Respir Med Res. 2021 May 17;80:100829. doi: 10.1016/j.resmer.2021.100829. Online ahead of print.

ABSTRACT

BACKGOUND: Elexacaftor-tezacaftor-ivacaftor partially restores cystic fibrosis transmembrane conductance regulator function, and has been shown to induce significant clinical improvement in patients with at least one Phe508del allele. Yet little data exist on patient perspectives following elexacaftor-tezacaftor-ivacaftor initiation.

METHODS: A mixed methods study was conducted using an online 13-item questionnaire (including 9 closed questions and 4 open questions), submitted from July 10th to August 21th 2020 to French patients aged 12 years and older with advanced CF who were treated with elexacaftor-tezacaftor-ivacaftor. Their responses were summarized as numbers (%), and free-text items were analysed using a grounded theory approach.

RESULTS: Of 245 patients who started elexacaftor-tezacaftor-ivacaftor in France, 101 (41%) participated. Median [IQR] age was 35 [28-41] years and duration of elexacaftor-tezacaftor-ivacaftor treatment was 4.3 [3.0-5.6] months. Patients generally reported a rapid impact on respiratory symptoms, sleep quality, general well-being and physical self-esteem, and a reduction in overall treatment burden. The majority of patients contrasted treatment burden, symptom severity, depression and a closed future marked by death or transplantation before elexacaftor-tezacaftor-ivacaftor, to renewed and unexpected physical strength, leading to greater self-confidence, autonomy and long-term planning, after treatment initiation. A small number of patients expressed concerns, mainly regarding changes in body representation and/or the fear of becoming dependent on the treatment.

CONCLUSION: After initiation of elexacaftor-tezacaftor-ivacaftor, CF patients with advanced disease reported rapid and positive physical, psychological and social effects, which translated into improved quality of life and the formulation of new life goals.

PMID:34091202 | DOI:10.1016/j.resmer.2021.100829

J Cyst Fibros. 2021 Jun 2:S1569-1993(21)00161-2. doi: 10.1016/j.jcf.2021.05.010. Online ahead of print.

ABSTRACT

BACKGROUND: We assessed the diagnostic performances of homeostasis model assessment indices (HOMA) of β-cell function (HOMA-%β) and of insulin resistance (HOMA-IR) for cystic fibrosis related diabetes (CFRD) screening.

METHODS: Data were collected from a prospective cohort of 228 patients with CF (117 adults and 111 children). Fasting insulin and glucose levels were measured to calculate HOMA-%β and HOMA-IR. HOMA-%β <100 indicated insulin secretion deficiency and HOMA-IR >1 insulin resistance. Both were used to calculate sensitivity, specificity, and positive and negative predictive values (PPV and NPV). Two-hour oral glucose tolerance tests (2h-OGTT) defined CFRD. Analyses were conducted separately for children and adults. Performances of HOMA-%β and HOMA-IR were calculated at inclusion, for each year of follow-up and for pooled data over the follow-up period.

RESULTS: Sensitivity, specificity, NPV and PPV were respectively: 88%, 45%, 98% and 11% for HOMA-%β and 42%, 48%, 91% and 6% for HOMA-IR in the pooled data of children; and 83%, 18%, 90% and 10% for HOMA-%β, and 39%, 80%, 92% and 18% for HOMA-IR in the pooled data of adults. Combining HOMA-%β and HOMA-IR did not improve performances.

CONCLUSION: Within both age groups, HOMA-%β <100 provided good sensitivity and NPV. HOMA-IR >1 had low sensitivity. Calculation of the HOMA-%β could be an interesting first-line screening approach to exclude CFRD and thus avoid unnecessary OGTT in patients for whom value is ≥100. However, HOMA-%β<100 does not support the diagnosis of CFRD and should be complemented by OGTT.

PMID:34090803 | DOI:10.1016/j.jcf.2021.05.010

J Cyst Fibros. 2021 Jun 2:S1569-1993(21)00163-6. doi: 10.1016/j.jcf.2021.05.012. Online ahead of print.

ABSTRACT

BACKGROUND: Females with cystic fibrosis (CF) have been shown to have worse pulmonary exacerbation (PEx) related outcomes compared to males. However, it is unknown if sex differences in treatment patterns are contributing to these outcomes. Thus, we sought to explore sex differences in treatment patterns in the Standardized Treatment of Pulmonary Exacerbations (STOP) cohort.

