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1.
Microbes Infect ; : 105317, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38452852

RESUMEN

The discovery of bacterial microcolonies in tonsillar tissue of patients with tonsillar hyperplasia has raised the question of their role in provoking the local immune response. Tonsils collected from patients undergoing tonsillectomy were stained for three clinically relevant bacterial taxa and lymphocytes. The bacterial composition and abundance of microcolonies was investigated using a combination of laser-microdissection, amplicon sequencing and Droplet Digital polymerase chain reaction. Microcolonies were detected in most samples (32/35) with a high prevalence of Haemophilus influenzae (78% of samples). B and T cell lymphocytes were significantly higher in the epithelium adjacent to microcolonies compared to epithelium distal to microcolonies. Furthermore, significant positive and negative correlations were identified between bacterial taxa and lymphocytes. Genus Streptococcus, which includes Group A Streptococcus (traditionally described as the main pathogen of tonsillar hyperplasia), was found in low abundance in this study. These results suggest other potential pathogens may be involved in stimulating the local immune response leading to tonsillar hyperplasia.

2.
Microbiol Spectr ; 12(2): e0170923, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38168683

RESUMEN

Polymyxin B and ethylenediaminetetraacetic acid are antimicrobials possessing antibiofilm activity. They act by displacement and chelation, respectively, of divalent cations in bacterial membranes and may therefore act synergistically when applied in combination. If so, this combination of agents may be useful for the treatment of diseases like cystic fibrosis (CF), in which biofilms are present on the respiratory epithelium. We used checkerboard assays to investigate the synergy between these agents using reference strains Pseudomonas aeruginosa ATCC 27853 and Staphylococcus aureus ATCC 6538 in planktonic form. We then determined the efficacy of each agent against biofilms of both species grown on 96-pin lids and proceeded to combination testing against the P. aeruginosa reference strain and 10 clinical isolates from patients with CF. Synergism was observed for planktonic forms of both species and for biofilms of P. aeruginosa. The susceptibility of biofilms of P. aeruginosa clinical isolates to these agents was variable compared to the laboratory reference strain. This combination of agents may be useful in the management of biofilm-associated conditions, particularly those amenable to topical therapies. These results provide a basis upon which the antimicrobial and antibiofilm efficacy of preparations containing these agents may be enhanced.IMPORTANCEBacteria living in biofilms produce a protective matrix which makes them difficult to kill. Patients with severe respiratory disease often have biofilms. Polymyxin B is an antibiotic commonly used in topical medications, such as eye drops and nasal sprays. Ethylenediaminetetraacetic acid (EDTA) is used widely as a preservative in medication but also has antimicrobial properties. It has been hypothesized that Polymyxin B and EDTA could have a synergistic relationship: when used in combination their antimicrobial effect is enhanced. Here, we evaluated the levels at which Polymyxin B and EDTA work together to kill common pathogens Pseudomonas aeruginosa and Staphylococcus aureus. We found that Polymyxin B and EDTA were synergistic. This synergy may be useful in the management of planktonic infection with P. aeruginosa and S. aureus, or biofilm infection with P. aeruginosa. This synergy may be beneficial in the treatment of respiratory biofilms, in which P. aeruginosa biofilms are common.


Asunto(s)
Antiinfecciosos , Fibrosis Quística , Infecciones por Pseudomonas , Infecciones Estafilocócicas , Humanos , Polimixina B/uso terapéutico , Ácido Edético , Pseudomonas aeruginosa , Staphylococcus aureus , Antibacterianos/uso terapéutico , Antiinfecciosos/uso terapéutico , Biopelículas , Fibrosis Quística/microbiología , Pruebas de Sensibilidad Microbiana
3.
Expert Rev Clin Immunol ; 19(8): 911-920, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37378564

