Cross-transmission is not the source of new Mycobacterium abscessus infections in a multi-centre cohort of cystic fibrosis patients.

Clin Infect Dis. 2019 Jun 19;:

Authors: Doyle RM, Rubio M, Dixon G, Hartley J, Klein N, Coll P, Harris KA

Abstract
BACKGROUND: Mycobacterium abscessus is an extensively drug resistant pathogen that causes pulmonary disease particularly in cystic fibrosis (CF) patients. Identifying direct patient-to-patient transmission of M. abscessus is critically important in directing infection control policy for the management of risk in CF patients. A variety of clinical labs have used molecular epidemiology to investigate transmission. However there is still conflicting evidence as to how M. abscessus is acquired and whether cross-transmission occurs. Recently labs have applied whole-genome sequencing (WGS) to investigate this further and in this study we investigate whether WGS can reliably identify cross-transmission in M. abscessus.
METHODS: We retrospectively sequenced the whole genomes of 145 M. abscessus isolates from 62 patients seen at four hospitals in two countries over 16 years.
RESULTS: We have shown that a comparison of a fixed number of core single nucleotide variants (SNVs) alone cannot be used to infer cross-transmission in M. abscessus but does provide enough information to replace multiple existing molecular assays. We detected one episode of possible direct patient-to-patient transmission in a sibling pair. We found that patients acquired unique M. abscessus strains even after spending considerable time on the same wards with other M. abscessus positive patients.
CONCLUSIONS: This novel analysis has demonstrated that the majority of patients in this study have not acquired M. abscessus through direct patient-patient transmission or a common reservoir. Tracking transmission using WGS will only realise its full potential with proper environmental screening as well as patient sampling.

PMID: 31225586 [PubMed - as supplied by publisher]

Paediatric and adult bronchiectasis: Specific management with coexisting asthma, COPD, rheumatological disease and inflammatory bowel disease.

Respirology. 2019 Jun 20;:

Authors: Maglione M, Aksamit T, Santamaria F

Abstract
Bronchiectasis, conventionally defined as irreversible dilatation of the bronchial tree, is generally suspected on a clinical basis and confirmed by means of chest high-resolution computed tomography. Clinical manifestations, including chronic productive cough and endobronchial suppuration with persistent chest infection and inflammation, may deeply affect quality of life, both in children/adolescents and adults. Despite many cases being idiopathic or post-infectious, a number of specific aetiologies have been traditionally associated with bronchiectasis, such as cystic fibrosis (CF), primary ciliary dyskinesia or immunodeficiencies. Nevertheless, bronchiectasis may also develop in patients with bronchial asthma; chronic obstructive pulmonary disease; and, less commonly, rheumatological disorders and inflammatory bowel diseases. Available literature on the development of bronchiectasis in these conditions and on its management is limited, particularly in children. However, bronchiectasis may complicate the clinical course of the underlying condition at any age, and appropriate management requires an integration of multiple skills in a team of complementary experts to provide the most appropriate care to affected children and adolescents. The present review aims at summarizing the current knowledge and available evidence on the management of bronchiectasis in the other conditions mentioned and focuses on the new therapeutic strategies that are emerging as promising tools for improving patients' quality of life.

PMID: 31222879 [PubMed - as supplied by publisher]

Prevalence and Etiology of Community-acquired Pneumonia in Immunocompromised Patients.

Clin Infect Dis. 2019 Apr 24;68(9):1482-1493

Authors: Di Pasquale MF, Sotgiu G, Gramegna A, Radovanovic D, Terraneo S, Reyes LF, Rupp J, González Del Castillo J, Blasi F, Aliberti S, Restrepo MI, GLIMP Investigators

