Immune response in children with COVID-19 is characterized by lower levels of T cell activation than infected adults.

Eur J Immunol. 2020 Jun 27;:

Authors: Moratto D, Giacomelli M, Chiarini M, Savarè L, Saccani B, Motta M, Timpano S, Poli P, Paghera S, Imberti L, Cannizzo S, Quiros-Roldan E, Marchetti G, Badolato R

Abstract
XX XXX This article is protected by copyright. All rights reserved.

PMID: 32592406 [PubMed - as supplied by publisher]

Clinical response to lumacaftor-ivacaftor in patients with cystic fibrosis according to baseline lung function.

J Cyst Fibros. 2020 Jun 23;:

Authors: Burgel PR, Durieu I, Chiron R, Mely L, Prevotat A, Murris-Espin M, Porzio M, Abely M, Reix P, Marguet C, Macey J, Sermet-Gaudelus I, Corvol H, Bui S, Biouhee T, Hubert D, Munck A, Lemonnier L, Dehillotte C, Silva JD, Paillasseur JL, Martin C, French Cystic Fibrosis Reference Network study group

Abstract
BACKGROUND: Phase 3 trials have demonstrated the safety and efficacy of lumacaftor-ivacaftor (LUMA-IVA) in patients with cystic fibrosis (CF) homozygous for the Phe508del CFTR mutation and percent predicted forced expiratory volume in 1 s (ppFEV1) between 40 and 90. Marketing authorizations have been granted for patients at all levels of ppFEV1.
METHODS: To evaluate the safety and effectiveness of LUMA-IVA over the first year of treatment in patients with ppFEV1<40 or ppFEV1≥90 in comparison with those with ppFEV1 [40-90[. Analysis of data collected during a real world study, which included all patients aged ≥12 years who started LUMA-IVA in 2016 across all 47 French CF centers.
RESULTS: 827 patients were classified into 3 subgroups according to ppFEV1 at treatment initiation (ppFEV1<40, n = 121; ppFEV1 [40-90[, n = 609; ppFEV1≥90, n = 97). Treatment discontinuation rate was higher in ppFEV1<40 patients (28.9%) than in those with ppFEV1 [40-90[(16.4%) or ppFEV1≥90 (17.5%). In patients with uninterrupted treatment, significant increase in ppFEV1 occurred in the ppFEV1 [40-90[subgroup (+2.9%, P<0.001), and in those ppFEV1<40 (+0.5%, P = 0.03) but not in those with ppFEV1≥90 (P = 0.46). Compared with the year prior to initiation, the number of days of intravenous antibiotics were reduced in all subgroups, although 72% of patients with ppFEV1<40 still experienced at least one exacerbation/year under LUMA-IVA. Comparable increase in body mass index was seen in the three subgroups.
CONCLUSION: Phe508del homozygous CF patients benefit from LUMA-IVA at all levels of baseline lung function, but the characteristics and magnitude of the response vary depending on ppFEV1 at baseline.

PMID: 32591294 [PubMed - as supplied by publisher]

Cystic Fibrosis-Related Pancreatic Cysts Decrease in Size and Number Upon Treatment With Cystic Fibrosis Transmembrane Conductance Regulator Modulators.

Pancreas. 2020 Jul;49(6):e50-e51

Authors: de Vries JM, Green D, Kucera JN, Fabbrini AL, Kidder M, Brown J, Wilsey M

PMID: 32590622 [PubMed - as supplied by publisher]

Lipopolymers and lipids from lung surfactants in association with N-acetyl-l-cysteine: characterization and cytotoxicity.

Chem Phys Lipids. 2020 Jun 23;:104936

Authors: Bujan A, Del Valle Alonso S, Chiaramoni NS

Abstract
In the present work, we obtained polymeric diacetylene liposomes that can associate N-Acetyl-L-Cysteine (NAC), a broad spectrum mucolytic. The reason for studying these formulations is that they could be applied in the future as NAC delivery systems, with a possible dose reduction but maintaining its effect. Liposomes used herein are obtained by a photopolymerization reaction, thus gaining stability and rigidity. Lipids belonging to lung surfactant were added in different ratios to the formulations in order to maximize its possible interaction with the lung tissue. Because of lipopolymer stability, the oral or nasal route could be appropriated. This formulation could efficiently transport NAC to exert its mucolytic activity and help in diseases such as cystic fibrosis, which has abnormal mucus production. Also, this type of treatment could be useful in other types of diseases, interacting with the mucus layer and making the lung tissue more permeable to other therapies. Formulations so obtained presented high levels of polymerization. Also, they present small hollow fibers structures with a high number of polymeric units. These types of arrangements could present advantages in the field of drug delivery, giving the possibility of a controlled release. Lipopolymers with lipids from lung surfactant associated with NAC are promising complexes in order to treat not only respiratory illnesses. The stability of the formulation would allow its inoculation through other routes such as the oral one, helping the reposition of NAC as an antioxidant drug. Finally, these formulations are non-toxic and easy to produce.