RESUMEN

INTRODUCTION: Chronic rhinosinusitis (CRS) is characterized by inflammation of the paranasal sinus mucosa persisting for more than 12 weeks. This condition is associated with reduced quality-of-life and causes a high direct and indirect economic burden. Several pathogenic factors have been attributed to CRS, including bacterial and fungal biofilms on the sinonasal mucosa. Biofilms are well-established contributors to recalcitrance to treatment in other chronic inflammatory mucosal conditions such as cystic fibrosis and otitis media. AREAS COVERED: This review will present an overview of the role of biofilms in CRS, including the evidence for biofilms being present on the sinonasal mucosa and their implications for disease severity. Furthermore, the interactions between biofilms and host-mediated immune factors are explored. EXPERT OPINION: The eradication of biofilms has been a focus of research shortly after their recognition as a cause of disease. The currently available methodologies for identifying biofilms on mucosal surfaces are not sufficiently well-developed to be used in a clinical setting. A more accurate, cheaper, faster approach for biofilm detection is necessary, and molecular techniques may provide the possibility for this.


Asunto(s)
Rinitis , Sinusitis , Humanos , Mucosa Nasal/microbiología , Biopelículas , Enfermedad Crónica
4.
Int Forum Allergy Rhinol ; 13(10): 1962-1965, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-36846913

RESUMEN

KEY POINTS: Bacterial composition is uniform in the sinuses of postviral olfactory dysfunction patients. Significant reduction of genus Corynebacterium in PVOD patients compared to controls.


Asunto(s)
Trastornos del Olfato , Senos Paranasales , Humanos , Olfato , Cavidad Nasal , Bacterias
5.
Laryngoscope ; 133(10): 2490-2495, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-36644968

RESUMEN

OBJECTIVES: Bacterial biofilms on the sinonasal mucosa, especially biofilms of Staphylococcus aureus, are associated with greater severity and recalcitrance of chronic rhinosinusitis (CRS). There are few, if any, antibiofilm agents suitable for sinonasal application available for the management of this problem. Nasodine® Nasal Spray (Nasodine) is a 0.5% povidone-iodine-based formulation that has been developed for sinonasal application. We investigated the antibiofilm efficacy of Nasodine to determine whether it may be a candidate for the treatment of biofilm-associated CRS. METHODS: Biofilms of S. aureus ATCC 6538 were grown in vitro using the Centers for Disease Control biofilm reactor. Intact biofilms were treated by immersion in 0.9% saline (control), half concentration Nasodine, or full concentration Nasodine for between 5 min and 6 h. Further biofilm cells were dispersed into suspension then treated for between 30 s and 5 min. Surviving bacteria were then enumerated by culture and counting colonies, and the log10 reduction in viable bacteria was compared with control. RESULTS: Nasodine demonstrated time and concentration-dependent bacterial killing against intact biofilm. Statistically significant reductions in viable bacteria from intact biofilms were seen with exposures as brief as 5 min. Nasodine consistently eradicated dispersed biofilm within 1 min. CONCLUSION: Nasodine is highly active against biofilms of S. aureus ATCC 6538 in vitro. Biofilm killing is impeded by the presence of the intact biofilm structure. LAY SUMMARY: In chronic rhinosinusitis (CRS), bacterial communities called biofilms are associated with more severe inflammation. An iodine-based nasal spray called Nasodine almost completely eradicates bacterial biofilms after 6 h of exposure. Nasodine may be useful for treating CRS. Laryngoscope, 133:2490-2495, 2023.


Asunto(s)
Rinitis , Sinusitis , Humanos , Staphylococcus aureus , Rociadores Nasales , Sinusitis/complicaciones , Biopelículas , Povidona Yodada/farmacología , Enfermedad Crónica , Rinitis/complicaciones
6.
Mol Neurodegener ; 18(1): 2, 2023 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-36609403

