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Erschienen in: Internal and Emergency Medicine 1/2019

29.09.2018 | IM - REVIEW

The pathogenetic mechanisms of cough in idiopathic pulmonary fibrosis

verfasst von: Elena Bargagli, Maria Di Masi, Marco Perruzza, Lucia Vietri, Laura Bergantini, Elena Torricelli, Giulia Biadene, Giovanni Fontana, Federico Lavorini

Erschienen in: Internal and Emergency Medicine | Ausgabe 1/2019

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Abstract

Idiopathic pulmonary fibrosis is a peripheral subpleural interstitial lung disorder limited to the lung not involving the airways. It has a poor prognosis (survival less than 5 years) and commonly an interstitial pneumonia radiological pattern. Patients complain of a chronic dry cough in 80% of cases. A cough is often the first symptom of this rare disease, preceding dyspnea by years, and is associated with a poor prognosis, high dyspnea scores and low FVC percentages. The pathogenetic mechanisms leading to coughing in IPF are unclear. This review focuses on recent evidence of cough pathophysiology in this disease. Gastroesophageal reflux may promote coughing in IPF patients; bile salts and pepsin may be abundant in BAL of these patients, inducing overproduction of TGF-β by airway epithelial cells and mesenchymal transition with fibroblast recruitment/activation and extracellular matrix deposition. Patients have an enhanced cough reflex to capsaicin and substance P with respect to control subjects. Moreover, patients with the MUC5B polymorphism show more severe coughing as MUC5B encodes for the dominant mucin in the honeycomb cysts of IPF patients. Comorbidities, including asthma, gastroesophageal reflux, hypersensitivity pneumonitis, bronchiectasis, chronic obstructive pulmonary disease and emphysema, can induce coughing in IPF patients. There is no clear explanation of the causes of coughing in IPF. Further research into the pathophysiology of IPF and the pathogenetic mechanisms of coughing is necessary to improve survival and quality of life.
Literatur
1.
Zurück zum Zitat Ryerson CJ, Abbritti M, Ley B et al (2011) Cough predicts prognosis in idiopathic pulmonary fibrosis. Respirology 16(6):969–975CrossRefPubMed Ryerson CJ, Abbritti M, Ley B et al (2011) Cough predicts prognosis in idiopathic pulmonary fibrosis. Respirology 16(6):969–975CrossRefPubMed
2.
Zurück zum Zitat Hope-Gill BDM, Hilldrup S, Davies C et al (2003) A study of the cough reflex in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 168:995–1002CrossRefPubMed Hope-Gill BDM, Hilldrup S, Davies C et al (2003) A study of the cough reflex in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 168:995–1002CrossRefPubMed
3.
Zurück zum Zitat Vigeland CL, Hughes AH, Horton MR et al (2017) Etiology and treatment of cough in idiopathic pulmonary fibrosis. Respir Med 123:98–104CrossRefPubMed Vigeland CL, Hughes AH, Horton MR et al (2017) Etiology and treatment of cough in idiopathic pulmonary fibrosis. Respir Med 123:98–104CrossRefPubMed
4.
Zurück zum Zitat Kilduff CE, Counter MJ, Thomas GA et al (2014) Effect of acid suppression therapy on gastroesophageal reflux and cough in idiopathic pulmonary fibrosis: an intervention study. Cough 10:4CrossRefPubMedPubMedCentral Kilduff CE, Counter MJ, Thomas GA et al (2014) Effect of acid suppression therapy on gastroesophageal reflux and cough in idiopathic pulmonary fibrosis: an intervention study. Cough 10:4CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Madison JM, Irwin RS (2005) Chronic cough in adults with interstitial lung disease. Curr Opin Pulm Med 11(5):412–416CrossRefPubMed Madison JM, Irwin RS (2005) Chronic cough in adults with interstitial lung disease. Curr Opin Pulm Med 11(5):412–416CrossRefPubMed
7.
Zurück zum Zitat Sumner H, Woodcock A, Kolsum U et al (2013) Predictors of objective cough frequency in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 187:943–949CrossRefPubMed Sumner H, Woodcock A, Kolsum U et al (2013) Predictors of objective cough frequency in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 187:943–949CrossRefPubMed
8.
