NSAID-exacerbated respiratory disease (N-ERD): a population study

BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) may exacerbate respiratory symptoms. A recent EAACI position paper recommended the use of an acronym, N-ERD (NSAID-exacerbated respiratory disease), for this hypersensitivity associated with asthma or chronic rhinosinusitis (CRS) with or without nasal polyposis. Our aim was to estimate the prevalence of N-ERD and identify factors associated with N-ERD.MethodsIn 2016, a cross-sectional questionnaire survey of a random adult population of 16 000 subjects aged 20–69 years was performed in Helsinki and Western Finland. The response rate was 51.5%.ResultsThe prevalence was 1.4% for N-ERD, and 0.7% for AERD. The prevalence of N-ERD was 6.9% among subjects with asthma and 2.7% among subjects with rhinitis.The risk factors for N-ERD were older age, family history of asthma or allergic rhinitis, long-term smoking and exposure to environmental pollutants. Asthmatic subjects with N-ERD had a higher risk of respiratory symptoms, severe hypersensitivity reactions and hospitalisations than asthmatic subjects without N-ERD. The sub-phenotype of N-ERD with asthma was most symptomatic. Subjects with rhinitis associated with N-ERD, which would not be included in AERD, had the least symptoms.ConclusionWe conclude that the prevalence of N-ERD was 1.4% in a representative Finnish adult population sample. Older age, family history of asthma or allergic rhinitis, cumulative exposure to tobacco smoke, secondhand smoke, and occupational exposures increased odds of N-ERD. N-ERD was associated with significant morbidity.

Demographic patterns of human antibody levels to Simulium damnosum s.l. saliva in onchocerciasis-endemic areas: An indicator of exposure to vector bites

Background In onchocerciasis endemic areas in Africa, heterogenous biting rates by blackfly vectors on humans are assumed to partially explain age- and sex-dependent infection patterns with Onchocerca volvulus. To underpin these assumptions and further improve predictions made by onchocerciasis transmission models, demographic patterns in antibody responses to salivary antigens of Simulium damnosum s.l. are evaluated as a measure of blackfly exposure. Methodology/Principal findings Recently developed IgG and IgM anti-saliva immunoassays for S. damnosum s.l. were applied to blood samples collected from residents in four onchocerciasis endemic villages in Ghana. Demographic patterns in antibody levels according to village, sex and age were explored by fitting generalized linear models. Antibody levels varied between villages but showed consistent patterns with age and sex. Both IgG and IgM responses declined with increasing age. IgG responses were generally lower in males than in females and exhibited a steeper decline in adult males than in adult females. No sex-specific difference was observed in IgM responses. Conclusions/Significance The decline in age-specific antibody patterns suggested development of immunotolerance or desensitization to blackfly saliva antigen in response to persistent exposure. The variation between sexes, and between adults and youngsters may reflect differences in behaviour influencing cumulative exposure. These measures of antibody acquisition and decay could be incorporated into onchocerciasis transmission models towards informing onchocerciasis control, elimination, and surveillance.

Stroke and Ischemic Heart Disease With Enzyme-inducing Antiseizure Medications: Time to Change Prescribing Habits

Importance: Enzyme-inducing antiseizure medications (eiASMs) have been hypothesized to be associated with long-term risks of cardiovascular disease. Objective: To quantify and model the putative hazard of cardiovascular disease secondary to eiASM use. Design, Setting, and Participants: This cohort study covered January 1990 to March 2019 (median [IQR] follow-up, 9 [4–15], years). The study linked primary care and hospital electronic health records at National Health Service hospitals in England. People aged 18 years or older diagnosed as having epilepsy after January 1, 1990, were included. All eligible patients were included with a waiver of consent. No patients were approached who withdrew consent. Analysis began January 2021 and ended August 2021. Exposures: Receipt of 4 consecutive EI ASMs (carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, rufinamide, or topiramate) following an adult-onset (age >/=18 years) epilepsy diagnosis or repeated exposure in a weighted cumulative exposure model. Main Outcomes and Measures: Three cohorts were isolated, 1 of which comprised all adults meeting a case definition for epilepsy diagnosed after 1990, 1 comprised incident cases diagnosed after 1998 (hospital linkage date), and 1 was limited to adults diagnosed with epilepsy at 65 years or older. Outcome was incident cardiovascular disease (ischemic heart disease or ischemic or hemorrhagic stroke). Hazard of incident cardiovascular disease was evaluated using adjusted propensity-matched survival analyses and weighted cumulative exposure models. Results: Of 10,916,166 adults, 50,888 (.6%) were identified as having period-prevalent cases (median [IQR] age, 32 [19–50] years; 16 584 [53%] female), of whom 31,479 (62%) were diagnosed on or after 1990 and were free of cardiovascular disease at baseline. In a propensity-matched Cox proportional hazards model adjusted for age, sex, baseline socioeconomic status, and cardiovascular risk factors, the hazard ratio for incident cardiovascular disease was 1.21 (95% CI, 1.06–1.39) for those receiving eiASMs. The absolute difference in cumulative hazard diverges by more than 1% and greater after 10 years. For those with persistent exposure beyond 4 prescriptions, the median hazard ratio increased from a median (IQR) of 1.54 (1.28–1.79) when taking a relative defined daily dose of an eiASM of 1 to 2.38 (1.52–3.56) with a relative defined daily dose of 2 throughout a maximum of 25 years' follow-up compared with those not receiving an eiASM. The hazard was elevated but attenuated when restricting analyses to incident cases or those diagnosed when older than 65 years. Conclusions and Relevance: The hazard of incident cardiovascular disease is higher in those receiving eiASMs. The association is dose dependent and the absolute difference in hazard seems to reach clinical significance by approximately 10 years from first exposure.

