Aims
Drug hypersensitivity reactions (DHR) to antibiotics are common and a substantial issue in managing patients with cystic fibrosis (CF). This study aimed to assess the prevalence and clinical ...features as well as risk factors of DHR to antibiotics in CF.
Method
A 20‐year retrospective study was conducted among 226 CF patients (100 children and 126 adults) attending our centre. The Swedish Registry for Cystic Fibrosis and electronic medical records enabled us to ascertain the number and routes of antibiotic courses. All suspected DHR were evaluated.
Results
The patients had a total of 16 910 antibiotic courses, of which 6832 (40%) were intravenously administered. Of 226 enrolled CF patients, 70 (31%) developed overall 131 DHR to antibiotics. The prevalence of DHR increased with advancing age (P < .001). Beta‐lactams elicited 71% of all DHR and piperacillin was the most common single culprit (30% of intravenous and 24% of all DHR). Reactions were mild to moderate and mostly limited to skin; no severe cutaneous adverse reactions were observed. Additionally, anaphylaxis was rare, constituting 2.3% (3/131) of all DHR. Patients with DHR were exposed to significantly more courses of antibiotics than those without DHR (median 124 vs. 46, retrospectively, P < .001).
Conclusions
DHR to antibiotics, particularly to beta‐lactams, are increased in CF patients, and associated with a higher number of cumulative exposures because of recurrent infections. However, severe cutaneous or systemic DHR, such as anaphylaxis, appear to be rare.
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.AIMSWe 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.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 >6 years initiating lumacaftor/ivacaftor (LUM/IVA) in 2018 were compared 12 months pre- and post-treatment initiation.MATERIAL AND METHODSThis 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 >6 years initiating lumacaftor/ivacaftor (LUM/IVA) in 2018 were compared 12 months pre- and post-treatment initiation.People with CF (n = 743) had >10 times more inpatient and outpatient specialist visits annually vs controls (n = 7406). Those aged >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 <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 <18 decreased by 5·4 days (95% CI: 2·9, 7·9).RESULTSPeople with CF (n = 743) had >10 times more inpatient and outpatient specialist visits annually vs controls (n = 7406). Those aged >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 <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 <18 decreased by 5·4 days (95% CI: 2·9, 7·9).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.CONCLUSIONCF 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.
The presence of co-morbidities, including underlying respiratory problems, has been identified as a risk factor for severe COVID-19 disease. Information on the clinical course of SARS-CoV-2 infection ...in children with cystic fibrosis (CF) is limited, yet vital to provide accurate advice for children with CF, their families, caregivers and clinical teams.
Cases of SARS-CoV-2 infection in children with CF aged less than 18 years were collated by the CF Registry Global Harmonization Group across 13 countries between 1 February and 7 August 2020.
Data on 105 children were collated and analysed. Median age of cases was ten years (interquartile range 6–15), 54% were male and median percentage predicted forced expiratory volume in one second was 94% (interquartile range 79–104). The majority (71%) of children were managed in the community during their COVID-19 illness. Out of 24 children admitted to hospital, six required supplementary oxygen and two non-invasive ventilation. Around half were prescribed antibiotics, five children received antiviral treatments, four azithromycin and one additional corticosteroids. Children that were hospitalised had lower lung function and reduced body mass index Z-scores. One child died six weeks after testing positive for SARS-CoV-2 following a deterioration that was not attributed to COVID-19 disease.
SARS-CoV-2 infection in children with CF is usually associated with a mild illness in those who do not have pre-existing severe lung disease.
A significant decline in pulmonary exacerbation rates has been reported in CF patients homozygous for F508del treated with lumacaftor/ivacaftor. However, it is still unclear whether this reduction ...reflects a diminished microbiological burden.
The aim of this study was to determine the impact of lumacaftor/ivacaftor on the bacterial and fungal burden.
The study is a prospective multicenter cohort study including 132 CF patients homozygous for F508del treated with lumacaftor/ivacaftor.
Clinical parameters as well as bacterial and fungal outcomes 1 year after initiation of lumacaftor/ivacaftor were compared to data from 2 years prior to initiation of the treatment. Changes in the slope of the outcomes before and after the onset of treatment were assessed.
Lung function measured as ppFEV1 (
< 0.001), body mass index (BMI) in adults (
< 0.001), and BMI
-score in children (
= 0.007) were improved after initiation of lumacaftor/ivacaftor. In addition, the slope of the prevalence of
(
= 0.007) and
(
< 0.001) shifted from positive to negative, that is, became less prevalent, 1 year after treatment, while the slope for
(
= 0.009),
spp (
= 0.026), and
(
< 0.001) shifted from negative to positive.
The current study showed a significant improvement in clinical parameters and a reduction of some of CF respiratory microorganisms 1 year after starting with lumacaftor/ivacaftor. However, no significant changes were observed for
, or
, key pathogens in the CF context.
•Fungal prevalence and diversity in the cystic fibrosis (CF) airways increased over time.•Candida dubliniensis in the CF airways was associated with a decline in lung function.•Persistent Candida ...albicans over time was associated with a decline in lung function.•Persistent Aspergillus fumigatus over time was associated with a decline in lung function.•In CF, co-detection of yeast and bacteria had a negative impact on lung function.
