Autonomous sweat extraction and analysis applied to cystic fibrosis and glucose monitoring using a fully integrated wearable platform.

Proc Natl Acad Sci U S A. 2017 Apr 17;:

Authors: Emaminejad S, Gao W, Wu E, Davies ZA, Yin Yin Nyein H, Challa S, Ryan SP, Fahad HM, Chen K, Shahpar Z, Talebi S, Milla C, Javey A, Davis RW

Abstract
Perspiration-based wearable biosensors facilitate continuous monitoring of individuals' health states with real-time and molecular-level insight. The inherent inaccessibility of sweat in sedentary individuals in large volume (≥10 µL) for on-demand and in situ analysis has limited our ability to capitalize on this noninvasive and rich source of information. A wearable and miniaturized iontophoresis interface is an excellent solution to overcome this barrier. The iontophoresis process involves delivery of stimulating agonists to the sweat glands with the aid of an electrical current. The challenge remains in devising an iontophoresis interface that can extract sufficient amount of sweat for robust sensing, without electrode corrosion and burning/causing discomfort in subjects. Here, we overcame this challenge through realizing an electrochemically enhanced iontophoresis interface, integrated in a wearable sweat analysis platform. This interface can be programmed to induce sweat with various secretion profiles for real-time analysis, a capability which can be exploited to advance our knowledge of the sweat gland physiology and the secretion process. To demonstrate the clinical value of our platform, human subject studies were performed in the context of the cystic fibrosis diagnosis and preliminary investigation of the blood/sweat glucose correlation. With our platform, we detected the elevated sweat electrolyte content of cystic fibrosis patients compared with that of healthy control subjects. Furthermore, our results indicate that oral glucose consumption in the fasting state is followed by increased glucose levels in both sweat and blood. Our solution opens the possibility for a broad range of noninvasive diagnostic and general population health monitoring applications.

PMID: 28416667 [PubMed - as supplied by publisher]

Age-dependent variation of fecal calprotectin in cystic fibrosis and healthy children.

J Cyst Fibros. 2017 Apr 14;:

Authors: Garg M, Leach ST, Coffey MJ, Katz T, Strachan R, Pang T, Needham B, Lui K, Ali F, Day AS, Appleton L, Moeeni V, Jaffe A, Ooi CY

Abstract
BACKGROUND: Fecal calprotectin may be used as a non-invasive method to assess the effect of novel therapies on the gut in cystic fibrosis (CF).
METHOD: Stools from CF patients and healthy controls (HC) (0-10years old) were prospectively collected for evaluation of temporal trends.
RESULTS: 130 CF samples (64 subjects) and 114 HC samples (101 subjects) were collected. Overall, fecal calprotectin levels were different in CF patients and HC from 0 to 10years (P=0.0002). Fecal calprotectin in CF was significantly lower than HC from 0 to 1years (P=0.03) and demonstrated an upward trajectory until 4years. From >4 to 10years calprotectin was consistently higher in CF patients compared with HC (P=0.007).
CONCLUSIONS: Fecal calprotectin levels in children with CF and HC were age-dependent and had distinct trajectories. Careful interpretation of calprotectin is required if used in drug trials for CF, particularly in children less than 4years old.

PMID: 28416415 [PubMed - as supplied by publisher]

Telemedicine is the way forward for the management of Cystic Fibrosis - the case in favour: The debate: Telemedicine is the future for CF care.

Paediatr Respir Rev. 2017 Mar 15;:

Authors: Ketchell RI

Abstract
Despite rapid changes in Information and Communication Technology, outpatient chronic disease management has changed very little in decades. However, the introduction of Telemedicine defined here as the use of remote patient-centred clinical services including the use of video and audio connections, telemonitoring and mobile applications provides us with an ideal opportunity to revolutionise care. Its appeal in cystic fibrosis (CF) care is clear offering better access to services, the opportunity of earlier intervention and improved monitoring and self management through virtual clinics and the use of real-time applications for adherence monitoring. It has the potential to reduce costs and has been shown to be effective in other chronic disease conditions. There is a lack of good quality data in CF and studies are needed to provide supportive evidence. Nonetheless, it would seem that telemedicine is the future of CF care.

