Skin wipe test: A simple, inexpensive, and fast approach in the diagnosis of cystic fibrosis.

Pediatr Pulmonol. 2020 Apr 06;:

Authors: Ďurč P, Foret F, Homola L, Malá M, Pokojová E, Vinohradská H, Dastych M, Krausová D, Nagy D, Bede O, Dřevínek P, Skalická V, Kubáň P

Abstract
OBJECTIVE: To assess the performance of a newly developed skin wipe test (SWT) for the diagnosis of cystic fibrosis (CF).
STUDY DESIGN: Spontaneously formed sweat from the forearm was wiped by a cotton swab moistened with 100 µL of deionized (DI) water and extracted into 400 µL of DI water (SWT). The conventional Macroduct sweat test (ST) was performed simultaneously. SWT samples of 114 CF patients, 76 healthy carriers, and 58 controls were analyzed by capillary electrophoresis with contactless conductivity detection and Cl- /K+ and (Cl-  + Na+ )/K+ ion ratios were evaluated. Chloride concentrations from Macroduct ST were analyzed coulometrically.
RESULTS: Analysis of 248 SWT samples and simultaneous Macroduct ST samples showed comparable method performance. Two ion ratios, Cl- /K+ and (Cl-  + Na+ )/K+ , from the SWT samples and Cl- values from the ST samples were evaluated to diagnose CF. Sensitivity of the SWT method using the Cl- /K+ ratio (cutoff value 3.9) was 93.9%, compared to 99.1% when using the (Cl-  + Na+ )/K+ ratio (cutoff value 5.0) and 98.3% in using Macroduct Cl- (cutoff value higher or equal to 60 mmol/L). The methods' specificities were 97.8%, 94.0%, and 100.0%, respectively.
CONCLUSIONS: The developed SWT method with capillary electrophoretic analysis for CF diagnosis performs comparably to the conventional Macroduct ST. The SWT method is simple, fast, inexpensive, and completely noninvasive. Use of an ion ratio in obtained SWT samples is proposed as a new diagnostic parameter that shows significant promise in CF diagnostics.

PMID: 32250037 [PubMed - as supplied by publisher]

Antioxidant Micronutrients and Essential Fatty Acids Supplementation on Cystic Fibrosis Outcomes: A Systematic Review.

J Acad Nutr Diet. 2020 Apr 02;:

Authors: Simon MISDS, Dalle Molle R, Silva FM, Rodrigues TW, Feldmann M, Forte GC, Marostica PJC

Abstract
Antioxidant micronutrients and essential fatty acids supplementation intake appears to have a protective effect in some diseases such as cardiovascular disease, cancer, and asthma. The aim of this study was to perform a systematic review to evaluate the effects of these nutrients on nutritional and clinical outcomes of patients with cystic fibrosis (CF). This is a systematic review of randomized clinical trials (RCTs) in CF. MEDLINE (via PubMed), Embase, and Scopus databases were searched for RCTs published from 1948 through February 2019. Two investigators independently reviewed the titles and abstracts and then extracted the data from the included studies using a standardized predesigned form. Two reviewers independently performed the quality assessment of the RCTs according to the Cochrane risk of bias tools. A total of 4,792 studies were identified, and 23 were eligible (8 antioxidant micronutrient and 15 essential fatty acids). The interventions found were beta-carotene, zinc, magnesium, multivitamin, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), linoleic acid and lipid matrix with choline supplementation. A significant improvement was observed in: (a) pulmonary function with magnesium (n=1) and essential fatty acids (n=2) supplementation; (b) less pulmonary exacerbations with beta-carotene (n=1), zinc (n=1), antioxidant-enriched multivitamin (n=1) and essential fatty acids (n=2) supplementation. One study with antioxidant-enriched multivitamin and four studies with EPA/DHA supplementation reported significant reductions in inflammatory markers. Nutritional status was not modified by antioxidants supplementation in any of the studies, while in five studies there was an improvement with fatty acids supplementation. The risk of bias of the majority of the parallel studies was high. The benefits of antioxidants or DHA/EPA supplementation for CF, although observed in some studies, are not consistent enough to recommend routine use of these supplements. The mechanisms of action of these nutrients, dose levels and timing should be further explored in future studies.

