Chronic COUGH Management in Interstitial Lung DisEase (COUGH-LESS)

COUGH-LESS: Chronic COUGH Management in Interstitial Lung DisEase - Non-pharmacological Strategies and Solutions

Interstitial Lung Disease (ILD) includes chronic, disabling and progressive respiratory conditions marked by lung inflammation and fibrosis. The quality of life and functionality of people with ILD is affected by a plethora of debilitating symptoms such as dyspnoea fatigue and cough. Among them, chronic cough (a cough lasting more than 8 weeks) reigns as one of the most prevalent and challenging, despite receiving far less attention from researchers than other symptoms. Chronic cough affects up to 8 out of 10 individuals with ILD and it is associated with a worse prognosis, mortality, and the need for lung transplantation. This condition showed a significant impact in people's life (e.g., urinary incontinence, speech interferences, depression, chest pain, couples sleeping in separate bedrooms, avoidance of public areas, reduced social interaction, and work absenteeism), further contributing to the decreased health-related quality of life experienced by this population. Managing chronic cough is, therefore, urgently needed. The general aim of this study is to explore the effects of a non-pharmacological cough control treatment on cough-related quality of life in people with ILD. The specific aims of this study are: i) to explore short- and mid-term effects of the non-pharmacological cough control treatment on cough related outcomes (e.g., cough frequency and intensity, dyspnoea, fatigue, cough self-efficacy, health-related quality of life and emotional status); ii) to identify (if any) adverse effects of this therapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Interstitial Lung Disease; Chronic Cough
• Intervention / Treatment: Behavioral: Non-pharmacological cough control therapy; Behavioral: Healthy lifestyle

Detailed Description

Interstitial Lung Disease (ILD) comprises chronic, disabling, and progressive respiratory conditions marked by lung inflammation and fibrosis. The quality of life and functionality of people with ILD is affected by a plethora of debilitating symptoms such as dyspnoea, fatigue, and cough. Among them, chronic cough reigns as one of the most prevalent and challenging, despite receiving far less attention from researchers than other symptoms.

Chronic cough (a cough lasting for > 8 weeks) and affects up to 8 out of 10 individuals with ILD. It is associated with a worse prognosis, mortality, and the need for lung transplantation. This condition also causes urinary incontinence, interferes with speech, and presents psychosocial and physical manifestations, such as depression and chest pain. Chronic cough can also lead to relationship problems, such as couples sleeping in separate bedrooms, avoidance of public areas, reduced social interaction, and work absenteeism, further contributing to the decreased health-related quality of life experienced by this population. Managing chronic cough is, therefore, urgently needed.

Currently, there is no approved drug to manage chronic cough in people with ILD. Conversely, non-pharmacologic cough control therapies have demonstrated similar efficacy without side effects. Studies have shown that non-pharmacological cough control therapy can improve cough-related quality of life and reduce cough frequency in individuals with refractory (i.e., cough that lasts despite optimal treatment) chronic cough. Promising results were observed in a case-study on people with chronic cough and ILD. However, well-designed randomized controlled trials (RCTs) with adequate power are needed to establish the effects of non-pharmacological cough control therapy on people with ILD.

The primary aim of this study is to explore the effects of a non-pharmacological cough control treatment on cough-related quality of life in people with ILD. The specific aims of this study are: i) to explore short- and mid-term effects of the non-pharmacological cough control treatment on cough related outcomes (e.g., cough frequency and intensity, dyspnea, fatigue, cough self-efficacy, health-related quality of life and emotional status); ii) to identify (if any) adverse effects of this therapy.

COUGH-LESS randomized trial Potential participants will be identified and recruited through the pulmonology services of the Centro Hospitalar do Baixo Vouga (CHBV) and Centro Hospitalar de Entre-o-Douro e Vouga (CHEDV).

Study design Participants will be randomly assigned to an experimental (EG) or control group (CG) using an online software. Assessments will be conducted at baseline, post-intervention and 3 and 6 months after the intervention. To detect a 2-point between-group difference in the LCQ after 5 weeks, 20 participants per group (n=40) will be required, with 80% power and a significance level of 5%. Previous studies indicate losses to follow up of 50% and thus we will aim to recruit 60 individuals.

