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Colorectal cancer (CRC) remains the third leading cause of cancer-related death worldwide. Here, we aimed to uncover the mechanism underlying the transcription factor fifth Ewing variant protein (FEV) in CRC. Transcriptome differential expression in human CRC and adjacent tissues was analyzed using GSE143939, GSE142279, GSE196006, and GSE200427 datasets, and the intersecting genes were screened by comparing them with the list of transcription factors in the Human TFBD database, followed by KEGG enrichment analysis. FEV expression was significantly reduced in CRC, and upregulation of FEV inhibited cell growth and tumor progression in CRC. The highly expressed genes in CRC were mainly enriched to the Wnt signaling pathway, and WNT2 is the core initiator of the Wnt signaling pathway. Two binding sites for FEV are present on the WNT2 promoter. WNT2 promoted the proliferation, migration, and invasion of CRC cells. FEV repressed WNT2 transcription by binding to the WNT2 promoter. Collectively, our data revealed that a novel FEV/WNT2 axis is critical for CRC progression. Strategies targeting this specific signaling axis might be developed to treat patients with CRC. [ABSTRACT FROM AUTHOR]

The aim of this research was to examine the existence of broncho-obstruction of the airways in patients suffering from chronic obstructive pulmonary disease, as well as changes in resistance values in this part of the bronchial tree after inhalation of salbutamol.

BACKGROUND: Asthma is a major public health concern due to its persistent inflammation of the airways. The intricate and widely variable epidemiology of asthma among nations and populations is a result of the interplay between genetic, environmental, and socioeconomic factors. OBJECTIVE: This study aims to investigate whether VitD supplementation can reduce the frequency of exacerbations (including the frequency of exacerbations requiring systemic corticosteroids and the frequency of exacerbations necessitating trips to the hospital or emergency room, or both) and improve pulmonary function (clinical indicators such as the FEV1% predicted value). METHODS: Computers were used to search Pubmed, Medline, ISI Web of Science, Embase, Cachrane Library, CNKI, CBM, VIP, and the Wanfang Database. Asthma/asthma, VitD/VitD, lung function/lung function, retrieval time is from database setup to October 8, 2021, to search all randomized controlled trials (RCTs) on the effect of VitD on human asthma and to retroactively incorporate references to literature were all included in the search criteria. After rigorous screening, quality evaluation, and data extraction of the included literature by two reviewers independently, heterogeneity tests and sensitivity analyses were performed. RESULTS: The findings show that a total of 12 relevant studies meeting the inclusion criteria were finally included, including 649 cases in the experimental group and 646 cases in the control group. VitD intervention reduced the number of asthma exacerbations, including the rate of exacerbations requiring systemic corticosteroid therapy and the rate of acute exacerbations requiring emergency department or hospital visits or both. CONCLUSIONS: In the outcome of lung function (FEV1% predicted value), it was shown that VitD supplementation improved lung function; in the outcome of serum 25-hydroxyVitD levels, it was shown that VitD supplementation increased serum 25-hydroxyVitD levels. [ABSTRACT FROM AUTHOR]

• Ceiling effects in therapeutic benefit are commonly understood to impact cystic fibrosis. • Day-to-day variation in measured FEV 1 is common. • Floor and ceiling effects can be exaggerated in the presence of measurement error. • Estimation of ceiling effects should account for biasing effects of measurement error. Clinical trials often demonstrate treatment efficacy through change in forced expiratory volume in one second (FEV 1), comparing single FEV 1 measurements from post- versus pre-treatment timepoints. Day-to-day variation in measured FEV 1 is common for reasons such as diurnal variation and intermittent health changes, relative to a stable, monthly average. This variation can alter estimation of associations between change in FEV 1 and baseline in predictable ways, through a phenomenon called regression to the mean. We quantify and explain day-to-day variation in percent-predicted FEV 1 (ppFEV 1) from 4 previous trials, and we present a statistical, data-driven explanation for potential bias in ceiling and floor effects due to commonly observed amounts of variation. We recommend accounting for variation when assessing associations between baseline value and change in CF outcomes in single-arm trials, and we consider possible impact of variation on conventional standards for study eligibility. [ABSTRACT FROM AUTHOR]

[Display omitted] The 57Fe Mössbauer isomer shift is not directly related to the oxidation state of iron, and therefore the evaluation of the oxidation state of iron from the isomer shift is problematic. The oxidation state affects the isomer shift only to the extent that it affects the Fe–X bond lengths. The isomer shift can be estimated based on the average Fe–X interatomic distance. [ABSTRACT FROM AUTHOR]

The relationship between carbon monoxide diffusing capacity (DLCO) measurement in patients being evaluated for heart transplantation is poorly understood. We collected pretransplant pulmonary function testing (PFT) data on 157 transplant recipients over a 10-year span. Due to a few common reasons such as intensive care unit hospitalization, only 47% of candidates underwent DLCO measurement. However, there were no differences in outcomes regardless of whether or not the test was available to guide candidate selection. No PFT value correlated with pulmonary complications and only forced expiratory volume in 1 second correlated with survival. We conclude that in subjects otherwise eligible for heart transplantation, DLCO measurement carries no significant discriminatory power. Furthermore, due to extensive variability in utilization, arguments on the grounds of equity could be made to eliminate such testing.

Background: Spirometry is a commonly used lung function test. It assesses respiratory functions by measuring the air volume and the rate at which a person can exhale from lungs filled to their total capacity. The most helpful spirometry parameters are: forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF). Pregnancy derives an altered physiological state due to hormonal and anatomical changes that affect the respiratory system. Despite that, spirometry is less commonly done during pregnancy, and if done, test results are evaluated against non-pregnancy references.Objective: This study aimed to explore spirometry profiles in pregnant and non-pregnant women and describe their differences.Methodology: This cross-sectional study involved age-matched pregnant and non-pregnant participants recruited from Mnazi Moja ANC and Muhimbili University (MUHAS). A digital spirometer was used to assess respiratory function. Data were entered and analyzed using SPSS version 23. The mean spirometry values of pregnant participants were compared to those of non-pregnant participants using an independent sample t-test. A p-value of < 0.05 was considered statistically significant.Results: The study included 92 pregnant and 98 non-pregnant participants subjected to spirometry. Both FVC and FEV1 values were significantly lower in pregnant than in non-pregnant participants (2.7 ± 0.5 L vs. 2.9 ± 0.5 L; p < 0.01 and 2.2 ± 0.4 L vs. 2.5 ± 0.4 L; p < 0.01 respectively). In addition, pregnant participants had significantly lower mean PEF values than their non-pregnant counterparts (303 ± 84 L/min versus 353 ± 64 L/min; p < 0.01).Conclusion: Spirometry test values are lower in pregnancy than in non-pregnant participants.Recommendations: Interpreting the spirometry test values of pregnant women using references obtained from non-pregnant women may be inappropriate. Future studies should evaluate the appropriateness of predicting spirometry values of pregnant women using reference equations derived from non-pregnant women. [ABSTRACT FROM AUTHOR]

Background: Impaired lung function is associated with a higher risk of developing lung cancer. However, lung function is a dynamic variable and must be evaluated longitudinally. This study reports on the relationship between accelerated lung function decline and development of lung cancer.Research Question: Is accelerated lung function decline associated with the development of lung cancer?Study Design and Methods: A longitudinal, observational study was performed by using epidemiologic data from two population-based studies comprising subjects assessed biannually from 2001 to 2019 in South Korea. Eligible subjects were between 40 and 69 years of age and were followed up by using spirometry. Spirometry measurements were made at each follow-up. Patients with a decline in FEV1 > 60 mL per year were defined as rapid FEV1 decliners. The relationship between lung cancer and rapid FEV1 decline was evaluated by using adjusted Cox regression models with covariates, including age, sex, smoking history, FEV1/FVC, and WBC count.Results: Among the 8,549 eligible subjects, 1,287 (15.1%) had rapid FEV1 decline, and 48 (0.6%) had newly developed lung cancer. The risk of lung cancer development was increased in the subjects aged ≥ 45 years and those with ≥ 30 pack-years of smoking, low baseline FEV1/FVC, low forced expiratory flow between 25% and 75% of vital capacity, rapid FEV1 decline, and increased WBC count. Rapid FEV1 decline was an independent risk factor for lung cancer development (adjusted hazard ratio, 2.34; 95% CI, 1.28-4.28; P = .006). Time-dependent net reclassification improvement showed a benefit of FEV1 decline rate in determining subjects at risk of lung cancer when added to conventional practice (categorical, 0.32 [95% CI, 0.00-0.64]; continuous, 0.83 [95% CI, 0.14-1.25]).Interpretation: The FEV1 decline rate may be a potential biomarker for lung cancer development. Further study is needed to identify whether patients with rapid FEV1 decline warrant lung cancer assessment or screening. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) Is an aggressive hematological malignancy that recurs In approximately 50% of cases. Elevated homing and uncontrolled expansion are characteristics of AML cells. Here, we identified that Fifth Ewing Variant (FEV) regulates the homing and expansion of AML cells. We found that FEV was re-expressed in 30% of primary AML samples and in almost all relapsed AML samples, and FEV expression levels were significantly higher in relapsed samples compared to primary samples. Interference of FEV expression in AML cell lines delayed leukemic progression and suppressed homing and proliferation. Moreover, FEV directly activated integrin subunit alpha 4 (ITGA4) transcription in a dose-dependent manner. Inhibition of integrin a4 activity with natalizumab (NZM) reduced the migration and colony-forming abilities of blasts and leukemic-initiating cells (LICs) in both primary and relapsed AML. Thus, our study suggested that FEV maintains the homing and expansion of AML cells by activating ITGA4 transcription and that targeting ITGA4 inhibits the colony-forming and migration capacities of blasts and LICs. Thus, these findings suggested that the FEV-ITGA4 axis may be a therapeutic target for both primary and relapsed AML. [ABSTRACT FROM AUTHOR]

Background: An improved understanding of how severe asthma heterogeneity affects response could inform treatment decisions., Objectives: Characterize heterogeneity and benralizumab responsiveness in patients grouped by predefined Severe Asthma Research Program clusters using a multivariate approach., Methods: In post-hoc analyses of the randomized, double-blind, placebo-controlled phase III SIROCCO (NCT01928771) and CALIMA (NCT01914757) studies, patients with severe asthma who received benralizumab or placebo were assigned to clusters using an established discriminant function to analyze 11 clinical characteristics simultaneously. The annualized asthma exacerbation rate, exacerbation incidence, and lung function were analyzed across clusters., Results: Patients (n = 2,281) met criteria for four of five clusters: cluster 2 (early-onset moderate asthma, n = 393), cluster 4 (early-onset severe asthma, n = 386), cluster 3 (late-onset severe asthma, n = 641), and cluster 5 (late-onset severe, obstructed asthma, n = 861); no patients met cluster 1 criteria. Exacerbation rate reductions were significant in late-onset severe asthma (-48% [95% CI, -61% to -31%]; P < .0001) and late-onset severe, obstructed asthma (-50% [95% CI, -59% to -38%]; P < .0001), with nonsignificant reductions in early-onset clusters. These differences could not be fully explained by blood eosinophil count differences. Values for improvements in FEV 1 were significant in late-onset severe asthma (+133 mL [95% CI, 66-200]; P = .0001) and late-onset severe, obstructed asthma (+160 mL [95% CI, 85-235]; P < .0001) while maintaining acute bronchodilator responsiveness., Conclusions: Benralizumab reduced exacerbations and improved lung function, primarily in late-onset asthma clusters. This multivariate approach to identify subphenotypes, potentially reflecting pathobiological mechanisms, can guide therapy beyond univariate approaches., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale: Identification of younger adults at high risk of developing chronic obstructive pulmonary disease (COPD) could lead to implementation of preventive measures before disease onset and halt progression.Objectives: To investigate the prevalence, characteristics, and prognosis of individuals with early COPD in the general population.Methods: We investigated 105,630 randomly chosen adults from a Danish contemporary population-based cohort. Early COPD was defined as FEV1/FVC less than the lower limit of normal in individuals under 50 years of age with 10 pack-years or greater of tobacco consumption.Measurements and Main Results: Among 8,064 individuals under 50 years of age with 10 pack-years or greater of tobacco consumption, 1,175 (15%) had early COPD, of whom 58% were current smokers. Individuals with early COPD more often had chronic respiratory symptoms, severe lung function impairment, asthma, and a history with bronchitis/pneumonia. During the 14.4-year follow-up, we observed 117 acute hospitalizations with obstructive lung disease, 227 acute hospitalizations with pneumonia, and 185 deaths among the 8,064 younger adults. Compared with individuals without COPD, those with early COPD had multivariable adjusted hazard ratios of 6.42 (95% confidence interval, 3.39-12.2) for acute obstructive lung disease hospitalizations, 2.03 (1.43-2.88) for acute pneumonia hospitalizations, and 1.79 (1.28-2.52) for all-cause mortality.Conclusions: Among individuals under 50 years of age and 10 pack-years or greater of tobacco consumption from the general population, 15% fulfill criteria of early COPD. Individuals with early COPD more often have chronic respiratory symptoms and severe lung function impairment, and an increased risk of acute respiratory hospitalizations and early death. [ABSTRACT FROM AUTHOR]