Abstract
BACKGROUND: The correct management of immunocompromised patients with pneumonia is debated. We evaluated the prevalence, risk factors, and characteristics of immunocompromised patients coming from the community with pneumonia.
METHODS: We conducted a secondary analysis of an international, multicenter study enrolling adult patients coming from the community with pneumonia and hospitalized in 222 hospitals in 54 countries worldwide. Risk factors for immunocompromise included AIDS, aplastic anemia, asplenia, hematological cancer, chemotherapy, neutropenia, biological drug use, lung transplantation, chronic steroid use, and solid tumor.
RESULTS: At least 1 risk factor for immunocompromise was recorded in 18% of the 3702 patients enrolled. The prevalences of risk factors significantly differed across continents and countries, with chronic steroid use (45%), hematological cancer (25%), and chemotherapy (22%) the most common. Among immunocompromised patients, community-acquired pneumonia (CAP) pathogens were the most frequently identified, and prevalences did not differ from those in immunocompetent patients. Risk factors for immunocompromise were independently associated with neither Pseudomonas aeruginosa nor non-community-acquired bacteria. Specific risk factors were independently associated with fungal infections (odds ratio for AIDS and hematological cancer, 15.10 and 4.65, respectively; both P = .001), mycobacterial infections (AIDS; P = .006), and viral infections other than influenza (hematological cancer, 5.49; P < .001).
CONCLUSIONS: Our findings could be considered by clinicians in prescribing empiric antibiotic therapy for CAP in immunocompromised patients. Patients with AIDS and hematological cancer admitted with CAP may have higher prevalences of fungi, mycobacteria, and noninfluenza viruses.

PMID: 31222287 [PubMed - in process]

Structural identification of a hotspot on CFTR for potentiation.

Science. 2019 06 21;364(6446):1184-1188

Authors: Liu F, Zhang Z, Levit A, Levring J, Touhara KK, Shoichet BK, Chen J

Abstract
Cystic fibrosis is a fatal disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). Two main categories of drugs are being developed: correctors that improve folding of CFTR and potentiators that recover the function of CFTR. Here, we report two cryo-electron microscopy structures of human CFTR in complex with potentiators: one with the U.S. Food and Drug Administration (FDA)-approved drug ivacaftor at 3.3-angstrom resolution and the other with an investigational drug, GLPG1837, at 3.2-angstrom resolution. These two drugs, although chemically dissimilar, bind to the same site within the transmembrane region. Mutagenesis suggests that in both cases, hydrogen bonds provided by the protein are important for drug recognition. The molecular details of how ivacaftor and GLPG1837 interact with CFTR may facilitate structure-based optimization of therapeutic compounds.

PMID: 31221859 [PubMed - in process]

Clinical development of triple-combination CFTR modulators for cystic fibrosis patients with one or two F508del alleles.

ERJ Open Res. 2019 Apr;5(2):

Authors: Taylor-Cousar JL, Mall MA, Ramsey BW, McKone EF, Tullis E, Marigowda G, McKee CM, Waltz D, Moskowitz SM, Savage J, Xuan F, Rowe SM

Abstract
Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator gene (CFTR) that result in diminished quantity and/or function of the CFTR anion channel. F508del-CFTR, the most common CF-causing mutation (found in ∼90% of patients), causes severe processing and trafficking defects, resulting in decreased CFTR quantity and function. CFTR modulators are medications that increase the amount of mature CFTR protein (correctors) or enhance channel function (potentiators) at the cell surface. Combinations of CFTR correctors and potentiators (i.e. lumacaftor/ivacaftor, tezacaftor/ivacaftor) have demonstrated clinical benefit in subsets of patients. However, none are approved for patients with CF heterozygous for F508del-CFTR and a minimal function mutation, i.e. a mutation that produces either no protein or protein that is unresponsive to currently approved CFTR modulators. Next-generation CFTR correctors VX-659 and VX-445, each in triple combination with tezacaftor and ivacaftor, improve CFTR processing, trafficking and function in vitro and have demonstrated clinical improvements in phase 2 studies in patients with CF with one or two F508del-CFTR alleles. Here, we present the rationale and design of four randomised phase 3 studies, and their open-label extensions, evaluating VX-659 (ECLIPSE) or VX-445 (AURORA) plus tezacaftor and ivacaftor in patients with one or two F508del-CFTR alleles.

PMID: 31218221 [PubMed]

Cystic fibrosis disease severity correlates with plasma levels of desmosine and isodesmosine, biomarkers of elastin degradation.

ERJ Open Res. 2019 Apr;5(2):

Authors: Ma S, Geraghty P, Dabo A, McCarthy C, McElvaney NG, Turino GM

Abstract
Novel methodological approaches now demonstrate that the unique elastin degradation products desmosine and isodesmosine are detectable in plasma of cystic fibrosis patients and correlate to lung function, exacerbation frequency and disease progression http://bit.ly/2VwZOcx.

PMID: 31218219 [PubMed]

Novel Population Pharmacokinetic Approach to Explain the Differences between Cystic Fibrosis Patients and Healthy Volunteers via Protein Binding.

