Although chronic low-grade inflammation does not cause immediate clinical symptoms, over the longer term, it can enhance other insults or age-dependent damage to organ systems and thereby contribute to age-related disorders, such as respiratory disorders, heart disease, metabolic disorders, autoimmunity, and cancer. However, the molecular mechanisms governing low-level inflammation are largely unknown. We discovered that Bcl-2–interacting killer (Bik) deficiency causes low-level inflammation even at baseline and the development of spontaneous emphysema in female but not male mice. Similarly, a single nucleotide polymorphism that reduced Bik levels was associated with increased inflammation and enhanced decline in lung function in humans. Transgenic expression of Bik in the airways of Bik-deficient mice inhibited allergen- or LPS-induced lung inflammation and reversed emphysema in female mice. Bik deficiency increased nuclear but not cytosolic p65 levels because Bik, by modifying the BH4 domain of Bcl-2, interacted with regulatory particle non-ATPase 1 (RPN1) and RPN2 and enhanced proteasomal degradation of nuclear proteins. Bik deficiency increased inflammation primarily in females because Bcl-2 and Bik levels were reduced in lung tissues and airway cells of female compared with male mice. Therefore, controlling low-grade inflammation by modifying the unappreciated role of Bik and Bcl-2 in facilitating proteasomal degradation of nuclear proteins may be crucial in treating chronic age-related diseases.

In experimental settings, replacing old wood stoves with new wood stoves results in reduced personal exposure to household air pollution. We tested this assumption by measuring PM_2.5 and levoglucosan concentrations inside homes and correlated them with wood stove age. Methods: Thirty homes in the Albuquerque, NM area were monitored over a seven-day period using in-home particulate monitors placed in a common living area during the winter months. Real-time aerosol monitoring was performed, and filter samples were analyzed gravimetrically to calculate PM_2.5 concentrations and chemically to determine concentrations of levoglucosan. A linear regression model with backward stepwise elimination was performed to determine the factors that would predict household air pollution measures. Results: In this sample, 73.3% of the households used wood as their primary source of heating, and 60% burned daily or almost daily. The mean burn time over the test week was 50 ± 38 h, and only one household burned wood 24/day (168 h). The average PM_2.5 concentration (standard deviation) for the 30 homes during the seven-day period was 34.6 µg/m³ (41.3 µg/m³), and median (min, max) values were 15.5 µg/m³ (7.3 µg/m³, 193 µg/m³). Average PM_2.5 concentrations in 30 homes ranged from 0–15 μg/m³ to >100 μg/m³. Maximum PM_2.5 concentrations ranged from 100–200 μg/m³ to >3000 μg/m³. The levoglucosan levels showed a linear correlation with the total PM_2.5 collected by the filters (R² = 0.92). However, neither mean nor peak PM_2.5 nor levoglucosan levels were correlated with the age (10.85 ± 8.54 years) of the wood stove (R² ≤ 0.07, p > 0.23). The final adjusted linear regression model showed that average PM_2.5 was associated with reports of cleaning the flue with a beta estimate of 35.56 (3.47–67.65) and R² = 0.16 (p = 0.04). Discussion: Cleaning the flue and not the wood stove age was associated with household air pollution indices. Education on wood stove maintenance and safe burning practices may be more important in reducing household air pollution than the purchase of new stoves.