Biomarkers To Monitor Exacerbations in Cystic Fibrosis.

Expert Rev Respir Med. 2017 Mar 16;:

Authors: Gray RD, Downey D, Taggart CC

PMID: 28299964 [PubMed - as supplied by publisher]

Cystic fibrosis patients in Canada live nearly a decade longer than those in US, study finds.

BMJ. 2017 Mar 15;356:j1346

Authors: McCarthy M

PMID: 28298317 [PubMed - in process]

The most appropriate therapeutic strategy for acute lower respiratory tract infections: a Delphi-based approach.

J Chemother. 2017 Mar 15;:1-13

Authors: Blasi F, Concia E, Del Prato B, Giusti M, Mazzei T, Polistena B, Rossi A, Stefani S, Novelli A, On behalf of the *MASTER working group

Abstract
Lower respiratory tract infections (LRTIs) cause high morbidity and mortality worldwide. Empiric therapy often base the choice of antibiotic treatment on antibacterial spectrum of the agent rather than on its pharmacological properties or the pathogen resistance profile. Inappropriate prescribing leads to therapeutic failure and antibiotic resistance, with increasing direct and indirect health costs. A consensus on appropriate prescribing in LRTI therapy was appraised by this Delphi exercise, based on a panel of 70 pulmonologists, coordinated by a Scientific Committee of nine experts in respiratory medical care. Full or very high consensus was reached on several issues, including the role of oral cephalosporins in first-line treatments of LRTIs and the appropriateness of cefditoren, with balanced spectrum and high intrinsic activity, in LRTI treatment. Evidence-based medicine approach and a comprehensive process of disease management, from diagnosis to therapy and follow-up, should guide antibiotic prescribing.

PMID: 28298164 [PubMed - as supplied by publisher]

Peptide modification results in the formation of a dimer with a 60-fold enhanced antimicrobial activity.

PLoS One. 2017;12(3):e0173783

Authors: Thamri A, Létourneau M, Djoboulian A, Chatenet D, Déziel E, Castonguay A, Perreault J

Abstract
Cationic antimicrobial peptides (CAMPs) occur naturally in numerous organisms and are considered as a class of antibiotics with promising potential against multi-resistant bacteria. Herein, we report a strategy that can lead to the discovery of novel small CAMPs with greatly enhanced antimicrobial activity and retained antibiofilm potential. We geared our efforts towards i) the N-terminal cysteine functionalization of a previously reported small synthetic cationic peptide (peptide 1037, KRFRIRVRV-NH2), ii) its dimerization through a disulfide bond, and iii) a preliminary antimicrobial activity assessment of the newly prepared dimer against Pseudomonas aeruginosa and Burkholderia cenocepacia, pathogens responsible for the formation of biofilms in lungs of individuals with cystic fibrosis. This dimer is of high interest as it does not only show greatly enhanced bacterial growth inhibition properties compared to its pep1037 precursor (up to 60 times), but importantly, also displays antibiofilm potential at sub-MICs. Our results suggest that the reported dimer holds promise for its use in future adjunctive therapy, in combination with clinically-relevant antibiotics.

PMID: 28296935 [PubMed - in process]

Sequential Burkholderia cenocepacia Isolates from Siblings with Cystic Fibrosis Show Increased Lung Cell Attachment.

Am J Respir Crit Care Med. 2017 Mar 15;195(6):832-835

Authors: Cullen L, O'Connor A, Drevinek P, Schaffer K, McClean S

PMID: 28294652 [PubMed - in process]

Evaluation of Functional Characteristics of 4 Oscillatory Positive Pressure Devices in a Simulated Cystic Fibrosis Model.

