Occupational exposure to inhaled pollutants and risk of airflow obstruction: a large UK population-based UK Biobank cohort.

BACKGROUND: Although around 10% to 15% of COPD burden can be attributed to workplace exposures, little is known about the role of different airborne occupational pollutants (AOP). The main aim of the study was to assess the effect size of the relationship between various AOP, their level and duration of exposure with airflow obstruction (AFO). METHODS: A cross-sectional analysis was conducted in 228 614 participants from the UK Biobank study who were assigned occupational exposure using a job exposure matrix blinded to health outcome. Adjusted prevalence ratios (PRs) and 95% CI for the risk of AFO for ever and years of exposure to AOPs were estimated using robust Poisson model. Sensitivity analyses were conducted for never-smokers, non-asthmatic and bi-pollutant model. RESULTS: Of 228 614 participants, 77 027 (33.7%) were exposed to at least one AOP form. 35.5% of the AFO cases were exposed to vapours, gases, dusts or fumes (VGDF) and 28.3% to dusts. High exposure to vapours increased the risk of occupational AFO by 26%. Exposure to dusts (adjusted PR=1.05; 95% CI 1.01 to 1.08), biological dusts (1.05; 1.01 to 1.10) and VGDF (1.04; 1.01 to 1.07) showed a significantly increased risk of AFO, however, statistically not significant following multiple testing. There was no significant increase in risk of AFO by duration (years) of exposure in current job. The results were null when restricted to never-smokers and when a bi-pollutant model was used. However, when data was analysed based on the level of exposure (low, medium and high) compared with no exposure, directionally there was increase in risk for those with high exposure to vapours, gases, fumes, mists and VGDF but statistically significant only for vapours. CONCLUSION: High exposure (in current job) to airborne occupational pollutants was suggestive of higher risk of AFO. Future studies should investigate the relationship between lifetime occupational exposures and COPD.

Model-based evaluation of the long-term cost-effectiveness of systematic case-finding for COPD in primary care.

INTRODUCTION: 'One-off' systematic case-finding for COPD using a respiratory screening questionnaire is more effective and cost-effective than routine care at identifying new cases. However, it is not known whether early diagnosis and treatment is beneficial in the longer term. We estimated the long-term cost-effectiveness of a regular case-finding programme in primary care. METHODS: A Markov decision analytic model was developed to compare the cost-effectiveness of a 3-yearly systematic case-finding programme targeted to ever smokers aged ≥50 years with the current routine diagnostic process in UK primary care. Patient-level data on case-finding pathways was obtained from a large randomised controlled trial. Information on the natural history of COPD and treatment effects was obtained from a linked COPD cohort, UK primary care database and published literature. The discounted lifetime cost per quality-adjusted life-year (QALY) gained was calculated from a health service perspective. RESULTS: The incremental cost-effectiveness ratio of systematic case-finding versus current care was £16 596 per additional QALY gained, with a 78% probability of cost-effectiveness at a £20 000 per QALY willingness-to-pay threshold. The base case result was robust to multiple one-way sensitivity analyses. The main drivers were response rate to the initial screening questionnaire and attendance rate for the confirmatory spirometry test. DISCUSSION: Regular systematic case-finding for COPD using a screening questionnaire in primary care is likely to be cost-effective in the long-term despite uncertainties in treatment effectiveness. Further knowledge of the natural history of case-found patients and the effectiveness of their management will improve confidence to implement such an approach.

Is ambient air pollution associated with onset of sudden infant death syndrome: a case-crossover study in the UK.

OBJECTIVES: Air pollution has been associated with increased mortality and morbidity in several studies with indications that its effect could be more severe in children. This study examined the relationship between short-term variations in criteria air pollutants and occurrence of sudden infant death syndrome (SIDS). DESIGN: We used a case-crossover study design which is widely applied in air pollution studies and particularly useful for estimating the risk of a rare acute outcome associated with short-term exposure. SETTING: The study used data from the West Midlands region in the UK. PARTICIPANTS: We obtained daily time series data on SIDS mortality (ICD-9: 798.0 or ICD-10: R95) for the period 1996-2006 with a total of 211 SIDS events. PRIMARY OUTCOME MEASURES: Daily counts of SIDS events. RESULTS: For an IQR increase in previous day pollutant concentration, the percentage increases (95% CI) in SIDS were 16 (6 to 27) for PM10, 1 (-7 to 10) for SO2, 5 (-4 to 14) for CO, -17 (-27 to -6) for O3, 16 (2 to 31) for NO2 and 2 (-3 to 8) for NO after controlling for average temperature and national holidays. PM10 and NO2 showed relatively consistent association which persisted across different lag structures and after adjusting for copollutants. CONCLUSIONS: The results indicated ambient air pollutants, particularly PM10 and NO2, may show an association with increased SIDS mortality. Thus, future studies are recommended to understand possible mechanistic explanations on the role of air pollution on SIDS incidence and the ways in which we might reduce pollution exposure among infants.

