Whole Exome Re-Sequencing Implicates CCDC38 and Cilia Structure and Function in Resistance to Smoking Related Airflow Obstruction

Chronic obstructive pulmonary disease (COPD) is a leading cause of global morbidity and mortality and, whilst smoking remains the single most important risk factor, COPD risk is heritable. Of 26 independent genomic regions showing association with lung function in genome-wide association studies, eleven have been reported to show association with airflow obstruction. Although the main risk factor for COPD is smoking, some individuals are observed to have a high forced expired volume in 1 second (FEV₁) despite many years of heavy smoking. We hypothesised that these “resistant smokers” may harbour variants which protect against lung function decline caused by smoking and provide insight into the genetic determinants of lung health. We undertook whole exome re-sequencing of 100 heavy smokers who had healthy lung function given their age, sex, height and smoking history and applied three complementary approaches to explore the genetic architecture of smoking resistance. Firstly, we identified novel functional variants in the “resistant smokers” and looked for enrichment of these novel variants within biological pathways. Secondly, we undertook association testing of all exonic variants individually with two independent control sets. Thirdly, we undertook gene-based association testing of all exonic variants. Our strongest signal of association with smoking resistance for a non-synonymous SNP was for rs10859974 (P = 2.34×10⁻⁴) in CCDC38, a gene which has previously been reported to show association with FEV₁/FVC, and we demonstrate moderate expression of CCDC38 in bronchial epithelial cells. We identified an enrichment of novel putatively functional variants in genes related to cilia structure and function in resistant smokers. Ciliary function abnormalities are known to be associated with both smoking and reduced mucociliary clearance in patients with COPD. We suggest that genetic influences on the development or function of cilia in the bronchial epithelium may affect growth of cilia or the extent of damage caused by tobacco smoke.     

The subgingival microbiome of clinically healthy current and never smokers

Dysbiotic oral bacterial communities have a critical role in the etiology and progression of periodontal diseases. The goal of this study was to investigate the extent to which smoking increases risk for disease by influencing the composition of the subgingival microbiome in states of clinical health. Subgingival plaque samples were collected from 200 systemically and periodontally healthy smokers and nonsmokers. 16S pyrotag sequencing was preformed generating 1 623 713 classifiable sequences, which were compared with a curated version of the Greengenes database using the quantitative insights into microbial ecology pipeline. The subgingival microbial profiles of smokers and never-smokers were different at all taxonomic levels, and principal coordinate analysis revealed distinct clustering of the microbial communities based on smoking status. Smokers demonstrated a highly diverse, pathogen-rich, commensal-poor, anaerobic microbiome that is more closely aligned with a disease-associated community in clinically healthy individuals, suggesting that it creates an at-risk-for-harm environment that is primed for a future ecological catastrophe.     

Dental Health in Smokers with and without COPD

The association between chronic obstructive pulmonary disease (COPD) and periodontal disease is sparsely studied. The aim was to describe the co-variation of periodontitis and lung function impairment in smokers. The hypothesis was that the destructive processes in the mouth and the lungs are interdependent due to a general individual susceptibility to detrimental effects of tobacco smoke. Smokers with COPD (n = 28) stage II and III according to GOLD guidelines and smokers without COPD (n = 29) and healthy non-smokers (n = 23) participated in the study. The groups of smokers were matched for cumulative exposure to tobacco smoke. Radiographic, general and dental clinical examination, lung function measurements and quality of life (SF-36) assessment were conducted. The relationship between respiratory and dental outcomes was analyzed. Dental health, assessed by plaque, gingival bleeding, periodontal pocket depth and loss of teeth was impaired in the smokers compared with non-smokers with no major differences between smokers with and without COPD. There was, however, a weak correlation between periodontitis and emphysema/impaired diffusion capacity. Impaired quality of life was associated with smoking and impaired lung function but not influenced by dental status. In conclusion periodontitis was strongly associated with smoking, weakly associated with lung tissue destruction and very weakly or even not at all associated with chronic airflow limitation. The results indicate that, although there was a co-variation between periodontitis and pathologic lung processes in smokers, the risk of developing COPD, as defined by spirometric outcomes, is not associated with the risk of impaired dental health in smokers.     

