Introduction Heart failure (HF) in hypertrophic cardiomyopathy (HCM) is associated with high morbidity and mortality. Predictors of HF, in particular the role of myocardial fibrosis and microvascular ischemia remain unclear. We assessed the predictive value of cardiovascular magnetic resonance (CMR) for development of HF in HCM in an observational cohort study. Methods Serial patients with HCM underwent CMR, including adenosine first-pass perfusion, left atrial (LA) and left ventricular (LV) volumes indexed to body surface area ( i ) and late gadolinium enhancement (%LGE- as a % of total myocardial mass). We used a composite endpoint of HF death, cardiac transplantation, and progression to NYHA class III/IV. Results A total of 543 patients with HCM underwent CMR, of whom 94 met the composite endpoint at baseline. The remaining 449 patients were followed for a median of 5.6 years. Thirty nine patients (8.7%) reached the composite endpoint of HF death (n = 7), cardiac transplantation (n = 2) and progression to NYHA class III/IV (n = 20). The annual incidence of HF was 2.0 per 100 person-years, 95% CI (1.6–2.6). Age, previous non-sustained ventricular tachycardia, LV end-systolic volume indexed to body surface area (LVESVI), LA volume index ; LV ejection fraction, %LGE and presence of mitral regurgitation were significant univariable predictors of HF, with LVESVI (Hazard ratio (HR) 1.44, 95% confidence interval (95% CI) 1.16–1.78, p = 0.001), %LGE per 10% (HR 1.44, 95%CI 1.14–1.82, p = 0.002) age (HR 1.37, 95% CI 1.06–1.77, p = 0.02) and mitral regurgitation (HR 2.6, p = 0.02) remaining independently predictive on multivariable analysis. The presence or extent of inducible perfusion defect assessed using a visual score did not predict outcome (p = 0.16, p = 0.27 respectively). Discussion The annual incidence of HF in a contemporary ambulatory HCM population undergoing CMR is low. Myocardial fibrosis and LVESVI are strongly predictive of future HF, however CMR visual assessment of myocardial perfusion was not.

Asthma has increased in recent decades worldwide, with prevalence up to 15%. In the United States, the direct cost of uncontrolled asthma is estimated at more than $300 billion during next 20 years.1 Allergic sensitization in early life, particularly multiple sensitization, carries the greatest risk for later asthma2 and therefore primary prevention must target infancy, before sensitization occurs. Evidence has emerged that exposure to a high dose of allergen early in life can drive the developing immune system toward a state of tolerance.

Atrial fibrillation (AF) in hypertrophic cardiomyopathy (HC) is associated with significant symptomatic deterioration, heart failure, and thromboembolic disease. There is a need for better mechanistic insight and improved identification of at risk patients. We used cardiovascular magnetic resonance (CMR) to assess predictors of AF in HC, in particular the role of myocardial fibrosis. Consecutive patients with HC referred for CMR 2003 to 2013 were prospectively enrolled. CMR parameters including left ventricular volumes, presence and percentage of late gadolinium enhancement in the left ventricle (%LGE) and left atrial volume index (LAVi) were measured. Overall, 377 patients were recruited (age 62 +/- 14 years, 73% men). Sixty-two patients (16%) developed new-onset AF during a median follow up of 4.5 (interquartile range 2.9 to 6.0) years. Multivariable analysis revealed %L GE (hazard ratio [HR] 1.3 per 10% (confidence interval: 1.0 to 1.5; p = 0.02), LAVi (HR 1.4 per 10 mL/m(2) [1.2 to 1.5; p < 0.001]), age at HC diagnosis, nonsustained ventricular tachycardia and diabetes to be independent predictors of AF. We constructed a simple risk prediction score for future AF based on the multivariable model with a Harrell's Cstatistic of 0.73. In conclusion, the extent of ventricular fibrosis and LA volume independently predicted AF in patients with HC. This finding suggests a mechanistic relation between fibrosis and future AF in HC. CMR with quantification of fibrosis has incremental value over LV and LA measurements in risk stratification for AF. A risk prediction score may be used to identify patients at high risk of future AF who may benefit from more intensive rhythm monitoring and a lower threshold for oral anticoagulation. Crown Copyright (C) 2020 Published by Elsevier Inc. All rights reserved.

