Psychol Res Behav Manag. 2022 Jun 28;15:1601-1605. doi: 10.2147/PRBM.S322425. eCollection 2022.

ABSTRACT

OBJECTIVE: This exploratory study examines the prevalence of adverse childhood experiences (ACEs) in adults with cystic fibrosis (CF).

DESIGN: Childhood exposure to 16 ACEs was measured during an annual review assessment (N = 80).

METHODS: CF patients (n = 80) attending the All Wales Adult CF Service for a routine annual review assessment completed an adapted version of the Centers for Disease Control and Prevention (CDC) short-form ACE questionnaire alongside measures of psychological well-being.

RESULTS: In this sample, 65 (78%) reported at least one type of childhood adversity and 11 (14%) experienced four or more ACEs. Parental divorce or separation and verbal abuse were the most frequently reported ACEs. Illness related trauma in childhood was also prevalent with 52 (64%) reporting having experienced a painful or frightening medical procedure and 23 (28%) feeling forced to have treatment or a procedure.

CONCLUSION: Individuals with CF reported a number of childhood traumas including trauma relating to medical procedures. Those with a history of ACEs may have increased risks of emotional and physical difficulties and may benefit from additional support from the CF psychosocial team.

PMID:35789731 | PMC:PMC9250325 | DOI:10.2147/PRBM.S322425

BMJ Case Rep. 2022 Jul 4;15(7):e250643. doi: 10.1136/bcr-2022-250643.

ABSTRACT

A man in his 50s was admitted with 4 months of myalgia, headaches, hypercalcaemia and declining renal function on a background of lung transplantation for cystic fibrosis 5 years prior. MRI confirmed myositis and a muscle biopsy revealed invasive muscular microsporidial infection. Positron emission tomography(PET)/CT revealed widespread dissemination of the infection. Albendazole was commenced and after a 1 week systemic inflammatory response syndrome, the patient made a significant recovery and was discharged home. PCR testing confirmed the species as Anncaliia algerae, which is known to infect mosquitoes, larvae and contaminate water supplies. This case highlights the need to relentlessly pursue a diagnosis and to consider atypical pathology in immune compromised patients. A tissue sample yielded highly beneficial and unexpected results. A multispecialty approach was essential given the varied infection manifestations, which included myositis, keratitis and possible central nervous system, vocal cord, parapharyngeal and renal involvement.

PMID:35787491 | DOI:10.1136/bcr-2022-250643

Biomed Pharmacother. 2022 Jul 1;153:113373. doi: 10.1016/j.biopha.2022.113373. Online ahead of print.

ABSTRACT

Anoctamin 1 (ANO1) is a calcium-activated chloride channel found in various cell types and is overexpressed in non-small cell lung cancer (NSCLC), a major cause of cancer-related mortality. With the rising interest in development of druggable compounds for NSCLC, there has been a corresponding rise in interest in ANO1, a novel drug target for NSCLC. However, as ANO1 inhibitors that have been discovered simultaneously exhibit both the functions of an inhibition of ANO1 channel as well as a reduction of ANO1 protein levels, it is unclear which of the two functions directly causes the anticancer effect. In this study, verteporfin, a chemical compound that reduces ANO1 protein levels was identified through high-throughput screening. Verteporfin did not inhibit ANO1-induced chloride secretion but reduced ANO1 protein levels in a dose-dependent manner with an IC50 value of ~300 nM. Moreover, verteporfin inhibited neither P2Y receptor-induced intracellular Ca2+ mobilization nor cystic fibrosis transmembrane conductance regulator (CFTR) channel activity, and molecular docking studies revealed that verteporfin bound to specific sites of ANO1 protein. Confirming that verteporfin reduces ANO1 protein levels, we then investigated the molecular mechanisms involved in its effect on NSCLC cells. Interestingly, verteporfin decreased ANO1 protein levels, the EGFR-STAT3 pathway as well as ANO1 mRNA expression. Verteporfin reduced the viability of ANO1-expressing cells (PC9, and gefitinib-resistant PC9) and induced apoptosis by increasing caspase-3 activity and PARP-1 cleavage. However, it did not affect hERG channel activity. These results show that the anticancer mechanism of verteporfin is caused via the down-regulation of ANO1.

