Macrophages as drivers of an opportunistic infection.

Microb Cell. 2017 Sep 13;4(10):362-364

Authors: Vergunst AC, Carranza NL, Zhang L, Gomes MC, Tasrini Y, Meijer AH, O'Callaghan D

Abstract
Opportunistic pathogens are a worldwide cause of mortality and morbidity, and infections with intrinsically antibiotic-resistant pathogens have a large clinical, social and economic impact. Bacteria belonging to the Burkholderia cepacia complex (Bcc), ubiquitous in natural and industrial environments, are notorious pathogens for individuals with cystic fibrosis (CF). In addition, Burkholderia cenocepacia is emerging as the culprit of non-CF related, sometimes fatal infections. Knowledge of the underlying infection mechanism of these pathogens is important for efficient treatment, however, to date not much is known about the lifestyle of Bcc bacteria during infection. In our recent study published in PLoS Pathogens, we provide experimental evidence that macrophages are critically important for proliferation of B. cenocepacia, and are major drivers of fatal pro-inflammatory infections in zebrafish larvae. This is in agreement with recent clinical information showing that B. cenocepacia is mainly localised in phagocytes in infected CF lungs. A predominant intramacrophage stage and a host-detrimental role for macrophages have major implications for treatment strategies of both CF and non-CF infections. Intracellular survival of bacteria traditionally classified as extracellular, including Staphylococcus aureus and Pseudomonas aeruginosa, is an emerging theme. Our finding that macrophages are essential for proliferation of B. cenocepacia in the host suggests a new paradigm for Bcc infections and urges the development of novel anti-infectious therapies to efficiently disarm these intrinsically antibiotic resistant facultative intracellular pathogens.

PMID: 29082233 [PubMed]

Bacterial infections in patients with primary ciliary dyskinesia: Comparison with cystic fibrosis.

Chron Respir Dis. 2017 Nov;14(4):392-406

Authors: Wijers CD, Chmiel JF, Gaston BM

Abstract
Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder associated with severely impaired mucociliary clearance caused by defects in ciliary structure and function. Although recurrent bacterial infection of the respiratory tract is one of the major clinical features of this disease, PCD airway microbiology is understudied. Despite the differences in pathophysiology, assumptions about respiratory tract infections in patients with PCD are often extrapolated from cystic fibrosis (CF) airway microbiology. This review aims to summarize the current understanding of bacterial infections in patients with PCD, including infections with Pseudomonas aeruginosa, Staphylococcus aureus, and Moraxella catarrhalis, as it relates to bacterial infections in patients with CF. Further, we will discuss current and potential future treatment strategies aimed at improving the care of patients with PCD suffering from recurring bacterial infections.

PMID: 29081265 [PubMed - in process]

Correcting for tissue nitrogen excretion in multiple breath washout measurements.

PLoS One. 2017;12(10):e0185553

Authors: Kane M, Rayment JH, Jensen R, McDonald R, Stanojevic S, Ratjen F

Abstract
Nitrogen excreted from body tissues impacts the calculation of multiple breath nitrogen washout (MBWN2) outcomes. The aim of this study was to determine the effect of tissue N2 on MBWN2 outcomes in both healthy subjects and patients with CF and to assess whether it is possible to correct for tissue N2. The contribution of tissue N2 to MBWN2 outcomes was estimated by comparing MBWN2-derived functional residual capacity (FRCN2) to FRC measured by body plethysmography (FRCpleth) and by comparing MBW outcome measures derived from MBWN2 and sulfur hexafluoride MBW (MBWSF6). Compared to plethysmography and MBWSF6, MBWN2 overestimated FRC and lung clearance index (LCI). Application of mathematical tissue N2 corrections reduced FRCN2 values closer to FRCpleth in health and reduced LCIN2 in both health and CF, but did not explain all of the differences observed between N2-dependent and -independent techniques. Use of earlier washout cut-offs could reduce the influence of tissue N2. Applying tissue N2 corrections to LCIN2 measurements did not significantly affect the interpretation of treatment effects reported in a previously published interventional trial. While tissue N2 excretion likely has an impact on MBWN2 outcomes, better understanding of the nature of this phenomenon is required before routine correction can be implemented into current MBWN2 protocols.

PMID: 29020072 [PubMed - indexed for MEDLINE]

Inflammatory markers as exacerbation risk factors after asthma therapy switch from inhaled steroids to montelukast.

