Curr Opin Pediatr. 2021 Jun 1;33(3):294-301. doi: 10.1097/MOP.0000000000001017.

ABSTRACT

PURPOSE OF REVIEW: The purpose of this review is to discuss the most recent data describing the impact of coronavirus disease 2019 (COVID-19) on the pediatric population with chronic pulmonary disease. We specifically focus on children with asthma, cystic fibrosis (CF), and lung transplant recipients.

RECENT FINDINGS: Children with asthma, CF, and lung transplant recipients do not appear to have an increased risk of morbidity or mortality with COVID-19 infection compared to the general pediatric population. Data does not support the change or withdrawal of any asthma or CF maintenance medications; however, does advocate for the cessation of aerosolized medications whenever possible to minimize transmission risk. It may not be necessary to adjust immunosuppressive therapy when managing COVID-19 in pediatric lung transplant patients. Mechanisms of infection in airway epithelial cells in children may differ from adults, resulting in a milder phenotype.

SUMMARY: Current data about pediatric patients with chronic lung disease infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is promising but remains scarce. Additional study is needed to definitively understand the complex interplay of the SARS-CoV-2 virus in the airway of children with chronic lung disease, how it differs from adults, and how best to manage the symptoms of acute infection.

PMID:33938475 | DOI:10.1097/MOP.0000000000001017

Eur J Clin Microbiol Infect Dis. 2021 May 3. doi: 10.1007/s10096-021-04263-w. Online ahead of print.

ABSTRACT

We conducted a prospective, observational study at the Adult CF Center, Ospedale Policlinico, Milano, Italy, from March 2017 to September 2019 to assess the prevalence and serotypes of Streptococcus pneumoniae (SP) in adults with CF naive to pneumococcal vaccination. Spontaneous sputum samples from 129 patients were analyzed for SP DNA and serotyped. SP was found in 24 subjects (19%) and the most common serotypes were 19F (16%), 4 (6%), and 9VA (3%). Higher FEV1 and non-pseudomonas infection significantly associate with SP on sputum. These results define a subgroup of patients that might deserve implementation of microbiological techniques directed to pneumococcal detection.

PMID:33937933 | DOI:10.1007/s10096-021-04263-w

Appl Microbiol Biotechnol. 2021 May 3. doi: 10.1007/s00253-021-11274-2. Online ahead of print.

ABSTRACT

Nitric oxide (NO), the highly reactive radical gas, provides an attractive strategy in the control of microbial infections. NO not only exhibits bactericidal effect at high concentrations but also prevents bacterial attachment and disperses biofilms at low, nontoxic concentrations, rendering bacteria less tolerant to antibiotic treatment. The endogenously generated NO by airway epithelium in healthy populations significantly contributes to the eradication of invading pathogens. However, this pathway is often compromised in patients suffering from chronic lung infections where biofilms dominate. Thus, exogenous supplementation of NO is suggested to improve the therapeutic outcomes of these infectious diseases. Compared to previous reviews focusing on the mechanism of NO-mediated biofilm inhibition, this review explores the applications of NO for inhibiting biofilms in chronic lung infections. It discusses how abnormal levels of NO in the airways contribute to chronic infections in cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and primary ciliary dyskinesia (PCD) patients and why exogenous NO can be a promising antibiofilm strategy in clinical settings, as well as current and potential in vivo NO delivery methods. KEY POINTS : • The relationship between abnormal NO levels and biofilm development in lungs • The antibiofilm property of NO and current applications in lungs • Potential NO delivery methods and research directions in the future.

PMID:33937932 | DOI:10.1007/s00253-021-11274-2

Radiol Artif Intell. 2020 Sep 30;2(5):e190226. doi: 10.1148/ryai.2020190226. eCollection 2020 Sep.

ABSTRACT

PURPOSE: To develop and validate a deep learning (DL) algorithm to identify poor-quality lateral airway radiographs.

MATERIALS AND METHODS: A total of 1200 lateral airway radiographs obtained in emergency department patients between January 1, 2000, and July 1, 2019, were retrospectively queried from the picture archiving and communication system. Two radiologists classified each radiograph as adequate or inadequate. Disagreements were adjudicated by a third radiologist. The radiographs were used to train and test the DL classifiers. Three technologists and three different radiologists classified the images in the test dataset, and their performance was compared with that of the DL classifiers.

