Plasma thymic stromal lymphopoietin (TSLP) in adults with non-severe asthma: the EGEA study.

Thymic stromal lymphopoietin (TSLP), a cytokine involved in severe asthma treatment, was never studied in non-severe asthma.Among 969 adults from a large epidemiological study, cross-sectional analyses showed that plasma TSLP levels were associated with increased age and BMI, male sex, smoking and high TSLP levels (one IQR increase) with current asthma and poor lung function. High TSLP levels were also associated with persistence of asthma attacks (aOR=2.14 (95% CI 1.23 to 3.72)) and dyspnoea (aOR=2.71 (95% CI 1.39 to 5.28)) 10 years later.Our results suggest that TSLP could be a cytokine of interest in non-severe asthma, and its determinants of circulating levels could be considered in asthma management.

Respiratory function in uncomplicated type 1 diabetes: Blunted during exercise even though normal at rest!

AIMS: Type 1 diabetes is associated with a substantially increased risk of impaired lung function, which may impair aerobic fitness. We therefore aimed to examine the ventilatory response during maximal exercise and the pulmonary diffusion capacity function at rest in individuals with uncomplicated type 1 diabetes. METHODS: In all, 17 adults with type 1 diabetes free from micro-macrovascular complications (glycated haemoglobin: 8.0 ± 1.3%), and 17 non-diabetic adults, carefully matched to the type 1 diabetes group according to gender, age, level of physical activity and body composition, participated in our study. Lung function was assessed by spirometry and measurements of the combined diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) at rest. Subjects performed a maximal exercise test during which the respiratory parameters were measured. RESULTS: At rest, DLCO (30.4 ± 6.1 ml min-1  mmHg-1 vs. 31.4 ± 5.7 ml min-1 mmHg-1 , respectively, p = 0.2), its determinants Dm (membrane diffusion capacity) and Vc (pulmonary capillary volume) were comparable among type 1 diabetes and control groups, respectively. Nevertheless, spirometry parameters (forced vital capacity = 4.9 ± 1.0 L vs. 5.5 ± 1.0 L, p < 0.05; forced expiratory volume 1 = 4.0 ± 0.7 L vs. 4.3 ± 0.7 L, p < 0.05) were lower in individuals with type 1 diabetes, although in the predicted normal range. During exercise, ventilatory response to exercise was different between the two groups: tidal volume was lower in type 1 diabetes vs. individuals without diabetes (p < 0.05). Type 1 diabetes showed a reduced VO2max (34.7 ± 6.8 vs. 37.9 ± 6.3, respectively, p = 0.04) in comparison to healthy subjects. CONCLUSIONS: Individuals with uncomplicated type 1 diabetes display normal alveolar-capillary diffusion capacity and at rest, while their forced vital capacity, tidal volumes and VO2 are reduced during maximal exercise.

Identification of novel genes influencing eosinophil-specific protein levels in asthma families.

BACKGROUND: Eosinophils play a key role in the asthma allergic response by releasing cytotoxic molecules such as eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) that generate epithelium damages. OBJECTIVE: We sought to identify genetic variants influencing ECP and EDN levels in asthma-ascertained families. METHODS: We performed univariate and bivariate genome-wide association analyses of ECP and EDN levels in 1018 subjects from the EGEA study with follow-up in 153 subjects from the Saguenay-Lac-Saint-Jean study and combined the results of these 2 studies through meta-analysis. We then conducted Bayesian statistical fine mapping together with quantitative trait locus and functional annotation analyses to identify the most likely functional genetic variants and candidate genes. RESULTS: We identified 5 genome-wide significant loci (P &lt; 5 × 10^-8) including 7 distinct signals associated with ECP and/or EDN levels. The genes targeted by our fine mapping and functional search include RNASE2 and RNASE3 (14q11), which encode EDN and ECP, respectively, and 4 other genes that regulate ECP and EDN levels. These 4 genes were JAK1 (1p31), a transcription factor that plays a key role in the immune response and acts as a potential therapeutic target for eosinophilic asthma; ARHGAP25 (2p13), which is involved in leukocyte recruitment to inflammatory sites; NDUFA4 (7p21), which encodes a component of the mitochondrial respiratory chain and is involved in cellular response to stress; and CTSL (9q22), which is involved in immune response, extracellular remodeling, and allergic inflammation. CONCLUSION: Analysis of specific phenotypes produced by eosinophils allows the identification of genes that play a major role in allergic response and inflammation, and offers potential therapeutic targets for asthma.

