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Welcome back to another installment of Dr Euan's TGIF Blog!
Last week, I covered the topic of post covid anosmia, or loss in sense of smell. Another very topical issue is that of LONG Covid and that prolonged cough we may get after recovering from the initial SARS COV 2 infection.
This was even reported recently in the Straits Times:
Q: What is LONG Covid?
Some people who have been infected with the virus that causes COVID-19 can experience long-term effects from their infection, known as post-COVID conditions (PCC) or long COVID.
People call post-COVID conditions by many names, including: long COVID, long-haul COVID, post-acute COVID-19, post-acute sequelae of SARS CoV-2 infection (PASC), long-term effects of COVID, and chronic COVID.
Post-COVID conditions can include a wide range of ongoing health problems; these conditions can last weeks, months, or years.
Post-COVID conditions are found more often in people who had severe COVID-19 illness, but anyone who has been infected with the virus that causes COVID-19 can experience post-COVID conditions, even people who had a mild illness or no symptoms from COVID-19.
People who are not vaccinated against COVID-19 and become infected may also be at higher risk of developing post-COVID conditions compared to people who were vaccinated and had breakthrough infections.
While most people with post-COVID conditions have evidence of infection or COVID-19 illness, in some cases, a person with post-COVID conditions may not have tested positive for the virus or known they were infected.
CDC and partners are working to understand more about who experiences post-COVID conditions and why including whether groups disproportionately impacted by COVID-19 are at higher risk.
In my practice, one of the things I try to prepare my patients for is that it is very common to have symptoms after a bad infectious disease, especially if it hits the lungs. So, when a patient comes in, I ask them “could your symptoms be a part of healing?”
The most common symptom that signifies healing is a lingering or prolonged cough because coughing is your lung’s way of sweeping out dead cells. In the case of COVID-19, this cough could last for as long as six months after the viral infection, especially if the patient contracted Omicron because it is more airway dependent than the original strain.
As a doctor, coughing or breathlessness that lingers beyond three months catches my attention. My biggest concern is seeing symptoms that may suggest post COVID-19 interstitial lung disease because that can be life threatening if not well managed. If caught early treatment can help stop the progression of the disease and prevent permanent lung scarring.
Coughing is a natural reflex for our body to clear the throat and airways of unwanted materials such as mucus or irritant particles. In response to these triggers, the nerve endings in the airways/lungs are stimulated and these signal the brain to produce coughing responses.
In Covid-19, the immune system responds by activating its defence system. This leads to inflammation in an attempt to eliminate the virus. Persistent coughs result from inflammation in the airways/lungs even after you have recovered from Covid-19. This is the basis for mechanisms leading to persistent coughs:
Inflamed upper airways :
When fluids produced drip down the back of your throat and cause a "post-nasal drip", you will have the urge to "clear your throat", swallow or cough.
Affected lungs and lower airways:
The swelling of lung tissue will trigger coughs as the body senses the presence of an irritant even if there is no fluid present; hence the cough will be dry.
Inflammation of neural pathways:
When there is an inflammation lurking, the nervous system will be involved – either the brain or nerves; hence this type of cough is not primarily from the respiratory tissues, but is a reaction from the nervous system.
While this is not common, it is debilitating for the person experiencing it, especially for those who were first afflicted with severe COVID illness. Tissue scarring is the formation of fibrous tissue when normal tissue is destroyed by disease, injury, or surgery. A respiratory specialist has to diagnose and manage this lung tissue scarring, also known as interstitial lung disease.
Q: How common is this post-COVID prolonged cough?
Longitudinal studies in the general population have not been reported so far, but in the UK Office for National Statistics COVID-19 Infection Survey, the proportion of patients who remain symptomatic at 5 weeks after infection was estimated at 21·0% (95% CI 19·9–22·1%), and cough was the second most common persistent symptom (11·4% [10·5–12·2%]), fatigue being the first. The estimated prevalence of patients symptomatic at 12 weeks was 9·9% (6·7–14·7%), but a specific rate for cough has not yet been reported. In online surveys, the cough was reported in 20–30% of still symptomatic patients 2–3 months after the onset of symptoms of COVID-19.
An ENT specialist may perform a nasoendoscopy to observe the nose & throat to assess the coughing
When Should I see a Specialist for persistent cough after Covid-19?
