Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05616780 |
| Other study ID # |
46246 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 16, 2023 |
| Est. completion date |
May 31, 2023 |
Study information
| Verified date |
March 2024 |
| Source |
Manchester Metropolitan University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Obstructive lung disease is defined by limitations in expiratory airflow, caused by excess
mucus, loss of muscle tone, and structural changes. Over time airflow reduction can lead to
gas trapping in the lungs (hyperinflation). Hyperinflation is linked to diminished exercise
tolerance, shortness of breath, and a poor quality of life. Early treatment options include
inhalers and pulmonary rehabilitation; however, surgical intervention and oxygen therapy may
be required in the later stages. More prompt, accurate diagnosis will help to improve patient
outcomes and optimise their treatment pathways.
Two methodologies used to determine lung volumes and hyperinflation, are nitrogen washout and
body plethysmography. The accuracy of each in defining lung volumes in patients with
obstructive lung disease is debated in literature. Plethysmography requires the patient to
sit in an enclosed box and perform a panting manoeuvre and uses measured changes in volume
and pressure to derive lung volumes. Plethysmography has been suggested to overestimate lung
volumes in patients with obstructive lung disease. On the other hand, nitrogen washout relies
on 'washing out' all the nitrogen from the lungs to calculate lung volumes. Gas trapping and
poor airflow circulation that occurs in patients with airflow obstruction may lead to
underestimated lung volumes.
This study will aim to investigate if there is a significant difference between lung volumes
obtained by both nitrogen washout and body plethysmography in patients with obstructive lung
disease. Subjects with mild, moderate, severe, and very severe obstruction, including those
with no obstruction for comparison will be included, with approximately 10 from each group.
They will be asked if they consent to undergo an extra test during their routine hospital
appointment, which will add ~15 minutes to their visit.
Description:
Obstructive lung disease is defined by limitations in expiratory airflow, caused by excess
mucus, loss of muscle tone, and structural changes. Over time airflow reduction can lead to
gas trapping in the lungs (hyperinflation). Hyperinflation is linked to diminished exercise
tolerance, shortness of breath, and a poor quality of life. Early treatment options include
inhalers and pulmonary rehabilitation; however, surgical intervention and oxygen therapy may
be required in the later stages. More prompt, accurate diagnosis will help to improve patient
outcomes and optimise their treatment pathways.
Two methodologies used to determine lung volumes and hyperinflation, are nitrogen washout and
body plethysmography. The accuracy of each in defining lung volumes in patients with
obstructive lung disease is debated in literature. Plethysmography requires the patient to
sit in an enclosed box and perform a panting manoeuvre and uses measured changes in volume
and pressure to derive lung volumes. Plethysmography has been suggested to overestimate lung
volumes in patients with obstructive lung disease. On the other hand, nitrogen washout relies
on 'washing out' all the nitrogen from the lungs to calculate lung volumes. Gas trapping and
poor airflow circulation that occurs in patients with airflow obstruction may lead to
underestimated lung volumes.
This study will aim to investigate if there is a significant difference between lung volumes
obtained by both nitrogen washout and body plethysmography in patients with obstructive lung
disease. Subjects with mild, moderate, severe, and very severe obstruction, including those
with no obstruction for comparison will be included, with approximately 10 from each group.
They will be asked if they consent to undergo an extra test during their routine hospital
appointment, which will add ~15 minutes to their visit.
Expiratory airflow limitation is the hallmark of obstructive pulmonary disease; Parenchymal
remodelling, mucous impaction, oedema, and a decrease of smooth muscle tone all contribute to
the structural and anatomical changes that occur (O'Donnell, 2006). Individuals with
bronchiectasis and chronic obstructive pulmonary disease often have inflammation in their
airways (COPD). Impaired mucociliary clearance and increased mucus production are caused by
inflammation that occurs inside the airway epithelium. Because of increased connective tissue
deposition, the bronchial walls thicken, and the lumen of the airways decrease over time
(Hogg, 2004). Airflow obstruction is defined as a reduction in expiratory airflow when
compared to the total volume of air exhaled and is investigated by a test called spirometry.
