Mechanisms and management of cough in interstitial lung disease

ABSTRACT

Introduction

Many patients with interstitial lung diseases (ILDs), especially fibrotic ILDs, experience chronic cough. It negatively impacts both physical and psychological well-being. Effective treatment options are limited.

Areas covered

The pathophysiology of chronic cough in IPF is complex and involves multiple mechanisms, including mechanical distortion of airways, parenchyma, and nerve fibers. The pathophysiology of cough in other fibrosing ILDs is poorly understood and involves various pathways. The purpose of this review is to highlight mechanisms of chronic cough and to present therapeutic evidence for its management in the most commonly occurring diffuse fibrosing lung diseases including idiopathic pulmonary fibrosis (IPF), connective tissue disease-related interstitial lung disease (CTD-ILD), sarcoidosis-related ILD (Sc-ILD), chronic hypersensitivity pneumonitis-related ILD (CHP-ILD), and post-COVID-19-related interstitial lung disease (PC-ILD).

Expert opinion

This review guides the management of chronic cough in fibrosing ILDs. In this era of precision medicine, chronic cough management should be individualized in each interstitial lung disease.

KEYWORDS:

• Interstitial lung disease (ILD)
• Chronic cough
• Cough hypersensitivity
• Idiopathic pulmonary fibrosis
• Connective tissue disease
• Chronic hypersensitivity pneumonitis
• Sarcoidosis
• Post-COVID-19 interstitial lung disease

Article highlights

• Cough is the most prevalent symptom of interstitial lung disease. Data regarding the management of cough is limited by many confounding factors. Cough is highly influenced by the placebo effect; hence the results of small, open-label trials must be interpreted with caution.

• In idiopathic pulmonary fibrosis, the management of cough starts with identifying and treating secondary causes of cough. Antifibrotics, particularly, pirfenidone decrease cough frequency. The use of inhaled or systemic steroids is generally not recommended. In selected patients, a short course of prednisone can be considered. Low dose opioids can be considered in some patients if cough remains troublesome despite other interventions.

• In Systemic Sclerosis, the management of cough mirrors coughs management in idiopathic pulmonary fibrosis. Cough severity correlates with disease progression. Improvement in cough serves as a useful surrogate marker of treatment response in systemic sclerosis-related interstitial lung disease.

• Chronic cough in patients with rheumatoid arthritis-related interstitial lung disease may respond to immunosuppressive therapy. Some patients with follicular bronchitis (often present with productive cough and sinus symptoms) may respond to erythromycin.

• Chronic cough in Sjogren Syndrome is due to multiple mechanisms. In addition to inflammation and fibrosis, dryness of airways (large and small) causes frequent and debilitating cough spells. Secretagogues (pilocarpine) or nebulized saline solution may relieve coughing spells. Although these patients may have positive bronchodilator response, cough generally does not respond to bronchodilators.

• Chronic cough in sarcoidosis is secondary to granulomatous inflammation and airway hyperreactivity. Cough generally responds to systemic steroids. Evidence of benefit from inhaled corticosteroid (ICS) therapy is limited and is based on small trials. There is conflicting evidence regarding its use in sarcoidosis, therefore, ICS therapy is generally not recommended for chronic cough in patients with sarcoidosis. Bronchodilator therapy can be considered in a subset of patients demonstrating bronchial hyperreactivity.

• In chronic hypersensitivity pneumonitis-related interstitial lung disease, the mainstay of treatment remains avoidance of the sensitizing agent. In some cases, corticosteroids± immunosuppressive therapy is considered.

• There are no specific guidelines for the management of cough in post-COVID-19 lung fibrosis. General guidelines for chronic cough can be followed for cough management. Systemic steroids can be used in the setting of COVID-19-related organizing pneumonia. There is no role for systemic steroids in the management of chronic cough in the setting of fibrosing interstitial lung disease.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.