PMID: 32589880 [PubMed - as supplied by publisher]

The Remaining Barriers to Normalcy in CF: Advances in Assessment of CF Lung Disease.

Pediatr Pulmonol. 2020 Jun 26;:

Authors: Muston HN, Perrem L, Davis MD, Ratjen F, Ren CL

Abstract
Despite early diagnosis of cystic fibrosis (CF) through newborn screening, a substantial proportion of infants and young children with CF still demonstrate physiologic and structural evidence of lung disease progression, such as obstructive airway disease and bronchiectasis. The growing availability of highly effective CF transmembrane conductance regulatory modulator therapy to the vast majority of people with CF has led to the potential to alter the natural history of CF lung disease, but in order to assess the full impact of these therapies on CF lung disease and to help guide treatment, sensitive measures of early and mild disease are needed. Chest imaging using computed tomography or magnetic resonance imaging is one approach, but technologic barriers and/or concern about exposure to ionizing radiation may limit its use. However, advances in physiologic measurement techniques and exhaled breath analysis offer another option for assessment of CF lung disease This article is protected by copyright. All rights reserved.

PMID: 32589821 [PubMed - as supplied by publisher]

Survey of Patients with Cystic Fibrosis and Caregivers Decisions Regarding CFTR Modulators.

Pediatr Pulmonol. 2020 Jun 26;:

Authors: George A, Smith B, Sawicki GS, Goetz DM

Abstract
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators are a novel approach to CF management that has become more readily available chronic CF therapies for certain populations of patients with CF. A cross-sectional survey of adults with CF and caregivers of pediatric patients with CF was done in two CF Centers to better understand the decision-making process including the potential influence of social media, CF care-teams, and family members on their decision whether to begin a CFTR modulator. For the 90 participants, the most common influences in the decision to start modulator therapy were the CF providers/care teams (n=63), parents (n=49) and individuals with CF (n=27). The most impactful influence in the decision-making process were providers/care team (n=47) and parents (n=18). Social media was an influence for only 12 respondents, with an overall positive impact. Information from the CF Foundation was an influence for 12 participants and the main influence for 6 participants. The most common reasons for stopping LUM-IVA were having TEZ-IVA as an option (n=25) and side-effects (n=15). Family and CF clinicians were the two main influences on the decision to initiate modulator therapy. CF clinicians were seen to be the most influential source. Social media had less influence on the decision-making process than expected despite the wide presence of the CF community online. This article is protected by copyright. All rights reserved.

PMID: 32589808 [PubMed - as supplied by publisher]

Periodontal condition and periodontal risk assessment in adult patients with cystic fibrosis.

Ann Agric Environ Med. 2020 Jun 19;27(2):235-239

Authors: Pawlaczyk-Kamieńska T, Borysewicz-Lewicka M, Śniatała R

Abstract
INTRODUCTION: The presence of chronic inflammation in the mouth, such as infectious disease of the periodontal tissues, may be the reservoir of microorganisms that are not usually present, including Pseudomonas aeruginosa.
OBJECTIVE: The purpose of the study was to create a profile of periodontal conditions and periodontal risk assessment in adult patients with cystic fibrosis.
MATERIAL AND METHODS: The study involved 22 patients with cystic fibrosis (CF) aged 29.43 years. The following parameters were included in the clinical study: number and cause of permanent teeth loss (excluding third molars), the presence of plaque (PCR), bleeding on probing (BOP), probing pocket depth (PPD), clinical attachment level (CAL). On the basis of obtained clinical data, the periodontal status and the periodontal risk were determined.
RESULTS: The study showed healthy periodontal tissues in 9 people (41%), gingivitis in 5 (23%), and mild periodontitis in 8 (36.36%). The periodontal risk in the vast majority of patients (90.91%) was at a low level - only 2 people, on average.
CONCLUSIONS: The poor oral hygiene in CF patients indicates the need to develop standards of dental care for this group aimed at education and elimination of risk factors for oral diseases. The obtained results of clinical trials do not rule out the likelihood of auto-infections of the respiratory system originating from periodontal tissues, which, in CF patients, may adversely affect the general state of health and conducted therapy.