Preliminary Results of National Amyotrophic Lateral Sclerosis (ALS) Registry Risk Factor Survey Data

BackgroundThe National ALS Registry is made up of two components to capture amyotrophic lateral sclerosis (ALS) cases: national administrative databases (Medicare, Medicaid, Veterans Health Administration and Veterans Benefits Administration) and self-identified cases captured by the Registry’s web portal. This study describes self-reported characteristics of U.S. adults with ALS using the data collected by the National ALS Registry web portal risk factor surveys only from October 19, 2010 through December 31, 2013.ObjectiveTo describe findings from the National ALS Registry’s web portal risk factor surveys.MeasurementsThe prevalence of select risk factors among adults with ALS was determined by calculating the frequencies of select risk factors—smoking and alcohol (non, current and former) histories, military service and occupational history, and family history of neurodegenerative diseases such as ALS, Alzheimer’s and/or Parkinson’s.ResultsNearly half of survey respondents were ever smokers compared with nearly 41% of adults nationally. Most respondents were ever drinkers which is comparable to national estimates. The majority were light drinkers. Nearly one-quarter of survey respondents were veterans compared with roughly 9% of US adults nationally. Most respondents were retired or disabled. The industries in which respondents were employed for the longest time were Professional and Scientific and Technical Services. When family history of neurodegenerative diseases in first degree relatives was evaluated against our comparison group, the rates of ALS were similar, but were higher for Parkinson’s disease, Alzheimer’s disease and any neurodegenerative diseases.ConclusionsThe National ALS Registry web portal, to our knowledge, is the largest, most geographically diverse collection of risk factor data about adults living with ALS. Various characteristics were consistent with other published studies on ALS risk factors and will allow researchers to generate hypotheses for future research.     

The Taxonomy Statistic Uncovers Novel Clinical Patterns in a Population of Ischemic Stroke Patients

In this paper, we describe a simple taxonomic approach for clinical data mining elaborated by Marczewski and Steinhaus (M-S), whose performance equals the advanced statistical methodology known as the expectation-maximization (E-M) algorithm. We tested these two methods on a cohort of ischemic stroke patients. The comparison of both methods revealed strong agreement. Direct agreement between M-S and E-M classifications reached 83%, while Cohen’s coefficient of agreement was κ = 0.766(P < 0.0001). The statistical analysis conducted and the outcomes obtained in this paper revealed novel clinical patterns in ischemic stroke patients. The aim of the study was to evaluate the clinical usefulness of Marczewski-Steinhaus’ taxonomic approach as a tool for the detection of novel patterns of data in ischemic stroke patients and the prediction of disease outcome. In terms of the identification of fairly frequent types of stroke patients using their age, National Institutes of Health Stroke Scale (NIHSS), and diabetes mellitus (DM) status, when dealing with rough characteristics of patients, four particular types of patients are recognized, which cannot be identified by means of routine clinical methods. Following the obtained taxonomical outcomes, the strong correlation between the health status at moment of admission to emergency department (ED) and the subsequent recovery of patients is established. Moreover, popularization and simplification of the ideas of advanced mathematicians may provide an unconventional explorative platform for clinical problems.     

Serum Taurine and Stroke Risk in Women: A Prospective,Nested Case-Control Study

Background

Taurine (2-aminoethanesulfonic acid), a conditionally essential sulfur-containing amino acid, is mainly obtained from diet in humans. Experimental studies have shown that taurine’s main biological actions include bile salt conjugation, blood pressure regulation, anti-oxidation, and anti-inflammation.

Methods

We conducted a prospective case-control study nested in the New York University Women’s Health Study, a cohort study involving 14,274 women enrolled since 1985. Taurine was measured in pre-diagnostic serum samples of 241 stroke cases and 479 matched controls.

