There is increasing evidence that chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation in the airways and lung parenchyma; however, little is known about the inflammatory response during acute COPD exacerbation. The objectives of this study were (1) to determine if inflammatory markers associated with neutrophilic inflammation and activation increase at times of acute COPD exacerbation relative to the clinically stable state, and (2) to determine whether the presence of acute bacterial or viral infection at the time of COPD exacerbation could be correlated with increases in sputum markers of inflammation. Induced sputum was collected from patients with COPD when they were clinically stable, during the time of an acute exacerbation, and 1 mo later. Sputum was analyzed at each time point for soluble markers associated with neutrophilic inflammation; myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-␣), and interleukin-8 (IL-8). Serologic assays on acute and convalescent sera were performed for respiratory viruses, and induced sputum was also subject to quantitative bacterial cultures, viral cultures, and polymerase chain reaction (PCR) for detection of respiratory viruses. Fourteen of the 50 patients enrolled in the study met predetermined criteria for an acute COPD exacerbation over the 15-mo study period. TNF-␣ and IL-8 were significantly elevated in the sputum of patients during acute COPD exacerbation compared with when they were clinically stable (p ϭ 0.01 and p ϭ 0.05, respectively). Concentrations of these cytokines declined significantly 1 mo after the exacerbation. Three of 14 patients (21%) had confirmed bacterial or viral respiratory tract infections. Patients with documented infection did not demonstrate greater increases in sputum levels of inflammatory cytokines during exacerbations compared with patients without demonstrable infection. We conclude that markers of airway neutrophilic inflamation increase at the time of acute COPD exacerbation and then decline 1 mo later, and that this acute inflammatory response appears to occur independently of a demonstrable viral or bacterial airway infection.

The cellular inhibitor of apoptosis 2 (cIAP2/HIAP1) is a potent inhibitor of apoptotic death. In contrast to the other members of the IAP family, cIAP2 is transcriptionally inducible by nuclear factor-B in response to multiple triggers. We demonstrate here that cIAP2 ؊/؊ mice exhibit profound resistance to lipopolysaccharide (LPS)-induced sepsis, specifically because of an attenuated inflammatory response. We show that LPS potently upregulates cIAP2 in macrophages and that cIAP2 ؊/؊ macrophages are highly susceptible to apoptosis in a LPS-induced proinflammatory environment. Hence, cIAP2 is critical in the maintenance of a normal innate immune inflammatory response.

After many years of fusion research, the conditions needed for a D–T fusion reactor have been approached on the Tokamak Fusion Test Reactor (TFTR) [Fusion Technol. 21, 1324 (1992)]. For the first time the unique phenomena present in a D–T plasma are now being studied in a laboratory plasma. The first magnetic fusion experiments to study plasmas using nearly equal concentrations of deuterium and tritium have been carried out on TFTR. At present the maximum fusion power of 10.7 MW, using 39.5 MW of neutral-beam heating, in a supershot discharge and 6.7 MW in a high-βp discharge following a current rampdown. The fusion power density in a core of the plasma is ≊2.8 MW m−3, exceeding that expected in the International Thermonuclear Experimental Reactor (ITER) [Plasma Physics and Controlled Nuclear Fusion Research (International Atomic Energy Agency, Vienna, 1991), Vol. 3, p. 239] at 1500 MW total fusion power. The energy confinement time, τE, is observed to increase in D–T, relative to D plasmas, by 20% and the ni(0) Ti(0) τE product by 55%. The improvement in thermal confinement is caused primarily by a decrease in ion heat conductivity in both supershot and limiter-H-mode discharges. Extensive lithium pellet injection increased the confinement time to 0.27 s and enabled higher current operation in both supershot and high-βp discharges. Ion cyclotron range of frequencies (ICRF) heating of a D–T plasma, using the second harmonic of tritium, has been demonstrated. First measurements of the confined alpha particles have been performed and found to be in good agreement with TRANSP [Nucl. Fusion 34, 1247 (1994)] simulations. Initial measurements of the alpha ash profile have been compared with simulations using particle transport coefficients from He gas puffing experiments. The loss of alpha particles to a detector at the bottom of the vessel is well described by the first-orbit loss mechanism. No loss due to alpha-particle-driven instabilities has yet been observed. D–T experiments on TFTR will continue to explore the assumptions of the ITER design and to examine some of the physics issues associated with an advanced tokamak reactor.