Mucin Biopolymers and Their Barrier Function at Airway Surfaces

Song, Daniel; Cahn, Devorah; Duncan, Gregg A.

doi:10.1021/acs.langmuir.0c02410

Cited by 55 publications

(56 citation statements)

References 66 publications

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“…Analysis of respiratory droplet composition has revealed the presence of lung surfactant and the absence of mucin, implicating the smaller airways as a more probable site of generation than the upper airways (44). However, mucus exists in the upper airways as a hydrogel (45). Evaporating hydrogels naturally develop a thin film of water over free air surfaces in the process of seeking equilibrium with moisture in the air (46).…”

Section: Discussionmentioning

confidence: 99%

COVID-19 symptoms reduce with targeted hydration of the nose, larynx and trachea

George

Scheuch²,

Seifart

et al. 2021

Preprint

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Dirty air and poor access to healthcare threatens the lives of billions of people in low-income regions of the world. We investigated whether upper-airway hydration might alter two-phase flow in the airways on normal tidal breathing and be a useful, safe, easily distributed non-drug intervention for limiting risks of COVID-19. In observational human volunteer studies involving 464 human subjects in Marburg, Germany (357 normal subjects), Boston, US (20 healthy subjects), and Bangalore, India (87 subjects recently tested positive for COVID-19), we find that respiratory droplet generation increases by up to 4 orders of magnitude with up to 1% total body mass dehydration (n=20), and in dehydration-associated states of advanced age (n=357), elevated BMI-age (n=148), and SARS-CoV-2 infection (n=87). Hydration of the nose, larynx and trachea in a protocol of exercise-induced dehydration by the nasal inhalation of calcium-rich hypertonic salt droplets of mean diameter 8-12 μm diminished respiratory droplet numbers and increased oxygenation relative to a non-treatment control (P<0.05). In a randomized double-blinded nasal-saline control study, thrice-a-day delivery of the calcium-rich hypertonic salts (active) over three days suppressed respiratory droplet generation by 51% +/- 11% and increased oxygen saturation by 48.08% ± 9.61% (P<0.001) in COVID-19 positive subjects (n=20), while no changes in exhaled aerosol (P=0.235) or oxygen saturation (P=0.533) were observed in the nasal-saline control group (n=20). In the active group 47% of patients discharged with no self-reported symptoms while all of the subjects in the nasal saline group discharged with lingering symptoms. Hydration of the upper airways appears promising as a non-drug approach for reducing risks of lower respiratory-tract infections such as COVID-19.

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Section: Discussionmentioning

confidence: 99%

COVID-19 symptoms reduce with targeted hydration of the nose, larynx and trachea

George

Scheuch²,

Seifart

et al. 2021

Preprint

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“…The airways in the LRT of the adult lung has approximately 23 generations of bifurcations with the trachea being the zeroth generation and the terminal bronchioles number 23. In the LRT, the ASL has two distinct layers depending on the generation: (i) a complex hydrogel mucus layer that is directly exposed to the inhaled/exhaled air and acts as a clearance vehicle and protective barrier against foreign particles and pathogens (up to generation [15][16], and (ii) a periciliary fluid-like layer in which the cilia beat and which up to generation 15-16 is below the first layer (for generation >17 only the periciliary fluid-like layer remains) [e.g., see 33,34]. The primary component of the overall ASL in healthy humans is water, with a nonvolatile solid fraction of approximately 1.1-2.3% wt [35,36].…”

mentioning

confidence: 99%

Exhaled particles from nanometre to millimetre and their origin in the human respiratory tract

Bagheri

Schlenczek

Turco

et al. 2021

Preprint

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Detailed knowledge of the properties of exhaled particles from the human respiratory tract for all genders and ages is essential to determine the modes of transmission of airborne diseases. This applies not only to the current COVID-19 pandemic, but also to many others, be it measles, seasonal influenza or tuberculosis. To date, there are no data on the individual-specific concentrations and sizes of exhaled particles over the entire size range from nanometre to millimetre. Here we present a comprehensive data set, measured by particle size spectrometry and in-line holography covering the entire size range from 132 healthy volunteers aged 5 to 80 years for a defined set of breathing and vocalisation activities. We find age to have a large effect on small particle concentrations (<5 microns), doubling in children during adolescence and in adults over a 30-year period. In contrast, gender, body mass index, smoking or exercise habits have no discernible influence. Particles >20 microns show on average no measurable dependence on the type of vocalisation with the exception of shouting. We show evidence that particles <5 microns mainly originate in the lower respiratory tract, 5-15 microns in the larynx/pharynx, and >15 microns in the oral cavity.

