Repeated hot water and steam disinfection of pari LC Plus® nebulizers alters nebulizer output.

J Cyst Fibros. 2019 Feb 18;:

Authors: Collins MS, Murray TS

PMID: 30792172 [PubMed - as supplied by publisher]

Cystic fibrosis and portal hypertension: Distal splenorenal shunt can prevent the need for future liver transplant.

J Pediatr Surg. 2019 Feb 02;:

Authors: Lemoine C, Lokar J, McColley SA, Alonso EM, Superina R

Abstract
BACKGROUND: The management of portal hypertension (PHT) in children with well compensated cirrhosis and cystic fibrosis (CF) is controversial. We present our experience with distal splenorenal shunting (DSRS) for the treatment of PHT as an alternative to liver transplantation (LT).
METHODS: Between 2008 and 2017, 5 CF children underwent a DSRS at a pediatric hepatobiliary and transplantation referral center. LT (n = 9) was reserved for patients with decompensated cirrhosis. Statistical analysis was done using the paired t-test (p < 0.05 considered significant).
RESULTS: Mean PELD/MELD score was significantly lower for DSRS patients than LT (3 ± 6 vs 28 ± 4, p < 0.001). All 5 DSRS patients had grade III-IV varices. One bled prior to surgery. After DSRS, spleen size decreased significantly from 8.4 ± 1.5 cm to 4.4 ± 1.8 cm (p = 0.019). Mean platelet count remained stable (87.8 ± 48 to 91.8 ± 35, p = 0.9). There were no postoperative complications. No DSRS patient experienced variceal bleeding following shunt creation. Liver function tests remained stable in the DSRS group, and no patient required a liver transplant (median follow up 4.65 years, range 1.24-7.79).
CONCLUSIONS: Patients with cystic fibrosis who have well-compensated cirrhosis and symptomatic portal hypertension can be palliated with distal splenorenal shunting and do not need liver transplants. These patients can undergo shunting with minimal morbidity.
TYPE OF STUDY: Case series with no comparison group.
LEVEL OF EVIDENCE: IV.

PMID: 30792095 [PubMed - as supplied by publisher]

Antifibrinolytic Agents for Hemoptysis Management in Adults with Cystic Fibrosis.

Chest. 2019 Feb 18;:

Authors: Al-Samkari H, Shin K, Cardoni L, Pighetti EH, Rits S, McMahon L, Perkins R, Uluer A, Connors JM

Abstract
BACKGROUND: Hemoptysis is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). Antifibrinolytic agents have demonstrated efficacy in a broad range of bleeding disorders and conditions. We examine use of antifibrinolytic agents to manage hemoptysis in CF. We developed a clinical treatment pathway for inpatient and outpatient use, and report on rates of admission for bleeding before and after implementation.
METHODS: All adult CF patients treated with systemic antifibrinolytic agents over a 54-month period according to the treatment pathway were analyzed. Data collected included demographics, baseline CF-related characteristics, and bleeding and treatment parameters. Effectiveness of the pathway was evaluated via comparison of annualized hemoptysis admission rate before and after pathway enrollment.
RESULTS: 72 distinct episodes of hemoptysis treated with antifibrinolytic agents were analyzed in a total of 21 adult CF patients. Two-thirds of episodes treated involved moderate or massive hemoptysis. Bleeding ceased after a median of two days. Outpatient treatment was associated with a 50% reduction in annualized hemoptysis admission rate following pathway enrollment (2.44 vs. 1.23 admissions per year, P=0.0024) which was independent of other changes in management. Antifibrinolytic therapy was well-tolerated. One central catheter-associated upper extremity deep vein thrombosis was observed in a patient with previous thrombosis in the same vessel.
CONCLUSIONS: A pathway utilizing systemic antifibrinolytic therapy to treat hemoptysis in CF patients was associated with a reduction in hospital admissions. No serious adverse events were observed. Additional studies are needed to further define the benefits of systemic antifibrinolytic use in CF patients.

PMID: 30790551 [PubMed - as supplied by publisher]

Identifying Factors that Facilitate Treatment Adherence in Cystic Fibrosis: Qualitative Analyses of Interviews with Parents and Adolescents.

