Showing papers on "Pulmonary diffusion published in 2020"

Epigenetic Age Acceleration and Chronic Health Conditions Among Adult Survivors of Childhood Cancer.

Abstract: BACKGROUND Mounting evidence supports the occurrence of accelerating aging among long-term survivors of childhood cancer. We aimed to investigate epigenetic age acceleration (EAA) in survivors and evaluate associations between EAA, treatment exposures, health behaviors, and chronic health conditions (CHCs). METHODS Genome-wide methylation data were generated with Infinium EPIC BeadChip on blood-derived DNA from 2139 survivors and 282 frequency matched controls from the St Jude Lifetime Cohort Study. EAAs were estimated as residuals from a linear regression of epigenetic age (Levine's clock) against chronological age. Adjusted least square mean (ALSM) of EAA was calculated and compared between survivors and controls, across treatment exposures and health behaviors. Associations of EAA with 20 clinically assessed CHCs were evaluated with multivariable piecewise-exponential models. All statistical tests for P values below were 2-sided. RESULTS EAA was statistically significantly higher in survivors than controls (ALSM = 0.63, 95% confidence interval [CI] = 0.26 to 1.01 vs -3.61, 95% CI = -4.43 to 2.80). In a multivariable model among survivors, statistically significantly higher EAA (P < .05) was observed in those exposed to chest radiotherapy, abdomen or pelvic radiotherapy, alkylating agents, glucocorticoids, or epipodophyllotoxins. Compared with survivors with favorable health behaviors (ALSM = 0.26, 95% CI=-0.36 to 0.87), EAA was statistically significantly higher among survivors with intermediate (ALSM = 1.07, 95% CI = 0.59 to 1.54) or unfavorable health behaviors (ALSM = 1.45, 95% CI = 0.60 to 2.30). In time-to-event analyses, statistically significant associations were identified between EAA tertiles and incidence of 7 CHCs: hypertension (3rd vs 1st tertile, relative rate [RR] = 1.83, 95% CI = 1.17 to 2.83), myocardial infarction (RR = 2.91, 95% CI = 1.27 to 7.21), obesity (RR = 1.39, 95% CI = 1.17 to 1.66), obstructive pulmonary deficit (RR = 1.86, 95% CI = 0.95 to 3.77), peripheral motor neuropathy (RR = 2.89, 95% CI = 1.24 to 6.97), peripheral sensory neuropathy (RR = 2.04, 95% CI = 0.99 to 4.26), and pulmonary diffusion deficits (RR = 2.75, 95% CI = 0.95 to 7.63). CONCLUSIONS EAA is statistically significantly higher in survivors of childhood cancer than in noncancer controls and is associated with specific treatment exposures, unfavorable health behaviors, and presence of specific CHCs.

The physiology of rowing with perspective on training and health

Abstract: This review presents a perspective on the expansive literature on rowing. The PubMed database was searched for the most relevant literature, while some information was obtained from books. Following the life span of former rowers paved the way to advocate exercise for health promotion. Rowing involves almost all muscles during the stroke and competition requires a large oxygen uptake, which is challenged by the pulmonary diffusion capacity and restriction in blood flow to the muscles. Unique training adaptations allow for simultaneous engagement of the legs in the relatively slow movement of the rowing stroke that, therefore, involves primarily slow-twitch muscle fibres. Like other sport activities, rowing is associated with adaptation not only of the heart, including both increased internal diameters and myocardial size, but also skeletal muscles with hypertrophy of especially slow-twitch muscle fibres. The high metabolic requirement of intense rowing reduces blood pH and, thereby, arterial oxygen saturation decreases as arterial oxygen tension becomes affected. Competitive rowing challenges most systems in the body including pulmonary function and circulatory control with implication for cerebral blood flow and neuromuscular activation. Thus, the physiology of rowing is complex, but it obviously favours large individuals with arms and legs that allow the development of a long stroke. Present inquiries include the development of an appropriately large cardiac output despite the Valsalva-like manoeuvre associated with the stroke, and the remarkable ability of the brain to maintain motor control and metabolism despite marked reductions in cerebral blood flow and oxygenation.

