Can pertussis lead to the onset of gastroesophageal reflux. How does whooping cough affect the digestive system. What are the long-term implications of pertussis on gastrointestinal health. Are there overlapping symptoms between whooping cough and GERD. How can healthcare providers differentiate between pertussis-related reflux and primary GERD.

The Nature of Whooping Cough: An Overview

Whooping cough, also known as pertussis, is a highly contagious respiratory disease caused by the bacterium Bordetella pertussis. This illness has been a significant public health concern for centuries, with its characteristic “whoop” sound during coughing fits being a telltale sign of infection.

Pertussis typically progresses through three stages:

1. Catarrhal stage: Mild cold-like symptoms
2. Paroxysmal stage: Severe coughing fits
3. Convalescent stage: Gradual recovery

During the paroxysmal stage, patients experience intense bouts of coughing that can lead to vomiting, exhaustion, and in severe cases, rib fractures. These coughing fits can persist for weeks or even months, earning pertussis the moniker “100-day cough” in some cultures.

Epidemiology and Vaccination Challenges

Despite widespread vaccination programs, pertussis remains a global health issue. Epidemiological studies have shown cyclical outbreaks occurring every 3-5 years, even in countries with high vaccination rates. This persistence can be attributed to several factors:

• Waning immunity from acellular pertussis vaccines
• Genetic changes in circulating B. pertussis strains
• Increased awareness and improved diagnostic techniques

Is the current pertussis vaccine effective in providing long-term immunity? Research indicates that while the acellular pertussis vaccine is safer than its whole-cell predecessor, it may offer shorter-lived protection. A study by Klein et al. (2012) found that protection against pertussis waned during the five years after the fifth dose of the DTaP vaccine, highlighting the need for improved vaccination strategies.

Gastroesophageal Reflux Disease: A Brief Introduction

Gastroesophageal reflux disease (GERD) is a chronic condition where stomach contents flow back into the esophagus, causing symptoms such as heartburn, regurgitation, and difficulty swallowing. While GERD is often associated with lifestyle factors and anatomical abnormalities, recent research has begun to explore potential links between respiratory infections and the onset of reflux symptoms.

What are the primary mechanisms behind GERD? The lower esophageal sphincter (LES), a ring of muscle at the junction of the esophagus and stomach, plays a crucial role in preventing reflux. When this sphincter weakens or relaxes inappropriately, it allows stomach acid to flow back into the esophagus, leading to GERD symptoms.

The Cough Reflex: Bridging Respiratory and Digestive Systems

To understand the potential link between pertussis and GERD, it’s essential to examine the cough reflex and its impact on both the respiratory and digestive systems. The cough reflex is a complex neurological mechanism designed to protect the airways from irritants and foreign substances.

How does the cough reflex work? When irritants stimulate sensory nerve endings in the airways, a signal is sent to the cough center in the brain stem. This triggers a coordinated series of muscle contractions, including:

• Closure of the glottis
• Contraction of expiratory muscles
• Sudden opening of the glottis, resulting in the characteristic cough sound

During a cough, intrathoracic pressure can increase significantly, potentially affecting the function of the lower esophageal sphincter. In the case of pertussis, where coughing fits are severe and prolonged, this repeated increase in pressure could theoretically lead to weakening or dysfunction of the LES.

Exploring the Pertussis-GERD Connection: Observational Findings

While the link between pertussis and new-onset GERD has not been extensively studied, observational evidence suggests a potential association. Clinicians have reported cases where patients developed persistent reflux symptoms following pertussis infection, even in individuals with no prior history of GERD.

What evidence supports the connection between pertussis and GERD? Several factors contribute to this hypothesized link:

1. Prolonged coughing fits causing increased intra-abdominal pressure
2. Potential damage to the lower esophageal sphincter due to repeated strain
3. Alterations in esophageal motility as a result of the infection
4. Possible neurological changes affecting the coordination of swallowing and LES function

It’s important to note that while these observations are intriguing, more rigorous scientific studies are needed to establish a definitive causal relationship between pertussis and GERD.

Diagnostic Challenges: Differentiating Pertussis-Related Reflux from Primary GERD

One of the challenges in studying the pertussis-GERD connection is the overlap in symptoms between the two conditions. Both can present with cough, particularly at night, making it difficult to distinguish between pertussis-induced reflux and primary GERD.

How can healthcare providers differentiate between these conditions? Several diagnostic tools and approaches can be employed:

• Detailed patient history, including the onset and progression of symptoms
• PCR testing for Bordetella pertussis
• 24-hour pH monitoring to assess esophageal acid exposure
• Endoscopy to evaluate for esophageal damage
• Impedance testing to detect non-acid reflux

The Reflux Symptom Index (RSI) and Cough Severity Index (CSI) are validated tools that can be used to assess the severity of reflux and cough symptoms, respectively. These instruments may help in tracking the progression of symptoms and response to treatment.

Potential Mechanisms of Pertussis-Induced GERD

While the exact mechanisms by which pertussis might lead to GERD are not fully understood, several hypotheses have been proposed based on our current knowledge of both conditions:

1. Mechanical Stress on the LES

The intense and prolonged coughing associated with pertussis can place significant mechanical stress on the lower esophageal sphincter. This repeated strain may lead to weakening or dysfunction of the LES, potentially predisposing individuals to reflux.

2. Alterations in Esophageal Motility

Pertussis infection may affect the nerves controlling esophageal motility, leading to impaired clearance of refluxed material. This could exacerbate reflux symptoms and increase the risk of esophageal damage.

3. Inflammation and Tissue Damage

The inflammatory response to B. pertussis infection may extend beyond the respiratory tract, potentially affecting the esophagus and surrounding tissues. This inflammation could contribute to alterations in LES function and esophageal sensitivity.

