Th17 associated cytokines in sputum samples from patients with cystic fibrosis.

Pathog Dis. 2020 Sep 02;:

Authors: Oshalim M, Johansson E, Rabe H, Gilljam M, Lindblad A, Jönsson B

Abstract
Cystic fibrosis (CF) is a genetic disease leading to chronic bacterial airway infection and inflammation. T helper 17 (Th17) cells are identified by their production of interleukin (IL)-17A, which recruit neutrophils to the site of airway infection. IL-23 is an important inducer of IL-17 and IL-22 production. The aim of this study was to study the role of Th17 cells in CF airway infection by measuring the levels of Th17 associated cytokines in sputum from CF patients with or without airway infection and by comparison with non-CF-controls. In a cross-sectional screening study, cytokine levels were measured with a Th17 multiplex cytokine ELISA. Significantly lower levels of IL-17A and IL-23 were found in sputa from infected CF patients. The lowest levels of IL-17A were found in patients chronically infected with P. aeruginosa, which also had the lowest IL-17/IL-22 ratio, while children had a higher ratio. Children also had higher IL-23 levels than adults. IL-1ß and IL-10 were significantly lower in CF sputum compared to controls. Thus, in our study CF patients with chronic infections had a lower production of Th17 associated cytokines in sputum compared with non-infected CF patients and infected patient without CF.

PMID: 32876666 [PubMed - as supplied by publisher]

Using Near-Peer Teaching to Address Concepts of Cystic Fibrosis in Undergraduate Medical Learners.

MedEdPORTAL. 2020 Aug 28;16:10961

Authors: LeClair RJ, Binks AP

Abstract
Introduction: Cystic fibrosis (CF) is a high-yield undergraduate medical education topic that lends itself to adaptability of content. We used a CF case paired with activities to deliver content in a near-peer teaching session. First-year (M1) and second-year (M2) medical students contributed acquired knowledge of protein structure and obstructive lung disease, respectively, to generate a concept map and address discussion questions.
Methods: Combined groups of M1 and M2 students reviewed a CF case and a concept map prompt. For 30 minutes, they created a concept map describing connections between molecular biology and clinical manifestations. We summarized by reviewing concept maps and discussion questions. The efficacy of the session was determined by comparing exam performance of class attenders and nonattenders (M2) and performance on questions related and unrelated to the exercise (M1). We also determined students' perception of the session and incorporation of additional core competencies.
Results: M2 students' performance was 3.8% higher (p = .296) and M1 students' performance was 1.8% higher (p = .286) than their respective controls. Students commented positively on the exercise and perceived more than one core competency as part of the session.
Discussion: Although there was no significant improvement in exam performance, this curriculum used near-peer teaching to reinforce previously learned material and apply recently acquired material in an engaging format without detriment to either group. This method can be adapted to different learner groups and provides an opportunity to deliver and assess other core medical competencies.

PMID: 32875098 [PubMed - in process]

Transition From Pediatric to Adult Care for Young Adults With Chronic Respiratory Disease.

Respir Care. 2020 Sep 01;:

Authors: Willis LD

Abstract
Advances in medicine and technology have led to improved survival rates of children with chronic respiratory disease such as cystic fibrosis, neuromuscular disease, and ventilator dependence. Survival into adulthood has created the need for adult specialists for conditions originating in childhood. Transition from pediatric to adult health care is a process that requires advanced planning and preparation and is not a one-time transfer event. Transition should be standard practice, but many children with special health care do not experience successful transition outcomes. Barriers to successful transition include lack of a standardized process, inadequate planning, and poor communication. Adverse outcomes have occurred in cases of abrupt or haphazard transfers. A successful transition process includes early introduction and ongoing discussion that engages the adolescent to plan and prepare for the eventual transfer of care. Care responsibilities should be gradually shifted from the parent to the adolescent in a manner appropriate for the adolescent's age and developmental status. Good communication and collaboration between pediatric and adult care teams is crucial to ensure a smooth transfer of care. Incorporating the 6 core elements of transition can be helpful in developing a successful transition program. This narrative review summarizes the literature for health care transition from pediatric to adult care including the rationale, barriers, factors associated with successful transition, and special considerations. The intent of this review is to increase clinician awareness of health care transitions and the components necessary for an effective transfer of young adults with chronic respiratory disease. Understanding the transition process is an important consideration for both pediatric and adult clinicians, including respiratory therapists.

