Cough In Idiopathic Pulmonary Fibrosis Research Articles

A Continuous Intestinal Absorption Model to Predict Drug Enterohepatic Recirculation in Healthy Humans: Nalbuphine as a Model Substrate.

Nalbuphine (NAL) is a κ-agonist/μ-antagonist opioid being developed as an oral extended formulation (ER) for the treatment of chronic cough in idiopathic pulmonary fibrosis and itch in prurigo nodularis. NAL is extensively glucuronidated and likely undergoes enterohepatic recirculation (EHR). The purpose of this work is to develop pharmacokinetic models for NAL absorption and enterohepatic recirculation (EHR). Clinical pharmacokinetic (PK) data sets in healthy subjects from three trials that included IV, oral solution, and ER tablets in fed and fasted state and two published trials were used to parametrize a novel partial differential equation (PDE)-based model, termed "PDE-EHR" model. Experimental inputs included in vitro dissolution and permeability data. The model incorporates a continuous intestinal absorption framework, explicit liver and gall bladder compartments, and compartments for systemic drug disposition. The model was fully PDE-based with well-stirred compartments achieved by rapid diffusion. The PDE-EHR model accurately reproduces NAL concentration-time profiles for all clinical data sets. NAL disposition simulations required inclusion of both parent and glucuronide recirculation. Inclusion of intestinal P-glycoprotein efflux in the simulations suggests that NAL is not expected to be a victim or perpetrator of P-glycoprotein-mediated drug interactions. The PDE-EHR model is a novel tool to predict EHR and food/formulation effects on drug PK. The results strongly suggest that even intravenous dosing studies be conducted in fasted subjects when EHR is suspected. The modeling effort is expected to aid in improved prediction of dosing regimens and drug disposition in patient populations.

Productive cough associated with patient-reported outcomes and computed tomography analysis results in idiopathic pulmonary fibrosis: a single centre cross-sectional study.

The high frequency of productive cough in idiopathic pulmonary fibrosis (IPF) impacts quality of life. Reduced normal lung volume is linked to cough severity, predicting poorer outcomes. Insights could enhance IPF management and patient wellbeing. https://bit.ly/4bPOCzC.

Morphine for treatment of cough in idiopathic pulmonary fibrosis (PACIFY COUGH): a prospective, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial

Idiopathic pulmonary fibrosis is a progressive fibrotic lung disease, with most patients reporting cough. Currently, there are no proven treatments. We examined the use of low dose controlled-release morphine compared with placebo as an antitussive therapy in individuals with idiopathic pulmonary fibrosis. The PACIFY COUGH study is a phase 2, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial done in three specialist centres in the UK. Eligible patients aged 40-90 years had a diagnosis of idiopathic pulmonary fibrosis within 5 years, self-reported cough (lasting >8 weeks), and a cough visual analogue scale (VAS) score of 30 mm or higher. Patients were randomly assigned (1:1) to placebo twice daily or controlled-release morphine 5 mg orally twice daily for 14 days followed by crossover after a 7-day washout period. Patients were randomised sequentially to a sequence group defining the order in which morphine and placebo were to be given, according to a computer-generated schedule. Patients, investigators, study nurses, and pharmacy personnel were masked to treatment allocation. The primary endpoint was percentage change in objective awake cough frequency (coughs per h) from baseline as assessed by objective digital cough monitoring at day 14 of treatment in the intention-to-treat population, which included all randomised participants. Safety data were summarised for all patients who took at least one study drug and did not withdraw consent. This study was registered at ClinicalTrials.gov, NCT04429516, and has been completed. Between Dec 17, 2020, and March 21, 2023, 47 participants were assessed for eligibility and 44 were enrolled and randomly allocated to treatment. Mean age was 71 (SD 7·4) years, and 31 (70%) of 44 participants were male and 13 (30%) were female. Lung function was moderately impaired; mean forced vital capacity (FVC) was 2·7 L (SD 0·76), mean predicted FVC was 82% (17·3), and mean predicted diffusion capacity of carbon monoxide was 48% (10·9). Of the 44 patients who were randomised, 43 completed morphine treatment and 41 completed placebo treatment. In the intention-to-treat analysis, morphine reduced objective awake cough frequency by 39·4% (95% CI -54·4 to -19·4; p=0·0005) compared with placebo. Mean daytime cough frequency reduced from 21·6 (SE 1·2) coughs per h at baseline to 12·8 (1·2) coughs per h with morphine, whereas cough rates did not change with placebo (21·5 [SE 1·2] coughs per h to 20·6 [1·2] coughs per h). Overall treatment adherence was 98% in the morphine group and 98% in the placebo group. Adverse events were observed in 17 (40%) of 43 participants in the morphine group and six (14%) of 42 patients in the placebo group. The main side-effects of morphine were nausea (six [14%] of 43 participants) and constipation (nine [21%] of 43). One serious adverse event (death) occurred in the placebo group. In patients with cough related to idiopathic pulmonary fibrosis, low dose controlled-release morphine significantly reduced objective cough counts over 14 days compared with placebo. Morphine shows promise as an effective treatment to palliate cough in patients with idiopathic pulmonary fibrosis, and longer term studies should be the focus of future research. The Jon Moulton Charity Trust.

