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Background and Purpose: Fibrotic lung remodelling after a respiratory viral infection represents a debilitating clinical sequela. Studying or managing viral–fibrotic sequela remains challenging, due to limited therapeutic options and lack of understanding of mechanisms. This study determined whether protein disulfide isomerase A3 (PDIA3) and secreted phosphoprotein 1 (SPP1), which are associated with pulmonary fibrosis, can promote influenza‐induced lung fibrotic remodelling and whether inhibition of PDIA3 or SPP1 can resolve viral‐mediated fibrotic remodelling. Experimental Approach: A retrospective analysis of TriNetX data sets was conducted. Serum from healthy controls and influenza A virus (IAV)‐infected patients was analysed. An inhibitor of PDIA3, punicalagin, and a neutralizing antibody for SPP1 were administered in mice. Macrophage cells treated with macrophage colony‐stimulating factor (M‐CSF) were used as a cell culture model. Key Results: The TriNetX data set showed an increase in lung fibrosis and decline in lung function in flu‐infected acute respiratory distress syndrome (ARDS) patients compared with non‐ARDS patients. Serum samples revealed a significant increase in SPP1 and PDIA3 in influenza‐infected patients. Lung PDIA3 and SPP1 expression increased following viral infection in mouse models. Punicalagin administration 2 weeks after IAV infection in mice caused a significant decrease in lung fibrosis and improved oxygen saturation. Administration of neutralizing SPP1 antibody decreased lung fibrosis. Inhibition of PDIA3 decreased SPP1secretion from macrophages, in association with diminished disulfide bonds in SPP1. Conclusion and Implications: The PDIA3–SPP1 axis promotes post‐influenza lung fibrosis in mice and that pharmacological inhibition of PDIA3 or SPP1 can treat virus‐induced lung fibrotic sequela. [ABSTRACT FROM AUTHOR]

Although evidence has documented the associations of ambient air pollution with chronic respiratory diseases (CRDs) and lung function, the underlying metabolic mechanisms remain largely unclear. How does the metabolomic signature for air pollution relate to CRD risk, respiratory symptoms, and lung function? We retrieved 171,132 participants free of COPD and asthma at baseline from the UK Biobank, who had data on air pollution and metabolomics. Exposures to air pollutants (particulate matter with diameter ≤ 2.5 μm [PM 2.5 ], particulate matter with a diameter ≤ 10 μm, nitrogen oxide [NO X ], and NO 2) were assessed for 4 years before baseline considering residential address histories. We used 10-fold cross-validation elastic net regression to identify air pollution-associated metabolites. Multivariable Cox models were used to assess the associations between metabolomic signatures and CRD risk. Mediation and pathway analysis were conducted to explore the metabolic mechanism underlying the associations. During a median follow-up of 12.51 years, 8,951 and 5,980 incident COPD and asthma cases were recorded. In multivariable Cox regressions, air pollution was positively associated with CRD risk (eg, hazard ratio per interquartile range increment in PM 2.5 , 1.09; 95% CI, 1.06-1.13). We identified 103, 86, 85, and 90 metabolites in response to PM 2.5 , particulate matter with a diameter ≤ 10 μm, NO X , and NO 2 exposure, respectively. The metabolomic signatures showed significant associations with CRD risk (hazard ratio per SD increment in PM 2.5 metabolomic signature, 1.11; 95% CI, 1.09-1.14). Mediation analysis showed that peripheral inflammatory and erythrocyte-related markers mediated the effects of metabolomic signatures on CRD risk. We identified 14 and 12 perturbed metabolic pathways (energy metabolism and amino acid metabolism pathways, etc) for PM 2.5 and NO X metabolomic signatures. Our study identifies metabolomic signatures for air pollution exposure. The metabolomic signatures showed significant associations with CRD risk, and inflammatory- and erythrocyte-related markers partly mediated the metabolomic signatures-CRD links. [ABSTRACT FROM AUTHOR]

