Diminished Lung Function Research Articles

Citrullination, a novel posttranslational modification of elastin, is involved in COPD pathogenesis.

Elastin is an extracellular matrix protein (ECM) that supports elasticity of the lung, and in patients with chronic obstructive pulmonary disease (COPD) and emphysema, the structural changes that reduce the amount of elastic recoil, lead to loss of pulmonary function. We recently demonstrated that elastin is a target of peptidyl arginine deiminase (PAD) enzyme-induced citrullination, thereby leading to enhanced susceptibility of this ECM protein to proteolysis. This study aimed to investigate the impact of PAD activity in vivo and furthermore assessed whether pharmacological inhibition of PAD activity protects against pulmonary emphysema. Using a Serpina1a-e knockout mouse model, previously shown to develop inflammation-mediated emphysema, we validated the involvement of PADs in airway disease. In line with emphysema development, intratracheal administration of lipopolysaccharide in combination with PADs provoked significant airspace enlargement (P < 0.001) and diminished lung function, including loss of lung tissue elastance (P = 0.0217) and increases in lung volumes (P = 0.0463). Intraperitoneal treatment of mice with the PAD inhibitor, BB-Cl-amidine, prevented PAD/LPS-mediated lung function decline and emphysema and reduced levels of citrullinated airway elastin (P = 0.0199). These results provide evidence for the impact of PADs on lung function decline, indicating promising potential for the future development of PAD-based therapeutics for preserving lung function in patients with COPD.NEW & NOTEWORTHY This study provides evidence for the impact of peptidyl arginine deiminase (PAD) enzymes on lung function decline, indicating promising potential for the future development of PAD-based therapeutics for preserving lung function in patients with COPD.

Late-Onset Asthma: A Review

Asthma is a chronic respiratory condition with a growing global prevalence, affecting millions of individuals annually. While asthma can develop at any age, late-onset asthma is a specific phenotype that begins in adulthood, as recognized by the Global Initiative for Asthma (GINA) in its 2024 guidelines. This form of asthma is often associated with several predisposing factors, including gender, obesity, occupational exposure, rhinitis, respiratory infections, smoking, stress, and diminished lung function. Unlike early-onset asthma, which frequently involves a history of allergies, late-onset asthma tends to lack allergic triggers, making it a distinct and challenging form of the disease. Managing late-onset asthma is often more complex, as it typically requires higher doses of corticosteroids and demonstrates a reduced responsiveness to standard steroid treatments. The exact mechanisms and pathophysiological processes contributing to the increased severity and poorer clinical outcomes in late-onset asthma remain largely unclear. This uncertainty often leads to underdiagnosis and inadequate management, further complicating patient care. Phenotypic analysis is recommended to improve treatment outcomes. This includes assessing clinical features and utilizing biomarkers, such as inflammatory markers and immunoglobulin E (IgE) levels, to guide targeted therapy when conventional steroid treatments are insufficient. However, there is a significant need for further research to elucidate the underlying mechanisms of late-onset asthma. This literature review is essential to develop more effective, personalized treatment strategies that can address the unique challenges posed by this asthma phenotype, ultimately leading to better management and improved patient outcomes.

Mediation analysis of cognitive function in the relationship between pulmonary function and depression among middle-aged and older adults.

This study aims to explore the association between declining lung function and depression in middle-aged and older adults, with a special focus on the mediating role of cognitive function. This study utilizes self-reported and physical examination data from 5345 individuals participating in the 2015 cycle of the China Health and Retirement Longitudinal Study (CHARLS) to explore the role of cognitive function changes in mediating the effects of diminished lung function on depression among middle-aged and older adults. Multivariate linear regression analysis revealed a positive correlation between pulmonary and cognitive functions (β = 0.003, 95% CI: 0.002∼0.003, P < 0.01) and a negative correlation between cognitive function and depression (β = -0.279, 95% CI: -0.330-0.228, P < 0.01). Cognitive function plays a mediating role in linking pulmonary function with depression, exhibiting a mediation effect of -0.0007 and a total effect of -0.0046, wherein the mediation effect contributes to 15.22% of the total effect. For females, the mediating effect of cognitive function was stronger (β = -0.0013, 95% CI: -0.0018∼-0.0008, P < 0.01) than it was for males (β = -0.0006, 95% CI: -0.0009∼-0.0003, P < 0.01). The study underscores the importance of monitoring lung and cognitive functions as interconnected factors contributing to the mental health of middle-aged and older adults. It suggests that interventions aimed at improving pulmonary health and cognitive function may help mitigate depressive symptoms among middle-aged and older adults. Further research is warranted to validate these findings across diverse cultural and demographic settings. Geriatr Gerontol Int 2024; 24: 1210-1217.

