scholarly journals Dynamics of the upper airway microbiome in the pathogenesis of asthma-associated persistent wheeze in preschool children

2017 ◽  
Author(s):  
Shu Mei Teo ◽  
Howard HF Tang ◽  
Danny Mok ◽  
Louise M Judd ◽  
Stephen C Watts ◽  
...  
Keyword(s):  
Preschool Children ◽  
Airway Inflammation ◽  
Birth Cohort ◽  
Allergic Sensitization ◽  
Upper Airway ◽  
Lower Airway ◽  
Small Range ◽  
Viral Pathogens ◽  
Asthma Phenotype ◽  
Airway Microbiome

ABSTRACTRepeated cycles of infection-associated lower airway inflammation drives the pathogenesis of persistent wheezing disease in children. Tracking these events across a birth cohort during their first five years, we demonstrate that >80% of infectious events indeed involve viral pathogens, but are accompanied by a shift in the nasopharyngeal microbiome (NPM) towards dominance by a small range of pathogenic bacterial genera. Unexpectedly, this change in NPM frequently precedes the appearance of viral pathogens and acute symptoms. In non-sensitized children these events are associated only with “transient wheeze” that resolves after age three. In contrast, in children developing early allergic sensitization, they are associated with ensuing development of persistent wheeze, which is the hallmark of the asthma phenotype. This suggests underlying pathogenic interactions between allergic sensitization and antibacterial mechanisms.

scholarly journals Upper and lower airway inflammation in severe asthmatics: a guide for a precision biologic treatment

2020 ◽  
Vol 14 ◽  
pp. 175346662096515
Author(s):  
Manuela Latorre ◽  
Elena Bacci ◽  
Veronica Seccia ◽  
Maria Laura Bartoli ◽  
Cristina Cardini ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Asthma Control ◽  
Allergic Sensitization ◽  
Biological Assessment ◽  
Lower Airway ◽  
High Dose ◽  
Eligibility Criteria ◽  
Serum Ige ◽  
Nasal Cytology ◽  
Blood Eosinophils

Background and aims: Severe asthma may require the prescription of one of the biologic drugs currently available, using surrogate markers of airway inflammation (serum IgE levels and allergic sensitization for anti-IgE, or blood eosinophils for anti-IL5/IL5R). Our objective: to assess upper and lower airway inflammation in severe asthmatics divided according to the eligibility criteria for one of the target biologic treatments. Methods: We selected 91 severe asthmatics, uncontrolled despite high-dose ICS-LABA, and followed for >6 months with optimization of asthma treatment. Patients underwent clinical, functional and biological assessment, including induced sputum and nasal cytology. They were then clustered according to the eligibility criteria for omalizumab or mepolizumab/benralizumab. Results: Four clusters were selected: A (eligible for omalizumab, n = 23), AB (both omalizumab and mepolizumab, n = 26), B (mepolizumab, n = 22) and C (non-eligible for both omalizumab and mepolizumab, n = 20). There was no difference among clusters for asthma control (Asthma Control Test and Asthma Control Questionnaire 7), pre-bronchodilator forced expiratory volume in 1 s, serum IgE and fractional exhaled nitric oxide levels. Sputum eosinophils were numerically higher in clusters AB and B, in agreement with the higher levels of blood eosinophils. Allergic rhinitis was more frequent in clusters A and AB, while chronic rhinosinusitis with nasal polyps prevalence increased progressively from A to C. Eosinophils in nasal cytology were higher in clusters AB, B and C. Conclusion: Eosinophilic upper and lower airway inflammation is present in the large majority of severe asthmatics, independently from the prescription criteria for the currently available biologics, and might suggest the use of anti-IL5/IL5R or anti IL4/13 also in patients without blood eosinophilia. The reviews of this paper are available via the supplemental material section.

scholarly journals Regulation of Interaction between the Upper and Lower Airways in United Airway Disease

2019 ◽  
Vol 7 (2) ◽  
pp. 27 ◽  
Author(s):  
Akira Kanda ◽  
Yoshiki Kobayashi ◽  
Mikiya Asako ◽  
Koichi Tomoda ◽  
Hideyuki Kawauchi ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Inhaled Corticosteroids ◽  
Upper Airway ◽  
Airway Disease ◽  
Comprehensive Approach ◽  
Lower Airway ◽  
T Helper 2 ◽  
Neural Modulation ◽  
Lower Airways ◽  
Novel Therapeutic

The concept of united airway disease comprises allergic rhinitis (AR) with asthma, and eosinophilic chronic rhinosinusitis (ECRS) with asthma. It embodies a comprehensive approach to the treatment of upper and lower airway inflammation. The treatment of upper airway inflammation reduces asthma symptoms and decreases the dose of inhaled corticosteroids (ICS) necessary to treat asthma. However, little is known about the mechanisms of interaction between upper and lower airway inflammation. Here we review these mechanisms, focusing on neural modulation and introduce a novel therapeutic approach to united airway disease using a fine-particle ICS. Our understanding of the relationship between the upper and lower airways and its contribution to T helper 2 (Th2)-skewed disease, such as AR and/or ECRS with asthma, has led us to this novel therapeutic strategy for a comprehensive approach to the treatment of upper airway inflammation with asthma.

scholarly journals Exploring protocol bias in airway microbiome studies: one versus two PCR steps and 16S rRNA gene region V3 V4 versus V4