4. Neurological Changes

Pertussis toxin, produced by B. pertussis, is known to affect various neurological functions. It’s possible that this toxin could interfere with the complex neural networks controlling esophageal function and the cough reflex, leading to increased susceptibility to GERD.

Are these mechanisms supported by current research? While these hypotheses are plausible based on our understanding of pertussis and GERD pathophysiology, further studies are needed to elucidate the specific mechanisms involved in pertussis-induced reflux.

Implications for Patient Care and Management

The potential link between pertussis and new-onset GERD has important implications for patient care and management. Healthcare providers should be aware of this possible association and consider the following approaches:

• Monitoring for reflux symptoms in patients recovering from pertussis
• Early intervention and treatment of GERD symptoms to prevent complications
• Long-term follow-up to assess the persistence of reflux symptoms post-pertussis
• Consideration of GERD in the differential diagnosis of persistent cough following pertussis infection

How should clinicians approach the management of pertussis-related reflux? A multidisciplinary approach involving pulmonologists, gastroenterologists, and primary care physicians may be beneficial. Treatment strategies may include:

1. Proton pump inhibitors or H2 receptor antagonists to reduce acid production
2. Lifestyle modifications to minimize reflux (e.g., dietary changes, elevation of the head during sleep)
3. Prokinetic agents to improve esophageal motility
4. Speech therapy techniques to reduce cough and throat clearing behaviors

It’s important to note that while these interventions may be helpful, their efficacy specifically for pertussis-induced GERD has not been extensively studied and may require individualized approaches.

Future Research Directions and Unanswered Questions

The potential link between pertussis and new-onset GERD opens up several avenues for future research. Key questions that remain to be addressed include:

• What is the incidence of new-onset GERD following pertussis infection?
• Are there specific risk factors that predispose individuals to developing GERD after pertussis?
• How long do reflux symptoms persist following pertussis infection?
• Are there differences in GERD incidence or severity between vaccinated and unvaccinated individuals who contract pertussis?
• Can early intervention prevent the development of chronic GERD in pertussis patients?

To address these questions, several types of studies could be conducted:

1. Prospective cohort studies following pertussis patients to assess GERD incidence
2. Case-control studies comparing GERD prevalence in individuals with and without a history of pertussis
3. Mechanistic studies investigating the effects of pertussis infection on esophageal function
4. Clinical trials evaluating the efficacy of various interventions for pertussis-related reflux

What role might advanced diagnostic techniques play in elucidating the pertussis-GERD connection? Novel approaches such as reflux scintigraphy, as described by Burton et al. (2020), could provide valuable insights into the patterns of reflux in pertussis patients. These techniques may help differentiate pertussis-related reflux from other forms of GERD and guide targeted treatment strategies.

Public Health Implications and Preventive Strategies

If a significant link between pertussis and GERD is established, it could have important public health implications. The potential for long-term gastrointestinal complications following pertussis infection would add to the already substantial burden of this disease and underscore the importance of effective prevention strategies.

How might this impact vaccination policies and recommendations? Several considerations arise:

• Reinforcing the importance of pertussis vaccination and booster doses
• Exploring the development of improved pertussis vaccines with longer-lasting immunity
• Implementing targeted vaccination strategies for high-risk groups
• Enhancing public education about the potential long-term consequences of pertussis

Additionally, healthcare systems may need to adapt to provide comprehensive follow-up care for pertussis patients, including screening for GERD and other potential long-term sequelae.

Conclusion and Future Perspectives

The putative link between pertussis and new-onset gastroesophageal reflux disease represents an intriguing area of research at the intersection of respiratory and gastrointestinal medicine. While observational evidence suggests a potential association, further studies are needed to establish a definitive causal relationship and elucidate the underlying mechanisms.

As our understanding of this connection grows, it may lead to improved management strategies for pertussis patients and inform public health policies regarding vaccination and disease prevention. The exploration of this link also highlights the complex interplay between different organ systems and the importance of considering systemic effects in infectious diseases.

Ultimately, unraveling the pertussis-GERD connection could contribute to better patient outcomes, reduced disease burden, and advances in our understanding of both conditions. As research in this area progresses, healthcare providers should remain vigilant for signs of GERD in pertussis patients and consider this potential complication in their overall management approach.

A putative link between pertussis and new onset of gastroesophageal reflux an observational study

1. Kent A, Heath PT. Pertussis. Medicine
2014;42:8-10. [Google Scholar]

2. Gabutti G, Azzari C, Bonanni P, Prato R, Tozzi AE, Zanetti A, et al.. Pertussis. Hum Vaccin Immunother
2015;11:108-17. [PMC free article] [PubMed] [Google Scholar]

3. Bhattacharyya S, Ferrari MJ, Bjornstad ON. Species interactions may help explain the erratic periodicity of whooping cough dynamics. Epidemics
2018;23:64-70. [PubMed] [Google Scholar]

4. Gideon Informatics, Inc., Berger S.
Pertussis: Global status. Los Angeles: Gideon Informatics, Inc.; 2018. [Google Scholar]

5. Klein NP, Bartlett J, Fireman B, Rowhani-Rahbar A, Baxter R.
Comparative effectiveness of acellular versus whole-cell pertussis vaccines in teenagers. Pediatrics
2013;131:e1716-22. [PubMed] [Google Scholar]

6. Klein NP, Bartlett J, Rowhani-Rahbar A, Fireman B, Baxter R.
Waning protection after fifth dose of acellular pertussis vaccine in children. N Engl J Med
2012;367:1012-9. [PubMed] [Google Scholar]

7. Misegades LK, Winter K, Harriman K, Talarico J, Messonnier NE, Clark TA, et al.. Association of childhood pertussis with receipt of 5 doses of pertussis vaccine by time since last vaccine dose, California, 2010. JAMA
2012;308:2126-32. [PubMed] [Google Scholar]

