CF Clinic Research Articles

Detection of the epidemic Pseudomonas aeruginosa AUST-03 (ST242) strain in people with cystic fibrosis in South Africa.

Pseudomonas aeruginosa AUST-03 (ST242) has been reported to cause epidemics in people with CF (pwCF) from Australia and has been associated with multidrug resistance and increased morbidity and mortality. Here, we report an epidemic P. aeruginosa (AUST-03) strain in South African pwCF detected at a public hospital and characterize the genomic antibiotic resistance determinants. The P. aeruginosa AUST-03 (ST242) study isolates were analysed with whole genome sequencing using the Illumina NextSeq2000 platform. Raw sequencing reads were processed using the Jekesa pipeline and multilocus sequence typing and genomic antibiotic resistance characterization was performed using public databases. Genetic relatedness between the study isolates and global P. aeruginosa ST242 from public databases was determined using a maximum-likelihood phylogenetic tree. Antibiotic susceptibility testing was performed using the disk diffusion and broth microdilution techniques. A total of 11 P. aeruginosa AUST-03 isolates were isolated from two children with CF. The majority (8/11) of these isolates were multidrug-resistant (MDR) or extensively drug resistant; and the multidrug efflux pumps MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM were the most clinically relevant antibiotic resistance determinants and were detected in all of the isolates. The study isolates were the most closely related to a 2020 P. aeruginosa AUST-03 (ST242) CF isolate from Russia. Epidemic MDR P. aeruginosa strains are present at South African public CF clinics and need to be considered when implementing segregation and infection control strategies to prevent possible spread and outbreaks.

P410 Patient satisfaction after transition to adult CF clinic

P410 Patient satisfaction after transition to adult CF clinic

The airway microbiome of persons with cystic fibrosis correlates with acquisition and microbiological outcomes of incident Stenotrophomonas maltophilia infection.

Chronic infection with Stenotrophomonas maltophilia in persons with cystic fibrosis (pwCF) has been linked to an increased risk of pulmonary exacerbations and lung function decline. We sought to establish whether baseline sputum microbiome associates with risk of S. maltophilia incident infection and persistence in pwCF. pwCF experiencing incident S. maltophilia infections attending the Calgary Adult CF Clinic from 2010-2018 were compared with S. maltophilia-negative sex, age (+/-2 years), and birth-cohort-matched controls. Infection outcomes were classified as persistent (when the pathogen was recovered in ≥50% of cultures in the subsequent year) or transient. We assessed microbial communities from prospectively biobanked sputum using V3-V4 16S ribosomal RNA (rRNA) gene sequencing, in the year preceding (Pre) (n = 57), at (At) (n = 22), and after (Post) (n = 31) incident infection. We verified relative abundance data using S. maltophilia-specific qPCR and 16S rRNA-targeted qPCR to assess bioburden. Strains were typed using pulse-field gel electrophoresis. Twenty-five pwCF with incident S. maltophilia (56% female, median 29 years, median FEV1 61%) with 33 total episodes were compared with 56 uninfected pwCF controls. Demographics and clinical characteristics were similar between cohorts. Among those with incident S. maltophilia infection, sputum communities did not cluster based on infection timeline (Pre, At, Post). Communities differed between the infection cohort and controls (n = 56) based on Shannon Diversity Index (SDI, p = 0.04) and clustered based on Aitchison distance (PERMANOVA, p = 0.01) prior to infection. At the time of incident S. maltophilia isolation, communities did not differ in SDI but clustered based on Aitchison distance (PERMANOVA, p = 0.03) in those that ultimately developed persistent infection versus those that were transient. S. maltophilia abundance within sputum was increased in samples from patients (Pre) relative to controls, measuring both relative (p = 0.004) and absolute (p = 0.001). Furthermore, S. maltophilia abundance was increased in sputum at incident infection in those who ultimately developed persistent infection relative to those with transient infection, measured relatively (p = 0.04) or absolute (p = 0.04), respectively. Microbial community composition of CF sputum associates with S. maltophilia infection acquisition as well as infection outcome. Our study suggests sputum microbiome may serve as a surrogate for identifying infection risk and persistence risk.

