Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Imperial College London | OTHER |
| Queen's University, Belfast | OTHER |
| Monash University | OTHER |
Not provided
Not provided
Not provided
Not provided
Persistent cough is a distressing symptom for people with respiratory disorders. Patients also often experience an ongoing urge-to-cough that prompts coughing, and which fails to resolve the sensation. Understanding how the brain controls cough and the urge-to-cough could lead to new cough suppressing therapies. The overall objective of this project is to use functional brain imaging (fMRI) to identify brain regions that are involved in the exaggerated urge-to-cough in humans with chronic cough. Our focus will be on the brainstem where information from the airways first arrives in the central nervous system.
Peripheral effects of ATP via P2X3 receptors
ATP has been shown to be a tussive agent particularly on chronic cough patients who were more sensitive than non-cough subjects to inhaled ATP. ATP has been shown to augment the cough response to capsaicin in patients with asthma. Gefapixant at a single oral dose of 50 mg did not modulate capsaicin cough responses in normal volunteers and chronic cough subjects while inhibiting ATP-induced cough particularly in chronic cough subjects. These observations would suggest that ATP has a direct effect on a subset sensory neurons that evoke coughing through the activation of P2X3 receptors.
The use of fMRI to provide insights into the peripheral and central sites of activation by ATP/P2X3 activation We have generated functional brain imaging (fMRI) data to suggest that the different brain circuits in receipt of nodose and jugular ganglia neuron inputs (as identified in animal studies) are conserved in humans. When inhaled, the tussigenic compound capsaicin (from hot chili peppers) indiscriminately stimulates both nodose and jugular chemosensitive afferents and we have published that capsaicin inhalation produces brain activations in the primary sensory, anterior and mid-insula, cingulate, premotor, motor and orbitofrontal cortices. These regions are presumed to encode perceptual awareness of airway irritation, and the associated emotional, cognitive and behavioral (motor) consequences. For example, activity in the human primary sensory cortex (which receives jugular ganglia inputs in animal studies) correlates with an individual's perception of airway irritation (their perceived need/ urge to cough) while activity in the insula (in receipt of nodose inputs) relates closely to the actual magnitude of the delivered stimulus independent of perception. We have now built upon these published findings by using high resolution brainstem fMRI during the inhalation of ATP (expected to only activate P2X2/3 expressing nodose-derived airway afferents) versus capsaicin (expected to activate both jugular and nodose chemosensitive afferents). Our results are striking and reveal that ATP inhalation evokes an in increased signal level in the brainstem regions corresponding to the nTS, while capsaicin inhalation produces activations in both the nTS and in an area of the dorsal spinal trigeminal nucleus on the lateral margins of the brainstem that contains the paratrigeminal nucleus. Indeed, our healthy participants did not cough as much to ATP compared to capsaicin, consistent with studies cough in animals and humans and the relatively poor cough-evoking properties of ATP in healthy humans. However, the perception of airway irritation was identical between ATP and capsaicin stimuli. We believe that cough production will ultimately be dependent upon activation of the neural circuit that integrates in the paratrigeminal nucleus (i.e.' the jugular afferent pathway) and therefore we hypothesize that there is an upregulation of the capacity of ATP to act via jugular ganglia pathways in chronic cough patients.
The fMRI studies described above provide an exciting opportunity to assess for the first time which primary airway afferent pathways are likely excited or sensitized by ATP and, in turn, what aspects of the central processing of airway sensory information is altered by ATP. We have reported previously that patients with chronic cough display functional brain responses consistent with a state of central sensitization that closely resembles the central sensitization accompanying chronic pain.
