Evaluation of a Respiratory Muscle Training Program Restricting Nasal Breathing With FeelBreathe® Device in COPD Patients
Phase: NA
Conditions: Pulmonary Disease, Chronic Obstructive, Breathing Exercises, Exercise Tolerance
Sponsor: University of Cadiz

Official title: EVALUATION OF A RESPIRATORY MUSCLE TRAINING 
PROGRAM RESTRICTING NASAL BREATHING WITH FEELBREATHE® 
DEVICE IN COPD PATIENTS 
 
Date of the document: 04-04th-2017 
 
 
 

Background 
 
The benefits of pulmonary rehabilitation programs (RP) in chronic obstructive 
pulmonary disease (COPD) patients have been shown and are recognized as an effective 
tool for improving dyspnea, exercise tolerance and quality of life in all the 
guidelines(1)(2)(3).  
 
Inspiratory muscles training (IMT) has been used as a complement added to the 
supervised pulmonary RP and some studies have shown an improvement in the 
inspiratory muscles strength, tolerance to exercise (Oxygen uptake efficiency slope), 
dyspnea and distance walked in the six minutes walking test (6MWT) after a inspiratory 
muscles training program in patients with COPD (4).  
 
The Feelbreathe® device, tested in our study can be used in static and dynamic 
situations (5) and is a nasal ventilatory flow restriction device made by a strip of 
hypoallergenic material (3M Spain, S.A. Medical Specialties / O.E.M.) that is placed 
and adhered under the nostrils impairing the free pass of air through the nose by 
producing resistance to flow. The Feelbreathe® device (FB) has been authorized by the 
Spanish Agency for Medicines and Health Products for application on COPD patients 
(Expedient 521/15/EC. AEMPS-Madrid-Spain-Patent Nº: P200902402).  
 
Previous studies have shown that an increased airflow resistance while breathing 
nasally, during exercise, increases the breathing effort (6) which may potentially 
improve the exercise tolerance (7) and energy efficiency (8). In healthy subjects FB has 
shown changes in lung ventilation, gas exchange and heart rate during exercise with 
improvements on ventilatory efficiency (9). 
 
So, the objective of this study was to assess the effects of a nasal restriction 
device for inspiratory muscle training adding to a rehabilitation program on exercise 
capacity (Oxygen uptake efficiency slope), quality of life, dyspnea and inspiratory 
muscle strength in stable COPD patients. 
 
 
STUDY PROTOCOL AND STATISTICAL ANALYSIS PLAN 
 
Participants 
 
Subjects were recruited from the Pneumology outpatient of the University 
Hospital Puerta del Mar in Cádiz (Spain). Consecutive patients were screened by 
reviewing their charts and by interview. Inclusion criteria were diagnosis of COPD 
according to guidelines criteria (1) (10) with moderate or severe airflow obstruction 
(GOLD 2 or 3)(10), dyspnea grade 2 or greater by mMRC scale and a stable clinical 
condition for at least 2 months. Exclusion criteria were poor compliance, treatment with 
oxygen therapy or non-invasive mechanical ventilation, CO2 retention, medical 
conditions that can produce or increase dyspnea on exercise in addition to COPD 
(cardiovascular, metabolic or other respiratory diseases) or osteoarticular or 
neuromuscular diseases that may limit the correct performance of the 6MWT. A total of 
36 patients were included in this study.  
 

Written informed consent was obtained from all patients before starting the 
study. This clinical trial received ethical approval from the Ethics Committee University 
Hospital Puerta del Mar and met the requirements of the Declaration of Helsinki. 
 
 
Design 
 
Participants were randomly assigned according to a computer-generated 
randomization table to three groups: 1) those who participated in the supervised RP 
using the Feelbreathe® device (FB group), 2) those who participated in the supervised 
RP with oronasal breathing without Feelbreathe® device (ONB group) and, 3) those 
included in the control group (CG) which received standard medical recommendation 
for patients with COPD. 
 
