Publications

Mucous hypersecretion is an important feature of obstructive airway diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. Multiple stimuli induce mucin production via activation of an epidermal growth factor receptor (EGFR) cascade, but the mechanisms that exaggerate mucin production in obstructive airway diseases remain unknown. In this study, we show that binding of CCL20, a G protein-coupled receptor (GPCR) ligand that is upregulated in the airways of subjects with obstructive airway diseases, to its unique GPCR CCR6 induces MUC5AC mucin production in human airway epithelial (NCI-H292) cells via metalloprotease TNF-α-converting enzyme (TACE)-dependent EGFR activation. We also show that EGFR activation by its potent ligand TGF-α induces reactivation of EGFR via binding of endogenously produced CCL20 to its receptor CCR6 in NCI-H292 cells but not in normal human bronchial epithelial (NHBE) cells, exaggerating mucin production in the NCI-H292 cells. In NCI-H292 cells, TGF-α stimulation induced two phases of EGFR phosphorylation (EGFR-P). The second EGFR-P was TACE-dependent and was responsible for most of the total mucin induced by TGF-α. Binding of endogenously produced CCL20 to CCR6 increased the second EGFR-P and subsequent mucin production induced by TGF-α. In NHBE cells, TGF-α-induced EGFR activation did not lead to significant CCL20 production or to EGFR rephosphorylation, and less mucin was produced. We conclude that NCI-H292 cells but not NHBE cells produce CCL20 in response to EGFR activation, which leads to a second phase of EGFR-P and subsequent exaggerated mucin production. These findings have potentially important therapeutic implications in obstructive airway diseases.

CONTEXT

In 2005, the Healthcare Effectiveness Data and Information Set (HEDIS) introduced a quality measure to assess the receipt of disease-modifying antirheumatic drugs (DMARDs) among patients with rheumatoid arthritis (RA).

OBJECTIVE

To identify sociodemographic, community, and health plan factors associated with DMARD receipt among Medicare managed care enrollees.

DESIGN, SETTING, AND PARTICIPANTS

We analyzed individual-level HEDIS data for 93,143 patients who were at least 65 years old with at least 2 diagnoses of RA within a measurement year (during 2005-2008). Logistic regression models with generalized estimating equations were used to determine factors associated with DMARD receipt and logistic regression was used to adjust health plan performance for case mix.

MAIN OUTCOME MEASURES

Receipt or nonreceipt of DMARD.

RESULTS

The mean age of patients was 74 years; 75% were women and 82% were white. Overall performance on the HEDIS measure for RA was 59% in 2005, increasing to 67% in 2008 (P for trend <.001). The largest difference in performance was based on age: patients aged 85 years and older had a 30 percentage point lower rate of DMARD receipt (95% confidence interval [CI], -29 to -32 points; P < .001), compared with patients 65 to 69 years of age, even after adjusting for other factors. Lower percentage point rates were also found for patients who were men (-3 points; 95% CI, -5 to -2 points; P < .001), of black race (-4 points; 95% CI, -6 to -2 points; P < .001), with low personal income (-6 points; 95% CI, -8 to -5 points; P < .001), with the lowest zip code-based socioeconomic status (-4 points; 95% CI, -6 to 2 points; P < .001), or enrolled in for-profit health plans (-4 points; 95% CI, -7 to 0 points; P < .001); and in the Middle Atlantic region (-7 points; 95% CI, -13 to -2 points; P < .001) and South Atlantic regions (-11 points; 95% CI, -20 to -3 points; P < .001) as compared with the Pacific region. Performance varied widely by health plan, ranging from 16% to 87%.

CONCLUSIONS

Among Medicare managed care enrollees carrying a diagnosis of RA between 2005 and 2008, 63% received a DMARD. Receipt of DMARDs varied based on demographic factors, socioeconomic status, geographic location, and health plan.