8. Quinn HE, Snelling TL, Macartney KK, McIntyre PB. Duration of protection after first dose of acellular pertussis vaccine in infants. Pediatrics
2014;133:e513-9. [PubMed] [Google Scholar]

9. Kaczmarek MC, Valenti L, Kelly HA, Ware RS, Britt HC, Lambert SB. Sevenfold rise in likelihood of pertussis test requests in a stable set of Australian general practice encounters, 2000-2011. Med J Aust
2013;198:624-8. [PubMed] [Google Scholar]

10. Witt MA, Katz PH, Witt DJ. Unexpectedly limited durability of immunity following acellular pertussis vaccination in preadolescents in a North American outbreak. Clin Infect Dis
2012;54:1730-5. [PubMed] [Google Scholar]

11. Baxter R, Bartlett J, Rowhani-Rahbar A, Fireman B, Klein NP. Effectiveness of pertussis vaccines for adolescents and adults: case-control study. BMJ
2013;347:f4249. [PubMed] [Google Scholar]

12. Cherry JD. Adult pertussis in the pre- and post-vaccine eras: lifelong vaccine-induced immunity?
Expert Rev Vaccines
2014;13:1073-80. [PubMed] [Google Scholar]

13. De Serres G, Shadmani R, Duval B, Boulianne N, Dery P, Douville Fradet M, et al.. Morbidity of pertussis in adolescents and adults. J Infect Dis
2000;182:174-9. [PubMed] [Google Scholar]

14. Smith JA, Aliverti A, Quaranta M, McGuinness K, Kelsall A, Earis J, et al.. Chest wall dynamics during voluntary and induced cough in healthy volunteers. J Physiol
2012;590:563-74. [PMC free article] [PubMed] [Google Scholar]

15. Polverino M, Polverino F, Fasolino M, Ando F, Alfieri A, De Blasio F.
Anatomy and neuro-pathophysiology of the cough reflex arc. Multidiscip Respir Med
2012;7:5. [PMC free article] [PubMed] [Google Scholar]

16. Belafsky PC, Postma GN, Koufman JA. Validity and reliability of the reflux symptom index (RSI). J Voice
2002;16:274-7. [PubMed] [Google Scholar]

17. Shembel AC, Rosen CA, Zullo TG, Gartner-Schmidt JL. Development and validation of the cough severity index: a severity index for chronic cough related to the upper airway. Laryngoscope
2013;123:1931-6. [PubMed] [Google Scholar]

18. Moore A, Harnden A, Grant CC, Patel S, Irwin RS, Panel CEC. Clinically diagnosing pertussis-associated cough in adults and children: CHEST guideline and expert panel report. Chest
2019;155:147-54. [PMC free article] [PubMed] [Google Scholar]

19. Burton L, Falk G, Baumgart K, Beattie J, Simpson S, Van der Wall H. Esophageal clearance in laryngopharyngeal reflux disease: Correlation of reflux scintigraphy and 24-hour impedance/pH in a cohort of refractory symptomatic patients. Mol Imaging Radionucl Ther
2020;29:7-16. [PMC free article] [PubMed] [Google Scholar]

20. Burton L, Falk G, Beattie J, Novakovic D, Simpson S, Wall H.
Findings from a novel scintigraphic gastroesophageal reflux study in asymptomatic volunteers. Am J Nucl Med Mol Imaging
2020;10:342-8. [PMC free article] [PubMed] [Google Scholar]

21. Burton L, Falk GL, Parsons S, Cusi M, Van Der Wall H. Benchmarking of a simple scintigraphic test for gastrooesophageal reflux disease that assesses oesophageal disease and its pulmonary complications. Mol Imaging Radionucl Ther
2018;27:113-20. [PMC free article] [PubMed] [Google Scholar]

22. Falk G, Beattie J, Ing A, Falk S, Magee M, Burton L, et al.. Scintigraphy in laryngopharyngeal and gastroesophageal reflux disease: A definitive diagnostic test?
World J Gastroenterol
2015;21:3619-27. [PMC free article] [PubMed] [Google Scholar]

23. Falk GL, Vivian SJ. Laryngopharyngeal reflux: diagnosis, treatment and latest research. Eur Surg
2016;48:74-91. [Google Scholar]

24. Vertigan AE, Bone SL, Gibson PG. Development and validation of the Newcastle laryngeal hypersensitivity questionnaire. Cough
2014;10:1. [PMC free article] [PubMed] [Google Scholar]

25. Hosmer DW, Lemeshow S.
Applied logistic regression. New York: J. Wiley & Sons, Inc.; 1989. [Google Scholar]

26. Zhu W, Zeng N, Wang N.
Sensitivity, specificity, accuracy, associated confidence interval and ROC analysis with practical SASR implementations. NorthEast SAS users group, health care and life sciences [Internet]. 2010. Available from: https://www.lexjansen.com/nesug/nesug10/hl/hl07.pdf [Google Scholar]

27. Khoma O, Falk SE, Burton L, Van der Wall H, Falk GL. Gastro-Oesophageal reflux and aspiration: Does laparoscopic fundoplication significantly decrease pulmonary aspiration?
Lung
2018;196:491-6. [PubMed] [Google Scholar]

28. Falk M, Van der Wall H, Falk GL. Differences between scintigraphic reflux studies in gastrointestinal reflux disease and laryngopharyngeal reflux disease and correlation with symptoms. Nucl Med Commun
2015;36:625-30. [PubMed] [Google Scholar]

29. Morice AH. Airway reflux as a cause of respiratory disease. Breathe
2013;9:256. [Google Scholar]

30. Khoma O, Burton L, Falk MG, Van der Wall H, Falk GL. Predictors of reflux aspiration and laryngo-pharyngeal reflux. Esophagus
2020;17:355-62. [PubMed] [Google Scholar]

