Obstructive and restrictive spirometry from school age to adulthood: three birth cohort studies.

Background: Spirometric obstruction and restriction are two patterns of impaired lung function which are predictive of poor health. We investigated the development of these phenotypes and their transitions through childhood to early adulthood. Methods: In this study, we analysed pooled data from three UK population-based birth cohorts established between 1989 and 1995. We applied descriptive statistics, regression modelling and data-driven modelling to data from three population-based birth cohorts with at least three spirometry measures from childhood to adulthood (mid-school: 8-10 years, n = 8404; adolescence: 15-18, n = 5764; and early adulthood: 20-26, n = 4680). Participants were assigned to normal, restrictive, and obstructive spirometry based on adjusted regression residuals. We considered two transitions: from 8-10 to 15-18 and from 15-18 to 20-26 years. Findings: Obstructive phenotype was observed in ∼10%, and restrictive in ∼9%. A substantial proportion of children with impaired lung function in school age (between one third in obstructive and a half in restricted phenotype) improved and achieved normal and stable lung function to early adulthood. Of those with normal lung function in school-age, <5% declined to adulthood. Underweight restrictive and obese obstructive participants were less likely to transit to normal. Maternal smoking during pregnancy and current asthma diagnosis increased the risk of persistent obstruction and worsening. Significant associate of worsening in restrictive phenotypes was lower BMI at the first lung function assessment. Data-driven methodologies identified similar risk factors for obstructive and restrictive clusters. Interpretation: The worsening and improvement in obstructive and restrictive spirometry were observed at all ages. Maintaining optimal weight during childhood and reducing maternal smoking during pregnancy may reduce spirometry obstruction and restriction and improve lung function. Funding: MRC Grant MR/S025340/1.

Deriving and validating an asthma diagnosis prediction model for children and young people in primary care.

Introduction: Accurately diagnosing asthma can be challenging. We aimed to derive and validate a prediction model to support primary care clinicians assess the probability of an asthma diagnosis in children and young people. Methods: The derivation dataset was created from the Avon Longitudinal Study of Parents and Children (ALSPAC) linked to electronic health records. Participants with at least three inhaled corticosteroid prescriptions in 12-months and a coded asthma diagnosis were designated as having asthma. Demographics, symptoms, past medical/family history, exposures, investigations, and prescriptions were considered as candidate predictors. Potential candidate predictors were included if data were available in ≥60% of participants. Multiple imputation was used to handle remaining missing data. The prediction model was derived using logistic regression. Internal validation was completed using bootstrap re-sampling. External validation was conducted using health records from the Optimum Patient Care Research Database (OPCRD). Results: Predictors included in the final model were wheeze, cough, breathlessness, hay-fever, eczema, food allergy, social class, maternal asthma, childhood exposure to cigarette smoke, prescription of a short acting beta agonist and the past recording of lung function/reversibility testing. In the derivation dataset, which comprised 11,972 participants aged <25 years (49% female, 8% asthma), model performance as indicated by the C-statistic and calibration slope was 0.86, 95% confidence interval (CI) 0.85-0.87 and 1.00, 95% CI 0.95-1.05 respectively. In the external validation dataset, which included 2,670 participants aged <25 years (50% female, 10% asthma), the C-statistic was 0.85, 95% CI 0.83-0.88, and calibration slope 1.22, 95% CI 1.09-1.35. Conclusions: We derived and validated a prediction model for clinicians to calculate the probability of asthma diagnosis for a child or young person up to 25 years of age presenting to primary care. Following further evaluation of clinical effectiveness, the prediction model could be implemented as a decision support software.

Risk factors for PICU admission and death among children and young people hospitalized with COVID-19 and PIMS-TS in England during the first pandemic year.