Results

There was no statistically significant association between serum taurine and stroke risk in the overall study population. The adjusted ORs for stroke were 1.0 (reference), 0.87 (95% CI, 0.59–1.28), and 1.03 (95% CI, 0.69–1.54) in increasing tertiles of taurine (64.3–126.6, 126.7–152.9, and 153.0–308.5 nmol/mL, respectively). A significant inverse association between serum taurine and stroke risk was observed among never smokers, with an adjusted OR of 0.66 (95% CI, 0.37–1.18) and 0.50 (95% CI, 0.26–0.94) for the second and third tertile, respectively (p for trend = 0.01), but not among past or current smokers (p for interaction < 0.01).

Conclusions

We observed no overall association between serum taurine and stroke risk, although a protective effect was observed in never smokers, which requires further investigation.Taurine, Stroke, Epidemiology, Prospective, Case-control study, NYUWHS.     

Using “Big Data” to Capture Overall Health Status: Properties and Predictive Value of a Claims-Based Health Risk Score

BackgroundInvestigators across many fields often struggle with how best to capture an individual’s overall health status, with options including both subjective and objective measures. With the increasing availability of “big data,” researchers can now take advantage of novel metrics of health status. These predictive algorithms were initially developed to forecast and manage expenditures, yet they represent an underutilized tool that could contribute significantly to health research. In this paper, we describe the properties and possible applications of one such “health risk score,” the DxCG Intelligence tool.MethodsWe link claims and administrative datasets on a cohort of U.S. workers during the period 1996–2011 (N = 14,161). We examine the risk score’s association with incident diagnoses of five disease conditions, and we link employee data with the National Death Index to characterize its relationship with mortality. We review prior studies documenting the risk score’s association with other health and non-health outcomes, including healthcare utilization, early retirement, and occupational injury.

Results and Conclusions

We find that the risk score is associated with outcomes across a variety of health and non-health domains. These examples demonstrate the broad applicability of this tool in multiple fields of research and illustrate its utility as a measure of overall health status for epidemiologists and other health researchers.     

Nicotine in smokers,non-smokers and room air

Nicotine is commonly observed in smokers' urine, and this circumstance was used as a means of developing atmospheric pressure ionization (API) mass spectrometric techniques for the detection of volatile components of urine which behave as bases in the gas phase. When these methods where applied in an examination of urinary bases of non-smokers who shared the laboratory areas with smokers, nicotine was found to be present to the extent of about 5% of that observed for smokers. Two routes of nicotine transfer seemed possible: water and air. The water supply was found to be nicotine-free. An air analysis method was devised; this showed that nicotine was present in the laboratory air, so that the probable route of transfer for non-smokers is through room air.     

Relationship of Self-Rated Health to Stroke Incidence and Mortality in Older Individuals with and without a History of Stroke: A Longitudinal Study of the MRC Cognitive Function and Ageing (CFAS) Population

Introduction

Poor self-rated health (SRH) has been associated with increased risk of death and poor health outcomes even after adjusting for confounders. However its’ relationship with disease-specific mortality and morbidity has been less studied. SRH may also be particularly predictive of health outcomes in those with pre-existing conditions. We studied whether SRH predicts new stroke in older people who have never had a stroke, or a recurrence in those with a prior history of stroke.

Methods

MRC CFAS I is a multicentre cohort study of a population representative sample of people in their 65th year and older. A comprehensive interview at baseline included questions about presence of stroke, self-rated health and functional disability. Follow-up at 2 years included self-report of stroke and stroke death obtained from death certificates. Multiple logistical regression determined odds of stroke at 2 years adjusting for confounders including disability and health behaviours. Survival analysis was performed until June 2014 with follow-up for up to 13 years.

Results

11,957 participants were included, of whom 11,181 (93.8%) had no history of stroke and 776 (6.2%) one or more previous strokes. Fewer with no history of stroke reported poor SRH than those with stroke (5 versus 21%). In those with no history of stroke, poor self-rated health predicted stroke incidence (OR 1.5 (1.1–1.9)), but not stroke mortality (OR 1.2 (0.8–1.9)) at 2 years nor for up to 13 years (OR 1.2(0.9–1.7)). In those with a history of stroke, self-rated health did not predict stroke incidence (OR 0.9(0.6–1.4)), stroke mortality (OR 1.1(0.5–2.5)), or survival (OR 1.1(0.6–2.1)).