Gulixian Mahemuti, Hui Zhang, Jing Li, Nueramina Tieliwaerdi, Lili Ren Respiratory Department, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Province, People’s Republic of China Background and objective: Theophylline has been used for decades to treat both acute and chronic asthma. Despite its longevity in the practitioner’s formulary, no detailed meta-analysis has been performed to determine the conditions, including concomitant medications, under which theophylline should be used for acute exacerbations of asthma. We aimed to quantify the usefulness and side effects of theophylline with or without ethylene diamine (aminophylline) in acute asthma, with particular emphasis on patient subgroups, such as children, adults, and concomitant medications.Methods: We searched PubMed, EMBASE, The Cochrane Library, ClinicalTrials.gov, and the WHO Clinical Trials Registry for randomized, controlled clinical trials. We planned a priori subgroup analyses by time post-medication, concomitant medication, control type, and age.Results: We included 52 study arms from 42 individual trials. Of these, 29 study arms included an active control, such as adrenaline, beta-2 agonists, or leukotriene receptor antagonists, and 23 study arms compared theophylline (with or without ethylene diamine) with placebo or no drug. Theophylline significantly reduced heart rate when compared with active control (p=0.01) and overall duration of stay (p=0.002), but beta-2 agonists were superior to theophylline at improving forced expiratory volume in one second (FEV1) (p=0.002). Theophylline was not significantly different from other drugs in its effects on respiratory rate, forced vital capacity (FVC), peak expiratory flow rate, admission rate, use of rescue medication, oxygen saturation, or symptom score. Closer examination of the data revealed that the medications given in addition to theophylline or control significantly changed the effectiveness of theophylline (subgroup difference: p