Meta-Analysis of Clinical Efficacy and Safety of Ligustrazine in the Treatment of Idiopathic Pulmonary Fibrosis.

Abstract: Objective To systematically review the efficacy and safety of Ligustrazine in the treatment of idiopathic pulmonary fibrosis (IPF). Methods The electronic literature databases (PubMed, EMbase, CNKI, WanFang database, and VIP) were retrieved through a computer to find out the randomized controlled trials (RCT) of Ligustrazine in the treatment of IPF according to the inclusion/exclusion criteria screening test. Cochrane's bias risk table was also used to evaluate the quality of the study and to extract effective data. RevMan 5.3 was used for statistical analysis. Results A total of 7 RCTs (a total of 366 patients, including 196 in experimental and 170 in control group). Compared with the control group, Ligustrazine could improve the clinical symptoms ([OR] = 2.20, 95% CI [1.40, 3.46], P=0.0006), lung function (VC % [MD] = 3.92, 95% CI [0.68, 7.17], P=0.02), (TLC% [MD] = 4.94, 95% CI [0.37, 9.52], P=0.03), the pulmonary diffusion function (DLCO % [MD] = 9.12, 95% CI [5.70, 12.55], P < 0.00001), and arterial blood gas analysis (PaO2 [MD] = 7.11, 95% CI [1.96, 12.25], P=0.007) (PaCO2 [MD] = -2.42, 95% CI [-4.36, -0.49], P=0.01) of IPF patients, respectively. However, FEV1/FVC % ([MD] = 9.37, 95% CI [-1.23, 19.97], P=0.08) and adverse reactions ([MD] = 0.35, 95% CI [0.02, 5.36], P=0.45) were not significantly improved. Conclusion Ligustrazine has certain clinical efficacy in the treatment of IPF, but the safety of applying it and the adverse reactions need to be further analyzed and determined. It can be considered as a new alternative and complementary medicine to be promoted and recommended for use in medical units in various countries in the world and it solved the difficult problem of conventional drug treatment of IPF; therefore, more research strength can be put in the treatment of the pathological mechanism of IPF for further exploration. The study was registered under registration number CRD42020193626.

Transcriptomic modifications in developmental cardiopulmonary adaptations to chronic hypoxia using a murine model of simulated high-altitude exposure.

Abstract: Mechanisms driving adaptive developmental responses to chronic high-altitude (HA) exposure are incompletely known. We developed a novel rat model mimicking the human condition of cardiopulmonary adaptation to HA starting at conception and spanning the in utero and postnatal timeframe. We assessed lung growth and cardiopulmonary structure and function and performed transcriptome analyses to identify mechanisms facilitating developmental adaptations to chronic hypoxia. To generate the model, breeding pairs of Sprague-Dawley rats were exposed to hypobaric hypoxia (equivalent to 9,000 ft elevation). Mating, pregnancy, and delivery occurred in hypoxic conditions. Six weeks postpartum, structural and functional data were collected in the offspring. RNA-Seq was performed on right ventricle (RV) and lung tissue. Age-matched breeding pairs and offspring under room air (RA) conditions served as controls. Hypoxic rats exhibited significantly lower body weights and higher hematocrit levels, alveolar volumes, pulmonary diffusion capacities, RV mass, and RV systolic pressure, as well as increased pulmonary artery remodeling. RNA-Seq analyses revealed multiple differentially expressed genes in lungs and RVs from hypoxic rats. Although there was considerable similarity between hypoxic lungs and RVs compared with RA controls, several upstream regulators unique to lung or RV were identified. We noted a pattern of immune downregulation and regulation patterns of immune and hormonal mediators similar to the genome from patients with pulmonary arterial hypertension. In summary, we developed a novel murine model of chronic hypoxia exposure that demonstrates functional and structural phenotypes similar to human adaptation. We identified transcriptomic alterations that suggest potential mechanisms for adaptation to chronic HA.