Factors associated with work productivity among people with COPD: Birmingham COPD Cohort.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are more likely to take time off work (absenteeism) and report poor performance at work (presenteeism) compared to those without COPD. Little is known about the modifiable factors associated with these work productivity outcomes. AIM: To assess the factors associated with work productivity among COPD patients. METHODS: Cross-sectional analysis of baseline data from a subsample (those in paid employment) of the Birmingham COPD Cohort study. Absenteeism was defined by self-report over the previous 12 months. Presenteeism was assessed using the Stanford Presenteeism Scale. Logistic regression analysis was used to assess the effects of sociodemographic, clinical and occupational characteristics on work productivity. RESULTS: Among 348 included participants, increasing dyspnoea was the only factor associated with both absenteeism and presenteeism (p for trend<0.01). Additionally, increasing history of occupational exposure to vapours, gases, dusts or fumes (VGDF) was independently associated with presenteeism (p for trend<0.01). CONCLUSIONS: This is the first study to identify important factors associated with poor work productivity among patients with COPD. Future studies should evaluate interventions aimed at managing breathlessness and reducing occupational exposures to VGDF on work productivity among patients with COPD.

Occupational COPD and job exposure matrices: a systematic review and meta-analysis.

BACKGROUND: The association between occupational exposure and COPD reported previously has mostly been derived from studies relying on self-reported exposure to vapors, gases, dust, or fumes (VGDF), which could be subjective and prone to biases. The aim of this study was to assess the strength of association between exposure and COPD from studies that derived exposure by job exposure matrices (JEMs). METHODS: A systematic search of JEM-based occupational COPD studies published between 1980 and 2015 was conducted in PubMed and EMBASE, followed by meta-analysis. Meta-analysis was performed using a random-effects model, with results presented as a pooled effect estimate with 95% confidence intervals (CIs). The quality of study (risk of bias and confounding) was assessed by 13 RTI questionnaires. Heterogeneity between studies and its possible sources were assessed by Egger test and meta-regression, respectively. RESULTS: In all, 61 studies were identified and 29 were included in the meta-analysis. Based on JEM-based studies, there was 22% (pooled odds ratio =1.22; 95% CI 1.18-1.27) increased risk of COPD among those exposed to airborne pollutants arising from occupation. Comparatively, higher risk estimates were obtained for general populations JEMs (based on expert consensus) than workplace-based JEM were derived using measured exposure data (1.26; 1.20-1.33 vs 1.14; 1.10-1.19). Higher risk estimates were also obtained for self-reported exposure to VGDF than JEMs-based exposure to VGDF (1.91; 1.72-2.13 vs 1.10; 1.06-1.24). Dusts, particularly biological dusts (1.33; 1.17-1.51), had the highest risk estimates for COPD. Although the majority of occupational COPD studies focus on dusty environments, no difference in risk estimates was found for the common forms of occupational airborne pollutants. CONCLUSION: Our findings highlight the need to interpret previous studies with caution as self-reported exposure to VGDF may have overestimated the risk of occupational COPD.

Birmingham COPD Cohort: a cross-sectional analysis of the factors associated with the likelihood of being in paid employment among people with COPD.

