Cystic fibrosis-related diabetes (CFRD) and cognitive function in adults with cystic fibrosis

Chadwick, H.K.; Abbott, Janice; Hurley, Margaret Anne; Dye, Louise; Lawton, Clare; Mansfield, Michael W.; Peckham, Daniel

doi:10.1016/j.jcf.2021.04.014

Cited by 4 publications

(6 citation statements)

References 83 publications

(88 reference statements)

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“…Besides expression in epithelial cells, CFTR is widely distributed in the brain and may have neuromodulatory functions. 9 The elevated rates of depression, anxiety, attention deficit hyperactivity disorder (ADHD), and neurocognitive impairment in people with CF [10][11][12][13][14] likely reflect psychosocial stressors including symptom and treatment burden 15 ; neuropsychiatric complications of chronic malabsorption and bronchiectasis with progressive infection and inflammation; and perhaps also disruption of neuronal CFTR function. This raises the possibility that restoration of CFTR function could directly or indirectly improve the mental health of people with CF.…”

Section: Introductionmentioning

confidence: 99%

Management of neuropsychiatric symptoms in adults treated with elexacaftor/tezacaftor/ivacaftor

Baroud

Chaudhary

Georgiopoulos

2023

Pediatric Pulmonology

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Introduction: Reports of neuropsychiatric symptoms proximal to cystic fibrosis transmembrane conductance regulator (CFTR) modulator initiation are emerging, but their prevalence and management remain poorly characterized.Methods: Retrospective chart review was used to categorize symptom trajectories of all adults at a single CF Center who initiated elexacaftor/tezacaftor/ivacaftor (ETI) before March 2022 and subsequently had ≥1 outpatient visit with the consulting CF psychiatrist. For those who developed neuropsychiatric symptoms probably related to ETI and modified treatment in response, the strategy resulting in greatest improvement with acceptable physical course and tolerability was identified. Ratings were made by a psychiatrist not involved in clinical care.Results: Of 148 adults initiating ETI, 31 were psychiatrically evaluated, 16 of whom developed new/worsening and unexpected neuropsychiatric symptoms probably related to ETI, including neurocognitive (word finding, brain fog, memory, attention/ concentration), insomnia, depression, anxiety, fatigue/low energy, mania/hypomania, other distress. This group had higher maximum lifetime Generalized Anxiety Disorder-7 scores (14.42 ± 0.96; p = 0.05) than those with improved, unchanged, or worsening/possibly related symptoms (N = 15; 9.9 ± 1.82). Treatment strategies resulting in much/very much improvement included pharmacologic interventions, psychotherapy, and dose reduction/discontinuing ETI.Conclusions: Although many people initiating ETI experience improved physical and mental health and quality of life, a subset report worsening neurocognition, mood, and anxiety. As novel therapies are developed, ascertaining and evaluating neuropsychiatric symptoms in clinical and research settings is advisable. Larger studies are needed to characterize prevalence, course, and risk factors (e.g., age, gender, clinical status, pharmacokinetics/pharmacogenomics, drug−drug interactions) for neuropsychiatric adverse events related to CFTR modulators and guide effective management.

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Section: Introductionmentioning

confidence: 99%

Management of neuropsychiatric symptoms in adults treated with elexacaftor/tezacaftor/ivacaftor

Baroud

Chaudhary

Georgiopoulos

2023

Pediatric Pulmonology

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“…Evidently, patients with CFRD have a significantly reduced health-related quality of life, and their diagnosis and treatment require the coordinated work of specialists from various fields of medicine [ 21 , 22 ]. Moreover, they have difficulties with higher-level processes known as “executive function”, which demand greater cognitive load and recruit the prefrontal cortex [ 23 ]. CFRD is associated with poor prognosis in individuals with CF, while early diagnosis and aggressive treatment contribute to improvement in survival [ 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

Cystic Fibrosis-Related Diabetes in Poland

Rachel

Biesiadecki

Galiniak

2022

IJERPH

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Cystic fibrosis (CF) is the most common autosomal recessive inherited monogenic disease in Caucasians. As medical technology progresses and the quality of patient care improves, the survival time of patients with CF has increased, which results in more frequent comorbidities such as cystic fibrosis-related diabetes (CFRD). CFRD is the result of abnormal glucose metabolism characterized primarily by insulin deficiency, exacerbated periodically by insulin resistance. The aim of our study was to analyze the epidemiology of patients with CFRD in Poland on the basis of data collected from six CF treatment centers. Analyses were performed on 1157 CF patients who were treated at one of the six CF care centers. CFRD was diagnosed according to standard criteria. All data including demographics, types of CFTR mutations, CFRD duration, and microorganisms in the sputum were obtained from the patients’ medical history. Our study indicates that the prevalence of CFRD in Poland is 12.9%. CFRD was most often diagnosed between the ages of 11 and 20 (60% of patients), while 23% of patients were diagnosed between 21 and 30 years of age. Furthermore, we observed that approximately 3–5% of patients under the age of 10 had CFRD. We found out that the type of mutation did not affect the frequency of CFRD development. Factors that increased the risk of developing CFRD include underweight and chronic Pseudomonas aeruginosa infection. Due to the extended lifespan of CF patients, the number of CFRD patients is currently increasing. We believe that the results of our study may complement information from other studies or may be useful in planning health policy in Poland.