Sarcoidosis staging primarily has relied on the Scadding chest radiographic system, although chest CT imaging is finding increased clinical use. Whether standardized chest CT scan assessment provides additional understanding of lung function beyond Scadding stage and demographics is unknown and the focus of this study. We used National Heart, Lung, and Blood Institute study Genomics Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) cases of sarcoidosis (n = 351) with Scadding stage and chest CT scans obtained in a standardized manner. One chest radiologist scored all CT scans with a visual scoring system, with a subset read by another chest radiologist. We compared demographic features, Scadding stage and CT scan findings, and the correlation between these measures. Associations between spirometry and diffusing capacity of the lungs for carbon monoxide (D lco) results and CT scan findings and Scadding stage were determined using regression analysis (n = 318). Agreement between readers was evaluated using Cohen's κ value. CT scan features were inconsistent with Scadding stage in approximately 40% of cases. Most CT scan features assessed on visual scoring were associated negatively with lung function. Associations persisted for FEV 1 and D lco when adjusting for Scadding stage, although some CT scan feature associations with FVC became insignificant. Scadding stage was associated primarily with FEV 1 , and inclusion of CT scan features reduced significance in association between Scadding stage and lung function. Multivariable regression modeling to identify radiologic measures explaining lung function included Scadding stage for FEV 1 and FEV 1 to FVC ratio (P <. 05) and marginally for D lco (P <. 15). Combinations of CT scan measures accounted for Scadding stage for FVC. Correlations among Scadding stage and CT scan features were noted. Agreement between readers was poor to moderate for presence or absence of CT scan features and poor for degree and location of abnormality. In this study, CT scan features explained additional variability in lung function beyond Scadding stage, with some CT scan features obviating the associations between lung function and Scadding stage. Whether CT scan features, phenotypes, or endotypes could be useful for treating patients with sarcoidosis needs more study. [ABSTRACT FROM AUTHOR]

Introduction: People with HIV (PWH) have nearly twice the risk of emphysema than people without HIV. This risk, which has been associated with HIV-mediated changes in the lung immune environment and more extensive radiographic emphysema, may result in different patterns of airflow limitation on pulmonary function testing (PFT) than those traditionally used in people without HIV. Methods: In this prospective cohort of PWH in Atlanta, Georgia, we analyzed PFT and chest computed tomography data from July 2013 through June 2018. After comparing the prevalence of PFT measures of airflow limitation for those with and without radiographic emphysema, we used binary recursive partitioning to identify PFT measures that differentiated between PWH with and without radiographic emphysema. Results: Among 167 PWH who had both PFT and computed tomography data during the study period, 89 (53%) had radiographic emphysema. Those with radiographic emphysema were more likely to have airflow limitations on PFTs. Recursive partitioning identified partitions at a forced expiratory volume in 1 second to forced vital capacity ratio (FEV1/FVC) of 0.78 and a residual volume of 116% predicted. These partitions enabled the identification of 84 (94%) PWH with radiographic emphysema, in contrast to the traditional diagnostic criteria of an FEV1/FVC ratio of 0.7, which only identified 49 (55%) of those with radiographic emphysema. Conclusions: Emphysema in PWH may have different patterns of airflow limitation on PFTs that are not adequately captured by traditional diagnostic criteria. Future studies can seek to validate these findings and determine optimal thresholds for diagnosing HIV-associated emphysema. [ABSTRACT FROM AUTHOR]

Background: The association of lung function with the risk of developing prodromal and clinical-diagnosed Parkinson's disease (PD) and with the risk of mortality among individuals with PD remains unknown. Objective: To prospectively examine the associations of lung function with the risk of prodromal, clinical-diagnosed PD, and PD-related mortality in participants of the UK Biobank. Methods: Included were 452,518 participants free of PD at baseline. Baseline lung function, including forced expiratory volume in 1-s (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), and FEV1/FVC ratio, was assessed. Eight prodromal features were measured using self-reported diagnoses, hospital admission, and primary care data. Incident PD cases were identified using linkages with hospital admission, death register, and self-report. Vital status and date of death were provided by the UK National Health Service (NHS) and the NHS Central Register. We used Cox proportional hazard models to evaluate these associations. Results: Poor lung function was associated with higher risk of PD in a dose-response relationship: the adjusted hazard ratio comparing the lowest vs. the highest lung function quintile was 1.18 (95% CI, 1.02– 1.37) for FEV1, 1.14 (95% CI, 0.99– 1.29) for FVC, and 1.23 (95% CI, 1.08– 1.41) for PEF (p-trend <0.05 for all). Similar results were obtained for risk of prodromal PD and mortality among individuals with PD. Conclusions: The current study showed that individuals with poor lung function had a high future risk of prodromal and clinical PD and a higher rate of PD-related mortality. [ABSTRACT FROM AUTHOR]