31. Kulig M, Nocon M, Vieth M, Leodolter A, Jaspersen D, Labenz J, et al.. Risk factors of gastroesophageal reflux disease: methodology and first epidemiological results of the ProGERD study. J Clin Epidemiol
2004;57:580-9. [PubMed] [Google Scholar]

32. Paoletti G, Melone G, Ferri S, Puggioni F, Baiardini I, Racca F, et al.. Gastroesophageal reflux and asthma: when, how, and why. Curr Opin Allergy Clin Immunol
2021;21:52-8. [PubMed] [Google Scholar]

33. Soane M, Jackson A, Maskell D, Allen A, Keig P, Dewar A, et al.. Interactions of Bordetella pertussis with human respiratory mucosa in vitro. Resp Med
2000;94:791-9. [PubMed] [Google Scholar]

34. Zanasi A, Fontana GA, Mutolo D.
Cough: Pathophysiology, diagnosis and treatment. Dordrecht: Springer; 2020. [Google Scholar]

35. Chung KF, McGarvey L, Mazzone SB. Chronic cough as a neuropathic disorder. Lancet Respir Med
2013;1:414-22. [PubMed] [Google Scholar]

36. Cunningham KM, Horowitz M, Riddell PS, Maddern GJ, Myers JC, Holloway RH, et al.. Relations among autonomic nerve dysfunction, oesophageal motility, and gastric emptying in gastro-oesophageal reflux disease. Gut
1991;32:1436-40. [PMC free article] [PubMed] [Google Scholar]

37. Ayazi S, DeMeester SR, Hsieh CC, Zehetner J, Sharma G, Grant KS, et al.. Thoraco-abdominal pressure gradients during the phases of respiration contribute to gastroesophageal reflux disease. Dig Dis Sci
2011;56:1718-22 [PubMed] [Google Scholar]

38. Turb Turbyville JC. Applying principles of physics to the airway to help explain the relationship between asthma and gastroesophageal reflux. Med Hypotheses
2010;74:1075-80. [PubMed] [Google Scholar]

39. Ford PA, Barnes PJ, Usmani OS. Chronic cough and Holmes- Adie syndrome. Lancet
2007;369:342. [PubMed] [Google Scholar]

40. Brown CA, Mehler PS. Medical complications of self-induced vomiting. Eat Disord
2013;21:287-94. [PubMed] [Google Scholar]

41. Hershcovici T, Mashimo H, Fass R.
The lower esophageal sphincter. J Neurogastroenterol Motil
2011;23:819-30. [PubMed] [Google Scholar]

42. Sloan S, Kahrilas PJ. Impairment of esophageal emptying with hiatal hernia. Gastroenterology
1991;100:596-605. [PubMed] [Google Scholar]

43. Pandolfino JE, Zhang QG, Ghosh SK, Han A, Boniquit C, Kahrilas PJ. Transient lower esophageal sphincter relaxations and reflux: mechanistic analysis using concurrent fluoroscopy and high-resolution manometry. Gastroenterology
2006;131:1725-33. [PubMed] [Google Scholar]

44. El-Serag H. Role of obesity in GORD-related disorders. Gut
2008;57:281-4. [PubMed] [Google Scholar]

Whooping cough – NHS

Whooping cough (pertussis) is a bacterial infection of the lungs and breathing tubes. It spreads very easily and can sometimes cause serious problems. It’s important for babies and children to get vaccinated against it.

Check if you or your child has whooping cough

The first signs of whooping cough are similar to a cold, such as a runny nose and sore throat (a high temperature is uncommon).

After about a week, you or your child:

• will get coughing bouts that last for a few minutes and are worse at night
• may make a “whoop” sound – a gasp for breath between coughs (young babies and some adults may not “whoop”)
• may have difficulty breathing after a coughing bout and may turn blue or grey (young infants)
• may bring up a thick mucus, which can make you vomit
• may become very red in the face (more common in adults)

The cough may last for several weeks or months.

Urgent advice: Ask for an urgent GP appointment or get help from NHS 111 if:

• your baby is under 6 months old and has symptoms of whooping cough
• you or your child have a very bad cough that is getting worse
• you’ve been in contact with someone with whooping cough and you’re pregnant
• you or your child has been in contact with someone with whooping cough and have a weakened immune system

Whooping cough can spread very easily. It’s best to call the GP before you go in. They might suggest talking over the phone.

Check symptoms on 111 online (for children aged 5 and over) or call 111 (for children under 5).

Whooping cough can be dangerous

Babies under 6 months old with whooping cough have an increased chance of having problems such as:

• dehydration
• breathing difficulties
• pneumonia
• seizures (fits)

Whooping cough is less severe in older children and adults but coughing may cause problems including:

• sore ribs
• hernia
• middle ear infections
• pee leaking out when you cough (urinary incontinence)

Immediate action required: Call 999 or go to A&E if:

• your or your child’s lips, tongue, face or skin suddenly turn blue or grey (on black or brown skin this may be easier to see on the palms of the hands or the soles of the feet)
• you or your child are finding it hard to breathe properly (shallow breathing)
• you or your child have chest pain that’s worse when breathing or coughing – this could be a sign of pneumonia
• your child is having seizures (fits)

Treatment for whooping cough

Treatment for whooping cough depends on your age and how long you’ve had the infection.

Hospital treatment is usually needed if you have severe whooping cough, or your baby is under 6 months old and has whooping cough.

If whooping cough is diagnosed within 3 weeks of the infection, you’ll be given antibiotics to help stop it spreading to others. Antibiotics may not reduce symptoms.

If you’ve had whooping cough for more than 3 weeks, you’re no longer contagious and do not need antibiotics.

Important

Keep taking the antibiotics until you’ve completed the course, even if you feel better. Stopping treatment too soon could lead to the infection coming back.