PMID:35785700 | DOI:10.1016/j.biopha.2022.113373

Prev Med Rep. 2022 Jun 9;28:101852. doi: 10.1016/j.pmedr.2022.101852. eCollection 2022 Aug.

ABSTRACT

One in three grade 7 to 12 students in Canada report trying vaping or e-cigarettes. Despite consequences like nicotine addiction, impaired brain development, increased respiratory symptoms, and association with an increased risk of COVID-19 diagnosis, 48% of youth believe occasional vaping has little to no risk. There is a clear need for youth to learn about vaping consequences. We developed and piloted a novel free interactive educational program on vaping risks which has been used by over 800 grade 7 to 9 students. In post-program surveys, students reported a subjective increase in knowledge about the health consequences of vaping.

PMID:35785407 | PMC:PMC9243163 | DOI:10.1016/j.pmedr.2022.101852

Front Pharmacol. 2022 Jun 15;13:890284. doi: 10.3389/fphar.2022.890284. eCollection 2022.

ABSTRACT

Airway epithelium plays critical roles in regulating airway surface liquid (ASL), the alteration of which causes mucus stasis symptoms. Allicin is a compound released from garlic and harbors the capacity of lung-protection. However, the potential regulatory effects of allicin on airway epithelium remain elusive. This study aimed to investigate the effects of allicin on ion transport across airway epithelium and evaluate its potential as an expectorant. Application of allicin induced Cl- secretion across airway epithelium in a concentration-dependent manner. Blockade of cystic fibrosis transmembrane conductance regulator (CFTR) or inhibition of adenylate cyclase-cAMP signaling pathway attenuated allicin-induced Cl- secretion in airway epithelial cells. The in vivo study showed that inhaled allicin significantly increased the ASL secretion in mice. These results suggest that allicin induces Cl- and fluid secretion across airway epithelium via activation of CFTR, which might provide therapeutic strategies for the treatment of chronic pulmonary diseases associated with ASL dehydration.

PMID:35784719 | PMC:PMC9241074 | DOI:10.3389/fphar.2022.890284

Front Immunol. 2022 Jun 16;13:915261. doi: 10.3389/fimmu.2022.915261. eCollection 2022.

ABSTRACT

Specialized pro-resolving lipid mediators (SPMs) as lipoxins (LX), resolvins (Rv), protectins (PD) and maresins (MaR) promote the resolution of inflammation. We and others previously reported reduced levels of LXA4 in bronchoalveolar lavages from cystic fibrosis (CF) patients. Here, we investigated the role of CF airway epithelium in SPMs biosynthesis, and we evaluated its sex specificity. Human nasal epithelial cells (hNEC) were obtained from women and men with or without CF. Lipids were quantified by mass spectrometry in the culture medium of hNEC grown at air-liquid interface and the expression level and localization of the main enzymes of SPMs biosynthesis were assessed. The 5-HETE, LXA4, LXB4, RvD2, RvD5, PD1 and RvE3 levels were significantly lower in samples derived from CF patients compared with non-CF subjects. Within CF samples, the 12-HETE, 15-HETE, RvD3, RvD4, 17-HODHE and PD1 were significantly lower in samples derived from females. While the mean expression levels of 15-LO, 5-LO and 12-LO do not significantly differ either between CF and non-CF or between female and male samples, the SPMs content correlates with the level of expression of several enzymes involved in SPMs metabolism. In addition, the 5-LO localization significantly differed from cytoplasmic in non-CF to nucleic (or nuclear envelope) in CF hNEC. Our studies provided evidence for lower abilities of airway epithelial cells derived from CF patients and more markedly, females to produce SPMs. These data are consistent with a contribution of CF airway epithelium in the abnormal resolution of inflammation and with worse pulmonary outcomes in women.