Zurück zum Zitat Horton MR, Santopietro V, Mathew L et al (2012) Thalidomide for the treatment of cough in idiopathic pulmonary fibrosis: a randomized trial. Ann Intern Med 157:398–406CrossRefPubMed Horton MR, Santopietro V, Mathew L et al (2012) Thalidomide for the treatment of cough in idiopathic pulmonary fibrosis: a randomized trial. Ann Intern Med 157:398–406CrossRefPubMed
9.
Zurück zum Zitat Lavorini F, Spina D, Walker MJ et al (2016) Antitussive effect of carcainium chloride in patients with chronic cough and idiopathic interstitial pneumonias: a pilot study. Pulm Pharmacol Ther 40:91–94CrossRefPubMed Lavorini F, Spina D, Walker MJ et al (2016) Antitussive effect of carcainium chloride in patients with chronic cough and idiopathic interstitial pneumonias: a pilot study. Pulm Pharmacol Ther 40:91–94CrossRefPubMed
10.
Zurück zum Zitat Birring SS, Wijsenbeek MS, Agrawal S et al (2017) A novel formulation of inhaled sodium cromoglycate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial. Lancet Respir Med 5(10):806–815CrossRefPubMed Birring SS, Wijsenbeek MS, Agrawal S et al (2017) A novel formulation of inhaled sodium cromoglycate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial. Lancet Respir Med 5(10):806–815CrossRefPubMed
11.
Zurück zum Zitat Fahim A, Dettmar PW, Morice AH et al (2011) Gastroesophageal reflux and idiopathic pulmonary fibrosis: a prospective study. Medicina (Kaunas) 47(4):200–205 Fahim A, Dettmar PW, Morice AH et al (2011) Gastroesophageal reflux and idiopathic pulmonary fibrosis: a prospective study. Medicina (Kaunas) 47(4):200–205
12.
Zurück zum Zitat Lee JS, Song JW, Wolters PJ et al (2012) Bronchoalveolar lavage pepsin in acute exacerbation of idiopathic pulmonary fibrosis. Eur Respir J 39(2):352–358CrossRefPubMed Lee JS, Song JW, Wolters PJ et al (2012) Bronchoalveolar lavage pepsin in acute exacerbation of idiopathic pulmonary fibrosis. Eur Respir J 39(2):352–358CrossRefPubMed
13.
Zurück zum Zitat Raghu G, Yang ST, Spada C, Hayes J et al (2006) Treatment of acid gastroesophageal reflux in idiopathic pulmonary fibrosis: a case series. Chest 129(3):794–800CrossRefPubMed Raghu G, Yang ST, Spada C, Hayes J et al (2006) Treatment of acid gastroesophageal reflux in idiopathic pulmonary fibrosis: a case series. Chest 129(3):794–800CrossRefPubMed
14.
Zurück zum Zitat Lee JS, Ryu JH, Elicker BM et al (2011) Gastroesophageal reflux therapy is associated with longer survival in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 184(12):1390–1394CrossRefPubMedPubMedCentral Lee JS, Ryu JH, Elicker BM et al (2011) Gastroesophageal reflux therapy is associated with longer survival in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 184(12):1390–1394CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Lee JS, Collard HR, Anstrom KJ et al (2013) Anti-acid treatment and disease progression in idiopathic pulmonary fibrosis: an analysis of data from three randomised controlled trials. Lancet Respir Med 1(5):369–376CrossRefPubMedPubMedCentral Lee JS, Collard HR, Anstrom KJ et al (2013) Anti-acid treatment and disease progression in idiopathic pulmonary fibrosis: an analysis of data from three randomised controlled trials. Lancet Respir Med 1(5):369–376CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Pillai M, Olson AL, Huie TJ et al (2012) Obstructive sleep apnea does not promote esophageal reflux in fibrosing interstitial lung disease. Respir Med 106:1033–1039CrossRefPubMedPubMedCentral Pillai M, Olson AL, Huie TJ et al (2012) Obstructive sleep apnea does not promote esophageal reflux in fibrosing interstitial lung disease. Respir Med 106:1033–1039CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Ing AJ, Ngu MC, Breslin AB (1994) Pathogenesis of chronic persistent cough associated with gastroesophageal reflux. Am J Respir Crit Care Med 149:160–167CrossRefPubMed Ing AJ, Ngu MC, Breslin AB (1994) Pathogenesis of chronic persistent cough associated with gastroesophageal reflux. Am J Respir Crit Care Med 149:160–167CrossRefPubMed
19.
