The role of epigenetics in multi-generational transmission of asthma: An NIAID workshop report-based narrative review.

There is mounting evidence that environmental exposures can result in effects on health that can be transmitted across generations, without the need for a direct exposure to the original factor, for example, the effect of grandparental smoking on grandchildren. Hence, an individual's health should be investigated with the knowledge of cross-generational influences. Epigenetic factors are molecular factors or processes that regulate genome activity and may impact cross-generational effects. Epigenetic transgenerational inheritance has been demonstrated in plants and animals, but the presence and extent of this process in humans are currently being investigated. Experimental data in animals support transmission of asthma risk across generations from a single exposure to the deleterious factor and suggest that the nature of this transmission is in part due to changes in DNA methylation, the most studied epigenetic process. The association of father's prepuberty exposure with offspring risk of asthma and lung function deficit may also be mediated by epigenetic processes. Multi-generational birth cohorts are ideal to investigate the presence and impact of transfer of disease susceptibility across generations and underlying mechanisms. However, multi-generational studies require recruitment and assessment of participants over several decades. Investigation of adult multi-generation cohorts is less resource intensive but run the risk of recall bias. Statistical analysis is challenging given varying degrees of longitudinal and hierarchical data but path analyses, structural equation modelling and multilevel modelling can be employed, and directed networks addressing longitudinal effects deserve exploration as an effort to study causal pathways.

Differential Effects of Cannabis and Tobacco on Lung Function in Mid-Adult Life.

Rationale: Evidence suggests that the effects of smoking cannabis on lung function are different from tobacco. However, long-term follow-up data are scarce and mostly based on young adults. Objectives: To assess the effects of cannabis and tobacco on lung function in mid-adult life. Methods: Cannabis and tobacco use were reported at ages 18, 21, 26, 32, 38, and 45 years in a population-based cohort study of 1,037 participants. Spirometry, plethysmography, and carbon monoxide transfer factor were measured at age 45. Associations between lung function and cannabis use were adjusted for tobacco use. Measurements and Main Results: Data were available from 881 (88%) of 997 surviving participants. Cumulative cannabis use was associated with lower FEV1/FVC ratios, owing to a tendency toward higher FVCs. Cannabis use was also associated with higher TLC, FRC, residual volume, and Va along with lower midexpiratory flows, airway conductance, and transfer factor. Quitting regular cannabis use between assessments was not associated with changes in spirometry. Conclusions: Cannabis use is associated with higher lung volumes, suggesting hyperinflation. There is evidence of increased large-airway resistance and lower midexpiratory airflow, but impairment of FEV1/FVC ratio is because of higher FVC. This pattern of effects is different to those of tobacco. We provide the first evidence that lifetime cannabis use may be associated with impairment of gas transfer.

Assessing secondhand and thirdhand tobacco smoke exposure in Canadian infants using questionnaires, biomarkers, and machine learning.

BACKGROUND: As smoking prevalence has decreased in Canada, particularly during pregnancy and around children, and technological improvements have lowered detection limits, the use of traditional tobacco smoke biomarkers in infant populations requires re-evaluation. OBJECTIVE: We evaluated concentrations of urinary nicotine biomarkers, cotinine and trans-3'-hydroxycotinine (3HC), and questionnaire responses. We used machine learning and prediction modeling to understand sources of tobacco smoke exposure for infants from the CHILD Cohort Study. METHODS: Multivariable linear regression models, chosen through a combination of conceptual and data-driven strategies including random forest regression, assessed the ability of questionnaires to predict variation in urinary cotinine and 3HC concentrations of 2017 3-month-old infants. RESULTS: Although only 2% of mothers reported smoking prior to and throughout their pregnancy, cotinine and 3HC were detected in 76 and 89% of the infants' urine (n = 2017). Questionnaire-based models explained 31 and 41% of the variance in cotinine and 3HC levels, respectively. Observed concentrations suggest 0.25 and 0.50 ng/mL as cut-points in cotinine and 3HC to characterize SHS exposure. This cut-point suggests that 23.5% of infants had moderate or regular smoke exposure. SIGNIFICANCE: Though most people make efforts to reduce exposure to their infants, parents do not appear to consider the pervasiveness and persistence of secondhand and thirdhand smoke. More than half of the variation in urinary cotinine and 3HC in infants could not be predicted with modeling. The pervasiveness of thirdhand smoke, the potential for dermal and oral routes of nicotine exposure, along with changes in public perceptions of smoking exposure and risk warrant further exploration.