Pulm Pharmacol Ther. 2016 Aug;39:7-13

Authors: Ciółkowski J, Mazurek H, Hydzik P, Stasiowska B

Abstract
BACKGROUND: Asthma guidelines allow anti-leukotriene medications to be used as an alternative to inhaled corticosteroids (ICS) in second-step intensity therapy. The aim of the study was to analyze the risk factors of exacerbations, particularly inflammatory markers, during the 12-month period following therapy reduction from an ICS to montelukast in young patients with mild asthma.
METHODS: A total of 84 patients (aged 7-18 years old) with mild asthma controlled by low-dose ICS, had their treatment switched to montelukast. Exhaled nitric oxide (eNO), sputum eosinophils (sEos), and bronchial hyperreactivity (BHR) were assessed at the beginning and then every three months throughout the one-year period. The patients with asthma exacerbations (first severe or third mild) were discontinued from the study.
RESULTS: Over the study period, 22 patients (26%) discontinued montelukast due to asthma exacerbations. An increased risk of exacerbations was noted among patients with initial sEos above 2.5% (relative risk, RR 36.6; 95% CI: 7.1-189.3; p < 0.001), as well as those with augmented BHR (RR 9.5; 2.8-31.6; p < 0.001), or eNO greater than 20 ppb (RR 3.7; 95% CI: 1.3-10.7; p = 0.013). An increase in BHR and eNO was observed during the last visit before exclusion.
CONCLUSIONS: After switching treatment from a low-dose ICS, montelukast maintained control of asthma symptoms in 75% of patients. High sEos before the treatment change was the strongest exacerbation risk factor. In patients with asthma controlled by low-dose ICS and low inflammatory markers, treatment could be safely switched to montelukast.

PMID: 27234706 [PubMed - indexed for MEDLINE]

Corrector combination therapies for F508del-CFTR.

Curr Opin Pharmacol. 2017 Oct 25;34:105-111

Authors: Hanrahan JW, Matthes E, Carlile G, Thomas DY

Abstract
These are exciting times in the development of therapeutics for cystic fibrosis (CF). New correctors and potentiators of the cystic fibrosis transmembrane conductance regulator (CFTR) are being developed in academic laboratories and pharmaceutical companies, and the field is just beginning to understand their mechanisms of action. Studies of CFTR modulators are also yielding insight into the general principles and strategies that can be used when developing pharmacological chaperones, a new class of drugs. Combining two or even three correctors with a potentiator is an especially promising approach which should may lead to further improvements in efficacy and clinical benefit for patients.

PMID: 29080476 [PubMed - as supplied by publisher]

A missense mutation in SLC26A3 is associated with human male subfertility and impaired activation of CFTR.

Sci Rep. 2017 Oct 27;7(1):14208

Authors: Wedenoja S, Khamaysi A, Shimshilashvili L, Anbtawe-Jomaa S, Elomaa O, Toppari J, Höglund P, Aittomäki K, Holmberg C, Hovatta O, Tapanainen JS, Ohana E, Kere J

Abstract
Chloride absorption and bicarbonate excretion through exchange by the solute carrier family 26 member 3 (SLC26A3) and cystic fibrosis transmembrane conductance regulator (CFTR) are crucial for many tissues including sperm and epithelia of the male reproductive tract. Homozygous SLC26A3 mutations cause congenital chloride diarrhea with male subfertility, while homozygous CFTR mutations cause cystic fibrosis with male infertility. Some homozygous or heterozygous CFTR mutations only manifest as male infertility. Accordingly, we studied the influence of SLC26A3 on idiopathic infertility by sequencing exons of SLC26A3 in 283 infertile and 211 control men. A heterozygous mutation c.2062 G > C (p.Asp688His) appeared in nine (3.2%) infertile men, and additionally, in two (0.9%) control men, whose samples revealed a sperm motility defect. The p.Asp688His mutation is localized in the CFTR-interacting STAS domain of SLC26A3 and enriched in Finland, showing a significant association with male infertility in comparison with 6,572 Finnish (P < 0.05) and over 120,000 global alleles (P < 0.0001) (ExAC database). Functional studies showed that while SLC26A3 is a strong activator of CFTR-dependent anion transport, SLC26A3-p.Asp688His mutant retains normal Cl(-)/HCO3(-) exchange activity but suppresses CFTR, despite unaffected domain binding and expression. These results suggest a novel mechanism for human male infertility─impaired anion transport by the coupled SLC26A3 and CFTR.

