Promoting Emotional Wellness in Children with CF, Part I: Child And Family Resilience.

Pediatr Pulmonol. 2020 Jul 13;:

Authors: Prieur MG, Christon LM, Mueller A, Smith BA, Georgiopoulos AM, Boat TF, Filigno SS

Abstract
Attention should be given to individual and family wellbeing from a child's first interaction with the medical team and continuing throughout development, especially for families who experience chronic illnesses, such as cystic fibrosis (CF). While much attention has been given to the mental health of people with CF 12 years and older, this paper explores various areas for CF teams to assess and provide additional resources during the first 12 years of a child's life to promote child and family wellness. In this paper, we discuss parental mental health, social determinants of health, adherence/self-care, nutrition, attention to family lifestyle factors, engagement with school and peers, and modulator therapy for this age group of people with CF. This is the first of two companion papers which examines emotional wellness of children during the early years. The second paper examines mental health assessment and intervention for children under 12. Both encourage teams to strive to promote optimal child and family emotional health and wellness, emphasizing holistic health promotion and prevention, early identification, and intervention. This article is protected by copyright. All rights reserved.

PMID: 32658376 [PubMed - as supplied by publisher]

Network-based characterization of disease-disease relationships in terms of drugs and therapeutic targets.

Bioinformatics. 2020 Jul 01;36(Supplement_1):i516-i524

Authors: Iida M, Iwata M, Yamanishi Y

Abstract
MOTIVATION: Disease states are distinguished from each other in terms of differing clinical phenotypes, but characteristic molecular features are often common to various diseases. Similarities between diseases can be explained by characteristic gene expression patterns. However, most disease-disease relationships remain uncharacterized.
RESULTS: In this study, we proposed a novel approach for network-based characterization of disease-disease relationships in terms of drugs and therapeutic targets. We performed large-scale analyses of omics data and molecular interaction networks for 79 diseases, including adrenoleukodystrophy, leukaemia, Alzheimer's disease, asthma, atopic dermatitis, breast cancer, cystic fibrosis and inflammatory bowel disease. We quantified disease-disease similarities based on proximities of abnormally expressed genes in various molecular networks, and showed that similarities between diseases could be explained by characteristic molecular network topologies. Furthermore, we developed a kernel matrix regression algorithm to predict the commonalities of drugs and therapeutic targets among diseases. Our comprehensive prediction strategy indicated many new associations among phenotypically diverse diseases.
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID: 32657408 [PubMed - in process]

Molecular characterization of Mycobacterium abscessus subspecies isolated from patients attending an Italian Cystic Fibrosis Centre.

New Microbiol. 2020 Jun 13;43(3)

Authors: Teri A, Sottotetti S, Arghittu M, Girelli D, Biffi A, D'Accico M, Daccò V, Gambazza S, Pizzamiglio G, Trovato A, Tortoli E, Colombo C, Cariani L

Abstract
Mycobacterium abscessus (MABS) infection represents significant management challenge in cystic fibrosis (CF) patients. This retrospective study (2005-2016) aims to determine the prevalence of the subspecies of MABS isolated from CF patients, to evaluate the persistence over the years of a single subspecies of MABS and to correlate mutations responsible for macrolides and amikacin resistance with MIC values. We investigated 314 strains (1 isolate/patient/year) isolated from the lower respiratory tract of 51 chronically infected CF patients. Sequencing of rpoB gene was performed to identify the MABS subspecies. The erm(41) gene was sequenced to differentiate the strains with and without inducible macrolide resistance. Regions of 23S and 16S rRNA were sequenced to investigate mutations responsible for constitutive resistance to macrolides and aminoglycosides, respectively. Antibiotic susceptibility, using commercial microdilution plates, was evaluated according to CLSI. M. abscessus subsp. abscessus accounted for 64% of the isolates, bolletii subspecies for 16% and massiliense subspecies for 20%. All the massiliense strains presented truncated erm(41) gene while 12 abscessus strains presented the mutation T28->C in the erm(41) gene, which makes it inactive. The 23S rRNA analysis did not show constitutive resistance to macrolides in any strain. Mutation of the 16S rRNA gene was highlighted in 2 strains out of 314, in agreement with high MIC values. The correct identification at the subspecies level and the molecular analysis of 23S rRNA, 16S rRNA and erm gene is useful to guide the treatment strategy in patients with M. abscessus lung infection.

