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.