The association between maternal and infant dietary exposures and risk of allergic disease development is an area of considerable scientific uncertainty. This study aims to compare dietary habits during pregnancy and lactation in two allergy birth cohorts born in the same location approximately 10 years apart, a timeframe characterised by changes in government dietary advice. The FAIR cohort is a whole birth cohort born between 2001-2002. The 3rdgeneration cohort was born between 2010-2018. Both cohorts were set up on the Isle of Wight (UK) to investigate food allergy prevalence. Nutrition and allergy related data was collected prospectively from recruitment and throughout the infant's early life. Here we present dietary questionnaire data that was collected in the third trimester of pregnancy and at three months of age. Data was available for 1331 participants (969 FAIR and 362 3rdgeneration). A higher proportion of FAIR mothers avoided peanuts during pregnancy (55.6 vs 6.8%, p < 0.05). Parity was the strongest predictive factor, indicating first time mothers were more likely to exclude peanut (OR 1.65, 95% CI 1.25-2.17, p < 0.05). FAIR mothers ate tree nuts and seeds less frequently than 3rdgeneration mothers (p < 0.05). Mothers from the FAIR study were more likely to exclude specific foods during lactation (p < 0.05). Between 2001-2018, maternal consumption of peanut and tree nuts during pregnancy has decreased. First time mothers more likely to restrict their diets, irrespective of the government advice at the time.

Cohort Profile Update: The Isle of Wight Whole Population Birth Cohort (IOWBC) S Hasan Arshad,* Veeresh Patil, Frances Mitchell, Stephen Potter, Hongmei Zhang, Susan Ewart, Linda Mansfield, Carina Venter, John W Holloway and Wilfried J Karmaus 3 David Hide Asthma and Allergy Research Centre, Isle of Wight, St. Mary’s Hospital, Newport, UK, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK, Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, TN, USA, Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, MI, USA, Section of Allergy and Immunology, University of Colorado, Children Hospital Colorado, Denver, CO, USA and Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK

Perceived self-efficacy is the belief that one can manage prospective situations. Good asthma self-management self-efficacy is associated with better asthma outcomes. However, a well-developed and validated tool to measure adolescent asthma self-management self-efficacy is lacking. Our objective was to develop and validate an Adolescent Asthma Self-Efficacy Questionnaire (AASEQ). The first stage of the study included a review of the literature, interviews with adolescents with asthma and consultations with parents and relevant healthcare professionals to develop a prototype scale. To assess reliability and validity, a further group of adolescents completed the prototype scale, the General Self-Efficacy Scale and KidCOPE (measures coping styles). Retesting was undertaken to assess longitudinal validity. Interviews with 28 adolescents and consultations with other stakeholders resulted in a 38-item prototype scale. Key themes were medication, symptom management, triggers, knowledge, attitude and beliefs around asthma, supportive relationships, schools and healthcare professionals. The prototype scale was completed by 243 adolescents. Factor and reliability analysis reduced it to a 27-item scale with four subsections: symptom management; medication; friends, family and school; and asthma beliefs. The 27-item scale had respectable to excellent internal consistency (α's 0.78–0.91) with results that were stable over time (intra-class correlation=0.82) in 63 subjects who completed it twice. Better adolescent asthma self-efficacy was associated with better general self-efficacy and indices of better asthma management. The AASEQ is a reliable and valid tool that is likely to aid future research and practice focused on adolescent asthma self-management and could be a useful intermediate outcome measure to assess the impact of behavioural interventions.

