Search

Background/objectives: The association between adverse childhood experiences (ACEs) and asthma severity among United States (US) adults with asthma has not been well documented. In addition, whether gender differences exist in this association has been underexplored. We aimed to examine the prevalence of asthma severity in the US adult population with asthma and investigate the association between ACEs and asthma severity by using data from non-institutionalized US adults with asthma. Methods: This cross-sectional study used data from the Adult 2019 and 2020 Behavioral Risk Factor Surveillance System (BRFSS) Asthma Call-Back Survey (ACBS), a survey of US adults aged 18 years or older in 31 US states and Puerto Rico. A total of 22934 adults with asthma participated in 2019 and 2020 ACBS. The 11 BRFSS ACE variables encompassing abuse and household dysfunction were used as ACE measures. ACE measures were summed up as cumulative ACE scores (continuous) and categorized (zero, one ACE, two ACEs, ≥ three ACEs). Asthma severity was categorized as intermittent or persistent. Weighted logistic regression models were used to assess associations of the cumulative ACE score, categorical ACE measures, and the 11 individual ACE responses with asthma severity controlling confounders. Gender differences were explored by stratifying by gender. Results: The prevalence of persistent asthma among US adults with asthma was 45.3%. The mean cumulative ACE score in adults with intermittent vs. persistent asthma was (2.43 vs. 2.70, p-value < 0.05). About 22% of adults with asthma had no ACEs, 19% had one ACE, 14% had two ACEs, and 45% had three or more ACEs. A one-unit increase in ACEs score was associated with a 5.4% increase in the odds of persistent asthma (adjusted odds ratio, aOR = 1.054 (95% confidence interval, CI = 1.01–1.10). Experiencing ≥ three ACEs compared to no ACEs was associated with 31% increased odds of persistent asthma (aOR = 1.31, 95% CI = 1.01–1.70). Individual ACE items significantly associated with persistent asthma include parent/adult ever touched you sexually (aOR = 1.33, 95% CI = 1.03–1.74), adult tried to make you touch them (aOR = 1.34, 95% CI = 1.01–1.79), any adult forced you to have sex (aOR = 1.44, 95% CI = 1.04–1.20), parental separation/divorce (aOR = 1.31, 95% CI = 1.05–1.63), and household alcohol abuse (aOR = 1.24, 95% CI = 1.01–1.53). In women, experiencing one ACE and ≥ three ACEs (compared to no ACEs) was associated with 51% and 60% increased odds of persistent asthma, respectively (aOR = 1.51, 95% CI = 1.02–2.23; aOR = 1.60, 95% CI = 1.12–2.27). No significant association was observed between ACEs and asthma severity in men; however, experiencing household physical violence (compared to no household physical violence) was associated with persistent asthma in men (aOR = 1.69, 95% CI = 1.18–2.42). Conclusions: In this cross-sectional study of US adults with asthma, exposure to ACEs was associated with higher odds of asthma overall and in women. These findings highlight the importance of preventive strategies and early interventions to reduce ACEs, potentially mitigating asthma’s severity in adulthood.

This study examined the association between caregivers’ self-rated general health, poor physical/mental health days, disease morbidity and asthma control in children from the United States with current asthma. The data analyzed for this study were obtained from 7522 children aged 0–17 years who participated in the 2012–2014, 2015–2017, 2018, and 2019 cycles of the Behavioral Risk Factor Surveillance System Asthma Call-back Survey (ACBS). We employed univariate analysis to describe the study population and weighted binary logistic regression to examine the association of predictors with asthma control. Approximately 50% of the children had uncontrolled asthma. The results show that caregivers who reported fair general health had a 61% higher likelihood of reporting uncontrolled asthma in their children compared to those who reported good/very good/excellent health (adjusted odds ratio [aOR] = 1.61; 95% confidence interval [CI], 1.14–2.26). Poor caregiver general health did not reach statistical significance in predicting uncontrolled asthma (aOR = 1.05, 95% CI, 0.62–1.75). Furthermore, having 1 to 14 poor physical/mental health days ([aOR] = 1.70; 95% CI, 1.28–2.227) and ≥15 poor physical/mental health days (aOR = 1.82, 95% CI, 1.31–2.53) was predictive of uncontrolled asthma in children. Additionally, endorsing one reported disease (aOR = 1.49, 95% CI, 1.15–1.93) and ≥2 diseases (aOR = 1.38, 95% CI, 1.08–1.78) was associated with uncontrolled child asthma. These findings underscore the association between caregivers’ self-reported general health, poor mental/physical health days, disease morbidity and uncontrolled asthma among children from the U.S. with asthma. Pediatricians and child health practitioners should recall the importance of this relationship. To facilitate the identification of caregivers at risk and provide more comprehensive and effective care for children with asthma, healthcare practitioners should utilize every child asthma care encounter to inquire about the overall health of caregivers.

