Incidental thyroid carcinoma in an endemic goiter area in Italy: histopathological features and predictors of a common finding.

PURPOSE: The occurrence and histopathological features of incidental thyroid carcinoma (ITC) vary considerably among populations from different geographical regions. The aim of this study is to assess the prevalence and histopathological characteristics of ITC in patients who underwent thyroid surgery for apparently benign thyroid diseases in an endemic goiter area in Italy. METHODS: A total of 649 consecutive patients (531 females and 118 males; mean age, 52.9 ± 11.0 years), who underwent thyroid surgery at the Endocrine Surgery Unit of the tertiary care "Renato Dulbecco" University Hospital (Catanzaro, Italy) in the period between years 2017 and 2022, were included in this retrospective study. A comprehensive histopathological examination was performed on surgically excised thyroid tissue. Logistic regression analysis was employed to identify potential predictors of ITC. RESULTS: The histopathological examination revealed the presence of ITC in 81 patients, accounting for 12.5% of the total study population. The female to male ratio was found to be 6.4 to 1. Among the patients with ITC, 72 had papillary carcinoma (PTC), with 53 of these tumors being microcarcinomas (microPTC). Additionally, 5 patients had follicular thyroid carcinoma, 2 patients had low-risk follicular cell-derived thyroid neoplasms, 1 patient had an oncocytic carcinoma, and 1 patient had a medullary thyroid carcinoma. Logistic regression analysis demonstrated a significant association between female sex and incidental microPTC. CONCLUSIONS: These findings provide further evidence of the common occurrence of ITC, typically in the form of microPTC, among individuals who undergo thyroid surgery for apparently benign thyroid diseases.

Coexistence of Hashimoto's Thyroiditis in Differentiated Thyroid Cancer: Post-Operative Monitoring of Anti-Thyroglobulin Antibodies and Assessment of Treatment Response.

INTRODUCTION: Differentiated thyroid carcinoma (DTC) is frequently found in conjunction with autoimmune thyroid disorders, particularly Hashimoto's thyroiditis (HT). This study investigates the impact of coexisting HT on the persistence of an indeterminate response to therapy due to positive anti-thyroglobulin antibodies (AbTg), measured via competitive immunoassay, in a consecutive patient series from Calabria, Southern Italy. METHODS: This retrospective longitudinal study analyzed 259 consecutive DTC patients managed at the Endocrinology Unit of Renato Dulbecco Hospital (Catanzaro, Italy) up to 2023. Patients with medullary and undifferentiated thyroid carcinoma, partial thyroidectomy, less than six months of post-operative monitoring, or missing clinical data were excluded. Demographic information, histological findings, initial tumor stage, and ATA risk category were collected. The response to therapy was assessed based on ATA guidelines. RESULTS: Among the 259 patients, 29% had coexisting HT. Patients with HT exhibited distinct characteristics: a higher proportion of females (87.0% vs. 74.7%), a shorter post-operative monitoring duration (median 3 vs. 5 years), and a higher prevalence of papillary thyroid carcinoma (PTC) (97.4% vs. 86.3%). The tumor size, lymph node involvement, and distant metastasis were similar between the groups, with patients without HT having a higher incidence of extrathyroidal tumor extension. However, the initial TNM stage and ATA risk category did not differ significantly. At the six-month follow-up, HT patients showed a higher rate of indeterminate responses, primarily due to positive AbTg. After 12 months, the response categories aligned, with decreasing AbTg levels in the HT group. After 24 months, most patients with long-term follow-up demonstrated an excellent response to DTC therapy, irrespective of HT coexistence. CONCLUSIONS: While HT does not worsen DTC prognosis, it may result in indeterminate responses. AbTg measurements in the peri-operative period should be encouraged to facilitate post-operative monitoring, emphasizing the importance of using standardized assays. Further research in larger populations with extended follow-up is needed to comprehensively understand the HT-DTC relationship.

The anticancer effects of Metformin in the male germ tumor SEM-1 cell line are mediated by HMGA1.

