Effects of High Flow Nasal Cannula on Sputum Clearance in Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Acute exacerbation of COPD usually presents with more sputum production leading to worsening airflow obstruction. Often patients complain of sensation of sputum (phlegm) stuck in throat, which leads to worsening cough and respiratory distress. In an acute exacerbation setting high flow nasal cannula (HFNC), which is a modality that provides humidified and warm oxygenated air at flow of upto 60L/min, has shown to reduce blood carbon dioxide level and respiratory rate. However, studies investigating other effects of HFNC in this setting are lacking. To investigators' knowledge, this is the first study investigating effects of HFNC on sputum clearance in COPD patients.

The purpose of the study is to determine the effects of HFNC on sputum clearance in acute exacerbation of COPD. Primary objective of the study is to determine whether HFNC improves clearability and wettability of sputum produced during acute exacerbation of COPD. Secondary objectives of the study include subjective assessment of cough severity as well as need for escalation of care after HFNC use versus conventional flow nasal oxygen (CFNO) use.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Obstructive Pulmonary Disease; COPD Exacerbation; Airflow Obstruction
• Intervention / Treatment: Device: High Flow Nasal Cannula

Detailed Description

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and the 4th leading cause of mortality in the world. Acute exacerbation of COPD usually presents with more sputum production leading to worsening airflow obstruction. During an exacerbation, high flow nasal cannula (HFNC) has shown to reduce blood carbon dioxide level and respiratory rate. However, studies investigating other effects of HFNC in this setting are lacking. To investigators' knowledge, this is the first study investigating effects of HFNC on sputum clearance in COPD patients.

Patients with a diagnosis of acute exacerbation of COPD who are receiving oxygen therapy via conventional nasal cannula or are on room air will be randomized into high flow nasal cannula (HFNC) or conventional flow nasal oxygen (CFNO) group for 24 hours. HFNC group will receive heated (approximately 37 ⁰C) and humidified (100% relative humidity) oxygenated gas delivered at high flow at 50L/min. CFNO group will receive ambient temperate and non-humidified oxygenated gas delivered at flow of up to 8L/min (standard care). Sputum sample will be collected at time = 0 hours (baseline), 4 +/- 1 hours, 8 +/- 2 hours and 24 +/- 2 hours. Visual analogue score (VAS) regarding cough severity and Breathlessness, Cough and Sputum Scale (BCSS) regarding cough frequency and ease will be obtained at time = 0 and 24 hours.

Primary outcomes of the study are the difference in clearability and wettability of sputum sample. Clearability is measured by the distance sputum sample travels in an artificial trachea after a simulated cough. The longer the displacement, the more the clearability. Wetability is measured by determining the contact angle the sputum sample makes on a glass surface. The smaller the contact angle, the more the wettability. Secondary outcomes include subjective assessment of cough using VAS and BCSS scales, as well as need for escalation of care.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years old
2. Known COPD or high probability of the disease according to treating physician based on clinical history, physical examination and chest imaging.
3. Hospital admission for acute exacerbation of COPD defined by 2018 GOLD report as acute worsening of respiratory symptoms (more than baseline cough, sputum purulence or volume, dyspnea or wheeze) that result in additional therapy.
4. Presence of one or more of following: increase in sputum production, change in sputum color or difficulty in expectorating sputum.

Exclusion Criteria:

1. Inability to obtain informed consent from the patient or legally authorized representative.
2. Inability of the subject to cooperate with protocol.
3. Presence of idiopathic bronchiectasis or cystic fibrosis.
4. Patients with poor short term prognosis not expected to survive the hospitalization.
5. Massive hemoptysis.
6. Patients presenting with coma (Glasgow coma scale <10) or circulatory shock.
7. Respiratory failure requiring non-invasive ventilation (NIV) or endotracheal intubation.
8. Severely impaired cough, impaired swallowing or chronic aspiration due to neuromuscular disorder.
9. Facial deformity or injury leading to difficulty in wearing high flow nasal cannula appropriately.
10. Enrollment in other investigative protocols with apparent overlap.
11. Prisoners

