Introduction

Cough is the most important airway defence mechanism but it is also a major symptom of respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD) (CDC, 2010). Cough helps to remove potentially harmful substances from entering the respiratory system and clears excessive secretions from the airways. It begins with a brief inspiration (inspiratory phase), followed by expiration against a closed glottis (compression phase), which leads to increased intrapulmonary pressure such that the opening of the glottis evokes a rapid expiratory airflow (expulsive phase). Expiration reflex is a variation of cough triggered by mechanical probing of the glottis, laryngeal vocal folds, and tracheal mucosa without an initial inspiratory effort. While objects detected in the glottis or larynx are removed by the expiratory reflex, those in the deeper parts of the airways may require an inspiratory effort to generate a high airflow velocity for removal by coughing (Mazzone & Undem, 2016)
Acute and subacute coughs (<8 weeks of duration) (Irwin, French, Chang, Altman & Panel*, 2018) are usually resulted from upper respiratory tract infections caused by viruses or bacteria. These coughs are often resolved once the infection is cleared from the airways. However, chronic cough, also known as cough hypersensitivity syndrome, is a condition with a long-standing hypersensitivity or dysregulation of the vagal nervous system (Chung, 2011; Morice, Faruqi, Wright, Thompson & Bland, 2011). The four most common background disorders for chronic coughs are asthma, eosinophilic bronchitis, chronic rhinosinusitis and oesophageal reflux disease (Chung & Pavord, 2008). Some patients cough excessively due to airway nerve hypersensitivity, without any known pathological complications (Buday, Kovacikova, Ruzinak & Plevkova, 2017). Cough in chronic respiratory tract diseases is an unpleasant experience and may represent an exaggerated reflex.
Pharmaceutical products are formulated as inhalation aerosols for faster onset of action in the treatment of respiratory diseases. Inhaled therapeutic agents can be delivered as liquid or dry powder aerosols using one of the three delivery platforms: nebulisers, pressurised metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs). Over the years, there has been clinical reports of cough induced by inhaled pharmaceutical aerosols. This article aims to systemically review the literature on clinical studies of inhaled therapeutics to unravel the cause of cough stimulation. This would provide insight on how cough-associated adverse events may be minimised. An understanding of the cough physiology and different types of airways stimulant are necessary before investigating the impact of inhalation products on evoking cough.