PMID:35784330 | PMC:PMC9244846 | DOI:10.3389/fimmu.2022.915261

Hong Kong Physiother J. 2022 Jun;42(1):5-14. doi: 10.1142/S1013702522500019. Epub 2021 Jun 11.

ABSTRACT

BACKGROUND: Autonomic nervous system balance is altered in cystic fibrosis (CF), although its influence on physical fitness has been poorly explored.

OBJECTIVE: This study aimed to evaluate the association of heart rate variability (HRV) with exercise capacity and levels of daily physical activity in children and adolescents with mild-to-moderate CF.

METHODS: A cross-sectional study including individuals with CF aged 6-18 years, not under CFTR modulator therapy, was performed. Sociodemographic (age, sex) and clinical information (airway colonization, pancreatic insufficiency, and genotyping) were collected. In addition, exercise capacity (modified shuttle test - MST), lung function (spirometry), body composition (bioimpedance), levels of daily physical activity (5-day accelerometer), and HRV (both at rest and during the MST) were evaluated.

RESULTS: 30 individuals (20 females) aged 11 . 2 ± 3 . 7 years, mean FEV 1 62 . 8 ± 27 . 6 %, were included. A sympathovagal balance (LF/HF) increase ( p < 0 . 001 ) during the MST was shown, indicating a predominance of sympathetic modulation. The standard deviation of all RR intervals (SDNN) and the high frequency (HF) index during exercise correlated significantly with FEV1 ( r = 0 . 45 , p = 0 . 01 and r = 0 . 46 , p = 0 . 01 ; respectively). MST distance also correlated positively and significantly with SDNN ( r = 0 . 43 , p = 0 . 01 ), square root of the mean of the sums of squares of frequencies between RR intervals greater than 50 ms - RMSSD ( r = 0 . 53 , p < 0 . 01 ), low frequency - LF ( r = 0 . 48 , p < 0 . 01 ), HF ( r = 0 . 64 , p < 0 . 01 ), dispersion of points perpendicular to the short-term identity line - SD1 ( r = 0 . 40 , p = 0 . 02 ) and negatively with LF/HF ( r =- 0 . 57 , p < 0 . 01 ). Regarding daily physical activity, SDNN at rest ( r = 0 . 37 , p = 0 . 04 ) and exercise ( r = 0 . 41 , p = 0 . 02 ) showed positive correlations with time in moderate-to-vigorous activities. When normalizing the SDNN and classifying individuals as normal or altered, those presenting altered SDNN showed poorest FEV1 ( p = 0 . 001 ) and lower exercise capacity ( p = 0 . 027 ).

CONCLUSION: HRV correlates with lung function, exercise capacity and levels of daily physical activity in children and adolescents with CF. The study highlights the influence of CF on autonomic function and suggests HRV measurement as an easy tool to be used in clinical settings as an alternative marker to monitor CF individuals.

PMID:35782696 | PMC:PMC9244599 | DOI:10.1142/S1013702522500019

Front Cell Infect Microbiol. 2022 Jun 16;12:859181. doi: 10.3389/fcimb.2022.859181. eCollection 2022.

