Reference Ranges for the Cough Responsiveness to Inhaled Mannitol

Cough is the most common reason why people seek medical attention in developed countries. The main mechanisms for prolonged cough are hypersensitivity of the cough reflex arc, sputum production, and constriction of the airway smooth muscles. Recognition of the mechanism in each cough patient is essential for the efficient management of prolonged cough. At present, there are no feasible tests for everyday clinical work to recognize cough reflex arc hypersensitivity.

Mannitol test was originally developed for asthma diagnostics. We have recently shown that it can also be used to investigate hypersensitive cough reflex arc. The purpose of the present study is to create reference ranges for normal cough responsiveness to inhaled mannitol. Without them, the test cannot be utilized in everyday clinical work. For that purpose we will perform mannitol test in 140 subjects, who are at least 18 years old and without any chronic respiratory symptoms or disorders. The subjects will be recruited in three centers: University of Eastern Finland and: John Hunter Hospital in Australia.The material will be collected 1.9.2021-31.12.2023. We apply funding for both personnel and material expences, to carry out this study.

Study Overview

• Status: Recruiting
• Conditions: Cough
• Intervention / Treatment: Diagnostic test: Mannitol challenge

• Study Type: Interventional
• Enrollment (Anticipated): 140
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Heikki O Koskela, MD; Phone Number: +358 447172795; Email: heikki.koskela@kuh.fi
• Study Contact Backup: Name: Hanna M Nurmi, MD; Phone Number: +358 447179973; Email: hanna.nurmi@kuh.fi

Study Locations

• Australia
  • New South Wales
    • Newcastle, New South Wales, Australia, 2305
      • Recruiting
      • John Hunter Hospital
      • Contact: John D Brannan, PhD; Phone Number: +61 435 206 232; Email: john.brannan@health.nsw.gov.au
• Finland
  • Kuopio, Finland, 70029
    • Recruiting
    • Kuopio University Hospital
    • Contact: Heikki O Koskela, MD; Phone Number: +358 447172795; Email: heikki.koskela@kuh.fi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age 18 years or older
• capable to understand the purpose of the study
• female/male ratio approximately 50%/50% in both of the following age groups:
• 50% aged 18- 50 yrs, and 50 % aged 51 - 90 years

Exclusion Criteria:

• Current daily smoking
• Ex-smoking with a greater than 10 pack years' daily smoking history or with stopping of daily smoking less than one year ago
• Pregnancy and breastfeeding
• A doctor's diagnosis of any respiratory diseases, including both upper and lower airway diseases, lung parenchymal diseases and the sleep apnoea syndrome
• A doctor's diagnosis of gastro-oesophageal reflux disease or symptoms suggestive of it
• Current use of angiotensin-converting enzyme inhibitors
• Upper respiratory tract infection ('flu') within 4 weeks
• Any current (within 4 weeks) cough 8
• Chronic (over 2 months' duration) cough during the last 12 months
• Wheezing during the last 12 months
• Attacks of shortness of breath or cough at night during the last 12 months
• Symptoms of rhinitis in a prolonged fashion during the last 12 months
• Heartburn or regurgitation once a week or more often during the last 3 months
• Abnormal anatomy of the respiratory organs, which may affect the deposition of the mannitol powder
• Any previous operations to the respiratory organs that can affect the deposition of the mannitol powder
• Unable to provide written informed consent to participate in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy persons; The responses of the healthy subjects are utilized to create reference ranges for a normal cough response to mannitol	Diagnostic test: Mannitol challenge; Inhalation challenge with dry powder of mannitol with a maximal cumulative dose of 635 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cough-to-dose ratio	calculated as the number of coughs per 100 mg of total cumulative dose of mannitol	Coughs are recorded during the 60 seconds after each mannitol dose

Collaborators and Investigators

• Sponsor: Kuopio University Hospital
• Collaborators: John Hunter Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2022
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: September 1, 2021
• First Submitted That Met QC Criteria: September 1, 2021
• First Posted (Actual): September 5, 2021

Study Record Updates

• Last Update Posted (Estimate): March 9, 2023
• Last Update Submitted That Met QC Criteria: March 8, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Cough; Physiological Effects of Drugs; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Mannitol
• Other Study ID Numbers: 5801151

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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