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Background: Airway macrophages (AM), crucial for the immune response in chronic obstructive pulmonary disease (COPD), are exposed to environmental particulate matter (PM), which they retain in their cytoplasm as black carbon (BC). However, whether AM BC accurately reflects environmental PM2.5 exposure, and can serve as a biomarker of COPD outcomes, is unknown.Methods: We analyzed induced sputum from participants at 7 of 12 sites SPIROMICS sites for AM BC content, which we related to exposures and to lung function and respiratory outcomes. Models were adjusted for batch (first vs. second), age, race (white vs. non-white), income (<$35,000, $35,000~$74,999, ≥$75,000, decline to answer), BMI, and use of long-acting beta-agonist/long-acting muscarinic antagonists, with sensitivity analysis performed with inclusion of urinary cotinine and lung function as covariates.Results: Of 324 participants, 143 were current smokers and 201 had spirometric-confirmed COPD. Modeled indoor fine (< 2.5 μm in aerodynamic diameter) particulate matter (PM2.5) and urinary cotinine were associated with higher AM BC. Other assessed indoor and ambient pollutant exposures were not associated with higher AM BC. Higher AM BC was associated with worse lung function and odds of severe exacerbation, as well as worse functional status, respiratory symptoms and quality of life.Conclusion: Indoor PM2.5 and cigarette smoke exposure may lead to increased AM BC deposition. Black carbon content in AMs is associated with worse COPD morbidity in current and former smokers, which remained after sensitivity analysis adjusting for cigarette smoke burden. Airway macrophage BC, which may alter macrophage function, could serve as a predictor of experiencing worse respiratory symptoms and impaired lung function. [ABSTRACT FROM AUTHOR]

Background: Airway macrophages (AM), crucial for the immune response in chronic obstructive pulmonary disease (COPD), are exposed to environmental particulate matter (PM), which they retain in their cytoplasm as black carbon (BC). However, whether AM BC accurately reflects environmental PM2.5 exposure, and can serve as a biomarker of COPD outcomes, is unknown. Methods: We analyzed induced sputum from participants at 7 of 12 sites SPIROMICS sites for AM BC content, which we related to exposures and to lung function and respiratory outcomes. Models were adjusted for batch (first vs. second), age, race (white vs. non-white), income (<$35,000, $35,000~$74,999, ≥$75,000, decline to answer), BMI, and use of long-acting beta-agonist/long-acting muscarinic antagonists, with sensitivity analysis performed with inclusion of urinary cotinine and lung function as covariates. Results: Of 324 participants, 143 were current smokers and 201 had spirometric-confirmed COPD. Modeled indoor fine (< 2.5 μm in aerodynamic diameter) particulate matter (PM2.5) and urinary cotinine were associated with higher AM BC. Other assessed indoor and ambient pollutant exposures were not associated with higher AM BC. Higher AM BC was associated with worse lung function and odds of severe exacerbation, as well as worse functional status, respiratory symptoms and quality of life. Conclusion: Indoor PM2.5 and cigarette smoke exposure may lead to increased AM BC deposition. Black carbon content in AMs is associated with worse COPD morbidity in current and former smokers, which remained after sensitivity analysis adjusting for cigarette smoke burden. Airway macrophage BC, which may alter macrophage function, could serve as a predictor of experiencing worse respiratory symptoms and impaired lung function. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Insulin resistance (IR) may be a risk factor for lung disease, but objective evidence is limited. We sought to define the relationship of longitudinal IR with radiographic imaging outcomes and examiner-identified incident lung disease in the Framingham Offspring Study. RESEARCH DESIGN AND METHODS: Participants without baseline lung disease underwent repeated measurements of fasting insulin and glucose levels over an average period of 13.6 years, from which time-weighted average HOMA-IR was calculated. Each participant then underwent a cardiac gated whole-lung computed tomography scan, which was analyzed for the presence of emphysema, interstitial lung abnormalities (ILAs), and quantitative airway features. Incident lung disease was determined by a study examiner. The relationship of HOMA-IR to these outcomes was estimated in models adjusted for demographics, BMI, and lifetime smoking. RESULTS: A total of 875 participants with longitudinal IR data and outcomes were identified. Their mean age was 51.5 years, and BMI was 26.7 kg/m2. HOMA-IR was temporally unstable, with a within-person SD approximately two-thirds of the between-person SD. In adjusted models, a 1 SD increase in log(HOMA-IR) z score was associated with higher odds of qualitative emphysema (odds ratio [OR] 1.33; 95% CI 1.04–1.70), ILAs (OR 1.35; 95% CI 1.05–1.74), and modest increases in airway wall thickness and wall area percentage. These radiographic findings were corroborated by a positive association of HOMA-IR with incident lung disease. CONCLUSIONS: IR is associated with radiographic lung abnormalities and incident lung disease. Deeper phenotyping is necessary to define mechanisms of IR-associated lung injury. [ABSTRACT FROM AUTHOR]