Demographic and clinical data were recorded. Dyspnea was assessed by the 
modified Medical Research Council (mMRC) dyspnea questionnaire (11) and quality of 
life by the COPD Assessment Test (CAT) questionnaire (12). Spirometry was 
performed according to American Thoracic Society criteria (13)(14) {Formatting 
Citation} (Spirometer CPX, Cardinal Health, Hoechberg, Germany). Then, they 
performed a resting electrocardiogram (QRS Universal ECG, QRS, Plymouth, MN, 
USA). PImax was measured during a maximal, static inspiratory effort measured at the 
mouth (Micro RPM, Micro Medical Ltd., Chatham, Kent, UK). PImax was recorded as 
the highest value averaged over 1s from three maneuvers that varied by less than 10% 
and was measured based on three maximal reproducible respiratory efforts. Then, an 
incremental test on treadmill (Technogym Run Race 1400HC, Gambettola, Italy) was 
performed to determine the VO2peak (Circuit Spirometry Vmax 29C, Sensormedics, 
USA).While performing the tests, the cardiac response was measured every 10s (JECG 
12 Canal, Friedberg, Alemania). Blood oxygen saturation percentage (Ear oximeter, 
Hewlett-Packard 47201A, Corvallis, EEUU) and respiratory gas exchange were 
measured every 5 sand breath by breath respectively, throughout the test. Finally, one 
week apart, the patients performed the 6MWT according to the ATS guideline (15). 
 
All tests were performed according to a standardized protocol before starting the 
training and 2 days after its completion. 
 
 
Training program 
 
Participants carried out a supervised RP for 8 weeks, 3 days per week. The 
training sessions lasted 60 minutes and included a warning up phase, a main phase and a 
recovery phase. After each session, Borg's perceived exertion was measured. The RP 
included aerobic exercise on cycle ergometer and on treadmill (progressing since 10’ to 
30’ and since 40 to 75% of the reserve heart rate (RHR) or 6-7 score based on Borg's 
perceived exertion), strengthening of lower and upper limb muscles groups, breathing 
exercises (pursed lip breathing, diaphragmatic and abdominal breathing and 
diaphragmatic mobility) and finally stretching exercises. 
 
In the FB group, for restricted nasal breathing, at the beginning of the training 
program, the small size device was used (4 mm). The size of the device was 
progressively increasing according to the patient adaptation to the 5 or 6 mm device, 

depending on the score on Borg's perceived exertion scale. If the patient has a score 
under 4 after the RP sessions the size of the FB device was increased. 
FB was placed under the nostrils, using sterile gloves and assessing the patient 
did not have mucus or injuries. The device was used during the RP and patients were 
invited to have a physiological breathing by nasal inspirations and mouth expirations.  
 
Statistical Analysis 
Descriptive data of the participants are expressed as mean ± standard deviation 
or number and percentage for continuous and categorical variables respectively. 
Percentage of change (%Change) for each variable was calculated as: 
 
%Change = (mean(Post-test value) – mean(Pre-test value) / mean(Pre-test value)) * 100 
 
Differences among RP (between differences) and between pre- and post RP tests within 
each breathing condition (within differences) were analysed using a Bayesian 
hierarchical model. 6MWT distance, PImax and CAT were considered as continuous 
variables while mMRC dyspnea was treated as an ordinal variable. To analyse 
differences at baseline only a categorical variable indicating the RP (GC, ONB or FB) 
was introduced in the model as predictor. However, to analyse both between and within 
differences RP, time (pre- or post-PR) and their interaction were introduced as predictor 
variables. Due to the sample size in our study we choose to analyse our data using 
Bayesian inference since it has proven to be a proper method of statistical inference for 
small sample size (16)(17). Inference was performed based on the 95% credible interval 
(95% CrI) which contains a range of values where we can be 95% certain that the true 
value lie given the data at hand and the model fitted. The Bayesian hierarchical model 
was fitted using the package brms  for the R programming language for statistical 
computing and graphics (18). All parameters estimated showed a good convergence 
with values of 𝑅̂ = 1 and number of effective sample size > 1000. Further analysis can 
be found in the supplemental file while the code and the dataset to replicate it are stored 
in https://github.com/JorgeDelro/COPD_2_1. 
 
 
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