Identifying which children and young people (CYP) are most vulnerable to serious infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important to guide protective interventions. To address this question, we used data for all hospitalizations in England among 0-17 year olds from 1 February 2019 to 31 January 2021. We examined how sociodemographic factors and comorbidities might be risk factors for pediatric intensive care unit (PICU) admission among hospitalizations due to the following causes: Coronavirus Disease 2019 (COVID-19) and pediatric inflammatory multi-system syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the first pandemic year (2020-2021); hospitalizations due to all other non-traumatic causes in 2020-2021; hospitalizations due to all non-traumatic causes in 2019-2020; and hospitalizations due to influenza in 2019-2020. Risk of PICU admission and death from COVID-19 or PIMS-TS in CYP was very low. We identified 6,338 hospitalizations with COVID-19, of which 259 were admitted to a PICU and eight CYP died. We identified 712 hospitalizations with PIMS-TS, of which 312 were admitted to a PICU and fewer than five CYP died. Hospitalizations with COVID-19 and PIMS-TS were more common among males, older CYP, those from socioeconomically deprived neighborhoods and those who were of non-White ethnicity (Black, Asian, Mixed or Other). The odds of PICU admission were increased in CYP younger than 1 month old and decreased among 15-17 year olds compared to 1-4 year olds with COVID-19; increased in older CYP and females with PIMS-TS; and increased for Black compared to White ethnicity in patients with COVID-19 and PIMS-TS. Odds of PICU admission in COVID-19 were increased for CYP with comorbidities and highest for CYP with multiple medical problems. Increases in odds of PICU admission associated with different comorbidities in COVID-19 showed a similar pattern to other causes of hospitalization examined and, thus, likely reflect background vulnerabilities. These findings identify distinct risk factors associated with PICU admission among CYP with COVID-19 or PIMS-TS that might aid treatment and prevention strategies.

Associations between a smoke-free homes intervention and childhood admissions to hospital in Scotland: an interrupted time-series analysis of whole-population data.

BACKGROUND: Many children are exposed to second-hand smoke in the home and are at increased risk of asthma and other respiratory conditions. In Scotland, a public health mass-media campaign was launched on March 24, 2014, called Take it Right Outside (TiRO), with a focus on reducing the exposure of children to domestic second-hand smoke. In this study, our aim was to establish whether the TiRO campaign was followed by a decrease in hospital admissions for childhood asthma and other respiratory conditions related to second-hand smoke exposure across Scotland. METHODS: For an interrupted time-series analysis, data were obtained on all hospital admissions in Scotland between 2000 and 2018 for children aged younger than 16 years. We studied changes in the monthly incidence of admissions for conditions potentially related to second-hand smoke exposure (asthma, lower respiratory tract infection, bronchiolitis, croup, and acute otitis media) per 1000 children following the 2014 TiRO campaign, while considering national legislation banning smoking in public spaces from 2006. We considered asthma to be the primary condition related to second-hand smoke exposure, with monthly asthma admissions as the primary outcome. Gastroenteritis was included as a control condition. The analysis of asthma admissions considered subgroups stratified by age and area quintile of the Scottish Index of Multiple Deprivations (SIMD). FINDINGS: 740 055 hospital admissions were recorded for children. 138 931 (18·8%) admissions were for respiratory conditions potentially related to second-hand smoke exposure, of which 32 342 (23·3%) were for asthma. After TiRO in 2014, we identified a decrease relative to the underlying trend in the slope of admissions for asthma (-0·48% [-0·85 to -0·12], p=0·0096) in younger children (age <5 years), but not in older children (age 5-15 years). Asthma admissions did not change after TiRO among children 0-15 years of age when data were analysed according to area deprivation quintile. Following the 2006 legislation, independent of TiRO, asthma admissions decreased in both younger children (-0·36% [-0·67 to -0·05], p=0·021) and older children (-0·68% [-1·00 to -0·36], p<0·0001), and in children from the most deprived (SIMD 1; -0·49% [-0·87 to -0·11], p=0·011) and intermediate deprived (SIMD 3; -0·70% [-1·17 to -0·23], p=0·0043) area quintiles, but not in those from the least deprived (SIMD 5) area quintile. INTERPRETATION: Our findings suggest that smoke-free home interventions could be an important tool to reduce asthma admissions in young children, and that smoke-free public space legislation might improve child health for many years, especially in the most deprived communities. FUNDING: University of Aberdeen Research Excellence Framework 2021 Impact Support Award Scheme.