RESULTS: The training set had 961 radiographs and the test set had 239. The best DL classifier (ResNet-50) achieved sensitivity, specificity, and area under the receiver operating characteristic curve of 0.90 (95% confidence interval [CI]: 0.86, 0.94), 0.82 (95% CI: 0.76, 0.90), and 0.86 (95% CI: 0.81, 0.91), respectively. Interrater agreement for technologists was fair (Fleiss κ, 0.36 [95% CI: 0.29, 0.43]), while that for radiologists was moderate (Fleiss κ, 0.59 [95% CI: 0.52, 0.66]). Cohen κ value comparing the consensus rating of ResNet-50 iterations from fivefold cross-validation, consensus technologists' rating, and consensus radiologists' rating to the ground truth were 0.76 (95% CI: 0.63, 0.89), 0.49 (95% CI: 0.37, 0.61), and 0.66 (95% CI: 0.54, 0.78), respectively.

CONCLUSION: The development and validation of DL classifiers to distinguish between adequate and inadequate lateral airway radiographs is reported. The classifiers performed significantly better than a group of technologists and as well as the radiologists.© RSNA, 2020.

PMID:33937841 | PMC:PMC8082369 | DOI:10.1148/ryai.2020190226

Front Pediatr. 2021 Apr 14;9:656584. doi: 10.3389/fped.2021.656584. eCollection 2021.

ABSTRACT

A 2-month-old male infant presented with white colored stools 1 month after birth. There was no jaundice of the skin, mucous membrane, or sclera; his liver was enlarged (4 cm below the ribs), and his liver function tests showed slightly elevated total bilirubin (TB), direct bilirubin (DB), and total bile acid (TBA). An abdominal doppler ultrasound showed no signs of biliary atresia. Genetic testing revealed a CFTR hemizygous mutation site (c.223C>T) in exon 3 and exon 2-3 heterozygous deletion mutation. The infant's stool turned yellow after oral administration of pancreatic tablets. Finally, the infant was diagnosed with cystic fibrosis (CF). Review of literature revealed five children (including the infant in this case study) with CF who presented with white stool. All five children had anemia, four had edema and hypoproteinemia, five had changes in stool color (it was pistachio-green color in two patients, pale colored in one, acholic stool in one, and white stool in one), two had cholestasis, one infant had delayed meconium discharge, and three children had delayed growth and hepatomegaly. Two children had an abnormal sweat test, one had a F508del compound heterozygous mutation, and one had three mutation sites (C.214G>G/A, P.A72T; C.650A>A/G, P.E217G, and C.3406G>G/A, P. A1136T), which was a compound heterozygous mutation. So, CF could be included in the differential diagnosis of infants with white stool. Genetic testing could confirm an early diagnosis of CF. Pancreatic replacement therapy has been shown to be beneficial for improving the digestive function.

PMID:33937153 | PMC:PMC8081048 | DOI:10.3389/fped.2021.656584

Front Cell Infect Microbiol. 2021 Apr 16;11:665759. doi: 10.3389/fcimb.2021.665759. eCollection 2021.

