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Rationale: Idiopathic pulmonary fibrosis is a fatal and progressive disease with limited treatment options. Objectives: We sought to assess the efficacy and safety of CC-90001, an oral inhibitor of c-Jun N-terminal kinase 1, in patients with idiopathic pulmonary fibrosis. Methods: In a Phase 2, randomized (1:1:1), double-blind, placebo-controlled study (ClinicalTrials.gov ID: NCT03142191), patients received CC-90001 (200 or 400 mg) or placebo once daily for 24 weeks. Background antifibrotic treatment (pirfenidone) was allowed. The primary endpoint was change in the percentage of predicted FVC (ppFVC) from baseline to Week 24; secondary endpoints included safety. Measurements and Main Results: In total, 112 patients received at least one dose of study drug. The study was terminated early because of a strategic decision made by the sponsor. Ninety-one patients (81%) completed the study. The least-squares mean changes from baseline in ppFVC at Week 24 were -3.1% (placebo), -2.1% (200 mg), and -1.0% (400 mg); the differences compared with placebo were 1.1% (200 mg; 95% confidence interval: -2.1, 4.3; P = 0.50) and 2.2% (400 mg; 95% confidence interval: -1.1, 5.4; P = 0.19). Adverse event frequency was similar in patients in the combined CC-90001 arms versus placebo. The most common adverse events were nausea, diarrhea, and vomiting, which were more frequent in patients in CC-90001 arms versus placebo. Fewer patients in the CC-90001 arms than in the placebo arm experienced cough and dyspnea. Conclusions: Treatment with CC-90001 over 24 weeks led to numerical improvements in ppFVC in patients with idiopathic pulmonary fibrosis compared with placebo. CC-90001 was generally well tolerated, which was consistent with previous studies. Clinical trial registered with www.clinicaltrials.gov (NCT03142191).
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Fibrosis Pulmonar Idiopática , Humanos , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/fisiopatología , Método Doble Ciego , Masculino , Femenino , Anciano , Persona de Mediana Edad , Resultado del Tratamiento , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , AdultoRESUMEN
Background: Idiopathic pulmonary fibrosis (IPF) carries significant mortality and unpredictable progression, with limited therapeutic options. Designing trials with patient-meaningful endpoints, enhancing the reliability and interpretability of results, and streamlining the regulatory approval process are of critical importance to advancing clinical care in IPF. Methods: A landmark in-person symposium in June 2023 assembled 43 participants from the US and internationally, including patients with IPF, investigators, and regulatory representatives, to discuss the immediate future of IPF clinical trial endpoints. Patient advocates were central to discussions, which evaluated endpoints according to regulatory standards and the FDA's 'feels, functions, survives' criteria. Results: Three themes emerged: 1) consensus on endpoints mirroring the lived experiences of patients with IPF; 2) consideration of replacing forced vital capacity (FVC) as the primary endpoint, potentially by composite endpoints that include 'feels, functions, survives' measures or FVC as components; 3) support for simplified, user-friendly patient-reported outcomes (PROs) as either components of primary composite endpoints or key secondary endpoints, supplemented by functional tests as secondary endpoints and novel biomarkers as supportive measures (FDA Guidance for Industry (Multiple Endpoints in Clinical Trials) available at: https://www.fda.gov/media/162416/download). Conclusions: This report, detailing the proceedings of this pivotal symposium, suggests a potential turning point in designing future IPF clinical trials more attuned to outcomes meaningful to patients, and documents the collective agreement across multidisciplinary stakeholders on the importance of anchoring IPF trial endpoints on real patient experiences-namely, how they feel, function, and survive. There is considerable optimism that clinical care in IPF will progress through trials focused on patient-centric insights, ultimately guiding transformative treatment strategies to enhance patients' quality of life and survival.