METHODS: Data for 220 participants from the STOP cohort were analyzed. Multivariable regression models were used to assess if female sex was associated with duration of treatment with IV antibiotics and inpatient length of stay. Secondary outcomes included antibiotic selection, adjunctive therapies, mean FEV1pp and CFRSD-CRISS respiratory symptom scores at the four study assessments.

RESULTS: In our adjusted model, the average number of IV antibiotic treatment days was 13% higher in females compared to males (IRR 1.13, 95% CI=1.02,1.25; p=0.02). We found no sex differences in inpatient length of stay, number of IV antibiotics, antibiotic selection or initiation of adjunctive therapies. Overall, females had higher CFRSD-CRISS scores at the end of IV therapy indicating worse symptom severity (23.6 for females vs. 18.5 for males, p=0.03).

CONCLUSIONS: Despite females having a longer treatment duration, our findings demonstrate that males and females are receiving similar treatments which suggest that the outcome disparities in females with CF may not be due to failure to provide the same level of care. Further research dedicated to sex differences in CF is necessary to understand why clinical outcomes differ between males and females.

PMID:34090802 | DOI:10.1016/j.jcf.2021.05.012

Lancet. 2021 Jun 5;397(10290):2195-2211. doi: 10.1016/S0140-6736(20)32542-3.

ABSTRACT

Cystic fibrosis is a monogenic disease considered to affect at least 100 000 people worldwide. Mutations in CFTR, the gene encoding the epithelial ion channel that normally transports chloride and bicarbonate, lead to impaired mucus hydration and clearance. Classical cystic fibrosis is thus characterised by chronic pulmonary infection and inflammation, pancreatic exocrine insufficiency, male infertility, and might include several comorbidities such as cystic fibrosis-related diabetes or cystic fibrosis liver disease. This autosomal recessive disease is diagnosed in many regions following newborn screening, whereas in other regions, diagnosis is based on a group of recognised multiorgan clinical manifestations, raised sweat chloride concentrations, or CFTR mutations. Disease that is less easily diagnosed, and in some cases affecting only one organ, can be seen in the context of gene variants leading to residual protein function. Management strategies, including augmenting mucociliary clearance and aggressively treating infections, have gradually improved life expectancy for people with cystic fibrosis. However, restoration of CFTR function via new small molecule modulator drugs is transforming the disease for many patients. Clinical trial pipelines are actively exploring many other approaches, which will be increasingly needed as survival improves and as the population of adults with cystic fibrosis increases. Here, we present the current understanding of CFTR mutations, protein function, and disease pathophysiology, consider strengths and limitations of current management strategies, and look to the future of multidisciplinary care for those with cystic fibrosis.

PMID:34090606 | DOI:10.1016/S0140-6736(20)32542-3

Int J Pharm. 2021 Jun 2:120768. doi: 10.1016/j.ijpharm.2021.120768. Online ahead of print.

ABSTRACT

Certain pulmonary diseases, such as cystic fibrosis (CF), non-CF bronchiectasis, chronic obstructive pulmonary disease, and ventilator-associated pneumonia, are usually accompanied by respiratory tract infections due to the physiological alteration of the lung immunological defenses. Recurrent infections may lead to chronic infection through the formation of biofilms. Chronic biofilm-based infections are challenging to treat using antimicrobial agents. Therefore, effective ways to eradicate biofilms and thus relieve respiratory tract infection require the development of efficacious agents for biofilm destruction, the design of delivery carriers with biofilm-targeting and/or penetrating abilities for these agents, and the direct delivery of them into the lung. This review provides an in-depth description of biofilm-based infections caused by pulmonary diseases and focuses on current existing agents that are administered by inhalation into the lung to treat biofilm, which include i) inhalable antimicrobial agents and their combinations, ii) non-antimicrobial adjuvants such as matrix-targeting enzymes, mannitol, glutathione, cyclosporin A, and iii) liposomal formulations of anti-biofilm agents. Finally, novel agents that have shown promise against pulmonary biofilms as well as traditional and new devices for pulmonary delivery of anti-biofilm agents into the lung are also discussed.

PMID:34089796 | DOI:10.1016/j.ijpharm.2021.120768

J Cyst Fibros. 2021 Jun 1:S1569-1993(21)00116-8. doi: 10.1016/j.jcf.2021.04.006. Online ahead of print.

