cases of pulmonary involvement have been reported. Moreover, there are no reports in the literature on treatment of this condition, especially with lung transplantation.

The authors report a case of scleromyxoedema in a young man with neurological, skin and respiratory involvement, the latter being mainly characterized by pulmonary emphysema. Due to the serious respiratory compromise, and to the stability of the systemic lesions, a bilateral lung transplantation was performed with successful results at 4.5 yrs.

In conclusion, lung transplantation may be required in patients with severe respiratory failure caused by scleromyxoedema.
Mucosal inflammation in severe glucocorticoid-dependent asthma
Authors: Vrugt B , Wilson S , Underwood J , Bron A , de Bruyn R , Bradding P , Holgate ST , Djukanovic R , Aalbers R
Published: October 2002

To improve our understanding of the inflammatory mechanisms underlying severe disease, a biopsy study was performed comparing 15 clinically unstable glucocorticoid-dependent asthmatics, 10 mild asthmatics, and 10 control subjects. Compared with mild asthma, severe asthma was characterized by reduced mucosal eosinophilia. Whilst no significant differences were found in the numbers of mast cells, neutrophils, CD3+ and CD4+ T-cells between the three groups, up to a 4-fold increase In the numbers of activated T-lymphocytes bearing the interleukin (IL)-2 receptor (IL-2R) was found in the mucosa in severe asthma compared to mild asthma (p = 0.03) and control subjects (p = 0.003). Compared to control subjects, the mucosa of severe asthmatics contained significantly (p = 0.02) higher numbers of IL-5+ cells, with no differences between mild and severe disease. In contrast, staining for the anti-IL-4 monoclonal antibody 3H4 revealed that biopsies from mild asthmatics contained more IL4+ cells than biopsies from severe asthmatics and control subjects (p = 0.0008). In the severe asthmatics, a close correlation (r(s) = 0.76, p = 0.005) was found between the numbers of IL-2R-bearing cells and the variability in peak expiratory flow. In conclusion, persistent T-cell activation is a prominent feature of severe asthma. These results also indicate that interleukin-5, and not interleukin-4, is upregulated in severe disease.
CD69 surface expression on human lung eosinophils after segmental allergen provocation
Authors: Julius P , Luttmann W , Knoechel B , Kroegel C , Matthys H , Virchow JC
Published: October 2002

CD69 expression on eosinophils is observed in asthma and has been proposed as a marker of eosinophil activation. The role of allergens in the in vivo regulation of CD69 expression on eosinophils, however, remains incompletely understood. It was therefore investigated whether CD69 expression on eosinophils can be induced by allergen provocation in vivo. Ten allergic asthmatics were studied by segmental allergen provocation. Two segments of the right and left lung were challenged with allergen or saline. CD69 expression was determined by flow cytometry and concentrations of interleukins were analysed by enzyme-linked immunosorbent assay in bronchoalveolar lavage (BAL) fluid. Expression of CD69 on BAL eosinophils in the segments lavaged 10 min following saline instillation (28.3+/-8.8 specific mean fluorescence (SMF)) was not significantly different to segments lavaged 10 min after allergen (80.2+/-21.8 SMF) and segments lavaged 18 h after saline challenge (87.2+/-23.3 SMF). However, CD69 expression on eosinophils increased significantly 18 h after allergen challenge (128.6+/-21.9 SMF, p<0.03) which was accompanied by elevated granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations (114.9+/-42.9 pg x mL(-1), p<0.05). CD69 expression on eosinophils and GM-CSF concentrations correlated 18 h following allergen provocation (r = 0.7, p<0.025). These results suggest that in allergic asthma there is an allergen dependent, endobronchial upregulation of eosinophil activation as assessed by CD69 expression on eosinophils.
Changes in levels of catalase and glutathione in erythrocytes of patients with stable asthma, treated with beclomethasone dipropionate
Authors: Pennings HJ , Borm PJ , Evelo CT , Wouters EF
Published: October 2002