Hematological Effects and Benchmark Doses of Long-Term Co-Exposure to Benzene, Toluene, and Xylenes (BTX) in BTX-Exposed Petrochemical Workers Cohort (BEPWC)

Background Ubiquitous benzene, toluene, and xylenes (BTX) frequently occur together. Exposure to single BTX component and BTX-rich mixtures could induce hematological effects. However, it still needs to clarify the hematological influences of long-term co-exposure to BTX components, and propose reference exposure levels (REL) base on their hematological effects. Objective We sought to evaluate the hematological effects of long-term BTX co-exposure and estimate REL based on these effects. Methods We established BTX-Exposed Petrochemical Workers Cohort (BEPWC), quantified long-term BTX exposure levels by calculating cumulative exposure doses (CED), and detected multiple hematologic parameters in both baseline and follow-up stages. Generalized weighted quantile sum (gWQS) regression models were used to evaluate the combined effects of BTX components and identify their contributions. Benchmark Dose (BMD) Software was used to calculate BMD and the lower confidence limits (BMDL). Results Most hematologic parameters were decreased after four-year follow-up (P<0.05). We found a positive association of benzene with the decline in monocyte counts (β = 0.012), and a negative association of toluene with the decline in mean corpuscular hemoglobin concentrations (β =-0.905) after false discovery rate (FDR) adjustment. The associations of BTX components with the decline in hematologic parameters were mostly significantly stronger in subjects with higher baseline parameters, males, drinkers, and overweighted subjects (FDR-adjusted Pinteraction <0.05). BTX components had positive combined effects on the decline in monocyte counts, red blood cell counts, and hemoglobin concentrations (Ptrend for WQS index <0.05). BMD (and BMDL) for CED levels of benzene, toluene, and xylene were estimated at 2.138 (1.559), 1.449 (1.325), and 2.937 (2.312) mg/m3×year, respectively. Conclusions Our study revealed complex hematological effects of long-term BTX occupational co-exposure, and proposed some REL-TWA around 0.01 ppm for BTX components based on their hematological effects. All these findings are worthy of further investigation.

Time course of serum uric acid accumulation and the risk of diabetes mellitus

Background The impact of long-term serum uric acid (SUA) exposure and time course of SUA accumulation on diabetes mellitus (DM) is unknown. This study aimed to evaluate the association of cumulative SUA (cumSUA) exposure and its accumulation time course with risk of DM. Methods This prospective study included 46,434 participants without DM and underwent three examinations at 2006, 2008, and 2010. CumSUA from 2006 to 2010 was calculated, multiplying mean values between consecutive examinations by time intervals between visits. Time course of SUA accumulation was categorized as the slope of SUA versus time from 2006 to 2010, or by splitting the overall accumulation into an early (cumSUA06-08) and late accumulation (cumSUA08-10). Results During 6.99 years of follow-up, we identified 2971 incident DM cases. In the fully adjusted model, a higher risk of DM was observed in participants with the highest quartile of cumSUA (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.17–1.46), cumulative burden >0 (HR, 1.23; 95% CI, 1.08–1.40), and with 6 year of hyperuricemia exposure duration (HR, 1.25; 95% CI, 1.01–1.55). When considering the time course of SUA accumulation, participants with a negative slope (HR, 1.05; 95% CI, 1.01–1.12), or combined with cumSUA ≥ median and a negative slope had elevated risk of DM (HR, 1.58; 95% CI, 1.18–2.11). Conclusions Incident DM risk depends on cumulative exposure of SUA and time course of SUA accumulation. Early SUA accumulation resulted in a greater risk increase compared with later accumulation, emphasizing the importance of optimal SUA control early in life.