Introduction: Germ cell tumors (GCTs) are the most common type of cancer in young men. These tumors usually originate from the testis, but they can occasionally develop from extragonadal sites probably due to primordial germ cells (PGCs) migration errors. Cisplatin-based chemotherapy is usually effective for male GCTs, but the risk of toxicity is high and new therapeutic strategies are needed. Although Metformin (Met) has been widely studied as a potential cancer treatment over the past decades, there is limited evidence to support its use in treating male GCTs. Additionally, the mechanism by which it acts on tumor cells is still not entirely understood. Methods: SEM-1 cells, a newly established human cell line of extragonadal origin, were treated with Met. Cell viability was studied by MTT assay, while cell migration and invasion were studied by the wound healing assay and the transwell assay, respectively. The effect of Met on 3D spheroid formation was determined by seeding SEM-1 cells in appropriate cell suspension culture conditions, and cell cycle was characterized by flow cytometry. Factors involved in PGCs migration and GCT invasion, such as IGFBP1, IGF1R, MMP-11 and c-Kit, together with cyclin D1 (a key regulator of cell cycle progression), and the upstream factor, HMGA1, were determined by immunoblots. Results: Treatment of SEM-1 cells with Met resulted in a potent and dose-dependent reduction of cell proliferation, as evidenced by decreased nuclear abundance of cyclin D1 and cell cycle arrest in G1 phase. Also, Met prevented the formation of 3D spheroids, and blocked cell migration and invasion by reducing the expression of IGFBP1, IGF1R and MMP-11. Both, IGFBP1 and MMP-11 are under control of HMGA1, a chromatin-associated protein that is involved in the regulation of important oncogenic, metabolic and embryological processes. Intriguingly, an early reduction in the nuclear abundance of HMGA1 occurred in SEM-1 cells treated with Met. Conclusions: Our results document the antiproliferative and antimigratory effects of Met in SEM-1 cells, providing new insights into the potential treatments for male GCTs. The anticancer properties of Met in SEM-1 cells are likely related to its ability to interfere with HMGA1 and downstream targets, including cyclin D1, the IGFs system, and MMP-11.

Oleuropein Counteracts Both the Proliferation and Migration of Intra- and Extragonadal Seminoma Cells.

Recent and growing literature has reported that oleuropein (OLE), the main polyphenol in olive leaf extract, inhibits tumor cell proliferation and reduces the invasiveness properties of cancer cells; therefore, OLE may play a significant role in the development of new drugs for cancer treatment. These antineoplastic properties have been reported in many experimental cancer models, but the effect of OLE on seminoma cells is yet to be evaluated. In the present study, we demonstrate, for the first time, that OLE reduces cell viability in both intra- and extragonadal TCAM-2 and SEM-1 seminoma cells, respectively, in a dose-dependent manner. As shown by Western-blot analysis, OLE exposure reduced cyclin-D1 expression and upregulated p21Cip/WAF1, concomitantly affecting the upstream pathway of NF-κB, leading to the reduction of its nuclear content, thereby suggesting that OLE could modulate cell-cycle regulators by inhibiting NF-κB. Moreover, Annexin V staining revealed that OLE induced apoptosis in cancer cells and upregulated the pro-apoptotic factor BAX. Through wound-healing scratch and transmigration assays, we also demonstrated that OLE significantly reduced the migration and motility of TCAM-2 and SEM-1 cells, and downregulated the expression of TGFß-1, which is known to be the main pro-fibrotic factor involved in the acquisition of the migratory and invasive properties of cancer cells. Collectively, our results indicate that OLE reduces seminoma cell proliferation, promotes apoptosis, and counteracts cell migration and motility. Further studies are needed to explore the molecular mechanisms underlying these observed effects.

Insulin Resistance and Cancer: In Search for a Causal Link.

Insulin resistance (IR) is a condition which refers to individuals whose cells and tissues become insensitive to the peptide hormone, insulin. Over the recent years, a wealth of data has made it clear that a synergistic relationship exists between IR, type 2 diabetes mellitus, and cancer. Although the underlying mechanism(s) for this association remain unclear, it is well established that hyperinsulinemia, a hallmark of IR, may play a role in tumorigenesis. On the other hand, IR is strongly associated with visceral adiposity dysfunction and systemic inflammation, two conditions which favor the establishment of a pro-tumorigenic environment. Similarly, epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNA, in IR states, have been often associated with tumorigenesis in numerous types of human cancer. In addition to these observations, it is also broadly accepted that gut microbiota may play an intriguing role in the development of IR-related diseases, including type 2 diabetes and cancer, whereas potential chemopreventive properties have been attributed to some of the most commonly used antidiabetic medications. Herein we provide a concise overview of the most recent literature in this field and discuss how different but interrelated molecular pathways may impact on tumor development.