If your symptoms like persistent cough do not improve or do worsen despite simple cough medications, or they are limiting your quality of life after more than four weeks, you should consult a Specialist.
On top of the cough symptoms, there may also be signs of a secondary bacterial infection that you should look out for besides Covid-19, such as:
● change in the type of cough
● a change in the sputum/phlegm (visible blood)
● new symptoms developed (fevers, chest pain, racing heart or worsening breathlessness)
● significant weight loss
● night sweats
Q: Doc, is this a COVID rebound?
COVID-19 rebound” occurs when a person infected with the COVID-19 virus recovers and tests negative, only to retest positive and/or develop symptoms a few days to a week later.
The Centers for Disease Control and Prevention (CDC) issued an advisory in late May reporting that some patients with a normal immune response who have completed a five-day course of Paxlovid treatment for COVID-19 experience another bout of illness two to eight days afterwards.
These patients tested negative for the virus immediately after treatment, then re-tested positive and had recurring symptoms in the following week.
There are no reports so far of serious illness from COVID-19 rebound, and the CDC isn’t currently recommending any further treatment. It does seem possible to transmit the virus during COVID-19 rebound, however, so re-isolating is important to protect those around you.
Q: Is this a post-infective "asthmatic bronchitis": cough?
The post-viral bronchial hyper-reactivity syndrome can also occur after Covid-19 recovery.
To quote a prominent ID specialist, Dr Leong Hoe Nam, who says:
"This means that the airways become very sensitive after a Covid-19 infection causing it to hyper react to triggers such as smoke, cold air and cold drinks, which may result in a prolonged cough," he says.
For persistent cough, you can consider taking Cough medicine such as Codeine, Prospan
Q: What home remedies can I try?
Here are 9 home remedies you can try at home for that prolonged cough, post Covid:
Inhale steam. Inhaling steam 2-3 times a day can help loosen trapped mucus and reduce the frequency of coughing.
Take over-the-counter (OTC) cough suppressants. Codeine-containing cough syrups can help you sleep when taken before bed. Avoid relying on these too much since they can be addictive.
Get plenty of rest. Give your immune system plenty of time to recover by getting adequate rest, and aim to sleep more than 7-9 hours a night.
Elevate your head and chest. Place a wedge under your pillow, as sleeping with your head and chest in an elevated position prevents the mucus from obstructing your airways and thus can help prevent you from coughing.
Drink plenty of water. Staying hydrated is one of the important things to do while recovering from any virus, including COVID-19.
Have tea with honey. Drinking warm ginger tea with honey can help relieve sore throat coughing.
Drink turmeric lattes. Warm milk with turmeric can help soothe the throat and works as an excellent expectorant.
Suck on lozenges. If you do not want to use OTC cough syrups, you can try sucking on lozenges to lubricate your throat.
Practising diaphragmatic breathing:
Sit up straight, with one hand on your abdomen and the other on your chest.
Inhale slowly and deeply through your nostrils and feel your stomach expand with each breath.
Exhale slowly out through your mouth.
Repeat 5-6 times or more each minute for 15-20 minutes.
If your cough does not subside even with home remedies, do schedule an appointment with your doctor. If an underlying medical condition is hindering your body’s ability to clear the cough, your doctor may order more investigations or put you on stronger medications.
Q: Doc, what treatments are available for this post COVID cough?
If your cough persists for an extended period, you should consult your doctor / see a Specialist.
There are various services and treatments for persistent coughs that affect your daily routine.
Acute coughs that are short-lived generally only require outpatient treatment with the help of over-the-counter medications such as cough syrups. However, chronic coughs that last up to eight weeks or more will require consultations from specialists and treatments.
Your Specialist will carry out a thorough examination to better understand the cause of persistent coughs. Those examinations include:
● radiologic imaging (chest X-rays, computerised tomography (CT) scan)
● breathing tests (spirometry, fractional exhaled nitric oxide measurements)
● allergy testing
● blood tests
● dynamic exercise testing
If the Doctor expects Interstitial Lung Disease may be the cough of the persistent cough, patients may be asked to do a CT Scan
Once the results from the examination have been obtained, the Specialist will be able to prescribe appropriate treatments based on the reason for the persistent coughs. Those treatments for the different causes include:
● steroid nasal sprays
● prescribed inhaled steroids
● inhaled bronchodilators
Effectiveness Of Each Of These Treatments
There are two different causes of persistent coughs that your Specialist will treat, and those causes are:
Antihistamines and steroid nasal sprays will be prescribed if this is the cause of your cough. This treatment will help reduce the swelling and inflammation in your nasal passages.