Lung-Kidney Axis in Cystic Fibrosis: Early Urinary Markers of Kidney Injury Correlate with Neutrophil Activation and Worse Lung Function.

Adult people with cystic fibrosis (PwCF) have a higher risk of end-stage kidney disease than the general population. The nature and mechanism of kidney disease in CF are unknown. This study quantifies urinary kidney injury markers and examines the hypothesis that neutrophil activation and lung infection are associated with early kidney injury in CF. Urinary total protein, albumin, and markers of kidney injury and neutrophil activation, normalized to creatinine, as well as urinary immune cells, were quantified in CF (n = 48) and healthy (n = 33) cohorts. Infection burden and chronicity were defined by sputum culture and serum titers of anti-bacterial antibodies. PwCF had increased urinary protein levels, consisting of low-molecular-weight tubular injury markers, independent of glomerular filtration rate (eGFR). This finding suggests subclinical renal injury processes. Urinary analysis of the CF cohort identified different associations of urinary injury markers with aminoglycoside exposure, lung function, and neutrophil activation. High urinary KIM-1 levels and increased prevalence of neutrophils among urine immune cells correlated with decreased lung function in PwCF. The relationship between tubular injury and decreased lung function was most prominent in patients harboring chronic Pseudomonas aeruginosa infection. Increased urinary tubular injury markers in PwCF suggest early subclinical renal injury not readily detected by eGFR. The strong association of high urinary KIM-1 and neutrophils with diminished lung function and high Pseudomonas aeruginosa burden suggests that pulmonary disease may contribute to renal injury in CF.

Monomeric compounds from natural products for the treatment of pulmonary fibrosis: a review.

Pulmonary fibrosis (PF) is the end stage of lung injury and chronic lung diseases that results in diminished lung function, respiratory failure, and ultimately mortality. Despite extensive research, the pathogenesis of this disease remains elusive, and effective therapeutic options are currently limited, posing a significant clinical challenge. In addition, research on traditional Chinese medicine and naturopathic medicine is hampered by several complications due to complex compositionand lack of reference compounds. Natural product monomers, possessing diverse biological activities and excellent safety profiles, have emerged as potential candidates for preventing and treating PF. The effective anti-PF ingredients identified can be generally divided into flavonoids, saponins, polysaccharides, and alkaloids. Specifically, these monomeric compounds can attenuate inflammatory response, oxidative stress, and other physiopathological processes of the lung through many signaling pathways. They also improve pulmonary factors. Additionally, they ameliorate epithelial-mesenchymal transition (EMT) and fibroblast-myofibroblast transdifferentiation (FMT) by regulating multiple signal amplifiers in the lungs, thereby mitigating PF. This review highlights the significant role of monomer compounds derived from natural products in reducing inflammation, oxidative stress, and inhibiting EMT process. The article provides comprehensive information and serves as a solid foundation for further exploration of new strategies to harness the potential of botanicals in the treatment of PF.

Lung function trajectories from school age to adulthood and their relationship with markers of cardiovascular disease risk

RationaleLung function in early adulthood is associated with subsequent adverse health outcomes.ObjectivesTo ascertain whether stable and reproducible lung function trajectories can be derived in different populations and investigate their association...

Early-life pulmonary viral infection leads to long-term functional and lower airway structural changes in the lungs.

Early-life respiratory virus infections have been correlated with enhanced development of childhood asthma. In particular, significant numbers of respiratory syncytial virus (RSV)-hospitalized infants go on to develop lung disease. It has been suggested that early-life viral infections may lead to altered lung development or repair that negatively impacts lung function later in life. Our data demonstrate that early-life RSV infection modifies lung structure, leading to decreased lung function. At 5 wk postneonatal RSV infection, significant defects are observed in baseline pulmonary function test (PFT) parameters consistent with decreased lung function as well as enlarged alveolar spaces. Lung function changes in the early-life RSV-infected group continue at 3 mo of age. The altered PFT and structural changes induced by early-life RSV were mitigated in TSLPR-/- mice that have previously been shown to have reduced immune cell accumulation associated with a persistent Th2 environment. Importantly, long-term effects were demonstrated using a secondary RSV infection 3 mo following the initial early-life RSV infection and led to significant additional defects in lung function, with severe mucus deposition within the airways, and consolidation of the alveolar spaces. These studies suggest that early-life respiratory viral infection leads to alterations in lung structure/repair that predispose to diminished lung function later in life.NEW & NOTEWORTHY These studies outline a novel finding that early-life respiratory virus infection can alter lung structure and function long-term. Importantly, the data also indicate that there are critical links between inflammatory responses and subsequent events that produce a more severe pathogenic response later in life. The findings provide additional data to support that early-life infections during lung development can alter the trajectory of airway function.

