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Μαΐ 14
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- Rook's Textbook of Dermatology, 9th edn. Christoph...
- Therapeutic effect of microneedling and autologous...
- The effect of autologous activated platelet-rich p...
- Incubatory environment of the scalp impacts pre-em...
- Management of Massive Hemoptysis with Oren Friedman
- Mismatch repair cancer syndrome (MMRCS) : Multiple...
- Issue Information - TOC
- Clinical Thyroidology for the Public – Highlighted...
- Augmentation of the infraorbital rim in orthognath...
- Epigenetics and immunotherapy: The current state o...
- Molecular cloning and characterization of DNGR-1 i...
- Bone Quality Characteristics Obtained by Fourier T...
- Augmentation of the infraorbital rim in orthognath...
- Portal Hypertensive Biliopathy Presents with Massi...
- Multicentric Castleman disease of hyaline vascular...
- Five-year outcomes of an oropharynx-directed treat...
- Palmar melanoma: A tertiary centre experience
- Circumscribed palmoplantar hypokeratosis: successf...
- In vivo microvascular imaging of cutaneous actinic...
- Neutrophil to Lymphocyte Ratio Decreases After Tre...
- Merkel cell carcinoma: morphologic aspects on refl...
- Scalp threading with polydioxanone monofilament th...
- High-Grade Transformation (Dedifferentiation) of A...
- Pathogenicity of ADAR1 mutation in a Chinese famil...
- A novel frameshift mutation of the ADAR1 gene in a...
- Expression of the filaggrin gene in umbilical cord...
- Neutrophil Extracellular Traps are associated with...
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Κυριακή 14 Μαΐου 2017
Rook's Textbook of Dermatology, 9th edn. Christopher Griffiths, Jonathan Barker, Tanya Bleiker, Robert Chalmers, Daniel Creamer, eds. Publisher: Wiley-Blackwell, 2016; 4696 pp. ISBN: 978-1118441190. Price £522.50.
http://ift.tt/2rgzDYG
Therapeutic effect of microneedling and autologous platelet-rich plasma in the treatment of atrophic scars: A randomized study
Summary
Background
New treatments and techniques were being added over the last few years to treat atrophic scars with variable results and adverse effects.
Aim of the work
The aim of this study was to evaluate and compare the therapeutic efficacy and safety of microneedling, autologous platelet-rich plasma, and combination of both procedures in the treatment of atrophic scars.
Patients and methods
This study included 90 patients with atrophic scars and were classified randomly into three groups: I: 28 patients treated with microneedling, one session every 4 weeks; II: 34 patients treated with intradermal injection of platelet-rich plasma, one session every 2 weeks; and III: 28 patients treated with alternative sessions of each microneedling and platelet-rich plasma, 2 weeks between each session, for a maximum of six sessions.
Results
There was a statistically significant improvement in the appearance of atrophic scars, with reduction in the scores associated with the clinical evaluation scale for atrophic scarring in all groups, but the improvement was more obvious in group III.
Conclusions
Although a single treatment may give good results, combination between skin needling and platelet-rich plasma is more effective, safe with less number of sessions in all types of atrophic scars.
http://ift.tt/2rg9TeQ
The effect of autologous activated platelet-rich plasma injection on female pattern hair loss: A randomized placebo-controlled study
Summary
Background
Hair is an essential part of a woman's appearance and attractiveness. This is reflected in the predominantly psychological morbidity that can be associated with female pattern hair loss. Platelet-rich plasma(PRP) has been used in numerous fields of medicine. Recently, PRP has received growing attention as a potential therapeutic tool for hair loss.
Objective
To evaluate the efficacy and safety of autologous platelet-rich plasma in the treatment of female pattern hair loss.
Materials and methods
Thirty female patients with female pattern hair loss were randomly assigned to receive autologous PRP injection into a selected area, and another area was injected with normal saline as a placebo. Sessions were performed weekly for a maximum total of four sessions. Patients were followed up 6 months after the end of last session. The outcome was assessed both subjectively and objectively.