ABSTRACT

P. aeruginosa is classified as a priority one pathogen by the World Health Organisation, and new drugs are urgently needed, due to the emergence of multidrug-resistant (MDR) strains. Antimicrobial-resistant nosocomial pathogens such as P. aeruginosa pose unwavering and increasing threats. Antimicrobial stewardship has been a challenge during the COVID-19 pandemic, with a majority of those hospitalized with SARS-CoV2 infection given antibiotics as a safeguard against secondary bacterial infection. This increased usage, along with increased handling of sanitizers and disinfectants globally, may further accelerate the development and spread of cross-resistance to antibiotics. In addition, P. aeruginosa is the primary causative agent of morbidity and mortality in people with the life-shortening genetic disease cystic fibrosis (CF). Prolonged periods of selective pressure, associated with extended antibiotic treatment and the actions of host immune effectors, results in widespread adaptive and acquired resistance in P. aeruginosa found colonizing the lungs of people with CF. This review discusses the arsenal of resistance mechanisms utilized by P. aeruginosa, how these operate under high-stress environments such as the CF lung and how their interconnectedness can result in resistance to multiple antibiotic classes. Intrinsic, adaptive and acquired resistance mechanisms will be described, with a focus on how each layer of resistance can serve as a building block, contributing to multi-tiered resistance to antimicrobial activity. Recent progress in the development of anti-resistance adjuvant therapies, targeting one or more of these building blocks, should lead to novel strategies for combatting multidrug resistant P. aeruginosa. Anti-resistance adjuvant therapy holds great promise, not least because resistance against such therapeutics is predicted to be rare. The non-bactericidal nature of anti-resistance adjuvants reduce the selective pressures that drive resistance. Anti-resistance adjuvant therapy may also be advantageous in facilitating efficacious use of traditional antimicrobials, through enhanced penetration of the antibiotic into the bacterial cell. Promising anti-resistance adjuvant therapeutics and targets will be described, and key remaining challenges highlighted. As antimicrobial stewardship becomes more challenging in an era of emerging and re-emerging infectious diseases and global conflict, innovation in antibiotic adjuvant therapy can play an important role in extending the shelf-life of our existing antimicrobial therapeutic agents.

PMID:33937104 | PMC:PMC8085337 | DOI:10.3389/fcimb.2021.665759

Front Pharmacol. 2021 Apr 15;12:601438. doi: 10.3389/fphar.2021.601438. eCollection 2021.

ABSTRACT

The demographics of the population with cystic fibrosis (CF) is continuously changing, with nowadays adults outnumbering children and a median predicted survival of over 40 years. This leads to the challenge of treating an aging CF population, while previous research has largely focused on pediatric and adolescent patients. Chronic inflammation is not only a hallmark of CF lung disease, but also of the aging process. However, very little is known about the effects of an accelerated aging pathology in CF lungs. Several chronic lung disease pathologies show signs of chronic inflammation with accelerated aging, also termed "inflammaging"; the most notable being chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). In these disease entities, accelerated aging has been implicated in the pathogenesis via interference with tissue repair mechanisms, alterations of the immune system leading to impaired defense against pulmonary infections and induction of a chronic pro-inflammatory state. In addition, CF lungs have been shown to exhibit increased expression of senescence markers. Sustained airway inflammation also leads to the degradation and increased turnover of cystic fibrosis transmembrane regulator (CFTR). This further reduces CFTR function and may prevent the novel CFTR modulator therapies from developing their full efficacy. Therefore, novel therapies targeting aging processes in CF lungs could be promising. This review summarizes the current research on CF in an aging population focusing on accelerated aging in the context of chronic airway inflammation and therapy implications.

PMID:33935699 | PMC:PMC8082404 | DOI:10.3389/fphar.2021.601438

CPT Pharmacometrics Syst Pharmacol. 2021 May 2. doi: 10.1002/psp4.12626. Online ahead of print.

ABSTRACT

Rare diseases affect 10% of the first-world population, yet over 95% lack even a single pharmaceutical treatment. In the present age of information, we need ways to leverage our vast data and knowledge to streamline therapeutic development and lessen this gap. Here, we develop and implement an innovative informatic approach to identify therapeutic molecules, using the Connectivity Map and LINCS L1000 databases and disease-associated transcriptional signatures and pathways. We apply this to cystic fibrosis (CF), the most common genetic disease in people of northern European ancestry leading to chronic lung disease and reduced lifespan. We selected and tested 120 small molecules in a CF cell line, finding 8 with activity, and confirmed 3 in primary CF airway epithelia. Although chemically diverse, the transcriptional profiles of the hits suggest a common mechanism associated with the unfolded protein response and/or TNFα signaling. This study highlights the power of informatics to help identify new therapies and reveal mechanistic insights while moving beyond target-centric drug discovery.

PMID:33934548 | DOI:10.1002/psp4.12626

Swiss Med Wkly. 2021 Apr 13;151:w20496. doi: 10.4414/smw.2021.20496. eCollection 2021 Apr 12.