Identification of potential biomarkers in the peripheral blood of neonates with bronchopulmonary dysplasia using WGCNA and machine learning algorithms.

Bronchopulmonary dysplasia (BPD) is often seen as a pulmonary complication of extreme preterm birth, resulting in persistent respiratory symptoms and diminished lung function. Unfortunately, current diagnostic and treatment options for this condition are insufficient. Hence, this study aimed to identify potential biomarkers in the peripheral blood of neonates affected by BPD. The Gene Expression Omnibus provided the expression dataset GSE32472 for BPD. Initially, using this database, we identified differentially expressed genes (DEGs) in GSE32472. Subsequently, we conducted gene set enrichment analysis on the DEGs and employed weighted gene co-expression network analysis (WGCNA) to screen the most relevant modules for BPD. We then mapped the DEGs to the WGCNA module genes, resulting in a gene intersection. We conducted detailed functional enrichment analyses on these overlapping genes. To identify hub genes, we used 3 machine learning algorithms, including SVM-RFE, LASSO, and Random Forest. We constructed a diagnostic nomogram model for predicting BPD based on the hub genes. Additionally, we carried out transcription factor analysis to predict the regulatory mechanisms and identify drugs associated with these biomarkers. We used differential analysis to obtain 470 DEGs and conducted WGCNA analysis to identify 1351 significant genes. The intersection of these 2 approaches yielded 273 common genes. Using machine learning algorithms, we identified CYYR1, GALNT14, and OLAH as potential biomarkers for BPD. Moreover, we predicted flunisolide, budesonide, and beclomethasone as potential anti-BPD drugs. The genes CYYR1, GALNT14, and OLAH have the potential to serve as diagnostic biomarkers for BPD. This may prove beneficial in clinical diagnosis and prevention of BPD.

Defining and Promoting Pediatric Pulmonary Health: Developing Biomarkers for Pulmonary Health.

Children with inherited and/or acquired respiratory disorders often arrive in adolescence and adulthood with diminished lung function that might have been detected and prevented had better mechanisms been available to identify and to assess progression of disease. Fortunately, advances in genetic assessments, low-cost diagnostics, and minimally- invasive novel biomarkers are being developed to detect and to treat respiratory diseases before they give rise to loss of life or lung function. This paper summarizes the Developing Biomarkers for Pulmonary Health sessions of the National Heart, Lung, and Blood Institute- sponsored 2021 Defining and Promoting Pediatric Pulmonary Health workshop. These sessions discussed genetic testing, pulse oximetry, exhaled nitric oxide, and novel biomarkers related to childhood lung diseases.

Effect of Obesity on Lung Function in the Pediatric and Adult Populations with Asthma: A Review.

Obesity and asthma are major global health concerns, particularly in industrialized nations. Obesity has been shown to have detrimental effects on the respiratory system and lung function owing to metabolic issues and immunological consequences. Research has indicated that obese patients with asthma (atopic or T2-high and non-atopic or T2-low) have diminished lung function in terms of functional residual capacity (FRC), residual volume (RV), expiratory reserve volume (ERV), the FEV1/FVC ratio, and FEF 25-75% due to mechanical fat loading on the diaphragm and central adiposity when compared to non-obese asthmatic patients. Therefore, it is plausible that changes in lung function are the result of a combination of mechanical (fat loading on the diaphragm, central adiposity, bronchial hyper-reactivity, and an increase in cholinergic tone), environmental (diet and exercise), and inflammatory factors (local and systemic), which can lead to the obesity-related asthma phenotype characterized by severe asthma symptoms, poor response to corticosteroid treatment, loss of lung function, and poor quality of life from an early age.

Lung function tracking in children with perinatally acquired HIV following early antiretroviral therapy initiation

IntroductionLung disease remains a frequent complication in children with perinatal HIV infection (CHIV) and exposure without infection (CHEU), resulting in diminished lung function. In CHIV, early antiretroviral therapy (ART) initiation...

Evaluation of Peak Inspiratory Flow Rate in Hospitalized Palliative Care Patients with COPD.