Results
There was a statistical significant difference between PRP and placebo areas (P<.005) regarding both hair density and hair thickness as measured by a folliscope. The hair pull test became negative in PRP-injected areas in 25 patients (83%) with average number of three hairs. Global pictures showed a significant improvement in hair volume and quality together with a high overall patient satisfaction in PRP-injected sites, and these results were maintained during the 6-month follow- up.
Conclusion
Platelet-rich plasma injections can be regarded as an alternative for the treatment of female pattern hair loss with minimal morbidity and a low cost-to-benefit ratio.
http://ift.tt/2qhGp35
Incubatory environment of the scalp impacts pre-emergent hair to affect post-emergent hair cuticle integrity
Summary
Objectives
To determine whether the oxidative stress transmitted to newly grown hair from an unhealthy scalp has physical consequences to the cuticular condition and function.
Methods
A uniquely designed 24-week clinical study included 8 weeks of pretreatment with a cosmetic shampoo and 16 weeks of treatment with either a potentiated zinc pyrithione (ZPT) antidandruff shampoo or a placebo cosmetic shampoo. This clinical design allowed the growth and acquisition of hair samples under conditions of varying but known scalp health as a result of treating a dandruff/seborrheic dermatitis (D/SD) population. Two complementary methods were used to characterize the integrity of the cuticular surface. Hair surface hydrophobicity was assessed by quantifying water wetting force using a Wilhelmy balance method. Surface structure and porosity were assessed using dynamic vapor sorption (DVS) to gravimetrically quantify water sorption.
Results
Chemical oxidative stress to pre-emergent hair has been shown to have negative consequences to hair surface structure. Compared to a placebo shampoo control, use of a potentiated ZPT shampoo improved scalp health and significantly improved the following attributes associated with healthy hair: hair surface hydrophobicity (surface energy) and cuticular moisture barrier effectiveness (dynamic vapor sorption).
Conclusions
Pre-emergent hair can be negatively impacted by the oxidative stress that occurs with an unhealthy scalp, possibly due to metabolic activity of resident microbes. Manifestations of the oxidative stress include altered cuticle surface properties that are responsible for its protective function; these effects are similar in type to those observed by bleaching post-emergent hair. These alterations have the potential to make the hair, once emerged from the scalp, more susceptible to the cumulative physical and chemical insults responsible for hair feel and look, fiber integrity, and overall retention.
http://ift.tt/2qHTlQZ
Management of Massive Hemoptysis with Oren Friedman
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
Mismatch repair cancer syndrome (MMRCS) : Multiple hyperpigmented and hypopigmented skin areas, brain malformations, pilomatricomas, a second childhood malignancy, a Lynch syndrome (LS)-associated tumour in a relative and parental consanguinity.
Clinical Thyroidology for the Public – Highlighted Article
From Clinical Thyroidology for the Public: If you are planning a pregnancy, currently pregnant, or in the postpartum period, it's important to stay up to date on the latest guidelines on thyroid disease and pregnancy. Read More….
We welcome your feedback and suggestions. Let us know what you want to see in this publication.
Feedback & SuggestionsThe post Clinical Thyroidology for the Public – Highlighted Article appeared first on American Thyroid Association.
http://ift.tt/2pMyrvT
Augmentation of the infraorbital rim in orthognathic surgery
Mid-face augmentation via a Le Fort I osteotomy is a commonly performed operation. Advancement of the upper jaw and associated structures (nose, lower cheek areas) can certainly improve function as well as facial aesthetics and harmony. Often, in patients with severe mid-face deficiency, hypoplasia of the maxilla extends all the way up to the infraorbital rims. The receding infraorbital rim contributes to the negative vector of the globes. In patients with this level of mid-face hypoplasia, while advancing the maxilla at the Le Fort I level satisfies all of the requirements for orthognathic surgery, the deficient infraorbital rim remains unchanged and can actually accentuate the negative vector of the globes.
