Mechanism of Cough

Cough is a protective reflex serving a normal physiologic function of clearing

excessive secretions and debris from the pulmonary tract.
The cough reflex has 3 components: an afferent sensory limb, a central
processing center, and an efferent limb. [3]
The trigeminal, glossopharyngeal, and vagus nerves supply the afferent
pathways for cough receptors; the vagus, through its pharyngeal, superior
laryngeal, and pulmonary branches, supplies the large majority of these
receptors.
Receptors are located throughout the airway from the pharynx to the terminal
bronchioles, with the greatest concentration located in the larynx, carina, and
the bifurcation of larger bronchi. [7]
Three types of receptors are predominant [8, 9, 10] :


Rapidly adapting receptors (RARs) that respond to mechanical stimuli,

cigarette smoke, ammonia, acidic and alkaline solutions, hypotonic and
hypertonic saline, pulmonary congestion, pulmonary congestion, atelectasis,
and bronchoconstriction



Slowly adapting receptors (SARs)




Nociceptors on C-fibers that respond to chemical stimuli as well as

inflammatory and immunological mediators such as histamine, bradykinin,
prostaglandins, substance P, capsaicin, and acidic pH


Afferent impulses are transmitted to the cough center of the brain, located in
the nucleus tractus solitarius of the medulla of the brainstem, which is
connected to the central respiratory generator.
To complete the reflex arc, efferent impulses leave the medulla and travel to the
larynx and tracheobronchial tree via the vagus while the phrenic and spinal
motor nerves of C3 to S2 supply the intercostals muscles, abdominal wall,
diaphragm, and pelvic floor. [7]
This cough reflex has been shown to have neuroplasticity such that a
hypersensitive response is elicited over time due to the cough itself inducing
chronic irritation and inflammation and tissue remodeling. [9] Both peripheral
(increase in sensitivity of cough receptors) and central (changes in central
processing in the brainstem) sensitization can account for an exaggerated cough
response that is common in patients and further contributes to the
maintenance of chronic cough. [10]
Recently, the term chronic cough hypersensitivity syndrome has been proposed
as the new way to label chronic cough owing to the fact that the underlying
abnormality leading to chronic coughing is an abnormally sensitive cough
reflex. [11,12, 13] Indeed, evidence suggests that members of the transient
receptor potential (TRP) ion channel family, specifically the vanilloid 1 (TRPV1)
and ankyrin 1 (TRPA1) channels, are receptors that mediate
cough. [14] Patients with chronic cough hypersensitivity syndrome have a
negative workup and lack of response to common treatments and are
characterized by having a sensation of a tickle or itch in the throat, as well as
being sensitive to triggers such as cold air, eating, and odors. [11]

Causes of Chronic Cough

The etiologies of chronic cough are numerous and may include pathology from
the nose and nasopharynx to the distal bronchial tree. Obvious causes such as
smoking and angiotensin-converting enzyme (ACE) inhibitor use can be easily
ascertained from the history. After this, the challenge for the clinician lies in
how to efficiently and systematically evaluate the patient without an overly
exhaustive workup. Further compounding this is the fact that oftentimes more
than one condition is simultaneously present.
Prospective studies have shown that 3 conditions account for the etiologic cause
of chronic cough in 92-100% of immunocompetent, nonsmoking patients with
normal chest radiograph findings. [15] In order of frequency, they are as follows:
1. Upper airway cough syndrome (UACS), previously referred to as postnasal
drip syndrome (PNDS)
2. Asthma
3. Gastroesophageal reflux disease (GERD)
These 3 conditions make up what is called the pathogenic triad of chronic
cough.
A fourth etiology that deserves mention is nonasthmatic eosinophilic bronchitis
(NAEB), which is relatively common, easy to diagnose and treat, and should be
considered early on in the diagnostic evaluation.
Another way to categorize the etiologies is to draw a distinction between cough
due to eosinophilic airway diseases (asthma and NAEB) and noneosinophilic
chronic cough. [16] Eosinophilic airway diseases have airway inflammation due to
eosinophils, which can be diagnosed by raised induced sputum eosinophil counts
and increased exhaled nitric oxide levels. They are also associated with good
steroid responsiveness. [16]
The physician who focuses on diagnosing and treating these conditions can very
successful at treating chronic cough.
A study by Cash et al found that of 58 pediatric patients with chronic cough
presenting to otolaryngology clinics at a single tertiary care academic medical
center, the primary causes of their condition were infection (39.7%), airway
hyperreactivity (24.1%), and GERD (24.1%). [17]

Upper airway cough syndrome

 PNDS refers to the sensation of secretions from the nose or sinuses that drain
into the pharynx in addition to nasal discharge and frequent throat clearing.
Unfortunately, this is largely based on patients’ subjective symptoms, which
frequently do not show any significant physical examination findings. In fact,
20% of patients with PNDS-induced cough are unaware of the presence of
postnasal drip or its link to their cough. [18] Even the presence of mucus in the
oropharynx or cobblestoning of the oropharyngeal mucosa only suggest this as a
cause. These findings are sensitive but not specific. [15]

Chronic Cough
Updated: Jan 27, 2016
 Author: Henry Haipei Chen, MD, MBA;
http://emedicine.medscape.com/article/1048560-overview