Zurück zum Zitat Hoppo T, Jarido V, Pennathur A et al (2011) Antireflux surgery preserves lung function in patients with gastroesophageal reflux disease and end-stage lung disease before and after lung transplantation. Arch Surg 146(9):1041–1047CrossRefPubMed Hoppo T, Jarido V, Pennathur A et al (2011) Antireflux surgery preserves lung function in patients with gastroesophageal reflux disease and end-stage lung disease before and after lung transplantation. Arch Surg 146(9):1041–1047CrossRefPubMed
20.
Zurück zum Zitat Linden PA, Gilbert RJ, Yeap BY et al (2006) Laparoscopic fundoplication in patients with end-stage lung disease awaiting transplantation. J Thorac Cardiovasc Surg 131(2):438–446CrossRefPubMed Linden PA, Gilbert RJ, Yeap BY et al (2006) Laparoscopic fundoplication in patients with end-stage lung disease awaiting transplantation. J Thorac Cardiovasc Surg 131(2):438–446CrossRefPubMed
21.
Zurück zum Zitat Harrison NK (2004) Idiopathic pulmonary fibrosis: a nervous cough? Pulm Pharmacol Ther 17:347–350CrossRefPubMed Harrison NK (2004) Idiopathic pulmonary fibrosis: a nervous cough? Pulm Pharmacol Ther 17:347–350CrossRefPubMed
25.
Zurück zum Zitat Mazzone SB, McLennan L, McGovern AE et al (2007) Representation of capsaicin-evoked urge-to-cough in the human brain using functional magnetic resonance imaging. Am J Respir Crit Care Med 176:327–332CrossRefPubMed Mazzone SB, McLennan L, McGovern AE et al (2007) Representation of capsaicin-evoked urge-to-cough in the human brain using functional magnetic resonance imaging. Am J Respir Crit Care Med 176:327–332CrossRefPubMed
26.
Zurück zum Zitat Alexis NE, Hu SC, Zeman K et al (2001) Induced sputum derives from the central airways: confirmation using a radiolabelled aerosol bolus delivery technique. Am J Respir Crit Care Med 164:1964–1970CrossRefPubMed Alexis NE, Hu SC, Zeman K et al (2001) Induced sputum derives from the central airways: confirmation using a radiolabelled aerosol bolus delivery technique. Am J Respir Crit Care Med 164:1964–1970CrossRefPubMed
27.
Zurück zum Zitat Birring SS, Parker D, McKenna S et al (2005) Sputum eosinophilia in idiopathic pulmonary fibrosis. Inflamm Res 54:51–56CrossRefPubMed Birring SS, Parker D, McKenna S et al (2005) Sputum eosinophilia in idiopathic pulmonary fibrosis. Inflamm Res 54:51–56CrossRefPubMed
28.
Zurück zum Zitat Kinder BW, Brown KK, Schwarz MI et al (2008) Baseline BAL neutrophilia predicts early mortality in idiopathic pulmonary fibrosis. Chest 133:226–232CrossRefPubMed Kinder BW, Brown KK, Schwarz MI et al (2008) Baseline BAL neutrophilia predicts early mortality in idiopathic pulmonary fibrosis. Chest 133:226–232CrossRefPubMed
29.
Zurück zum Zitat Ricci A, Felici L, Mariotta S et al (2004) Neurotrophin and neurotrophin receptor protein expression in the human lung. Am J Respir Cell Mol Biol 30:12–19CrossRefPubMed Ricci A, Felici L, Mariotta S et al (2004) Neurotrophin and neurotrophin receptor protein expression in the human lung. Am J Respir Cell Mol Biol 30:12–19CrossRefPubMed
30.
Zurück zum Zitat Donnerer J, Schuligoi R, Stein C (1992) Increased content and transport of substance P and calcitonin gene-related peptide in sensory nerves innervating inflamed tissue: evidence for a regulatory function of nerve growth factor in-vivo. Neuroscience 49:693–698CrossRefPubMed Donnerer J, Schuligoi R, Stein C (1992) Increased content and transport of substance P and calcitonin gene-related peptide in sensory nerves innervating inflamed tissue: evidence for a regulatory function of nerve growth factor in-vivo. Neuroscience 49:693–698CrossRefPubMed
31.