BACKGROUND: Employment rates among those with chronic obstructive pulmonary disease (COPD) are lower than those without COPD, but little is known about the factors that affect COPD patients' ability to work. METHODS: Multivariable analysis of the Birmingham COPD Cohort Study baseline data was used to assess the associations between lifestyle, clinical, and occupational characteristics and likelihood of being in paid employment among working-age COPD patients. RESULTS: In total, 608 of 1,889 COPD participants were of working age, of whom 248 (40.8%) were in work. Older age (60-64 years vs 30-49 years: odds ratio [OR] =0.28; 95% confidence interval [CI] =0.12-0.65), lower educational level (no formal qualification vs degree/higher level: OR =0.43; 95% CI =0.19-0.97), poorer prognostic score (highest vs lowest quartile of modified body mass index, airflow obstruction, dyspnea, and exercise (BODE) score: OR =0.10; 95% CI =0.03-0.33), and history of high occupational exposure to vapors, gases, dusts, or fumes (VGDF; high VGDF vs no VGDF exposure: OR =0.32; 95% CI =0.12-0.85) were associated with a lower probability of being employed. Only the degree of breathlessness of BODE was significantly associated with employment. CONCLUSION: This is the first study to comprehensively assess the characteristics associated with employment in a community sample of people with COPD. Future interventions should focus on managing breathlessness and reducing occupational exposures to VGDF to improve the work capability among those with COPD.

Targeted case finding for chronic obstructive pulmonary disease versus routine practice in primary care (TargetCOPD): a cluster-randomised controlled trial.

BACKGROUND: Many individuals with chronic obstructive pulmonary disease (COPD) remain undiagnosed worldwide. Health-care organisations are implementing case-finding programmes without good evidence of which are the most effective and cost-effective approaches. We assessed the effectiveness and cost-effectiveness of two alternative approaches to targeted case finding for COPD compared with routine practice. METHODS: In this cluster-randomised controlled trial, participating general practices in the West Midlands, UK, were randomly assigned (1:1), via a computer-generated block randomisation sequence, to either a targeted case-finding group or a routine care group. Eligible patients were ever-smokers aged 40-79 years without a previously recorded diagnosis of COPD. Patients in the targeted case-finding group were further randomly assigned (1:1) via their household to receive either a screening questionnaire at the general practitioner (GP) consultation (opportunistic) or a screening questionnaire at the GP consultation plus a mailed questionnaire (active). Respondents reporting relevant respiratory symptoms were invited for post-bronchodilator spirometry. Patients, clinicians, and investigators were not masked to allocation, but group allocation was concealed from the researchers who performed the spirometry assessments. Primary outcomes were the percentage of the eligible population diagnosed with COPD within 1 year (defined as post-bronchodilator forced expiratory volume in 1 s [FEV1] to forced vital capacity [FVC] ratio <0·7 in patients with symptoms or a new diagnosis on their GP record) and cost per new COPD diagnosis. Multiple logistic and Poisson regression were used to estimate effect sizes. Costs were obtained from the trial. This trial is registered with ISRCTN, number ISRCTN14930255. FINDINGS: From Aug 10, 2012, to June 22, 2014, 74 818 eligible patients from 54 diverse general practices were randomly assigned and completed the trial. At 1 year, 1278 (4%) cases of COPD were newly detected in 32 789 eligible patients in the targeted case-finding group compared with 337 (1%) cases in 42 029 patients in the routine care group (adjusted odds ratio [OR] 7·45 [95% CI 4·80-11·55], p<0·0001). The percentage of newly detected COPD cases was higher in the active case-finding group (822 [5%] of 15 378) than in the opportunistic case-finding group (370 [2%] of 15 387; adjusted OR 2·34 [2·06-2·66], p<0·0001; adjusted risk difference 2·9 per 100 patients [95% CI 2·3-3·6], p<0·0001). Active case finding was more cost-effective than opportunistic case finding (£333 vs £376 per case detected, respectively). INTERPRETATION: In this well established primary care system, routine practice identified few new cases of COPD. An active targeted approach to case finding including mailed screening questionnaires before spirometry is a cost-effective way to identify undiagnosed patients and has the potential to improve their health. FUNDING: National Institute for Health Research.

A Preliminary Assessment of the Role of Ambient Nitric Oxide Exposure in Hospitalization with Respiratory Syncytial Virus Bronchiolitis.