PMID: 32249071 [PubMed - as supplied by publisher]

Association between faecal pH and fat absorption in children with cystic fibrosis on a controlled diet and enzyme supplements dose.

Pediatr Res. 2020 Apr 04;:

Authors: Calvo-Lerma J, Roca M, Boon M, Colombo C, de Koning B, Fornés-Ferrer V, Masip E, Garriga M, Bulfamante A, Asensio-Grau A, Andrés A, de Boeck K, Hulst J, Ribes-Koninckx C

Abstract
BACKGROUND: Despite treatment with pancreatic enzyme replacement therapy (PERT), patients with cystic fibrosis (CF) can still suffer from fat malabsorption. A cause could be low intestinal pH disabling PERT. The aim of this study was to assess the association between faecal pH (as intestinal pH surrogate) and coefficient of fat absorption (CFA). Additionally, faecal free fatty acids (FFAs) were quantified to determine the amount of digested, but unabsorbed fat.
METHODS: In a 24-h pilot study, CF patients followed a standardised diet with fixed PERT doses, corresponding to theoretical optimal doses determined by an in vitro digestion model. Study variables were faecal pH, fat and FFA excretion, CFA and transit time. Linear mixed regression models were applied to explore associations.
RESULTS: In 43 patients, median (1st, 3rd quartile) faecal pH and CFA were 6.1% (5.8, 6.4) and 90% (84, 94), and they were positively associated (p < 0.001). An inverse relationship was found between faecal pH and total fat excretion (p < 0.01), as well as total FFA (p = 0.048). Higher faecal pH was associated with longer intestinal transit time (p = 0.049) and the use of proton pump inhibitors (p = 0.009).
CONCLUSIONS: Although the clinical significance of faecal pH is not fully defined, its usefulness as a surrogate biomarker for intestinal pH should be further explored.
IMPACT: Faecal pH is a physiological parameter that may be related to intestinal pH and may provide important physiopathological information on CF-related pancreatic insufficiency. Faecal pH is correlated with fat absorption, and this may explain why pancreatic enzyme replacement therapy is not effective in all patients with malabsorption related to CF.Use of proton pump inhibitors is associated to higher values of faecal pH. Faecal pH could be used as a surrogate biomarker to routinely monitor the efficacy of pancreatic enzyme replacement therapy in clinical practice.Strategies to increase intestinal pH in children with cystic fibrosis should be targeted.

PMID: 32247283 [PubMed - as supplied by publisher]

Cystic fibrosis in Turkey.

Lancet Respir Med. 2020 Apr;8(4):e17

Authors: Dogru D, Çakır E, Eyüboğlu TŞ, Pekcan S, Özçelik U, board members and the working group of the Cystic Fibrosis Registry of Turkey

PMID: 32246929 [PubMed - as supplied by publisher]

Diagnostic markers of allergic bronchopulmonary aspergillosis in patients with severe asthma.

Mycoses. 2020 Apr 04;:

Authors: Kozlova Y, Frolova E, Uchevatkina A, Filippova L, Aak O, Burygina E, Taraskina A, Vasilyeva N, Klimko N

Abstract
INTRODUCTION: Allergic bronchopulmonary aspergillosis (ABPA) is a lung disease in patients with asthma or cystic fibrosis (CF) caused by chronic allergic inflammation to Aspergillus spp. antigens. The role of different immunological mediators in the formation of chronic allergic inflammation in patients with ABPA is not sufficiently explored.
OBJECTIVES: This study aimed to investigate serum levels of thymic stromal lymphopoietin (TSLP), thymus and activated chemokine (TARC) as well as IL-8 in patients with ABPA, and to evaluate their diagnostic and monitoring value in the disease. Patients/methods Prospective study included 21 patients with ABPA, 25 patients with severe asthma with fungal sensitization (SAFS), 37 patients with severe asthma without fungal sensitization (SAwFS), and 16 healthy people. In patients with ABPA the serum levels of biomarkers were determined at baseline and after 12 weeks of itraconazole therapy. Serum levels of total IgE, Aspergillus-fumigatus specific IgE, TSLP, TARC, IL-8 were analyzed by enzyme-linked immunosorbent assay.
RESULTS: In patients with ABPA we established significantly higher serum levels of TARC, IL-8, total IgE, Aspergillus-fumigatus specific IgE, and peripheral blood eosinophil counts, compared to patients with SAwFS. There were no differences in TSLP levels between the examined groups of patients. Serum TARC levels were positively correlated to serum total IgE levels, A. fumigatus-specific IgE levels and peripheral blood eosinophil counts and also negatively correlated to lung function (FEV1 ). Longitudinally, serum levels TARC, total IgE and peripheral blood eosinophil counts significant decreased after treatment of ABPA.
CONCLUSION: TARC is a useful test in diagnosing and monitoring response to the antifungal treatment of patients with ABPA.