Dry powder inhalers are an effective yet costly COPD medication-delivery device. Patients must possess a minimum peak inspiratory flow rate (PIFR) for inhaled medication to be properly deposited into the lungs. Hospitalized palliative-care patients with diminished lung function due to advanced COPD may not possess the minimum PIFR (30 L/min) for adequate drug delivery. This study aims to quantify PIFR values for hospitalized palliative-care patients with advanced COPD to evaluate whether these patients meet the minimum PIFR requirements. Hospitalized patients ≥18 years old with a palliative-care consultation were eligible if they had a diagnosis of advanced COPD (GOLD C or D). Patients were excluded if they lacked decision-making capacity or had a positive COVID-19 test within the previous 90 days. Three PIFR values were recorded utilizing the In-CheckTM device, with the highest of the three PIFR attempts being utilized for statistical analysis. Eighteen patients were enrolled, and the mean of the highest PIFR readings was 72.5 L/min (±29 L/min). Post hoc analysis indicated 99.9% power when comparing the average best PIFR to the minimum PIFR (30 L/min) but only 51.4% power when compared to the optimal PIFR (60 L/min). This study found that palliative-care patients possess the minimum PIFR for DPI drug delivery.

Use of Omadacycline as a Component of Mycobacterium Abscessus Eradication in an Adolescent With Cystic Fibrosis.

Lung damage caused by non-tuberculous mycobacteria (NTM) infections can be devastating to individuals that are predisposed to chronic respiratory colonization. Cystic fibrosis patients are at increased risk for diminished lung function and increased mortality from NTM pulmonary infections. Treatment regimens are often intense and prolonged. The case described in this report is of a 16-year-old male with cystic fibrosis infected with Mycobacterium abscessus who showed evidence of severe nodular pulmonary disease on chest computerized tomography. His intensive treatment phase was complicated by neutropenia and drug resistance, leading to the use of omadacycline. Because of rapid improvement clinically and on computed tomography, he was successfully treated with a modified, less intense continuation phase that included azithromycin, omadacycline, and inhaled amikacin. The patient also was switched from tezacaftor/ivacaftor to elexacaftor/tezacaftor/ivacaftor during the course of NTM treatment.

Aging-Related Mechanisms Contribute to Corticosteroid Insensitivity in Elderly Asthma.

Asthma in elderly populations is an increasing health problem that is accompanied by diminished lung function and frequent exacerbations. As potent anti-inflammatory drugs, corticosteroids are commonly used to reduce lung inflammation, improve lung function, and manage disease symptoms in asthma. Although effective for most individuals, older patients are more insensitive to corticosteroids, making it difficult to manage asthma in this population. With the number of individuals older than 65 continuing to increase, it is important to understand the distinct mechanisms that promote corticosteroid insensitivity in the aging lung. In this review, we discuss corticosteroid insensitivity in asthma with an emphasis on mechanisms that contribute to persistent inflammation and diminished lung function in older individuals.

Efficacy of Omadacycline-Containing Regimen in a Mouse Model of Pulmonary Mycobacteroides abscessus Disease.

Mycobacteroides abscessus is an opportunistic pathogen in people with structural lung conditions such as bronchiectasis, chronic obstructive pulmonary disease, and cystic fibrosis. Pulmonary M. abscessus infection causes progressive symptomatic and functional decline as well as diminished lung function and is often incurable with existing antibiotics. We investigated the efficacy of a new tetracycline, omadacycline, in combination with existing antibiotics recommended to treat this indication, in a mouse model of M. abscessus lung disease. Amikacin, azithromycin, bedaquiline, biapenem, cefoxitin, clofazimine, imipenem, linezolid, and rifabutin were selected as companions to omadacycline. M. abscessus burden in the lungs of mice over a 4-week treatment duration was considered the endpoint. Omadacycline in combination with linezolid, imipenem, cefoxitin, biapenem, or rifabutin exhibited early bactericidal activity compared to any single drug. Using three M. abscessus isolates, we also determined the in vitro frequency of spontaneous resistance against omadacycline to be between 1.9 × 10-10 and 6.2 × 10-10 and the frequency of persistence against omadacycline to be between 5.3 × 10-6 and 1.3 × 10-5. Based on these findings, the combination of omadacycline and select drugs that are included in the recent treatment guidelines may exhibit improved potency to treat M. abscessus lung disease. IMPORTANCE M. abscessus disease incidence is increasing in the United States. This disease is difficult to cure with existing antibiotics. In this study, we describe the efficacy of a new tetracycline antibiotic, omadacycline, in combination with an existing antibiotic to treat this disease. A mouse model of M. abscessus lung disease was used to assess the efficacies of these experimental treatment regimens. Omadacycline in combination with select existing antibiotics exhibited bactericidal activity during the early phase of treatment.