Some in vitro studies have indicated a possible link between respiratory syncytial virus (RSV) infection and exposure to Nitric Oxide (NO). However, these studies used much higher NO concentrations than normally found in the ambient environment. This preliminary study explored whether an association was present with short-term exposure to NO in the environment. RSV-related admission data between November 2011 and February 2012 were obtained from Sheffield Children's Hospital. The dates of admission were linked to contemporaneous ambient NO derived from sentinel air monitors. The case-crossover design was used to study the relationship between daily RSV admissions and NO, controlling for temperature and relative humidity. We found little evidence of association between daily RSV admission rates and exposure to ambient NO at different lags or average exposure across several lags. The findings should, however, be viewed with caution due to the low number of events observed during the time frame. It is possible that the apparent lack of association may be accounted for by the timing of the seasonal RSV epidemic in relation to peaks in NO concentrations. A larger study incorporating a wider range of RSV and NO peaks would determine whether said peaks enhanced the number of RSV hospitalizations in children.

Cancer Mortality Risks from Long-term Exposure to Ambient Fine Particle.

BACKGROUND: Few studies have assessed long-term effects of particulate matter (PM) with aerodynamic diameter < 2.5 µm (PM2.5) on mortality for causes of cancer other than the lung; we assessed the effects on multiple causes. In Hong Kong, most people live and work in urban or suburban areas with high-rise buildings. This facilitates the estimation of PM2.5 exposure of individuals, taking into account the height of residence above ground level for assessment of the long-term health effects with sufficient statistical power. METHODS: We recruited 66,820 persons who were ≥65 in 1998 to 2001 and followed up for mortality outcomes until 2011. Annual concentrations of PM at their residential addresses were estimated using PM2.5 concentrations measured at fixed-site monitors, horizontal-vertical locations, and satellite data. We used Cox regression model to assess the HR of mortality for cancer per 10 µg/m(3) increase of PM2.5 RESULTS: PM2.5 was associated with increased risk of mortality for all causes of cancer [HR, 1.22 (95% CI, 1.11-1.34)] and for specific cause of cancer in upper digestive tract [1.42 (1.06-1.89)], digestive accessory organs [1.35 (1.06-1.71)] in all subjects; breast [1.80 (1.26-2.55)] in females; and lung [1.36 (1.05-1.77)] in males. CONCLUSIONS: Long-term exposures to PM2.5 are associated with elevated risks of cancer in various organs. IMPACT: This study is particularly timely in China, where compelling evidence is needed to support the pollution control policy to ameliorate the health damages associated with economic growth. Cancer Epidemiol Biomarkers Prev; 25(5); 839-45. ©2016 AACR.

STROBE-Long-Term Exposure to Ambient Fine Particulate Air Pollution and Hospitalization Due to Peptic Ulcers.

Little is known about the effect of air pollution on the gastrointestinal (GI) system. We investigated the association between long-term exposures to outdoor fine particles (PM2.5) and hospitalization for peptic ulcer diseases (PUDs) in a large cohort of Hong Kong Chinese elderly.A total of 66,820 subjects aged ≥65 years who were enrolled in all 18 Government Elderly Health Service centers of Hong Kong participated in the study voluntarily between 1998 and 2001. They were prospectively followed up for more than 10 years. Annual mean exposures to PM2.5 at residence of individuals were estimated by satellite data through linkage with address details including floor level. All hospital admission records of the subjects up to December 31, 2010 were retrieved from the central database of Hospital Authority. We used Cox regression to estimate the hazard ratio (HR) for PUD hospitalization associated with PM2.5 exposure after adjustment for individual and ecological covariates.A total of 60,273 subjects had completed baseline information including medical, socio-demographic, lifestyle, and anthropometric data at recruitment. During the follow-up period, 1991 (3.3%) subjects had been hospitalized for PUD. The adjusted HR for PUD hospitalization per 10 µg/m of PM2.5 was 1.18 (95% confidence interval: 1.02-1.36, P = 0.02). Further analysis showed that the associations with PM2.5 were significant for gastric ulcers (HR 1.29; 1.09-1.53, P = 0.003) but not for duodenal ulcers (HR 0.98; 0.78 to 1.22, P = 0.81).Long-term exposures to PM2.5 were associated with PUD hospitalization in elder population. The mechanism underlying the PM2.5 in the development of gastric ulcers warrants further research.

Respiratory symptoms and cross-shift lung function in relation to cotton dust and endotoxin exposure in textile workers in Nepal: a cross-sectional study.

