Thomas Ritz - US grants

[unreadable] DESCRIPTION (provided by applicant): [unreadable] [unreadable] Breathing training (BT) has long been proposed as an adjunctive treatment for asthma, but little controlled evidence is available on its efficacy. Recently, a hypoventilation training has been recommended that claims improvements in asthma control by raising basal pCO2 levels. Physiological research supports the rationale of the technique, and a number of controlled trials have demonstrated limited benefits of the training. However, because none of these studies has provided evidence for increases in basal pCO2 levels across training, the central assumption of the hypoventilation training idea remains untested. Based on this rationale and the evidence from respiratory physiology, we recently developed and pilot-tested a home-based pCO2 biofeedback assisted BT with a handheld capnometry device for asthma patients. The primary goal of this training was to teach patients how to increase their basal pCO2 levels. The results showed that this procedure was successful in relieving symptoms, improving control of asthma, and reducing diurnal variability of lung function, an objective indicator of asthma severity. We are proposing a 4-year study to systematically assess the efficacy of hypoventilation-based BT as an adjunct treatment for asthma. The study is a randomized, controlled trial comparing the short- and long-term benefits of 5 sessions of hypoventilation training compared to a control intervention of breathing regularity and awareness training. We will randomize a total of 120 asthma patients. The outcome will be evaluated by a multi-level standard measures test battery of asthma control including measures of pathophysiology (peak flow variability, airway inflammation by exhaled nitric oxide, airway hyperreactivity to methacholine, basal lung function), self- reported asthma control and symptoms, and self-medication behavior (bronchodilator use). Effects on, asthma management (corticoid inhaler adherence, perceived control and efficacy of management, perceived triggers), general well-being (perceived health, stress, anxiety, depression), and cardio-respiratory function in daily life (multi-system ambulatory respiratory inductance plethysmography, capnometry, spiromtery) will also be assessed. We expect substantial benefits of the capnometry-assisted breathing training on asthma control, We will also explore the role of improvements in asthma management and general well- being (perceived health, stress, anxious and depressed mood) through training as a mediators of change in asthma control, as well as the potential of exhaled nitric oxide to predict clinically significant change in other asthma control measures throughout therapy. This study will explore the benefits of a novel breathing training for asthma patients added to their regular medication treatment. The trainings aims at reducing hyperventilation, which is known to make asthma worse, but which has not been targeted successfully by prior breathing training methods. We expect our training to improve asthma control, reduce symptoms and medication needs, as well as improve patients' well-being. [unreadable] [unreadable] Public Health Relevance Paragraph: Research suggests that asthma patients may often hyperventilate, which makes their symptoms worse. In this project we will test a breathing training that reduces hyperventilation with the help of a hand-held device that helps patients monitor their breathing. Patients will participate in a four-week intervention with five training sessions and breathing home exercises, which is expected to improve their asthma control and well-being. [unreadable] [unreadable] [unreadable]

Abstract Asthma is a chronic inflammatory airway disease, with an increasing prevalence, that is associated with a substantial burden on quality of life for patients and financial burden on society. Despite progress in the pharmacological treatment, overall asthma control remains unsatisfactory and treatment non-adherence is extremely high. The available research, much of which was conducted by investigators on this proposal, suggests that asthma may be associated with changes in brain structure and biochemistry, as well as increased risk for cognitive impairment and dementia. However, little is known about the impact of asthma on cognitive function and associated central nervous system processes, especially for in middle- to older age patients. Prior research has also not characterized the relationship between key domains of cognitive function and possible changes in brain structure, chemistry, and function specific to asthma. Additionally, the role of biobehavioral factors (such as mood, sleep, or inflammation) and asthma-specific factors (severity, duration, medication, airway inflammation) in explaining some of these deficits in asthma and aging has not been explored. We therefore propose to compare 126 adults 40-69 years old, diagnosed with asthma, and stratified for age (three decades) and asthma severity, with 66 age-matched non-asthmatic controls using cognitive tests that include processing speed, episodic memory, and executive function. Participants will also undergo neuroimaging. Structural magnetic resonance imaging (MRI) will focus on hippocampal volume. Diffusion tensor imaging (DTI) will be used to measure integrity of white matter integrity, which is associated with processing speed. Proton magnetic resonance spectroscopy (1HMRS) will measure metabolites linked to neuronal degeneration (N-acetyl aspartate, NAA) and glial inflammation (myo-inositol, mI). Three functional MRI scans will measure brain activity under different cognitive conditions: (a) a resting state scan to examine functional connectivity of brain networks; (b) a subsequent memory task to assess the role of hippocampal activation in the service of memory encoding, and (c) a modulation task that measures the ability of the cognitive control network to increase brain activity in fronto-parietal regions as task demands increase. We will also examine whether cognitive impairments are mediated by distinct brain changes extrapolated from prior research on aging and pilot research on respiratory disease. In addition, we will study a potential role of depressive mood, sleep quality and systemic inflammation, as well as asthma-relevant variables in mediating these associations. We hypothesize that asthma patients, compared to controls, will demonstrate accelerated brain aging as demonstrated by cognitive deficits and brain changes, which increase in magnitude with older age. Thus, this proposal will provide fundamental information to develop future preventative and intervention efforts to mitigate the potentially adverse effects of asthma on brain and cognition. A multidisciplinary research team with extensive experience in mental health in asthma patients, as well as neuroimaging across the lifespan will conduct the study.