PMID: 28416301 [PubMed - as supplied by publisher]

All the "RAGE" in lung disease: The receptor for advanced glycation endproducts (RAGE) is a major mediator of pulmonary inflammatory responses.

Paediatr Respir Rev. 2017 Mar 18;:

Authors: Oczypok EA, Perkins TN, Oury TD

Abstract
The receptor for advanced glycation endproducts (RAGE) is a pro-inflammatory pattern recognition receptor (PRR) that has been implicated in the pathogenesis of numerous inflammatory diseases. It was discovered in 1992 on endothelial cells and was named for its ability to bind advanced glycation endproducts and promote vascular inflammation in the vessels of patients with diabetes. Further studies revealed that RAGE is most highly expressed in lung tissue and spurred numerous explorations into RAGE's role in the lung. These studies have found that RAGE is an important mediator in allergic airway inflammation (AAI) and asthma, pulmonary fibrosis, lung cancer, chronic obstructive pulmonary disease (COPD), acute lung injury, pneumonia, cystic fibrosis, and bronchopulmonary dysplasia. RAGE has not yet been targeted in the lungs of paediatric or adult clinical populations, but the development of new ways to inhibit RAGE is setting the stage for the emergence of novel therapeutic agents for patients suffering from these pulmonary conditions.

PMID: 28416135 [PubMed - as supplied by publisher]

Upregulation of CFTR in patients with endometriosis and its involvement in NFκB-uPAR dependent cell migration.

Oncotarget. 2017 Mar 22;:

Authors: Huang W, Jin A, Zhang J, Wang C, Tsang LL, Cai Z, Zhou X, Chen H, Chan HC

Abstract
Endometriotic tissues exhibit high migration ability with the underlying mechanisms remain elusive. Our previous studies have demonstrated that cystic fibrosis transmembrane conductance regulator (CFTR) acts as a tumor suppressor regulating cell migration. In the present study, we explored whether CFTR plays a role in the development of human endometriosis. We found that both mRNA and protein expression levels of CFTR and urokinase-type plasminogen activator receptor (uPAR) were significantly increased in ectopic endometrial tissues from patients with endometriosis compared to normal endometrial tissues from women without endometriosis and positively correlated. In human endometrial Ishikawa (ISK) cells, overexpression of CFTR stimulated cell migration with upregulated NFκB p65 and uPAR. Knockdown of CFTR inhibited cell migration. Furthermore, inhibition of NFκB with its inhibitors (curcumin or Bay) significantly reduced the expression of uPAR and cell migration in the CFTR-overexpressing ISK cells. Collectively, the present results suggest that the CFTR-NFκB-uPAR signaling may contribute to the progression of human endometriosis, and indicate potential targets for diagnosis and treatment.

PMID: 28415617 [PubMed - as supplied by publisher]

Study suggests hidden epidemic in CF patients.

Science. 2016 Nov 11;354(6313):695

Authors: Kupferschmidt K

PMID: 27846586 [PubMed - indexed for MEDLINE]

Use of Nebulized Antimicrobials for the Treatment of Respiratory Infections in Invasively Mechanically Ventilated Adults: A Position Paper from the European Society of Clinical Microbiology and Infectious Diseases.

Clin Microbiol Infect. 2017 Apr 13;:

Authors: Rello J, Solé-Lleonart C, Rouby JJ, Chastre J, Blot S, Poulakou G, Luyt CE, Riera J, Palmer LB, Pereira JM, Felton T, Dhanani J, Bassetti M, Welte T, Roberts JA