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Fibrosis Pulmonar Idiopática , Defensa del Paciente , Humanos , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , National Institutes of Health (U.S.) , Calidad de Vida , Reproducibilidad de los Resultados , Estados Unidos , Capacidad Vital , Ensayos Clínicos como AsuntoRESUMEN
OBJECTIVES: To investigate the prognostic utility of 28 serum biomarkers in systemic sclerosis (SSc), SSc-associated interstitial lung disease (SSc-ILD) and clinically relevant disease subgroups. METHODS: Participants with sera, high-resolution computed tomography, and lung function within 12 months of baseline were identified from the Australian Scleroderma Cohort Study. Baseline was the time of serum collection. 27 of the prespecified 28 serum biomarkers were analysed and biomarker associations with mortality and ILD progression were investigated in univariable and multivariable analyses, including within disease subgroups and combined with established risk factors for poorer prognosis in SSc. RESULTS: 407 participants were identified, 252 (61.9%) with SSc-ILD. The median follow up after biomarker measurement was 6.31 (3.11-9.22) years. 16 biomarkers were associated with increased mortality. High levels of VCAM-1 were most strongly associated with mortality (HR 3.55; 95%CI 2.37-5.33; p< 0.001). Five additional biomarkers had a HR > 2: SP-D (2.28, 1.57-3.31; p< 0.001), E-selectin (2.19; 1.53-3.14; p< 0.001), IL-6 (2.15 1.50-3.09; p< 0.001), MMP3 (1.42-2.95; p< 0.001) and ET-1 (2.03, 1.40-2.92; p< 0.001). 11 biomarkers were independently associated with mortality following adjustment for sex, age and baseline forced vital capacity (FVC%predicted). Three biomarkers were associated with ILD progression at one year follow up: CXCL4 (OR 2.67, 1.46-4.88; p= 0.001), MMP-1 (2.56, 1.43-4.59; p= 0.002) and ET-1 (2.18, 1.24-3.83; p= 0.007). CONCLUSION: Multiple biomarkers, especially VCAM-1, E-Selectin, SP-D and CXCL4, provide prognostic utility beyond that of established risk factors for patients with SSc.
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OBJECTIVE: To investigate the clinical utility of small airway function indices for early identification of GOLD stage 0 chronic obstructive pulmonary disease (COPD). METHODS: This retrospective study enrolled 137 participants at our institution between January 2017 and December 2018, comprising 40 healthy controls, 46 individuals with GOLD stage 0 COPD, and 51 patients with established COPD. Pulmonary function was assessed using the PowerCube spirometry system (GANSHORN, Germany). Parameters evaluated included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, and small airway function indicators. RESULTS: The COPD cohort exhibited significantly lower values across all lung function measures compared to the other two groups, particularly for dynamic lung volume parameters such as FEV1%predicted and FEV1/FVC%. Small airway function indices, including FEV3%predicted, FEF75%predicted, FEF50%predicted, FEF25%predicted, and MMEF%predicted, were markedly decreased in the COPD group (all p-values <0.001). Receiver operating characteristic (ROC) curve analysis demonstrated that MMEF/FVC% and FEV3/FVC% had high diagnostic accuracy for COPD, with MMEF/FVC% exhibiting the optimal sensitivity and specificity. CONCLUSION: Small airway function indices, especially MMEF/FVC%, can serve as effective tools for early identification of GOLD stage 0 COPD. Incorporation of these findings into clinical practice may facilitate early diagnosis and intervention, thereby improving treatment outcomes and patient quality of life.
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BACKGROUND: Ozone (O3) exposure interrupts normal lung development in animal models. Epidemiologic evidence further suggests impairment with higher long-term O3 exposure across early and middle childhood, although study findings to date are mixed and few have investigated vulnerable subgroups. METHODS: Participants from the CANDLE study, a pregnancy cohort in Shelby County, TN, in the ECHO-PATHWAYS Consortium, were included if children were born at gestational age >32 weeks, completed a spirometry exam at age 8-9, and had a valid residential history from birth to age 8. We estimated lifetime average ambient O3 exposure based on each child's residential history from birth to age 8, using a validated fine-resolution spatiotemporal model. Spirometry was performed at the age 8-9 year study visit to assess Forced Expiratory Volume in the first second (FEV1) and Forced Vital Capacity (FVC) as primary outcomes; z-scores were calculated using sex-and-age-specific reference equations. Linear regression with robust variance estimators was used to examine associations between O3 exposure and continuous lung function z-scores, adjusted for child, sociodemographic, and home environmental factors. Potential susceptible subgroups were explored using a product term in the regression model to assess effect modification by child sex, history of bronchiolitis in infancy, and allergic sensitization. RESULTS: In our sample (n = 648), O3 exposure averaged from birth to age 8 was modest (mean 26.6 [SD 1.1] ppb). No adverse associations between long-term postnatal O3 exposure were observed with either FEV1 (ß = 0.12, 95% CI: -0.04, 0.29) or FVC (ß = 0.03, 95% CI: -0.13, 0.19). No effect modification by child sex, history of bronchiolitis in infancy, or allergic sensitization was detected for associations with 8-year average O3. CONCLUSIONS: In this sample with low O3 concentrations, we did not observe adverse associations between O3 exposures averaged from birth to age 8 and lung function in middle childhood.
