Frances Mitchell

Influence of atopy and asthma on exhaled nitric oxide in an unselected birth cohort study.

Background Asthma is considered to be associated with elevated levels of exhaled nitric oxide (FeNO). The nature of this relationship and how it is influenced by atopy are still not resolved. Methods The Isle of Wight birth cohort (N=1456) was reassessed at 18 years of age. Participants able to attend the research centre were assessed by questionnaires, skin prick testing and FeNO in order to explore the interrelationship between asthma, atopy and FeNO. Results Atopy was significantly associated with higher levels of FeNO. However, the level of FeNO for non-atopic asthmatic participants was no different to the non-atopic no-asthma group. The highest levels of FeNO were seen in subjects with both atopy and asthma. In addition, FeNO was positively associated with increasing atopic burden as evidenced by increasing FeNO with increasing skin prick testing positivity, and with increasing severity of atopic asthma as evidenced by the number of attacks of wheezing. FeNO and current inhaled corticosteroid use were not significantly associated. Conclusions FeNO behaves as a biomarker of atopy and the “allergic asthma” phenotype rather than asthma itself. This may explain why FeNO-guided asthma treatment outcomes have proved to be of limited success where atopic status has not been considered and accounted for.

What does adolescent undiagnosed-wheeze represent? Findings from the Isle of Wight Cohort

We sought to characterise adolescent wheeze in the absence of asthma, which we termed “undiagnosed wheeze”. The Isle of Wight Birth Cohort (n=1,456) was reviewed at 1, 2, 4, 10 and 18 yrs. Using questionnaire responses, “asthma” was defined as “ever had asthma” plus either “wheezing in the last 12 months” or “taking asthma treatment in the last 12 months”; “undiagnosed wheeze” as “wheeze in the last 12 months” but “no” to “ever had asthma”; and remaining subjects termed “non-wheezers”. Undiagnosed wheeze (prevalence 4.9%) accounted for 22% of wheezing at 18 yrs. This was largely adolescent-onset with similar symptom frequency and severity to diagnosed asthma. However, undiagnosed wheezers had significantly higher forced expiratory volume in 1 s to forced vital capacity ratio, less bronchodilator reversibility and bronchial hyperresponsiveness, and were less frequently atopic than asthmatics. Undiagnosed wheezers had earlier smoking onset, higher smoking rates and monthly paracetamol use than non-wheezers. Logistic regression identified paracetamol use (OR 1.11, 95% CI 1.01–1.23; p=0.03), smoking at 18 yrs (OR 2.54, 95% CI 1.19–5.41; p=0.02), rhinitis at 18 yrs (OR 2.82, 95% CI 1.38–5.73; p=0.004) and asthmatic family history (OR 2.26, 95% CI 1.10–4.63; p=0.03) as significant independent risk factors for undiagnosed wheeze. Undiagnosed wheeze is relatively common during adolescence, differs from diagnosed asthma and has strong associations with smoking and paracetamol use. Better recognition of undiagnosed wheeze and assessment of potential relevance to adult health is warranted.

Barriers and facilitators to asthma self-management in adolescents: a systematic review of qualitative and quantitative studies

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.

An outreaching model of tertiary difficult asthma care reduces adverse asthma outcomes and healthcare utilisation costs

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 http://ow.ly/YClKM

Barriers and facilitators to self-management of asthma in adolescents: an interview study to inform development of a novel intervention

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.

Tetanus vaccination is associated with differential DNA-methylation: Reduces the risk of asthma in adolescence

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 18years 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 HumanMethylation450K 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 0.5×10-5, FDR-adjusted p value 2.1×10-4) 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 18years 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.