Data collection Assessments will be conducted at baseline, post-intervention and 3 and 6 months after the intervention.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ana L Oliveira, PhD; Phone Number: 00351913937469; Email: alao@ua.pt
• Study Contact Backup: Name: Alda Marques, PhD; Phone Number: 27121 00351234372462; Email: amarques@ua.pt

Study Locations

• Portugal
  • Aveiro, Portugal
    • Aveiro University
    • Contact: Ana L Oliveira; Phone Number: +351913937469; Email: alao@ua.pt
    • Contact: Ana S Grave, MSc
    • Contact: Alda Marques, PhD
    • Contact: Diogo Tecelão, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

i) Adults (>18 years old) ii) Clinical diagnosis of ILD iii) Presenting chronic cough (> 8 weeks of duration) iv) People with access to a virtual meeting platform/telephone.

Exclusion Criteria:

i) Self-reports of moderate or large sputum production (> 2 tablespoons); ii) Actual or suspected exacerbation of the respiratory condition in the last month; iii) Upper respiratory tract infection (e.g. cold); iv) Use of angiotensin-converting enzyme inhibitor medication; v) Changes in prescribed medication in the last month; vi) Signs of cognitive impairment or significant cardiovascular, neurological and/or musculoskeletal disease that may limit participation in the program; vii) Inability to read or speak Portuguese; viii) Inability to provide informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Control Group	Behavioral: Healthy lifestyle; Over seven weeks (1 session per week, except session 5, which will be 2 weeks after session 4) using a one-on-one hybrid model. In session 1, participants will receive general education about exercise and physical activity. Session 2 will cover education about diet. Session 3 will focus on stress management. Session 4 will cover relaxation techniques, and session 5 will reinforce all aspects previously considered.
Experimental: COUGH-LESS Programme	Behavioral: Non-pharmacological cough control therapy; Over seven weeks (1 session per week, except session 5, which will be 2 weeks after session 4) using a one-on-one hybrid model. In session 1, participants will receive general education about chronic cough, introduction to cough suppression and goal setting. Session 2 will cover education about chronic cough in ILD, cough triggers and training in cough suppression techniques. Session 3 will focus on hydration techniques, laryngeal hygiene, and breathing exercises to control coughing. Session 4 will reinforce all aspects of non-pharmacological cough control treatment, and session 5 will explore the sustainability of cough control strategies after the program using real-life case scenarios.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Leicester Cough Questionnaire (LCQ)	The LCQ is a reliable, responsive questionnaire recommended by various guidelines for assessing chronic cough. This questionnaire comprises 21 questions referring to the two weeks prior to completing it. The LCQ assesses three domains (psychological, social and physical) and also gives a total score. The maximum score that can be obtained on the LCQ is 21 points in total (7 in each domain) where higher scores translate into a higher quality of life related to coughing.	One measurement will be assessed at baseline, 7 weeks after interventions and 3 and 6 months after the intervention.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Modified British Medical Research Council Dyspnea Scale (mMRC)	The mMRC has been validated for the Portuguese population and is a predictor of increased severity in people with ILD.	One measurement will be assessed at baseline, 7 weeks after interventions and 3 and 6 months after the intervention.
Change in Cough Visual Analogic Scale (CVAS)	The CVAS will be used to measure intensity and frequency of cough. This scale consists of a 10 cm line ranging from 0 (no severity/intensity) to 10 (extreme severity/intensity) and is moderately responsive.	One measurement will be assessed at baseline, 7 weeks after (post-intervention) and 3 and 6 months after the intervention.
Change in Chronic Airways Assessment Test (CAAT)	CAT will be used to measure quality of life related to respiratory symptoms. This scale ranges from 0 to 45, where higher values mean a lower quality of life related to respiratory symptoms in people with ILD.	One measurement will be assessed at baseline, 7 weeks after (post-intervention) and 3 and 6 months after the intervention.
Change in One minute sit-to-stand test (1min-STS)	The 1min-STS will be used to assess functional capacity. It will be counted the maximum number of repetitions completed in 1 minute while sitting and standing on a chair.	One measurement will be assessed at baseline, 7 weeks after (post-intervention) and 3 and 6 months after the intervention.
