Bronchoalveolar lavage and response to cyclophosphamide in scleroderma interstitial lung disease

Charlie Strange, Marcy B. Bolster, Michael D. Roth, Richard M. Silver, Arthur Theodore, Jonathan Goldin, Philip Clements, Joanie Chung, Robert M. Elashoff, Robert Suh, Edwin A. Smith, Daniel E. Furst, Donald P. Tashkin, Philip J. Clements, Robert Elashoff, Michael Roth, Daniel Furst, Ken Bulpitt, Dinesh Khanna, Wen Ling Joanie Chung & 80 others Sherrie Viasco, Mildred Sterz, Lovlette Woolcock, Xiaohong Yan, Judy Ho, Sarinnapha Vasunilashorn, Irene Da Costa, James R. Seibold, David J. Riley, Judith K. Amorosa, Vivien M. Hsu, Deborah A. McCloskey, Julianne E. Wilson, John Varga, Dean Schraufnagel, Andrew Wilbur, David Lapota, Shiva Arami, Patricia Cole-Saffold, Robert Simms, Peter Clarke, Joseph Korn, Kimberley Tobin, Melynn Nuite, Richard Silver, Marcie Bolster, Steve Schabel, Edwin Smith, June Arnold, Katie Caldwell, Michael Bonner, Robert A Wise, Fredrick Wigley, Barbara White, Laura Hummers, Mark Bohlman, Albert Polito, Gwen Leatherman, Edrick Forbes, Marie Daniel, Virginia Steen, Charles Read, Cirrelda Cooper, Sean Wheaton, Anise Carey, Adriana Ortiz, Maureen Mayes, Ed Parsley, Sandra Oldham, Tan Filemon, Samantha Jordan, Marilyn Perry, Kari Connolly, Jeffrey Golden, Paul Wolters, Richard Webb, John Davis, Christine Antolos, Carla Maynetto, Naomi Rothfield, Mark Metersky, Richard Cobb, Macha Aberles, Fran Ingenito, Elena Breen, Kamal Mubarak, Jose L. Granda, Joseph Silva, Zora Injic, Ronika Alexander, Steven Springmeyer, Steven Kirkland, Jerry Molitor, Richard Hinke, Amanda Mondt, Mitchell Olman, Barri Fessler, Colleen Sanders, Louis Heck, Tina Parkhill

Research output: Contribution to journalArticle

Abstract

Rationale: The presence of inflammatory cells on bronchoalveolar lavage is often used to predict disease activity and the need for therapy in systemic sclerosis-associated interstitial lung disease. Objectives: To evaluate whether lavage cellularity identifies distinct subsets of disease and/or predicts cyclophosphamide responsiveness. Methods: Patients underwent baseline lavage and/or high-resolution computed tomography as part of a randomized placebo-controlled trial of cyclophosphamide versus placebo (Scleroderma Lung Study) to determine the effect of therapy on forced vital capacity. Patients with 3% or greater polymorphonuclear and/or 2% or greater eosinophilic leukocytes on lavage and/or ground-glass opacification on computed tomography were eligible for enrollment. Measurements and Main Results: Lavage was performed in 201 individuals, including141 of the 158 randomized patients. Abnormal cellularity was present in 101 of these cases (71.6%) and defined a population with a higher percentage of men (P 5 0.04), more severe lung function, including a worse forced vital capacity (P 5 0.003), worse total lung capacity (P = 0.005) and diffusing capacity of the lung for carbon monoxide (P = 0.004), more extensive ground-glass opacity (P = 0.005), and more extensive fibrosis in the right middle lobe (P = 0.005). Despite these relationships, the presence or absence of an abnormal cell differential was not an independent predictor of disease progression or response to cyclophosphamide at 1 year (P = not significant). Conclusions: The presence of an abnormal lavage in the Scleroderma Lung Study defined patients with more advanced interstitial lung disease but added no additional value to physiologic and computed tomography findings as a predictor of progression or treatment response. Clinical trial registeredwithwww.clinicaltrials.gov (NCT 000004563).