Association Between Occupational Exposure to Formaldehyde and Cognitive Impairment

Objective:To our knowledge, no study has investigated the effect of exposure to formaldehyde on cognition in the general population. Our objective was to examine the association between occupational exposure to formaldehyde and cognitive impairment in middle-aged and young- old adults (≥45 years).Methods:In the French CONSTANCES cohort, cognitive function was assessed with a standardized battery of seven cognitive tests to evaluate global cognitive function, episodic verbal memory, language abilities and executive functions (e.g., Digit Symbol Substitution Test, DSST). A global cognitive score was created using principal component analysis. Cognitive impairment was assessed in reference to norms of neuropsychological battery according to age, sex and education. Lifetime exposure to formaldehyde was assessed using a French job-exposure matrix created in the framework of the Matgéné project. After performing multiple imputation, separate modified Poisson regression models were used to evaluate the association between cognitive impairment (<25th percentile) and formaldehyde exposure (exposed/never exposed), exposure duration, cumulative exposure index (CEI), and combination of CEI and time of last exposure.Results:Among 75 322 participants (median age: 57.5 years, women: 53%), 8% were exposed to formaldehyde during their professional life. These participants were at higher risk of global cognitive impairment (for global cognitive score: adjusted relative risk, aRR, 1.17, 95% confidence interval, CI: 1.11-1.23), after adjusting for confounders (age, sex, education, income, solvent exposure, Effort–Reward Imbalance, night-shift, repetitive, and noisy work). They were at higher risk of cognitive impairment for all cognitive domains explored. Longer exposure duration and high CEI were associated with cognitive impairment, with a dose-effect relationship for exposure duration. Recent exposure was associated with impairment in all cognitive domains. Time did not fully attenuate formaldehyde-associated cognitive deficits especially in highly exposed individuals (for DSST: high past exposure aRR 1.23, 95%CI: 1.11-1.36; high recent exposure: aRR 1.24, 95%CI: 1.13-1.35).Conclusion:Our findings highlight the long-term detrimental effect of formaldehyde exposure on cognitive health in a relatively young population.

Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Toward an Individualized Approach

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), characterized by the presence of autoantibodies to neutrophil cytoplasmic antigens, proteinase 3 (PR3), and myeloperoxidase (MPO), typically involves small blood vessels of the respiratory tract and kidneys. It includes distinct clinical syndromes: microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic GPA. GPA is commonly associated with PR3-ANCA, while MPA is associated with MPO-ANCA. AAVs have a complex pathogenesis, influenced by genetics and environmental factors. There is evidence for a loss of tolerance to neutrophil proteins, which leads to ANCA-mediated neutrophil activation and injury, with effector T cells and activation of the alternative pathway of the complement also involved. Advances in immunosuppressive treatment have drastically reduced mortality of AAV in the past decades, opting for a more individualized approach. Careful assessment of ANCA specificity, disease activity, organ damage, and quality of life allows for a tailored immunosuppressive therapy. Contemporary AAV treatment is characterized by regimens that minimize the cumulative exposure to glucocorticoids and cyclophosphamide, and novel approaches including complement blockage and immunosuppressant combinations might be the standard of care in the future. In this review, we examine the pathogenesis, clinical approach, and evidence-based treatment options for the management of AAV patients.

Association of Quantified Costal Cartilage Calcification and Long-Term Cumulative Blood Glucose Exposure: The Multi-Ethnic Study of Atherosclerosis

