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 Claypool & 12 others Dianne 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

226 Citations (Scopus)

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

Fingerprint

Prospective Studies
Lung
Cystic Fibrosis Transmembrane Conductance Regulator
Nutrition Surveys
Funnel Chest
Mitral Valve Prolapse
Scoliosis
Cytokines
Body Mass Index
Infection
Mycobacterium avium Complex
Mutation
Regulator Genes
Interleukin-12
Mycobacterium
Mitogens
Natural Killer Cells
Healthy Volunteers
Flow Cytometry
Cell Count

Keywords

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

ASJC Scopus subject areas

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

Cite this

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

In: American Journal of Respiratory and Critical Care Medicine, Vol. 178, No. 10, 15.11.2008, p. 1066-1074.

Research output: Contribution to journalArticle

Kim, RD, Greenberg, DE, Ehrmantraut, ME, Guide, SV, Ding, L, Shea, Y, Brown, MR, Chernick, M, Steagall, WK, Glasgow, CG, Lin, J, Jolley, C, Sorbara, L, Raffeld, M, Hill, S, Avila, N, Sachdev, V, Barnhart, LA, Anderson, VL, Claypool, R, Hilligoss, DM, Garofalo, M, Fitzgerald, A, Anaya-O'Brien, S, Darnell, D, DeCastro, R, Menning, HM, Ricklefs, SM, Porcella, SF, Olivier, KN, Moss, J & Holland, SM 2008, 'Pulmonary nontuberculous mycobacterial disease: Prospective study of a distinct preexisting syndrome', American Journal of Respiratory and Critical Care Medicine, vol. 178, no. 10, pp. 1066-1074. https://doi.org/10.1164/rccm.200805-686OC
Kim, Richard D. ; Greenberg, David E. ; Ehrmantraut, Mary E. ; Guide, Shireen V. ; Ding, Li ; Shea, Yvonne ; Brown, Margaret R. ; Chernick, Milica ; Steagall, Wendy K. ; Glasgow, Connie G. ; Lin, JingPing ; Jolley, Clara ; Sorbara, Lynn ; Raffeld, Mark ; Hill, Suvimol ; Avila, Nilo ; Sachdev, Vandana ; Barnhart, Lisa A. ; Anderson, Victoria L. ; Claypool, Reginald ; Hilligoss, Dianne M. ; Garofalo, Mary ; Fitzgerald, Alan ; Anaya-O'Brien, Sandra ; Darnell, Dirk ; DeCastro, Rosamma ; Menning, Heather M. ; Ricklefs, Stacy M. ; Porcella, Stephen F. ; Olivier, Kenneth N. ; Moss, Joel ; Holland, Steven M. / Pulmonary nontuberculous mycobacterial disease : Prospective study of a distinct preexisting syndrome. In: American Journal of Respiratory and Critical Care Medicine. 2008 ; Vol. 178, No. 10. pp. 1066-1074.
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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.",
keywords = "Bronchiectasis, Cystic fibrosis, IFN-γ/IL-12, Immunodeficiency, Leanness",
author = "Kim, {Richard D.} and Greenberg, {David E.} and Ehrmantraut, {Mary E.} and Guide, {Shireen V.} and Li Ding and Yvonne Shea and Brown, {Margaret R.} and Milica Chernick and Steagall, {Wendy K.} and Glasgow, {Connie G.} and JingPing Lin and Clara Jolley and Lynn Sorbara and Mark Raffeld and Suvimol Hill and Nilo Avila and Vandana Sachdev and Barnhart, {Lisa A.} and Anderson, {Victoria L.} and Reginald Claypool and Hilligoss, {Dianne M.} and Mary Garofalo and Alan Fitzgerald and Sandra Anaya-O'Brien and Dirk Darnell and Rosamma DeCastro and Menning, {Heather M.} and Ricklefs, {Stacy M.} and Porcella, {Stephen F.} and Olivier, {Kenneth N.} and Joel Moss and Holland, {Steven M.}",
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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

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