Objectives To measure past dental caries experience in people with cystic fibrosis and to compare the results with a control group of people without cystic fibrosis. Methods A cross-sectional study of 92 adults with cystic fibrosis and 92 adults without cystic fibrosis was undertaken in Cork University Dental School and Hospital. The median age for study group and control group participants was 31 years and 27 years, respectively. All participants completed a detailed questionnaire before undergoing a clinical examination that recorded demographic, social and oral health variables. Caries was recorded using the Decayed, Missing and Filled Teeth (DMFT) index. All data were statistically analysed using the Wilcoxon rank-sum test, chi-squared test and Fisher's test. Negative binomial models were also used to analyse data. Results The study group had a higher mean DMFT score compared to the control group (6.52, 0.99, 0.41, 3.89 versus 5.33, 0.18, 0.11, 3.68). While the study group had a higher DMFT, the only component that was statistically significant between the groups was the Decayed Teeth component (p <0.001). Conclusion In this study, the cohort of people with cystic fibrosis had more caries than people without cystic fibrosis. Further research is required to establish if underlying systemic conditions, social and behavioural factors, or a combination of the aforementioned are responsible for a higher caries experience in this study group.

BACKGROUND:Primary ciliary dyskinesia (PCD) is a rare condition characterised by dysmotile, immotile, or absent cilia. As a result of the impairment in respiratory mucociliary clearance, patients with PCD typically develop neonatal respiratory distress, nasal congestion, otitis media and recurrent respiratory infections leading to bronchiectasis and structural lung changes. These changes have been shown by chest computed tomography (CT) to develop in infancy and early childhood. Recent development and refinement of radiation-reducing CT techniques have allowed significant radiation dose reductions, with chest CT doses now in the range of chest radiography (CR). AIM:To evaluate the efficacy of ultra-low dose CT (ULDCT) chest in identifying pulmonary changes within a PCD paediatric patient cohort. METHODS:Paediatric patients with PCD who presented for routine clinical outpatient follow-up within the study period, were eligible for inclusion in the study. ULDCT and CR were performed on these patients and the results compared. Comparison metrics included radiation dose, subjective and objective image quality and disease severity. RESULTS:Six paediatric patients (mean age 9 years) underwent clinically indicated ULDCT chest examinations and CR for surveillance of their PCD. The mean effective dose was 0.08 ± 0.02 mSv, a dose that approximates that of a frontal and lateral chest radiograph. The average Brody II score across the entire cohort was 12.92, with excellent inter-rater reliability and intra-class correlation coefficient (ICC) of 0.98. The average Chrispin-Norman score on CR was 1 with excellent inter-rater reliability and ICC of 0.92. CONCLUSION:ULDCT demonstrates superior diagnostic capabilities, minimal radiation dose penalty, and high interobserver reliability in comparison to CR. Thus, we advocate for ULDCT to be the preferred modality for surveillance imaging in paediatric PCD.

In this study, we used routine ultra-low dose computed tomography scans of patients with cystic fibrosis to predict bone mineral density (BMD). A strong correlation was found between the attenuation of trabecular bone in thoracic vertebrae and the BMD in the proximal femur and lumbar spine as measured on DEXA. Osteoporosis is a serious global health concern with millions of people affected worldwide. A particularly vulnerable cohort in developing osteoporosis are patients with cystic fibrosis (CF). Bone mineral density (BMD) is typically measured with dual energy X-ray absorptiometry (DEXA) scanning; however, this comes at a cost to the healthcare system and an exposure to ionising radiation. In our institution, patients with cystic fibrosis undergo routine ultra-low dose computed tomography (ULDCT) for monitoring of disease progression. The aim of this study was to assess the validity of estimating BMD using data derived from ULDCT scans. Adult CF patients were included if they had undergone a routine ULDCT scan within 12 months of a DEXA scan. Additionally, 100 non-CF patients with non-contrast standard dose CT scans were selected to act as the control group. Trabecular bone density (T-BD) at T4, T7 and T10 was measured on PACS in Hounsfield units (HU) and compared to DEXA scan results and a formula developed to the predict BMD. Fifty-two female and 62 male patients were included with mean ages of 34.4 and 35.1 respectively. Moderately strong correlation was found between the T-BD and BMD of both the lumbar spine (r = 0.629, p < 0.001) and proximal femur (r = 0.649, p < 0.001). Receiver operator characteristic (ROC) curve analysis found a sensitivity and specificity of 0.700 and 0.714 respectively at predicting osteoporosis at T-BD of 193.33 HU or below. T-BD measured on ULDCT may be a valuable tool in the early identification of CF patients at risk of osteoporosis.