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“…Mucins have been reported as the major cause of nonspecific bindings and background signals in many immunoassays using mucosal samples, 8 due to their ability to bind to a variety of solid surfaces. 9,10 Mucins are a family of glycoproteins that are widely present in the upper respiratory system 10 , with high molecular weight, high glycosylation, and abundance of negative charge groups. We postulated that mucins were the source of the background signal in our assay.…”

Section: Resultsmentioning

confidence: 99%

Femtomolar SARS-CoV-2 Antigen Detection Using the Microbubbling Digital Assay with Smartphone Readout Enables Antigen Burden Quantitation and Dynamics Tracking

Chen

Zhao

Feng

et al. 2021

Preprint

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Background: Little is known about the dynamics of SARS-CoV-2 antigen burden in respiratory samples in different patient populations at different stages of infection. Current rapid antigen tests cannot quantitate and track antigen dynamics with high sensitivity and specificity in respiratory samples. Methods: We developed and validated an ultra-sensitive SARS-CoV-2 antigen assay with smartphone readout using the Microbubbling Digital Assay previously developed by our group, which is a platform that enables highly sensitive detection and quantitation of protein biomarkers. A computer vision-based algorithm was developed for microbubble smartphone image recognition and quantitation. A machine learning-based classifier was developed to classify the smartphone images based on detected microbubbles. Using this assay, we tracked antigen dynamics in serial swab samples from COVID patients hospitalized in ICU and immunocompromised COVID patients. Results: The limit of detection (LOD) of the Microbubbling SARS-CoV-2 Antigen Assay was 0.5 pg/mL (10.6 fM) recombinant nucleocapsid (N) antigen or 4000 copies/mL inactivated SARS-CoV-2 virus in nasopharyngeal (NP) swabs, comparable to many rRT-PCR methods. The assay had high analytical specificity towards SARS-CoV-2. Compared to EUA-approved rRT-PCR methods, the Microbubbling Antigen Assay demonstrated a positive percent agreement (PPA) of 97% (95% confidence interval (CI), 92-99%) in symptomatic individuals within 7 days of symptom onset and positive SARS-CoV-2 nucleic acid results, and a negative percent agreement (NPA) of 97% (95% CI, 94-100%) in symptomatic and asymptomatic individuals with negative nucleic acid results. Antigen positivity rate in NP swabs gradually decreased as days-after-symptom-onset increased, despite persistent nucleic acid positivity of the same samples. The computer vision and machine learning-based automatic microbubble image classifier could accurately identify positives and negatives, based on microbubble counts and sizes. Total microbubble volume, a potential marker of antigen burden, correlated inversely with Ct values and days-after-symptom-onset. Antigen was detected for longer periods of time in immunocompromised patients with hematologic malignancies, compared to immunocompetent individuals. Simultaneous detectable antigens and nucleic acids may indicate the presence of replicating viruses in patients with persistent infections. Conclusions: The Microbubbling SARS-CoV-2 Antigen Assay enables sensitive and specific detection of acute infections, and quantitation and tracking of antigen dynamics in different patient populations at various stages of infection. With smartphone compatibility and automated image processing, the assay is well-positioned to be adapted for point-of-care diagnosis and to explore the clinical implications of antigen dynamics in future studies.

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Mucin Biopolymers and Their Barrier Function at Airway Surfaces

Cited by 55 publications

References 66 publications

COVID-19 symptoms reduce with targeted hydration of the nose, larynx and trachea

COVID-19 symptoms reduce with targeted hydration of the nose, larynx and trachea

Exhaled particles from nanometre to millimetre and their origin in the human respiratory tract

Femtomolar SARS-CoV-2 Antigen Detection Using the Microbubbling Digital Assay with Smartphone Readout Enables Antigen Burden Quantitation and Dynamics Tracking

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