Unexpected radiation pneumonitis after SIRT with significant decrease in DLCO with internal radiation exposure: a case report.

Abstract: In the last years, Selective Internal Radiation Therapy (SIRT), using biocompatible Yttrium-90 (90Y) labeled microspheres have emerged for the treatment of malignant hepatic tumors. Unfortunately, a significant part of 90Y-labeled microspheres may shunt to the lungs after intraarterial injection. It can be predictable by infusing technetium-99 m-labeled macro-aggregated albumin particles through a catheter placed in the proper hepatic artery depending on the lobe to be treated with performing a quantitative lung scintigraphy. Radiation pneumonitis (RP) can occur 1 to 6 months after the therapy, which is a rare but severe complication of SIRT. Prompt timing of steroid treatment is important due to its high mortality rate. On the other hand, pulmonary diffusion capacity measured by carbon monoxide (DLCO) is an excellent way to measure the diffusing capacity because carbon monoxide is present in minimal amount in venous blood and binds to hemoglobin in the same manner as oxygen. Some authors reported that the most consistent changes after radiation therapy (RT) are recorded with this quantitative reproducible test. The relationship between the proportional reductions in DLCO and the severity of RP developing after this therapy may prove to be clinically significant. We herein present a patient who developed RP after SIRT that could be quantified using DLCO. To the best of our knowledge, this case is the first who developed unexpected RP after SIRT with significant decrease in DLCO with internal radiation exposure. RP is a very rare complication and may lead to a fatal outcome. Decline in DLCO could be a valuable parameter for follow-up and to identify potential candidates for RP and could be also another trigger for administration of steroid therapy with prompt timing in this patient group.

Clinical utility of a composite scoring system including Charlson Comorbidity Index score in patients with interstitial lung disease

Abstract: Background Prognostic factors have yet to be established for patients with interstitial lung disease (ILD). We aimed to clarify whether the Charlson Comorbidity Index score (CCIS) could help predict disease prognosis in patients with ILD. Methods Among ILD patients treated between April 2013 and April 2017, we retrospectively assessed the relationship between baseline clinical parameters including age, sex, CCIS, ILD diagnosis, pulmonary function test results, and 3-year ILD-related events including cause-specific death and first acute exacerbation (AE). Results We assessed 180 patients (mean age, 74 years), all of whom underwent pulmonary function testing including percentage predicted diffusion capacity for carbon monoxide (%DLco). Underlying pathologies included idiopathic pulmonary fibrosis (IPF) in 57 cases, idiopathic nonspecific interstitial pneumonia (iNSIP) and collagen vascular disease-related interstitial pneumonia in 117 cases, and chronic hypersensitivity pneumonia (CHP) in 6 cases. A composite scoring system comprising IPF diagnosis, CCIS, and %DLco provided a favorable C-index (0.825) for predicting 3-year ILD-related events. The nomogram for 3-year prognosis revealed the largest contributions from CCIS, %DLco and IPF diagnosis. Conclusions This composite scoring system accounting for IPF diagnosis, CCIS, and %DLco could provide a useful tool for predicting prognosis in relatively mild ILD patients tolerated to pulmonary diffusion capacity testing.

Relationship between pulmonary function and albuminuria in type 2 diabetic patients with preserved renal function