http://ift.tt/2qklk6h
Epigenetics and immunotherapy: The current state of play
Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Jennifer Dunn, Sudha Rao
Cancer cells employ a number of mechanisms to escape immunosurveillance and facilitate tumour progression. The recent explosion of interest in immunotherapy, especially immune checkpoint blockade, is a result of discoveries about the fundamental ligand-receptor interactions that occur between immune and cancer cells within the tumour microenvironment. Distinct ligands expressed by cancer cells engage with cell surface receptors on immune cells, triggering inhibitory pathways (such as PD-1/PD-L1) that render immune cells immunologically tolerant. Importantly, recent studies on the role of epigenetics in immune evasion have exposed a key role for epigenetic modulators in augmenting the tumour microenvironment and restoring immune recognition and immunogenicity. Epigenetic drugs such as DNA methyltransferase and histone deacetylase inhibitors can reverse immune suppression via several mechanisms such as enhancing expression of tumour-associated antigens, components of the antigen processing and presenting machinery pathways, immune checkpoint inhibitors, chemokines, and other immune-related genes. These discoveries have established a highly promising basis for studies using combined epigenetic and immunotherapeutic agents as anti-cancer therapies. In this review, we discuss the exciting role of epigenetic immunomodulation in tumour immune escape, emphasising its significance in priming and sensitising the host immune system to immunotherapies through mechanisms such as the activation of the viral defence pathway. With this background in mind, we highlight the promise of combined epigenetic therapy and immunotherapy, focusing on immune checkpoint blockade, to improve outcomes for patients with many different cancer types.
http://ift.tt/2pzIM2h
Molecular cloning and characterization of DNGR-1 in rhesus macaques
Source:Molecular Immunology, Volume 87
Author(s): Wen-Rong Yao, Lei Yu, Dong Li, Gui-Bo Yang
DC, NK lectin group receptor-1 (DNGR-1), also known as C-type lectin domain family 9 member A (CLEC9A), is a promising target for immunological therapeutics and vaccination against tumors and viruses. However, little is known about its property in rhesus macaques. In this study, we cloned rhesus macaque DNGR-1 cDNA, and found that its coding region could encode a 241-amino acid polypeptide with 91.7% sequence identity and similar antigenicity to that of humans. Both free and cell surface rhesus macaque DNGR-1 expressed in vitro could bind to apoptotic/dead cells induced by serum deprivation or freeze-thaw, and to pyroptotic cells stimulated with PMA and LPS. We also demonstrated that rhesus macaque DNGR-1 mRNA was present in all the examined tissues, with the highest in lymph nodes, spleen, blood, and thymus. The expression of DNGR-1 that is highly similar to that of humans warranted the usefulness of rhesus macaques in testing human therapeutics and vaccines targeting DNGR-1, especially those for HIV/AIDS.
http://ift.tt/2qkn0fK
Bone Quality Characteristics Obtained by Fourier Transform Infrared and Raman Spectroscopic Imaging
Publication date: Available online 14 May 2017
Source:Journal of Oral Biosciences
Author(s): Hiromi Kimura-Suda, Teppi Ito
BackgroundBone strength, which is an indicator of the risk of fracture, is determined by bone mass (bone mineral density, 70%) and bone quality (30%). Bone quality results from a combination of various material and structural properties, making it difficult to determine a suitable method for the evaluation of bone quality based on clinical measurements. Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy are powerful techniques for the assessment of bone quality and reveal similar information on molecular structures; however, this molecular information is based on different physical phenomena. Therefore, a comparison of FTIR and Raman spectra is required for an accurate assessment of bone quality.HighlightWe previously assessed the bone quality of femurs from rats with chronic kidney disease (CKD) using FTIR imaging, and found the carbonate-to-phosphate ratio in the hydroxyapatite was significantly reduced compared to control rats; however, there was no difference in crystallinity. Therefore, we focused on the crystallinity of the femoral cortical bone in rats with CKD, and compared the PO43- bands in FTIR spectra in detail with those in the Raman spectra.ConclusionThe PO43- bands in the FTIR spectra were affected by changes in calcium phosphate composition rather than by changes in crystal size. Thus, FTIR is more suitable for the evaluation of mineral maturity than crystallinity; Raman spectroscopy is more sensitive to crystallinity than FTIR.
