Proteomic biomarkers of long-term lung function decline in textile workers: a 35-year longitudinal study.

BACKGROUND: Occupational exposures contribute significantly to obstructive lung disease among textile workers. However, biomarkers associated with such declines are not available. OBJECTIVES: We conducted a large-scale proteomic study to explore protein biomarkers potentially associated with long-term lung function decline. METHODS: Shanghai Textile Workers Cohort was established in 1981 with 35 years of follow-up, assessing textile workers' lung functions every five years. Quantitative serum proteomics was performed on all 453 workers at 2016 survey. We employed four distinct models to examine the association between forced expiratory volume in one second (FEV1) and proteins, and consolidated the findings using an aggregated Cauchy association test. Furthermore, proteomic data of UK Biobank (UKB) was used to explore the associations of potential protein markers and decline of FEV1, and the interactions of these proteins were examined through STRING database. Associations were also externally validated using two-sample Mendelian randomizations (MR). RESULTS: 15 of 907 analyzed proteins displayed potential associations with long-term FEV1 decline, including two hemoglobin subunits: hemoglobin subunit beta (HBB, FDR-qACAT = 0.040), alpha globin chain (HBA2, FDR-qACAT = 0.045), and four immunoglobulin subunits: immunoglobulin kappa variable 3-7 (IGKV3-7, FDR-qACAT = 0.003), immunoglobulin heavy chain variable region (IgH, FDR-qACAT = 0.011). Five proteins were significantly associated with the rate of decline of FEV1 in UKB, in which RAB6A, LRRN1, and BSG were also found to be associated with proteins identified in Shanghai Textile Workers Cohort using STRING database. MR indicated bidirectional associations between HBB and FEV1 (P < 0.05), while different immunoglobulin subunits exhibited varying associations with FEV1. IMPACT STATEMENT: We performed a large-scale proteomic study of the longest-follow-up pulmonary function cohort of textile workers to date. We discovered multiple novel proteins associated with long-term decline of FEV1 that have potential for identifying new biomarkers associated with long-term lung function decline among occupational populations, and may identify individuals at risk, as well as potential pharmaceutical targets for early intervention.

The Impact of Chest Binding on Pulmonary Functions of Trans and Gender Diverse Youth.

PURPOSE: There is a scarcity of information regarding the health consequences of chest binding and its effects on pulmonary functions (PFs). This study aimed to evaluate binding practices, physical outcomes, and effects on PFs of trans or gender diverse (TGD) youth who bind. METHODS: The TGD and control groups underwent pulmonary function tests (PFTs), with the TGD group undergoing testing both with their binder and after removal. We additionally evaluated binding practices and its physical outcomes. RESULTS: 33 TGD participants with a mean age of 20.15 ± 2.76 and 31 controls with a mean age of 20.74 ± 2.95 years were included. A large majority reported physical side effects, back pain being the most common. The comparison of PFTs of the TGD group with and without binder showed that vital capacity , forced vital capacity, and forced expiratory volume in 1 second values were significantly lower in the presence of a binder (both % predicted and L) (p < .005). Binding duration (both lifetime and weekly) did not correlate with PFTs, however, the ratio of change in forced expiratory volume -1/ forced vital capacity induced by binding correlated with weekly binding duration. When we separately compared the PFTs of the TGD group with and without binder to the control group, we found no significant difference. DISCUSSION: Despite the abundance of physical side effects, comparison with the control group does not support long-lasting effects of binding on PF; however, it indicates acute restrictive impairment without a significant effect on airflow obstruction in youth who bind. These findings hold significance in facilitating well-informed decision-making processes pertaining to binding practices.

[Stable chronic obstructive pulmonary disease treated by adjunctive therapy of electrothermal acupuncture: a randomized controlled trial].

