Pulmonary Function Using Non-invasive Forced Oscillometry

Study Overview
=================
Brief Summary
-----------------
The purpose of this observational study is to measure pulmonary function in term and preterm infants with and without pulmonary disease including respiratory distress syndrome, bronchopulmonary dysplasia, transient tachypnea of the newborn, meconium aspiration syndrome, and response to treatments given to newborn infants with lung diseases using a non-invasive airway oscillometry system.

Detailed Description
-----------------
TremoFlo™ N-100 (For Investigational Use Only) Airwave Oscillometry System™ (THORASYS Thoracic Medical Systems Inc. Montreal, Quebec, Canada) is a technology for measuring lung mechanics without patient effort. Pulmonary function testing using flow-volume and lung volumes is one of the most widely used tests to objectively measure lung function in adults. Such measurements are dependent on effort and coordination by the patient which is not possible for newborn infants. The minimum age for spirometry is typically 6 years to master the technique. Therefore, newborn infants usually require forced exhalation, flow interruption, and often sedation/anesthesia in order to obtain accurate pulmonary function measurements. Infant pulmonary function testing can be time-consuming and expensive to perform in newborn infants. This has limited the utilization of this potentially informative method of studying lung function. Measurements of lung function will be particularly informative during transition from having lungs filled with fluid during intra-uterine life to having lungs filled with air in extra-uterine life in preterm and term babies without lung disease, as well as in newborn infants with lung diseases including respiratory distress syndrome, bronchopulmonary dysplasia, transient tachypnea of the newborn, meconium aspiration syndrome, and after the effects of treatments given to newborn infants with lung diseases. The TremoFlo device uses the forced oscillation technique during spontaneous infant breathing and notably does not require any sedation to perform. The forced oscillation technique measures lung function by superimposing a gentle multi-frequency airwave onto the infant's respiratory airflow while the infant breathes spontaneously. Only a short period of breathing is required to obtain a reliable measurement of airway resistance and reactance. Oscillometry has been successfully utilized to quantify lung function in asthmatic children and adults with chronic obstructive pulmonary disease, but never previously in infants. This proposal brings this non-invasive technique of measuring lung function to the neonatal population to identify changes in respiratory mechanics between term and pre-term gestations and quantify fluctuations in infant lung function in response to disease progression and therapeutic intervention. The ease of oscillometry that only requires tidal breathing eliminates the need for patient cooperation and maneuvers that previously excluded lung function testing in the neonatal intensive care unit. This proposal will evaluate the feasibility and clinical value of oscillometry in newborns, both to detect changes in premature compared to full-term gestations as well as disease cohorts by introducing functional measures of lung function to bedside care.

Official Title
-----------------
Pulmonary Function Using Non-invasive Forced Oscillometry Respiratory Testing: A Prospective Observational Study

Conditions
-----------------
Infant, Premature, Diseases, Infant, Newborn, Diseases, Bronchopulmonary Dysplasia, Respiratory Distress Syndrome, Newborn, Meconium Aspiration Syndrome, Transient Tachypnea of the Newborn

Intervention / Treatment
-----------------
* Device: Non-invasive forced airway oscillometry


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Infants with gestational age at least 22 weeks at birth Infants off ventilator/continuous positive airway pressure ≥ 12 hours Infants whose parents/legal guardians have provided consent Exclusion Criteria: Infants with major malformation Infants with a neuromuscular condition that affects respiration Infants with terminal illness Infants with a decision made to withhold or limit support

Ages Eligible for Study
-----------------
Minimum Age: 1 Day
Maximum Age: 2 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: This will be a single center prospective observational study with pre-specified Aims and Hypotheses
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Non-invasive forced airway oscillometry<br>Analyze lung function using forced airway oscillometry in preterm infants and term infants with and without lung disease with both cross-sectional and longitudinal comparisons. Aim 1: Lung function in term and preterm infants without lung disease (anticipated n=264) Aim 2: Lung function in preterm infants with respiratory distress syndrome (RDS) who develop bronchopulmonary dysplasia (BPD) and preterm infants with RDS who do not develop BPD (anticipated n=264) Aim 3: Lung function measurements in infants with common neonatal lung diseases (including RDS, BPD, meconium aspiration syndrome, and transient tachypnea of the newborn) and controls without lung disease (anticipated n=570) Aim 4: Lung function in infants with lung disease before and after common therapeutic interventions | Device: Non-invasive forced airway oscillometry<br>* This is a non-invasive device will measure lung function in spontaneously breathing infants. Infants will have a cushioned mask placed on his/her face and the device will take measurements as the infant breathes normally.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the reactance curve (AXR) | AXR as an overall measure of reactance quantified by oscillometry | 40 weeks' postmenstrual age or discharge until 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R7-20 | Difference between resistance at 7 Hz and 20 Hz quantified by oscillometry | 40 weeks' postmenstrual age or discharge until 2 years | 
| R7 | Resistance at 7 Hz quantified by oscillometry | 40 weeks' postmenstrual age or discharge until 2 years | 
| X7 | Reactance at 7 Hz quantified by oscillometry | 40 weeks' postmenstrual age or discharge until 2 years | 
| R11 | Resistance at 11 Hz quantified by oscillometry | 40 weeks' postmenstrual age or discharge until 2 years | 
| R19 | Resistance at 19 Hz quantified by oscillometry | 40 weeks' postmenstrual age or discharge until 2 years | 
| X11 | Reactance at 11 Hz quantified by oscillometry | 40 weeks' postmenstrual age or discharge until 2 years | 
| X19 | Reactance at 19 Hz quantified by oscillometry | 40 weeks' postmenstrual age or discharge until 2 years | 
| Impedance R(f) | Resistance as a function of frequency R(f) quantified by oscillometry | 40 weeks' postmenstrual age or discharge until 2 years | 
| Impedance x(f) | Reactance as a function of frequency x(f) quantified by oscillometry | 40 weeks' postmenstrual age or discharge until 2 years | 
| Resonance frequency | Resonance frequency quantified by oscillometry | 40 weeks' postmenstrual age or discharge until 2 years | 
| Tidal volume | Tidal volume measured in mL/kg quantified by oscillometry | 40 weeks' postmenstrual age or discharge until 2 years | 
| Respiratory rate | Respiratory rate in breaths per minute | 40 weeks' postmenstrual age or discharge until 2 years | 
| Longer-term pulmonary outcomes | Severe morbidity: respiratory support including or CPAP or ventilation or tracheostomy; moderate morbidity: supplemental oxygen; treatment with daily pulmonary medications; ≥2 rehospitalizations for respiratory illness; ≥3 episodes of wheeze ≥2 weeks apart; mild morbidity: treatment with intermittent pulmonary medications; ≥2 episodes of wheeze ≥2 weeks apart; ≥2 medical visits for respiratory illness ≥2 weeks apart; 1 rehospitalization for respiratory illness) | Up to 2 years |