Introduction: Italian Cystic Fibrosis Registry (ICFR) collects data of patients with cystic fibrosis (CF) through the collaboration with Italian CF referral and support Centres (Italian law 548/93). It aims at analysing medium and long-term clinical and epidemiological trends, identifying healthcare needs at regional and national levels, contributing to healthcare programmes, and resource allocation. Italian data are also compared at international level through the collaboration with the European CF Registry for sharing epidemiological data on general aspects like CF epidemiology and specific topics such as the use of CFTR modulators., Objectives: The purpose of this Report is to provide updated demographic and clinical data of the Italian FC population for the years 2021 and 2022, to contribute essential information for the implementation of projects aimed at improving the management of patients affected by this disease., Design: Analyses and results presented in this Report pertain to patients currently under care at Italian National Referral and Support Centres for Cystic Fibrosis and Paediatric Hospital 'Bambino Gesù' in the 2021-2022 period. Data were submitted by clinical Centres through a dedicated web-based software and underwent dual quality control (QC) measures: automated quantitative QC within the software and secondary QC at the European level before the integration into the European Cystic Fibrosis Registry. These measures ensure data completeness, accuracy, and longitudinal consistency with European core data., Setting and Participants: A total of 27 CF Centres, including referral and support centres, as well as 'Bambino Gesù' Children's Hospital CF centre, submitted their data to ICFR for the years 2021-2022. Althourgh CF Centres in Verona and Messina do not use the ICFR software, their data are centrally collected and subsequently forwarded to the European Registry. Data from service centres in Treviso and Rovereto are transmitted via the Verona CF Centre. Data from Sardinia Centre are currently unavailable., Results: The results section provides a comprehensive overview of various aspects of CF epidemiology and patient characteristics. 1.Demography: in 2021 and 2022, 5,977 and 6,077 CF patients were respectively included in the ICFR, with median ages of 23.3 and 23.7 years. The prevalence rates were 10.1 and 10.3 per 100,000 residents in Italy for the respective years, with males comprising 51.6% on average. The distribution by age showed a higher frequency among patients aged 7 to 35 years; adult patients constituted 63.5% on average in both years. 2. Diagnosis: most CF patients were diagnosed before the age of two (mean value 57.9%), with a significant percentage diagnosed in adult age (35.4% in 2021 and 25.6% in 2022). 3.New diagnoses: there were 113 new diagnoses in 2021 and 121 in 2022, with estimated incidences of 1 in 9,097 living births in 2021 and 1 in 6,232 in 2022. 4. Genetics: genetic analyses were conducted on 99.9% of patients, revealing CFTR gene mutations in over 98% of cases. The F508del mutation was the most common (44% of alleles in 2021), with 18% of patients having at least one "residual function" mutation. Gating mutations were present in 3.4% of Italian patients, while 20% had at least one-stop codon mutation. 5.Lung function: lung function, measured by percent predicted (pp)FEV1 (Forced Expiratory Volume in the first second) progressively declined before adulthood, with the majority of paediatric patients (92.8% in 2021 and 93.8% in 2022) maintaining a ppFEV1≥70%. 6.Nutrition: critical periods for nutrition were identified as the first 6 months of life and adolescence, with higher prevalence of malnourished male adolescents compared to females. Suboptimal BMI values were more common in adult females (28.7% in 2021 and 26.9% in 2022) compared to males (14.2% in 2021 and 12.6% in 2022). 7. Complications: CF-related liver disease without cirrhosis was prevalent in patients under 18 years (21.9% in 2021 and 21.2 in 2022), while CF-related diabetes was most frequent in adults (24.2%). 8.Transplantation: over the two-year period, 28 patients underwent double-lung transplantation, with median ages of 29.1 in 2021 and 35.3 in 2022, respectively. Median waiting times ranged from 9.4 to 11.6 months. 9.Microbiology: chronic Pseudomonas aeruginosa infection affected 37.2% of adult patients in 2021 and 36.0% in 2022, compared to 7.4% and 6.5% in paediatric patients. Staphylococcus aureus infection rates were 34.6% and 42.2% in 2021 among adults and 34.4% and 36.7% in 2022 among paediatric patients. 10. Mortality: a total of 34 patients died during the 2021-22 period (19 females, 15 males), with median ages at death of 43.7 years in 2021 and 46 years in 2022 (excluding transplanted patients)., Conclusions: The present Report is an update of the data published in the past years and summarizes the main epidemiological and clinical data regarding Italian CF subjects in the years 2021 and 2022. The number of patients registered in 2021 was 5,977, while in 2022 was 6,077. The population coverage estimates for 2022 to be around 97%. In 2020, 60.5% of patients were older than 18 years, in 2022 adult patients account for 63.5% of the Italian CF population. Over the years, therefore, an increase in the median age of Italian CF patients has been observed, reaching 23.7 years in 2022. The absolute number of new diagnoses per year remains substantially unchanged over the years (a total of 234 in the period under review). The median age at diagnosis in 2022 was 2.5 months, 62.6% of subjects are really diagnosed within the first year of life and almost 90% of them are diagnosed through neonatal screening. In 2022, almost all patients underwent genetic analysis (99.9%). Data collected confirm the great variability among Italian CF patients. As regards respiratory function, what is reported in previous reports is here confirmed, with an ever-increasing percentage of subjects under the age of 18 having normal respiratory function, moreover, less than 1% of paediatric patients has a severe lung function (ppFEV1<40). The marked improvement in this indicator in the adult population seems to be mainly due to the introduction from 2021 in Italy of therapy with highly effective CFTR modulators. At the same time, the close positive correlation between nutritional status and respiratory function is confirmed for the adult population. As regards chronic infection by Pseudomonas aeruginosa, in 2022, a reduction in the percentage of chronic infection is observed both among adults (36% vs 38.8% in 2020) and in paediatric patients (6.5% vs 7.6% in 2020). The most frequent complication in both paediatric and adult populations is liver disease (respectively, in 24.2% and 41.3% of subjects). In the two-year period, 34 patients died; their median age at death was between 43 and 46 years (transplant patients excluded); only two patients under the age of 18 died in the period 2021 and 2022, confirming once again that mortality in paediatric age is a rare event. The data presented in this Report shows how the register can be a national and international point of reference for CF patients and the scientific community, a tool for describing the Italian CF population over the years, and a starting point for planning epidemiological studies and clinical studies.

Rationale: Less invasive, nonsurgical approaches are needed to treat severe emphysema.Objectives: To evaluate the effectiveness and safety of the Spiration Valve System (SVS) versus optimal medical management.Methods: In this multicenter, open-label, randomized, controlled trial, subjects aged 40 years or older with severe, heterogeneous emphysema were randomized 2:1 to SVS with medical management (treatment) or medical management alone (control).Measurements and Main Results: The primary efficacy outcome was the difference in mean FEV1 from baseline to 6 months. Secondary effectiveness outcomes included: difference in FEV1 responder rates, target lobe volume reduction, hyperinflation, health status, dyspnea, and exercise capacity. The primary safety outcome was the incidence of composite thoracic serious adverse events. All analyses were conducted by determining the 95% Bayesian credible intervals (BCIs) for the difference between treatment and control arms. Between October 2013 and May 2017, 172 participants (53.5% male; mean age, 67.4 yr) were randomized to treatment (n = 113) or control (n = 59). Mean FEV1 showed statistically significant improvements between the treatment and control groups-between-group difference at 6 and 12 months, respectively, of 0.101 L (95% BCI, 0.060-0.141) and 0.099 L (95% BCI, 0.048-0.151). At 6 months, the treatment group had statistically significant improvements in all secondary endpoints except 6-minute-walk distance. Composite thoracic serious adverse event incidence through 6 months was greater in the treatment group (31.0% vs. 11.9%), primarily due to a 12.4% incidence of serious pneumothorax.Conclusions: In patients with severe heterogeneous emphysema, the SVS shows significant improvement in multiple efficacy outcomes, with an acceptable safety profile.Clinical trial registered with www.clinicaltrials.gov (NCT01812447). [ABSTRACT FROM AUTHOR]

Genetic factors are known to influence sport performance. The aim of the present study was to assess genetic variants in genes coding for proteins potentially modulating activity of brain emotion centres in a group of 621 elite athletes (212 endurance, 183 power and 226 combat athletes) and 672 sedentary controls. Ten statistically significant variants were identified in genes encoding elements of serotoninergic, catecholaminergic and hypothalamic-pituitary-adrenal systems in different sport groups. Of those the rs860573 variant in the FEV gene coding for transcription factor exclusively expressed in neurons of the central serotonin system is the only one whose frequency significantly differentiates all the groups of athletes studied, regardless of discipline, from the controls (p = 0.000026). Our results support the hypothesis that genetic variants potentially affecting mental processes and emotions, particularly in the serotonergic pathway, also influence the predispositions to athletic performance. [ABSTRACT FROM AUTHOR]

Rationale: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory properties that could benefit adults with comprised pulmonary health.Objective: To investigate n-3 PUFA associations with spirometric measures of pulmonary function tests (PFTs) and determine underlying genetic susceptibility.Methods: Associations of n-3 PUFA biomarkers (α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid [DPA], and docosahexaenoic acid [DHA]) were evaluated with PFTs (FEV1, FVC, and FEV1/FVC) in meta-analyses across seven cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (N = 16,134 of European or African ancestry). PFT-associated n-3 PUFAs were carried forward to genome-wide interaction analyses in the four largest cohorts (N = 11,962) and replicated in one cohort (N = 1,687). Cohort-specific results were combined using joint 2 degree-of-freedom (2df) meta-analyses of SNP associations and their interactions with n-3 PUFAs.Results: DPA and DHA were positively associated with FEV1 and FVC (P < 0.025), with evidence for effect modification by smoking and by sex. Genome-wide analyses identified a novel association of rs11693320-an intronic DPP10 SNP-with FVC when incorporating an interaction with DHA, and the finding was replicated (P2df = 9.4 × 10-9 across discovery and replication cohorts). The rs11693320-A allele (frequency, ∼80%) was associated with lower FVC (PSNP = 2.1 × 10-9; βSNP = -161.0 ml), and the association was attenuated by higher DHA levels (PSNP×DHA interaction = 2.1 × 10-7; βSNP×DHA interaction = 36.2 ml).Conclusions: We corroborated beneficial effects of n-3 PUFAs on pulmonary function. By modeling genome-wide n-3 PUFA interactions, we identified a novel DPP10 SNP association with FVC that was not detectable in much larger studies ignoring this interaction. [ABSTRACT FROM AUTHOR]

Rationale: Obstructive lung disease is diagnosed by a decreased ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC); however, there is no universally accepted lower limit of normal for the FEV1/FVC ratio. Current established reference values use the Third National Health and Nutrition Examination Survey (NHANES III) database. In 2012, the Global Lung Initiative (GLI) introduced GLI12, which is a compilation reference set that uses standard deviation values to define normal spirometry.Objectives: To evaluate the changes in classification of obstructive spirometry with use of GLI12 compared with NHANES III in a heterogeneous, multiracial population.Methods: We evaluated the spirometry studies conducted in our pulmonary function laboratory between January 2005 and December 2015. NHANES III reference equations were calculated to predict lower limits of normal for FEV1, FVC, and FEV1/FVC. GLI12 values were established using European Respiratory Society published computer software. FEV1 severity was graded using 2005 American Thoracic Society guidelines for NHANES III and using z-score-based criteria for GLI12. Asymmetric partition analysis evaluated agreement between the reference sets.Results: A total of 11,888 studies were evaluated. Obstruction was diagnosed in 2,857 studies using NHANES III versus 2,489 studies using GLI12. Agreement regarding the presence or absence of obstruction occurred in 2,483 of studies with obstruction and 9,025 studies without obstruction (agreement, 96.8%; κ = 0.91). Of the studies with obstruction, 1,595 had agreement in severity grading. Overall, agreement regarding obstruction and severity grading occurred in 10,620 studies, representing 89.3% of all studies. A total of 380 studies (3.2%) had discordance regarding the presence or absence of obstruction, 34.0% (844 of the 2,483 obstruction studies) had a one-degree of change in FEV1 disease severity scoring, with 44 cases (1.8%) that had changes of two categories in FEV1 severity scores. No studies had greater than two degrees of change. Asymmetric partition analysis suggested that the highest clinically significant changes were seen in older individuals, particularly African American men older than 65.Conclusions: Our evaluation suggests that there is moderate overall agreement between NHANES III and GLI12. We found a 3.2% change in classification of obstruction when transitioning from NHANES III to GLI12. When incorporating a z-score-based FEV1 and GLI12 reference set, 10.7% of the spirometry studies had a change in their categorization. The disagreement between the two datasets was most pronounced in elderly subjects. Although we cannot endorse one reference set over the other, we highlight the potential implications of adopting the GLI12 reference sets and suggest caution when interpreting spirometry in the elderly. [ABSTRACT FROM AUTHOR]

Numerous studies reporting on the health effects of wood dust have been published over many decades. For the clear majority of these studies, their use for setting a science-based occupational exposure level is problematic due generally to insufficient exposure measurement data, inadequate participant follow-up, and lack of control for confounding variables. However, there exists a robust data set from a large longitudinal lung function study that provides a scientifically sound basis for establishing an occupational limit of 5 mg/m3 inhalable wood dust. The choice of this data set and its application for this purpose are presented in this review. [ABSTRACT FROM AUTHOR]

Objective: To compare the plasma level of surfactant protein-A in apparently healthy smokers, stable and exacerbation Chronic Obstructive Pulmonary Disease (COPD) patients. Methods: This was a comparative study conducted from January, 2015 to March, 2016. This study was conducted on 87 subjects of both gender and age between 30-70 years. Of the total 87 subjects; 29 subjects were "healthy smokers" selected from general population as control group. Another 29 were "stable COPD" patients free of exacerbation since last six weeks. Lastly, another 29 subjects were "exacerbated COPD" patients with 7-10 days of exacerbation. COPD was diagnosed on the basis of relevant history and spirometry showing post bronchodilator FEV1/FVC <0.70. Surfactant Protein-A level (ng/ml) was estimated by a specific solid phase enzyme linked immunosorbent assay (ELISA) using automated EIA analyzer. Results: The SP-A levels, determined by competitive ELISA, was significantly higher (P<0.025) in healthy smokers (44.19±39.17 ng/ml) and exacerbated (43.86±40.17) than the stable COPD (25.89±18.85) patients. The lung function parameters (FEV1, FVC and FEV1/FVC) were lower in COPD patients compared to healthy smokers and were related to the duration of smoking. Conclusion: Current smokers and exacerbated patients had higher values of SP-A protein than stable COPD patients since they had stopped smoking. [ABSTRACT FROM AUTHOR]

