Airway mucus plugs are frequently identified on CT scans of patients with COPD with a smoking history without mucus-related symptoms (ie, cough, phlegm silent mucus plugs).
In patients with COPD, ...what are the risk and protective factors associated with silent airway mucus plugs? Are silent mucus plugs associated with functional, structural, and clinical measures of disease?
We identified mucus plugs on chest CT scans of participants with COPD from the COPDGene study. The mucus plug score was defined as the number of pulmonary segments with mucus plugs, ranging from 0 to 18, and categorized into three groups (0, 1-2, and ≥ 3). We determined risk and protective factors for silent mucus plugs and the associations of silent mucus plugs with measures of disease severity using multivariable linear and logistic regression models.
Of 4,363 participants with COPD, 1,739 had no cough or phlegm. Among the 1,739 participants, 627 (36%) had airway mucus plugs identified on CT scan. Risk factors of silent mucus plugs (compared with symptomatic mucus plugs) were older age (OR, 1.02), female sex (OR, 1.40), and Black race (OR, 1.93) (all P values < .01). Among those without cough or phlegm, silent mucus plugs (vs absence of mucus plugs) were associated with worse 6-min walk distance, worse resting arterial oxygen saturation, worse FEV1 % predicted, greater emphysema, thicker airway walls, and higher odds of severe exacerbation in the past year in adjusted models.
Mucus plugs are common in patients with COPD without mucus-related symptoms. Silent mucus plugs are associated with worse functional, structural, and clinical measures of disease. CT scan-identified mucus plugs can complement the evaluation of patients with COPD.
The CDKN2A locus encodes for tumor suppressor genes p16INK4a and p14Arf which are frequently inactivated in human skin tumors. The purpose of this study was to determine the relationship between loss ...of INK4a/Arf activity and inflammation in the development of ultraviolet (UV) radiation‐induced skin tumors. Panels of INK4a/Arf‐/− mice and wild‐type (WT) mice were treated with a single dose of UVB (200 mJ/cm2). For long‐term studies, these mice were irradiated with UVB (200 mJ/cm2) three times weekly for 30 weeks. At the end of the experiment, tissues were harvested from mice and assayed for inflammatory biomarkers and cytokines. A single dose of UVB resulted in a significant increase in reactive oxygen species (ROS) and 8‐dihydroxyguanosine (8‐oxo‐dG) lesions in INK4a/Arf−/− mice compared to WT mice. When subjected to chronic UVB, we found that 100% of INK4a/Arf−/‐ mice had tumors, whereas there were no tumors in WT controls after 24 weeks of UVB exposure. The increase in tumor development correlated with a significant increase in nuclear factor (NF)‐κB, cyclooxygenase‐2 (COX‐2), prostaglandin E2 (PGE2) and its receptors both in UVB‐exposed skin and in the tumors. A significant increase was seen in inflammatory cytokines in skin samples of INK4a/Arf‐/‐ mice following treatment with chronic UVB radiation. Furthermore, significantly more CD11b+Gr1+ myeloid cells were present in UVB‐exposed INK4a/Arf‐/‐ mice compared to WT mice. Our data indicate that by targeting UVB‐induced inflammation, it may be possible to prevent UVB‐induced skin tumors in individuals that carry CDKN2A mutation.
PDF