In asthmatic patients, antioxidant defence is decreased. Although inhaled corticosteroids decrease asthmatic inflammation and modulate reactive oxygen species (ROS) generation, little is known of their effect on cellular antioxidant levels. The aim of this study was to evaluate the effect of inhaled beclomethasone dipropionate (BDP; 1,000 microg x day(-1)) on erythrocyte antioxidant levels in stable asthmatic patients. Forty patients with stable, mild asthma were treated in a double-blind, placebo-controlled, parallel-group study with BDP 250 microg, two puffs b.i.d. for 6 weeks. At entry and every 2 weeks during treatment, erythrocyte antioxidant levels, haematological parameters, pulmonary function tests and asthma symptoms were determined. The results show that during treatment with BDP, erythrocyte catalase levels increased (at entry (mean +/-SEM) 41+/-4, after 6 weeks 54+/-4 micromol H2O2 x min(-1) x g haemoglobin (Hb)(-1), p = 0.05 in comparison with placebo). Erythrocyte total glutathione levels significantly decreased after 6 weeks treatment with BDP (from 7.0+/-0.4 to 6.6+/-0.3 micromol x g Hb(-1) (p = 0.04)). In the BDP-treated patients, blood eosinophil counts were higher in patients who responded with an increase in erythrocyte catalase levels during BDP treatment, as compared to those not responding ((mean +/-SEM) 340+/-39 and 153+/-52x10(6) cells x L(-1), respectively, p = 0.05). The present study shows that treatment with inhaled bedomethasone dipropionate results in changes in antioxidant levels in erythrocytes of patients with stable, mild asthma.
Respiratory epithelial ion transport in patients with disseminated bronchiectasis
Authors: Danner I , Boisseau P , Chailleux E , Escande D
Published: October 2002

The nosological limits between disseminated bronchiectasis and cystic fibrosis (CF) remain unclear. In patients with isolated congenital bilateral absence of the vas deferens, a forme fruste of the CF disease, a normal baseline nasal transepithelial potential difference (PD) but an impaired response to pharmacological interventions have been reported. The purpose of the present study was to explore ion transport in respiratory epithelium from patients with disseminated bronchiectasis. The PD under both baseline and pharmacological interventions was investigated in 13 healthy subjects, six patients with genetically proven CF and 15 patients with disseminated bronchiectasis as confirmed by computed tomography scan. Baseline PD was similar in the control and bronchiectasis groups but, as expected, was significantly more negative in the CF group. Patients with bronchiectasis responded to pharmacological tests (sequential perfusion with amiloride, chloride-free solution, isoprenaline and uridine triphosphate (UTP) similarly to healthy subjects. In contrast, CF patients exhibited an increased response to amiloride and an impaired response to chloride-free solution and isoprenaline. The data show that patients with disseminated bronchiectasis exhibit normal electrophysiological properties in their nasal epithelium. Nasal transepithelial potential difference including pharmacological tests may appear a valuable diagnostic procedure for cystic fibrosis with disseminated bronchiectasis.
Increased frequency of cystic fibrosis deltaF508 mutation in bronchiectasis associated with rheumatoid arthritis
Authors: Puechal X , Fajac I , Bienvenu T , Desmazes-Dufeu N , Hubert D , Kaplan JC , Menkes CJ , Dusser DJ
Published: October 2002

This study investigated the clinical characteristics and the possible involvement of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in patients with symptomatic diffuse bronchiectasis (DB) associated with rheumatoid arthritis (RA). Twenty-six patients with both RA and DB (group RA+DB) and control groups of 29 consecutive patients with RA but no bronchiectasis (group RA) and 29 patients with symptomatic DB of unknown origin (group DB) were prospectively studied. Among the patients of the RA+DB group, four (15.4%) were heterozygous for the CFTR gene deltaF508 mutation, whereas no deltaF508 mutation was found in patients of the RA and the DB groups (both, p<0.05). This frequency of deltaF508 mutation was also higher than the expected frequency (2.8%) in the general European population (p<0.04). Sweat chloride values and nasal potential differences were normal in three out of four patients carrying the deltaF508 mutation. In the RA+DB group, those with deltaF508 mutation had more frequent chronic sinusitis (p<0.05), a trend toward a more severe pulmonary involvement, and a lower value of nasal potential differences (p<0.01) whereas their rheumatic features had no particularity. In the RA+DB group, patients with adult-onset bronchiectasis (including two with deltaF508 mutation) had a greater reduction in total lung capacity (p<0.05) and lower nasal potential differences (p<0.005) than those with childhood-onset bronchiectasis. This study suggests a possible deleterious effect of the cystic fibrosis transmembrane conductance regulator mutated protein in the airways which may predispose to the development and severity of bronchiectasis in patients suffering from rheumatoid arthritis.
Sputum endothelin-1 is increased in cystic fibrosis and chronic obstructive pulmonary disease
Authors: Chalmers GW , Macleod KJ , Sriram S , Thomson LJ , McSharry C , Stack BH , Thomson NC
Published: October 2002