PMID: 32873753 [PubMed - as supplied by publisher]

Immune response of polarized cystic fibrosis airway epithelial cells infected with Influenza A virus.

J Cyst Fibros. 2020 Aug 29;:

Authors: Sofoluwe A, Zoso A, Bacchetta M, Lemeille S, Chanson M

Abstract
BACKGROUND: Cystic fibrosis (CF), a genetic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, is characterized by dysfunction of the immune response in the airway epithelium that leads to prolonged infection, colonization and exacerbated inflammation. In this study, we determined the gene expression profile of airway epithelial cells knockdown for CFTR (CFTR KD) in response to bacterial and viral challenges.
METHODS: In a first approach, polarized CFTR KD and their control counterpart (CFTR CTL) cells were stimulated with P. aeruginosa-derived virulence factor flagellin. Next, we developed a model of Influenza A virus (IAV) infection in CTL and CFTR KD polarized cells. mRNA was collected for transcriptome analysis.
RESULTS: Beside the expected pro-inflammatory response, Gene Set Enrichment Analysis highlighted key molecular pathways and players involved in IAV and anti-viral interferon signaling. Although IAV replication was similar in both cell types, multiplex gene expression analysis revealed changes of key immune genes dependent on time of infection that were found to be CFTR-dependent and/or IAV-dependent. Interferons are key signaling proteins/cytokines in the antibacterial and antiviral response. To evaluate their impact on the altered gene expression profile in CFTR responses to pathogens, we measured transcriptome changes after exposure to Type I-, Type II- and Type III-interferons.
CONCLUSIONS: Our findings reveal target genes in understanding the defective immune response in the CF airway epithelium in the context of viral infection. Information provided in this study would be useful to understand the dysfunctional immune response of the CF airway epithelium during infection.

PMID: 32873524 [PubMed - as supplied by publisher]

Interferon-gamma-activated macrophages infected with Burkholderia cenocepacia process and present bacterial antigens to T-cells by class I and II major histocompatibility complex molecules.

Emerg Microbes Infect. 2020 Sep 01;:1-38

Authors: Rosales-Reyes R, Garza-Villafuerte P, Vences-Vences D, Aubert DF, Aca-Teutle R, Ortiz-Navarrete VF, Bonifaz LC, Carrero-Sánchez JC, Olivos-García A, Valvano MA, Santos-Preciado JI

Abstract
Burkholderia cenocepacia is an emerging opportunistic pathogen often causing fatal pulmonary infections in people with cystic fibrosis and chronic granulomatous disease. Intracellular survival in macrophages within a membrane-bound vacuole (BcCV) that delays acidification and maturation into lysosomes is a hallmark of B. cenocepacia infection. Intracellular B. cenocepacia induce a strong inflammatory response leading to macrophage cell death by pyroptosis through the secretion of a bacterial effector deamidase that results in the activation of the pyrin inflammasome. However, how or whether infected macrophages can process and present B. cenocepacia antigens to activate T-cells has not been explored. Engulfed bacterial protein antigens are cleaved into small peptides in the late endosomal major histocompatibility class II complex (MHC) compartment (MIIC). Here, we demonstrate that BcCVs and MIICs have overlapping features and interferon-gamma-activated macrophages infected with B. cenocepacia can process bacterial antigens for presentation by class II MHC molecules to CD4+ T-cells and by class I MHC molecules to CD8+ T-cells. We also show that infected macrophages release processed bacterial peptides into the extracellular medium, stabilizing empty class I MHC molecules of bystander cells. Together, we conclude that BcCVs acquire MIIC characteristics, supporting the notion that macrophages infected with B. cenocepacia contribute to establishing an adaptive immune response against the pathogen.

PMID: 32873215 [PubMed - as supplied by publisher]

Comparative Analysis of Streptococcus pneumoniae Type I Restriction-Modification Loci: Variation in hsdS Gene Target Recognition Domains.