Pharmaceutics. 2019 Jun 18;11(6):

Authors: Shah NR, Bulitta JB, Kinzig M, Landersdorfer CB, Jiao Y, Sutaria DS, Tao X, Höhl R, Holzgrabe U, Kees F, Stephan U, Sörgel F

Abstract
The pharmacokinetics in patients with cystic fibrosis (CF) has long been thought to differ considerably from that in healthy volunteers. For highly protein bound β-lactams, profound pharmacokinetic differences were observed between comparatively morbid patients with CF and healthy volunteers. These differences could be explained by body weight and body composition for β-lactams with low protein binding. This study aimed to develop a novel population modeling approach to describe the pharmacokinetic differences between both subject groups by estimating protein binding. Eight patients with CF (lean body mass [LBM]: 39.8 ± 5.4kg) and six healthy volunteers (LBM: 53.1 ± 9.5kg) received 1027.5 mg cefotiam intravenously. Plasma concentrations and amounts in urine were simultaneously modelled. Unscaled total clearance and volume of distribution were 3% smaller in patients with CF compared to those in healthy volunteers. After allometric scaling by LBM to account for body size and composition, the remaining pharmacokinetic differences were explained by estimating the unbound fraction of cefotiam in plasma. The latter was fixed to 50% in male and estimated as 54.5% in female healthy volunteers as well as 56.3% in male and 74.4% in female patients with CF. This novel approach holds promise for characterizing the pharmacokinetics in special patient populations with altered protein binding.

PMID: 31216743 [PubMed]

Intranasal Corticosteroids for the Management of Chronic Rhinosinusitis or Nasal Polyposis in Cystic Fibrosis: A Review of Clinical Effectiveness

Book. 2019 03 18

Authors: Tran K, McCormack S

Abstract
The aim of this report is to review the clinical effectiveness of the use of intranasal corticosteroids for the management of cystic fibrosis related chronic rhinosinusitis or nasal polyposis.

PMID: 31219688

Reduced exercise ventilatory efficiency in Cystic Fibrosis adults with normal to moderately impaired lung function.

J Appl Physiol (1985). 2019 Jun 20;:

Authors: Di Paolo M, Teopompi E, Savi D, Crisafulli E, Longo C, Tzani P, Longo F, Ielpo A, Pisi G, Cimino G, Simmonds NJ, Neder JA, Chetta A, Palange P

Abstract
RATIONALE: Despite being a hallmark and an independent prognostic factor in several cardiopulmonary diseases, ventilatory efficiency - i.e. minute ventilation/carbon dioxide output relationship (V'E/V'CO2) has never been systematically explored in cystic fibrosis (CF).
OBJECTIVE: To provide a comprehensive frame of reference regarding measures of ventilatory efficiency in CF adults with normal to moderately impaired lung function and to confirm the hypothesis that V'E/V'CO2 is a sensitive marker of early lung disease.
METHODS: CF patients were divided into 3 groups according to their spirometry: normal (G1), mild impairment (G2) and moderate impairment (G3) in lung function. All participants underwent incremental cardiopulmonary exercise testing on a cycle-ergometer. Lowest V'E/V'CO2 ratio (nadir) and the slope and the intercept of the linear region of the V'E/V'CO2 relationship were contrasted in a two-center retrospective analysis involving 72 CF patients and 36 healthy controls (HC).
RESULTS: Compared to HC, CF patients had significantly higher V'E/V'CO2 nadir, slope and intercept (p<0.001, p<0.001 and p=0.049, respectively). Subgroup analysis revealed significant differences in nadir (p=0.001) and slope (p=0.012) values even between HC and G1. Dynamic hyperinflation related negatively with slope (p=0.045) and positively with intercept (p=0.001), whilst no impact on nadir was observed.
CONCLUSIONS: Ventilatory inefficiency is a clear feature of adults with CF, even among patients with normal spirometry. V'E/V'CO2 nadir seems to be the most reliable metric to describe ventilatory efficiency in CF adults. Further prospective studies are needed to clarify whether V'E/V'CO2 could represent an useful marker in the evaluation of early lung disease in CF.

PMID: 31219769 [PubMed - as supplied by publisher]

Late diagnosis and poor nutrition in cystic fibrosis diagnosed before implementation of newborn screening.