Rationale: In cystic fibrosis (CF), body composition alterations are observed. The prevalence of obesity in CF is increasing, with evidence suggesting a subsequent increase in cardiometabolic risk. We sought to assess body composition using analytic morphomics from ultra-low-dose thoracic computed tomography (CT) scans in patients with CF on the triple CFTR (cystic fibrosis transmembrane conductance regulator) modulator therapy elexacaftor/tezacaftor/ivacaftor (ETI). Objectives: Our objective was to use analytical morphomics on routine ultra-low-dose CTs to assess patterns of change in body composition in patients with CF on ETI therapy. Methods: Forty-two patients with CF on ETI who had baseline and follow-up ultra-low-dose thoracic CT imaging were retrospectively analyzed. The CTs were acquired at a radiation dose equivalent to two frontal chest X-rays using our previously published acquisition parameters. The Bhalla score was used as a marker of structural lung disease severity. Analytic morphomics variables, including cross-sectional area and attenuation of pectoralis muscle, visceral fat (epicardial and upper abdominal), and subcutaneous fat, were extracted using the validated image segmentation software CoreSlicer. Paired-samples mean testing (Wilcoxon matched-pairs signed-rank test) and Spearman rank correlation analyses were performed. Results: Total Bhalla scores significantly improved over time in patients on ETI (P < 0.0001). In addition, body composition also changed, with an increase in the cross-sectional area of subcutaneous and epicardial visceral fat (P < 0.0001 and P = 0.0062, respectively). In those with a normal BMI at follow-up, epicardial and subcutaneous fat had also increased significantly in the interval (P = 0.0066 and P = 0.0002, respectively). Conclusions: In CF, ETI produced a significant improvement in structural lung disease over time; however, it also resulted in an increase in visceral and subcutaneous fat. The analytic morphomics methodology presented herein may help identify those patients for aggressive primary prevention strategies and permit the creation of more personalized nutritional plans.

Background: Clinical trials with elexacaftor/tezacaftor/ivacaftor (ETI) in people with cystic fibrosis were associated with significant improvements in % predicted forced expiratory volume in 1 s (FEV1 % pred), sweat chloride, weight and quality of life in the respiratory domain from the cystic fibrosis questionnaire revised (CFQ-R). Limited data exist on its effect on structural lung disease and inflammatory cytokines. Methods: In a real-world setting with 61 people with cystic fibrosis, we prospectively recorded FEV1, sweat chloride, body mass index (BMI) and CFQ-R at baseline, 3 and 6 months after commencement of ETI. In addition, changes in ultra-low-dose (ULD) computed tomography (CT) Bhalla score, peripheral-blood and sputum inflammatory cytokines and patient-reported outcome measures (PROMs), including sino-nasal outcomes test-22 (SNOT-22) and fatigue scale (FACIT-Fatigue). Results: Significant improvements in FEV1 % pred (p=0.0001), sweat chloride (p<0.0001) and BMI (p=0.0147) after ETI treatment were noted. ULD-CT scores demonstrated reductions in peri-bronchial thickening, mucus plugging and total Bhalla score (p<0.001), and improvements in emphysema extent (p<0.0027). Improvements in systemic inflammatory status were seen with a reduction in interleukin (IL)-1 beta (p=0.0049), IL-6 and IL-8 (p<0.0001), and increasing IL-10 (p=0.004). Sputum cytokine analysis was not performed as only four of 61 patients spontaneously expectorated sputum after ETI. PROMs improved significantly for the SNOT-22 (p<0.0001), FACIT-Fatigue score (p=0.0001) and CFQ-R domains, including respiratory (p<0.0001), physical (p=0.007), vitality (p=0.0004), treatment burden (p=0.0028), health (p=0.0007), social (p=0.0073), weight (p=0.0068) and role/school domain (p=0.0018). Conclusion: ETI responders, demonstrate significant improvements in CT imaging, circulating cytokines and PROMs, which may be of further use evaluating cystic fibrosis transmembrane conductance regulator modulation treatment response.