Comparative primary paediatric nasal epithelial cell culture differentiation and RSV-induced cytopathogenesis following culture in two commercial media.

The culture of differentiated human airway epithelial cells allows the study of pathogen-host interactions and innate immune responses in a physiologically relevant in vitro model. As the use of primary cell culture has gained popularity the availability of the reagents needed to generate these cultures has increased. In this study we assessed two different media, Promocell and PneumaCult, during the differentiation and maintenance of well-differentiated primary nasal epithelial cell cultures (WD-PNECs). We compared and contrasted the consequences of these media on WD-PNEC morphological and physiological characteristics and their responses to respiratory syncytial virus (RSV) infection. We found that cultures generated using PneumaCult resulted in greater total numbers of smaller, tightly packed, pseudostratified cells. However, cultures from both media resulted in similar proportions of ciliated and goblet cells. There were no differences in RSV growth kinetics, although more ciliated cells were infected in the PneumaCult cultures. There was also significantly more IL-29/IFNλ1 secreted from PneumaCult compared to Promocell cultures following infection. In conclusion, the type of medium used for the differentiation of primary human airway epithelial cells may impact experimental results.

A systematic review of associations between maternal exposures during pregnancy other than smoking and antenatal fetal measurements.

BACKGROUND: Reduced birth weight is associated with many maternal environmental exposures during pregnancy, but the gestational age at onset of this association is unknown. We have previously reported associations between maternal smoking and fetal size. OBJECTIVE: To report on our systematic review of the literature describing associations between antenatal size and growth and maternal exposures during pregnancy. DATA SOURCES: Electronic databases (OVID and EMBASE) and web sites for cohort studies were searched. Studies were eligible if they examined associations between maternal environmental exposures (including ambient air exposure, diet and alcohol) and antenatal fetal ultrasound measurements. The Navigation Guide was used to assess the strength of evidence. RESULTS: There were 451 abstracts identified and 36 papers were included of which maternal diet was the exposure of interest in 15, maternal ambient air exposure in 10, maternal alcohol in 3 and other exposures in 8. The first paper was published in 2006. Associations were present between exposures and fetal measurements in 18% of comparisons with second trimester measurements and in 46% of comparisons with third trimester measurements. In the third trimester, when an association was present, reduced head size was most commonly (58%) associated with current or previous maternal exposure, with reduced length being least commonly (32%) associated and reduced weight being intermediate (52%). In the third trimester, increased maternal nitrogen dioxide exposure was associated with reduced head size was associated with in all seven studies identified and reduced fetal weight in five out of six studies. CONCLUSION: There is sufficient evidence of toxicity in the context of maternal exposure to nitrogen dioxide and reduced third trimester fetal head size. There is currently insufficient evidence of toxicity with regard to maternal exposures to dietary factors, alcohol and environmental chemicals and reduced fetal size.

Glutathione S-Transferase Genotype Protects against In Utero Tobacco-linked Lung Function Deficits.

Rationale:In utero tobacco exposure is associated with reduced lung function from infancy. Antioxidant enzymes from the glutathione S-transferase (GST) family may protect against these lung function deficits.Objectives: To assess the long-term effect of in utero smoke exposure on lung function into adulthood, and to assess whether GSTT1 and GSTM1 active genotypes have long-term protective effects on lung function.Methods: In this longitudinal study based on a general population (n = 253), lung function was measured during infancy and at 6, 11, 18, and 24 years. GSTM1 and GSTT1 genotype was analyzed in a subgroup (n = 179). Lung function was assessed longitudinally from 6 to 24 years (n = 199).Measurements and Main Results: Exposure to maternal in utero tobacco was associated with lower FEV1 and FVC longitudinally from 6 to 24 years (mean difference, -3.87% predicted, P = 0.021; -3.35% predicted, P = 0.035, respectively). Among those homozygous for the GSTM1-null genotype, in utero tobacco exposure was associated with lower FEV1 and FVC compared with those with no in utero tobacco exposure (mean difference, -6.2% predicted, P = 0.01; -4.7% predicted, P = 0.043, respectively). For those with GSTM1 active genotype, there was no difference in lung function whether exposed to maternal in utero tobacco or not. In utero tobacco exposure was associated with deficits in lung function among those with both GSTT1-null and GSTT1-active genotypes.Conclusions: Certain GST genotypes may have protective effects against the long-term deficits in lung function associated with in utero tobacco exposure. This offers potential preventative targets in antioxidant pathways for at-risk infants of smoking mothers.

Variants in genes coding for glutathione S-transferases and asthma outcomes in children.

Our hypothesis was that children with mutations in genes coding for glutathione S-transferases (GST) have worse asthma outcomes compared with children with active type genotype. Data were collected in five populations. The rs1695 single nucleotide polymorphism (GSTP1) was determined in all cohorts (3692 children) and GSTM1 and GSTT1 null genotype were determined in three cohorts (2362 children). GSTT1 null (but not other genotypes) was associated with a minor increased risk for asthma attack and there were no significant associations between GST genotypes and asthma severity. Interactions between GST genotypes and SHS exposure or asthma severity with the study outcomes were nonsignificant. We find no convincing evidence that the GST genotypes studied are related to asthma outcomes.

Airway function in infancy is linked to airflow measurements and respiratory symptoms from childhood into adulthood.

INTRODUCTION: Increasing evidence suggests that poor lung function in adulthood is determined very early in life. Our study aims were: (1) identify factors associated with early infant lung function; (2) quantify the link between early infant lung function and early adult lung function; and (3) identify environmental and inherited factors which predict lung function throughout the post-natal growth period. METHODS: In this longitudinal study, 253 individuals were recruited antenatally. Lung function and allergy testing occurred at 1, 6, 12 months, 6, 11, 18, and 24 years of age. The relationship between lung function at 1 month (V'maxFRC) and spirometry variables at each follow-up was evaluated. Early life predictors of spirometry were assessed longitudinally using linear mixed models. RESULTS: V'maxFRC correlated positively with FEF25-75% at every assessment from 6 to 24 years and FEV1 /FVC at 11 and 24 years and inversely with airway responsiveness at 6 and 18 years. Maternal asthma and smoking in pregnancy were associated with lower FEV1 from 6 to 24 years (-99 mL, P = 0.03; -77 mL, P = 0.045 respectively). Lower V'maxFRC at 1 month was associated with asthma and wheeze through to 24 years. CONCLUSION: Lung airflow measurements track from birth into early adulthood, suggesting a permanent and stable airway framework is laid down in the antenatal period. Lower infant airway function is associated with respiratory symptoms into adulthood, indicating the link is clinically important. Antenatal and early life exposures must be addressed in order to maximize airway growth and reduce lifelong respiratory compromise.

Lung function trajectories from pre-school age to adulthood and their associations with early life factors: a retrospective analysis of three population-based birth cohort studies.

BACKGROUND: Maximal lung function in early adulthood is an important determinant of mortality and COPD. We investigated whether distinct trajectories of lung function are present during childhood and whether these extend to adulthood and infancy. METHODS: To ascertain trajectories of FEV1, we studied two population-based birth cohorts (MAAS and ALSPAC) with repeat spirometry from childhood into early adulthood (1046 participants from 5-16 years and 1390 participants from 8-24 years). We used a third cohort (PIAF) with repeat lung function measures in infancy (V'maxFRC) and childhood (FEV1; 196 participants from 1 month to 18 years of age) to investigate whether these childhood trajectories extend from early life. We identified trajectories using latent profile modelling. We created an allele score to investigate genetic associations of trajectories, and constructed a multivariable model to identify their early-life predictors. FINDINGS: We identified four childhood FEV1 trajectories: persistently high, normal, below average, and persistently low. The persistently low trajectory (129 [5%] of 2436 participants) was associated with persistent wheezing and asthma throughout follow-up. In genetic analysis, compared with the normal trajectory, the pooled relative risk ratio per allele was 0·96 (95% CI 0·92-1·01; p=0·13) for persistently high, 1·01 (0·99-1·02; p=0·49) for below average, and 1·05 (0·98-1·13; p=0·13) for persistently low. Most children in the low V'maxFRC trajectory in infancy did not progress to the low FEV1 trajectory in childhood. Early-life factors associated with the persistently low trajectory included recurrent wheeze with severe wheezing exacerbations, early allergic sensitisation, and tobacco smoke exposure. INTERPRETATION: Reduction of childhood smoke exposure and minimisation of the risk of early-life sensitisation and wheezing exacerbations might reduce the risk of diminished lung function in early adulthood. FUNDING: None.

Pro-inflammatory mediator responses from neonatal airway epithelial cells and early childhood wheeze.

BACKGROUND: Airway epithelial cell (AEC) function differs between children with and without asthma. Here, we associated neonatal AEC function with asthma symptoms at 4 years of age. METHODS: Nasal AEC were collected from neonates within 48 h of birth. Cells were cultured and stimulated with tumor necrosis factor alpha/interleukin-1 beta (TNFα/IL-1ß), lipopolysaccharide (LPS), or house dust mite (HDM). Absolute concentrations of pro-inflammatory mediators in the culture supernatant were quantified and expressed as median [interquartile range] in pg/mg protein. A parent-completed respiratory questionnaire was returned when the child was 4 years old. RESULTS: AEC were successfully cultured in 139 neonates, of whom 120 were contacted at 4 years and 91 (76%) questionnaires were returned. Sixteen children had wheezed ever and 11 had recent wheeze. At birth, when compared to those with no recent wheeze, supernatants from cultured neonatal AEC from the children with recent wheeze had reduced median IL-8 (CXCL8) release after treatment with culture medium alone (P = 0.049), with TNFα/IL-1ß (P < 0.001) and LPS (P = 0.004). Additionally, and when compared to those with no recent wheeze, 4 year olds with recent wheeze had reduced neonatal AEC release of IL-6 (P = 0.013), GMCSF (P = 0.012), and ICAM-1 (P = 0.017) after treatment with TNFα/IL-1ß and reduced release of ICAM-1 (P = 0.038) and RANTES (P = 0.042) after treatment with HDM. CONCLUSIONS: Abnormalities in AEC function are present at birth before the onset of childhood wheeze. The relationship between reduced AEC function at birth and wheeze at 4 years was not exclusive, suggesting that post-natal factors are required for the AEC abnormality to translate into symptoms.

Differences in Body Mass Index between Siblings Who Are Discordant for Exposure to Antenatal Maternal Smoking.

BACKGROUND: Maternal smoking during pregnancy is associated with increased childhood body mass index (BMI), but the relationship may be due to confounding by maternal factors. This study tested the hypothesis that siblings born to mothers who begin to smoke between pregnancies will have higher BMI than older unexposed siblings. METHODS: Maternal details from the Aberdeen Maternity and Neonatal Databank were linked to the Study of Trends in Obesity in North East Scotland which holds offspring BMI at 5 years of age. Change in maternal smoking status between pregnancies was linked to offspring BMI and also to the difference in BMI between siblings. RESULTS: Maternal smoking status in successive pregnancies was linked to child BMI at age 5 years in 6581 mother-child pairs of whom 718 included sibling pars. Children whose mothers had quit, started smoking or smoked in consecutive pregnancies had higher BMI compared with those not exposed to maternal smoking. Siblings born after onset of maternal smoking had higher mean BMI z score (0.19, 95% confidence interval (CI) 0.01, 0.36) compared with unexposed older siblings. Mean BMI z score was also higher by mean of 0.10 (95% CI 0.01, 0.20) in younger sibling compared with older siblings born to mothers who smoked in both pregnancies. BMI z score was not significantly different between siblings whose mothers quit between pregnancies. CONCLUSIONS: In utero exposure to maternal smoking during pregnancy may increase the likelihood of increased BMI in childhood.

