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American Journal of Respiratory and... May 2022Cross-sectional analysis of mucus plugs in computed tomography (CT) lung scans in the Severe Asthma Research Program (SARP)-3 showed a high mucus plug phenotype. To...
Cross-sectional analysis of mucus plugs in computed tomography (CT) lung scans in the Severe Asthma Research Program (SARP)-3 showed a high mucus plug phenotype. To determine if mucus plugs are a persistent asthma phenotype and if changes in mucus plugs over time associate with changes in lung function. In a longitudinal analysis of baseline and Year 3 CT lung scans in SARP-3 participants, radiologists generated mucus plug scores to assess mucus plug persistence over time. Changes in mucus plug score were analyzed in relation to changes in lung function and CT air trapping measures. In 164 participants, the mean (range) mucus plug score was similar at baseline and Year 3 (3.4 [0-20] vs. 3.8 [0-20]). Participants and bronchopulmonary segments with a baseline plug were more likely to have plugs at Year 3 than those without baseline plugs (risk ratio, 2.8; 95% confidence interval [CI], 2.0-4.1; < 0.001; and risk ratio, 5.0; 95% CI, 4.5-5.6; < 0.001, respectively). The change in mucus plug score from baseline to Year 3 was significantly negatively correlated with change in FEV% predicted ( = -0.35; < 0.001) and with changes in CT air trapping measures (all values < 0.05). Mucus plugs identify a persistent asthma phenotype, and susceptibility to mucus plugs occurs at the subject and the bronchopulmonary segment level. The association between change in mucus plug score and change in airflow over time supports a causal role for mucus plugs in mechanisms of airflow obstruction in asthma.
Topics: Asthma; Cross-Sectional Studies; Humans; Lung; Mucus; Respiratory Function Tests
PubMed: 35104436
DOI: 10.1164/rccm.202110-2265OC -
Science Translational Medicine Nov 2022Not all patients with cancer and severe neutropenia develop fever, and the fecal microbiome may play a role. In a single-center study of patients undergoing...
Not all patients with cancer and severe neutropenia develop fever, and the fecal microbiome may play a role. In a single-center study of patients undergoing hematopoietic cell transplant ( = 119), the fecal microbiome was characterized at onset of severe neutropenia. A total of 63 patients (53%) developed a subsequent fever, and their fecal microbiome displayed increased relative abundances of , a species of mucin-degrading bacteria ( = 0.006, corrected for multiple comparisons). Two therapies that induce neutropenia, irradiation and melphalan, similarly expanded and additionally thinned the colonic mucus layer in mice. Caloric restriction of unirradiated mice also expanded and thinned the colonic mucus layer. Antibiotic treatment to eradicate before caloric restriction preserved colonic mucus, whereas reintroduction restored mucus thinning. Caloric restriction of unirradiated mice raised colonic luminal pH and reduced acetate, propionate, and butyrate. Culturing in vitro with propionate reduced utilization of mucin as well as of fucose. Treating irradiated mice with an antibiotic targeting or propionate preserved the mucus layer, suppressed translocation of flagellin, reduced inflammatory cytokines in the colon, and improved thermoregulation. These results suggest that diet, metabolites, and colonic mucus link the microbiome to neutropenic fever and may guide future microbiome-based preventive strategies.
Topics: Mice; Animals; Gastrointestinal Microbiome; Propionates; Hematopoietic Stem Cell Transplantation; Verrucomicrobia; Mucus; Mucins; Diet; Neutropenia; Neoplasms
PubMed: 36383683
DOI: 10.1126/scitranslmed.abo3445 -
Current Biology : CB Aug 2021Mucus is a slimy hydrogel that lines the mucosal surfaces in our body, including the intestines, stomach, eyes, lungs and urogenital tract. This glycoprotein-rich...
Mucus is a slimy hydrogel that lines the mucosal surfaces in our body, including the intestines, stomach, eyes, lungs and urogenital tract. This glycoprotein-rich network is truly the jack of all trades. As a barrier, it lubricates surfaces, protects our cells from physical stress, and selectively allows the passage of nutrients while clearing out pathogens and debris. As a home to our microbiota, it supports a level of microbial diversity that is unattainable with most culture methods. As a reservoir of complex carbohydrate structures called glycans, it plays critical roles in controlling cell adhesion and signaling, and it alters the behavior and spatial distribution of microbes. On top of all this, mucus regulates the passage of sperm during fertilization, heals wounds, helps us smell, and prevents the stomach from digesting itself, to name just a few of its functions. Given these impressive features, it is no wonder that mucus crosses boundaries of species and kingdoms - mucus gels are made by organisms ranging from the simplest metazoans to corals, snails, fish, and frogs. It is also no surprise that mucus is exploited in everyday applications, including foods, cosmetics, and other products relevant to medicine and industry.
