Airway Sensory Nerve Density Is Increased in Chronic Cough. 2021

Clare O Shapiro, and Becky J Proskocil, and Laura J Oppegard, and Emily D Blum, and Nicole L Kappel, and Christopher H Chang, and Allison D Fryer, and David B Jacoby, and Richard W Costello, and Matthew G Drake
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Oregon Health & Science University, Portland, Oregon; and.

Rationale: Chronic cough is characterized by frequent urges to cough and a heightened sensitivity to inhaled irritants. Airway sensory nerves trigger cough. We hypothesized that sensory nerve density is increased in chronic cough, which may contribute to excessive and persistent coughing.Objectives: To measure airway nerve density (axonal length) and complexity (nerve branching, neuropeptide expression) in humans with and without chronic cough.Methods: Bronchoscopic human airway biopsies were immunolabeled for nerves and the sensory neuropeptide substance P. Eosinophil peroxidase was also quantified given previous reports showing associations between eosinophils and nerve density. Three-dimensional image z-stacks of epithelium and subepithelium were generated using confocal microscopy, and from these z-stacks, total nerve length, the number of nerve branch points, substance P expression, and eosinophil peroxidase were quantified within each airway compartment.Measurements and Main Results: Nerve length and the number of branch points were significantly increased in epithelium, but not subepithelium, in chronic cough compared with healthy airways. Substance P expression was scarce and was similar in chronic cough and healthy airways. Nerve length and branching were not associated with eosinophil peroxidase nor with demographics such as age and sex in either group.Conclusions: Airway epithelial sensory nerve density is increased in chronic cough, suggesting sensory neuroplasticity contributes to cough hypersensitivity.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011984 Sensory Receptor Cells Specialized afferent neurons capable of transducing sensory stimuli into NERVE IMPULSES to be transmitted to the CENTRAL NERVOUS SYSTEM. Sometimes sensory receptors for external stimuli are called exteroceptors; for internal stimuli are called interoceptors and proprioceptors. Nerve Endings, Sensory,Neurons, Sensory,Neuroreceptors,Receptors, Neural,Neural Receptors,Receptors, Sensory,Sensory Neurons,Sensory Receptors,Nerve Ending, Sensory,Neural Receptor,Neuron, Sensory,Neuroreceptor,Receptor Cell, Sensory,Receptor Cells, Sensory,Receptor, Neural,Receptor, Sensory,Sensory Nerve Ending,Sensory Nerve Endings,Sensory Neuron,Sensory Receptor,Sensory Receptor Cell
D012137 Respiratory System The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. Respiratory Tract,Respiratory Systems,Respiratory Tracts,System, Respiratory,Tract, Respiratory
D001999 Bronchoscopy Endoscopic examination, therapy or surgery of the bronchi. Bronchoscopic Surgical Procedures,Surgical Procedures, Bronchoscopic,Bronchoscopic Surgery,Surgery, Bronchoscopic,Bronchoscopic Surgeries,Bronchoscopic Surgical Procedure,Bronchoscopies,Surgeries, Bronchoscopic,Surgical Procedure, Bronchoscopic
D002908 Chronic Disease Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care (Dictionary of Health Services Management, 2d ed). For epidemiological studies chronic disease often includes HEART DISEASES; STROKE; CANCER; and diabetes (DIABETES MELLITUS, TYPE 2). Chronic Condition,Chronic Illness,Chronically Ill,Chronic Conditions,Chronic Diseases,Chronic Illnesses,Condition, Chronic,Disease, Chronic,Illness, Chronic
D003371 Cough A sudden, audible expulsion of air from the lungs through a partially closed glottis, preceded by inhalation. It is a protective response that serves to clear the trachea, bronchi, and/or lungs of irritants and secretions, or to prevent aspiration of foreign materials into the lungs. Coughs
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults

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