PMID: 32656572 [PubMed - as supplied by publisher]

Urinary System and Renal Involvement in Children With Cystic Fibrosis.

Iran J Kidney Dis. 2020 Jul;14(4):278-281

Authors: Esfandiar N, Khanbabaee G, Riazi Kermani K

Abstract
INTRODUCTION: A few data on the prevalence of renal involvement in cystic fibrosis and its spectrum in childhood is available. In the present study, we conducted a prospective study on children who had cystic fibrosis and evaluated their renal involvement. In fact, the aim of the study was to provide data on the clinical consequences of proper identification of kidney disease in a group of children with cystic fibrosis.
METHODS: This prospective study was conducted on 55 consecutive patients with previous diagnosis of cystic fibrosis during a threeyear period and at least 3 months to over 5 years or more follow-up. The inclusion criteria was the diagnosis of cystic fibrosis which was made by clinical presentation of cystic fibrosis and laboratory results. Initially, patients' medical records were reviewed and relevant data were collected. A 24-hour urine collection (or a random urine sampling in very young infants) was used to assess crystalluria and renal function was evaluated by blood sampling.
RESULTS: Totally, 55 patients with cystic fibrosis were admitted in two hospitals with the mean age of 8.22 ± 5.66 years. GFR totally reduced in 34.5%. The overall prevalence of hypercalciuria was estimated to be 60%, while hyperoxaluria, hypocitraturia, and hyperuricosuria in 41.8%, 24.5%, and 47.3%; respectively.
CONCLUSION: Crystalluria is a common consequence of cystic fibrosis in childhood. The prevailing crystalluric finding includes hypercalciuria followed by hyperuricosuria, and hyperoxaluria. During disease GFR may be decreased due to several reasons such as nephrotoxic drugs usage.

PMID: 32655022 [PubMed - in process]

Why the immune system fails to mount an adaptive immune response to a COVID-19 infection.

Transpl Int. 2020 07;33(7):824-825

Authors: Ahmadpoor P, Rostaing L

PMID: 32236983 [PubMed - indexed for MEDLINE]

Coping, Attributions, and Health Functioning Among Adolescents with Chronic Illness and Their Parents: Reciprocal Relations Over Time.

J Clin Psychol Med Settings. 2019 12;26(4):495-506

Authors: D'Angelo CM, Mrug S, Grossoehme D, Schwebel DC, Reynolds N, Guion Reynolds K

Abstract
The purpose of the study was to identify bidirectional and longitudinal links between attributions, coping, and health functioning among adolescents with chronic illness and their parents. Religious/spiritual coping, attributional styles, and health functioning were assessed among adolescents with chronic illness at two time points approximately 21 months apart. Parental coping and attributions at both time points were also measured. Longitudinal links between variables were tested using an autoregressive cross-lagged path model; adolescent age and disease differences were evaluated via multigroup modeling. Poorer adolescent health functioning at baseline predicted higher use of parent optimistic attributional style at follow-up. Adolescent optimistic attributional style at baseline predicted more positive and less negative religious/spiritual coping at follow-up; adolescent negative religious/spiritual coping at baseline predicted more positive religious/spiritual coping at follow-up. Parent optimistic attributional style and positive religious/spiritual coping at baseline predicted the same constructs among adolescents at follow-up. With respect to age differences, parental negative religious/spiritual coping at baseline was associated with poorer health functioning among younger, but not older, adolescents at follow-up. There were no disease differences in the model. Important links were identified in this family-based model of coping, attributions, and health functioning. The results highlight specific targets for interventions to improve health functioning and coping among adolescents with chronic illness, including parental religious/spiritual coping and adolescent attributional style.

