Many respiratory clinical trials require participants to establish responsiveness to bronchodilators as an inclusion criterion. For many years, ATS/ERS guidelines recommended defining a significant response to bronchodilators as a 12% and 200 mL increase in FEV1. In more recent years, some criteria have suggested the use of percent predicted values or z-scores. At MERIT, our spirometry collection platform is highly configurable and allows clients to set cutoffs as needed to comply with guidelines.
Serial spirometry is a common endpoint in respiratory trials, particularly in treatments for COPD. Serial spirometry refers to repeated spirometry measurements over predefined time points. For example, participants might perform spirometry at 30 and 5 minutes pre-dose, followed by 15 minute, 30 minute, and 1, 3, 6, and 12 hours post-dose. This allows for the characterization of lung function over a longer period of time, which may be particularly appropriate for long-acting beta agonist (LABA) and long-acting muscarinic agonist (LAMA) treatments.
Exercise challenges can be used to diagnose asthma, but they are also used as a primary endpoint in clinical trials for Exercise Induced Bronchoconstriction (EIB). For example, it could be used to evaluate the protective effect of a once-daily treatment compared with a twice-daily treatment against EIB. For example, a primary endpoint could be percent decrease from pre-exercise FEV1 following exercise challenge at 12 hours post dose at the end of the treatment period.
Oscillometry (also known as Impulse Oscillometry or IOS) is a method for measuring mechanical properties of the airways, lung tissue, and chest wall during tidal breathing. Oscillometry applies an oscillating pressure signal usually at the mouth. Oscillometry is frequently used in pediatric and elderly populations as it requires minimal patient cooperation and can be performed by patients who are unable to perform spirometry.
Methacholine challenges are a dose-response test where subjects inhale an increasing dose of methacholine chloride solution via nebulizer, performing spirometry within a certain time frame after each dose, until they reach the provocative dose or provocative concentration of methacholine required to cause a 20% drop (PD20 or PC20) in FEV1, which is considered a positive challenge. Methacholine challenge tests are sometimes used to diagnose asthma but are also used in clinical trials to establish bioequivalence. For example, methacholine bronchoprovocation challenges are often the primary endpoint for generic albuterol sulfate studies due to the focus on FEV1.
Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) is used to assess the lung’s ability to transfer gas from inspired air to the bloodstream. DLCO measures the partial pressure difference between inspired and expired carbon monoxide. DLCO may be used in clinical trials of treatments for respiratory diseases such as COPD, Cystic Fibrosis (CF), Asthma, and Interstitial Lung Disease (ILD).
Fractional Exhaled Nitric Oxide (FeNO) is a simple, noninvasive method of measuring airway inflammation, more specifically T2, or allergic/eosinophilic inflammation. FeNO is measured by breathing into a portable device that assesses the level of nitric oxide in the air that is expelled from the lungs. FeNO could be used to predict the likelihood of responsiveness to inhaled corticosteroids (ICS) for population enrichment in clinical trials; for example, inclusion criteria in asthma trials to find responders to ICS.
The 6-minute walk test is a self-paced assessment of a patient’s exercise tolerance and functional capacity. The test requires no specialized equipment and simply asks the patient to walk as far as possible on a flat, hard surface for 6 minutes. Standardized guidelines from the ATS/ERS were first released in 2002 and were updated in 2017. The 6-minute walk test may be used as an endpoint in a number of studies that focus on respiratory diseases including ILD, COPD, idiopathic pulmonary fibrosis, CF, and sarcoidosis. Cardiovascular conditions such as heart failure and peripheral artery disease could be assessed with the 6-minute walk test as well. It might also be used to evaluate impairment from Parkinson’s disease, multiple sclerosis, or spinal atrophy.