Publications

Several components of air pollution have been linked to asthma. In addition to the well-studied critera air pollutants, such as nitrogen dioxide, sulfur dioxide, and ozone, diesel exhaust and diesel exhaust particles (DEPs) also appear to play a role in respiratory and allergic diseases. Diesel exhaust is composed of vapors, gases, and fine particles emitted by diesel-fueled compression-ignition engines. DEPs can act as nonspecific airway irritants at relatively high levels. At lower levels, DEPs promote release of specific cytokines, chemokines, immunoglobulins, and oxidants in the upper and lower airway. Release of these mediators of the allergic and inflammatory response initiates a cascade that can culminate in airway inflammation, mucus secretion, serum leakage into the airways, and bronchial smooth muscle contraction. DEPs also may promote expression of the T(subscript)H(/subscript)2 immunologic response phenotype that has been associated with asthma and allergic disease. DEPs appear to have greater immunologic effects in the presence of environmental allergens than they do alone. This immunologic evidence may help explain the epidemiologic studies indicating that children living along major trucking thoroughfares are at increased risk for asthmatic and allergic symptoms and are more likely to have objective evidence of respiratory dysfunction.

OBJECTIVE

To examine whether recommendations made by the U.S. Panel on Cost-Effectiveness in Health and Medicine (Panel Report) have been associated with changes in how cost-effectiveness analyses are conducted.

METHODS

We examined whether studies published after the Panel Report was issued and which cited the Panel Report were more likely to follow its recommendations on discounting, quality-adjusted life years (QALYs), and incremental ratios than (1) studies published before the Panel Report, and (2) studies published after the Panel Report but that did not cite the Panel Report. We used the Science Citation Index to identify all studies citing the Panel Report that were also empirical, cost-effectiveness analyses (n=18). We randomly selected two groups for comparison (N=54). Studies were compared using contingency tables.

RESULTS

Significantly more studies that cited the Panel Report used a 3% discount rate than did post-report comparison studies (p=0.03) and pre-report comparison studies (p=0.03). There was a nonsignificant trend for studies citing the Panel Report to be more likely to use QALYs and incremental ratios (range of p=0.11 to p=0.20).

CONCLUSIONS

We found evidence that the Panel Report had an impact on practice. However, 31% of the studies citing the Panel Report did not follow the recommendation to use a 3% discount rate, and only 28% followed all three recommendations.

Based largely on studies of cell lines in vitro and of transgenic mouse models, disruptions of transforming growth factor (TGF) beta signaling are thought to contribute to the development and progression of human breast cancer. However, whether and how TGF-beta signaling becomes disrupted during human breast cancer development in vivo remains largely unknown. To address this question, we have compared the patterns of expression and activation of the postreceptor components of the TGF-beta signaling pathway, the so-called Smads, in human breast cancer cell lines with those in breast carcinoma specimens. None of the breast carcinoma cell lines were growth arrested by TGF-beta in vitro. Each of the tumor cell lines expressed normal levels of Smad2 and -3. Moreover, TGF-beta treatment induced phosphorylation of Smad2 (Smad2P) in each of these lines, except those that lacked TGF-beta type II receptors. Moreover, only one of the cell lines failed to express Smad4. Among 456 cases of human breast carcinoma assembled in tissue microarrays, the majority (92%) expressed Smad2, Smad2P, as well as Smad4, indicating their ability to proliferate within a microenvironment that contains bioactive TGF-beta. Thirty cases (6.6%) failed to express Smad2P, suggesting the loss of TGF-beta receptor signaling. Nine cases (2%) failed to express Smad4, and 3 of these also failed to express Smad2P. Thus, the phenotypes of breast tumors in vivo paralleled that of human breast cancer cell lines in terms of Smad2P and Smad4 expression. Loss of Smad signaling was not associated with any particular histological subtype, histological or nuclear grade, estrogen- or progesterone receptor expression, or HER2/neu expression. Loss of Smad4 was inversely correlated with the presence of axillary lymph node metastases. Most importantly, among patients with stage II breast cancer, lack of Smad2P expression in the tumor was strongly associated with shorter overall survival. Finally, analysis of a small cohort of hereditary breast cancers failed to reveal any association between BRCA1 or BRCA2 genotype and alterations in Smad signaling.