Publications

BACKGROUND & AIMS

Most previous population-based studies of mortality in inflammatory bowel disease (IBD) did not account for medication use. We evaluated mortality by IBD medication use among members of the Kaiser Permanente Northern California IBD Registry.

METHODS

The retrospective, population-based cohort study included 9032 persons who received at least one inpatient or 2 outpatient diagnoses of IBD during 1996-2002. Age and sex standardized mortality ratios measured the associations between IBD and all-cause and cause-specific mortality. Age, sex, and smoking adjusted odds ratios measured the association of mortality by IBD medication use.

RESULTS

Compared with health plan members without IBD, mortality was increased in patients with Crohn's disease (CD) (1.4; 95% confidence interval, 1.2-1.6) but not ulcerative colitis (UC) (1.0; 95% CI, 0.9-1.2). CD was associated with increased mortality from infectious and parasitic diseases (4.1; 95% CI, 1.7-8.5), septicemia (6.8; 95% CI, 2.2-15.8), small intestinal cancer (48.1; 95% CI, 5.8-17.4), respiratory diseases (1.9; 95% CI, 1.3-2.7), digestive diseases other than IBD (2.4; 95% CI, 1.0-4.8), and liver diseases (2.6; 95% CI, 1.0-5.3). UC was associated with increased mortality from digestive diseases other than IBD (3.9; 95% CI, 2.4-6.0). The relationship with CD mortality was 0.7 for aminosalicylates (95% CI, 0.5-1.1), 1.3 (95% CI, 0.9-1.9) for immunomodulators, and 1.0 (95% CI, 0.7-1.4) for corticosteroids. Among patients with UC, these odds ratios were 0.8 (95% CI, 0.5-1.1) for aminosalicylates, 0.5 (95% CI, 0.3-0.9) for immunomodulators, and 0.8 (95% CI, 0.6-1.1) for corticosteroids.

CONCLUSIONS

Mortality is increased in CD. Infections, respiratory diseases, and digestive diseases are important specific causes of death. IBD medication use has varying associations with mortality.

Airway inflammation and epithelial remodeling are two key features of asthma. IL-13 and other cytokines produced during T helper type 2 cell-driven allergic inflammation contribute to airway epithelial goblet cell metaplasia and may alter epithelial-mesenchymal signaling, leading to increased subepithelial fibrosis or hyperplasia of smooth muscle. The beneficial effects of corticosteroids in asthma could relate to their ability to directly or indirectly decrease epithelial cell activation by inflammatory cells and cytokines. To identify markers of epithelial cell dysfunction and the effects of corticosteroids on epithelial cells in asthma, we studied airway epithelial cells collected from asthmatic subjects enrolled in a randomized controlled trial of inhaled corticosteroids, from healthy subjects and from smokers (disease control). By using gene expression microarrays, we found that chloride channel, calcium-activated, family member 1 (CLCA1), periostin, and serine peptidase inhibitor, clade B (ovalbumin), member 2 (serpinB2) were up-regulated in asthma but not in smokers. Corticosteroid treatment down-regulated expression of these three genes and markedly up-regulated expression of FK506-binding protein 51 (FKBP51). Whereas high baseline expression of CLCA1, periostin, and serpinB2 was associated with a good clinical response to corticosteroids, high expression of FKBP51 was associated with a poor response. By using airway epithelial cells in culture, we found that IL-13 increased expression of CLCA1, periostin, and serpinB2, an effect that was suppressed by corticosteroids. Corticosteroids also induced expression of FKBP51. Taken together, our findings show that airway epithelial cells in asthma have a distinct activation profile and identify direct and cell-autonomous effects of corticosteroid treatment on airway epithelial cells that relate to treatment responses and can now be the focus of specific mechanistic studies.

BACKGROUND

One type of fecal occult blood test (FOBT), the unrehydrated guaiac fecal occult blood test (GT), is recommended by the United States Preventive Services Task Force and the Institute of Medicine for use in screening programs, but it has relatively low sensitivity as a single test for detecting advanced colonic neoplasms (cancer and adenomatous polyps > or = 1 cm in diameter). Thus, improving the sensitivity of FOBT should make colon cancer screening programs that use these tests more effective.

METHODS

We assessed prospectively the performance characteristics of two newer FOBTs in 5841 subjects at average risk for colorectal cancer in a large group-model managed care organization. The tests evaluated included a sensitive GT, a fecal immunochemical test (FIT), and the combination of both tests. Patients with positive and negative test results were advised to have colonoscopy and sigmoidoscopy, respectively. Sensitivity and specificity for detecting advanced neoplasms in the left colon within 2 years after the FOBT screening were evaluated for the two tests administered separately and in combination.

RESULTS

A total of 139 patients were diagnosed with advanced colorectal neoplasms (n = 14 cancers, n = 128 adenomas) within the 2 years following their initial FOBT screening. Sensitivity for detecting cancer was 81.8% (95% confidence interval [CI] = 47.8% to 96.8%) for the FIT alone and 64.3% (95% CI = 35.6% to 86.0%) for the sensitive GT and the combination test. Sensitivity for detecting advanced colorectal adenomas was 41.3% (95% CI = 32.7% to 50.4%) for the sensitive GT, 29.5% (95% CI = 21.4% to 38.9%) for the FIT, and 22.8% (95% CI =16.1% to 31.3%) for the combination test. Specificity for detecting cancer and adenomas was 98.1% (95% CI = 97.7% to 98.4%) and 98.4% (95% CI = 98.0% to 98.7%), respectively, for the combination test; 96.9% (95% CI = 96.4% to 97.4%) and 97.3% (95% CI = 96.8% to 97.7%), respectively, for the FIT; and 90.1% (95% CI = 89.3% to 90.8%) and 90.6% (95% CI = 89.8% to 91.4%), respectively, for the sensitive GT.

CONCLUSIONS

The FIT has high sensitivity and specificity for detecting left-sided colorectal cancer, and it may be a useful replacement for the GT.

BACKGROUND

Morbidity from asthma disproportionately affects black people. Whether this excess morbidity is fully explained by differences in asthma severity, access to care, or socioeconomic status (SES) is unknown.

METHODS

We assessed whether there were racial disparities in asthma management and outcomes in a managed care organization that provides uniform access to health care and then determined to what degree these disparities were explained by differences in SES, asthma severity, and asthma management. We prospectively studied 678 patients from a large, integrated health care delivery system. Patients who had been hospitalized for asthma were interviewed after discharge to ascertain information about asthma history, health status, and SES. Small-area socioeconomic data were ascertained by means of geocoding and linkage to the US Census 2000. Patients were followed up for subsequent emergency department (ED) visits or hospitalizations (median follow-up, 1.9 years).

RESULTS

Black race was associated with a higher risk of ED visits (hazard ratio [HR], 1.93; 95% confidence interval [CI], 1.39-2.66) and hospitalizations (HR, 1.89; 95% CI, 1.30-2.76). This finding persisted after adjusting for SES and differences in asthma therapy (adjusted HR for ED visits, 1.73; 95% CI, 1.07-2.81; and adjusted HR for hospitalizations, 2.01; 95% CI, 1.33-3.02).

CONCLUSIONS

Even in a health care setting that provides uniform access to care, black race was associated with worse asthma outcomes, including a greater risk of ED visits and hospitalizations. This association was not explained by differences in SES, asthma severity, or asthma therapy. These findings suggest that genetic differences may underlie these racial disparities.