Conclusions

Poor self-rated health predicts risk of stroke at 2 years but not stroke mortality among the older population without a previous history of stroke. SRH may be helpful in predicting who may be at risk of developing a stroke in the near future.     

Shunt in the diagnosis of initial lung lesion in smokers

Cigarette smoking is an important risk factor for all respiratory tract diseases. Unfortunately, the symptoms develop slowly, thus patients feel the consequences of the slowly developing inflammation too late. The inflammation first develops in the area of respiratory bronchioles. In this stage, the disease is asymptomatic. The study included a sample of 31 smokers, mean age 36.38 years, with normal spirometry indices, acid-base status and arterial blood gases. The mean smoking index was 11.28 smoking/years. All subjects were healthy, without any subjective health problems or disease indicators. The aim was to define dead lung area (V/Q) as an early indicator of changes in smokers. Study results demonstrated the mean shunt value in smokers of 8.25%, which showed positive correlation with smoking. The shunt size yielded negative correlation with the forced expiratory volume in one second and midexpiratory flow in smokers. In conclusion, determination of lung shunt is a simple method that is sensitive enough in the diagnosis of initial lung lesion due to cigarette smoking.     

Myofibroblast expression in airways and alveoli is affected by smoking and COPD

Background

Chronic obstructive pulmonary disease (COPD) is characterized by structural changes in alveoli and airways. Our aim was to analyse the numbers of alpha-smooth muscle actin (α-SMA) positive cells, as a marker of myofibroblasts, in different lung compartments in non-smokers and smokers with normal lung function or COPD.

Methods

α-SMA, tenascin-C (Tn-C) and EDA-fibronectin in alveolar level and airways were assayed by immunohistochemistry and quantified by image analysis. Immunohistochemical findings were correlated with clinical data. α-SMA protein was also analysed by Western blotting from fibroblastic cells cultured from peripheral lung of non-smokers, smokers without COPD and smokers with COPD.

Results

In many cases, the endings of the detached alveolar walls were widened, the structures of which were named as widened alveolar tips. Widened alveolar tips contained α-SMA positive cells, which were obviously myofibroblasts. There were less alveolar tips containing positive cells for α-SMA in alveoli and α-SMA positive cells in bronchioles in smokers and in COPD compared to non-smokers. The quantity of α-SMA positive cells was increased in bronchi in COPD. Tn-C was elevated in bronchi in COPD and smokers’ lung. The α-SMA protein level was 1.43-fold higher in stromal cells cultured from non-smokers than in those of smokers.

Conclusions

Myofibroblasts are localized variably in normal and diseased lung. This indicates that they have roles in both regeneration of lung and pathogenesis of COPD. The widened alveolar tips, these newly characterized histological structures, seemed to be the source of myofibroblasts at the alveolar level.     

Impact of functional status at six months on long term survival in patients with ischaemic stroke: prospective cohort studies

Objective To estimate the impact on long term survival of functional status at six months after ischaemic stroke.Design Prospective cohort study.Settings Three cohorts: Oxfordshire community stroke project, Lothian stroke register, and the first international stroke trial (in the United Kingdom).Participants 7710 patients with ischaemic stroke registered between 1981 and 2000 and followed up for a maximum of 19 years.Main outcome measures Functional status at six months after stroke assessed with modified Rankin scale or “two simple questions.” Mortality during follow-up. Survival analysis with Kaplan-Meier curves, log rank test, and Cox’s regression model.Results In a combined analysis of all three cohorts, among patients who survived to assessment six months after the index stroke, the subsequent median length of survival among those independent in daily living and those dependent was 9.7 years (95% confidence interval 8.9 to 10.6) and 6.0 years (5.7 to 6.4), respectively. In a combined analysis of the Oxfordshire and Lothian cohorts, subsequent median survival fell progressively from 12.9 years (10.0 to 15.9) for patients with a Rankin score of 0-1 at six months after the stroke to 2.5 years (1.4 to 3.5) for patients with a Rankin score of 5. All previously stated differences in median survival were significant (log rank test P<0.001). The influence of functional outcome on survival remained significant (P<0.05) in each cohort after adjustment for relevant covariates (such as age, presence of atrial fibrillation, visible infarct on computed tomography, subtype of stroke) in a Cox’s regression model.Conclusion Functional status six months after an ischaemic stroke is associated with long term survival. Early interventions that reduce dependency at six months might have positive effects on long term survival.     