Abstract
With an established role in cystic fibrosis and bronchiectasis, nebulized antibiotics are increasingly being used to treat respiratory infections in critically ill invasively mechanically ventilated adult patients. Although there is limited evidence describing their efficacy and safety, in an era of need for new strategies to enhance antibiotic effectiveness because of a shortage of new agents and increases in antibiotic resistance, the potential of nebulization of antibiotics to optimize therapy is considered of high interest, particularly in patients infected with multidrug-resistant (MDR) pathogens. This Position Paper of the European Society of Clinical Microbiology and Infectious Diseases provides recommendations based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology regarding the use of nebulized antibiotics in invasively mechanically ventilated adults, based on a systematic review and meta-analysis of the existing literature (last search July 2016). Overall, the panel recommends to avoid use of nebulized antibiotics in clinical practice, due to a weak level of evidence of their efficacy and the high potential for underestimated risks of adverse events (particularly, respiratory complications). Higher quality evidence is urgently needed to inform clinical practice. Priorities of future research are detailed in the second part of the Position Paper as a guidance for researchers in this field. In particular, the panel identified an urgent need for randomized clinical trials of nebulized antibiotic therapy as part of a substitution approach to treatment of pneumonia due to MDR pathogens.

PMID: 28412382 [PubMed - as supplied by publisher]

Clostridium difficile and cystic fibrosis: management strategies and the role of faecal transplantation.

Paediatr Respir Rev. 2017 Mar 14;:

Authors: Dunwoody R, Steel A, Landy J, Simmonds N

Abstract
Clostridium difficile is a bacterial infection that colonises the gut in susceptible hosts. It is associated with exposure to healthcare settings and antibiotic use. It could be assumed that cystic fibrosis (CF) patients are a high-risk group for C.difficile. However, despite high carriage rates, CF patients have low rates of active disease. There are guidelines for the treatment of C.difficile, however little is published specific to treating C.difficile in CF. This article provides an overview of the current management strategies for C.difficile in CF, including a description of the first faecal transplantation in this patient population.

PMID: 28411069 [PubMed - as supplied by publisher]

Phenotypes of Rapid Cystic Fibrosis Lung Disease Progression during Adolescence and Young Adulthood.

Am J Respir Crit Care Med. 2017 Apr 14;:

Authors: Szczesniak RD, Li D, Su W, Brokamp C, Pestian J, Seid M, Clancy JP

Abstract
RATIONALE: Individuals with cystic fibrosis are at risk for prolonged drops in lung function, clinically termed rapid decline, during discreet periods of the disease.
OBJECTIVES: To identify phenotypes of rapid pulmonary decline and determine how these phenotypes are related to patient characteristics.
METHODS: A longitudinal cohort study of cystic fibrosis patients aged 6-21 years was conducted using the Cystic Fibrosis Foundation Patient Registry. A statistical approach for clustering longitudinal profiles, sparse functional principal components analysis, was used to classify patients into distinct phenotypes by evaluating trajectories of FEV1 decline. Phenotypes were compared with respect to baseline and mortality characteristics.
MEASUREMENTS AND MAIN RESULTS: Three distinct phenotypes of rapid decline were identified, corresponding to early, middle and late timing of maximal FEV1 loss, in the overall cohort (n=18,387). The majority of variation (first functional principal component: 94%) among patient profiles was characterized by differences in mean longitudinal FEV1 trajectories. Average degree of rapid decline was similar among phenotypes (roughly -3% predicted/year); however, average timing differed, with early, middle and late phenotypes experiencing rapid decline at 12.9, 16.3 and 18.5 years of age, respectively. Individuals with the late phenotype had the highest initial FEV1 but experienced the greatest loss of lung function. The early phenotype was more likely to have respiratory infections and acute exacerbations at baseline or to develop them subsequently, compared to other phenotypes.
CONCLUSIONS: By identifying phenotypes and associated risk factors, timing of interventions may be more precisely targeted for subgroups at highest risk of lung function loss.

PMID: 28410569 [PubMed - as supplied by publisher]

Genomics: Tool to predict and prevent male infertility.

Front Biosci (Schol Ed). 2017 Jun 01;9:448-508

Authors: Halder A, Kumar P, Jain M, Kalsi AK

Abstract
A large number of human diseases arise as a result of genetic abnormalities. With the advent of improved molecular biology techniques, the genetic etiology of male infertility is increasing. The common genetic factors responsible for male infertility are chromosomal abnormalities, Yq microdeletion and cystic fibrosis. These are responsible for approximately 30 percent cases of male infertility. About 40 percent cases of male infertility are categorized as idiopathic. These cases may be associated with genetic and genomic abnormalities. During last few years more and more genes are implicated in male infertility leading to decline in prevalence of idiopathic etiology. In this review we will summarize up to date published works on genetic etiologies of male infertility including our own works. We also briefly describe reproductive technologies used to overcome male infertility, dangers of transmitting genetic disorders to offspring and ways to prevent transmission of genetic disorders during assisted reproduction. At the end we will provide our points on how genomic information can be utilized for prediction and prevention of male infertility in coming years.

