Outcomes of Childhood Asthma and Wheezy Bronchitis. A 50-Year Cohort Study

Rationale: Cohort studies suggest that airflow obstruction is established early in life, manifests as childhood asthma and wheezy bronchitis, and continues into early adulthood. Although an association between childhood asthma and chronic obstructive pulmonary disease (COPD) in later life has been demonstrated, it is unclear if childhood wheezy bronchitis is associated with COPD. Objectives: To investigate whether childhood wheezy bronchitis increases the risk of COPD in the seventh decade. Methods: A cohort of children recruited in 1964 at age 10 to 15 years, which was followed up in 1989, 1995, and 2001, was followed up again in 2014 when at age 60 to 65 years. Discrete time-to-event and linear mixed effects models were used. Measurements and Main Results: FEV1 and FVC were measured. COPD was defined as post-bronchodilator FEV1/FVC <0.7. Childhood wheezing phenotype was related to 1989, 1995, 2001, and 2014 spirometry data. Three hundred thirty subjects, mean age 61 years, were followed up: 38 with childhood asthma; 53 with childhood wheezy bronchitis; and 239 control subjects (of whom 57 developed adulthood-onset wheeze between ages 16 and 46 yr). In adjusted multivariate analyses, childhood asthma was associated with an increased risk of COPD (odds ratio, 6.37; 95% confidence interval, 3.73–10.94), as was childhood wheezy bronchitis (odd ratio 1.81; 95% confidence interval, 1.12–2.91). The COPD risk increased with childhood asthma, and wheezy bronchitis was associated with reduced FEV1 that was evident by the fifth decade and not an accelerated rate of FEV1 decline. In contrast, adulthood-onset wheeze was associated with accelerated FEV1 decline. Conclusions: Childhood wheezy bronchitis and asthma are associated with an increased risk of COPD and reduced ventilatory function

Zooplankton Gut Passage Mobilizes Lithogenic Iron for Ocean Productivity

Iron is an essential nutrient for phytoplankton, but low concentrations limit primary production and associated atmospheric carbon drawdown in large parts of the world’s oceans [1 and 2]. Lithogenic particles deriving from aeolian dust deposition, glacial runoff, or river discharges can form an important source if the attached iron becomes dissolved and therefore bioavailable [3, 4 and 5]. Acidic digestion by zooplankton is a potential mechanism for iron mobilization [6], but evidence is lacking. Here we show that Antarctic krill sampled near glacial outlets at the island of South Georgia (Southern Ocean) ingest large amounts of lithogenic particles and contain 3-fold higher iron concentrations in their muscle than specimens from offshore, which confirms mineral dissolution in their guts. About 90% of the lithogenic and biogenic iron ingested by krill is passed into their fecal pellets, which contain ∼5-fold higher proportions of labile (reactive) iron than intact diatoms. The mobilized iron can be released in dissolved form directly from krill or via multiple pathways involving microbes, other zooplankton, and krill predators. This can deliver substantial amounts of bioavailable iron and contribute to the fertilization of coastal waters and the ocean beyond. In line with our findings, phytoplankton blooms downstream of South Georgia are more intensive and longer lasting during years with high krill abundance on-shelf. Thus, krill crop phytoplankton but boost new production via their nutrient supply. Understanding and quantifying iron mobilization by zooplankton is essential to predict ocean productivity in a warming climate where lithogenic iron inputs from deserts, glaciers, and rivers are increasing [7, 8, 9 and 10]

The health benefits of reduced air pollution: value and trade-offs

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Secondhand smoke (SHS) exposures: Workplace exposures, related perceptions of SHS risk, and reactions to smoking in catering workers in smoking and nonsmoking premises