Joint Effects of Smoking and Silicosis on Diseases to the Lungs

Smokers are subject to being more susceptible to the long-term effects of silica dust, whilst it remains unclear whether the joint effect of smoking and silicosis differs amongst diseases to the lungs; this study aims to address this knowledge gap. This was a historical cohort study comprised of 3202 silicotics in Hong Kong during 1981–2005 who were followed up till 31/12/2006. We estimated the standardized mortality ratio (SMR) in the smoking and never smoking silicotics using the mortality rates of male general population indiscriminately by smoking status, but these SMRs were regarded as biased. We adjusted these biased SMRs using “smoking adjustment factors (SAF)”. We assessed the multiplicative interaction between smoking and silicosis using ‘relative silicosis effect (RSE)’ that was the ratio of SAF-corrected SMR of smoking silicotics to the never smokers. A RSE differs significantly from one implies the presence of multiplicative interaction. A significant excess SMR was observed for respiratory diseases (lung cancer, chronic obstructive pulmonary diseases [COPD], silicosis) and other diseases to the lungs (pulmonary heart disease, tuberculosis). All the ‘biased-SMRs’ in smokers were higher than those in never smokers, but the SAF-corrected SMRs became higher in never smokers. The RSE was 0.95 (95%CI: 0.37–3.55), 0.94 (95%CI: 0.42–2.60), and 0.81 (95%CI: 0.60–1.19) for lung cancer, COPD, and silicosis; whilst it was 1.21 (95%CI: 0.32–10.26) for tuberculosis and 1.02 (95%CI: 0.16–42.90) for pulmonary heart disease. This study firstly demonstrated the joint effect of smoking and silicosis may differ amongst diseases to the lungs, but power is limited.     

Recognizing Complex Upper Extremity Activities Using Body Worn Sensors

To evaluate arm-hand therapies for neurological patients it is important to be able to assess actual arm-hand performance objectively. Because instruments that measure the actual quality and quantity of specific activities in daily life are lacking, a new measure needs to be developed. The aims of this study are to a) elucidate the techniques used to identify upper extremity activities, b) provide a proof-of-principle of this method using a set of activities tested in a healthy adult and in a stroke patient, and c) provide an example of the method’s applicability in daily life based on readings taken from a healthy adult. Multiple devices, each of which contains a tri-axial accelerometer, a tri-axial gyroscope and a tri-axial magnetometer were attached to the dominant hand, wrist, upper arm and chest of 30 healthy participants and one stroke patient, who all performed the tasks ‘drinking’, ‘eating’ and ‘brushing hair’ in a standardized environment. To establish proof-of-principle, a prolonged daily life recording of 1 participant was used to identify the task ‘drinking’. The activities were identified using multi-array signal feature extraction and pattern recognition algorithms and 2D-convolution. The activities ‘drinking’, ‘eating’ and ‘brushing hair’ were unambiguously recognized in a sequence of recordings of multiple standardized daily activities in a healthy participant and in a stroke patient. It was also possible to identify a specific activity in a daily life recording. The long term aim is to use this method to a) identify arm-hand activities that someone performs during daily life, b) determine the quantity of activity execution, i.e. amount of use, and c) determine the quality of arm-hand skill performance.     