RESUMEN

BACKGROUND: Alzheimer's disease (AD) is neuropathologically characterized by amyloid-beta (Aß) plaques and neurofibrillary tangles. The main protein components of these hallmarks include Aß40, Aß42, tau, phosphor-tau, and APOE. We hypothesize that genetic variants influence the levels and solubility of these AD-related proteins in the brain; identifying these may provide key insights into disease pathogenesis. METHODS: Genome-wide genotypes were collected from 441 AD cases, imputed to the haplotype reference consortium (HRC) panel, and filtered for quality and frequency. Temporal cortex levels of five AD-related proteins from three fractions, buffer-soluble (TBS), detergent-soluble (Triton-X = TX), and insoluble (Formic acid = FA), were available for these same individuals. Variants were tested for association with each quantitative biochemical measure using linear regression, and GSA-SNP2 was used to identify enriched Gene Ontology (GO) terms. Implicated variants and genes were further assessed for association with other relevant variables. RESULTS: We identified genome-wide significant associations at seven novel loci and the APOE locus. Genes and variants at these loci also associate with multiple AD-related measures, regulate gene expression, have cell-type specific enrichment, and roles in brain health and other neuropsychiatric diseases. Pathway analysis identified significant enrichment of shared and distinct biological pathways. CONCLUSIONS: Although all biochemical measures tested reflect proteins core to AD pathology, our results strongly suggest that each have unique genetic architecture and biological pathways that influence their specific biochemical states in the brain. Our novel approach of deep brain biochemical endophenotype GWAS has implications for pathophysiology of proteostasis in AD that can guide therapeutic discovery efforts focused on these proteins.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/metabolismo , Estudio de Asociación del Genoma Completo , Péptidos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Placa Amiloide/patología , Fenotipo , Apolipoproteínas E/metabolismo , Proteínas tau/metabolismo
7.
Methods Mol Biol ; 2588: 105-130, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36418685

RESUMEN

Cultivation-independent (molecular) analysis of the oral microbiota can provide a comprehensive picture of microbial community composition, yet there is an at-times bewildering array of approaches that can be employed. This chapter introduces some of the key considerations when undertaking microbiota research and describes two alternative bioinformatic pipelines for conducting such studies. The descriptions are based on analysis of bacterial 16S ribosomal RNA gene sequences, but can be easily adapted for analysis of other microbial taxa such as fungi.


Asunto(s)
Biología Computacional , Microbiota , Microbiota/genética , ARN Ribosómico 16S/genética
8.
Microbiol Spectr ; 10(6): e0123922, 2022 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-36318025

RESUMEN

Despite antibiotics being the primary medical treatment for recurrent tonsillitis, the impact of antibiotics on the tonsillar microbiome is not well understood. This study aimed to determine the effect of amoxicillin with clavulanate on the composition and quantity of bacteria in the tonsils of children with recurrent tonsillitis. A multicenter randomized clinical trial in Auckland, New Zealand was undertaken between August 1, 2017, and June 30, 2018. Sixty children undergoing tonsillectomy for the indication of recurrent tonsillitis were recruited for this study. Following random allocation, 30 participants were prescribed amoxicillin with clavulanate for the week before surgery. The remaining 30 received no antibiotics. Immediately following surgery, the crypts of the right and left tonsils were swabbed. Bacterial 16S rRNA gene-targeted amplicon sequencing and histological techniques were utilized. In the control group, there were significantly higher relative abundances of Haemophilus, Streptococcus, Neisseria, and Porphyromonas. Members from the genera Fusobacterium and Treponema were found to be significantly more abundant in the antibiotic group. There were no significant differences in the absolute quantities of bacteria between the groups. Microscopic examination found fewer bacterial microcolonies present in the tonsillar crypts of participants in the antibiotic group. Streptococcus pyogenes was not present in these bacterial microcolonies. These results suggest that a single course of antibiotics has a significant impact on the tonsil microbiota composition. The duration of this effect and the effect that the altered microbiome has on the course of the condition need to be determined. IMPORTANCE Several studies have identified the presence of multiple pathogenic bacteria in hyperplastic adenoids and palatine tonsils. However, there are currently no studies that utilize this technology to investigate the effect of oral antibiotics in children with recurrent tonsillitis on the tonsillar microbiome. This is the first study to investigate the effect of antibiotics on the microbiome of tonsillar tissue in children with recurrent tonsillitis using molecular techniques. This study has shown that participants who received amoxicillin with clavulanate immediately before tonsillectomy had a significantly reduced number of bacterial taxa commonly associated with recurrent tonsillitis, as well as the number of bacterial microcolonies observed in the tonsillar crypts. This novel finding suggests that either the effect of antibiotics is not sustained or that they are not an effective treatment for recurrent tonsillitis.