Factors associated with breast-feeding initiation and continuation in Canadian-born and non-Canadian-born women: a multi-centre study.

OBJECTIVE: To identify factors associated with breast-feeding initiation and continuation in Canadian-born and non-Canadian-born women. DESIGN: Prospective cohort of mothers and infants born from 2008 to 2012: the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study. SETTING: General community setting in four Canadian provinces. PARTICIPANTS: In total, 3455 pregnant women from Vancouver, Edmonton, Winnipeg and Toronto between 2008 and 2012. RESULTS: Of 3010 participants included in the current study, the majority were Canadian-born (75·5 %). Breast-feeding initiation rates were high in both non-Canadian-born (95·5 %) and Canadian-born participants (92·7 %). The median breast-feeding duration was 10 months in Canadian-born participants and 11 months in non-Canadian-born participants. Among Canadian-born participants, factors associated with breast-feeding initiation and continuation were older maternal age, higher maternal education, living with their partner and recruitment site. Rooming-in during the hospital stay was also associated with higher rates of breast-feeding initiation, but not continuation at 6-month postpartum. Factors associated with non-initiation of breast-feeding and cessation at 6-month postpartum were maternal smoking, living with a current smoker, caesarean birth and early-term birth. Among non-Canadian-born participants, maternal smoking during pregnancy was associated with lower odds of breast-feeding initiation and lower odds of breast-feeding continuation at 6 months, and older maternal age and recruitment site were associated with breast-feeding continuation at 6 months. CONCLUSIONS: Although Canadian-born and non-Canadian-born women in the CHILD cohort have similar breast-feeding initiation rates, breast-feeding initiation and continuation are more strongly associated with socio-demographic characteristics in Canadian-born participants. Recruitment site was strongly associated with breast-feeding continuation in both groups and may indicate geographic disparities in breast-feeding rates nationally.

Associations between lung and endothelial function in early middle age.

BACKGROUND AND OBJECTIVE: Chronic lung disease is associated with impaired endothelial function and this may be a risk factor for poor cardiovascular health. It is unknown if there is an association between lung and endothelial function in the general population. We investigated associations between lung and endothelial function in a population-based cohort of 38-year-old men and women. METHODS: Systemic endothelial function was measured using peripheral arterial tonometry to calculate the Framingham reactive hyperaemia index. Lung function was assessed using spirometry, plethysmographic lung volumes, airway conductance and gas transfer. Associations between lung and endothelial function were assessed with and without adjustment for potential confounding factors using regression analyses. RESULTS: Sex modified the association between lung and endothelial function. Among women, lower values of pre- and post-bronchodilator spirometry, total lung capacity and functional residual capacity (FRC) were associated with worse endothelial function (P < 0.05). These associations persisted after adjustment for smoking, asthma diagnoses, fitness and body mass index. Associations were weaker among men: only FRC, airway conductance and post-bronchodilator forced expiratory volume in 1 s (FEV1 )/forced vital capacity (FVC) ratios were associated with endothelial function. Endothelial function was not associated with gas transfer in either sex. CONCLUSION: Lower lung volumes and airflow obstruction are associated with endothelial dysfunction among women. There is weaker evidence for an association between airway and endothelial function in men. These findings may partly explain the increased risk of cardiovascular disease among people with poor lung function, but suggest that there are sex differences in this association.

Maternal Metabolic Complications in Pregnancy and Offspring Behavior Problems at 2 Years of Age.