PMID: 32588599 [PubMed - in process]

Ion transport mechanisms for smoke inhalation-injured airway epithelial barrier.

Cell Biol Toxicol. 2020 Jun 25;:

Authors: Chang J, Chen Z, Zhao R, Nie HG, Ji HL

Abstract
Smoke inhalation injury is the leading cause of death in firefighters and victims. Inhaled hot air and toxic smoke are the predominant hazards to the respiratory epithelium. We aimed to analyze the effects of thermal stress and smoke aldehyde on the permeability of the airway epithelial barrier. Transepithelial resistance (RTE) and short-circuit current (ISC) of mouse tracheal epithelial monolayers were digitized by an Ussing chamber setup. Zonula occludens-1 tight junctions were visualized under confocal microscopy. A cell viability test and fluorescein isothiocyanate-dextran assay were performed. Thermal stress (40 °C) decreased RTE in a two-phase manner. Meanwhile, thermal stress increased ISC followed by its decline. Na+ depletion, amiloride (an inhibitor for epithelial Na+ channels [ENaCs]), ouabain (a blocker for Na+/K+-ATPase), and CFTRinh-172 (a blocker of cystic fibrosis transmembrane regulator [CFTR]) altered the responses of RTE and ISC to thermal stress. Steady-state 40 °C increased activity of ENaCs, Na+/K+-ATPase, and CFTR. Acrolein, one of the main oxidative unsaturated aldehydes in fire smoke, eliminated RTE and ISC. Na+ depletion, amiloride, ouabain, and CFTRinh-172 suppressed acrolein-sensitive ISC, but showed activating effects on acrolein-sensitive RTE. Thermal stress or acrolein disrupted zonula occludens-1 tight junctions, increased fluorescein isothiocyanate-dextran permeability but did not cause cell death or detachment. The synergistic effects of thermal stress and acrolein exacerbated the damage to monolayers. In conclusion, the paracellular pathway mediated by the tight junctions and the transcellular pathway mediated by active and passive ion transport pathways contribute to impairment of the airway epithelial barrier caused by thermal stress and acrolein. Graphical abstract Thermal stress and acrolein are two essential determinants for smoke inhalation injury, impairing airway epithelial barrier. Transcellular ion transport pathways via the ENaC, CFTR, and Na/K-ATPase are interrupted by both thermal stress and acrolein, one of the most potent smoke toxins. Heat and acrolein damage the integrity of the airway epithelium through suppressing and relocating the tight junctions.

PMID: 32588239 [PubMed - as supplied by publisher]

Recurrent hypertrophic pulmonary osteoarthropathy in an adult with bronchiectasis.

Respirol Case Rep. 2020 Aug;8(6):e00602

Authors: Tekiteki A, Good WR, Diggins B, Anderson G, Wong CA

Abstract
Hypertrophic pulmonary osteoarthropathy (HPOA) is a well-documented complication of pulmonary malignancy and cystic fibrosis (CF). However, HPOA associated with exacerbations of non-CF bronchiectasis has only been reported once previously in an adolescent. We describe a case of an adult patient with bronchiectasis and HPOA, whose joint symptoms flared during pulmonary exacerbations and improved with treatment of each exacerbation.

PMID: 32587699 [PubMed]

Luteolin reduces fluid hypersecretion by inhibiting TMEM16A in interleukin-4 treated Calu-3 airway epithelial cells.

