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153,154 In addition, particle-related exposures other than cigarette smoking, which similarly complex metal and disrupt iron homeostasis, elevate BHR in a dose-dependent manner

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However, pathological and high-resolution imaging evidence has changed this understanding: progressive destruction and loss of terminal bronchioles can precede alveolar parenchymal destruction or a significant decline in overall lung function, suggesting that SAD may be the initial step in the disease cascade ( This paradigm shift also explains why patients with similar traditional lung function measures exhibit significant differences in the burden of airway structural damage and clinical outcomes

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