PMID: 29079751 [PubMed - in process]

A common mechanism for CFTR potentiators.

J Gen Physiol. 2017 Oct 27;:

Authors: Yeh HI, Sohma Y, Conrath K, Hwang TC

Abstract
Cystic fibrosis (CF) is a channelopathy caused by loss-of-function mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a phosphorylation-activated and adenosine triphosphate (ATP)-gated chloride channel. In the past few years, high-throughput drug screening has successfully realized the first US Food and Drug Administration-approved therapy for CF, called ivacaftor (or VX-770). A more recent CFTR potentiator, GLPG1837 (N-(3-carbamoyl-5,5,7,7-tetramethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-2-yl)-1H-pyrazole-3-carboxamide), has been shown to exhibit a higher efficacy than ivacaftor for the G551D mutation, yet the underlying mechanism of GLPG1837 remains unclear. Here we find that despite their differences in potency and efficacy, GLPG1837 and VX-770 potentiate CFTR gating in a remarkably similar manner. Specifically, they share similar effects on single-channel kinetics of wild-type CFTR. Their actions are independent of nucleotide-binding domain (NBD) dimerization and ATP hydrolysis, critical steps controlling CFTR's gate opening and closing, respectively. By applying the two reagents together, we provide evidence that GLPG1837 and VX-770 likely compete for the same site, whereas GLPG1837 and the high-affinity ATP analogue 2'-deoxy-N(6)-(2-phenylethyl)-adenosine-5'-O-triphosphate (dPATP) work synergistically through two different sites. We also find that the apparent affinity for GLPG1837 is dependent on the open probability of the channel, suggesting a state-dependent binding of the drug to CFTR (higher binding affinity for the open state than the closed state), which is consistent with the classic mechanism for allosteric modulation. We propose a simple four-state kinetic model featuring an energetic coupling between CFTR gating and potentiator binding to explain our experimental results.

PMID: 29079713 [PubMed - as supplied by publisher]

Ivacaftor withdrawal syndrome in cystic fibrosis patients with the G551D mutation.

J Cyst Fibros. 2017 Oct 24;:

Authors: Trimble AT, Donaldson SH

Abstract
Ivacaftor use can lead to dramatic health improvements in cystic fibrosis (CF) patients with gating mutations. Here, we report five instances of dramatic clinical decline following withdrawal of ivacaftor in three individuals with the G551D-CFTR mutation. In each case, the patient's lung function and symptoms rapidly deteriorated after cessation of treatment. Awareness of this phenomenon should inform both clinical practices as well as the design of future clinical trials of highly active CFTR modulators.

PMID: 29079142 [PubMed - as supplied by publisher]

Diagnostic and prognostic significance of systemic alkyl quinolones for P. aeruginosa in cystic fibrosis: A longitudinal study; response to comments.

J Cyst Fibros. 2017 Oct 24;:

Authors: Barr HL, Halliday N, Barrett DA, Williams P, Forrester DL, Peckham D, Williams K, Smyth AR, Honeybourne D, Whitehouse JL, Nash EF, Dewar J, Clayton A, Knox AJ, Cámara M, Fogarty AW

PMID: 29079141 [PubMed - as supplied by publisher]

Use of ferrets for electrophysiologic monitoring of ion transport.

PLoS One. 2017;12(10):e0186984

Authors: Kaza N, Raju SV, Cadillac JM, Trombley JA, Rasmussen L, Tang L, Dohm E, Harrod KS, Rowe SM

Abstract
Limited success achieved in translating basic science discoveries into clinical applications for chronic airway diseases is attributed to differences in respiratory anatomy and physiology, poor approximation of pathologic processes, and lack of correlative clinical endpoints between humans and laboratory animal models. Here, we discuss advantages of using ferrets (Mustela putorus furo) as a model for improved understanding of human airway physiology and demonstrate assays for quantifying airway epithelial ion transport in vivo and ex vivo, and establish air-liquid interface cultures of ferret airway epithelial cells as a complementary in vitro model for mechanistic studies. We present data here that establishes the feasibility of measuring these human disease endpoints in ferrets. Briefly, potential difference across the nasal and the lower airway epithelium in ferrets could be consistently assessed, were highly reproducible, and responsive to experimental interventions. Additionally, ferret airway epithelial cells were amenable to primary cell culture methods for in vitro experiments as was the use of ferret tracheal explants as an ex vivo system for assessing ion transport. The feasibility of conducting multiple assessments of disease outcomes supports the adoption of ferrets as a highly relevant model for research in obstructive airway diseases.