OBJECTIVE: To assess the effect and safety of electrothermal acupuncture in adjunctive treatment of stable chronic obstructive pulmonary disease (COPD) in patients. METHODS: Sixty-six stable COPD patients were randomly divided into an observation group and a control group, with 33 cases in each group. The patients in the control group were treated with bronchodilator inhalation combined with respiratory training for 4 weeks. In the observation group, on the basis of the treatment as the control group, electrothermal acupuncture was delivered at bilateral Quchi (LI 11), Zusanli (ST 36) and Sanyinjiao (SP 6), and the conventional filiform needling was operated at the supplementary acupoints selected according to the individual syndrome. The interventions in the observation group were given once every two days, 3 treatments a week, for consecutive 4 weeks. Before and after treatment completion, the lung functions (forced expiratory volume in the first second [FEV1], forced vital capacity [FVC], FEV1/FVC and the percentage of diffusing capacity of the lungs for carbon monoxide [DLCO%]), 6 min walking distance (6MWD) and the score of COPD assessment test (CAT) were compared between the two groups. The attacks of acute exacerbation were recorded in 1-year follow-up visit in the two groups and the safety of electrothermal acupuncture was evaluated. RESULTS: After treatment, FEV1, FVC, FEV1/FVC, DLCO% and 6MWD were increased (P<0.01, P<0.05), and CAT scores were decreased (P<0.01) in the two groups compared with those before treatment. FEV1, FVC, FEV1/FVC and 6MWD were higher and CAT score was lower in the observation group when compared with those of the control group (P<0.05). In the 1-year follow-up visit, the cases of acute exacerbation in the observation group were fewer than that in the control group (P<0.05). There were no treatment-related adverse reactions in the observation group. CONCLUSION: On the basis of bronchodilator inhalation and respiratory training, electrothermal acupuncture can ameliorate the lung function, strengthen motor ability, reduce the cases of acute exacerbation safely and effectively in the patients with stable COPD.

Clinical and Functional Outcomes Associated with Quality of Life in Patients with Lymphangioleiomyomatosis: A Cross-Sectional Study.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare (twenty-one per million female inhabitants) neoplastic cystic lung disease that impairs health-related quality of life (HRQoL). However, the factors associated with impaired quality of life in patients with LAM are poorly understood. OBJECTIVE: To assess the clinical, psychosocial, and functional characteristics associated with impaired quality of life in patients with LAM. METHODS: This was a cross-sectional study performed on two nonconsecutive days. HRQoL (SF-36 and CRQ), lung function tests, anxiety and depression symptoms (HADS), maximal (CPET and ISWT), and submaximal exercise capacity (6MWT) were assessed. Linear associations among outcomes were assessed using Pearson's correlation and multivariate tests. RESULTS: Forty-five women with LAM (46 ± 10.years; FEV1,74%pred) were evaluated. The lowest SF-36 scores were observed for general health and vitality and the highest for the physical and social domains. The lowest CRQ scores were observed for dyspnea and fatigue, and the highest were for the emotional function and self-control domains. Sixteen (35%) women had anxiety, and 8 (17%) had depression symptoms. Most of the SF-36 and CRQ domains were associated with anxiety and depression symptoms (from r = 0.4 to r = 0.7; p < 0.05) and exercise capacity (from r = 0.3 to r = 0.5; p < 0.05). Lung function parameters were weakly or not associated with quality of life domains. After multiple linear regression, HRQoL was independently associated with depression symptoms and physical capacity but not with lung function. CONCLUSION: Our results show that aerobic capacity and depression symptoms are the main factors, rather than lung function, related to quality of life in patients with LAM.

Long-term lung function recovery after ECMO versus non-ECMO management in acute respiratory failure: a systematic review and meta-analysis.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly employed to support lung function in patients with acute respiratory failure (ARF). However, the long-term outcomes of the approach have not been encouraging when compared to those of conventional mechanical ventilation. Further, the long-term effects of ECMO on lung function and recovery are unclear. For this review, we examined the long-term lung function outcomes of patients with ARF treated with and without ECMO. METHODS: We searched the Embase, CENTRAL, Web of Science, and PubMed sites for studies comparing long-term (≥ 6 months) pulmonary function test results in patients with ARF treated with and without ECMO published until January 2024. We conducted a meta-analysis for percentage predicted values. RESULTS: We included five studies. Our meta-analysis showed similar values of forced vital capacity (FVC%) (MD, 0.47; 95% CI, -3.56-4.50) and forced expiratory flow in the first second % (MD, 1.79; 95% CI, -2.17-5.75) in patients with ARF treated with or without ECMO. The FEV1/FVC % values were slightly higher in patients treated with ECMO than in those without ECMO (MD, 2.03; 95% CI, 0.01-4.04; p-value = 0.05). According to the meta-analysis, the values for total lung capacity % (MD, -3.20; 95% CI, -8.83-2.44) and carbon monoxide diffusion capacity % (MD, -0.72; 95% CI, -3.83-2.39) were also similar between patients undergoing ECMO and those without it. CONCLUSION: The meta-analysis of a small number of studies with significant selection bias indicates that patients with ARF treated with ECMO may have comparable long-term pulmonary function recovery to those treated with conventional strategies. Further investigations including a larger number of patients and focusing on the long-term impact of ECMO are needed to supplement the current evidence.

