Dr. Olivier’s research focuses on bronchiectasis, a condition that damages the body's ability to clear mucus from the airways and increases risk of severe lung infections by nontuberculous mycobacteria (NTM), which commonly are found in wet environments such as streams, rivers, and marshes. People with inflammatory lung disease such as cystic fibrosis are particularly vulnerable to this condition.
Bronchiectasis and chronic lung infections caused by NTM in the United States are steadily on the rise but difficult to diagnose and treat. NTM lung infection treatment currently requires multiple drugs taken for months or even years. Many patients develop significant intolerance to the drugs, do not respond to standard treatment, or develop recurrent infections after discontinuing therapy.
Dr. Olivier hopes to contribute to reducing the impact of such infections by studying common genetic characteristics of the people who suffer from them, defining how the infections lead to disease, and ultimately developing more effective, efficient treatments.
In collaboration with the NIAID epidemiology unit, Dr. Olivier and colleagues used healthcare claims databases coupled with observational data gathered from patients at the NIH Clinical Center to characterize the increasing prevalence and female predominance of bronchiectasis and NTM, as well as associated healthcare costs and comorbid conditions. They also identified environmental and atmospheric factors associated with NTM disease in high-risk populations such as people with cystic fibrosis and people age 65 years and older.
Dr. Olivier's studies of respiratory ciliary function, conducted through the NIH Rare Diseases Clinical Research Network, led to the discovery of potential defects in nitric oxide synthesis as well as Toll-like receptor signaling associated with altered ciliary beat frequency in patients with idiopathic bronchiectasis and chronic NTM infection. The studies found that these defects can be bypassed in the lab using methods that may have therapeutic potential, such as application of nitric oxide analogs or by signaling downstream with PDE5 inhibitors such as sildenafil.
Multi-site studies conducted by Dr. Olivier and his collaborators seek to address potential genetic risk loci that might explain overlapping characteristics of health conditions such as cystic fibrosis, primary ciliary dyskinesia, connective tissue disorders including Marfan or Ehlers-Danlos syndromes, and immune-related disorders. They also seek to better define host susceptibility and disease pathogenesis through candidate gene analysis coupled with whole exome and whole genome analyses of carefully phenotyped populations.
Dr. Olivier's experiences in evaluating and managing large patient cohorts enrolled in bronchiectasis and mycobacterial natural history protocols, as well as his efforts to foster research partnerships with industry, have allowed assessment of novel therapeutic approaches for treating refractory NTM lung disease, such aerosolized liposomal amikacin for inhalation.