PMID: 30612251 [PubMed - indexed for MEDLINE]

Discordant courses of COVID-19 in a cohabiting couple of lung transplant recipients.

Transpl Infect Dis. 2020 Jul 12;:e13410

Authors: Desmazes-Dufeu N, Coltey B, Amari L, Gouitaa M, Touzery C, Reynaud-Gaubert M, Chanez P, Cassir N

Abstract
COVID-19 is a novel infectious disease caused by SARSCoV-2 that emerged in late 2019 and which is now a pandemic. Solid organ transplant recipients are perceived to be at increased risk of severe COVID-19 due to their chronic use of immunosuppressive drugs (ISDs) and to their associated conditions. Scarce data are available on the optimized management of ISDs in these patients and on its impact on presentation, clinical course, viral shedding, and outcome. We report here two cases of COVID-19 in a cohabiting couple of lung transplant recipients for cystic fibrosis, who had different ISDs management and who developed discordant courses of their disease. Our findings suggest that the degree of their immunosuppression might be a reason for their different course and that ISDs might prove partially protective.

PMID: 32654244 [PubMed - as supplied by publisher]

Incorporating Patient and Caregiver Feedback into Lung Transplant Referral Guidelines for Individuals with Cystic Fibrosis - Preliminary Findings from a Novel Paradigm.

Clin Transplant. 2020 Jul 12;:e14038

Authors: Smith PJ, Dunitz JM, Lucy A, Hempstead SE, Tallarico E, Faro A, Pilewski JM, Ramos KJ

Abstract
BACKGROUND: Lung transplantation is a common therapeutic option for individuals with cystic fibrosis (CF) and advanced lung disease, yet many individuals with CF are not appropriately referred for evaluation. The present study sought to enhance CF transplant referral guidelines by integrating patient-centered input to identify possible psychosocial barriers contributing to suboptimal referral for appropriate CF transplant candidates.
METHODS: As a component of developing the Cystic Fibrosis Foundation (CFF) Lung Transplant Referral Consensus Guidelines, we convened a focus group of lung transplant recipients with CF and two spouses of CF recipients. Each session involved standardized approaches to elicit qualitative, thematic content.
RESULTS: CF patients and caregivers characterized five areas for improvement, which were integrated into formal CFF referral guidelines. These included 1) timing of transplant discussion with CF providers, 2) accuracy of transplant-related knowledge and expectations, 3) stigma associated with the need for transplantation, 4) treatment team transition issues, and 5) social support and mental health concerns. Earlier introduction of transplant, greater details regarding manageable aspects of treatment, and greater provision of social support were all associated with better psychosocial experiences.
CONCLUSIONS: Integrating patient-centered input into guidelines development yielded important and previously unknown psychosocial barriers contributing to suboptimal transplant referral.

PMID: 32654238 [PubMed - as supplied by publisher]

Diffusion and Characterization of Pseudomonas aeruginosa Aminoglycoside Resistance in an Italian Regional Cystic Fibrosis Centre.

Adv Exp Med Biol. 2020 Jul 12;:

Authors: Mangiaterra G, Cedraro N, Citterio B, Simoni S, Vignaroli C, Biavasco F

Abstract
AIMS: Extensively-drug-resistant Pseudomonas aeruginosa constitutes a serious threat to patients suffering from Cystic Fibrosis (CF). In these patients, P. aeruginosa lung infection is commonly treated with aminoglycosides, but treatments are largely unsuccessful due a variety of resistance mechanisms. Here we investigate the prevalence of resistance to gentamicin, amikacin and tobramycin and the main aminoglycoside resistance genes found in P. aeruginosa strains isolated at a regional CF centre.
RESULTS: A total number of 147 randomly selected P. aeruginosa strains isolated from respiratory samples sent by the Marche regional Cystic Fibrosis Centre to the Microbiology lab, were included in this study. Of these, 78 (53%) were resistant to at least one of the three aminoglycosides tested and 27% were resistant to all three antibiotics, suggesting a major involvement of a chromosome-encoded mechanism, likely MexXY-OprM efflux pump overexpression. A specific pathogenic clone (found in 7/78 of the aminoglycoside resistant strains) carrying ant(2″)-Ia was isolated over time from the same patient, suggesting a role for this additional resistance gene in the antibiotic unresponsiveness of CF patients.
CONCLUSIONS: The MexXY-OprM efflux pump is confirmed as the resistance determinant involved most frequently in P. aeruginosa aminoglycoside resistance of CF lung infections, followed by the ant(2″)-Ia-encoded adenylyltransferase. The latter may prove to be a novel target for new antimicrobial combinations against P. aeruginosa.

PMID: 32654097 [PubMed - as supplied by publisher]

Rational use of mucoactive medications to treat pediatric airway disease.

Paediatr Respir Rev. 2020 Jun 16;:

Authors: Linssen RSN, Ma J, Bem RA, Rubin BK

Abstract
Many airway diseases in children, notably bronchiolitis, cystic fibrosis (CF), non-CF bronchiectasis including primary ciliary dyskinesia, pneumonia, and severe asthma are associated with retention of airway secretions. Medications to improve secretions clearance, the mucoactive medications, are employed to treat these diseases with varying degrees of success. This manuscript reviews evidence for the use of these medications and future directions of study.

PMID: 32653467 [PubMed - as supplied by publisher]

Book Review: Imaging in Pediatric Pulmonology, 2nd Edition. Robert H. Cleveland, Edward Y. Lee - Editors.

Pediatr Pulmonol. 2020 Jul 11;:

Authors: Donnelly LF

Abstract
It was my pleasure to review Imaging in Pediatric Pulmonology 2nd Edition. Dr. Robert H. Cleveland, the sole editor of the first edition, is back as a co-editor. Dr. Cleveland is a Professor Emeritus at Harvard Medical School and Boston Children's Hospital. This article is protected by copyright. All rights reserved.

PMID: 32652871 [PubMed - as supplied by publisher]

Bugs, breathing and blood pressure: Microbiota-gut-brain axis signalling in cardiorespiratory control in health and disease.

J Physiol. 2020 Jul 11;:

Authors: O'Connor KM, Lucking EF, Cryan JF, O'Halloran KD

Abstract
There is clear evidence of physiological effects of the gut microbiota on whole body function in health and disease. Microbiota-gut-brain axis signalling is recognised as a key player in behavioural disorders such as depression and anxiety. Recent evidence suggests that the gut microbiota affects neurocontrol networks responsible for homeostatic functions that are essential for life. We consider the evidence suggesting the potential for the gut microbiota to shape cardiorespiratory homeostasis. In various animal models of disease, there is an association between cardiorespiratory morbidity and perturbed gut microbiota, with strong evidence in support of a role of the gut microbiota in the control of blood pressure. Interventions that target the gut microbiota or manipulate the gut-brain axis, such as short-chain fatty acid supplementation, prevent hypertension in models of obstructive sleep apnoea. Emerging evidence points to a role for the microbiota-gut-brain axis in the control of breathing and ventilatory responsiveness, relevant to cardiorespiratory disease. There is also evidence for an association between the gut microbiota and disease severity in people with asthma and cystic fibrosis. There are many gaps in the knowledge base and an urgent need to better understand the mechanisms by which gut health and dysbiosis contribute to cardiorespiratory control. Nevertheless, there is a growing consensus that manipulation of the gut microbiota could prove an efficacious adjunctive strategy in the treatment of common cardiorespiratory diseases, which are the leading causes of morbidity and mortality. This article is protected by copyright. All rights reserved.