Assessment and Management of Cough in Idiopathic Pulmonary Fibrosis: A Narrative Review.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal disease with an unknown cause. It is characterized by symptoms such as cough and breathlessness, which significantly impact patients' quality of life. Cough, in particular, has emerged as a burdensome symptom for individuals with IPF. The etiology of cough in IPF patients is believed to be complex, involving factors related to the disease itself, such as increased sensitivity of cough nerves, lung structural changes, inflammation, and genetic factors, as well as comorbidities and medication effects. Unfortunately, effective treatment options for cough in IPF remain limited, often relying on empirical approaches based on studies involving chronic cough patients in general and the personal experience of physicians. Medications such as opioids and neuromodulators are commonly prescribed but have shown suboptimal efficacy, imposing significant physical, psychological, and economic burdens on patients. However, there is hope on the horizon, as specific purinergic P2 receptor ligand-gated ion channel (P2X3) inhibitors have demonstrated promising antitussive effects in ongoing clinical trials. This review aims to provide a comprehensive overview of the evaluation and management of cough in IPF patients, as well as highlight emerging pharmacological and non-pharmacological approaches that target the cough reflex and are currently being investigated in clinical settings.

Characteristics of idiopathic pulmonary fibrosis -associated cough. a case-control study

BackgroundMost patients with idiopathic pulmonary fibrosis (IPF) complain of cough. IPF-associated cough is widely characterized as dry or non-productive. The aim of this study was to compare chronic cough in early stage IPF patients to cough in subjects with chronic cough from a community-based sample and, especially, to investigate whether cough in IPF is less productive than chronic cough in a community-based sample.MethodsThe IPF cough population consisted of 46 biopsy-confirmed patients who complained of chronic cough. Control population consisted of subjects with chronic cough, gathered by a community-based email survey sent to public service employees and the Finnish Pensioners’ Federation. A case-control setting was applied by having four age, gender, and smoking-status matched subjects from the community sample for each IPF cough patient. A cough specific quality of life questionnaire (Leicester Cough Questionnaire (LCQ)) was filled in by all subjects. The LCQ questionnaire contains 19 questions, each question is scored from 1 to 7 and total score from 3 to 21 with a smaller value indicating more severe impairment.ResultsThe sputum production frequency, as assessed by LCQ question 2, was 5.0 (3.0-6.0) in the IPF chronic cough population and 5.0 (3.0–6.0) in the community-based chronic cough population (median and interquartile range p= 0.72). The LCQ total score was 14.8 (11.5-18.1) in the IPF chronic cough population and 15.4 (13.0–17.5) in the community-based chronic cough population (p=0.76). The domain impact scores were physical, 4.9 (3.9–6.1) vs. 5.1 (4.5–5.6) (p=0.80); psychological, 4.6 (3.7–5.9) vs. 4.7 (3.9–5.7) (p=0.90); and social, 5.5 (3.7–6.5) vs. 5.5 (4.5–6.3) (p=0.84), respectively. Furthermore, cough response to paint or fumes, cough disturbing sleep, and cough frequency per day did not differ between the groups.ConclusionCough in early stage IPF patients was not distinguishable from chronic cough in the community-based population by LCQ. Especially, there was no difference in the self-reported frequency of cough-associated sputum production.

Industry Update, October 2022.

Industry Update, October 2022.

Cough in Idiopathic Pulmonary Fibrosis

Chronic cough is experienced by most patients with idiopathic pulmonary fibrosis (IPF). It is often the first symptom and is associated with reduced quality of life, increased rates of depression and anxiety, more severe physiological impairment, and disease progression. Although not fully understood, recent gains in understanding the pathophysiology of chronic cough in IPF have been made. The pathophysiology is likely multifactorial and includes alterations in mucous production and clearance, architectural distortion, and increased cough reflex sensitivity, suggesting a role for targeted therapies and multidisciplinary treatment. Modifiable comorbidities can also induce cough in patients with IPF. There is a renewed emphasis on measuring cough in IPF, with clinical trials of novel and repurposed therapies for chronic cough emerging in this population. This review provides an update on the clinical characteristics, pathophysiology, and measurement of chronic cough in patients with IPF and summarizes recent developments in non-pharmacological and pharmacological therapies.

