Studies as a basis for a possible introduction of newborn screening for cystic fibrosis in Sweden

Background: Cystic fibrosis (CF) is the most common life-shortening autosomal recessive disease in Caucasians. It is a multi-organ disease that results from mutations in the gene that encodes the CF transmembrane conductance regulator (CFTR) protein, which regulates ion transport at epithelial surfaces. The main clinical characteristics are progressive pulmonary disease and pancreatic insufficiency. Not long ago most affected patients died in childhood. The outlook for patients with CF has improved steadily over the years, as a result of more aggressive therapy and care in specialised centres. Current understanding of the molecular-biological defect that underlies CF will lead to new treatments. To benefit from these new treatments, patients should have as few irreversible lesions as possible. An early CF diagnosis by newborn screening is therefore highly desired. The overall aim of this thesis was to provide a basis for discussion of whether CF should be included in the national newborn screening programme in Sweden. Paper I is a multi-centre study in which we analysed the CFTR mutation in 75% of the Swedish CF population (331 patients). The three most common CFTR mutations were deltaF508 68.3%, 394delTT 8.5% and 3659delC 7.9%, comprising 84.6% of the CF alleles in the material. This result shows that newborn screening for CF with an IRT/DNA approach is possible in Sweden. Paper II is a questionnaire study of parental attitudes towards newborn screening for CF in which the parents of 143 CF patients and parents of children in two age-matched control groups participated. A majority of the parents, 70-86% in the different groups of parents, supported screening for CF. The parental attitude of CF parents was independent of the age of the child, the delay of diagnosis as experienced by the parents, and the well-being of the CF child at the time of diagnosis. Paper III is a questionnaire study to the parents of the same 143 CF patients as in Paper II to investigate their experiences after the clinical CF diagnosis of their child, and to find out the effects of the diagnosis on the family. The parental experiences on receiving a clinical CF diagnosis were intense and emotional. The parents stated that the CF diagnosis greatly influenced other family members, such as siblings and grandparents. A majority of the CF families had not experienced any change in relationships within the family, or in the social life of the family, one year after the diagnosis. Paper IV is a register study of 119 CF patients born between 1974 and 2001 in which we studied disease progression over time for lung, liver, nutritional and overall morbidity with Kaplan-Meier curves and proportional hazards regressions. The median age at diagnosis of the patients was 5 months. The patients with overall morbidity at diagnosis showed a slow decline of symptoms, with half of the patients becoming free of overall morbidity after 4.8 years; however, the patients who were older than 24 months at diagnosis had a lower probability of becoming free of morbidity (crude hazards ratio 0.14 [95% confidence interval 0.04, 0.45]) than those with an earlier diagnosis, at the age of 2-12 months (p < 0.01). Paper V is a register study of all patients in the Stockholm CF Centre register with the diagnosis of CF and two verified CFTR mutations, in total 220 patients. CFTR mutations or larger deletions were found in all patients with classic CF. There was no statistical difference in lung function using the mixed model analysis for the different mutation groups studied. Patients born after 1985 had better lung function (FEV1 and FVC) than those born earlier. Conclusion: Our studies show that the conditions for a newborn screening programme for CF in Sweden are good and that a majority of parents in Sweden support the inclusion of CF in the newborn screening programme

Lived experiences for individuals with cystic fibrosis who have undergone lung transplantation: a qualitative study

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Impact of COVID-19 infection on lung function and nutritional status amongst individuals with cystic fibrosis:A global cohort study