Methods to Study Protein-Binding to Pseudogene Transcripts.

One of the most commonly described biological feature of processed pseudogenes is the ability to influence the expression of their parental coding genes. As evidenced in several studies, the high sequence similarity between these RNA pairs sets up a certain level of competition for posttranscriptional regulators, including, among others, RNA-binding proteins (RBPs). RBPs may affect, positively or negatively, the stability of bound mRNAs, so that, if an overexpressed pseudogene competes with its homologous coding gene, the downstream protein synthesis would change, with potential pathological consequences. Given these premises, a rigorous and comprehensive understanding of interactions between pseudogene-parental gene RNA pairs and RBPs could provide further insights into the biological bases of complex diseases, such as cancer, cardiovascular disease, and type 2 diabetes, identifying novel predictive and/or prognostic biomarkers.Herein, we detail easily adaptable protocols of plasmid-based molecular cloning and RNA-electrophoretic mobility shift assay (EMSA) used in our laboratory for determining the interaction between a cytoplasmatic stabilizing protein (αCP1) and the pseudogene-parental gene RNA pair HMGA1-p /HMGA1. We also offer a general overview of RNA immunoprecipitation procedures and present novel bioinformatic tools for predicting RBPs binding sites on pseudogene transcripts.

Daycare attendance and asthma control, Asthma Call-back Survey 2012-2014.

OBJECTIVE: To examine the association between daycare attendance and asthma control among children aged 0 to 4 years with asthma. METHODS: We analyzed 2012-2014 data from the Behavioral Risk Factor Surveillance System Asthma Call-back Survey on 388 children with asthma aged 0 to 4 years with information on daycare attendance in the past 12 months. We calculated weighted prevalence ratios to assess the association between daycare attendance and asthma control (categorized based on day-time and nighttime asthma symptoms, activity limitation, and short-acting beta agonist use). Adjusted models controlled for parent or guardian education, household income, race, sex, cost barriers to asthma care, long-term control medication use, and the number of other children in the child's household. RESULTS: In this sample of children with asthma, representative of 520,400 children in 26 U.S. states, 34% attended daycare in the past 12 months. Only 32% of children who attended daycare in the past 12 months reported having an asthma action plan on file at the daycare they most recently attended. Presence of the asthma triggers of pets, mold, and smoking in a child's daycare were reported to be uncommon. Prevalence of uncontrolled asthma was 44% in children who attended daycare in the past 12 months and 68% in children who did not. The adjusted prevalence ratio between daycare attendance and uncontrolled asthma was 0.96 (95% confidence interval 0.73, 1.25). CONCLUSIONS: When adjusting for covariates, we observed no evidence of an association between daycare attendance in early life and uncontrolled asthma.

The Role of Diet on Insulin Sensitivity.

Growing evidence shows that dietary composition has a marked impact on the risk of developing obesity, type 2 diabetes (T2D), cardiovascular disease (CVD), certain types of endocrine cancer and many other intertwined metabolic and reproductive disorders, all featured by insulin resistance (IR) [...].

MicroRNA-1281 as a Novel Circulating Biomarker in Patients With Diabetic Retinopathy.

Objective: Recently, the role of circulating miRNAs as non-invasive biomarkers for the identification and monitoring of diabetes microvascular complications has emerged. Herein, we aimed to: identify circulating miRNAs differentially expressed in patients with and without diabetic retinopathy (DR); examine their predictive value; and understand their pathogenic impact. Methods: Pooled serum samples from randomly selected matched patients with type 2 diabetes, either with or without DR, were used for initial serum miRNA profiling. Validation of the most relevant miRNAs was thereafter conducted by RT-qPCR in an extended sample of patients with DR and matched controls. Results: Following miRNA profiling, 43 miRNAs were significantly up- or down-regulated in patients with DR compared with controls. After individual validation, 5 miRNAs were found significantly overexpressed in patients with DR. One of them, miR-1281, was the most up-regulated and appeared to be specifically related to DR. Furthermore, secreted levels of miR-1281 were increased in high glucose-cultured retinal cells, and there was evidence of a potential link between glucose-induced miR-1281 up-regulation and DR. Conclusion: Our findings suggest miR-1281 as a circulating biomarker of DR. Also, they highlight the pathogenic significance of miR-1281, providing insights for a new potential target in treating DR.