Pulmonary Recovery 12 Months after Non-Severe and Severe COVID-19: The Prospective Swiss COVID-19 Lung Study

Background: Lung function impairment persists in some patients for months after acute coronavirus disease 2019 (COVID-19). Long-term lung function, radiological features, and their association remain to be clarified. Objectives: We aimed to prospectively investigate lung function and radiological abnormalities over 12 months after severe and non-severe COVID-19. Methods: 584 patients were included in the Swiss COVID-19 lung study. We assessed lung function at 3, 6, and 12 months after acute COVID-19 and compared chest computed tomography (CT) imaging to lung functional abnormalities. Results: At 12 months, diffusion capacity for carbon monoxide (DLCO_corr) was lower after severe COVID-19 compared to non-severe COVID-19 (74.9% vs. 85.2% predicted, p < 0.001). Similarly, minimal oxygen saturation on 6-min walk test and total lung capacity were lower after severe COVID-19 (89.6% vs. 92.2%, p = 0.004, respectively, 88.2% vs. 95.1% predicted, p = 0.011). The difference for forced vital capacity (91.6% vs. 96.3% predicted, p = 0.082) was not statistically significant. Between 3 and 12 months, lung function improved in both groups and differences in DLCO between non-severe and severe COVID-19 patients decreased. In patients with chest CT scans at 12 months, we observed a correlation between radiological abnormalities and reduced lung function. While the overall extent of radiological abnormalities diminished over time, the frequency of mosaic attenuation and curvilinear patterns increased. Conclusions: In this prospective cohort study, patients who had severe COVID-19 had diminished lung function over the first year compared to those after non-severe COVID-19, albeit with a greater extent of recovery in the severe disease group.

Symptomatic preterm infants suffer from lung function deficits, regardless of bronchopulmonary dysplasia.

The long-term respiratory consequences for children with bronchopulmonary dysplasia (BPD) are well known. However, there is little emphasis on monitoring preterm infants without BPD. Few studies have explored the lung function status of infants with the symptoms of chronic lung disease of prematurity (CLD). To evaluate functional lung deficits in preterm infants with CLD, and to assess the perinatal determinants of diminished lung function. In our cross-sectional study, 132 preterm infants with symptomatic CLD underwent infant pulmonary function testing (iPFT) at a median post-term age of 0.9 years. The iPFT included bodypletysmography, compliance measurement, tidal breath analysis, and rapid thoracoabdominal compression. The relationships between the respective z scores of the iPFT parameters and perinatal characteristics, postnatal treatment, and BPD status were investigated. Seventy-threepatients (55.3%) were born before the 28th week of gestation, and 92 (69.7%) met the BPD criteria. Functional deficits were detected in 85.8%. The obstructive ventilatory pattern was more prevalent than restrictive (36.3 vs. 12.4%, p < 0.001). Infants with restriction had lower birth weight (BW) and required a longer duration of oxygenotherapy. In a univariate model, the lung function correlated with the duration of invasive mechanical ventilation, gestational week, and BW. In a general linear model, BPD status was not an additional determinant of the iPFT results. IPFT may reveal significant functional deficits in preterm infants with CLD even without BPD. The current symptoms and perinatal factors may be more important determinants of functional deficits than the BPD status itself.

Childhood lung function following perinatal HIV infection and early antiretroviral therapy initiation: a cross-sectional study.

Despite the introduction of antiretroviral therapy (ART), HIV-associated pulmonary complications remain prevalent in children following perinatal HIV infection. In the post-ART era the incidence of opportunistic infections has decreased; however, non-infectious complications including diminished lung function are common. It is unclear whether early initiation of ART influences lung function later in life.We performed a cross-sectional study examining pulmonary function tests (PFT) (spirometry, plethysmography, carbon monoxide diffusing capacity) in HIV-unexposed (HU), HIV-exposed-uninfected (HEU) and perinatally HIV-infected children on early ART (HIV+) recruited from the Cape Town arms of the CHER and IMPAACT 1060 trials. PFT was performed once children could participate (October 2013 to January 2020). Global Lung Initiative reference software was used for Z-standardisation of lung function by sex, age and height.In total 394 children (HU n=90, HEU n=162, HIV+ n=142) underwent PFT, median age 8.7 (IQR 7.7–9.8) years. HIV+ had ART initiated at a median age of 17.6 (8.0–36.7) weeks. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC Z-scores were similar in all groups. Plethysmography demonstrated air-trapping with increased total lung capacity (TLC), functional residual capacity, residual volume (RV) and RV/TLC Z-scores in HIV+. There were no differences in alveolar volume; however, diffusing capacity was increased in HIV+.Our findings indicate that following perinatal HIV infection, early ART may attenuate HIV-associated lung disease and is associated with normal childhood spirometry. However plethysmography demonstrates that small airway dysfunction is more pronounced in HIV+. Longitudinal follow-up is required to assess if these children are at risk of obstructive airway disease later in life.

