TY - JOUR
T1 - Pulmonary nontuberculous mycobacterial disease
T2 - Prospective study of a distinct preexisting syndrome
AU - Kim, Richard D.
AU - Greenberg, David E.
AU - Ehrmantraut, Mary E.
AU - Guide, Shireen V.
AU - Ding, Li
AU - Shea, Yvonne
AU - Brown, Margaret R.
AU - Chernick, Milica
AU - Steagall, Wendy K.
AU - Glasgow, Connie G.
AU - Lin, JingPing
AU - Jolley, Clara
AU - Sorbara, Lynn
AU - Raffeld, Mark
AU - Hill, Suvimol
AU - Avila, Nilo
AU - Sachdev, Vandana
AU - Barnhart, Lisa A.
AU - Anderson, Victoria L.
AU - Claypool, Reginald
AU - Hilligoss, Dianne M.
AU - Garofalo, Mary
AU - Fitzgerald, Alan
AU - Anaya-O'Brien, Sandra
AU - Darnell, Dirk
AU - DeCastro, Rosamma
AU - Menning, Heather M.
AU - Ricklefs, Stacy M.
AU - Porcella, Stephen F.
AU - Olivier, Kenneth N.
AU - Moss, Joel
AU - Holland, Steven M.
PY - 2008/11/15
Y1 - 2008/11/15
N2 - 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.
AB - 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.
KW - Bronchiectasis
KW - Cystic fibrosis
KW - IFN-γ/IL-12
KW - Immunodeficiency
KW - Leanness
UR - http://www.scopus.com/inward/record.url?scp=57349187991&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=57349187991&partnerID=8YFLogxK
U2 - 10.1164/rccm.200805-686OC
DO - 10.1164/rccm.200805-686OC
M3 - Article
C2 - 18703788
AN - SCOPUS:57349187991
SN - 1073-449X
VL - 178
SP - 1066
EP - 1074
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 10
ER -