Asunto(s)
Microbiota , Tonsilitis , Niño , Humanos , Amoxicilina/uso terapéutico , Ácido Clavulánico/farmacología , Ácido Clavulánico/uso terapéutico , ARN Ribosómico 16S/genética , Tonsilitis/tratamiento farmacológico , Tonsilitis/cirugía , Tonsilitis/microbiología , Microbiota/genética , Antibacterianos/uso terapéutico , Streptococcus pyogenes/genética
9.
Front Pharmacol ; 13: 840323, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35770097

RESUMEN

The role of bacterial biofilms in chronic and recalcitrant diseases is widely appreciated, and the treatment of biofilm infection is an increasingly important area of research. Chronic rhinosinusitis (CRS) is a complex disease associated with sinonasal dysbiosis and the presence of bacterial biofilms. While most biofilm-related diseases are associated with highly persistent but relatively less severe inflammation, the presence of biofilms in CRS is associated with greater severity of inflammation and recalcitrance despite appropriate treatment. Oral antibiotics are commonly used to treat CRS but they are often ineffective, due to poor penetration of the sinonasal mucosa and the inherently antibiotic resistant nature of bacteria in biofilms. Topical non-antibiotic antibiofilm agents may prove more effective, but few such agents are available for sinonasal application. We review compounds with antibiofilm activity that may be useful for treating biofilm-associated CRS, including halogen-based compounds, quaternary ammonium compounds and derivatives, biguanides, antimicrobial peptides, chelating agents and natural products. These include preparations that are currently available and those still in development. For each compound, antibiofilm efficacy, mechanism of action, and toxicity as it relates to sinonasal application are summarised. We highlight the antibiofilm agents that we believe hold the greatest promise for the treatment of biofilm-associated CRS in order to inform future research on the management of this difficult condition.

10.
Int J Pediatr Otorhinolaryngol ; 157: 111128, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35421675

RESUMEN

INTRODUCTION: Paediatric tonsillar hyperplasia (TH) is associated with a spectrum of presentations ranging from recurrent tonsillitis (RT) to sleep-disordered breathing (SDB). The underlying pathogenesis of tonsillar hyperplasia remains poorly understood. Previous studies have implicated bacterial microcolonies as targets of host inflammatory cells and as a potential driver of the chronic inflammation seen in TH. The role of atopy in tonsillar hyperplasia is also largely unknown. In this study, we aimed to determine the allergic responses and microbial factors that may influence TH in children. MATERIALS AND METHODS: Paired tonsils and a serum sample were collected from 21 children undergoing tonsillectomy for RT or SDB in the Auckland region. The disposition of immunoglobulin isotypes (IgG, A, M and E) and local inflammatory cells on histological sections of tonsil tissue were determined using immunohistochemistry techniques. Aeroallergen specific IgE (sIgE) and Staphylococcal enterotoxin C specific IgE (SEC-specific IgE) were measured in serum and tonsil tissue using the ImmunoCAP® system. Finally, tonsil bacterial microcolonies were then excised from histological slides using laser microdissection techniques, before undergoing bacterial and fungal amplicon sequencing. RESULTS: There were no significant differences in any of the measured variables between children with RT and SDB symptoms. IgE staining was not associated with increased levels of mast cells, leukocytes or plasma cells. However, sIgE positivity was more frequently found in local tissue than in serum (p = 0.025). A significant association was observed between tissue sIgE levels and tissue SEC-specific IgE levels (r2 = 0.95, p = 0.0001). The most abundant bacterial and fungal genera identified in the microcolonies were Fusobacterium, Sphingomonas, Porphyromonas, Prevotella and Malassezia. DISCUSSION: These results suggest that there is a local IgE response in children with TH. Local IgE production is unrelated to systemic atopy and may play a key role in the pathogenesis of TH. This is the first study to determine the microbial composition of microcolonies in tonsil tissue. These findings enhance current understanding of the microbiology of tonsils in children with TH and have important implications for antibiotic strategies.