Introduction: Smoke-free workplace legislation often exempts certain venues. Do smoking (exempted) and nonsmoking (nonexempted) catering premises' workers in Hong Kong report different perceptions of risk from and reactions to nearby smoking as well as actual exposure to secondhand smoke (SHS)? Methods: In a cross-sectional survey of 204 nonsmoking catering workers, those from 67 premises where smoking is allowed were compared with workers from 36 nonsmoking premises in Hong Kong on measures of perceptions of risk and behavioral responses to self-reported SHS exposure, plus independent exposure assessment using urinary cotinine. Results: Self-reported workplace SHS exposure prevalence was 57% (95% CI = 49%-65%) in premises prohibiting and 100% (95% CI = 92%-100%) in premises permitting smoking (p < .001). Workers in smoking-permitted premises perceived workplace air quality as poorer (odds ratio [OR] = 9.3, 95% CI = 4.2-20.9) with higher associated risks (OR = 3.7, 95% CI = 1.6-8.6) than workers in smoking-prohibited premises. Workers in smoking-prohibited premises were more bothered by (OR = 0.2, 95% CI = 0.1-0.5) and took more protective action to avoid SHS (OR = 0.2, 95% CI = 0.1-0.4) than workers in smoking-permitted premises. Nonwork exposure was negatively associated with being always bothered by nearby smoking (OR = 0.3, 95% CI = 0.1-0.9), discouraging nearby smoking (OR = 0.5, 95% CI = 0.2-1.1), and discouraging home smoking (OR = 0.4, 95% CI = 0.2-0.9). Urinary cotinine levels were inversely related to workers' avoidance behavior but positively related to their perceived exposure-related risks. Conclusions: Different workplace smoking restrictions predicted actual SHS exposure, exposure-related risk perception, and protective behaviors. Workers from smoking-permitted premises perceived greater SHS exposure-related risks but were more tolerant of these than workers in smoking-prohibited premises. This tolerance might indirectly increase both work and nonwork exposures. © The Author 2011. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.postprin

Smoking behaviour among female airline cabin crew from ten Asian countries

Objective - To identify factors related to the high prevalence of smoking behaviour among a sample of female airline cabin crew of Asian origin. Design - A questionnaire-based cross-sectional survey of 585 Asian women, aged 20-41 years working as experienced cabin crew for a major international airline. Main outcome measures - Subjects answered questions on their knowledge of the consequences of smoking, the per¬ceived effects of smoking, their per¬ceptions of the social images of smoking and non-smoking women, and current and past smoking behaviour. Subjects also rated women depicted in cigarette, cosmetic, alcohol and luxury goods ad¬vertisements using ten predefined social descriptors. Results -An overall current smoking prevalence of 26 % (95 % confidence in¬terval 22-30 %) was identified, with wide variation according to national origin of subjects. More than 75 % of respondents were aware of the commonly emphasized hazards of smoking, and no significant differences were found in health knowl¬edge between smokers and non-smokers. However, only about half of the subjects correctly identified the interactions be¬tween smoking and oral contraceptive use and the increased risk for heavy smokers of dying before the age of 65 years. More smokers than non-smokers believed cigarettes could help control body weight. Smokers emphasized posi¬tive effects of smoking more than non-smokers, and smokers tended to perceive women depicted in cigarette advertise¬ments as attractive, elegant, fit, sociable, and adventurous to a greater degree than did non-smokers. Conclusions - There was no difference in health knowledge about tobacco-related diseases between smokers and non-smokers. It seems, therefore, that health risks alone are not reason enough for smokers to change smoking behaviour in this study population. Instead, health promotion should emphasize the social detriment of smoking for women, and restrictions on the depiction of positive social images in tobacco advertising should be considered.published_or_final_versio

Neutron cryo-crystallography captures the protonation state of ferryl heme in a peroxidase

Heme enzymes activate oxygen through formation of transient iron-oxo (ferryl) intermediates of the heme iron. A long-standing question has been the nature of the iron-oxygen bond and, in particular, the protonation state. We present neutron structures of the ferric derivative of cytochrome c peroxidase and its ferryl intermediate; these allow direct visualization of protonation states. We demonstrate that the ferryl heme is an Fe(IV)=O species and is not protonated. Comparison of the structures shows that the distal histidine becomes protonated on formation of the ferryl intermediate, which has implications for the understanding of O–O bond cleavage in heme enzymes. The structures highlight the advantages of neutron cryo-crystallography in probing reaction mechanisms and visualizing protonation states in enzyme intermediates

Syntaxin 16 is a master recruitment factor for cytokinesis

Recently it was shown that both recycling endosome and endosomal sorting complex required for transport (ESCRT) components are required for cytokinesis, in which they are believed to act in a sequential manner to bring about secondary ingression and abscission, respectively. However, it is not clear how either of these complexes is targeted to the midbody and whether their delivery is coordinated. The trafficking of membrane vesicles between different intracellular organelles involves the formation of soluble N-ethylmalei­mide–sensitive factor attachment protein receptor (SNARE) complexes. Although membrane traffic is known to play an important role in cytokinesis, the contribution and identity of intracellular SNAREs to cytokinesis remain unclear. Here we demonstrate that syntaxin 16 is a key regulator of cytokinesis, as it is required for recruitment of both recycling endosome–associated Exocyst and ESCRT machinery during late telophase, and therefore that these two distinct facets of cytokinesis are inextricably linked