Pathogens. 2020 Aug 29;9(9):

Authors: Oliver MB, Swords WE

Abstract
Streptococcus pneumoniae (pneumococcus) is a respiratory commensal pathogen that causes a range of infections, particularly in young children and the elderly. Pneumococci undergo spontaneous phase variation in colony opacity phenotype, in which DNA rearrangements within the Type I restriction-modification (R-M) system specificity gene hsdS can potentially generate up to six different hsdS alleles with differential DNA methylation activity, resulting in changes in gene expression. To gain a broader perspective of this system, we performed bioinformatic analyses of Type I R-M loci from 18 published pneumococcal genomes, and one R-M locus sequenced for this study, to compare genetic content, organization, and homology. All 19 loci encoded the genes hsdR, hsdM, hsdS, and at least one hsdS pseudogene, but differed in gene order, gene orientation, and hsdS target recognition domain (TRD) content. We determined the coding sequences of 87 hsdS TRDs and excluded seven from further analysis due to the presence of premature stop codons. Comparative analyses revealed that the TRD 1.1, 1.2, and 2.1 protein sequences had single amino acid substitutions, and TRD 2.2 and 2.3 each had seven differences. The results of this study indicate that variability exists among the gene content and arrangements within Type I R-M loci may provide an additional level of divergence between pneumococcal strains, such that phase variation-mediated control of virulence factors may vary significantly between individual strains. These findings are consistent with presently available transcript profile data.

PMID: 32872494 [PubMed]

Dependence of the Staphylococcal Volatilome Composition on Microbial Nutrition.

Metabolites. 2020 Aug 27;10(9):

Authors: Jenkins CL, Bean HD

Abstract
In vitro cultivation of staphylococci is fundamental to both clinical and research microbiology, but few studies, to-date, have investigated how the differences in rich media can influence the volatilome of cultivated bacteria. The objective of this study was to determine the influence of rich media composition on the chemical characteristics of the volatilomes of Staphylococcus aureus and Staphylococcus epidermidis. S. aureus (ATCC 12600) and S. epidermidis (ATCC 12228) were cultured in triplicate in four rich complex media (brain heart infusion (BHI), lysogeny broth (LB), Mueller Hinton broth (MHB), and tryptic soy broth (TSB)), and the volatile metabolites produced by each culture were analyzed using headspace solid-phase microextraction combined with comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (HS-SPME-GC×GC-TOFMS). When comparing the chemical compositions of the staph volatilomes by the presence versus absence of volatiles produced in each medium, we observed few differences. However, when the relative abundances of volatiles were included in the analyses, we observed that culturing staph in media containing free glucose (BHI and TSB) resulted in volatilomes dominated by acids and esters (67%). The low-glucose media (LB and MHB) produced ketones in greatest relative abundances, but the volatilome compositions in these two media were highly dissimilar. We conclude that the staphylococcal volatilome is strongly influenced by the nutritional composition of the growth medium, especially the availability of free glucose, which is much more evident when the relative abundances of the volatiles are analyzed, compared to the presence versus absence.

PMID: 32867100 [PubMed]

The effects of taurine supplementation on obesity, blood pressure and lipid profile: A meta-analysis of randomized controlled trials.

Eur J Pharmacol. 2020 Aug 29;:173533

Authors: Guan L, Miao P

Abstract
Taurine plays a pivotal role in regulating glucose and lipid metabolism, blood pressure homeostasis, and obesity largely due to its cytoprotective, antioxidant, and anti-inflammatory actions. Despite promising data from animal studies in this scenario, the efficacy of taurine supplementation in human studies has been inconsistent. The main objective of this meta-analysis was to appraise the effects of taurine supplementation on liver markers and, secondarily, to explore anthropometric measures as well. Pubmed, SCOPUS, Web of Science, and Google Scholar were searched from inception to April 2020. There were 12 eligible peer-reviewed studies meeting the inclusion criteria. Most studies were conducted in patients with liver or metabolic dysregulation (diabetes, hepatitis, fatty liver, obesity, cystic fibrosis, chronic alcoholism, and cardiac surgery). The taurine dosage varied from 0.5 to 6 g/d for 15 days to 6 months. Pooled effect sizes suggested a significant effect of taurine administration on systolic blood pressure (weighted mean difference (WMD): -4.67 mm Hg; 95%CI, -9.10 to -0.25), diastolic blood pressure (WMD: -2.90 mm Hg; 95%CI, -4.29 to -1.52), total cholesterol (WMD: -10.87 mg/dl; 95%CI, -16.96 to -4.79), and triglycerides (WMD: -13.05 mg/dl; 95%CI, -25.88 to -0.22); however, it had no effect on fasting blood glucose (WMD: 0.06 mg/dl), HDL-C (WMD: 0.90 mg/dl), LDL-C (WMD: -6.17 mg/dl), as well as on body mass index (WMD: -0.46 kg/m2) and body weight (WMD: -0.47 kg) as the anthropometric measures. These findings indicate that, in patients with liver dysregulation, taurine supplementation can lower blood pressure and improve the lipid profile by reducing total cholesterol and triglyceride levels.