PMID: 28410128 [PubMed - in process]

Magnesium for treating sickle cell disease.

Cochrane Database Syst Rev. 2017 Apr 14;4:CD011358

Authors: Than NN, Soe HH, Palaniappan SK, Abas AB, De Franceschi L

Abstract
BACKGROUND: Sickle cell disease is an autosomal recessive inherited haemoglobinopathy which causes painful vaso-occlusive crises due to sickle red blood cell dehydration. Vaso-occlusive crises are common painful events responsible for a variety of clinical complications; overall mortality is increased and life expectancy decreased compared to the general population. Experimental studies suggest that intravenous magnesium has proven to be well-tolerated in individuals hospitalised for the immediate relief of acute (sudden onset) painful crisis and has the potential to decrease the length of hospital stay. Some in vitro studies and open studies of long-term oral magnesium showed promising effect on pain relief but failed to show its efficacy. The studies show that oral magnesium therapy may prevent sickle red blood cell dehydration and prevent recurrent painful episodes. There is a need to access evidence for the impact of oral and intravenous magnesium effect on frequency of pain, length of hospital stay and quality of life.
OBJECTIVES: To evaluate the effects of short-term intravenous magnesium on the length of hospital stay and quality of life in children and adults with sickle cell disease. To determine the effects of long-term oral magnesium therapy on the frequency of painful crises and the quality of life in children and adults with sickle cell disease.
SEARCH METHODS: We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books.Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 01 December 2016.Date of last search of other resources (clinical trials registries): 29 March 2017.
SELECTION CRITERIA: We searched for published and unpublished randomized controlled studies of oral or intravenous magnesium compared to placebo or no magnesium.
DATA COLLECTION AND ANALYSIS: Authors independently assessed the study quality and extracted the data using standard Cochrane methodologies.
MAIN RESULTS: We included five randomized placebo-controlled studies with a total of 386 participants (aged three to 53 years). Two shorter parallel studies (n = 306) compared intravenous magnesium sulphate to placebo (normal saline) for admission to hospital due to a vaso-occlusive crisis, for which we were able to analyse data. The quality of evidence was moderate for studies presenting this comparison mainly due to limitations due to risk of bias and imprecision. Two of the three longer-term studies comparing oral magnesium pidolate to placebo had a cross-over design. The third was a parallel factorial study which compared hydroxyurea and oral magnesium to each other and to placebo over a longer period of time; we only present the comparison of oral magnesium to placebo from this study. The quality of evidence was very low with uncertainty of the estimation.The eight-hourly dose levels in the two studies of intravenous magnesium were different; one used 100 mg/kg while the second used 40 mg/kg. Only one of these studies (n = 104) reported the mean daily pain score while hospitalised (a non-significant difference between groups, moderate quality evidence). The second study (n = 202) reported a number of child- and parent-reported quality of life scores. None of the scores showed any difference between treatment groups (low quality evidence). Data from one study (n = 106) showed no difference in length of stay in hospital between groups (low quality evidence). Both studies reported on adverse events, but not defined by severity as we had planned. One study showed significantly more participants receiving intravenous magnesium experienced warmth at infusion site compared to placebo; there were no differences between groups for other adverse events (low quality evidence).Three studies (n = 80) compared oral magnesium pidolate to placebo. None of them reported data which we were able to analyse. One study (n = 24) reported on the number of painful days and stated there was no difference between two groups (low quality evidence). None of the studies reported on quality of life or length of hospital stay. Two studies (n = 68) reported there were no differences in levels of magnesium in either plasma or red blood cells (moderate quality evidence). Two studies (n = 56) reported adverse events. One reported episodes of mild diarrhoea and headache, all of which resolved without stopping treatment. The second study reported adverse events as gastrointestinal disorders, headache or migraine, upper respiratory infections and rash; which were all evenly distributed across treatment groups (moderate quality evidence).
AUTHORS' CONCLUSIONS: Moderate to low quality evidence showed neither intravenous magnesium and oral magnesium therapy has an effect on reducing painful crisis, length of hospital stay and changing quality of life in treating sickle cell disease. Therefore, no definitive conclusions can be made regarding its clinical benefit. Further randomized controlled studies, perhaps multicentre, are necessary to establish whether intravenous and oral magnesium therapies have any effect on improving the health of people with sickle cell disease.