Transmission electron microscopy of transbronchial lung cryobiopsy samples in a cohort of fibrotic interstitial lung disease patients - feasibility and implications of endothelial alterations.

We evaluated the utility of transmission electron microscopy (TEM) in transbronchial lung cryobiopsy (TBLC) samples from 16 consecutive patients undergoing routine evaluation of fibrotic interstitial lung disease (ILD). Next to routine pathology examination, 1 to 2 TBLC samples were prepared for TEM analysis and evaluated using a Zeiss LEO EM 910. Subpleural cryobiopsies and unfrozen excision biopsies from fresh lobectomy tissue of non-ILD lung cancer patients served as controls. TEM provided high-quality images with only minor cryoartifacts as compared to controls. Furthermore, in several ILD patients we found marked microvascular endothelial abnormalities like luminal pseudopodia-like protrusions and inner surface defects. These were extensively present in four (25%), moderately present in seven (43.8%), and largely absent in five (31.3%) patients. A higher degree of TEM endothelial abnormalities was associated with younger age, non-specific interstitial pneumonia pattern, higher broncho-alveolar lavage lymphocyte count, positive autoantibodies, and lower spirometry, diffusion capacity and oxygenation biomarkers. We conclude that TEM evaluation of TBLC samples from ILD patients is feasible, while the observed microvascular alterations warrant further evaluation.

Impact of metals exposure on lung function and serum club cell secretory protein among schoolchildren: A mixture and mediation analysis.

Particulate matter (PM) and its harmful components are significant contributors to respiratory diseases and impaired lung function, especially in children. Club cell secretory protein (CC16) is a maker of lung epithelium or club cell injuries. To date, the relationship between metals related with PM and CC16 and lung function impairment has been overlooked in children. We enrolled 603 schoolchildren exposed to different levels of PM in China. We found per doubling increase, urinary thallium, and iron was associated with a 3.42 % (95 % CI: 0.01, 6.72) and 3.09 % (95 % CI: 0.55, 5.56) decrease of serum CC16, respectively, whereas urinary cadmium was associated with a 4.74 % (95 % CI: 1.29, 8.31) increase of serum CC16. The Bayesian kernel machine regression (BKMR) model confirmed these associations and showed a potential synergistic interaction between thallium and cadmium. Urinary metal mixtures were associated with lower CC16 when they were below the 35th percentile compared with their median. Serum CC16 mediated 11.47 % (95 % CI: 0.06, 45.00) of the association between urinary thallium and FEV1/FVC decline. The inverted U-shaped association with CC16 and the mediation role of CC16 on associations with lung function provide insight into the mechanisms underlying lung injury induced by metals related with PM.

Efficacy of medical education combined with extended care on adherence to inhaled glucocorticoids and clinical effects in patients with bronchial asthma.

OBJECTIVE: To observe the clinical efficacy of medical education combined with extended care in patients with bronchial asthma and its effect on adherence to inhaled glucocorticoids. METHODS: Ninety-eight patients with bronchial asthma were divided into the control group and the experimental group, n = 49, by utilizing the random number table method. The control group was given routine education and care as well as routine out-of-hospital instructions, and the experimental group was given medical education and extended care based on the control group. Asthma disease knowledge mastery, asthma control, quality of life, medication adherence and lung function were compared between both groups, and the number of asthma attacks and re-hospitalizations were recorded. RESULTS: The experimental group performed higher scores of health knowledge, asthma control test and quality of life, rate of complete adherence, forced expiratory volume in one second (FEV1), peak expiratory flow rate, and FEV1/forced vital capacity. The number of asthma attacks and the times of re-hospitalizations were lower in the experimental group (all p < 0.05). CONCLUSION: Medical education combined with extended care can improve bronchial asthma patients' mastery of asthma disease knowledge, effectively control patients' conditions, enhance patients' quality of life and lung function, increase patients' adherence to inhaled glucocorticoids, and reduce the recurrence of bronchial asthma patients.

