Extracellular cadmium in the bronchoalveolar space of long-term tobacco smokers with and without COPD and its association with inflammation

Figures & data

Table 1 Characteristics of the groups of the study cohort

Clinical information	Smokers with COPD	Smokers without COPD	Nonsmokers
Number	12	17	19
Sex, male/female	5/7	8/9	13/6
Smoking (range) (pack years)	40 (20–60)	35 (5–60)	0
Age (range) (years)	61.5 (48–73)*,###	53 (41–65)	54 (41–72)
FEV1 (range) (L)	1.81 (0.94–3.77)***,###	3.10 (2.03–4.96)	3.70 (2.41–4.76)
FEV1 (range) (%pred)	59 (39–98)***,###	93 (80–119)	101 (74–125)
FVC (range) (L)	3.28 (1.6–5.81)*	4.26 (2.67–6.72)	4.36 (2.79–6.30)
FVC (range) (%pred)	85 (59–113)*	92 (75–116)	93 (78–124)
FEV1/FVC (range) (%)	57 (45–65)***,###	76 (71–88)	81 (73–91)
DLCO (range) (mL min^−1)	13.3 (6.46–22.7)***,##	19.8 (11.7–26.6)*	25.4 (17.5–33.0)
DLCO (range) (%pred)	51 (27–78)***,##	74 (50–90)**	90 (67–109)
BAL fluid (range) (10^3 cells/mL)
Total cells	237 (100–1,283)**	342 (118–1,196)***	122 (53–172)
Neutrophils	9 (2–24)**	6 (1–27)***	2 (0–22)
Macrophages	205 (80–1,039)**	307 (107–1,083)*	91 (47–149)
Lymphocytes	12 (0–192)	11 (4–79)	5 (0–40)
Basophils	0 (0–7)	0 (0–1)	0
Eosinophils	2 (0–30)***,#	0 (0–7)	0 (0–4)

Notes: Data are presented as median (range). Comparison between smokers with COPD and healthy nonsmokers:

* P<0.05,

** P<0.01, and

*** P<0.001; comparison between smokers with COPD and smokers without COPD:

# P<0.05,

## P<0.01, and

### P<0.001.

Abbreviations: DL_CO, diffusion capacity; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; BAL, bronchoalveolar lavage.

Figure 1 Concentrations (µg/L) of cadmium (Cd) in cell-free BAL fluid samples from smokers with (n=12) or without (n=17) COPD compared with healthy nonsmokers (n=19).

Notes: Data shown as median with individual values. P-values according to Mann–Whitney U-test.
Abbreviation: BAL, bronchoalveolar lavage.

Figure 2 Relationship between cadmium (Cd) in the airways and inflammatory cells in blood.

Notes: Concentrations of Cd in cell-free BAL fluid samples and (A) neutrophils in blood (all smokers: R=0.46, P=0.03, n=23; smokers with COPD only: R=0.86, P=0.001, n=10) and (B) CD8⁺ T-cells in blood (all smokers: R=0.44, P=0.04, n=21; smokers with COPD only: R=0.41, P=0.24, n=10). All correlations analyzed with Spearman rank correlation test.
Abbreviation: BAL, bronchoalveolar lavage.

Figure 3 Relationship between cadmium (Cd) and messenger RNA for TNF-α in the airways.

Notes: Concentrations of Cd in cell-free BAL fluid and macrophage TNF-α at mRNA levels in BAL cells (all smokers: R=0.60, P=0.03, n=10; smokers with COPD only: R=0.97, P=0.002, n=6). All correlations analyzed with Spearman rank correlation test.

Abbreviations: BAL, bronchoalveolar lavage; MQ, macrophage; TNF-α, tumor necrosis factor alpha.

Figure 4 Relationship between cadmium (Cd) and molecular markers of inflammation in the airways.

Notes: Concentrations of Cd in cell-free BAL fluid samples and (A) IL-6 in sputum (all smokers: R=0.69, P=0.001, n=20; smokers with COPD only: R=0.86, P<0.001, n=11) and (B) IL-8 in sputum (all smokers: R=0.62, P=0.006, n=18; smokers with COPD only: R=0.67, P=0.04, n=10) and (C) MMP-9 in sputum (all smokers: R=0.60, P=0.008, n=18; smokers with COPD only: R=0.64, P=0.048, n=10). All correlations analyzed with Spearman rank correlation test.
Abbreviations: BAL, bronchoalveolar lavage; IL, interleukin.

Figure 5 Effect of cadmium (Cd) on the archetype chemokine IL-8 in macrophage-like cells in vitro.

Notes: Concentrations of IL-8 (median with 25th–75th percentiles, pg/mL) after stimulation of derived macrophages from five different healthy nonsmokers by CdCl₂. The induced increase in IL-8 concentrations correlated with the concentration of CdCl₂ (µM) in a statistically significant manner (R=0.57, P<0.001, duplicate samples, five different donors). Correlation analyzed with Spearman rank correlation test.
Abbreviations: CdCl₂, cadmium chloride; IL, interleukin.