Background: Factors associated with severe COVID-19 infection have been identified; however, the impact of infection on longer-term outcomes is unclear. The objective of this study was to examine the impact of COVID-19 infection on the trajectory of lung function and nutritional status in people with cystic fibrosis (pwCF). Methods: This is a retrospective global cohort study of pwCF who had confirmed COVID-19 infection diagnosed between January 1, 2020 and December 31, 2021. Forced expiratory volume in one second percent predicted (ppFEV1) and body mass index (BMI) twelve months prior to and following a diagnosis of COVID-19 were recorded. Change in mean ppFEV1 and BMI were compared using a t-test. A linear mixed-effects model was used to estimate change over time and to compare the rate of change before and after infection. Results: A total of 6,500 cases of COVID-19 in pwCF from 33 countries were included for analysis. The mean difference in ppFEV1 pre- and post-infection was 1.4 %, (95 % CI 1.1, 1.7). In those not on modulators, the difference in rate of change pre- and post-infection was 1.34 %, (95 % CI -0.88, 3.56) per year (p = 0.24) and -0.74 % (-1.89, 0.41) per year (p = 0.21) for those on elexacaftor/tezacaftor/ivacaftor. No clinically significant change was noted in BMI or BMI percentile before and after COVID-19 infection. Conclusions: No clinically meaningful impact on lung function and BMI trajectory in the year following infection with COVID-19 was identified. This work highlights the ability of the global CF community to unify and address critical issues facing pwCF.</p

Impact of COVID-19 infection on lung function and nutritional status amongst individuals with cystic fibrosis: A global cohort study

Background: Factors associated with severe COVID-19 infection have been identified; however, the impact of infection on longer-term outcomes is unclear. The objective of this study was to examine the impact of COVID-19 infection on the trajectory of lung function and nutritional status in people with cystic fibrosis (pwCF). Methods: This is a retrospective global cohort study of pwCF who had confirmed COVID-19 infection diagnosed between January 1, 2020 and December 31, 2021. Forced expiratory volume in one second percent predicted (ppFEV1) and body mass index (BMI) twelve months prior to and following a diagnosis of COVID-19 were recorded. Change in mean ppFEV1 and BMI were compared using a t-test. A linear mixed-effects model was used to estimate change over time and to compare the rate of change before and after infection. Results: A total of 6,500 cases of COVID-19 in pwCF from 33 countries were included for analysis. The mean difference in ppFEV1 pre- and post-infection was 1.4 %, (95 % CI 1.1, 1.7). In those not on modulators, the difference in rate of change pre- and post-infection was 1.34 %, (95 % CI -0.88, 3.56) per year (p = 0.24) and -0.74 % (-1.89, 0.41) per year (p = 0.21) for those on elexacaftor/tezacaftor/ivacaftor. No clinically significant change was noted in BMI or BMI percentile before and after COVID-19 infection. Conclusions: No clinically meaningful impact on lung function and BMI trajectory in the year following infection with COVID-19 was identified. This work highlights the ability of the global CF community to unify and address critical issues facing pwCF

The Effects of Aspergillus fumigatus Colonization on Lung Function in Patients with Cystic Fibrosis

Aspergillus fumigatus is commonly isolated from CF airways. However, the impact on CF lung progression is not completely understood. In this study, using a 16-year retrospective observational cohort study (2000–2015) that included 132 patients, we determined the annual lung function, measured as percent predicted forced expiratory volume in the first second (ppFEV1), decline before and after the first colonization with A. fumigatus. Further, in the same individual, the ratios of lung function when patients were colonized with A. fumigatus and when they were not were calculated. The impact of eradication, with antifungal treatment or spontaneously, was assessed. The annual ppFEV1 was significantly lower after the first colonization with A. fumigatus. Furthermore, within the same individual, colonization with A. fumigatus for two and three years in a row was associated with 4.3% and 7.9% lower ppFEV1, respectively, compared to when not colonized. Finally, patients who eradicated A. fumigatus the following two years after colonization exhibited 9.9% and 14.5% higher ppFEV1 compared to patients who continued to produce cultures with A. fumigatus for two and three years. Our study demonstrated that A. fumigatus colonization was associated with a negative impact on lung function in the long term and eradication, spontaneously or with treatment, was associated with a better pulmonary outcome

Telemedicine and home spirometry in cystic fibrosis : A prospective multicenter study