Asunto(s)
Enfermedades Faríngeas , Síndromes de la Apnea del Sueño , Tonsilectomía , Tonsilitis , Niño , Humanos , Hiperplasia/patología , Inmunoglobulina E , Tonsila Palatina/patología , Enfermedades Faríngeas/patología , Tonsilitis/microbiología
11.
Sci Rep ; 11(1): 21940, 2021 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-34753993

RESUMEN

The role of Staphylococcus aureus in the pathogenesis of the chronic sinonasal disease chronic rhinosinusitis (CRS), has not been definitively established. Comparative analyses of S. aureus isolates from CRS with those from control participants may offer insight into a possible pathogenic link between this organism and CRS. The intra- and inter-subject S. aureus strain-level diversity in the sinuses of patients with and without CRS were compared in this cross-sectional study. In total, 100 patients (CRS = 64, control = 36) were screened for S. aureus carriage. The overall carriage prevalence of S. aureus in this cohort was 24% (CRS n = 13, control n = 11). Cultured S. aureus isolates from 18 participants were strain-typed using spa gene sequencing. The bacterial community composition of the middle meatus was assessed using amplicon sequencing targeting the V3V4 hypervariable region of the bacterial 16S rRNA gene. S. aureus isolates cultured from patients were grown in co-culture with the commensal bacterium Dolosigranulum pigrum and characterised. All participants harboured a single S. aureus strain and no trend in disease-specific strain-level diversity was observed. Bacterial community analyses revealed a significant negative correlation in the relative abundances of S. aureus and D. pigrum sequences, suggesting an antagonistic interaction between these organisms. Co-cultivation experiments with these bacteria, however, did not confirm this interaction in vitro. We saw no significant associations of CRS disease with S. aureus strain types. The functional role that S. aureus occupies in CRS likely depends on other factors such as variations in gene expression and interactions with other members of the sinus bacterial community.


Asunto(s)
Sinusitis/microbiología , Staphylococcus aureus/aislamiento & purificación , Adulto , Portador Sano , Enfermedad Crónica , Estudios Transversales , Femenino , Genes Bacterianos , Humanos , Masculino , Persona de Mediana Edad , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/genética
12.
Front Cell Infect Microbiol ; 11: 585625, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34595125

RESUMEN

Background: Chronic rhinosinusitis (CRS) is a globally prevalent inflammatory condition of the paranasal sinuses which severely impairs patients' quality of life. An animal model of unilateral sinusitis by transient sinus occlusion has been described previously in rabbits. The aim of this study was to characterise the sinusitis rabbit model by investigating temporal and bilateral changes in the bacterial community and mucosal inflammation. Methods: Development of sinusitis was achieved by endoscopically placing Merocel ® , a sterile nasal packing material, in the left middle meatus of six New Zealand white rabbits for four weeks. After a total period of 14 weeks, rabbits were assessed for sinusitis by endoscopic examination, magnetic resonance imaging (MRI) and histology. Swabs from the left and right middle meatus were obtained for bacterial community analysis at three time points (week 0, week 4, week 14) during the study. Results: Endoscopic evaluation showed unilateral inflammation in all animals examined after the 4-week blocking period and at week 14. Notably, inflammatory changes were also seen in the contralateral sinus of all animals at week 4. MRI images demonstrated unilateral sinus opacification at week 4 in two rabbits, and partial unilateral sinus opacification at week 14 in one rabbit only. Histological analyses revealed substantial spatial heterogeneity of mucosal inflammation with inconsistent findings across all animals. No significant differences in mucosal inflammatory markers (such as goblet cell hyperplasia, epithelial denudation and oedema) could be identified between nostrils at week 14. The bacterial community in the rabbit sinuses was heavily dominated by Helicobacter at week 0 (baseline). At the end of the blocking period (week 4), bacterial alpha and beta diversity were significantly increased in both nostrils. The bacterial community composition at week 14 had primarily returned to baseline, reflecting the endoscopic and radiological results. Conclusion: This study reaffirmed the ability for development of sinusitis without inoculation of any pathogens in a rabbit model. We were able to demonstrate bilateral sinonasal mucosal inflammation, by inducing unilateral sinus blockage, which resulted in significant changes to the sinonasal bacterial community. These findings may explain some of the clinical observations seen in CRS and warrant further research to reveal potential implications for its therapeutic management.