Korean J Physiol Pharmacol. 2020 Jul 01;24(4):329-338

Authors: Kim HJ, Woo J, Nam YR, Seo Y, Namkung W, Nam JH, Kim WK

Abstract
Rhinorrhea in allergic rhinitis (AR) is characterized by the secretion of electrolytes in the nasal discharge. The secretion of Cl- and HCO3- is mainly regulated by cystic fibrosis transmembrane conductance regulator (CFTR) or via the calciumactivated Cl- channel anoctamin-1 (ANO1) in nasal gland serous cells. Interleukin-4 (IL-4), which is crucial in the development of allergic inflammation, increases the expression and activity of ANO1 by stimulating histamine receptors. In this study, we investigated ANO1 as a potential therapeutic target for rhinorrhea in AR using an ANO1 inhibitor derived from a natural herb. Ethanolic extracts (30%) of Spirodela polyrhiza (SPEtOH) and its five major flavonoids constituents were prepared. To elucidate whether the activity of human ANO1 (hANO1) was modulated by SPEtOH and its chemical constituents, a patch clamp experiment was performed in hANO1-HEK293T cells. Luteolin, one of the major chemical constituents in SPEtOH, significantly inhibited hANO1 activity in hANO1-HEK293T cells. Further, SPEtOH and luteolin specifically inhibited the calcium-activated chloride current, but not CFTR current in human airway epithelial Calu-3 cells. Calu-3 cells were cultured to confluency on transwell inserts in the presence of IL-4 to measure the electrolyte transport by Ussing chamber. Luteolin also significantly inhibited the ATP-induced increase in electrolyte transport, which was increased in IL-4 sensitized Calu-3 cells. Our findings indicate that SPEtOH- and luteolin may be suitable candidates for the prevention and treatment of allergic rhinitis. SPEtOH- and luteolin-mediated ANO1 regulation provides a basis for the development of novel approaches for the treatment of allergic rhinitis-induced rhinorrhea.

PMID: 32587127 [PubMed]

Sputum neutrophil elastase in bronchiectasis: a Southern European cohort study.

Eur Respir J. 2020 Jun 25;:

Authors: Gramegna A, Aliberti S, Sibila O, Di Francesco C, Sotgiu G, Perea L, Terranova L, Oriano M, Pilocane T, Saderi L, Chalmers JD, Marchisio P, Blasi F

PMID: 32586875 [PubMed - as supplied by publisher]

Complete Genome Sequence of Pseudomonas aeruginosa Strain AA2 (LMG 27630), an Early Isolate Recovered from the Airway of a German Cystic Fibrosis Patient.

Microbiol Resour Announc. 2020 Jun 25;9(26):

Authors: Sass A, Coenye T

Abstract
Pseudomonas aeruginosa is an opportunistic pathogen that is able to cause various infections, including airway infections in cystic fibrosis patients. Here, we present the complete closed and annotated genome sequence of P. aeruginosa AA2, an isolate obtained early during infection of the respiratory tract of a German cystic fibrosis patient.

PMID: 32586869 [PubMed]

Lumacaftor/ivacaftor improves liver cholesterol metabolism but does not influence hypocholesterolemia in patients with cystic fibrosis.

J Cyst Fibros. 2020 Jun 22;:

Authors: Gelzo M, Iacotucci P, Caputo M, Cernera G, Comegna M, Carnovale V, Corso G, Castaldo G

Abstract
BACKGROUND: Cystic fibrosis (CF) patients have reduced intestinal absorption of sterols and, despite enhanced endogenous synthesis, low plasma cholesterol. Lumacaftor/ivacaftor CFTR protein modulator therapy is used to improve the clinical outcome of CF patients homozygous for F508del mutation (homo-deltaF508). Aim of the study is to evaluate the cholesterol metabolism and hepatobiliary injury/function in adult homo-deltaF508 patients, before and after lumacaftor/ivacaftor treatment. Baseline parameters in homo-deltaF508 patients were compared to those in CF patients compound heterozygous for F508del mutation and another severe mutation (hetero-deltaF508).
METHODS: Cholesterol metabolism was evaluated measuring plasma phytosterols and cholestanol, as intestinal absorption markers, and lathosterol, as liver biosynthesis marker. We quantified serum vitamin E, as nutritional marker. We evaluated liver injury by aspartate aminotransferase (AST) and alanine transaminase (ALT), biliary injury by γ-glutamyltransferase (γGT) and AP, and the liver function by bilirubin and albumin.
RESULTS: Before the treatment, homo-deltaF508 patients (n = 20) had significantly lower cholesterol and vitamin E compared to hetero-deltaF508 (n = 20). Lumacaftor/ivacaftor treatment caused: 1) further reduction of cholesterol; 2) lathosterol reduction, suggesting a normalization of endogenous synthesis; 3) cholestanol and vitamin E increment, indicating an improvement of lipid digestion/absorption. Vitamin E difference (after-before treatment) was positively associated to treatment months. Alkaline phosphatase was also reduced.
CONCLUSIONS: These data suggest an effect of lumacaftor/ivacaftor on cholesterol metabolism and enterohepatic flux in CF patients. However, lumacaftor/ivacaftor does not promote the increase of cholesterol serum concentration that on the contrary declines. Further studies are needed to research the real mechanism causing this reduction.