Many patients with cystic fibrosis (CF) have airflow obstruction, with peribronchial and peribronchiolar fibrosis. Endothelin (ET)-1 is a potent bronchoconstrictor with mitogenic activity for airway smooth muscle. Do the levels of ET-1 in sputum support the putative role of ET-1 in contributing to airway remodelling with airflow obstruction in CF? The levels of ET-1 in plasma, saliva and sputum from 12 adult patients with CF not in exacerbation (spontaneous sputum), 17 normal control subjects (induced sputum) and as an additional control population, nine patients with stable chronic obstructive pulmonary disease (COPD) (seven spontaneous sputum) were measured. Total and differential sputum cell counts were performed. Median (interquartile range) sputum ET-1 level was elevated in CF (77.6 (29.0-122.8) pg x mL(-1)) compared to normal subjects (6.00 (2.8-14.8) pg x mL(-1)) and COPD (16.4 (6.8-38.2) pg x mL(-1)), and in COPD compared to normal subjects. There was a slight elevation of plasma ET-1 level in CF (5.3 (3.2-6.0) pg x mL(-1)) compared to normal subjects (3.1 (1.7-4.4) pg x mL(-1)) and COPD (3.3 (2.7-4.2) pg x mL(-1)). Sputum and saliva ET-1 levels were significantly higher than plasma levels in all groups, suggesting local production or release in the respiratory tract. Sputum differential cell counts revealed pronounced neutrophilia in CF and COPD compared to normal subjects. Sputum endothelin-1 concentrations are elevated in cystic fibrosis sputum compared to chronic obstructive pulmonary disease, and in cystic fibrosis and chronic obstructive pulmonary disease compared to normal subjects. The role of endothelin-1 in contributing to airflow obstruction through bronchoconstriction and mitogenesis in cystic fibrosis needs now to be explored.
Cytokine-induced airway epithelial ICAM-1 upregulation: quantification by high-resolution scanning and transmission electron microscopy
Authors: Zhu J , Rogers AV , Burke-Gaffney A , Hellewell PG , Jeffery PK
Published: October 2002

The aim of this study was to investigate the variation of intercellular adhesion molecule (ICAM)-1 which occurs between individual airway epithelial cells of distinct phenotype. 16HBE14o- (16HBE) and BEAS-2B cell lines and human airway explants were cultured with medium alone or a mixture of tumour necrosis factor (TNF)-alpha (10 ng x mL(-1)) and interferon (IFN)-gamma (40 ng x mL(-1)) before being immunogold-labelled and examined quantitatively using sensitive high-resolution electron microscopic techniques. By enzyme-linked immunosorbent assay there was a 1.6-fold increase of ICAM-1 in the BEAS-2B cells following the cytokine mix which was not apparent in the 16HBE cells. However, high-resolution scanning electron microscopy demonstrated that an upregulation had occurred; median and ranges for gold particle number per 10 microm2 cell surface were: 7.9 (0-40) for nonstimulated and 19.1 (0-60 for stimulated) (p<0.01, Mann-Whitney U-test). The value for the nonstimulated BEAS-2B cells was 24.2 (0-60), 3-times higher that the constitutive expression in the 16HBE cells (p<0.01), whereas following stimulation, it was 68.5 (20-130) (p<0.01). Values for explant epithelial outgrowths were similar to the 16HBE cells. Immunohistochemistry of the explanted mucosa showed both constitutive and upregulated expression of epithelial ICAM-1 associated with basal and indeterminate cells rather than with ciliated or goblet cells. These results using high-resolution techniques indicate that there is marked cell-to-cell variation in cellular adhesion molecule expression and that it is the basal cells and less well differentiated (indeterminate) epithelial cells which are likely to play key roles in leukocyte retention via intercellular adhesion molecule-1.
Apoptosis in the course of granulomatous inflammation in pulmonary sarcoidosis
Authors: Kunitake R , Kuwano K , Miyazaki H , Hagimoto N , Nomoto Y , Hara N
Published: October 2002

