A fixation method for the optimisation of western blotting.

Sci Rep. 2019 Apr 30;9(1):6649

Authors: Xu J, Sun H, Huang G, Liu G, Li Z, Yang H, Jin L, Cui X, Shi L, Ma T, Kameyama A, Dong W

Abstract
Western blotting is the most extensively used technique for the identification and characterisation of proteins and their expression levels. One of the major issues with this technique is the loss of proteins from the blotted membrane during the incubation and washing steps, which affects its sensitivity and reproducibility. Here, we have optimised the fixation conditions for immunoblotting and lectin blotting on electroblotted polyvinylidene difluoride and nitrocellulose membranes, using a combination of organic solvents and heating. Loss of proteins from polyvinylidene difluoride membranes was greatly reduced using this approach, the intensity of lectin blotting and immunoblotting was shown to increase 2.8- to 15-fold and 1.8- to 16-fold, respectively, compared with that samples without treated. Using the optimised method, cystic fibrosis transmembrane regulator and hypoxia-inducible factor 1, two difficult-to-analyse proteins with important physiological and pathological roles, were effectively detected. Additionally, it may help the identification of novel diagnostic markers for prostate cancer.

PMID: 31040299 [PubMed - in process]

One year prospective survey of azole resistance in Aspergillus fumigatus at a French cystic fibrosis reference centre: prevalence and mechanisms of resistance.

J Antimicrob Chemother. 2019 Apr 30;:

Authors: Lavergne RA, Morio F, Danner-Boucher I, Horeau-Langlard D, David V, Hagen F, Meis JF, Le Pape P

Abstract
BACKGROUND: Studies on Aspergillus fumigatus azole resistance in cystic fibrosis patients are scarce despite the fact that it is the most frequently isolated fungus from respiratory samples from these individuals.
OBJECTIVES: To evaluate resistance prevalence, investigate mechanisms of resistance and explore the relationship between resistant isolates by genotyping.
METHODS: We conducted a prospective 1 year study (from 1 January to 31 December 2015), based on the investigation of up to five colonies per sample from cystic fibrosis patients.
RESULTS: Twenty-three (6.5%) isolates among the 355 tested were resistant to at least one triazole drug, using the EUCAST reference method, leading to a prevalence of 6.8% (6/88 patients). Analysis of resistance mechanisms highlighted TR34/L98H (n = 10), TR46/Y121F/T289A (n = 1), WT cyp51A (n = 11) and F46Y/M172V/N248T/D255E/E427K (n = 1). No genotype was shared between patients.
CONCLUSIONS: This study showed a relatively stable resistance prevalence in comparison with the previous study conducted in 2010-11 (8%), although resistance mechanisms varied between the two studies.

PMID: 31038164 [PubMed - as supplied by publisher]

Sequencing as a first-line methodology for cystic fibrosis carrier screening.

Genet Med. 2019 Apr 30;:

Authors: Beauchamp KA, Johansen Taber KA, Grauman PV, Spurka L, Lim-Harashima J, Svenson A, Goldberg JD, Muzzey D

Abstract
PURPOSE: Medical society guidelines recommend offering genotyping-based cystic fibrosis (CF) carrier screening to pregnant women or women considering pregnancy. We assessed the performance of sequencing-based CF screening relative to genotyping, in terms of analytical validity, clinical validity, clinical impact, and clinical utility.
METHODS: Analytical validity was assessed using orthogonal confirmation and reference samples. Clinical validity was evaluated using the CFTR2 database. Clinical impact was assessed using ~100,000 screened patients. Three screening strategies were compared: genotyping 23 guideline-recommended variants ("CF23"), sequencing all coding bases in CFTR ("NGS"), and sequencing with large copy-number variant (CNV) identification ("NGS + CNV"). Clinical utility was determined via self-reported actions of at-risk couples (ARCs).
RESULTS: Analytical accuracy of NGS + CNV was 100% for SNVs, indels, and CNVs; interpretive clinical specificity relative to CFTR2 was 99.5%. NGS + CNV detected 58 ARCs, 18 of whom would have gone undetected with CF23 alone. Most ARCs (89% screened preconceptionally, 56% prenatally) altered pregnancy management, and no significant differences were observed between ARCs with or without at least one non-CF23 variant.
CONCLUSION: Modern NGS and variant interpretation enable accurate sequencing-based CF screening. Limiting screening to 23 variants does not improve analytical validity, clinical validity, or clinical utility, but does fail to detect approximately 30% (18/58) of ARCs.