PMID: 32652603 [PubMed - as supplied by publisher]

Cystic fibrosis-related diabetes: an update on pathophysiology, diagnosis, and treatment.

J Pediatr Endocrinol Metab. 2020 Jul 13;:

Authors: Alves C, Della-Manna T, Albuquerque CTM

Abstract
Cystic fibrosis (CF) is a highly prevalent autosomal recessive disorder that is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene (7q31.2), which encodes the CFTR chloride-anion channel that is expressed in several tissues. Life expectancy has increased significantly over the past few decades due to therapeutic advances and early diagnosis through neonatal screening. However, new complications have been identified, including CF-related diabetes (CFRD). The earliest detectable glycemic abnormality is postprandial hyperglycemia that progresses into fasting hyperglycemia. CFRD is associated with a decline in lung function, impairments in weight gain and growth, pubertal development, and increased morbidity and mortality. Annual screening with oral glucose tolerance test is recommended beginning at the age of 10, and screenings are recommended for any age group during the first 48 h of hospital admission. Fasting plasma glucose levels ≥126 mg/dL (7.0 mmol/L) or 2-h postprandial plasma glucose levels ≥200 mg/dL (11.1 mmol/L) that persist for more than 48 h are diagnostic criteria for CFRD. Under stable health condition, the diagnosis is made when laboratory abnormalities in accordance with the American Diabetes Association criteria are detected for the first time; however, levels of HbA1c <6.5% do not rule out the diagnosis. Treatment for CFRD includes insulin replacement and a hypercaloric and hyperproteic diet that does not restrict carbohydrates, fats or salt, and diabetes self-management education. The most important CFRD complications are nutritional and pulmonary disease deterioration, though the microvascular complications of diabetes have already been described.

PMID: 32651985 [PubMed - as supplied by publisher]

Phosphorylation of the Chaperone-Like HspB5 Rescues Trafficking and Function of F508del-CFTR.

Int J Mol Sci. 2020 Jul 08;21(14):

Authors: Degrugillier F, Aissat A, Prulière-Escabasse V, Bizard L, Simonneau B, Decrouy X, Jiang C, Rotin D, Fanen P, Simon S

Abstract
Cystic Fibrosis is a lethal monogenic autosomal recessive disease linked to mutations in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. The most frequent mutation is the deletion of phenylalanine at position 508 of the protein. This F508del-CFTR mutation leads to misfolded protein that is detected by the quality control machinery within the endoplasmic reticulum and targeted for destruction by the proteasome. Modulating quality control proteins as molecular chaperones is a promising strategy for attenuating the degradation and stabilizing the mutant CFTR at the plasma membrane. Among the molecular chaperones, the small heat shock protein HspB1 and HspB4 were shown to promote degradation of F508del-CFTR. Here, we investigated the impact of HspB5 expression and phosphorylation on transport to the plasma membrane, function and stability of F508del-CFTR. We show that a phosphomimetic form of HspB5 increases the transport to the plasma membrane, function and stability of F508del-CFTR. These activities are further enhanced in presence of therapeutic drugs currently used for the treatment of cystic fibrosis (VX-770/Ivacaftor, VX-770+VX-809/Orkambi). Overall, this study highlights the beneficial effects of a phosphorylated form of HspB5 on F508del-CFTR rescue and its therapeutic potential in cystic fibrosis.

PMID: 32650630 [PubMed - as supplied by publisher]

You are my death: the shattered temporalities of zombie time.