Respir Care. 2017 Mar 14;:

Authors: Van Fleet H, Dunn DK, McNinch NL, Volsko TA

Abstract
BACKGROUND: Oscillatory positive expiratory pressure (OPEP) is an airway clearance therapy that delivers positive pressure and air-flow oscillations during exhalation. This study described functional characteristic differences of 4 OPEP devices during an active exhalation in a simulated model. We hypothesized peak pressure (Ppeak), positive expiratory pressure (PEP), oscillatory frequency (f), and pressure amplitude will differ, depending upon the device used, device resistance setting, and time (repeated consecutive active exhalations through the device).
METHODS: The ASL 5000 was scripted to simulate pulmonary mechanics of a pediatric cystic fibrosis patient with moderate to severe lung disease. Airway resistance was standardized at 17.1 cm H2O/L/s, pulmonary compliance at 42.1 mL/cm H2O, active exhalation at 22 breaths/min, and tidal volume at 409 mL. Resistance settings for the Acapella, RC-Cornet, Flutter, and Aerobika were adjusted to low, medium, and high. Values for f, Ppeak, PEP, and pressure amplitude were recorded for 1 min and graphically displayed.
RESULTS: Significant effects for time, device, and resistance (P < .01) were noted for Ppeak, PEP, and pressure amplitude at each resistance level, demonstrating that the devices functioned differently as more than one repetition of a series of consecutive active exhalations are performed. Significant interaction effects for device, resistance level, and time indicate inconsistent output for Ppeak (P < .01), PEP (P < .01), and pressure amplitude (P < .01). Oscillatory f values fell within the respective manufacturers' operational parameters. The Aerobika provided the most consistent pressure amplitude across resistance settings and produced the highest mean pressure amplitude at medium and high resistance settings.
CONCLUSION: Statistically significant and clinically relevant variations in Ppeak, PEP, and pressure amplitude occurred between devices and within a device, as the resistance setting changed. The combination of device, time, and resistance settings affects OPEP device output for pressure, amplitude, and oscillatory frequency. Functional variations may impact therapeutic effectiveness, warranting additional study to determine clinical impact.

PMID: 28292973 [PubMed - as supplied by publisher]

Lung organoids: current uses and future promise.

Development. 2017 Mar 15;144(6):986-997

Authors: Barkauskas CE, Chung MI, Fioret B, Gao X, Katsura H, Hogan BL

Abstract
Lungs are composed of a system of highly branched tubes that bring air into the alveoli, where gas exchange takes place. The proximal and distal regions of the lung contain epithelial cells specialized for different functions: basal, secretory and ciliated cells in the conducting airways and type II and type I cells lining the alveoli. Basal, secretory and type II cells can be grown in three-dimensional culture, with or without supporting stromal cells, and under these conditions they give rise to self-organizing structures known as organoids. This Review summarizes the different methods for generating organoids from cells isolated from human and mouse lungs, and compares their final structure and cellular composition with that of the airways or alveoli of the adult lung. We also discuss the potential and limitations of organoids for addressing outstanding questions in lung biology and for developing new drugs for disorders such as cystic fibrosis and asthma.

PMID: 28292845 [PubMed - in process]

Adherence and Recursive Perception Among Young Adults with Cystic Fibrosis.

Anthropol Med. 2017 Apr;24(1):65-80

Authors: Oddleifson DA, Sawicki GS

Abstract
Adherence to prescribed treatment is a pressing issue for adolescents and young adults with cystic fibrosis (CF). This paper presents two narratives from the thematic analysis of unstructured interviews with 14 adolescents, young adults, and older adults living with CF. Through a new identity-based framework termed recursive perception that draws focus on how an individual perceives how others view them, it explores the social context of adherence and self-care among young adults with CF. It demonstrates that an individual's understanding of self and desire to maintain a certain image for peers can be deeply embedded in adherence and self-care patterns, leading individuals to feel they need to choose between tending to their health needs and living their lives. This suggests that current biomedical innovation in CF care must be complemented with renewed efforts to find effective means to empower young adults with CF to successfully navigate the social challenges of their illness and avoid the pitfalls of nonadherence that can lead to a permanent worsening of their health condition.