PMID: 28409830 [PubMed - as supplied by publisher]

Hypoxia and the hypoxia-regulated transcription factor HIF-1α suppress the host defence of airway epithelial cells.

Innate Immun. 2017 May;23(4):373-380

Authors: Polke M, Seiler F, Lepper PM, Kamyschnikow A, Langer F, Monz D, Herr C, Bals R, Beisswenger C

Abstract
Chronic diseases of the respiratory tract, such as cystic fibrosis, are associated with mucosal and systemic hypoxia. Innate immune functions of airway epithelial cells are required to prevent and control infections of the lung parenchyma. The transcription factor hypoxia-inducible factor 1α (HIF-1α) regulates cellular adaptation to low oxygen conditions. Here, we show that hypoxia and HIF-1α regulate innate immune mechanisms of cultured human bronchial epithelial cells (HBECs). Exposure of primary HBECs to hypoxia or the prolyl hydroxylase inhibitor dimethyloxaloylglycine (DMOG) resulted in a significantly decreased expression of inflammatory mediators (IL-6, IFN-γ-induced protein 10) in response to ligands for TLRs (flagellin, polyI:C) and Pseudomonas aeruginosa, whereas the expression of inflammatory mediators was not affected by hypoxia or DMOG in the absence of microbial factors. Small interfering RNA-mediated knockdown of HIF-1α in HBECs and in the bronchial epithelial cell line Calu-3 resulted in increased expression of inflammatory mediators. The inflammatory response was decreased in lungs of mice stimulated with inactivated P. aeruginosa under hypoxia. These data suggest that hypoxia suppresses the innate immune response of airway epithelial cells via HIF-1α.

PMID: 28409544 [PubMed - in process]

Body composition and lung function in children with cystic fibrosis and meconium ileus.

Eur J Pediatr. 2017 Apr 13;:

Authors: Doulgeraki A, Petrocheilou A, Petrocheilou G, Chrousos G, Doudounakis SE, Kaditis AG

Abstract
The aim of this study was to explore whether history of meconium ileus (MI) at birth in children and adolescents with cystic fibrosis (CF) adversely affects body composition and lung function in later life. Data of children and adolescents with CF who underwent spirometry and DXA as part of their routine care were analyzed. Associations between MI (explanatory variable) and areal bone mineral density (total body less head-TBLH aBMD), lean tissue mass (LTM), and fat mass (FM) (outcomes) were assessed using general linear models. Potential relationships of TBLH aBMD, LTM, and FM with FEV1 (additional outcome) were also explored. One hundred and one subjects with CF (mean age 14 ± 3 years) were included, 19 (18.8%) of whom had history of MI. Negative associations were demonstrated between history of MI and FEV1 (P = 0.04), TBLH aBMD (P = 0.03), and FM (P < 0.01) but not between history of MI and LTM (P = 0.07) after adjustment for other variables. Lung function was positively associated with TBLH aBMD (P < 0.01) and LTM (P = 0.02) but not with FM (P = 0.20).
CONCLUSION: Among children and adolescents with CF, those with history of MI have lower bone mineral density, FM, and lung function. What is Known: • Among children and adolescents with cystic fibrosis, those with history of meconium ileus in the neonatal period are at risk of having lower body mass index percentile and FEV 1 percent predicted. What is New: • Children and adolescents with cystic fibrosis and history of meconium ileus have decreased bone mineral density and fat mass compared to patients without such history. • Lower lung function in children with MI coexists with suboptimal bone mineral density.

PMID: 28409283 [PubMed - as supplied by publisher]

CFTR Gene Mutations in the Egyptian Population: Current and Future Insights for Genetic Screening Strategy.