1107. Three Year Longitudinal Assessment of Pseudomonas aeruginosa (Pa) Antibiotic Susceptibility in Children with Cystic Fibrosis (CF) in the Era of Modulator Therapy

Abstract Background CF is a genetic disease characterized by chronic lung infection, often with Pseudomonas aeruginosa (Pa). It is widely accepted that increasing antibiotic resistance develops in Pa following repeated antibiotic exposure. With the advent of elexacaftor/tezacaftor/ivacaftor (ETI) modulator therapy, we wished to assess Pa antibiotic resistance to beta-lactam and fluoroquinolone (FQ) antibiotics in both children receiving ETI, and those not eligible for ETI (nonETI) who continue to experience recurrent pulmonary exacerbation (PEx) and require repeated antibiotic treatment. Methods We examined current patterns of antibiotic resistance over 3 years for a cohort of 11 children with CF having 5 or more positive sputum cultures for Pa between January 2020-December 2022 obtained from CF clinic and hospital PEx sputum samples. Chart review included: demographic data; dates of PEx/hospitalization; dates of CF clinic visits; dates and results of CF sputum cultures; and antibiotics used and dates for intravenous (IV) and oral (PO) treatment courses. Results Six males and 5 females were reviewed (6/11 [54%] were Hispanic), with 3/11 (27%) on ETI therapy (average age 14.6 yr), and 8/11 (73%) not on ETI therapy (average age 11.6 yr). Average age at acquisition of Pa was 10.2 yrs. The average number of cultures yielding Pa over 3 years was 11 for both ETI and nonETI subjects. Average number of IV antibiotic courses was 6 for nonETI, but 0 for ETI subjects, while the average number of oral (PO) FQ courses with ciprofloxacin/levofloxacin was 6 in nonETI, and only 1 in ETI subjects. No increase in antibiotic resistance was noted against any IV antibiotic over 3 years of observation (Table), but of the 9 subjects (both ETI and nonETI) who received PO FQ, 5 (55%) were documented to have at least one nonsusceptible isolate, as shown for one 16 year old nonETI subject (Figure). Conclusion Current antibiotic/pulmonary management of children with CF was not associated with an increased risk of IV antibiotic resistance over 3 years of observation despite repeated exposure for PEx (mean of 6 IV antibiotic courses per nonETI subject), but susceptibility to FQ decreased in 55% of those treated over 3 years following repeated FQ oral therapy courses. Disclosures All Authors: No reported disclosures

Alcohol and opiate misuse in adults with cystic fibrosis.

International consensus statements on depression and anxiety in adolescents and adults with cystic fibrosis(awCF) recommend assessment for comorbid substance misuse. However, at CF centers, the frequency and impact of substance misuse have not been well characterized, and best practices for prevention, identification, and evidence-based treatment have not been routinely implemented. Medical records of 148 awCF over 3 years were reviewed to determine the prevalence of substance misuse (alcohol or opiates) and its relationship with clinical variables and healthcare utilization. Independent sample ttest for continuous outcomes and χ2 test for binary outcomes were used to compare groups with and without substance misuse. Substance misuse was documented in 28 (19%) awCF, equally distributed between alcohol (n = 13) and opiates (n = 15). Adults with substance misuse were more likely to be male. The prevalence of diagnosed anxiety and depression did not differ significantly between groups, but those with substance misuse had more severe anxiety (Generalized Anxiety Disorder-7 Item [GAD-7]: 10.0 ± 6.1 vs. 3.3 ± 4.4; p < 0.001) and depressive symptoms (Patient Health Questionnaire-9: 10.4 ± 6.5 vs. 4.0 ± 4.8; p < 0.001). Adults with substance misuse had higher annual rates of missed outpatient CF visits, more frequent "sick" visits, more frequent and longer hospitalizations, and a higher mortality rate. In awCF, substance misuse is common and associated with adverse indicators of emotional and physical health, including via proxy of service utilization, suggesting that systematic approaches to addressing substance misuse in CF clinics should be considered. Prospective, longitudinal study is warranted to elucidate the complex relationships between depression, anxiety, substance misuse, and health outcomes in individuals with CF.

P333 Refresh: patient experience of an online healthy eating webinar designed specifically for adults with cystic fibrosis on CFTR modulators

Since the introduction of elexacaftor/tezacaftor/ivacaftor (ETI) many patients with CF have experienced weight gain. In response to an increasing number of patients’ BMI rising above 25Kg/m2, more patients requesting weight loss advice and dietitians recognising a lack of healthy eating knowledge, a healthy eating webinar (and supporting handouts) was developed and delivered to patients at a regional CF Centre between May 2021-Febuary 2022. Patients who stated they wanted to lose weight or those who had a BMI ≥25Kg/m2 were invited to attend via a telephone call or during CF clinic appointments.

