Pulmonary Measurement Services
As a leading core lab, we help study teams optimize the most appropriate measurement equipment on the market, and provide exceptional overreading, data management and site support services for your trial.
Spirometry is the most widely used pulmonary function measurement to capture efficacy in respiratory studies related to diseases such as Chronic Obstructive Pulmonary Disease (COPD), asthma, and cystic fibrosis. It is also used as a safety end point in other studies to ensure that the lungs are not adversely affected by the drug being researched.
The test procedures include FVC, SVC, IC, and MVV. Among the many indices measured are the common end points: FEV1, FVC, FEV1/FVC, SVC, IC. From the versatile configurability of the spirometer, each study will have its own customized run-time reporting and messaging which includes warnings about technique and protocol violation. Realtime overreading provides experienced measurement-quality feedback and guidance to sites during testing.
Spirometry provides good measurement of the volumes and flow rates of air that can be respired, it cannot measure residual or trapped gas in the lung, distribution of flow rates, diffusion of the gas into and out of the blood, so other techniques are offered where these indices are required.
PEF, FEV1, FEV6 are standard measurements which can be made by the subject at home on a daily basis. Small electronic or mechanical devices are available according to the requirement, and the electronic version can be used in conjunction with an eDiary to prompt for measurement, record values, warn of possible exacerbations and transmit readings in real time.
To assess the effectiveness of small airways in quickly delivering respired gas to the alveoli, a washout technique is offered that determines the clearance time of the lung, over a number of breaths. The inert nitrogen component is substituted in the test gas and the washout behavior of the retained nitrogen characterizes the small airways. This test is useful in determining the severity of CF, obliterative bronchiolitis and disorders associated with environmental or occupational agents. Gas distribution may be used also in COPD studies to measure efficacy.
Dilution, N2 Washout or Plethysmography are the commonly used testing methods. The most common end points are FRC (Functional Residual Capacity), RV (Residual Volume), and TLC (Total Lung Capacity). Other endpoints include LCI (Lung Clearance Index) and VCE (cumulative net volume expired during the multi-breath washout.)
Residual volume (RV), the amount of air that remains in a person’s lungs after fully exhaling, cannot be measured directly using spirometry. We offer two techniques to indirectly measure RV: Gas dilution and body plethysmography. Gas dilution employs a gas which is re-breathed until its concentration stabilizes, allowing the un-respired volume to be calculated from the dilution it causes to the test-gas volume. When trapped gas, which cannot mix with respired gas, needs to be measured, plethysmography is available. This involves the subject sitting in a hermetically sealed chamber and breathing through a spirometer vented to the outside. As the subject breathes, the respired volume is measured along with the pressure in the chamber. Simplistically the pressure in the chamber would drop according to the volume reduction exhaled through the wall. Differences in this equality are caused by compression of trapped thoracic gas the volume of which can be calculated from the difference. Additionally the plethysmograph can introduce a momentary occlusion of the airway with a shutter, and using the instantaneous airway pressure measured, airway resistance (RAW) can be calculated.
To get respired oxygen into the blood, the blood/air membrane which forms the walls of the alveoli has to allow the oxygen to diffuse through it into the surrounding blood-flow. The surface area of the alveolar wall, the wall thickness and the oxygen pressure in the alveoli each influence this process. Since this is the sole objective of the lungs, measuring the capacity of the membrane to diffuse oxygen provides an important index. The technique uses small concentrations of carbon monoxide to diffuse into the blood thus naming the index DLco, Diffusion of the Lung for Carbon Monoxide. The technique also provides indices of Va alveolar volume and KCO diffusing factor, normalized to lung volume. DLco is often used as an inclusion criterion in COPD and IPF studies to assess the degree of severity of the disease. It is also used in respiratory safety studies, for example in inhaled insulin, or drugs which target other areas but might affect respiratory function, e.g. mucoactive agents.
Fractional exhaled nitric oxide (FENO)
Fractional exhaled nitric oxide is a common measurement in asthma studies. The body produces nitric oxide as a vasodilator to increase perfusion in areas of inflammation. This gas can be detected in very small concentrations in the vicinity of such regions. In the trachea and bronchi, inflammation due to asthma will cause an increase in natural levels. Concentrations greater than about 25 ppb in exhaled breath are suggestive of inflammation, which may be caused by asthma. Other causes such as ciliary dyskinesia can also yield elevated concentrations.
Bronchial sensitivity to allergenic agents, a primary cause of asthma, can be tested using a challenge test. The test supplies increasing concentrations of a provocation agent whilst monitoring the effect on bronchoconstriction by spirometry. Agents such as Methacholine, histamine and cold air are used. Abnormal responses correlate with a proneness to asthma.
This test gives a clinic-performed real-life index of how far a subject with a cardiorespiratory disorder can walk in six minutes. The iCardiac implementation of this measurement adheres to the FDA recommended procedure by the use of a wrist worn oximeter and a remote wireless monitor indicating heart rate and saturation. This allows the subject to progress unaided without encouragement and produce a representative distance whilst being continuously monitored for safety. The test is often used in COPD studies to corroborate reported changes due to treatment.
A measurement of maximum inspiratory and expiratory pressure that can be created by the lung. These indices are important when investigating restrictive diseases, neuromuscular disorders and how well a subject would be able to inhale a drug from certain dispensers. Dry powder devices are an example.