The impact of SHS exposure on health status and exacerbations among patients with COPD

Secondhand smoke (SHS) is a major contributor to indoor air pollution. Because it contains respiratory irritants, it may adversely influence the clinical course of persons with chronic obstructive pulmonary disease (COPD). We used data from nonsmoking members of the FLOW cohort of COPD (n = 809) to elucidate the impact of SHS exposure on health status and exacerbations (requiring emergency department visits or hospitalization). SHS exposure was measured by a validated survey instrument (hours of exposure during the past week). Physical health status was measured by the SF-12 Physical Component Summary Score and disease-specific health-related quality of life (HRQL) by the Airways Questionnaire 20-R. Health care utilization for COPD was determined from Kaiser Permanente Northern California computerized databases. Compared to no SHS exposure, higher level SHS exposure was associated with poorer physical health status (mean score decrement −1.78 points; 95% confidence interval [CI] −3.48 to −0.074 points) after controlling for potential confounders. Higher level SHS exposure was also related to poorer disease-specific HRQL (mean score increment 0.63; 95% CI 0.016 to 1.25) and less distance walked during the Six-Minute Walk test (mean decrement −50 feet; 95% CI −102 to 1.9). Both lower level and higher level SHS exposure was related to increased risk of emergency department (ED) visits (hazard ratio [HR] 1.40; 95% CI 0.96 to 2.05 and HR 1.41; 95% CI 0.94 to 2.13). Lower level and higher level SHS exposure were associated with a greater risk of hospital-based care for COPD, which was a composite endpoint of either ED visits or hospitalizations for COPD (HR 1.52; 95% CI 1.06 to 2.18 and HR 1.40; 95% CI 0.94 to 2.10, respectively). In conclusion, SHS was associated with poorer health status and a greater risk of COPD exacerbation. COPD patients may comprise a vulnerable population for the health effects of SHS

Matrix metalloproteinase-9 predicts pulmonary status declines in α1-antitrypsin deficiency

<p>Abstract</p> <p>Background</p> <p>Matrix metalloproteinase-9 (MMP-9) may be important in the progression of emphysema, but there have been few longitudinal clinical studies of MMP-9 including pulmonary status and COPD exacerbation outcomes.</p> <p>Methods</p> <p>We utilized data from the placebo arm (n = 126) of a clinical trial of patients with alpha₁-antitrypsin deficiency (AATD) and emphysema to examine the links between plasma MMP-9 levels, pulmonary status, and COPD exacerbations over a one year observation period. Pulmonary function, computed tomography lung density, incremental shuttle walk test (ISWT), and COPD exacerbations were assessed at regular intervals over 12 months. Prospective analyses used generalized estimating equations to incorporate repeated longitudinal measurements of MMP-9 and all endpoints, controlling for age, gender, race-ethnicity, leukocyte count, and tobacco history. A secondary analysis also incorporated highly-sensitive C-reactive protein levels in predictive models.</p> <p>Results</p> <p>At baseline, higher plasma MMP-9 levels were cross-sectionally associated with lower FEV₁(p = 0.03), FVC (p < 0.001), carbon monoxide transfer factor (p = 0.03), resting oxygen saturation (p = 0.02), and ISWT distance walked (p = 0.02) but were not associated with radiographic lung density or total lung capacity (TLC). In longitudinal analyses, MMP-9 predicted a further decline in transfer factor (p = 0.04) and oxygen saturation (p < 0.001). MMP-9 also predicted worsening lung density (p = 0.003), increasing TLC (p = 0.02), and more frequent COPD exacerbations over follow-up (p = 0.003). Controlling additionally for hs-CRP levels did not substantively change the longitudinal associations between MMP-9 and these outcomes.</p> <p>Conclusions</p> <p>Increased plasma MMP-9 levels generally predicted pulmonary status declines, including worsening transfer factor and lung density as well as greater COPD exacerbations in AATD-associated emphysema.</p

Effects of short-term treatment with atorvastatin in smokers with asthma - a randomized controlled trial

&lt;b&gt;Background&lt;/b&gt; The immune modulating properties of statins may benefit smokers with asthma. We tested the hypothesis that short-term treatment with atorvastatin improves lung function or indices of asthma control in smokers with asthma.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; Seventy one smokers with mild to moderate asthma were recruited to a randomized double-blind parallel group trial comparing treatment with atorvastatin (40 mg per day) versus placebo for 4 weeks. After 4 weeks treatment inhaled beclometasone (400 ug per day) was added to both treatment arms for a further 4 weeks. The primary outcome was morning peak expiratory flow after 4 weeks treatment. Secondary outcome measures included indices of asthma control and airway inflammation.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; At 4 weeks, there was no improvement in the atorvastatin group compared to the placebo group in morning peak expiratory flow [-10.67 L/min, 95% CI -38.70 to 17.37, p=0.449], but there was an improvement with atorvastatin in asthma quality of life score [0.52, 95% CI 0.17 to 0.87 p=0.005]. There was no significant improvement with atorvastatin and inhaled beclometasone compared to inhaled beclometasone alone in outcome measures at 8 weeks.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; Short-term treatment with atorvastatin does not alter lung function but may improve asthma quality of life in smokers with mild to moderate asthma. Clinicaltrials.gov identifier: NCT0046382

High-Precision Radio and Infrared Astrometry of LSPM J1314+1320AB - I : Parallax, Proper Motions, and Limits on Planets