Azithromycin for the Treatment of Chronic Cough in Idiopathic Pulmonary Fibrosis: A Randomized Controlled Crossover Trial.

Rationale: Patients with idiopathic pulmonary fibrosis (IPF) frequently suffer from chronic cough that is difficult to treat, which substantially affects their quality of life. Azithromycin has been demonstrated to relieve chronic cough in some populations; however, this has not been investigated in patients with IPF. Objectives: To determine the safety and efficacy of azithromycin for the treatment of chronic cough in patients with IPF. Methods: In a double-blind randomized controlled crossover trial, patients with IPF underwent two 12-week intervention periods (azithromycin 500 mg three times per week or placebo three times per week). The primary outcome was the change in cough-related quality of life as measured by the Leicester Cough Questionnaire (LCQ). Secondary outcomes included cough severity as measured by the Visual Analog Scale (VAS), health-related quality of life as assessed by the St. George's Respiratory Questionnaire, and objective cough frequency as measured by audiovisual readings from 24-hour respiratory polygraphy. Results: Twenty-five patients were randomized (23 men, 2 women); 20 patients completed the study. The mean (standard deviation [SD]) age was 67 (8) years, the mean (SD) forced vital capacity was 65 (16) percent predicted, and the diffusing capacity of the lung for carbon monoxide was 43 (16) percent predicted. The mean (SD) baseline LCQ scores were 11.7 (3.7) and 11.3 (3.3) for the azithromycin period and the placebo period, respectively, and the corresponding mean (SD) cough VAS scores were 5.6 (2.3) and 5.8 (2.1). There was no significant change in the LCQ score or the VAS score with azithromycin or with placebo. Similarly, there was no significant difference between the azithromycin period and the placebo period for change in polygraphy-measured cough frequency. Gastrointestinal adverse effects were more frequent with azithromycin than with placebo (diarrhea, 43% vs. 5%; P = 0.03). Conclusions: This randomized controlled trial does not support the use of low-dose azithromycin for chronic cough in patients with IPF.Clinical trial registered with www.clinicaltrials.gov (NCT02173145).

Chinese herbal medicines for the treatment of cough in idiopathic pulmonary fibrosis: A protocol for systematic review and meta-analysis.

Background:Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with unknown etiology and hidden onset, which causes major health problems worldwide. Cough is a typical manifestation of IPF, which is usually characterized by cough without phlegm, and seriously affects the quality of life (QOL) of patients. At present, the treatment of IPF is mainly focused on prolonging survival time and improving lung function, such as pirfenidone, nintedanib, and N-acetylcysteine (NAC), but lack of effective measures to improve the QOL. Chinese herbal medicines (CHMs) is widely used in the clinical treatment of IPF. The adjuvant treatment of CHMs can effectively reduce the clinical symptoms of patients. Therefore, we designed this study to evaluate the role of CHMs in the treatment of cough in IPF.Method:This systematic review and meta-analysis will extract all randomized controlled trials (RCTs) related to the treatment of IPF from the following electronic database without date or language restrictions: PubMed, EMBASE, Cochrane CENTRAL, CNKI, VIP, CBM, and Wanfang database. The primary outcomes will be cough frequency and QOL, while secondary outcomes will include safety events. The methodologic quality of RCTs will be assessed using the Cochrane risk assessment tool. The I2 test will be used to identify the extent of heterogeneity, and funnel plot analysis will be used to test the publication deviation (the number of studies included >10). We will use RevMan5.3 software for data synthesis and analysis.Result:This review evaluates the efficacy and safety of CHMs in combination therapy on cough frequency, the quality of life, adverse reactions and safety incidents in patients with IPF.Conclusion:This study protocol will be used to evaluate the efficacy and safety of CHMs in combination with conventional therapy in treatment of cough in IPF.OSF Registration DOI:10.17605/OSF.IO/JKQYV.

Cough, an unresolved problem in interstitial lung diseases.

Many patients with interstitial lung diseases (ILDs), especially fibrotic ILDs, experience chronic cough. Cough has a major impact on wellbeing, affecting both physical and psychological aspects of life. The pathophysiology of cough in ILDs is poorly understood and currently no good antitussive therapy exists. Research on cough in ILDs is increasing. A recent proof-of-concept study with nebulized sodium cromoglycate for patients with idiopathic pulmonary fibrosis (IPF)-related cough showed a promising effect on cough. Observational data suggest that antifibrotic pirfenidone might reduce cough in IPF. Studies on the effect of acid inhibition on cough in ILDs show contradicting results. The first steps in analyzing new treatment options for chronic cough in patients with ILDs, especially in IPF, have been taken, but an effective treatment is still lacking.