Blood eosinophil cationic protein and eosinophil-derived neurotoxin are associated with different asthma expression and evolution in adults.

BACKGROUND: Eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) are proteins released by activated eosinophils whose role in adult asthma remains unclear. OBJECTIVE: To study associations between ECP, EDN and various asthma characteristics in adults from the Epidemiological Study on the Genetics and Environment of Asthma (EGEA). METHODS: Plasma ECP and EDN levels were measured by ELISA. Cross-sectional analyses were performed in 941 adults (43±16 years old, 39% with asthma) at EGEA2 (2003-2007). Longitudinal analyses investigated the associations between EDN level at EGEA2 and changes in asthma characteristics between EGEA2 and EGEA3 (2011-2013, n=817). We used generalised estimated equations adjusted for age, sex, smoking status and body mass index to take into account familial dependence. RESULTS: At EGEA2, both high ECP and EDN levels were associated with current asthma (adjusted OR (aOR) (95% CI): 1.69 (1.35-2.12) and 2.12 (1.76-2.57)). Among asthmatics, high EDN level was associated with asthma attacks (aOR: 1.50 (1.13-1.99)), wheezing and breathlessness (aOR: 1.38 (1.05-1.80)), use of asthma treatments (aOR: 1.91 (1.37-2.68)) and bronchial hyper-responsiveness (aOR: 2.03 (1.38-2.97)), even after further adjustment on ECP. High ECP level was associated with high neutrophil count and tended to be associated with chronic bronchitis. High EDN level at EGEA2 was associated with persistent asthma (aOR: 1.62 (1.04-2.52)), nocturnal symptoms (aOR from 2.19 to 3.57), worsening wheezing and breathlessness (aOR: 1.97 (1.36-2.85)) and nocturnal shortness of breath (aOR: 1.44 (1.04-1.98)) between EGEA2 and EGEA3. CONCLUSIONS: EDN and ECP were associated with different asthma expression in adults. EDN could be a potential biomarker to monitor asthma evolution in adults.

Association between occupational exposure to irritant agents and a distinct asthma endotype in adults.

AIM: The biological mechanisms of work-related asthma induced by irritants remain unclear. We investigated the associations between occupational exposure to irritants and respiratory endotypes previously identified among never asthmatics (NA) and current asthmatics (CA) integrating clinical characteristics and biomarkers related to oxidative stress and inflammation. METHODS: We used cross-sectional data from 999 adults (mean 45 years old, 46% men) from the case-control and familial Epidemiological study on the Genetics and Environments of Asthma (EGEA) study. Five respiratory endotypes have been identified using a cluster-based approach: NA1 (n=463) asymptomatic, NA2 (n=169) with respiratory symptoms, CA1 (n=50) with active treated adult-onset asthma, poor lung function, high blood neutrophil counts and high fluorescent oxidation products level, CA2 (n=203) with mild middle-age asthma, rhinitis and low immunoglobulin E level, and CA3 (n=114) with inactive/mild untreated allergic childhood-onset asthma. Occupational exposure to irritants during the current or last held job was assessed by the updated occupational asthma-specific job-exposure matrix (levels of exposure: no/medium/high). Associations between irritants and each respiratory endotype (NA1 asymptomatic as reference) were studied using logistic regressions adjusted for age, sex and smoking status. RESULTS: Prevalence of high occupational exposure to irritants was 7% in NA1, 6% in NA2, 16% in CA1, 7% in CA2 and 10% in CA3. High exposure to irritants was associated with CA1 (adjusted OR aOR, (95% CI) 2.7 (1.0 to 7.3)). Exposure to irritants was not significantly associated with other endotypes (aOR range: 0.8 to 1.5). CONCLUSION: Occupational exposure to irritants was associated with a distinct respiratory endotype suggesting oxidative stress and neutrophilic inflammation as potential associated biological mechanisms.