Asunto(s)
Senos Paranasales , Sinusitis , Animales , Enfermedad Crónica , Humanos , Inflamación , Cavidad Nasal , Senos Paranasales/diagnóstico por imagen , Calidad de Vida , Conejos , Sinusitis/diagnóstico por imagen
13.
Int J Otolaryngol ; 2021: 7428955, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34567126

RESUMEN

The purpose of this review is to summarise contemporary knowledge of sinonasal tissue remodelling during chronic rhinosinusitis (CRS), a chronic disease involving long-term inflammation of the paranasal sinuses and nasal passage. The concept of tissue remodelling has significant clinical relevance because of its potential to cause irreversibility in chronic airway tissues. Recent studies have indicated that early surgical treatment of CRS may improve clinical outcome. Tissue remodelling has been described in the literature extensively with no consensus on how remodelling is defined. This review describes various factors implicated in establishing remodelling in sinonasal tissues with a special mention of asthma as a comorbid condition. Some of the main histological features of remodelling include basement membrane thickening and collagen modulation. This may be an avenue of research with regard to targeted therapy against remodelling in CRS.

15.
Int Forum Allergy Rhinol ; 11(9): 1355-1366, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33877743

RESUMEN

BACKGROUND: Despite the widespread prescription of antibiotics for the treatment of chronic rhinosinusitis (CRS), their efficacy remains uncertain. Limited penetration of systemic antibiotics into the sinonasal mucosa has been reported previously by this group. This study aimed to investigate the short-term effects of antibiotics on the sinus and gut microbiota as well as any relationships these had with drug distribution. METHODS: Thirty subjects undergoing functional endoscopic sinus surgery for CRS were randomized to one of three groups: (1) doxycycline (100 mg daily for 7 days); (2) roxithromycin (300 mg daily for 7 days); and (3) control (no antibiotics given). Sinonasal and stool samples collected before and after treatment were analyzed using 16S ribosomal RNA (rRNA) gene-targeted amplicon sequencing and Droplet Digital polymerase chain reaction (PCR) for bacterial community composition and the quantification of bacterial DNA, respectively. RESULTS: There were no significant major bacterial community shifts or changes to bacterial diversity and load following the treatment period in all patient groups. Non-significant trend reductions were observed in gut microbial diversity with antibiotics. For the roxithromycin group, sinonasal bacterial diversity was negatively correlated with serum drug levels and reduced overall compared to controls (p < 0.05). The relative abundance of Staphylococcus ASV129 in sinonasal samples reduced with increasing mucus doxycycline levels (p = 0.01). CONCLUSION: Antibiotic prescription for CRS should be further investigated because of preliminary evidence of poor sinonasal drug penetration, unproven efficacy, and the potential impact of dysbiosis in the sinuses and off-target sites. Further studies should consider distinguishing the presence of DNA from viable and nonviable bacteria.