Original languageEnglish (US)
Pages (from-to)91-98
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume177
Issue number1
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

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Therapeutic Irrigation
Interstitial Lung Diseases
Bronchoalveolar Lavage
Cyclophosphamide
Vital Capacity
Tomography
Lung
Glass
Placebos
Lung Volume Measurements
Total Lung Capacity
Systemic Scleroderma
Carbon Monoxide
Disease Progression
Leukocytes
Fibrosis
Therapeutics
Randomized Controlled Trials
Clinical Trials
Population

Keywords

  • Scleroderma lung study
  • Systemic sclerosis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Bronchoalveolar lavage and response to cyclophosphamide in scleroderma interstitial lung disease. / Strange, Charlie; Bolster, Marcy B.; Roth, Michael D.; Silver, Richard M.; Theodore, Arthur; Goldin, Jonathan; Clements, Philip; Chung, Joanie; Elashoff, Robert M.; Suh, Robert; Smith, Edwin A.; Furst, Daniel E.; Tashkin, Donald P.; Clements, Philip J.; Elashoff, Robert; Roth, Michael; Furst, Daniel; Bulpitt, Ken; Khanna, Dinesh; Chung, Wen Ling Joanie; Viasco, Sherrie; Sterz, Mildred; Woolcock, Lovlette; Yan, Xiaohong; Ho, Judy; Vasunilashorn, Sarinnapha; Da Costa, Irene; Seibold, James R.; Riley, David J.; Amorosa, Judith K.; Hsu, Vivien M.; McCloskey, Deborah A.; Wilson, Julianne E.; Varga, John; Schraufnagel, Dean; Wilbur, Andrew; Lapota, David; Arami, Shiva; Cole-Saffold, Patricia; Simms, Robert; Clarke, Peter; Korn, Joseph; Tobin, Kimberley; Nuite, Melynn; Silver, Richard; Bolster, Marcie; Schabel, Steve; Smith, Edwin; Arnold, June; Caldwell, Katie; Bonner, Michael; Wise, Robert A; Wigley, Fredrick; White, Barbara; Hummers, Laura; Bohlman, Mark; Polito, Albert; Leatherman, Gwen; Forbes, Edrick; Daniel, Marie; Steen, Virginia; Read, Charles; Cooper, Cirrelda; Wheaton, Sean; Carey, Anise; Ortiz, Adriana; Mayes, Maureen; Parsley, Ed; Oldham, Sandra; Filemon, Tan; Jordan, Samantha; Perry, Marilyn; Connolly, Kari; Golden, Jeffrey; Wolters, Paul; Webb, Richard; Davis, John; Antolos, Christine; Maynetto, Carla; Rothfield, Naomi; Metersky, Mark; Cobb, Richard; Aberles, Macha; Ingenito, Fran; Breen, Elena; Mubarak, Kamal; Granda, Jose L.; Silva, Joseph; Injic, Zora; Alexander, Ronika; Springmeyer, Steven; Kirkland, Steven; Molitor, Jerry; Hinke, Richard; Mondt, Amanda; Olman, Mitchell; Fessler, Barri; Sanders, Colleen; Heck, Louis; Parkhill, Tina.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 177, No. 1, 01.01.2008, p. 91-98.

