Respiratory
Idiopathic Pulmonary Fibrosis-Related Chronic Cough:
Burden, Mechanisms, Management
The publication of this interactive infographic was supported by Trevi Therapeutics.
EMJ. 2026;11[2]:42-43. https://doi.org/10.33590/emj/751WS6IA
Acknowledgement: Medical Writing assistance was provided by Yolande Chalmers, EMJ, London, UK.
What is Chronic Cough?
The mean number of coughs in patients with IPF is
acute cough <3 weeks
subacute
3–8 weeks
chronic
8 weeks
It is reported in approximately
80%
of patients with IPF.3,4
Chronic cough, defined as a cough that lasts ≥8 weeks, is highly prevalent in patients with IPF.1,2
672–905 coughs/day.5,6
Coughs tend to be more frequent and more severe in the daytime than at night.7,8
Cough severity can impact lung function, disease progression, and transplant-free survival.9
Explore more
Larger annualised decline in lung oxygen-transfer capacity9
−3.30% predicted/year
(95% CI: −5.27–−1.34)9
DLCO reflects how efficiently oxygen moves from the lungs into the bloodstream. A lower DLCO indicates reduced gas-exchange efficiency due to worsening fibrosis.10
Higher likelihood of disease progression9
HR: 0.43 (95% CI: 0.09–0.77)
Progression was defined as worsening respiratory symptoms, decline in lung function (FVC or DLCO), or radiologic worsening over 12 months.
Reduced transplant-free survival9
HR: 1.40 (95% CI: 1.15–1.70)
Measured as time from baseline to death or lung transplantation.
Cough Effects on Patient QoL
Daily functioning
impairment4,12
Physical pain7
Shortness of breath7,12
Anxiety/ depression7,12
Social isolation/
embarrassment4,7,9,12
Urinary incontinence9
Sleep disturbance7
Fatigue4,9
Chronic cough impairs quality of life, causes fatigue, negatively impacts sleep, and is socially isolating.4,7,11
Cough Hypersensitivity
In cough hypersensitivity, nerve signals become overactive and cause increased cough response to normal or subthreshold triggers.
Common triggers include:3,14-16
Singing, talking, laughing
Aerosols, scents, and odours
Temperature changes
Changes in body position
Eating, drinking
Exercise
Dysregulation of Nervous System Pathways Can Lead to Cough Hypersensitivity17-19
1
2
3
4
5
C
B
A
Role of Opioid Receptors and Cough Hypersensitivity
Opioid receptor signalling modulates sensitisation by reducing central and peripheral excitatory neurotransmission and enhancing central inhibitory pathways.17-19
Chemoreceptors
Mechanoreceptors
Peripheral nervous system
CNS
κ-opioid
μ-opioid
Brainstem
neurone*
NK1
NMDA
Vagal nerve terminal
κ and µ opioid receptors in the CNS14,20-23
κ receptors are present in the nucleus of the solitary tract, where the brain first processes cough signals from afferent nerves
κ and µ opioid receptors are found in respiratory-related regions of the brainstem and spinal cord, as well as higher brain regions
Excitatory (ascending)
Inhibitory (descending)
κ and µ opioid receptors are present on vagal afferent nerve fibres
Opioid receptor signalling in the lung reduces afferent firing and neurotransmitter release, inhibiting signals travelling to the CNS
κ and µ opioid receptors in the lungs14,20-23
κ-opioid
μ-opioid
NaV1.7
NaV1.8
NK1
TRPA1
P2X3
TRPV1
Vagal afferent
terminal
TRPA1
TRPV4
References and Abbreviations
Fatigue4,9
Sleep disturbance7
Urinary incontinence9
Social isolation/
embarrassment4,7,9,12
Anxiety/ depression7,12
Shortness of breath7,12
Physical pain7
Daily functioning
impairment4,12
"Now I do have a problem if I talk a lot... I was teaching engineering classes over Zoom™ [Zoom Video Communications, Inc., San Jose, California, USA], and I got to the point where I couldn't lecture the students anymore because I couldn't stop coughing. I had to give up my teaching position."12
"My cough was really so deep that it felt like I broke my ribs, and my ribs became so cramped that I couldn't even twist [my body]."13
*The receptors in the image sit in higher regions of the brain as well as the brainstem.
"[My mother's] inability to get up and move around when she wanted [to] resulted in depression."13
"I can sense that people look at each other and go, 'Wow, he's really coughing', whether or not they know I have an illness."12
In a survey of patients with chronic cough, 24% reported urinary incontinence.11
"I can only sleep... for maybe an hour and a half or two hours before I have to get up and cough."13
"On my worst days, coughing will wipe you out for an entire day...