Interaction of Cigarette Smoking and Polygenic Risk Score on Reduced Lung Function

The risk of airflow limitation and chronic obstructive pulmonary disease (COPD) is influenced by combinations of cigarette smoking and genetic susceptibility, yet it remains unclear whether gene-by-smoking interactions are associated with quantitative measures of lung function. To assess the interaction of cigarette smoking and polygenic risk score in association with reduced lung function. This UK Biobank cohort study included UK citizens of European ancestry aged 40 to 69 years with genetic and spirometry data passing quality control metrics. Data was analyzed from July 2020 to March 2021. PRS of combined forced expiratory volume in 1 second (FEV1) and percent of forced vital capacity exhaled in the first second (FEV1/FVC), self-reported pack-years of smoking, ever- vs never-smoking status, and current- vs former- or never-smoking status. FEV1/FVC was the primary outcome. Models were used to test for interactions with models, including the main effects of PRS, different smoking variables, and their cross-product terms. The association between pack-years of smoking and FEV1/FVC were compared for those in the highest vs lowest decile of estimated genetic risk for low lung function. We included 319 730 individuals, of whom 24 915 (8%) had moderate-to-severe COPD cases, and 44.4% were men. Participants had a mean (SD) age 56.5 of (8.02) years. The PRS and pack-years were significantly associated with lower FEV1/FVC (PRS: β, -0.03; 95% CI, -0.031 to -0.03; pack-years: β, -0.0064; 95% CI, -0.0064 to -0.0063) and the interaction term (β, -0.0028; 95% CI, -0.0029 to -0.0026). A stepwise increment in estimated effect sizes for these interaction terms was observed per 10 pack-years of smoking exposure. The interaction of PRS with 11 to 20, 31 to 40, and more than 50 pack-years categories were β (interaction) -0.0038 (95% CI, -0.0046 to -0.0031); -0.013 (95% CI, -0.014 to -0.012); and -0.017 (95% CI, -0.019 to -0.016), respectively. There was evidence of significant interaction between PRS with ever- or never- smoking status (β, interaction; -0.0064; 95% CI, -0.0068 to -0.0060) and current or not-current smoking (β, interaction; -0.0091; 95% CI, -0.0097 to -0.0084). For any given level of pack-years of smoking exposure, FEV1/FVC was significantly lower for individuals in the tenth decile (ie, highest risk) than the first decile (ie, lowest risk) of genetic risk. For every 20 pack-years of smoking, those in the tenth decile compared with the first decile of genetic risk showed nearly a 2-fold reduction in FEV1/FVC. COPD is characterized by diminished lung function, and our analyses suggest there is substantial interaction between genome-wide PRS and smoking exposures. While smoking was associated with decreased lung function across all genetic risk categories, the associations were strongest in individuals with higher estimated genetic risk.

Lung function improves after delayed treatment with CNP-miR146a following acute lung injury

Acute respiratory distress syndrome (ARDS) is a highly morbid pulmonary disease characterized by hypoxic respiratory failure. Its pathogenesis is characterized by unrestrained oxidative stress and inflammation, with long-term sequelae of pulmonary fibrosis and diminished lung function. Unfortunately, prior therapeutic ARDS trials have failed and therapy is limited to supportive measures. Free radical scavenging cerium oxide nanoparticles (CNP) conjugated to the anti-inflammatory microRNA-146a (miR146a), termed CNP-miR146a, have been shown to prevent acute lung injury in a pre-clinical model. In this study, we evaluated the potential of delayed treatment with CNP-miR146a at three or seven days after injury to rescue the lung from acute injury. We found that intratracheal CNP-miR146a administered three days after injury lowers pulmonary leukocyte infiltration, reduce inflammation and oxidative stress, lower pro-fibrotic gene expression and collagen deposition in the lung, and ultimately improve pulmonary function.