I Richmond, H Booth, C Ward and EH Walters
William Leech Centre for Lung Research, Freeman Hospital, Newcastle upon Tyne, United Kingdom.

We have studied intrasubject variability with respect to counts of immunostained inflammatory cells in snap frozen endobronchial biopsies from a group of patients with clinically mild to moderate stable asthma. Fiberoptic bronchoscopy was used to obtain endobronchial biopsies from the upper and lower lobes in 12 volunteer subjects with asthma on two separate occasions 1 mo apart. During this period there was no significant change in asthma treatment, symptom scores, pulmonary function, or airway hyperresponsiveness. With the aid of immunohistochemistry and interactive image analysis, subepithelial counts for T lymphocytes, T-lymphocyte subsets, and eosinophils were made. There was wide intrasubject variability between anatomic site and with time for all the inflammatory cell counts. In each case the intrasubject variability with time was greater than lobar differences. Power calculations were made to establish the optimal sample size required for each marker. We conclude that even in stable asthma considerable biologic variability compounds sampling variability. Such sources of variability need to be borne in mind when calculating the likely power of intervention studies using biopsy data as end points. Power calculations suggest that approximately 15 subjects would be an optimal number with little advantage in increasing beyond this.

This article has been cited by other articles:

				E. Bacci, S. Cianchetti, M. Bartoli, F. L. Dente, A. Di Franco, B. Vagaggini, and P. Paggiaro Low Sputum Eosinophils Predict the Lack of Response to Beclomethasone in Symptomatic Asthmatic Patients Chest, March 1, 2006; 129(3): 565 - 572. [Abstract] [Full Text] [PDF]

				E. Gamble, Y. Qiu, D. Wang, J. Zhu, A. M. Vignola{dagger}, C. Kroegel, F. Morell, T. T. Hansel, I. D. Pavord, K. F. Rabe, et al. Variability of bronchial inflammation in chronic obstructive pulmonary disease: implications for study design Eur. Respir. J., February 1, 2006; 27(2): 293 - 299. [Abstract] [Full Text] [PDF]

				W. W. Busse, A. Wanner, K. Adams, H. Y. Reynolds, M. Castro, B. Chowdhury, M. Kraft, R. J. Levine, S. P. Peters, and E. J. Sullivan Investigative Bronchoprovocation and Bronchoscopy in Airway Diseases Am. J. Respir. Crit. Care Med., October 1, 2005; 172(7): 807 - 816. [Abstract] [Full Text] [PDF]

				P. Chanez, A. Bourdin, I. Vachier, P. Godard, J. Bousquet, and A. M. Vignola Effects of Inhaled Corticosteroids on Pathology in Asthma and Chronic Obstructive Pulmonary Disease Proceedings of the ATS, November 1, 2004; 1(3): 184 - 190. [Abstract] [Full Text] [PDF]

				D N R Payne, Y Qiu, J Zhu, L Peachey, M Scallan, A Bush, and P K Jeffery Airway inflammation in children with difficult asthma: relationships with airflow limitation and persistent symptoms Thorax, October 1, 2004; 59(10): 862 - 869. [Abstract] [Full Text] [PDF]

				P. Jeffery, S. Holgate, and S. Wenzel Methods for the Assessment of Endobronchial Biopsies in Clinical Research: Application to Studies of Pathogenesis and the Effects of Treatment Am. J. Respir. Crit. Care Med., September 15, 2003; 168(6): S1 - 17. [Full Text] [PDF]

				S. Verbanck, D. Schuermans, M. Paiva, and W. Vincken Nonreversible conductive airway ventilation heterogeneity in mild asthma J Appl Physiol, April 1, 2003; 94(4): 1380 - 1386. [Abstract] [Full Text] [PDF]

				P.K. Jeffery, P. Venge, M.J. Gizycki, I. Egerod, R. Dahl, and P. Faurschou Effects of salmeterol on mucosal inflammation in asthma: a placebo-controlled study Eur. Respir. J., December 1, 2002; 20(6): 1378 - 1385. [Abstract] [Full Text] [PDF]

				B. D. Stone, T. Elias-Todd, J. Parrino, C. Ward, E. H. Walters, J. L. Faul, C. M. Burke, and L. W. Poulter EG-1 POSITIVE EOSINOPHILS IN ASTHMA Am. J. Respir. Crit. Care Med., July 1, 2001; 164(1): 171a - 172. [Full Text] [PDF]

				E.-M. KARJALAINEN, A. LAITINEN, M. SUE-CHU, A. ALTRAJA, L. BJERMER, and L. A. LAITINEN Evidence of Airway Inflammation and Remodeling in Ski Athletes with and without Bronchial Hyperresponsiveness to Methacholine Am. J. Respir. Crit. Care Med., June 1, 2000; 161(6): 2086 - 2091. [Abstract] [Full Text]

				J. L. FAUL, E. A. DEMERS, C. M. BURKE, and L. W. POULTER The Reproducibility of Repeat Measures of Airway Inflammation in Stable Atopic Asthma Am. J. Respir. Crit. Care Med., November 1, 1999; 160(5): 1457 - 1461. [Abstract] [Full Text]

				X. LI, C. WARD, F. THIEN, R. BISH, T. BAMFORD, X. BAO, M. BAILEY, J. W. WILSON, and E. HAYDN WALTERS An Antiinflammatory Effect of Salmeterol, a Long-acting beta 2 Agonist, Assessed in Airway Biopsies and Bronchoalveolar Lavage in Asthma Am. J. Respir. Crit. Care Med., November 1, 1999; 160(5): 1493 - 1499. [Abstract] [Full Text]

				S. LIM, A. JATAKANON, M. JOHN, T. GILBEY, B. J. O'CONNOR, K. F. CHUNG, and P. J. BARNES Effect of Inhaled Budesonide on Lung Function and Airway Inflammation . Assessment by Various Inflammatory Markers in Mild Asthma Am. J. Respir. Crit. Care Med., January 1, 1999; 159(1): 22 - 30. [Abstract] [Full Text]