ABSTRACT

Cystic fibrosis (CF) is a genetic disease caused by a bi-allelic mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. When the diagnosis cannot be confirmed by a positive sweat test or/and the identification of two CF-causing variants, international guidelines recommend the use of CFTR functional assays. These tests assess whether CFTR activity is normal or diminished/absent through measurement of CFTR-mediated chloride secretion/absorption. CFTR functional assays are not only useful for diagnostic purposes but can also serve as a surrogate outcome for clinical trials of CFTR modulators, which are emerging therapeutic agents designed to correct the malfunctioning protein. In the near future they could also be used as precision-medicine techniques, to help guidance and optimisation of treatment. Until now, sweat testing has been the only CFTR functional assay available in Switzerland. Since 2020, the Centre Hospitalier Universitaire Vaudois (CHUV) at Lausanne and the Lucerne Children’s Hospital perform nasal potential difference measurement. Moreover, The Ecole Polytechnique Fédérale de Lausanne (EPFL) established a reliable procedure to generate adult intestinal organoids, i.e., stem cell-derived in-vitro grown mini tissues, extracted from rectal biopsies, which can be used to assess CFTR function in vitro. This narrative review describes the most popular CFTR functional assays, as well as their indications, limitations and availability in Switzerland.

PMID:33934316 | DOI:10.4414/smw.2021.20496

Asian J Surg. 2021 Apr 28:S1015-9584(21)00237-2. doi: 10.1016/j.asjsur.2021.04.020. Online ahead of print.

ABSTRACT

BACKGROUND/OBJECTIVE: Lung transplantation is a well-established treatment in patients who have bronchiectasis with diffuse involvement, and with a progressive decline in respiratory function despite maximal medical therapy. We have aimed to present pre-transplantation factors and our results of lung transplantation for non-cystic fibrosis bronchiectasis.

METHODS: Patients who underwent lung transplantation for non-cystic fibrosis bronchiectasis between the dates of December 2016 and July 2019 were included. The patients' clinical parameters, pulmonary function tests, microbiological results, cardiac parameters, intraoperative data, and lung transplant outcomes were assessed retrospectively.

RESULTS: Bilateral lung transplantation for bronchiectasis were performed in eleven patients. The mean age was 36.5 years (range 22-57 years). There were 4 (36.4%) female patients and 7 (63.6%) male patients. All patients had a high score as per the bronchiectasis severity index (BSI). The FACED score was moderate in six patients and severe in five patients. Preoperative colonization with Pseudomonas aeruginosa was observed in five patients. Hospital mortality was 18.2% (2/11). The 1-year mortality was 27.2% (3/11). Eight patients were alive. The mean follow-up period of patients with survival was 28.2 months (range 13-42 months). One patient was diagnosed with chronic lung allograft dysfunction (CLAD). The 3-year survival rates were 73%.

CONCLUSION: Lung transplantation for bronchiectasis with end-stage lung disease can improve the quality of life and increase survival in selected patients. Further studies are needed to identify the optimal time for lung transplantation referral due to the availability of limited data.

PMID:33933356 | DOI:10.1016/j.asjsur.2021.04.020

J Cyst Fibros. 2021 Apr 28:S1569-1993(21)00114-4. doi: 10.1016/j.jcf.2021.04.004. Online ahead of print.

ABSTRACT

BACKGROUND: Body mass index (BMI) correlates with clinical outcomes in cystic fibrosis but has limitations. Body composition aberrations in CF are multifactorial. We sought to evaluate body composition and relationships with pulmonary function, bone health, and hospital admissions. Other aims included defining body composition indices in a cohort of children with CF.

METHODS: We conducted a retrospective review of patients with CF, age 8-18 years, seen at Nationwide Children's Hospital (2015-2020). Indices of body composition measured by dual-energy x-ray absorptiometry(DXA) scans. Data included fat mass, fat-free mass (FFM), forced expiratory volume in one second (FEV1%), bone mineral density (BMD), and hospital admissions. NWA was defined as BMI 5th-85th percentile, body fat percentage >85th percentile. FFMD defined as FFMI <10th percentile.

