Previous studies on smokeless tobacco use and head and neck cancer (HNC) have found inconsistent and often imprecise estimates, with limited control for cigarette smoking. Using pooled data from 11 ...US case-control studies (1981-2006) of oral, pharyngeal, and laryngeal cancers (6,772 cases and 8,375 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium, we applied hierarchical logistic regression to estimate odds ratios and 95% confidence intervals for ever use, frequency of use, and duration of use of snuff and chewing tobacco separately for never and ever cigarette smokers. Ever use (versus never use) of snuff was strongly associated with HNC among never cigarette smokers (odds ratio (OR) = 1.71, 95% confidence interval (CI): 1.08, 2.70), particularly for oral cavity cancers (OR = 3.01, 95% CI: 1.63, 5.55). Although ever (versus never) tobacco chewing was weakly associated with HNC among never cigarette smokers (OR = 1.20, 95% CI: 0.81, 1.77), analyses restricted to cancers of the oral cavity showed a stronger association (OR = 1.81, 95% CI: 1.04, 3.17). Few or no associations between each type of smokeless tobacco and HNC were observed among ever cigarette smokers, possibly reflecting residual confounding by smoking. Smokeless tobacco use appears to be associated with HNC, especially oral cancers, with snuff being more strongly associated than chewing tobacco.
Background Previous studies, mostly from Europe, suggest that early-life farming exposures protect against childhood asthma and allergy; few data exist on asthma and allergy in adults. Objective We ...sought to examine associations between early-life farming exposures and current asthma and atopy in an older adult US farming population. Methods We analyzed data from 1746 farmers and 1555 spouses (mean age, 63) from a case-control study nested within the Agricultural Health Study. Current asthma and early-life farming exposures were assessed via questionnaires. We defined atopy based on specific IgE > 0.70 IU/mL to at least 1 of 10 allergens measured in blood. We used logistic regression, adjusted for age, sex, race, state (Iowa or North Carolina), and smoking (pack years), to estimate associations between early-life exposures and asthma (1198 cases and 2031 noncases) or atopy (578 cases and 2526 noncases). Results Exposure to the farming environment in utero and in early childhood had little or no association with asthma but was associated with reduced odds of atopy. The strongest association was seen for having a mother who performed farm activities while pregnant (odds ratio, 0.60; 95% CI, 0.48-0.74) and remained significant in models with correlated early-life exposures including early childhood farm animal contact and raw milk consumption. Conclusions In a large US farming population, early-life farm exposures, particularly maternal farming activities while pregnant, were strongly associated with reduced risk of atopy in adults. These results extend previous work done primarily on childhood outcomes and suggest that protective associations of early-life farming exposures on atopy endure across the life course.
Age at menarche has been associated with various health outcomes. We aimed to identify potential causal effects of age at menarche on health-related traits in a hypothesis-free manner.
We conducted a ...Mendelian randomization phenome-wide association study (MR-pheWAS) of age at menarche with 17,893 health-related traits in UK Biobank (n = 181,318) using PHESANT. The exposure of interest was the genetic risk score for age at menarche. We conducted a second MR-pheWAS after excluding SNPs associated with BMI from the genetic risk score, to examine whether results might be due to the genetic overlap between age at menarche and BMI. We followed up a subset of health-related traits to investigate MR assumptions and seek replication in independent study populations.
Of the 17,893 tests performed in our MR-pheWAS, we identified 619 associations with the genetic risk score for age at menarche at a 5% false discovery rate threshold, of which 295 were below a Bonferroni-corrected P value threshold. These included potential effects of younger age at menarche on lower lung function, higher heel bone-mineral density, greater burden of psychosocial/mental health problems, younger age at first birth, higher risk of childhood sexual abuse, poorer cardiometabolic health, and lower physical activity. After exclusion of variants associated with BMI, the genetic risk score for age at menarche was related to 37 traits at a 5% false discovery rate, of which 29 were below a Bonferroni-corrected P value threshold. We attempted to replicate findings for bone-mineral density, lung function, neuroticism, and childhood sexual abuse using 5 independent cohorts/consortia. While estimates for lung function, higher bone-mineral density, neuroticism, and childhood sexual abuse in replication cohorts were consistent with UK Biobank estimates, confidence intervals were wide and often included the null.
The genetic risk score for age at menarche was related to a broad range of health-related traits. Follow-up analyses indicated imprecise evidence of an effect of younger age at menarche on greater bone-mineral density, lower lung function, higher neuroticism score, and greater risk of childhood sexual abuse in the smaller replication samples available; hence, these findings need further exploration when larger independent samples become available.