BACKGROUND:This study explores the effectiveness and safety of microbiome-directed antimicrobial therapy versus usual antimicrobial therapy in adult cystic fibrosis pulmonary exacerbations. METHODS:A multicentre two-arm parallel randomised control trial conducted across Europe/North-America enrolled 223 participants (January 2015 to August 2017). All participants were chronically colonised with Pseudomonas aeruginosa and were randomised 1:1 into two study arms. The "usual therapy" group received 2 weeks of intravenous ceftazidime 3 g thrice daily (for allergies: aztreonam 2 g thrice daily) and tobramycin 5-10 mg·kg-1 once daily. The "microbiome-directed" group received the same usual therapy plus an additional antibiotic with greatest presumed activity against the second, third and fourth most abundant genera present in the sputum microbiome, selected by a consensus expert treatment panel. The primary outcome was change in percentage of predicted forced expiratory volume in 1 s (ppFEV1) at 14 days post initiation of antibiotics. Secondary outcomes examined ppFEV1 at 7 days, 28 days and 3 months; time to next exacerbation; symptom burden at 7 days; health-related quality of life (HRQoL) at 28 days; and number of exacerbations and i.v. antibiotic days at 12 months. RESULTS:149 participants had an eligible exacerbation (usual therapy n=83, microbiome-directed therapy n=66). There was no difference between the groups for ppFEV1 at day 14 (-1.1%, 95% CI -3.9-1.7%; p=0.46), or ppFEV1 measured at other time points, or for time to next exacerbation (microbiome-directed versus usual therapy hazard ratio 0.91, 95% CI 0.60-1.38; p=0.66). The microbiome-directed group trended to have more i.v. days (median 42 days versus 28 days; p=0.08) and more subsequent exacerbations (median three versus two; p=0.044) the following year. There were no appreciable differences in symptom burden; however, HRQoL subscores were consistently worse in the microbiome-directed group (-4.3 points versus usual therapy, 95% CI -8.3--0.3 points; p=0.033). CONCLUSION:The addition of a third antibiotic based on sputum microbiome sequencing analysis did not result in improved clinical outcomes.

Background Five cystic fibrosis transmembrane conductance regulator (CFTR) modulator (CFTRm) therapies are approved for patients with cystic fibrosis (CF). Despite the established efficacy and safety of CFTRm therapy, variability exists in prescribing amongst CF physicians. Here, we describe prescriber factors influencing CFTRm use. Methods This observational study used clinical vignettes of patients with CF. Participants were adult pulmonologists and pediatricians specializing in respiratory medicine from Germany, Italy, UK, Ireland, and the Netherlands. Participants took part in a 3-step data collection process: (i) 60-minute individual telephone interview; (ii) decision exercise where physicians made a treatment decision about CFTRm on 10 clinical vignettes; and (iii) 30-minute web-assisted interview to provide rationale for treatment decisions. Univariate analysis, dimensionality reduction via factor analysis, and a random-effects logistic regression model were used to identify factors impacting CFTRm prescribing. Results Thirty-eight pulmonologists and 42 pediatricians provided 800 clinical decisions. Only 45 % of pulmonologists and 29 % of pediatricians prescribed a CFTRm for all eligible adult or pediatric vignettes. Pancreatic sufficiency decreased odds of prescribing a CFTRm (OR 0.106; 95 % CI 0.046, 0.244) whereas odds increased for patients’ age >12 years (OR 3.779; 95 % CI 1.579, 9.042). Physician characteristics associated with CFTRm prescribing were being proactive/pushing boundaries (OR 1.772; 95 % CI 1.153, 2.722), having previously prescribed LUM/IVA (OR 2.732; 95 % CI 1.070, 6.974), and belief CFTRm therapies could improve adherence (OR 1.440; 95 % CI 0.946, 2.192). Conclusions Behavioral characteristics, attitudes toward CFTRm therapies, and experience with CFTRm therapies impact physician CFTRm prescribing more than individual disease factors.