ABSTRACT

BACKGROUND: Lung disease can develop within the first year of life in infants with cystic fibrosis (CF). However, the frequency and severity of respiratory symptoms in infancy are not known.

METHODS: We assessed respiratory symptoms in 50 infants with CF and 50 healthy matched controls from two prospective birth cohort studies. Respiratory symptoms and respiratory rate were documented by standardized weekly interviews throughout the first year. Infants performed multiple breath washout in the first weeks of life.

RESULTS: We analyzed 4552 data points (2217 in CF). Respiratory symptoms (either mild or severe) were not more frequent in infants with CF (OR:1.1;95% CI:[0.76, 1.59]; p=0.6). Higher lung clearance index and higher respiratory rate in infants with CF were not associated with respiratory symptoms.

CONCLUSIONS: We found no difference in respiratory symptoms between healthy and CF infants. These data indicate that early CF lung disease may not be captured by clinical presentation alone.

PMID:34088612 | DOI:10.1016/j.jcf.2021.04.006

PLoS One. 2021 Jun 4;16(6):e0251881. doi: 10.1371/journal.pone.0251881. eCollection 2021.

ABSTRACT

INTRODUCTION: Asthma with airway mucus hypersecretion is an inadequately characterized variant of asthma. While several studies have reported that hypersecreting patients may carry genetic variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, many of those studies have been questioned for their numerous limitations and contradictory results.

OBJECTIVES: (1) To determine the presence of genetic variants of the CFTR gene in patients with asthma with and without airway mucus hypersecretion. (2) To identify the clinical, inflammatory and functional characteristics of the asthma phenotype with airway mucus hypersecretion.

METHOD: Comparative multicentre cross-sectional descriptive study that included 100 patients with asthma (39 hypersecretors and 61 non-hypersecretors). Asthmatic hypersecretion was defined as the presence of cough productive of sputum on most days for at least 3 months in 2 successive years. The patients were tested for fractional exhaled nitric oxide, spirometry, induced sputum cell count, total immunoglobulin E (IgE), peripheral blood eosinophil count, C-reactive protein, blood fibrinogen and blood albumin and underwent a skin prick test. Asthma control and quality of life were assessed by the Asthma Control Test and Mini Asthma Quality of Life questionnaires, respectively. Blood DNA samples were collected from the patients and next-generation sequencing using a MiSeq sequencer and the Illumina platform was used for the CFTR gene analysis.

RESULTS: Genetic differences were observed in the c.1680-870T>A polymorphism of the CFTR gene, significantly more evident in hypersecretors than in non-hypersecretors: 78.94% vs. 59.32% in the majority allele and 21.05% vs. 40.67% in the minority allele (p = 0.036). Clinically, asthma hypersecretors compared to non-hypersecretors were older (57.4 years vs. 49.4 years; p = 0.004); had greater asthma severity (58.9% vs. 23.7%; p = 0.005); experienced greater airway obstruction (FEV1/FVC% 64.3 vs. 69.5; p = 0.041); had poorer asthma control (60% vs. 29%; p = 0.021); had lower IgE levels (126.4 IU/mL vs. 407.6 IU/mL; p = 0.003); and were less likely to have a positive prick test (37.5% vs. 68.85%; p = 0.011).

CONCLUSION: The results suggest that patients with asthma and with mucus hypersecretion (1) may have a different phenotype and disease mechanism produced by an intronic polymorphism in the CFTR gene (NM_000492.3:c.1680-870T>A), and (2) may have a poorer clinical outcome characterized by severe disease and poorer asthma control with a non-allergic inflammatory phenotype.

PMID:34086689 | DOI:10.1371/journal.pone.0251881

Med Chem. 2021;17(5):554. doi: 10.2174/157340641705210524122637.

ABSTRACT

In the following article, the author reported an error in the abstract's result section [1]. The results section of the abstract has been changed as follows: Results: The main benefits (e.g., specialized centres for the treatment of CF exist or a new breakthrough in the gene therapy of CF has been made) and limitations (e.g., comorbidity of CF, lifelong and costly treatment, or adverse impact on patient's and caregiver's quality of life) in the treatment of CF are highlighted. The original results section of the abstract was published as: Results: The main benefits (e.g., specialized centres for the treatment of CF exist or a new breakthrough in the gene therapy of CF has been made) and limitations (e.g., comorbidity of CF, lifelong and costly treatment, or adverse impact on patient's and caregiver's quality of life) in the treatment of narcolepsy are highlighted. The original article can be found online at 10.2174/1573406412666160608113235.