Topics: Animals; Intestines; Microbiota; Mucous Membrane; Mucus; Nutrients
PubMed: 34375594
DOI: 10.1016/j.cub.2021.06.093 -
Allergology International : Official... Jul 2024Eosinophilic inflammation is primarily characterized by type 2 immune responses against parasitic organisms. In the contemporary human being especially in developed... (Review)
Review
Eosinophilic inflammation is primarily characterized by type 2 immune responses against parasitic organisms. In the contemporary human being especially in developed countries, eosinophilic inflammation is strongly associated with allergic/sterile inflammation, and constitutes an undesired immune reaction. This situation is in stark contrast to neutrophilic inflammation, which is indispensable for the host defense against bacterial infections. Among eosinophilic inflammatory disorders, massive accumulation of eosinophils within mucus is observed in certain cases, and is often linked to the distinctive clinical finding of mucus with high viscosity. Eosinophilic mucus is found in a variety of diseases, including chronic allergic keratoconjunctivitis, chronic rhinosinusitis encompassing allergic fungal sinusitis, eosinophilic otitis media, eosinophilic sialodochitis, allergic bronchopulmonary aspergillosis/mycosis, eosinophilic plastic bronchitis, and eosinophilic asthma. In these pathological conditions, chronic inflammation and tissue remodeling coupled with irreversible organ damage due to persistent adhesion of toxic substances and luminal obstruction may impose a significant burden on the body. Eosinophils aggregate in the hyperconcentrated mucus together with cell-derived crystals, macromolecules, and polymers, thereby affecting the biophysical properties of the mucus. This review focuses on the clinically significant challenges of mucus and discusses the consequences of activated eosinophils on the mucosal surface that impact mucus and persistent inflammation.
Topics: Humans; Eosinophilia; Mucus; Eosinophils; Animals; Sinusitis
PubMed: 38594175
DOI: 10.1016/j.alit.2024.03.002 -
Respiratory Care Mar 2021Positive expiratory pressure (PEP) therapy imposes expiratory flow resistance to increase airway diameter and enhance mucus clearance. PEP is achieved several ways....
BACKGROUND
Positive expiratory pressure (PEP) therapy imposes expiratory flow resistance to increase airway diameter and enhance mucus clearance. PEP is achieved several ways. Oscillatory PEP devices (OPEP) generate repeated occlusions that are known to reduce mucus viscosity. There are many marketed devices, but comparative performance is mostly unreported. The purpose of this study was to evaluate performance characteristics of many PEP/OPEP devices. For OPEP devices, we defined an optimal performance metric by creating an oscillation index that combines the OPEP performance characteristics.
METHODS
PEP devices (TheraPEP, EzPAP, VersaPAP, Resistex, AccuPEP, AccuPAP, and Threshold PEP) and OPEP devices (Acapella DH, Acapella DM, Acapella Choice, ShurClear, Aerobika, VibraPEP, vPEP, and PocketPEP with and without the Oxyjet attachment) were tested by adjusting simulated expiratory flow from 5 L/min to 30 L/min in increments of 5 L/min using a standard flow meter.
RESULTS
All devices showed varying performance characteristics. As expiratory flow increased, mean PEP increased for most devices. The TheraPEP showed a mean PEP of 13 cm HO across all settings. For OPEP devices, there was a major difference between pressure and flow waveforms. The Acapella DH, ShurClear, and Aerobika showed the highest flow amplitude, flow frequency, and oscillation index.
CONCLUSIONS
PEP devices behaved similarly and as expected, with increased pressure with increased flow (flow resistors) or flow independence (threshold resistors). There was much greater variation in the performance of the OPEP devices. A higher oscillation index indicates better mechanical performance characteristics. Many devices have similar characteristics. However, the devices with the highest oscillation index have the highest flow amplitude and frequency, which may indicate better clinical performance.
Topics: Equipment Design; Exhalation; Humans; Mucus; Physical Therapy Modalities; Positive-Pressure Respiration
PubMed: 32934102
DOI: 10.4187/respcare.08150 -
Science (New York, N.Y.) Oct 2020Colon mucus segregates the intestinal microbiota from host tissues, but how it organizes to function throughout the colon is unclear. In mice, we found that colon mucus...
Colon mucus segregates the intestinal microbiota from host tissues, but how it organizes to function throughout the colon is unclear. In mice, we found that colon mucus consists of two distinct O-glycosylated entities of Muc2: a major form produced by the proximal colon, which encapsulates the fecal material including the microbiota, and a minor form derived from the distal colon, which adheres to the major form. The microbiota directs its own encapsulation by inducing Muc2 production from proximal colon goblet cells. In turn, O-glycans on proximal colon-derived Muc2 modulate the structure and function of the microbiota as well as transcription in the colon mucosa. Our work shows how proximal colon control of mucin production is an important element in the regulation of host-microbiota symbiosis.