Mediterranean Diet Nutrients to Turn the Tide against Insulin Resistance and Related Diseases.

Insulin resistance (IR), defined as an attenuated biological response to circulating insulin, is a fundamental defect in obesity and type 2 diabetes (T2D), and is also linked to a wide spectrum of pathological conditions, such as non-alcoholic fatty liver disease (NAFLD), cognitive impairment, endothelial dysfunction, chronic kidney disease (CKD), polycystic ovary syndrome (PCOS), and some endocrine tumors, including breast cancer. In obesity, the unbalanced production of pro- and anti-inflammatory adipocytokines can lead to the development of IR and its related metabolic complications, which are potentially reversible through weight-loss programs. The Mediterranean diet (MedDiet), characterized by high consumption of extra-virgin olive oil (EVOO), nuts, red wine, vegetables and other polyphenol-rich elements, has proved to be associated with greater improvement of IR in obese individuals, when compared to other nutritional interventions. Also, recent studies in either experimental animal models or in humans, have shown encouraging results for insulin-sensitizing nutritional supplements derived from MedDiet food sources in the modulation of pathognomonic traits of certain IR-related conditions, including polyunsaturated fatty acids from olive oil and seeds, anthocyanins from purple vegetables and fruits, resveratrol from grapes, and the EVOO-derived, oleacein. Although the pharmacological properties and clinical uses of these functional nutrients are still under investigation, the molecular mechanism(s) underlying the metabolic benefits appear to be compound-specific and, in some cases, point to a role in gene expression through an involvement of the nuclear high-mobility group A1 (HMGA1) protein.

First Trimester Combined Test (FTCT) as a Predictor of Gestational Diabetes Mellitus.

Background-The first trimester combined test (FTCT) is an effective screening tool to estimate the risk of fetal aneuploidy. It is obtained by the combination of maternal age, ultrasound fetal nuchal translucency (NT) measurement, and the maternal serum markers free ß-human chorionic gonadotropin (ß-hCG) and pregnancy-associated plasma protein A (PAPP-A). However, conflicting data have been reported about the association of FTCT, ß-hCG, or PAPP-A with the subsequent diagnosis of gestational diabetes mellitus (GDM). Research design and methods-2410 consecutive singleton pregnant women were retrospectively enrolled in Calabria, Southern Italy. All participants underwent examinations for FTCT at 11-13 weeks (plus 6 days) of gestation, and screening for GDM at 16-18 and/or 24-28 weeks of gestation, in accordance with current Italian guidelines and the International Association Diabetes Pregnancy Study Groups (IADPSG) glycemic cut-offs. Data were examined by univariate and logistic regression analyses. Results-1814 (75.3%) pregnant women were normal glucose tolerant, while 596 (24.7%) were diagnosed with GDM. Spearman univariate analysis demonstrated a correlation between FTCT values and subsequent GDM diagnosis (ρ = 0.048, p = 0.018). The logistic regression analysis showed that women with a FTCT <1:10000 had a major GDM risk (p = 0.016), similar to women with a PAPP-A <1 multiple of the expected normal median (MoM, p = 0.014). Conversely, women with ß-hCG ≥2.0 MoM had a reduced risk of GDM (p = 0.014). Conclusions-Our findings indicate that GDM susceptibility increases with fetal aneuploidy risk, and that FTCT and its related maternal serum parameters can be used as early predictors of GDM.

Ambient air pollution and lung cancer risk among never-smokers in the Women's Health Initiative.