PMID: 31036917 [PubMed - as supplied by publisher]

Measuring lung function in airways diseases: current and emerging techniques.

Thorax. 2019 Apr 29;:

Authors: Petousi N, Talbot NP, Pavord I, Robbins PA

Abstract
Chronic airways diseases, including asthma, COPD and cystic fibrosis, cause significant morbidity and mortality and are associated with high healthcare expenditure, in the UK and worldwide. For patients with these conditions, improvements in clinical outcomes are likely to depend on the application of precision medicine, that is, the matching of the right treatment to the right patient at the right time. In this context, the identification and targeting of 'treatable traits' is an important priority in airways disease, both to ensure the appropriate use of existing treatments and to facilitate the development of new disease-modifying therapy. This requires not only better understanding of airway pathophysiology but also an enhanced ability to make physiological measurements of disease activity and lung function and, if we are to impact on the natural history of these diseases, reliable measures in early disease. In this article, we outline some of the key challenges faced by the respiratory community in the management of airways diseases, including early diagnosis, disease stratification and monitoring of therapeutic response. In this context, we review the advantages and limitations of routine physiological measurements of respiratory function including spirometry, body plethysmography and diffusing capacity and discuss less widely used methods such as forced oscillometry, inert gas washout and the multiple inert gas elimination technique. Finally, we highlight emerging technologies including imaging methods such as quantitative CT and hyperpolarised gas MRI as well as quantification of lung inhomogeneity using precise in-airway gas analysis and mathematical modelling. These emerging techniques have the potential to enhance existing measures in the assessment of airways diseases, may be particularly valuable in early disease, and should facilitate the efforts to deliver precision respiratory medicine.

PMID: 31036773 [PubMed - as supplied by publisher]

Activity of antibiotics against Staphylococcus aureus in an in vitro model of biofilms in the context of cystic fibrosis: influence of the culture medium.

Antimicrob Agents Chemother. 2019 Apr 29;:

Authors: Diaz Iglesias Y, Wilms T, Vanbever R, Van Bambeke F

Abstract
Staphylococcus aureus is a highly prevalent pathogen in the respiratory tract of young patients with cystic fibrosis (CF) and causes biofilm-related infections. Here, we set up an in-vitro model of biofilm grown in tryptic soy broth supplemented by glucose and NaCl (TGN) or in artificial sputum medium (ASM) and used it to evaluate on a pharmacodynamic basis the activity of antibiotics used in CF patients and active on staphylococci (meropenem, vancomycin, azithromycin, linezolid, rifampicin, ciprofloxacin, tobramycin). Rheological studies showed that ASM was more elastic than viscous, as also observed for sputa from CF patients, with elastic and viscous moduli respectively similar and slightly lower than those of CF sputa. Biofilms formed by MSSA ATCC 25923 and MRSA ATCC 33591 reached maturity after 24 h, with biomass (measured by crystal violet staining) and metabolic activity (assessed by following resazurin metabolization) being lower in ASM than in TGN, and viability (bacterial counts) being similar in both media. Full concentration-response curves of antibiotics obtained after 24 h incubation of biofilms showed that all antibiotics were drastically less potent and less efficient in ASM than in TGN towards viability, metabolic activity, and biomass. Tobramycin selected for small colony variants, specifically in biofilms grown in ASM; the auxotrophism of these variants could not be established. These data highlight the major influence exerted by the culture medium on S. aureus responsiveness to antibiotics in biofilms. Use of ASM may help to determine effective drug concentrations or to evaluate new therapeutic options against biofilms in CF patients.