http://ift.tt/2qgx6k5
Augmentation of the infraorbital rim in orthognathic surgery
Publication date: Available online 14 May 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): T. Fattahi, S. Salman, B. Steinberg
Mid-face augmentation via a Le Fort I osteotomy is a commonly performed operation. Advancement of the upper jaw and associated structures (nose, lower cheek areas) can certainly improve function as well as facial aesthetics and harmony. Often, in patients with severe mid-face deficiency, hypoplasia of the maxilla extends all the way up to the infraorbital rims. The receding infraorbital rim contributes to the negative vector of the globes. In patients with this level of mid-face hypoplasia, while advancing the maxilla at the Le Fort I level satisfies all of the requirements for orthognathic surgery, the deficient infraorbital rim remains unchanged and can actually accentuate the negative vector of the globes. This article explains our approach in augmentation of the deficient infraorbital rim using alloplastic silicone implants at the time of a Le Fort I osteotomy.
http://ift.tt/2pLQIZf
Portal Hypertensive Biliopathy Presents with Massive Bleeding during ERCP after Balloon Sphincteroplasty in a Noncirrhotic Saudi Sickler Patient
Portal hypertensive biliopathy (PHB) is described as abnormalities of the walls of the biliary tree secondary to portal hypertension. Gastrointestinal bleeding caused by PHB is rare. PHB as a cause of serious bleeding after sphincteroplasty during ERCP is extremely rare. Here, we report a case of PHB in a young Saudi male with cell sickle anemia who developed massive hemorrhage during ERCP after balloon dilation of the ampulla of Vater. We further discussed the diagnosis and management. To the best of our knowledge, no such case has been reported.
http://ift.tt/2pKZuYq
Multicentric Castleman disease of hyaline vascular variant presenting with unusual systemic manifestations: a case report
Castleman disease is a rare lymphoproliferative disorder presenting with localized or disseminated lymphadenopathy and systemic manifestations. It can be categorized in numerous ways, such as unicentric versus...
http://ift.tt/2rfsNU8
Five-year outcomes of an oropharynx-directed treatment approach for unknown primary of the head and neck
Source:Oral Oncology, Volume 70
Author(s): Kenneth Shung Hu, Waleed Fouad Mourad, Mauricio E. Gamez, Wilson Lin, Adam Saul Jacobson, Mark Stephen Persky, Mark L. Urken, Bruce E. Culliney, Zujun Li, Theresa Nguyen Tran, Stimson Pryor Schantz, Juskaran Chadha, Louis Benjamin Harrison
PurposeSquamous cell carcinoma of unknown primary (SCCHNUP) is commonly treated with comprehensive radiation to the laryngopharynx and bilateral necks. In 1998, we established a departmental policy to treat SCCHNUP with radiation directed to the oropharynx and bilateral neck.MethodsFrom 1998–2011, 60 patients were treated – N1: 18%, N2: 75% and N3: 7%. 82% underwent neck dissection. 55% received IMRT and 62% underwent concurrent chemoradiotherapy.ResultsAt median follow-up of 54months, 5 patients failed regionally and 4 emerged with a primary (tongue base, hypopharynx and thoracic esophagus). Five-year rates of regional control, primary emergence, distant metastasis, disease-free survival and overall survival were 90%, 10%, 20%, 72% and 79%, respectively. The 5year rate of primary emergence in a non-oropharynx site was 3%.ConclusionThis is the first demonstration that an oropharynx-directed approach yields low rates of primary emergence in SCCHNUP with excellent oncologic outcomes.
http://ift.tt/2pKKVDt
Palmar melanoma: A tertiary centre experience
Abstract
Acral melanoma is the most common subtype of melanoma in darker-pigmented individuals, and recent studies report that acral melanoma shows unique behaviours compared to other subtypes.1 Previous reports indicate that localization of melanoma on the palm is extremely rare.2 Therefore, we report our experience with palmar melanoma in Korean patients through a retrospective analysis.