Objectives Prenatal maternal metabolic problems such as pre-pregnancy adiposity, excess gestational weight gain, and gestational diabetes mellitus (GDM) are associated with an increased risk of psychopathology in offspring. We examined whether these exposures were linked to symptoms of emotional and behavioral problems in offspring at 2 years of age, or if associations were due to confounding variables. Methods Data from 815 mother-child pairs enrolled at the Edmonton site of the Canadian Healthy Infant Longitudinal Development cohort were used to examine associations between gestational metabolic complications and scores on the externalizing and internalizing scales of the Child Behavior Checklist (CBCL-1½ to 5) at age two. Associations between maternal metabolic complications and offspring psychopathology were assessed before and after adjustment for gestational diet, socioeconomic status (SES), postpartum depression (PPD), prenatal smoking and breastfeeding. Results Pre-pregnancy body mass index and GDM, but not gestational weight gain, predicted more offspring externalizing and internalizing problems. However, after adjustment for confounding variables, these associations were no longer statistically significant. Post-hoc analyses revealed that gestational diet accounted for unique variance in both externalizing (semi-partial rdiet = - 0.20, p < 0.001) and internalizing (semi-partial rdiet = - 0.16, p = 0.01) problems. PPD and SES also accounted for a similar amount of variance for both externalizing (semi-partial rPPD = 0.17, p < 0.001; rses = - 0.11, p = 0.03) and internalizing problems (semi-partial rPPD = 0.21, p < 0.001; rses = - 0.14, p = 0.004). Conclusions for Practice Since the confounding effect of gestational diet persisted after adjustment for, and was similar in magnitude to, SES and PPD, future research should consider the impact of unhealthy prenatal diets on offspring neurodevelopment.

Ventilation inhomogeneity in infants with recurrent wheezing.

BACKGROUND: The care of infants with recurrent wheezing relies largely on clinical assessment. The lung clearance index (LCI), a measure of ventilation inhomogeneity, is a sensitive marker of early airway disease in children with cystic fibrosis, but its utility has not been explored in infants with recurrent wheezing. OBJECTIVE: To assess ventilation inhomogeneity using LCI among infants with a history of recurrent wheezing compared with healthy controls. METHODS: This is a case-control study, including 37 infants with recurrent wheezing recruited from outpatient clinics, and 113 healthy infants from a longitudinal birth cohort, the Canadian Healthy Infant Longitudinal Development study. All infants, at a time of clinical stability, underwent functional assessment including multiple breath washout, forced expiratory flows and body plethysmography. RESULTS: LCI z-score values among infants with recurrent wheeze were 0.84 units (95% CI 0.41 to 1.26) higher than healthy infants (mean (95% CI): 0.26 (-0.11 to 0.63) vs -0.58 (-0.79 to 0.36), p<0.001)). Nineteen percent of recurrently wheezing infants had LCI values that were above the upper limit of normal (>1.64 z-scores). Elevated exhaled nitric oxide, but not symptoms, was associated with abnormal LCI values in infants with recurrent wheeze (p=0.05). CONCLUSIONS: Ventilation inhomogeneity is present in clinically stable infants with recurrent wheezing.

Phenotypes of sleep-disordered breathing symptoms to two years of age based on age of onset and duration of symptoms.