J Clin Psychol Med Settings. 2019 Feb 21;:

Authors: Nicolais CJ, Bernstein R, Saez-Flores E, McLean KA, Riekert KA, Quittner AL

Abstract
Cystic fibrosis (CF) is a progressive, genetic disease affecting multiple organ systems. Treatments are complex and take 2-4 h per day. Adherence is 50% or less for pulmonary medications, airway clearance, and enzymes. Prior research has identified demographic and psychological variables associated with better adherence; however, no study has extensively identified facilitators of treatment adherence (e.g., adaptive behaviors and cognitions) in a sample of parents and adolescents. Forty-three participants were recruited from four CF centers as part of a larger measurement study. Participants included 29 parents (72% mothers; 72% Caucasian) and 14 adolescents (ages 11-20, 64% female, 71% Caucasian). Participants completed semi-structured interviews to elicit barriers to adherence. However, facilitators of adherence naturally emerged, therefore indicating need for further exploration. Interviews were audiotaped, transcribed and content-analyzed in NVivo to identify those behaviors and beliefs that facilitated adherence, using a phenomenological analysis. Frequencies of these themes were tabulated. Nine themes emerged, with individual codes subsumed under each. Themes included social support, community support, organizational strategies, "intrinsic characteristics," combining treatments with pleasurable activity, flexibility, easier or faster treatment, prioritizing treatments, and negative effects of non-adherence. Results demonstrated the importance of identifying strategies that positively affect adherence. Interventions that are strength-focused, build on prior success, and utilize positive models generated by those who have successfully integrated CF treatments into their lives are more likely to be efficacious.

PMID: 30790101 [PubMed - as supplied by publisher]

Mycobacterium chimaera Pulmonary Disease in Cystic Fibrosis Patients, France, 2010-2017.

Emerg Infect Dis. 2019 Mar;25(3):611-613

Authors: Larcher R, Lounnas M, Dumont Y, Michon AL, Bonzon L, Chiron R, Carriere C, Klouche K, Godreuil S

Abstract
We report Mycobacterium chimaera pulmonary disease in 4 patients given a diagnosis of cystic fibrosis in a university hospital in Montpellier, France. All patients had M. chimaera-positive expectorated sputum specimens, clinical symptoms of pulmonary exacerbation, or a decrease in spirometry test results that improved after specific treatment.

PMID: 30789330 [PubMed - in process]

Nanopillared Surfaces Disrupt Pseudomonas aeruginosa Mechano-responsive Upstream Motility.

ACS Appl Mater Interfaces. 2019 Feb 21;:

Authors: Rosenzweig R, Perinbam K, Ly VK, Ahrar S, Siryaporn A, Yee AF

Abstract
Pseudomonas aeruginosa is an opportunistic, multi-drug resistant, human pathogen that forms biofilms in environments with fluid flow, such as the lungs of cystic fibrosis patients, industrial pipelines, and medical devices. P. aeruginosa twitches upstream on surfaces by the cyclic extension and retraction of their mechano-responsive type IV pili motility appendages. The prevention of upstream motility, host invasion, and infectious biofilm formation in fluid flow systems remains an unmet challenge. Here, we describe the design and application of scalable nanopillared surface structures fabricated using nanoimprint lithography that reduce upstream motility and colonization by P. aeruginosa. We used flow channels to induce a shear stress typically found in catheter tubes and microscopy analysis to investigate the impact of nanopillared surfaces with different packing fractions on upstream motility trajectory, displacement, velocity, and surface attachment. We found that densely packed, sub-cellular nanopillared surfaces, with pillar periodicities ranging from 200-600 nm and widths ranging from 70-215 nm, inhibit the mechano-responsive upstream motility and surface attachment. This bacteria-nanostructured surface interface effect allows us to tailor surfaces with specific nanopillared geometries for disrupting cell motility and attachment in fluid flow systems.

PMID: 30789254 [PubMed - as supplied by publisher]

Etiological involvement of CFTR in apparently unrelated human diseases.

Mol Cell Oncol. 2019;6(1):1558874

Authors: Galluzzi L, Kroemer G

PMID: 30788425 [PubMed]

Extreme recurrent massive hemoptysis in a cystic fibrosis patient requiring 22 separate embolization procedures prior to lung transplantation: A case report.