This article is protected by copyright. All rights reserved.
http://ift.tt/2rdVDDI
Circumscribed palmoplantar hypokeratosis: successful treatment with the 10,600-nm carbon dioxide fractional laser
Abstract
Circumscribed palmoplantar hypokeratosis (CPH) is a rare benign dermatosis of unknown etiology with characteristic clinical features presenting as a round well-demarcated depressed erythematous lesion on the palm and sole. The typical histologic features include an abrupt decrease in thickness of stratum corneum, forming a sharp stair at the edge.1 Although various therapies have been tried, none have been established as a treatment of choice.1,2 Here, we report a case of CPH successfully treated with the 10,600-nm carbon dioxide fractional laser (CO2FL).
This article is protected by copyright. All rights reserved.
http://ift.tt/2rf8ztH
In vivo microvascular imaging of cutaneous actinic keratosis, Bowen's disease and squamous cell carcinoma using Dynamic optical coherence tomography
Abstract
Background
A clear distinction between actinic keratosis (AK), Bowen's disease (BD) and squamous cell carcinoma (SCC) cannot reliably be made by clinical and dermoscopic evaluation alone. Dynamic optical coherence tomography (D-OCT) is a novel angiographic variant of OCT that allows for non-invasive, in vivo evaluation of the cutaneous microvascular morphology.
Objective
To investigate the microvascular structures of AK, BD and invasive SCC using D-OCT in order to gain insights into the microvascular morphology of lesions in the spectrum of keratinocyte skin cancers.
Methods
47 patients with a total of 54 lesions (18 AK, 12 BD and 24 SCC) were included in the study. D-OCT still-images of AK, BD, SCC at three predefined skin depths were prepared and randomized, creating a study set of 162 D-OCT images. Three observers performed blinded evaluations of the randomized study-set assessing multiple parameters including the different types of vascular morphology. Non-blinded quantitative measurements of vascular diameter were also performed.
Results
The blinded observer analysis suggest that D-OCT evaluation of the vascular morphology may aid in distinguishing AK, BD and SCC lesions. We identified two vascular shapes that presented significantly differently across the lesion types, namely 'blobs' and 'curves'. A strong presence of blobs at 300μm skin depth was characteristically seen in a third of BD cases, while not or only slightly present in AK and SCC lesions. Vascular curves were predominantly present in AK lesions.
Conclusion
We identified various vascular D-OCT features that may aid in non-invasively differentiating subtypes within the keratinocyte skin cancer spectrum.
This article is protected by copyright. All rights reserved.
http://ift.tt/2qFGmPO
Neutrophil to Lymphocyte Ratio Decreases After Treatment of Psoriasis with Therapeutic Antibodies
Abstract
Although neutrophils are a histologic hallmark of psoriasis, it is unclear whether neutrophils are simply effector cells or drive pathogenesis. A recent psoriasis study with murine models evaluated various chemokines, lipids, and cytokines proposing that neutrophils are key players in positive feedback loops perpetuating the disease.1 Additionally, when neutrophils are depleted in pustular psoriasis, the disease drastically improves.2 There is mounting evidence supporting the use of neutrophil to lymphocyte ratio (NLR) as a marker of inflammation in active psoriasis. While absolute neutrophil counts (ANC) varies significantly amongst individuals, NLR may serve as an individually-normalized measure of relative neutrophil counts in psoriasis patients, and has been shown to be elevated in psoriasis patients with severe disease.3-5
This article is protected by copyright. All rights reserved.