Cadmium-induced lung injury disrupts immune cell homeostasis in the secondary lymphoid organs in mice.

Cadmium (Cd) is a well-known toxic heavy metal that poses significant health risks, particularly through inhalation, smoking, and the consumption of contaminated food. Exposure to cadmium is linked to the development and exacerbation of chronic lung diseases such as pulmonary fibrosis and chronic obstructive pulmonary disease (COPD). This study investigated the systemic effects of intratracheal cadmium chloride (0.5 mg/kg) instillation in C57BL/6 mice. All parameters, including inflammation assessment, lung function evaluation (using Flexi-vent), and immunophenotyping of T-cells in secondary lymphoid organs (mediastinal lymph nodes and spleen), were analyzed 14 days after cadmium exposure. The results demonstrated that cadmium exposure led to significant immune cell infiltration in bronchoalveolar lavage (BAL) fluid, altered pro-inflammatory cytokine levels, and was associated with impaired lung function, characterized by increased lung resistance and Newtonian resistance. Analysis of T-cell populations revealed no significant changes in total T-cells in mediastinal lymph nodes and spleen, but a decrease in CD4+ T-cells and an increase in CD8+ T-cells were observed. These findings suggest that cadmium disrupts T-cell homeostasis in secondary lymphoid organs. Further research is crucial to elucidate the mechanisms underlying cadmium-induced lung injury and immune dysregulation, essential for developing effective therapeutic interventions against chronic lung diseases caused by cadmium exposure.

Periostin in Bronchiolitis Obliterans Syndrome after Lung Transplant.

The utility of measuring serum periostin levels for predicting the occurrence of bronchiolitis obliterans syndrome (BOS) after lung transplantation remains underexplored. We analyzed differentially expressed genes (DEGs) between initially transplanted lung tissue and lung tissue with BOS from four patients. Periostin levels were assessed in 97 patients who had undergone lung transplantation 1 year post-transplantation and at the onset of BOS. The association between periostin levels and BOS, as well as their correlation with the decline in forced expiratory volume in one second (FEV1), was evaluated. Periostin levels in the BOS group were significantly higher than those in the control group (p < 0.001) and the stable group (p < 0.001). Periostin levels at the onset of BOS were significantly higher than those 1 year post-transplantation in the BOS group (p < 0.001). The serum periostin levels at the time of BOS diagnosis showed a positive correlation with the reduction in FEV1 (%) (r = 0.745, p < 0.001). The increase in the serum periostin levels at the time of BOS diagnosis compared with those 1 year post-transplantation was positively correlated with reduction in FEV1 (%) (r = 0.753, p < 0.001). Thus, serum periostin levels may serve as biomarkers for predicting a decline in lung function in patients with BOS after lung transplantation.

Effects of single and combined urinary polycyclic aromatic hydrocarbon effects on lung function in the U.S. adult population.