Circulating biomarkers of nitric oxide bioactivity and impaired muscle vasoreactivity to exercise in adults with uncomplicated type 1 diabetes.

AIMS/HYPOTHESIS: Early compromised endothelial function challenges the ability of individuals with type 1 diabetes to perform normal physical exercise. The exact mechanisms underlying this vascular limitation remain unknown, but may involve either formation or metabolism of nitric oxide (NO), a major vasodilator, whose activity is known to be compromised by oxidative stress. METHODS: Muscle microvascular reactivity (near-infrared spectroscopy) to an incremental exhaustive bout of exercise was assessed in 22 adults with uncomplicated type 1 diabetes (HbA1c 64.5 ± 15.7 mmol/mol; 8.0 ± 1.4%) and in 21 healthy individuals (18-40 years of age). NO-related substrates/metabolites were also measured in the blood along with other vasoactive compounds and oxidative stress markers; measurements were taken at rest, at peak exercise and after 15 min of recovery. Demographic characteristics, body composition, smoking status and diet were comparable in both groups. RESULTS: Maximal oxygen uptake was impaired in individuals with type 1 diabetes compared with in healthy participants (35.6 ± 7.7 vs 39.6 ± 6.8 ml min-1 kg-1, p < 0.01) despite comparable levels of habitual physical activity (moderate to vigorous physical activity by accelerometery, 234.9 ± 160.0 vs 280.1 ± 114.9 min/week). Compared with non-diabetic participants, individuals with type 1 diabetes also displayed a blunted exercise-induced vasoreactivity (muscle blood volume at peak exercise as reflected by ∆ total haemoglobin, 2.03 ± 5.82 vs 5.33 ± 5.54 µmol/l; interaction 'exercise' × 'group', p < 0.05); this was accompanied by lower K+ concentration (p < 0.05), reduced plasma L-arginine (p < 0.05)-in particular when HbA1c was high (mean estimation: -4.0, p < 0.05)-and lower plasma urate levels (p < 0.01). Nonetheless, exhaustive exercise did not worsen lipid peroxidation or other oxidative stress biomarkers, and erythrocytic enzymatic antioxidant resources were mobilised to a comparable extent in both groups. Nitrite and total nitrosation products, which are potential alternative NO sources, were similarly unaltered. Graphical abstract CONCLUSIONS/INTERPRETATION: Participants with uncomplicated type 1 diabetes displayed reduced availability of L-arginine, the essential substrate for enzymatic nitric oxide synthesis, as well as lower levels of the major plasma antioxidant, urate. Lower urate levels may reflect a defect in the activity of xanthine oxidase, an enzyme capable of producing NO from nitrite under hypoxic conditions. Thus, both canonical and non-canonical NO production may be reduced. However, neither of these changes exacerbated exercise-induced oxidative stress. TRIAL REGISTRATION: clinicaltrials.gov NCT02051504.

Residential exposure to outdoor air pollution and adult lung function, with focus on small airway obstruction.