Radiol Case Rep. 2019 Apr;14(4):472-475

Authors: Margono E, Hoffmann JC

Abstract
While bronchial artery embolization is an established, safe, and effective treatment for massive hemoptysis from a variety of causes including cystic fibrosis, patients rarely require more than 2 angiography and embolization treatments during their lifetime. We present a rare case of massive, recurrent hemoptysis requiring a total of 22 angiography and embolization procedures over a period of 8 years, prior to the patient receiving a double lung transplant.

PMID: 30787964 [PubMed]

Chronic infection by controlling inflammation.

Nat Microbiol. 2019 Mar;4(3):378-379

Authors: Filloux A, Davies JC

Abstract

PMID: 30787479 [PubMed - in process]

National Survey on the Management of Adult Bronchiectasis in Belgium.

COPD. 2019 Feb 21;:1-3

Authors: Schoovaerts K, Lorent N, Goeminne P, Aliberti S, Dupont L

Abstract
The increasing prevalence and incidence of bronchiectasis leads to a substantial health care burden. Quality standards for the management of bronchiectasis were formulated by the British Thoracic Society following publication of guidelines in 2010. They can be used as a benchmark for quality of care. It is, however, unclear how and whether they apply outside of the UK. Between May and November 2017, we conducted an online survey among respiratory physicians caring for adult bronchiectasis patients in Belgium. About 186 cases were submitted by 117 treating physicians. Patients were mostly female (58%), of Caucasian descent (84%) with a remarkably low median age of 59.8 (IQR 47-73) years. 41% had Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus and/or Enterobacteriaceae isolated from respiratory samples in the past. 21% had three or more exacerbations, however, more than 58% were receiving long-term oral antibiotics (of which 90% azithromycin). In 40% of patients the diagnostic testing was insufficient. Surveillance of sputum bacteriology in stable patients and composing a self-management plan was missing in 53% and 68% of patients, respectively. Airway clearance techniques were implemented in 84%. Respiratory physicians complied with 60% or more to five out of the eight applicable quality standards, which is encouraging. Increasing educational act could further raise awareness and increase quality of care.

PMID: 30786778 [PubMed - as supplied by publisher]

Identifying exceptional cystic fibrosis care services: combining statistical process control with focus groups

Book. 2019 2

Authors: MacNeill SJ, Pierotti L, Mohammed MA, Wildman M, Boote J, Harrison S, Carr SB, Cullinan P, Elston C, Bilton D

Abstract
BACKGROUND: The Cystic Fibrosis (CF) Registry collects clinical data on all patients attending specialist CF centres in the UK. These data have been used to make comparisons between centres on key outcomes such as forced expiratory volume in 1 second (FEV1) using simple rankings, which promote the assumption that those with the highest measures provide ‘better’ care.
OBJECTIVES: To explore whether or not using statistical ‘process control’ charts that move away from league tables and adjusting for case mix (age, where appropriate; sex; CF genotype; pancreatic sufficiency; and socioeconomic status) could identify exceptional CF care services in terms of clinically meaningful outcomes. Then, using insight from patients and clinicians on what structures, processes and policies are necessary for delivering good CF care, to explore whether or not care is associated with observed differences in outcomes.
DESIGN: Cross-sectional analyses.
SETTING: Specialist CF centres in the UK.
PARTICIPANTS: Patients aged ≥ 6 years attending specialist CF centres and clinicians at these centres.
MAIN OUTCOME MEASURES: FEV1% predicted.
DATA SOURCES: Annual reviews taken from the UK CF Registry (2007–15).
RESULTS: We studied FEV1 in many different ways and in different periods. In our analyses of both adult and paediatric centres, we observed that some centres showed repeated evidence of ‘special-cause variation’, with mean FEV1 being greater than the mean in some cases and lower than the mean in others. Some of these differences were explained by statistical adjustment for different measures of case mix, such as age, socioeconomic status, genotype and pancreatic sufficiency. After adjustment, there was some remaining evidence of special-cause variation for some centres. Our data at these centres suggest that there may be an association with the use of intravenous antibiotics. Workshops and focus groups with clinicians at paediatric and adult centres identified a number of structures, processes and policies that were felt to be associated with good care. From these, questionnaires for CF centre directors were developed and disseminated. However, the response rate was low, limiting the questionnaires’ use. Focus groups with patients to gain their insights into what is necessary for the delivery of good care identified themes similar to those identified by clinicians, and a patient questionnaire was developed based on these insights.
LIMITATIONS: Our data analyses suggest that differences in intravenous antibiotic usage may be associated with centre-level outcomes; this needs to be explored further in partnership with the centres. Our survey of centre directors yielded a low response, making it difficult to gain useful knowledge to inform further discussions with sites.
CONCLUSIONS: Our findings confirm that the CF Registry can be used to identify differences in clinical outcomes between centres and that case mix might explain some of these differences. As such, adjustment for case mix is essential when trying to understand how and why centres differ from the mean.
FUTURE WORK: Future work will involve exploring with clinicians how care is delivered so that we can understand associations between care and outcomes. Patients will also be asked for their perspectives on the care they receive.
FUNDING: The National Institute for Health Research Health Services and Delivery Research programme.

