MORE INFLAMMATION THAN LUNG IN EMPHYSEMA

To the Editor :

I believe there may be an error in the computation of quantitative measures of inflammation in emphysema, as described by Retamales and colleagues (1). In their paper, Table 3 reports inflammatory cell numbers, presumably per lung, with macrophages, lymphocytes, CD4 lymphocytes, CD8 lymphocytes, and CD20 lymphocytes all having a multiplier of 10¹². The numbers of macrophages and CD8 lymphocytes in severe emphysema were 4,000 × 10¹² and 1,400 × 10¹², respectively. Simple arithmetic shows that these values are virtually impossible.

Using round numbers to make the point, a typical lymphocyte approximates 10 µm (0.01 mm, or 0.001 cm, 10³ cm) in diameter. Assuming cubic geometry for computational simplicity, each cell occupies about 10⁹ cm³. Thus, one billion (10 ⁹) cells would occupy about 1 cm³. The volume of 1 L would be occupied by 10¹² cells. Retamales and colleagues report 4,000 times that volume (4,000 L) of macrophages and 1,400 (L) of CD8 lymphocytes in Table 3.

Is it possible that the 10¹² exponent is incorrect, and that it should be 10 ⁹ or something smaller? Even at a 10⁹ multiplier, 4 L of macrophages would be physically impossible.

This arithmetic question aside, the authors are to be commended for their careful quantitative histology and morphometry, the intriguing link between adenoviral infection and emphysema severity, and the important and notable (2) insights for the pathogenesis of severe obstructive lung disease.

Asthma, Allergy, and Airway Research Center, Pittsburgh, Pennsylvania

1. Retamales I, Elliott WM, Meshi B, Coxson HO, Pare PD, Sciurba FC, Rogers RM, Hayashi S, Hogg JC. Amplification of inflammation in emphysema and its association with latent adenoviral infection. Am J Respir Crit Care Med 2001; 164: 469-473 [Abstract/Free Full Text].

2. Shapiro SD. End-stage chronic obstructive pulmonary disease. The cigarette is burned out but inflammation rages on. Am J Respir Crit Care Med 2001; 164: 339-340 [Free Full Text].

From the Authors:

We write in reply to Dr. Calhoun's inquiry concerning our estimates of the number of inflammatory cells in the lungs of patients with severe COPD (1). The quantitative approach that we used is designed to calculate the fraction of the tissue and airspace taken up by a particular cell type. This volume fraction was converted to a volume of cells by multiplying it by the total volume of tissue and air measured from the preoperative CT scan. The number of cells was then calculated by dividing the calculated total volume of each cell type by previously reported values of the volume of single fixed cells (2). In our initial analysis, we expressed the number of cells per surface area in cm² and then corrected this to number per m² by multiplying by 10 ⁴. Unfortunately, when we expressed the cells as the total number in the lung to account for the fact that the surface area was markedly reduced in severe emphysema, we made a calculation error. When we re-examined the spread sheet after receiving Dr. Calhoun's letter, we discovered (to our chagrin) that this conversion factor was inadvertently carried over, resulting in numbers that were too large by a factor of 10 ⁴. This means that the exponent in column 1 of Table 3 from our paper should be the 8th power rather than the 12th for all the cells except the eosinophils, which should be to the 4th power. We regret any inconvenience this may cause and thank Dr. Calhoun for pointing out that we needed to check our arithmetic. However, our main point that the inflammatory process present in the lungs of patients with severe COPD is amplified compared with persons with similar smoking histories that do not develop airway obstruction is unchanged.

Hospital San Borja-Arriaran, Santiago, Chile

W. Mark Elliott, Bernard Meshi, Harvey O. Coxson, Shizu Havashi, Peter D. Pate, and James C. Hogg

St. Paul's Hospital, Vancouver, Canada

1. Retamales I, Elliott WM, Meshi B, Coxson HO, Pare PD, Sciurba FC, Rogers RM, Hayashi S, Hogg JC. Amplification of inflammation in emphysema and its association with latent adenoviral infection. Am J Respir Crit Care Med 2001; 164: 469-473 .

2. Schmid-Schonbein GW, Shih YY, Chien S. Morphometry of human leukocytes. Blood 1980; 56: 866-875 [Abstract/Free Full Text].