PMID: 29077751 [PubMed - in process]

The Rationale and Evidence for Use of Inhaled Antibiotics to Control Pseudomonas aeruginosa Infection in Non-cystic Fibrosis Bronchiectasis.

J Aerosol Med Pulm Drug Deliv. 2017 Oct 27;:

Authors: Dhand R

Abstract
Non-cystic fibrosis bronchiectasis (NCFBE) is a chronic inflammatory lung disease characterized by irreversible dilation of the bronchi, symptoms of persistent cough and expectoration, and recurrent infective exacerbations. The prevalence of NCFBE is on the increase in the United States and Europe, but no licensed therapies are currently available for its treatment. Although there are many similarities between NCFBE and cystic fibrosis (CF) in terms of respiratory symptoms, airway microbiology, and disease progression, there are key differences, for example, in response to treatment, suggesting differences in pathogenesis. This review discusses possible reasons underlying differences in response to inhaled antibiotics in people with CF and NCFBE. Pseudomonas aeruginosa infections are associated with the most severe forms of bronchiectasis. Suboptimal levels of antibiotics in the lung increase the mutation frequency of P. aeruginosa and lead to the development of mucoid strains characterized by formation of a protective polysaccharide biofilm. Mucoid strains of P. aeruginosa are associated with a chronic infection stage, requiring long-term antibiotic therapy. Inhaled antibiotics provide targeted delivery to the lung with minimal systemic toxicity and adverse events compared with oral/intravenous routes of administration, and they could be alternative treatment options to help address some of the treatment challenges in the management of severe cases of NCFBE. This review provides an overview of completed and ongoing trials that evaluated inhaled antibiotic therapy for NCFBE. Recently, several investigators conducted phase 3 randomized controlled trials with inhaled aztreonam and ciprofloxacin in patients with NCFBE. While the aztreonam trial results were not associated with significant clinical benefit in NCFBE, initial results reported from the inhaled ciprofloxacin (dry powder for inhalation and liposome-encapsulated/dual-release formulations) trials hold promise. A more targeted approach could identify specific populations of NCFBE patients who benefit from inhaled antibiotics.

PMID: 29077527 [PubMed - as supplied by publisher]

Diagnosis and management of cystic fibrosis: summary of NICE guidance.

BMJ. 2017 Oct 26;359:j4574

Authors: Villanueva G, Marceniuk G, Murphy MS, Walshaw M, Cosulich R, Guideline Committee

PMID: 29074599 [PubMed - in process]

Do cystic fibrosis centres with the lowest FEV1 still use the least amount of intravenous antibiotics? A registry-based comparison of intravenous antibiotic use among adult CF centres in the UK.

J Cyst Fibros. 2017 Oct 23;:

Authors: Hoo ZH, Campbell MJ, Curley R, Walters SJ, Wildman MJ

Abstract
BACKGROUND: The Epidemiologic Study of Cystic Fibrosis using 1995-1996 and 2003-2005 data found that CF centres with lowest FEV1 tended to use fewer intravenous antibiotics. We repeated the analyses using 2013-2014 UK CF registry data to determine if this was still the case.
METHODS: Analysing data for 2013 and 2014 separately, 28 adult CF centres were ranked according to median % age-adjusted FEV1. The top 7 centres were placed in the 'upper quarter' (best FEV1), the bottom 7 centres in 'lower quarter' (lowest FEV1), and the rest in 'middle half'. IV use was stratified according to %FEV1, then compared between the three groups.
RESULTS: Centres in the 'upper quarter' and 'middle half' used significantly more IV antibiotics compared to centres in the 'lower quarter' (van Elteren test P-value<0.001). Regression analyses showed that people with CF attending centres in the 'upper quarter' or 'middle half' are 30-50% more likely to receive at least one IV course per year compared to people attending centres in the 'lower quarter'.
CONCLUSIONS: CF centres with lowest FEV1 are still distinguished by lower use of intravenous antibiotics.