Abstract: Albuminuria is the early manifestation of the pathogenesis of diabetic nephropathy (DN). The current study was to investigate the relationship of pulmonary function with albuminuria in type 2 diabetic patients with preserved renal function to evaluate the role of pulmonary function in the early stage of DN. A total of 326 patients with type 2 diabetes mellitus (T2DM) including 270 without albuminuria and 56 with albuminuria, and 265 non-diabetic patients were enrolled. The patients’ general information, and the parameters of pulmonary function, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, total lung capacity (TLC), diffusion capacity for carbon monoxide of lung (DLCO) were compared between T2DM and control groups, as well as T2DM patients with and without albuminuria groups. All pulmonary function parameters were expressed as a percentage of those predicted (%pred). Logistic regression models were constructed to test the association of albuminuria and pulmonary function. The values of FVC%pred, FEV1%pred, TLC%pred and DLCO%pred were lower, and the proportion of subjects with FVC%pred < 80, FEV1%pred < 80, and DLCOc%pred < 80 was higher in T2DM subjects than controls (all P < 0.05). Subgroup analysis of diabetic patients showed that the values of FVC%pred, FEV1%pred, TLC%pred, and DLCOc%pred (97.18 ± 13.45, 93.95 ± 14.51, 90.64 ± 9.97, 87.27 ± 13.13, respectively) were significantly lower in T2DM subjects with albuminuria than those without albuminuria (103.94 ± 14.12, 99.20 ± 14.25, 93.79 ± 10.36, 92.62 ± 13.45, all P < 0.05). There was a significantly negative correlation between the urine albumin-to-creatinine ratio (UACR) and DLCOc%pred (r = − 0.143, P = 0.010) in spearman linear correlation test. In logistic regression analysis, the FVC%pred (OR 0.965, 95%CI 0.944–0.988), FEV1%pred (OR 0.975, 95%CI 0.954–0.996), and DLCOc%pred (OR 0.974, 95%CI 0.951–0.998) were independently associated with albuminuria after adjustments for smoking index, duration, HbA1c, FBG, and TG. Our results demonstrated albuminuria is associated with a restrictive pulmonary function as well as pulmonary diffusion function in T2DM with preserved renal function, which remind us to be alert of the pulmonary function decline even in the early stage of DN.

Cytokine storm and immunoregulatory therapy of coronavirus pneumonia

Abstract: Cytokine storm, a runaway overwhelming immune response, plays an important part in the pathogenesis of coronavirus The virus hijacks the immune system, resulting in a loss of negative feedback on the immune regulation and an overproduction of inflammatory cytokines, which subsequently impairs the pulmonary diffusion function and leads to multi-organ dysfunction A series of progresses have been achieved in studies targeting the coronavirus cytokine storm, such as granulocyte colony-stimulating factor, tocilizumab, camostat mesylate, and blood purification treatment, which may provide effective ways to alleviate the coronavirus disease 2019 (COVID-19) epidemic Nevertheless, further clinical verifications of the above research findings are requested due to the unique pathology of COVID-19 This paper reviews the advances in cytokine storm and immunoregulatory therapy of coronavirus pneumonia

Epigenome-wide association studies of three social determinants of health and implications for lung functions among survivors of childhood cancer

Abstract: Background Emerging evidence suggests that social determinants of health (SDOH) may influence health and wellness through an epigenetic mechanism in the general population. However, the social epigenomic approach has not yet been applied to survivors of childhood cancer, a vulnerable population with elevated risk for chronic health conditions (CHCs). Methods Study participants were drawn from the St Jude Lifetime Cohort, a hospital-based retrospective cohort with prospective follow up. DNA methylation (DNAm) profiling was generated based on blood derived DNA collected during follow-up visit. SDOH included educational attainment, personal income, and area deprivation index (ADI) based on baseline or follow-up questionnaires and geocoding. CHCs were clinically assessed with severity grade. Results We included 258 childhood cancer survivors of African ancestry (AA) (median time from diagnosis=25.2 years, interquartile range [IQR]=19.9-32.1 years) and 1,618 survivors of European ancestry (EA) (median time from diagnosis=27.3, IQR=21.1-33.7 years). Through epigenome-wide association studies, we identified 130 SDOH-CpG associations including educational attainment (N=88), personal income (N=23), and ADI (N=19) at epigenome-wide significance level (P Conclusions We demonstrated striking DNAm signatures associated with multiple SDOH factors (educational attainment, personal income, and ADI) and many epigenome-wide significant CpG sites resembling the effect of smoking exposure. We also identified an exemplified racial health disparity in pulmonary diffusion deficit between AA and EA survivors and illuminated DNAm as potential mechanistic mediators for SDOH factors using a social epigenomic approach.