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
Experimental: High flow nasal cannula (HFNC) group; The HFNC group will receive heated (approximately 37 ⁰C) and humidified (100% relative humidity) oxygenated gas delivered at high flow at 50L/min. Flow could be decreased to as low as 30L/min and temperature to 31 ⁰C as per patient's tolerance.	Device: High Flow Nasal Cannula; The HFNC group will receive heated and humidified oxygenated gas delivered at high flow.; Other Names: Fisher and Paykel AIRVO humidified high flow system
No Intervention: Conventional flow nasal oxygen (CFNO) group; The conventional flow nasal oxygen (CFNO) group is the control group which will receive ambient temperature and non-humidified oxygen delivered at flow rates of up to 8L/min (standard care).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clearability of sputum sample at baseline	Clearability is measured by the distance sputum sample travels in an artificial trachea after a simulated cough. The longer the displacement, the more the clearability.	Sputum sample will be collected at time = 0 hours (baseline)
Clearability of sputum sample at 6 hours	Clearability is measured by the distance sputum sample travels in an artificial trachea after a simulated cough. The longer the displacement, the more the clearability.	Sputum sample will be collected at time = 6 +/- 2 hours
Clearability of sputum sample at 24 hours	Clearability is measured by the distance sputum sample travels in an artificial trachea after a simulated cough. The longer the displacement, the more the clearability.	Sputum sample will be collected at time = 24 +/- 2 hours
Wettability of sputum sample at baseline	Wetability is measured by determining the contact angle the sputum sample makes on a glass surface. The smaller the contact angle, the more the wettability.	Sputum sample will be collected at time = 0 hours (baseline)
Wettability of sputum sample at 6 hours	Wetability is measured by determining the contact angle the sputum sample makes on a glass surface. The smaller the contact angle, the more the wettability.	Sputum sample will be collected at time = 6 +/-2 hours
Wettability of sputum sample at 24 hours	Wetability is measured by determining the contact angle the sputum sample makes on a glass surface. The smaller the contact angle, the more the wettability.	Sputum sample will be collected at time = 24 +/-2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cough severity	Subjective assessment of change in cough severity using a 0mm to 100mm visual analogue scale (VAS) with 0mm being no cough to 100mm being worse cough ever.	Visual analogue score regarding cough severity will be obtained at time = 0 hours (baseline), and time = 24 hours.
Change in cough frequency and easiness	Subjective assessment of cough frequency and easiness using Breathlessness, Cough and Sputum Scale (BCSS) with score ranging from 0 to 12, 0 being no cough, no difficulty breathing and no trouble due to sputum and 12 being severe difficulty breathing, constant cough and constant trouble due to sputum.	Breathlessness, Cough and Sputum Scale (BCSS) regarding cough frequency and ease will be obtained at time = 0 hours (baseline), and time = 24 hours.
Number of participants with need for escalation of care	Need for escalation of care including non-invasive ventilation (NIV), endotracheal intubation or transfer to higher level of care.	Need for escalation will be documented at any time throughout subject's participation which is upto 24 hours.

Collaborators and Investigators

• Sponsor: Tufts Medical Center
• Collaborators: Virginia Commonwealth University
• Investigators: Principal Investigator: Nicholas Hill, MD, Tufts Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2020
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: December 16, 2019
• First Submitted That Met QC Criteria: January 2, 2020
• First Posted (Actual): January 3, 2020

Study Record Updates

• Last Update Posted (Actual): September 7, 2023
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: sputum; high flow nasal cannula; chronic obstructive pulmonary disease; COPD exacerbation; clearability; wetability
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Chronic Disease; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: IRB#13356

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Currently there is no plan to share IPD.

Drug and device information, study documents

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