How to ease the symptoms of whooping cough

There are some things you can do to help ease the symptoms of whooping cough.

Don’t

• do not give a child under 16 paracetamol and ibuprofen at the same time – always check first with a GP or pharmacist

• do not give aspirin to children under 16

• do not take cough medicines – they’re not suitable for young children and do not help with this type of cough

How long whooping cough is contagious

If you have whooping cough, you’re contagious from about 6 days after the start of cold-like symptoms to 3 weeks after the coughing starts.

If you start antibiotics within 3 weeks of starting to cough, it will reduce the time you’re contagious for.

Important

Stay off school, work or nursery until 48 hours after starting antibiotics, or 3 weeks after your symptoms started if you’ve not had antibiotics.

The whooping cough vaccine

The whooping cough vaccine protects babies and children from getting whooping cough. That’s why it’s important to have all the routine NHS vaccinations.

The whooping cough vaccine is routinely given as part of the:

• 6-in-1 vaccine – for babies at 8, 12 and 16 weeks
• 4-in-1 pre-school booster – for children aged 3 years 4 months

If you’re pregnant you should also have the whooping cough vaccine – ideally between 16 and 32 weeks.

Find out more about the whooping cough vaccination in pregnancy

Page last reviewed: 21 March 2023
Next review due: 21 March 2026

What is chronic cough? | Chikina S.Yu.

For citation. Chikina S.Yu. What is chronic cough? // RMJ. 2015. No. 18. S. 1101–1105.

Introduction
Cough is one of the most common respiratory symptoms and at the same time one of the most intractable problems of modern clinical medicine. Cough is divided into acute (lasting less than 3 weeks) and chronic (lasting more than 8 weeks). Cough lasting 3 to 8 weeks. called subacute, it can be the result of an acute respiratory viral infection with a longer course (hence it is often called post-infectious cough) or the onset of a chronic cough [1]. Acute and subacute cough can stop spontaneously even without special treatment, such patients do not always go to the doctor. In contrast, chronic cough is a more severe condition; it accompanies many chronic respiratory diseases and at the same time can cause serious complications: gastroesophageal reflux (GER), urinary incontinence, insomnia, cause psychological, social and family problems and, finally, significantly reduce the quality of life of patients [2].

Cough triad
Over the past few decades, the view of the causes and pathogenesis of chronic cough has changed many times. Initially, cough was called chronic in any chronic respiratory diseases: chronic obstructive pulmonary disease (COPD), lung cancer, idiopathic pulmonary fibrosis. In the 1990s The theory of the “cough triad” has been formed, according to which the causes of chronic cough are most often bronchial asthma (BA), GER, or chronic rhinitis [3].

Bronchial asthma
Cough is one of the common symptoms of asthma and often accompanies other manifestations of it (suffocation attacks, episodes of shortness of breath, wheezing). Asthma is the cause of chronic cough in 24-29% of cases in adult non-smokers [4]. However, in a small percentage of patients, cough may be the predominant or only symptom of asthma. In such cases, one speaks of a cough variant of BA [4]. Thus, asthma should always be considered as a potential cause of chronic cough. If a patient with chronic cough tests positive for a bronchodilator on spirometry with a bronchodilation test, the diagnosis is usually straightforward. But often, when examining a patient, there are no wheezing in the lungs, and the study of pulmonary function does not reveal signs of reversible bronchial obstruction. In this case, bronchoprovocation tests are indicated, which help to identify bronchial hyperreactivity, typical of asthma. In addition, in many cases AD is accompanied by blood and/or sputum eosinophilia. Confirmation of the diagnosis of cough asthma is the disappearance of cough on the background of anti-asthma therapy. If it is not possible to perform a bronchoprovocation test, a trial of anti-asthma therapy with inhaled corticosteroids is recommended (recommendation grade A) [44]. In general, the approach to the treatment of cough asthma does not differ from the treatment of the classical form of this disease. As a rule, against the background of therapy with inhaled bronchodilators and corticosteroids, improvement occurs by the end of the first week of treatment, although the complete disappearance of cough may require continued therapy for up to 8 weeks. [44].

Gastroesophageal reflux
GER is the second most common cause of chronic cough. Although the classic manifestation of GER is heartburn, chronic cough is more associated with regurgitation (belching). Heartburn is a symptom of acid reflux, while more than half of patients with GER are non-acid in nature, therefore, such patients do not experience heartburn [3]. In this situation, the lack of classic GER symptoms and the widely available diagnostic tests to confirm this diagnosis puts the clinician in a difficult position. Signs of non-acid reflux are symptoms of an irritable colon, belching with air or food eaten, and postprandial cough (occurring approximately 10 minutes after eating when the lower esophageal sphincter opens) [3]. Belching with air (gaseous reflux) is considered a physiological phenomenon, since it prevents intestinal swelling. However, in individuals with chronic cough, even gaseous reflux can provoke coughing due to irritation of oropharyngeal receptors by air flow [5].

Chronic rhinitis
In the recent past, the fact that chronic cough can be associated with chronic rhinitis of any etiology was considered undeniable. Chronic rhinitis or chronic diseases of the paranasal sinuses are often accompanied by the so-called postnasal drip, i.e., the flow of nasal mucus along the back of the pharynx, which, mechanically irritating the cough receptors of the nasopharynx and oropharynx, can cause coughing. However, experts have now come to the conclusion that postnasal drip is a physiological process and by itself cannot be an adequate explanation for chronic cough [5]. On the other hand, chronic rhinitis may have an allergic origin, in which case the chronic cough is more likely to be associated with asthma.