ABSTRACT

Bacteria of the genus Achromobacter are environmental germs, with an unknown reservoir. It can become opportunistic pathogens in immunocompromised patients, causing bacteremia, meningitis, pneumonia, or peritonitis. In recent years, Achromobacter xylosoxidans has emerged with increasing incidence in patients with cystic fibrosis (CF). Recent studies showed that A. xylosoxidans is involved in the degradation of the respiratory function of patients with CF. The respiratory ecosystem of patients with CF is colonized by bacterial species that constantly fight for space and access to nutrients. The type VI secretion system (T6SS) empowers this constant bacterial antagonism, and it is used as a virulence factor in several pathogenic bacteria. This study aimed to investigate the prevalence of the T6SS genes in A. xylosoxidans isolated in patients with CF. We also evaluated clinical and molecular characteristics of T6SS-positive A. xylosoxidans strains. We showed that A. xylosoxidans possesses a T6SS gene cluster and that some environmental and clinical isolates assemble a functional T6SS nanomachine. A. xylosoxidans T6SS is used to target competing bacteria, including other CF-specific pathogens. Finally, we demonstrated the importance of the T6SS in the internalization of A. xylosoxidans in lung epithelial cells and that the T6SS protein Hcp is detected in the sputum of patients with CF. Altogether, these results suggest for the first time a role of T6SS in CF-lung colonization by A. xylosoxidans and opens promising perspective to target this virulence determinant as innovative theranostic options for CF management.

PMID:35782124 | PMC:PMC9245596 | DOI:10.3389/fcimb.2022.859181

Arch Bronconeumol. 2022 Jun 20:S0300-2896(22)00453-7. doi: 10.1016/j.arbres.2022.06.003. Online ahead of print.

NO ABSTRACT

PMID:35781398 | DOI:10.1016/j.arbres.2022.06.003

J Vis Exp. 2022 Jun 14;(184). doi: 10.3791/63882.

ABSTRACT

Diseases of the conducting airway such as asthma, cystic fibrosis (CF), primary ciliary dyskinesia (PCD), and viral respiratory infections are major causes of morbidity and mortality worldwide. In vitro platforms using human bronchial epithelial cells (HBECs) have been instrumental to our understanding of the airway epithelium in health and disease. Access to HBECs from individuals with rare genetic diseases or rare mutations is a bottleneck in lung research. Induced pluripotent stem cells (iPSCs) are readily generated by "reprogramming" somatic cells and retain the unique genetic background of the individual donor. Recent advances allow for the directed differentiation of iPSCs to lung epithelial progenitor cells, alveolar type 2 cells, as well as the cells of the conducting airway epithelium via basal cells, the major airway stem cells. Here we outline a protocol for the maintenance and expansion of iPSC-derived airway basal cells (hereafter iBCs) as well as their trilineage differentiation in air-liquid interface (ALI) cultures. iBCs are maintained and expanded as epithelial spheres suspended in droplets of extracellular matrix cultured in a primary basal cell medium supplemented with inhibitors of TGF-ß and BMP signaling pathways. iBCs within these epithelial spheres express key basal markers TP63 and NGFR, can be purified by fluorescence activated cell sorting (FACS), and when plated on porous membranes in standard ALI culture conditions, differentiate into a functional airway epithelium. ALI cultures derived from healthy donors are composed of basal, secretory and multiciliated cells and demonstrate epithelial barrier integrity, motile cilia, and mucus secretion. Cultures derived from individuals with CF or PCD recapitulate the dysfunctional CFTR-mediated chloride transport or immotile cilia, the respective disease-causing epithelial defects. Here, we present a protocol for the generation of human cells that can be applied for modeling and understanding airway diseases.

PMID:35781291 | DOI:10.3791/63882

Lancet Respir Med. 2022 Jun 29:S2213-2600(22)00253-3. doi: 10.1016/S2213-2600(22)00253-3. Online ahead of print.

NO ABSTRACT

PMID:35779568 | DOI:10.1016/S2213-2600(22)00253-3

Pediatr Pulmonol. 2022 Jul 2. doi: 10.1002/ppul.26047. Online ahead of print.

ABSTRACT

Pediatric pulmonology publishes original research, review articles, and case reports on a wide variety of pediatric respiratory disorders. In this article, we summarized the past year's publications in sleep medicine and reviewed selected literature from other journals in this field. We focused on original research articles exploring aspects of sleep-disordered breathing in patients with underlying conditions such as Cystic Fibrosis, asthma, and sickle cell disease. We also explored sleep-disordered breathing risk factors, monitoring, diagnosis, and treatment; and included recent recommendations for drug-induced sleep endoscopy and ways to monitor and improve PAP adherence remotely. This article is protected by copyright. All rights reserved.