PMID: 30789690

Human and Extracellular DNA Depletion for Metagenomic Analysis of Complex Clinical Infection Samples Yields Optimized Viable Microbiome Profiles.

Cell Rep. 2019 Feb 19;26(8):2227-2240.e5

Authors: Nelson MT, Pope CE, Marsh RL, Wolter DJ, Weiss EJ, Hager KR, Vo AT, Brittnacher MJ, Radey MC, Hayden HS, Eng A, Miller SI, Borenstein E, Hoffman LR

Abstract
Metagenomic sequencing is a promising approach for identifying and characterizing organisms and their functional characteristics in complex, polymicrobial infections, such as airway infections in people with cystic fibrosis. These analyses are often hampered, however, by overwhelming quantities of human DNA, yielding only a small proportion of microbial reads for analysis. In addition, many abundant microbes in respiratory samples can produce large quantities of extracellular bacterial DNA originating either from biofilms or dead cells. We describe a method for simultaneously depleting DNA from intact human cells and extracellular DNA (human and bacterial) in sputum, using selective lysis of eukaryotic cells and endonuclease digestion. We show that this method increases microbial sequencing depth and, consequently, both the number of taxa detected and coverage of individual genes such as those involved in antibiotic resistance. This finding underscores the substantial impact of DNA from sources other than live bacteria in microbiological analyses of complex, chronic infection specimens.

PMID: 30784601 [PubMed - in process]

Severe asthma and bronchiectasis.

J Asthma. 2019 Feb 20;:1-5

Authors: García-Clemente M, Enríquez-Rodríguez AI, Iscar-Urrutia M, Escobar-Mallada B, Arias-Guillén M, López-González FJ, Madrid-Carbajal C, Pérez-Martínez L, Gonzalez-Budiño T

Abstract
OBJECTIVE: The aim of our study was to determine the tomographic findings and prevalence of bronchiectasis in our population of patients with severe asthma, and to identify factors associated with the presence of bronchiectasis in these patients.
MATERIALS AND METHODS: We retrospectively collected data from the medical histories of patients referred to the asthma unit of our hospital, with a diagnosis of severe asthma between 2015 and 2017. Patients with ABPA, cystic fibrosis, immunodeficiency or systemic disease were excluded. High-resolution thorax-computed tomodensitography (HRCT) was performed in all patients. A standardized protocol was applied in data collection.
RESULTS: A total of 108 patients comprising 50 men (46%) and 58 women (54%) were included in the study. Of the 108 patients, 59 (55%) had at least one abnormality detected by HRCT, the most commonly reported abnormalities being bronchiectasis (35%), bronchial wall thickening (33%), emphysema (7%), atelectasis area (6%), mosaic attenuation due to air trapping (4%), and "tree in bud" image (2%). Subjects with bronchiectasis were older (p = 0.001), had a longer asthma history (p = 0.048), had poorer pulmonary function tests with lower FVC (p = 0.031), had more severe bronchial obstruction with lower FEV1 (p = 0.008) and had lower FEV1/FVC (p = 0.003). They also experienced more frequent hospitalizations in the previous year (p = 0.019) and received treatment with omalizumab more frequently (p = 0.049). Plasma eosinophil count and IgE levels were comparable in both groups. In the multivariate analysis, the presence of bronchiectasis was associated with ages older than 40 (OR: 8.3; 95% CI: 1.7-41.2) and chronic airflow obstruction (OR: 5.4; 95% CI: 1.9-15.3).
CONCLUSIONS: We found that in patients with severe asthma, the prevalence of bronchiectasis is high and that bronchiectasis is associated with a longer asthma history, greater severity and, more importantly, chronic airflow obstruction. These findings are still insufficient evidence to considere features of asthma-bronchiectasis overlap syndrome, a distinct phenotype of severe asthma, but bronchiectasis is a frequent phenomenon leading to a more severe disease with frequent exacerbations. The performance of thorax HRCT on patients with severe asthma can help to evaluate management strategies for the disease in order to improve treatment and prognosis.

