Abnormal Nasal Nitric Oxide Production, Ciliary Beat Frequency, and Toll-like Receptor Response in Pulmonary Nontuberculous Mycobacterial Disease Epithelium

• Published in: American journal of respiratory and critical care medicine Vol. 187; no. 12; pp. 1374 - 1381
• Main Authors: Fowler, Cedar J., Olivier, Kenneth N., Leung, Janice M., Smith, Caroline C., Huth, Andrea G., Root, Heather, Kuhns, Douglas B., Logun, Carolea, Zelazny, Adrian, Frein, Cathleen A., Daub, Janine, Haney, Carissa, Shelhamer, James H., Bryant, Clare E., Holland, Steven M.
• Format: Journal Article
• Language: English
• Published: New York, NY American Thoracic Society 15.06.2013
• Subjects: Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Bacterial diseases; Biological and medical sciences; Cilia - physiology; Cystic fibrosis; Disease; Dyskinesia; Female; Human bacterial diseases; Humans; Infections; Infectious diseases; Intensive care medicine; Lung Diseases - metabolism; Lung Diseases - microbiology; Lung Diseases - physiopathology; Male; Medical sciences; Middle Aged; Mutation; Mycobacterium Infections, Nontuberculous - metabolism; Mycobacterium Infections, Nontuberculous - physiopathology; Nitric oxide; Nitric Oxide - biosynthesis; Nose; Patients; Pneumology; Respiratory Mucosa - physiopathology; Toll-Like Receptors - physiology; Tuberculosis and atypical mycobacterial infections; Womens health; Lung disease; Intensive care; Beat frequency; Respiratory disease; Toll like receptor; Nasopharynx; Mycobacterial infection; Epithelium; Differential diagnostic; nontuberculous mycobacteria infections; Infection; Nitric oxide; Nose; Production; nasal nitric oxide; Bacteriosis; Toll-like receptors; cilia beat frequency; Frequency response; Resuscitation; Cilia
• ISSN: 1073-449X; 1535-4970; 1535-4970
• DOI: 10.1164/rccm.201212-2197OC

Pulmonary nontuberculous mycobacterial (PNTM) disease has increased over the past several decades, especially in older women. Despite extensive investigation, no consistent immunological abnormalities have been found. Using evidence from diseases such as cystic fibrosis and primary ciliary dyskinesia, in which mucociliary dysfunction predisposes subjects to high rates of nontuberculous mycobacterial disease that increase with age, we investigated correlates of mucociliary function in subjects with PNTM infections and healthy control subjects. To define ex vivo characteristics of PNTM disease. From 2009 to 2012, 58 subjects with PNTM infections and 40 control subjects were recruited. Nasal nitric oxide (nNO) was determined at the time of respiratory epithelial collection. Ciliary beat frequency at rest and in response to Toll-like receptor (TLR) and other agonists was determined using high-speed video microscopy. We found decreased nNO production, abnormally low resting ciliary beat frequency, and abnormal responses to agonists of TLR2, -3, -5, -7/8, and -9 in subjects with PNTM compared with healthy control subjects. The low ciliary beat frequency in subjects with PNTM was normalized ex vivo by augmentation of the NO-cyclic guanosine monophosphate pathway without normalization of their TLR agonist responses. Impaired nNO, ciliary beat frequency, and TLR responses in PNTM disease epithelium identify possible underlying susceptibility mechanisms as well as possible avenues for directed investigation and therapy.