PMID:34086549 | DOI:10.2174/157340641705210524122637

Physiol Rep. 2021 Jun;9(11):e14886. doi: 10.14814/phy2.14886.

ABSTRACT

Cystic fibrosis (CF) is a life-limiting autosomal recessive genetic disease caused by variants in the CFTR gene, most commonly by the [F508del] variant. Although CF is a classical Mendelian disease, genetic variants in several modifier genes have been associated with variation of the clinical phenotype for pulmonary and gastrointestinal function and urogenital development. We hypothesized that whole genome sequencing of a well-phenotyped CF populations might identify novel variants in known, or hitherto unknown, modifier genes. Whole genome sequencing was performed on the Illumina HiSeq X platform for 98 clinically diagnosed cystic fibrosis patient samples from the Adult CF Clinic at the University of California San Diego (UCSD). We compared protein-coding, non-silent variants genome wide between CFTR [F508del] homozygotes vs CFTR compound heterozygotes. Based on a single variant score test, we found 3 SNPs in common variants (MAF >5%) that occurred at significantly different rates between homozygous [F508del]CFTR and compound heterozygous [F508del]CFTR patients. The 3 SNPs were all located in one gene on chromosome 2: Tensin 1 (TNS1: rs3796028; rs2571445: and rs918949). We observed significantly lower BMIs in homozygous [F508del]CFTR patients who were also homozygous for Tensin 1 rs918949 (T/T) (p = 0.023) or rs2571445 (G/G) (p = 0.02) variants. The Tensin 1 gene is thus a potential modifier gene for low BMI in CF patients homozygous for the [F508del]CFTR variant.

PMID:34086412 | DOI:10.14814/phy2.14886

ERJ Open Res. 2021 May 31;7(2):00076-2021. doi: 10.1183/23120541.00076-2021. eCollection 2021 Apr.

ABSTRACT

BACKGROUND: Despite the increasing prevalence of Achromobacter xylosoxidans lung infection in patients with cystic fibrosis (CF), its clinical pathogenicity remains controversial. The objective of this study was to evaluate the effects of this emerging bacterium on lung disease severity in CF children.

METHODS: This case-control retrospective study took place in two French paediatric CF centres. 45 cases infected by A. xylosoxidans were matched for age, sex, CFTR genotypes and pancreatic status to 45 never-infected controls. Clinical data were retrieved from clinical records over the 2 years before and after A. xylosoxidans initial infection.

RESULTS: At infection onset, lung function was lower in cases compared with controls (p=0.006). Over the 2 years prior to A. xylosoxidans acquisition, compared with controls, cases had more frequent pulmonary exacerbations (p=0.02), hospitalisations (p=0.05), and intravenous (p=0.03) and oral (p=0.001) antibiotic courses. In the 2 years following A. xylosoxidans infection, cases remained more severe with more frequent pulmonary exacerbations (p=0.0001), hospitalisations (p=0.0001), and intravenous (p=0.0001) and oral antibiotic courses (p=0.0001). Lung function decline tended to be faster in cases (-5.5% per year) compared with controls (-0.5% per year).

CONCLUSIONS: This case-control study demonstrates that A. xylosoxidans occurs more frequently in the patients with the worse lung disease. Further studies assessing the pathogenicity of this emerging pathogen and international treatment recommendations are warranted.

PMID:34084788 | PMC:PMC8165377 | DOI:10.1183/23120541.00076-2021

Respirol Case Rep. 2021 May 25;9(6):e00783. doi: 10.1002/rcr2.783. eCollection 2021 Jun.

ABSTRACT

Exophiala dermatitidis is a black fungus that rarely causes respiratory infection. We report a case of E. dermatitidis pneumonia with bronchiectasis that relapsed after 11 months of voriconazole (VRCZ) treatment in a rheumatoid arthritis (RA) patient with bronchiectasis. A 65-year-old woman with RA and abnormal findings on chest radiography was referred for assessment of chronic cough and increased sputum production. She underwent bronchoscopy, and E. dermatitidis was identified from bronchoalveolar lavage fluid (BALF). Exophiala dermatitidis chronic lower respiratory tract infection and pneumonia were diagnosed. Although her condition improved after 11 months of VRCZ treatment, chest computed tomography (CT) images showed worsening at five months after the cessation of VRCZ treatment and E. dermatitidis was again detected in BALF. Re-administration of VRCZ for two years improved symptoms and chest CT images, and her condition is currently stable. In patients with bronchiectasis, E. dermatitidis pneumonia might require prolonged antifungal treatment.