OBJECTIVE: Childhood sleep-disordered breathing (SDB) symptoms may comprise multiple phenotypes depending on craniofacial anatomy, tonsil and adenoid growth, body habitus, and rhinitis symptoms. The primary objective of this study is to identify and characterize the different SDB phenotypes to two years of age. METHODS: Data from 770 infants in the Edmonton sub-cohort of the Canadian Healthy Infant Longitudinal Study (CHILD) were analyzed to identify SDB phenotypes based on age of onset and duration of symptoms. Parents completed the 22-item sleep-related breathing disorder (SRBD) scale. Children with a SRBD ratio greater than 0.33 were considered positive for SDB at each quarterly assessment between three months and two years. The STATA Proc trajectory extension identified SDB phenotypes based on their age of onset and duration of symptoms and attributed the percentage chance of a participant being assigned to each phenotype. Multivariate linear regression identified factors associated with increased risk of being assigned to each SDB phenotype. RESULTS: Trajectory analysis identified four phenotypes: no SDB (65.7%), early-onset SDB (15.7%) with peak symptoms at nine months, late-onset SDB (14.2%) with peak symptoms at 18 months, and persistent SDB (5.3%) with symptoms from 3 to 24 months. Rhinitis was associated with all three SDB symptom trajectories (p < 0.05). Children with gastroesophageal reflux disease presented with early (p = 0.03) and late SDB (p < 0.001). Maternal obstructive sleep apnea syndrome (OSAS) was associated with persistent (p = 0.01) and late SDB (p < 0.001). Atopy (positive skin prick test at one year) was associated with persistent SDB (p = 0.04). Infants born prior to 36.5 weeks gestational age were more likely to present with late SDB (p = 0.03). CONCLUSION: Childhood SDB symptoms, rather than being a homogenous disorder, may comprise multiple overlapping phenotypes each with unique risk factors.

Associations between blood eosinophils and decline in lung function among adults with and without asthma.

Eosinophilic inflammation and airway remodelling are characteristic features of asthma, but the association between them is unclear. We assessed associations between blood eosinophils and lung function decline in a population-based cohort of young adults.We used linear mixed models to analyse associations between blood eosinophils and spirometry at 21, 26, 32 and 38 years adjusting for sex, smoking, asthma and spirometry at age 18 years. We further analysed associations between mean eosinophil counts and changes in spirometry from ages 21 to 38 years.Higher eosinophils were associated with lower forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratios and lower FEV1 % predicted values for both pre- and post-bronchodilator spirometry (all p-values ≤0.048). Although eosinophil counts were higher in participants with asthma, the associations between eosinophils and spirometry were similar among participants without asthma or wheeze. Participants with mean eosinophil counts >0.4×109 cells·L-1 between 21 and 38 years had greater declines in FEV1/FVC ratios (difference 1.8%, 95% CI 0.7-2.9%; p=0.001) and FEV1 values (difference 3.4% pred, 95% CI 1.5-5.4% pred); p=0.001) than those with lower counts.Blood eosinophils are associated with airflow obstruction and enhanced decline in lung function, independently of asthma and smoking. Eosinophilia is a risk factor for airflow obstruction even in those without symptoms.

How much atopy is attributable to common childhood environmental exposures? A population-based birth cohort study followed to adulthood.

Background: The rising prevalence of atopic diseases implies a strong influence of environmental determinants. Epidemiological studies have identified several early life exposures that appear to influence the risk of developing atopic sensitization, but the combined influence of these exposures is unknown. We sought to estimate the proportion of atopy that could be attributed to common childhood exposures associated with atopic sensitization in adolescence and young adulthood. Methods: Atopic sensitization was measured by skin-prick tests for common aeroallergens in a population-based New Zealand birth cohort at ages 13 and 32 years. The independent effects of previously identified risk and protective factors for atopic sensitization were assessed using multiple logistic regression. Population attributable fractions were calculated for atopic sensitization in childhood and adulthood. Results: Tobacco smoke exposure, dog and cat ownership, nail-biting and thumb-sucking, attending pre-school day care, and household crowding were associated with a lower risk of atopic sensitization whereas breastfeeding was associated with a higher risk. Population attributable fractions for combined effects of these environmental factors suggest that they may account for 58% of atopic sensitization at age 13 and 49% at age 32 years. Conclusions: A substantial proportion of atopic sensitization appears to be attributable to common childhood environmental and lifestyle factors, and the influence of these exposures persists into adulthood. The absolute risks attributable to these exposures will be different in other cohorts and we cannot assume that these associations are necessarily causal. Nevertheless, the findings suggest that identifiable childhood environmental factors contribute substantially to atopic sensitization.

Breastfeeding, maternal asthma and wheezing in the first year of life: a longitudinal birth cohort study.