Background: Vertebral compression fractures (VCF) change the natural spinal alignment and inevitably lead to a decreased quality of life.Objective: The aim of the study was to evaluate changes in pulmonary function after VCF were treated by radiofrequency kyphoplasty (RF-TVA).Methods: Twenty-five patients were treated with RF-TVA and analyzed in 3 subgroups taking into account the spinal location of the VCF. Pain as measured by visual analogue scale (VAS), Oswestry-Disability-Index (ODI), vertebral height, forced expiratory volume in 1 second (FEV1), and peak expiratory flow (PEF) were assessed before, directly after and 30 days after RF-TVA.Results: The mean vertebral height was improved in all subgroups, with a minor reduction from one to 30 days postoperatively. The mean VAS and ODI significantly decreased in the main and upper diaphragm groups from baseline to the follow-up after 30 days. Patients treated below the main diaphragm region showed a significant improvement of ODI and a clear trend to significant improvements of VAS. PEF and FEV1 were significantly improved in the main diaphragm group. FEV1 also increased significantly in the upper diaphragm group with a clear trend to significance in the lower diaphragm group.Conclusions: Results indicate that RF-TVA may improve pulmonary function especially in cases where fractures are located in the main spinal region of the diaphragm. [ABSTRACT FROM AUTHOR]

Objective: Clinical trial research have provided evidence that omega-3 may have larger potential benefits for treating cystic fibrosis (CF). This study's objective was to assess the impact of three supplementation on pediatric CF patients., Methods: Scopus, PubMed/Medline, Web of Science, Cochrane, and Embase databases were searched from commencement until July 20, 2022 using standard keywords to identify all randomized controlled studies (RCTs) examining the effects of omega-3 supplementation on young patients with CF. The eligible studies were subjected to a random-effects model meta-analysis., Results: A meta-analysis of 12 the eligible studies was performed. Findings of the study showed that omega-3 supplementation significantly increased the levels of docosahexaenoic acid (weighted mean [WMD]: 2.06%, 95% confidence interval [CI]: 1.29, 2.82, p < 0.001) and eicosapentaenoic acid (WMD: 0.32%, 95% CI: 0.15, 0.48, p < 0.001) as well as decreased arachidonic acid (WMD: -0.78%, 95% CI: -1.50, -0.05, p = 0.035) and C-receptive protein (CRP) (WMD: -3.76 mg/L, 95% CI: -7.42, -0.10, p = 0.044) especially when used in higher doses and for a longer period of time compared to the control group. However, no significant effect was observed on other factors including forced expiratory volume 1, forced vital capacity as well as anthropometric parameters. In addition, high heterogeneity was reported for all fatty acids, but heterogeneity was low and nonsignificant for other variables., Conclusion: The finding showed that in pediatric patients with CF, omega-3 supplementation showed benefits only in plasma fatty acid profile and serum CRP., (© 2023 Wiley Periodicals LLC.)

Introduction: Diurnal variability in airways has most commonly been reported using peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1). Characteristics of variability in small, mid and large airways caliber are expected to be different but have not been studied. Aim: The aim of the study was to assess diurnal variation in small mid and large airways caliber using FEF25, FEF50, FEF75 and FEF25-75 along with PEF and FEV1 in healthy subjects. Materials and Methods: Spirometry was performed in 161 healthy subjects twice in a day. Diurnal variability in FEF25, FEF50, FEF75, FEF25-75, PEF and FEV1 were determined and compared. Results: It revealed that all parameters exhibit significant diurnal variability. Diurnal variability is highest in large airways and lowest in smaller airways. Conclusion: Proximal airways show greater diurnal variation in their caliber than distal airways as reflected by greater variability in PEF as compared to FEV1.

Ethnopharmacological relevance Over the past few decades, there have been significant scientific advances leading to improved understanding of asthma as a disease and treatment providing immediate relief. However, prevention of recurrent attacks, exacerbations and disease cure remains a challenge. Ayurveda refers to bronchial asthma as Tamaka Swasa and it is well explained in Charaka Samhita . Management of asthma in Ayurveda includes removal of vitiated Kapha through Shodhana, Shamana procedures, herbal and herbomineral formulations in addition to advising a healthy lifestyle and diet. Several clinical trials on Ayurvedic formulations for treatment of asthma are reported, however, whole system management of asthma has rarely been studied in the manner in which it is actually being practiced. Ayurveda therapeutics provides Dosha specific approaches, which needs biological investigation. Aim of the study The objective of our study was to investigate lung functions and cytokine changes in Asthmatic individuals in response to Ayurvedic intervention. Methods The study design was approved by the Institutional Ethics Committee of Tilak Ayurveda Mahavidyalaya (TAMV) & Sheth Tarachand Ramnath Charitable Ayurveda Hospital and followed guidelines of the Declaration of Helsinki and Tokyo for humans. It was conducted as a whole system individualized pragmatic clinical trial and written consent of patients was collected before enrollment. One hundred and fifteen patients with mild-to-moderate asthma were divided into 2 sub-groups depending on their disease subsets and administered phenotype specific ayurvedic interventions. Seventy six asthma patients completed the treatment. Serum IgE levels, blood eosinophil counts, spirometry and blood cytokine levels were measured before the start of treatment and six months at the end of treatment. Age and sex matched healthy participants (n=69) were recruited in the study for comparison of cytokines levels. Results Significant improvements in FEV1(% predicted) (p<0.0001) and FVC (% predicted) (p=0.0001) was observed in asthmatic patients who underwent Ayurvedic treatment. Circulating levels of IgE (p<0.03) and eosinophil numbers (p=0.001) reduced significantly in the asthmatics after Ayurvedic treatment. This was associated with significant reduction in levels of circulating cytokines. Levels of Th2, Th1 and inflammatory cytokines in the peripheral blood were higher than healthy control participants at baseline (p values <0.0001) and reduced significantly after ayurvedic intervention. Conclusion This proof of concept study highlights the potential benefits and possible mechanism of Ayurvedic interventions in patients with mild-to-moderate asthma. The interventions significantly reduced IgE and eosinophil count, also improved lung function and reduced levels of circulating Th2 cytokines. [ABSTRACT FROM AUTHOR]