Background: Attenuation of transforming growth factor β by blocking angiotensin II has been shown to reduce emphysema in a murine model. General population studies have demonstrated that the use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) is associated with reduction of emphysema progression in former smokers and that the use of ACEis is associated with reduction of FEV1 progression in current smokers.Research Question: Is use of ACEi and ARB associated with less progression of emphysema and FEV1 decline among individuals with COPD or baseline emphysema?Methods: Former and current smokers from the Genetic Epidemiology of COPD Study who attended baseline and 5-year follow-up visits, did not change smoking status, and underwent chest CT imaging were included. Adjusted linear mixed models were used to evaluate progression of adjusted lung density (ALD), percent emphysema (%total lung volume <-950 Hounsfield units [HU]), 15th percentile of the attenuation histogram (attenuation [in HU] below which 15% of voxels are situated plus 1,000 HU), and lung function decline over 5 years between ACEi and ARB users and nonusers in those with spirometry-confirmed COPD, as well as all participants and those with baseline emphysema. Effect modification by smoking status also was investigated.Results: Over 5 years of follow-up, compared with nonusers, ACEi and ARB users with COPD showed slower ALD progression (adjusted mean difference [aMD], 1.6; 95% CI, 0.34-2.9). Slowed lung function decline was not observed based on phase 1 medication (aMD of FEV1 % predicted, 0.83; 95% CI, -0.62 to 2.3), but was when analysis was limited to consistent ACEi and ARB users (aMD of FEV1 % predicted, 1.9; 95% CI, 0.14-3.6). No effect modification by smoking status was found for radiographic outcomes, and the lung function effect was more pronounced in former smokers. Results were similar among participants with baseline emphysema.Interpretation: Among participants with spirometry-confirmed COPD or baseline emphysema, ACEi and ARB use was associated with slower progression of emphysema and lung function decline.Trial Registry: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Biologic therapies are emerging as an option to treat a subset of patients with severe asthma, however no direct comparison between these agents has been conducted. Furthermore, heterogeneity of outcomes in clinical trials makes it difficult to compare these agents and traditional therapies. The extent to which this heterogeneity exists has major implications for evidence-based decisions and is yet to be fully reported. We conducted a literature search to examine outcomes currently being used in clinical trials for asthma. The Cochrane Library and Clinicaltrials.gov were searched for clinical trials of asthma interventions. We limited our search to phase 2 through 4 clinical trials in adults, as early-phase trials tend to have pharmacodynamic and pharmacokinetic endpoints as primary outcomes. Interventions for acute exacerbations were excluded. We identified 117 studies and subsequently identified 111 outcomes. The most prevalent outcomes were asthma control and symptom severity, FEV1, and change in ACQ scale. Twenty patient-reported outcomes instruments were identified and de-facto standard asthma outcomes and PROs were under-reported in examined literature. Existing quality of life tools did not capture the day-to-day experience or the unique treatment burden from oral corticosteroids for patient with severe asthma. Compounding the absence of trials directly comparing therapies, the significant variation we identified in outcome definitions and measurement create hurdles to effectively compare traditional and biologic therapies. With the growing number of clinical trials evaluating advanced therapies such as biologics, a wide range of primary and secondary outcomes are evaluated. A core outcome set created by relevant stakeholders is needed to collectively evaluate pooled outcomes in order to allow more meaningful comparisons of asthma therapies and to incorporate the patient experience. [ABSTRACT FROM AUTHOR]

Lung transplant is now an established modality for a broad spectrum of end-stage pulmonary diseases. According to the International Society for Heart and Lung Transplantation Registry, more than 50,000 lung transplants have been performed worldwide, with nearly 11,000 recipients of lung transplants alive in the United States. With the increasing use of lung transplant, pulmonologists must be cognizant of the common as well as the unique posttransplant dermatologic complications. Immunosuppression, infections, and a variety of medications and environmental exposures can contribute to these complications. This review aims to provide representative pictures and describe the pathogenesis, epidemiologic characteristics, and clinical manifestations of dermatologic complications encountered among recipients of lung transplants. [ABSTRACT FROM AUTHOR]