The impact of breastfeeding on respiratory health is uncertain, particularly when the mother has asthma. We examined the association of breastfeeding and wheezing in the first year of life.We studied 2773 infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Caregivers reported on infant feeding and wheezing episodes at 3, 6 and 12 months. Breastfeeding was classified as exclusive, partial (supplemented with formula or complementary foods) or none.Overall, 21% of mothers had asthma, 46% breastfed for at least 12 months and 21% of infants experienced wheezing. Among mothers with asthma, breastfeeding was inversely associated with infant wheezing, independent of maternal smoking, education and other risk factors (adjusted rate ratio (aRR) 0.52; 95% CI 0.35-0.77 for ≥12 versus <6 months breastfeeding). Compared with no breastfeeding at 6 months, wheezing was reduced by 62% with exclusive breastfeeding (aRR 0.38; 95% CI 0.20-0.71) and by 37% with partial breastfeeding supplemented with complementary foods (aRR 0.63; 95% CI 0.43-0.93); however, breastfeeding was not significantly protective when supplemented with formula (aRR 0.89; 95% CI 0.61-1.30). Associations were not significant in the absence of maternal asthma (p-value for interaction <0.01).Breastfeeding appears to confer protection against wheezing in a dose-dependent manner among infants born to mothers with asthma.

Determinants of peripheral airway function in adults with and without asthma.

BACKGROUND AND OBJECTIVE: Peripheral airway involvement in asthma remains poorly understood. We investigated impulse oscillometry (IOS) measures of peripheral airway function in a population-based birth cohort. METHODS: Pre- and post-bronchodilator spirometry and IOS measures of respiratory resistance and reactance were measured in 915 participants at age 38 years. RESULTS: Current asthma was associated with impairments in both spirometry and IOS parameters. These impairments were greater in men and in those with childhood persistent asthma. Spirometry and IOS values for those whose asthma was in remission were not different to non-asthmatic participants. There were significant changes in IOS in both asthmatic and non-asthmatic participants after bronchodilator, but between-group differences persisted. Higher BMIs were associated with impairments in IOS but not spirometry. Cumulative tobacco use was associated with spirometric airflow obstruction in both sexes, whereas cannabis use was associated with impairments in IOS in women. Despite higher lifetime exposure, there were few associations between cannabis and IOS in men. CONCLUSION: Asthma is associated with abnormalities in IOS measures of peripheral airway dysfunction. This association is stronger in men and in those with asthma persisting since childhood. Tobacco and cannabis use are associated with different patterns of spirometry and IOS abnormalities and may affect the bronchial tree at different airway generations with differences in susceptibility between sexes.

Harmonization of Food-Frequency Questionnaires and Dietary Pattern Analysis in 4 Ethnically Diverse Birth Cohorts.

BACKGROUND: Canada is an ethnically diverse nation, which introduces challenges for health care providers tasked with providing evidence-based dietary advice. OBJECTIVES: We aimed to harmonize food-frequency questionnaires (FFQs) across 4 birth cohorts of ethnically diverse pregnant women to derive robust dietary patterns to investigate maternal and newborn outcomes. METHODS: The NutriGen Alliance comprises 4 prospective birth cohorts and includes 4880 Canadian mother-infant pairs of predominantly white European [CHILD (Canadian Healthy Infant Longitudinal Development) and FAMILY (Family Atherosclerosis Monitoring In earLY life)], South Asian [START (SouTh Asian birth cohoRT)-Canada], or Aboriginal [ABC (Aboriginal Birth Cohort)] origins. CHILD used a multiethnic FFQ based on a previously validated instrument designed by the Fred Hutchinson Cancer Research Center, whereas FAMILY, START, and ABC used questionnaires specifically designed for use in white European, South Asian, and Aboriginal people, respectively. The serving sizes and consumption frequencies of individual food items within the 4 FFQs were harmonized and aggregated into 36 common food groups. Principal components analysis was used to identify dietary patterns that were internally validated against self-reported vegetarian status and externally validated against a modified Alternative Healthy Eating Index (mAHEI). RESULTS: Three maternal dietary patterns were identified-"plant-based," "Western," and "health-conscious"-which collectively explained 29% of the total variability in eating habits observed in the NutriGen Alliance. These patterns were strongly associated with self-reported vegetarian status (OR: 3.85; 95% CI: 3.47, 4.29; r2 = 0.30, P < 0.001; for a plant-based diet), and average adherence to the plant-based diet was higher in participants in the fourth quartile of the mAHEI than in the first quartile (mean difference: 46.1%; r2 = 0.81, P < 0.001). CONCLUSION: Dietary data collected by using FFQs from ethnically diverse pregnant women can be harmonized to identify common dietary patterns to investigate associations between maternal dietary intake and health outcomes.