Although a growing body of evidence suggests that chronic exposure to outdoor air pollution is linked to a decline in lung function, data on flow at low lung volumes that may be more specific of small airway obstruction are still scarce. We aimed to study the associations between residential exposure to air pollution and lung function, with specific focus on small airways obstruction. We assessed 2995 French participants (aged between 40 and 65) in the ELISABET cross-sectional survey. Residential exposures to nitrogen dioxide (NO2), particulate matter with a diameter <10 µm (PM10) and sulphur dioxide (SO2) were assessed. The spirometric parameters were forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and forced expiratory flow between 25% and 75% of FVC (FEF25-75) and at 75% of FVC (FEF75). Coefficients in linear regression models were expressed as the z-score [95% confidence interval] for an increment of 5 µg/m3 in NO2 and 2 µg/m3 in PM10 and SO2. NO2 was associated with significantly lower values of FEV1 (-0.10 [-0.15;-0.05]), FVC (-0.06 [-0.11;-0.02]), FEV1/FVC (-0.07 [-0.11;-0.03]), FEF25-75 (-0.09 [-0.14;-0.05]) and FEF75 (-0.08 [-0.12;-0.04]). PM10 was associated with significantly lower values of FEV1 (-0.10 [-0.15;-0.04]), FVC (-0.06 [-0.11;-0.01]), FEV1/FVC (-0.06 [‒0.11;-0.01]), FEF25-75 (-0.08 [-0.13;-0.03]) and FEF75 (-0.08 [-0.12;-0.04]). SO2 was associated with significantly lower values of FEV1 (-0.09 [-0.16;-0.02]), FEV1/FVC (-0.07 [-0.13;-0.01]), FEF25-75 (-0.09 [-0.15;-0.02]) and FEF75 (-0.08 [-0.14;-0.03]) but not FVC (-0.05 [-0.11; 0.009]). Even though spatial variations in pollutant levels were low, residential exposure to outdoor air pollution was associated with lower lung function, including lower FEF25-75 and FEF75 suggesting small airway obstruction.

High level of fluorescent oxidation products and worsening of asthma control over time.

High Fluorescent oxidation products level (FlOPs), a global oxidative stress biomarker, was associated cross-sectionally with poor asthma outcomes but its longitudinal association with asthma evolution has never been examined. We aimed to study the associations between FlOPs level at baseline and changes in current asthma, asthma attacks and asthma control status over 8 years. We used data from the second survey of the French EGEA cohort study as baseline and the third survey as follow-up. At baseline, the mean age of the 489 participants with ever asthma was 39 (± 16) years, 49% were women. Among participants with controlled asthma at baseline, high FlOPs level was significantly associated with worsening of asthma control at follow-up (odds-ratio adjusted for age, sex and smoking status (95% CI): 2.27 (1.32-3.90). No other significant associations were observed. In conclusion, results suggest FlOPs as a predictor of asthma evolution in adults and a good candidate marker in asthma management.

Data-driven adult asthma phenotypes based on clinical characteristics are associated with asthma outcomes twenty years later.

BACKGROUND: Research based on cluster analyses led to the identification of particular phenotypes confirming phenotypic heterogeneity of asthma. The long-term clinical course of asthma phenotypes defined by clustering analysis remains unknown, although it is a key aspect to underpin their clinical relevance. We aimed to estimate risk of poor asthma events between asthma clusters identified 20 years earlier. METHODS: The study relied on two cohorts of adults with asthma with 20-year follow-up, ECRHS (European Community Respiratory Health Survey) and EGEA (Epidemiological study on Genetics and Environment of Asthma). Regression models were used to compare asthma characteristics (current asthma, asthma exacerbations, asthma control, quality of life, and FEV1 ) at follow-up and the course of FEV1  between seven cluster-based asthma phenotypes identified 20 years earlier. RESULTS: The analysis included 1325 adults with ever asthma. For each asthma characteristic assessed at follow-up, the risk for adverse outcomes differed significantly between the seven asthma clusters identified at baseline. As compared with the mildest asthma phenotype, ORs (95% CI) for asthma exacerbations varied from 0.9 (0.4 to 2.0) to 4.0 (2.0 to 7.8) and the regression estimates (95% CI) for FEV1 % predicted varied from 0.6 (-3.5 to 4.6) to -9.9 (-14.2 to -5.5) between clusters. Change in FEV1 over time did not differ significantly across clusters. CONCLUSION: Our findings show that the long-term risk for poor asthma outcomes differed between comprehensive adult asthma phenotypes identified 20 years earlier, and suggest a strong tracking of asthma activity and impaired lung function over time.

The association between blood cadmium and glycated haemoglobin among never-, former, and current smokers: A cross-sectional study in France.