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Contaminantes Atmosféricos , Bronquiolitis , Ozono , Femenino , Embarazo , Humanos , Niño , Lactante , Contaminantes Atmosféricos/análisis , Pulmón , Capacidad Vital , Ozono/toxicidad , Ozono/análisis , Volumen Espiratorio Forzado , Exposición a Riesgos AmbientalesRESUMEN
Fractional vegetation cover (FVC) has changed significantly under various disturbances over northern China in recent decades. This research examines the dynamics of FVC and how it is affected by climate and human activity during the period of 1990-2018 in northern China. The effects of climate change (i.e., temperature, precipitation, solar radiation, and soil moisture) and human activity (socioeconomic data and land use) on vegetation coverage change in northern China from 1990 to 2018 were quantified using the Sen + Mann-Kendall test, partial correlation analysis, and structural equation modelling (SEM) methods. The findings of this research indicate the following: (1) From 1990 to 2018, the overall trend in FVC in northern China was increased. The areas with obvious increases were mainly situated on the northern slope of Tianshan Mountains, Xinjiang, the Loess Plateau, the Northeast China Plain, and the Sanjiang Plain, while the areas with distinct degradation were located in the Inner Mongolia Plateau, the Changbai Mountain and the eastern part of north China. (2) In the past 29 years, the FVC in northern China has been mainly affected by precipitation and soil moisture. (3) Based on structural equation modelling, we discovered that certain variables impacted the main factors influencing the amount of FVC in northern China. Human activity has had a larger impact on FVC than climate change. Our findings can accelerate the comprehension of vegetation dynamics and their underlying mechanisms and provide a theoretical basis for regional ecological environmental protection.
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Cambio Climático , Ecosistema , Humanos , China , Actividades Humanas , Temperatura , SueloRESUMEN
Coal mining can significantly impact vegetation evolution, yet the limited information on its patterns and driving factors hampers efforts to mitigate these effects and reclaim abandoned mines. This study aimed to 1) examine vegetation evolution in a semiarid steppe watershed in northeast China; and 2) characterize the driving factors behind this evolution. We analyzed the impact of twelve selected driving factors on fractional vegetation coverage (FVC) from 2000 to 2021 using a dimidiate pixel model, Sen's slope analysis, Mann-Kendall trend test, coefficient of variation analysis, and Geodetector model. At a significance level of α = 0.05, our findings revealed a south-to-north decline pattern in FVC, a significant decrease trend in proximity to coal mines, and a notable increase trend adjacent to river channels. Approximately 37% of the watershed exhibited low FVC, while the overall temporal trend across the watershed was deemed insignificant. Areas surrounding the mines experienced a substantial reduction in FVC due to coal mining activities, while FVC variations across the watershed were linked to precipitation, temperature, and soil type. FVC predictions improved notably when interactions between multiple two-way factors were considered. Each driving factors displayed an optimal range (e.g., precipitation = 63-71 mm) for maximizing FVC. Given the study watershed's status as a national energy base, understanding vegetation responses to coal mining and climate-environment changes is crucial for sustaining fragile terrestrial ecosystems and socioeconomic development. Achieving a long-time balance between coal extraction and ecological protection is essential. The study outcomes hold significant promise for advancing ecological conservation, vegetation restoration, and mitigation of environmental degradation in semiarid regions affected by extensive coal mining and climate fluctuations. These findings contribute to the strategic management of such areas, promoting sustainable practices amidst evolving environmental challenges.
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Minas de Carbón , Ecosistema , Pradera , Temperatura , China , Carbón MineralRESUMEN
BACKGROUND: Pulmonary function is very important for the healthy development of children and adolescents. However, fewer studies have been conducted on pulmonary function trends in children and adolescents in remote areas. The aim of this study was to estimate the forced vital capacity (FVC) trend and its relationship with body mass index (BMI) among young people in Xinjiang during 1985-2014 using data from seven successive national surveys. METHODS: A total of 19,449 Xinjiang children and adolescents aged 7-18 years were extracted from the Chinese National Survey on Students' Constitution and Health. Height, weight, and FVC were measured repeatedly in each survey. FVC comparisons between adjacent surveys by age and sex were conducted by nonparametric Kruskal-Wallis after Kolmogorov-Smirnov of normality. One-way ANOVA and least significant difference(LSD) method was used to compare differences in FVC levels of Xinjiang children and adolescents with different BMI. The relationship between BMI and FVC was investigated using a nonlinear regression model. RESULTS: The FVC levels of Xinjiang children and adolescents peaked in 2000, with overall FVC levels being 8.7% higher in 2000 than in 1985. Since then, a substantial decline occurred, contrasting to 2000, with FVC levels decreasing by 27% in 2014, which was still lower than that in 1985 by 20.73%. The proportion of overnutrition boys increased from 0.2% in 1985 to 22.1% in 2014, and girls from 0.5% in 1985 to 14.5% in 2014. An inverted U-shape association between FVC and BMI values was obtained for Xinjiang children and adolescents. CONCLUSIONS: Targeted measures should be carried out in schools to control BMI levels to ensure good lung function in children and adolescents in Xinjiang. Future studies should pay more attention to other factors affecting FVC, such as dietary behaviour, physical activity, and racial differences among children and adolescents.
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Índice de Masa Corporal , Humanos , Adolescente , Niño , Masculino , China/epidemiología , Femenino , Capacidad Vital/fisiología , Encuestas EpidemiológicasRESUMEN
Traffic-Related Air Pollution (TRAP) exposure has been connected to significant health impacts among children. A cross-sectional comparative study was conducted among school children in Malaysia to determine the relationship between their exposure to TRAP and respiratory health effects. Air monitoring was conducted in schools and residences, while the children's routines were investigated using a diary of daily activities. Respondents' background and respiratory symptoms were obtained from a validated questionnaire, while a spirometry test was performed to determine their lung function status. The distances between schools and residences from the had contributed to the higher concentration of air pollutants in this study, which had associations with the children's respiratory symptoms and lung function status. PM2.5 was the main predictor influencing the respondents' respiratory symptoms and lung function abnormalities. In conclusion, exposure of school children to a high TRAP level might increase their risk of getting respiratory symptoms and lung function reduction.
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Contaminantes Atmosféricos , Contaminación del Aire , Niño , Humanos , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Estudios Transversales , Exposición a Riesgos Ambientales , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/análisis , Pulmón , Material Particulado/toxicidad , Material Particulado/análisisRESUMEN
Pompe disease is a rare, progressive, and metabolic myopathy. Reduced pulmonary function is one of the main problems seen in adult patients with late-onset Pompe disease (LOPD). We aimed to explore the association between changes over time in pulmonary function and in patient-reported outcome measures (PROMs), in these patients treated with enzyme replacement therapy (ERT). This is a post hoc analysis of two cohort studies. Pulmonary function was assessed as forced vital capacity in the upright position (FVCup ). As PROMs, we assessed the physical component summary score (PCS) of the Medical Outcome Study 36-item Short-Form Health Survey (SF-36) and daily life activities (Rasch-Built Pompe-Specific Activity [R-PACT] scale). We fitted Bayesian multivariate mixed-effects models. In the models of PROMs, we assumed a linear association with FVCup , and adjusted for time (nonlinear), sex, and age and disease duration at the start of ERT. One hundred and one patients were eligible for analysis. PCS and R-PAct were positively associated with FVCup , while their relation with time was nonlinear (initial increase then decrease). A 1%-point increase in FVCup is expected to increase PCS by 0.14 points (95% Credible Interval: [0.09;0.19]) and R-PACT by 0.41 points [0.33;0.49] at the same time point. In the first year of ERT, we expect a change of PCS and R-PAct scores by +0.42 and +0.80 points, and in the 5th year of +0.16 and +0.45, respectively. We conclude that the physical domain of quality of life and daily life activities improve when FVCup increases during ERT.
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Enfermedad del Almacenamiento de Glucógeno Tipo II , Humanos , Adulto , Enfermedad del Almacenamiento de Glucógeno Tipo II/tratamiento farmacológico , Calidad de Vida , Teorema de Bayes , Terapia de Reemplazo Enzimático , Medición de Resultados Informados por el Paciente , alfa-Glucosidasas/uso terapéuticoRESUMEN
OBJECTIVE: Asthma is known as one of the most common chronic inflammatory diseases characterized by recurrent obstruction and inflammation of the airways. Probiotics are defined as a group of beneficial living microorganisms that are beneficial in many disorders, including allergies. The aim of this study was to investigate the probiotic supplement effects on improvement of clinical asthma symptom and changes in the pattern of Th17-related inflammatory cytokines in asthmatic patients. METHODS: This was a randomized controlled clinical trial with parallel, double-blind groups. Forty patients with asthma were enrolled and received 1 capsule/day of a probiotic supplement for 8 weeks. Respiratory function tests; and the level of IL-6, IL-17, IL-21 and TGF-ß were evaluated at the baseline and end of intervention. RESULTS: The results showed that the level of IL-6 and IL-17 in patients after receiving probiotics was reduced and expression of TGF-ß was increased as compared to the baseline. Also, the expression of IL-17 and IL-21 in the probiotic group was significantly lower than the placebo group at the end of the intervention. In addition, an improvement in pulmonary function tests and clinical symptoms was observed after receiving probiotics. CONCLUSIONS: Eight-weeks treatment with a probiotic supplementation suggests that it may effect on Th17 cells-associated IL-6, IL-17 and TGF-ß; and Forced Expiratory Volume in 1 s and Forced Vital Capacity. Taken together, these results suggest that probiotics may have the ability to affect neutrophilic asthma and they can possibly be used besides common treatments for patients with neutrophilic asthma.