PMID: 30784336 [PubMed - as supplied by publisher]

Whole Genome Sequence Analysis of Burkholderia contaminans FFH2055 Strain Reveals the Presence of Putative β-Lactamases.

Curr Microbiol. 2019 Feb 19;:

Authors: Degrossi JJ, Merino C, Isasmendi AM, Ibarra LM, Collins C, Bo NE, Papalia M, Fernandez JS, Hernandez CM, Papp-Wallace KM, Bonomo RA, Vazquez MS, Power P, Ramirez MS

Abstract
Burkholderia contaminans is a member of the Burkholderia cepacia complex (Bcc), a pathogen with increasing prevalence among cystic fibrosis (CF) patients and the cause of numerous outbreaks due to the use of contaminated commercial products. The antibiotic resistance determinants, particularly β-lactamases, have been poorly studied in this species. In this work, we explored the whole genome sequence (WGS) of a B. contaminans isolate (FFH 2055) and detected four putative β-lactamase-encoding genes. In general, these genes have more than 93% identity with β-lactamase genes found in other Bcc species. Two β-lactamases, a class A (Pen-like, suggested name PenO) and a class D (OXA-like), were further analyzed and characterized. Amino acid sequence comparison showed that Pen-like has 82% and 67% identity with B. multivorans PenA and B. pseudomallei PenI, respectively, while OXA-like displayed strong homology with class D enzymes within the Bcc, but only 22-44% identity with available structures from the OXA family. PCR reactions designed to study the presence of these two genes revealed a heterogeneous distribution among clinical and industrial B. contaminans isolates. Lastly, blaPenO gene was cloned and expressed into E. coli to investigate the antibiotic resistance profile and confers an extended-spectrum β-lactamase (ESBL) phenotype. These results provide insight into the presence of β-lactamases in B. contaminans, suggesting they play a role in antibiotic resistance of these bacteria.

PMID: 30783798 [PubMed - as supplied by publisher]

Normative growth charts for Shwachman-Diamond syndrome from Italian cohort of 0-8 years old.

BMJ Open. 2019 Jan 17;9(1):e022617

Authors: Cipolli M, Tridello G, Micheletto A, Perobelli S, Pintani E, Cesaro S, Maserati E, Nicolis E, Danesino C, Italian Registry Organization

Abstract
OBJECTIVES: Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder. Its predominant manifestations include exocrine pancreatic insufficiency, bone marrow failure and skeletal abnormalities. Patients frequently present failure to thrive and susceptibility to short stature. Average birth weight is at the 25th percentile; by the first birthday, >50% of patients drop below the third percentile for height and weight.The study aims at estimating the growth charts for patients affected by SDS in order to give a reference tool helpful for medical care and growth surveillance through the first 8 years of patient's life.
SETTING AND PARTICIPANTS: This retrospective observational study includes 106 patients (64 M) with available information from birth to 8 years, selected among the 122 patients included in the Italian National Registry of SDS and born between 1975 and 2016. Gender, birth date and auxological parameters at repeated assessment times were collected. The General Additive Model for Location Scale and Shape method was applied to build the growth charts. A set of different distributions was used, and the more appropriate were selected in accordance with the smallest Akaike information criterion.
RESULTS: A total of 408 measurements was collected and analysed. The median number of observations per patient amounted to 3, range 1-11. In accordance with the methods described, specific SDS growth charts were built for weight, height and body mass index (BMI), separately for boys and girls.The 50th and 3rd percentiles of weight and height of the healthy population (WHO standard references) respectively correspond to the 97th and 50th percentiles of the SDS population (SDS specific growth charts), while the difference is less evident for the BMI.
CONCLUSIONS: Specific SDS growth charts obtained through our analysis enable a more appropriate classification of patients based on auxological parameters, representing a useful reference tool for evaluating their growth during childhood.

