Weight loss has been recognized as a feature of advanced emphysema and a factor of poor prognosis, but its mechanisms remain obscure. Studies have demonstrated high serum concentrations of TNF-a (cachexin) in chronic obstructive pulmonary disease (COPD) patients with emphysema. Pink puffers (PP) COPD patients have worse tissue oxygenation when compared with blue bloaters (BB) COPD patients. Consequently, PP patients would become cachectic, whereas BB patients with better tissue oxygenation would not. The aim of this study is to test the hypothesis that malnutrition in emphysema is a cytokine-mediated marker of chronic progressive tissue hypoxia. Thirty male COPD patients, without clinical or laboratory evidence of infection and severe air way obstruction (FEV1 < 1.5 l) were allocated: 16 as pink puffers (PP) and 14 as blue bloaters (BB). Lung function measurements included FEV1, FVC, RV, TLC, DLCO and arterial blood gases on room air. TNF-a serum levels were measured by immunoenzymic method (ELISA). Tissue oxygenation was assessed from oxygen delivery (DO2), PvO2 and oxygen extraction ratio (O2ER) obtained after right heart catheterization with Swan Ganz catheter. PP patients demonstrated lower DLCO and higher TLC, FRC and PaO2 from BB. We found that oxygen delivery was better in our BB than in PP patients (CI 2.9 +/- 0.2 vs 2.5 +/- 0.4 l/min/m2--P < 0.01, DO2 16.1 +/- 2.1 vs 13.1 +/- 0.2 ml/min/kg--P < 0.001) and the same was found for tissue oxygenation (PvO2 34.6 +/- 2.9 vs 31.2 +/- 3.8 mmHg--P < 0.01, O2ER 0.27 +/- 0.02 vs 0.34 +/- 0.06%--P < 0.001). The TNF-a values were higher in PP (31.3 +/- 26 pg/ml vs 15.2 +/- 9.9 pg/ml--P < 0.05) and their percent fat-free mass (%FFM) was 49.6 +/- 11.5 vs 42 +/- 8%--P < 0.001. We found that COPD patients with lower DO2 had increased TNF-a levels; but the correlations between TNF-a serum levels and PvO2 or O2ER were not statistically significant. TNF-a levels were elevated in PP patients with tissue hypoxia and may be a factor contributing to the weight loss of these patients.

Background: It has been suggested that the Hering-Breuer reflex (HBR) is unimportant in adults during normal tidal breathing and that it is elicited only if tidal volume is increased above a certain critical threshold. Objective: The aim of this study was (1) to study the occurrence of the HBR in adults with normal pulmonary function and (2) to examine if changes in lung mechanics have any effect on the HBR. Methods: We examined 11 adults with normal pulmonary function, 8 patients with chronic destructive pulmonary disease (COPD) and 3 with interstitial fibrosis (IF). All subjects were lightly sedated with fentanyl, intubated and ventilated with a Servo-900 ventilator. Inspiratory and expiratory flow (and after integration, volume) and mouth pressure were recorded from the endotracheal tube with a pneumotachograph and a pressure transducer. Pressure support ventilation was applied in all patients and functional residual capacity (FRC) was measured with the N₂ washout method. Mean (Te_mean) and maximal expiratory time (Te_max) were determined for each individual for 20 breaths. Following several breaths to establish a stable baseline the airway was occluded at end inspiration by a shutter. A positive HBR was interpreted as longer Te_occ than Te_max (Te_occ/Te_max, %). Occlusion was maintained until negative airway pressure occurred and the occlusion time (Te_occ) was measured. We attempted occlusions after the addition of 5 cm H₂O positive end-expiratory pressure (PEEP) and subsequently with 10, 15 and 20 cm H₂O PEEP. Te_occ was measured of progressively larger lung volumes. To examine the HBR sensitivity in the three groups, we plotted the lung volumes of occlusion against the corresponding Te_occ/Te_max. Results: The ratio Te_occ/Te_max increased from 167.5 ± 82.5 at normal FRC to 474 ± 200.2 s (PEEP₂₀). On the contrary, in patients with COPD, Te_occ/Te_max increased from 125.2 ± 34 to 193.7 ± 74.2 (p < 0.05). Conclusions: The HBR was positive in all subjects. COPD patients were found to be less sensitive to volume changes when compared with normal controls and with IF patients.

To compare the effects of salmeterol, an adrenergic drug, and ipratropium bromide, an anticholinergic drug, on breathlessness and gas exchange during exercise in patients with chronic obstructive lung disease (COPD), we performed a progressive treadmill exercise test on 15 patients on 3 days (24 h apart), after inhalation placebo, ipratropium bromide (120 micrograms) or salmeterol (50 micrograms) in a randomized fashion. Dyspnoea during exercise was evaluated from the regression slope between Borg scale (BS) scores and distance walked each minute on the treadmill. The regression was expressed as the distance walked at BS score 5, the threshold load of dyspnoea (TLD) and breakpoint load of dyspnoea. During and after the exercise, oxygen saturation was monitored by pulse oxymeter and we measured the lower SaO2 during exercise and the recovery time of SaO2 after exercise. In comparison to placebo inhalation we found the same small but significant improvement in airflow limitation after salmeterol or ipratropium inhalation, also the distance walked on treadmill increased after bronchodilators. After bronchodilators the magnitude of oxyhaemoglobin desaturation with exercise was similar to that observed after placebo but the duration of the recovery from sustained SaO2 desaturation after exercise was shorter to the same extent as after ipratropium or salmeterol. Dyspnoeic sensation, when assessed by the TLD and by the distance walked at BS score 5, was decreased after salmeterol and after ipratropium bromide to a similar extent. We conclude that the salmeterol, when given in conventional doses, produces significant improvement in the airway obstruction in the recovery of postexercise HbO2 desaturation and in dyspnoeic sensation in patients with COPD, effects which were similar to those observed after inhalation of the anticholinergic agent ipratropium bromide.