The relationship between body fat and respiratory function in young adults.

The relationship between adiposity and respiratory function is poorly understood. Most studies investigating this have used indirect measures of body fat and few have assessed how changes in adiposity influence lung function.Body fat measured by bio-electrical impedance analysis, body mass index, waist circumference, spirometry, body plethysmography and transfer factor were measured at ages 32 and 38 years in 361 non-smoking, non-asthmatic participants from a population-based birth cohort.Higher percentage body fat was associated with lower spirometric and plethysmographic lung volumes, but not with airflow obstruction, or transfer factor at 32 years. Changes in adiposity between ages 32 and 38 years were inversely associated with changes in lung volumes. These associations were generally stronger in men than women, but an association between increasing adiposity and lower airway function (forced expiratory volume in 1 s/forced vital capacity) was only found in women. Similar associations were found for body mass index and waist circumference.Higher percentage body fat is associated with lower lung volumes. Direct and indirect measures of adiposity had similar associations with lung function. Adiposity had a greater effect on lung volumes in men than women but was associated with airway function only in women. There was little evidence that adiposity influenced transfer factor.

Cognitive Enhancement in Infants Associated with Increased Maternal Fruit Intake During Pregnancy: Results from a Birth Cohort Study with Validation in an Animal Model.

In-utero nutrition is an under-studied aspect of cognitive development. Fruit has been an important dietary constituent for early hominins and humans. Among 808 eligible CHILD-Edmonton sub-cohort subjects, 688 (85%) had 1-year cognitive outcome data. We found that each maternal daily serving of fruit (sum of fruit plus 100% fruit juice) consumed during pregnancy was associated with a 2.38 point increase in 1-year cognitive development (95% CI 0.39, 4.37; p<0.05). Consistent with this, we found 30% higher learning Performance index (PI) scores in Drosophila offspring from parents who consumed 30% fruit juice supplementation prenatally (PI: 85.7; SE 1.8; p<0.05) compared to the offspring of standard diet parents (PI: 65.0 SE 3.4). Using the Drosophila model, we also show that the cyclic adenylate monophosphate (cAMP) pathway may be a major regulator of this effect, as prenatal fruit associated cognitive enhancement was blocked in Drosophila rutabaga mutants with reduced Ca(2+)-Calmodulin-dependent adenylyl cyclase. Moreover, gestation is a critical time for this effect as postnatal fruit intake did not enhance cognitive performance in either humans or Drosophila. Our study supports increased fruit consumption during pregnancy with significant increases in infant cognitive performance. Validation in Drosophila helps control for potential participant bias or unmeasured confounders.

Thumb-Sucking, Nail-Biting, and Atopic Sensitization, Asthma, and Hay Fever.