STATISTICS: T-tests compared NWA, FFMD and clinical measurements. Pearson correlations analyzed fat-free mass index (FFMI), fat mass index (FMI), BMI and clinical measurements.

RESULTS: This study included 114 patients. Mean age 12 years, 72 female. A high prevalence of FFMD existed (n=66, 38.6%). FMI and FFMI correlated with FEV1% (r: 0.23, p:0.01, r: 0.36, p<0.001, respectively) and BMD (r: 0.29, p:0.002). FMI and hospital admissions were related (r:-0.23,p:0.01). FFMD was associated with 9.5% lower FEV1% (p=0.001) and lower BMD Z-score by 1.1 (p<0.001) when compared to no FFMD.

CONCLUSION: This cohort of children with CF had a high prevalence of FFMD and low prevalence of NWA. FFMD was associated with worsened clinical measurements. Patients with FFMD need additional exercise or nutritional intervention. Heterogeneity of body composition definitions creates need for more research.

PMID:33933345 | DOI:10.1016/j.jcf.2021.04.004

Value Health. 2021 May;24(5):744-752. doi: 10.1016/j.jval.2020.11.016. Epub 2021 Feb 18.

ABSTRACT

OBJECTIVES: Health technology assessments (HTA) rely on head-to-head comparisons. We searched for intraindividual comparisons (IIC) qualifying as head-to-head design to develop comparative evidence.

METHODS: Gemeinsamer Bundesausschuss (G-BA) appraisals between January 2011 and April 2020 were reviewed for inclusion of IIC. Identified IIC were grouped according to disease characteristics into nonprogressive, progressive, irregular, or symmetrical conditions. Evaluation of IIC by Institut für Qualität und Wirschaftlichkeit im Gesundheitswesen (IQWIG) and acceptance of IIC by G-BA were determined, and criteria for the usage and quality of IIC were developed.

RESULTS: A total of 483 appraisals finalized between January 2011 and April 2020 were reviewed. Eleven appraisals included IIC: nonacog beta (hemophilia B), turoctocog alpha (hemophilia A), emicizumab (2 appraisals: hemophilia A), pasireotide (unresectable pituitary tumor), lomitapid (homozygous familial hypercholesterolemia), glycerol phenylbutyrate (2 appraisals: urea cycle disorders), asfotase alfa (hypophosphatasia), lumacaftor (cystic fibrosis), and larotrectinib (NTRK+ solid tumors). All those appraisals related to rare genetic conditions with hemophilia and its bleeding rate are considered mainly a nonprogressive condition. All the other diseases show progressive disease characteristics. None of the identified IIC has been accepted by G-BA. Inconsistencies of before/after study design, lack of clarity on treatments prior to the switch, and different time intervals were among the most commonly cited methodological concerns.

CONCLUSIONS: IICs provide a rare opportunity to determine comparative effectiveness in distinct clinical settings that are not suitable or difficult to randomize into parallel groups. While manufacturers and researchers should aim for highest methodological standards when running an IIC, HTA bodies should accept IIC in distinct settings when determining relative effectiveness.

PMID:33933244 | DOI:10.1016/j.jval.2020.11.016

Stem Cells. 2021 May 1. doi: 10.1002/stem.3386. Online ahead of print.

