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The pathogenetic mechanisms of cough in idiopathic pulmonary fibrosis

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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.

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Abbreviations

IPF:

Idiopathic pulmonary fibrosis

ILD:

Interstitial lung diseases

HRCT:

High resolution computed tomography

BAL:

Bronchoalveolar lavage

GER:

Gatroesophageal reflux

NSIP:

Non specific interstitial pneumonia

FVC:

Forced vital capacity

TGF-β:

Tumour growth factor

UIP:

Usual interstitial pneumonia

GPCR:

G-Protein coupled receptor

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Funding

The study was unfunded.

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Authors and Affiliations

  1. Section of Respiratory Diseases and Lung Transplantation, Department of Clinical Medicine and Neurosciences, Siena University Hospital, Siena, Italy

    Elena Bargagli, Marco Perruzza, Lucia Vietri & Laura Bergantini

  2. Section of Respiratory Medicine, Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy

    Maria Di Masi, Elena Torricelli, Giulia Biadene, Giovanni Fontana & Federico Lavorini

Authors
  1. Elena Bargagli
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  2. Maria Di Masi
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  3. Marco Perruzza
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  4. Lucia Vietri
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  5. Laura Bergantini
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  6. Elena Torricelli
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  7. Giulia Biadene
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  8. Giovanni Fontana
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  9. Federico Lavorini
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Correspondence to Elena Bargagli.

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Statement of human and animal rights

All procedures were in accordance with the ethical standard of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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Bargagli, E., Di Masi, M., Perruzza, M. et al. The pathogenetic mechanisms of cough in idiopathic pulmonary fibrosis. Intern Emerg Med 14, 39–43 (2019). https://doi.org/10.1007/s11739-018-1960-5

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  • DOI: https://doi.org/10.1007/s11739-018-1960-5

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