BACKGROUND: Ambient air pollution is classified as a human carcinogen by the International Agency for Research on Cancer (IARC). However, epidemiologic studies supporting this classification have focused on lung cancer mortality rather than incidence, and spatial and temporal resolutions of exposure estimates have varied considerably across studies. METHODS: We evaluated the association of outdoor air pollution and lung cancer incidence among never-smoking participants of the Women's Health Initiative (WHI) study, a large, US-based cohort of postmenopausal women (N = 65,419; 265 cases). We used geospatial models to estimate exposures to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) based on residential addresses at baseline and throughout follow-up. We also characterized exposures to traffic-related air pollution by proximity to major roadways. We estimated hazard ratios (HRs) for the risk of lung cancer in association with these exposure metrics using Cox proportional hazards regression models. RESULTS: No compelling associations of PM2.5 and NO2 exposures with lung cancer risk were observed. An increased risk of lung cancer was observed when comparing those individuals with residences <50 versus ≥200 meters from a primary limited access highway (HR = 5.23; 95% confidence interval = 1.94, 14.13). CONCLUSIONS: Our results do not exclude lung cancer risk estimates observed in association with PM2.5 and NO2 exposures identified in previous studies. Our results suggest that residential proximity to major roadways may be a proxy for carcinogenic exposures not correlated with PM2.5 or NO2 levels. New studies of air pollution and lung cancer incidence should characterize additional aspects of proximity to major roadways.

Impaired Lung Function, Lung Disease, and Risk of Incident Dementia.

Rationale: Growing evidence suggests that compromised lung health may be linked to dementia and worsening cognitive ability. Objectives: To test the hypothesis that impaired lung function or lung disease in midlife is associated with greater risk of incident dementia and mild cognitive impairment (MCI) later in life. Methods: A total of 14,184 Atherosclerosis Risk in Communities study participants who underwent spirometry and were asked about lung health (1987-1989) were followed. Dementia and MCI were defined by hospitalization diagnosis codes (1987-2013) in the whole cohort and with adjudication among 42% who attended a comprehensive neurocognitive examination (2011-2013). Measurements and Main Results: In analysis using adjudicated outcomes, odds of dementia or MCI were higher among participants with restrictive (multivariable-adjusted odds ratio, 1.58; 95% confidence interval, 1.14-2.19) and obstructive lung disease (multivariable-adjusted odds ratio, 1.33; 95% confidence interval, 1.07-1.64), compared with those without disease or respiratory symptoms. Associations were similar in analyses restricted to nonsmokers, and present for both Alzheimer's disease-related dementia and cerebrovascular etiologies. Low FEV1% predicted and FVC% predicted were also associated with increased dementia risk. Conclusions: Midlife lung disease and reduced lung function were associated with modestly increased odds of dementia and MCI later in life. Magnitudes of association were more pronounced for restrictive impairment than for obstructive lung disease. These associations were present in smokers and nonsmokers. If the observed associations are causal, policy and public health efforts to reduce smoking and improve air quality may have the added benefit of preventing the development of dementia and MCI.

Declining Lung Function and Cardiovascular Risk: The ARIC Study.

BACKGROUND: Pulmonary dysfunction predicts incident cardiovascular disease (CVD). OBJECTIVES: The purpose of this study was to evaluate whether longitudinal decline in lung function is associated with incident heart failure (HF), coronary heart disease (CHD), and stroke. METHODS: Among 10,351 participants in the ARIC (Atherosclerosis Risk In Communities) study free of CVD, rapid lung function decline was defined as the greatest quartile (n = 2,585) of decline in either forced expiratory volume in 1 s (FEV1) (>1.9% decline/year) or forced vital capacity (FVC) (>2.1% decline/year) over 2.9 ± 0.2 years. The relationship between rapid decline in FEV1 or FVC and subsequent incident HF, CHD, stroke, or a composite of these was assessed using multivariable Cox regression adjusting for the baseline spirometry value, demographics, height, body mass index, heart rate, diabetes, hypertension, low-density lipoprotein, use of lipid-lowering medication, N-terminal fragment of prohormone for B-type natriuretic peptide, and smoking. RESULTS: The mean age was 54 ± 6 years, 56% were women, and 81% were white. At 17 ± 6 years of follow-up, HF occurred in 14%, CHD 11%, stroke 6%, and the composite in 24%. Rapid decline in FEV1 and in FVC were both associated with a heightened risk of incident HF (hazard ratio [HR]: 1.17; 95% confidence interval [CI]: 1.04 to 1.33; p = 0.010; and HR: 1.27; 95% CI: 1.12 to 1.44; p < 0.001; respectively), with rapid decline in FEV1 most prognostic in the first year of follow-up (HR: 4.22; 95% CI: 1.34 to 13.26; p = 0.01). Rapid decline in FEV1 was also associated with incident stroke (HR: 1.25; 95% CI: 1.04 to 1.50; p = 0.015). CONCLUSIONS: A rapid decline in lung function, assessed by serial spirometry, is associated with a higher incidence of subsequent CVD, particularly incident HF.