Background Asthma is now widely recognised to be a heterogeneous disease. The last two decades have seen the identification of a number of biological targets and development of various novel therapies. Despite this, asthma still represents a significant health and economic burden worldwide. Why some individuals should continue to suffer remains unclear. Methods The Wessex Asthma Cohort of Difficult Asthma (WATCH) is an ongoing ‘real-life’, prospective study of patients in the University Hospital Southampton Foundation Trust (UHSFT) Difficult Asthma service. Research data capture is aligned with the extensive clinical characterisation required of a commissioned National Health Service (NHS) Specialist Centre for Severe Asthma. Data acquisition includes detailed clinical, health and disease-related questionnaires, anthropometry, allergy and lung function testing, radiological imaging (in a small subset) and collection of biological samples (blood, urine and sputum). Prospective data are captured in parallel to clinical follow up appointments, with data entered into a bespoke database. Discussion The pragmatic ongoing nature of the WATCH study allows comprehensive assessment of the real world clinical spectrum seen in a Specialist Asthma Centre and allows a longitudinal perspective of deeply phenotyped patients. It is anticipated that the WATCH cohort would act as a vehicle for potential collaborative asthma studies and will build upon our understanding of mechanisms underlying difficult asthma.

Background: Asthma prognosis is thought to be influenced in some part by age of onset and female hormonal status but the mechanisms remain unclear. Aim: To explore differences in clinical presentation between men and women in a population of adult onset difficult asthmatics. Methods: 380 patients aged 17-85 years were recruited into the Wessex AsThma CoHort of difficult asthma (WATCH). Asthma history, questionnaires and biological measurements were taken at enrolment. Those with onset ≥19 were split by sex to explore differences in disease. Results: Age of asthma diagnosis was available in 335 of 380 patients with 48% reporting diagnosis at 19 years or older. Men with adult onset difficult asthma had significantly later age of diagnosis and higher FeNO than women. Their perception of disease severity was less and BMI significantly lower than females. Men had higher IgE, lower propensity to salicylate sensitivity and greater level of airway obstruction though this was not specific to age of onset. Additional sex differences in lung function reported within the total WATCH cohort were not seen in this subset of difficult asthmatics. Significance a=<0.001, b=<0.005 Conclusion: Several features of difficult adult onset asthma differ by sex, suggesting potential sex-specific disease influences. This supports the need for further sex-specific studies that might result in new sex-stratified asthma treatments.

Background: Whether the nature of early-onset difficult adult asthma differs by sex remains unclear. Aim: To assess clinical characteristics of early-onset difficult asthma in adulthood stratified by sex. Method: The Wessex AsThma CoHort of difficult asthma (WATCH) at University Hospital Southampton (UHS) UK has enrolled 380 patients from the UHS tertiary difficult asthma clinics. We compared clinical characteristics between sexes in patients with early-onset difficult asthma (age of diagnosis ≤18 years). Results: 190 patients had early-onset difficult asthma; 72.1% female (F) and 27.9% male (M). Median age of diagnosis (F vs M) was 5.0 yrs v 3.0 yrs (p=0.033) with a disease duration of 30.0 yrs v 41.5 yrs (p=0.047). Significant differences in comorbidities (F vs M) existed for salicylate sensitivity (29.9% v 8.0% p=0.002), depression (49.6% v 23.8% p=0.004) and bronchiectasis (7.4% v 21.6% p=0.006). No significant differences were seen for atopy, rhinitis, GORD, obesity, other functional comorbidities (dysfunctional breathing, vocal cord dysfunction and anxiety) or healthcare utilisation. F had a higher prevalence for maintenance oral steroids use (41.6% v 24.5% p=0.029). M showed significantly greater airflow obstruction (M vs F); FEV1 67.9% pred. v 81.7%, FEV1/FVC 62.1% pred. v 71.8% and FEF25-75 35.9% pred. v 56.8% (p<0.001), and higher smoking prevalence (52.8% v 36.5% p=0.040). Conclusion: Early-onset difficult asthma in adulthood was predominantly female, but showed different features by sex. Females had higher prevalence of depression, salicylate sensitivity and steroid dependency, while males were diagnosed earlier, had higher smoking prevalence, worse lung function and associated bronchiectasis.

BACKGROUND AND OBJECTIVE:Despite literature that spans twenty years describing the barriers to asthma self-management in adolescents, successful, clinically based interventions to address this important issue are lacking. Given the limitations of some of the previous studies, we conducted a study that aimed to gain a broader insight into barriers and facilitators to self-management of asthma by adolescents, not just adherence to treatment, and triangulated their views with those of their parents and healthcare professionals.METHODS:Focus groups and interviews were conducted separately for 28 adolescents with asthma aged 12-18 years, 14 healthcare professionals and 12 parents. Focus groups and interviews were audio-recorded, and transcripts from each participant group were analysed separately using inductive thematic analysis. We triangulated the three perspectives by comparing themes that had emerged from each analysis.RESULTS:Adolescents', parents' and healthcare professionals' views were summarized into ten related themes that included forgetting and routines, knowledge, embarrassment and confidence, communication with healthcare professionals, triggers, support at school, apathy and taking responsibility. We found that adolescents, parents and healthcare professionals raised similar barriers and facilitators to self-management and our results provide further validation for previous studies.CONCLUSION AND CLINICAL RELEVANCE:Our study highlights that healthcare professionals may need to consider a range of psychological and contextual issues influencing adolescents' ability to effectively self-manage their asthma, in particular, how they implement treatment routines and the understanding that adolescents have of their condition and treatments. Crucially, healthcare professionals need to consider how this information is communicated and ensure they facilitate open, inclusive, two-way consultations. From this more comprehensive understanding, we have developed interventional strategies that healthcare professionals can utilize to empower adolescents to improve their asthma self-management.

Introduction Heart failure develops in 3%–5% of patients with hypertrophic cardiomyopathy (HCM) and is associated with a ten-fold increase in mortality. Myocardial perfusion abnormalities using positron emission tomography (PET) predict patients at increased risk of heart failure and death, however the mechanism of these perfusion defects has not been demonstrated, nor has the added prognostic value of perfusion imaging over late gadolinium imaging been established. Methods We measured simultaneous pressure and flow in the proximal left anterior descending artery in 33 HCM and 20 control patients at rest and during hyperemia, allowing calculation of wave intensity (WIA). Patients underwent quantitative first-pass perfusion cardiovascular magnetic resonance (CMR). We prospectively recruited a further 328 HCM patients for CMR, including adenosine first pass perfusion, LV and LA volumes and late gadolinium enhancement (LGE). We followed patients for development of heart failure, with a composite endpoint of heart failure death, cardiac transplantation and unplanned heart failure hospitalisation. Results Patients with HCM had a lower coronary flow reserve than controls (1.9±0.8 versus 2.7±0.9, p=0.001). Coronary hemodynamics in HCM were characterised by a very large backward compression wave during systole (38%±11% versus 21±6%, p<0.001) and a proportionately smaller backward expansion wave (33%±6% versus 27±8%, p=0.006) compared to controls. Patients with severe left ventricular outflow tract (LVOT) obstruction had a bisferiens pressure waveform resulting in an additional proximally originating deceleration wave during systole. The proportion of waves acting to accelerate coronary flow increased with hyperemia and the magnitude of change was proportional to the myocardial perfusion reserve. (r=0.62, p<0.001). During a median follow up of 3.2 years, 32 patients met the heart failure endpoint. Baseline left atrial volume indexed to body surface area, LAVi, (HR 1.38 (1.2–1.6), p<0.001),%late gadolinium enhanceme,t%LGE (HR 1.03 (95% CI 1.01–1.05), p=0.03), LV ejection fraction (EF, 0.93 (0.9–0.97) p<0.001) and NYHA class at baseline were all univariate predictors of heart failure outcomes. On multivariable analysis, LAVi,%LGE, NYHA class, LVESVi and MR remained predictive. Presence or extent of inducible perfusion defect did not predict outcome (p=0.94, p=0.61 respectively). Discussion Coronary flow in patients with HCM is deranged. Distally, compressive deformation of intra-myocardial blood vessels during systole result in an abnormally large backward compression wave, while proximally, severe LVOT obstruction is associated with an additional deceleration wave. Perfusion abnormalities in HCM are not simply a consequence of supply/demand mismatch or remodelling of the intra-myocardial blood vessels but represent a dynamic interaction with myocardial mechanics which may be amenable to treatment. In our prognostic study, we identified that while replacement fibrosis was a likely mechanism of progression to heart failure, LAVi as a more global measure of ventricular dysfunction was the strongest prognostic marker in HCM. Although perfusion using PET predicted development of heart failure in HCM, perfusion imaging with CMR did not predict outcome. Perfusion defects in HCM are complex and multifactorial, however do not correlate directly with outcome in large, prospective studies and should not be included in risk stratification scores.

Background: Improved characterisation of Obese-Asthma phenotypes is the first step to better understanding of the relationship between these conditions. Aims: To characterise the Obese-Difficult Asthma phenotype seen in clinical practice. Methods: We studied patients enrolled (n=380) from a tertiary difficult asthma clinic (Southampton, UK) into a longitudinal cohort (WATCH) study. Results: Obesity (BMI>30) was found in 47.0% of the cohort with a female predominance (52.3% female v 36.8% male; p=0.005). Atopy and peripheral eosinophil count did not differ with obesity but fractional exhaled nitric oxide (FeNO) was lower in obese subjects (median 12.7 v 18.9; p=0.002). There were no significant differences in lung function. Obese patients had worse asthma control (median ACQ6 2.7 v 2.2; p=0.001). Psychological comorbidity (HADS score) was higher in obesity for depression (median HADS 6 vs 3; p=0.001), anxiety (7 v 6; p=0.009) and combined (13 v 9; p=0.001). Vocal cord dysfunction was commoner in obesity (p=0.031); dysfunctional breathing, rhinitis and GORD were not. Previous (p=0.03) or current (p=0.02) diagnosis of obstructive sleep apnoea was increased in obesity. More workdays were lost in the last year due to asthma amongst obese subjects (mean 41.45 v 28.93; p=0.03). Biological therapy and maintenance oral corticosteroids (OCS) did not differ. Conclusion: Obese asthmatics appear to perceive their symptoms as more severe, have a greater prevalence of functional co-morbidities and lose a greater number of days to illness, but have lower airway inflammation as assessed by FeNO. Different mechanisms may be driving symptoms in Obese-Difficult Asthma, requiring specific assessment and management strategies.

The Isle of Wight (IOW) cohort includes three generations: 1st generation (F0, grandparents; n=1536), the 2nd generation (F1, n=1456), and the 3rd generation (F2, n=452). The overall objective is to investigate cross generational transfer of risk for allergic diseases. All three generations of the IOW cohort have been assessed for asthma and allergic diseases and information on relevant environmental exposures have been collected. Recruitment and assessment of the IOW 3rd Generation cohort is ongoing; mothers have been assessed twice during pregnancy, while children are being assessed at 3, 12, 24, 36 and 72 months of age for allergic diseases wheeze, eczema and rhinitis using standardized questionnaires. Since the inception of the 3rd Generation study in 2010, 452 children have been born into the cohort whose mothers or fathers are participants of the original IOW cohort. 367 children have been assessed at 3 months, 243 at 12 months, 151 at 24 months and 123 at 36 months. Wheeze occurred in 30.5% (107/351) at 3 months and 29.4% (95/323) at 12 months; eczema occurred in 21.4% (69/323) at 3 months and 24.8% (79/318) at 12 months and nasal symptoms 28.0% (99/353) at 3 months and 15.9% (43/271) at 24 months. Period prevalence of current wheeze, eczema and nasal symptoms was high in the 3rd Generation cohort. The format of recruiting 3 generations of a cohort will provide valuable information on disease risk across generations and associated mechanisms for common diseases such as asthma and allergy.