PMID: 28292207 [PubMed - in process]

Immunization with outer membrane proteins (OprF and OprI) and flagellin B protects mice from pulmonary infection with mucoid and nonmucoid Pseudomonas aeruginosa.

J Microbiol Immunol Infect. 2017 Feb 20;:

Authors: Hassan R, El-Naggar W, Abd El-Aziz AM, Shaaban M, Kenawy HI, Ali YM

Abstract
BACKGROUND: Pseudomonas aeruginosa is a Gram-negative opportunistic bacterium, which considered as a common cause of nosocomial infection and life-threatening complications in immunocompromized and cystic fibrosis patients. Here, we evaluate the protective effect of recombinant vaccines composed of outer membrane proteins OprF and OprI alone or in combination with flagellin B against mucoid and nonmucoid pseudomonas infection.
METHODS: BALB/C mice were immunized subcutaneous using OprF and OprI with or without flagellin B and antibody titers were determined. Serum bactericidal and opsonophagocytosis activities of immunized and control sera were estimated against mucoid and nonmucoid pseudomonas strains. Lung tissue sections from immunized and nonimmunized mice were analyzed and the levels of peripheral neutrophils infiltration into the lung and tissue inflammation were scored.
RESULTS: Subcutaneous immunization using OprF and OprI with or without flagellin B elicited higher antibody titers against OprF, OprI, and flagellin B. The produced antibodies successfully opsonized both mucoid and nonmucoid strains with subsequent activation of the terminal pathway of complement that enhances killing of nonmucoid strains via complement-mediated lysis. Furthermore, opsonized mucoid and nonmucoid strains showed enhanced opsonophagocytosis via human peripheral neutrophils, a mechanism that kills P. aeruginosa when complement mediated lysis is not effective especially with mucoid strains. Immunized mice also showed a significant prolonged survival time, lower bacteremia, and reduced lung damage when compared with control nonimmunized mice.
CONCLUSION: Our data showed that mice immunized with OprF/OprI or OprF/OprI and flagellin B are significantly protected from infection caused by mucoid and nonmucoid strains of P. aeruginosa.

PMID: 28291719 [PubMed - as supplied by publisher]

Outcomes Following Bronchial Artery Embolisation for Haemoptysis in Cystic Fibrosis.

Cardiovasc Intervent Radiol. 2017 Mar 13;:

Authors: Flight WG, Barry PJ, Bright-Thomas RJ, Butterfield S, Ashleigh R, Jones AM

Abstract
BACKGROUND: Bronchial artery embolisation (BAE) is recommended for the treatment of massive haemoptysis in cystic fibrosis (CF), but there are no randomised controlled trials of this therapy and its role in sub-massive haemoptysis is unclear. This study aimed to determine the outcomes and safety of BAE in adults with CF.
MATERIALS AND METHODS: All patients with CF undergoing BAE at our centre between March 2011 and January 2015 were identified at the time of the procedure. Patient records were reviewed at hospital discharge, death or one month post-procedure (whichever was soonest). Follow-up continued to January 2016. Severity of haemoptysis was classified as: massive (>240 ml/24 h or >100 ml/day for ≥2 days), moderate-severe (>20 ml/24 h) or mild (<20 ml/24 h).
RESULTS: Twenty-seven patients underwent 51 BAE procedures over a median follow-up period of 26 months (range 1-54). Ten patients (37%) required more than one BAE during the study. BAE was performed for massive haemoptysis in 18 cases (35%). Haemoptysis recurred after 31 (61%) of BAE procedures with no difference in recurrence rates between massive and sub-massive haemoptysis. Side effects were reported after 61% of procedures with chest pain the most common adverse event . Mortality after first BAE in the study was 3.9% at 30 days and 14.8% at 12 months. No significant predictors of mortality were identified.
CONCLUSIONS: BAE is often effective in controlling haemoptysis but is associated with considerable morbidity and high recurrence rates.