We will extend upon these findings by determining whether ATP-sensitive pathways in the brainstem and brain are altered in patients with chronic cough, and in doing so provide insight into whether ATP effects vagal afferent processing through an interaction with nodose and/ or jugular neural pathways.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Chronic cough participant | Experimental | Twenty-five (25) Idiopathic chronic cough patients, defined as refractory to disease modifying therapies (eg anti-asthma medications), will be recruited. Participants will attend two sessions. In the first they will inhale in a single breath a nebulized solutions of increasing doses of Adenosine Triphosphate (ATP; 0.2-300 milliM) and capsaicin (0.5-125 microM) to determine their individual cough and urge-to-cough thresholds. In the second session, participants will undergo functional brain imaging (fMRI) for 1 hour while inhaling over 24 seconds randomly administered nebulized solutions of saline, or threshold doses of ATP or capsaicin. |
|
| Healthy control participant | Experimental | Twenty-five (25) appropriately age and sex matched healthy non-smoking individuals will be recruited as the comparison group. Participants will attend two sessions. In the first they will inhale in a single breath a nebulized solutions of increasing doses of ATP (0.2-300 milliM) and capsaicin (0.5-125 microM) to determine their individual cough and urge-to-cough thresholds. In the second session, participants will undergo fMRI for 1 hour while inhaling over 24 seconds randomly administered nebulized solutions of saline, or threshold doses of ATP or capsaicin. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Adenosine Triphosphate | Drug | Participants will inhale escalating concentrations of Adenosine Triphosphate (ATP) to induce cough and the urge-to-cough |
|
| Measure | Description | Time Frame |
|---|---|---|
| Brainstem Neural Activations to Capsaicin | fMRI will be used to determine the location and magnitude of neural responses in the brainstem during Capsaicin inhalation: in particular, the nucleus of the solitary tract and the paratrigeminal nucleus. fMRI non-invasively measures Blood Oxygen Level Dependent (BOLD) signals in the brain which can be used to identify regions of the brain that increase activity associated with the inhaled stimuli. BOLD signals detected are to be reported as % BOLD signal change in response to Capsaicin greater than control saline. | fMRI was performed in a single session on the day of the cough challenge testing session and not more than seven days after. |
| Brainstem Neural Activations to ATP | fMRI will be used to determine the location and magnitude of neural responses in the brainstem during ATP inhalation: in particular, the nucleus of the solitary tract and the paratrigeminal nucleus. fMRI non-invasively measures Blood Oxygen Level Dependent (BOLD) signals in the brain which can be used to identify regions of the brain that increase activity associated with the inhaled stimuli. BOLD signals detected are to be reported as % BOLD signal change in response to ATP greater than control saline. | fMRI was performed in a single session on the day of the cough challenge testing session and not more than seven days after. |
| Measure | Description | Time Frame |
|---|---|---|
| Behavioral Responses During Cough Challenge Testing: Cough Sensitivity to Capsaicin | Participant responses (cough and the urge-to-cough) evoked by Capsaicin will be measured by counting audible coughs to doubling doses of Capsaicin and by asking participants to rate their perception of urge-to-cough using visual analogue scales (VAS) to each dose. Thresholds for cough sensitivity are to be reported as microM. Cu is the threshold dose required to elicit a non-zero urge-to-cough rating. C2 is the threshold dose required to elicit two audible coughs. Smax is the largest dose that could be inhaled for 24s without eliciting an audible cough. fMRI dose was the dose used during fMRI scanning. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Stuart Mazzone, PhD | University of Melbourne | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The University of Melbourne | Parkville | Victoria | 3010 | Australia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18424325 | Background | Chung KF, Pavord ID. Prevalence, pathogenesis, and causes of chronic cough. Lancet. 2008 Apr 19;371(9621):1364-74. doi: 10.1016/S0140-6736(08)60595-4. | |
| 25186267 | Background | Morice AH, Jakes AD, Faruqi S, Birring SS, McGarvey L, Canning B, Smith JA, Parker SM, Chung KF, Lai K, Pavord ID, van den Berg J, Song WJ, Millqvist E, Farrell MJ, Mazzone SB, Dicpinigaitis P; Chronic Cough Registry. A worldwide survey of chronic cough: a manifestation of enhanced somatosensory response. Eur Respir J. 2014 Nov;44(5):1149-55. doi: 10.1183/09031936.00217813. Epub 2014 Sep 3. |
Not provided
Not provided
IPD will not be shared
Not provided
Not provided
Not provided
Not provided
Not provided