PMID: 30782681 [PubMed - in process]

Remodeling of O Antigen in Mucoid Pseudomonas aeruginosa via Transcriptional Repression of wzz2.

MBio. 2019 Feb 19;10(1):

Authors: Cross AR, Goldberg JB

Abstract
Pseudomonas aeruginosa is an opportunistic pathogen that causes chronic lung infections in people with cystic fibrosis (CF). Chronic P. aeruginosa isolates generally do not express O antigen and often have a mucoid phenotype, which is characterized by the overproduction of the exopolysaccharide alginate. Therefore, O antigen expression and the mucoid phenotype may be coordinately regulated upon chronic adaption to the CF lung. Here we demonstrate that PDO300, a mucoid strain derived from the nonmucoid laboratory isolate PAO1, does not produce very long O antigen due to decreased expression of Wzz2, the very long O antigen chain length control protein, and that mucoid clinical isolates express reduced levels of Wzz2 compared to nonmucoid isolates. Further, we show that forcing the expression of very long O antigen by PDO300, by providing wzz2 in trans, does not alter alginate production, suggesting that sugar precursors are not limited between the two biosynthesis pathways. Moreover, we confirm that AmrZ, a transcription factor highly expressed in mucoid strains, is a negative regulator of wzz2 promoter activity and very long O antigen expression. These experiments identify the first transcriptional regulator of O antigen chain length in P. aeruginosa and support a model where transition to a chronic mucoid phenotype is correlated with downregulation of very long O antigen through decreased Wzz2 production.IMPORTANCE Detection of mucoid Pseudomonas aeruginosa, characterized by the overproduction of alginate, is correlated with the establishment of a chronic pulmonary infection and disease progression in people with cystic fibrosis (CF). In addition to the overproduction of alginate, loss of O antigen lipopolysaccharide production is also selected for in chronic infection isolates. In this study, we have identified the regulatory network that inversely regulates O antigen and alginate production. Understanding the regulation of these chronic phenotypes will elucidate mechanisms that are important for the establishment of a long-term P. aeruginosa lung infection and ultimately provide an opportunity for intervention. Preventing P. aeruginosa from chronically adapting to the CF lung environment could provide a better outcome for people who are infected.

PMID: 30782665 [PubMed - in process]

Successful control of exacerbation of Allergic Bronchopulmonary Aspergillosis due to Aspergillus terreus in a cystic fibrosis patient with short-term adjunctive therapy with voriconazole: A case report.

J Mycol Med. 2019 Feb 16;:

Authors: Hassanzad M, Mortezaee V, Bongomin F, Poorabdollah M, Sharifynia S, Maleki M, Hedayati N, Velayati AA, Hedayati MT

Abstract
A 12-year-old boy with cystic fibrosis (CF) and a history of glucocorticoid-dependent allergic bronchopulmonary aspergillosis (ABPA) was referred to our hospital. The ABPA was diagnosed when he was 8 years old and he had been treated with several course of oral glucocorticoids for recurrent exacerbations. He was readmitted when aged 12 with a history of worsening shortness of breath and chest tightness. A recurrence of ABPA was diagnosed based on eosinophilia and elevation of Aspergillusspecific IgE and IgG, and total IgE. Thoracic high-resolution computed tomography (HRCT) showed central bronchiectasis with parenchymal infiltrates. The treatment started with itraconazole and oral corticosteroid. After 2 months of treatment, he was re-admitted to the hospital due to a progressive worsening of respiratory symptoms. Chest HRCT revealed the a sub segmental atelectasis in the left lung. Microscopic examination of sputum and BAL samples demonstrated septate hyphae consistent with Aspergillus species. Sputum and BAL culture yielded Aspergillus ochraceus and Aspergillus terreus, which were both sensitive to itraconazole and voriconazole. The treatment was switched to voriconazole and the patient showed significant clinical, serological and mycological improvement after three months. This case shows that voriconazole may be used as an alternative for treatment of ABPA due to Aspergillus terreus.