BACKGROUND: The hygiene hypothesis suggests that early-life exposure to microbial organisms reduces the risk of developing allergies. Thumb-sucking and nail-biting are common childhood habits that may increase microbial exposures. We tested the hypothesis that children who suck their thumbs or bite their nails have a lower risk of developing atopy, asthma, and hay fever in a population-based birth cohort followed to adulthood. METHODS: Parents reported children's thumb-sucking and nail-biting habits when their children were ages 5, 7, 9, and 11 years. Atopic sensitization was defined as a positive skin-prick test (≥2-mm weal) to ≥1 common allergen at 13 and 32 years. Associations between thumb-sucking and nail-biting in childhood, and atopic sensitization, asthma, and hay fever at these ages were assessed by using logistic regression with adjustments for sex and other potential confounding factors: parental atopy, breastfeeding, pet ownership, household crowding, socioeconomic status, and parental smoking. RESULTS: Thirty-one percent of children were frequent thumb-suckers or nail-biters at ≥1 of the ages. These children had a lower risk of atopic sensitization at age 13 years (odds ratio 0.67, 95% confidence interval 0.48-0.92, P = .013) and age 32 years (odds ratio 0.61, 95% confidence interval 0.46-0.81, P = .001). These associations persisted when adjusted for multiple confounding factors. Children who had both habits had a lower risk of atopic sensitization than those who had only 1. No associations were found for nail-biting, thumb-sucking, and asthma or hay fever at either age. CONCLUSIONS: Children who suck their thumbs or bite their nails are less likely to have atopic sensitization in childhood and adulthood.

The Effect of Cigarette Smoking on Lung Function in Young Adults with Asthma.

RATIONALE: Life-course persistent asthma and tobacco smoking are risk factors for irreversible airflow obstruction. It is often assumed that smoking and asthma have additive or multiplicative effects on the risk for airflow obstruction, but this has not been demonstrated in prospective studies of children with persistent asthma. OBJECTIVES: To investigate the effects of smoking and asthma on the development of airflow obstruction in a population-based birth cohort followed to age 38 years. METHODS: Reports of childhood asthma from ages 9, 11, and 13 and self-reports of adult asthma at ages 32 and 38 years were used to define childhood-onset persistent asthma (n = 91), late-onset asthma (n = 93), asthma in remission (n = 85), and nonasthmatic (n = 572) phenotypes. Cumulative tobacco smoking histories and spirometry were obtained at ages 18, 21, 26, 32, and 38 years. Analyses were by generalized estimating equations adjusting for childhood spirometry, body mass index, age, and sex. MEASUREMENTS AND MAIN RESULTS: Smoking history and childhood-onset persistent asthma were both associated with lower FEV1/FVC ratios. Associations between smoking and FEV1/FVC ratios were different between asthma phenotypes (interaction P < 0.001). Smoking was associated with lower prebronchodilator and post-bronchodilator FEV1/FVC ratios among subjects without asthma and those with late-onset or remittent asthma, but smoking was not associated with lower FEV1/FVC ratios among those with childhood-onset persistent asthma. CONCLUSIONS: Childhood-onset persistent asthma is associated with airflow obstruction by mid-adult life, but this does not seem to be made worse by tobacco smoking. We found no evidence that smoking and childhood-persistent asthma have additive or multiplicative effects on airflow obstruction.

Effects of quitting cannabis on respiratory symptoms.

Smoking cannabis is associated with symptoms of bronchitis. Little is known about the persistence of symptoms after stopping cannabis use. We assessed associations between changes in cannabis use and respiratory symptoms in a population-based cohort of 1037 young adults. Participants were asked about cannabis and tobacco use at ages 18, 21, 26, 32 and 38 years. Symptoms of morning cough, sputum production, wheeze, dyspnoea on exertion and asthma diagnoses were ascertained at the same ages. Frequent cannabis use was defined as ≥52 occasions over the previous year. Associations between frequent cannabis use and respiratory symptoms were analysed using generalised estimating equations with adjustments for tobacco smoking, asthma, sex and age. Frequent cannabis use was associated with morning cough (OR 1.97, p<0.001), sputum production (OR 2.31, p<0.001) and wheeze (OR 1.55, p<0.001). Reducing or quitting cannabis use was associated with reductions in the prevalence of cough, sputum and wheeze to levels similar to nonusers.Frequent cannabis use is associated with symptoms of bronchitis in young adults. Reducing cannabis use often leads to a resolution of these symptoms.