PMID: 28289842 [PubMed - as supplied by publisher]

The Cystic Fibrosis Survival Gap: Why Do Canadians Fare Better Than Americans?

Ann Intern Med. 2017 Mar 14;:

Authors: Flume PA, VanDevanter DR

PMID: 28289748 [PubMed - as supplied by publisher]

Assessment of ciliary phenotype in primary ciliary dyskinesia by micro-optical coherence tomography.

JCI Insight. 2017 Mar 09;2(5):e91702

Authors: Solomon GM, Francis R, Chu KK, Birket SE, Gabriel G, Trombley JE, Lemke KL, Klena N, Turner B, Tearney GJ, Lo CW, Rowe SM

Abstract
Ciliary motion defects cause defective mucociliary transport (MCT) in primary ciliary dyskinesia (PCD). Current diagnostic tests do not assess how MCT is affected by perturbation of ciliary motion. In this study, we sought to use micro-optical coherence tomography (μOCT) to delineate the mechanistic basis of cilia motion defects of PCD genes by functional categorization of cilia motion. Tracheae from three PCD mouse models were analyzed using μOCT to characterize ciliary motion and measure MCT. We developed multiple measures of ciliary activity, integrated these measures, and quantified dyskinesia by the angular range of the cilia effective stroke (ARC). Ccdc39(-/-) mice, with a known severe PCD mutation of ciliary axonemal organization, had absent motile ciliary regions, resulting in abrogated MCT. In contrast, Dnah5(-/-) mice, with a missense mutation of the outer dynein arms, had reduced ciliary beat frequency (CBF) but preserved motile area and ciliary stroke, maintaining some MCT. Wdr69(-/-) PCD mice exhibited normal motile area and CBF and partially delayed MCT due to abnormalities of ciliary ARC. Visualization of ciliary motion using μOCT provides quantitative assessment of ciliary motion and MCT. Comprehensive ciliary motion investigation in situ classifies ciliary motion defects and quantifies their contribution to delayed mucociliary clearance.

PMID: 28289722 [PubMed - in process]

DNA methylation at modifier genes of lung disease severity is altered in cystic fibrosis.

Clin Epigenetics. 2017;9:19

Authors: Magalhães M, Rivals I, Claustres M, Varilh J, Thomasset M, Bergougnoux A, Mely L, Leroy S, Corvol H, Guillot L, Murris M, Beyne E, Caimmi D, Vachier I, Chiron R, De Sario A

Abstract
BACKGROUND: Lung disease progression is variable among cystic fibrosis (CF) patients and depends on DNA mutations in the CFTR gene, polymorphic variations in disease modifier genes, and environmental exposure. The contribution of genetic factors has been extensively investigated, whereas the mechanism whereby environmental factors modulate the lung disease is unknown. In this project, we hypothesized that (i) reiterative stress alters the epigenome in CF-affected tissues and (ii) DNA methylation variations at disease modifier genes modulate the lung function in CF patients.
RESULTS: We profiled DNA methylation at CFTR, the disease-causing gene, and at 13 lung modifier genes in nasal epithelial cells and whole blood samples from 48 CF patients and 24 healthy controls. CF patients homozygous for the p.Phe508del mutation and ≥18-year-old were stratified according to the lung disease severity. DNA methylation was measured by bisulfite and next-generation sequencing. The DNA methylation profile allowed us to correctly classify 75% of the subjects, thus providing a CF-specific molecular signature. Moreover, in CF patients, DNA methylation at specific genes was highly correlated in the same tissue sample. We suggest that gene methylation in CF cells may be co-regulated by disease-specific trans-factors. Three genes were differentially methylated in CF patients compared with controls and/or in groups of pulmonary severity: HMOX1 and GSTM3 in nasal epithelial samples; HMOX1 and EDNRA in blood samples. The association between pulmonary severity and DNA methylation at EDNRA was confirmed in blood samples from an independent set of CF patients. Also, lower DNA methylation levels at GSTM3 were associated with the GSTM3*B allele, a polymorphic 3-bp deletion that has a protective effect in cystic fibrosis.
CONCLUSIONS: DNA methylation levels are altered in nasal epithelial and blood cell samples from CF patients. Analysis of CFTR and 13 lung disease modifier genes shows DNA methylation changes of small magnitude: some of them are a consequence of the disease; other changes may result in small expression variations that collectively modulate the lung disease severity.

