Pulmonary nontuberculous mycobacterial disease: Prospective study of a distinct preexisting syndrome

Richard D. Kim, David E. Greenberg, Mary E. Ehrmantraut, Shireen V. Guide, Li Ding, Yvonne Shea, Margaret R. Brown, Milica Chernick, Wendy K. Steagall, Connie G. Glasgow, JingPing Lin, Clara Jolley, Lynn Sorbara, Mark Raffeld, Suvimol Hill, Nilo Avila, Vandana Sachdev, Lisa A. Barnhart, Victoria L. Anderson, Reginald ClaypoolDianne M. Hilligoss, Mary Garofalo, Alan Fitzgerald, Sandra Anaya-O'Brien, Dirk Darnell, Rosamma DeCastro, Heather M. Menning, Stacy M. Ricklefs, Stephen F. Porcella, Kenneth N. Olivier, Joel Moss, Steven M. Holland

Research output: Contribution to journalArticle

240 Scopus citations

Abstract

Rationale: Pulmonary nontuberculous mycobacterial (PNTM) disease is increasing, but predisposing features have been elusive. Objectives: To prospectively determine the morphotype, immunophenotype, and cystic fibrosis transmembrane conductance regulator genotype in a large cohort with PNTM. 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, LPS, and cytokines was performed. Anthropometric measurements were compared with National Health and Nutrition Examination Survey (NHANES) age- and ethnicity-matched female control subjects extracted from the NHANES 2001-2002 dataset. Measurements and Main Results: Patients were 59.9 (±9.8 yr [SD]) old, and 5.4 (±7.9 yr) from diagnosis to enrollment. Patients were 95% female, 91% white, and 68% lifetime nonsmokers. A total of 46 were infected with Mycobacterium avium complex, M. xenopi, or M. kansasii; 17 were infected with rapidly growing mycobacteria. Female patients were significantly taller (164.7 vs. 161.0 cm; P < 0.001) and thinner (body mass index, 21.1 vs. 28.2; P < 0.001) than matched NHANES control subjects, and thinner (body mass index, 21.1 vs. 26.8; P = 0.002) than patients with disseminated non-tuberculous mycobacterial infection. A total of 51% of patients had scoliosis, 11% pectus excavatum, and 9% mitral valve prolapse, all significantly more than reference populations. Stimulated cytokine production was similar to that of healthy control subjects, including the IFN-γ/IL-12 pathway. CD4+, CD8+, B, and natural killer cell numbers were normal. A total of 36% of patients had mutations in the cystic fibrosis transmembrane conductance regulator gene. Conclusions: Patients with PNTM infection are taller and leaner than control subjects, with high rates of scoliosis, pectus excavatum, mitral valve prolapse, and cystic fibrosis transmembrane conductance regulator mutations, but without recognized immune defects.

Original languageEnglish (US)
Pages (from-to)1066-1074
Number of pages9
JournalAmerican journal of respiratory and critical care medicine
Volume178
Issue number10
DOIs
StatePublished - Nov 15 2008

Keywords

  • Bronchiectasis
  • Cystic fibrosis
  • IFN-γ/IL-12
  • Immunodeficiency
  • Leanness

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Fingerprint Dive into the research topics of 'Pulmonary nontuberculous mycobacterial disease: Prospective study of a distinct preexisting syndrome'. Together they form a unique fingerprint.

  • Cite this

    Kim, R. D., Greenberg, D. E., Ehrmantraut, M. E., Guide, S. V., Ding, L., Shea, Y., Brown, M. R., Chernick, M., Steagall, W. K., Glasgow, C. G., Lin, J., Jolley, C., Sorbara, L., Raffeld, M., Hill, S., Avila, N., Sachdev, V., Barnhart, L. A., Anderson, V. L., ... Holland, S. M. (2008). Pulmonary nontuberculous mycobacterial disease: Prospective study of a distinct preexisting syndrome. American journal of respiratory and critical care medicine, 178(10), 1066-1074. https://doi.org/10.1164/rccm.200805-686OC