Research output: Contribution to journalArticle

Strange, C, Bolster, MB, Roth, MD, Silver, RM, Theodore, A, Goldin, J, Clements, P, Chung, J, Elashoff, RM, Suh, R, Smith, EA, Furst, DE, Tashkin, DP, Clements, PJ, Elashoff, R, Roth, M, Furst, D, Bulpitt, K, Khanna, D, Chung, WLJ, Viasco, S, Sterz, M, Woolcock, L, Yan, X, Ho, J, Vasunilashorn, S, Da Costa, I, Seibold, JR, Riley, DJ, Amorosa, JK, Hsu, VM, McCloskey, DA, Wilson, JE, Varga, J, Schraufnagel, D, Wilbur, A, Lapota, D, Arami, S, Cole-Saffold, P, Simms, R, Clarke, P, Korn, J, Tobin, K, Nuite, M, Silver, R, Bolster, M, Schabel, S, Smith, E, Arnold, J, Caldwell, K, Bonner, M, Wise, RA, Wigley, F, White, B, Hummers, L, Bohlman, M, Polito, A, Leatherman, G, Forbes, E, Daniel, M, Steen, V, Read, C, Cooper, C, Wheaton, S, Carey, A, Ortiz, A, Mayes, M, Parsley, E, Oldham, S, Filemon, T, Jordan, S, Perry, M, Connolly, K, Golden, J, Wolters, P, Webb, R, Davis, J, Antolos, C, Maynetto, C, Rothfield, N, Metersky, M, Cobb, R, Aberles, M, Ingenito, F, Breen, E, Mubarak, K, Granda, JL, Silva, J, Injic, Z, Alexander, R, Springmeyer, S, Kirkland, S, Molitor, J, Hinke, R, Mondt, A, Olman, M, Fessler, B, Sanders, C, Heck, L & Parkhill, T 2008, 'Bronchoalveolar lavage and response to cyclophosphamide in scleroderma interstitial lung disease', American Journal of Respiratory and Critical Care Medicine, vol. 177, no. 1, pp. 91-98. https://doi.org/10.1164/rccm.200705-655OC
Strange, Charlie ; Bolster, Marcy B. ; Roth, Michael D. ; Silver, Richard M. ; Theodore, Arthur ; Goldin, Jonathan ; Clements, Philip ; Chung, Joanie ; Elashoff, Robert M. ; Suh, Robert ; Smith, Edwin A. ; Furst, Daniel E. ; Tashkin, Donald P. ; Clements, Philip J. ; Elashoff, Robert ; Roth, Michael ; Furst, Daniel ; Bulpitt, Ken ; Khanna, Dinesh ; Chung, Wen Ling Joanie ; Viasco, Sherrie ; Sterz, Mildred ; Woolcock, Lovlette ; Yan, Xiaohong ; Ho, Judy ; Vasunilashorn, Sarinnapha ; Da Costa, Irene ; Seibold, James R. ; Riley, David J. ; Amorosa, Judith K. ; Hsu, Vivien M. ; McCloskey, Deborah A. ; Wilson, Julianne E. ; Varga, John ; Schraufnagel, Dean ; Wilbur, Andrew ; Lapota, David ; Arami, Shiva ; Cole-Saffold, Patricia ; Simms, Robert ; Clarke, Peter ; Korn, Joseph ; Tobin, Kimberley ; Nuite, Melynn ; Silver, Richard ; Bolster, Marcie ; Schabel, Steve ; Smith, Edwin ; Arnold, June ; Caldwell, Katie ; Bonner, Michael ; Wise, Robert A ; Wigley, Fredrick ; White, Barbara ; Hummers, Laura ; Bohlman, Mark ; Polito, Albert ; Leatherman, Gwen ; Forbes, Edrick ; Daniel, Marie ; Steen, Virginia ; Read, Charles ; Cooper, Cirrelda ; Wheaton, Sean ; Carey, Anise ; Ortiz, Adriana ; Mayes, Maureen ; Parsley, Ed ; Oldham, Sandra ; Filemon, Tan ; Jordan, Samantha ; Perry, Marilyn ; Connolly, Kari ; Golden, Jeffrey ; Wolters, Paul ; Webb, Richard ; Davis, John ; Antolos, Christine ; Maynetto, Carla ; Rothfield, Naomi ; Metersky, Mark ; Cobb, Richard ; Aberles, Macha ; Ingenito, Fran ; Breen, Elena ; Mubarak, Kamal ; Granda, Jose L. ; Silva, Joseph ; Injic, Zora ; Alexander, Ronika ; Springmeyer, Steven ; Kirkland, Steven ; Molitor, Jerry ; Hinke, Richard ; Mondt, Amanda ; Olman, Mitchell ; Fessler, Barri ; Sanders, Colleen ; Heck, Louis ; Parkhill, Tina. / Bronchoalveolar lavage and response to cyclophosphamide in scleroderma interstitial lung disease. In: American Journal of Respiratory and Critical Care Medicine. 2008 ; Vol. 177, No. 1. pp. 91-98.
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abstract = "Rationale: The presence of inflammatory cells on bronchoalveolar lavage is often used to predict disease activity and the need for therapy in systemic sclerosis-associated interstitial lung disease. Objectives: To evaluate whether lavage cellularity identifies distinct subsets of disease and/or predicts cyclophosphamide responsiveness. Methods: Patients underwent baseline lavage and/or high-resolution computed tomography as part of a randomized placebo-controlled trial of cyclophosphamide versus placebo (Scleroderma Lung Study) to determine the effect of therapy on forced vital capacity. Patients with 3{\%} or greater polymorphonuclear and/or 2{\%} or greater eosinophilic leukocytes on lavage and/or ground-glass opacification on computed tomography were eligible for enrollment. Measurements and Main Results: Lavage was performed in 201 individuals, including141 of the 158 randomized patients. Abnormal cellularity was present in 101 of these cases (71.6{\%}) and defined a population with a higher percentage of men (P 5 0.04), more severe lung function, including a worse forced vital capacity (P 5 0.003), worse total lung capacity (P = 0.005) and diffusing capacity of the lung for carbon monoxide (P = 0.004), more extensive ground-glass opacity (P = 0.005), and more extensive fibrosis in the right middle lobe (P = 0.005). Despite these relationships, the presence or absence of an abnormal cell differential was not an independent predictor of disease progression or response to cyclophosphamide at 1 year (P = not significant). Conclusions: The presence of an abnormal lavage in the Scleroderma Lung Study defined patients with more advanced interstitial lung disease but added no additional value to physiologic and computed tomography findings as a predictor of progression or treatment response. Clinical trial registeredwithwww.clinicaltrials.gov (NCT 000004563).",
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T1 - Bronchoalveolar lavage and response to cyclophosphamide in scleroderma interstitial lung disease