INTRODUCTION: The association between cadmium levels in the body and diabetes has been extensively studied, with sometimes contrasting results. Smoking is the primary non-occupational source of cadmium, and constitutes a risk factor for diabetes. One can therefore hypothesize that the putative association with cadmium is actually explained by tobacco. To fully control for this confounding factor, we studied the relationship between blood cadmium and glycated haemoglobin (HbA1c) levels separately in never-, former and current smokers. METHODS: We studied a sample of 2749 middle-aged adults from the cross-sectional ELISABET survey in and around the cities of Lille and Dunkirk; none had chronic kidney disease or a history of haematological disorders, and none were taking antidiabetic medication. The blood cadmium level-HbA1c associations in never-, former and current smokers were studied in separate multivariate models. The covariables included age, sex, city, educational level, tobacco consumption (or passive smoking, for the never-smokers), body mass index, estimated glomerular filtration rate, and (to take account of the within-batch effect) the cadmium batch number. RESULTS: In the multivariate analysis, a significant association between cadmium and HbA1c levels was found in all three smoking status subgroups. A 0.1 µg/L increment in blood cadmium was associated with an HbA1c increase [95% confidence interval] of 0.016% [0.003; 0.029] among never-smokers, 0.024% [0.010; 0.037] among former smokers, and 0.020% [0.012; 0.029] among current smokers. CONCLUSIONS: The observation of a significant association between the blood cadmium concentration and HbA1c levels in a group of never-smokers strengthens the hypothesis whereby diabetes is associated with cadmium per se and not solely with tobacco use. The small effect size observed in our population of never smokers with low levels of exposure to cadmium suggested that the risk attributable to this metal is not high. However, the impact of exposure to high cadmium levels (such as occupational exposure) on the risk of diabetes might be of concern.

Does the oxidative stress play a role in the associations between outdoor air pollution and persistent asthma in adults? Findings from the EGEA study.

BACKGROUND: Evidences that oxidative stress plays a role in the associations between outdoor air pollution and asthma are growing. We aimed to study the role of plasma fluorescent oxidation products levels (FlOPs; an oxidative stress-related biomarker), as potential mediators, in the associations between outdoor air pollution and persistent asthma. METHODS: Analyses were conducted in 204 adult asthmatics followed up in the French case-control and family study on asthma (EGEA; the Epidemiological study of the Genetic and Environmental factors of Asthma). Persistent asthma was defined as having current asthma at EGEA2 (baseline, 2003-2007) and EGEA3 (follow-up, 2011-2013). Exposures to nitrogen dioxide, nitrogen oxides, road traffic, particulate matter with a diameter ≤ 10 µm (PM10) and ≤ 2.5 µm were estimated by ESCAPE models (2009-2010), and ozone (O3) by IFEN models (2004). We used a mediation analysis to assess the mediated effect by FlOPs levels and the interaction between FlOPs levels and air pollution. RESULTS: FlOPs levels increased with PM10 and O3 (adjusted ß = 0.04 (95%CI 0.001-0.08), aß = 0.04 (95%CI 0.009-0.07) per 10 µg/m3, respectively), and the risk of persistent asthma increased with FlOPs levels (aOR = 1.81 (95%CI 1.08-3.02)). The risk of persistent asthma decreased with exposures to NO2, NOx and PM2.5 (aOR ranging from 0.62 to 0.94), and increased with exposures to PM10, O3, O3-summer and road traffic, the greater effect being observed for O3 (aOR = 1.78, 95% CI 0.73-4.37, per 10 µg/m3). Using mediation analysis, we observed a positive total effect (aOR = 2.16, 95%CI 0.70-11.9), a positive direct effect of O3 on persistent asthma (OR = 1.68, 95%CI 0.57-7.25), and a positive indirect effect mediated by FIOPs levels (aOR = 1.28 (95%CI 1.01-2.29)) accounting for 41% of the total effect. CONCLUSIONS: Our results add insights on the role of oxidative stress in the association between air pollution and persistent asthma.

Outdoor air pollution, exhaled 8-isoprostane and current asthma in adults: the EGEA study.