Maternal exposure to ambient air pollution and fetal growth in North-East Scotland: A population-based study using routine ultrasound scans.

BACKGROUND: Maternal ambient air pollution exposure is associated with reduced birthweight. Few studies have examined the effect on growth in utero and none have examined the effect of exposure to particulates less than 2.5µm (PM2.5) and possible effect modification by smoking status. OBJECTIVES: Examine the effect of maternal exposure to ambient concentrations of PM10, PM2.5 and nitrogen dioxide (NO2) for in utero fetal growth, size at birth and effect modification by smoking status. METHODS: Administratively acquired second and third trimester fetal measurements (bi-parietal diameter, femur length and abdominal circumference), birth outcomes (weight, crown heel length and occipito-frontal circumference) and maternal details were obtained from routine fetal ultrasound scans and maternity records (period 1994-2009). These were modelled against residential annual pollution concentrations (calendar year mean) adjusting for covariates and stratifying by smoking status. RESULTS: In the whole sample (n=13,775 pregnancies), exposure to PM10, PM2.5 and NO2 was associated with reductions in measurements at birth and biparietal diameter from late second trimester onwards. Among mothers who did not smoke at all during pregnancy (n=11,075), associations between biparietal diameter and pollution exposure remained significant but were insignificant among those who did smoke (n=2700). Femur length and abdominal circumference were not significantly associated with pollution exposure. CONCLUSIONS: Fetal growth is strongly associated with particulates exposure from later in second trimester onwards but the effect appears to be subsumed by smoking. Typical ambient exposures in this study were relatively low compared to other studies and given these results, it may be necessary to consider reducing recommended "safe" ambient air exposures.

A systematic review of maternal smoking during pregnancy and fetal measurements with meta-analysis.

BACKGROUND: Maternal smoking during pregnancy is linked to reduced birth weight but the gestation at onset of this relationship is not certain. We present a systematic review of the literature describing associations between maternal smoking during pregnancy and ultrasound measurements of fetal size, together with an accompanying meta-analysis. METHODS: Studies were selected from electronic databases (OVID, EMBASE and Google Scholar) that examined associations between maternal smoking or smoke exposure and antenatal fetal ultrasound measurements. Outcome measures were first, second or third trimester fetal measurements. RESULTS: There were 284 abstracts identified, 16 papers were included in the review and the meta-analysis included data from eight populations. Maternal smoking was associated with reduced second trimester head size (mean reduction 0.09 standard deviation (SD) [95% CI 0.01, 0.16]) and femur length (0.06 [0.01, 0.10]) and reduced third trimester head size (0.18 SD [0.13, 0.23]), femur length (0.27 SD [0.21, 0.32]) and estimated fetal weight (0.18 SD [0.11, 0.24]). Higher maternal cigarette consumption was associated with a lower z score for head size in the second (mean difference 0.09 SD [0, 0.19]) and third (0.15 SD [0.03, 0.26]) trimesters compared to lower consumption. Fetal measurements were not reduced for those whose mothers quit before or after becoming pregnant compared to mothers who had never smoked. CONCLUSIONS: Maternal smoking during pregnancy is associated with reduced fetal measurements after the first trimester, particularly reduced head size and femur length. These effects may be attenuated if mothers quit or reduce cigarette consumption during pregnancy.

Changes in the relationship between asthma and associated risk factors over fifty years.