Topics: Animals; Colon; Feces; Gastrointestinal Microbiome; Glycosylation; Mice; Mice, Knockout; Mucin-2; Mucus; Transcription, Genetic
PubMed: 33093110
DOI: 10.1126/science.aay7367 -
Respiratory Research Mar 2019Small airways disease (SAD) is a cardinal feature of chronic obstructive pulmonary disease (COPD) first recognized in the nineteenth century. The diverse... (Review)
Review
Small airways disease (SAD) is a cardinal feature of chronic obstructive pulmonary disease (COPD) first recognized in the nineteenth century. The diverse histopathological features associated with SAD underpin the heterogeneous nature of COPD. Our understanding of the key molecular mechanisms which drive the pathological changes are not complete. In this article we will provide a historical overview of key histopathological studies which have helped shape our understanding of SAD and discuss the hallmark features of airway remodelling, mucous plugging and inflammation. We focus on the relationship between SAD and emphysema, SAD in the early stages of COPD, and the mechanisms which cause SAD progression, including bacterial colonization and exacerbations. We discuss the need to specifically target SAD to attenuate the progression of COPD.
Topics: Airway Remodeling; Animals; Disease Progression; Forecasting; Humans; Inflammation; Lung; Mucus; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Smoking
PubMed: 30832670
DOI: 10.1186/s12931-019-1017-y -
The Cochrane Database of Systematic... Nov 2019Chest physiotherapy is widely prescribed to assist the clearance of airway secretions in people with cystic fibrosis (CF). Positive expiratory pressure (PEP) devices... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chest physiotherapy is widely prescribed to assist the clearance of airway secretions in people with cystic fibrosis (CF). Positive expiratory pressure (PEP) devices provide back pressure to the airways during expiration. This may improve clearance by building up gas behind mucus via collateral ventilation and by temporarily increasing functional residual capacity. The developers of the PEP technique recommend using PEP with a mask in order to avoid air leaks via the upper airways and mouth. In addition, increasing forced residual capacity (FRC) has not been demonstrated using mouthpiece PEP. Given the widespread use of PEP devices, there is a need to determine the evidence for their effect. This is an update of a previously published review.
OBJECTIVES
To determine the effectiveness and acceptability of PEP devices compared to other forms of physiotherapy as a means of improving mucus clearance and other outcomes in people with CF.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. The electronic database CINAHL was also searched from 1982 to 2017. Most recent search of the Group's CF Trials Register: 20 February 2019.
SELECTION CRITERIA
Randomised controlled studies in which PEP was compared with any other form of physiotherapy in people with CF. This included, postural drainage and percussion (PDPV), active cycle of breathing techniques (ACBT), oscillating PEP devices, thoracic oscillating devices, bilevel positive airway pressure (BiPaP) and exercise.
DATA COLLECTION AND ANALYSIS
Three authors independently applied the inclusion and exclusion criteria to publications, assessed the risk of bias of the included studies and assessed the quality of the evidence using the GRADE recommendations.
MAIN RESULTS
A total of 28 studies (involving 788 children and adults) were included in the review; 18 studies involving 296 participants were cross-over in design. Data were not published in sufficient detail in most of these studies to perform any meta-analysis. In 22 of the 28 studies the PEP technique was performed using a mask, in three of the studies a mouthpiece was used with nose clips and in three studies it was unclear whether a mask or mouthpiece was used. These studies compared PEP to ACBT, autogenic drainage (AD), oral oscillating PEP devices, high-frequency chest wall oscillation (HFCWO) and BiPaP and exercise. Forced expiratory volume in one second was the review's primary outcome and the most frequently reported outcome in the studies (24 studies, 716 participants). Single interventions or series of treatments that continued for up to three months demonstrated little or no difference in effect between PEP and other methods of airway clearance on this outcome (low- to moderate-quality evidence). However, long-term studies had equivocal or conflicting results regarding the effect on this outcome (low- to moderate-quality evidence). A second primary outcome was the number of respiratory exacerbations. There was a lower exacerbation rate in participants using PEP compared to other techniques when used with a mask for at least one year (five studies, 232 participants; moderate- to high-quality evidence). In one of the included studies which used PEP with a mouthpiece, it was reported (personal communication) that there was no difference in the number of respiratory exacerbations (66 participants, low-quality evidence). Participant preference was reported in 10 studies; and in all studies with an intervention period of at least one month, this was in favour of PEP. The results for the remaining outcome measures (including our third primary outcome of mucus clearance) were not examined or reported in sufficient detail to provide any high-quality evidence; only very low- to moderate-quality evidence was available for other outcomes. There was limited evidence reported on adverse events; these were measured in five studies, two of which found no events. In a study where infants performing either PEP or PDPV experienced some gastro-oesophageal reflux , this was more severe in the PDPV group (26 infants, low-quality evidence). In PEP versus oscillating PEP, adverse events were only reported in the flutter group (five participants complained of dizziness, which improved after further instructions on device use was provided) (22 participants, low-quality evidence). In PEP versus HFCWO, from one long-term high-quality study (107 participants) there was little or no difference in terms of number of adverse events; however, those in the PEP group had fewer adverse events related to the lower airways when compared to HFCWO (high-certainty evidence). Many studies had a risk of bias as they did not report how the randomisation sequence was either generated or concealed. Most studies reported the number of dropouts and also reported on all planned outcome measures.