Wellcome Open Res. 2020;5:135

Authors: O'Brien M

Abstract
This essay considers the relationship between the experience of life shortening chronic illness and the current COVID-19 crisis. Martin O'Brien uses his experience of living with cystic fibrosis to interrogate the temporal experience of living within a global pandemic. He returns to his concept of zombie time, the temporal experience of living longer than expected, in order to understand the presence of death as a way of life. The essay uses some of O'Brien's own art practices, and an analysis of his own sick, coughing body in order to think through what it means to live with cystic fibrosis during a pandemic, which mimics much of its features. O'Brien argues that we are currently occupying a widespread zombie time, which frames other people as carriers of death, and that we must find ways of being together in order to survive.

PMID: 32647752 [PubMed]

Cholestasis in Benign Recurrent Intrahepatic Cholestasis 2.

ACG Case Rep J. 2020 Jun;7(6):e00412

Authors: Arthur Lorio E, Valadez D, Alkhouri N, Loo N

Abstract
Benign recurrent intrahepatic cholestasis represents a rare class of autosomal recessive chronic cholestasis disorders, usually presenting with recurrent episodes of intense pruritus and jaundice. We report a 27-year-old woman presenting with benign recurrent intrahepatic cholestasis type 2 due to heterozygosity in ABCB11. Interestingly, she was also found to be heterozygous in cystic fibrosis transmembrane conductance regulator, NPHP4, and A1ATD (SERPINA1), which may explain the severe nature of her disease expression because heterozygosity in each of these genes has been associated with cholestasis. Finally, she exhibited a response to steroids that may have implications for future treatment of bile salt export pump-related diseases.

PMID: 32647738 [PubMed]

Impact of Socioeconomic Position on Access to the US Lung Transplant Waiting List in a Matched Cystic Fibrosis Cohort.

Ann Am Thorac Soc. 2020 Jul 10;:

Authors: Lehr CJ, Fink AK, Skeans M, Faro A, Fernandez G, Dasenbrook E, Valapour M

Abstract
RATIONALE: Referrals for lung transplant and transplant rates in the United States are lower than in Canada for patients with advanced cystic fibrosis (CF) lung disease. Further study of factors limiting access are needed to optimize referral and transplant for this population.
OBJECTIVE(S): To determine the effect of socioeconomic position, while accounting for disease severity, on the likelihood of wait-listing for lung transplant in the United States.
METHODS: A case-control study of 3110 patients (1555 waitlisted, 1555 never waitlisted) in the linked CF Foundation Patient Registry/Scientific Registry of Transplant Recipients was performed with 1:1 matching for age, forced expiratory volume in 1 second (FEV1), and year. Logistic regression was performed with univariate and multivariate analyses accounting for eight clinical factors (sex, oxygen use, body mass index, hemoptysis, forced vital capacity, methicillin resistant Staphylococcus aureus, multi-drug resistant Pseudomonas aeruginosa, IV antibiotic days) and seven socioeconomic factors (race, marital status, education, health insurance, median zip code income, distance to transplant program). The CF Health Score and Socioeconomic Barrier Score were created based on summation of variables. Interactions between scores were calculated.
RESULTS: We found an inverse relationship between the probability of wait-listing and CF Health Score and Socioeconomic Barrier Score. As the CF Health Score decreased (less healthy), the probability of wait-listing increased by 69.3% from a score of 7 to 2. As the Socioeconomic Barrier Score decreased (fewer barriers), the probability of wait-listing increased by 31.7% from a score of ≥ 5 to 1). Regardless of illness severity, socioeconomic barriers presented an impediment to wait-listing. Individuals with higher Socioeconomic Barrier Scores accessed transplant about half as often as those with lower scores at the same level of medical severity. Analysis of interactions demonstrated a higher probability of wait-listing for individuals with moderate health severity and fewer social barriers compared with sicker individuals with more socioeconomic barriers.
CONCLUSIONS: Accrual of socioeconomic barriers limits access to lung transplant irrespective of disease severity, a finding of substantial concern for CF patients and for transplant providers. Future interventions can focus on this at-risk population early in the disease course.

PMID: 32649218 [PubMed - as supplied by publisher]

Integration of Mental Health Screening and Treatment into Cystic Fibrosis Clinics: Evaluation of Initial Implementation in 84 Programs Across the United States.