ABSTRACT

The mammalian airways are lined by a continuous epithelial layer that is maintained by diverse populations of resident multipotent stem cells. These stem cells are responsible for replenishing the epithelium both at homeostasis and following injury, making them promising targets for stem cell and genetic-based therapies for a variety of respiratory diseases. However, the mechanisms that regulate when and how these stem cells proliferate, migrate, and differentiate remains incompletely understood. Here, we find that the high mobility group (HMG) domain transcription factor Lef-1 regulates proliferation and differentiation of mouse tracheal basal cells. We demonstrate that conditional deletion of Lef-1 stalls basal cell proliferation at the G1/S transition of the cell cycle, and that Lef-1 knockout cells are unable to maintain luminal tracheal cell types in long-term air-liquid interface culture. RNA sequencing analysis revealed that Lef-1 knockout (Lef-1KO) results in downregulation of key DNA damage response and cell cycle progression genes, including the kinase Chek1. Furthermore, chemical inhibition of Chek1 is sufficient to stall basal cell self-renewal in a similar fashion as Lef-1 deletion. Notably, the cell cycle block imposed by Lef-1KO in vitro is transient and basal cells eventually compensate to proliferate normally in a Chek1-independent manner. Finally, Lef-1KO cells were unable to fully regenerate tracheal epithelium following injury in vivo. These findings reveal that Lef-1 is essential for proper basal cell function. Thus, modulating Lef-1 function in airway basal cells may have applications in regenerative medicine. © AlphaMed Press 2021 SIGNIFICANCE STATEMENT: Airway basal cells (BCs) are the primary progenitor cells of the conducting airway epithelium and thus are promising targets for durable genetic- and cell-based therapies of lung diseases such as cystic fibrosis. However, the mechanisms that govern their regenerative abilities are not fully understood. The authors' show that Lef-1, an effector of Wnt signaling, is critical for BC cell cycle progression through G1/S and influences BC differentiation in vitro. Loss of Lef-1 significantly reduces the capacity of BC to regenerate the tracheal epithelium in vivo following injury. Manipulating Lef-1 expression in BCs may provide opportunities to modulate the regenerative capacity of BCs and their progeny.

PMID:33932322 | DOI:10.1002/stem.3386

Appl Environ Microbiol. 2021 Apr 30:AEM.00369-21. doi: 10.1128/AEM.00369-21. Online ahead of print.

ABSTRACT

Burkholderia cepacia complex bacteria comprises opportunistic pathogens causing chronic respiratory infections in cystic fibrosis (CF) patients. These microorganisms produce an exopolysaccharide named cepacian, which is considered a virulence determinant. To find genes implicated in the regulation of cepacian biosynthesis, we characterized an evolved nonmucoid variant (17616nmv) derived from the ancestor, Burkholderia multivorans ATCC 17616, after prolonged stationary phase. Lack of cepacian biosynthesis was correlated with downregulation of the expression of bce genes implicated in its biosynthesis. Furthermore, genome sequencing of the variant identified the transposition of the mobile element IS406 upstream the coding sequence of an hns-like gene (Bmul_0158) encoding a histone-like nucleoid structuring protein, a known global transcriptional repressor. This IS element upregulated the expression of Bmul_0158 by 4-fold. Transcriptome analysis identified the global effects of this mutation on gene expression, with major changes in genes implicated in motility, pili synthesis, type VI secretion, and chromosome associated functions. Concomitant with these differences, the nonmucoid variant displays reduced adherence to a CF lung bronchial cell line, reduced surface hydrophobicity, forms smaller cellular aggregates, but has an increase in swimming and swarming motilities. Finally, analysis of the GC content of the upstream region of differentially expressed genes led to the identification of various genomic regions, possibly acquired by horizontal gene transfer, which were transcriptionally repressed by the increased expression of Bmul_0158 gene in the 17616nmv strain. Taken together, the results revealed a significant role for this H-NS protein in the regulation of B. multivorans persistence- and virulence-associated genes.IMPORTANCEMembers of the histone-like nucleoid-structuring (H-NS) family of proteins, present in many bacteria, are important global regulators of gene expression. Many of the regulated genes were acquired horizontally and include pathogenicity islands and prophages, among others. Additionally, H-NS can play a structural role by bridging and compacting DNA, presenting a crucial role in cell physiology. Several virulence phenotypes have been frequently identified in several bacteria as dependent on H-NS activity. Here, we describe an H-NS-like protein of the opportunistic pathogen Burkholderia multivorans, a species commonly infecting the respiratory tract of cystic fibrosis patients. Our results indicate that this protein is involved in regulating virulence traits such as exopolysaccharide biosynthesis, adhesion to biotic surfaces, cellular aggregation, and motility. Furthermore, this H-NS-like protein, is one out of eight orthologs present in B. multivorans ATCC 17616 genome, posing relevant questions to be investigated on how these proteins coordinate the expression of virulence traits.