Estrogen Therapy and Ischemic Stroke in Women with Diabetes Aged Over 55 Years: A Nation-Wide Prospective Population-Based Study in Taiwan

This study explores the possible association between the risk of ischemic stroke and conjugated equine estrogen (CEE) use in women who are over 55 years old and have diabetes. Data from the National Health Insurance system of Taiwan were used to identify 428 women over 55 years old with diabetes who used CEE (0.625 mg daily) from 2003 to 2009. For comparison, 21026 women with diabetes who were from the same cohort and did not use estrogen were used as a control group, excluding patients with previous ischemic stroke at the baseline. The propensity score method was used to identify a 1:3 ratio for the matched cohort (n = 1284). Covariates used for propensity score-matching included age and comorbidities. Cox’s proportional hazard model was applied to estimate the relationship between CEE use and ischemic stroke. The overall incidence of ischemic stroke was significantly lower in patients using CEE than in the control group (0.9% compared with 3.0%, p = 0.016). Further analyses using Cox’s proportional hazard model revealed that after adjusting for age, comorbidities, socioeconomic status, urbanization, and other medications associated with ischemic stroke, a lower risk was present in patients with CEE use (hazard ratio: 0.34; 95% confidence interval: 0.12–0.97). Time of menopause could not be identified because of the nature of the database. CEE might decrease the risk of ischemic stroke in women with diabetes aged over 55 years, according to this population-based study.     

Joint Effect of Education and Main Lifetime Occupation on Late Life Health: A Cross-Sectional Study of Older Adults in Xiamen,China

Background

The effects of education and occupation on health have been well documented individually, but little is known about their joint effect, especially their cumulative joint effect on late life health.

Methods

We enrolled 14,292 participants aged 60+ years by multistage sampling across 173 communities in Xiamen, China, in 2013. Heath status was assessed by the ability to perform six basic activities of daily life. Education was classified in four categories: ‘Illiterate’, ‘Primary’, ‘Junior high school’ and ‘Senior high school and beyond’. Main lifetime occupation was also four categorized: ‘Employed’, ‘Farmer’, ‘Jobless’ and ‘Others’. Odds ratios (ORs) were estimated by random-intercept multilevel models regressing health status on education and main lifetime occupation with or without their interactions, adjusting by some covariates.

Results

Totally, 13,880 participants had complete data, of whom 12.5% suffered from disability, and ‘Illiterate’ and ‘Farmer’ took up the greatest proportion (33.01% and 42.72%, respectively). Participants who were higher educated had better health status (ORs = 0.62, 0.46, and 0.44 for the ‘Primary’, ‘Junior high school’, and ‘Senior high school and beyond’, respectively, in comparison with ‘Illiterate’). Those who were long term jobless in early life had poorest heath (ORs = 1.88, 95% CI 1.47 to 2.40). Unexpectedly, for the farmers, the risk of poor health gradually increased in relation to higher education level (ORs = 1.26, 1.28, 1.40 and 2.24, respectively). For the ‘Employed’, similar ORs were obtained for the ‘Junior high school’ and ‘Senior high school and beyond’ educated (both ORs = 1.01). For the ‘Farmer’ and ‘Jobless’, participants who were ‘Illiterate’ and ‘Primary’ educated also showed similar ORs.

Conclusions

Both education and main lifetime occupation were associated with late life health. Higher education was observed to be associated with better health, but such educational advantage was mediated by main lifetime occupation.     

Measuring and Validating a General Cancer Predisposition Perception Scale: An Adaptation of the Revised-IPQ-Genetic Predisposition Scale

Background

Illness perceptions are linked to individual help-seeking and preventive behaviors. Previous illness perception studies have identified five dimensions of illness-related experience and behaviour. The Revised Illness Perception Questionnaire (IPQ-R) for genetic predisposition (IPQ-R-GP) was developed to measure illness perceptions in those genetically-predisposed to blood disease. We adapted the IPQ-R-GP to measure perceptions of generalized cancer predisposition. This paper describes the development and validation of the Cancer Predisposition Perception Scale (CPPS).

Methods

The draft CPPS scale was first administered to 167 well Hepatitis B carriers and 123 other healthy individuals and the factor structure was examined using Exploratory Factor Analysis. Then the factor structure was confirmed in a second sample comprising 148 healthy controls, 150 smokers and 152 passive smokers using Confirmatory Factor Analysis (CFA).