AU - Strange, Charlie

AU - Bolster, Marcy B.

AU - Roth, Michael D.

AU - Silver, Richard M.

AU - Theodore, Arthur

AU - Goldin, Jonathan

AU - Clements, Philip

AU - Chung, Joanie

AU - Elashoff, Robert M.

AU - Suh, Robert

AU - Smith, Edwin A.

AU - Furst, Daniel E.

AU - Tashkin, Donald P.

AU - Clements, Philip J.

AU - Elashoff, Robert

AU - Roth, Michael

AU - Furst, Daniel

AU - Bulpitt, Ken

AU - Khanna, Dinesh

AU - Chung, Wen Ling Joanie

AU - Viasco, Sherrie

AU - Sterz, Mildred

AU - Woolcock, Lovlette

AU - Yan, Xiaohong

AU - Ho, Judy

AU - Vasunilashorn, Sarinnapha

AU - Da Costa, Irene

AU - Seibold, James R.

AU - Riley, David J.

AU - Amorosa, Judith K.

AU - Hsu, Vivien M.

AU - McCloskey, Deborah A.

AU - Wilson, Julianne E.

AU - Varga, John

AU - Schraufnagel, Dean

AU - Wilbur, Andrew

AU - Lapota, David

AU - Arami, Shiva

AU - Cole-Saffold, Patricia

AU - Simms, Robert

AU - Clarke, Peter

AU - Korn, Joseph

AU - Tobin, Kimberley

AU - Nuite, Melynn

AU - Silver, Richard

AU - Bolster, Marcie

AU - Schabel, Steve

AU - Smith, Edwin

AU - Arnold, June

AU - Caldwell, Katie

AU - Bonner, Michael

AU - Wise, Robert A

AU - Wigley, Fredrick

AU - White, Barbara

AU - Hummers, Laura

AU - Bohlman, Mark

AU - Polito, Albert

AU - Leatherman, Gwen

AU - Forbes, Edrick

AU - Daniel, Marie

AU - Steen, Virginia

AU - Read, Charles

AU - Cooper, Cirrelda

AU - Wheaton, Sean

AU - Carey, Anise

AU - Ortiz, Adriana

AU - Mayes, Maureen

AU - Parsley, Ed

AU - Oldham, Sandra

AU - Filemon, Tan

AU - Jordan, Samantha

AU - Perry, Marilyn

AU - Connolly, Kari

AU - Golden, Jeffrey

AU - Wolters, Paul

AU - Webb, Richard

AU - Davis, John

AU - Antolos, Christine

AU - Maynetto, Carla

AU - Rothfield, Naomi

AU - Metersky, Mark

AU - Cobb, Richard

AU - Aberles, Macha

AU - Ingenito, Fran

AU - Breen, Elena

AU - Mubarak, Kamal

AU - Granda, Jose L.