Acta Paediatr. 2019 Jun 19;:

Authors: Pedersen MG, Højte C, Olesen HV, Pressler T, Skov M

Abstract
AIM: Denmark has a high standard cystic fibrosis care. However, newborn screening was not implemented until 2016. This article describes the clinical status of cystic fibrosis patients at time of diagnosis prior to newborn screening.
METHODS: Patients diagnosed with cystic fibrosis in Denmark in 2010-2014 were reviewed using the Danish Cystic Fibrosis Registry as well as patient files. Parameters collected were age at diagnosis, gender, weight, height, forced expiratory volume at 1 second, cystic fibrosis transmembrane regulator-genotype, lung bacteriology at diagnosis and previous diagnoses.
RESULTS: A total of 63 patients were diagnosed in the study period. The most typical pre-cystic fibrosis diagnoses were asthma and pneumonia. The median age at diagnosis was 1.4 years for the pancreatic insufficient and 27.3 years for the pancreatic sufficient patients. Of the pancreatic insufficient patients, 21% had moderate to severe malnutrition with BMI below minus 2 SD and 40% had moderate to severe stunting with height below minus 2 SD.
CONCLUSION: Diagnosis was delayed considerably compared to diagnosis by newborn screening in other countries. Many cystic fibrosis patients diagnosed due to clinical symptoms were moderately to severely underweight or stunted at diagnosis This article is protected by copyright. All rights reserved.

PMID: 31218749 [PubMed - as supplied by publisher]

Response to Comment on "An extracellular matrix fragment drives epithelial remodeling and airway hyperresponsiveness".

Sci Transl Med. 2019 Jun 19;11(497):

Authors: Patel DF, Gaggar A, Blalock JE, Gregory LG, Lloyd CM, Snelgrove RJ

Abstract
We provide further evidence to support our assertion that PGP is a potent regulator of epithelial remodeling.

PMID: 31217333 [PubMed - in process]

Investigation of the Binding Affinity of a Broad Array of l-Fucosides with Six Fucose-Specific Lectins of Bacterial and Fungal Origin.

Molecules. 2019 Jun 18;24(12):

Authors: Thai Le S, Malinovska L, Vašková M, Mező E, Kelemen V, Borbás A, Hodek P, Wimmerová M, Csávás M

Abstract
Series of multivalent α-l-fucoside containing glycoclusters and variously decorated l-fucosides were synthesized to find potential inhibitors of fucose-specific lectins and study the structure-binding affinity relationships. Tri- and tetravalent fucoclusters were built using copper-mediated azide-alkyne click chemistry. Series of fucoside monomers and dimers were synthesized using various methods, namely glycosylation, an azide-alkyne click reaction, photoinduced thiol-en addition, and sulfation. The interactions between compounds with six fucolectins of bacterial or fungal origin were tested using a hemagglutination inhibition assay. As a result, a tetravalent, α-l-fucose presenting glycocluster showed to be a ligand that was orders of magnitude better than a simple monosaccharide for tested lectins in most cases, which can nominate it as a universal ligand for studied lectins. This compound was also able to inhibit the adhesion of Pseudomonas aeruginosa cells to human epithelial bronchial cells. A trivalent fucocluster with a protected amine functional group also seems to be a promising candidate for designing glycoconjugates and chimeras.

PMID: 31216664 [PubMed - in process]

Absence of evidence that respiratory viral infections influence pediatric lung transplantation outcomes: results of the CTOTC-03 study.

Am J Transplant. 2019 Jun 19;:

Authors: Sweet SC, Chin H, Conrad C, Hayes D, Heeger PS, Faro A, Goldfarb S, Melicoff-Portillo E, Mohanakumar T, Odim J, Schecter M, Storch GA, Visner G, Williams NM, Kesler K, Danziger-Isakov L

Abstract
Based on reports in adult lung transplant recipients, we hypothesized that community acquired respiratory viral infections (CARV) would be a risk factor for poor outcome after pediatric lung transplant. We followed 61 pediatric lung transplant recipients for 2+ years or until they met a composite primary endpoint including bronchiolitis obliterans syndrome (BOS)/obliterative bronchiolitis, re-transplantation or death. Blood, bronchoalveolar lavage and nasopharyngeal specimens were obtained with standard of care visits. Nasopharyngeal specimens were obtained with respiratory viral symptoms. Respiratory specimens were interrogated for respiratory viruses using multiplex PCR. Donor-specific HLA antibodies, self-antigens, and Elispot reactivity were also evaluated. Survival was 84% (1 year) and 68% (3 years). BOS incidence was 20% (1 year) and 38% (3 years). The primary endpoint was met in 46% of patients. CARV was detected in 156 patient visits (74% enterovirus/rhinovirus). We did not find a relationship between CARV recovery from respiratory specimens and the primary endpoint (HR 0.64 (0.25, 1.59), P=0.335) or between CARV and the development of allo- or autoimmune humoral or cellular responses. These findings raise the possibility that the immunologic impact of CARV following pediatric lung transplant is different than that observed in adults. This article is protected by copyright. All rights reserved.