PMID: 32871172 [PubMed - as supplied by publisher]

In Search of "hepatic factor:" Lack of Evidence for ALK1 Ligands BMP9 and BMP10.

Am J Respir Crit Care Med. 2020 Sep 01;:

Authors: Capasso TL, Trucco SM, Hindes M, Schwartze T, Bloch JL, Kreutzer J, Cook SC, Hinck CS, Treggiari D, Feingold B, Hinck AP, Roman BL

PMID: 32871084 [PubMed - as supplied by publisher]

Erratum: Cardiopulmonary Exercise Testing Provides Additional Prognostic Information in Cystic Fibrosis.

Am J Respir Crit Care Med. 2020 Sep 01;202(5):780

Authors:

PMID: 32870034 [PubMed - as supplied by publisher]

Analysis of hospital management of chronic respiratory diseases in light of the "Maps of Health Needs" project in Poland.

Adv Respir Med. 2020;88(4):297-304

Authors: Jahnz-Różyk K, Czajkowska-Malinowska M, Krenke K, Sands D, Batura-Gabryel H, Kabicz P, Diaków E, Więckowska B

Abstract
INTRODUCTION: The "Maps of Health Needs" project has been carried out in Poland since 2016 and its purpose is to implement quality-promoting and organisational solutions in the Polish healthcare system. This paper is the analysis of hospitalisations for chronic respiratory diseases recorded in Polish National Health Fund databases in 2014.
MATERIAL AND METHODS: The study included 122,000 hospitalisations of adults and 22,000 hospitalisations of children. Epidemio-logical parameters (incidence and prevalence) and major hospitalisation parameters were determined through statistical analysis.
RESULTS: The highest registered incidence was observed in asthma patients (548 per 100,000 inhabitants) followed by COPD patients (233 per 100,000 inhabitants). Asthma patients were also characterised by the highest prevalence, with lower values being observed in COPD patients. In the group of adults, patients aged 65 years or older and 80 years or older accounted for 44% and 14% of hospitalised adults respectively. The analysis also revealed that 66% of hospitalisations of adults included patients with asthma, COPD and respiratory failure. The development of respiratory failure prolongs hospitalisation and increases both in-hospital and post-discharge mortality. In children, 90% of the identified hospitalisations were for asthma, chronic inflammatory lung diseases and cystic fibrosis.
CONCLUSIONS: The results of the study demonstrate that pulmonary obstructive diseases are associated with a considerable burden. Therefore, corrective actions within the Polish healthcare system are required to decrease the number of hospitalisations for these diseases.

PMID: 32869262 [PubMed - in process]

Accelerated Approval or Risk Reduction? How Response Biomarkers Advance Therapeutics through Clinical Trials in Cystic Fibrosis.

Trends Mol Med. 2020 Aug 28;:

Authors: Mayer-Hamblett N, VanDevanter DR

Abstract
Progress in the development of new therapies for cystic fibrosis (CF) has benefited from therapeutically responsive biomarkers to streamline drug development. Paradoxically, these response biomarkers have been proven to be essential even in the presence of data demonstrating a lack of correlation with clinical outcomes across individuals with CF. This finding is unsurprising, particularly in the setting of a rare disease given complex disease processes and an often-limited pool of clinically effective therapies by which to link biomarkers and clinical responsiveness. While many response biomarkers will be unable to progress from their status as markers of biological efficacy to either established correlates of clinical efficacy or surrogate endpoints, they remain critical to the overall success of therapeutic development.

PMID: 32868171 [PubMed - as supplied by publisher]

Worsening pulmonary outcomes during sex reassignment therapy in a transgender female with cystic fibrosis (CF) and asthma/allergic bronchopulmonary aspergillosis: a case report.

BMC Pulm Med. 2020 Aug 31;20(1):234

Authors: Lam GY, Goodwin J, Wilcox P, Quon BS

Abstract
BACKGROUND: Cystic Fibrosis (CF) is a hereditary pulmonary and extra-pulmonary disease that occurs equally in men and women. However, a difference in morbidity and mortality rates between the sexes has been long documented. Similarly, a sex-disparity in disease severity has been reported in asthma as well. Studies done to date point to estrogen as a possible cause of this sex disparity in pulmonary outcomes in both conditions.
CASE PRESENTATION: Here, we describe a case of a patient with CF and asthma/allergic bronchopulmonary aspergillosis (ABPA) undergoing sex reassignment therapy (male-to-female) and the negative impact it had on her lung function and frequency of pulmonary exacerbations in the context of increasing doses of exogenous estrogen.
CONCLUSIONS: This case raises the possibility of a link between estrogen and worsening pulmonary outcomes and the need for further studies into transgender individuals with CF and/or asthma/ABPA as well as those undergoing high dose estrogen therapy for other indications.

PMID: 32867730 [PubMed - in process]

MmpL3 Inhibition: A New Approach to Treat Nontuberculous Mycobacterial Infections.

Int J Mol Sci. 2020 Aug 27;21(17):

Authors: Sethiya JP, Sowards MA, Jackson M, North EJ

Abstract
Outside of Mycobacterium tuberculosis and Mycobacterium leprae, nontuberculous mycobacteria (NTM) are environmental mycobacteria (>190 species) and are classified as slow- or rapid-growing mycobacteria. Infections caused by NTM show an increased incidence in immunocompromised patients and patients with underlying structural lung disease. The true global prevalence of NTM infections remains unknown because many countries do not require mandatory reporting of the infection. This is coupled with a challenging diagnosis and identification of the species. Current therapies for treatment of NTM infections require multidrug regimens for a minimum of 18 months and are associated with serious adverse reactions, infection relapse, and high reinfection rates, necessitating discovery of novel antimycobacterial agents. Robust drug discovery processes have discovered inhibitors targeting mycobacterial membrane protein large 3 (MmpL3), a protein responsible for translocating mycolic acids from the inner membrane to periplasm in the biosynthesis of the mycobacterial cell membrane. This review focuses on promising new chemical scaffolds that inhibit MmpL3 function and represent interesting and promising putative drug candidates for the treatment of NTM infections. Additionally, agents (FS-1, SMARt-420, C10) that promote reversion of drug resistance are also reviewed.

PMID: 32867307 [PubMed - in process]

Optimization of nitric oxide donors for investigating biofilm dispersal response in Pseudomonas aeruginosa clinical isolates.

Appl Microbiol Biotechnol. 2020 Aug 31;:

Authors: Cai YM, Webb JS

Abstract
Pseudomonas aeruginosa biofilms contribute heavily to chronic lung infection in cystic fibrosis patients, leading to morbidity and mortality. Nitric oxide (NO) has been shown to disperse P. aeruginosa biofilms in vitro, ex vivo and in clinical trials as a promising anti-biofilm agent. Traditional NO donors such as sodium nitroprusside (SNP) have been extensively employed in different studies. However, the dosage of SNP in different studies was not consistent, ranging from 500 nM to 500 μM. SNP is light sensitive and produces cyanide, which may lead to data misinterpretation and inaccurate predictions of dispersal responses in clinical settings. New NO donors and NO delivery methods have therefore been explored. Here we assessed 7 NO donors using P. aeruginosa PAO1 and determined that SNP and Spermine NONOate (S150) successfully reduced > 60% biomass within 24 and 2 h, respectively. While neither dosage posed toxicity towards bacterial cells, chemiluminescence assays showed that SNP only released NO upon light exposure in M9 media and S150 delivered much higher performance spontaneously. S150 was then tested on 13 different cystic fibrosis P. aeruginosa (CF-PA) isolates; most CF-PA biofilms were significantly dispersed by 250 μM S150. Our work therefore discovered a commercially available NO donor S150, which disperses CF-PA biofilms efficiently within a short period of time and without releasing cyanide, as an alternative of SNP in clinical trials in the future. KEY POINTS: • S150 performs the best in dispersing P. aeruginosa biofilms among 7 NO donors. • SNP only releases NO in the presence of light, while S150 releases NO spontaneously. • S150 successfully disperses biofilms formed by P. aeruginosa cystic fibrosis clinical isolates.

PMID: 32865612 [PubMed - as supplied by publisher]

Antibiotic eluting sinus stents.

Laryngoscope Investig Otolaryngol. 2020 Aug;5(4):598-607

Authors: Thompson HM, Lim DJ, Banks C, Grayson JW, Ayinala S, Cho DY, Woodworth BA

Abstract
Objectives: Chronic rhinosinusitis (CRS) is a multifactorial disease affecting up to 16% of the United States population and disproportionately affecting the cystic fibrosis (CF) patient population. Despite treating the underlying infection, the use of systemic antibiotics has shown little efficacy in alleviation of symptom burden. This review seeks to discuss recent research on novel antibiotic eluting stent therapy in vitro and within animal models as well as the factors that contribute to its efficacy.
Data Sources: PubMed literature review.
Review Methods: A review of all published literature related to antibiotic eluting sinus stents was conducted to integrate and summarize this innovative approach to chronic sinus infections.
Results: Placement of the ciprofloxacin sinus stent (CSS) and ciprofloxacin-ivacaftor sinus stent (CISS) exhibited improvement in endoscopic and radiographic findings in rabbit CRS models. While the CSS showed an overall trend toward improvement in microscopic findings and a reduction in biofilm mass, there remained a significant quantity of planktonic bacteria due to antibiotic depletion from an initial burst release in the first 48 hours of stent placement. The CISS and ciprofloxacin-azithromycin sinus stents (CASSs) exhibited controlled antibiotic release over the study period leading to greatly reduced planktonic bacterial load and biofilm mass. In vitro studies indicate that CASS may be just as efficacious at reducing biofilm mass.
Conclusion: Antibiotic eluting sinus stents show significant promise as a novel therapeutic strategy for CRS. The CISS may have particular promise for the CF patient population by addressing both the infectious and genetic components of disease. Animal studies demonstrate significant promise for translation into human studies. Human clinical trials are warranted to determine the efficacy of antibiotic sinus stents in human patients.
Level of Evidence: NA.

PMID: 32864430 [PubMed]

Longitudinal monitoring of sinonasal and oral bacterial reservoirs to prevent chronic lung infection in people with cystic fibrosis.

ERJ Open Res. 2020 Jul;6(3):

Authors: Passarelli Mantovani R, Sandri A, Boaretti M, Burlacchini G, Li Vigni V, Scarazzai M, Melotti P, Signoretto C, Lleo MM

Abstract
Background: Paranasal sinuses act as bacterial reservoirs and contribute to transmitting bacteria to the lower airway of patients with cystic fibrosis (CF). Also, passage of bacteria from the oral cavity to the lungs may occur.
Methods: We evaluated the presence of Pseudomonas aeruginosa, Staphylococcus aureus, Stenotrophomonas maltophilia, Achromobacter xylosoxidans and Serratia marcescens in sputum and nasal lavage of 59 patients with CF, and also collected saliva and used toothbrushes from 38 of them. We assessed the clonal identity of the strains isolated from the different samples by pulsed-field gel electrophoresis.
Results: About 80% of the patients were positive for at least one of the bacterial species examined in nasal lavage and sputum. Among the subjects with positive sputum, 74% presented the same species in the nasal lavage and saliva, and 26% on their toothbrush. S. aureus was the most abundant species in all samples. Clonal identity (≥80% similarity) of the strains isolated among the different samples from each patient was confirmed in almost all cases. Longitudinal observation helped to identify five patients who were colonised in the lower airways after an initial period of nasal or oral colonisation.
Conclusion: Nasal and oral sites act as bacterial reservoirs, favouring the transmission of potentially pathogenic microorganisms to the lower airway. The lack of eradication from these sites might undermine the antibiotic therapy applied to treat the lung infection, allowing the persistence of the bacteria within the patient if colonisation of these sites is not assessed, and no specific therapy is performed.