OBJECTIVES: Inhalation of a cotton-based particulates has previously been associated with respiratory symptoms and impaired lung function. This study investigates the respiratory health of Nepalese textile workers in relation to dust and endotoxin exposure. METHODS: A total of 938 individuals from four sectors (garment, carpet, weaving and recycling) of the textile industry in Kathmandu, Nepal completed a health questionnaire and performed spirometry. A subset (n=384) performed cross-shift spirometry. Personal exposure to inhalable dust and airborne endotoxin was measured during a full shift for 114 workers. RESULTS: The overall prevalence of persistent cough, persistent phlegm, wheeze ever, breathlessness ever and chest tightness ever was 8.5%, 12.5%, 3.2%, 6.5% and 12.3%, respectively. Symptoms were most common among recyclers and least common among garment workers. Exposure to inhalable dust significantly predicted persistent cough and chest tightness. Exposure to endotoxin did not have any independent predictive effect. Significant cross-shift reduction in forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were found (p<0.001 for both) being largest for FEV1 in the recyclers (-143 mL), and least in the garment workers (-38 mL; p=0.012). Exposure to inhalable dust predicted a cross-shift reduction in FEV1. CONCLUSIONS: This study is the first to investigate the respiratory health of Nepalese cotton workers. The measured association between inhalable dust exposure and reporting of respiratory symptoms and across-shift decrement in FEV1 and FVC indicates that improved dust control measures should be instituted, particularly in the recycling and carpet sectors. The possible role of other biologically active agents of cotton dust beyond endotoxin should be further explored.

Satellite-Based Estimates of Long-Term Exposure to Fine Particles and Association with Mortality in Elderly Hong Kong Residents.

BACKGROUND: A limited number of studies on long-term effects of particulate matter with aerodynamic diameter < 2.5 µm (PM2.5) on health suggest it can be an important cause of morbidity and mortality. In Asia where air quality is poor and deteriorating, local data on long-term effects of PM2.5 to support policy on air quality management are scarce. OBJECTIVES: We assessed long-term effects of PM2.5 on the mortality in a single Asian city. METHODS: For 10-13 years, we followed up a cohort of 66,820 participants ≥ 65 years of age who were enrolled and interviewed in all 18 Elderly Health Centres of the Department of Health, Hong Kong, in 1998-2001. Their residential addresses were geocoded into x- and y-coordinates, and their proxy exposures to PM2.5 at their addresses in 1 × 1 km grids were estimated from the U.S. National Aeronautics and Space Administration (NASA) satellite data. We used Cox regression models to calculate hazard ratios (HRs) of mortality associated with PM2.5. RESULTS: Mortality HRs per 10-µg/m3 increase in PM2.5 were 1.14 (95% CI: 1.07, 1.22) for all natural causes, 1.22 (95% CI: 1.08, 1.39) for cardiovascular causes, 1.42 (95% CI: 1.16, 1.73) for ischemic heart disease, 1.24 (95% CI: 1.00, 1.53) for cerebrovascular disease, and 1.05 (95% CI: 0.90, 1.22) for respiratory causes. CONCLUSIONS: Our methods in using NASA satellite data provide a readily accessible and affordable approach to estimation of a sufficient range of individual PM2.5 exposures in a single city. This approach can expand the capacity to conduct environmental accountability studies in areas with few measurements of fine particles. CITATION: Wong CM, Lai HK, Tsang H, Thach TQ, Thomas GN, Lam KB, Chan KP, Yang L, Lau AK, Ayres JG, Lee SY, Chan WM, Hedley AJ, Lam TH. 2015. Satellite-based estimates of long-term exposure to fine particles and association with mortality in elderly Hong Kong residents. Environ Health Perspect 123:1167-1172; http://dx.doi.org/10.1289/ehp.1408264.

Effects of antenatal multiple micronutrient supplementation on lung function in mid-childhood: follow-up of a double-blind randomised controlled trial in Nepal.

