Only in recent years have diagnostic and therapeutic advances lengthened the life expectancy for patients who have cystic fibrosis sufficiently to allow some of them to live into adulthood. Health care professionals have been focusing on survival issues and are only recently beginning to look at quality of life issues, such as sexuality, of these patients. The purpose of the study was to create a sexual profile of adults with cystic fibrosis which would describe their sexuality and sexual concerns. A questionnaire was developed and sent to all of the adult cystic fibrosis patients (19 years of age and older) in British Columbia (50 patients), all of whom attend the Shaughnessy Hospital Adult CF Clinic in Vancouver. The 62% response rate provided data for the sexual profile which indicated that 90% of the respondents were sexually active. Only a small number of subjects reported sexual difficulties in their relationships. Concerns about the impact of CF on their sexuality included: the effect of the potentially limited lifespan on their relationships, practical considerations such as fatigue and coughing during sexual activity, and poor body image. A major issue for CF males is that most of them are infertile due to CF. How and when men should be told about this issue was an important question for the CF Clinic staff. Responses indicated that men thought they should find out from either the physician in the pediatric CF clinic or the physician in the adult CF clinic. Furthermore, 100% of the men suggested that this issue be discussed with males before the age of 19 years. Limitations and recommendations of the research are discussed. A major recommendation is for physicians and other health care professionals in CF clinics to give patients the opportunity to discuss sexual issues. / Education, Faculty of / Educational and Counselling Psychology, and Special Education (ECPS), Department of / Graduate

Pseudomonas aeruginosa is a Gram-negative bacterium implicated in several clinical contexts. In its association with immunocompromised hosts including cystic fibrosis patients, P. aeruginosa is able to exploit the host immune response to acquire key factors essential to its adaptation. As such, key virulence factors including the Type III Secretion System (T3SS), initially essential in acute infection, is reduced in its significance in chronic colonization. On the contrary, other phenotypes are essential for the altered priorities in chronic colonization. The signals of the host immune response initiating the phenotypic switch from the expression of acute virulence factors to chronic virulence factors have not been well defined. Additionally, the function of the type VI secretion system (T6SS), a protein secretion apparatus, in chronic infection has been well established. Clinical isolates obtained from acute and chronic P. aeruginosa infections suggested selective regulation of the T6SS, namely up regulation of the H3-T6SS in chronic infection. We used murine models of infection to understand the in vivo transcriptional regulation of the T6SS of PAO1. Itaconate, an anti-inflammatory metabolite generated by the host, selectively upregulated transcription of a H3-T6SS-associated locus, vgrG3. Here we present evidence to show how the host immune response, namely metabolic changes in response to infection may be exploited to support the organism’s adaptation to the lung microenvironment. In the evaluation of such a phenotypic response notable in chronic infections, the Type VI Secretion System (T6SS) of P. aeruginosa is selectively regulated by a host-specific metabolic product, itaconate. While P. aeruginosa contains genetic clusters for three (H1-, H2-, and H3-T6SS) evolutionarily distinct T6SSs, we found the H3-T6SS to be up-regulated significantly (p<0.05) in the presence of this anti-inflammatory signal. Characterization of this response reveals that itaconate induces metabolic stress in P. aeruginosa. In an acute pneumoniae mouse model, deletion of the H3-T6SS locus results in increased colonization of the murine lung. Analysis of bronchoalveolar lavage fluid from wild type and H3-T6SS null-infected mice reveals alterations in metabolic pathways including purine metabolism, carbon metabolism, and arginine biosynthesis. Overall our work outlines the H3-T6SS as a phenotypic response to metabolic stress induced by the host immune response, serving to mediate pathways essential in pathogenesis. Further understanding of such phenotypes as the T6SS implicated in chronic infection is essential in treatment interventions in the clinic.

The aim of this dissertation is to explore experiences and describe outcomes of healthcare transition in cystic fibrosis (CF). Chapter one introduces the central concepts of this dissertation, describes current gaps in the literature on healthcare transition in cystic fibrosis and introduces the Expanded Socioecological Model for Adolescent and Young Adult Readiness for Transition (Expanded SMART), which guides the three studies of this dissertation. Chapter two is a qualitative meta-synthesis of 63 studies describing adolescent, young adult, and parent experiences of healthcare transition across a variety of chronic conditions. Chapter three is a qualitative study exploring perceptions of CF management responsibility among a sample of 15 adolescent with CF and parent dyads. Chapter four uses national Cystic Fibrosis Foundation Patient Registry data to examine healthcare transition outcomes associated with participation in the transition preparation program CF R.I.S.E. Chapter five synthesizes the three studies of this dissertation and provides recommendations for practice, policy, and research.

BACKGROUND: Cystic fibrosis (CF) patients grow poorly and tend to be malnourished. They frequently suffer from lung infections necessitating the repeated use of antibiotics. AIM: This study was conducted to determine whether supplementation with a probiotic Lactobacillus reuteri (L. reuteri) could reduce the incidence and duration of lung infections, and whether this would impact on their anthropometric data. The secondary purpose was to compare the nutritional status of the CF patients attending CF clinics in Kwazulu-Natal (KZN) with CF patients attending CF clinics in Cape Town (CT). METHODS: Twenty three CF patients 6-31 years of age from 2 CF clinics in Kwazulu-Natal started the study although only 16 patients completed it. The study was a randomized, double blind, placebo controlled crossover trial with six months on placebo and six months on probiotic. Weight, height, mid arm circumference (MAC), triceps skin fold thickness (TSF), forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured, sputum collected and a symptom diary completed over the 12 month period. Anthropometric data of CF patients attending CF clinics in CT was obtained from the publication by Westwood & Saitowitz (1999). RESULTS: Compliance with taking the L. reuteri was poor. Most took only 50% of the required daily dose. Probiotic supplementation showed a slight (non significant) trend to improve FEV1 and FVC, while no significant difference could be seen in the number and duration of the lung infections. Sputum analysis showed a non significant trend towards the probiotic reducing the number of bacteria in the sputum. There was a significant reduction of symptoms for fever, running nose, sore throat and ear ache while on placebo. There was a significant increase in weight gained off probiotic compared to the probiotic period. The changes in height, weight for age (WFA) percentiles, height for age (HFA) percentiles, WFA and HFA Z-scores, percentage expected weight for age and percentage expected height for age all showed no difference whether on or off probiotic. Over half the CF children in the KZN clinics were underweight for their actual height compared to one third in the CT clinics with a higher number of subjects below the 5th percentile for MAC and TSF readings compared to CT. CONCLUSION: Due to a small sample size and poor compliance no firm conclusions could be drawn. However a slight (non significant) improvement could be seen in favour of the probiotic for FEV1, FVC, and sputum analysis. Although all other findings were not significantly different it would be of benefit to carry out further investigation with improved compliance with the probiotic to see if the parameters set out above could be improved. The KZN and CT CF groups were comparable and the nutritional status of CF patients on KZN was well below that of the CT CF clinics and further monitoring would need to be carried out.