Front Genet. 2017;8:37

Authors: El-Seedy AS, Shafiek H, Kitzis A, Ladevèze V

PMID: 28408918 [PubMed - in process]

Patient knowledge and pulmonary medication adherence in adult patients with cystic fibrosis.

Patient Prefer Adherence. 2017;11:691-698

Authors: Lin AH, Kendrick JG, Wilcox PG, Quon BS

Abstract
BACKGROUND AND OBJECTIVES: Patient knowledge of lung function (ie, forced expiratory volume in 1 s [FEV1]% predicted) and the intended benefits of their prescribed pulmonary medications might play an important role in medication adherence, but this relationship has not been examined previously in patients with cystic fibrosis (CF).
METHODS: All patients diagnosed with CF and without prior lung transplantation were invited to complete knowledge and self-reported medication adherence questionnaires during routine outpatient visits to the Adult CF Clinic, St Paul's Hospital, Vancouver, Canada from June 2013 to August 2014.
RESULTS: A total of 142 out of 167 (85%) consecutive adults attending CF clinic completed patient knowledge and medication adherence survey questionnaires. Sixty-four percent of the patients recalled their last FEV1% predicted value within 5%, and 70% knew the intended benefits of all their prescribed medications. Self-reported adherence rates were highest for inhaled antibiotics (81%), azithromycin (87%), and dornase alpha (76%) and lowest for hypertonic saline (47%). Individuals who knew their FEV1% predicted value within 5% were more likely to self-report adherence to dornase alpha (84% vs 62%, P=0.06) and inhaled antibiotics (88% vs 64%, P=0.06) compared to those who did not, but these associations were not statistically significant. There were no significant associations observed between patient knowledge of intended medication benefits and self-reported medication adherence.
CONCLUSION: Contrary to our hypothesis, disease- and treatment-related knowledge was not associated with self-reported medication adherence. This suggests other barriers to medication adherence should be targeted in future studies aiming to improve medication adherence in adults with CF.

PMID: 28408806 [PubMed - in process]

Airway Clearance Techniques for Primary Ciliary Dyskinesia; is the Cystic Fibrosis literature portable?

Paediatr Respir Rev. 2017 Mar 16;:

Authors: Schofield LM, Duff A, Brennan C

Abstract
Primary Ciliary Dyskinesia (PCD) is a rare inherited disease with impaired mucociliary clearance. Airway clearance techniques (ACTs) are commonly recommended for patients with PCD to facilitate mucus clearance, despite a lack of evidence in this group. Current physiotherapy practice in PCD is based on evidence extrapolated from the field of Cystic Fibrosis (CF). This paper focuses on the available evidence and outlines challenges in extrapolating evidence between the conditions for best clinical practice.

PMID: 28408202 [PubMed - as supplied by publisher]

Diagnosis of biofilm infections in cystic fibrosis patients.

APMIS. 2017 Apr;125(4):339-343

Authors: Høiby N, Bjarnsholt T, Moser C, Jensen PØ, Kolpen M, Qvist T, Aanaes K, Pressler T, Skov M, Ciofu O

Abstract
Chronic Pseudomonas aeruginosa biofilm lung infection in cystic fibrosis patients is the best described biofilm infection in medicine. The initial focus can be the paranasal sinuses and then follows repeated colonization and infection of the lungs by aspiration. The matrix of the biofilms is dominated by alginate and the pathogenesis of tissue damage is immune complex-mediated chronic inflammation dominated by polymorphonuclear leukocytes and their products (DNA, oxygen radicals and proteases). The P. aeruginosa biofilm infection can be diagnosed by microscopy of lung tissue, sputum and mucus from the paranasal sinuses, where aggregates of the bacteria are found surrounded by the abundant alginate matrix. Specific PNA-FISH probes can be used to identify P. aeruginosa and other pathogens in situ in the biofilms. Growth of mucoid colonies from the locations mentioned above is also diagnostic for biofilm infection. Rise of specific anti-P. aeruginosa antibodies is likewise diagnostic, IgG in serum in case of lung infection, sIgA in saliva or nasal secretions in case of paranasal sinus infection. Similar approaches have been developed to diagnose chronic biofilm infections in cystic fibrosis caused by other pathogens e.g., Stenotrophomonas, Burkholderia multivorans, Achromobacter xylosoxidans and Mycobacterium abscessus complex.