A randomised trial of prenatal multiple micronutrient supplementation in Nepalese women increased birthweight and weight at 2 years of age in offspring, compared to those born to mothers who only received iron and folic acid supplements. Further follow-up of this cohort provided an opportunity to investigate the effect of antenatal multiple micronutrients on subsequent lung function by measuring spirometry at 7-9 years of age in C: hildren born during the trial. 841 children (80% of the cohort) were seen at mean±sd 8.5±0.4 years. Technically successful spirometry results were obtained in 793 (94.3%) children, 50% of whom had been randomised to micronutrient supplementation. Background characteristics, including anthropometry, were similar in the two allocation groups. Lung function was also similar, mean (95% CI) difference in z-scores (supplementation minus control) was -0.08 (-0.19-0.04), -0.05 (-0.17-0.06) and -0.04 (-0.15-0.07) for forced expiratory volume in 1 s (FEV1), forced vital capacity and FEV1/FVC, respectively. Compared with healthy white children, FEV1 and FVC in the "healthy" Nepalese children were ∼1 (∼13%) z-score lower, with no difference in FEV1/FVC. We conclude that, compared with routine iron and folic acid, multiple micronutrient supplementation during pregnancy has no effect on spirometric lung function in Nepalese children at 8.5 years of age.

Understanding health beliefs and behaviour in workers with suspected occupational asthma.

INTRODUCTION: Long delays from symptom onset to the diagnosis of occupational asthma have been reported in the UK, Europe and Canada and workers are often reluctant to seek medical help or workplace solutions for their symptoms. Reducing this delay could improve workers' quality of life, and reduce the societal cost of occupational asthma. This study aimed to explore reasons behind such delays. METHODS: A purposive sample of 20 individuals diagnosed with, or under investigation for, occupational asthma (median age = 52; 70% male; 80% white British) undertook a single semi-structured interview. Interviews were transcribed verbatim and thematic analysis was undertaken in order to explore health beliefs and identify barriers to diagnosis. RESULTS: Four themes were identified: (1) workers' understanding of symptoms, (2) working relationships, (3) workers' course of action and (4) workers' negotiation with healthcare professionals. Understanding of symptoms varied between individuals, from a lack of insight into the onset, pattern and nature of symptoms, through to misunderstanding of what they represented, or ignorance of the existence of asthma as a disease entity. Workers described reluctance to discuss health issues with managers and peers, through fear of job loss and a perceived lack of ability to find a solution. The evolution of workers' understanding depended upon how actively they looked to define symptoms or seek a solution. Proactive workers were motivated to seek authoritative help and negotiate inadequate healthcare encounters with GPs. CONCLUSION: Understanding workers' health beliefs will enable policy makers and clinicians to develop better workplace interventions that may aid diagnosis and reduce delay in identifying occupational asthma.

Maternal vitamin D and E intakes during pregnancy are associated with asthma in children.

Are maternal vitamin D and E intakes during pregnancy associated with asthma in 10-year-old children? In a longitudinal study of 1924 children born to women recruited during pregnancy, maternal vitamin D intake during pregnancy was assessed by the Food Frequency Questionnaire (FFQ) and vitamin E by FFQ and plasma α-tocopherol; respiratory questionnaires were completed for the 10-year-old children. Their treatment for asthma was also ascertained using administrative data. Longitudinal analyses included data collected at 1, 2, 5 and 10 years. Symptom data were available for 934 (49%) children and use of asthma medication for 1748 (91%). In the children maternal vitamin D intake during pregnancy was negatively associated with doctor-diagnosed asthma at 10 years of age (OR per intake quintile 0.86, 95% CI 0.74-0.99) and over the first 10 years (hazard ratio 0.90, 95% CI 0.81-1.00). Maternal plasma α-tocopherol at 11 weeks gestation was negatively associated with children receiving asthma treatment (OR per standard deviation increase 0.52, 95% CI 0.31-0.87). Maternal vitamin E intake was negatively associated with doctor-diagnosed asthma (OR 0.89, 95% CI 0.81-0.99) in the first 10 years. Low maternal vitamin D and E intakes during pregnancy are associated with increased risk of children developing asthma in the first 10 years of life. These associations may have significant public health implications.

Effect of antenatal multiple micronutrient supplementation on anthropometry and blood pressure in mid-childhood in Nepal: follow-up of a double-blind randomised controlled trial.

