Editorial
Refractory Chronic Cough at the Crossroads
La tos crónica refractaria en la encrucijada
Adalberto Pacheco
Centro Médico Habana 17, Madrid, Spain
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Typical symptoms are a tingling or itching in the throat followed by coughing fits that last for seconds or minutes.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Difficulties in the management of CRC derive from its complicated mechanism, which has been described as a reflex arc consisting of a peripheral component and another complex central component, partially subject to voluntary control, in the presence of hypersensitivity or an excessive tussigenic response originating in one or both of the components; this is called cough hypersensitivity syndrome (CHS).<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a> The neurobiological basis of CHS is the dysfunction of the neurological pathways activated by the TRPV1, TRPA1 and P2X3 receptors, which causes the cough to convert from a merely defensive reflex to a hypersensitive reflex.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> In addition, functional MRI studies have shown that patients with chronic cough show a decrease in inhibitory impulses from the brain tissues toward the cough center.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">As a result of this hypersensitivity, chronic cough patients experience an increase in the sensation of laryngeal irritability (paresthesia), excessive cough in response to non-tussigenic triggers such as speaking or laughing (allotussia), or disproportionate responses to cough triggers such as strong fumes or smells (hypertussia). Patients report that these symptoms occur the laryngeal area, leading Australian specialists to develop the concept of laryngeal hypersensitivity syndrome as a key factor in the analysis of CRC.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> In laryngoscopic examination, laryngeal hypersensitivity is observed as a pathological adduction of the vocal cords as an abnormal motor response, which is very frequently combined with the sensory response mentioned above in patients with CRC. Furthermore, the timing of the inflow of stimuli from the peripheral component to the cough center located in the spinal cord will determine the appearance of central hypersensitivity. The capsaicin test that measures cough hypersensitivity in the laboratory has been shown to be useful in the clinical follow-up of CRC patients but it is not as effective in patients with predominantly central hypersensitivity.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Under these premises, attempts to improve the frequency of cough in CRC have focused on decreasing both peripheral and central hypersensitivity. Leaving aside the causes, and concentrating on the altered neurobiological status, the most promising advance in the area of peripheral sensory receptors has been treatment with P2X3 receptor antagonists.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> However, the origin of the dysfunction of these receptors remains an unresolved problem. Nevertheless, the most obvious practical clinical difficulty when faced with a patient with CRC derives from the depth of the study to be performed. Areas in which the study of a patient with CRC might need to be expanded are currently hot topics of discussion: firstly, the verification of the composition of the gastroesophageal reflux (GER) material that reaches the upper airway, which might be liquid or gaseous, acid or non-acid, and a more comprehensive study of reflux physiology in which ineffective esophageal motility can play a decisive role in chronic cough, but which are rarely analyzed in depth<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>; and secondly, the study of extrathoracic hypersensitivity that some authors agree to be the underlying cause of the so-called neurogenic cough, determined essentially by the identification and measurement of the adductor reflex of vocal cords, which if reduced contributes to the relief of CRC.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> In the first case, antiacid therapy with high-dose proton pump inhibitors for at least 2 months is not always effective because reflux may be more closely associated with esophageal motility problems or the presence of pepsin in vocal cord tissue.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> In the second case, laryngeal neuromuscular rehabilitation programs have shown efficacy in laryngeal dysfunction. These interventions act on the sensory and motor components of the laryngeal area and also teach the patient to consciously try to inhibit the cough, <span class="elsevierStyleItalic">i.e.</span> intervening in central hypersensitivity.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11,13</span></a> Studies of neuromodulators such as amitriptyline, gabapentin or pregabalin combined with rehabilitative therapy have already shown high rates of improvement in CRC.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> However, 2 problems in the management of long-term CRC emerge with these procedures: 1) tolerance to neuromodulators, frequent side effects, and durability of benefit after discontinuation, and 2) poor adherence to laryngeal rehabilitation exercises.</p><p id="par0025" class="elsevierStylePara elsevierViewall">To recap, a dual peripheral and central approach to the management of the patient with CRC is essential, but many aspects of the complexity of this syndrome at its two extremes and how they are interrelated remain unknown, so management is at a critical stage. Future research in 3 areas should shed more light on this dual issue of CRC: 1) improved reliability of tests for peripheral triggers, such as the analysis of airway reflux using Peptest (RDBiomed, Cottingham, UK), a method that detects pepsin from anti-human pepsin monoclonal antibodies either in saliva or in bronchoalveolar lavage<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>; 2) the potential convergence in a single patient of inducers of peripheral inflammation of the cough reflex arc, such as allergens, respiratory virus and GER material; and 3) a more assiduous exploration of extrathoracic hypersensitivity.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Any attempt to improve the study of CRC patients necessarily involves the collaboration of the ENT, gastroenterology and pulmonology departments. A clear example in this regard is the study of the impact of extrathoracic reflux on laryngeal functioning, which is summed up in 2 parts: paradoxical vocal cord movement and loss of laryngeal mechanical sensitivity. Both events can cause 2 types of symptoms: acute dyspnea, predominantly during inspiration, consistent with laryngospasms, and chronic cough developing as a glottal opening mechanism<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> in response to aspiration. For all these reasons, a key challenge in the investigation of cough is to improve the understanding of the pathophysiology of the cough reflex, in both its peripheral, upper airway, lower airway and upper digestive tract components, and its association with the central nervous system, identifying new targets for drug therapy. However, this dimension of the problem is a difficult objective to analyze <span class="elsevierStyleItalic">in vivo</span>, so better models of cough in animals that express the mechanisms of human cough are needed.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Pacheco A. La tos crónica refractaria en la encrucijada. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 3 | 1 | 4 |
| 2024 October | 65 | 14 | 79 |
| 2024 September | 50 | 18 | 68 |
| 2024 August | 69 | 42 | 111 |
| 2024 July | 48 | 20 | 68 |
| 2024 June | 56 | 39 | 95 |
| 2024 May | 101 | 35 | 136 |
| 2024 April | 41 | 22 | 63 |
| 2024 March | 51 | 14 | 65 |
| 2024 February | 31 | 24 | 55 |
| 2023 June | 2 | 0 | 2 |
| 2023 May | 1 | 0 | 1 |
| 2023 March | 7 | 3 | 10 |
| 2023 February | 55 | 13 | 68 |
| 2023 January | 37 | 41 | 78 |
| 2022 December | 52 | 37 | 89 |
| 2022 November | 62 | 21 | 83 |
| 2022 October | 50 | 32 | 82 |
| 2022 September | 33 | 22 | 55 |
| 2022 August | 34 | 47 | 81 |
| 2022 July | 39 | 37 | 76 |
| 2022 June | 26 | 32 | 58 |
| 2022 May | 27 | 27 | 54 |
| 2022 April | 36 | 21 | 57 |
| 2022 March | 43 | 32 | 75 |
| 2022 February | 17 | 22 | 39 |
| 2020 October | 1 | 0 | 1 |
| 2020 September | 2 | 0 | 2 |
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