Difficult asthma is a heterogeneous state, pragmatically defined by the British Thoracic Society (BTS) as "persistent symptoms and/or frequent exacerbations despite treatment at step 4 or step 5 treatment" [1, 2]. It is frequently associated with aggravating comorbidities, causes significant morbidity and healthcare costs, and requires rigorous systematic assessment and treatment approaches [3–7]. Though few exist, referral to a specialist centre with appropriate multidisciplinary expertise and supporting technical resource is recommended [8]. It is unclear whether such care can be effectively delivered in a peripheral healthcare setting. We report initial outcomes of such a care pathway on the Isle of Wight (IOW), UK. Outreaching specialist asthma care can significantly benefit patients with difficult asthma in peripheral settings We would like to thank all the staff at the David Hide Asthma and Allergy Research Centre, Isle of Wight, UK.

Background: Low birth weight and gestational maternal smoking have been linked with reduced lung function in children in many cross sectional studies. However, these associations have not yet been assessed with repeated measurements of lung function. Our aim was to investigate the effects of birth weight, gestational age, and gestational maternal smoking on lung function in children at age 10 and 18 years.Methods: In the Isle of Wight birth cohort spirometry was performed at age 10 and 18 years. Information on birth weight and gestational age were obtained from hospital records. Mothers were asked about smoking during pregnancy. We employed linear mixed models to estimate the effect of these risk factors on repeated measurements of lung function. We considered maternal asthma, sex, neonatal intensive care unit admission, height, socio-economic status, personal smoking in participants at age 18, body mass index and environmental tobacco smoke exposure as potential confounders. Finally, we used path analysis to determine links between birth weight, gestational age and gestational maternal smoking on lung function at age 10 and 18 years.Results: Linear mixed models showed that with every 1 kg increase in birth weight, Forced expiratory volume in one second (FEV1) increased by 42.6 +/- 17.2 mL and Forced expiratory flow between 25% and 75% (FEF25-75) of Forced vital capacity (FVC) increased by 95.5 +/- 41.2 mL at age 18 years after adjusting for potential confounders. Path analysis suggested that birth weight had positive direct effects on FEV1 and FEF25-75 and positive indirect effect on FVC at 10 years which were carried forward to 18 years. Additionally, results also suggested a positive association between gestational age and FEV1, FVC and FEF25-75 at ages 10 and 18 years and an inverse association between gestational smoke exposure and FEV1/FVC ratio and FEF25-75 at age 18 years.Conclusions: Higher birth weight and gestational age were associated with higher FEV1, FVC and FEF25-75 and maternal smoking during pregnancy was associated with reduced FEV1/FVC ratio and FEF25-75. The use of path analysis can improve our understanding of underlying "causal" pathways among different prenatal and childhood factors that affect lung function in both pre-adolescent and adolescent periods. (C) 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

It is unclear why some children with persistent wheeze continue wheezing into adulthood whilst in other subjects wheezing subsides. To assess this the Isle of Wight Birth Cohort (n=1,456) was reviewed at 1, 2, 4, 10 and 18-years with recording of current wheeze at each visit. At 10-years, 4 wheeze phenotypes were defined. Persistent-Wheezers (PW) wheezed in the first 4 years of life and at 10-years (n = 125). We have previously shown that this group suffered significantly in childhood. We studied them further at 18-years and compared those in this group who were still wheezing (n = 72) versus those who were not (n =53) to identify factors associated with ongoing disease in PW. The results showed that those still wheezing at 18 were more likely to be atopic (74% vs 36% p=0.001) and have rhinitis (76% vs 36.2% p<0.001) at 18, be female (56% vs 25.5% p =0.001), be diagnosed with asthma aged 10 (84% vs 68% p=0.042) and 18 (95% vs 6.5% p<0.001).They were less likely to have smoke exposure at 4 (43% vs 63% p=0.036) and 10 (41% vs 61% p=0.049) years but had comparable personal smoking prevalence at 18 and cumulative tobacco exposure over the first 18 years of life. They showed higher levels of exhaled nitric oxide (mean Log10 1.6 vs 1.4 p=0.028) at 18 plus bronchial hyper reactivity (log10 DRS+10) at 10 (1.9 vs 1.5 p=0.003) and at 18 (1.4 vs 1.1 p=0.001). The persistence of PW from childhood into young adulthood is associated with clearly identifiable factors which could help flag up the risk of ongoing disease into adulthood. Whether addressing these factors in childhood can reduce the burden of ongoing disease into adulthood is a matter for future research focus.