PMID: 30782501 [PubMed - as supplied by publisher]

Decreased Antibiotic Utilization After Sinus Surgery in Cystic Fibrosis Patients With Lung Transplantation.

Am J Rhinol Allergy. 2019 Feb 20;:1945892419830624

Authors: Cheng TZ, Choi KJ, Honeybrook AL, Zakare-Fagbamila RT, Gray AL, Snyder LD, Palmer SM, Abi-Hachem R, Jang DW

Abstract
BACKGROUND: Patients with cystic fibrosis (CF) who have undergone lung transplantation frequently require hospitalizations and antibiotic treatments for respiratory tract infections. Although endoscopic sinus surgery (ESS) improves sinonasal quality of life in CF patients, it is unclear if ESS offers additional benefit in terms of antibiotics for pulmonary infection, hospitalization, and pulmonary function.
OBJECTIVE: To determine whether ESS impacts antibiotic use or hospitalizations for pulmonary indications or pulmonary function in CF patients after lung transplantation.
METHODS: This is a single-institution retrospective study of all patients who underwent lung transplantation for CF from 2005 to 2017. Patients who underwent ESS at least 1 year after transplant were included. Paired bivariate analyses were performed to determine whether there was a difference in the frequency and length of hospitalizations for pulmonary indications, number of antibiotic courses (intravenous and oral) for pulmonary exacerbations, and forced expiratory volume in 1 second (FEV1) slope in the 6 months before versus after ESS. Perioperative antibiotics and hospitalizations were not included in the analyses. Least squares regression was utilized to analyze FEV1 trends.
RESULTS: A total of 20 patients underwent 36 ESS during the study period. There was significantly higher antibiotic utilization in the 6 months before ESS (0.89 ± 1.03) compared to the 6 months after ESS (0.33 ± 0.53) ( P = .002). The frequency and length of hospitalizations, FEV1 slope, and FEV1 trend before and after ESS were not significantly different.
CONCLUSION: Our results suggest that ESS is associated with a reduction in the frequency of antibiotic utilization for respiratory tract infections in lung transplant recipients with CF. A prospective study is needed to investigate these relationships further.

PMID: 30781973 [PubMed - as supplied by publisher]

Iron in Lung Pathology.

Pharmaceuticals (Basel). 2019 Feb 15;12(1):

Authors: Zhang V, Nemeth E, Kim A

Abstract
The lung presents a unique challenge for iron homeostasis. The entire airway is in direct contact with the environment and its iron particulate matter and iron-utilizing microbes. However, the homeostatic and adaptive mechanisms of pulmonary iron regulation are poorly understood. This review provides an overview of systemic and local lung iron regulation, as well as the roles of iron in the development of lung infections, airway disease, and lung injury. These mechanisms provide an important foundation for the ongoing development of therapeutic applications.

PMID: 30781366 [PubMed]

Engineered transfer RNAs for suppression of premature termination codons.

Nat Commun. 2019 Feb 18;10(1):822

Authors: Lueck JD, Yoon JS, Perales-Puchalt A, Mackey AL, Infield DT, Behlke MA, Pope MR, Weiner DB, Skach WR, McCray PB, Ahern CA

Abstract
Premature termination codons (PTCs) are responsible for 10-15% of all inherited disease. PTC suppression during translation offers a promising approach to treat a variety of genetic disorders, yet small molecules that promote PTC read-through have yielded mixed performance in clinical trials. Here we present a high-throughput, cell-based assay to identify anticodon engineered transfer RNAs (ACE-tRNA) which can effectively suppress in-frame PTCs and faithfully encode their cognate amino acid. In total, we identify ACE-tRNA with a high degree of suppression activity targeting the most common human disease-causing nonsense codons. Genome-wide transcriptome ribosome profiling of cells expressing ACE-tRNA at levels which repair PTC indicate that there are limited interactions with translation termination codons. These ACE-tRNAs display high suppression potency in mammalian cells, Xenopus oocytes and mice in vivo, producing PTC repair in multiple genes, including disease causing mutations within cystic fibrosis transmembrane conductance regulator (CFTR).

PMID: 30778053 [PubMed - in process]