P196 Use of nose clips for routine spirometry helps maximise forced expiratory outcome measures in cystic fibrosis clinics

Spirometry is used in CF patients to monitor progression of lung disease. Whilst nose clips (NC) are recommended by some guidelines there is no current consensus on their use during spirometry testing (Chavasse et al., 2003 European Respiratory Journal). The COVID-19 pandemic saw an escalation in the use of home monitoring including portable spirometers often resulting in reduced compliance with spirometry guidance. We examined the effect of NC on spirometry measurements in patients attending the CF clinic at Southampton Children’s Hospital.

Clinician perspectives on barriers and solutions to symptom management in cystic fibrosis

People living with cystic fibrosis (PLwCF) experience high symptom burden. 146 clinicians completed online surveys regarding barriers and solutions to symptom management between September and October 2020. The surveys contained both closed-ended and free-text entries. The symptom management specialists that CF clinicians most wished to consult included mental health (88, 65%), palliative care (59, 41%), and pain specialists (48, 33%). Barriers to symptom management included concerns about controlled substances prescribed for symptom control causing addiction and precluding transplantation, a lack of trust and collaboration among clinical specialties, a lack of symptom management specialists with CF expertise, and a worry about the affordability of specialist-level symptom management care. Potential solutions included non-pharmacological approaches, expanding access to affordable specialist symptom management care, the creation of clinical care guidelines for symptom management in CF, and having CF clinicians and symptom management specialists work alongside each other in CF clinic to build interdisciplinary trust and education.

Survey of exercise testing and training in cystic fibrosis clinics in the UK: a decade of progress

ObjectivesRegular exercise testing is recommended for people with cystic fibrosis (pwCF), as is the provision and regular review of exercise training programmes. A previous survey on exercise testing and training...

Incidence of transaminitis in adults with cystic fibrosis taking elexacaftor/tezacaftor/ivacaftor

BackgroundCystic fibrosis (CF) transmembrane conductance regulator modulators are a cornerstone of CF treatment. However, many patients develop CF liver disease (CFLD) over time, and previous data indicate a risk for transaminase elevation with modulator use. Elexacaftor/tezacaftor/ivacaftor is a commonly prescribed modulator with broad efficacy among CF genomic profiles. Theoretically, elexacaftor/tezacaftor/ivacaftor drug-induced liver injury could exacerbate and further worsen CFLD, but holding modulators can cause a decline in clinical status. ObjectivesThis study was designed to determine the real-world incidence of transaminase elevations in adult patients with CF taking elexacaftor/tezacaftor/ivacaftor. MethodsThis exploratory, retrospective descriptive study included all adults with CF-prescribed elexacaftor/tezacaftor/ivacaftor at our institution’s outpatient CF clinic. We explored transaminase elevations in 2 separate outcomes: incidence of transaminase elevations of more than 3 times the upper limit of normal (ULN), and transaminase elevations of 25% or more above baseline. Results83 patients were prescribed elexacaftor/tezacaftor/ivacaftor. Nine patients (11%) experienced an elevation of more than 3 times ULN and 62 (75%) experienced an elevation of 25% or more above baseline. The median days to transaminase elevation were 108 and 135 days, respectively. Therapy was not discontinued due to transaminase elevations in any of the patients. ConclusionTransaminase elevations among adults taking elexacaftor/tezacaftor/ivacaftor were common but did not result in discontinuation of therapy. Pharmacists should be reassured of the liver safety profile of this important medication for patients with CF.

Canadian Cystic Fibrosis–related Diabetes Clinical Practice Survey: Analysis of Current Practices and Gaps in Clinical Care

ObjectivesOur aim in this study was to identify challenges and gaps in Canadian practices in screening, diagnosis, and treatment of cystic fibrosis–related diabetes (CFRD), with the goal of informing a Canadian-specific guideline for CFRD. MethodsWe conducted an online survey of health-care professionals (97 physicians and 44 allied health professionals) who care for people living with CF (pwCF) and/or CFRD (pwCFRD). ResultsMost pediatric centres followed <10 pwCFRD and adult centres followed >10 pwCFRD. Children with CFRD are usually followed at a separate diabetes clinic, whereas adults with CFRD may be followed by respirologists, nurse practitioners, or endocrinologists in a CF clinic or in a separate diabetes clinic. Less than 25% of pwCF had access to an endocrinologist with a special interest or expertise in CFRD. Many centres perform screening oral glucose tolerance testing with fasting and 2-hour time points. Respondents, especially those working with adults, also indicate use of additional tests for screening not currently recommended in CFRD guidelines. Pediatric practitioners tend to only use insulin to manage CFRD, whereas adult practitioners are more likely to use repaglinide as an alternative to insulin. ConclusionsAccess to specialized CFRD care may be a challenge for pwCFRD in Canada. There appears to be wide heterogeneity of CFRD care organization, screening, and treatment among health-care providers caring for pwCF and/or pwCFRD across Canada. Practitioners working with adult pwCF are less likely to adhere to current clinical practice guidelines than practitioners working with children.

