Cough hypersensitivity and suppression in COPD

Abstract

Cough reflex hypersensitivity (CRH) and impaired cough suppression are features of chronic refractory cough (CRC). Little is known about cough suppression and CRH in cough associated with chronic obstructive pulmonary disease (COPD). This study investigated the ability of participants with COPD to suppress cough during a cough challenge test in comparison to participants with CRC and healthy subjects. This study also investigated whether CRH is associated with chronic cough in COPD.Participants with COPD (n=27), CRC (n=11), and healthy subjects (n=13) underwent capsaicin challenge test with and without attempts to self-suppress cough in a randomised order over 2 visits, 5 days apart. For participants with COPD, the presence of self-reported chronic cough was documented, and objective 24-h cough frequency was measured.Amongst participants with COPD, those with chronic cough (n=16) demonstrated heightened cough reflex sensitivity (CRS) compared to those without chronic cough (n=11); geometric mean (sd) capsaicin dose thresholds for 5 coughs (C5) 3.36 (6.88) versus 44.50 (5.90) µmol·L−1 respectively (p=0.003). Participants with CRC also had heightened CRS compared to healthy participants; geometric mean (sd) C5 3.86 (5.13) versus 45.89 (3.95) µmol·L−1 respectively (p<0.001). Participants with COPD were able to suppress capsaicin-evoked cough, regardless of the presence or absence of chronic cough; geometric mean (sd) capsaicin dose thresholds for 5 coughs without self-suppression attempts (C5) and with (CS5) were 3.36 (6.88) versus 12.80 (8.33) µmol·L−1 (p<0.001) and 44.50 (5.90) versus 183.2 (6.37) µmol·L−1 (p=0.006) respectively. This was also the case for healthy participants (C5 versus CS5: 45.89 (3.95) versus 254.40 (3.78) µmol·L−1, p=0.033), but not those with CRC, who were unable to suppress capsaicin-evoked cough (C5 versus CS5: 3.86 (5.13) versus 3.34 (5.04) µmol·L−1, p=0.922). C5 and CS5 were associated with objective 24-h cough frequency in participants with COPD; ρ=−0.430, p=0.036 and ρ=−0.420, p=0.041 respectively.Participants with COPD-chronic cough and CRC both have heightened cough reflex sensitivity but in contrast, only participants with CRC were unable to suppress capsaicin evoked cough. This suggests differing mechanisms of cough between participants with COPD and CRC, and the need for disease specific approaches to its management.

Cough hypersensitivity and chronic cough

“…Volitional cough suppression involves a brain network important for general motor response inhibition 107 , 110 , 111 . Patients with refractory chronic cough have attenuated volitional cough suppression 112 , 113 and impaired engagement of this cough inhibition network 101 . Cough and related brain activity are also modulated by acute painful stimuli applied to the skin 86 , 114 , via an extension of the conditioned pain modulation (CPM) phenomenon whereby noxious stimuli applied to one part of the body inhibit the processing of noxious stimuli applied elsewhere.…”

“…Components of these inhibitory systems that regulate cough use the inhibitory neurotransmitter GABA, and GABA receptor agonists modify evoked coughing in animals and in humans 115 , 116 . Patients with COPD do not have altered volitional cough suppression 112 , suggesting that distinct neural endotypes contribute to chronic cough 81 .…”

The burden and impact of chronic cough in severe disease

“…COPD patients with chronic cough have significantly lowered capsaicin threshold for cough, meaning that they are more susceptible to cough. However, COPD patients can suppress this cough to a certain degree, which is contrary to patients with refractory chronic cough [9 ▪ ]. As perhaps could be expected, a recent study showed that COPD patients’ cough sensitivity is heightened during exacerbations, as measured by capsaicin test [32 ▪ ].…”

“…Also, the central nervous system can inhibit cough signals, but some patients may have a decreased cough inhibition in the central nervous system, further increasing their tendency to cough [7,8]. Mechanistic studies suggest that the causative mechanisms likely differ between different diseases, which may have implications for the choice of treatment [9 ▪ ,10]. These differences may also explain differences in the presentation and burden of cough, but this has not been studied.…”

WAO-ARIA consensus on chronic cough - Part II: Phenotypes and mechanisms of abnormal cough presentation — Updates in COVID-19

“…In another report, chronic cough, or its suppression, was studied in COPD patients and compared to patients with chronic refractory cough (CRC), or to healthy subjects. 162 All subjects with chronic cough, being COPD or CRC patients, had increased HCR when compared to subjects without chronic cough, being COPD patients or healthy individuals. Also, non-coughing COPD patients had comparable cough reflex sensitivity to healthy subjects.…”