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Asma , Probióticos , Humanos , Asma/tratamiento farmacológico , Interleucina-17 , Citocinas , Interleucina-6/uso terapéutico , Células Th17 , Probióticos/uso terapéutico , Factor de Crecimiento Transformador beta , Método Doble CiegoRESUMEN
INTRODUCTION: Abnormal lung function in people with multiple sclerosis (PwMS) could be considered as the result of muscle weakness or MS-specific structural central nervous system (CNS) abnormalities as a precipitant factor for the worsening of motor impairment or cognitive symptoms. METHODS: This is a cross-sectional observational study in PwMS. Forced spirometry was conducted, and normative metrics of forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and the relation FEV1/FVC were calculated. Qualitative and quantitative brain magnetic resonance imaging (MRI) examinations were carried out. RESULTS: A total of 371 PwMS were included in the study. Of those, 196 (53%) had RRMS, 92 (25%) SPMS, and 83 (22%) PPMS. Low FVC and FEV1 was present in 16 (8%), 16 (19%), and 23 (25%) of the patients in the RRMS, PPMS, and SPMS, respectively. PwMS with T2-FLAIR lesions involving the corpus callosum (CC) had a significantly higher frequency of abnormally low FVC and FEV1 (OR 3.62; 95% CI 1.33-9.83; p = 0.012) than patients without lesions in that region. This association remained significant in the RRMS group (OR 10.1; 95% CI 1.3-67.8; p 0.031) when the model excluded PPMS and SPMS. According to our study, for every increase of 1 z score of FVC, we observed an increase of 0.25 cm3 of hippocampal volume (ß 0.25; 95% CI 0.03-0.47; p 0.023) and 0.43 cm3 of left hippocampus volume (ß 0.43; 95% CI 0.16-0.71; p 0.002). CONCLUSIONS: We observed an incremental prevalence of abnormally low pulmonary function tests that parallels a sequence from more early relapsing courses to long-standing progressive courses (RRMS to PPMS or SPMS).
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Esclerosis Múltiple Crónica Progresiva , Esclerosis Múltiple , Humanos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Estudios Transversales , Imagen por Resonancia Magnética , Capacidad Vital , Pulmón/diagnóstico por imagenRESUMEN
Five countries in the Lancang-Mekong region, including Myanmar, Laos, Thailand, Cambodia, and Vietnam, are facing the threat of deforestation, despite having a high level of forest coverage. Quantitatively assessing the forest ecosystem status and its variations based on remote sensing products for vegetation parameters is a crucial prerequisite for the ongoing phase of our future project. In this study, we analyzed forest health in the year 2020 using four vegetation indicators: forest coverage index (FCI), leaf area index (LAI), fraction of green vegetation cover (FVC), and gross primary productivity (GPP). Additionally, we introduced an ecosystem quality index (EQI) to assess the quality of forest health. To understand the long-term trends in the vegetation indicators and EQI, we also performed a linear regression analysis from 2010 to 2020. The results revealed that Laos ranked as the top-performing country for forest ecosystem status in the Lancang-Mekong region in 2020. However, the long-term trend analysis results showed that Cambodia experienced the most significant decline across all indicators, while Vietnam and Thailand demonstrated varying degrees of improvement. This study provides a quality assessment of forest health and its variations in the Lancang-Mekong region, which is crucial for implementing effective conservation strategies.
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Ecosistema , Tecnología de Sensores Remotos , Bosques , Cambodia , TailandiaRESUMEN
Economic development has rapidly progressed since the implementation of reform and opening up policies, posing significant challenges to sustainable development, especially to vegetation, which plays a crucial role in maintaining ecosystem service functions and promoting green low-carbon transformations. In this study, we estimated the fractional vegetation cover (FVC) in Shandong Province from 2000 to 2020 using the Google Earth Engine (GEE) platform. The spatial and temporal changes in FVC were analyzed using gravity center migration analysis, trend analysis, and geographic detector, and the vegetation changes of different land use types were analyzed to reveal the internal driving mechanism of FVC changes. Our results indicate that vegetation cover in Shandong Province was in good condition during the period 2000 to 2020. The high vegetation cover classes dominated, and overall changes were relatively small, with the center of gravity of vegetation cover generally shifting towards the southwest. Land use type, soil type, population density, and GDP factors had the most significant impact on vegetation cover change in Shandong Province. The interaction of these factors enhanced the effect on vegetation cover change, with land use type and soil type having the highest degree of influence. The observational results of this study can provide data support for the policy makers to formulate new ecological restoration strategies, and the findings would help facilitate the sustainability management of regional ecosystem and natural resource planning.