Associations between outdoor air pollution and asthma in adults are still scarce, and the underlying biological mechanisms are poorly understood. Our aim was to study the associations between 1) long-term exposure to outdoor air pollution and current asthma, 2) exhaled 8-isoprostane (8-iso; a biomarker related to oxidative stress) and current asthma, and 3) outdoor air pollution and exhaled 8-iso.Cross-sectional analyses were conducted in 608 adults (39% with current asthma) from the first follow-up of the French case-control and family study on asthma (EGEA; the Epidemiological study of the Genetic and Environmental factors of Asthma). Data on nitrogen dioxide, nitrogen oxides, particulate matter with a diameter ≤10 and ≤2.5 µm (PM10 and PM2.5), road traffic, and ozone (O3) were from ESCAPE (European Study of Cohorts for Air Pollution Effects) and IFEN (French Institute for the Environment) assessments. Models took account of city and familial dependence.The risk of current asthma increased with traffic intensity (adjusted (a)OR 1.09 (95% CI 1.00-1.18) per 5000 vehicles per day), with O3 exposure (aOR 2.04 (95% CI 1.27-3.29) per 10 µg·m-3) and with exhaled 8-iso concentration (aOR 1.50 (95% CI 1.06-2.12) per 1 pg·mL-1). Among participants without asthma, exhaled 8-iso concentration increased with PM2.5 exposure (adjusted (a)ß 0.23 (95% CI 0.005-0.46) per 5 µg·m-3), and decreased with O3 and O3-summer exposures (aß -0.20 (95% CI -0.39- -0.01) and aß -0.52 (95% CI -0.77- -0.26) per 10 µg·m-3, respectively).Our results add new insights into a potential role of oxidative stress in the associations between outdoor air pollution and asthma in adults.

Sources of household air pollution: The association with lung function and respiratory symptoms in middle-aged adult.

INTRODUCTION: The objective of the present study was to investigate the relationship between sources of household air pollution, respiratory symptoms and lung function. METHODS: 3039 adults aged from 40 to 65 participated in the 2011-2013 ELISABET cross-sectional survey in northern France. Lung function was measured using spirometry. During a structured interview, respiratory symptoms, household fuels, exposure to moulds, and use of ventilation were recorded on a questionnaire. RESULTS: The self-reported presence of mould in at least two rooms (not including the bathroom and the kitchen) was associated with a 2.5% lower predicted forced expiratory volume in 1 s (95% confidence interval, -4.7 to -0.29; p-trend <0.05) and a higher risk of wheezing (p-trend < 0.001). Visible condensation was associated with wheezing (p < .05) and chronic cough (p < .05). There were no significant associations with the type of household fuel or inadequate ventilation/aeration. Similar results were found when the analyses were restricted to participants without known respiratory disease. CONCLUSION: Our results suggest that the presence of mould (known to be associated with more severe asthma symptoms) could also have an impact on respiratory symptoms and lung function in the general population and in populations without known respiratory disease.

Lifelong Voluntary Exercise Modulates Age-Related Changes in Oxidative Stress.

The hypothesis that aging and regular physical activity could influence oxidative stress has been studied by comparing antioxidant activities (superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GR), ascorbic acid and α-Tocopherol) and malondialdehyde level (MDA) in four groups: young sedentary (n=15; age: 20.3±2.8 years; YS), young active (n=16; age: 21.4±1.9 years; YA), old sedentary (n=15; age: 65.1±3.5 years; OS) and old active (n=17; age: 67.2±4.8 years; OA). Antioxidant activities and MDA level were assessed at rest and after an incremental exercise. There was no difference in resting antioxidant activities and lipid peroxidation between YS and OS. However, resting SOD and GR activities were higher in YA compared to OA (p<0.01 and p<0.05, respectively) and resting MDA level was higher in OA compared to YA (p<0.01). After exercise, a significant increase in SOD and GPX activities was observed in YS, YA and OA (p<0.01). Likewise, after exercise a significant increase of MDA level in YA, OS and OA (p<0.01) was observed. In addition, the comparison of YA to OA and YS to OA revealed similar antioxidant activities and lipid peroxidation between YS and OA, whereas antioxidant activities were higher in YA compared to OA. These data suggest that beneficial effects of regular physical activity in antioxidant defense and lipid peroxidation damage could be impaired by the aging process and that regular physical activity in older adults could maintain age-related decreases in antioxidant defense.

