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Published ahead of print on October 11, 2002, doi:10.1164/rccm.200208-842OC

Am. J. Respir. Crit. Care Med., Volume 167, Number 5, March 2003, 771-778

A more recent version of this article appeared on March 1, 2003
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Submitted on August 9, 2002
Accepted on October 8, 2002

Bronchoscopic Lung Volume Reduction Using Tissue Engineering Principles

Edward P Ingenito1*, Robert L Berger1, A. Cortney Henderson2, John J Reilly1, Larry Tsai1, and Andrew Hoffman3

1 Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA, 2 Biomedical Engineering, Boston University, Boston, MA, USA, 3 Animal Medicine, Tufts University School of Veterinary Medicine, N. Grafton, MA, USA

* To whom correspondence should be addressed. E-mail: eingenito{at}partners.org.

Bronchoscopic Lung Volume Reduction (BLVR), a minimally invasive procedure based on tissue engineering principles, was performed in six sheep with papain-induced experimental emphysema. Physiologic measurements, at baseline, after formation of emphysema, and at three and nine weeks after BLVR, included lung volumes, diffusing capacity (DLco), pressure-volume relationships for the lung (CL) and chest wall (CWpass), pleural pressures generated during active respiratory muscle contraction (CWact), lung resistance and dynamic elastance. The animal model displayed hyperinflation ({Delta}TLC +8%; {Delta}RV +66%), reduced DLco ({Delta}DLco = -21%) and elevated airway resistance ({Delta}Raw = +76%) that resembled advanced human emphysema. BLVR was well tolerated without complications, and reduced lung volumes ({Delta}TLC -16%; {Delta}RV -55%) in a pattern that resulted in significant improvements in vital capacity ({Delta}VC = 10%). At autopsy, well-organized, peripheral scars associated with tissue contraction were observed at 33 of the 36 (91%) treated sites. There was no evidence of infection, abscess or granuloma formation, or allergic reaction. Scar tissue, generated by BLVR, replaced hyper-inflated lung, reduced overall lung volume, and improved respiratory function safely and consistently. The BLVR technology employed in this study addresses the limitations identified in our prior attempt at bronchoscopic lung volume reduction therapy, and appears safe and effective enough to justify a trial in humans.
Key words: Lung volume reduction, emphysema




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