BACKGROUND: Childhood asthma is a common condition whose prevalence is changing. We hypothesized that the relationship between asthma and associated risk factors has changed over a 50-year period. METHODS: An ecological study design was used. Children aged 8-13 attending schools in Aberdeen city were surveyed on seven occasions between 1964 and 2014. The following were determined: history of asthma, history of eczema, parental smoking, parental asthma, sex and socio-economic status. Analysis was by a structural change model with two knots. The outcome reported was the change in odds ratio between asthma and a given risk factor during a given period. RESULTS: There were 23,241 questionnaires distributed and 17,439 returned (75%). The odds ratio (OR) for a child with asthma to have eczema increased between 1989 and 1999 by 1.031 [95% CI 1.028, 1.035] and by 1.042 between 2004 and 2014 [1.038, 1.047]. The OR for a child with asthma to have a parent who smoked rose by 1.032 [1.028, 1.036] between 1989 and 1999 and by 1.043 [1.038, 1.047] between 2004 and 2014), and to have a parent with asthma (1.027 [1.022, 1.031] for 1994-99 and 1.042 [1.037, 1.048] for 2004-2014). The OR for a child with asthma being male, but not and being from the most deprived communities, rose between 1989-1999 and 2004-2014. CONCLUSIONS: The relationship between asthma prevalence and particular risk factors changed over the 50-year period of study, and this might reflect changes in children's environment and/or susceptibility.

An interview study of pregnant women who were provided with indoor air quality measurements of second hand smoke to help them quit smoking.

BACKGROUND: Maternal smoking can cause health complications in pregnancy. Particulate matter (PM2.5) metrics applied to second hand smoke (SHS) concentrations provide indoor air quality (IAQ) measurements and have been used to promote smoking behaviour change among parents of young children. Here, we present the qualitative results from a study designed to use IAQ measurements to help pregnant women who smoke to quit smoking. METHODS: We used IAQ measurements in two centres (Aberdeen and Coventry) using two interventions: 1. In Aberdeen, women made IAQ measurements in their homes following routine ultrasound scan; 2. In Coventry, IAQ measurements were added to a home-based Stop Smoking in Pregnancy Service. All women were invited to give a qualitative interview to explore acceptability and feasibility of IAQ measurements to help with smoking cessation. A case study approach using grounded theory was applied to develop a typology of pregnant women who smoke. RESULTS: There were 39 women recruited (18 in Aberdeen and 21 in Coventry) and qualitative interviews were undertaken with nine of those women. Diverse accounts of smoking behaviours and experiences of participation were given. Many women reported changes to their smoking behaviours during pregnancy. Most women wanted to make further changes to their own behaviour, but could not commit or felt constrained by living with a partner or family members who smoked. Others could not envisage quitting. Using themes emerging from the interviews, we constructed a typology where women were classified as follows: 'champions for change'; 'keen, but not committed'; and 'can't quit, won't quit'. Three women reported quitting smoking alongside participation in our study. CONCLUSIONS: Pregnant women who smoke remain hard to engage,. Although providing IAQ measurements does not obviously improve quit rates, it can support changes in smoking behaviour in/around the home for some individuals. Our typology might offer a useful assessment tool for midwives.

Primary Paediatric Bronchial Airway Epithelial Cell in Vitro Responses to Environmental Exposures.

The bronchial airway epithelial cell (BAEC) is the site for initial encounters between inhaled environmental factors and the lower respiratory system. Our hypothesis was that release of pro inflammatory interleukins (IL)-6 and IL-8 from primary BAEC cultured from children will be increased after in vitro exposure to common environmental factors. Primary BAEC were obtained from children undergoing clinically indicated routine general anaesthetic procedures. Cells were exposed to three different concentrations of lipopolysaccharide (LPS) or house dust mite allergen (HDM) or particulates extracted from side stream cigarette smoke (SSCS). BAEC were obtained from 24 children (mean age 7.0 years) and exposed to stimuli. Compared with the negative control, there was an increase in IL-6 and IL-8 release after exposure to HDM (p ≤ 0.001 for both comparisons). There was reduced IL-6 after higher compared to lower SSCS exposure (p = 0.023). There was no change in BAEC release of IL-6 or IL-8 after LPS exposure. BAEC from children are able to recognise and respond in vitro with enhanced pro inflammatory mediator secretion to some inhaled exposures.

Factors associated with quality of life in children with asthma living in Scotland.