PMID: 31036685 [PubMed - as supplied by publisher]

Mucoid Pseudomonas aeruginosa and regional inflammation in the cystic fibrosis lung.

J Cyst Fibros. 2019 Apr 26;:

Authors: Malhotra S, Hayes D, Wozniak DJ

Abstract
BACKGROUND: Pseudomonas aeruginosa is the prominent bacterial pathogen in the cystic fibrosis (CF) lung and contributes to significant morbidity and mortality. Though P. aeruginosa strains initially colonizing the CF lung have a nonmucoid colony morphology, they often mutate into mucoid variants that are associated with clinical deterioration. Both nonmucoid and mucoid P. aeruginosa variants are often co-isolated on microbiological cultures of sputum collected from CF patients. With regional variation in bronchiectasis, tissue damage, inflammation, and microbial colonization, lobar distribution of nonmucoid and mucoid P. aeruginosa variants may impact local microenvironments in the CF lung, but this has not been well-studied.
METHODS: We prospectively collected lobe-specific bronchoalveolar lavage (BAL) fluid from a CF patient cohort (n = 14) using a standardized bronchoscopic protocol where collection was performed in 6 lobar regions. The lobar BAL specimens were plated on P. aeruginosa-selective media and proinflammatory cytokines (IL-1, TNF, IL-6 and IL-8) were measured via cytokine array. Correlations between infecting P. aeruginosa variants (nonmucoid, mucoid, or mixed-variant populations), the lobar regions in which these variants were found, and regional proinflammatory cytokine concentrations were measured.
RESULTS: P. aeruginosa mucoid and nonmucoid variants were homogenously distributed throughout the CF lung. However, infection with mucoid variants (found within single- or mixed-variant populations) was associated with significantly greater regional inflammation. The upper and lower lobes of the CF lung did not exhibit differences in inflammatory cytokine concentrations.
CONCLUSIONS: Mucoid P. aeruginosa infection is a microbial determinant of regional inflammation within the CF lung.

PMID: 31036488 [PubMed - as supplied by publisher]

Early glucose abnormalities are associated with pulmonary inflammation in young children with cystic fibrosis.

J Cyst Fibros. 2019 Apr 26;:

Authors: Prentice BJ, Ooi CY, Strachan RE, Hameed S, Ebrahimkhani S, Waters SA, Verge CF, Widger J

Abstract
BACKGROUND: Children with CF are insulin deficient from infancy but very little is known about the impact of glucose abnormalities in early life. We aimed to identify and describe interstitial glucose levels in CF children <6 years and to evaluate the association with pulmonary infection and inflammation.
METHODS: We assessed 18 children (5 females) with median age of 3.2 years (range 0∙9-5.5) with Continuous Glucose Monitoring for 3 days. Bronchoalveolar lavage (BAL) fluid was cultured for known pathogenic microbial agents and assessed for total white blood cells, percentage of neutrophils and IL-8 level.
RESULTS: Peak sensor glucose (SG) was >11.1 mmol/L in 39% of participants. The percentage neutrophil count on BAL was positively correlated with elevated SG (peak SG rs = 0.48, p = .044) and with glucose variability (SG standard deviation r = 0.62, β = 38.5, p = .006). BAL IL-8 level was significantly correlated with all measures of CGM hyperglycemia including % time > 7.8 mmol/L (p = .008) and standard deviation (p < .001). Participants with a history of Pseudomonas aeruginosa had a higher % time > 7.8 mmol/L glucose (16% versus 3%, p = .015).
CONCLUSION: Children with CF frequently demonstrate elevated SG levels before age 6 years, which are associated with increased pulmonary inflammation and Pseudomonas aeruginosa infection. Transient SG elevations into the diabetic range (≥11.1 mmol/L) were identified in children from 1 year of age.

PMID: 31036487 [PubMed - as supplied by publisher]

Cystic fibrosis program characteristics associated with adoption of 2013 infection prevention and control recommendations.