Asthmatics' condition may worsen due to Covid; hence specialists may advise them to continue with their prescribed inhaled steroids and/or bronchodilators. These treatments will help reduce the swelling of airways and improve the flow of breathing by widening the narrowed air passages.
Well, dear friends, I hope this blog post has given you some insight and useful pointers for that dreaded POST COVID cough!
If you are interested and would like to see Dr Euan about your Post-Covid cough, you can contact us at Euan's ENT Surgery & Clinic to make an appointment.
Here are some references you may want to look up if you are keen to learn more.
Meanwhile, have a restful cough-free weekend!
2. Zhou F, Yu T, Du R. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–1062. [PMC free article] [PubMed] [Google Scholar]
3. Dhand R, Li J. Coughs and sneezes: their role in transmission of respiratory viral infections, including SARS-CoV-2. Am J Respir Crit Care Med. 2020;202:651–659. [PMC free article] [PubMed] [Google Scholar]
4. Hulme K, Dogan S, Parker SM, Deary V. ‘Chronic cough, cause unknown’: A qualitative study of patient perspectives of chronic refractory cough. J Health Psychol. 2019;24:707–716. [PubMed] [Google Scholar]
7. Grant MC, Geoghegan L, Arbyn M. The prevalence of symptoms in 24,410 adults infected by the novel coronavirus (SARS-CoV-2; COVID-19): A systematic review and meta-analysis of 148 studies from 9 countries. PLoS One. 2020;15 [PMC free article] [PubMed] [Google Scholar]
9. Garrigues E, Janvier P, Kherabi Y. Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19. J Infect. 2020;81:e4–e6. [PMC free article] [PubMed] [Google Scholar]
10. Halpin SJ, McIvor C, Whyatt G. Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation. J Med Virol. 2021;93:1013–1022. [PubMed] [Google Scholar]
11. Wong AW, Shah AS, Johnston JC, Carlsten C, Ryerson CJ. Patient-reported outcome measures after COVID-19: a prospective cohort study. Eur Respir J. 2020;56 [PMC free article] [PubMed] [Google Scholar]
12. Goërtz YMJ, Van Herck M, Delbressine JM. Persistent symptoms 3 months after a SARS-CoV-2 infection: the post-COVID-19 syndrome? ERJ Open Res. 2020;6:00542–02020. [PMC free article] [PubMed] [Google Scholar]
13. Mandal S, Barnett J, Brill SE. ‘Long-COVID’: a cross-sectional study of persisting symptoms, biomarker and imaging abnormalities following hospitalisation for COVID-19. Thorax. 2020;76:396–398. [PMC free article] [PubMed] [Google Scholar]
15. Cheng D, Calderwood C, Skyllberg E, Ainley A. Clinical characteristics and outcomes of adult patients admitted with COVID-19 in East London: a retrospective cohort analysis. BMJ Open Respir Res. 2021;8 [PMC free article] [PubMed] [Google Scholar]
17. D'Cruz RF, Waller MD, Perrin F. Chest radiography is a poor predictor of respiratory symptoms and functional impairment in survivors of severe COVID-19 pneumonia. ERJ Open Res. 2021;7:00655–02020. [PMC free article] [PubMed] [Google Scholar]
18. Chopra V, Flanders SA, O'Malley M, Malani AN, Prescott HC. Sixty-day outcomes among patients hospitalized with COVID-19. Ann Intern Med. 2020;11:M20–5661. [PMC free article] [PubMed] [Google Scholar]
19. Arnold DT, Hamilton FW, Milne A. Patient outcomes after hospitalisation with COVID-19 and implications for follow-up: results from a prospective UK cohort. Thorax. 2021;76:399–401. [PMC free article] [PubMed] [Google Scholar]
20. Sonnweber T, Sahanic S, Pizzini A. Cardiopulmonary recovery after COVID-19 — an observational prospective multi-center trial. Eur Respir J. 2020 doi: 10.1183/13993003.03481-2020. published online Dec 10. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
21. Xiong Q, Xu M, Li J. Clinical sequelae of COVID-19 survivors in Wuhan, China: a single-centre longitudinal study. Clin Microbiol Infect. 2021;27:89–95. [PMC free article] [PubMed] [Google Scholar]