PMID: 28289476 [PubMed - in process]

Staphylococcus aureus survives in cystic fibrosis macrophages forming a reservoir for chronic pneumonia.

Infect Immun. 2017 Mar 13;:

Authors: Li C, Wu Y, Riehle A, Ma J, Kamler M, Gulbins E, Grassmé H

Abstract
Staphylococcus aureus (S. aureus) plays an important role in sepsis, pneumonia, wound infections and cystic fibrosis (CF), which is caused by mutations of the cystic fibrosis transmembrane conductance regulator (Cftr). Pulmonary S. aureus infections in CF often occur very early and prior to colonization with other pathogens, in particular Pseudomonas aeruginosa Here, we demonstrate that CF mice are highly susceptible to pulmonary infections with S. aureus and fail to clear the pathogen during infection. S. aureus is internalized by Cftr-deficient macrophages in the lung, but these macrophages are unable to kill intracellular bacteria. This failure might be caused by a defect in fusion of phagosomes with lysosomes, while this process rapidly occurs in wild-type macrophages and serves to kill intracellular pathogens. Transplantation of infected Cftr-deficient alveolar macrophages into the lung of non-infected CF mice is sufficient to induce pneumonia. This suggests that intracellular survival of S. aureus in macrophages may serve the pathogen to chronically infect CF lungs.

PMID: 28289144 [PubMed - as supplied by publisher]

Survival Comparison of Patients With Cystic Fibrosis in Canada and the United States: A Population-Based Cohort Study.

Ann Intern Med. 2017 Mar 14;:

Authors: Stephenson AL, Sykes J, Stanojevic S, Quon BS, Marshall BC, Petren K, Ostrenga J, Fink AK, Elbert A, Goss CH

Abstract
Background: In 2011, the median age of survival of patients with cystic fibrosis reported in the United States was 36.8 years, compared with 48.5 years in Canada. Direct comparison of survival estimates between national registries is challenging because of inherent differences in methodologies used, data processing techniques, and ascertainment bias.
Objective: To use a standardized approach to calculate cystic fibrosis survival estimates and to explore differences between Canada and the United States.
Design: Population-based study.
Setting: 42 Canadian cystic fibrosis clinics and 110 U.S. cystic fibrosis care centers.
Patients: Patients followed in the Canadian Cystic Fibrosis Registry (CCFR) and U.S. Cystic Fibrosis Foundation Patient Registry (CFFPR) between 1990 and 2013.
Measurements: Cox proportional hazards models were used to compare survival between patients followed in the CCFR (n = 5941) and those in the CFFPR (n = 45 448). Multivariable models were used to adjust for factors known to be associated with survival.
Results: Median age of survival in patients with cystic fibrosis increased in both countries between 1990 and 2013; however, in 1995 and 2005, survival in Canada increased at a faster rate than in the United States (P < 0.001). On the basis of contemporary data from 2009 to 2013, the median age of survival in Canada was 10 years greater than in the United States (50.9 vs. 40.6 years, respectively). The adjusted risk for death was 34% lower in Canada than the United States (hazard ratio, 0.66 [95% CI, 0.54 to 0.81]). A greater proportion of patients in Canada received transplants (10.3% vs. 6.5%, respectively [standardized difference, 13.7]). Differences in survival between U.S. and Canadian patients varied according to U.S. patients' insurance status.
Limitation: Ascertainment bias due to missing data or nonrandom loss to follow-up might affect the results.
Conclusion: Differences in cystic fibrosis survival between Canada and the United States persisted after adjustment for risk factors associated with survival, except for private-insurance status among U.S. patients. Differential access to transplantation, increased posttransplant survival, and differences in health care systems may, in part, explain the Canadian survival advantage.
Primary Funding Source: U.S. Cystic Fibrosis Foundation.