Insight into clinical, laboratory, and GIT ultrasound diagnostic findings of cystic fibrosis in pediatrics

BackgroundCystic fibrosis (CF) is a multisystem disorder. Gastrointestinal tract (GIT) involvement presently requires medical attention, and this improves the survival rate of patients with CF. GIT imaging has an essential role in the early detection of GIT affection. This study aimed to quantify the abdominal symptoms and their relationship to clinical findings, abdominal ultrasound scoring system, and laboratory parameters, correlating GIT manifestation with ultrasound diagnostic findings.MethodsThis was a cross-sectional study that included 60 patients diagnosed with CF based on clinical manifestations and confirmed by a positive sweat chloride test ≥ 60 mmol/L and/or genetic analysis (CFTR gene mutation; a copy from each parent) in the CF clinic in the Children’s Hospital, in a period of 12 months.ResultsRecurrent abdominal pain (RAP) was the most common GIT manifestation, followed by abdominal distension and steatorrhea. Ultrasonography (US) showed that the most frequent findings were pancreatic lipomatosis in 16 patients (26.7%), the next common finding was heterogeneous coarse hepatic parenchyma in 14 patients (23.3%), while the least finding was the thickened bowel walls in 2 patients (3.3%). Abdominal US scoring revealed that the highest burden of GIT symptoms was clearly associated with pancreatic lipomatosis and liver steatosis with the highest score (6/7) (p = 0.048), while bowel wall thickness (BWT) had the lowest score (3/7) (Table 4).ConclusionThis study reveals that abdominal US is a non-invasive investigation that helps in the early detection of GIT involvement in CF. RAP is a common GIT manifestation and may reflect a major pathology. Moreover, a significant relationship was detected between RAP and pancreatic cystosis and lipomatosis. Therefore, the study also highlights the importance of US as a routine non-invasive follow-up tool for patients with CF and suggests close monitoring of patients with CF by abdominal US performed every 6 to 12 months.

The natural history and genetic diversity of Haemophilus influenzae infecting the airways of adults with cystic fibrosis

Haemophilus influenzae is a Gram-negative pathobiont, frequently recovered from the airways of persons with cystic fibrosis (pwCF). Previous studies of H. influenzae infection dynamics and transmission in CF predominantly used molecular methods, lacking resolution. In this retrospective cohort study, representative yearly H. influenzae isolates from all pwCF attending the Calgary Adult CF Clinic with H. influenzae positive sputum cultures between 2002 and 2016 were typed by pulsed-field gel electrophoresis. Isolates with shared pulsotypes common to ≥ 2 pwCF were sequenced by Illumina MiSeq. Phylogenetic and pangenomic analyses were used to assess genetic relatedness within shared pulsotypes, and epidemiological investigations were performed to assess potential for healthcare associated transmission. H. influenzae infection was observed to be common (33% of patients followed) and dynamic in pwCF. Most infected pwCF exhibited serial infections with new pulsotypes (75% of pwCF with ≥ 2 positive cultures), with up to four distinct pulsotypes identified from individual patients. Prolonged infection by a single pulsotype was only rarely observed. Intra-patient genetic diversity was observed at the single-nucleotide polymorphism and gene content levels. Seven shared pulsotypes encompassing 39% of pwCF with H. influenzae infection were identified, but there was no evidence, within our sampling scheme, of direct patient-to-patient infection transmission.

Behavioral Health Screening in Military Cystic Fibrosis Centers: A Survey.