PMID:34084534 | PMC:PMC8144837 | DOI:10.1002/rcr2.783

Front Pharmacol. 2021 May 18;12:682299. doi: 10.3389/fphar.2021.682299. eCollection 2021.

ABSTRACT

Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in defective ion transport in the airways. Addition of a functioning CFTR gene into affected airway cells has the potential to be an effective treatment for lung disease. The therapeutic efficacy of airway gene transfer can be quantified in animal models by assessing ion transport in the treated nasal epithelium using the nasal potential difference (PD) measurement technique. The nasal PD technique is routinely used in CF mice, however when applied to a recently developed CF rat model those animals did not tolerate the initial nasal PD assessment, therefore the procedure was firstly optimised in rats. This study evaluated the effect of lentiviral (LV)-mediated CFTR airway gene delivery on nasal PD in a CFTR knockout rat model. LV gene vector containing the CFTR gene tagged with a V5 epitope tag (LV-V5-CFTR) was delivered to the nasal epithelium of CF rats, and one week later nasal PD was analysed. This study demonstrated for the first time that LV-V5-CFTR treatment produced a mean correction of 46% towards wild-type chloride response in treated CF rats. Transduced cells were subsequently identifiable using V5 immunohistochemical staining. These findings in the nose validate the use of airway gene therapy for future lung based experiments.

PMID:34084147 | PMC:PMC8167067 | DOI:10.3389/fphar.2021.682299

J Cyst Fibros. 2021 May 31:S1569-1993(21)00131-4. doi: 10.1016/j.jcf.2021.05.004. Online ahead of print.

ABSTRACT

CFTR function is required for normal mucociliary clearance (MCC) and cough-assisted clearance (CC). Lumacaftor-ivacaftor is approved for use in people with cystic fibrosis (CF) carrying two copies of F508del-CFTR. In this observational study performed at four study sites, we characterized the effect of lumacaftor-ivacaftor on mucociliary and cough clearance and related this to other clinical and research endpoints after one month of treatment. Twenty-five adolescents and adults were enrolled. No effect on whole lung MCC was observed, but CC was significantly increased. Sweat chloride improved by 18 mEq/L in this group, indicating a modest restoration of CFTR activity, but no demonstrable change in FEV1 or lung clearance index was observed. We speculate that the modest effect of lumacaftor-ivacaftor on CFTR function was insufficient to yield an improvement in MCC.

PMID:34083123 | DOI:10.1016/j.jcf.2021.05.004

Allergol Select. 2021 May 27;5:162-179. doi: 10.5414/ALX02234E. eCollection 2021.

ABSTRACT

An expert workshop in collaboration of the German Society of Allergy and Clinical Immunology (DGAKI) and the Japanese Society of Allergy (JSA) provided a platform for key opinion leaders of both countries aimed to join expertise and to highlight current developments and achievements in allergy research. Key domains of the meeting included the following seven main sections and related subchapters: 1) basic immunology, 2) bronchial asthma, 3) prevention of allergic diseases, 4) food allergy and anaphylaxis, 5) atopic dermatitis, 6) venom allergy, and 7) upper airway diseases. This report provides a summary of panel discussions of all seven domains and highlights unmet needs and project possibilities of enhanced collaborations of scientific projects.

PMID:34079922 | PMC:PMC8167740 | DOI:10.5414/ALX02234E

BMJ Paediatr Open. 2021 May 18;5(1):e001057. doi: 10.1136/bmjpo-2021-001057. eCollection 2021.

ABSTRACT

OBJECTIVE: To understand how a child with a stable chronic disease and his/her parents shape his/her daily life participation, we assessed: (1) the parents' goals regarding the child's daily life participation, (2) parental strategies regarding the child's participation and () how children and their parents interrelate when their goals regarding participation are not aligned.