AU - Silva, Joseph

AU - Injic, Zora

AU - Alexander, Ronika

AU - Springmeyer, Steven

AU - Kirkland, Steven

AU - Molitor, Jerry

AU - Hinke, Richard

AU - Mondt, Amanda

AU - Olman, Mitchell

AU - Fessler, Barri

AU - Sanders, Colleen

AU - Heck, Louis

AU - Parkhill, Tina

PY - 2008/1/1

Y1 - 2008/1/1

N2 - Rationale: The presence of inflammatory cells on bronchoalveolar lavage is often used to predict disease activity and the need for therapy in systemic sclerosis-associated interstitial lung disease. Objectives: To evaluate whether lavage cellularity identifies distinct subsets of disease and/or predicts cyclophosphamide responsiveness. Methods: Patients underwent baseline lavage and/or high-resolution computed tomography as part of a randomized placebo-controlled trial of cyclophosphamide versus placebo (Scleroderma Lung Study) to determine the effect of therapy on forced vital capacity. Patients with 3% or greater polymorphonuclear and/or 2% or greater eosinophilic leukocytes on lavage and/or ground-glass opacification on computed tomography were eligible for enrollment. Measurements and Main Results: Lavage was performed in 201 individuals, including141 of the 158 randomized patients. Abnormal cellularity was present in 101 of these cases (71.6%) and defined a population with a higher percentage of men (P 5 0.04), more severe lung function, including a worse forced vital capacity (P 5 0.003), worse total lung capacity (P = 0.005) and diffusing capacity of the lung for carbon monoxide (P = 0.004), more extensive ground-glass opacity (P = 0.005), and more extensive fibrosis in the right middle lobe (P = 0.005). Despite these relationships, the presence or absence of an abnormal cell differential was not an independent predictor of disease progression or response to cyclophosphamide at 1 year (P = not significant). Conclusions: The presence of an abnormal lavage in the Scleroderma Lung Study defined patients with more advanced interstitial lung disease but added no additional value to physiologic and computed tomography findings as a predictor of progression or treatment response. Clinical trial registeredwithwww.clinicaltrials.gov (NCT 000004563).

AB - Rationale: The presence of inflammatory cells on bronchoalveolar lavage is often used to predict disease activity and the need for therapy in systemic sclerosis-associated interstitial lung disease. Objectives: To evaluate whether lavage cellularity identifies distinct subsets of disease and/or predicts cyclophosphamide responsiveness. Methods: Patients underwent baseline lavage and/or high-resolution computed tomography as part of a randomized placebo-controlled trial of cyclophosphamide versus placebo (Scleroderma Lung Study) to determine the effect of therapy on forced vital capacity. Patients with 3% or greater polymorphonuclear and/or 2% or greater eosinophilic leukocytes on lavage and/or ground-glass opacification on computed tomography were eligible for enrollment. Measurements and Main Results: Lavage was performed in 201 individuals, including141 of the 158 randomized patients. Abnormal cellularity was present in 101 of these cases (71.6%) and defined a population with a higher percentage of men (P 5 0.04), more severe lung function, including a worse forced vital capacity (P 5 0.003), worse total lung capacity (P = 0.005) and diffusing capacity of the lung for carbon monoxide (P = 0.004), more extensive ground-glass opacity (P = 0.005), and more extensive fibrosis in the right middle lobe (P = 0.005). Despite these relationships, the presence or absence of an abnormal cell differential was not an independent predictor of disease progression or response to cyclophosphamide at 1 year (P = not significant). Conclusions: The presence of an abnormal lavage in the Scleroderma Lung Study defined patients with more advanced interstitial lung disease but added no additional value to physiologic and computed tomography findings as a predictor of progression or treatment response. Clinical trial registeredwithwww.clinicaltrials.gov (NCT 000004563).

KW - Scleroderma lung study

KW - Systemic sclerosis

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JF - American Journal of Respiratory and Critical Care Medicine

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