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Annals of Allergy, Asthma & Immunology... Nov 2023Airways diseases are typically accompanied by inflammation, which has long been known to contribute to obstruction, mucus hypersecretion, dyspnea, cough, and other... (Review)
Review
Airways diseases are typically accompanied by inflammation, which has long been known to contribute to obstruction, mucus hypersecretion, dyspnea, cough, and other characteristic symptoms displayed in patients. Clinical interventions, therefore, often target inflammation to reverse lung pathology and reduce morbidity. The airways and lungs are densely innervated by subsets of nerve fibers, which are not only impacted by pulmonary inflammation but, in addition, likely serve as important regulators of immune cell function. This bidirectional neuroimmune crosstalk is supported by close spatial relationships between immune cells and airway nerve fibers, complementary neural and immune signaling pathways, local specialized airway chemosensory cells, and dedicated reflex circuits. In this article, we review the recent literature on this topic and present state-of-the-art evidence supporting the role of neuroimmune interactions in airway inflammation. In addition, we extend this evidence to synthesize considerations for the clinical translation of these discoveries to improve the management of patients with airway disease.
Topics: Humans; Inflammation; Pneumonia; Lung; Cough; Signal Transduction; Mucus
PubMed: 37517657
DOI: 10.1016/j.anai.2023.07.020 -
Current Opinion in Pulmonary Medicine Jan 2024Chronic bronchitis is a phenotype of chronic obstructive pulmonary disease (COPD), characterized by chronic cough and sputum production, associated with an increased... (Review)
Review
PURPOSE OF REVIEW
Chronic bronchitis is a phenotype of chronic obstructive pulmonary disease (COPD), characterized by chronic cough and sputum production, associated with an increased rate of COPD exacerbations and hospital admissions, a more rapid decline in lung function and reduced life expectancy. Despite optimal medical therapy, chronic bronchitis remains difficult to treat. Interventional bronchoscopic procedures offer novel therapeutic approaches to this highly symptomatic condition.
RECENT FINDINGS
A characteristic feature of chronic bronchitis is the presence of an abnormal epithelium with excessive mucus producing cells, parasympathetic overactivity, and airway inflammation. Metered cryospray and bronchial rheoplasty are designed to target this abnormal epithelium to reduce mucus production and inflammation. Targeted lung denervation aims to reduce parasympathetic overactivity, which may drive mucus hypersecretion. Here, we review the available evidence to determine the safety and efficacy across the bronchoscopic interventions.
SUMMARY
Interventional bronchoscopy is a rapidly expanding field and its application in the treatment of chronic bronchitis has been recognized by the Global initiative for chronic Obstructive Lung Disease (GOLD). The outcomes from the latest clinical trials will guide future treatment approaches in patients with difficult to treat chronic bronchitis.
Topics: Humans; Bronchitis, Chronic; Pulmonary Disease, Chronic Obstructive; Lung; Chronic Disease; Inflammation; Bronchitis
PubMed: 37942820
DOI: 10.1097/MCP.0000000000001036 -
Cell Host & Microbe Dec 2023Exclusive enteral nutrition (EEN) with fiber-free diets is an effective steroid-sparing treatment to induce clinical remission in children with Crohn's disease (CD)....
Exclusive enteral nutrition (EEN) with fiber-free diets is an effective steroid-sparing treatment to induce clinical remission in children with Crohn's disease (CD). However, the mechanism underlying the beneficial effects of EEN remains obscure. Using a model of microbiota-dependent colitis with the hallmarks of CD, we find that the administration of a fiber-free diet prevents the development of colitis and inhibits intestinal inflammation in colitic animals. Remarkably, fiber-free diet alters the intestinal localization of Mucispirillum schaedleri, a mucus-dwelling pathobiont, which is required for triggering disease. Mechanistically, the absence of dietary fiber reduces nutrient availability and impairs the dissimilatory nitrate reduction to ammonia (DNRA) metabolic pathway of Mucispirillum, leading to its exclusion from the mucus layer and disease remission. Thus, appropriate localization of the specific pathobiont in the mucus layer is critical for disease development, which is disrupted by fiber exclusion. These results suggest strategies to treat CD by targeting the intestinal niche and metabolism of disease-causing microbes.