All participants were initially screened via telephone interviews for inclusion and exclusion criteria and gave written, informed consent prior to study enrolment. Refractory and unexplained chronic cough were diagnosed by a respiratory or laryngology specialist or general practitioner and inclusion required cough of at least 6 months duration with no abnormalities on chest X-ray or CT scan.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Chronic Cough Participant | Twenty-nine (29) Idiopathic chronic cough patients, defined as refractory to disease modifying therapies (eg anti-asthma medications), were recruited. Participants attended two sessions. In the first they inhaled in a single breath nebulized solutions of increasing doses of Adenosine Triphosphate (ATP; 0.2-300 microM) and capsaicin (0.5-125 microM) to determine their individual cough and urge-to-cough thresholds. In the second session, participants underwent functional brain imaging (fMRI) for 1 hour while inhaling over 24 seconds randomly administered nebulized solutions of saline, or threshold doses of ATP or capsaicin. |
| FG001 | Healthy Control Participant | Twenty-nine (29) appropriately age and sex matched healthy non-smoking individuals were recruited as the comparison group. Participants attended two sessions. In the first they inhaled in a single breath nebulized solutions of increasing doses of Adenosine Triphosphate (ATP; 0.2-300 microM) and capsaicin (0.5-125 microM) to determine their individual cough and urge-to-cough thresholds. In the second session, participants underwent functional brain imaging (fMRI) for 1 hour while inhaling over 24 seconds randomly administered nebulized solutions of saline, or threshold doses of ATP or capsaicin. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Chronic Cough Participant | Twenty-nine (29) Idiopathic chronic cough patients, defined as refractory to disease modifying therapies (eg anti-asthma medications), were recruited. Participants attended two sessions. In the first they inhaled in a single breath nebulized solutions of increasing doses of Adenosine Triphosphate (ATP; 0.2-300 microM) and capsaicin (0.5-125 microM) to determine their individual cough and urge-to-cough thresholds. In the second session, participants underwent functional brain imaging (fMRI) for 1 hour while inhaling over 24 seconds randomly administered nebulized solutions of saline, or threshold doses of ATP or capsaicin. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Brainstem Neural Activations to Capsaicin | fMRI will be used to determine the location and magnitude of neural responses in the brainstem during Capsaicin inhalation: in particular, the nucleus of the solitary tract and the paratrigeminal nucleus. fMRI non-invasively measures Blood Oxygen Level Dependent (BOLD) signals in the brain which can be used to identify regions of the brain that increase activity associated with the inhaled stimuli. BOLD signals detected are to be reported as % BOLD signal change in response to Capsaicin greater than control saline. | Cough participants displayed characteristic signs and symptoms of refractory chronic cough. 1 participant from each group withdrew prior to completion of the primary endpoint investigation. | Posted | Mean | Standard Deviation | Percentage change in BOLD signal | fMRI was performed in a single session on the day of the cough challenge testing session and not more than seven days after. |
|
Participants were monitored for adverse events during the two sessions they attended: the 1 hour cough challenge testing session and subsequent 1 hour fMRI scanning session.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Chronic Cough Participant | Twenty-five (29) Idiopathic chronic cough patients, defined as refractory to disease modifying therapies (eg anti-asthma medications), were recruited. Participants attended two sessions. In the first they inhaled in a single breath a nebulized solutions of increasing doses of Adenosine Triphosphate (ATP; 0.2-300 microM) and capsaicin (0.5-125 microM) to determine their individual cough and urge-to-cough thresholds. In the second session, participants underwent functional brain imaging (fMRI) for 1 hour while inhaling over 24 seconds randomly administered nebulized solutions of saline, or threshold doses of ATP or capsaicin. Adenosine Triphosphate: Participants inhaled escalating concentrations of Adenosine Triphosphate (ATP) to induce cough and the urge-to-cough Capsaicin: Participants inhaled escalating concentrations of capsaicin to induce cough and the urge-to-cough Functional Brain Imaging: Participants had scans of their brain activity using 3 Tesla (3T) brainstem restricted functional brain imaging (fMRI) |
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Stuart Mazzone | The University of Melbourne | +61383446457 | stuart.mazzone@unimelb.edu.au |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Oct 22, 2018 | Aug 17, 2023 | Prot_SAP_ICF_000.pdf |
Not provided
| ID | Term |
|---|---|
| D003371 | Cough |
| ID | Term |
|---|---|
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D000255 | Adenosine Triphosphate |
| D002211 | Capsaicin |
| D059907 | Functional Neuroimaging |
| ID | Term |
|---|---|
| D000227 | Adenine Nucleotides |
| D011685 | Purine Nucleotides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
Not provided
Not provided
The experiment will consist of two sessions. The first session will involve questionnaires, followed by measures of sensitivity and behavioural responses to tussive (cough evoking) stimulation. The second session will involve functional brain imaging measures of responses to tussive stimulation.