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Ecosistema , Monitoreo del Ambiente , China , Conservación de los Recursos Naturales , Suelo , Desarrollo SostenibleRESUMEN
BACKGROUND: Lung function tests (LFTs) are a collection of clinical examinations used to assess lung function and monitor potential declines in the lungs, respiratory muscles, and chest wall's mechanical performance. This cross-sectional study aimed to identify the relation of age and height to lung function. MATERIAL AND METHODS: The study was conducted at AlHussein Medical City, 70 adult male subjects were enrolled in the study. All subjects were screened physically to ensure that they were normal and there were no respiratory disorders that could affect the lung function. Age and height were taken for these subjects, forced vital capacity (FVC), FEV1 (Forced expiratory volume in first second) as well as FEV1 /FVC ratio were measured. RESULTS: The results of the study showed that the average values of FVC and FEV1 were 4.75 and 3.88 respectively. There was a significant negative correlation observed between age and FVC (r=0.48), FEV1 (r= 0.6). Also there was a significant positive correlation noticed between Height and FVC (r = 0.62), FEV1 (r =0.69). There was a very high correlation evidenced between FEV1 and FVC, the relation between FEV1 and FVC is practically height and age-independent. CONCLUSION: Our study highlights a great interest in the study of the relation between age, height, and lung function. The study also creates simple and convenience equations that can be used for reference standards in clinical practice to give reasonable theoretical values for a large sector of the population.
CONTEXTE: Les tests de fonction pulmonaire (TFP) regroupent une série d'examens cliniques utilisés pour évaluer la fonction pulmonaire et surveiller d'éventuelles réductions des performances mécaniques des poumons, des muscles respiratoires et de la paroi thoracique. Cette étude transversale visait à déterminer la relation entre l'âge et la taille et la fonction pulmonaire. MATÉRIEL ET MÉTHODES: L'étude a été menée à la ville médicale Al-Hussein. Soixante-dix sujets masculins adultes ont été inscrits à l'étude. Tous les sujets ont été soumis à un examen physique pour s'assurer qu'ils étaient en bonne santé et ne présentaient pas de troubles respiratoires susceptibles d'affecter la fonction pulmonaire. L'âge et la taille de ces sujets ont été relevés, et la capacité vitale forcée (CVF), le VEMS (volume expiratoire maximal en une seconde) ainsi que le rapport VEMS/CVF ont été mesurés. RÉSULTATS: Les résultats de l'étude ont montré que les valeurs moyennes de la CVF et du VEMS étaient respectivement de 4,75 et 3,88. Une corrélation négative significative a été observée entre l'âge et la CVF (r = 0,48) ainsi qu'entre l'âge et le VEMS (r = 0,6). De plus, une corrélation positive significative a été remarquée entre la taille et la CVF (r = 0,62) ainsi qu'entre la taille et le VEMS (r = 0,69). Une corrélation très élevée a été mise en évidence entre le VEMS et la CVF, la relation entre le VEMS et la CVF est pratiquement indépendante de la taille et de l'âge. CONCLUSION: Notre étude met en évidence un intérêt particulier pour l'étude de la relation entre l'âge, la taille et la fonction pulmonaire. L'étude crée également des équations simples et pratiques qui peuvent être utilisées comme référence dans la pratique clinique pour fournir des valeurs théoriques raisonnables pour une grande partie de la population. Mots-clés: VEMS, CVF, VEMS/CVF, Spirométrie.
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Pulmón , Adulto , Humanos , Masculino , Volumen Espiratorio Forzado/fisiología , Estudios Transversales , Espirometría/métodos , Pruebas de Función Respiratoria , Capacidad Vital/fisiologíaRESUMEN
Background and Objectives: Progressive pulmonary fibrosis (PPF) is a recently described term reserved for patients with fibrotic ILD other than idiopathic pulmonary fibrosis (IPF) with fast clinical deterioration. Here, survival and prognostic biomarkers at the time of diagnosis for PPF are investigated in a fibrotic ILD other than IPF cohort (non-IPF). Materials and Methods: Patients diagnosed during the period of 2012-2018 at the ILD Center of Excellence (St. Antonius Hospital, Nieuwegein, The Netherlands) with a fibrotic ILD were included in this study. The presence of PPF was investigated using the criteria from the updated IPF/PPF guideline during the first year after diagnosis. Logistic regression analysis was used to determine risk factors for PPF. A Kaplan-Meier survival analysis with log-rank test was conducted to analyze survival in patients with and without PPF. Results: This study included 304 non-IPF patients and, for comparison, 379 IPF patients. In non-IPF patients, 146 (46%) fulfilled ≥2 criteria for PPF. These patients had a median transplant-free survival rate of 2.9 ± 0.4 years, which was worse than non-IPF patients without PPF (10.1 ± 1.8 years, p < 0.001). The risk for PPF was increased in patients with FVC < 50% (odds ratio (OR) of 2.50, 95% CI = 1.01-6.17, p = 0.047) or DLCOc ≤ 35% (OR = 2.57, 95% CI = 1.24-5.35, p = 0.011). In the first 3 years after diagnosis, survival in PPF and IPF is the same, while in the following years IPF has a significantly worse survival. Conclusions: The non-IPF cohort with PPF had a significantly worse transplant-free survival compared with the non-IPF cohort without PPF. Independent risk factors for PPF in non-IPF were FVC < 50% and DLCOc ≤ 35%.