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Christine Drengenes ◽  
Tomas M. L. Eagan ◽  
Ingvild Haaland ◽  
Harald G. Wiker ◽  
Rune Nielsen
Keyword(s):  
16S Rrna ◽  
16S Rrna Gene ◽  
Bacterial Load ◽  
Marker Gene ◽  
Gene Region ◽  
Lower Airway ◽  
Rrna Gene ◽  
Wide Range ◽  
Airway Microbiome ◽  
The Impact

Abstract Background Studies on the airway microbiome have been performed using a wide range of laboratory protocols for high-throughput sequencing of the bacterial 16S ribosomal RNA (16S rRNA) gene. We sought to determine the impact of number of polymerase chain reaction (PCR) steps (1- or 2- steps) and choice of target marker gene region (V3 V4 and V4) on the presentation of the upper and lower airway microbiome. Our analyses included lllumina MiSeq sequencing following three setups: Setup 1 (2-step PCR; V3 V4 region), Setup 2 (2-step PCR; V4 region), Setup 3 (1-step PCR; V4 region). Samples included oral wash, protected specimen brushes and protected bronchoalveolar lavage (healthy and obstructive lung disease), and negative controls. Results The number of sequences and amplicon sequence variants (ASV) decreased in order setup1 > setup2 > setup3. This trend appeared to be associated with an increased taxonomic resolution when sequencing the V3 V4 region (setup 1) and an increased number of small ASVs in setups 1 and 2. The latter was considered a result of contamination in the two-step PCR protocols as well as sequencing across multiple runs (setup 1). Although genera Streptococcus, Prevotella, Veillonella and Rothia dominated, differences in relative abundance were observed across all setups. Analyses of beta-diversity revealed that while oral wash samples (high biomass) clustered together regardless of number of PCR steps, samples from the lungs (low biomass) separated. The removal of contaminants identified using the Decontam package in R, did not resolve differences in results between sequencing setups. Conclusions Differences in number of PCR steps will have an impact of final bacterial community descriptions, and more so for samples of low bacterial load. Our findings could not be explained by differences in contamination levels alone, and more research is needed to understand how variations in PCR-setups and reagents may be contributing to the observed protocol bias.

scholarly journals Changes in the Upper and Lower Pharyngeal Airway Spaces Associated with Rapid Maxillary Expansion

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Fitin Aloufi ◽  
Charles B. Preston ◽  
Khalid H. Zawawi
Keyword(s):  
Orthodontic Treatment ◽  
Upper Airway ◽  
Rapid Maxillary Expansion ◽  
Lower Airway ◽  
Control Group ◽  
Maxillary Expansion ◽  
Pharyngeal Airway ◽  
Significant Difference ◽  
And Gender ◽  
Maxillary Constriction

Objectives. The primary objectives of this retrospective study were first to compare the upper and lower pharyngeal airway spaces between orthodontic patients with and without maxillary constriction and second to evaluate the effect of rapid maxillary expansion (RME) on these airway spaces. A secondary objective was to compare the mode of breathing between groups. Materials and Methods. The experimental (RME) group consisted of 30 patients (mean age, years, 16 boys and 14 girls) with maxillary constriction who were treated with hyrax-type RME. The control group comprised the records of age- and gender matched patients (mean age, years, 16 boys and 14 girls) with no maxillary constriction but requiring nonextraction comprehensive orthodontic treatment. Cephalometric measurements in the sagittal dimension of upper and lower airway spaces for the initial and final records were recorded. Mode of breathing and length of treatment were also compared. Results. The sagittal dimension of the upper airway increased significantly in the RME group ( mm) compared to the control group ( mm), . However, there was no significant difference in the lower pharyngeal airway measurement between the RME group () and the control group (), . There was no significant difference with respect to mode of breathing between the two groups (). Conclusion. Rapid maxillary expansion (RME) during orthodontic treatment may have a positive effect on the upper pharyngeal airway, with no significant change on the lower pharyngeal airway.

Effects of pharyngeal lubrication on the opening of obstructed upper airway

1992 ◽  
Vol 72 (6) ◽  
pp. 2311-2316 ◽  
Author(s):  
H. Miki ◽  
W. Hida ◽  
Y. Kikuchi ◽  
T. Chonan ◽  
M. Satoh ◽  
...  
Keyword(s):  
Hypoglossal Nerve ◽  
Muscle Tone ◽  
Upper Airway ◽  
Intraluminal Pressure ◽  
Lower Airway ◽  
Before And After ◽  
Airway Opening ◽  
Cervical Trachea ◽  
Artificial Surfactant ◽  
Stimulation Of

We examined the effect of electrical stimulation of the hypoglossal nerve and pharyngeal lubrication with artificial surfactant (Surfactant T-A) on the opening of obstructed upper airway in nine anesthetized supine dogs. The upper airway was isolated from the lower airway by transecting the cervical trachea. Upper airway obstruction was induced by applying constant negative pressures (5, 10, 20, and 30 cmH2O) on the rostral cut end of the trachea. Peripheral cut ends of the hypoglossal nerves were electrically stimulated by square-wave pulses at various frequencies from 10 to 30 Hz (0.2-ms duration, 5–7 V), and the critical stimulating frequency necessary for opening the obstructed upper airway was measured at each driving pressure before and after pharyngeal lubrication with artificial surfactant. The critical stimulation frequency for upper airway opening significantly increased as upper airway pressure became more negative and significantly decreased with lubrication of the upper airway. These findings suggest that greater muscle tone of the genioglossus is needed to open the occluded upper airway with larger negative intraluminal pressure and that lubrication of the pharyngeal mucosa with artificial surfactant facilitates reopening of the upper airway.

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