Not provided
Not provided
Not provided
Not provided
|
| Capsaicin | Drug | Participants will inhale escalating concentrations of capsaicin to induce cough and the urge-to-cough |
|
| Functional Brain Imaging | Other | Participants will have scans of their brain activity using 3 Tesla (3T) brainstem restricted functional brain imaging (fMRI) |
|
|
| Thresholds for cough sensitivity were measured during a 1 hr session prior to fMRI scanning |
| Behavioral Responses During Cough Challenge Testing: Cough Sensitivity to ATP | Participant responses (cough and the urge-to-cough) evoked by ATP will be measured by counting audible coughs to doubling doses of ATP and by asking participants to rate their perception of urge-to-cough using visual analogue scales (VAS) to each dose. Thresholds for cough sensitivity are to be reported as milliM. Cu is the threshold dose required to elicit a non-zero urge-to-cough rating. C2 is the threshold dose required to elicit two audible coughs. Smax is the largest dose that could be inhaled for 24s without eliciting an audible cough. fMRI dose was the dose used during fMRI scanning. | Thresholds for cough sensitivity were measured during a 1 hr session prior to fMRI scanning |
| Behavioral Responses to Cough Challenge Testing: Urge to Cough Ratings to Capsaicin and ATP | Participant responses (cough and the urge-to-cough) evoked by ATP will be measured by counting audible coughs to doubling doses of ATP and by asking participants to rate their perception of urge-to-cough using visual analogue scales (VAS) to each dose.Urge-to-cough score is reported by the participant using a Bog scale ranging from 0 (no urge) to 10 (most intense urge imaginable) where the higher score, the worse the outcome. Cu is the threshold dose required to elicit a non-zero urge-to-cough rating. C2 is the threshold dose required to elicit two audible coughs. Smax is the largest dose that could be inhaled for 24s without eliciting an audible cough. fMRI dose was the dose used during fMRI scanning. | Urge-to-cough ratings were reported during the 1 hour cough challenge testing session and during the subsequent fMRI scanning session |
| 24429206 | Background | Chung KF, McGarvey L, Mazzone SB. Chronic cough as a neuropathic disorder. Lancet Respir Med. 2013 Jul;1(5):414-22. doi: 10.1016/S2213-2600(13)70043-2. Epub 2013 May 3. |
| 17575093 | Background | Mazzone SB, McLennan L, McGovern AE, Egan GF, Farrell MJ. Representation of capsaicin-evoked urge-to-cough in the human brain using functional magnetic resonance imaging. Am J Respir Crit Care Med. 2007 Aug 15;176(4):327-32. doi: 10.1164/rccm.200612-1856OC. Epub 2007 Jun 15. |
| 26860344 | Background | Ando A, Smallwood D, McMahon M, Irving L, Mazzone SB, Farrell MJ. Neural correlates of cough hypersensitivity in humans: evidence for central sensitisation and dysfunctional inhibitory control. Thorax. 2016 Apr;71(4):323-9. doi: 10.1136/thoraxjnl-2015-207425. Epub 2016 Feb 9. |
| 25467586 | Background | Abdulqawi R, Dockry R, Holt K, Layton G, McCarthy BG, Ford AP, Smith JA. P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study. Lancet. 2015 Mar 28;385(9974):1198-205. doi: 10.1016/S0140-6736(14)61255-1. Epub 2014 Nov 25. |
| BG001 | Healthy Control Participant | Twenty-nine (29) appropriately age and sex matched healthy non-smoking individuals were recruited as the comparison group. Participants attended two sessions. In the first they inhaled in a single breath nebulized solutions of increasing doses of Adenosine Triphosphate (ATP; 0.2-300 microM) and capsaicin (0.5-125 microM) to determine their individual cough and urge-to-cough thresholds. In the second session, participants underwent functional brain imaging (fMRI) for 1 hour while inhaling over 24 seconds randomly administered nebulized solutions of saline, or threshold doses of ATP or capsaicin. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Hull Cough Hypersensitivity Questionnaire (HARQ) score | Participants will be asked to self-report on symptoms related to airway reflux. Each item requires a rating on a 6-point Likert scale from 0 to 5 and is related to an aspect of airway reflux. The HARQ is scored by adding the total ratings (range 0-70). A higher score indicates a worse outcome. | Mean | Standard Deviation | units on a scale |