PMID: 32246509 [PubMed - as supplied by publisher]

Leveraging early markers of cystic fibrosis structural lung disease to improve outcomes.

Eur Respir J. 2020 Apr;55(4):

Authors: Flume PA, VanDevanter DR

PMID: 32245773 [PubMed - as supplied by publisher]

Seven P's of publication practices.

J Cyst Fibros. 2020 Feb 21;:

Authors: Bell SC, Flume PA, Castellani C

PMID: 32245683 [PubMed - as supplied by publisher]

Recent Strategic Advances in CFTR Drug Discovery: An Overview.

Int J Mol Sci. 2020 Mar 31;21(7):

Authors: Rusnati M, D'Ursi P, Pedemonte N, Urbinati C, Ford RC, Cichero E, Uggeri M, Orro A, Fossa P

Abstract
Cystic fibrosis transmembrane conductance regulator (CFTR)-rescuing drugs have already transformed cystic fibrosis (CF) from a fatal disease to a treatable chronic condition. However, new-generation drugs able to bind CFTR with higher specificity/affinity and to exert stronger therapeutic benefits and fewer side effects are still awaited. Computational methods and biosensors have become indispensable tools in the process of drug discovery for many important human pathologies. Instead, they have been used only piecemeal in CF so far, calling for their appropriate integration with well-tried CF biochemical and cell-based models to speed up the discovery of new CFTR-rescuing drugs. This review will give an overview of the available structures and computational models of CFTR and of the biosensors, biochemical and cell-based assays already used in CF-oriented studies. It will also give the reader some insights about how to integrate these tools as to improve the efficiency of the drug discovery process targeted to CFTR.

PMID: 32244346 [PubMed - as supplied by publisher]

Treatment of Cystic Fibrosis Patients Homozygous for F508del with Lumacaftor-Ivacaftor (Orkambi®) Restores Defective CFTR Channel Function in Circulating Mononuclear Cells.

Int J Mol Sci. 2020 Mar 31;21(7):

Authors: Favia M, Gallo C, Guerra L, De Venuto D, Diana A, Polizzi AM, Montemurro P, Mariggiò MA, Leonetti G, Manca A, Casavola V, Conese M

Abstract
The treatment of cystic fibrosis (CF) patients homozygous for the F508del mutation with Orkambi®, a combination of a corrector (lumacaftor) and a potentiator (ivacaftor) of the mutated CFTR protein, resulted in some amelioration of the respiratory function. However, a great variability in the clinical response was also observed. The aim of this study was to evaluate the response to Orkambi® in a small cohort of F508del/F508del patients (n = 14) in terms of clinical and laboratory parameters, including ex vivo CFTR activity in mononuclear cells (MNCs), during a 12-month treatment. Patients responded with an increase in percent predicted forced expiratory volume in 1 s (FEV1%) and body mass index (BMI) as well as with a decrease in white blood cell (WBC) total counts and serum C-reactive protein (CRP) levels, although not significantly. Sweat chloride and CFTR-dependent chloride efflux were found to decrease and increase, respectively, as compared with pre-therapy values. CFTR and BMI showed a statistically significant correlation during Orkambi® treatment. Clustering analysis showed that CFTR, BMI, sweat chloride, FEV1%, and WBC were strongly associated. These data support the notion that CFTR-dependent chloride efflux in MNCs should be investigated as a sensitive outcome measure of Orkambi® treatment in CF patients.

PMID: 32244302 [PubMed - as supplied by publisher]

Three-axis accelerometer system for comparison of gait parameters in children with cystic fibrosis and healthy peers.