AimsAnecdotal reports have suggested increased soft tissue calcification in individuals with long-term exposures to high blood glucose. The association of costal cartilage calcification (CCC), a reliably quantifiable marker obtainable from non-contrast cardiac computed tomography (CT) with cumulative fasting blood glucose (FBG) exposure, is unknown. In this study, we aimed to determine the association between quantified CCC and cumulative glucose exposure using non-contrast coronary artery calcium (CAC) scoring computed tomography (CT) images in the Multi-Ethnic Study of Atherosclerosis (MESA).MethodsThe volume of bilateral CCC was quantified in high-density pixels (threshold of Hounsfield Unit&gt;180) using the CAC scoring CT images acquired in the 5th MESA exam. Prior long-term cumulative exposure to FBG was calculated by area under the FBG-time curve over ten years before the time of the CT exam.ResultsA total of 2,305 participants (mean age: 69, female/male: 1.3) were included in this study. The median CCC volume was lower in females than males (1158 mm3 [IQR: 1751] vs. 3054 mm3 [3851], p&lt;0.001). In cross-sectional analysis, quantified CCC was associated with FBG (9% increase per SD) and HbA1c (7% increase per SD) at the CT exam only in female participants after adjustment for age, race, BMI, and glomerular filtration rate. Only in female participants, quantified CCC was also associated with prior cumulative FBG (3% increase per decile change). In the subgroup of females with zero CAC scores, the adjusted CCC was still associated with FBG (13% increase per SD) at the time of CT exam and with prior cumulative FBG exposure (4% increase per decile change) before the CT exam.ConclusionsThe CCC, a reliably quantified marker in non-contrast cardiac CT, is associated with 10-year cumulative FBG exposure only in female participants, even those with zero CAC.

Indoor Air Quality Campaign in an Occupied Low-Energy House with a High Level of Spatial and Temporal Discretization

Background and gaps. The topic of indoor air quality (IAQ) in low-energy buildings has received increasing interest over the past few years. Often based on two measurement points and on passive measurements over one week, IAQ studies are struggling to allow the calculation of pollutants exposure. Objectives. We would like to improve the evaluation of the health impacts, through measurements able to estimate the exposure of the occupants. Methodology. This article presents detailed IAQ measurements taken in an energy-efficient occupied house in France. Two campaigns were conducted in winter and spring. Total volatile organic compounds (TVOC), formaldehyde, the particle numbers and PM2.5, carbon dioxide (CO2), relative humidity (RH), temperature (T), ventilation airflows, and weather conditions were dynamically measured in several points. Laboratory and low-cost devices were used, and an inter-comparison was carried out for them. A survey was conducted to record all the daily activities of the inhabitants. IAQ performance indicators based on the different pollutants were calculated. Results. PM2.5 cumulative exposure did not exceed the threshold available in the literature. Formaldehyde concentrations were high, in the kitchen, where the average concentrations exceeded the threshold. However, the formaldehyde cumulative exposure of the occupants did not exceed the threshold. TVOC concentrations were found to reach the threshold. With these measurements performed with high spatial and temporal discretization, we showed that such detailed data allow for a better-quality health impacts assessment and for a better understanding of the transport of pollutants between rooms.

Dental fluorosis among people and livestock living on Gihaya Island in Lake Kivu, Rwanda

Background Dental fluorosis is caused by prolonged exposure to excessive fluoride during the period of permanent tooth formation and is characterized by tooth discoloration, pitting, and loss of shape. Communities living near Lake Kivu in Western Rwanda exhibit a high prevalence of dental fluorosis; however, data on prevalence and risk factors are scarce. Methods This cross sectional, quantitative study used a One Health approach to investigate dental fluorosis prevalence among people and livestock and to measure fluoride content in the environment. In 2018, oral health examinations were conducted to assess the prevalence of fluorosis in children (aged 9 to 15 years), cattle and goats residing on Gihaya Island (Rwanda, East Africa). All children and cattle/goats meeting basic eligibility criteria (e.g., island residence) were invited to participate. Presence and severity of dental fluorosis was categorized according to the Dean’s Fluorosis Index. Samples of local foods, water, soil and grass were collected from communal sources and individual households and analyzed for fluoride content using standard laboratory techniques. Descriptive and binomial analyses (Fisher Exact Test) were used to assess this dataset. Results Overall, 186 children and 85 livestock owners (providing data of 125 livestock -23 cattle and 102 goats) participated. Dental fluorosis was recorded in 90.7% of children and 76% of livestock. Moderate to severe fluorosis was observed in 77% children while goats and cattle most often exhibited mild or absent/questionable severity, respectively. Water from Lake Kivu (used primarily for human cooking water and livestock drinking water) contained fluoride levels that were consistently higher than the maximum threshold (1.5 mg/L) recommended by the World Health Organization. Other sources (borehole and rainwater) were within safe limits. All food, soil and grass samples contained fluoride. The highest levels were observed in porridge (0.5 mg/g) and small fishes (1.05 mg/g). Conclusions Altogether, dental fluorosis was highly prevalent among children and goats on Gihaya Island with various food and water sources contributing a cumulative exposure to fluoride. An immediate and coordinated response across human, animal and water professionals is needed to reduce fluoride exposure within safe limits for island residents.