Oxidative stress biomarkers and asthma characteristics in adults of the EGEA study.

Asthma is an oxidative stress related disease, but associations with asthma outcomes are poorly studied in adults. We aimed to study the associations between several biomarkers related to oxidative stress and various asthma outcomes.Cross-sectional analyses were conducted in 1388 adults (mean age 43 years, 44% with asthma) from the Epidemiological Study of the Genetics and Environment of Asthma (EGEA2). Three blood antioxidant enzyme activities (biomarkers of response to oxidative stress) and exhaled breath condensate 8-isoprostanes and plasma fluorescent oxidation products (FlOPs) levels (two biomarkers of damage) were measured. Associations between biomarkers and 1) ever asthma and 2) asthma attacks, asthma control and lung function in participants with asthma were evaluated using regression models adjusted for age, sex and smoking.Biomarkers of response were unrelated to asthma outcomes. Higher 8-isoprostane levels were significantly associated with ever asthma (odds ratio for one interquartile range increase 1.28 (95% CI 1.06-1.67). Among participants with asthma, 8-isoprostane levels were negatively associated with adult-onset asthma (0.63, 0.41-0.97) and FlOPs levels were positively associated with asthma attacks (1.33, 1.07-1.65), poor asthma control (1.30, 1.02-1.66) and poor lung function (1.34, 1.04-1.74).Our results suggest that 8-isoprostanes are involved in childhood-onset asthma and FlOPs are linked to asthma expression.

Forced midexpiratory flow between 25% and 75% of forced vital capacity is associated with long-term persistence of asthma and poor asthma outcomes.

BACKGROUND: Whether small-airway obstruction contributes to the long-term evolution of asthma remains unknown. OBJECTIVES: Our aim was to assess whether the level of forced midexpiratory flow between 25% and 75% of forced vital capacity (FEF25-75) was associated with the persistence of current asthma over 20 years and the subsequent risk for uncontrolled asthma independently of FEV1. METHODS: We studied 337 participants (142 children and 225 adults) with current asthma (asthma attacks or treatment in the past 12 months) recruited to the Epidemiological Study on the Genetics and Environment of Asthma (EGEA1) and followed up at the 12- and 20-year surveys. Persistent current asthma was defined by current asthma reported at each survey. A lung function test and a methacholine challenge test were performed at EGEA1 and EGEA2. Adjusted odds ratios (ORs) were estimated for FEF25-75 decreased by 10% of predicted value. RESULTS: A reduced level of FEF25-75 at EGEA1 increased the risk of long-term asthma persistence (adjusted OR, 1.14; 95% CI, 1.00-1.29). In children the association remained significant after further adjustment for FEV1 and in participants with FEV1 of greater than 80% of predicted value. A reduced FEF25-75 level at EGEA1 was significantly associated with more severe bronchial hyperresponsiveness (P < .0001) and with current asthma a decade later, with an association that tended to be stronger in those with (adjusted OR, 1.44; 95% CI, 1.14-1.81) compared with those without (adjusted OR, 1.21; 95% CI, 1.05-1.41) asthma exacerbation. CONCLUSION: Our analysis is the first to suggest that small-airway obstruction, as assessed based on FEF25-75, might contribute to the long-term persistence of asthma and the subsequent risk for poor asthma outcomes independently from effects of the large airways.

Effect of Iterative Reconstruction on the Detection of Systemic Sclerosis-related Interstitial Lung Disease: Clinical Experience in 55 Patients.

