None listed
Conditions
Brief summary
Interstitial lung disease (ILD) is a group of disorders where the lung tissue become damaged and scarred, often resulting in lung fibrosis. This makes it hard for oxygen to get into the lungs, which can make it hard to breathe. Currently there are limited treatment options for breathlessness in ILD. Many patients still experience debilitating breathlessness despite being on maximum treatment. New scientific evidence supports the idea that abnormal signals from nerves in the lungs, muscles and oxygen-sensors contribute to breathlessness in this condition. The purpose of this investigation is to better understand why this happens. We are specifically investigating whether specialized sensors that respond to stretch/pressure in the lungs become hyperactive in people who have ILD. We know these “lung sensors” are important in other lung disease such as asthma but there are few studies in ILD. It is hoped that our work will pave the way for future studies targeting these sensors in order to reduce breathlessness in people with ILD. In this randomised crossover study, participants with fibrotic ILD will attend 3 study visits: Visit one: complete health-related questionnaires, undergo assessment of lung function and be familiarised with study procedures. Visit two and three: Through a nebuliser, participants will be given either fentanyl (to block the “lung sensors”) or 0.9% saline (control). A nebuliser is a machine that converts liquid medication into a fine mist, which is breathed in through a mask or mouthpiece. In this way medication is able to reach the lungs directly. Participants will be given only one type of nebulised medication per visit , the order is randomly chosen. Participants will not be told which one they are receiving. In both experimental visits, a small blood sample will be drawn from a vein in the arm. This is to measure the amount of fentanyl that gets into the blood. Participants will then do an exercise test on a stationary bike. Breathing, blood pressure and heart rate information will be recorded. Participants will be asked about their level of exertion and breathlessness.
Interventions
It is known that peripheral chemoreceptors, lung afferents and skeletal muscle afferents all contribute to the regulation of breathing during physical exertion. Moreover, in chronic obstructive pulmonary disease (COPD), another common cause of exertion-related dyspnoea, there is emerging evidence that the sensitivity of these sensory afferent populations is dysregulated leading to exaggerated respiratory and cardiovascular responses. However, despite such sensory afferent pathways representing a potentially important therapeutic target for ameliorating exertional-dyspnoea in interstitial lung disease (ILD), their role in the control of breathing during exercise in ILD has not been studied. Therefore, our overarching hypothesis is that aberrant activation of chemoreceptors, lung receptor afferents and/or skeletal muscle afferents drives exertional-dyspnoea and limits exercise capacity in patients with fibrotic ILD. In order to test this hypothesis, three inter-related sub-studies will be conducted. This describes the intervention/exposure of sub-study two: Brief name: Effect of pulmonary afferents on dyspnoea and exercise capacity All sessions (familiarisation and experimental visits) will be conducted at the Human Cardiorespiratory Physiology Laboratory, Level 7, Respiratory Physiology Department, Auckland City Hospital, Auckland District Health Board. Each visit will be conducted in a 'one-on-one' setting. 1) Familiarisation visit (~60min): the investigator will explain the nature of the procedures, answer any questions and obtain written informed consent form. Anthropometric (height, weight), demographic, thorough medical history and clinical assessment (Health screening Questionnaire, measurement of oxygen saturation) will be conducted. Questionnaires will be used to assess activity-related dyspnoea (Modified Medical Research Council Dyspnoea Scale) , health related quality of life (King’s Brief Interstitial Lung Disease Questionnaire) , and anxiety and depression (Hospital Anxiety and Depression Scale). Baseline spirometry will be performed according to established guidelines (participants will breathe in and out through a handheld spirometer for approximately 10 seconds while wearing a nose clip). Participant will be familiarised with the study procedure. This consists of: -all measuring instruments will be attached to the participant -participant will be shown the nebuliser. The participant will have brief exposure (i.e nebuliser mask attached to face or use of mouthpiece) to nebulisation of 0.9% saline for the purpose of familiarisation with the mask/mouthpiece, sound of the nebuliser and sensation of mist generated by the nebuliser. -participant will peddle briefly on the exercise ergometer (less than 5 minutes) -the investigator will explain the experiment process 2) Experimental visits (~60min): Participants will attend two visits separated by ~ 7 days. Participants will be given either nebulisation of 100 mcg of fentanyl citrate or nebulisation of control (0.9% saline). The order will be randomised and single blinded. Following treatment venous blood samples for fentanyl will be taken. Samples taken following nebulisation of control will be discarded. Samples taken following nebulisation of fentanyl will be stored in a secure location and only to be analysed if there is a positive result and/or a need to exclude systemic effect. Exactly 10 minutes following nebulisation participants will then perform a symptom-limited incremental cycle exercise test on a cycle ergometer in accordance with international guidelines (ACC/AHA 2002). During the cycle exercise test ventilation will be measured continuously with a oro-nasal mask or mouthpiece (Hans Rudolph). Heart rate will be continuously measured using an electrocardiogram (12-lead). Oxygen saturation will be continuously measured with finger pulse oximeter. During the exercise test blood pressure will be measured during the last 45s of each stage (each stage is 2 minutes) using an automated sphygmomanometer (SunTech). At the end of the exercise participants will be asked about their perceived level of exertion and breathlessness. The investigator (carrying out all trials) is a qualified medical doctor and holds a current Advanced Cardiac Life Support (ACLS) Level 7 certification. The investigator is experienced with all the procedures employed.
Sponsors
University of Auckland
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
• Patients with fibrotic ILD (total lung capacity <80% predicted; FEV1/FVC > 0.7 and standard HRCT criteria (British Thoracic Society guidelines 2008) • Aged 18 years or over
Exclusion criteria
• More than 10 pack year smoking history • Evidence of significant emphysema on CT scan • Pulmonary Sarcoidosis • Currently taking regular inhaled therapy for airways disease • Serious co-morbidities that may contribute to dyspnoea and/or reduce exercise capacity including: o Severe respiratory disease other than ILD (e.g., chronic obstructive pulmonary disease) o Pulmonary hypertension o Severe obesity (Body mass index > 35 kg/m2) o Severe orthopaedic impairment or rheumatologic disease o Significant neurological disease o Infection or pyrexial illness • Presence of any contraindications to cardiopulmonary exercise testing o Unstable angina or recent acute myocardial infarction o Uncontrolled arrhythmias causing symptoms or haemodynamic compromise o Symptomatic severe aortic stenosis o Oxygen saturation <85% at rest on room air o Uncontrolled heart failure o Uncontrolled asthma o Uncontrolled thyroid disorders o Mental impairment leading to inability to cooperate • Current pregnancy • Allergy or intolerance to fentanyl • Use of anti-depressants (i.e monoamine oxidase inhibitors, serotonin reuptake inhibitors, serotonin norephinephrine re-uptake inhibitors) in the last 14 days • Use of opioid medications (eg morphine, fentanyl, oxycodone, hydromorphone, methadone, codeine) in the previous 4 weeks. • Current users of recreational drugs • Current abusers of alcohol • Inability to fully or appropriately provide consent (e.g., language issue, reading capability) • Underlying medical conditions, which in the opinion of the Investigator place the participant at unacceptably high risk for participating in the study.
Outcome results
None listed