Am J Infect Control. 2019 Apr 26;:

Authors: Stoudemire W, Jiang X, Zhou JJ, Maykowski P, Kosorok MR, Muhlebach MS, Saiman L

Abstract
BACKGROUND: The Cystic Fibrosis (CF) Foundation disseminated an updated guideline for infection prevention and control (IP&C) practices for CF care programs in 2013. Assessing adoption rates of IP&C recommendations is crucial to evaluate their impact.
METHODS: CF care programs provided their written IP&C policies for CF. Policies were analyzed to determine adoption of selected recommendations new in 2013, as well as recommendations made in both 2003 and 2013. Weighted adoption scores were analyzed for association with program characteristics.
RESULTS: The median number of new recommendations adopted by each program was 7 (mean 6.3, range 0-9). The most commonly adopted new recommendations were universal mask use by patients in both inpatient and outpatient settings (85% and 87%, respectively) and contact precautions for CF patients in inpatient and outpatient settings (90% for both). The least frequently adopted new recommendations were the "6-foot rule" in inpatient settings (n = 66, 53%) and auditing disinfection of surfaces in clinic (n = 64, 49%). Larger program size was associated with a higher weighted adoption score (odds ratio [OR] 1.9, P =.02).
CONCLUSIONS: Whereas most programs adopted more than one-half of the selected IP&C recommendations assessed, adoption was variable. Efforts to improve adoption of IP&C recommendations should focus on smaller programs with fewer resources.

PMID: 31036402 [PubMed - as supplied by publisher]

Efficacy of model-based iterative reconstruction in cystic fibrosis assessment using CT.

Clin Radiol. 2019 Apr 26;:

Authors: Lin S, Lin M, Lau KK

Abstract
AIM: To evaluate the efficacy of model-based iterative reconstruction (MBIR) constructed non-enhanced ultra-low dose (ULD) computed tomography (CT) of the chest to evaluate cystic fibrosis (CF) pathology.
MATERIALS AND METHODS: ULD-CT was compared with chest X-ray and standard adaptive statistical iterative reconstructed (ASIR) non-enhanced low-dose CT (LD-CT). The effective radiation dose was calculated from the recorded dose-length product (DLP) values and compared between the two CT methods. Identification of pathology was compared between ULD-CT and chest X-ray. It was hypothesised that ULD-CT would be superior to chest X-ray in the identification of CF pathology at lower doses than LD-CT.
RESULTS: The mean effective radiation dose of ULD-CT was 0.073 mSv, comparable to one chest X-ray, which was a 94% reduction compared to LD-CT. Compared to chest X-ray, ULD-CT detected on average, 2.3 more regions of bronchiectasis per study and better delineated varicose and cystic forms of bronchiectasis (p≤0.0001). ULD-CT identified four-times more mucous plugging than chest X-ray (p<0.000001) and twice the amount of consolidation (p=0.0002).
CONCLUSION: ULD-CT is superior to chest X-ray in quantifying CF disease and achieves remarkable radiation doses significantly lower than LD-CT, comparable to one chest radiograph. The present results suggest that MBIR-constructed ULD-CT is an effective imaging technique for CF surveillance, with potential applications in other disease settings.

PMID: 31036312 [PubMed - as supplied by publisher]

A GRIM fate for human neutrophils in airway disease.

J Leukoc Biol. 2018 10;104(4):657-659

Authors: Mitchell TC

PMID: 30066961 [PubMed - indexed for MEDLINE]

Microbiologic changes observed over 48 weeks of treatment with inhaled liposomal ciprofloxacin in subjects with non-cystic fibrosis bronchiectasis and chronic Pseudomonas aeruginosa lung infection.

Clin Microbiol Infect. 2019 Apr 26;:

Authors: VanDevanter DR, Gonda I, Dahms J, Cipolla D, Davis AM, Chalmers JD, Froehlich J

Abstract
OBJECTIVES: Non-cystic fibrosis bronchiectasis (NCFBE) with Pseudomonas aeruginosa (Pa) has been associated with increased pulmonary exacerbation (PEx) and mortality risk. European Respiratory Society guidelines conditionally recommend inhaled antimicrobials for persons with NCFBE, Pa, and ≥3 PEx/year. We report microbiologic results of two randomized, 48-week placebo-controlled trials of ARD-3150 (inhaled liposomal ciprofloxacin) in NCFBE subjects with Pa and PEx history [Lancet Respir Med 2019;7:213-26].
METHODS: Respiratory secretions from 582 subjects receiving up to six 28-day on/off treatment cycles were analyzed for sputum Pa, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Escherichia coli densities, Pa susceptibilities to ciprofloxacin and nine other antimicrobials, and prevalence of other bacterial opportunists. Associations between PEx risk and sputum density, antimicrobial susceptibility, and opportunist prevalence changes were studied.
RESULTS: Sputum Pa density reductions from Baseline after ARD-3150 treatments ranged from 1.77 [95%CI 2.13, 1.40] versus 0.54 [0.89, 0.19] log10CFU/gram for placebo (second period) to 2.07 [2.45, 1.69] versus 0.70 [1.11, 0.29] log10CFU/gram for placebo (fourth period) with only modest correlation between density reduction magnitude and PEx benefit. ARD-3150 (but not placebo) treatment was associated with increased Pa ciprofloxacin minimum inhibitory concentrations (MICs) but not emergence of other bacterial opportunists across the study; ciprofloxacin MIC50 increased from 0.5 to 1 mcg/mL, MIC90 increased from 4 to 16 mcg/mL. Other antimicrobial MICs were mostly unaffected.
CONCLUSION: Microbiologic changes over 48 weeks of ARD-3150 treatment appear modest. Ciprofloxacin (but not other antimicrobial) susceptibility decreases were observed that did not appear to preclude PEx risk reduction benefit.

PMID: 31035017 [PubMed - as supplied by publisher]

Osteopathic Manipulative Medicine Consultations for Hospitalized Patients.

J Am Osteopath Assoc. 2019 May 01;119(5):299-306

Authors: Levy VJ, Holt CT, Haskins AE

Abstract
Context: Although osteopathic manipulative treatment (OMT) is predominantly known for its benefits in improving musculoskeletal pain, many studies have examined the effects of OMT on hospitalized patients with a variety of conditions, showing improved outcomes in conditions such as pneumonia, postoperative and postpartum recovery, preterm newborn recovery, and newborn feeding dysfunction.
Objective: To determine the reasons osteopathic manipulative medicine (OMM) consultations are being ordered at a tertiary care teaching hospital.
Methods: This descriptive study was conducted at an academic medical center with a well-established electronic health record system. A retrospective review examined data on all OMM consultations between January 1, 2015, and June 30, 2015. Reasons for consultations in a free text field were grouped into categories of "primary reason for consult" by a single reviewer. Demographics and patient location were also assessed.
Results: Of 1310 total consultations included in the study, 620 (47.0%) listed a musculoskeletal complaint as the primary or only reason for a consultation, 231 (18.0%) of which were for back pain, followed by neck pain (69 [5.0%]) and headache (46 [4.0%]). The next most common reason for consultation was for newborn feeding difficulty (352 [27.0%]) or other newborn consultation (66 [5.0%]). A total of 272 consultations (21.0%) were not limited to musculoskeletal complaints and included general nonspecific discomfort (96 [7.0%]) or respiratory complaint (53 [4.0%]). A total of 209 (16.0%) consultations noted patients to be postoperative; 124 (9.5%) to be postpartum; 57 (4.4%) to have cystic fibrosis; and 21 (1.6%) to have constipation.
Conclusion: The majority of inpatient OMM consultations were placed for musculoskeletal complaints, followed by newborn feeding problems. Although it is clear that some physicians think that OMT will help their patients for the aforementioned conditions, the number was still quite low, suggesting that many physicians may be unaware that OMT can help patients with conditions such as respiratory disorder, postoperative recovery, and constipation. There are many opportunities for treatment teams to be ordering OMM consultations as a way to reduce morbidity in their patients.

PMID: 31034068 [PubMed - in process]

Oxidative stress and abnormal bioactive lipids in early cystic fibrosis lung disease.

J Cyst Fibros. 2019 Apr 25;:

Authors: Scholte BJ, Horati H, Veltman M, Vreeken RJ, Garratt LW, Tiddens HAWM, Janssens HM, Stick SM, Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF)

Abstract
BACKGROUND: Clinical data indicate that airway inflammation in children with cystic fibrosis (CF) arises early, is associated with structural lung damage, and predicts progression. In bronchoalveolar lavage fluid (BALF) from CFTR mutant mice, several aspects of lipid metabolism are abnormal that contributes to lung disease. We aimed to determine whether lipid pathway dysregulation is also observed in BALF from children with CF, to identify biomarkers of early lung disease and potential therapeutic targets.
METHODS: A comprehensive panel of lipids that included Sphingolipids, oxylipins, isoprostanes and lysolipids, all bioactive lipid species known to be involved in inflammation and tissue remodeling, were measured in BALF from children with CF (1-6 years, N = 33) and age-matched non-CF patients with unexplained inflammatory disease (N = 16) by HPLC-MS/MS. Lipid data were correlated with chest CT scores and BALF inflammation biomarkers.
RESULTS: The ratio of long chain to very long chain ceramide species (LCC/VLCC) and lysolipid levels were enhanced in CF compared to non-CF patients, despite comparable neutrophil counts and bacterial load. In CF patients both LCC/VLCC and lysolipid levels correlated with inflammation and chest CT scores. The ceramide precursors Sphingosine, Sphinganine, Sphingomyelin, correlated with inflammation, whilst the oxidative stress marker isoprostane correlated with inflammation and chest CT scores. No correlation between lipids and current bacterial infection in CF (N = 5) was observed.
CONCLUSIONS: Several lipid biomarkers of early CF lung disease were identified, which point toward potential disease monitoring and therapeutic approaches that can be used to complement CFTR modulators.

PMID: 31031161 [PubMed - as supplied by publisher]

Mapping the sites of localization of epithelial sodium channel (ENaC) and CFTR in segments of the mammalian epididymis.

J Mol Histol. 2019 Apr;50(2):141-154

Authors: Sharma S, Hanukoglu I

Abstract
The sperm produced in the seminiferous tubules pass through the rete testis, efferent ducts, and epididymis. The epididymis has three distinct regions known as caput, corpus, and cauda. The transit through the epididymis is an essential process in sperm maturation. The lumen of each epididymal region has a unique fluid composition regulated by many ion channels and transporters in the epithelial cells. The objective of this study was to map the sites of localization of ion channels ENaC and CFTR along the length of the mouse and rat epididymis using confocal microscopic imaging. The integrity of the fine structure of the tissues was verified by fluorescent phalloidin staining of actin filaments visualized by high-resolution confocal microscopy. The 2D and 3D images showed preservation of the stereocilia. Based on these images we determined morphometric parameters of the epithelial cells and ducts. ENaC and CFTR immunofluorescence appeared almost continuously on the apical membrane of caput and in smooth muscle myoid cells. In cauda, CFTR expression was observed continuously in long stretches of epithelium interrupted by clusters of cells that showed no CFTR expression. Similar patterns of localization were observed in both mouse and rat samples. Mutations in the CFTR gene are known to result in male infertility. Based on the widespread presence of ENaC along the epididymis we suggest that mutations in ENaC subunits may also be associated with male infertility. The diverse phenotypes associated with CFTR mutations may be due to malfunction of CFTR at specific subcellular locations in the male reproductive system.

PMID: 30659401 [PubMed - indexed for MEDLINE]

Combination therapy.