PMID: 32864382 [PubMed]

Comparison of four agar media for the enumeration of the Mycobacterium abscessus complex.

Int J Mycobacteriol. 2020 Jul-Sep;9(3):289-292

Authors: Moore JE, Millar BC

Abstract
Background: Traditional culture of nontuberculous mycobacteria (NTMs) has involved egg-based formulations (Lowenstein-Jensen medium) or defined media (Middlebrook formulations), which have disadvantages of composition complexity, availability, and cost. This study quantitatively compared three non-selective, non-blood based basal agars with Columbia blood agar (CBA), to enumerate Mycobacterium abscessus complex organisms in pure culture.
Methods: M. abscessus subsp. massiliense, M. abscessus subsp. bolletii, and M. abscessus subsp. abscessus were employed. Inocula of each of these were counted on three basal agar media, including (i) standard plate count agar (SPCA), (ii) tryptone soya agar (TSA), and (iii) Mueller-Hinton agar (MHA) and compared to counts on CBA.
Results: All NTM isolates of all subspecies grew successfully on all four media examined. The growth was most profuse on SPCA, with a mean colony diameter of 3 mm, whereas the mean colony diameter on all other media was 1 mm. Statistically, there was no significant difference in counts when comparing CBA with SPCA or MHA (P > 0.05), whereas there was a statistically significant difference between CBA and TSA (P = 0.01). There was no statistically significant difference between SPCA and MHA (P = 0.53).
Conclusion: This study indicates that SPCA and MHA are equally effective as CBA, when enumerating of M. abscessus complex organisms. Employment of TSA gave significantly lower counts than CBA (P = 0.01) and therefore should not be employed when enumerating these organisms. SPCA yielded the most profuse growth of all media examined. In addition to these advantages, given that SPCA does (i) not require blood as a medium constituent, (ii) is simple to reconstitute, (iii) is relatively cheap, and (iv) is widely available commercially, this study endorses employment of SPCA for the nonselective culture of M. abscessus complex organisms, including enumeration.

PMID: 32862162 [PubMed - in process]

Relationship Between Estrogen Treatment and Skeletal Health in Women With Cystic Fibrosis.

Am J Med Sci. 2020 Jun 06;:

Authors: Wu M, Bettermann EL, Arora N, Hunt WR, McCracken C, Tangpricha V

Abstract
BACKGROUND: Patients with cystic fibrosis (CF) are at risk for CF-related bone disease. Women with CF may use estrogen supplementation for reasons other than skeletal health. It is unknown whether estrogen therapy has a beneficial impact on skeletal health in women with CF.
METHODS: In this retrospective cohort study of women with CF followed at a single CF center, the lumbar spine bone mineral density (BMD) of women with CF exposed to supplemental and not exposed to supplemental estrogen were compared. Spline function models included the main effect of estrogen exposure and the interaction between age and estrogen supplementation.
RESULTS: Of the 145 subjects analyzed, 44 subjects were exposed to supplemental estrogen. The baseline characteristics of estrogen exposed and unexposed subjects were similar except for use of CF transmembrane conductance regulator modulators and anti-osteoporosis medications. Women exposed to estrogen reached peak BMD around 21 years of age, but women not exposed to estrogen reached peak BMD around 25 years of age. A significant interaction of age and estrogen supplementation indicated that the lumbar spine BMD trajectories differed by exposure group.
CONCLUSIONS: Our study demonstrates that few women with CF of reproductive age are prescribed estrogen therapy. Furthermore, estrogen exposure up to age 21 is associated with improved BMD, but estrogen exposure after age 21 does not appear to be associated with improved BMD. Further studies are needed to understand the reasons for the low rates of estrogen use in young women with CF and the optimal timing, dose and formulation of estrogen prescription.

PMID: 32861400 [PubMed - as supplied by publisher]

Transparency and diversity in cystic fibrosis research - Authors' reply.

Lancet. 2020 Aug 29;396(10251):602

Authors: McCoy KS, Heijerman H, Taylor-Cousar JL, Waltz D, Sosnay PR, Ramsey BW, Rowe S, Welter J

PMID: 32861305 [PubMed - in process]