[Display omitted] The discriminatory and racist policy of historical redlining in the United States during the 1930s played a role in perpetuating contemporary environmental health disparities. Our objectives were to determine associations between home and school pollutant exposure (fine particulate matter [PM 2.5 ], NO 2) and respiratory outcomes (Composite Asthma Severity Index, lung function) among school-aged children with asthma and examine whether associations differed between children who resided and/or attended school in historically redlined compared to non-redlined neighborhoods. Children ages 6 to 17 with moderate-to-severe asthma (N = 240) from 9 US cities were included. Combined home and school exposure to PM 2.5 and NO 2 was calculated based on geospatially assessed monthly averaged outdoor pollutant concentrations. Repeated measures of Composite Asthma Severity Index and lung function were collected. Overall, 37.5% of children resided and/or attended schools in historically redlined neighborhoods. Children in historically redlined neighborhoods had greater exposure to NO 2 (median: 15.4 vs 12.1 parts per billion) and closer distance to a highway (median: 0.86 vs 1.23 km), compared to those in non-redlined neighborhoods (P <.01). Overall, PM 2.5 was not associated with asthma severity or lung function. However, among children in redlined neighborhoods, higher PM 2.5 was associated with worse asthma severity (P <.005). No association was observed between pollutants and lung function or asthma severity among children in non-redlined neighborhoods (P >.005). Our findings highlight the significance of historical redlining and current environmental health disparities among school-aged children with asthma, specifically, the environmental injustice of PM 2.5 exposure and its associations with respiratory health. [ABSTRACT FROM AUTHOR]

This article summarises key themes from a symposium held during the recent European Respiratory Society congress, which took place in Vienna, Austria, 7–11 September 2024. The symposium was sponsored by GSK and entitled 'Striving for disease stability in COPD: Giving patients more of their best days'. During the session, the speakers (MeiLan Han, Lowie Vanfleteren and Dave Singh) highlighted the specific challenges of chronic obstructive pulmonary disease (COPD), such as its unpredictable and unstable nature, with additional insights provided from patients with COPD in the form of video interviews. The faculty discussed whether treatment standards and goals should be more ambitious to provide all patients the stability and predictability they deserve and the opportunity to do more while living with COPD. [ABSTRACT FROM AUTHOR]

Background: In asthma, sex-steroids signaling is recognized as a critical regulator of disease pathophysiology. However, the paradoxical role of sex-steroids, especially estrogen, suggests that an upstream mechanism or even independent of estrogen plays an important role in regulating asthma pathophysiology. In this context, in our previous studies, we explored kisspeptin (Kp) and its receptor Kiss1R's signaling in regulating human airway smooth muscle cell remodeling in vitro and airway hyperresponsiveness (AHR) in vivo in a mouse (wild-type, WT) model of asthma. In this study, we evaluated the effect of endogenous Kp in regulating AHR and remodeling using Kiss1R knockout (Kiss1R−/−) mice. Methods: C57BL/6J WT (Kiss1R+/+) and Kiss1R−/− mice, both male and female, were intranasally challenged with mixed-allergen (MA) and/or phosphate-buffered saline (PBS). We used flexiVent analysis to assess airway resistance (Rrs), elastance (Ers), and compliance (Crs). Following this, broncho-alveolar lavage (BAL) was performed for differential leukocyte count (DLC) and cytokine analysis. Histology staining was performed using hematoxylin and eosin (H&E) for morphological analysis and Masson's Trichrome (MT) for collagen deposition. Additionally, lung sections were processed for immunofluorescence (IF) of Ki-67, α-smooth muscle actin (α-SMA), and tenascin-c. Results: Interestingly, the loss of Kiss1R exacerbated lung function and airway contractility in mice challenged with MA, with more profound effects in Kiss1R−/− female mice. MA-challenged Kiss1R−/− mice showed a significant increase in immune cell infiltration and proinflammatory cytokine levels. Importantly, the loss of Kiss1R aggravated Th2/Th17 biased cytokines in MA-challenged mice. Furthermore, histology of lung sections from Kiss1R−/− mice showed increased collagen deposition on airway walls and mucin production in airway cells compared to Kiss1R+/+ mice. In addition, immunofluorescence analysis showed loss of Kiss1R significantly aggravated airway remodeling and subsequently AHR. Conclusions: These findings demonstrate the importance of inherent Kiss1R signaling in regulating airway inflammation, AHR, and remodeling in the pathophysiology of asthma. [ABSTRACT FROM AUTHOR]