Comparison Between 64Cu-PSMA-617 PET/CT and 18F-Choline PET/CT Imaging in Early Diagnosis of Prostate Cancer Biochemical Recurrence.

PURPOSE: To evaluate the diagnostic performance of 64Cu-PSMA-617 positron emission tomography (PET) with computed tomography (CT) for restaging prostate cancer after biochemical recurrence (BCR) and to compare it with 18F-choline PET/CT in a per-patient analysis. PATIENTS AND METHODS: An observational study was performed of 43 patients with BCR after laparoscopic radical prostatectomy who underwent 64Cu-PSMA-617 PET/CT and subsequently 18F-choline PET/CT for restaging. The detection rates (DR) of 64Cu-PSMA-617 PET/CT and of 18F-choline PET/CT were calculated by standardized maximum uptake value (SUVmax) at 4 hours and SUVmax at 1 hour as reference, respectively. Furthermore, univariate logistic regression analysis was carried out to identify independent predictive factors of positivity with 64Cu-PSMA-617 PET/CT. RESULTS: An overall positivity with 64Cu-PSMA-617 PET/CT was found in 32 patients (74.4%) versus 19 (44.2%) with 18F-choline PET/CT. Specifically, after stratifying for prostate-specific antigen (PSA) values, we found a good performance of 64Cu-PSMA-617 PET/CT at low PSA levels compared to 18F-choline PET/CT, with a DR of 57.1% versus 14.3% for PSA 0.2-0.5 ng/mL (P = .031), and of 60% versus 30% with PSA 0.5-1 ng/mL. At univariate binary logistic regression analysis, PSA level was the only independent predictor of 64Cu-PSMA-617 PET/CT positivity. No significant difference in terms of DR for both 64Cu-PSMA-617 PET/CT and 18F-choline PET/CT was found according to different Gleason score subgroups. CONCLUSION: In our study cohort, a better performance was observed for 64Cu-PSMA-617 PET/CT compared to 18F-choline PET/CT in restaging after BCR, especially in patients with low PSA values.

Asthma Morbidity, Comorbidities, and Modifiable Factors Among Older Adults.

BACKGROUND: Asthma morbidity is increased among older adults, especially older adult women. Interventions to improve asthma control in this population are not well described. OBJECTIVE: The objective of this study was to identify risk factors (including modifiable factors) associated with asthma-related hospitalizations and emergency department or urgent care center visits (ED/UCV) among older adults. A secondary objective was to investigate sex differences in variables relevant to asthma control. METHODS: Data were obtained from 14,076 older adults ≥65 years with active asthma participating in the 2006-2010 Behavioral Risk Factor Surveillance System Asthma Call-back Survey (a random-digit dialed survey) in 40 US states, the District of Columbia, and Puerto Rico, representative of >2.6 million persons. Weighted, adjusted logistic regression was conducted. RESULTS: One or more asthma-related hospitalizations in the past year were reported by 5.7% (95% confidence interval [95% CI] = 5.0% to 6.4%) of participants; 10.6% (95% CI = 9.7% to 11.5%) reported ≥1 asthma-related ED/UCV. Compared with older adults without asthma-related hospitalizations, adjusted odds were higher among those with ≥1 asthma-related hospitalization for chronic obstructive pulmonary disease (COPD), coronary artery disease, depression, cockroaches or mold in the home, and cost barriers to asthma-related health care or medication. All these factors, except for cockroaches, were associated with asthma-related ED/UCV. Compared with males, adjusted odds were higher among females for COPD, depression, obesity, and cost barriers to asthma-related health care or medication. CONCLUSIONS: Among older adults, asthma-related hospitalizations and ED/UCV were associated with clinical comorbidities, mold in the home, and financial barriers to asthma-related health care. Interventions addressing modifiable factors could reduce asthma morbidity among older adults.

Lung function decline over 25 years of follow-up among black and white adults in the ARIC study cohort.