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“…First, there may be no causal link between an observed change in mental health and the use of a CFTR modulator 7 . PwCF are at elevated risk for a variety of mental health conditions, including depression, anxiety, neurocognitive and attentional difficulties, sleep disturbance, body image/eating concerns, and substance misuse 13–16 . This may be driven by the mental health impacts of disease‐specific stressors including pulmonary exacerbations and treatment burden, 17–19 as well as by shared pathways affecting both physical and mental health in pwCF (e.g., inflammation and its metabolic effects, gut dysbiosis, social determinants of health) 20–22 .…”

Section: Introductionmentioning

confidence: 99%

“…7 PwCF are at elevated risk for a variety of mental health conditions, including depression, anxiety, neurocognitive and attentional difficulties, sleep disturbance, body image/eating concerns, and substance misuse. [13][14][15][16] This may be driven by the mental health impacts of disease-specific stressors including pulmonary exacerbations and treatment burden, [17][18][19] as well as by shared pathways affecting both physical and mental health in pwCF (e.g., inflammation and its metabolic effects, gut dysbiosis, social determinants of health). [20][21][22] To date these negative side-effects have been reported in singlecenter studies, case reports, and case series 5,6,[9][10][11][12]23,24 ; however, larger epidemiologic studies are needed to better characterize these relationships.…”

mentioning

confidence: 99%

“…7 CFTR is expressed not only in epithelial cells but also throughout the central nervous system (CNS) 30,31 ; the enteric division of the ANS, where CFTR is also expressed, has bidirectional connections with the CNS. 32 It is, therefore, conceivable both that defective CFTR proteins impact baseline neuropsychiatric functioning in pwCF 16 and that CFTR modulation may in turn alter it. 33 Ivacaftor, for example, binds to receptors and transporters that regulate neurotransmission, similar to some psychotropic medications.…”

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confidence: 99%

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Positive and negative impacts of elexacaftor/tezacaftor/ivacaftor: Healthcare providers' observations across US centers

Bathgate

Muther

Georgiopoulos

et al. 2023

Pediatric Pulmonology

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BackgroundElexacaftor/tezacaftor/ivacaftor (ETI) has been associated with unprecedented clinical improvements, transforming the management of cystic fibrosis (CF). However, side effects with implications for safety and well‐being have been reported, including neuropsychiatric changes. This study aimed to better characterize the emerging positive and negative impacts of ETI.MethodsThe Cystic Fibrosis Foundation's Mental Health Advisory Committee distributed a 26‐item survey to US CF care teams to assess clinician observations of patient‐reported experiences with ETI. Survey responses measured the prevalence of these effects in five domains: (1) positive physical and psychological effects, (2) sleep difficulties, (3) cognitive difficulties, (4) worsening mental health, and (5) concerns about the future and finances.ResultsSeventy‐five healthcare providers responded from a pediatric, adult, and combined centers. Positive physical effects of ETI and increased optimism were reported in the upper quartiles (50%–100%) and rated as having a significant impact on daily functioning. Sleep and cognitive difficulties were reported in 1%–24%, with slight impacts on functioning, and psychological symptoms (e.g., increased stress, depression, anxiety) and new psychiatric medications were reported in 1%–24%, with moderate impacts. Concerns about the future were reported in 1%–24%, with minimal impacts.ConclusionAcross US centers, providers most often observed positive physical effects of ETI. However, a variety of negative side effects were also reported, including sleep disruptions and worsening psychological functioning, which should be systematically monitored by CF teams. These national‐level data are a first step in evaluating the prevalence and consequences of these side effects and can directly inform future studies.

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Cystic fibrosis-related diabetes (CFRD) and cognitive function in adults with cystic fibrosis

Cited by 4 publications

References 83 publications

Management of neuropsychiatric symptoms in adults treated with elexacaftor/tezacaftor/ivacaftor

Management of neuropsychiatric symptoms in adults treated with elexacaftor/tezacaftor/ivacaftor

Cystic Fibrosis-Related Diabetes in Poland

Positive and negative impacts of elexacaftor/tezacaftor/ivacaftor: Healthcare providers' observations across US centers

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