The effect of smoking cessation and steroid treatment on emphysema in guinea pigs.

BACKGROUND: Emphysema induced by cigarette smoking is characterized by an inflammatory process, which is resistant to steroid and remains active in lung tissue long after smoking has stopped. Latent adenoviral infection (Ad5) increases emphysema development and the inflammatory response to cigarette smoke and, in allergic lung inflammation, suppresses anti-inflammatory effects of steroids. OBJECTIVES: The present study was designed to examine the effect of smoking cessation and steroid treatment on lung emphysema and inflammation in a guinea pig model of emphysema and to determine if latent adenoviral infection induces resistance to the inflammatory effects of steroid. METHODS: Latent adenovirus or sham infected animals exposed to room air or cigarette smoke for 16 weeks were either sacrificed immediately or treated with dexamethasone or diluent for an additional 5 weeks without smoke exposure. Lung morphometry, inflammatory cells and mediators were studied. RESULTS: Smoking cessation was associated with an increase in lung surface area and surface area to volume ratio. Smoking cessation was also associated with decreases in lung neutrophils, CD4 cells, and IL-8, RANTES and IFN-gamma mRNAs to control levels. Steroid treatment significantly lowered neutrophils, eosinophils and IFN-gamma mRNA and, while adenoviral infection did not alter these steroid-induced changes, it independently increased airway wall neutrophils and CD8 cells. CONCLUSION: Smoking cessation decreases lung inflammation and latent adenoviral infection does not induce steroid resistance in this animal model.

Cerebrovascular Responsiveness to Hypercapnia Is Stable over Six Months in Older Adults.

The primary purpose of this Brain in Motion (BIM) sub-study was to determine the 6-month stability of resting blood flow velocity and cerebrovascular responsiveness to a euoxic hypercapnic challenge in a group of physically inactive community dwelling men and men aged ≥55 yrs (range 55-92 yrs). At baseline and 6 months later 88 women (65±6 yr) and 78 men (67±7 yr) completed a hypercapnic challenge (step changes from resting end-tidal PCO2 ((PETCO2) to +1, +5 and +8 mmHg above rest) while cerebral blood flow velocity was assessed using transcranial Doppler ultrasound. Peak velocity of the middle cerebral artery (MCAv) was increased (p<0.05) at the second visit during rest (51±2 vs. 52±4); however, these differences were abolished (p>0.05) when MCAv was normalized to PETCO2. During hypercapnia, MCAv tended to be increased at follow-up, but this finding was absent when MCAv/PETCO2 was compared across time. Cerebrovascular reactivity (i.e., ΔMCAv/ΔPETCO2) was similar (p>0.05) between testing occasions regardless of the approach taken (i.e., considering only the lower step [from +1 to +5 mmHg]; the upper step [+5 to +8 mmHg]; or the complete test taken together). In conclusion, this study has shown that cerebral blood flow and cerebrovascular responsiveness to acute euoxic hypercapnia are stable in older, healthy adults over a 6-month period. Modest changes in MCAv over time must be viewed in the context of underlying differences in PETCO2, an important finding with implications for future studies considering cerebral blood flow velocity.

Emphysematous lung destruction by cigarette smoke. The effects of latent adenoviral infection on the lung inflammatory response.

This study was designed to test the hypothesis that cigarette smoke-induced inflammation and emphysema are amplified by the presence of latent adenoviral (Ad) infection, and to determine whether this emphysematous process can be reversed by all-trans-retinoic acid (RA) treatment. The results confirm that in guinea pigs, chronic cigarette-smoke exposure caused lesions similar to human centrilobular emphysema. They also show that latent Ad infection combined with cigarette-smoke exposure caused an excess increase in lung volume (P < 0.001), air-space volume (P < 0.001), and lung weight (P < 0.01), and further decrease in surface-to-volume ratio (P < 0.001) compared with smoke exposure alone. RA treatment failed to reverse these emphysematous changes. Analysis of inflammatory response in parenchymal and airway tissue showed that smoking caused an increase of polymorphonuclear leukocytes (PMNs) (P < 0.0002), macrophages (P < 0.001), and CD4 cells (P < 0.0009), and that latent Ad infection independently increased PMNs (P < 0.001), macrophages (P = 0.003), and CD8 cells (P < 0.001). We conclude that latent Ad infection amplifies the emphysematous lung destruction and increases the inflammatory response produced by cigarette-smoke exposure. In this study, the increase in CD4 was associated with cigarette smoke and the increase in CD8 cells with latent Ad infection.