PMID: 32586737 [PubMed - as supplied by publisher]

Tezacaftor/ivacaftor in people with cystic fibrosis who stopped lumacaftor/ivacaftor due to respiratory adverse events.

J Cyst Fibros. 2020 Jun 22;:

Authors: Schwarz C, Sutharsan S, Epaud R, Klingsberg RC, Fischer R, Rowe SM, Audhya PK, Ahluwalia N, You X, Ferro TJ, Duncan ME, Bruinsma BG

Abstract
BACKGROUND: Increased rates of respiratory adverse events have been observed in people ≥12 years of age with cystic fibrosis homozygous for the Phe508del-CFTR mutation treated with lumacaftor/ivacaftor, particularly in those with percent predicted forced expiratory volume in 1 s (ppFEV1) of <40%. We evaluated the safety, tolerability, and efficacy of tezacaftor/ivacaftor in people with cystic fibrosis homozygous for Phe508del-CFTR who discontinued lumacaftor/ivacaftor due to treatment-related respiratory signs or symptoms.
METHODS: Participants ≥12 years of age with cystic fibrosis homozygous for Phe508del-CFTR with ppFEV1 of ≥25% and ≤90% were randomized 1:1 and treated with tezacaftor/ivacaftor or placebo for 56 days.
RESULTS: Of 97 participants, 94 (96.9%) completed the study. The primary endpoint was incidence of predefined respiratory adverse events of special interest (chest discomfort, dyspnea, respiration abnormal, asthma, bronchial hyperreactivity, bronchospasm, and wheezing): tezacaftor/ivacaftor, 14.0%; placebo, 21.3%. The adverse events were mild or moderate in severity. None were serious or led to treatment interruption or discontinuation. Overall, the discontinuation rate was similar between groups. The mean (SD) ppFEV1 at baseline was 44.6% (16.1%) with tezacaftor/ivacaftor and 48.0% (18.1%) with placebo. The posterior mean difference in absolute change in ppFEV1 from baseline to the average value of days 28 and 56 was 2.7 percentage points with tezacaftor/ivacaftor vs placebo.
CONCLUSIONS: Tezacaftor/ivacaftor was generally safe, well tolerated, and efficacious in people ≥12 years of age with cystic fibrosis homozygous for Phe508del-CFTR with ppFEV1 of ≥25% and ≤90% who previously discontinued lumacaftor/ivacaftor due to treatment-related respiratory signs or symptoms.

PMID: 32586736 [PubMed - as supplied by publisher]

Cardiovascular Risk and Cardiovascular Health Behaviours in the Transition from Childhood to Adulthood.

Can J Cardiol. 2020 Jun 22;:

Authors: Chung RJ, Mackie AS, Baker A, de Ferranti SD

Abstract
The prevention and management of cardiovascular risk factors during the transition from childhood to adulthood is critically important in defining cardiovascular health trajectories. Unfortunately, many young people fall out of clinical care during this important time, leading to worsening cardiovascular risk and missed opportunities to modify future outcomes. The field of healthcare transition has evolved to support young people with complex health needs in developing self-management and self-advocacy skills in order to promote positive health outcomes despite changes in healthcare providers and resources. While transitional care efforts are largely focused on childhood-onset chronic illnesses such as sickle cell disease and cystic fibrosis, young people with cardiovascular risk factors such as hypertension, obesity, and dyslipidemia also stand to benefit from structured supports to ensure continuity in care and positive health behaviors. Upon the backdrop of the broader healthcare transition literature we offer practical insights and suggestions for ensuring young people with cardiovascular risk factors experience uninterrupted high-quality care and support as they enter the adult healthcare system. Starting transition preparation in early adolescence, actively engaging all key stakeholders throughout the process, and remaining mindful of the developmental underpinnings and social context of transition are keys to success.

PMID: 32585325 [PubMed - as supplied by publisher]

Development and Implementation of Clinical Outcome Measures for Automated Collection Within Specialty Pharmacy Practice.