Cough hypersensitivity syndrome
Not all patients with chronic cough show signs of asthma, chronic rhinitis, and GER, and trial therapy for these diseases also does not always lead to a reduction in cough. Previously, in such cases, they spoke of an “idiopathic” cough. However, studies in recent years have led to the conclusion that chronic cough should not be regarded as a symptom of any disease, but as an independent disease, since in different diseases cough has the same characteristics and similar conditions of occurrence. As a result, in recent years, the theory of cough hypersensitivity syndrome has been formed [6].
According to this theory, under certain circumstances, the sensitivity of cough receptors located in the mucous membrane of the upper and lower respiratory tract increases, which leads to their reaction to provoking factors that do not cause a cough in a healthy person: chemical (tobacco smoke, pungent odors, acute, peppered or salty food), mechanical (speech or physical activity, dry food, change in body position), temperature (change in temperature of inhaled air).

Cough hypersensitivity syndrome includes a cough that is not explained by any disease, accompanied by a sensation of tickling or irritation in the throat or behind the sternum, dysphonia / hoarseness [6]. Cough hypersensitivity is not an allergic reaction, since it is based on a different pathophysiological mechanism.
The universal trigger for chronic cough is upper respiratory tract infection. After the elimination of the pathogen, the cough reflex usually returns to a normal level, but sometimes the patient retains an increased sensitivity of cough receptors even to weak stimuli for a long time after an acute respiratory infection [5]. Cough hypersensitivity syndrome can be genetically determined [7] or can be formed against the background of a chronic inflammatory process in the airways. The exact mechanism for the transition from acute/subacute cough to chronic is currently not fully understood; it may include a different combination of biological, neurological, genetic, immunological mechanisms and environmental factors (air temperature, infection, irritants, pollutants). Unfortunately, at present there are no methods for assessing the sensitivity of cough receptors that could be used in everyday clinical practice, so the diagnosis of cough hypersensitivity remains exclusively clinical. It has been established that chronic cough is twice as common in women of middle, especially perimenopausal age (40–50 years) as compared with men of the same age. It is assumed that the reason for gender differences in the prevalence of chronic cough lies in the need for increased protection of the respiratory tract of women from aspiration during pregnancy [6].

Treatment of chronic cough
According to the experts of the European Respiratory Society, the treatment of chronic cough should begin with an attempt to establish its cause (history taking, lung x-ray, clinical blood test, spirometry with a bronchodilation test, ENT consultation). If asthma, chronic diseases of the nose and paranasal sinuses or GER are detected, patients are shown specific treatment according to the established diagnosis. In the absence of clear signs of a specific disease after the initial examination, a trial therapy for 8 weeks is recommended. sequentially with asthma (inhaled corticosteroids), antireflux (proton pump inhibitors) drugs and intranasal steroids. A decrease in cough with one of these treatment options is regarded as indirect confirmation of the corresponding cause of the cough. In the absence of the effect of trial therapy, further examination of the patient is recommended using more complex diagnostic methods: computed tomography (CT) of the lungs, bronchoscopy, bronchoprovocation tests, gastroscopy, etc. (Fig. 1) [8].

Non-specific therapy for chronic cough consists of the use of cough suppressants and other symptomatic treatment to reduce the severity of cough during the period of examination of the patient and before the start of specific therapy or when it is ineffective. Today, there are no drugs that can effectively reduce chronic idiopathic cough. According to the theory of cough hypersensitivity, in order to eliminate cough in such patients, it is necessary to reduce the sensitivity of cough receptors in the respiratory tract. Such drugs are currently being developed.
Table 1 lists drugs that can reduce chronic idiopathic cough with varying degrees of effectiveness [9].
Morphine and central antipsychotics (amitriptyline, gabapentin, pregabalin), in addition to the ability to suppress cough, have a powerful psychotropic effect, which significantly limits their use. Codeine may have an antitussive effect in some categories of patients, which, however, has not been confirmed in all studies, but the optimal duration of its use has not been studied, therefore, long-term use of codeine in patients with chronic cough is not recommended [10]. A modern practitioner can use dextromethorphan, which is part of the combined over-the-counter cough medicines, or ambroxol, but the antitussive activity of these drugs is low [10, 11]. With GER-induced cough and the absence of the effect of antireflux therapy, baclofen can be prescribed, but its effectiveness is also insufficient [10]. Lidocaine can reduce the intensity of cough due to the local anesthetic effect on the receptors of the oropharyngeal zone, however, the same effect increases the risk of aspiration of saliva, bronchial secretions and food, therefore, in routine medical practice, it should not be used as an antitussive agent [12]. Macrolides are effective in the treatment of whooping cough and Mycoplasma pneumoniae and Chlamydia pneumoniae infections that are accompanied by cough, in addition, they can reduce inflammation in the airways in patients with COPD and bronchiectasis and, possibly, thereby reduce the severity of cough [13, 14], and can also reduce the intensity of GER-induced cough. However, due to the insufficient amount of evidence-based information, this aspect of their use, as well as phosphodiesterase inhibitors [15], has not yet entered routine medical practice.

Thus, today we cannot effectively treat chronic idiopathic cough, but we can try to prevent its development. It was mentioned above that chronic cough in most cases begins as an acute cough with an acute infection of the upper respiratory tract, and its chronicity, as a rule, contributes to chronic inflammation in the mucous membrane of the respiratory tract [5]. Therefore, timely and active treatment of acute respiratory infection and acute inflammation can theoretically reduce the risk of acute cough becoming chronic. It is known that, on the one hand, not any inflammation requires antibiotics, on the other hand, not only antibiotics have an anti-inflammatory effect on the respiratory tract.