AUTHORS' CONCLUSIONS
The evidence provided by this review is of variable quality, but suggests that all techniques and devices described may have a place in the clinical treatment of people with CF. Following meta-analyses of the effects of PEP versus other airway clearance techniques on lung function and patient preference, this Cochrane Review demonstrated that there was high-quality evidence that showed a significant reduction in pulmonary exacerbations when PEP using a mask was compared with HFCWO. It is important to note that airway clearance techniques should be individualised throughout life according to developmental stages, patient preferences, pulmonary symptoms and lung function. This also applies as conditions vary between baseline function and pulmonary exacerbations.
Topics: Cystic Fibrosis; Drainage, Postural; Forced Expiratory Volume; Humans; Mucociliary Clearance; Mucus; Physical Therapy Modalities; Positive-Pressure Respiration; Randomized Controlled Trials as Topic; Respiratory Therapy
PubMed: 31774149
DOI: 10.1002/14651858.CD003147.pub5 -
BMJ Case Reports Apr 2022Mucus fishing syndrome is a chronic inflammatory ocular surface condition characterised by repetitive self-extraction of mucous strands from the eye.A man in his 30s...
Mucus fishing syndrome is a chronic inflammatory ocular surface condition characterised by repetitive self-extraction of mucous strands from the eye.A man in his 30s presented with bilateral ocular redness, itch, irritation, tearing and sticky mucoid discharge for 3 months. Examination disclosed bilateral bulbar and tarsal conjunctival injection. Fluorescein staining disclosed a well-circumscribed area of tarsal conjunctival epithelial defect near the inferior lacrimal punctum in both eyes. The patient admitted to a habit of mechanically removing mucus from his eyes several times a day. Demonstration of the mucus extraction process disclosed direct contact of his fingers with the excoriated tarsal conjunctiva in each eye. He was diagnosed with mucus fishing syndrome and his condition resolved within a month after he stopped fishing mucus from his eyes and had a course of topical antibiotics and steroids.Mucus fishing syndrome is an important diagnostic consideration in patients with chronic conjunctivitis.
Topics: Humans; Male; Conjunctiva; Conjunctivitis; Eye Diseases; Mucus; Syndrome
PubMed: 35396241
DOI: 10.1136/bcr-2022-249188 -
International Journal of Molecular... Nov 2020Preterm births are a global health priority that affects 15 million babies every year worldwide. There are no effective prognostic and therapeutic strategies relating to... (Review)
Review
Preterm births are a global health priority that affects 15 million babies every year worldwide. There are no effective prognostic and therapeutic strategies relating to preterm delivery, but uterine infections appear to be a major cause. The vaginal epithelium is covered by the cervicovaginal mucus, which is essential to health because of its direct involvement in reproduction and functions as a selective barrier by sheltering the beneficial lactobacilli while helping to clear pathogens. During pregnancy, the cervical canal is sealed with a cervical mucus plug that prevents the vaginal flora from ascending toward the uterine compartment, which protects the fetus from pathogens. Abnormalities of the cervical mucus plug and bacterial vaginosis are associated with a higher risk of preterm delivery. This review addresses the current understanding of the cervicovaginal mucus and the cervical mucus plug and their interactions with the microbial communities in both the physiological state and bacterial vaginosis, with a focus on gel-forming mucins. We also review the current state of knowledge of gel-forming mucins contained in mouse cervicovaginal mucus and the mouse models used to study bacterial vaginosis.
Topics: Animals; Cervix Uteri; Female; Humans; Infectious Disease Transmission, Vertical; Mice; Microbiota; Mucins; Mucus; Pregnancy; Pregnancy Complications, Infectious; Vagina; Vaginosis, Bacterial
PubMed: 33158227
DOI: 10.3390/ijms21218266