|
| Newcastle Laryngeal Hypersensitivity Questionnaire (LHQ) score | Participants will be asked to self-report on sensations related to laryngeal hypersensitivity. Each item requires a rating on a 7-point Likert scale from 1 to 7 and is related to an upper airway sensation in one of three domains (throat obstruction, throat pain/thermal), throat tickle). The HLQ is scored by averaging the ratings in each domain and then adding the average domain scores (range 3-21). A higher score indicates a better outcome. | Mean | Standard Deviation | units on a scale |
|
| Leicester Cough Questionnaire (LCQ) score | Participants will be asked to self-report on the impact of cough on their quality of life. Each item requires a rating on a 7-point Likert scale from 1 to 7 and is related to the impact of cough in one of three domains (physical, psychological social). The LCQ is scored by averaging the ratings in each domain and then adding the average domain scores (range 3-21). A higher score indicates a better outcome. | Mean | Standard Deviation | units on a scale |
|
Twenty-nine (29) refractory chronic cough patients, defined as refractory to disease modifying therapies (eg anti-asthma medications), were recruited. Participants attended two sessions. In the first they inhaled in a single breath nebulized solutions of increasing doses of Adenosine Triphosphate (ATP; 0.2-300 microM) and capsaicin (0.5-125 microM) to determine their individual cough and urge-to-cough thresholds. In the second session, participants underwent functional brain imaging (fMRI) for 1 hour while inhaling over 24 seconds randomly administered nebulized solutions of saline, or threshold doses of ATP or capsaicin. |
| OG001 | Healthy Control Participant | Twenty-nine (29) appropriately age and sex matched healthy non-smoking individuals were recruited as the comparison group. Participants attended two sessions. In the first they inhaled in a single breath nebulized solutions of increasing doses of Adenosine Triphosphate (ATP; 0.2-300 microM) and capsaicin (0.5-125 microM) to determine their individual cough and urge-to-cough thresholds. In the second session, participants underwent functional brain imaging (fMRI) for 1 hour while inhaling over 24 seconds randomly administered nebulized solutions of saline, or threshold doses of ATP or capsaicin. |
|
|
|
| Primary | Brainstem Neural Activations to ATP | fMRI will be used to determine the location and magnitude of neural responses in the brainstem during ATP inhalation: in particular, the nucleus of the solitary tract and the paratrigeminal nucleus. fMRI non-invasively measures Blood Oxygen Level Dependent (BOLD) signals in the brain which can be used to identify regions of the brain that increase activity associated with the inhaled stimuli. BOLD signals detected are to be reported as % BOLD signal change in response to ATP greater than control saline. | Cough participants displayed characteristic signs and symptoms of refractory chronic cough. 1 participant from each group withdrew prior to completion of the primary endpoint investigation. | Posted | Mean | Standard Deviation | Percent change in BOLD signal | fMRI was performed in a single session on the day of the cough challenge testing session and not more than seven days after. |
|
|
|
|
| Secondary | Behavioral Responses During Cough Challenge Testing: Cough Sensitivity to Capsaicin | Participant responses (cough and the urge-to-cough) evoked by Capsaicin will be measured by counting audible coughs to doubling doses of Capsaicin and by asking participants to rate their perception of urge-to-cough using visual analogue scales (VAS) to each dose. Thresholds for cough sensitivity are to be reported as microM. Cu is the threshold dose required to elicit a non-zero urge-to-cough rating. C2 is the threshold dose required to elicit two audible coughs. Smax is the largest dose that could be inhaled for 24s without eliciting an audible cough. fMRI dose was the dose used during fMRI scanning. | Cough participants displayed characteristic signs and symptoms of refractory chronic cough. | Posted | Mean | Standard Error | microM | Thresholds for cough sensitivity were measured during a 1 hr session prior to fMRI scanning |
|
|
|
|