PMID: 28407432 [PubMed - in process]

Biofilms and host response - helpful or harmful.

APMIS. 2017 Apr;125(4):320-338

Authors: Moser C, Pedersen HT, Lerche CJ, Kolpen M, Line L, Thomsen K, Høiby N, Jensen PØ

Abstract
Biofilm infections are one of the modern medical world's greatest challenges. Probably, all non-obligate intracellular bacteria and fungi can establish biofilms. In addition, there are numerous biofilm-related infections, both foreign body-related and non-foreign body-related. Although biofilm infections can present in numerous ways, one common feature is involvement of the host response with significant impact on the course. A special characteristic is the synergy of the innate and the acquired immune responses for the induced pathology. Here, we review the impact of the host response for the course of biofilm infections, with special focus on cystic fibrosis, chronic wounds and infective endocarditis.

PMID: 28407429 [PubMed - in process]

Microenvironmental characteristics and physiology of biofilms in chronic infections of CF patients are strongly affected by the host immune response.

APMIS. 2017 Apr;125(4):276-288

Authors: Jensen PØ, Kolpen M, Kragh KN, Kühl M

Abstract
In vitro studies of Pseudomonas aeruginosa and other pathogenic bacteria in biofilm aggregates have yielded detailed insight into their potential growth modes and metabolic flexibility under exposure to gradients of substrate and electron acceptor. However, the growth pattern of P. aeruginosa in chronic lung infections of cystic fibrosis (CF) patients is very different from what is observed in vitro, for example, in biofilms grown in flow chambers. Dense in vitro biofilms of P. aeruginosa exhibit rapid O2 depletion within <50-100 μm due to their own aerobic metabolism. In contrast, in vivo investigations show that P. aeruginosa persists in the chronically infected CF lung as relatively small cell aggregates that are surrounded by numerous PMNs, where the activity of PMNs is the major cause of O2 depletion rendering the P. aeruginosa aggregates anoxic. High levels of nitrate and nitrite enable P. aeruginosa to persist fueled by denitrification in the PMN-surrounded biofilm aggregates. This configuration creates a potentially long-term stable ecological niche for P. aeruginosa in the CF lung, which is largely governed by slow growth and anaerobic metabolism and enables persistence and resilience of this pathogen even under the recurring aggressive antimicrobial treatments of CF patients. As similar slow growth of other CF pathogens has recently been observed in endobronchial secretions, there is now a clear need for better in vitro models that simulate such in vivo growth patterns and anoxic microenvironments in order to help unravel the efficiency of existing or new antimicrobials targeting anaerobic metabolism in P. aeruginosa and other CF pathogens. We also advocate that host immune responses such as PMN-driven O2 depletion play a central role in the formation of anoxic microniches governing bacterial persistence in other chronic infections such as chronic wounds.

PMID: 28407427 [PubMed - in process]

A short history of microbial biofilms and biofilm infections.

APMIS. 2017 Apr;125(4):272-275

Authors: Høiby N

Abstract
The observation of aggregated microbes surrounded by a self-produced matrix adhering to surfaces or located in tissues or secretions is old since both Leeuwenhoek and Pasteur have described the phenomenon. In environmental and technical microbiology, biofilms, 80-90 years ago, were already shown to be important for biofouling on submerged surfaces, for example, ships. The concept of biofilm infections and their importance in medicine was, however, initiated in the early 1970s by the observation of heaps of Pseudomonas aeruginosa cells in sputum and lung tissue from chronically infected cystic fibrosis patients. The term biofilm was introduced into medicine in 1985 by J. W. Costerton. During the following decades, the number of published biofilm articles and methods for studying biofilms increased rapidly and it was shown that adhering and nonadhering biofilm infections are widespread in medicine. The medical importance of biofilm infections is now generally accepted and guidelines for prophylaxis, diagnosis, and treatment have been published.

PMID: 28407426 [PubMed - in process]