Lung fibroblasts from patients with emphysema show a reduced proliferation rate in culture.

Emphysema is characterised by a loss of alveolar structure, as reflected in elastic recoil and gas exchange. As fibroblasts play a key role in the maintenance of structure, the current authors hypothesised that their proliferation might be constitutively impaired in lung emphysema. Using explant cultures, lung fibroblasts were obtained from resected lungs of 10 patients with emphysema (median forced expiratory volume in one second (FEV1) 40% predicted) and 10 control patients (FEV1, 95% pred). The doubling time (DT) was measured over 4 days under standard conditions (10% foetal calf serum) prior and after cryopreservation. Additionally, in seven samples per group the total population doubling level (PDL) was determined. In emphysema, mean+/-sem DT was 33.6+/-2.8 h compared with 24.8+/-1.4 h in controls. The differences in DT were preserved after cryopreservation. Groups also differed in the initial slope of the PDL plot during long-term culture (up to 35 days). However, the median (range) maximum PDL did not differ significantly between groups (13.8 (7.4-22.6) versus 20.2 (11.2-25.5)). The current authors, therefore, suggest that the reduced proliferation rate in vitro of lung fibroblasts from patients with emphysema reflects a persistent, intrinsic failure of cellular replacement and maintenance in this disease, possibly in relation to pre-term aging.

Direct measurement of BDP and 17-BMP in bronchial and peripheral lung tissue after inhalation of HFA- vs CFC-driven aerosols.

Indirect assessments have shown a superior lung deposition of HFA-BDP (Ventolair/Qvar) compared to CFC-BDP (Aerobec). The aim of this study was to assess the concentrations of BDP and its metabolite 17-BMP in airways and peripheral tissue from resected lung specimens after inhalation of these BDP formulations. Immediately prior to surgery for lung cancer, 10 patients inhaled 1000 microg of either CFC-BDP (n = 5) or HFA-BDP (n = 5) Mouthwash was collected after inhalation, and serum before, during, and after surgery. There was no significant difference between CFC and HFA in the concentration of 17-BMP in bronchi (median, 4365 vs 4121 pg/g tissue). After CFC, concentrations of 17-BMP were lower in peripheral tissue (1424 vs 2089 pg/g; ANCOVA, p = 0.001) and in serum taken immediately after inhalation (688 vs 1219 pg/ml, p < 0.01). Furthermore, the CFC group showed a higher concentration of BDP in the mouthwash (17,660 vs 1320 ng/ml, p < 0.05), but the concentration of 17-BMP was lower (452 vs 1028 ng/ml, n.s.). These findings indicate a predominantly peripheral deposition of HFA-BDP, in line with previous data. They also provide evidence for a faster uptake and metabolism of HFA-BDP, probably because BDP is dissolved in HFA and has a smaller particle size distribution than the CFC suspensions.

Montelukast attenuates the airway response to hypertonic saline in moderate-to-severe COPD.

This study assessed the effect of the leukotriene receptor antagonist montelukast on hypertonic saline-induced airway obstruction. A total of 29 patients with chronic obstructive pulmonary disease (forced expiratory volume in one second (FEV1), 42+/-4% predicted) received either 10 mg montelukast and 3 h later placebo via metered-dose inhaler (MDI) (M), or placebo and 3 h later 200 microg salbutamol (S), or two doses of placebo (P), in a randomised order. Patients inhaled salbutamol 1 h after MDI and the challenge was performed 15 min later (3% saline, 5 min). Data are given as per cent changes versus baseline. Compared to P, S caused significant bronchodilation in FEV1 (7.3%) and forced inspiratory volume in one second (FIV1) (4.5%), and M in FIV1 (1.5%). The saline-induced fall in FEV1 was lower after M (-5.8%), compared with S (-10.3%) and P (-13.1%). FEV1 (11.3%) and FIV1 (7.6%) was improved over baseline after recovery by M but not P and S. Recovery times regarding FEV1 (8.5 min) and FIV1 (15.2 min) were shortest after M, respective values for S being 16.8 and 20.4 min, and for P 15.9 and 21.2 min. Effects were strongest in patients with low baseline FEV1 and/or inhaled corticosteroids. Data from this study indicate beneficial effects of montelukast on hypertonic saline-induced airway responses in patients with chronic obstructive pulmonary disease, particularly those with severe disease. The major effect was an accelerated recovery leading to values above baseline.