Asthma and chronic obstructive pulmonary disease are characterized by chronic airway inflammation. Studies using bronchoalveolar lavage (BAL) have shown an increased proportion of eosinophils in the BAL fluid from asthmatics compared with that from normal subjects, whereas studies of chronic obstructive pulmonary disease (COPD) have shown increased numbers of neutrophils. Induced sputum allows sampling of respiratory tract secretions from patients and control subjects, providing a noninvasive method of studying airway secretions and allowing characterization of cells and measurement of soluble markers. We investigated whether induced sputum was a useful method of studying airway fluid from patients with moderate to severe COPD and whether it could be used to compare inflammation in this condition with that in asthma. An initial reproducibility study was undertaken. Sputum was induced twice in 13 patients with severe COPD at a 14-d interval. Total and differential cell counts were carried out and were found to be reproducible over this period. Sputum was then induced in 14 patients with COPD, 23 patients with asthma, 12 healthy cigarette smokers, and 16 normal nonsmoking control subjects. We found a significant increase in neutrophils and increased concentrations of tumor necrosis factor-alpha (TNF alpha) and interleukin-8 (IL-8) in the patients with COPD compared with the smoking and nonsmoking control subjects. Interleukin-8, but not TNF alpha, was significantly higher in the COPD group than in the asthmatic group. We conclude that the cytokines TNF alpha and IL-8 may be involved in the inflammation in COPD.

The role of glucocorticoids in the treatment of chronic obstructive pulmonary disease (COPD) is controversial. We have previously described high numbers of neutrophils and high concentrations of the inflammatory cytokines interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha), and of the cell activation markers eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), myeloperoxidase (MPO), and human neutrophil lipocalin (HNL) in COPD patients as compared with controls, and have postulated that the cytokines TNF-alpha and IL-8 play a role in propagating the inflammatory response in COPD. We have now studied the effects of inhaled and oral glucocorticoids on these inflammatory indices in induced sputum. Initially, we studied the effect of a 2-wk course of inhaled budesonide (800 mg twice daily for 2 wk) in 13 patients with severe COPD (mean FDV1: 35% predicted). There was no clinical benefit in either lung function or symptom scores, and no significant change in the inflammatory indices as measured by total and differential cell counts and concentrations of TNF-alpha eosinophil activation markers ECP and EPO, and neutrophil activation markers MPO and HNL. Because the lack of anti-inflammatory effect might have been due to poor drug delivery as a result of severe airflow limitation, we undertook a study examining the antiinflammatory effect of oral prednisolone (30 mg daily for 2 wk) in patients with COPD and undertook the same measurements in 10 patients with atopic asthma. Sputum eosinophil numbers, ECP, and EPO were significantly reduced in the asthmatic patients but were not modified in COPD. This confirms the clinical impression that inhaled steroids have little antiinflammatory effect, at least in the short term in this group of patients, and suggests that the inflammatory process in COPD is resistant to the antiinflammatory effect of glucocorticoids.

Cigarette smoking is associated with an increased risk of respiratory tract infections, chronic airway disease, and cardiovascular diseases, all of which may be modulated by endogenous nitric oxide (NO). We have investigated whether cigarette smoking reduces the production of endogenous NO. We compared exhalations of 41 current cigarette smokers with normal lung function and 73 age-matched non-smoking controls. Peak exhaled NO levels were measured by a modified chemiluminescence analyzer. The effects of inhaling a single cigarette in smokers were also measured. In control subjects we also measured the effects of inhalation of NO itself and carbon monoxide, both constituents of tobacco smoke. Peak exhaled NO concentrations were significantly reduced in smokers (42 +/- 3.9 compared with 88 +/- 2.7 parts per billion in nonsmokers, p < 0.01), with a significant relation between the exhaled NO and cigarette consumption (r = 0.77, p < 0.001). Smoking a single cigarette also significantly (p < 0.02), but transiently, reduced exhaled NO. Inhalation of carbon monoxide and NO had no effect on exhaled NO in normal subjects. Cigarette smoking decreased exhaled NO, suggesting that it may inhibit the enzyme NO synthase. Since endogenous NO is important in defending the respiratory tract against infection, in counteracting bronchoconstriction and vasoconstriction, and in inhibiting platelet aggregation, this effect may contribute to the increased risks of chronic respiratory and cardiovascular disease in cigarette smokers.

