Pulmonary nontuberculous mycobacterial disease: prospective study of a distinct preexisting syndrome.
BACKGROUND
Pulmonary nontuberculous mycobacterial (PNTM) disease is increasing, but predisposing features have been elusive.


OBJECTIVE
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.


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 nontuberculous 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-gamma/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.
Kim
Richard D
RD
Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892-1684, USA.
Greenberg
David E
DE
Ehrmantraut
Mary E
ME
Guide
Shireen V
SV
Ding
Li
L
Shea
Yvonne
Y
Brown
Margaret R
MR
Chernick
Milica
M
Steagall
Wendy K
WK
Glasgow
Connie G
CG
Lin
JingPing
J
Jolley
Clara
C
Sorbara
Lynn
L
Raffeld
Mark
M
Hill
Suvimol
S
Avila
Nilo
N
Sachdev
Vandana
V
Barnhart
Lisa A
LA
Anderson
Victoria L
VL
Claypool
Reginald
R
Hilligoss
Dianne M
DM
Garofalo
Mary
M
Fitzgerald
Alan
A
Anaya-O'Brien
Sandra
S
Darnell
Dirk
D
DeCastro
Rosamma
R
Menning
Heather M
HM
Ricklefs
Stacy M
SM
Porcella
Stephen F
SF
Olivier
Kenneth N
KN
Moss
Joel
J
Holland
Steven M
SM
D000368:Aged; D001827:Body Height; D016022:Case-Control Studies; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D005260:Female; D005660:Funnel Chest / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009165:Mycobacterium Infections, Nontuberculous / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D018410:Pneumonia, Bacterial / Q000209:etiology*; D011446:Prospective Studies; D012307:Risk Factors; D012600:Scoliosis / Q000150:complications; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects; D013577:Syndrome; D013851:Thinness / Q000150:complications
D019005:Cystic Fibrosis Transmembrane Conductance Regulator