Hypercapnia has been accepted during nasal intermittent positive pressure ventilation (nIPPV) and during subsequent spontaneous breathing in patients with chronic hypercapnic respiratory failure (HRF) due to COPD. We tested the hypothesis that nIPPV aimed at normalizing PaCO2 will reduce PaCO2 during subsequent spontaneous breathing. For that purpose 14 consecutive inpatients (age 61.4 +/- 9.9 years) with chronic HRF due to COPD were established on passive pressure-controlled nIPPV in a stepwise approach. Assisted ventilation with supplemental oxygen to reach normoxemia was started followed by passive ventilation with a stepwise increment in the inspiratory pressure and finally by a stepwise increase in the respiratory rate to establish normocapnia. Baseline pulmonary function parameters were: FEV1 0.97 +/- 0.43 l, PaCO2 59.5 +/- 8.4 mmHg, PaO2 49.9 +/- 7.8 mmHg, HCO3- 35.6 +/- 5.2 mmol/l, pH 7.39 +/- 0.04. Normoxemia as well as normocapnia was thus established by decreasing PaCO2 by 19.5 +/- 7.0 mmHg during nIPPV within 8.8 +/- 3.8 days (P < 0.001) (inspiratory pressure 29.8 +/- 3.8 mmHg, respiratory rate 22.9 +/- 1.9 BPM). Spontaneous PaCO2 measured 4 h after cessation of nIPPV decreased to 46.0 +/- 5.5 mmHg (P < 0.001), and HCO3- decreased to 27.2 +/- 3.0 mmol/l (P < 0.001). At 6 months of follow-up, II patients continued nIPPV with stable blood gases and with a decrease of P0.1/Plmax from 9.4 +/- 4.3% to 5.9 +/- 2.0% (P < 0.005). In conclusion, normalization of PaCO2 by passive nIPPV in patients with HRF due to COPD is possible and leads to a significant reduction of PaCO2 during subsequent spontaneous breathing and is associated with improved parameters of respiratory muscle function.

T lymphocytes expressing the alpha E beta 7 integrin are localized and selectively retained in mucosal tissues. To investigate a potential relationship between alpha E beta 7 expression and pulmonary inflammation, the distribution of alpha E beta 7-bearing CD4+ and CD8+ T cells in peripheral blood and bronchoalveolar lavage (BAL) fluids obtained from patients with allergic asthma, sarcoidosis, hypersensitivity pneumonitis, and idiopathic pulmonary fibrosis (IPF) was determined. In contrast to the distribution in peripheral blood, BAL fluid from these patients contained high number of cells expressing alpha E beta 7 with markedly different expression patterns on CD4 or CD8 cells as well as among the various diseases. Despite similar numbers of activated CD4 cells, alpha E beta 7+CD4+ T cells ranged from 15% in asthmatics to 70% in IPF. In contrast, even in normal individuals, 60% to 90% of BAL fluid CD8+ T cells express alpha E beta 7, suggesting differential induction mechanisms on CD4 and CD8 cells. In vitro experiments revealed that a substantial proportion of peripheral blood CD+ T cells express alpha E beta 7 after stimulation with anti-CD3 antibodies, and up to 80% positive cells were found after the addition of TGF-beta. In contrast, less than 10% of CD4 cells express this particular integrin after in vitro stimulation, and the presence of TGF-beta only increased the number to 30%. Supernatants from in vitro-activated BAL cells as well as concentrated BAL fluid from patients with high alpha E beta 7 expression had no further enhancing effect. However, crosslinking of alpha 4 beta 1-, but not beta 2-integrins, significantly increased the number of alpha E beta 7 expressing CD4+ and CD8+ T cells, even in the absence of TGF-beta. These data indicate that in addition to TGF-beta, the interaction of particular T-cell subsets with specific endothelial cell and extracellular matrix proteins may upregulate alpha E beta 7 integrin expression and thereby contribute to the selective accumulation of these cells in inflammatory lung diseases.

Not all asthma can be adequately controlled, despite the use of high-dose inhaled corticosteroids. Because cysteinyl-leukotrienes (Cys-LT) have been implicated in the pathogenesis of asthma, we hypothesized that the leukotriene receptor antagonist zafirlukast, in combination with high-doses of inhaled corticosteroids, might be efficacious in severe asthma. In a double-blind, parallel group study, 368 chronic adult asthmatic patients treated with inhaled corticosteroids (1,000 to 4,000 microgram/d), who had a predefined level of asthma symptoms during the run in period of the study, were randomly assigned to receive additional treatment with a high dose of zafirlukast (80 mg twice daily) (n = 180) or placebo (n = 188) for 6 wk. Compared with placebo, zafirlukast produced a significant improvement over baseline in the primary study endpoint of mean morning peak expiratory flow rate (PEFR) (18.7 L/min versus 1.5 L/min, p < 0.001), as well as in evening PEFR (p < 0.01), FEV(1) (p < 0.05), daytime symptom score (p < 0.001), and beta(2)-agonist use (p < 0.001). Furthermore, zafirlukast significantly reduced the risk of an exacerbation of asthma (odds ratio [OR]: 0.61; 95% confidence interval [CI]: 0.38 to 0.99) and the risk of patients requiring a further increase in asthma controller therapy (OR: 0.4; 95% CI: 0.2 to 0.8). In conclusion, in patients taking high-dose inhaled corticosteroids, zafirlukast improves pulmonary function and asthma symptoms, and reduces the risk of an asthma exacerbation, suggesting that the contribution of leukotrienes to asthma symptoms and exacerbations is not adequately controlled by high-dose inhaled corticosteroids.

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 mg . day -1 ) on erythrocyte antioxidant levels in stable asthmatic patients.Forty patients with stable, mild asthma were treated in a double-blind, placebocontrolled, parallel-group study with BDP 250 mg, 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 (meanSEM) 414, after 6 weeks 544 mmol H 2 O 2 . min -1 . g haemoglobin (Hb) -1 , p=0.05 in comparison with placebo). Erythrocyte total glutathione levels significantly decreased after 6 weeks treatment with BDP (from 7.00.4 to 6.60.3 mmol . 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 ((meanSEM) 34039 and 15352610 6 cells . 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. Eur Respir J 1999; 13: 1260±1266.

The data suggest that therapeutic progress and cessation of smoking can provide distinctive savings of direct costs and even more of indirect costs of AB and CB.