PMID:33931418 | DOI:10.1128/AEM.00369-21

J Cyst Fibros. 2021 Apr 27:S1569-1993(21)00104-1. doi: 10.1016/j.jcf.2021.03.022. Online ahead of print.

ABSTRACT

Chronic rhinosinusitis (CRS) affects nearly all individuals with cystic fibrosis (CF) and is thought to serve as a reservoir for microbiota that subsequently colonize the lung. To better understand the microbial ecology of CRS, we generated a 16S rRNA gene sequencing profile of sinus mucus from CF-CRS patients. We show that CF-CRS sinuses harbor bacterial diversity not entirely captured by clinical culture. Culture data consistently identified the dominant organism in most patients, though lower abundance bacteria were not always identified. We also demonstrate that bacterial communities dominated by Staphylococcus spp. were significantly more diverse compared to those dominated by Pseudomonas spp. Diversity was not significantly associated with clinical factors or patient age, however, younger subjects yielded a much wider range of bacterial diversity. These data mirror bacterial community dynamics in the lung and provide additional insight into the role of sinus microbiota in chronic airway disease progression.

PMID:33931358 | DOI:10.1016/j.jcf.2021.03.022

J Am Pharm Assoc (2003). 2021 Apr 20:S1544-3191(21)00160-6. doi: 10.1016/j.japh.2021.04.005. Online ahead of print.

ABSTRACT

BACKGROUND: As a result of the coronavirus disease 2019 (COVID-19) pandemic, institutions needed innovative solutions to provide care. With implementation of telehealth, a cystic fibrosis (CF) pharmacist was able to incorporate a virtual medication tour during appointments.

OBJECTIVE: The purpose of our study was to describe the uptake and impact of pharmacist-led virtual medication tours during telehealth visits in the CF clinic setting.

PRACTICE DESCRIPTION: Before the COVID-19 pandemic, a CF pharmacist participated in in-person multidisciplinary team visits to complete medication history reconciliation, assess adherence, assess efficacy and address possible adverse effects of medications, and work collaboratively with the CF care team and patient to create therapeutic plans. The virtual medication tour described in this study was completed in addition or as a complement to these pre-existing pharmacist roles and responsibilities.

PRACTICE INNOVATION: Patients seen via telehealth visit were asked to provide a virtual tour of their medications. A pharmacist completed medication history and evaluated whether storage conditions were appropriate in regard to temperature, humidity, light exposure, and accessibility to children.

EVALUATION METHODS: A pharmacist recorded findings from the virtual medication tours and made interventions when appropriate. Descriptive statistics were used for analysis.

RESULTS: Of 20 patients seen via telehealth for a quarterly visit during the first 3 months after implementation, 13 were willing to participate in a virtual medication tour. Before the visit, 25% had information missing from their medication list. Virtual medication tour allowed for resolution of this information 80% of the time. Three of the 4 participating patients with a child under 12 years old had medications stored in a location accessible to children.

CONCLUSION: A virtual medication tour led by a pharmacist can be successfully incorporated into telehealth visits and was accepted by a majority of patients. Most patients stored medications appropriately but might benefit from education on poison prevention practices.

PMID:33931355 | DOI:10.1016/j.japh.2021.04.005

J Am Pharm Assoc (2003). 2021 Apr 15:S1544-3191(21)00161-8. doi: 10.1016/j.japh.2021.04.006. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive genetic disease requiring complex, lifelong medication regimens. Given the importance of medication in CF treatment, pharmacists are vital CF care team members in the care of people living with CF (PwCF).

OBJECTIVES: This study aimed to (1) define patients' CF medication experiences and educational needs and (2) investigate the CF outpatient clinic and community pharmacist's role in addressing patient challenges.

METHODS: A work system approach informed by the Systems Engineering Initiative for Patient Safety (SEIPS) model was used to characterize knowledge and perception of CF medication regimens, educational modalities, and pharmacist interactions for PwCF. Semistructured interviews were conducted with adults living with CF at a CF center clinic. Data analyses identified relationships between the themes in the data and 4 SEIPS work system domains: tasks, tools and technology, person, and environment.