Gait Posture. 2020 Feb 26;78:60-64

Authors: Ergin E, Savci S, Ozcan Kahraman B, Tanriverdi A, Ozsoy I, Atakul G, Volkan A, Asilsoy S, Uzuner N

Abstract
BACKGROUND: Cystic Fibrosis (CF), affecting functional exercise capacity generally measured by submaximal exercise test such as 6min walk test, is a progressive, autosomal recessive and metabolic disorder. Three-axis accelerometers, which are used during gait, are an easy way to assess gait parameters in patients and healthy individuals. Gait parameters were significantly associated with clinical outcomes of COPD. However, the association between gait parameters and clinical outcomes in children with CF is unclear.
RESEARCH QUESTION: Do clinical outcomes in CF have an important role in determining gait parameters?.
METHODS: Twenty-one CF and 21 healthy subjects participated in this case-control study. Body composition was evaluated using Tanita-BC 418. Respiratory and knee extension muscle strengths were assessed. Functional exercise capacity was evaluated using the 6-min walk test (6MWT). Spatiotemporal gait parameters were evaluated using a validated wireless inertial sensing device (G-Sensor, BTS Bioengineering S.p.A., Italy) during the 6MWT and 7-meter gait test.
RESULTS: MIP, the distance of 6MWT, and stride length were significantly lower in the CF group compare to healthy children (p<0.05). Gait speed and functional exercise capacity, cadence and functional exercise capacity, quadriceps muscle strength, FEV1, fat-free mass were found to be correlated in CF patients (p<0.05).
SIGNIFICANCE: The aerobic capacity and gait parameters were affected in CF patients with mild disease severity in our study. Clinical outcomes were associated with gait parameters in CF patients. This is the first study to use the 3-axis accelerometer to evaluate functional exercise capacity and gait parameters of CF and healthy children. A three-axis accelerometer can be used to assess functional exercise capacity and gait parameters in CF patients at the clinics.

PMID: 32244190 [PubMed - as supplied by publisher]

Peptides as surface coatings of nanoparticles that penetrate human cystic fibrosis sputum and uniformly distribute in vivo following pulmonary delivery.

J Control Release. 2020 Mar 31;:

Authors: Leal J, Peng X, Liu X, Arasappan D, Wylie DC, Schwartz SH, Fullmer JJ, McWilliams BC, Smyth HDC, Ghosh D

Abstract
Therapeutic delivery of drug and gene delivery systems have to traverse multiple biological barriers to achieve efficacy. Mucosal administration, such as pulmonary delivery in cystic fibrosis (CF) disease, remains a significant challenge due to concentrated viscoelastic mucus, which prevents drugs and particles from penetrating the mucus barrier. To address this problem, we used combinatorial peptide-presenting phage libraries and next-generation sequencing (NGS) to identify hydrophilic, net-neutral charged peptide coatings that enable penetration of human CF mucus ex vivo with ~600-fold better penetration than control, improve uptake into lung epithelial cells compared to uncoated or PEGylated-nanoparticles, and exhibit enhanced uniform distribution and retention in the mouse lung airways. These peptide coatings address multiple delivery barriers and effectively serve as excellent alternatives to standard PEG surface chemistries to achieve mucus penetration and address some of the challenges encountered using these chemistries. This biomolecule-based strategy can address multiple delivery barriers and hold promise to advance efficacy of therapeutics for diseases like CF.

PMID: 32243979 [PubMed - as supplied by publisher]

Correcting CFTR: New Gene Editing Strategies for Rescuing CFTR Function Ex Vivo.

Cell Stem Cell. 2020 Apr 02;26(4):476-478

Authors: Ryan AL

Abstract
Gene correction presents one of few options for a cure for all patients with cystic fibrosis. This commentary discusses new applications of CRISPR-based gene editing technology with increased efficiency and specificity to correct the cystic fibrosis transmembrane regulator (CFTR) function in patient-specific primary epithelial cells.

PMID: 32243806 [PubMed - as supplied by publisher]

Regional Structure-function in Cystic Fibrosis Lung Disease Using Hyperpolarized 129Xe and Ultrashort Echo Magnetic Resonance Imaging.

Am J Respir Crit Care Med. 2020 Apr 03;:

Authors: Thomen RP, Walkup LL, Roach DJ, Higano N, Schapiro A, Brody A, Clancy JP, Cleveland ZI, Woods JC

PMID: 32243189 [PubMed - as supplied by publisher]

Bacterial etiology of community-acquired pneumonia in immunocompetent hospitalized patients and appropriateness of empirical treatment recommendations: an international point-prevalence study.