PMID: 29074367 [PubMed - as supplied by publisher]

A first description of the Colombian national registry for rare diseases.

BMC Res Notes. 2017 Oct 26;10(1):514

Authors: Mateus HE, Pérez AM, Mesa ML, Escobar G, Gálvez JM, Montaño JI, Ospina ML, Laissue P

Abstract
OBJECTIVE: Orphan diseases must be considered a public health concern, underlying country-specific challenges for their accurate and opportune diagnosis, classification and management. Orphan disease registries have not yet been created in South America, a continent having a population of ~ 415 million inhabitants. In Colombia ~ 3 million of patients are affected by rare diseases. The aim of the present study was to establish the first Colombian national registry for rare diseases. The registry was created after the establishment of laws promoting the development of clinical guidelines for diagnosis, management, census and registry of patients suffering rare diseases.
RESULTS: In total, 13,215 patients were recorded in the Colombian registry. The survey reported 653 rare diseases. The most common diseases were congenital factor VIII deficiency (hemophilia A) (8.5%), myasthenia gravis (6.4%), von Willebrand disease (5.9%), short stature due to growth hormone qualitative anomaly (4.2%), bronchopulmonary dysplasia (3.9%) and cystic fibrosis (3.2%). Although, a marked under-reporting of cases was observed, some pathologies displayed similar behavior to that reported by other initiatives and databases. The data currently available in the registry provides a baseline for improvement regarding local and regional surveys and the start for better understanding rare diseases in Colombia.

PMID: 29073918 [PubMed - in process]

CFTR potentiators: from bench to bedside.

Curr Opin Pharmacol. 2017 Oct 23;34:98-104

Authors: Jih KY, Lin WY, Sohma Y, Hwang TC

Abstract
One major breakthrough in cystic fibrosis research in the past decade is the development of drugs that target the root cause of the disease-dysfunctional CFTR protein. One of the compounds, Ivacaftor or Kalydeco, which has been approved for clinical use since 2012, acts by promoting the gating function of CFTR. Our recent studies have led to a gating model that features an energetic coupling between NBD dimerization and gate opening/closing in CFTR's TMDs. Based on this model, we showed that ATP analogs can enhance CFTR gating by facilitating NBD dimerization, whereas Ivacaftor works by stabilizing the open channel conformation of the TMDs. This latter idea also explains the near omnipotence of Ivacaftor. Furthermore, this model marks multiple approaches to synergistically boost the open probability of CFTR by influencing distinct molecular events that control gating conformational changes.

PMID: 29073476 [PubMed - as supplied by publisher]

The Man in the Paper Mask: One (Mask) for All and All for…..Cystic Fibrosis?

Am J Respir Crit Care Med. 2017 Oct 26;:

Authors: Simmonds NJ, Bush A

PMID: 29072847 [PubMed - as supplied by publisher]

Grass pollen sublingual immunotherapy tablets provide long-term relief of grass pollen-associated allergic rhinitis and reduce the risk of asthma: findings from a retrospective, real-world database subanalysis.

Expert Rev Clin Immunol. 2017 Oct 26;:

Authors: Devillier P, Wahn U, Zielen S, Heinrich J

Abstract
BACKGROUND: We assessed real-world, long-term effectiveness of two marketed sublingual immunotherapy (SLIT) tablets for allergic rhinitis (AR), and their impact on allergic asthma (AA) onset/progression.
RESEARCH DESIGN AND METHODS: Retrospective, longitudinal German prescription database subanalysis of AR patients receiving 5- or 1-grass pollen SLIT tablets (n=1,466/1,385), versus patients not using allergy immunotherapy (AIT) (n=71,275).
MAIN OUTCOME MEASURES: Primary endpoint: change over time in AR symptomatic medication prescriptions after treatment cessation; secondary endpoints: new asthma onset, and change over time in asthma medication prescriptions during treatment/follow-up periods.
RESULTS: Mean number of AR medication prescriptions was significantly decreased during follow-up (of up to 6 years) with both SLIT tablets versus the non-AIT group (p<0.001). Over the full-analysis period, proportions of patients with new-onset asthma were 8.8% (odds ratio: 0.676, p=0.011), 10.3% (odds ratio: 0.720, p=0.060) and 11.6% in the 5- and 1-grass pollen SLIT tablet and non-AIT groups, respectively. For all treatment-analysis periods, both SLIT tablet groups were associated with fewer asthma medication prescriptions versus non-AIT controls.
CONCLUSIONS: These findings confirm the real-world benefits of 5- and 1-grass-pollen SLIT tablets in slower AR progression, reduced risk of new asthma onset in the non-asthmatic population, and slower asthma progression in the asthmatic population.