PURPOSE: To evaluate the effect of iterative reconstruction on the depiction of systemic sclerosis-related interstitial lung disease (ILD) when the radiation dose is reduced by 60%. MATERIALS AND METHODS: This study was based on retrospective interpretation of prospectively acquired data over a 12-month period and approved by the institutional review board. The requirement to obtain informed consent was waived. Fifty-five chest computed tomographic (CT) examinations were performed in 38 women and 17 men (mean age, 55.8 years; range, 23-82 years) by using a dual-source CT unit with (a) both tubes set at similar energy (120 kVp) and (b) the total reference milliampere seconds (ie, 110 mAs) split up in a way that 40% was applied to tube A and 60% to tube B. Two series of images were generated simultaneously from the same dataset: (a) standard-dose images (generated from both tubes) reconstructed with filtered back projection (group 1, the reference standard) and (b) reduced-dose images (generated from tube A; 60% dose reduction) reconstructed with sinogram-affirmed iterative reconstruction (SAFIRE) (group 2). In both groups, the analyzed parameters comprised the image noise and the visualization and conspicuity of CT features of ILD. Two readers independently analyzed images from both groups. Results were compared by using the Wilcoxon test for paired samples; the 95% confidence interval was calculated when appropriate. RESULTS: The mean level of objective noise in group 2 was significantly lower than that in group 1 (22.02 HU vs 26.23 HU, respectively; P < .0001). The CT features of ILD in group 1 were always depicted in group 2, with subjective conspicuity scores (a) improved in group 2 for ground-glass opacity, reticulation, and bronchiectasis and/or bronchiolectasis and (b) identical in both groups for honeycombing. The interobserver agreement for their depiction was excellent in both groups (κ, 0.84-0.98). CONCLUSION: Despite a 60% dose reduction, images reconstructed with SAFIRE allowed similar detection of systematic sclerosis-related ILD compared with the reference standard.

Utility of measuring FEV0.75/FVC ratio in preschoolers with uncontrolled wheezing disorder.

Uncontrolled wheezing disorder is common in preschoolers and disease control assessment is challenging as parents frequently overestimate the extent to which their child's disease is controlled. This is the first study of forced expiratory volume in t s (FEVt)/forced vital capacity (FVC) ratio measurements (i.e. FEV1/FVC, FEV0.75/FVC and FEV0.5/FVC) in wheezy preschoolers in relation to disease control. Our objective was to evaluate whether FEVt/FVC ratios less than the lower limit of normal (LLN; z-score <-1.64) were associated with uncontrolled wheezing disorder in preschoolers.Valid FVC, FEV1, FEV0.75 and FEV0.5 values were obtained in 92 healthy and 125 wheezy (62% uncontrolled) children (3-5 years). Associations between spirometry value

Blood granulocyte patterns as predictors of asthma phenotypes in adults from the EGEA study.

To what extent blood granulocyte patterns may predict asthma control remains under-studied. Our aim was to study associations between blood neutrophilia and eosinophilia and asthma control outcomes in adults.Analyses were conducted in 474 asthmatics from the first follow-up of the Epidemiological Study on the Genetics and Environment of Asthma (EGEA2), including 242 asthmatics who were adults a decade earlier (EGEA1). At EGEA2, asthma control was assessed using the Global Initiative for Asthma definition (2015), and asthma exacerbations by use of urgent care or courses of oral corticosteroids in the past year. Blood EOSlo/EOShi was defined as 2.10). EOShi was associated with higher bronchial hyperresponsiveness (BHR) (OR (95% CI) 2.21 (1.24-3.97)), poor lung function (p=0.02) and higher total IgE level (p=0.002). Almost 50% of asthmatics had a persistent pattern between surveys. Persistent NEUhi was associated with poor asthma control at EGEA2 (OR (95% CI) 3.09 (1.18-7.05)). EOShi at EGEA1 and persistent EOShi were associated with higher BHR (OR (95% CI) 2.36 (1.10-5.07) and 3.85 (1.11-13.34), respectively), poor lung function (p<0.06) and higher immunoglobulin E level (p<10-4) at EGEA2.Granulocyte patterns were differently associated with asthma outcomes, suggesting specific roles for each one, which could be tested as predictive signatures.