PMID: 28288488 [PubMed - as supplied by publisher]

Forskolin-induced Swelling in Intestinal Organoids: An In Vitro Assay for Assessing Drug Response in Cystic Fibrosis Patients.

J Vis Exp. 2017 Feb 11;(120):

Authors: Boj SF, Vonk AM, Statia M, Su J, Vries RR, Beekman JM, Clevers H

Abstract
Recently-developed cystic fibrosis transmembrane conductance regulator (CFTR)-modulating drugs correct surface expression and/or function of the mutant CFTR channel in subjects with cystic fibrosis (CF). Identification of subjects that may benefit from these drugs is challenging because of the extensive heterogeneity of CFTR mutations, as well as other unknown factors that contribute to individual drug efficacy. Here, we describe a simple and relatively rapid assay for measuring individual CFTR function and response to CFTR modulators in vitro. Three dimensional (3D) epithelial organoids are grown from rectal biopsies in standard organoid medium. Once established, the organoids can be bio-banked for future analysis. For the assay, 30-80 organoids are seeded in 96-well plates in basement membrane matrix and are then exposed to drugs. One day later, the organoids are stained with calcein green, and forskolin-induced swelling is monitored by confocal live cell microscopy at 37 °C. Forskolin-induced swelling is fully CFTR-dependent and is sufficiently sensitive and precise to allow for discrimination between the drug responses of individuals with different and even identical CFTR mutations. In vitro swell responses correlate with the clinical response to therapy. This assay provides a cost-effective approach for the identification of drug-responsive individuals, independent of their CFTR mutations. It may also be instrumental in the development of future CFTR modulators.

PMID: 28287550 [PubMed - in process]

Feasibility of placebo-controlled trial designs for new CFTR modulator evaluation.

J Cyst Fibros. 2017 Mar 08;:

Authors: VanDevanter DR, Mayer-Hamblett N, Boyle M

Abstract
BACKGROUND: New CFTR modulators are in development that sponsors anticipate will be comparable or superior to approved modulators. Testing these agents for efficacy will require either placebo-controlled or active-comparator trials.
METHODS: We surveyed US CF physicians and their patients eligible to receive approved modulators or their families for willingness to participate in placebo-controlled modulator trials of varying duration.
RESULTS: Interest in placebo-controlled trials of short duration (2-4weeks) was greatest, with few respondents, particularly among patient respondents, willing to consider 6month studies. Patients/families with access to approved modulators were consistently less interested in placebo-controlled modulator trials of any duration.
CONCLUSIONS: Sample size and interpretability advantages of placebo-controlled trials outweigh alternative active-comparator trials, but must consider physician and patient thresholds for forgoing treatment with approved modulators. Enrollment will be most feasible for short-duration trials and those conducted among populations without access to approved modulators.

PMID: 28284527 [PubMed - as supplied by publisher]

Association between glucose intolerance and bacterial colonisation in an adult population with cystic fibrosis, emergence of Stenotrophomonas maltophilia.