J Manag Care Spec Pharm. 2020 Jul;26(7):901-909

Authors: Patel K, Chim YL, Grant J, Wascher M, Nathanson A, Canfield S

Abstract
BACKGROUND: Johns Hopkins Specialty Pharmacy Services recognized the need to identify and develop standardized collection methods for clinical outcome measures (COMs) to demonstrate program quality and value to third-party payers, manufacturers, and internal stakeholders.
OBJECTIVE: To define specialty COMs and develop a framework for standardized data collection and reporting.
METHODS: COMs for specialty pharmacy disease states (cystic fibrosis; hepatitis C; inflammatory conditions in dermatology, gastroenterology and rheumatology; and multiple sclerosis) were identified through a literature search, collaboration with specialty pharmacists, and committee review. Once identified, these measures were distributed to internal and external stakeholders that included specialty clinic team members, drug manufacturers, and third-party payers for input and validation. A standardized process for discrete documentation and data collection of these measures was implemented using case management software, electronic medical record integration, and informatics support.
RESULTS: 28 COMs were identified. The various data sources used to collect the COMs were incorporated into an automated virtual dashboard to allow for regular review and sharing with clinicians, leadership, and other key stakeholders. The virtual dashboard included COMs with data derived from electronic medical records (n = 9), patient-reported outcomes based on responses to pharmacist-delivered questions (n = 11), and pharmacist assessment of outcomes (n = 8). The completed virtual dashboard was further refined to allow for reporting of both population and patient-level outcome results on a quarterly basis.
CONCLUSIONS: This project describes methods to standardize documentation, data collection, and reporting of clinical outcomes data for multiple specialty conditions in a health system-integrated specialty pharmacy program. Through literature review and stakeholder consultation, a variety of potential COMs were identified for further evaluation of feasibility and value considering documentation and data collection requirements. Incorporation of COMs into a virtual dashboard will help facilitate the evaluation of program effectiveness, quality improvement planning, and sharing with stakeholders. Additional opportunities exist to further standardize COMs across the pharmacy industry to allow for future benchmarking and standardized evaluation of patient care programs.
DISCLOSURES: No funding supported the writing of this article. The authors have no relevant conflicts of interest to disclose. This study was presented as a poster presentation at the APhA Annual Meeting, March 2018, Nashville, TN, and as a platform presentation at the Eastern States Conference, May 2018, Hershey, PA.

PMID: 32584676 [PubMed - as supplied by publisher]

Understanding the interplay between factors that influence bone mineral density in CF.

Pediatr Pulmonol. 2020 Jun 25;:

Authors: Gur M, Bar-Yoseph R, Diab G, Hanna M, Rozen G, Daud F, Keidar Z, Toukan Y, Masarweh K, Nir V, Gut G, Hakim F, Bentur L

Abstract
BACKGROUND AND OBJECTIVES: Multiple factors affect bone mineral density (BMD) in cystic fibrosis (CF). Our aim was to perform comprehensive analyses of parameters potentially contributing to BMD.
METHODS: A prospective single center study assessing BMD, and correlations with multiple parameters including pancreatic status, lung functions, six-minute walk test (6MWT), clinical score (modified Shwachman-Kulczycki (SK) score), vitamin D, nutritional intake, hand-grip strength (HGS), habitual physical activity (smart watches) and QOL (SF-36 questionnaire).
RESULTS: Forty CF patients, mean age 18.3±8.1 years, FEV1 74.7±17.9% predicted. Fifteen (37.5%) and 11 (27.5%) had osteopenia and osteoporosis, respectively. BMD was similar in pancreatic sufficient (PS, n=15) and insufficient (PI, n=25); median hip z-score -1.5 (-2.7-(-0.2) vs. -1.5 (-3.5-0.7), p=0.79; spine -0.8 (-2.2-2) vs. -1.2 (-4.4-1.5), p=0.39 in PS vs. PI, respectively. BMD correlated with HGS (r=0.72, p<0.001 hip; r=0.52, p=0.001 spine) and fat-free mass index (r=0.81, p<0.001 hip; r=0.63, p<0.001 spine). BMD z-score correlated weakly with SK score and moderately with SF-36 general health. Data from smart watches, nutrition questionnaire and 6MWT did not correlate with BMD. In a multivariate model, age and SK score predicted spine z-score BMD.
CONCLUSIONS: A substantial number of CF patients have low BMD. Similar rates in PS and PI suggest that other factors, such as disease severity, may contribute to low BMD. SK and age, which can easily be obtained even with limited resources, were the best predictors of low BMD. Further larger multi-center studies are warranted to evaluate the contribution of multifactorial etiologies to low BMD in CF. This article is protected by copyright. All rights reserved.