PMID:35779240 | DOI:10.1002/ppul.26047

J Heart Lung Transplant. 2022 Jun 4:S1053-2498(22)01973-8. doi: 10.1016/j.healun.2022.05.018. Online ahead of print.

ABSTRACT

BACKGROUND: Pre-existing chronic kidney disease (CKD) may have an impact on post-lung transplant survival and the development of end stage kidney disease (ESKD).

METHODS: We analyzed the US transplant database from 2006 to 2020. Adult patients who received their first lung transplant and were not on dialysis were included. Multivariable Cox regression was used to assess the effect of pretransplant eGFR on mortality and cumulative incidence competing risk was used to explore the effect on ESKD.

RESULTS: The adjusted hazard ratio (aHR) for mortality showed a "U" shaped association with eGFR with a rising mortality at <60 and >100 ml/min/1.73m2. The increase in mortality with higher eGFR was only seen in those <30 year and were primarily in whites with a lower body mass index and in patients with cystic fibrosis (CF). The aHR for ESKD increased below an eGFR of 100 rising to 1.74 at an eGFR of 60. Any decrease in eGFR between listing and transplant >10% was associated with higher risk of ESKD.

CONCLUSIONS: The U-shaped association of pretransplant eGFR with post-transplant mortality correlated with younger age, lower BMI and a diagnosis of CF. The aHR for ESKD following lung transplantation increased exponentially with worsening eGFR pretransplant.

PMID:35778259 | DOI:10.1016/j.healun.2022.05.018

Eur Respir J. 2022 Jul 1:2200209. doi: 10.1183/13993003.00209-2022. Online ahead of print.

NO ABSTRACT

PMID:35777769 | DOI:10.1183/13993003.00209-2022

Am J Respir Crit Care Med. 2022 Jul 1. doi: 10.1164/rccm.202202-0309OC. Online ahead of print.

ABSTRACT

RATIONALE: MUC5AC and MUC5B are the predominant secreted polymeric mucins in mammalian airways. They contribute differently to the pathogenesis of various muco-obstructive and interstitial lung diseases, and their genes are separately regulated, but whether they are packaged together or in separate secretory granules is not known.

OBJECTIVES: To determine the packaging of MUC5AC and MUC5B within individual secretory granules in mouse and human airways under varying conditions of inflammation and along the proximal-distal axis.

METHODS: Lung tissue was obtained from mice stimulated to upregulate mucin production by the cytokines IL-1β and IL-13 or by porcine pancreatic elastase. Human lung tissue was obtained from donated normal lungs, biopsies of transplanted lungs, and explanted COPD lungs. MUC5AC and MUC5B were labelled with antibodies from different animal species or, in mice only, by transgenic chimeric mucin-fluorescent proteins, and imaged by widefield deconvolution or Airyscan fluorescence microscopy.

MEASUREMENTS AND MAIN RESULTS: In both mouse and human airways, most secretory granules contained both mucins interdigitating within the granules. Smaller numbers of granules contained MUC5B alone, and even fewer contained MUC5AC alone.

CONCLUSIONS: MUC5AC and MUC5B are variably stored both in the same and in separate secretory granules of both mice and humans. The high fraction of granules containing both mucins under a variety of conditions makes it unlikely that their secretion can be differentially controlled as a therapeutic strategy. This work also advances knowledge of the packaging of mucins within secretory granules to understand mechanisms of epithelial stress in the pathogenesis of chronic lung diseases.

PMID:35776514 | DOI:10.1164/rccm.202202-0309OC

Acta Biomed. 2022 Jul 1;93(3):e2022133. doi: 10.23750/abm.v93i3.12842.

ABSTRACT

BACKGROUND AND AIM: Cystic fibrosis (CF), is due to CF transmembrane conductance regulator (CFTR) loss of function, and is associated with comorbidities. The increasing longevity of CF patients has been associated with increased cancer risk besides the other known comorbidities. The significant heterogeneity among patients, suggests potential epigenetic regulation. Little attention has been given to how CFTR influences microRNA (miRNA) expression and how this may impact on biological processes and pathways.