Thiol derivatives: erdosteine ​​
One of the common and well-known drugs are thiol derivatives, which include acetylcysteine, carbocysteine ​​and erdosteine ​​registered in the Russian Federation. In addition to the known mucoactive properties, these drugs have powerful antioxidant activity, which causes anti-inflammatory and anti-adhesive effects [16].
Like other representatives of thiols, erdosteine ​​has a triple effect on the respiratory tract. First, it is a powerful mucolytic and increases the activity of mucociliary clearance, promoting the elimination of bacteria from the respiratory tract [17]. Secondly, erdosteine ​​is an effective antioxidant that can suppress oxidative processes in the respiratory tract and lung tissue that develop during acute and chronic inflammation, and thus have an anti-inflammatory effect. The antioxidant activity of erdosteine ​​is higher than that of other representatives of thiols [18]. Thirdly, the drug has a direct anti-adhesive activity, destroying the pilin protein molecules on the surface of the bacterial cell, which serve to attach the bacterium to the epithelium of the respiratory tract [19].
For clinicians, it is important that erdosteine ​​increases the concentration of antibiotics, in particular amoxicillin [20] and clarithromycin [21], in bronchial secretion, without affecting their concentration in blood serum, and enhances the effectiveness of treatment compared with antibiotic therapy in combination with placebo .

Erdostein accelerates the resolution of exacerbations of chronic bronchitis (CB), eliminates clinical symptoms faster and promotes the elimination of bacterial pathogens (Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae) from the bronchi compared with placebo [20].
In 2010, a meta-analysis of 15 randomized controlled clinical trials involving a total of 1046 patients with CB or COPD showed that erdosteine ​​was faster than placebo and other mucolytics in reducing the clinical symptoms of an exacerbation; in particular, cough frequency decreased by 81%, cough intensity by 70% compared with placebo. The overall efficacy of erdosteine, as assessed by physicians, was also higher than that of placebo and other mucolytics [22].
With long-term use in patients with CB/COPD, erdosteine ​​may also have a preventive effect, reducing the frequency of future exacerbations of these diseases. At 1991 M. Fioretti et al. in a double-blind, placebo-controlled study, the effect of erdosteine ​​on the frequency of exacerbations of chronic bronchitis in 184 patients was evaluated. The number of patients who did not have exacerbations during the study period was significantly higher in the erdosteine ​​group (48.9%) than in the placebo group (12.6%) [23]. The larger, randomized, multicenter, double-blind, placebo-controlled EQUALIFE trial in 155 patients with moderate COPD who received oral erdosteine ​​600 mg/day or placebo for 8 months. in the cold season, showed that after 8 months. treatment, the number of COPD exacerbations and associated hospitalizations in the erdosteine ​​group was significantly less than in the placebo group: 0. 94±1.12 compared to 1.38±1.30 and 0.16±0.57 compared to 0.31±0.74 exacerbations/hospitalizations per patient, respectively. The total length of stay in the hospital was also shorter among patients treated with erdosteine ​​(70 days compared to 163 days in the placebo group). In general, erdosteine ​​reduced the frequency of COPD exacerbations by 36.9%, the duration of hospitalizations by 57%. In addition, a significant improvement in lung function, exercise tolerance and quality of life was shown during treatment with erdosteine ​​compared with placebo [24].
Erdostein is well tolerated: in terms of the frequency of side effects among 1046 patients, it did not differ from placebo and other mucolytics [22]. The maximum duration of its continuous use today is 8 months. [24]. The results of a large international RESTORE study are currently awaiting, in which the duration of continuous use of erdosteine ​​in patients with COPD was 1 year.

Conclusion
In recent years, a significant step has been made in understanding the nature of chronic cough. On the basis of the data obtained, a new pathogenetic concept of chronic cough as an independent disease was formulated, which makes it possible to explain its occurrence in almost any clinical situation. Currently, new drugs are being developed that affect the sensitivity of cough receptors in the respiratory tract, however, today, in the absence of effective drugs to eliminate chronic cough, based on the published results of clinical studies, it is logical to assume that the use of erdosteine ​​in acute respiratory infections can reduce the bacterial or viral load on the respiratory way, reduce the severity of inflammation in the bronchial wall and prevent the formation of cough hypersensitivity syndrome.