Six-minute Walking Test (6MWT)	The 6MWT will be used also to measure functional capacity and has been validated in people with ILD. The walked total distance during the six minutes will be counted.	One measurement will be assessed at baseline, 7 weeks after (post-intervention) and 3 and 6 months after the intervention.
Change in Cough Hypersensitivity Questionnaire (CHQ)	The CHQ comprises 23 questions related to cough-causing stimuli and coughing sensations. This questionnaire scores rages from 0 to 23 points, where higher scores mean a greater presence and severity of stimuli and triggers of cough and sensations in the larynx.	One measurement will be assessed at baseline, 7 weeks after (post-intervention) and 3 and 6 months after the intervention.
Change in Hospital Anxiety and Depression Scale (HADS)	HADS is an easy-to-use scale that is subdivided into two domains (anxiety symptoms and depressive symptoms). Their score varies from 0 to 21 in each subdomain, where a score between 0 and 7 is considered 'normal', between 8 and 10 indicates a "mild" level, between 11 and 14 a "moderate" level, and between 15 and 21 "severe" levels of anxiety and depression symptoms.	One measurement will be assessed at baseline, 7 weeks after (post-intervention) and 3 and 6 months after the intervention.
Change in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-FS)	FACIT-FS assesses fatigue where a higher score translates into lower fatigue. This scale is commonly used in the ILD population to assess fatigue, presenting good reliability and feasibility.	One measurement will be assessed at baseline, 7 weeks after (post-intervention) and 3 and 6 months after the intervention.
Change in King's Brief Interstitial Lung Disease (K-BILD)	K-BILD will be used to assess health related quality of life. This scale encompasses three domains: psychological, dyspnoea, activities, and respiratory symptoms where higher scores define a high health related quality of life.	One measurement will be assessed at baseline, 7 weeks after (post-intervention) and 3 and 6 months after the intervention.
Interviews	Participants will be invited to take part in face-to-face, semi-structured individual interviews the impact of both interventions (control and experimental group).	One measurement will be assessed at baseline and 7 weeks after (post-intervention)
Adherence to the COUGH-LESS programme	Participants' number of sessions attended to the intervention will be registered.	Only one measurement will be assessed after 7 weeks after baseline (post-intervention).
Occurrence of adverse events	The occurrence of adverse events in participants will be registered according to CTCAE v4.0.	One measurement will be assessed at 7 weeks after baseline (post-intervention) and 3 and 6 months after the intervention.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in number of hospitalizations	Patients' number of hospitalizations in the previous year and during the follow-up period, as well as the length of stay for each hospitalization, will be assessed by asking the patient to self-report.	One measurement will be assessed at 7 weeks after baseline (post-intervention) and 3 and 6 months after the intervention.
Change in acute exacerbations	Patients' number of acute exacerbations will be assessed by asking the patient to self-report.	One measurement will be assessed at 7 weeks after baseline (post-intervention) and 3 and 6 months after the intervention.
Interstitial Lung Disease- Gender, Age and Physiology model (ILD-GAP model)	ILD-GAP model measures the severity of the disease based on the diagnosis, sex and respiratory function test values to create a score that can vary between 0 and 8. The greater the severity of the disease, the higher the ILD-GAP model.	Only one measurement will be assessed on baseline. This will be used as a descriptive measure.

Collaborators and Investigators

• Sponsor: Aveiro University
• Collaborators: Centro Hospitalar de Entre o Douro e Vouga; Fundação para a Ciência e a Tecnologia; Centro Hospitalar do Baixo Vouga

Study record dates

Study Major Dates

• Study Start (Estimated): December 20, 2027
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): July 30, 2028

Study Registration Dates

• First Submitted: July 30, 2024
• First Submitted That Met QC Criteria: January 14, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 14, 2025
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Interstitial Lung Disease; Chronic Cough; Non-pharmacological cough control therapy
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Chronic Cough; Lung Diseases; Lung Diseases, Interstitial; Cough; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Expectorants; Respiratory System Agents; Anti-Obesity Agents; Sympathomimetics; Vasoconstrictor Agents; Nasal Decongestants; Appetite Depressants; Phenylpropanolamine; Guaifenesin; Chlorpheniramine, phenylpropanolamine drug combination
• Other Study ID Numbers: 2023.01387.BDANA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No