Complementary and Alternative Medicines/Therapies (CAM) are commonly used by US asthma adults, yet little is known about recent trends in their use. Our aim was to report trends in CAM use among US adults with current asthma. We conducted a serial cross-sectional study using nationally representative data from the BRFSS Asthma Call-Back Survey (ACBS) collected between 2008 and 2019 (sample size per cycle, 8222 to 14,227). The exposure was calendar time, as represented by ACBS cycle, while the main outcomes were use of at least one CAM and eleven alternative therapies. We analyzed CAM use overall and by population subgroups based on age, gender, race/ethnicity, income, and daytime and night-time asthma symptoms. Our findings show that there was an increase in the use of at least one CAM from 41.3% in 2008 to 47.9% in 2019 (p-trend < 0.001) and an upward trend in the use of herbs, aromatherapy, yoga, breathing exercises, homeopathy, and naturopathy (p-trend < 0.05). However, the use of vitamins, acupuncture, acupressure, reflexology, and other CAM therapies remained stable (p-trend > 0.05). These trends varied according to population characteristics (age, sex, race, income) and asthma symptoms. In conclusion, our study suggests that CAM use among US adults with current asthma is either increasing or stable, and further studies are needed to explore the factors influencing these trends.

The hallmark of HIV/AIDS is a gradual depletion of CD4 T cells. Despite effective control by antiretroviral therapy (ART), a significant subgroup of people living with HIV (PLHIV) fails to achieve complete immune reconstitution, deemed as immune non-responders (INRs). The mechanisms underlying incomplete CD4 T cell recovery in PLHIV remain unclear. In this study, CD4 T cells from PLHIV were phenotyped and functionally characterized, focusing on their mitochondrial functions. The results show that while total CD4 T cells are diminished, cycling cells are expanded in PLHIV, especially in INRs. HIV-INR CD4 T cells are more activated, displaying exhausted and senescent phenotypes with compromised mitochondrial functions. Transcriptional profiling and flow cytometry analysis showed remarkable repression of mitochondrial transcription factor A (mtTFA) in CD4 T cells from PLHIV, leading to abnormal mitochondrial and T cell homeostasis. These results demonstrate a sequential cellular paradigm of T cell over-activation, proliferation, exhaustion, senescence, apoptosis, and depletion, which correlates with compromised mitochondrial functions. Therefore, reconstituting the mtTFA pathway may provide an adjunctive immunological approach to revitalizing CD4 T cells in ART-treated PLHIV, especially in INRs.

Breast cancer, as the most prevalent cancer in women, is responsible for more than 15% of new cancer cases and about 6.9% of all cancer-related death in the US. A major cause of therapeutic failure in breast cancer is the development of resistance to chemotherapy, especially for triple-negative breast cancer (TNBC). Therefore, how to overcome chemoresistance is the major challenge to improve the life expectancy of breast cancer patients. Our studies demonstrate that TNBC cells surviving the chronic treatment of chemotherapeutic drugs show significantly higher expression of the dual serine/threonine and tyrosine protein kinase (DSTYK) than non-treated parental cells. In our in vitro cellular models, DSTYK knockout via the CRISPR/Cas9-mediated technique results in apoptotic cell death of chemoresistant cells upon drug treatment. Moreover, DSTYK knockout promotes chemotherapeutic drug-induced tumor cell death in an orthotopic mouse model. These findings suggest that DSTYK exerts an important and previously unknown role in promoting chemoresistance. Our studies provide fundamental insight into the role of DSTYK in chemoresistance in TNBC cells and lay the foundation for the development of new strategies targeting DSTYK for improving TNBC therapy.

HIV infection leads to a phenomenon of inflammaging, in which chronic inflammation induces an immune aged phenotype, even in individuals on combined antiretroviral therapy (cART) with undetectable viremia. In this study, we investigated T cell homeostasis and telomeric DNA damage and repair machineries in cART-controlled HIV patients at risk for inflammaging. We found a significant depletion of CD4 T cells, which was inversely correlated with the cell apoptosis in virus-suppressed HIV subjects compared to age-matched healthy subjects (HS). In addition, HIV CD4 T cells were prone to DNA damage that extended to chromosome ends—telomeres, leading to accelerated telomere erosion—a hallmark of cell senescence. Mechanistically, the DNA double-strand break (DSB) sensors MRE11, RAD50, and NBS1 (MRN complex) remained intact, but both expression and activity of the DNA damage checkpoint kinase ataxia-telangiectasia mutated (ATM) and its downstream checkpoint kinase 2 (CHK2) were significantly suppressed in HIV CD4 T cells. Consistently, ATM/CHK2 activation, DNA repair, and cellular functions were also impaired in healthy CD4 T cells following ATM knockdown or exposure to the ATM inhibitor KU60019 in vitro, recapitulating the biological effects observed in HIV-derived CD4 T cells in vivo. Importantly, ectopic expression of ATM was essential and sufficient to reduce the DNA damage, apoptosis, and cellular dysfunction in HIV-derived CD4 T cells. These results demonstrate that failure of DSB repair due to ATM deficiency leads to increased DNA damage and renders CD4 T cells prone to senescence and apoptotic death, contributing to CD4 T cell depletion or dysfunction in cART-controlled, latent HIV infection.