This is the third in a series of four papers updating the European Cystic Fibrosis Society (ECFS) standards for the care of people with CF. This paper focuses on recognising and addressing CF health issues. The guidance was produced with wide stakeholder engagement, including people from the CF community, using an evidence-based framework. Authors contributed sections, and summary statements which were reviewed by a Delphi consultation. Monitoring and treating airway infection, inflammation and pulmonary exacerbations remains important, despite the widespread availability of CFTR modulators and their accompanying health improvements. Extrapulmonary CF-specific health issues persist, such as diabetes, liver disease, bone disease, stones and other renal issues, and intestinal obstruction. These health issues require multidisciplinary care with input from the relevant specialists. Cancer is more common in people with CF compared to the general population, and requires regular screening. The CF life journey requires mental and emotional adaptation to psychosocial and physical challenges, with support from the CF team and the CF psychologist. This is particularly important when life gets challenging, with disease progression requiring increased treatments, breathing support and potentially transplantation. Planning for end of life remains a necessary aspect of care and should be discussed openly, honestly, with sensitivity and compassion for the person with CF and their family. CF teams should proactively recognise and address CF-specific health issues, and support mental and emotional wellbeing while accompanying people with CF and their families on their life journey.

AIM:To investigate the prevalence of gingivitis and periodontitis, and the oral hygiene status of adults with cystic fibrosis (CF) in the Republic of Ireland. MATERIALS AND METHODS:A case-control study in the form of a clinical examination of 92 adults with a diagnosis of CF was carried out in the adult CF unit in Cork University Hospital. A 40-item questionnaire was used to capture socio-demographic variables and medical and dental information. Two calibrated examiners carried out a periodontal assessment on participants, using the WHO-recommended CPI-modified index, and oral hygiene status was measured using the Greene-Vermillion index. The results were compared with a population-based control group of similar socio-demographic profile. RESULTS:Oral hygiene levels (plaque and calculus) were significantly worse in people with CF, with a median plaque index of 0.83 (interquartile range [IQR] 0.333-1.542) in the CF group compared with 0.5 (IQR 0.167-0.667) in the non-CF group. Calculus index in the CF group was 0.33 (IQR 0.17-0.83) compared with 0.33 (IQR 0.125-0.33) in the non-CF group. However, periodontal disease levels were significantly lower in the CF group. Gingivitis (bleeding on probing ≥ 10% sites) was seen in 67.4% of the CF group, compared with 83.7% of the non-CF group, OR 0.365 (95% confidence interval [CI] 0.181-0.736), relative risk (RR) 0.779 (95% CI 0.655-0.928). Mild periodontitis (periodontal probing depth [PPD] < 5 mm) was seen in 15.2% of the CF group, compared with 31.5% of the non-CF group, OR 0.390 (CI 0.190-0.800), RR 0.483 (95% CI 0.273-0.852). Severe periodontitis (PPD ≥ 6 mm) was seen in 0% of the CF group, compared with 9.8% of the non-CF group. There was a tendency, albeit non-significant, towards reduced periodontitis in PWCF who regularly took antibiotics, particularly azithromycin. CONCLUSIONS:In this study, adults with CF had poor oral hygiene practices, with high levels of plaque and calculus. Despite this finding, adults with CF had lower levels of clinical gingivitis and periodontitis than seen in a non-CF control group. Further study is required to examine the causes of this phenomenon.

The major cause of mortality in people with cystic fibrosis (pwCF) is progressive lung disease characterised by acute and chronic infections, the accumulation of mucus, airway inflammation, structural damage and pulmonary exacerbations. The prevalence of Pseudomonas aeruginosa rises rapidly in the teenage years, and this organism is the most common cause of chronic lung infection in adults with cystic fibrosis (CF). It is associated with an accelerated decline in lung function and premature death. New P. aeruginosa infections are treated with antibiotics to eradicate the organism, while chronic infections require long-term inhaled antibiotic therapy. The prevalence of P. aeruginosa infections has decreased in CF registries since the introduction of CF transmembrane conductance regulator modulators (CFTRm), but clinical observations suggest that chronic P. aeruginosa infections usually persist in patients receiving CFTRm. This indicates that pwCF may still need inhaled antibiotics in the CFTRm era to maintain long-term control of P. aeruginosa infections. Here, we provide an overview of the changing perceptions of P. aeruginosa infection management, including considerations on detection and treatment, the therapy burden associated with inhaled antibiotics and the potential effects of CFTRm on the lung microbiome. We conclude that updated guidance is required on the diagnosis and management of P. aeruginosa infection. In particular, we highlight a need for prospective studies to evaluate the consequences of stopping inhaled antibiotic therapy in pwCF who have chronic P. aeruginosa infection and are receiving CFTRm. This will help inform new guidelines on the use of antibiotics alongside CFTRm.

