Chronic cough is a prevalent and often debilitating symptom that can significantly impact a person's quality of life. While various respiratory and non-respiratory conditions can trigger chronic cough, a specific type known as neurogenic cough is increasingly recognized as an important cause. This article delves into the causes, symptoms, and treatment options for neurogenic cough, providing a comprehensive understanding of this complex condition.
Understanding Chronic Cough
A cough is considered acute if it lasts less than 3 weeks, often resulting from upper respiratory tract viral infections like the common cold. However, when a cough persists for more than 8 weeks, it is classified as chronic. Chronic cough can linger for months or even years, posing a significant challenge for both patients and healthcare providers due to its persistent nature and the limited efficacy of current antitussive therapies.
Prevalence and Contributing Factors
Chronic cough is widespread in the community, with studies reporting prevalence rates ranging from 9% to 33%. Environmental pollution, to which we are increasingly exposed, may contribute to the rising incidence of chronic cough.
Traditional Approaches to Chronic Cough Management
National guidelines for diagnosing and managing cough often advocate an anatomico-diagnostic approach, focusing on identifying and treating the underlying cause. Common conditions associated with chronic cough, particularly when chest radiographs are normal, include eosinophilic airway diseases (asthma, cough variant asthma, and eosinophilic bronchitis) and conditions like gastro-oesophageal reflux disease (GORD) and post-nasal drip syndrome (rhinosinusitis).
Neurogenic Cough: A Neuropathic Perspective
Recent research suggests that chronic cough, particularly when it persists despite addressing potential underlying causes, may be a neuropathic condition. This perspective is supported by several observations:
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- Patients often report sensory symptoms indicative of upper airway and laryngeal neural dysfunction.
- Coughing can be triggered by low-level physical and chemical stimuli, suggesting cough reflex hypersensitivity.
- Mechanisms underlying peripheral and central augmentation of afferent cough pathways have been identified.
- Success in treating chronic cough with neuropathic pain medications like gabapentin and amitriptyline further supports this concept.
Causes of Neurogenic Cough
The vagus nerves can be damaged or injured in a number of different ways, any of which may lead to the development of neurogenic cough or other vagally-mediated neurogenic symptoms. The most common cause of vagal neuropathy is a viral upper respiratory infection (URI). Anatomically, the vagi come out of the brain and track along the front of the spine. In the throat, the vagi live just under the lining membranes, and this makes them susceptible to damage from some infections.
The Vagus Nerve and its Role in Cough
The vagus nerve, the tenth cranial nerve, plays a crucial role in controlling the respiratory and digestive systems. Vagal symptoms can include nausea, bloating, heartburn, hoarseness, cough, shortness of breath, choking, and asthma. In the context of cough, the vagus nerve is responsible for the sensation that a cough is needed and the act of coughing itself.
Cough Hypersensitivity Syndrome
Many patients with chronic cough complain of a persistent tickling or irritating sensation in the throat or a choking sensation. Urge-to-cough is a distinct sensation that, with increasing levels of cough stimulation, has a lower threshold and occurs before the cough itself. The combination of irritation in the throat or upper chest, cough triggered by non-tussive stimulus such as talking or laughing (allotussia), and increased cough sensitivity to inhaled stimuli (hypertussia) suggest a disorder of airway sensory neural function, leading to the term "cough hypersensitivity syndrome."
This syndrome suggests that disordered sensory neural function, and hence the cough hypersensitivity which underlies chronic cough in general, reflects an underlying sensory neuropathy. The European Respiratory Society defines cough hypersensitivity syndrome as "a clinical syndrome characterised by troublesome coughing often triggered by low levels of thermal, mechanical, or chemical exposure."
Mechanisms Underlying Cough Hypersensitivity
Several mechanisms can contribute to cough hypersensitivity:
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- Sensory afferent nerves can be sensitized by neuroactive molecules, such as nerve growth factor, altering their activation profiles and facilitating afferent encoding signals in response to irritant stimuli.
- Sensitization may be related to altered expression of ion channels and other receptor molecules, including TRPV1, which regulates afferent nerve excitability to many chemical stimuli.
- Cough hypersensitivity can be induced when normal afferent signals are augmented by central events through the interaction of different subsets of afferent neurons in the brainstem.
- Neuropeptides expressed in airway nociceptors and mechanosensors can reduce the cough reflex threshold through convergence onto common second-order neurons in the brainstem, amplifying incoming signals.