J Cyst Fibros. 2017 Mar 08;:

Authors: Lehoux Dubois C, Boudreau V, Tremblay F, Lavoie A, Berthiaume Y, Rabasa-Lhoret R, Coriati A

Abstract
BACKGROUND: Diabetes is common in cystic fibrosis (CF). Glucose can be detected in the airway when the blood glucose is elevated, which favours bacterial growth. We investigated the relationship between dysglycemia and lung pathogens in CF.
METHODS: Cross-sectional and prospective analysis of CF patients (N=260) who underwent a 2h-oral glucose tolerance test. Clinical data was collected.
RESULTS: Stenotrophomonas maltophilia (S. maltophilia) was the sole bacteria increased in dysglycemic (AGT: 20.2%, CFRD: 21.6%) patients compared to normotolerants (NGT: 8.7%). S. maltophilia positive patients with dysglycemia had more pulmonary exacerbation events compared to NGTs (1.22 vs 0.63, P=0.003). The interaction between S. maltophilia colonisation and glucose tolerance status significantly increases the risk of lower lung function (P=0.003). Its growth was not affected by the evolution of the glucose tolerance after three years follow-up.
CONCLUSION: Prevalence of S. maltophilia was higher in dysglycemic patients, supporting the idea that S. maltophilia is a marker of disease severity in CF.

PMID: 28284526 [PubMed - as supplied by publisher]

Dietary intake and lipid profile in children and adolescents with cystic fibrosis.

J Cyst Fibros. 2017 Mar 07;:

Authors: Woestenenk JW, Schulkes DA, Schipper HS, van der Ent CK, Houwen RH

Abstract
BACKGROUND: Cystic fibrosis (CF) patients are advised to derive 35% of their daily energy intake from dietary fat. Whether this high fat intake is associated with dyslipidaemia is unknown. We described the lipid profile and dietary intake in paediatric patients with CF.
METHODS: 110 fasting lipid concentrations of 110 Dutch patients with CF were studied, along with 86 measurements of dietary intake. For the total group and for boys and girls separately, the lipid profile and the dietary intake were investigated. The cross-sectional relationship between the lipid concentrations and dietary intake was determined.
RESULTS: The mean dietary fat intake was ≥35% of the total energy intake, along with a considerable consumption of saturated fat. We found lower concentrations of cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol, and increased concentrations of triglyceride and triglyceride to high-density lipoprotein cholesterol ratios. Lipid concentrations were not associated with dietary fat intake.
CONCLUSION: This study lacks variation in dietary fat intake to exclude an effect on lipid concentrations as the distribution of dietary fat intake remained constant at a high level. Elevated triglyceride concentrations and triglyceride to high-density lipoprotein cholesterol ratios suggest an increased risk of cardiovascular disease. Any negative consequences of a high dietary fat intake on the overall lipid profile later in life cannot be excluded.

PMID: 28283399 [PubMed - as supplied by publisher]

Interactions between Neutrophils and Pseudomonas aeruginosa in Cystic Fibrosis.

Pathogens. 2017 Mar 09;6(1):

Authors: Rada B

Abstract
Cystic fibrosis (CF) affects 70,000 patients worldwide. Morbidity and mortality in CF is largely caused by lung complications due to the triad of impaired mucociliary clearance, microbial infections and chronic inflammation. Cystic fibrosis airway inflammation is mediated by robust infiltration of polymorphonuclear neutrophil granulocytes (PMNs, neutrophils). Neutrophils are not capable of clearing lung infections and contribute to tissue damage by releasing their dangerous cargo. Pseudomonas aeruginosa is an opportunistic pathogen causing infections in immunocompromised individuals. P. aeruginosa is a main respiratory pathogen in CF infecting most patients. Although PMNs are key to attack and clear P. aeruginosa in immunocompetent individuals, PMNs fail to do so in CF. Understanding why neutrophils cannot clear P. aeruginosa in CF is essential to design novel therapies. This review provides an overview of the antimicrobial mechanisms by which PMNs attack and eliminate P. aeruginosa. It also summarizes current advances in our understanding of why PMNs are incapable of clearing P. aeruginosa and how this bacterium adapts to and resists PMN-mediated killing in the airways of CF patients chronically infected with P. aeruginosa.

PMID: 28282951 [PubMed - in process]