22. Zhao YM, Shang YM, Song WB. Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery. EClinicalMedicine. 2020;25 [PMC free article] [PubMed] [Google Scholar]
23. Valiente-De Santis L, Perez-Camacho I, Sobrino B. Clinical and immunoserological status 12 weeks after infection with COVID-19: prospective observational study. medRxiv. 2020 doi: 10.1101/2020.10.06.20206060. published online Dec 10. (preprint). [CrossRef] [Google Scholar]
24. Stavem K, Ghanima W, Olsen MK, Gilboe HM, Einvik G. Persistent symptoms 1·5–6 months after COVID-19 in non-hospitalised subjects: a population-based cohort study. Thorax. 2020 doi: 10.1136/thoraxjnl-2020-216377. published online December 3. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
25. Petersen MS, Kristiansen MF, Hanusson KD. Long COVID in the Faroe Islands-a longitudinal study among non-hospitalized patients. Clin Infect Dis. 2020 doi: 10.1093/cid/ciaa1792. published online Nov 30. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
26. Klein H, Asseo K, Karni N. Onset, duration and unresolved symptoms, including smell and taste changes, in mild COVID-19 infection: a cohort study in Israeli patients. Clin Microbiol Infect. 2021 https://doi:10.1016/j.cmi.2021.02.008 published online Feb 16. [PMC free article] [PubMed] [Google Scholar]
27. Guler SA, Ebner L, Beigelman C. Pulmonary function and radiological features four months after COVID-19: first results from the national prospective observational Swiss COVID-19 lung study. Eur Respir J. 2021;57 [PMC free article] [PubMed] [Google Scholar]
28. Assaf G, Davis H, McCorkell L, Wei H, O'Neill B, Akrami A. The COVID-19 Body Politic Slack Group; London, UK: 2020. What does COVID-19 recovery actually look like? An analysis of the prolonged COVID-19 symptoms survey by patient-led research team.https://patientresearchcovid19.com/research/report-1/ [Google Scholar]
29. Sudre CH, Murray B, Varsavsky T. Attributes and predictors of Long-COVID: analysis of COVID cases and their symptoms collected by the Covid Symptoms Study App. medRxiv. 2020 doi: 10.1101/2020.10.19.20214494. published online Dec 19. (preprint). [CrossRef] [Google Scholar]
30. Office for National Statistics COVID-19 Infection Survey Coronavirus (COVID-19) https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases
32. Ojha V, Mani A, Pandey NN, Sharma S, Kumar S. CT in coronavirus disease 2019 (COVID-19): a systematic review of chest CT findings in 4410 adult patients. Eur Radiol. 2020;30:6129–6138. [PMC free article] [PubMed] [Google Scholar]
36. Mazzone SB, Tian L, Moe AAK, Trewella MW, Ritchie ME, McGovern AE. Transcriptional profiling of individual airway projecting vagal sensory neurons. Mol Neurobiol. 2020;57:949–963. [PubMed] [Google Scholar]
37. Davies J, Randeva HS, Chatha K. Neuropilin1 as a new potential SARSCoV2 infection mediator implicated in the neurologic features and central nervous system involvement of COVID19. Mol Med Rep. 2020;22:4221–4226. [PMC free article] [PubMed] [Google Scholar]
38. Brann DH, Tsukahara T, Weinreb C. Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia. Sci Adv. 2020;6 [PubMed] [Google Scholar]
39. Chen M, Shen W, Rowan NR. Elevated ACE-2 expression in the olfactory neuroepithelium: implications for anosmia and upper respiratory SARS-CoV-2 entry and replication. Eur Respir J. 2020;56 [PMC free article] [PubMed] [Google Scholar]
40. Shiers S, Ray PR, Wangzhou A. ACE2 and SCARF expression in human dorsal root ganglion nociceptors: implications for SARS-CoV-2 virus neurological effects. Pain. 2020;161:2494–2501. [PMC free article] [PubMed] [Google Scholar]
41. Kupari J, Häring M, Agirre E, Castelo-Branco G, Ernfors P. An atlas of vagal sensory neurons and their molecular specialization. Cell Rep. 2019;27:2508–2523.e4. [PMC free article] [PubMed] [Google Scholar]