Background: There are few data regarding the impact of nontuberculous mycobacterial lung disease (NTM-LD) on lung function during the clinical course of disease. This study aimed to assess the impact of NTM-LD on lung function decline.Methods: Treatment outcomes and spirometry data at diagnosis and at least three years later were obtained from 358 patients who were diagnosed with NTM-LD between January 1999 and November 2011 using the prospective NTM registry cohort. For analysis, patients were divided into three groups: those observed without treatment, those who had treatment success, and those in whom treatment failed.Results: The treatment-failure group (n = 68) had a significantly more rapid decline in FEV1 and FVC compared with the observation (n = 118) and treatment-success (n = 172) groups (-52.2, -30.8, and -28.2 mL/y, respectively; P = .023 for FEV1 decline; -50.4, -28.8, and -26.0 mL/y, respectively; P = .002 for FVC decline). After adjusting for confounding factors, patients with treatment failure had greater FEV1 and FVC declines than did those observed without treatment (adjusted P = .026 for FEV1 decline; adjusted P = .022 for FVC decline) or those treated successfully (adjusted P = .004 for FEV1 decline; adjusted P = .002 for FVC decline). Patients treated successfully had declines in FEV1 and FVC similar to those in the observation group.Conclusions: The change of lung function was variable over a median 5-year follow-up period. Treatment failure was associated with a substantial decline in lung function in NTM-LD. [ABSTRACT FROM AUTHOR]

The introduction of fully electric vehicles (FEVs) into the mainstream has raised concerns about the reliability of their electronic components such as IGBT. The great variability in IGBT failure times caused by the very different operating conditions experienced and the stochasticity of their degradation processes suggests the adoption of condition-based maintenance approaches. Thus, the development of methods for assessing their healthy state and predicting their remaining useful life (RUL) is of key importance. In this paper, we investigate the results of performing accelerated aging tests. Our objective is to discuss the design and the results of accelerated aging tests performed on three different IGBT types within the electrical powertrain health monitoring for increased safety (HEMIS) of FEVs European Community project. During the tests, several electric signals were measured in different operating conditions. The results show that the case temperature (TC) , the collector current (IC) , and the collector–emitter voltage $(V_{{\rm CE}})$ are the failure precursor parameters that can be used for the development of a prognostic and health monitoring (PHM) system for FEV IGBTs and other medium-power switching supplies. [ABSTRACT FROM PUBLISHER]

Background The Infant Study of Inhaled Saline (ISIS) in CF was the first multicenter clinical trial to utilize infant pulmonary function tests (iPFTs) as an endpoint. Methods Secondary analysis of ISIS data was conducted in order to assess feasibility of iPFT measures and their associations with respiratory symptoms. Standard deviations were calculated to aid in power calculations for future clinical trials. Results Seventy-three participants enrolled, 70 returned for the final visit; 62 (89%) and 45 (64%) had acceptable paired functional residual capacity (FRC) and raised volume measurements, respectively. Mean baseline FEV 0.5 , FEF 75 and FRC z -scores were 0.3 (SD: 1.2), − 0.2 (SD: 2.0), and 1.8 (SD: 2.0). Conclusions iPFTs are not appropriate primary endpoints for multicenter clinical trials due to challenges of obtaining acceptable data and near-normal average raised volume measurements. Raised volume measures have potential to serve as secondary endpoints in future clinical CF trials. [ABSTRACT FROM AUTHOR]

Aim. To develop a procedure for evaluating the efficacy of antiiflammatory agents in mild persistent bronchial asthma. Materials and methods. 76 patients with mild bronchial asthma were given long acting theophylline. If a complete clinical and functional effect was absent, the inhaled glucocorticosteroid budesonide was added to the therapy. Before and after therapy, the forced expiratory volume per second and forced vital capacity (FVC) were measured many times within 24 hours, by using two procedures: 1) that involving morning and diurnal tests using short acting B2-agonists and 2) that without a bronchodilator. The time of onset of the plateau of values of different functional indices obtained during monitoring and their dispersion in the stable state were automatically calculated. The reliability of indices for evaluating the efficiency of antiinflammatory therapy was compared. Results. There were great differences in the patients' response to therapy: a complete clinical and functional effect of therapy with long acting theophylline alone (n = 9) and in combination with budesonide (n = 56). Moreover, therapy-resistant patients (n = 11) were identified. When a complete therapeutic effect was achieved, the clinical symptoms of the disease disappeared before the onset of the plateau of values of the most reliable functional indices. A comparative analysis of the indices has indicated that the ratio of the morning value of FVC measured just after awakening to its best personal value throughout the study was most convenient for the patients and reliable. Conclusion. The authors propose to use the index "ratio of the morning value of FVC measured just after awakening to its best personal value the percentage", by calculating the dispersion of this index, which characterizes the steady state of the expiratory respiratory system in order to evaluate the efficiency of antiinflammatory therapy for bronchial asthma and to solve other problems that require functional monitoring.