METHODS: We assessed the changes in miRNAs and subsequently identified the affected molecular pathways using CFBE41o-, and IB3 human immortalized cell lines since they reflect the most common genetic mutations in CF patients, and 16HBE14o- cells were used as controls.

RESULTS: In the CF cell lines, 41 miRNAs showed significant changes (FC (log2) ≥ +2 or FC (log2) ≤ -2 and p-value≤0.05). Gene target analysis evidenced 511 validated miRNA target genes. Gene Ontology analysis evidenced cancer, inflammation, body growth, glucose, and lipid metabolism as the biological processes most impacted by these miRNAs. Protein-protein interaction and pathway analysis highlighted 50 significantly enriched pathways among which RAS, TGF beta, JAK/STAT and insulin signaling.

CONCLUSIONS: CFTR loss of function is associated with changes in the miRNA network, which regulates genes involved in the major comorbidities that affect CF patients suggesting that further research is warranted.

PMID:35775757 | DOI:10.23750/abm.v93i3.12842

J Epidemiol Glob Health. 2022 Jun 30. doi: 10.1007/s44197-022-00048-2. Online ahead of print.

ABSTRACT

OBJECTIVES: The Burkholderia cepacia complex (Bcc), which was originally thought to be a single species, represents a group of 24 distinct species that are often resistant to multiple antibiotics, and usually known to cause life-threatening pulmonary infections in cystic fibrosis patients. Herein we describe a series of non-respiratory Bcc infections, the risk factors and epidemiologic factors, in addition to the clinical course.

PATIENTS AND METHODS: This is a retrospective chart review of 44 patients with documented B. cepacia infections isolated from sites other than the respiratory tract admitted between June 2005 and February 2020 to the American University of Beirut Medical Center (AUBMC), a tertiary referral hospital for Lebanon and the Middle East region. The epidemiological background of these patients, their underlying risk factors, the used antibiotic regimens, and the sensitivities of the B. cepacia specimens were collected.

RESULTS: The majority of the Bcc infections (26/44, 59.1%) were hospital-acquired infections. The most common nationality of the patients was Iraqi (18/44, 40.9%), and the most common site of infection was bacteremia (17/44, 38.6%), followed by skin and soft tissues infections (16/44, 36.4%) and vertebral osteomyelitis (8/44, 18.2%). Most of the isolated B. cepacia were susceptible to ceftazidime, carbapenems, followed by TMP-SMX. Patients responded well to therapy with good overall outcome.

CONCLUSIONS: Bcc can cause infections outside the respiratory tract, mostly as hospital-acquired infections and in immunocompromised patients. Most patients were referred from countries inflicted by wars raising the possibility of a potential role of conflicts which need to be investigated in future studies. Directed therapy according to susceptibility results proved effective in most patients.

PMID:35773618 | DOI:10.1007/s44197-022-00048-2

Sci Rep. 2022 Jun 30;12(1):11114. doi: 10.1038/s41598-022-15375-4.

ABSTRACT

Studies of microbiota reveal inter-relationships between the microbiomes of the gut and lungs. This relationship may influence the progression of lung disease, particularly in patients with cystic fibrosis (CF), who often experience extraoesophageal reflux (EOR). Despite identifying this relationship, it is not well characterised. Our hypothesis is that the gastric and lung microbiomes in CF are related, with the potential for aerodigestive pathophysiology. We evaluated gastric and sputum bacterial communities by culture and 16S rRNA gene sequencing in 13 CF patients. Impacts of varying levels of bile acids, pepsin and pH on patient isolates of Pseudomonas aeruginosa (Pa) were evaluated. Clonally related strains of Pa and NTM were identified in gastric and sputum samples from patients with symptoms of EOR. Bacterial diversity was more pronounced in sputa compared to gastric juice. Gastric and lung bile and pepsin levels were associated with Pa biofilm formation. Analysis of the aerodigestive microbiomes of CF patients with negative sputa indicates that the gut can be a reservoir of Pa and NTM. This combined with the CF patient's symptoms of reflux and potential aspiration, highlights the possibility of communication between microorganisms of the gut and the lungs. This phenomenon merits further research.