BACKGROUND:Oral health impacts systemic health, individual well-being, and quality of life. It is important to identify conditions that may exacerbate oral disease to aid public health and policy development and promote targeted patient treatment strategies. Developmental defects can increase an individual's risk of dental caries, hypersensitivity, premature tooth wear, erosion, and poor aesthetics. As part of an ongoing study assessing oral health in adults with cystic fibrosis at Cork University Dental School and Hospital, a systematic review of available literature was conducted to assess the prevalence of enamel defects in people with cystic fibrosis.AIMS:To critically evaluate the literature to determine if the prevalence of developmental defects of enamel is higher in people with cystic fibrosis (PwCF).METHODS:Data Sources: Three online databases were searched Embase, Scopus, and Web of Science Core Collection. Studies that examined an association between cystic fibrosis and developmental defects of enamel were included in this systematic review.RESULTS:The initial search identified 116 publications from the following databases Embase, Web of Science Core Collection, and Scopus. Eleven studies were included for qualitative analysis. Nine studies concluded that PwCF had a higher prevalence of enamel defects than control people and one study found no difference in cystic fibrosis (CF) status. All studies had a risk of bias that may influence study results and their interpretation.CONCLUSIONS:The results of the systematic review show a consistent pattern that PwCF have a higher prevalence of DDE than people without CF. Genetic dysfunction, chronic systemic infections, and long-term antibiotic use are possible aetiological causes. This review highlights the need for future studies to investigate if DDEs are caused by the underlying CFTR mutation or as a consequence of disease manifestations and/or management.

OBJECTIVES:Cystic Fibrosis is an autosomal recessive condition. It is a multisystem disease treated with a broad range of pharmacological therapies, diet and nutrition, and physiotherapy. Previous studies suggest that people with cystic fibrosis have a higher prevalence of developmental defects of enamel which may place this population at a greater risk of developing oral diseases such as caries. The aim of this study was to assess a cohort of people with cystic fibrosis (PwCF) for the presence of developmental defects of enamel and compare the results with a control group of people without cystic fibrosis.METHODS:A cross sectional study involving 92 participants with cystic fibrosis and 92 controls was conducted in Cork University Dental School & Hospital. All participants completed a detailed questionnaire prior to undergoing a full clinical examination. The Developmental Defect of Enamel Index was used as a measurement index. All data was statistically analysed with the help of statisticians from Cystic Fibrosis Registry of Ireland.RESULTS:64 % (n = 59) of PwCF had enamel defects compared to just 30 % (n = 28) of people without cystic fibrosis. The median number of teeth affected by enamel defects in the study group was 1.5, compared to 0 in the control group.CONCLUSION:In this study the cohort of PwCF had more enamel defects than people without CF. Further research is required to investigate the aetiology of these findings.CLINICAL SIGNIFICANCE:Clinicians should be vigilant after teeth have erupted in PwCF as they may have an increased susceptibility to developmental defects of enamel.

This is the final of four papers updating standards for the care of people with CF. That this paper “Planning a longer life” was considered necessary, highlights how much CF care has progressed over the past decade. Several factors underpin this progress, notably increased numbers of people with CF with access to CFTR modulator therapy.As the landscape for CF changes, so do the hopes and aspirations of people with CF and their families. This paper reflects the need to consider people with CF not as a “problem” to be solved, but as a success, a potential and a voice to be heard. People with CF and the wider CF community have driven this approach, reflecting many of the topics in this paper. This exercise involved wide stakeholder engagement. People with CF are keen to contribute to research priorities and be involved in all stages of research. People with CF want healthcare professionals to respect them as individuals and consider the impact of our actions on the world around us.Navigating life presents challenges to all, but for people with CF these challenges are heightened and complex. In this paper we highlight the concerns and life moments that impact people with CF, and events that the CF team should aim to support, including the challenges around having a family.People with CF and their care teams must embrace the updated standards outlined in these four papers to enjoy the full potential for a healthier life.