INTRODUCTION: Asthma affects children's quality of life (QoL) but factors associated with QoL are not well understood. Our hypothesis was that there are factors linked to QoL which are amenable to treatment or environmental modification. METHODS: QoL was ascertained in a study designed to link environmental exposures to asthma outcomes. Univariate and multivariate analysis were used to determine which factors are associated with QoL. RESULTS: There were 553 children with asthma where QoL was determined, mean age 10.3 and 312 (58%) were boys. The median QoL score was 5.9 (interquartile range 4.6, 6.8). In the multivariate model, asthma severity (as evidenced by British Thoracic Society, BTS, treatment step), smoking exposure, socioeconomic status and rhinitis were associated with the QoL score. QoL score was reduced by (i) 30% [95% confidence interval 20, 39] for those on BTS step 4 compared to BTS step 1 treatment (ii) 11% [2, 19] for children with ≥ two resident smokers with reference to no resident smokers (iii) 3% [1, 5] for each quintile difference in deprivation compared to the most affluent and (iv) 9% [4, 14] for children with rhinitis compared to no rhinitis. CONCLUSIONS: The QoL for children with asthma in the UK is generally good. Clinicians caring children with asthma should consider routinely asking about smoke exposure and hayfever symptoms in addition to assessing asthma control.

Primary airway epithelial cell culture and asthma in children-lessons learnt and yet to come.

Until recently the airway epithelial cell (AEC) was considered a simple barrier that prevented entry of inhaled matter into the lung parenchyma. The AEC is now recognized as having an important role in the inflammatory response of the respiratory system to inhaled exposures, and abnormalities of these responses are thought to be important to asthma pathogenesis. This review first explores how the challenges of studying nasal and bronchial AECs in children have been addressed and then summarizes the results of studies of primary AEC function in children with and without asthma. There is good evidence that nasal AECs may be a suitable surrogate for the study of certain aspects of bronchial AEC function, although bronchial AECs remain the gold standard for asthma research. There are consistent differences between children with and without asthma for nasal and bronchial AEC mediator release following exposure to a range of pro-inflammatory stimulants including interleukins (IL)-1ß, IL-4, and IL-13. However, there are inconsistencies between studies, e.g., release of IL-6, an important pro-inflammatory cytokine, is not increased in children with asthma relative to controls in all studies. Future work should expand current understanding of the "upstream" signalling pathways in AEC, study AEC from children before the onset of asthma symptoms and in vitro models should be developed that replicate the in vivo status more completely, e.g., co-culture with dendritic cells. AECs are difficult to obtain from children and collaboration between centers is expected to yield meaningful advances in asthma understanding and ultimately help deliver novel therapies.

Diverging prevalences and different risk factors for childhood asthma and eczema: a cross-sectional study.

OBJECTIVE: To compare the prevalences of and risk factors for asthma, wheeze, hay fever and eczema in primary schoolchildren in Aberdeen in 2014. DESIGN: Cross-sectional survey. SETTING: Primary schools in Aberdeen, North-East Scotland. PARTICIPANTS: Children in Scottish school years primary 1-7 were handed a questionnaire by their class teacher to be completed by their parents and returned to the researchers by post or online. MAIN OUTCOME MEASURES: Lifetime history of asthma, eczema and hay fever, and recent history of wheeze. RESULTS: 41 schools agreed to participate (87%). 11,249 questionnaires were distributed and 3935 returned (35%). A parent-reported lifetime history of asthma, eczema and hay fever was present in 14%, 30% and 24% of children, respectively. The odds of lifetime asthma increased with age (OR 1.1 per year, 95% CI 1.1 to 1.2), male sex (OR 1.89, 95% CI 1.4 to 2.3), parental smoking (OR 1.7, 95% CI 1.2 to 2.3) and eczema (OR 6.6, 95% CI 5.2 to 8.4). Prevalence of recent wheeze was also reported to be 14% and was positively associated with male sex, parental smoking and eczema. In contrast, parental eczema was the only identified predictor of childhood eczema risk. CONCLUSIONS: The lifetime prevalence of asthma in primary schoolchildren was 14% in this survey, approximately half the prevalence of eczema. We report diverging prevalences in relation to previous studies in our locality, and different risk factors for asthma and eczema. These findings suggest that asthma and eczema are unlikely to have a common origin.