Literature
1. Morice A.H., McGarvey L., Pavord I. et al. Recommendations for the management of cough in adults // Thorax. 2006. Vol. 61. Suppl. 1. P. 1–2.
2. Ford A.C., Forman D., Moayyedi P., Morice A.H. Cough in the community: a cross sectional survey and the relationship to gastrointestinal symptoms // Thorax. 2006. Vol. 61. No. 11. P. 975–999.
3. Morice A.H. Chronic cough: diagnosis, treatment and psychological consequences // Breathe. 2006. Vol. 3. No. 2. P. 165–174.
4. Dicpinigaitis P.V. Chronic cough due to asthma: ACCP evidence-based clinical practice guidelines // Chest. 2006. Vol. 129. No. 1. Suppl. 75–79.
5. Song W.J., Chang Y.S., Morice A.H. Changing the paradigm for cough: does ‘cough hypersensitivity’ aid our understanding? // Asia Pac. Allergy. 2014. Vol. 4. No. 1. P. 3–13.
6. Morice A.H. Chronic cough hypersensitivity syndrome // Cough. 2013. Vol. 9. P. 14–17.
7. Smit L.A., Kogevinas M., Anto J.M. et al. Transient receptor potential genes, smoking, occupational exposures and cough in adults // Respir. Res. 2012. Vol. 13. P. 26.
8. Ojoo J.C., Everett C.F., Mulrennan S.A. et al. Management of patients with chronic cough using a clinical protocol: a prospective observational study // Cough. 2013. Vol. 9. P. 2.
9. Morjaria L.B. , Dickinson R.S., Morice A.H. Novel antitussive strategies. // Drug Discovery Today. 2013. Vol. 18. P. 380–388.
10 Bolser D.C. Cough suppressant and pharmacologic protussive therapy: ACCP evidence-based clinical practice guidelines // Chest. 2006. Vol. 129. Suppl. 1. P. 238–249.
11. Chang C.C., Cheng A.C., Chang A.B. Over-the-counter (OTC) medications to reduce cough as an adjunct to antibiotics for acute pneumonia in children and adults // Cochrane Database Syst. Rev. 2012. Vol. 2. D006088. doi: 10.1002/14651858.CD006088.pub3.
12. Belvisi M. G., Geppetti P. Cough. 7: Current and future drugs for the treatment of chronic cough // Thorax. 2004. Vol. 59. No. 5. P. 438–440.
13. Spagnolo P., Fabbri L.M., Bush A. Long-term macrolide treatment for chronic respiratory disease // Eur. Respir. J. 2013. Vol. 42. No. 1. P. 239-251.
14. Berkhof F.F., Doornewaardten Hertog N.E., Uil S.M. et al. Azithromycin and cough-specific health status in patients with chronic obstructive pulmonary disease and chronic cough: a randomized controlled trial // Respir. Res. 2013. Vol. 14. P. 12.
15. Chong J., Leung B., Poole P. Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease // Cochrane Database Syst. Rev. 2013. Vol. 11. CD002309. doi: 10.1002/14651858.CD002309.pub4.
16. Rahman I. Pharmacological antioxidant strategies as therapeutic interventions for COPD // Biochim. Biophys. acta. 2012. Vol. 1822. No. 5. P. 714–728.
17. Balsamo R., Lanata L., Egan C.G. Mucoactive drugs // Eur. Respir. Rev. 2010. Vol. 19. No. 116. P. 127–133.
18. Cogo R. Erdosteine: a new therapeutic weapon beyond the PEACE // Trends in Medicine. 2012. Vol. 12. No. 3. P. 133–142.
19. Braga P.C., Dal Sasso M., Sala M.T., Gianelle V. Effects of erdosteine ​​and its metabolites on bacterial adhesiveness // Arzneimittelforschung. 1999. Vol. 49. No. 4. P. 344–350.
20. Ricevuti G., Nazzone A., Uccelli E. et al. Influence of erdosteine, a mucolytic agent, on amoxicillin penetration into sputum in patients with an infectious exacerbation of chronic bronchitis // Thorax. 1988. Vol. 43. P. 585–590.
21. Braga P.C., Zuccotti T., Dal Sasso M. Bacterial aghesiveness: effects of the SH metabolite of erdosteine ​​(mucoactive drug) plus clarithromycin versus clarithromycin alone // Chemotherapy. 2001. Vol. 47. P. 208–214.
22. Cazzola M., Floriani I., Page C.P. The therapeutic efficacy of erdosteine ​​in the treatment of chronic obstructive bronchitis: a meta-analysis of individual patient data // Pulm. Pharmacol. Ther. 2010. Vol. 23. No. 2. P. 135–144.
23. Fioretti M., Bandera M. Prevention of exacerbation in chronic bronchitis patients with erdosteine ​​// Med. Praxis. 1991. Vol. 12. No. 4. P. 219–227.
24. Moretti M., Bottrighi P., Dallari R. et al. The effect of long-term treatment with erdosteine ​​on chronic obstructive pulmonary disease: the EQUALIFE Study // Drugs Exp. Clin. Res. 2004. Vol. 30. No. 4. P. 143–152.

Useful articles

Main page

About clinic

Press center

Useful articles

• Gastroenterology
• Diagnostics
• Cardiology
• Neurology
• Pediatrics
• Pulmonology
• Rheumatology
• Dentistry

Constipation (in adults)

Read

Helicobacter pylori

Read

Nutrition for digestive diseases

Read

Proper nutrition for weight loss

Read

Bitterness in the mouth: causes

Read

Pain in the right hypochondrium

Read

Polyps in the intestines

Read

Nausea and fever in adults

Read

CT of the lungs

Read

CT of the intestine

Read

MRI of the thyroid gland

Read

How to live with atrial fibrillation

Read

First aid for a heart attack

Read

How to behave after a hypertensive crisis

Read

Management of hypertensive cree for

Read

Blood Pressure Management Guide

Read

Pain in the left chest

Read

Nausea and weakness

Read

This is for you to see a cardiologist – 1. Getting ready for an appointment with a cardiologist

Read

This is for you to see a cardiologist – 2. Diagnosis, examination and treatment plan by a cardiologist

Read

This is for you to see a cardiologist – 3. Options for interaction with a cardiologist

Read

Thoracic protrusion spine

Read

Treatment of hernia without surgery

Read

Intracranial pressure

Read

Loss of coordination

Read

Stroke Rehabilitation

Read

Sensory Disorders

Read

First Aid for Syncope

Read

power for migraine

Read

Help for epilepsy

Read

Signs of a stroke in women

Read

Epilepsy attacks in adults

Read

What to do if bitten by an encephalitis tick

Read

What to do if there are signs of a stroke

Read

Concussion

Read

Dizziness during pregnancy

Read

Dizziness due to cervical osteochondrosis 9 0005

Read

How to deal with a panic attack

Read

Nighttime urination

Read

Child temperature

Read

Abdominal pain in children

Read

Temperature in a child under one year old

Read

Dry cough in a child

Read

Transparent snot in a child

Read

Vomiting in a child with fever

Read

The child has a temperature of 37

Read

Whooping cough children

Read

Measles in children

Read

Cuckoo method

Read

Sleep disorders in children

Read

Child has poor appetite

Read

Constant fatigue, lethargy in a child

Read

Cystitis in children

Read

Frequently ill children

Read

900 06 Sulfur plug in a child

Read

Rubella in children

Read

Otitis in children

Read

The child was bitten by a tick

Read

Treatment of tobacco dependence in COPD

Read

Coronavirus Pulmonary Rehabilitation Program

Read

Gout Surveillance Program

Read

Proper brushing of teeth

Read

* The prices indicated on the website are for informational purposes only and are subject to change at any time.