title: Pulmonary nontuberculous mycobacterial disease: prospective study of a distinct preexisting syndrome.
abstract: 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.
authors.affiliation: Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892-1684, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Kim
authors.forename: David E
authors.initials: DE
authors.lastname: Greenberg
authors.forename: Mary E
authors.initials: ME
authors.lastname: Ehrmantraut
authors.forename: Shireen V
authors.initials: SV
authors.lastname: Guide
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Shea
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Brown
authors.forename: Milica
authors.initials: M
authors.lastname: Chernick
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Steagall
authors.forename: Connie G
authors.initials: CG
authors.lastname: Glasgow
authors.forename: JingPing
authors.initials: J
authors.lastname: Lin
authors.forename: Clara
authors.initials: C
authors.lastname: Jolley
authors.forename: Lynn
authors.initials: L
authors.lastname: Sorbara
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.forename: Suvimol
authors.initials: S
authors.lastname: Hill
authors.forename: Nilo
authors.initials: N
authors.lastname: Avila
authors.forename: Vandana
authors.initials: V
authors.lastname: Sachdev
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Barnhart
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Anderson
authors.forename: Reginald
authors.initials: R
authors.lastname: Claypool
authors.forename: Dianne M
authors.initials: DM
authors.lastname: Hilligoss
authors.forename: Mary
authors.initials: M
authors.lastname: Garofalo
authors.forename: Alan
authors.initials: A
authors.lastname: Fitzgerald
authors.forename: Sandra
authors.initials: S
authors.lastname: Anaya-O'Brien
authors.forename: Dirk
authors.initials: D
authors.lastname: Darnell
authors.forename: Rosamma
authors.initials: R
authors.lastname: DeCastro
authors.forename: Heather M
authors.initials: HM
authors.lastname: Menning
authors.forename: Stacy M
authors.initials: SM
authors.lastname: Ricklefs
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Porcella
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Olivier
authors.forename: Joel
authors.initials: J
authors.lastname: Moss
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
mesh_terms: 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
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator