scholarly journals Inflammation in children with cystic fibrosis: contribution of bacterial production of long-chain fatty acids

2021 ◽  
Author(s):  
Erin Felton ◽  
Aszia Burrell ◽  
Hollis Chaney ◽  
Iman Sami ◽  
Anastassios C. Koumbourlis ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Fatty Acid ◽  
Antibiotic Treatment ◽  
Bacterial Production ◽  
Clinical Status ◽  
Achromobacter Xylosoxidans ◽  
List Type ◽  
Future Studies ◽  
Long Chain

Abstract Background Cystic fibrosis (CF) affects >70,000 people worldwide, yet the microbiologic trigger for pulmonary exacerbations (PExs) remains unknown. The objective of this study was to identify changes in bacterial metabolic pathways associated with clinical status. Methods Respiratory samples were collected at hospital admission for PEx, end of intravenous (IV) antibiotic treatment, and follow-up from 27 hospitalized children with CF. Bacterial DNA was extracted and shotgun DNA sequencing was performed. MetaPhlAn2 and HUMAnN2 were used to evaluate bacterial taxonomic and pathway relative abundance, while DESeq2 was used to evaluate differential abundance based on clinical status. Results The mean age of study participants was 10 years; 85% received combination IV antibiotic therapy (beta-lactam plus a second agent). Long-chain fatty acid (LCFA) biosynthesis pathways were upregulated in follow-up samples compared to end of treatment: gondoate (p = 0.012), oleate (p = 0.048), palmitoleate (p = 0.043), and pathways of fatty acid elongation (p = 0.012). Achromobacter xylosoxidans and Escherichia sp. were also more prevalent in follow-up compared to PEx (p < 0.001). Conclusions LCFAs may be associated with persistent infection of opportunistic pathogens. Future studies should more closely investigate the role of LCFA production by lung bacteria in the transition from baseline wellness to PEx in persons with CF. Impact Increased levels of LCFAs are found after IV antibiotic treatment in persons with CF. LCFAs have previously been associated with increased lung inflammation in asthma. This is the first report of LCFAs in the airway of persons with CF. This research provides support that bacterial production of LCFAs may be a contributor to inflammation in persons with CF. Future studies should evaluate LCFAs as predictors of future PExs.

scholarly journals Age-dependent effects of cord blood long-chain PUFA composition on BMI during the first 10 years of life

2014 ◽  
Vol 111 (11) ◽  
pp. 2024-2031 ◽  
Author(s):  
Marie Standl ◽  
Elisabeth Thiering ◽  
Hans Demmelmair ◽  
Berthold Koletzko ◽  
Joachim Heinrich
Keyword(s):  
Fatty Acid ◽  
Cord Blood ◽  
Phospholipid Fatty Acid ◽  
Birth Cohort Study ◽  
Related Factors ◽  
Pufa Ratio ◽  
Chain Pufa ◽  
Pufa Composition ◽  
Long Chain

In the present study, we investigated whether n-6 and n-3 long-chain PUFA (LC-PUFA) concentrations in cord blood (CB) serum are associated with BMI up to 10 years of age, after accounting for LC-PUFA composition at 2, 6 and 10 years. The study was based on 388 participants of the German LISAplus (Influence of Lifestyle-Related Factors on the Immune System and the Development of Allergies in Childhood Plus the Influence of Traffic Emissions and Genetics) birth cohort study carried out in Munich. BMI was measured at 2, 6 and 10 years of age. Serum phospholipid fatty acid concentrations were measured by GC in CB and in blood collected at 2, 6 and 10 years of age. The association between n-3 LC-PUFA and n-6 LC-PUFA concentrations and n-6:n-3 LC-PUFA ratio in CB serum glycerophospholipids and BMI z-scores was assessed using linear mixed models adjusted for LC-PUFA composition at follow-up and potential confounders. Interaction terms between time of follow-up and LC-PUFA concentrations in CB were included. There was no consistent association between n-6 and n-3 LC-PUFA concentrations in CB and BMI over time. However, there was a significant interaction between n-6:n-3 LC-PUFA ratio in CB and time of follow-up with respect to BMI (P= 0·0415): a negative effect at 2 years; no effect at 6 years; a positive effect at 10 years. BMI up to 10 years of age may be influenced by the n-6:n-3 ratio in CB serum glycerophospholipids in a time-varying fashion. The present results thereby highlight the importance of considering age when examining associations between fatty acid concentrations and BMI.

scholarly journals Circulating Very-Long-Chain SFA Concentrations Are Inversely Associated with Incident Type 2 Diabetes in US Men and Women

2019 ◽  
Vol 150 (2) ◽  
pp. 340-349 ◽  
Author(s):  
Andres V Ardisson Korat ◽  
Vasanti S Malik ◽  
Jeremy D Furtado ◽  
Frank Sacks ◽  
Bernard Rosner ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Arachidic Acid ◽  
Plasma Concentrations ◽  
Behenic Acid ◽  
Men And Women ◽  
Long Chain

ABSTRACT Background Very-long-chain SFAs (VLCSFAs), such as arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0), have demonstrated inverse associations with cardiometabolic conditions, although more evidence is needed to characterize their relation with risk of type 2 diabetes (T2D). In addition, little is known regarding their potential dietary and lifestyle predictors. Objective We aimed to examine the association of plasma and erythrocyte concentrations of VLCSFAs with incident T2D risk. Methods We used existing measurements of fatty acid concentrations in plasma and erythrocytes among 2854 and 2831 participants in the Nurses’ Health Study (NHS) and Health Professionals Follow-Up Study (HPFS), respectively. VLCSFAs were measured using GLC, and individual fatty acid concentrations were expressed as a percentage of total fatty acids. Incident T2D cases were identified by self-reports and confirmed by a validated supplementary questionnaire. Cox proportional hazards regression was used to evaluate the association between VLCSFAs and T2D, adjusting for demographic, lifestyle, and dietary variables. Results During 39,941 person-years of follow-up, we documented 243 cases of T2D. Intakes of peanuts, peanut butter, vegetable fat, dairy fat, and palmitic/stearic (16:0–18:0) fatty acids were significantly, albeit weakly, correlated with plasma and erythrocyte VLCSFA concentrations (|rs| ≤ 0.19). Comparing the highest with the lowest quartiles of plasma concentrations, pooled HRs (95% CIs) were 0.51 (0.35, 0.75) for arachidic acid, 0.43 (0.28, 0.64) for behenic acid, 0.40 (0.27, 0.61) for lignoceric acid, and 0.41 (0.27, 0.61) for the sum of VLCSFAs, after multivariate adjustments for demographic, lifestyle, and dietary factors. For erythrocyte VLCSFAs, only arachidic acid and behenic acid concentrations were inversely associated with T2D risk. Conclusions Our findings suggest that, in US men and women, higher plasma concentrations of VLCSFAs are associated with lower risk of T2D. More research is needed to understand the mechanistic pathways underlying these associations.

scholarly journals 730. Cefiderocol for the Treatment of Achromobacter xylosoxidans Infections in Two Lung Transplant Patients with Cystic Fibrosis

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S326-S327 ◽  
Author(s):  
Nathaniel C Warner ◽  
Luther Bartelt ◽  
Anne Lachiewicz ◽  
Anne Lachiewicz ◽  
Kathleen Marie Tompkins ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Transplant ◽  
Achromobacter Xylosoxidans ◽  
Transplant Recipients ◽  
Compassionate Use ◽  
Chronic Infections ◽  
Gram Negative ◽  
First Case ◽  
Lung Transplant Recipients

Abstract Background Achromobacter xylosoxidansis a highly resistant Gram-negative bacterium that causes chronic infections in patients with cystic fibrosis (CF). Treatment options for A. xylosoxidans are limited. In the peri-lung transplant setting, the treatment of A. xylosoxidans infections is especially challenging. Cefiderocol is a novel siderophore cephalosporin antibiotic with broad anti-Gram-negative activity, including against A. xylosoxidans. We report here two cases of compassionate use of cefiderocol in CF lung transplant recipients with A. xylosoxidans infection. Methods Cefiderocol was obtained through compassionate use from its manufacturer, with approval from the local Institutional Review Board. In the first case, it was used as salvage treatment, and in the second case as a planned part of the peri-transplant regimen. Results A male in his 20s with CF and a trimethoprim-sulfamethoxazole (TMP-SMX) allergy was chronically colonized by A. xylosoxidans, which was sensitive only to piperacillin–tazobactam (PIP-TAZ), and TMP-SMX. After lung transplant, he developed A. xylosoxidansbacteremia, and extended-infusion PIP-TAZ was started. Repeat bronchoscopy grew A. xylosoxidans. Due to lack of improvement, cefiderocol was added to PIP-TAZ with rapid clinical improvement. However, after completing his course, he was readmitted with A. xylosoxidans pneumonia. He was treated with 6 weeks of cefiderocol and imipenem and has been well since with an 8-month follow-up. In the second case, cefiderocol was used as part of the planned peri-transplant regimen for a female with CF in her late teens, with chronic A. xylosoxidans colonization, which was intermediate to PIP-TAZ, and resistant to all other drugs tested. Her native lungs grew 4+ A. xylosoxidans at the time of explant. Post-transplant, she was treated with 5 weeks of meropenem and 6 weeks of cefiderocol. At four-month follow-up, she is doing well. However, she is asymptomatically colonized with A. xylosoxidanspost-transplant. Isolates from both cases were susceptible to cefiderocol (case #1 MIC = 0.12; case #2 pretreatment MIC = 1, post-treatment MIC. Conclusion Cefiderocol may be a useful option for lung transplant recipients with A. xylosoxidans infections. Disclosures Anne Lachiewicz, MD, MPH, MicroGenDx: Consultant; Shionogi: Consultant.

scholarly journals Detection and monitoring of lung inflammation in cystic fibrosis during respiratory tract exacerbation using diffusion-weighted magnetic resonance imaging

2017 ◽  
Vol 50 (1) ◽  
pp. 1601437 ◽  
Author(s):  
Pierluigi Ciet ◽  
Silvia Bertolo ◽  
Mirco Ros ◽  
Eleni Rosalina Andrinopoulou ◽  
Valentina Tavano ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Cystic Fibrosis ◽  
Magnetic Resonance ◽  
Lung Function ◽  
Respiratory Tract ◽  
Antibiotic Treatment ◽  
Clinical Status ◽  
Control Group ◽  
Resonance Imaging ◽  
Weighted Magnetic Resonance Imaging

The aim was to investigate whether diffusion-weighted magnetic resonance imaging (DWI) detects and monitors inflammatory and lung function changes during respiratory tract exacerbations (RTE) treatment in patients with cystic fibrosis (CF).29 patients with RTE underwent DWI pre- and post-antibiotic treatment. A control group of 27 stable patients, matched for age and sex, underwent DWI with the same time gap as those undergoing RTE treatment. Clinical status and lung function were assessed at each DWI time point. The CF-MRI scoring system was used to assess structural lung changes in both CF groups.Significant reduction in the DWI score over the course of antibiotic treatment (p<0.0001) was observed in patients with RTE, but not in the control group. DWI score had a strong inverse correlation with clinical status (r=−0.504, p<0.0001) and lung function (r=−0.635, p<0.0001) in patients with RTE. Interestingly, there were persistent significant differences in the CF-MRI score between the RTE and control group at both baseline and follow-up (p<0.001), while the differences in DWI score were only observed at baseline (p<0.001).DWI is a promising imaging method for noninvasive detection of pulmonary inflammation during RTE, and may be used to monitor treatment efficacy of anti-inflammatory treatment.

scholarly journals Achromobacter xylosoxidans infection and resistance monitoring in adult cystic fibrosis patients

2021 ◽  
Vol 5 (7) ◽  
pp. 462-467
Author(s):  
V.R. Makhmutova ◽  
◽  
T.E. Gembitskaya ◽  
A.G. Chermensky ◽  
O.N. Titova ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Burkholderia Cepacia ◽  
Fatal Outcome ◽  
Burkholderia Cepacia Complex ◽  
Diffusion Method ◽  
Achromobacter Xylosoxidans ◽  
Disk Diffusion Method ◽  
Resistance Monitoring

Aim: to evaluate the infection rate and resistance of isolated Achromobacter xylosoxidans to carbapenems in adult cystic fibrosis patients (CF). Patients and Methods: a retrospective analysis of the results of culture test and time-of-flight mass spectrometry MALDI-TOF was conducted: 685 sputum samples of 58 adult CF patients for a period of 5 years (2016–2020). To assess the sensitivity to imipenem and meropenem, the agar gradient diffusion and disk diffusion method were used. Results: the incidence of infection with A. xylosoxidans in adult CF patients for the period from 2016 to 2020 when monitoring a single sample of patients (n=24) to evaluate the occurrence of this pathogen with increasing age ranged from 16.6% in 2016–2017, increasing to 37.5% in 2018–2019, and with a further reduction to 20.8% (associated with disease fatal outcome in 3 of the 9 infected patients). There was no statistically significant dependence of the fatal outcome on infection with A. xylosoxidans. When analyzing the entire pool of patients (n=58) from 2016 to 2020, the release frequency of Pseudomonas aeruginosa remains approximately the same, varying from 63.3% to 46.5% and maintaining a numerical advantage in all follow-up periods, while the A. xylosoxidans infection ranges from 13.7% to 39.3%. In 2016–2018, 50% of isolates were sensitive to carbapenems, in 2018 — 53.8% of isolates, in 2019–2020 — the activity of obtained isolates decreased to 37.5% and 30.7%, respectively. Conclusion: despite the dynamics of indicators and the sample size, the dynamics over 5 years maintained a group-wide proportion of microbiome species dominated primarily by Pseudomonas infection and A. xylosoxidans. In our follow-up, the activity of carbapenems in relation to A. xylosoxidans has almost halved. KEYWORDS: cystic fibrosis, Burkholderia cepacia complex, Achromobacter xylosoxidans, Pseudomonas aeruginosa, lethality, antibiotic resistance, carbapenems. FOR CITATION: Makhmutova V.R., Gembitskaya T.E., Chermensky A.G. et al. Achromobacter xylosoxidans infection and resistance monitoring in adult cystic fibrosis patients. Russian Medical Inquiry. 2021;5(7):462–467 (in Russ.). DOI: 10.32364/2587-6821-2021-5-7-462-467.

Relation between Fatty Acid Composition and Clinical Status or Genotype in Cystic Fibrosis Patients

2007 ◽  
Vol 51 (6) ◽  
pp. 541-549 ◽  
Author(s):  
Stephanie Van Biervliet ◽  
Griet Vanbillemont ◽  
Jean-Pierre Van Biervliet ◽  
Dimitri Declercq ◽  
Eddy Robberecht ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Acid Composition ◽  
Clinical Status
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