PMID: 31216376 [PubMed - as supplied by publisher]

Targeting bacterial biofilm: a new LecA multivalent ligand with inhibitory activity.

Chembiochem. 2019 Jun 19;:

Authors: Palmioli A, Sperandeo P, Polissi A, Airoldi C

Abstract
Biofilm formation by bacterial pathogens is a hallmark of chronic infections and is associated to increased antibiotic tolerance that makes pathogens difficult to eradicate with conventional antibiotic therapies. Infections caused by Pseudomonas aeruginosa are of great concern, especially for immunocompromised and cystic fibrosis patients. P. aeruginosa lectins LecA and LecB are virulence factors and play a key role in establishing biofilm; therefore, inhibition of the function of these proteins has potential in dismantling the bacterium from the protective biofilm environment and in restoring the activity of antibiotics. Here we report the NMR characterization of the binding of a galactose-based dendrimer (Gal18) to LecA. Moreover, we demonstrate the activity of Gal18 molecule in inhibiting P. aeruginosa biofilm formation in vitro.

PMID: 31216375 [PubMed - as supplied by publisher]

Hypertrophic osteoarthropathy presenting with joint pain in cystic fibrosis.

Arthritis Rheumatol. 2019 Jun 19;:

Authors: Clarke E, Bright-Thomas R

Abstract
A 19 year old man with cystic fibrosis (CF) presented with pain and swelling of both wrists in association with an infective respiratory exacerbation. His CF-related complications included clubbing, multilobar bronchiectasis, chronic infection with Pseudomonas aeruginosa, exocrine pancreatic insufficiency, cystic fibrosis related diabetes mellitus, and low body mass. This article is protected by copyright. All rights reserved.

PMID: 31216115 [PubMed - as supplied by publisher]

Emerging gene therapies for cystic fibrosis.

Expert Rev Respir Med. 2019 Jun 19;:

Authors: Miah KM, Hyde SC, Gill DR

Abstract
Introduction: Cystic fibrosis (CF) remains a life-threatening genetic disease, with few clinically effective treatment options. Gene therapy and gene editing strategies offer the potential for a one-time CF cure, irrespective of the CFTR mutation class. Areas covered: We review emerging gene therapies and gene delivery strategies for the treatment of CF particularly viral and non-viral approaches with potential to treat CF. Expert opinion: It was initially anticipated that the challenge of developing a gene therapy for CF lung disease would be met relatively easily. Following early proof-of-concept clinical studies, CF gene therapy has entered a new era with innovative vector designs, approaches to subvert the humoral immune system and increase gene delivery and gene correction efficiencies. Developments include integrating adenoviral vectors, rapamycin loaded nanoparticles and lung-tropic lentiviral vectors. The characterisation of novel cell types in the lung epithelium, including pulmonary ionocytes, may also encourage cell type-specific targeting for CF correction. We anticipate preclinical studies to further validate these strategies, which should pave the way for clinical trials. We also expect gene editing efficiencies to improve to clinically translatable levels, given advancements in viral and non-viral vectors. Overall, gene delivery technologies look more convincing in producing an effective CF gene therapy.

PMID: 31215818 [PubMed - as supplied by publisher]

Hepatocellular carcinoma in cystic fibrosis liver disease: a cautionary tale.

QJM. 2019 Jun 19;:

Authors: O'Brien C, Ramlaul N, Haughey A, Nolan N, Malone DE, Cormick AM

PMID: 31214693 [PubMed - as supplied by publisher]

Catabolism of Nucleic Acids by a Cystic Fibrosis Pseudomonas aeruginosa Isolate: An Adaptive Pathway to Cystic Fibrosis Sputum Environment.

