Bronchoalveolar Lavage and Response to Cyclophosphamide in Scleroderma Interstitial Lung Disease

Am J Respir Crit Care Med. 2008 Jan 1;177(1):91-8. doi: 10.1164/rccm.200705-655OC. Epub 2007 Sep 27.

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, including 141 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 = 0.04), more severe lung function, including a worse forced vital capacity (P = 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 registered with www.clinicaltrials.gov (NCT 000004563).

Trial registration: ClinicalTrials.gov NCT00004563.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Bronchoalveolar Lavage Fluid / immunology*
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use*
  • Double-Blind Method
  • Eosinophils / drug effects*
  • Eosinophils / immunology
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Leukocyte Count*
  • Lung Diseases, Interstitial / diagnostic imaging
  • Lung Diseases, Interstitial / drug therapy*
  • Lung Diseases, Interstitial / immunology
  • Male
  • Middle Aged
  • Neutrophils / drug effects*
  • Neutrophils / immunology
  • Scleroderma, Systemic / diagnostic imaging
  • Scleroderma, Systemic / drug therapy*
  • Scleroderma, Systemic / immunology
  • Tomography, Spiral Computed
  • Vital Capacity / drug effects

Substances

  • Immunosuppressive Agents
  • Cyclophosphamide

Associated data

  • ClinicalTrials.gov/NCT00004563