Jan Forbrich, et al, 'HIGH-PRECISION RADIO AND INFRARED ASTROMETRY OF LSPM J1314+1320AB. I.PARALLAX, PROPER MOTIONS, AND LIMITS ON PLANETS', The Astrophysical Journal, 827:22 (8pp), August 2016. doi:10.3847/0004-637X/827/1/22. © 2016. The American Astronomical Society. All rights reserved.We present multi-epoch astrometric radio observations with the Very Long Baseline Array (VLBA) of the young ultracool-dwarf binary LSPM J1314+1320AB . The radio emission comes from the secondary star. Combining the VLBA data with Keck near-infrared adaptive-optics observations of both components, a full astrometric fit of parallax ($\pi_{\rm abs}=57.975\pm0.045$ mas, corresponding to a distance of $d=17.249\pm0.013$ pc), proper motion ($\mu_{\rm \alpha cos \delta}=-247.99\pm0.10$ mas yr$^{-1}$, $\mu_{\delta}=-183.58\pm0.22$ mas yr$^{-1}$), and orbital motion is obtained. Despite the fact that the two components have nearly identical masses to within $\pm2$%, the secondary's radio emission exceeds that of the primary by a factor of $\gtrsim$30, suggesting a difference in stellar rotation history, which could result in different magnetic field configurations. Alternatively, the emission could be anisotropic and beamed toward us for the secondary but not for the primary. Using only reflex motion, we exclude planets of mass 0.7 to 10 $M_{\rm jup}$ with orbital periods of 600 to 10 days, respectively. Additionally, we use the full orbital solution of the binary to derive an upper limit for the semi-major axis of 0.23 AU for stable planetary orbits within this system. These limits cover a parameter space that is inaccessible with, and complementary to, near-infrared radial velocity surveys of ultracool dwarfs. Our absolute astrometry will constitute an important test for the astrometric calibration of Gaia.Peer reviewe

Directly measured secondhand smoke exposure and COPD health outcomes

BACKGROUND: Although personal cigarette smoking is the most important cause and modulator of chronic obstructive pulmonary disease (COPD), secondhand smoke (SHS) exposure could influence the course of the disease. Despite the importance of this question, the impact of SHS exposure on COPD health outcomes remains unknown. METHODS: We used data from two waves of a population-based multiwave U.S. cohort study of adults with COPD. 77 non-smoking respondents with a diagnosis of COPD completed direct SHS monitoring based on urine cotinine and a personal badge that measures nicotine. We evaluated the longitudinal impact of SHS exposure on validated measures of COPD severity, physical health status, quality of life (QOL), and dyspnea measured at one year follow-up. RESULTS: The highest level of SHS exposure, as measured by urine cotinine, was cross-sectionally associated with poorer COPD severity (mean score increment 4.7 pts; 95% CI 0.6 to 8.9) and dyspnea (1.0 pts; 95% CI 0.4 to 1.7) after controlling for covariates. In longitudinal analysis, the highest level of baseline cotinine was associated with worse COPD severity (4.7 points; 95% CI -0.1 to 9.4; p = 0.054), disease-specific QOL (2.9 pts; -0.16 to 5.9; p = 0.063), and dyspnea (0.9 pts; 95% CI 0.2 to 1.6 pts; p < 0.05), although the confidence intervals did not always exclude the no effect level. CONCLUSION: Directly measured SHS exposure appears to adversely influence health outcomes in COPD, independent of personal smoking. Because SHS is a modifiable risk factor, clinicians should assess SHS exposure in their patients and counsel its avoidance. In public health terms, the effects of SHS exposure on this vulnerable subpopulation provide a further rationale for laws prohibiting public smoking

Examination of the Effects of Heterogeneous Organization of RyR Clusters, Myofibrils and Mitochondria on Ca2+ Release Patterns in Cardiomyocytes

Spatio-temporal dynamics of intracellular calcium, [Ca2+]i, regulate the contractile function of cardiac muscle cells. Measuring [Ca2+]i flux is central to the study of mechanisms that underlie both normal cardiac function and calcium-dependent etiologies in heart disease. However, current imaging techniques are limited in the spatial resolution to which changes in [Ca2+]i can be detected. Using spatial point process statistics techniques we developed a novel method to simulate the spatial distribution of RyR clusters, which act as the major mediators of contractile Ca2+ release, upon a physiologically-realistic cellular landscape composed of tightly-packed mitochondria and myofibrils.We applied this method to computationally combine confocal-scale (~ 200 nm) data of RyR clusters with 3D electron microscopy data (~ 30 nm) of myofibrils and mitochondria, both collected from adult rat left ventricular myocytes. Using this hybrid-scale spatial model, we simulated reaction-diffusion of [Ca2+]i during the rising phase of the transient (first 30 ms after initiation). At 30 ms, the average peak of the simulated [Ca2+]i transient and of the simulated fluorescence intensity signal, F/F0, reached values similar to that found in the literature ([Ca2+]i 1 μM; F/F0 5.5). However, our model predicted the variation in [Ca2+]i to be between 0.3 and 12.7 μM (~3 to 100 fold from resting value of 0.1 μM) and the corresponding F/F0 signal ranging from 3 to 9.5. We demonstrate in this study that: (i) heterogeneities in the [Ca2+]i transient are due not only to heterogeneous distribution and clustering of mitochondria; (ii) but also to heterogeneous local densities of RyR clusters. Further, we show that: (iii) these structureinduced heterogeneities in [Ca2+]i can appear in line scan data. Finally, using our unique method for generating RyR cluster distributions, we demonstrate the robustness in the [Ca2+]i transient to differences in RyR cluster distributions measured between rat and human cardiomyocytes