Background: High Density Lipoprotein Cholesterol (HDL-C) has various anti-inflammatory, anti-atherogenic, anti-oxidant and anti-coagulant properties that improve vascular function. The utility of HDL-C as a biomarker of severity and predictor of survival was described in patients with pulmonary arterial hypertension (PAH). No prior study has assessed the utility of HDL-C in patients with Chronic Thromboembolic Pulmonary Hypertension (CTEPH). Objectives: We aim to measure HDL-C levels in CTEPH patients and compare it to those in PAH patients and controls and determine HDL-C associations with markers of disease severity, hemodynamics and mortality in CTEPH. Methods: We retrospectively included patients with CTEPH, identified from the Cleveland Clinic Pulmonary Hypertension Registry. All patients had right heart catheterization (RHC) and imaging studies consistent with CTEPH. We collected demographics, co-morbidities, baseline laboratory data including plasma HDL-C, six-minute walk test (6MWT), echocardiography and RHC. HDL-C levels were compared to a cohort of patients with cardiovascular risk factors and a previously published PAH cohort. Results: HDL-C levels were available for 90 patients with CTEPH (age: 57.4±13.9 years; female 40%), 69 patients with PAH (age: 46.7±12.8 years; female 90%) and 254 control subjects (age: 56.7±13 years; female 48%). HDL-C levels in CTEPH patients were lower compared to controls and higher compared to PAH patients (median, IQR: CTEPH: 44, 34–57 mg/dl; PAH: 35.3, 29–39 mg/dl; Control: 49, 40–60 mg/dl; p < 0.01 for both pairwise comparisons). In CTEPH, higher HDL-C was associated with decreased prevalence of right ventricular dilation on echocardiography (p = 0.02). 57 patients with CTEPH underwent pulmonary thromboendarterectomy, higher HDL-C was associated with a larger decrement in postoperative pulmonary vascular resistance (PVR) (r = 0.37, p = 0.049). HDL-C was not associated with mortality or other markers of disease severity. Conclusions: HDL-C levels in CTEPH patients were lower compared to control subjects, but higher compared to PAH patients. Higher HDL-C in CTEPH was associated with less right ventricular dilation and greater decrement in postoperative PVR. These data suggest that HDL-C may be a useful marker of small vessel disease in CTEPH. [ABSTRACT FROM AUTHOR]

Lung transplantation is now an established treatment for a broad spectrum of end-stage pulmonary diseases. According to the International Society for Heart and Lung Transplantation Registry, more than 50,000 lung transplants have been performed worldwide, with nearly 11,000 lung transplant recipients alive in the United States. With the increasing application of lung transplantation, pulmonologists must be cognizant of common complications unique to the postlung transplant period and the associated radiologic findings. The aim of this review is to describe clinical manifestations and prototypical radiographic features of both common and rare complications encountered in lung transplant recipients. [ABSTRACT FROM AUTHOR]

End-of-life decision-making is a complex process that can be extremely challenging. We describe a 42-year-old woman in an irreversible coma without an advance directive. The case serves to illustrate the complications that can occur in end-of-life decision-making and challenges in resolving difficult futility disputes. We review the role of advance directives in planning end-of-life care, the responsibility and historical performance of patient surrogates, the genesis of futility disputes, and approaches to resolving disputes. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 63-year-old female who was presented for sinus congestion evaluation and pressure with rhinorrhea where sinus computed tomography showed opacification of sinus where she underwent functional endoscopic sinus surgery.

The article reports on survey findings on the prevalence of public speaking anxiety in the graduate medical education population in the U.S., as of February 2016.

Background: The objective of this study is to investigate the frequency and clinicopathological features of idiopathic nodular glomerulosclerosis (ING) in Chinese patients, on which there has been no previously published information. Methods: Native kidney biopsies performed at a kidney histopathological center in Shanghai between January 1, 2009 and December 31, 2011 were retrospectively examined and relevant clinical data were reviewed. Results: All kidney biopsy specimens (3,480) were examined. After excluding specimens from patients with diabetes, fasting hyperglycemia or hemoglobin A1c elevation and other known entities associated with nodular glomerulosclerosis, 20 ING cases (1 in 174 biopsies) were identified. Patients with ING had a median age of 55.5 years, 16 (80 %) were male, 19 (95 %) had a body mass index (BMI) ≥25 kg/m [BMI ≥30 in 8 (40 %)], 18 (90 %) were hypertensive, 17 (85 %) had a history of cigarette smoking (mean pack-years 19.8 ± 2.4), and 10 (50 %) had hyperlipidemia. All 20 patients had >1 g/day proteinuria with a mean of 2.85 ± 0.33 g/day (seven had nephrotic-range proteinuria). Mean serum creatinine at the time of kidney biopsy was 4.23 ± 0.53 mg/dL (338.2 ± 44.7 μmol/L). Histopathologically, all specimens showed varying degrees of nodular glomerulosclerosis, glomerular basement membrane thickening, foot process effacement, interstitial fibrosis and arterial hyalinosis/sclerosis. Immunofluorescence was non-specific. At follow-up of 22.1 ± 1.15 days post-biopsy, six patients had developed end-stage renal failure and five had worsening serum creatinine concentrations not requiring dialysis. Conclusion: ING is rare and appears to be associated with overweight, hypertension and cigarette smoking in Chinese patients. [ABSTRACT FROM AUTHOR]