Cystic fibrosis (CF) is the most common life-threatening genetic illness in the United States. People with CF as well as their caregivers are up to three times more likely to report experiencing symptoms of depression and anxiety than those without CF. In 2016, the Cystic Fibrosis Foundation and the European Cystic Fibrosis Society came together to form the International Committee on Mental Health in CF and released guidelines outlining behavioral health (BH) screening recommendations for patients with CF and at least one primary caregiver. This study sought to characterize the role of BH care in routine CF treatment within the DoD health care system and identify potential opportunities for improvement. The resultant brief report is intended to elucidate and present identified areas of improvement as well as to inform further research projects in this field. A representative sample of program leaders (8 of 12; five program directors and three nurse coordinators) from all six affiliate CF centers in the DoD completed a 23-item web-based survey. This study sought to identify the following: (1) What tools are DoD affiliate CF centers using to screen patients with CF and their caregiver(s) for psychological distress and how often does screening take place? (2) What is the composition of the DoD's CF BH teams by specialty and to what degree are BH personnel available to support the needs of CF patients? (3) How comfortable are program directors and nurse coordinators in screening patients with CF and their caregiver(s) for indicators of psychological distress? (4) How familiar are CF BH teams with the use of the U.S. Military's Behavioral Health Data Portal (BHDP)? This descriptive study was approved by the Human Use Committee at the Tripler Army Medical Center. The results of this study indicated that 80% of the DoD affiliate CF centers are screening patients with CF who are 12 years and older and at least one caregiver at least annually for depression and anxiety with the Patient Health Questionnaire depression module and generalized anxiety disorder screening tool, respectively. Reported screening tools for suicidality were not standardized across centers. All respondents indicated that there is a designated social worker in their CF clinic team. Three-quarters of respondents reported that their social worker is physically present in CF clinics 75%-100% of the time. Other types of BH team members varied by clinic. Program directors and nurse coordinators on average indicated feeling "somewhat comfortable" in screening patients with CF for depression, anxiety, and suicidality. Eighty percent of program directors reported being "not so comfortable" in screening caregivers for depression, anxiety, and suicidality, with nurse coordinators on average reporting feeling "somewhat comfortable." Eighty percent of affiliate CF centers indicated that they are unaware of, are not utilizing, or do not have access to the BHDP to screen and record BH data for patients with CF or their caregiver(s). This study characterized routine CF BH care at DoD affiliate CF centers. Areas for improvement include the standardized use of screening tools for suicidality, increased provider comfort with screening, and streamlined recording and tracking of this data using the BHDP. Limitations of this study include inherent self-report bias, specifically social desirability bias. Steps toward suggested improvements and further utilization of the BHDP may improve BH care for patients with CF and their caregiver(s) in addition to facilitating future research.

Role of urinary NAG enzyme in early detection of renal impairment in cystic fibrosis patients

BackgroundCystic fibrosis (CF) is the most common life-limiting autosomal recessive disease among people in the USA and Europe with increased prevalence in Egypt. Affected children are in danger of acute kidney injury and the development of chronic renal disease through exposure to multiple nephrotoxic agents. N-acetyl beta-D-glucosaminidase (NAG) is a lysosomal enzyme present in high concentrations in the proximal tubular cells, thus raising urinary NAG levels to reflect tubular dysfunction. The aim of our study is to detect the role of the urinary NAG enzyme in the early detection of renal impairment in CF patients. This cross-sectional study enrolled 40 CF patients diagnosed in the CF Clinic in Children’s Hospital of Cairo University. They were age- and sex-matched to 40 healthy controls. All patients had glomerular filtration rate (GFR), serum creatinine, blood urea nitrogen (BUN), albumin/creatinine (A/C) ratio measured, urine analysis, urinary NAG enzyme using enzyme-linked immunosorbent assay (ELISA), and renal ultrasound (U/S) were done.ResultsOur study showed high levels of urinary NAG in cases with a significant difference between cases and controls (P value < 0.001). There was a significant correlation between urinary NAG enzyme elevation and A/C ratio in urine, nephrotoxic drugs administration, and duration of disease (P value = 0.002, 0.005, 0.019), respectively.ConclusionOur study suggested that the NAG enzyme is a good early detector of renal impairment in CF patients before the conventional laboratory assays become deranged.

290: Feasibility and acceptability of a medication schedule mobile application as part of CF care: A pilot, real-world, mobile health study in CF clinics

290: Feasibility and acceptability of a medication schedule mobile application as part of CF care: A pilot, real-world, mobile health study in CF clinics

59: The essential role of the community health worker in rural CF clinics

59: The essential role of the community health worker in rural CF clinics

124: Development and implementation of 2-sample OGTT in the outpatient CF clinic

124: Development and implementation of 2-sample OGTT in the outpatient CF clinic

119: A comprehensive, adaptive approach to effective telehealth in a pediatric CF clinic

119: A comprehensive, adaptive approach to effective telehealth in a pediatric CF clinic

74: Factors contributing to clinician responses to FEV1 indicated exacerbation signal (FIES) events in a pediatric CF clinic

74: Factors contributing to clinician responses to FEV1 indicated exacerbation signal (FIES) events in a pediatric CF clinic