Zurück zum Zitat Braun A, Lommatzsch M, Mannsfeldt A et al (1999) Cellular sources of enhanced brain-derived neurotrophic factor production in a mouse model of allergic inflammation. Am J Respir Cell Mol Biol 21:537–546CrossRefPubMed Braun A, Lommatzsch M, Mannsfeldt A et al (1999) Cellular sources of enhanced brain-derived neurotrophic factor production in a mouse model of allergic inflammation. Am J Respir Cell Mol Biol 21:537–546CrossRefPubMed
32.
Zurück zum Zitat Yao L, Zhang D, Bernd P (1997) Differential regulation of substance P by all members of the nerve growth factor family of neurotrophins in avian dorsal root ganglia throughout development. Neuroscience 79:1197–1206CrossRefPubMed Yao L, Zhang D, Bernd P (1997) Differential regulation of substance P by all members of the nerve growth factor family of neurotrophins in avian dorsal root ganglia throughout development. Neuroscience 79:1197–1206CrossRefPubMed
33.
Zurück zum Zitat Undem BJ, Hunter DD, Liu M et al (1999) Allergen-induced sensory neuroplasticity in airways. Int Arch Allergy Immunol 118:150–153CrossRefPubMed Undem BJ, Hunter DD, Liu M et al (1999) Allergen-induced sensory neuroplasticity in airways. Int Arch Allergy Immunol 118:150–153CrossRefPubMed
34.
Zurück zum Zitat Koltzenburg M (1999) The changing sensitivity in the life of the nociceptor. Pain 6:S93–S102CrossRefPubMed Koltzenburg M (1999) The changing sensitivity in the life of the nociceptor. Pain 6:S93–S102CrossRefPubMed
35.
Zurück zum Zitat Ricci A, Graziano P, Bronzetti E et al (2007) Increased pulmonary neurotrophin protein expression in idiopathic interstitial pneumonias. Sarcoidosis Vasc Diffuse Lung Dis 24:13–23PubMed Ricci A, Graziano P, Bronzetti E et al (2007) Increased pulmonary neurotrophin protein expression in idiopathic interstitial pneumonias. Sarcoidosis Vasc Diffuse Lung Dis 24:13–23PubMed
36.
Zurück zum Zitat Harrison NK, Dawes KE, Kwon OJ et al (1995) Effects of neuropeptides on human lung fibroblast proliferation and chemotaxis in vitro. Am J Physiol 268:L278–L283CrossRefPubMed Harrison NK, Dawes KE, Kwon OJ et al (1995) Effects of neuropeptides on human lung fibroblast proliferation and chemotaxis in vitro. Am J Physiol 268:L278–L283CrossRefPubMed
37.
38.
Zurück zum Zitat Seibold MA, Smith RW, Urbanek C (2013) The idiopathic pulmonary fibrosis honeycomb cyst contains a mucocilary pseudostratified epithelium. PLoS one 8(3):e58658CrossRefPubMedPubMedCentral Seibold MA, Smith RW, Urbanek C (2013) The idiopathic pulmonary fibrosis honeycomb cyst contains a mucocilary pseudostratified epithelium. PLoS one 8(3):e58658CrossRefPubMedPubMedCentral
39.
40.
Zurück zum Zitat Zhang Y, Noth I, Garcia JG, Kaminski N (2011) A variant in the promoter of MUC5B and idiopathic pulmonary fibrosis. N Engl J Med 364(16):1576–1577CrossRefPubMedPubMedCentral Zhang Y, Noth I, Garcia JG, Kaminski N (2011) A variant in the promoter of MUC5B and idiopathic pulmonary fibrosis. N Engl J Med 364(16):1576–1577CrossRefPubMedPubMedCentral
41.
Zurück zum Zitat Jiang Haiming, Yejia Hu, Shang Li et al (2015) Association between MUC5B polymorphism and susceptibility and severity of idiopathic pulmonary fibrosis Int J. Clin Exp Pathol 8(11):14953–14958 Jiang Haiming, Yejia Hu, Shang Li et al (2015) Association between MUC5B polymorphism and susceptibility and severity of idiopathic pulmonary fibrosis Int J. Clin Exp Pathol 8(11):14953–14958
42.
Zurück zum Zitat Andoh Y, Aikawa T, Shimura S et al (1992) Morphometric analysis of airways in idiopathic pulmonary fibrosis patients with mucous hypersecretion. Am Rev Respir Dis 145(1):175–179CrossRefPubMed Andoh Y, Aikawa T, Shimura S et al (1992) Morphometric analysis of airways in idiopathic pulmonary fibrosis patients with mucous hypersecretion. Am Rev Respir Dis 145(1):175–179CrossRefPubMed
43.