Asunto(s)
Microbiota , Rinitis , Sinusitis , Antibacterianos , Enfermedad Crónica , Humanos , ARN Ribosómico 16S/genética , Rinitis/tratamiento farmacológico , Sinusitis/tratamiento farmacológico
16.
Expert Rev Respir Med ; 15(9): 1187-1195, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33908842

RESUMEN

INTRODUCTION: The role of the microbiota in inflammatory airway diseases is unclear. Antimicrobial therapies have predominantly been guided by culture results. However, molecular sequencing has shown that the airway microbiota is much more complex and accurate modeling requires longitudinal analysis. AREAS COVERED: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses scoping review was performed by searching Medline, Scopus, and Web of Science databases for all longitudinal airway microbiota studies that utilized molecular techniques. 38 studies with 1,993 participants were included in this review. Healthy microbial communities were more diverse, individualized and stable over time. Acute infections resulted in changes in the microbiota that were detected earlier and more sensitively by molecular sequencing than culture. Distinct microbiota profiles have been demonstrated in chronic obstructive pulmonary disease patients associated with exacerbation frequency and severity. EXPERT OPINION: Longitudinal studies provide essential data on the stability of the microbiota over time and valuable information about the dynamic interactions between host, disease and microbes. We believe that molecular sequencing will be increasingly incorporated into research and clinical practice in the future. These advances can lead to improved diagnosis, enhanced prescribing guidance and reduce unnecessary antibiotic usage.


Asunto(s)
Microbiota , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Estudios Longitudinales , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Sistema Respiratorio
17.
Respir Res ; 22(1): 106, 2021 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-33849523

RESUMEN

BACKGROUND: Cystic fibrosis is a debilitating, autosomal recessive disease which results in chronic upper and lower airway infection and inflammation. In this study, four adult patients presenting with cystic fibrosis and chronic rhinosinusitis were recruited. Culture and molecular techniques were employed to evaluate changes in microbial profiles, host gene expression and antimicrobial resistance (AMR) in the upper respiratory tract over time. METHODS: Swab samples from the sinonasal cavity were collected at the time of surgery and at follow-up clinics at regular time intervals for up to 18 months. Nucleic acids were extracted, and DNA amplicon sequencing was applied to describe bacterial and fungal composition. In parallel, RNA was used to evaluate the expression of 17 AMR genes and two inflammatory markers (interleukins 6 and 8) using custom qPCR array cards. Molecular results were compared with routine sinus and sputum culture reports within each patient. RESULTS: Bacterial amplicon sequencing and swab culture reports from the sinonasal cavity were mostly congruent and relatively stable for each patient across time. The predominant species detected in patients P02 and P04 were Pseudomonas aeruginosa, Staphylococcus aureus in patient P03, and a mixture of Enterobacter and S. aureus in patient P01. Fungal profiles were variable and less subject specific than bacterial communities. Increased expressions of interleukins 6 and 8 were observed in all patients throughout the sampling period compared with other measured genes. The most prevalent AMR gene detected was ampC. However, the prevalence of AMR gene expression was low in all patient samples across varying time-points. CONCLUSIONS: We observed a surprising degree of stability of sinonasal microbial composition, and inflammatory and AMR gene expression across all patients post sinus surgery.


Asunto(s)
Fibrosis Quística/microbiología , Endoscopía/métodos , Microbiota , Procedimientos Quirúrgicos Otorrinolaringológicos , Senos Paranasales/microbiología , Rinitis/microbiología , Sinusitis/microbiología , Adulto , Enfermedad Crónica , Fibrosis Quística/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Senos Paranasales/cirugía , Proyectos Piloto , Periodo Posoperatorio , Rinitis/complicaciones , Rinitis/cirugía , Sinusitis/complicaciones , Sinusitis/cirugía , Adulto Joven
19.
Immun Inflamm Dis ; 9(1): 90-107, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33220024