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Fibrosis Pulmonar Idiopática , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico , Estimación de Kaplan-Meier , Factores de Riesgo , Pulmón , Países BajosRESUMEN
Background: Few studies have investigated the clinical efficacy and pulmonary side effects of different P2Y12 inhibitors in acute coronary syndrome (ACS) patients. The aim of this study was to explore the impact of forced expiratory volume in 1 second over forced vital capacity (FEV1/FVC) ratio on the clinical outcomes in ACS patients treated with dual antiplatelet therapy after percutaneous coronary intervention (PCI). Methods: ACS patients who underwent PCI, had documented pre-existing spirometry tests, and received aspirin with either ticagrelor or clopidogrel were enrolled for retrospective analysis. Results: Of the enrolled ACS patients, 275 and 247 received ticagrelor and clopidogrel, respectively. The incidence of wheeze was significantly higher in the ticagrelor group compared to the clopidogrel group within 360 days (14.91% vs. 8.09%, p = 0.016). Multivariable analysis revealed that ticagrelor treatment, as compared to clopidogrel treatment, independently predicted 1-year hospitalization for acute exacerbation (AE) of obstructive airway disease (hazard ratio: 3.44; 95% confidence interval: 1.92 to 6.15; p < 0.01). The receiver operating characteristic curve indicated that an FEV1/FVC ratio of 63.85% had the highest sensitivity and specificity for predicting the incidence of AE of obstructive airway disease within 1 year (p < 0.001). The 1-year hospitalization rate for AE of obstructive airway disease was significantly higher in the ticagrelor group when the FEV1/FVC ratio was < 63%. Conclusions: This study demonstrated higher incidence of wheeze and hospitalization for AE of obstructive airway disease in ACS patients treated with ticagrelor compared to clopidogrel. Furthermore, the FEV1/FVC ratio ≤ 63% in the ACS patients predicted hospitalization for AE of obstructive airway disease in 1 year.
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The G2019S mutation of LRRK2 represents a risk factor for idiopathic Parkinson's disease. Here, we investigate whether LRRK2 kinase activity regulates susceptibility to the environmental toxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). G2019S knock-in mice (bearing enhanced kinase activity) showed greater nigro-striatal degeneration compared to LRRK2 knock-out, LRRK2 kinase-dead and wild-type mice following subacute MPTP treatment. LRRK2 kinase inhibitors PF-06447475 and MLi-2, tested under preventive or therapeutic treatments, protected against nigral dopamine cell loss in G2019S knock-in mice. MLi-2 also rescued striatal dopaminergic terminal degeneration in both G2019S knock-in and wild-type mice. Immunoblot analysis of LRRK2 Serine935 phosphorylation levels confirmed target engagement of LRRK2 inhibitors. However, MLi-2 abolished phosphoSerine935 levels in the striatum and midbrain of both wild-type and G2019S knock-in mice whereas PF-06447475 partly reduced phosphoSerine935 levels in the midbrain of both genotypes. In vivo and ex vivo uptake of the 18-kDa translocator protein (TSPO) ligand [18F]-VC701 revealed a similar TSPO binding in MPTP-treated wild-type and G2019S knock-in mice which was consistent with an increased GFAP striatal expression as revealed by Real Time PCR. We conclude that LRRK2 G2019S, likely through enhanced kinase activity, confers greater susceptibility to mitochondrial toxin-induced parkinsonism. LRRK2 kinase inhibitors are neuroprotective in this model.