Nat Med. 2019 01;25(1):19

Authors: Stower H

Abstract

PMID: 30617328 [PubMed - indexed for MEDLINE]

Reply to 'F508del-CFTR is not corrected by thymosin α1'.

Nat Med. 2018 07;24(7):891-893

Authors: Romani L, Stincardini C, Giovagnoli S, Paci M, Villella VR, Sforna L, Renga G, Bellet MM, Costantini C, Puccetti P, Kroemer G, Maiuri L, Pessia M, Goldstein A, Garaci E

PMID: 29942090 [PubMed - indexed for MEDLINE]

Modulation of glucose-related metabolic pathways controls glucose level in airway surface liquid and fight oxidative stress in cystic fibrosis cells.

J Bioenerg Biomembr. 2019 Apr 27;:

Authors: Favia M, de Bari L, Lassandro R, Atlante A

Abstract
Direct and indirect evidences show that elevated glucose concentrations in airway surface liquid (ASL) promote lung infection by pathogens, playing a role in the progression of the Cystic Fibrosis (CF) disease. The joint action of transporter/s for glucose and of the cellular enzymes is essential in order to try to lower ASL glucose level. Inside the cell, the glycolysis and the pentose phosphate pathway (PPP) compete for the utilization of glucose-6-phosphate (G6P), the product in which glucose, after entry within the cell and phosphorylation, is trapped. The study aims to clarify whether, modulating the activity of enzymatic proteins and/or the level of metabolites/cofactors, involved in intracellular glucose utilization, a lowering of the extracellular glucose level in CF occurs. Biochemical approaches have enabled us to understand i) how G6P is shunted between glycolysis and PPP and ii) that mitochondria, more than enzymes/cofactors participating to the two cell glucose utilization pathways, are protagonists of the scene in counteracting the high ASL glucose level as well as oxidative stress in CF.

PMID: 31030390 [PubMed - as supplied by publisher]

Developmental and behavioral problems in preschool-aged primary ciliary dyskinesia patients.

Eur J Pediatr. 2019 Apr 27;:

Authors: Zengin Akkus P, Gharibzadeh Hizal M, Ilter Bahadur E, Ozmert EN, Eryilmaz Polat S, Ozdemir G, Karahan S, Yalcin E, Dogru Ersoz D, Kiper N, Ozcelik U

Abstract
Primary ciliary dyskinesia (PCD) causes a broad spectrum of disease. This study aims to explore the developmental, behavioral, and social-emotional aspects of preschool-aged children with PCD. Fourteen PCD, 17 cystic fibrosis (CF) patients and 15 healthy subjects were enrolled. Developmental features of the participants were evaluated with Ages and Stages Questionnaire. Parents of participants filled out the Child Behavior Checklist (CBCL). The number of children screened positive for developmental delay was statistically higher in the PCD group. Higher numbers of children with PCD were screened positive for developmental delay in communication and problem-solving domains. Delay in fine motor skill domain was more common in children with PCD and CF compared to healthy subjects. There was no difference among the three groups in terms of gross motor and personal-social development. None of the children in all three groups was shown to have social-emotional problems. In CBCL, patients with CF had higher internalizing problem scores. Externalizing and total problem scores did not differ between the three groups. However, among PCD patients, children with developmental delay on more than one domain had higher externalizing and total problem scores.Conclusion: The current study revealed that positive screening for developmental delay is more common in preschool-aged PCD patients compared to patients with CF and healthy children. What is Known: • Intelligence scores of school-aged PCD patients are similar to healthy subjects despite their higher internalizing problem scores on Child Behavior Checklist (CBCL). • School-aged PCD patients exhibit higher hyperactivity and inattention findings. What is New: • Positive screening for developmental delay in communication, problem-solving and fine motor skills is more common in preschool-aged PCD patients. • Preschool-aged PCD patients screened positive for developmental delay in more than one domain have higher externalizing and total problem scores on CBCL.

PMID: 31030258 [PubMed - as supplied by publisher]

Lavage lipidomics signatures in children with cystic fibrosis and protracted bacterial bronchitis.