Pediatr Pulmonol. 2020 Jul 10;:

Authors: Quittner AL, Abbott J, Hussain S, Ong T, Uluer A, Hempstead S, Lomas P, Smith B

Abstract
BACKGROUND: A large-scale epidemiological study of 6088 individuals with CF and 4102 caregivers in 9 countries documented elevated symptoms of depression and anxiety, leading to international guidelines for annual screening and follow-up. To facilitate national implementation, 84 CF programs funded a mental health coordinators (MHC). Implementation was evaluated after 1 year using the Consolidated Framework for Implementation Research (CFIR) to identify facilitators and barriers.
METHODS: A 45-item internet survey was developed to assess relevant CFIR implementation steps. Surveys were completed in 2016. It assessed five domains tailored to study aims: 1) Intervention Characteristics, 2) Outer Setting, 3) Inner Setting, 4) Characteristics of Individuals, and 5) Process of Implementation.
RESULTS: Response rate was 88%, with pediatric and adult programs equally represented. A majority of MHCs were social workers (54.1%) and psychologists (41.9%); 41% had joined the team in the past year. Facilitators across the 5 domains included universal uptake of screening tools, greater awareness and detection of psychological symptoms, reduced stigma, and positive feedback from patients and families. Barriers included limited staff time, space, and logistics.
DISCUSSION: This is the largest systematic effort to integrate mental health screening and treatment into the care of individuals with a serious, chronic illness and their caregivers. MHCs implementing screening, interpretation and follow-up reported positive results, and significant barriers. This national implementation effort demonstrated that depression and anxiety can be efficiently evaluated and treated in a complex, chronic disease. Future efforts include recommending the addition of screening scores to national CF Registries and examining their effects on health outcomes. This article is protected by copyright. All rights reserved.

PMID: 32649006 [PubMed - as supplied by publisher]

Steps Toward Cell Therapy for Cystic Fibrosis.

Am J Respir Cell Mol Biol. 2020 Jul 10;:

Authors: Koh KD, Erle DJ

PMID: 32648785 [PubMed - as supplied by publisher]

High Prevalence of Triazole-Resistant Aspergillus fumigatus sensu stricto in an Argentinean Cohort of Patients with Cystic Fibrosis.

Mycoses. 2020 Jul 10;:

Authors: Brito Devoto T, Hermida-Alva K, Posse G, Finquelievich JL, García-Effrón G, Cuestas ML

Abstract
BACKGROUND: Triazole resistance in Aspergillus fumigatus sensu stricto due to mutations in the cyp51A gene has been widely reported. Data from Argentina, and particularly from cystic fibrosis (CF) patients, are limited.
OBJECTIVES: to investigate the prevalence and molecular mechanisms of azole resistance in A. fumigatus sensu stricto recovered from this population.
METHODS: Ninety-three A. fumigatus isolates from 50 CF patients were retrospectively analyzed for azole resistance using the standard microbroth dilution method according to CLSI M38-A2 guidelines. Sequencing analysis of the cyp51A gene and its promoter region was conducted in those isolates displaying high MICs values to itraconazole, voriconazole and/or posaconazole.
RESULTS: Overall, 14% of isolates displayed high MIC values to at least one azole. Of them, 30.7% had the mutation TR34-L98H. No mutations in the cyp51A gene or its promoter were found in the remaining non-wild type strains. Therefore, other mechanisms associated with azole resistance can be highly prevalent in these isolates.
CONCLUSIONS: To the best of our knowledge, this is the first study in Latin America reporting azole resistant A. fumigatus strains recovered from respiratory secretions of CF patients. Noteworthy, the prevalence of azole resistance in A. fumigatus sensu stricto in the studied Argentinean CF population is alarmingly high.

PMID: 32648614 [PubMed - as supplied by publisher]