Asthma and allergy in teenagers and young adults, risk-factors and T-cell regulation

Asthma is one of the most common chronic diseases among teenagers and young adults. The prevalence of asthma among young adults in Sweden is approximately 7- 10%. Despite this, only a limited number of studies have focused on asthma, allergy and allergic inflammation in this age group. The aims of this thesis are to study the consequences of asthma and allergy in teenagers and young adults, incidence and riskfactors for death due to asthma, and deterioration in asthma prior and following transfer from pediatric to adult health care. As allergic inflammation is involved in a majority of asthma patients in this age-group we have further investigated a T cell mediated inflammatory mechanism with possible implications in monitoring and modulating autoimmune and allergic diseases. PAPER I During the 1994-2003 period 37 deaths due to asthma were identified. The incidence of asthma in 1-34 year-olds decreased during the period from 1.54 to 0.53 per million. Common risk-factors were under-treatment, poor adherence to prescribed treatment and adverse psychosocial situation. An alarming finding was that 11/37 deaths was probably caused by food allergy and 8/37 were associated with exposure to pet dander. PAPER II In a 5-year prospective follow-up study to identify risk factors for deterioration of asthma following transfer from pediatric to adult health care 150 teenagers with asthma were enrolled. Skin prick test at entrance revealed that 89% were sensitized towards at least one of tested allergens. A minority performed with impaired lung function without deterioration during the five-year follow up, while bronchial hyper responsiveness (BHR) was present in 71% of the subjects at entrance and among 59% at follow-up. Risk for persistence of BHR after five years was elevated by poor adherence and attenuated by regular physical activity. Working capacity decreased significantly during the study period without any correlation to risk factors examined. Paper III Interactions between the low-density lipoprotein receptor-related protein 1(LRP1) and thrombospondin-1 (TSP-1) is necessarily for T cell motility and that the motogenic LRP/TSP-1 mechanism antagonizes adhesion to ICAM-1 and fibronectin as well as TCR induced proliferative responses. This cascade mediates regulatory effects of IL-2 and IL-4. In addition expression of TSP-1, with known ability to protect against inflammation, was increased by IL-2. Paper IV T cell activation induces arrest of T cell motility through down-regulation of LRP1 synthesis a concomitant up-regulation of TSP-1 synthesis providing a mechanism for enhancement of adhesion of T cells to APC´s stimulating proliferative responses. Despite this arrest of motility, co-ligation with CD28 maintains a basal motility level by enhancing transport of LRP1 to the cell surface. Paper V Patients with allergy and psoriasis showed impaired T cell motility and decreased TSP- 1 expression compared to healthy controls. IL-2 was shown to up-regulate the impaired motility in patient to the same level as in controls indicating a reversible state probably excluding a constitutional defect

Internet-delivered cognitive-behaviour therapy for anxiety related to asthma : study protocol for a randomised controlled trial

Introduction There is an established association between asthma and anxiety. The overlap between asthma symptoms and symptoms of anxiety may cause individuals to overestimate their asthma severity and restrict their daily activities leading to a low quality of life. There is currently weak evidence for treatments targeting anxiety related to asthma, but cognitive–behavioural therapy (CBT) has shown some promising but mixed results. The current randomised controlled trial will investigate if exposure-based internet-delivered CBT (Internet-CBT) is more effective than treatment as usual+medical education (TAU+ME) to relieve symptoms of anxiety and asthma control. Methods and analysis 90 participants will be randomised 1:1 to 8 weeks of Internet-CBT or TAU+ME. The primary outcome, the patient-reported Catastrophising Asthma Scale, will be analysed from baseline to the primary endpoint at 16 weeks using hierarchical linear mixed model of the slope over time. Secondary outcomes, such as asthma control, quality of life and forced expiratory volume in 1 s, will be analysed correspondingly. Ethics and dissemination All participants will be informed about the study and leave their consent before study entry. All results will be analysed at group level and reported through publication in a peer-reviewed scientific journal within the field. The study received ethical approval by the Swedish Ethical Review Authority in January 2020 (ID: 2019-05985; 2022-01117-02)

Quality of life in adolescents with asthma, during the transition period from child to adult.

Aim: The present investigation was designed to evaluate the health-related quality of life (HRQOL) of adolescents with asthma between the age of 16 and 21, when they are transferred from paediatric to adult care. Methods: In this prospective study, 156 teenagers (69 females) with asthma were screened employing spirometry, a histamine challenge, skin prick test for allergy and filled out the 'Living with Asthma Questionnaire' both at the time of entry into the study and after 2 and 5 years of follow-up. An exercise test and questions concerning regular performed exercise were carried out at baseline and 5 years later. Results: At all three time-points, the HRQOL of the men was generally better than that of the women. At the same time, the HRQOL of both genders was significantly better, both in terms of the overall scores (P < 0.001) as well as the scores for most of the individual domains, in connection with the 5-year follow-up. The young women who exercised regularly at the time of their entry exhibited better HRQOL at this time than those who did not (P < 0.001), whereas regular exercise had no impact on the HRQOL of the young men. The women with severe asthma demonstrated a poorer HRQOL than those suffering from mild-to-moderate asthma. Conclusion: The HRQOL of adolescents with asthma improves with age. The pronounced positive correlation between regular exercise and HRQOL in female adolescents with asthma revealed here deserves special attention in the care of young women and deserves further exploration

Targeting excessive avoidance behavior to reduce anxiety related to asthma: A feasibility study of an exposure-based treatment delivered online

There is an established relationship between anxiety and asthma, which is associated with poor health outcomes. Most previous cognitive behavior therapies (CBT) have focused on comorbid panic disorder whereas anxiety related to asthma may rather be illness-specific. The feasibility of an online CBT targeting avoidance behavior in anxiety related to asthma was evaluated, using a pretest-posttest design. Thirty participants with self-reported anxiety related to asthma were offered an eight-week treatment with therapist support. Mean adherence was good (80% of content), and most participants (89%) reported adequate relief after treatment. Catastrophizing about asthma (CAS), assessed at 2 months after treatment, improved significantly with a large effect size (Cohen's d = 1.52). All secondary outcomes, including asthma control, avoidance behavior, fear of asthma symptoms and quality of life, improved significantly with moderate to large effect sizes (d: 0.40–1.44). All improvements were stable at 4 months follow up. Weekly ratings showed that a decrease in avoidance behavior predicted a decrease in CAS the following week throughout the treatment period. We conclude that CBT targeting avoidance behavior is a feasible treatment for anxiety related to asthma. The results justify investigation of efficacy and mechanisms of change in a randomized controlled trial.ClinicalTrials.gov, ID: NCT03486756