Results

Six-factors comprising 26 items provided optimal fit by eigen and scree-plot methods, accounting for 58.9% of the total variance. CFA indicated good fit of the six-factor model after further excluding three items. The six factors, Emotional representation (5 items), Illness coherence (4 items), Treatment control (3 items), Consequences (5 items), Internal locus of control (2 items) and External locus of control (4 items) demonstrated adequate-to-good subscale internal consistency (Cronbach’s α = 0.63–0.90). Divergent validity was suggested by low correlations with optimism, self-efficacy, and scales for measuring physical and psychological health symptoms.

Conclusion

The CPPS appears to be a valid measure of perceived predisposition to generic cancer risks and can be used to examine cancer-risk-related cognitions in individuals at higher and lower cancer risk.     

The Relative Impacts of Disease on Health Status and Capability Wellbeing: A Multi-Country Study

Background

Evaluations of the impact of interventions for resource allocation purposes commonly focus on health status. There is, however, also concern about broader impacts on wellbeing and, increasingly, on a person''s capability. This study aims to compare the impact on health status and capability of seven major health conditions, and highlight differences in treatment priorities when outcomes are measured by capability as opposed to health status.

Methods

The study was a cross-sectional four country survey (n = 6650) of eight population groups: seven disease groups with: arthritis, asthma, cancer, depression, diabetes, hearing loss, and heart disease and one health population ‘comparator’ group. Two simple self-complete questionnaires were used to measure health status (EQ-5D-5L) and capability (ICECAP-A). Individuals were classified by illness severity using condition-specific questionnaires. Effect sizes were used to estimate: (i) the difference in health status and capability for those with conditions, relative to a healthy population; and (ii) the impact of the severity of the condition on health status and capability within each disease group.

Findings

5248 individuals were included in the analysis. Individuals with depression have the greatest mean reduction in both health (effect size, 1.26) and capability (1.22) compared to the healthy population. The effect sizes for capability for depression are much greater than for all other conditions, which is not the case for health. For example, the arthritis group effect size for health (1.24) is also high and similar to that of depression, whereas for the same arthritis group, the effect size for capability is much lower than that for depression (0.55). In terms of severity within disease groups, individuals categorised as ''mild'' have similar capability levels to the healthy population (effect sizes <0.2, excluding depression) but lower health status than the healthy population (≥0.4).

Conclusion

Significant differences exist in the relative effect sizes across diseases when measured by health status and capability. In terms of treating morbidity, a shift in focus from health gain to capability gain would increase funding priorities for patients with depression specifically and severe illnesses more generally.     

Humans Have Antibodies against a Plant Virus: Evidence from Tobacco Mosaic Virus

Tobacco mosaic virus (TMV), a widespread plant pathogen, is found in tobacco (including cigarettes and smokeless tobacco) as well as in many other plants. Plant viruses do not replicate or cause infection in humans or other mammals. This study was done to determine whether exposure to tobacco products induces an immune response to TMV in humans. Using a sandwich ELISA assay, we detected serum anti-TMV antibodies (IgG, IgG1, IgG3, IgG4, IgA, and IgM) in all subjects enrolled in the study (20 healthy smokers, 20 smokeless-tobacco users, and 20 non-smokers). Smokers had a higher level of serum anti-TMV IgG antibodies than non-smokers, while the serum level of anti-TMV IgA from smokeless tobacco users was lower than smokers and non-smokers. Using bioinformatics, we also found that the human protein TOMM40L (an outer mitochondrial membrane 40 homolog – like translocase) contains a strong homology of six contiguous amino acids to the TMV coat protein, and TOMM40L peptide exhibited cross-reactivity with anti-TMV antibodies. People who smoke cigarettes or other tobacco products experience a lower risk of developing Parkinson’s disease, but the mechanism by which this occurs is unclear. Our results showing molecular mimicry between TMV and human TOMM40L raise the question as to whether TMV has a potential role in smokers against Parkinson’s disease development. The potential mechanisms of molecular mimicry between plant viruses and human disease should be further explored.