EXPERIENCE OF PROLONGED TIME OF USE OF TALIDOMIDE FOR THE TREATMENT OF COUGH OF DIFFICULT CONTROL IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS

PURPOSE: To show the safety of prolonged use of Thalidomide in the treatment of difficult control cough in idiopathic pulmonary fibrosis (IPF). METHODS: Descriptive, retrospective observational study. The clinical histories of the patients treated in the Pulmonology Department of the Alberto Sabogal Sologuren National Hospital, Callao – Peru, with the diagnosis of IPF who received treatment with Thalidomide for difficult control cough, from December 2013 to December 2015, were reviewed. RESULTS: Data of the population studied CONCLUSIONS: We present our experience of its use For a long time (mean 14 months) in patients with IPF, with good safety profile and low presentation of adverse effects, a single case of severe arterial hypotension took the patient to only 2 months of treatment, with the remainder of mild intensity. CLINICAL IMPLICATIONS: The etiology of cough in IPF is unknown, often disabling and resistant to traditional antitussive therapies. Thalidomide is an immune modulator, with anti-inflammatory and anti-angiogenic effects, similar to antifibrotic drugs its effect on cough in humans with IPF, was evaluated in 2012, in 98 participants, for 24 weeks showing a positive effect on quality of life measured with the Cough Life Quality Questionnaire. The IPF management guidelines recommend that thalidomide should not be considered a routine treatment of cough in IPF, even as a second-line therapy, until an additional benefit / risk assessment has been performed, our work Presents the experience of prolonged and safe use of Thalidomide, which must be confirmed with a clinical trial of a larger population and designed specifically for this purpose.

Randomised, double-blind, placebo-controlled pilot trial of omeprazole in idiopathic pulmonary fibrosis

BackgroundCough is a common, disabling symptom of idiopathic pulmonary fibrosis (IPF), which may be exacerbated by acid reflux. Inhibiting gastric acid secretion could potentially reduce cough. This study aimed to...

The pathogenetic mechanisms of cough in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis is a peripheral subpleural interstitial lung disorder limited to the lung not involving the airways. It has a poor prognosis (survival less than 5years) and commonly an interstitial pneumonia radiological pattern. Patients complain of a chronic dry cough in 80% of cases. A cough is often the first symptom of this rare disease, preceding dyspnea by years, and is associated with a poor prognosis, high dyspnea scores and low FVC percentages. The pathogenetic mechanisms leading to coughing in IPF are unclear. This review focuses on recent evidence of cough pathophysiology in this disease. Gastroesophageal reflux may promote coughing in IPF patients; bile salts and pepsin may be abundant in BAL of these patients, inducing overproduction of TGF-β by airway epithelial cells and mesenchymal transition with fibroblast recruitment/activation and extracellular matrix deposition. Patients have an enhanced cough reflex to capsaicin and substance P with respect to control subjects. Moreover, patients with the MUC5B polymorphism show more severe coughing as MUC5B encodes for the dominant mucin in the honeycomb cysts of IPF patients. Comorbidities, including asthma, gastroesophageal reflux, hypersensitivity pneumonitis, bronchiectasis, chronic obstructive pulmonary disease and emphysema, can induce coughing in IPF patients. There is no clear explanation of the causes of coughing in IPF. Further research into the pathophysiology of IPF and the pathogenetic mechanisms of coughing is necessary to improve survival and quality of life.

Nebulized Mannitol, Particle Distribution, and Cough in Idiopathic Pulmonary Fibrosis.