RESUMEN

INTRODUCTION: The pathophysiology and temporal dynamics of affected tissues in chronic rhinosinusitis (CRS) remain poorly understood. Here, we present a multiomics-based time-series assessment of nasal polyp biopsies from three patients with CRS, assessing natural variability over time and local response to systemic corticosteroid therapy. METHODS: Polyp tissue biopsies were collected at three time points over two consecutive weeks. Patients were prescribed prednisone (30 mg daily) for 1 week between Collections 2 and 3. Polyp transcriptome, proteome, and microbiota were assessed via RNAseq, SWATH mass spectrometry, and 16S ribosomal RNA and ITS2 amplicon sequencing. Baseline interpatient variability, natural intrapatient variability over time, and local response to systemic corticosteroids, were investigated. RESULTS: Overall, the highly abundant transcripts and proteins were associated with pathways involved in inflammation, FAS, cadherin, integrin, Wnt, apoptosis, and cytoskeletal signaling, as well as coagulation and B- and T-cell activation. Transcripts and proteins that naturally varied over time included those involved with inflammation- and epithelial-mesenchymal transition-related pathways, and a number of common candidate target biomarkers of CRS. Ten transcripts responded significantly to corticosteroid therapy, including downregulation of TNF, CCL20, and GSDMA, and upregulation of OVGP1, and PCDHGB1. Members of the bacterial genus Streptococcus positively correlated with immunoglobulin proteins IGKC and IGHG1. CONCLUSIONS: Understanding natural dynamics of CRS-associated tissues is essential to provide baseline context for all studies on putative biomarkers, mechanisms, and subtypes of CRS. These data further our understanding of the natural dynamics within nasal polypoid tissue, as well as local changes in response to systemic corticosteroid therapy.


Asunto(s)
Microbiota , Pólipos Nasales , Rinitis , Sinusitis , Corticoesteroides/uso terapéutico , Humanos , Pólipos Nasales/tratamiento farmacológico , Proteínas de Neoplasias , Rinitis/tratamiento farmacológico , Sinusitis/tratamiento farmacológico
20.
Int J Pediatr Otorhinolaryngol ; 138: 110338, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33152956

RESUMEN

INTRODUCTION: Tonsillectomy is the second most common surgical procedure performed in pediatric otolaryngology. Multiple courses of antibiotics are usually prescribed prior to surgical intervention. Surgery is indicated when patients reach a certain number of infective episodes, or their obstructive symptoms warrant intervention. Little is known about the role of tonsillectomy on long term postoperative antibiotic use. Recently, our group published a retrospective case series that described the clinical characteristics and outcomes of children under the age of 16 years who underwent tonsillectomy. This study is a follow-up on this previous case series and its purpose is to determine whether tonsillectomy in this group of children led to a reduction in the number of antibiotics prescribed in the year following surgery. METHODS: Data were collected from the clinical records departments of two district health boards in Auckland, New Zealand. Hospital morbidity records were reviewed for all children younger than 16 years old, who underwent a tonsillectomy between December 2015 and December 2017 in the Auckland region. All antibiotics prescribed following surgery were obtained from New Zealand's national community prescribing database. RESULTS: A total of 1538 children underwent tonsillectomy during the study period. Following surgery, antibiotics were prescribed to 828 (54%) patients at the time of discharge, with an average of 1.2 ± 0.1 courses in the year following surgery. This was significantly reduced compared to preoperative antibiotic intake (3.4 ± 0.1 courses) in the year preceding surgery (p < 0.001). Readmission within 30 days of discharge was not associated with increased antibiotic usage postoperatively. In the two weeks following surgery, 25% of patients were prescribed a course of antibiotics for a presumed postoperative infection. CONCLUSIONS: These findings support the benefit of tonsillectomy in reducing antibiotic consumption in the year following surgery. Furthermore, it has highlighted areas of practice, such as perioperative antibiotic prescription, which can be improved to further reduce the prescription of antibiotics for children with tonsillar hyperplasia.


Asunto(s)
Antibacterianos/administración & dosificación , Enfermedades Faríngeas , Pautas de la Práctica en Medicina/estadística & datos numéricos , Tonsilectomía , Tonsilitis , Adolescente , Niño , Humanos , Nueva Zelanda , Atención Perioperativa , Enfermedades Faríngeas/cirugía , Estudios Retrospectivos , Tonsilitis/cirugía
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