42. Meinhardt J, Radke J, Dittmayer C. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nat Neurosci. 2021;24:168–175. [PubMed] [Google Scholar]
44. Driessen AK, Farrell MJ, Mazzone SB, McGovern AE. Multiple neural circuits mediating airway sensations: recent advances in the neurobiology of the urge-to-cough. Respir Physiol Neurobiol. 2016;226:115–120. [PubMed] [Google Scholar]
46. Rosato PC, Leib DA. Neuronal interferon signaling is required for protection against herpes simplex virus replication and pathogenesis. PLoS Pathog. 2015;11 [PMC free article] [PubMed] [Google Scholar]
47. Undem BJ, Zaccone E, McGarvey L, Mazzone SB. Neural dysfunction following respiratory viral infection as a cause of chronic cough hypersensitivity. Pulm Pharmacol Ther. 2015;33:52–56. [PMC free article] [PubMed] [Google Scholar]
52. Chiu IM, von Hehn CA, Woolf CJ. Neurogenic inflammation and the peripheral nervous system in host defense and immunopathology. Nat Neurosci. 2012;15:1063–1067. [PMC free article] [PubMed] [Google Scholar]
53. Deng Z, Zhou W, Sun J, Li C, Zhong B, Lai K. IFN-γ enhances the cough reflex sensitivity via calcium influx in vagal sensory neurons. Am J Respir Crit Care Med. 2018;198:868–879. [PubMed] [Google Scholar]
55. Nahama A, Ramachandran R, Cisternas AF, Ji H. The role of afferent pulmonary innervation in ARDS associated with COVID-19 and potential use of resiniferatoxin to improve prognosis: a review. Med Drug Discov. 2020;5 [PMC free article] [PubMed] [Google Scholar]
56. Ray PR, Wangzhou A, Ghneim N. A pharmacological interactome between COVID-19 patient samples and human sensory neurons reveals potential drivers of neurogenic pulmonary dysfunction. Brain Behav Immun. 2020;89:559–568. [PMC free article] [PubMed] [Google Scholar]
58. Ntogwa M, Imai S, Hiraiwa R. Schwann cell-derived CXCL1 contributes to human immunodeficiency virus type 1 gp120-induced neuropathic pain by modulating macrophage infiltration in mice. Brain Behav Immun. 2020;88:325–339. [PubMed] [Google Scholar]
59. Ford AP, Undem BJ. The therapeutic promise of ATP antagonism at P2X3 receptors in respiratory and urological disorders. Front Cell Neurosci. 2013;7:267. [PMC free article] [PubMed] [Google Scholar]
60. Abdullah H, Heaney LG, Cosby SL, McGarvey LP. Rhinovirus upregulates transient receptor potential channels in a human neuronal cell line: implications for respiratory virus-induced cough reflex sensitivity. Thorax. 2014;69:46–54. [PubMed] [Google Scholar]
62. Atkinson SK, Morice AH, Sadofsky LR. Rhinovirus-16 increases ATP release in A549 cells without concomitant increase in production. ERJ Open Res. 2020;6:00159–02020. [PMC free article] [PubMed] [Google Scholar]
63. Smith JA, Kitt MM, Morice AH. Gefapixant, a P2X3 receptor antagonist, for the treatment of refractory or unexplained chronic cough: a randomised, double-blind, controlled, parallel-group, phase 2b trial. Lancet Respir Med. 2020;8:775–785. [PubMed] [Google Scholar]
64. Carr MJ, Hunter DD, Jacoby DB, Undem BJ. Expression of tachykinins in nonnociceptive vagal afferent neurons during respiratory viral infection in guinea pigs. Am J Respir Crit Care Med. 2002;165:1071–1075. [PubMed] [Google Scholar]
68. Netland J, Meyerholz DK, Moore S, Cassell M, Perlman S. Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J Virol. 2008;82:7264–7275. [PMC free article] [PubMed] [Google Scholar]
71. Ando A, Smallwood D, McMahon M, Irving L, Mazzone SB, Farrell MJ. Neural correlates of cough hypersensitivity in humans: evidence for central sensitisation and dysfunctional inhibitory control. Thorax. 2016;71:323–329. [PubMed] [Google Scholar]
72. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann Intern Med. 1994;121:953–959. [PubMed] [Google Scholar]