Airway Inflammation and Remodeling
Chronic cough is often associated with airway inflammation and remodeling. Studies have revealed damaged bronchial epithelium, basement membrane thickening, and chronic inflammatory infiltrates in airway biopsies from patients with unexplained chronic cough. Furthermore, an increased number of mast cells and features of airway wall remodeling have been reported. Inflammatory mediators, such as histamine, prostaglandin D2 and E2, TNFα, and IL-8, are also elevated in induced sputum samples.
Eosinophils, which co-localize with sensory airway nerves, may release mediators that maintain cough reflex hypersensitivity during airway inflammation. Inhalation of inflammatory mediators like bradykinin and PGE2 can upregulate the capsaicin cough response.
Neuronal Activation and Neuropeptides
Evidence suggests airway neuronal activation in chronic cough, with elevated levels of substance P and neurokinin A detected in induced sputum samples from asthmatic coughers. Levels of the neuropeptide calcitonin-gene-related peptide (CGRP) in airway lavage samples from children with chronic cough are positively correlated with capsaicin cough reflex sensitivity.
Symptoms of Neurogenic Cough
Symptoms of SNC may include:
- A persistent dry cough lasting for at least 8 weeks in adults or 4 weeks in children
- Sudden sensory sensations, such as a tickling throat or dry patches, just before a coughing episode starts
- Pain, burning, or tingling sensations in the throat
- Excessive throat clearing
- A feeling of something being caught in the throat
People may experience hundreds of coughing episodes daily. Severe coughing episodes may cause other symptoms, such as:
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- Stress incontinence
- Vomiting
- Laryngospasm - a short spasm of the vocal cords, making it difficult to speak or breathe temporarily
- Sleep disturbance
- Reduced quality of life, if coughing affects everyday activities, work, or relationships
Certain triggers may cause coughing episodes, such as:
- Talking
- Laughing
- Movement
- Inhaling cold air
- Strong smells
Diagnosis of Neurogenic Cough
Neurogenic cough is often a diagnosis of exclusion, meaning that other potential causes of chronic cough must be ruled out first. Doctors may perform tests to check for conditions like asthma, postnasal drip, chronic bronchitis, gastroesophageal reflux disease, medication side effects, and lung cancer.
If these tests are negative and standard cough treatments are ineffective, a doctor may consider a diagnosis of neurogenic cough. Certain symptoms may also point towards a neurogenic etiology, including:
- Onset after an illness or surgery that puts laryngeal nerves at risk
- Nonproductive cough
- Lack of response to antibiotics, asthma, or reflux medications
- Dysesthesias of the larynx
- Long duration of the complaint
Treatment Strategies for Neurogenic Cough
Treatment for neurogenic cough primarily focuses on symptom control. A multidisciplinary approach involving medical management, speech therapy, and, in some cases, procedural interventions may be necessary.
Medical Management
- Neuromodulators: Medications like gabapentin, pregabalin, and amitriptyline, traditionally used for neuropathic pain, can help modulate nerve activity and reduce cough frequency and intensity.
- Cough Suppressants: Medications like Tessalon Perles can help suppress the cough reflex.
- Amitriptyline (Elavil): Amitriptyline 10 mg. alone will stop neurogenic cough in 15% of people; most people need the combination of amitriptyline and gabapentin. Amitriptyline makes the gabapentin work better and the gabapentin makes the amitriptyline work better; their effects are synergistic in a beneficial way. Amitriptyline (Elavil) 5-10 mg. After you have been on the amitriptyline for a week, if you still have a neurogenic cough, start taking gabapentin 100 mg.
Speech Therapy
A speech-language specialist can teach patients techniques to control and suppress coughing, such as:
- Swallowing instead of coughing when feeling the urge to cough
- Sipping water
- Staying properly hydrated
- Avoiding smoking, caffeine, and alcohol
- Breathing through the nose rather than the mouth
- Avoiding straining when speaking
Procedural Interventions
For patients who do not respond to medical management, procedural interventions may be considered:
- Superior Laryngeal Nerve Block: This in-office procedure involves injecting a combination of triamcinolone and lidocaine near the superior laryngeal nerve to provide lasting relief.
- Vocal Fold Botox: Injections of Botox into the vocal folds can force them open and inhibit cough.
- Topical capsaicin: may provide some symptom relief in 63.7% of people and resulted in 75% or more cough reduction in 30.8% of individuals.
The Importance of a Unified Approach
The respiratory and digestive tracts are part of one unified system and the vagi are the driving neural network for every function and symptom, for example, neurogenic cough.
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