PMID:35773410 | DOI:10.1038/s41598-022-15375-4

Signal Transduct Target Ther. 2022 Jun 30;7(1):206. doi: 10.1038/s41392-022-01070-3.

ABSTRACT

Fibrosis is characterized by the excessive extracellular matrix deposition due to dysregulated wound and connective tissue repair response. Multiple organs can develop fibrosis, including the liver, kidney, heart, and lung. Fibrosis such as liver cirrhosis, idiopathic pulmonary fibrosis, and cystic fibrosis caused substantial disease burden. Persistent abnormal activation of myofibroblasts mediated by various signals, such as transforming growth factor, platelet-derived growth factor, and fibroblast growh factor, has been recongized as a major event in the occurrence and progression of fibrosis. Although the mechanisms driving organ-specific fibrosis have not been fully elucidated, drugs targeting these identified aberrant signals have achieved potent anti-fibrotic efficacy in clinical trials. In this review, we briefly introduce the aetiology and epidemiology of several fibrosis diseases, including liver fibrosis, kidney fibrosis, cardiac fibrosis, and pulmonary fibrosis. Then, we summarise the abnormal cells (epithelial cells, endothelial cells, immune cells, and fibroblasts) and their interactions in fibrosis. In addition, we also focus on the aberrant signaling pathways and therapeutic targets that regulate myofibroblast activation, extracellular matrix cross-linking, metabolism, and inflammation in fibrosis. Finally, we discuss the anti-fibrotic drugs based on their targets and clinical trials. This review provides reference for further research on fibrosis mechanism, drug development, and clinical trials.

PMID:35773269 | DOI:10.1038/s41392-022-01070-3

Clin Res Hepatol Gastroenterol. 2022 Jun 27:101977. doi: 10.1016/j.clinre.2022.101977. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Cystic fibrosis liver disease (CFLD) is the third leading cause of death in patients with cystic fibrosis (CF). We aim to determine the prevalence of CFLD in a cohort of adult patients with CF and to characterise liver involvement in this population highlighting the importance of histological diagnosis.

METHODS: We retrospectively studied a cohort of patients with CF. Inclusion criteria were age ≥ 18 and minimum 1 year of follow-up. We excluded lung transplant patients. CFLD was defined as having 2 out of 3 criteria: persistent elevation of transaminases and/or gamma-glutamyltransferase; abnormal ultrasound; and abnormal transient elastography. Non-invasive fibrosis biomarkers were calculated in CFLD patients. Adult-onset CFLD (Ad-CFLD) was defined as CFLD ≥18 years. Severe CFLD (s-CFLD) was defined as CFLD with cirrhosis and/or portal hypertension.

RESULTS: We included 113 patients. Median age was 29 years, 58 were male. Forty patients had CFLD. Median age at CFLD diagnosis was 10 years. Twenty-one patients had s-CFLD. Two s-CFLD patients had nodular regenerative hyperplasia, 1 had hepatocellular carcinoma and 4 underwent liver transplantation. Six patients had ad-CFLD. Both CFLD and s-CFLD groups were compared to a non-CFLD group. The CFLD group had significantly more males (p=0.034). S-CFLD group had worse pulmonary function (p=0.015).

CONCLUSION: Thirty five percent of adult patients with CF, mainly males, had CFLD. Nineteen percent had s-CFLD and had worse pulmonary function. With recent reports unravelling different pathophysiological mechanisms in CFLD, we believe it is important to better characterise liver involvement using liver biopsy.

PMID:35772685 | DOI:10.1016/j.clinre.2022.101977