Objectives Telehealth and home spirometry feasibility for children has been established, but their impact on cystic fibrosis (CF) disease progression remains unassessed. We aimed to evaluate the effects of telehealth and home spirometry on CF disease progression and care. Methods Children with CF aged 5–17 years from all Swedish CF centers were provided with home spirometers. A minimum of two in-person visits were replaced with telemedicine visits and participants were instructed to conduct home spirometry before visits. Linear mixed-effects models were used to compare annual CF disease trajectories during the intervention period and prepandemic period (1 January 2019 to 28 February 2020). Participants and caregivers completed study questionnaires. Results A total of 59 individuals completed the study over a mean (SD) period of 6.8 (1.4) months, made 3.1 (1.0) physical visits and 2.2 (0.6) telehealth visits per patient year during the study period. The mean difference (95% CI) between the intervention and prepandemic period progression rate for FEV1%, lung clearance index and BMI were −0.4 (−1.3 to 0.5, p = 0.39), 0.11 (−0.07 to 0.28, p = 0.25) and −0.02 (−0.13 to 0.08, p = 0.70), respectively. There were no major shifts in the incidence of airway pathogens, sputum cultures, or antibiotics use between the periods (p &gt; 0.05). The intervention did not increase stress. Almost all participants and caregivers expressed a desire to continue with home spirometry and telemedicine. Conclusion Combining telehealth and physical visits with access to home spirometry demonstrated comparable effectiveness as exclusively in-person care with enhanced flexibility and personalization of CF care

The Effects of Aspergillus fumigatus Colonization on Lung Function in Patients with Cystic Fibrosis

Aspergillus fumigatus is commonly isolated from CF airways. However, the impact on CF lung progression is not completely understood. In this study, using a 16-year retrospective observational cohort study (2000–2015) that included 132 patients, we determined the annual lung function, measured as percent predicted forced expiratory volume in the first second (ppFEV1), decline before and after the first colonization with A. fumigatus. Further, in the same individual, the ratios of lung function when patients were colonized with A. fumigatus and when they were not were calculated. The impact of eradication, with antifungal treatment or spontaneously, was assessed. The annual ppFEV1 was significantly lower after the first colonization with A. fumigatus. Furthermore, within the same individual, colonization with A. fumigatus for two and three years in a row was associated with 4.3% and 7.9% lower ppFEV1, respectively, compared to when not colonized. Finally, patients who eradicated A. fumigatus the following two years after colonization exhibited 9.9% and 14.5% higher ppFEV1 compared to patients who continued to produce cultures with A. fumigatus for two and three years. Our study demonstrated that A. fumigatus colonization was associated with a negative impact on lung function in the long term and eradication, spontaneously or with treatment, was associated with a better pulmonary outcome.</jats:p

Clinical, economic, and societal burden of cystic fibrosis and the impact of the CFTR modulator, lumacaftor/ivacaftor : an assessment using linked registry data in Sweden

Aims We aimed to describe the clinical, economic, and societal burdens of cystic fibrosis (CF) and impact of CF transmembrane conductance regulator modulator (CFTRm) treatment on people with CF, caregivers, and healthcare systems. Material and methods This retrospective study used linked real-world data from Swedish national population-based registries and the Swedish CF Quality Registry to assess clinical, economic, and societal burden and CFTR impact in CF. Records from people with CF and a ten-fold control population without CF matched by sex, birth year, and location were compared during 2019. Outcomes for a subset aged &gt;6 years initiating lumacaftor/ivacaftor (LUM/IVA) in 2018 were compared 12 months pre- and post-treatment initiation. Results People with CF (n = 743) had &gt;10 times more inpatient and outpatient specialist visits annually vs controls (n = 7406). Those aged &gt;18 had an additional 77·7 (95% CI: 70·3, 85·1) days of work absence, at a societal cost of €11,563 (95% CI: 10,463, 12,662), while caregivers of those aged &lt;18 missed an additional 6.1 (5.0, 7.2) workdays. With LUM/IVA treatment, people with CF (n = 100) had significantly increased lung function (mean change in ppFEV1 [3·8 points; 95% CI: 1·1, 6·6]), on average 0·5 (95% CI: −0·8, −0·2) fewer pulmonary exacerbations and 45·2 (95% CI: 13·3, 77·2) fewer days of antibiotics. Days of work lost by caregivers of people with CF aged &lt;18 decreased by 5·4 days (95% CI: 2·9, 7·9). Conclusion CF is associated with a high clinical economic and societal burden in Sweden. Improvements in clinical status observed in people with CF treated with LUM/IVA were reflected in reduced caregiver and societal burden