The influence of social support on COPD outcomes mediated by depression.

BACKGROUND: The purpose of this study was to explore the association between perceived social support and COPD outcomes and to determine whether the associations are mediated by depressive symptoms. METHODS: Subjects with COPD who were enrolled as part of SPIROMICS were included in this analysis. Questionnaires relating to quality of life, symptom burden, and functional status were administered at annual clinic visits for over a 3 year period. In both cross-sectional and longitudinal analyses, we examined the association of social support as measured by the FACIT-F with COPD outcomes. Cross sectional analyses used multivariable linear or logistic regression, adjusting for covariates. For longitudinal analyses, generalized linear mixed models with random intercepts were used. Models were adjusted with and without depressive symptoms and mediation analyses performed. RESULTS: Of the 1831 subjects with COPD, 1779 completed the FACIT- F questionnaire. In adjusted cross-sectional analysis without depressive symptoms, higher perceived social support was associated with better quality of life, well-being, 6 minute walk distance, and less dyspnea. When also adjusting for depressive symptoms, all associations between social support and COPD outcomes were attenuated and no longer statistically significant. Mediation analysis suggested that depressive symptoms explained the majority (> = 85%) of the association between social support and measured COPD outcomes. Results of the longitudinal analysis were consistent with the cross-sectional analyses. There was no association between social support and odds of exacerbations. CONCLUSION: Higher social support was associated with better COPD outcomes across several measures of morbidity including quality of life, respiratory symptoms, and functional status. In addition, these associations were largely attenuated when accounting for depressive symptoms suggesting that the beneficial association of social support with COPD outcomes may be largely mediated by the association between social support and depression. TRIAL REGISTRATION: SPIROMICS was approved by Institutional Review Boards at each center and all participants provided written informed consent (clinicaltrials.gov: NCT01969344).

Prospective CT screening for lung cancer in a high-risk population: HIV-positive smokers.

BACKGROUND: Epidemiological evidence suggests that HIV-infected individuals are at increased risk of lung cancer, but no data exist because large computed tomography (CT) screening trials routinely exclude HIV-infected participants. METHODS: From 2006 to 2013, we conducted the world's first lung cancer screening trial of 224 HIV-infected current/former smokers to assess the CT detection rates of lung cancer. We also used 130 HIV-infected patients with known lung cancer to determine radiographic markers of lung cancer risk using multivariate analysis. RESULTS: Median age was 48 years with 34 pack-years smoked. During 678 person-years, one lung cancer was found on incident screening. Besides this lung cancer case, 18 deaths (8%) occurred, but none were cancer related. There were no interim diagnoses of lung or extrapulmonary cancers. None of the pulmonary nodules detected in 48 participants at baseline were diagnosed as cancer by study end. The heterogeneity of emphysema across the entire lung as measured by CT densitometry was significantly higher in HIV-infected subjects with lung cancer compared with the heterogeneity of emphysema in those without HIV (p ≤ 0.01). On multivariate regression analysis, increased age, higher smoking pack-years, low CD4 nadir, and increased heterogeneity of emphysema on quantitative CT imaging were all significantly associated with lung cancer. CONCLUSIONS: Despite a high rate of active smoking among HIV-infected participants, only one lung cancer was detected in 678 patient-years. This was probably because of the young age of participants suggesting that CT screening of high-risk populations should strongly consider advanced age as a critical inclusion criterion. Future screening trials in urban American must also incorporate robust measures to ensure HIV patient compliance, adherence, and smoking cessation.

Calmodulin-dependent kinase I regulates adrenal cell expression of aldosterone synthase.

Aldosterone synthase (CYP11B2) is expressed in the adrenal glomerulosa and controls the capacity of the adrenal glomerulosa to produce aldosterone. Herein, human NCI-H295R (H295R) adrenocortical cells were used to define the calcium-dependent mechanisms regulating CYP11B2 gene transcription using reporter constructs containing CYP11B2 gene 5'-flanking DNA. Treatment of H295R cells with calcium/calmodulin-dependent protein kinase (CaMK) inhibitor (KN93) or calmodulin inhibitor (calmidazolium) blocked angiotensin II and potassium (K(+)) stimulation of CYP11B2 reporter gene expression. To determine which CaMK regulates CYP11B2, vectors containing the complete coding sequences for CaMKI, CaMKII, and CaMKIV were transfected with the CYP11B2 reporter construct. CaMKI augmented reporter expression when cellular calcium was elevated by ionomycin, whereas CaMKIV had a small effect, and CaMKII had no effect. To further study the role of CaMKs, constitutively active forms of CaMKI (CaMKI-295), II (CaMKII-290), and IV (CaMKIV-313) were transfected with CYP11B2 reporter constructs. CaMKI-295 and, to a lesser degree, CaMKIV-313 were able to stimulated reporter activity. Mutational analysis of the 5'-flanking region of CYP11B2 revealed that a cAMP regulatory element (-71/-64) was necessary for CaMKI induction of reporter gene activity. CaMKI expression was shown in adrenal cortex and H295R cells using immunohistochemistry and Western and Northern analyses. These findings suggest that CaMKI is involved in angiotensin II and K(+) stimulation of CYP11B2 transcription and, therefore, the capacity of the adrenal to produce aldosterone.