The aim of the work presented here was to determine the role of dry powder inhaler (DPI) counselling on inhalation technique and lung function test scores of the asthmatic patients. To decrease variability, asthmatic patients using an Aerolizer were enrolled in the study, as this was the most commonly prescribed DPI in outpatient clinics of Beni Suef University hospital. Each patient was subjected to three visits separated by 1 month each. In each visit, patient inhalation technique from the DPI was checked, and the number of mistakes was identified and corrected. Also, patients' peak expiratory flow (PEF) and forced expiratory volume in one second (FEV) presented as a percentage of the forced vital capacity (FVC) were checked. As the number of visits increased, the mean number of observed mistakes was significantly decreased ( p < 0.001). The most common repeated mistakes were 'To inhale fast' and 'To maintain a fast inhalation rate until the lungs are full'. In all age groups, there was a significant increase ( p < 0.001) in the pulmonary function test after the period of counselling. To improve and maintain the recommended inhalation technique of DPI and possibly improve patients' lung function test scores, counselling on proper DPI technique should be repeated at every possible opportunity. [ABSTRACT FROM AUTHOR]

The aim of this study was to characterize the circadian rhythm observed for forced expiratory volume in 1 s (FEV) in patients with persistent asthma being treated with inhaled corticosteroids. The database included 3379 FEV measurements from 189 patients with mild to moderate asthma. A model using the sum of two Sine functions with periods of 12 and 24 h and a constant component of mean circadian rhythm adequately described the circadian rhythm in FEV measurements over time. The model adequateness was evaluated by various approaches including visual predictive check (VPC), prediction-corrected VPC, standardized VPC and normalized prediction distribution error. Covariates tested included age, body weight, height, body mass index, baseline FEV, and sex. Age and height were found to have significant effects on the mean FEV level and no covariate was found to have an effect on the magnitude and timing of circadian rhythm. The model predicted that a minimum FEV occurred in the early morning and maximum FEV occurred in the early afternoon, with a population mean fluctuation of 170 mL, which is consistent with the finding that asthma symptoms usually exacerbate in the early morning for patients with persistent asthma. This developed model provides the first quantitative approach to describing FEV circadian rhythm with ICS background treatment and provided insight in designing future registration trials for asthma drug development. [ABSTRACT FROM AUTHOR]

This paper proposes an alternative approach for determining the most energy efficient route towards a destination. An innovative mesoscopic vehicular consumption model that is based on machine learning functionality is introduced and its application in a case study involving Fully Electric Vehicles (FEVs) is examined. The integration of this model in a routing engine especially designed for FEVs is also analyzed and a software architecture for implementing the proposed routing methodology is defined. In order to verify the robustness and the energy efficiency of this methodology, a system prototype has been developed and a series of field tests have been performed. The results of these tests are reported and significant conclusions are derived regarding the generated energy efficient routes. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is characterized by mutations of CFTR that lead to increased viscous secretions, bacterial colonization, and recurrent infections. Chronic Pseudomonas aeruginosa infection in persons with CF is associated with progressive and accelerated lung function decline despite aggressive antibiotic treatment. We report the management of respiratory infections in persons with CF with antibiotic therapy that was based on the recommendations of AtbFinder, a novel, rapid, culture-based diagnostic test system that employs a novel paradigm of antibiotic selection. AtbFinder mimics bacterial interactions with antibiotics at concentrations that can be achieved in affected tissues or organs and models conditions of interbacterial interactions within polymicrobial biofilms. This open-label, single-arm, investigator-initiated clinical study was designed to identify the efficacy of antibiotics selected using AtbFinder in persons with CF. Microbiological and clinical parameters were assessed following the change of antibiotic therapy to antibiotics selected with AtbFinder between January 2016 and December 2018 and retrospectively compared with clinical data collected between January 2013 and December 2015. We enrolled 35 persons with CF (33 with chronic P. aeruginosa colonization). Antibiotics selected using AtbFinder resulted in clearance of P. aeruginosa in 81.8% of subsequent cultures, decreased pulmonary exacerbations from 1.21 per patient per annum to 0, and an increase in predicted percent predicted forced expiratory volume in 1 s up to 28.4% from baseline. The number of systemic antibiotic courses used in patients after switching to the AtbFinder-selected therapy was reduced from 355 to 178. These findings describe the superiority of antibiotic regimens selected with AtbFinder compared with routine antimicrobial susceptibility testing.

Accurate forecasting of vehicular consumption is a task of primary importance for several applications. Herein, a vehicular consumption prediction model is proposed, with special emphasis on robustness and reliability. Both features are enabled due to the selection of general regression neural networks (GRNNs) for the implementation of the proposed model. GRNNs are widely used among neural networks because of their capabilities for fast learning and successful convergence to the solution. In particular, the designed GRNN is responsible for approximating the nonlinearities and the specificities between the factors identified as major contributors in vehicular consumption. In order to evaluate its efficiency, a case study involving the application of the introduced model in fully electric vehicles (FEVs) is examined. The performance of the proposed model is successfully validated using real measurements collected during a data acquisition field campaign. [ABSTRACT FROM AUTHOR]

Context: US EPA proposed a Reference Concentration for Libby amphibole asbestos based on the premise that pleural plaques are adverse and cause lung function deficits. Objective: We conducted a systematic review to evaluate whether there is an association between pleural plaques and lung function and ascertain whether results were dependent on the method used to identify plaques. Methods: Using the PubMed database, we identified studies that evaluated pleural plaques and lung function. We assessed each study for quality, then integrated evidence and assessed associations based on the Bradford Hill guidelines. We also compared the results of HRCT studies to those of X-ray studies. Results: We identified 16 HRCT and 36 X-ray studies. We rated six HRCT and 16 X-ray studies as higher quality based on a risk-of-bias analysis. Half of the higher quality studies reported small but statistically significant mean lung function decrements associated with plaques. None of the differences were clinically significant. Many studies had limitations, such as inappropriate controls and/or insufficient adjustment for confounders. There was little consistency in the direction of effect for the most commonly reported measurements. X-ray results were more variable than HRCT results. Pleural plaques were not associated with changes in lung function over time in longitudinal studies. Conclusion: The weight of evidence indicates that pleural plaques do not impact lung function. Observed associations are most likely due to unidentified abnormalities or other factors. [ABSTRACT FROM AUTHOR]