Inhaled interferon, a potential treatment for idiopathic pulmonary fibrosis, must be formulated with mannitol, which can cause bronchospasm and cough. Coughing during drug inhalation can be affected by many factors, but some factors are fixed by the needs of the formulation and inflammatory disease in the airways. A component of the cough response may be related to sites of deposition, particularly upper and central airways. If deposition sites are important, then manipulating the particle distribution of the aerosol may mitigate coughing. To design a therapeutic formulation and delivery system for formulations that contain mannitol, we tested the effect of particle distribution on cough during mannitol inhalation in volunteers with idiopathic pulmonary fibrosis. A solution of mannitol was formulated to match requirements for future interferon formulations (40 mg/mL, 220 mOsm/L). Mannitol aerosols were generated by using different nebulizers providing particle distributions that were expected to vary upper airway deposition. The nebulizer fill volume was adjusted to correct for differences in nebulizer efficiency with a target inhaled mass of 20 mg. Particle distributions were measured by cascade impaction (mass median aerodynamic diameters, 1.2 and 6.5 μm). Seven subjects with idiopathic pulmonary fibrosis participated in the study. To maximize deposition, the subjects were trained to inhale slowly and deeply (6 s inspiration). Spirometry was measured before and after inhalation. The study was carried out on separate days (day 1: 1.2 μm; day 2: 6.5 μm), and the pattern of coughing was observed. Coughing was often spontaneous and provoked by spirometry. When inhaling the 1.2-μm distribution, no subject coughed during inhalation. Six of the seven subjects coughed when inhaling the 6.5-μm particles. Spirometry was unaffected. In subjects with idiopathic pulmonary fibrosis, nebulized mannitol can cause coughing. Modifying the aerosol distribution prevents coughing during mannitol inhalation. Mannitol aerosols can be inhaled safely without bronchospasm. These data serve to inform future formulation and/or device combinations for planned interferon therapy.

Airway expression of Transient Receptor Potential (TRP) Vanniloid-1 and Ankyrin-1 channels is not increased in patients with Idiopathic Pulmonary Fibrosis.

Dry cough is a common symptom described in patients with Idiopathic Pulmonary Fibrosis (IPF) and impairs quality of life. The exact mechanisms causing cough in IPF remain unclear, however evidence suggests altered cough neurophysiology and sensitisation plays a role; IPF patients have an enhanced cough reflex sensitivity to inhaled capsaicin. The Transient Receptor Potential Vanniloid-1 channel (TRPV-1) has a role in the cough reflex and airway expression is increased in patients with chronic cough. The Ankyrin-1 receptor (TRPA-1) is often co-expressed. It was hypothesised that, like chronic cough patients, IPF patients have increased airway TRP receptor expression. Bronchial biopsies were obtained from 16 patients with IPF, 11 patients with idiopathic chronic cough and 8 controls without cough. All other causes of cough were rigorously excluded. Real-time quantitative Polymerase Chain Reaction was used to detect TRPV-1 and TRPA-1 mRNA expression with Immunohistochemistry demonstrating protein expression. Mean TRPV-1 and TRPA-1 gene expression was higher in IPF patients compared with controls, but the difference did not reach statistical significance. Immunostaining supported these findings. This study suggests that structural up-regulation of central airway TRP receptors is not the key mechanism for cough in IPF patients. It is probable that IPF cough results from altered neuronal sensitivity at multiple levels of the cough pathway.

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48-0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78-2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation. Patara Pharma.

P231 Respiratory breathing patterns and cough in idiopathic pulmonary fibrosis: awake, asleep and over time

P231 Respiratory breathing patterns and cough in idiopathic pulmonary fibrosis: awake, asleep and over time

Cough in idiopathic pulmonary fibrosis.

Many patients with idiopathic pulmonary fibrosis (IPF) complain of chronic refractory cough. Chronic cough is a distressing and disabling symptom with a major impact on quality of life. During recent years, progress has been made in gaining insight into the pathogenesis of cough in IPF, which is most probably "multifactorial" and influenced by mechanical, biochemical and neurosensory changes, with an important role for comorbidities as well. Clinical trials of cough treatment in IPF are emerging, and cough is increasingly included as a secondary end-point in trials assessing new compounds for IPF. It is important that such studies include adequate end-points to assess cough both objectively and subjectively. This article summarises the latest insights into chronic cough in IPF. It describes the different theories regarding the pathophysiology of cough, reviews the different methods to assess cough and deals with recent and future developments in the treatment of cough in IPF.

Cough in idiopathic pulmonary fibrosis: more than just a nuisance

Cough in idiopathic pulmonary fibrosis: more than just a nuisance

Nerves, Cough, and Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias. It has a poor prognosis with a median survival of approximately 3 years, and whilst new therapies are finally beginning to offer hope of improved survival, most patients will require palliation of symptoms as their disease progresses. Whilst all patients with IPF complain of breathlessness, up to 80% develop a distressing cough, which is detrimental to their quality of life and difficult to treat. This article examines the possible causes of cough in the wider context of current theories of the pathogenesis of IPF and its associated comorbidities, which may also cause or exacerbate cough. We examine the evidence for increased cough sensitivity in patients with IPF and neuroplasticity in animal models of lung pathology. Finally, we discuss new therapies that are becoming available to treat cough in IPF and their possible mechanisms of action, and which highlight the need for further, appropriately powered studies that include objective measures of cough as an outcome.