Publications

RATIONALE

Transforming growth factor (TGF)-beta has a central role in driving many of the pathological processes that characterize pulmonary fibrosis. Inhibition of the integrin alpha(v)beta6, a key activator of TGF-beta in lung, is an attractive therapeutic strategy, as it may be possible to inhibit TGF-beta at sites of alpha(v)beta6 up-regulation without affecting other homeostatic roles of TGF-beta.

OBJECTIVES

To analyze the expression of alpha(v)beta6 in human pulmonary fibrosis, and to functionally test the efficacy of therapeutic inhibition of alpha(v)beta6-mediated TGF-beta activation in murine bleomycin-induced pulmonary fibrosis.

METHODS

Lung biopsies from patients with a diagnosis of systemic sclerosis or idiopathic pulmonary fibrosis were stained for alpha(v)beta6 expression. A range of concentrations of a monoclonal antibody that blocks alpha(v)beta6-mediated TGF-beta activation was evaluated in murine bleomycin-induced lung fibrosis.

MEASUREMENTS AND MAIN RESULTS

Alpha(v)beta6 is overexpressed in human lung fibrosis within pneumocytes lining the alveolar ducts and alveoli. In the bleomycin model, alpha(v)beta6 antibody was effective in blocking pulmonary fibrosis. At high doses, there was increased expression of markers of inflammation and macrophage activation, consistent with the effects of TGF-beta inhibition in the lung. Low doses of antibody attenuated collagen expression without increasing alveolar inflammatory cell populations or macrophage activation markers.

CONCLUSIONS

Partial inhibition of TGF-beta using alpha(v)beta6 integrin antibodies is effective in blocking murine pulmonary fibrosis without exacerbating inflammation. In addition, the elevated expression of alpha(v)beta6, an activator of the fibrogenic cytokine, TGF-beta, in human pulmonary fibrosis suggests that alpha(v)beta6 monoclonal antibodies could represent a promising new therapeutic strategy for treating pulmonary fibrosis.

OBJECTIVES

To determine whether an educational intervention would improve depression assessment and appropriate referral. Secondary analyses tested whether referral led to depression improvement.

DESIGN

Training in the Assessment of Depression (TRIAD) was a three-group, nurse-randomized trial. Researchers interviewed randomly selected patients at baseline and 8 weeks.

SETTING

Three certified home healthcare agencies in Westchester County, New York.

PARTICIPANTS

Fifty-three medical/surgical nurses were randomized within agency to three intervention groups: full, minimal, or control. Research contact with nurses' patients (aged >65; N=477) yielded 256 (53.7%) enrolled subjects, 84 (17.6%) ineligibles, and 120 (25.2%) refusals; 233 of the 256 (87.1%) enrolled patients completed follow-up interviews.

INTERVENTION

Nurse training in clinically meaningful use of depression sections of Medicare's mandatory Outcome and Assessment Information Set (OASIS).

MEASUREMENTS

Nurse-assessed mood or anhedonia (OASIS) versus research assessments using the Structured Clinical Interview for Axis I Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Disorders (SCID); referrals for mental health evaluation (agency records), and depression severity (24-item Hamilton Depression Rating Scale; HDRS).

RESULTS

Referral rates for patients with (SCID) depressed mood or anhedonia (n=75) varied according to nurse group: 50.0% full intervention, 18.5% minimal, 21.4% control (P=.047). Rates for nondepressed patients (n=180) did not differ (4.9%, 2.0%, 5.8%, respectively; P=.60). In patients with major or minor depression (n=37), referral was associated with symptom improvement. Change in HDRS was 5 points greater in referred patients than others (P=.04). Concordance between OASIS and SCID did not differ between intervention groups.

CONCLUSION

TRIAD showed that training nurses to assess for depression using an approach developed in partnership with home healthcare agencies led to appropriate referral and care for depressed patients.