http://ift.tt/2rf21v5
Merkel cell carcinoma: morphologic aspects on reflectance confocal microscopy
Abstract
Merkel cell carcinoma (MCC) is an uncommon skin tumour with aggressive behaviour. Clinically, MCC usually appear as a fast growing red cherry nodule on the leg or face of elderly patients (1-4). Dermoscopically, it might reveal a reddish background with arborizing not in focus vessels, a pattern that is rather aspecific. Thus, the final diagnosis is routinely made by histopathologic examination and specific immunohistochemical stainings.
This article is protected by copyright. All rights reserved.
http://ift.tt/2qFxxFz
Scalp threading with polydioxanone monofilament threads: A novel, effective and safe modality for hair restoration
Abstract
The current medical treatment options for androgenetic alopecia (AGA), although effective, tend to show a plateauing off of the response with no further hair growth.1 Hair transplantation is unacceptable tomany patients owing to it being a surgical modality and/or the cost involved.
This article is protected by copyright. All rights reserved.
http://ift.tt/2rf41n4
High-Grade Transformation (Dedifferentiation) of Acinic Cell Carcinoma of the Parotid Gland: Report of an Unusual Variant
Acinic cell carcinoma with high-grade transformation of the salivary gland is an unusual variant with less than fifty cases being reported in the literature. It is characterized by a low- and high-grade component juxtaposed with one another and tends to take on a more aggressive clinical course than its low-grade counterpart, suggesting a poor clinical outcome. We, hereby, report a case of acinic cell carcinoma in a 48-year-old woman with a 6-month history of a right parotid facial swelling rapidly increasing in size. The tumor was initially resected; however, residual focal tissue subsequently revealed areas typical of low-grade acinic cell carcinoma as well as high-grade transformation/dedifferentiation via histopathology.
http://ift.tt/2qeUhuS
Pathogenicity of ADAR1 mutation in a Chinese family with dyschromatosis symmetrica hereditaria
Abstract
Dyschromatosis symmetrica hereditaria (DSH, OMIM 127400) is a rare pigmentary genodermatosis with an autosomal dominant mode of inheritance that is characterized by a mixture of hyperpigmented and hypopigmented macules on the dorsal regions of the extremities and freckle-like macules on the face. ADAR1 is the corresponding causal gene of DSH.1Here, we report a novel heterozygous mutation in the ADAR1 gene in a Chinese family with DSH that may potentially be responsible for the observed clinical presentations, which differ from those previously described.
This article is protected by copyright. All rights reserved.
http://ift.tt/2r5HdZO
A novel frameshift mutation of the ADAR1 gene in a Chinese patient with dyschromatosis symmetrica hereditaria and the dermoscopic features
Abstract
Dyschromatosis symmetrica hereditaria (DSH), which characterized by hyper- or hypopigmented macules on the dorsal aspect of distal extremities and freckle-like macules on the face, is a rare pigmented genodermatosis that usually restricted to the skin. Generally, DSH is considered autosomal dominant, and adenosine deaminase acting on the RNA-1 (ADAR1) gene is one of the responsible genes [1]. ADAR catalyses adenosine-to-inosine (A-to-I) editing of dsRNA substrates, which plays an important role in posttranscriptional regulatory processes. Here, we present a novel frameshift mutation of ADAR1 gene in a Chinese DSH pedigree.
This article is protected by copyright. All rights reserved.
http://ift.tt/2pKhUZf
Expression of the filaggrin gene in umbilical cord blood predicts eczema risk in infancy: a birth cohort study
Abstract
Background
Filaggrin gene (FLG) expression, particularly in the skin, has been linked to the development of the skin barrier and is associated with eczema risk. However, knowledge as to whether FLG expression in umbilical cord blood (UCB) is associated with eczema development and prediction is lacking.