73. Cortes Rivera M, Mastronardi C, Silva-Aldana CT, Arcos-Burgos M, Lidbury BA. Myalgic encephalomyelitis/chronic fatigue syndrome: a comprehensive review. Diagnostics. 2019;9:73. [Google Scholar]
74. Peiffer C, Costes N, Hervé P, Garcia-Larrea L. Relief of dyspnea involves a characteristic brain activation and a specific quality of sensation. Am J Respir Crit Care Med. 2008;177:440–449. [PubMed] [Google Scholar]
76. Guedj E, Campion J, Dudouet P. 18 F-FDG brain PET hypometabolism in patients with long COVID. Eur J Nucl Med Mol Imaging. 2021 doi: 10.1007/s00259-021-05215-4. published online Jan 26. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
79. Mazzone SB, McGarvey L. Mechanisms and rationale for targeted therapies in refractory and unexplained chronic cough. Clin Pharmacol Ther. 2020 doi: 10.1002/cpt.2003. published online Aug 4. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
80. Schroeder K, Fahey T. Systematic review of randomised controlled trials of over the counter cough medicines for acute cough in adults. BMJ. 2002;324:329–331. [PMC free article] [PubMed] [Google Scholar]
81. Chang CC, Cheng AC, Chang AB. Over-the-counter (OTC) medications to reduce cough as an adjunct to antibiotics for acute pneumonia in children and adults. Cochrane Database Syst Rev. 2014;10 [PubMed] [Google Scholar]
82. National Institute for Health and Care Excellence in collaboration with NHS England and NHS Improvement Managing COVID-19 symptoms (including at the end of life) in the community: summary of NICE guidelines. BMJ. 2020;369 [PubMed] [Google Scholar]
84. Hay AD, Little P, Harnden A. Effect of oral prednisolone on symptom duration and severity in nonasthmatic adults with acute lower respiratory tract infection: a randomized clinical trial. JAMA. 2017;318:721–730. [PMC free article] [PubMed] [Google Scholar]
85. Group RC. Dexamethasone in hospitalized patients with Covid-19—preliminary report. N Engl J Med. 2020 doi: 10.1056/NEJMoa2021436. published online Feb 25. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
86. Tomazini BM, Maia IS, Cavalcanti AB. Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19: the CoDEX randomized clinical trial. JAMA. 2020;324:1307–1316. [PMC free article] [PubMed] [Google Scholar]
89. Vertigan AE, Kapela SL, Ryan NM, Birring SS, McElduff P, Gibson PG. Pregabalin and speech pathology combination therapy for refractory chronic cough: a randomized controlled trial. Chest. 2016;149:639–648. [PubMed] [Google Scholar]
91. Chamberlain Mitchell SA, Garrod R, Clark L. Physiotherapy, and speech and language therapy intervention for patients with refractory chronic cough: a multicentre randomised control trial. Thorax. 2017;72:129–136. [PubMed] [Google Scholar]
92. Smith J, Allman D, Badri H. The neurokinin-1 receptor antagonist orvepitant is a novel antitussive therapy for chronic refractory cough: results from a phase 2 pilot study (VOLCANO-1) Chest. 2020;157:111–118. [PubMed] [Google Scholar]
93. Smith JA, Harle A, Dockry R. Aprepitant for cough in lung cancer: a randomised placebo-controlled trial and mechanistic insights. Am J Respir Crit Care Med. 2020 doi: 10.1164/rccm.202006-2359OC. published online Sept 23. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
94. Khalid S, Murdoch R, Newlands A. Transient receptor potential vanilloid 1 (TRPV1) antagonism in patients with refractory chronic cough: a double-blind randomized controlled trial. J Allergy Clin Immunol. 2014;134:56–62. [PubMed] [Google Scholar]
95. Belvisi MG, Birrell MA, Wortley MA. XEN-D0501, a novel transient receptor potential vanilloid 1 antagonist, does not reduce cough in patients with refractory cough. Am J Respir Crit Care Med. 2017;196:1255–1263. [PubMed] [Google Scholar]