Published ahead of print on August 14, 2008, doi:10.1164/rccm.200805-686OC Am. J. Respir. Crit. Care Med., Volume 178, Number 10, November 2008, 1066-1074 A more recent version of this article appeared on November 15, 2008
Submitted on May 7, 2008 Pulmonary Nontuberculous Mycobacterial Disease: Prospective Study of a Distinct Preexisting SyndromeRichard D Kim1,1 Immunophathogenesis Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA, 2 Translational Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, USA, 3 Department of Laboratory Medicine, Clinical Center, Bethesda, MD, USA, 4 Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA, 5 Pulmonary and Vascular Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, USA, 6 Molecular Pathology Service, National Cancer Institute, Bethesda, MD, USA, 7 Diagnostic Radiology Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA, 8 Cardiology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, USA, 9 Research Technologies Section, Genomics Unit, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, US Department of Health and Human Services, Hamilton, MT, USA * To whom correspondence should be addressed. E-mail: smh{at}nih.gov.
Background: Pulmonary nontuberculous mycobacterial (PNTM) disease is increasing, but predisposing features have been elusive.
Methods: We prospectively enrolled 63 patients with PNTM infection, each of whom had computerized tomography, echocardiogram, pulmonary function, and flow cytometry of peripheral blood. In vitro cytokine production in response to mitogen, lipopolysaccharide, and cytokines was performed. Anthropometric measurements were compared to National Health and Nutrition Examination Survey (NHANES) age and ethnicity-matched female controls extracted from the NHANES 2001-2002 dataset.
Results: Patients were 59.9 ± 9.8 yrs (SD) old, and 5.4 ± 7.9 yrs from diagnosis to enrollment. Patients were 95% female, 91% Caucasian, and 68% lifetime non-smokers. Forty-six were infected with M. avium complex (MAC), M. xenopi, or M. kansasii; 17 were infected with rapidly growing mycobacteria. Female patients were significantly taller (164.7 cm vs. 161.0 cm, p<0.001) and thinner (BMI 21.1 vs. 28.2, p<0.001) than matched NHANES controls, and thinner (BMI 21.1 vs. 26.8, p=0.002) than patients with disseminated NTM infection. Fifty-one percent of patients had scoliosis, 11% pectus excavatum, and 9% mitral valve prolapse, all significantly more than reference populations. Stimulated cytokine production was similar to healthy controls, including the IFN Key words: immunodeficiency, interferon gamma/IL-12, bronchiectasis, leanness, cystic fibrosis
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/IL-12 pathway. CD4+, CD8+, B, and NK cell numbers were normal. Thirty-six percent of patients had mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
Conclusions: Patients with PNTM infection are taller and leaner than controls, with high rates of scoliosis, pectus excavatum, mitral valve prolapse, and CFTR mutations, but without recognized immune defects.