Zurück zum Zitat Jaimchariyatam N, Tantipornsinchai W, Desudchit T et al (2016) Association between respiratory events and nocturnal gastroesophageal reflux events in patients with coexisting obstructive sleep apnea and gastroesophageal reflux disease. Sleep Med 22:33–38CrossRef Jaimchariyatam N, Tantipornsinchai W, Desudchit T et al (2016) Association between respiratory events and nocturnal gastroesophageal reflux events in patients with coexisting obstructive sleep apnea and gastroesophageal reflux disease. Sleep Med 22:33–38CrossRef
44.
Zurück zum Zitat Mermigkis C, Bouloukaki I, Antoniou K et al (2015) Obstructive sleep apnea should be treated in patients with idiopathic pulmonary fibrosis. Sleep Breath 19:385–391CrossRefPubMed Mermigkis C, Bouloukaki I, Antoniou K et al (2015) Obstructive sleep apnea should be treated in patients with idiopathic pulmonary fibrosis. Sleep Breath 19:385–391CrossRefPubMed
45.
Zurück zum Zitat Jung HK, Choung RS, Talley NJ (2010) Gastroesophageal reflux disease and sleep disorders: evidence for a causal link and therapeutic implications. J Neurogastroenterol Motil 16:22–29CrossRefPubMedPubMedCentral Jung HK, Choung RS, Talley NJ (2010) Gastroesophageal reflux disease and sleep disorders: evidence for a causal link and therapeutic implications. J Neurogastroenterol Motil 16:22–29CrossRefPubMedPubMedCentral
46.
Zurück zum Zitat Chan KK, Ing AJ, Laks L et al (2010) Chronic cough in patients with sleep-disordered breathing. Eur Respir J 35:368–372CrossRef Chan KK, Ing AJ, Laks L et al (2010) Chronic cough in patients with sleep-disordered breathing. Eur Respir J 35:368–372CrossRef
47.
Zurück zum Zitat Chilosi M, Poletti V, Murer B et al (2002) Abnormal re-epithelialization and lung remodelling in Idiopathic pulmonary fibrosis: the role of deltaN-p63. Lab Invest 82(10):1335–1345CrossRefPubMed Chilosi M, Poletti V, Murer B et al (2002) Abnormal re-epithelialization and lung remodelling in Idiopathic pulmonary fibrosis: the role of deltaN-p63. Lab Invest 82(10):1335–1345CrossRefPubMed
48.
Zurück zum Zitat Caliò A, Lever V, Rossi A et al (2017) Increased frequency of bronchiolar histotypes in lung carcinomas associated with idiopathic pulmonary fibrosis. Histopathology 71(5):725–735CrossRefPubMed Caliò A, Lever V, Rossi A et al (2017) Increased frequency of bronchiolar histotypes in lung carcinomas associated with idiopathic pulmonary fibrosis. Histopathology 71(5):725–735CrossRefPubMed
49.
Zurück zum Zitat Prasse A, Binder H, Schupp JC et al. (2018) BAL cell gene expression is indicative of outcome and airway basal cell involvement in IPF. Respir Crit Care Med (in press) Prasse A, Binder H, Schupp JC et al. (2018) BAL cell gene expression is indicative of outcome and airway basal cell involvement in IPF. Respir Crit Care Med (in press)
50.
Zurück zum Zitat Van Manen MJ, Birring SS, Vancheri C et al (2016) Cough in idiopathic pulmonary fibrosis. Eur Respir Rev 25(141):278–286CrossRefPubMed Van Manen MJ, Birring SS, Vancheri C et al (2016) Cough in idiopathic pulmonary fibrosis. Eur Respir Rev 25(141):278–286CrossRefPubMed
Metadaten
Titel
The pathogenetic mechanisms of cough in idiopathic pulmonary fibrosis
verfasst von
Elena Bargagli
Maria Di Masi
Marco Perruzza
Lucia Vietri
Laura Bergantini
Elena Torricelli
Giulia Biadene
Giovanni Fontana
Federico Lavorini
Publikationsdatum
29.09.2018
Verlag
Springer International Publishing
Erschienen in
Internal and Emergency Medicine / Ausgabe 1/2019
Print ISSN: 1828-0447
Elektronische ISSN: 1970-9366
DOI
https://doi.org/10.1007/s11739-018-1960-5

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