Airway inflammation is present in asthma and is thought to play a significant part in the development of airflow obstruction. In chronic obstructive pulmonary disease (COPD), neutrophilic inflammation is present in the airway lumen, whereas the submucosa displays a lymphocytic infiltrate. Less is known about the nature and mechanisms of inflammation in COPD than in asthma. Induced sputum allows noninvasive sampling of respiratory tract secretions from patients and control subjects, allowing characterization of cells and measurement of soluble markers. We exploited this technique in order to compare the presence and quantify specific markers of eosinophil and neutrophil activation in subjects with asthma or COPD, and control subjects. Differential cell counts showed significantly higher neutrophil percentages in the patients with COPD compared with other groups, while patients with asthma had higher numbers of eosinophils. The neutrophil markers myeloperoxidase (MPO), from primary granules in neutrophils, and human neutrophil lipocalin (HNL), released from secondary granules, were elevated in patients with asthma and COPD compared with control subjects but markedly more so in COPD. The difference between COPD and asthma was more marked for HNL than for MPO suggesting that HNL may be a better marker for discriminating between these conditions. Concentrations of the eosinophil granule protein, eosinophil cationic protein (ECP), and the eosinophil granule-derived enzyme, eosinophil peroxidase (EPO) were raised in the patients with asthma and those with COPD.

Abstractmay make it a more appropriate agent for testing the vasodilator response. Background -In patients with primary (Thorax 1997;52:369-372) pulmonary hypertension who respond to vasodilators acutely, survival can be im- Keywords: pulmonary hypertension, vasodilators, nitric proved by the long term use of calcium oxide, prostacyclin, calcium channel blockers. channel blockers. However, testing for such a response with calcium channel blockers or prostacyclin (PGI 2 ) may causeIn patients with primary pulmonary hyperhypotension and adversely affect gas extension an improvement in survival can be change. Nitric oxide (NO), which does not obtained by the long term administration of have these effects, could be a better test calcium channel blockers to those who respond agent.to vasodilators given acutely. 1 Calcium channel Methods -NO (10, 20, and 40 ppm for blockers have been used for this test procedure, 15 minutes), PGI 2 (1->10 ng/kg/min), and but their effect on systemic haemodynamics can oral nifedipine (10 mg, then 20 mg/h) were induce severe or even life threatening effects. 2 administered sequentially to 10 patients Because of its short half life and pulmonary after determination of the 24 hour spon-vasodilator effect, prostacyclin (PGI 2 ) has been taneous variability of their pulmonary and administered instead and is regarded as the systemic mean arterial pressures. Patients screening agent of choice.3 However, PGI 2 is were considered responders if the mean an equally potent systemic vasodilator and may pulmonary artery pressure or pulmonary impair pulmonary hypoxic vasoconstriction vascular resistance decreased by 20% or with resulting hypoxaemia. Recent studies have more.suggested that nitric oxide (NO), a selective Results -Six patients (60%) responded to pulmonary vasodilator, may be a better screenall three agents, and three to none of the ing agent.4 5 The purpose of the present study agents. One patient responded to PGI 2 was to evaluate the ability of NO to predict a only. In those who responded to vaso-response to calcium channel blockers, and to Medical ICU Division dilators, NO had no major effect on gas compare its effects on haemodynamics and gas venous blood samples were collected sim-ues of PAPspont for the responders were compared with those of the decrease in mean ultaneously for blood gas determinations. Derived variables were computed according to PAP obtained with each vasodilator using a Wilcoxon signed rank test. standard equations.Since a previous study from our ICU demonstrated a 24 hour variability of 11% in mean PAP and 14% in pulmonary vascular resistance ResultsAll results are expressed as mean (SD). Ten (PVR) in patients with pulmonary hypertension, in the absence of any drug ad-patients were studied, four of whom had primary pulmonary hypertension while in the others ministration, 7 these parameters were first recorded every hour for 24 hours without any pulmonary hypertension was associated with cirrhosis and portal hypertension (2), conpharmacological intervent...