PMID: 29072507 [PubMed - as supplied by publisher]

Pharmacological Chaperones: Beyond Conformational Disorders.

Handb Exp Pharmacol. 2017 Oct 26;:

Authors: Leidenheimer NJ

Abstract
Pharmacological chaperones (PCs) are small molecules that bind to nascent protein targets to facilitate their biogenesis. The ability of PCs to assist in the folding and subsequent forward trafficking of disease-causative protein misfolding mutants has opened new avenues for the treatment of conformational diseases such as cystic fibrosis and lysosomal storage disorders. In this chapter, an overview of the use of PCs for the treatment of conformational disorders is provided. Beyond the therapeutic application of PCs for the treatment of these disorders, pharmacological chaperoning of wild-type integral membrane proteins is discussed. Central to this discussion is the notion that the endoplasmic reticulum is a reservoir of viable but inefficiently processed wild-type protein folding intermediates whose biogenesis can be facilitated by PCs to increase functional pools. To date, the potential therapeutic use of PCs to enhance the biogenesis of wild-type proteins has received little attention. Here the rationale for the development of PCs that target WT proteins is discussed. Also considered is the likelihood that some commonly used therapeutic agents may exert unrecognized pharmacological chaperoning activity on wild-type targets in patient populations.

PMID: 29071508 [PubMed - as supplied by publisher]

The secreted polyketide boydone A is responsible for the anti-Staphylococcus aureus activity of Scedosporium boydii.

FEMS Microbiol Lett. 2017 Oct 24;:

Authors: Staerck C, Landreau A, Herbette G, Roullier C, Bertrand S, Siegler B, Larcher G, Bouchara JP, Fleury MJJ

Abstract
Usually living as a soil saprophyte, the filamentous fungus Scedosporium boydii may also cause various infections in human. Particularly, it is one of the major causative agents of fungal colonization of the airways in patients with cystic fibrosis (CF). To compete with other microorganisms in the environment, fungi have evolved sophisticated strategies, including the production of secondary metabolites with antimicrobial activity which may also help them to establish successfully within the respiratory tract of receptive hosts. Here, the culture filtrate from a human pathogenic strain of S. boydii was investigated searching for an antibacterial activity, mainly against the major CF bacterial pathogens. A high antibacterial activity against Staphylococcus aureus , including methicillin-resistant strains of this species, was observed. Bio-guided fractionation and analysis of the active fractions by nuclear magnetic resonance or by high performance-liquid chromatography and high resolution-electrospray ionization-mass spectrometry allowed us to identify boydone A as responsible for this antibacterial activity. Together these results suggest that this 6-membered cyclic polyketide could be one of the virulence factors of the fungus. Genes involved in the synthesis of this secreted metabolite are currently being identified in order to confirm the role of this polyketide in pathogenesis.

PMID: 29069388 [PubMed - as supplied by publisher]

Salivary lipids: A review.

Adv Clin Exp Med. 2017 Sep;26(6):1021-1029

Authors: Matczuk J, Żendzian-Piotrowska M, Maciejczyk M, Kurek K

Abstract
Saliva is produced by both large and small salivary glands and may be considered one of the most important factors influencing the behavior of oral cavity homeostasis. Secretion of saliva plays an important role in numerous significant biological processes. Saliva facilitates chewing and bolus formation as well as performs protective functions and determines the buffering and antibacterial prosperities of the oral environment. Salivary lipids appear to be a very important component of saliva, as their qualitative and quantitative composition can be changed in various pathological states and human diseases. It has been shown that disturbances in salivary lipid homeostasis are involved in periodontal diseases as well as various systemic disorders (e.g. cystic fibrosis, diabetes and Sjögren's syndrome). However, little is known about the role and composition of salivary lipids and their interaction with other important ingredients of human saliva, including proteins, glycoproteins and salivary mucins. The purpose of this review paper is to present the latest knowledge on salivary lipids in healthy conditions and in oral and systemic diseases.

PMID: 29068606 [PubMed - in process]