PMID: 32584478 [PubMed - as supplied by publisher]

Ivacaftor Reverses Airway Mucus Abnormalities in a Rat Model Harboring a Humanized G551D-CFTR.

Am J Respir Crit Care Med. 2020 Jun 25;:

Authors: Birket SE, Davis JM, Fernandez-Petty CM, Henderson AG, Oden AM, Tang L, Wen H, Hong J, Fu L, Chambers A, Fields A, Zhao G, Tearney GJ, Sorscher EJ, Rowe SM

Abstract
RATIONALE: Animal models have been highly informative for understanding characteristics, onset, and progression of cystic fibrosis (CF) lung disease. In particular, the CFTR-/- rat has revealed insights into the airway mucus defect characteristic of CF, but does not replicate a human-relevant CFTR variant.
OBJECTIVE: We hypothesized that a rat expressing a humanized version of CFTR, harboring the ivacaftor-sensitive variant G551D, could be used to test the impact of CFTR modulators on pathophysiologic development and correction.
METHODS: In this study, we describe a humanized-CFTR rat expressing the G551D variant, obtained by zinc finger nuclease editing of a human cDNA super-exon, spanning exon 2-27, with a 5' insertion site into the rat gene just beyond intron 1. This targeted insertion takes advantage of the endogenous rat promoter, resulting in appropriate expression compared to wild-type.
MEASUREMENTS AND MAIN RESULTS: The bioelectric phenotype of the epithelia recapitulates the expected absence of CFTR activity, which was restored with ivacaftor. Large airway defects, including depleted airway surface liquid and periciliary layers, delayed mucus transport rates, and increased mucus viscosity were normalized following administration of ivacaftor.
CONCLUSIONS: This model is useful to understand mechanisms of disease and the extent of pathology reversal with CFTR modulators.

PMID: 32584141 [PubMed - as supplied by publisher]

Management and outcomes of Burkholderia cepacia complex bacteremia in patients without cystic fibrosis: a retrospective observational study.

Eur J Clin Microbiol Infect Dis. 2020 Jun 25;:

Authors: Lee YM, Park KH, Moon C, Kim DY, Lee MS, Kim T, Choo EJ, Chong YP, Kim SH, Kim YS, Woo JH, Chang MS

Abstract
Burkholderia cepacia complex (BCC) is an emerging pathogen of nosocomial infection in chronic or critically ill patients without cystic fibrosis (CF). The objective was to evaluate the management and outcomes of BCC bacteremia in patients without CF. We conducted a retrospective study of non-CF adult patients with BCC bacteremia between January 1997 and December 2016 at 4 tertiary hospitals in South Korea. A total of 216 non-CF patients with BCC bacteremia were identified. Most cases were hospital-acquired (79.2%), and the most common source was a central venous catheter (CVC) (42.1%). The rates of susceptibility to trimethoprim-sulfamethoxazole and piperacillin-tazobactam of BCC isolates were high as 92.8% and 90.3%, respectively. The rates of susceptibility to ceftazidime, meropenem, and levofloxacin were 75.5%, 72.3%, and 64.1%, respectively. The 14-day, 30-day, and in-hospital mortality rate was 19.4%, 23.1%, and 31.0%, respectively. Female (OR = 3.1; 95% CI, 1.4-6.8), liver cirrhosis (OR = 6.2; 95% CI, 1.6-16.6), septic shock (OR = 11.2; 95% CI, 5.1-24.8), and catheter-related infection (OR = 2.6, 95% CI, 1.2-5.8) were the independent risk factors for 30-day mortality. The outcome did not differ according to type of antibiotics used. Among 91 patients with CVC-related BCC bacteremia, delayed CVC removal (> 3 days) had a higher rate of persistent bacteremia (54.5 vs. 26.1%; P = 0.03) and lower rate of clinical response (49.0 vs. 71.9%; P = 0.04), compared with early CVC removal (within 3 days). BCC bacteremia occurring in non-CF patients was mostly hospital-acquired and CVC-related. Early removal of the catheter is crucial in treatment of CVC-related BCC bacteremia.

PMID: 32583228 [PubMed - as supplied by publisher]

Cystic Fibrosis: Fighting Together Against Coronavirus Infection.

Front Med (Lausanne). 2020;7:307

Authors: Manti S, Parisi GF, Papale M, Mulè E, Aloisio D, Rotolo N, Leonardi S

PMID: 32582746 [PubMed]