Few studies have examined particulate matter (PM) exposure from self-reported use of wood stoves and other indoor combustion sources in urban settings in developed countries. We measured ...concentrations of indoor PM < 2.5 microns (PM2.5) for one week with the MicroPEM™ nephelometer in 36 households in the greater Oslo, Norway metropolitan area. We examined indoor PM2.5 levels in relation to use of wood stoves and other combustion sources during a 7 day monitoring period using mixed effects linear models with adjustment for ambient PM2.5 levels. Mean hourly indoor PM2.5 concentrations were higher (p = 0.04) for the 14 homes with wood stove use (15.6 μg/m3) than for the 22 homes without (12.6 μg/m3). Moreover, mean hourly PM2.5 was higher (p = 0.001) for use of wood stoves made before 1997 (6 homes, 20.2 μg/m3), when wood stove emission limits were instituted in Norway, compared to newer wood stoves (8 homes, 11.9 μg/m3) which had mean hourly values similar to control homes. Increased PM2.5 levels during diary-reported burning of candles was detected independently of concomitant wood stove use. These results suggest that self-reported use of wood stoves, particularly older stoves, and other combustion sources, such as candles, are associated with indoor PM2.5 measurements in an urban population from a high income country.
Bacterial exposure from house dust has been associated with asthma and atopy in children but whether these relationships are present in adults remains unclear.
We sought to examine associations of ...house dust microbiota with adult asthma, atopy, and hay fever.
Vacuumed bedroom dust samples from the homes of 879 participants (average age, 62 years) in the Agricultural Lung Health Study, a case-control study of asthma nested within a farming cohort, were subjected to 16S rRNA amplicon sequencing to characterize bacterial communities. We defined current asthma and hay fever using questionnaires and current atopy by blood specific IgE level > 0.70 IU/mL to 1 or more of 10 common allergens. We used linear regression to examine whether overall within-sample bacterial diversity differed by outcome, microbiome regression-based kernel association test to evaluate whether between-sample bacterial community compositions differed by outcome, and analysis of composition of microbiomes to identify differentially abundant bacterial taxa.
Overall diversity of bacterial communities in house dust was similar by asthma status but was lower (P < .05) with atopy or hay fever. Many individual bacterial taxa were differentially abundant (false-discovery rate, <0.05) by asthma, atopy, or hay fever. Several taxa from Cyanobacteria, Bacteroidetes, and Fusobacteria were more abundant with asthma, atopy, or hay fever. In contrast, several taxa from Firmicutes were more abundant in homes of individuals with adequately controlled asthma (vs inadequately controlled asthma), individuals without atopy, or individuals without hay fever.
Microbial composition of house dust may influence allergic outcomes in adults.
Lung Development Genes and Adult Lung Function Portas, Laura; Pereira, Miguel; Shaheen, Seif O ...
American journal of respiratory and critical care medicine,
09/2020, Letnik:
202, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Poor lung health in adult life may occur partly through suboptimal growth and development, as suggested by epidemiological evidence pointing to early life risk factors.
To systematically investigate ...the effects of lung development genes on adult lung function.
Using UK Biobank data, we tested the association of 391 genes known to influence lung development with FVC and FEV
/FVC. We split the dataset into two random subsets of 207,616 and 138,411 individuals, using the larger subset to select the most promising signals and the smaller subset for replication.
We identified 55 genes, of which 36 (16 for FVC, 19 for FEV
/FVC, and one for both) had not been identified in the largest, most recent genome-wide study of lung function. Most of these 36 signals were intronic variants; expression data from blood and lung tissue showed that the majority affect the expression of the genes they lie within. Further testing of 34 of these 36 signals in the CHARGE and SpiroMeta consortia showed that 16 replicated after Bonferroni correction and another 12 replicated at nominal significance level. Of the 55 genes, 53 fell into four biological categories whose function is to regulate organ size and cell integrity (growth factors; transcriptional regulators; cell-to-cell adhesion; extracellular matrix), suggesting that these specific processes are important for adult lung health.
Our study demonstrates the importance of lung development genes in regulating adult lung function and influencing both restrictive and obstructive patterns. Further investigation of these developmental pathways could lead to druggable targets.
Genome-wide association studies (GWASs) have identified numerous loci associated with lower pulmonary function. Pulmonary function is strongly related to smoking and has also been associated with ...asthma and dust endotoxin. At the individual SNP level, genome-wide analyses of pulmonary function have not identified appreciable evidence for gene by environment interactions. Genetic Risk Scores (GRSs) may enhance power to identify gene-environment interactions, but studies are few.
We analysed 2844 individuals of European ancestry with 1000 Genomes imputed GWAS data from a case-control study of adult asthma nested within a US agricultural cohort. Pulmonary function traits were FEV
, FVC and FEV
/FVC. Using data from a recent large meta-analysis of GWAS, we constructed a weighted GRS for each trait by combining the top (p value<5×10
) genetic variants, after clumping based on distance (±250 kb) and linkage disequilibrium (r
=0.5). We used linear regression, adjusting for relevant covariates, to estimate associations of each trait with its GRS and to assess interactions.