BACKGROUND: In 2002-04, we did a randomised controlled trial in southern Nepal, and reported that children born to mothers taking multiple micronutrient supplements during pregnancy had a mean birthweight 77 g greater than children born to mothers taking iron and folic acid supplements. Children born to mothers in the study group were a mean 204 g heavier at 2·5 years of age and their systolic blood pressure was a mean 2·5 mm Hg lower than children born to mothers in the control group. We aimed to follow up the same children to mid-childhood (age 8·5 years) to investigate whether these differences would be sustained. METHODS: For this follow-up study, we identified children from the original trial and measured anthropometry, body composition with bioelectrical impedance (with population-specific isotope calibration), blood pressure, and renal dimensions by ultrasound. We documented socioeconomic status, household food security, and air pollution. Main outcomes of the follow-up at 8 years were Z scores for weight-for-age, height-for-age, and body-mass index (BMI)-for-age according to WHO Child Growth Standards for children aged 5-19 years, and blood pressure. This study is registered with the International Standard Randomised Controlled Trial register, number ISRCTN88625934. FINDINGS: Between Sept 21, 2011, and Dec 7, 2012, we assessed 841 children (422 in the control group and 419 in the intervention group). Unadjusted differences (intervention minus control) in Z scores were 0·05 for weight-for-age (95% CI -0·09 to 0·19), 0·02 in height-for-age (-0·10 to 0·15), and 0·04 in BMI-for-age (-0·09 to 0·18). We recorded no difference in blood pressure. Adjusted differences were similar for all outcomes. INTERPRETATION: We recorded no differences in phenotype between children born to mothers who received antenatal multiple micronutrient or iron and folate supplements at age 8·5 years. Our findings did not extend to physiological differences or potential longer-term effects. FUNDING: The Wellcome Trust.

The effect of exposure to biomass smoke on respiratory symptoms in adult rural and urban Nepalese populations.

BACKGROUND: Half of the world's population is exposed to household air pollution from biomass burning. This study aimed to assess the relationship between respiratory symptoms and biomass smoke exposure in rural and urban Nepal. METHODS: A cross-sectional study of adults (16+ years) in a rural population (n = 846) exposed to biomass smoke and a non-exposed urban population (n = 802) in Nepal. A validated questionnaire was used along with measures of indoor air quality (PM2.5 and CO) and outdoor PM2.5. RESULTS: Both men and women exposed to biomass smoke reported more respiratory symptoms compared to those exposed to clean fuel. Women exposed to biomass were more likely to complain of ever wheeze (32.0 % vs. 23.5%; p = 0.004) and breathlessness (17.8% vs. 12.0%, p = 0.017) compared to males with tobacco smoking being a major risk factor. Chronic cough was similar in both the biomass and non-biomass smoke exposed groups whereas chronic phlegm was reported less frequently by participants exposed to biomass smoke. Higher PM2.5 levels (≥2 SDs of the 24-hour mean) were associated with breathlessness (OR = 2.10, 95% CI 1.47, 2.99) and wheeze (1.76, 1.37, 2.26). CONCLUSIONS: The study suggests that while those exposed to biomass smoke had higher prevalence of respiratory symptoms, urban dwellers (who were exposed to higher ambient air pollution) were more at risk of having productive cough.

TargetCOPD: a pragmatic randomised controlled trial of targeted case finding for COPD versus routine practice in primary care: protocol.

BACKGROUND: Many people with clinically significant chronic obstructive pulmonary disease (COPD) remain undiagnosed worldwide. There are a number of small studies which have examined possible methods of case finding through primary care, but no large RCTs that have adequately assessed the most cost-effective approach. METHODS/DESIGN: In this study, using a cluster randomised controlled trial (RCT) in 56 general practices in the West Midlands, we plan to investigate the effectiveness and cost-effectiveness of a Targeted approach to case finding for COPD compared with routine practice. Using an individual patient RCT nested in the Targeted arm, we plan also to compare the effectiveness and cost-effectiveness of Active case finding using a postal questionnaire (with supplementary opportunistic questionnaires), and Opportunistic-only case finding during routine surgery consultations.All ever-smoking patients aged 40-79 years, without a current diagnosis of COPD and registered with participating practices will be eligible. Patients in the Targeted arm who report positive respiratory symptoms (chronic cough or phlegm, wheeze or dyspnoea) using a brief questionnaire will be invited for further spirometric assessment to ascertain whether they have COPD or not. Post-bronchodilator spirometry will be conducted to ATS standards using an Easy One spirometer by trained research assistants.The primary outcomes will be new cases of COPD and cost per new case identified, comparing targeted case finding with routine care, and two types of targeted case finding (active versus opportunistic). A multilevel logistic regression model will be used to model the probability of detecting a new case of COPD for each treatment arm, with clustering of patients (by practice and household) accounted for using a multi-level structure.A trial-based analysis will be undertaken using costs and outcomes collected during the trial. Secondary outcomes include the feasibility, efficiency, long-term cost-effectiveness, patient and primary care staff views of each approach. DISCUSSION: This will be the largest RCT of its kind, and should inform how best to identify undiagnosed patients with COPD in the UK and other similar healthcare systems. Sensitivity analyses will help local policy-makers decide which sub-groups of the population to target first. TRIAL REGISTRATION: Current controlled trials ISRCTN14930255.