BACKGROUND:Many adolescents have poor asthma control and impaired quality of life despite the availability of modern pharmacotherapy. Research suggests that poor adherence to treatment and limited engagement in self-management could be contributing factors. OBJECTIVE:To conduct a systematic review of the barriers and facilitators to self-management of asthma reported by adolescents using a narrative synthesis approach to integrate the findings. DESIGN:MEDLINE, EMBASE, CINAHL, and PsycINFO were searched for all types of study design. Full papers were retrieved for study abstracts that included data from participants aged 12-18 years referring to barriers or facilitators of asthma self-management behaviors. RESULTS:Sixteen studies (5 quantitative and 11 qualitative) underwent data extraction, quality appraisal, and thematic analysis. Six key themes were generated that encompassed barriers and/or facilitators to self-management of asthma in adolescents: Knowledge, Lifestyle, Beliefs and Attitudes, Relationships, Intrapersonal Characteristics, and Communication. CONCLUSIONS:There is a pressing need to prepare adolescents for self-management, using age-appropriate strategies that draw on the evidence we have synthesized. Current clinical practice should focus on ensuring adolescents have the correct knowledge, beliefs, and positive attitude to self-manage their illness. This needs to be delivered in a supportive environment that facilitates two-way communication, fosters adolescents' self-efficacy to manage their disease, and considers the wider social influences that impinge on self-management. Pediatr Pulmonol. 2017;52:430-442. © 2016 Wiley Periodicals, Inc.

Background: Vaccinations have been suggested to be associated with increased risk of allergic diseases. Tetanus vaccination is one of the most frequently administered vaccines as a part of wound management and was also found to be associated with increased serum IgE levels. We hypothesized that the vaccination modifies the risk of allergic diseases through epigenetic changes such as DNA methylation.Method: Data on tetanus vaccination between 10 and 18 years of age was collected from a birth cohort established on the Isle of Wight UK in 1989. DNA methylation data were collected from individuals at different ages (at birth [n = 30], age 10 [n = 34], age 18 [n = 245] and during pregnancy [n = 121]) using the Illumina Infinium HumanMethylation450 K array. Firstly, we performed an epigenome-wide screening to identify cytosine-phosphate-guanine sites (CpGs) associated with tetanus vaccination in 18-year-olds. Secondly, we tested their association with asthma, allergic sensitization, eczema, serum IgE and pulmonary lung function (FVC, FEV1, FEV1/FVC, and FEF25-75%). We then described changes in the methylation of the selected CpG sites over age, and by vaccination status.Results: Tetanus vaccination was found to be associated with decreased methylation of cg14472551 (p value 0.5 x 10(-5), FDR-adjusted p value 2.1 x 10(-4)) and increased methylation of cg01669161 (p value 0.0007, FDR-adjusted p value 0.014). Both CpGs, in turn, were associated with decreased risk of asthma at 18 years of age. Cg14472551 is located in an intron of KIAA1549L, whose protein binds to a B-cell commitment transcription factor; cg01669161 is located between an antisense regulator of the proteasome assembly chaperone PSMG3, and TFAMP1, a pseudogene. Increased methylation of cg01669161 was also associated with decreased serum IgE levels.Conclusion: DNA methylation changes following tetanus vaccination may offer a novel prospect to explain a differential occurrence of asthma in adolescence. (C) 2016 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).