Front Microbiol. 2019;10:1199

Authors: Kumar SS, Penesyan A, Elbourne LDH, Gillings MR, Paulsen IT

Abstract
Pseudomonas aeruginosa is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). We undertook Biolog Phenotype Microarray testing of P. aeruginosa CF isolates to investigate their catabolic capabilities compared to P. aeruginosa laboratory strains PAO1 and PA14. One strain, PASS4, displayed an unusual phenotype, only showing strong respiration on adenosine and inosine. Further testing indicated that PASS4 could grow on DNA as a sole carbon source, with a higher biomass production than PAO1. This suggested that PASS4 was specifically adapted to metabolize extracellular DNA, a substrate present at high concentrations in the CF lung. Transcriptomic and proteomic profiling of PASS4 and PAO1 when grown with DNA as a sole carbon source identified a set of upregulated genes, including virulence and host-adaptation genes. PASS4 was unable to utilize N-Acetyl-D-glucosamine, and when we selected PASS4 mutants able to grow on this carbon source, they also displayed a gain in ability to catabolize a broad range of other carbon sources. Genome sequencing of the mutants revealed they all contained mutations within the purK gene, encoding a key protein in the de novo purine biosynthesis pathway. This suggested that PASS4 was a purine auxotroph. Growth assays in the presence of 2 mM adenosine and the complementation of PASS4 with an intact purK gene confirmed this conclusion. Purine auxotrophy may represent a viable microbial strategy for adaptation to DNA-rich environments such as the CF lung.

PMID: 31214142 [PubMed]

Inhaled corticosteroids, blood eosinophils, and FEV1 decline in patients with COPD in a large UK primary health care setting.

Int J Chron Obstruct Pulmon Dis. 2019;14:1063-1073

Authors: Whittaker HR, Müllerova H, Jarvis D, Barnes NC, Jones PW, Compton CH, Kiddle SJ, Quint JK

Abstract
Background: Inhaled corticosteroid (ICS)-containing medications slow rate of decline of FEV1. Blood eosinophil (EOS) levels are associated with the degree of exacerbation reduction with ICS. Purpose: We investigated whether FEV1 decline differs between patients with and without ICS, stratified by blood EOS level. Patients and methods: The UK Clinical Practice Research Datalink (primary care records) and Hospital Episode Statistics (hospital records) were used to identify COPD patients aged 35 years or older, who were current or ex-smokers with ≥2 FEV1 measurements ≥6 months apart. Prevalent ICS use and the nearest EOS count to start of follow-up were identified. Patients were classified at baseline as higher stratum EOS (≥150 cell/µL) on ICS; higher stratum EOS not on ICS; lower stratum EOS (<150 cells/µL) on ICS; and lower stratum EOS not on ICS. In addition, an incident ICS cohort was used to investigate the rate of FEV1 change by EOS and incident ICS use. Mixed-effects linear regression was used to compare rates of FEV1 change in mL/year. Results: A total of 26,675 COPD patients met our inclusion criteria (median age 69, 46% female). The median duration of follow up was 4.2 years. The rate of FEV1 change in prevalent ICS users was slower than non-ICS users (-12.6 mL/year vs -21.1 mL/year; P =0.001). The rate of FEV1 change was not significantly different when stratified by EOS level. The rate of FEV1 change in incident ICS users increased (+4.2 mL/year) vs -21.2 mL/year loss in non-ICS users; P<0.001. In patients with high EOS, incident ICS patients showed an increase in FEV1 (+12 mL/year) compared to non-ICS users whose FEV1 decreased (-20.8 mL/year); P<0.001. No statistical difference was seen in low EOS patients. Incident ICS use is associated with an improvement in FEV1 change, however, over time this association is lost. Conclusion: Regardless of blood EOS level, prevalent ICS use is associated with slower rates of FEV1 decline in COPD.

PMID: 31213788 [PubMed - in process]

Interactions between Aspergillus fumigatus and Pulmonary Bacteria: Current State of the Field, New Data, and Future Perspective.

J Fungi (Basel). 2019 Jun 12;5(2):

Authors: Briard B, Mislin GLA, Latgé JP, Beauvais A

Abstract
Aspergillus fumigatus and Pseudomonas aeruginosa are central fungal and bacterial members of the pulmonary microbiota. The interactions between A. fumigatus and P. aeruginosa have only just begun to be explored. A balance between inhibitory and stimulatory effects on fungal growth was observed in mixed A. fumigatus-P. aeruginosa cultures. Negative interactions have been seen for homoserine-lactones, pyoverdine and pyochelin resulting from iron starvation and intracellular inhibitory reactive oxidant production. In contrast, several types of positive interactions were recognized. Dirhamnolipids resulted in the production of a thick fungal cell wall, allowing the fungus to resist stress. Phenazines and pyochelin favor iron uptake for the fungus. A. fumigatus is able to use bacterial volatiles to promote its growth. The immune response is also differentially regulated by co-infections.

PMID: 31212791 [PubMed]