Tuberculosis risk from exposure to solid fuel smoke: a systematic review and meta-analysis.

BACKGROUND: Studies, particularly from low-income and middle-income countries, suggest that exposure to smoke from household air pollution (HAP) may be a risk factor for tuberculosis. The primary aim of this study was to quantify the risk of tuberculosis from HAP and explore bias and identify possible causes for heterogeneity in reported effect sizes. METHODS: A systematic review was conducted from original studies. Meta-analysis was performed using a random effects model, with results presented as a pooled effect estimate (EE) with 95% CI. Heterogeneity between studies was assessed. RESULTS: Twelve studies that considered active tuberculosis and reported adjusted effect sizes were included in the meta-analyses. The overall pooled EE (OR, 95% CI) showed a significant adverse effect (1.43, 1.07 to 1.91) and with significant heterogeneity between studies (I(2)=70.8%, p<0.001). When considering studies of cases diagnosed microbiologically, the pooled EE approached significance (1.26, 0.95 to 1.68). The pooled EE (OR, 95% CI) was significantly higher among those exposed only to biomass smoke (1.49, 1.08 to 2.05) when compared with the use of kerosene only (0.70, 0.13 to 3.87). Similarly, the pooled EE among women (1.61, 0.73 to 3.57) was greater than when both genders were combined (1.39, 1.01 to 1.92). There was no publication bias (Egger plot, p=0.136). Significant heterogeneity was observed in the diagnostic criteria for tuberculosis (coefficient=0.38, p=0.042). CONCLUSIONS: Biomass smoke is a significant risk factor for active tuberculosis. Most of the studies were small with limited information on measures of HAP.

Continuous terbutaline infusion in severe asthma in adults: a retrospective study of long-term efficacy and safety.

BACKGROUND: Long-term subcutaneous or intravenous infusion of terbutaline has been used to stabilize asthma in patients enduring frequent hospital admissions due to severe asthma despite maximum therapy. However, this treatment is not supported by significant body of evidence. AIM: To study long-term efficacy and safety of using continuous infusions of terbutaline in unstable severe asthma. METHODS: The available medical records of all patients received terbutaline infusions at a severe asthma unit between 1982 and 2008 were retrospectively studied. We retrieved data on treatment indication, asthma subtype, patient demographics, pre-treatment terbutaline trial outcome, duration of treatment, effect on lung function, hospital admissions, oral corticosteroids (OCSs) requirement, safety and side effects. RESULTS: Forty-two patients with adequate medical information were studied (31 females, mean age 43.6 years, 88% had type 1 brittle asthma and 12% had other severe asthma). This group of patients had a mean body mass index of 30.8 kg/m2, mean oral prednisolone or equivalent of 26.6 mg and mean predicted FEV1 of 66.8%. The mean treatment duration was 86.7 months (range 7-216). Long-term continuous terbutaline infusion significantly reduced hospital admissions (mean pre-treatment = 6.7 (95% CI 0.96-12.4) per annum, and mean annualized on-treatment admission = 3.3 (95% CI 0.63-6.9, p = 0.045). We observed overall reduction in OCSs use in 59% of patients with available data, but there was no significant change in lung function. Side effects related to terbutaline or the method of its infusion were common and some were serious especially when central venous access device were used. CONCLUSION: Continuous terbutaline infusion could be a treatment option for severe unstable asthma and may reduce hospital admissions. However, the treatment was associated with significant side effects and its use should be limited to centers possessing necessary expertise.