Eur J Clin Microbiol Infect Dis. 2020 Apr 03;:

Authors: Carugati M, Aliberti S, Sotgiu G, Blasi F, Gori A, Menendez R, Encheva M, Gallego M, Leuschner P, Ruiz-Buitrago S, Battaglia S, Fantini R, Pascual-Guardia S, Marin-Corral J, Restrepo MI, GLIMP Collaborators

Abstract
An accurate knowledge of the epidemiology of community-acquired pneumonia (CAP) is key for selecting appropriate antimicrobial treatments. Very few etiological studies assessed the appropriateness of empiric guideline recommendations at a multinational level. This study aims at the following: (i) describing the bacterial etiologic distribution of CAP and (ii) assessing the appropriateness of the empirical treatment recommendations by clinical practice guidelines (CPGs) for CAP in light of the bacterial pathogens diagnosed as causative agents of CAP. Secondary analysis of the GLIMP, a point-prevalence international study which enrolled adults hospitalized with CAP in 2015. The analysis was limited to immunocompetent patients tested for bacterial CAP agents within 24 h of admission. The CAP CPGs evaluated included the following: the 2007 and 2019 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA), the European Respiratory Society (ERS), and selected country-specific CPGs. Among 2564 patients enrolled, 35.3% had an identifiable pathogen. Streptococcus pneumoniae (8.2%) was the most frequently identified pathogen, followed by Pseudomonas aeruginosa (4.1%) and Klebsiella pneumoniae (3.4%). CPGs appropriately recommend covering more than 90% of all the potential pathogens causing CAP, with the exception of patients enrolled from Germany, Pakistan, and Croatia. The 2019 ATS/IDSA CPGs appropriately recommend covering 93.6% of the cases compared with 90.3% of the ERS CPGs (p < 0.01). S. pneumoniae remains the most common pathogen in patients hospitalized with CAP. Multinational CPG recommendations for patients with CAP seem to appropriately cover the most common pathogens and should be strongly encouraged for the management of CAP patients.

PMID: 32242314 [PubMed - as supplied by publisher]

TAS2R38 is a novel modifier gene in patients with cystic fibrosis.

Sci Rep. 2020 Apr 02;10(1):5806

Authors: Castaldo A, Cernera G, Iacotucci P, Cimbalo C, Gelzo M, Comegna M, Di Lullo AM, Tosco A, Carnovale V, Raia V, Amato F

Abstract
The clinical manifestation of cystic fibrosis (CF) is heterogeneous also in patients with the same cystic fibrosis transmembrane regulator (CFTR) genotype and in affected sibling pairs. Other genes, inherited independently of CFTR, may modulate the clinical manifestation and complications of patients with CF, including the severity of chronic sinonasal disease and the occurrence of chronic Pseudomonas aeruginosa colonization. The T2R38 gene encodes a taste receptor and recently its functionality was related to the occurrence of sinonasal diseases and upper respiratory infections. We assessed the T2R38 genotype in 210 patients with CF and in 95 controls, relating the genotype to the severity of sinonasal disease and to the occurrence of P. aeruginosa pulmonary colonization. The frequency of the PAV allele i.e., the allele associated with the high functionality of the T2R38 protein, was significantly lower in i) CF patients with nasal polyposis requiring surgery, especially in patients who developed the complication before 14 years of age; and ii) in CF patients with chronic pulmonary colonization by P. aeruginosa, especially in patients who were colonized before 14 years of age, than in control subjects. These data suggest a role for T2R38 as a novel modifier gene of sinonasal disease severity and of pulmonary P. aeruginosa colonization in patients with CF.

PMID: 32242045 [PubMed - in process]

[Screening audiological control in children of different ages after taking ototoxic medications].