J Cyst Fibros. 2019 Apr 24;:

Authors: Seidl E, Kiermeier H, Liebisch G, Ballmann M, Hesse S, Paul-Buck K, Ratjen F, Rietschel E, Griese M

Abstract
BACKGROUND: Balanced composition of a well-functioning pulmonary surfactant is crucial and essential for normal breathing. Here, we explored whether the composition of lipids recovered by broncho-alveolar lavage (BAL) in children with cystic fibrosis (CF) differ from children with protracted bacterial bronchitis (PBB) and controls. We wanted to differentiate, if alterations are primarily caused by the disease process or secondary due to an increased amount of cell-membrane lipids derived from inflammatory cells.
METHODS: Comprehensive lipidomics profiles of BAL fluid from children diagnosed with CF, PBB and controls were generated by electrospray ionization tandem mass spectrometry analysis. BAL cell differential and numbers were examined.
RESULTS: 55 children (37 patients with CF, 8 children with PBB and 10 controls) were included in this study. Results showed comparable total quantities of lipids in all groups. Phospholipids were the major lipid fraction and similar in all groups, whereas the fractions of cholesteryl esters were less and of free cholesterol were increased in children with CF. Among the phospholipids, patients with CF had higher proportion of the non-surfactant membrane-lipids in the classes phosphatidylethanolamine based plasmalogens (PE P), phosphatidylethanolmine (PE) and phosphatidylserine (PS), but a lower proportion of phosphatidylcholine (PC) compared to healthy controls. No such changes were identified in the BAL fluid of children diagnosed with PBB. No differences were observed for the surfactant lipids dipalmitoyl-phosphatidylcholin (PC 32:0) and phosphatidylglycerol (PG).
CONCLUSIONS: In CF patients with neutrophilic airway inflammation the lipid composition for surfactant phospholipid components were unchanged, whereas alteration in lipid profile were characteristic for those found in membranes of inflammatory cells. We suspect that the changes in CF were caused by the prolonged inflammation in contrast to a relatively short standing process in PBB.

PMID: 31029606 [PubMed - as supplied by publisher]

The role of geographical location and climate on recurrent Pseudomonas infection in young children with Cystic Fibrosis.

J Cyst Fibros. 2019 Apr 24;:

Authors: Warrier R, Skoric B, Vidmar S, Carzino R, Ranganathan S

Abstract
OBJECTIVES: To determine the association between residence and climate with risk of Pseudomonas aeruginosa (Pa) and other respiratory outcomes.
METHODS: We performed regular bronchoalveolar lavage and upper airway cultures in young children with CF to identify Pa infection. Children were classified for residence as regional or metropolitan. Bronchiectasis was detected on periodic chest computed tomography scans. Multilocus sequence typing determined Pa genotype. Lung function was assessed using Multiple Breath Washout.
RESULTS: Of infants diagnosed with CF between 2006 and 2017, 129 were included in the study. Seven patients moved between metropolitan and regional Victoria and were excluded from analysis. Of the remaining 122 subjects, seventy-four (61%) children resided in metropolitan areas and over half (54%) were male. There were 83 Pa episodes in the 122 children who lived consistently in a geographical location. The incidence rate was 0.15 episodes per person-years. We found weak evidence of a 15% increase in the rate of Pa episodes with increasing average annual maximum temperature (95%CI (0.98, 1.36); p = .086), while the rate of Pa acquision decreased with average annual 3 pm humidity (IRR = 0.96; 95%CI(0.92, 1.0008); p = .054). The rate of Pa episodes was 2.1 times higher in regional participants (95%CI (1.4, 3.1); p = .001) and risk of second episode was more than five times greater (HR 5.7; 95%CI 1.9, 17); p = .002). No difference between regions in lung clearance index and presence of bronchiectasis was detected.
CONCLUSION: Regional residence is associated with risk of acquiring recurrent infection with Pseudomonas aeruginosa in young children with CF.

PMID: 31029605 [PubMed - as supplied by publisher]