BACKGROUND: The impact of polycyclic aromatic hydrocarbons (PAHs) on lung function has garnered attention, but studies mostly focus on individual effect. This study investigates urinary PAH metabolites as biomarkers of exposure and assesses the relationships between single and combined exposures to nine urinary PAH metabolites and lung function in adults. METHODS: Data from 4040 adults in the 2007-2012 National Health and Nutrition Examination Survey (NHANES) were analyzed. Weighted generalized linear models estimated the effects of individual PAH metabolites on lung function. Additionally, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) were employed to evaluate the combined impacts of multiple PAH metabolites. RESULTS: Analyses of individual PAH metabolites revealed negative associations with lung function, excluding forced vital capacity (FVC). The WQS, qgcomp, and BKMR models consistently showed that exposure to multiple PAH metabolites was associated with lung function decrease. WQS indicated that 2-hydroxynaphthalene (2-NAP) was the largest contributor to the reductions in forced expiratory volume in 1 s (FEV1), FVC, peak expiratory flow (PEF), and forced expiratory flow from 25 to 75% of FVC (PEF25-75%). Additionally, 1-hydroxypyrene (1-PYR) was the primary PAH metabolite contributing to the decreases in FEV1/FVC and fractional exhaled nitric oxide (FeNO). The combined effect of urinary PAH metabolites did not affect FVC in the current smokers or FeNO in nonsmokers, but decreased FEV1/FVC in current smokers. CONCLUSION: This study strengthens the negative relationships between multiple PAH metabolites exposure and lung function in adults. Given the limitations of this study, including the lack of knowledge of other exposure pathways and the uncertainty of urinary metabolites, further research is necessary to explore the mechanisms underlying these associations and to address the limitations in exposure assessment.

The impact of hormones on lung development and function: an overlooked aspect to consider from early childhood.

The impact of hormones on the respiratory system constitutes a multifaceted and intricate facet of human biology. We propose a comprehensive review of recent advancements in understanding the interactions between hormones and pulmonary development and function, focusing on pediatric populations. We explore how hormones can influence ventilation, perfusion, and pulmonary function, from regulating airway muscle tone to modulating the inflammatory response. Hormones play an important role in the growth and development of lung tissues, influencing them from early stages through infancy, childhood, adolescence, and into adulthood. Glucocorticoids, thyroid hormones, insulin, ghrelin, leptin, glucagon-like peptide 1 (GLP-1), retinoids, cholecalciferol sex steroids, hormones derived from adipose tissue, factors like insulin, granulocyte-macrophage colony-stimulating factor (GM-CSF) and glucagon are key players in modulating respiratory mechanics and inflammation. While ample evidence underscores the impact of hormones on lung development and function, along with sex-related differences in the prevalence of respiratory disorders, further research is needed to clarify their specific roles in these conditions. Further research into the mechanisms underlying hormonal effects is essential for the development of customizing therapeutic approaches for respiratory diseases. Understanding the impact of hormones on lung function could be valuable for developing personalized monitoring approaches in both medical and surgical pediatric settings, in order to improve outcomes and the quality of care for pediatric patients.

Associations between vitamin A and K intake and lung function in the general US population: evidence from NHANES 2007-2012.

Introduction: While nutrition's critical role in enhancing respiratory health is acknowledged, the specific impacts of vitamins A and K on lung function remain largely unexplored. The study aimed to evaluate the relationships between vitamins A and K intake and lung function. Methods: The cross-sectional study focused on adults aged 20-79 with utilizing data from US National Health and Nutrition Examination Survey (NHANES) 2007-2012. Lung function was assessed by measuring forced expiratory volume (FEV1), forced vital capacity (FVC), and the ratio of these two values (FEV1/FVC). Regression model was performed to determine the associations between intake of vitamins A and K and outcomes. Results: Data of 10,034 participants (representing 142,965,892 adults in the US) were analyzed. After adjusting for relevant confounders, multivariable analysis revealed 1 µg/day increase of vitamin A intake was significantly associated with 0.03 ml increased FEV1 (p = 0.004) and 0.04 ml increased forced vital capacity (FVC) (p < 0.001). In addition, 1 µg/day increase in vitamin K intake was significantly associated with 0.11 ml increased FEV1 (p = 0.022). Neither vitamin A and K intake was associated with FEV1/FVC or presence of airway obstruction. Conclusions: In relatively healthy population of the US, greater vitamin A or K intake was independently associated with better lung function assessed by spirometry. Benefits of such vitamins for pulmonary health should be confirmed in future randomized controlled trials.

Lung Function Impairment Among Paint Factory Workers: A Cross-Sectional Analytical Study.

BACKGROUND: A paint factory or manufacturing is a vocation characterized by exposure to chemical hazards during production. Paint exposure plays a great role in the incidence of several health problems, particularly respiratory diseases. The study aims to assess the pattern of spirometric indices among the study population. METHODS: This cross-sectional study of paint factory workers (PFWs) assesses their spirometric findings in Delta State, Nigeria. The participants for this study were divided into two groups; the PFWs and the non-PFWs (NPFW) which serve as the control group. Hundred and 200 participants were recruited for the study group and control, respectively. RESULTS: Among the participants in the paint worker cohort, 45 individuals (45.0%) had been employed for less than five years while 14 (14.0%) had worked over 10 years. Eighty-eight (88%) are aware of PPE; however, only 12 (12.0%) use them always. Findings show that 178 (89.0%) vs. seven (7.0%) of NPFW and PFW had normal pulmonary function tests. The spirometric abnormalities within the PFW group were obstructive lung disease affecting 59 (59.0%) of the cohort while 34 (34.0%) had restrictive lung patterns. CONCLUSION: Exposure to volatile organic compounds (VOCs) emitted from paint fumes is associated with spirometric abnormalities with obstructive patterns more predominant than restrictive patterns.

No genetic causal relationship between lung function and osteoporosis - evidence from a mendelian randomization study.

For a long time, the decline in lung function has been regarded as a potential factor associated with the risk of osteoporosis (OP). Although several observational studies have investigated the relationship between lung function and OP, their conclusions have been inconsistent. Given that Mendelian randomization (MR) studies can help reduce the interference of confounding factors on outcomes, we adopted this approach to explore the causal relationship between lung function and OP at the genetic level. To investigate the potential causality between lung function (FVC, FEV1, FEV1/FVC, PEF) and OP, we conducted a MR analysis employing three approaches: inverse variance weighted (IVW), MR-Egger, and weighted median. We used Cochran's Q test to detect potential heterogeneity, MR-Egger regression to evaluate directional pleiotropy, and the MR-PRESSO method to evaluate horizontal pleiotropy. In addition, we used MR-PRESSO and MR radial methods to exclude SNPs exhibiting pleiotropic outliers. Upon identification of potential outliers, we removed them and subsequently ran MR analysis again to assess the reliability of our findings. The MR analysis suggested that there was no causal effect of lung function (FVC, PEF, FEV1/FVC, FEV1) on OP, which is consistent with the. results after excluding potential outliers using MR-PRESSO and MR radial. methods. Sensitivity analysis confirmed the reliability and consistency of these. results. The study concluded that there is no causal link between lung function and OP. The association found in observational studies might be attributable to shared risk factors.

The Upper Limit of Normal Rate of Lung Function Decline in Healthy Adults in the Framingham Heart Study.

BACKGROUND: Lung function declines over the course of adulthood; however, a consensus on the normal range of decline in an individual's lung function is lacking. RESEARCH QUESTION: What is the normal range and the upper limit of normal (ULN) decline in lung function in adults without prior tobacco use, occupational dust exposure, or a known diagnosis or symptoms of cardiopulmonary disease? STUDY DESIGN AND METHODS: A retrospective analysis of healthy individuals who have never smoked (N = 1,305) from the Framingham Heart Study with repeated lung function meeting standards for acceptability and reproducibility was conducted. Longitudinal change was derived using a linear mixed effects model and estimated to a 6-year interval. The ULN decline was defined as the 95th percentile. RESULTS: The mean follow-up between spirometry examinations was 5.5 years, whereas the mean follow-up between diffusing capacity for carbon monoxide studies was 5.9 years. Decline in FEV1, FVC, and D accelerated with age, whereas decline in FEV1/FVC decelerated with age. Decline varied with sex, age, and height. Over a 6-year period, the ULN decline in FEV1 ranged from 383 to 667 mL, and the ULN decline in Dlco ranged from 3.6 to 9.5 mL/min/mm Hg. Overall, male individuals had faster absolute rates of decline than female individuals, whereas relative (%) rates of decline were similar between sexes. INTERPRETATION: Lung function decline is nonlinear and accelerates with age. In this cohort, the ULN decline over 6 years often exceeded current guidelines for interpreting significant longitudinal change in lung function.

The impact of tangeretin combined with whey protein on exercise-induced bronchoconstriction in professional athletes: a placebo-controlled trial.

BACKGROUND: Exercise-induced bronchoconstriction (EIB) is highly prevalent in athletes. The objective of this study was to assess the therapeutic efficacy of daily tangeretin combined with whey protein supplementation over a period of 4 weeks in professional athletes with EIB. METHODS: Using a placebo-controlled, double-blind, paired, randomized trial design, a cohort of 30 professional athletes with EIB, consisting of 14 females and 16 males, was divided into two groups: the tangeretin combined with whey protein intervention group (TIG), and the placebo control group (PCG). Both the TIG and PCG underwent exercise challenge tests (ECT) and VO2max tests before (ECT1, V1) and after (ECT2, V2) the intervention. Blood (eosinophils, neutrophils, and basophils) and serum (interleukin-5, IL-5; interleukin-8, IL-8; Clara cell secretory protein-16, CC16; immunoglobulin E, IgE) levels were measured early in the morning of ECT1 and ECT2, respectively. Lung function was assessed immediately before and post-ECT immediately. RESULTS: Tangeretin combined with whey protein use for 4 weeks attenuated the decrease in forced expiratory volume in 1 s (FEV1) post trials (∆FEV1(ECT1-ECT2): mean (SD) TIG -7.51(6.9)% vs. PCG -2.33(11.49)%, p = 0.013). Tangeretin also substantially attenuated IL-5 concentration (∆IL-5(T1-T5): Tangeretin -19.4% vs Placebo + 8.37%, p = 0.022); IL-8 concentration (∆IL-8(T1-T5): Tangeretin -17.28% vs Placebo + 6.1%, p = 0.012); CC16 concentration (∆CC16(T1-T5): Tangeretin -11.77% vs Placebo + 24.19%); and IgE concentration in the serum (∆IgE(T1-T5): Tangeretin -24.1% vs Placebo -3.9%), and significantly decreased neutrophil count (∆N(T1-T5): Tangeretin -11.34% vs Placebo + 0.3%) and eosinophil count in blood (∆N(T1-T5): Tangeretin -38.5% vs Placebo + 4.35%). Compared with V1, VO2max (p = 0.042) and TLim (p = 0.05) of V2 were significantly increased in the TIG, and there was no significant change in the PCG. Meanwhile, six athletes in the TIG and 0 athletes in the PCG became EIB-negative at ECT2; the overall negative conversion rate of EIB was 40.00% in TCG. Additionally, the number of cough symptoms decreased from 9 to 3 and dyspnea from 4 to 2 in the TIG. CONCLUSION: After high-intensity exercise, athletes with EIB achieved significant improvements in lung function and blood inflammatory factors by combining tangeretin and whey protein supplementation. EIB athletes also showed longer exercise endurance and VO2max at 4 weeks after TI. In addition, some patient symptoms disappeared after combination supplementation. The effect of this treatment on professional athletes with EIB was beneficial.

Evaluating precision medicine tools in cystic fibrosis for racial and ethnic fairness.

Introduction: Patients with cystic fibrosis (CF) experience frequent episodes of acute decline in lung function called pulmonary exacerbations (PEx). An existing clinical and place-based precision medicine algorithm that accurately predicts PEx could include racial and ethnic biases in clinical and geospatial training data, leading to unintentional exacerbation of health inequities. Methods: We estimated receiver operating characteristic curves based on predictions from a nonstationary Gaussian stochastic process model for PEx within 3, 6, and 12 months among 26,392 individuals aged 6 years and above (2003-2017) from the US CF Foundation Patient Registry. We screened predictors to identify reasons for discriminatory model performance. Results: The precision medicine algorithm performed worse predicting a PEx among Black patients when compared with White patients or to patients of another race for all three prediction horizons. There was little to no difference in prediction accuracies among Hispanic and non-Hispanic patients for the same prediction horizons. Differences in F508del, smoking households, secondhand smoke exposure, primary and secondary road densities, distance and drive time to the CF center, and average number of clinical evaluations were key factors associated with race. Conclusions: Racial differences in prediction accuracies from our PEx precision medicine algorithm exist. Misclassification of future PEx was attributable to several underlying factors that correspond to race: CF mutation, location where the patient lives, and clinical awareness. Associations of our proxies with race for CF-related health outcomes can lead to systemic racism in data collection and in prediction accuracies from precision medicine algorithms constructed from it.