RESULTS: Thirty PwCF interviews highlighted 4 themes regarding health care experiences: (1) medication use experience, (2) medication education needs, (3) disease experience, and (4) pharmacist and pharmacy interactions. Patients reported complex medication regimens leading to challenges with medication adherence, although the benefit of treatment was recognized. Although a high level of disease-state knowledge was identified among the participants, PwCF desired to learn about CF medication benefits and adverse effects through credible sources using multiple modalities. Many reported a benefit of pharmacist involvement in their care.

CONCLUSION: Pharmacists are well-positioned to support PwCF in adherence, medication regimen management, and medication education. Opportunities exist for growth in these supportive roles of a pharmacist in both community and outpatient clinic settings.

PMID:33931354 | DOI:10.1016/j.japh.2021.04.006

PLoS One. 2021 Apr 30;16(4):e0250977. doi: 10.1371/journal.pone.0250977. eCollection 2021.

ABSTRACT

Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen that causes considerable human morbidity and mortality, particularly in nosocomial infections and individuals with cystic fibrosis. P. aeruginosa can adapt to surface growth by undergoing swarming motility, a rapid multicellular movement that occurs on viscous soft surfaces with amino acids as a nitrogen source. Here we tested the small synthetic host defense peptide, innate defense regulator 1018, and found that it inhibited swarming motility at concentrations as low as 0.75 μg/ml, well below the MIC for strain PA14 planktonic cells (64 μg/ml). A screen of the PA14 transposon insertion mutant library revealed 29 mutants that were more tolerant to peptide 1018 during swarming, five of which demonstrated significantly greater swarming than the WT in the presence of peptide. Transcriptional analysis (RNA-Seq) of cells that were inoculated on swarming plates containing 1.0 μg/ml peptide revealed differential expression of 1,190 genes compared to cells swarming on plates without peptide. Furthermore, 1018 treatment distinctly altered the gene expression profile of cells when compared to that untreated cells in the centre of the swarm colonies. Peptide-treated cells exhibited changes in the expression of genes implicated in the stringent stress response including those regulated by anr, which is involved in anaerobic adaptation, indicative of a mechanism by which 1018 might inhibit swarming motility. Overall, this study illustrates potential mechanisms by which peptide 1018 inhibits swarming surface motility, an important bacterial adaptation associated with antibiotic resistance, virulence, and dissemination of P. aeruginosa.

PMID:33930077 | DOI:10.1371/journal.pone.0250977

J Paediatr Child Health. 2021 Apr 30. doi: 10.1111/jpc.15536. Online ahead of print.

NO ABSTRACT

PMID:33929764 | DOI:10.1111/jpc.15536

Turk J Pediatr. 2021;63(2):218-222. doi: 10.24953/turkjped.2021.02.005.

ABSTRACT

BACKGROUND: Burkholderia cepacia complex (Bcc) comprises multi-drug resistant, Gram-negative, motile, and aerobic bacteria. Bcc causes severe nosocomial infections particularly in patients with intravascular catheters and in those with cystic fibrosis. We studied a Bcc outbreak in non-cystic fibrosis patients.

METHODS: We analyzed data from six patients hospitalized at our center. Blood cultures identified as infectious were incubated onto 5% blood sheep agar, chocolate agar, and eosin methylene blue (EMB) agar. We examined possible sites that could be sources of infection at the clinic. We confirmed isolations with pulsed-field gel electrophoresis (PFGE) tests.

RESULTS: The first patient was hospitalized due to left renal agenesis, urinary tract infection, and renal failure. Bcc was isolated in blood cultures obtained due to high fever on the third day of hospitalization. We stopped new patient hospitalizations after detecting Bcc in blood cultures of other five patients. We did not detect further positive specimens obtained from other clinic and the patient rooms. PFGE patterns were similar in all clinical isolates of Bcc indicating that the outbreak had originated from the source.

CONCLUSIONS: Bcc infection should be considered in cases of nosocomial outbreaks of multi-drug resistant organisms that require hospitalization at intensive care units. Control measures should be taken for prevention of nosocomial infections and required investigations should be done to detect the source of infection.

PMID:33929111 | DOI:10.24953/turkjped.2021.02.005