METHODS: This was a qualitative study design using a general inductive approach. Families of children 8-19 years with a stable chronic disease (cystic fibrosis, autoimmune disease or postcancer treatment) were recruited from the PROactive study. Simultaneous in-depth interviews were conducted separately with the child and parent(s). Analyses included constant comparison, coding and categorisation.

RESULTS: Thirty-one of the 57 invited families (54%) participated. We found that parents predominantly focus on securing their child's well-being, using participation as a means to achieve well-being. Moreover, parents used different strategies to either support participation consistent with the child's healthy peers or support participation with a focus on physical well-being. The degree of friction between parents and their child was based on the level of agreement on who takes the lead regarding the child's participation.

CONCLUSIONS: Interestingly, parents described participation as primarily a means to achieve the child's well-being, whereas children described participation as more of a goal in itself. Understanding the child's and parent's perspective can help children, parents and healthcare professionals start a dialogue on participation and establish mutual goals. This may help parents and children find ways to interrelate while allowing the child to develop his/her autonomy.

PMID:34079917 | PMC:PMC8137215 | DOI:10.1136/bmjpo-2021-001057

Ann Appl Stat. 2020 Jun;14(2):956-976. doi: 10.1214/20-aoas1335. Epub 2020 Jun 29.

ABSTRACT

Recurrent events are commonly encountered in longitudinal studies. The observation of recurrent events is often stopped by a dependent terminal event in practice. For this data scenario, we propose two sensible adaptations of the generalized accelerated recurrence time (GART) model (Sun et al., 2016) to provide useful alternative analyses that can offer physical interpretations while rendering extra flexibility beyond the existing work based on the accelerated failure time model. Our modeling strategies align with the rationale underlying the use of the survivors' rate function or the adjusted rate function to account for the presence of the dependent terminal event. For the proposed models, we identify and develop estimation and inference procedures, which can be readily implemented based on existing software. We establish the asymptotic properties of the new estimator. Simulation studies demonstrate good finite-sample performance of the proposed methods. An application to a dataset from the Cystic Fibrosis Foundation Patient Registry (CFFPR) illustrates the practical utility of the new methods.

PMID:34079614 | PMC:PMC8168595 | DOI:10.1214/20-aoas1335

NPJ Genom Med. 2021 Jun 2;6(1):41. doi: 10.1038/s41525-021-00203-x.

ABSTRACT

Autosomal recessive (AR) disorders pose a significant burden for public health. However, despite their clinical importance, epidemiology and molecular genetics of many AR diseases remain poorly characterized. Here, we analyzed the genetic variability of 508 genes associated with AR disorders based on sequencing data from 141,456 individuals across seven ethnogeographic groups by integrating variants with documented pathogenicity from ClinVar, with stringent functionality predictions for variants with unknown pathogenicity. We first validated our model using 85 diseases for which population-specific prevalence data were available and found that our estimates strongly correlated with the respective clinically observed disease frequencies (r = 0.68; p < 0.0001). We found striking differences in population-specific disease prevalence with 101 AR diseases (27%) being limited to specific populations, while an additional 305 diseases (68%) differed more than tenfold across major ethnogeographic groups. Furthermore, by analyzing genetic AR disease complexity, we confirm founder effects for cystic fibrosis and Stargardt disease, and provide strong evidences for >25 additional population-specific founder mutations. The presented analyses reveal the molecular genetics of AR diseases with unprecedented resolution and provide insights into epidemiology, complexity, and population-specific founder effects. These data can serve as a powerful resource for clinical geneticists to inform population-adjusted genetic screening programs, particularly in otherwise understudied ethnogeographic groups.

PMID:34078906 | DOI:10.1038/s41525-021-00203-x

Hosp Pediatr. 2021 Jun 2:hpeds.2020-004739. doi: 10.1542/hpeds.2020-004739. Online ahead of print.

ABSTRACT

OBJECTIVE: To describe the prevalence, types, and trends over time of medical technology assistance (TA) in patients at the age of transition to adult care with childhood onset chronic conditions (COCCs) cared for at children's hospitals.

PATIENTS AND METHODS: In this retrospective repeated annual cross-sectional cohort study of the Pediatric Health Information Systems inpatient data, patients with at least 1 hospitalization from January 1, 2008, to December 31, 2018 with a selected COCC were included. The COCCs investigated were brain and spinal cord malformation, cerebral palsy, heart and great vessel malformation, cystic fibrosis, sickle cell anemia, and chronic renal failure. TA was defined as requiring an indwelling medical device to maintain health status. Trends over time in TA were analyzed with the Cochran-Armitage test and generalized linear models.