Physically, you're exhausted."13
Cough is initiated by airway sensory nerves upon detection of stimuli or irritants
1
Ion channels and receptors on the vagal sensory nerves detect stimuli and signal to cough centres in the brainstem
2
3
Brainstem cough centers coordinate the motor response for cough
4
Motor neurones trigger respiratory muscles to provoke coughing
5
Higher brain regions process the urge, intensity, and suppression of cough
Central sensitisation17-19
C
Mechanisms in the CNS amplify nerve fibre inputs
Normal afferent nerve fibre activity can produce heightened cough responses
Reduced cough suppression occurs due to loss of inhibitory nerve activity
Signal transmission17-19
Amplified nerve signals are sent to the brain
B
Peripheral sensitisation17-19
Afferent nerve fibres become more excitable due to local tissue damage, mechanical stress, and loss of lung tissue
Triggering stimuli are more likely to cause afferent nerve activation
A
Cough
Vagus nerve
1. Morice AH et al. Eur Respir J. 2020;55(1):1901136.
2. Ryerson CJ et al. Respirology. 2011;16(6):969-75. 3. Vigeland CL et al. Respir Med. 2017;123:98-104.
4. Green R et al. Respir Res. 2024;25(1):325.
5. Maher TM et al. NEJM Evid. 2023;2(8):EVIDoa2300083.
6. Martinez FJ et al. Am J Respir Crit Care Med. 2022;205(9):1084-92.
7. Mann J et al. Front Rehabil Sci. 2021;2:751798.
8. Key AL et al. Cough. 2010;6:4.
9. Khor YH et al. Am J Respir Crit Care Med. 2024;210(8):1035-44.
10. Cleveland Clinic. Available at: https://my.clevelandclinic.org/health/diagnostics/15445-dlco. Last accessed: 27 November 2025.
11. Hirons B et al. Eur Respir J. 2022;60(suppl 66):7.
12. Graham CS et al. BMC Pulm Med. 2025;25(1):221.
13. FDA CDER. Available at: https://www.fda.gov/files/about%20fda/published/The-Voice-of-the-Patient--Idiopathic-Pulmonary-Fibrosis.pdf. Last accessed: 17 June 2026.
14. Birring SS et al. Lung. 2025;203(1):1-8.
15. Haji A, Ohi Y. Neuroscience. 2010;169(3):1168-77.
16. Singh N et al. J Thorac Dis. 2020;12(9):5179-93.
17. Chung KF et al. Nat Rev Dis Primers. 2022;8(1):45.
18. Krajnik M et al. Curr Opin Support Palliat Care. 2014;8(3)191-9.
19. Irwin RS et al. N Engl J Med. 2025;392(12):1203-14.
20. Volkow ND et al. N Engl J Med. 2016;374:1253-63.
21. Lalley PM. Respir Physiol Neurobiol. 2008;164(1-2):160-7.
22. Mazzone SB et al. Am J Respir Crit Care Med. 2007;176:327-32.
23. Kamei J et al. Eur J Pharmacol. 1990;187(2):281-6.
References
Abbreviations
CNS: central nervous system; DLco: diffusing capacity of the lung for carbon monoxide; FVC: forced vital capacity; HR: hazard ratio; IPF: idiopathic pulmonary fibrosis; NaV1.7: sodium voltage-gated channel alpha subunit 9; NaV1.8: sodium voltage-gated channel subtype 1.8; NK1: neurokinin 1 receptor; NMDA: N-methyl-D-aspartate receptor; P2X3: purinergic receptor P2X subtype 3; QoL: quality of life; TRPA1: transient receptor potential ankyrin 1; TRPV1: transient receptor potential vanilloid 1; TRPV4: transient receptor potential vanilloid 4; VAS: Visual Analog Scale.
X
"This cough has robbed me of my life. I cough when I talk. I cough when I laugh. I cough when I do bare minimal activity. The cycle of shortness of breath/cough is endless." (Trevi Therapeutics, data on file)
Vagal afferent terminal
TRPV1
Sensitisation in Chronic Cough
In a prospective, multicentre study of patients with IPF, greater cough severity (VAS ≥30 mm) at baseline was independently associated with:
Peripheral nervous system
κ-opioid
μ-opioid
NaV1.7
NaV1.8
NK1
TRPA1
P2X3
TRPV1
TRPA1
TRPV4
TRPV1
Vagal nerve terminal