Background: Metformin is associated with improved respiratory outcomes in asthma; however, metformin in COPD and asthma-COPD overlap (ACO) remains unexplored.Objective: To determine the association between metformin use and respiratory outcomes in COPD and ACO.Study Design and Methods: Participants with COPD (FEV1/FVC < 0.70) in the Genetic Epidemiology of COPD study (COPDGene®) were categorized as ACO (n = 510), defined as concurrent physician-diagnosed asthma before age 40 years, or COPD alone (n = 3459). We estimated the association of baseline metformin use with (1) rate of total and severe respiratory exacerbations during follow-up, (2) cross-sectional St. George's Respiratory Questionnaire (SGRQ) score, six-minute walk distance (6MWD), and post-bronchodilator FEV1 percent predicted (FEV1pp), and (3) 5-year change in SGRQ, 6MWD, and FEV1pp. We also examined change in SGRQ, 6MWD and FEV1pp among participants who initiated metformin during follow-up (n = 108) compared to persistent metformin non-users (n = 2080). Analyses were adjusted for sociodemographic factors, medications, and comorbidities.Results: Among participants with ACO, metformin use was associated with lower rate of total (adjusted incidence rate ratio [aIRR] 0.3; 95% confidence interval [95%CI] 0.11, 0.77) and severe exacerbations (aIRR 0.29; 95%CI 0.10, 0.89). Among participants with COPD alone, there was no association between metformin use with total (aIRR 0.98; 95%CI 0.62, 1.5) or severe exacerbations (aIRR 1.3; 95% CI 0.68, 2.4) (p-interaction < 0.05). Metformin use was associated with lower baseline SGRQ score (adjusted mean difference [aMD] - 2.7; 95%CI - 5.3, - 0.2) overall. Metformin initiation was associated with improved SGRQ score (aMD -10.0; 95% CI - 18.7, - 1.2) among participants with ACO but not COPD alone (p-interaction < 0.05). There was no association between metformin use and 6MWD or FEV1pp in any comparison.Conclusions: Metformin use was associated with fewer respiratory exacerbations and improved quality of life among individuals with ACO but not COPD alone. Results suggest a potential role for metformin in ACO which requires further prospective study.Trial Registry: NCT00608764. [ABSTRACT FROM AUTHOR]

Background. The study investigates the occurrence, severity, and outcomes of acute kidney injury (AKI) in octogenarians following heart valve surgery. Methods. All patients, age >80 years, not on dialysis and without kidney transplant, undergoing heart valve replacement at Mayo Clinic, Rochester, in the years 2002-2003 were enrolled. AKI was diagnosed based on AKIN criteria. Results. 209 octogenarians (88.0% aortic valve, 6.2% mitral valve, 1.0% tricuspid valve, and 4.8% multivalve) with (58.4%) and without CABG were studied. 34 (16.3%) had preexisting CKD. After surgery, 98 (46.8%) developed AKI. 76.5% of the AKI were in Stage 1, 9.2% in Stage 2, and 14.3% in Stage 3. 76.5% CKD patients developed AKI. Length of hospital stay was longer for AKI patients. More AKI patients were discharged to care facilities. Patient survival at 30 days and 1 year for AKI versus non-AKI was 88.8 versus 98.7%, p=0.003, and 76.5 versus 88.3%, p=0.025, respectively. With follow-up of 3.94±0.28 years, Kaplan-Meier analysis showed a reduced survival for AKI octogenarians. Preexisting CKD and large volume intraoperative fluid administration were independent AKI predictors. Conclusions. Nearly half of the octogenarians developed AKI after valve replacement surgery. AKI was associated with significant functional impairment and reduced survival. [ABSTRACT FROM AUTHOR]