Objective
This study sought to assess whether FLG expression in UCB associates with and predicts the development of eczema in infancy.
Methods
Infants enrolled in a birth cohort study (n = 94) were assessed for eczema at ages 3-, 6-, and 12-months. Five probes measuring FLG transcripts expression in UCB were available from genome-wide gene expression profiling. FLG genetic variants R501X, 2282del4, and S3247X were genotyped. Associations were assessed using Poisson regression with robust variance estimation. Area under the curve (AUC), describing the discriminatory/predictive performance of fitted models, was estimated from logistic regression.
Results
Increased level of FLG expression measured by probe A_24_P51322 was associated with reduced risk of eczema during the first year of life (RR = 0.60, 95% CI: 0.38-0.95). In contrast, increased level of FLG antisense transcripts measured by probe A_21_P0014075 was associated with increased risk of eczema (RR = 2.02, 95% CI: 1.10-3.72). In prediction models including FLG expression, FLG genetic variants, and sex, discrimination between children who will and will not develop eczema at 3-months of age was high (AUC: 0.91, 95% CI: 0.84-0.98).
Conclusions and Clinical Relevance
This study demonstrated, for the first time, that FLG expression in UCB is associated with eczema development in infancy. Moreover, our analysis provided prediction models that were capable of discriminating, to a great extent, between those who will and will not develop eczema in infancy. Therefore, early identification of infants at increased risk of developing eczema is possible and such high-risk newborns may benefit from early stratification and intervention.
This article is protected by copyright. All rights reserved.
http://ift.tt/2pxK9yv
Neutrophil Extracellular Traps are associated with disease severity and microbiota diversity in Chronic Obstructive Pulmonary Disease
Publication date: Available online 13 May 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Alison J. Dicker, Megan L. Crichton, Eleanor G. Pumphrey, Andrew J. Cassidy, Guillermo Suarez-Cuartin, Oriol Sibila, Elizabeth Furrie, Christopher J. Fong, Wasyla Ibrahim, Gill Brady, Gisli G. Einarsson, J Stuart Elborn, Stuart Schembri, Sara E. Marshall, Colin NA. Palmer, James D. Chalmers
BackgroundNeutrophil extracellular traps (NETs) have been observed in the airway in COPD, but their clinical and pathophysiological implications have not been defined.ObjectiveTo determine if NETs are associated with disease severity in COPD, and how they are associated with microbiota composition and airway neutrophil function.MethodsNET protein complexes (DNA-Elastase and Histone-Elastase complexes), cell free DNA and neutrophil biomarkers were quantified in soluble sputum and serum from COPD patients during periods of disease stability and during exacerbations, and compared to clinical measures of disease severity and sputum microbiome. Peripheral blood and airway neutrophil function was evaluated by flow cytometry ex vivo and experimentally following stimulation of NET formation.ResultsSputum NET complexes were associated with the severity of COPD evaluated using the composite GOLD scale (p<0.0001). This relationship was due to modest correlations between NET complexes and FEV1, symptoms evaluated by the COPD assessment test and higher levels of NET complexes in patients with frequent exacerbations (p=0.002). Microbiota composition was heterogeneous, but there was a correlation between NET complexes and both microbiota diversity (P=0.009) and dominance of Haemophilus spp operational taxonomic units. (P=0.01). Ex vivo airway neutrophil phagocytosis of bacteria was reduced in patients with elevated sputum NET complexes. Consistent results were observed regardless of the method of quantifying sputum NETs. Failure of phagocytosis could be induced experimentally by incubating healthy control neutrophils with COPD soluble sputum.ConclusionNET formation is increased in severe COPD and is associated with more frequent exacerbations and a loss of microbiota diversity.
Graphical abstract
Teaser
Neutrophil extracellular traps are associated with disease severity and loss of microbiota diversity in COPD, suggesting a role in disease pathogenesis and progression.http://ift.tt/2pJYEva