BACKGROUND: Interpretation of longitudinal information about lung function decline from middle to older age has been limited by loss to follow-up that may be correlated with baseline lung function or the rate of decline. We conducted these analyses to estimate age-related decline in lung function across groups of race, sex, and smoking status while accounting for dropout from the Atherosclerosis Risk in Communities Study. METHODS: We analyzed data from 13,896 black and white participants, aged 45-64 years at the 1987-1989 baseline clinical examination. Using spirometry data collected at baseline and two follow-up visits, we estimated annual population-averaged mean changes in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) by race, sex, and smoking status using inverse-probability-weighted independence estimating equations conditioning-on-being-alive. RESULTS: Estimated rates of FEV1 decline estimated using inverse-probability-weighted independence estimating equations conditioning on being alive were higher among white than black participants at age 45 years (e.g., male never smokers: black: -29.5 ml/year; white: -51.9 ml/year), but higher among black than white participants by age 75 (black: -51.2 ml/year; white: -26). Observed differences by race were more pronounced among men than among women. By smoking status, FEV1 declines were larger among current than former or never smokers at age 45 across all categories of race and sex. By age 60, FEV1 decline was larger among former and never than current smokers. Estimated annual declines generated using unweighted generalized estimating equations were smaller for current smokers at younger ages in all four groups of race and sex compared with results from weighted analyses that accounted for attrition. CONCLUSIONS: Using methods accounting for dropout from an approximately 25-year health study, estimated rates of lung function decline varied by age, race, sex, and smoking status, with largest declines observed among current smokers at younger ages.

Age at asthma onset and asthma self-management education among adults in the United States.

OBJECTIVE: Asthma self-management education improves asthma-related outcomes. We conducted this analysis to evaluate variation in the percentages of adults with active asthma reporting components of asthma self-management education by age at asthma onset. METHODS: Data from 2011 to 2012 Asthma Call-back Surveys were used to estimate percentages of adults with active asthma reporting six components of asthma self-management education. Components of asthma self-management education include having been taught to what to do during an asthma attack and receiving an asthma action plan. Differences in the percentages of adults reporting each component and the average number of components reported across categories of age at asthma onset were estimated using linear regression, adjusted for age, education, race/ethnicity, sex, smoking status, and years since asthma onset. RESULTS: Overall, an estimated 76.4% of adults with active asthma were taught what to do during an asthma attack and 28.7% reported receiving an asthma action plan. Percentages reporting each asthma self-management education component declined with increasing age at asthma onset. Compared with the referent group of adults whose asthma onset occurred at 5-14 years of age, the percentage of adults reporting being taught what to do during an asthma attack was 10% lower among those whose asthma onset occurred at 65-93 years of age (95% CI: -18.0, -2.5) and the average number of components reported decreased monotonically across categories of age at asthma onset of 35 years and older. CONCLUSIONS: Among adults with active asthma, reports of asthma self-management education decline with increasing age at asthma onset.

Active asthma and the prevalence of physician-diagnosed COPD.

INTRODUCTION: Despite the considerable overlap of asthma and chronic obstructive pulmonary disease (COPD), the extent to which the two diagnoses are the manifestations of the same disease remains unresolved. We conducted these analyses to evaluate the role of active asthma in the prevalence of physician-diagnosed COPD. METHODS: From 2006 through 2010, 74,209 adults aged 18-99 years and with a history of asthma participated in the Behavioral Risk Factor Surveillance System (BRFSS) Asthma Call-back Survey and responded to interview-administered questionnaires via telephone. We used publicly available data from 71,639 (97%) participants to identify respondents with and without active manifestations of asthma and self-reported, physician-diagnosed COPD. We generated population-weighted estimates of physician-diagnosed COPD prevalence and conducted linear regression to estimate associations between active asthma status and the prevalence of COPD among current smokers, former smokers, and lifetime nonsmokers separately. RESULTS: Physician-diagnosed COPD was reported in an estimated 29% of the population with any history of asthma, including both active and inactive asthma. Age-specific prevalences of physician-diagnosed COPD were consistently higher among adults with active asthma than adults without active asthma. Compared to inactive asthma, active asthma was associated with an 8.3% [95% confidence interval (CI) 6.1, 10.5] higher prevalence of physician-diagnosed COPD among lifetime nonsmokers, a 20.6% (95% CI 18.0, 23.3) higher prevalence among former smokers, and a 26.7% (95% CI 22.5, 30.9) higher prevalence among current smokers. CONCLUSIONS: Among adults with a history of asthma, active manifestations of asthma may play an important role in the epidemiology of COPD.