RESULTS: During the study, 381 289 unique patients accounted for 940 816 hospitalizations. Transition-aged patients (19-21 years old) represented 2.4% of all included hospitalizations over the 11-year period, whereas patients ages 21 and above represented 2.7%. The annual proportion of patients with TA increased significantly from 31.3% in 2008 to 36.9% in 2018, a 17.9% increase (P < .001).

CONCLUSIONS: In this cohort of patients with select COCCs hospitalized at children's hospitals, a substantial and growing number of patients at the age of transition to adult care required TA. Identifying adult providers with resources to manage COCCs and maintain medical devices placed in childhood is challenging. These trends warrant special attention to support the timely and successful transition of medically complex patients from pediatric to adult care.

PMID:34078644 | DOI:10.1542/hpeds.2020-004739

Ital J Pediatr. 2021 Jun 2;47(1):121. doi: 10.1186/s13052-021-01076-7.

ABSTRACT

BACKGROUND: Cystic Fibrosis Related Diabetes (CFRD) is a frequent comorbidity of patients with Cystic Fibrosis (CF). A worsening of clinical conditions appears before CFRD. It has been demonstrated a decline in pulmonary function and nutritional status also in patients with prediabetes. Few trials show that insulin may be beneficial in prediabetic CF patients, to date guidelines do not recommend for this condition.

CASE PRESENTATION: We report a case of a patient treated with insulin glargine at 13 years, due to glycemic intolerance, and with Lumacaftor/Ivacaftor at 15 years. A reduction of pulmonary exacerbations was observed after glargine therapy, also confirmed after the starting of Lumacaftor/ Ivacaftor in this patient. Pulmonary function improved only after the first year of glargine therapy, then a deterioration appeared due to the natural history of CF lung damage. During the COVID-19 lockdown, poor adherence to care contributed to diabetes mellitus onset needing high insulin requirements. After two weeks the patient returned to prediabetic condition and his previous dose of glargine.

CONCLUSIONS: our case highlights firstly that insulin glargine has contributed to preserve him from further clinical worsening due to prediabetes in the years before pandemic, secondly the negative impact of COVID-19 lockdown on the clinical course of a chronic disease as CF.

PMID:34078438 | DOI:10.1186/s13052-021-01076-7

Ann Pharmacother. 2021 Jun 2:10600280211022065. doi: 10.1177/10600280211022065. Online ahead of print.

ABSTRACT

OBJECTIVE: To review the available literature addressing alternative allergic bronchopulmonary aspergillosis (ABPA) treatment options for patients with cystic fibrosis (CF).

DATA SOURCES: A literature search of PubMed was performed (January 2002 to April 2021) using the following search terms: allergic bronchopulmonary aspergillosis, aspergillus-related lung disease, cystic fibrosis. Manufacturer prescribing information, clinical practice guidelines, and data from ClinicalTrials.gov were incorporated in the reviewed data.

STUDY SELECTION AND DATA EXTRACTION: Relevant English-language studies or those conducted in humans were considered for inclusion.

DATA SYNTHESIS: Available literature for alternative ABPA treatments in CF is lacking randomized controlled trials, but there is considerable support in case reports and case series describing the benefits in pediatric and adult patients. Recent literature has begun to explore the place in therapy for novel, corticosteroid-sparing treatment approaches. The alternative therapies summarized in this review all resulted in clinical improvement and subsequent discontinuation or dose reductions of oral corticosteroids, with minimal reported adverse drug effects.

RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Although corticosteroids are the cornerstone of ABPA management, the toxicities can be significant limitations in an already high-risk patient population. Patients may fail or become intolerant to guideline-recommended therapies and require alternative treatment approaches.

CONCLUSIONS: Alternative treatment modalities for ABPA in patients with CF, including azole antifungals, pulsed intravenous glucocorticoids, omalizumab, mepolizumab, and inhaled amphotericin, appear to be efficacious and well tolerated. Pharmacological properties including route of administration, storage and stability, beyond use dating, and adverse effects of the various treatment modalities must be considered when selecting a practical care plan for patients.

PMID:34078140 | DOI:10.1177/10600280211022065