Why and How do we sneeze ?Mechanism involved

Ravi Ram Saturday, November 23, 2013 No Comment
Chronic exposure to allergens can lead to hyperresponsiveness of the nasal mucosa. As a result, receptors upregulate
specific ion channels to increase the sensitivity and potency of their reflex response. Nasal stimuli also affect distant parts of
the body. Nerves in the sinus mucosa cause vasodilation; the lacrimal glands can be stimulated by nasal afferent triggers.
The sneeze is an airway defense mechanism that removes irritants from the nasal epithelial surface. It is generally benign,
but can lead to problems in certain circumstances. The afferent pathway involves histamine-mediated depolarization of H1
receptor-bearing type C trigeminal neurons and a complex coordination of reactions to effect a response.
Sneeze is defined as the involuntary expulsion of air containing irritants from nose.
Causes of sneeze:

Irritation of nasal mucosa



Excess fluid in airway


Components of sneeze reflex:

1.
Sneeze receptor
2.
 3.
Afferent nerve
4.
5.
Sneeze center
6.
7.
Efferent nerve
8.
9.
Effector muscle
10.
Mechanism for sneeze:
1.
Deep inspiration
2.
3.
Opened glottis
4.
5.
Expulsion of irritants from both nose and mouth
6.

Pathway for sneeze reflex:

1.
Irritation of nasal mucosa
2.
3.
Olfactory receptors or V cranial nerve endings
4.
5.
Stimulus pass via I and V cranial nerve and reach to Sneeze center in medulla – present in nucleus solitarious and
reticular formation
6.
7.
Efferent nerves from V, VII, IX, X cranial nerves and intercostal muscles
8.
9.
Activation of pharyngeal, tracheal and respiratory muscles
 10.
http://b2pointo.blogspot.com/2013/11/why-and-how-do-we-sneeze-mechanism.html

Neural mechanisms of sneeze.

Batsel HL, Lines AJ.

Abstract

Sneezes were induced in anestized cats by repetitive stimulation of the ethmoidal nerve. Activity of bulbar respiratory
neurons during sneezing was recorded extracellularly through tungsten microelectrodes. Most expiratory neurons
could be locked onto the stimulus pulses so that they responded either throughout inspiration as well as expiration or
so that they began responding at some time during inspiration. As inspiration approached termination, multiple
spiking occurred, finally to result in high-frequency bursts which just preceded active expiration. A fraction of
expiratory neurons were activated only in bursts. Latent expiratory neurons were recruited in sneezing. Inspiratory
neurons near nucleus ambiguus and most of those near fasciculus solitarius displayed similar response patterns
consisting of silent periods followed by delayed smooth activations. Temporal characteristics of the silent periods,
"inhibitory gaps," suggested that they resulted from inhibition whose source was the expiratory neurons which were
driven throughout inspriation. Some inspiratory neurons in the area of fasciculus solitarius failed to exhibit inhibitory
gaps.
https://www.ncbi.nlm.nih.gov/pubmed/1211469

A sneeze is a sudden and forceful expiration of air through the nose or sometimes partly through the mouth. Its
function is to clear the nasal passages of any irritants. However, sneezing is a common feature of the various nasal
disorders even though no irritant is present in the nasal passages. This is seen in upper respiratory tract infections
and allergic rhinitis, where the lining of the nasal cavity is inflamed as a result of infectious or immune-mediated
factors. Sneezing in these cases does little to clear out the nasal passages but may pass out excessive nasal mucus
(rhinorrhea) which is a concomitant feature.

Sneeze Reflex
The sneeze reflex can be triggered by even mild stimulation of the the nasal lining. When stimulated, the receptors
in the lining send impulses via the fifth cranial nerve (CN V / trigeminal nerve) to sneezingcenter in the medulla.
This triggers the sneeze reflexwhich is similar to the cough reflex, with the difference being that air is forced out
mainly through the nose by depressing the uvula.Rapid inspiration fills the lung with extra air. The epiglottis and the
vocal cords close tightly to build up pressure in the lungs. The expiratory muscles of respiration as well as accessory
respiratory muscles contract forcefully. This further increases the pressure in the lungs. Once a sufficiently high
pressure is reached, the vocal cords relax, the epiglottis opens and the air rushes out rapidly.
Due to the speed of the moving air, the terminal parts of the airway invaginates thereby creating slitswhich further
increases the pressure of the expired air. The depressed uvula in a sneeze reflex pushes the air out though the nose.
This entire process happens within seconds. Just as with a cough, the speed of the air rushing out through the nose
can be close to 100mph.
Common stimulation and tightly shutting the eyes while sneezing, may cause the lacrimal glands (tear glands) to
empty its contents thereby resulting in slightly watery eyes with sneezing. The irritation of the nasal passages triggers
the inflammatory response which causes mucus hypersecretion. This excess mucus is also forced out during
a sneeze in an aerosol fashion.

Sneeze and Light Reflex

Known as the photic sneeze reflex or ACHOO(autosomal dominant compelling helio-ophthalmic outburst), the
sudden exposure to bright light may elicit a sneeze in some people. The exact cause is unknown although there is
evidence that there is a familial tendency for this to occur. It may be related to local factors in the eye stimulating the
same pathway that sends impulses back to the sneeze center via the trigeminal nerve.
It is believed that optic nerve stimulation due to exposure to sudden bright light triggers impulses in the trigeminal
nerve via the opthalmic branch. This elicits the sneeze reflex.
The other theory is that this stems from the medulla as a crossing over of impulses from neighboring centers into
the sneezing center. Snatiation reflex, where stretching of the stomach causes sneezing, and sexual excitement or
an orgasm triggers sneezing may be due to central causes.