Topics: Humans; Child; Animals; Crohn Disease; Diet; Colitis; Treatment Outcome; Microbiota
PubMed: 37967555
DOI: 10.1016/j.chom.2023.10.016 -
Microbiome Research Reports 2023species are integral members of the human gut microbiota and these microbes have significant interactions with the intestinal mucus layer. This review delves into... (Review)
Review
species are integral members of the human gut microbiota and these microbes have significant interactions with the intestinal mucus layer. This review delves into -mucus dynamics, shedding light on the multifaceted nature of this relationship. We cover conserved features of -mucus interactions, such as mucus adhesion and positive regulation of goblet cell and mucus production, as well as species and strain-specific attributes of mucus degradation. For each interface, we explore the molecular mechanisms underlying these interactions and their potential implications for human health. Notably, we emphasize the ability of species to positively influence the mucus layer, shedding light on its potential as a mucin-builder and a therapeutic agent for diseases associated with disrupted mucus barriers. By elucidating the complex interplay between and intestinal mucus, we aim to contribute to a deeper understanding of the gut microbiota-host interface and pave the way for novel therapeutic strategies.
PubMed: 38045921
DOI: 10.20517/mrr.2023.37 -
Autophagy Nov 2023Mucus secretion from colonic goblet cells is an important host defense mechanism against the harsh lumenal environment. Yet how mucus secretion is regulated is not well...
Mucus secretion from colonic goblet cells is an important host defense mechanism against the harsh lumenal environment. Yet how mucus secretion is regulated is not well understood. We discovered that constitutive activation of macroautophagy/autophagy via BECN1 (beclin 1) relieves endoplasmic reticulum (ER) stress in goblet cells, which in turn produce a thicker and less penetrable mucus barrier. Pharmacological reduction of the ER stress or activation of the unfolded protein response (UPR) in mice, regardless of autophagy activation, lead to excess mucus secretion. This regulation of mucus secretion by ER stress is microbiota-dependent and requires the activity of the intracellular sensor NOD2 (nucleotide-binding oligomerization domain containing 2). Excess mucus production in the colon alters the gut microbiota and protects from chemical- and infection-driven inflammation. Our findings provide new insights into the mechanisms by which autophagy regulates mucus secretion and susceptibility to intestinal inflammation.BECN1- Beclin 1; ER- endoplasmic reticulum; UPR - unfolded protein response; NOD2 - nucleotide-binding oligomerization domain containing 2; IBD- inflammatory bowel disease; BCL2- B cell leukemia/lymphoma 2; TUDCA- tauroursodeoxycholic acid; ATG16L1- autophagy related 16 like 1; LRRK2- leucine-rich repeat kinase 2.
Topics: Animals; Mice; Beclin-1; Autophagy; Endoplasmic Reticulum Stress; Inflammation; Mucus; Nucleotides
PubMed: 37436421
DOI: 10.1080/15548627.2023.2228191 -
Cancers Jul 2023The vermiform appendix is a muscular cylindrical structure originating near the junction of the cecum and ileum, averaging 9 cm (5-35 cm) in size. As the most mobile... (Review)
Review
The vermiform appendix is a muscular cylindrical structure originating near the junction of the cecum and ileum, averaging 9 cm (5-35 cm) in size. As the most mobile viscera, it can adopt several positions, the most common being the retrocecal position. Perceived as an atavistic organ lacking physiological relevance, the vermiform appendix appears to be involved in immune function, serving in the maturation of B lymphocytes and the production of immunoglobulin A, in endocrine function, excreting amines and hormones in the 2-3 mL of mucus secreted daily, and in digestive function, by storing beneficial bacteria from where they can recolonize the colon. With a lumen of about 6 mm, the vermiform appendix has a reduced storage capacity, so any blockage of the appendix with fecoliths (fecaliths), seeds derailed from the colon, or enlarged lymph nodes prevents drainage and intraluminal accumulation of secreted mucus. Unable to relax, the appendix wall severely limits its intraluminal volume, so mucus accumulation leads to inflammation of the appendix, known generically as appendicitis. In addition, the vermiform appendix may be the site of the development of neoplastic processes, which may or may not involve mucus production, some of which can significantly affect the standard of living and ultimately lead to death. In general, mucinous tumors may have a better prognosis than non-mucinous tumors. This review takes a comprehensive path, starting by describing the anatomy and embryology of the vermiform appendix and further detailing its inflammatory pathologies, pathologies related to congenital anomalies, and appendix tumors, thus creating an up-to-date framework for better understanding, diagnosis, and treatment of these health problems.
