Table 1.
Study Population and Biologic Samples
| Parameter | TR: Healthy Nonsmokers | Fourth- to Sixth-Generation Bronchi: Healthy Nonsmokers | SAE* |
||
|---|---|---|---|---|---|
| Healthy Nonsmokers | Healthy Smokers | COPD-S | |||
| n | 27 | 21 | 63 | 73 | 37 |
| Sex, M/F | 17/10 | 15/6 | 40/23 | 53/20 | 28/9 |
| Ethnicity, B/W/O | 15/8/4 | 10/7/4 | 28/24/11 | 45/16/12 | 13/14/11 |
| Age, yr | 40 ± 8 | 40 ± 8 | 40 ± 12 | 43 ± 8 | 52 ± 7 |
| Smoking history | |||||
| Pack-years | — | — | — | 27 ± 16 | 38 ± 24 |
| Nicotine, ng/ml | — | — | — | 1,381 ± 1,624 | 1,680 ± 1,548 |
| Cotinine, ng/ml | — | — | — | 1,325 ± 1,034 | 1,469 ± 625 |
| Lung function† | |||||
| FEV1 | 107 ± 16 | 107 ± 17 | 106 ± 14 | 107 ± 14 | 82 ± 21 |
| FVC | 107 ± 14 | 106 ± 13 | 107 ± 13 | 110 ± 13 | 104 ± 21 |
| FEV1/FVC | 82 ± 5 | 82 ± 5 | 82 ± 6 | 80 ± 5 | 63 ± 7 |
| TLC | 97 ± 13 | 99 ± 13 | 100 ± 13 | 101 ± 12 | 105 ± 19 |
| DlCO | 98 ± 16 | 101 ± 16 | 99 ± 15 | 94 ± 11 | 76 ± 16 |
| Epithelial cells‡ | |||||
| Number recovered, ×106 | 2.2 ± 2.9 | 6.8 ± 2.9 | 6.6 ± 3.0 | 7.5 ± 3.3 | 6.3 ± 2.7 |
| Epithelial cells, % | 99.9 ± 0.2 | 99.7 ± 0.6 | 98.9 ± 1.5 | 98.9 ± 1.4 | 98.3 ± 1.6 |
| Inflammatory cells, % | 0.1 ± 0.2 | 0.3 ± 0.6 | 1.1 ± 1.5 | 1.1 ± 1.4 | 1.7 ± 1.6 |
| Differential cell count | |||||
| Ciliated, % | 48.5 ± 8.6 | 53.6 ± 6.6 | 71.8 ± 8.9 | 64.0 ± 12.0 | 60.1 ± 10.7 |
| Secretory, % | 6.3 ± 3.6 | 9.7 ± 4.0 | 6.8 ± 3.6 | 8.4 ± 4.4 | 11.6 ± 5.7 |
| Basal, % | 27.3 ± 9.2 | 22.6 ± 3.4 | 12.5 ± 6.5 | 14.3 ± 8.0 | 14.7 ± 8.2 |
| Undifferentiated, % | 17.7 ± 6.9 | 14.3 ± 5.0 | 7.8 ± 3.5 | 12.3 ± 6.7 | 11.9 ± 3.8 |
Definition of abbreviations: B = black; COPD-S = smokers with chronic obstructive pulmonary disease; DlCO = diffusing capacity of the lung for carbon monoxide; O = other; SAE = small airway epithelium; TLC = total lung capacity; TR = trachea; W = white.
Data are presented as mean ± SD. For nine of the healthy nonsmokers, TR, bronchial, and SAE samples were from the same subjects; in an additional one, TR and bronchial samples were from the same subject; in an additional nine, TR and SAE samples were from the same subject; and in an additional eight, bronchial and SAE samples were from the same subject.
Nonsmokers (NS) were comparable to healthy smokers (S) and COPD-S with regard to sex (P > 0.3). There were more black subjects among S than in the NS or COPD-S groups (P < 0.04). NS were comparable to S in age and all lung function parameters (P > 0.05 for all comparisons), except for DlCO, which was lower in S (P < 0.03). The number of epithelial cells recovered, percentage of epithelial cells, percentage of inflammatory cells, and percentage of basal cells (BCs) were comparable in S versus NS (P > 0.1). The percentage of ciliated cells was lower, and the percentages of secretory and undifferentiated cells were higher, in S than in NS (P < 0.03). COPD-S were older than NS and S (P < 10−5) and had lower FEV1, FEV1/FVC, and DlCO than NS and S (P < 10−9). TLC and FVC were comparable (P > 0.07). Pack-years of smoking was lower in COPD-S than in S (P < 0.003). The number of epithelial cells recovered, percentage of epithelial cells, percentage of inflammatory cells, and percentage of BCs were comparable in COPD-S versus NS and S (P > 0.05). The percentage of ciliated cells was lower, and the percentages of secretory and undifferentiated cells were higher, in COPD-S (P < 10−5 vs. NS; P > 0.05 vs. S). The percentage of secretory cells was lower in COPD-S than in S (P < 0.003).
Pulmonary function testing parameters are given as percent predicted values, with the exception of FEV1/FVC, which is reported as percentage observed. Values were measured prebronchodilator use in NS and S and post-bronchodilator use in COPD-S.
As a percentage of the TR, bronchial (large airway epithelium [LAE]) or SAE cells recovered. The percentage of inflammatory cells was higher in SAE (all groups) than in TR-NS (P < 0.001) and LAE-NS (P < 0.05). The percentage of ciliated cells was higher in the SAE of nonsmokers (SAE-NS) than in LAE-NS and TR-NS (P < 10−11 for both comparisons) and in LAE-NS than in TR-NS (P < 0.03). The percentage of secretory cells in LAE-NS was higher than in SAE-NS (P < 0.003) and TR-NS (P < 0.004). The percentage of basal cells was higher in TR-NS than in LAE-NS (P < 0.03) and SAE-NS (P < 10−12) and in LAE-NS than in SAE-NS (P < 10−11). The percentage of undifferentiated cells was higher in TR-NS than in SAE-NS and in LAE-NS than in SAE-NS (P < 10−4 for both comparisons).