Sarcoidosis is a chronic inflammatory disease of unknown aetiology characterized by the formation of non-necrotizing granulomas. The course of disease is usually self-limiting with the spontaneous resolution of granuloma. In the immune system, Fas antigen (Fas) and Fas ligand (FasL) are involved in the down regulation of immune reactions by inducing apoptosis. Therefore, it was hypothesized that the Fas/FasL pathway and apoptosis may be associated with the course of granulomatous inflammation in sarcoidosis. Terminal deoxynucleotidyl transferase-mediated biotin nick end-labelling (TUNEL) was performed to assess deoxyribonucleic acid strand breakages as a characteristic of apoptosis. Immunohistochemistry was also performed to detect Fas and FasL protein, and reverse transcriptase polymerase chain reaction (RT-PCR) and RT in situ PCR to detect FasL messenger ribonucleic acid (mRNA). Positive signals for TUNEL were detected in epithelioid histiocytes and lymphocytes within granulomas and in bronchoalveolar lavage (BAL) lymphocytes from patients with sarcoidosis. Positive signals for Fas were also detected in these cells. FasL mRNA was expressed in BAL lymphocytes from 15 of 20 patients with sarcoidosis, but from only one of 10 patients with normal lung parenchyma. FasL protein was expressed in lymphocytes surrounding and within the granuloma. There was a significant correlation between the result of TUNEL and clinical course in patients with sarcoidosis. Apoptosis in epithelioid histiocytes and inflammatory cells seems to participate in the course of granulomatous inflammation. Further studies are needed to determine the role of Fas, FasL and other regulatory factors in apoptosis in the granulomatous inflammation in pulmonary sarcoidosis.
Does the cellular bronchoalveolar lavage fluid profile reflect the severity of sarcoidosis?
Authors: Drent M , Jacobs JA , de Vries J , Lamers RJ , Liem IH , Wouters EF
Published: October 2002

The aim of this study was to assess whether the cellular bronchoalveolar lavage fluid (BALF) profile, particularly the number of polymorphonuclear neutrophils (PMNs), is associated with disease severity of sarcoidosis and its usefulness in determining remission. Twenty-six nonsmoking outpatients with sarcoidosis were included in this study. The patients were divided into two subgroups according to the absolute number of PMNs in BALF: < or =0.2x10(4) cells x mL(-1) (group 1; n = 15) and >0.2x10(4) cells x mL(-1) (group 2; n = 11). The radiographic stage, high-resolution computed tomography (HRCT) findings, 67Ga lung uptake as well as lung function tests differed significantly between group 1 and 2. Follow-up revealed that 14 (93.3%) patients of group 1 compared to four (36.4%) of group 2 recovered spontaneously without the help of corticosteroids. In contrast, no differences were found in the number of lymphocytes in BALF nor in the serum angiotensin converting enzyme (sACE) level between both groups. The number of PMNs, the transfer factor of the lungs for carbon monoxide (TL,CO), the forced expiratory volume in one second (FEV1) and one of the HRCT subscores discriminated between patients with different disease progression. Of these parameters the PMNs appeared to be the only one which differentiated patients who demonstrated remission and those who deteriorated. In conclusion, these results indicate that the number of polymorphonuclear neutrophils in bronchoalveolar lavage fluid distinguish between sarcoidosis patients who demonstrated remission and those having a more severe course of the disease. Whether polymorphonuclear neutrophils may be considered as markers of disease activity and/or prognosis in sarcoidosis needs further investigation.
Randomized trial of inhaled fluticasone propionate in chronic stable pulmonary sarcoidosis: a pilot study
Authors: du Bois RM , Greenhalgh PM , Southcott AM , Johnson NM , Harris TA
Published: October 2002

Pulmonary sarcoidosis is a disease in which the pathological processes are distributed along lymphatic pathways, particularly those around the bronchovascular bundles. Delivery of disease-modulating drugs by the inhaled route is therefore an attractive option. The aim of this study was to determine the efficacy of inhaled fluticasone propionate 2 mg x day(-1) in adults with stable pulmonary sarcoidosis. Forty-four adult patients (22 from each centre) were enrolled from outpatient clinics in two London teaching hospitals in a two centre, double-blind, randomized, placebo-controlled trial. Primary end points were home recordings of peak expiratory flow rate (PEFR), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC). Secondary end points were symptom scores, use of rescue bronchodilator medication, and clinic values for PEFR, FEV1, FVC, forced mid-expiratory flow (FEF25-75%), diffusion capacity of the lung for carbon monoxide (DL,CO), and total lung capacity (TLC). Symptom scores of cough, breathlessness and wheeze were lower in the active treatment group, but this did not reach statistical significance, and a general health perception assessment (Short Form (SF)-36) showed a difference between active and placebo treatment. No significant differences were found between the two groups in any physiological outcome measure. No new adverse reactions were detected. The results of this pilot study do not show an objective benefit of inhaled fluticasone propionate in pulmonary sarcoidosis where the disease is stable and is controlled without the use of inhaled corticosteroids.
Exhaled nitric oxide and sputum eosinophil markers of inflammation in asthmatic children
Authors: Piacentini GL , Bodini A , Costella S , Vicentini L , Mazzi P , Sperandio S , Boner AL
Published: October 2002

Exhaled nitric oxide and eosinophil sputum markers are considered noninvasive ways in which to evaluate airway inflammation in asthma. The aim of this study was to evaluate the relationships between these methods of evaluation in asthmatic children. In a cross-sectional study of 25 mild-moderate asthmatic children (aged 6-13 yrs, 10 patients on inhaled steroids) exhaled NO was measured along with induced sputum by inhalation of hypertonic saline solution. The sputum was processed for eosinophil count and eosinophil cationic protein (ECP) determination. Serum ECP and lung function (forced expiratory volume in one second (FEV1)) were also measured. A significant correlation was observed between exhaled NO and sputum eosinophils (r = 0.438, p = 0.032) as well as between sputum eosinophils and sputum ECP (r = 0.532, p<0.01). No correlation was observed among exhaled NO and serum ECP, sputum ECP, FEV1, respectively. Furthermore no correlation was observed between sputum eosinophil (%) and serum ECP and between sputum eosinophils and FEV1. There was no correlation among the investigated parameters in children treated with inhaled steroids. In conclusion, exhaled NO and sputum eosinophil counts are concordant in evaluating the degree of airway inflammation in patients with mild-to-moderate asthma. However, the association between these two noninvasive markers becomes less in steroid treated patients.
Childhood asthma: exhaled nitric oxide in relation to clinical symptoms
Authors: Artlich A , Busch T , Lewandowski K , Jonas S , Gortner L , Falke KJ
Published: October 2002

Bronchial asthma is associated with increased levels of exhaled nitric oxide which are suppressible by glucocorticosteroid inhalation. Children with bronchial asthma were studied to elucidate the relation between endogenous NO release and recent symptoms of bronchial obstruction. Twenty-five children with atopic asthma and 11 healthy control subjects were enrolled and exhaled NO was studied using chemiluminescence analysis. The subjects breathed purified air (<0.5 parts per billion (ppb) NO) exclusively through their mouths. Orally expired NO was measured during continuous nasal aspiration (1.3 L x min(-1)) to remove nasally produced NO. Nasal NO concentration was determined within the aspirated gas. Orally expired NO concentration was 2.5+/-0.3 ppb (mean +/-SEM) in healthy control subjects, 3.19+/-0.88 ppb (NS) in symptom-free children, and 8.28+/-0.81 ppb (p< or =0.01) in children with bronchial asthma who had had recent symptoms of bronchial obstruction. Similarly, in the subgroup of children treated regularly with inhaled glucocorticosteroids those with recent symptoms had significantly higher orally exhaled NO concentrations than healthy control subjects (9.5+/-1.5 ppb, p<0.05). The nasal NO concentration was 152.8+/-12.7 ppb in healthy control subjects and not significantly different in asthmatic children. In this group of asthmatic children, recent symptoms of bronchial obstruction were linked to significantly higher concentrations of NO in orally exhaled gas and to increased oral NO excretion rates. If substantiated by further studies, measurement of orally exhaled NO during nasal aspiration may become useful to monitor disease control in asthmatic children.