| Secondary | Behavioral Responses During Cough Challenge Testing: Cough Sensitivity to ATP | Participant responses (cough and the urge-to-cough) evoked by ATP will be measured by counting audible coughs to doubling doses of ATP and by asking participants to rate their perception of urge-to-cough using visual analogue scales (VAS) to each dose. Thresholds for cough sensitivity are to be reported as milliM. Cu is the threshold dose required to elicit a non-zero urge-to-cough rating. C2 is the threshold dose required to elicit two audible coughs. Smax is the largest dose that could be inhaled for 24s without eliciting an audible cough. fMRI dose was the dose used during fMRI scanning. | Cough participants displayed characteristic signs and symptoms of refractory chronic cough. | Posted | Mean | Standard Error | milliM | Thresholds for cough sensitivity were measured during a 1 hr session prior to fMRI scanning |
|
|
|
| Secondary | Behavioral Responses to Cough Challenge Testing: Urge to Cough Ratings to Capsaicin and ATP | Participant responses (cough and the urge-to-cough) evoked by ATP will be measured by counting audible coughs to doubling doses of ATP and by asking participants to rate their perception of urge-to-cough using visual analogue scales (VAS) to each dose.Urge-to-cough score is reported by the participant using a Bog scale ranging from 0 (no urge) to 10 (most intense urge imaginable) where the higher score, the worse the outcome. Cu is the threshold dose required to elicit a non-zero urge-to-cough rating. C2 is the threshold dose required to elicit two audible coughs. Smax is the largest dose that could be inhaled for 24s without eliciting an audible cough. fMRI dose was the dose used during fMRI scanning. | Cough participants displayed characteristic signs and symptoms of refractory chronic cough. | Posted | Mean | Standard Error | Score on a scale | Urge-to-cough ratings were reported during the 1 hour cough challenge testing session and during the subsequent fMRI scanning session |
|
|
|
|
| 0 |
| 29 |
| 0 |
| 29 |
| 0 |
| 29 |
| EG001 | Healthy Control Participant | Twenty-five (29) appropriately age and sex matched healthy non-smoking individuals were recruited as the comparison group. Participants attended two sessions. In the first they inhaled in a single breath a nebulized solutions of increasing doses of ATP (0.2-300 microM) and capsaicin (0.5-125 microM) to determine their individual cough and urge-to-cough thresholds. In the second session, participants underwent fMRI for 1 hour while inhaling over 24 seconds randomly administered nebulized solutions of saline, or threshold doses of ATP or capsaicin. Adenosine Triphosphate: Participants inhaled escalating concentrations of Adenosine Triphosphate (ATP) to induce cough and the urge-to-cough Capsaicin: Participants inhaled escalating concentrations of capsaicin to induce cough and the urge-to-cough Functional Brain Imaging: Participants had scans of their brain activity using 3 Tesla (3T) brainstem restricted functional brain imaging (fMRI) | 0 | 29 | 0 | 29 | 0 | 29 |
Not provided
Not provided
Not provided
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000072471 |
| Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D009711 | Nucleotides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012265 | Ribonucleotides |
| D053284 | Polyunsaturated Alkamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000475 | Alkenes |
| D006839 | Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |
| D002396 | Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D012991 | Solanaceous Alkaloids |
| D000470 | Alkaloids |
| D005229 | Fatty Acids, Monounsaturated |
| D005231 | Fatty Acids, Unsaturated |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D059906 | Neuroimaging |
| D003952 | Diagnostic Imaging |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D003943 | Diagnostic Techniques, Neurological |
| D008919 | Investigative Techniques |
| Capsaicin maximum tolerable dose Smax |
|
| Capsaicin fMRI dose |
|
| ATP maximum tolerable dose Smax |
|
| ATP fMRI dose |
|
| ATP Urge to Cough rating at Cu |
|
| ATP Urge to Cough rating at C2 |
|
| Capsaicin fMRI urge to cough rating |
|
| ATP fMRI urge to cough rating |
|
| Saline fMRI urge to cough rating |
|