Cost-effectiveness of a novel lipoarabinomannan test for tuberculosis in patients with HIV

BACKGROUND: A novel urine lipoarabinomannan assay (FujiLAM) has higher sensitivity and higher cost than the first-generation AlereLAM assay. We evaluated the cost-effectiveness of FujiLAM for tuberculosis testing among hospitalized people with HIV irrespective of symptoms. METHODS: We used a microsimulation model to project clinical and economic outcomes of three testing strategies: 1) sputum Xpert MTB/RIF (Xpert); 2) sputum Xpert plus urine AlereLAM (Xpert+AlereLAM); 3) sputum Xpert plus urine FujiLAM (Xpert+FujiLAM). The modelled cohort matched that of a two-country clinical trial. We applied diagnostic yields from a retrospective study (yields for Xpert/Xpert+AlereLAM/Xpert+FujiLAM among those with CD4<200/µL: 33%/62%/70%; among those with CD4≥200/µL: 33%/35%/47%). Costs of Xpert/AlereLAM/FujiLAM were USD15/3/6 (South Africa) and USD25/3/6 (Malawi). Xpert+FujiLAM was considered cost-effective if its incremental cost-effectiveness ratio (USD/year-of-life saved) was <$940 (South Africa) and <$750 (Malawi). We varied key parameters in sensitivity analysis and performed a budget impact analysis of implementing FujiLAM countrywide. RESULTS: Compared with Xpert+AlereLAM, Xpert+FujiLAM increased life expectancy by 0.2 years for those tested in South Africa and Malawi. Xpert+FujiLAM was cost-effective in both countries. Xpert+FujiLAM for all patients remained cost-effective compared with sequential testing and CD4-stratified testing strategies. FujiLAM use added 3.5% (South Africa) and 4.7% (Malawi) to five-year healthcare costs of tested patients, primarily reflecting ongoing HIV treatment costs among survivors. CONCLUSIONS: FujiLAM with Xpert for tuberculosis testing in hospitalized people with HIV is likely to increase life expectancy and be cost-effective at the currently anticipated price in South Africa and Malawi. Additional studies should evaluate FujiLAM in clinical practice settings

Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that 'low dose' theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of 'low dose' theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD. METHOD/DESIGN: TWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either 'low dose' theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1-5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring oral corticosteroids or antibiotics during the 52-week treatment period. DISCUSSION: The demonstration that 'low dose' theophylline increases the efficacy of inhaled corticosteroids in COPD by reducing the incidence of exacerbations is relevant not only to patients and clinicians but also to health-care providers, both in the UK and globally. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27066620 was registered on Sept. 19, 2013, and the first subject was randomly assigned on Feb. 6, 2014

The relationship between vitamin D status and muscle strength in young healthy adults from sunny climate countries currently living in the northeast of Scotland

Summary: The current study examined the relationship between vitamin D status and muscle strength in young healthy adults: residents (>6 months) and newcomers (0–3 months), originally from sunny climate countries but currently living in the northeast of Scotland. Our longitudinal data found a positive, albeit small, relationship between vitamin D status and knee extensor isometric strength.  Introduction: Vitamin D has been suggested to play a role in muscle health and function, but studies so far have been primarily in older populations for falls prevention and subsequent risk of fractures.  Methods: Vitamin D status was assessed in a healthy young adults from sunny climate countries (n = 71, aged 19–42 years) with 56% seen within 3 months of arriving in Aberdeen [newcomers; median (range) time living in the UK = 2 months (9–105 days)] and the remainder resident for >6 months [residents; 23 months (6–121 months)]. Participants attended visits every 3 months for 15 months. At each visit, fasted blood samples were collected for analysis of serum 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), carboxy-terminal collagen crosslinks (CTX) and N-terminal propeptide of type I collagen (P1NP). Maximal voluntary contractions (MVC) were performed for grip strength (both arms) and for maximal isometric strength of the knee extensors (right knee).  Results: There were small seasonal variations in 25(OH)D concentrations within the newcomers and residents, but no seasonal variation in bone turnover markers. There was a positive, albeit small, association between 25(OH)D and knee extensor maximal isometric strength. Mixed modelling predicted that for each 1 nmol/L increase in 25(OH)D, peak torque would increase by 1 Nm (p = 0.04).  Conclusions: This study suggests that vitamin D may be important for muscle health in young adults migrating from sunnier climates to high latitudes, yet the potential effect is small