Asunto(s)
Enfermedad de Parkinson , Trastornos Parkinsonianos , Animales , Cuerpo Estriado/metabolismo , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/metabolismo , Ratones , Mutación , Enfermedad de Parkinson/metabolismo , Trastornos Parkinsonianos/metabolismo , FosforilaciónRESUMEN
BACKGROUND: Recombinant human pentraxin-2 (rhPTX-2) significantly decreased decline in percent predicted forced vital capacity (FVC) and stabilized 6-min walk distance (6MWD) in patients with idiopathic pulmonary fibrosis (IPF) during the 28-week, placebo-controlled, randomized period of the Phase II PRM-151-202 study. Interim (76-week) data from the open-label extension (OLE) demonstrated sustained safety and efficacy with rhPTX-2 treatment. Here, we present the entire long-term OLE safety and efficacy data to 128 weeks. METHODS: Patients who completed the randomized PRM-151-202 study period were eligible for the OLE, during which all patients received rhPTX-2, having started rhPTX-2 (i.e., crossed from placebo) or continued rhPTX-2 after Week 28. rhPTX-2 was administered in 28-week cycles, with 10 mg/kg intravenous infusions (60 min) on Days 1, 3, and 5 in the first week of each cycle, then one infusion every 4 weeks up to Week 128. The OLE primary objective was to assess the long-term safety and tolerability of rhPTX-2. Other outcomes included FVC, 6MWD, and patient-reported outcomes (descriptive analysis). RESULTS: All 111 patients who completed the randomized period entered the OLE (n = 37 started rhPTX-2; n = 74 continued rhPTX-2); 57 (51.4%) completed to Week 128. The treatment-emergent adverse event (TEAE) profile was consistent with the randomized period, with the majority of TEAEs graded mild or moderate. Serious TEAEs occurred in 47 patients (42.3%), most frequently IPF (n = 11; 9.9%), pneumonia (n = 7; 6.3%), and acute respiratory failure (n = 3; 2.7%). Three patients underwent lung transplantation. Most serious TEAEs (and all 14 fatal events) were considered unrelated to rhPTX-2 treatment. For patients starting vs continuing rhPTX-2, mean (95% confidence interval) changes from baseline to Week 128 were, respectively, - 6.2% (- 7.7; - 4.6) and - 5.7% (- 8.0; - 3.3) for percent predicted FVC and - 36.3 m (- 65.8; - 6.9) and - 28.9 m (- 54.3; - 3.6) for 6MWD; however, conclusions were limited by patient numbers at Week 128. CONCLUSIONS: Long-term treatment (up to 128 weeks) with rhPTX-2 was well tolerated in patients with IPF, with no new safety signals emerging in the OLE. The limited efficacy data over 128 weeks may suggest a trend towards a treatment effect. Trial registration NCT02550873; EudraCT 2014-004782-24.
Asunto(s)
Fibrosis Pulmonar Idiopática , Proteínas Recombinantes , Humanos , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Proteínas Recombinantes/efectos adversos , Resultado del Tratamiento , Capacidad VitalRESUMEN
BACKGROUND AND OBJECTIVE: A proportion of patients with fibrotic hypersensitivity pneumonitis (fHP) follow a progressive disease course despite immunosuppressive treatment. Little is known about predictors of mortality in fHP. We aimed to investigate the impact of short-term lung function changes in fHP on mortality. METHODS: Baseline demographics for 145 consecutive patients with a multi-disciplinary team diagnosis of fHP, as well as baseline and 1-year follow-up of lung function, baseline echocardiographic findings, bronchoalveolar lavage (BAL) cellularity and all-cause mortality were recorded. Changes in forced vital capacity (FVC) ≥ 5% and ≥10%, and diffusion capacity of the lung for carbon monoxide (DLCO) ≥ 10% and ≥15% at 1 year were calculated. Cox proportional hazards analysis was performed to test for associations with mortality. RESULTS: Baseline lung function severity, age, presence of honeycombing on computed tomography (CT) and echocardiographic pulmonary arterial systolic pressure (PASP) ≥ 40 mm Hg were associated with early mortality, while BAL lymphocytosis was associated with improved survival. A decline in FVC ≥ 5% (hazard ratio [HR]: 3.10, 95% CI: 2.00-4.81, p < 0.001), FVC ≥ 10% (HR: 3.11, 95% CI: 1.94-4.99, p < 0.001), DLCO ≥ 10% (HR: 2.80, 95% CI: 1.78-4.42, p < 0.001) and DLCO ≥ 15% (HR: 2.92, 95% CI: 1.18-4.72, p < 0.001) at 1 year was associated with markedly reduced survival on univariable and multivariable analyses after correcting for demographic variables, disease severity, honeycombing on CT and treatment, as well as BAL lymphocytosis and PASP ≥ 40 mm Hg on echocardiography, in separate models. CONCLUSION: Worsening in FVC and DLCO at 1 year, including a marginal decline in FVC ≥ 5% and DLCO ≥ 10%, is predictive of markedly reduced survival in fHP.