PubMed: 37568688
DOI: 10.3390/cancers15153872 -
Advances in Colloid and Interface... Dec 2023Mucus is a viscoelastic material with non-linear rheological properties such as a yield stress of the order of a few hundreds of millipascals to a few tens of pascals,... (Review)
Review
Mucus is a viscoelastic material with non-linear rheological properties such as a yield stress of the order of a few hundreds of millipascals to a few tens of pascals, due to a complex network of mucins in water along with non-mucin proteins, DNA and cell debris. In this review, we discuss the origin of the yield stress in human mucus, the changes in the rheology of mucus with the occurrence of diseases, and possible clinical applications in disease detection as well as cure. We delve into the domain of mucus rheology, examining both macro- and microrheology. Macrorheology involves investigations conducted at larger length scales (∼ a few hundreds of μm or higher) using traditional rheometers, which probe properties on a bulk scale. It is significant in elucidating various mucosal functions within the human body. This includes rejecting unwanted irritants out of lungs through mucociliary and cough clearance, protecting the stomach wall from the acidic environment as well as biological entities, safeguarding cervical canal from infections and providing a swimming medium for sperms. Additionally, we explore microrheology, which encompasses studies performed at length scales ranging from a few tens of nm to a μm. These microscale studies find various applications, including the context of drug delivery. Finally, we employ scaling analysis to elucidate a few examples in lung, cervical, and gastric mucus, including settling of irritants in lung mucus, yielding of lung mucus in cough clearance and cilial beating, spreading of exogenous surfactants over yielding mucus, swimming of Helicobacter pylori through gastric mucus, and lining of protective mucus in the stomach. The scaling analyses employed on the applications mentioned above provide us with a deeper understanding of the link between the rheology and the physiology of mucus.
Topics: Humans; Cough; Irritants; Mucus; Mucins; Rheology; Viscosity
PubMed: 38039907
DOI: 10.1016/j.cis.2023.103049 -
Allergology International : Official... Jul 2024Airway mucus is a hydrogel with unique biophysical properties due to its primary water composition and a small proportion of large anionic glycoproteins or mucins. The... (Review)
Review
Airway mucus is a hydrogel with unique biophysical properties due to its primary water composition and a small proportion of large anionic glycoproteins or mucins. The predominant mucins in human mucus, MUC5AC and MUC5B, are secreted by specialized cells within the airway epithelium both in normal conditions and in response to various stimuli. Their relative proportions are correlated with specific inflammatory responses and disease mechanisms. The dysregulation of mucin expression is implicated in numerous respiratory diseases, including asthma, COPD, and cystic fibrosis, where the pathogenic role of mucus has been extensively described yet often overlooked. In airway diseases, excessive mucus production or impaired mucus clearance leads to mucus plugging, with secondary airway occlusion that contribute to airflow obstruction, asthma severity and poor control. Eosinophils and Charcot Leyden crystals in sputum contribute to the mucus burden and tenacity. Mucin may also contribute to eosinophil survival. Other mechanisms, including eosinophil-independent IL-13 release, mast-cell activation and non-type-2 (T2) cytokines, are also likely to participate in mucus pathobiology. An accurate assessment of mucus and its clinical and functional consequences require a thorough approach that includes evaluation of cellular predominance in sputum, airway cytokines and other inflammatory markers, mucus characteristics and composition and structural and functional impact measured by advanced lung imaging. This review, illustrated with clinical scenarios, provides an overview of current methods to assess mucus and its relevance to the choice of biologics to treat patients with severe asthma.
Topics: Humans; Asthma; Eosinophils; Biological Products; Mucus; Severity of Illness Index; Sputum; Mucins
PubMed: 38485545
DOI: 10.1016/j.alit.2024.03.001 -
The Journal of Allergy and Clinical... Jun 2024Postnasal drip (PND) is a common symptom encountered when evaluating subjects with sinonasal disease; it may be present without sinonasal disease or as a symptom of... (Review)
Review
Postnasal drip (PND) is a common symptom encountered when evaluating subjects with sinonasal disease; it may be present without sinonasal disease or as a symptom of laryngopharyngeal reflux. It is postulated that PND stems from dysfunction of normal mucus clearance mechanisms; however, there is no definitive evidence elucidating an exact pathophysiology. Compounding the uncertainties surrounding PND is the lack of an objective assessment tool. Instead, treating physicians must rely on subjective complaints and investigators utilize validated patient-reported outcome instruments, such as the Sino-Nasal Outcome Test, to determine treatment efficacy. This review seeks to discuss the current understanding of PND and evidence regarding effective treatment strategies.
Topics: Humans; Sinusitis; Laryngopharyngeal Reflux; Rhinitis; Patient Reported Outcome Measures; Sino-Nasal Outcome Test
PubMed: 38677587
DOI: 10.1016/j.jaip.2024.04.030