Disease status and cough to inhaled
agents
The cough patterns induced by aerosol products in healthy and diseased
people are different. For example, nebulised antibiotics cause
more severe coughing and wheezing in non-cystic fibrosis bronchiectasis
patients compared to cystic fibrosis patients
(Cipolla & Chan, 2013). Patients are
pre-treated with bronchodilators to reduce the frequency and severity of
these adverse events (Elkins et al.,
2006). Drug deposition profile may be affected by the extent of
bronchoconstriction, changes in bronchial blood flow, or the presence of
excess mucus or oedema. The consequences of reduced airway calibre lead
to increased drug deposition in the larger central airways, provoke
cough, and lead to insufficient delivery of drug to the target site
(Richards, Haas, Simpson, Britten, Renwick
& Holgate, 1988; Satia, Badri,
Al-Sheklly, Smith & Woodcock, 2016).
Asthma is one of the most common causes of chronic cough in non-smoking
adults (Morice, 2004). Moreover, cough as
a symptom is more common in patients with severe asthma.
Moderate-to-severe asthmatic patients suffer from persistent cough and
mucus hypersecretion (de Marco et al.,
2006). Cough impacts the quality of life of some asthmatic patients and
is a major contributor to poor asthma control
(Purokivi, Koskela & Kontra, 2013). The
incident rate of cough is significantly higher in asthmatic patients
than in healthy subjects (Bonvini &
Belvisi, 2017). Cough sensitivity to capsaicin and citrate does not
increase in asthma, whereas cough in response to hypertonicity is more
pronounced in asthmatic patients (Koskela,
Purokivi, Kontra, Taivainen & Tukiainen, 2008). Bronchoconstriction
mediators such as methacholine, substantial loss of respiratory heat and
water during exercise, and increased ATP levels associated with
inflammation may induce cough dyspnoea in asthmatic patients.
Similarly, COPD patients cough due to TRPV1 receptor activation or
substantial airway inflammation and subsequent release of inflammatory
mediators (e.g., tussive agents such as tachykinins, cough reflex
stimulants such as prostaglandins)
(Choudry, Fuller & Pride, 1989;
Joos, De Swert, Schelfhout & Pauwels,
2003). Anti-cholinergic tiotropium used as bronchodilator activity in
patients with asthma can help relieve symptoms and attenuates cough
(Birrell et al., 2014). Acrolein and
crotonaldehyde in cigarette smoke can also induce cough through
stimulating TRPA1 receptors. This suggests a potential role for TRPA1
receptors in coughs induced by cigarette smoke, which is closely linked
to COPD development (Mazzone & Undem,
2016). Furthermore, COPD coughs may be induced by increased protease
levels stimulating TRPV4 and TRPA1 receptors
(Grace et al., 2014), as well as through
mechanical stimulation by the excess mucus in the airways
(Hogg, 2004).
The frequency of cough in idiopathic pulmonary fibrosis (IPF) is even
higher than in asthma or COPD, even though it is a marker of poor
prognosis (Ryerson, Abbritti, Ley,
Elicker, Jones & Collard, 2011). TRPV1 and ATP (P2X3) receptors may be
involved in the generation of cough in IPF patients. Oral inhalation of
sodium cromoglicate can reduce the cough frequency of IPF patients by
31% (Birring et al., 2017). Inflammation
and mechanical distortion of the lungs may affect nerve fibres and
increase cough reflex sensitivity to mechanical stimulation of the chest
wall (Bonvini & Belvisi, 2017).
Increased cough response is also observed in patients with viral
respiratory infections (Empey, Laitinen,
Jacobs, Gold & Nadel, 1976). Viral infection exposes the sensory
nerves by damaging the airway epithelial cells, rendering them to higher
responsiveness to mechanical and chemical stimuli
(Empey, Laitinen, Jacobs, Gold & Nadel,
1976). Cough may also be induced by the production of
inflammation-associated mediators that sensitise sensory nerve endings
(Fuller & Jackson, 1990). Depending on
the respiratory disease status of the patient, cough can be induced by
mechanical or chemical stimulation of various ion channels, which
activates sensory nerves and the cough reflex. Understanding of the
cough pathophysiology has the potential to design drugs that target the
receptors of interest and provide quality of life to chronic lung
disease patients.