Vestn Otorinolaringol. 2020;85(1):40-44

Authors: Bogomilsky MR, Ishanova YS, Rakhmanova IV, Dyakonova IN, Zonenko OG, Shumilov PV

Abstract
AIM: To compare auditory function during screening of children of different age groups who received ototoxic therapy.
PATIENTS AND METHODS: Auditory function was studied in various categories of children receiving ototoxic drugs. Hearing was assessed by the registration of distortion product otoacoustic emission (DPOAE), short-latency evoked potentials (SLEP), tympanometry. Statistical processing was performed using the C program Statgraphics Centurion XV.
RESULTS: In this study, screening of auditory function in children suffering from cystic fibrosis and receiving ototoxic treatment revealed pathologic conditions of the middle ear according to tympanometry in 15.4% of cases, impaired auditory function in 28.2% of cases according to DPOAE. Early ototoxicosis presented as a decrease in the amplitude of the response at a frequency of 4 kHz, and a change in the structure of the DP-gram in the form of a shift to the low-frequency area. Examination of the auditory function of premature infants receiving potentially ototoxic drugs in the early neonatal period demonstrated that the administration of ototoxic drugs does not affect the maturation of outer hair cells.
CONCLUSION: Audiological control, such as tympanometry and registration of evoked otoacoustic remission should be included in the outpatient observation of children with a history of ototoxic drugs.

PMID: 32241987 [PubMed - in process]

Does disability level impact the relationship of muscle strength to walking performance in people with multiple sclerosis? a cross-sectional analysis.

Mult Scler Relat Disord. 2020 Mar 13;42:102052

Authors: Mañago MM, Callesen J, Dalgas U, Kittelson J, Schenkman M

Abstract
BACKGROUND AND PURPOSE: Strength training can improve muscle weakness in people with multiple sclerosis (MS), but does not consistently improve walking. Disability level may impact the relationship of muscle weakness and walking performance in people with MS, but few studies have investigated the impact of disability on the relationship of strength and walking. The purpose of this study was to compare the relationships of strength in lower body and trunk muscles to walking performance between mild and moderate disability groups in people with MS.
METHODS: Data from 36 participants with MS who had mild disability (Expanded Disability Status Scale - EDSS 0 to 3.5) and 36 participants who had moderate disability (EDSS 4.0 to 5.5) were analyzed. Hand-held dynamometry measured strength in eight muscle groups from the ankle, knee, hip, and trunk. Timed 25-Foot Walk (T25FW) and 6-Minute Walk Test (6MWT) measured walking speed and endurance, respectively. Pearson correlations and beta coefficients (ß) were reported for each bivariate relationship of muscle strength to T25FW and 6MWT from both mild and moderate disability groups. Linear regression was then used to compare differences in beta coefficients (Δß) between disability groups for the relationship of each muscle variable to T25FW and 6MWT. A positive Δß indicated a stronger relationship of strength to walking performance in the mild disability group, while a negative Δß favored the moderate disability group.
RESULTS: Overall, there were stronger Pearson correlations between muscle strength variables to T25FW and 6MWT in the mild (r = 0.57 to 0.77) compared to moderate disability group (r = 0.10 to 0.54). The mild disability group had significantly greater beta coefficients for T25FW with ankle dorsiflexion (Δß = 0.67, 95%CI: 0.27-1.07), knee extension (Δß = 0.68, 95%CI: 0.28-1.08), and hip abduction (Δß = 0.77, 95%CI: 0.01-1.52); and for 6MWT with knee extension (Δß = 0.47, 95%CI: 0.06 to 0.88).
DISCUSSION AND CONCLUSION: For people with MS, muscle strength in the lower extremity and trunk may be a more important contributor to T25FW in mild versus moderate disability, but not for 6MWT. While more studies are needed, these results may help to inform rehabilitation intervention when prioritizing strength training to improve walking.

PMID: 32240963 [PubMed - as supplied by publisher]

Pulmonary Aspergillosis: What the Generalist Needs to Know.

Am J Med. 2020 Mar 30;:

Authors: El-Baba F, Gao Y, Soubani AO

Abstract
Aspergillus spp. is a ubiquitous mold found commonly in our environment that can cause a spectrum of pulmonary disorders ranging from a hypersensitivity reaction to an acutely invasive disease with significant mortality. Allergic bronchopulmonary aspergillosis results from airway hypersensitivity from aspergillus colonization almost exclusively in patients with asthma and cystic fibrosis. Chronic pulmonary aspergillosis typically present in immunocompetent patients with underlying lung pathology. Treatment is primarily with antifungal agents; however other measures such as surgical resection may be necessary. Invasive pulmonary aspergillosis is a severe infection in immunocompromised patients and is characterized by invasion of pulmonary vasculature by the aspergillus hyphae. Recent advances in the diagnosis and management of invasive pulmonary aspergillosis include emerging risk factors such as critically ill patients, and those with chronic obstructive pulmonary disease and liver disease. In addition, noninvasive biomarkers have made it more easy to suspect and diagnose invasive pulmonary aspergillosis. There are more effective and better tolerated antifungal agents that have improved patients outcomes. This review introduces the spectrum of pulmonary aspergillosis geared towards generalists, including disease manifestations, most recent diagnostic criteria and first line treatment options. Involving a multidisciplinary team is vital to the early diagnosis and management of these diseases.

PMID: 32240631 [PubMed - as supplied by publisher]

Newborn screening timeliness quality improvement initiative: Impact of national recommendations and data repository.

PLoS One. 2020;15(4):e0231050

Authors: Sontag MK, Miller JI, McKasson S, Sheller R, Edelman S, Yusuf C, Singh S, Sarkar D, Bocchini J, Scott J, Ojodu J, Kellar-Guenther Y

Abstract
BACKGROUND: Newborn screening (NBS) aims to achieve early identification and treatment of affected infants prior to onset of symptoms. The timely completion of each step (i.e., specimen collection, transport, testing, result reporting), is critical for early diagnosis. Goals developed by the Secretary of Health and Human Services' Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) for NBS timeliness were adopted (time-critical results reported by five days of life, and non-time-critical results reported by day seven), and implemented into a multi-year quality improvement initiative (NewSTEPS 360) aimed to decrease the time to result reporting and intervention.
METHODS: The NBS system from specimen collection through reporting of results was assessed (bloodspot specimen collection, specimen shipping, sample testing, and result reporting). Annual data from 25 participating NBS programs were analyzed; the medians (and interquartile range, IQR) of state-specific percent of specimens that met the goal are presented.
RESULTS: The percent of specimens collected before 48 hours of life increased from 95% (88-97%) in 2016 to 97% (IQR 92-98%) in 2018 for the 25 states, with 20 (80%) of programs collecting more than 90% of the specimens within 48 hours of birth. Approximately 41% (IQR 29-57%) of specimens were transported within one day of collection. Time-critical result reporting in the first five days of life improved from 49% (IQR 26-74%) in 2016 to 64% (42%-71%) in 2018, and for non-time critical results from 64% (IQR 58%-78%) in 2016 to 81% (IQR 68-91%) in 2018. Laboratories open seven days a week in 2018 reported 95% of time-critical results within five days, compared to those open six days (62%), and five days (45%).
CONCLUSION: NBS programs that participated in NewSTEPs 360 made great strides in improving timeliness; however, ongoing quality improvement efforts are needed in order to ensure all infants receive a timely diagnosis.

PMID: 32240266 [PubMed - as supplied by publisher]

β2 adrenoceptor signaling regulates ion transport in 16HBE14o- human airway epithelial cells.

J Cell Physiol. 2020 Apr 02;:

Authors: Zhang RG, Yip CY, Pan KW, Cai MY, Ko WH

Abstract
We investigated the regulation of Cl- secretion by adrenoceptors in polarized 16HBE14o- human bronchial epithelial cells. Treatment with the nonselective β adrenoceptor agonist isoprenaline stimulated an increase in short-circuit current (ISC ), which was inhibited by the β adrenoceptor blocker propranolol. Treatment with procaterol, an agonist specific for the β2 adrenoceptor subtype, stimulated a similar increase in ISC , which was inhibited by the β2 adrenoceptor antagonist ICI 118551. Inhibitors of cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated Cl- channel (CaCC), but not K+ channel blockers, were able to inhibit the increase in ISC . "Trimultaneous" recording of ISC and intracellular cyclic adenosine monophosphate (cAMP) and Ca2+ levels in 16HBE14o- epithelia confirmed that the ISC induced by isoprenaline or procaterol involved both cAMP and Ca2+ signaling. Our results demonstrate that β2 adrenoceptors regulate Cl- secretion in the human airway epithelium by activating apical CFTRs and CaCCs via cAMP-dependent and intracellular Ca2+ -dependent mechanisms, respectively.

PMID: 32239700 [PubMed - as supplied by publisher]