To study the prevalence of fungal species in cystic fibrosis (CF) patients over a 16 years period. To examine the impact of Candida albicans (C. albicans), Candida dubliniensis (C. dubliniensis) and Aspergillus fumigatus (A. fumigatus) on lung function.
Observational single-center cohort study (2000–2015) including 133 CF patients (ages 6–66 years). Linear mixed models with autoregressive covariance matrix were used.
The most common fungus was C. albicans (prevalence 62%) followed by A. fumigatus (22%) and C. dubliniensis (11%). In the initial year of detection, there was no impact of C. albicans, C. dubliniensis or A. fumigatus on lung function. However, one and two years after detection of C. dubliniensis a reduction in percent predicted forced expiratory volume in the first second (ppFEV1) was observed of 3.8% (p = 0.022) and 4.1% (p = 0.017), respectively, compared with CF patients without these findings. Furthermore, patients with positive cultures for any of these fungal species for three consecutive years exhibited a decline in lung function: C. dubliniensis, 7.6% reduction in ppFEV1 (p = 0.001); A. fumigatus, 4.9% (p = 0.007); C. albicans, 2.6% (p = 0.014). The results were adjusted for age, CFTR genotype, chronic and intermittent P. aeruginosa colonization, and numbers of intravenous antibiotic treatments per year. Persistence of C. dubliniensis for three consecutive years was positively correlated to age and erythrocyte sedimentation rate (ESR) (both p = 0.001).
Cystic fibrosis patients who were cultured positive for C. dubliniensis, C. albicans or A. fumigatus in sputum exhibited a decline in ppFEV1 over time. The effect was most pronounced for C. dubliniensis.
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.
Abstract 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 FEV 1 %, 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 > 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.
AbstractBackgroundMonitoring changes in the epidemiology of cystic fibrosis (CF) pathogens is essential for clinical research, quality improvement, and clinical management. MethodsWe analyzed data ...reported to the European Cystic Fibrosis Society Patient Registry (ECFSPR) from 2011 to 2016 to determine the overall and the age-specific annual prevalence and incidence of selected CF pathogens and their trends during these years. The ECFSPR collects data on three chronic infections: Pseudomonas aeruginosa (PsA), Burkholderia cepacia complex Species (BCC) and Staphylococcus aureus (SA), as well as on the occurrence of non-tuberculous mycobacteria (NTM) and Stenotrophomonas maltophilia (SM). The same analyses were performed for different country groups, according to their gross national income (GNI). ResultsThe pathogens with the highest prevalence were SA and PsA, with prevalence, in 2016, equal to 38.3% and 29.8% respectively, followed by SM (8.1%). The pathogens with the lowest prevalence were NTM (3.3%) and BCC (3.1%). The overall prevalence and incidence significantly decreased for PsA; they also decreased for BCC, while they increased significantly for SA. The overall prevalence of NTM and SM increased significantly. The most considerable prevalence changes were observed for PsA, which decreased across all income country groups and all age strata (with the exception of 0–1 years) The prevalence and incidence of pathogens differed significantly according to GNI. ConclusionsThe epidemiology of CF pathogens in Europe has changed; epidemiologic data differ significantly among countries with different socio-economic status. The causes of these observations are multifactorial and include improvements in clinical care and infection control.
•Incidence of liver outcome evaluated in UDCA prescribing vs. non-prescribing centers.•No significant difference in cumulative incidence of portal hypertension was identified.•No significant ...differences in liver-related and other-cause mortality were found.
The efficacy and safety of ursodeoxycholic acid (UDCA) for the treatment of liver disease associated with cystic fibrosis (CF) are under discussion, and clinical practice varies among centers. The study aimed at evaluating if the incidence of severe liver disease differs between CF centers routinely prescribing or not prescribing UDCA.
We carried out a retrospective multicenter cohort study including 1591 CF patients (1192 patients from UDCA-prescribing centers and 399 from non-prescribing centers) born between 1990 and 2007 and followed from birth up to 31 December 2016. We computed the crude cumulative incidence (CCI) of portal hypertension (PH) at the age of 20 years in the two groups and estimated the subdistribution hazard ratio (HR) through a Fine and Gray model.
Over the observation period, 114 patients developed PH: 90 (7.6%) patients followed-up in UDCA prescribing centers and 24 (6.0%) in non-prescribing centers. The CCI of PH at 20 years was 10.1% (95% CI: 7.9-12.3) in UDCA-prescribing and 7.7% (95% CI: 4.6-10.7) in non-prescribing centers. The HR among patients followed in prescribing centers indicated no significant difference in the rate of PH either in the unadjusted model (HR: 1.21, 95% CI: 0.69-2.11) or in the model adjusted for pancreatic insufficiency (HR: 1.28, 95% CI: 0.77-2.12).
CF patients followed-up in UDCA prescribing centers did not show a lower incidence of PH as compared to those followed in centers not prescribing UDCA. These results question the utility of UDCA in reducing the occurrence of severe liver disease in CF.
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