The two measurements required to identify obstructive lung disease are FEV1 (forced
expiratory volume in the first second of expiration following a maximal inspiration) and FVC
(forced vital capacity - the maximal amount of air that can be exhaled forcibly following
maximal inhalation). For airflow obstruction to be diagnosed the FEV1/FVC ratio of must be
<70%. The FEV1 percent predicted is then used to determine the severity of obstruction
following this. Spirometry is commonly used to identify the presence of COPD (chronic
obstruction pulmonary disease) or the severity/absence of obstruction in diseases such as
asthma (Eschenbacher, 2016). TLC (total lung capacity) describes the amount of air in the
lungs at maximal inspiration, the expected amount is determined by height, age, weight,
ethnicity and gender. Chest wall deformities, tumours, level of physical activity and the
presence of respiratory disease can all alter an individual's TLC.
Often, as a result of chronic obstructive lung disease, hyperinflation occurs which is the
abnormal increase in FRC. This is caused by the imbalance between the reduction in airflow
from the lungs compared to the total volume of the lungs. Changes in elastic properties of
the lungs and impaired inspiratory muscle function also contribute to the extent of
hyperinflation over time (Gibson, 1996). Hyperinflation is associated with reduced exercise
capacity, dyspnoea and reduced quality of life. Individuals with COPD were found to spend 1/3
of the day standing/walking compared to healthy individuals of the same age who spent around
½ of the day doing so; such physical deconditioning significantly accelerates disease
progression (Cooper, 2009). Treatment and intervention that targets hyperinflation can
improve not only respiratory symptoms but also metabolic parameters and chronic inflammation.
Pulmonary rehabilitation, bronchodilators and oxygen therapy are often utilised, however,
surgical intervention such as lung volume reduction surgery (LVRS) is believed to provide the
most benefit (Criner, 2017). The accuracy of lung volume measurements is vital to determine
if interventional treatment (e.g., bronchodilators, LVRS, supplemental oxygen) have been
successful or if a patient needs surgical intervention.
Methods including body plethysmography, nitrogen washout, helium dilution, and the more novel
radiographic method utilising computed tomography (CT) are used by clinicians to calculate
lung volumes. They produce measurements comprising FRC (functional residual capacity), IC
(inspiratory capacity), and VC (vital capacity) which are used to calculate TLC (Delgado,
2019). Figure 1 gives a schematic of how these values relate to each other. The two methods
that are investigated in this research project are nitrogen washout and body plethysmography.
Nitrogen washout is a gas dilution technique that involves the patient breathing 100% oxygen
through a mouthpiece to remove the nitrogen from the lungs. The mouthpiece has a two-way
valve allowing the patient to breathe in oxygen whilst exhale through a pneumotach that
measures the concentration of nitrogen in the exhaled air until it reaches <1.5% (Wanger,
2005). Body plethysmography measures pressure variations in a chamber with a constant
temperature and volume. The patient must perform several breathing manoeuvres, including
tidal breathing and panting, through a pneumotach inside an air-tight chamber. Chest wall
collapse and expansion alters the pressure within the chamber, this is measured by
transducers and allows lung volume measurements to be taken (Delgado, 2019).
There has long been debate over the accuracy of lung volume measurement techniques, Garfield
et al stated that body plethysmography overestimates lung volumes in patients with airway
obstruction in comparison to CT (Garfield, 2012). Lufti et al more recently stated in their
research gas dilution techniques like nitrogen washout may underestimate TLC in patients with
obstructive lung disease (Lutfi, 2017). One case study looking at lung volumes in a single
patient with obstructive lung disease suggested that plethysmography may falsely elevate lung
volume measurements due to airway resistance and mouth compliance, whereas nitrogen washout
might underestimate volumes due to non-communicative areas of the lungs (Sue, 2013). On the
other hand, another study found, when comparing lung volumes derived from CT to body
plethysmography and helium dilution, in patients with obstructive lung disease, there was a
significant difference between CT and helium dilution but not CT and body plethysmography
(O'Donnell CR, 2010), suggesting plethysmography was the more accurate of the two. As helium
dilution and nitrogen washout both rely on gases mixing to determine lung volumes, perhaps
similar results may be seen if this was repeated using nitrogen washout. To the researcher's
knowledge there has not been a comparison between lung volumes obtained via nitrogen washout
and body plethysmography in patients with varying severities of obstructive lung disease. If
a significant difference is found between the methods, this could aid in choosing the most
appropriate and accurate lung volume measurement tool in patients with obstructive lung
disease. Such findings may shorten appointment times, improve patient treatment pathways and
reduce monetary costs to the hospital. COPD costs the NHS approximately 1.9 billion a year,
earlier intervention and treatment may help to reduce this burden (The_Lancet, 2018).