Each trait was highly significantly associated with its GRS (all three p values<8.9×10
). The inverse association of the GRS with FEV
/FVC was stronger for current smokers (p
=0.017) or former smokers (p
=0.064) when compared with never smokers and among asthmatics compared with non-asthmatics (p
=0.053). No significant interactions were observed between any GRS and house dust endotoxin.
Evaluation of interactions using GRSs supports a greater impact of increased genetic susceptibility on reduced pulmonary function in the presence of smoking or asthma.
In low- and middle-income countries, burning biomass indoors for cooking or heating has been associated with poorer lung function. In high-income countries, wood, a form of biomass, is commonly used ...for heating in rural areas with increasing prevalence. However, in these settings the potential impact of chronic indoor woodsmoke exposure on pulmonary function is little studied.
We evaluated the association of residential wood burning with pulmonary function in case-control study of asthma nested within a U.S. rural cohort.
Using sample weighted multivariable linear regression, we estimated associations between some and frequent wood burning, both relative to no exposure, in relation to forced expiratory volume in 1 s (
), forced vital capacity (FVC), their ratio (
), and fractional exhaled nitric oxide (FeNO). We examined effect modification by smoking or asthma status.
Among all participants and within smoking groups, wood burning was not appreciably related to pulmonary function. However, in individuals with asthma (
), frequent wood burning was significantly associated with lower
:
; 95% confidence interval (CI):
,
, FVC (
:
; 95% CI:
,
), and
(
:
; 95% CI:
,
), whereas no appreciable association was seen in individuals without asthma (
). These differences in association by asthma were statistically significant for
(
) and
(
). Frequent wood burning was also associated with higher FeNO levels in all individuals (
;
:
; 95% CI: 0.02, 0.2), but associations did not differ by asthma or smoking status.
Frequent exposure to residential wood burning was associated with a measure of airway inflammation (FeNO) among all individuals and with lower pulmonary function among individuals with asthma. This group may wish to reduce wood burning or consider using air filtration devices. https://doi.org/10.1289/EHP10734.
Plasma protein signatures of adult asthma Smilnak, Gordon J.; Lee, Yura; Chattopadhyay, Abhijnan ...
Allergy (Copenhagen),
March 2024, 2024-Mar, 2024-03-00, 20240301, Letnik:
79, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Background
Adult asthma is complex and incompletely understood. Plasma proteomics is an evolving technique that can both generate biomarkers and provide insights into disease mechanisms. We aimed to ...identify plasma proteomic signatures of adult asthma.
Methods
Protein abundance in plasma was measured in individuals from the Agricultural Lung Health Study (ALHS) (761 asthma, 1095 non‐case) and the Atherosclerosis Risk in Communities study (470 asthma, 10,669 non‐case) using the SOMAScan 5K array. Associations with asthma were estimated using covariate adjusted logistic regression and meta‐analyzed using inverse‐variance weighting. Additionally, in ALHS, we examined phenotypes based on both asthma and seroatopy (asthma with atopy (n = 207), asthma without atopy (n = 554), atopy without asthma (n = 147), compared to neither (n = 948)).
Results
Meta‐analysis of 4860 proteins identified 115 significantly (FDR<0.05) associated with asthma. Multiple signaling pathways related to airway inflammation and pulmonary injury were enriched (FDR<0.05) among these proteins. A proteomic score generated using machine learning provided predictive value for asthma (AUC = 0.77, 95% CI = 0.75–0.79 in training set; AUC = 0.72, 95% CI = 0.69–0.75 in validation set). Twenty proteins are targeted by approved or investigational drugs for asthma or other conditions, suggesting potential drug repurposing. The combined asthma‐atopy phenotype showed significant associations with 20 proteins, including five not identified in the overall asthma analysis.
Conclusion
This first large‐scale proteomics study identified over 100 plasma proteins associated with current asthma in adults. In addition to validating previous associations, we identified many novel proteins that could inform development of diagnostic biomarkers and therapeutic targets in asthma management.
We identified 115 proteins significantly related to asthma. Using limited data from published studies, we validated some proteins. Many were novel. Using a machine learning method, we constructed a proteomic score which provided additional predictive value for asthma. Notably, a druggable target search revealed that 20 proteins we identified are targets of approved or investigational drugs.Abbreviations: ALHS, Agricultural Lung Health Study; ARIC, Atherosclerosis Risk in Communities; CNTN1, contactin‐1; CRLD2, Cysteine‐rich secretory protein LCCL domain‐containing 2; IgE, Immunoglobulin E; PAPP‐A, Pappalysin‐1; ROBO2, roundabout homolog 2.
PDF