Background: Foundry workers are occupationally exposed to a variety of inhalable chemical substances. Occupational exposure to vapors, gases, dusts, and fumes can lead to adverse health effects on the respiratory system and cause chronic respiratory diseases, such as interstitial lung diseases (ILDs), chronic obstructive lung disease (COPD), chronic bronchitis, and emphysema. Research on respiratory symptoms, diseases, and lung function in foundry workers over the past few decades has been limited. The aim of this cross-sectional study was to assess the prevalence of respiratory symptoms and diseases and declined lung function of current foundry workers, ex-foundry workers, and unexposed controls. Methods: We assessed respiratory symptoms, diseases, and lung function among 335 current foundry workers, 64 ex-foundry workers, and 161 unexposed controls. The cumulative dust exposure (mg-y) of each participant was calculated, and the median cumulative dust exposure according to the main places of exposure was determined. Results: A higher prevalence of chronic bronchitis, as reported in a questionnaire, was found among current and ex-foundry workers compared to unexposed controls, even after adjusting for pack-years of smoking (p = 0.009). Additionally, cough and wheezing in adulthood without respiratory infection, and chronic rhinitis symptoms were more common among current and ex-foundry workers compared to unexposed controls. These differences remained significant even after adjusting for pack-years of smoking and body mass index (BMI) (p = 0.007 and p < 0.001, respectively). Impaired lung function was more prevalent among both ex-foundry workers (29.7%) and current foundry workers (15.5%) compared to the unexposed controls (8.7%), with the difference remaining significant even after adjusting for the pack-years of smoking and BMI (p = 0.009). According to the questionnaire, the number of physician-diagnosed cases of chronic obstructive pulmonary disease (COPD) or chronic bronchitis was unexpectedly low compared to the indications from the symptom questionnaire and lung function test results, suggesting a potential underdiagnosis. The prevalence of silicosis was low (0.8%) among current and ex-foundry workers. Conclusions: Respiratory symptoms are common among foundry workers. Current and ex-foundry workers exhibited lower lung function in spirometry compared to unexposed controls. There is a potential underdiagnosis of COPD and chronic bronchitis among foundry workers. [ABSTRACT FROM AUTHOR]

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

Background/Objectives: Obstructive sleep apnea (OSA) and obstructive lung diseases (OLD) are common and interdependent respiratory disorders, where one condition may contribute to the development and worsening of the other (OLDOSA syndrome). The term OLDOSA syndrome includes two different conditions: Overlap syndrome (OVS: OSA + chronic obstructive pulmonary disease, COPD) and Alternative Overlap syndrome (aOVS: OSA + Asthma). Data on the interactions between lung function and respiratory monitoring during sleep in OLDOSA patients are few and controversial. Our study aims to evaluate the impact of lung function impairment on sleep breathing disorders, paying attention to the lack of literature about comparisons between OVS, aOVS, and the impact of small airways disease (SAD) in these patients. Methods: In total, 101 patients with a diagnosis of OSA and asthma or COPD underwent pulmonary function tests (PFTs) and nocturnal home sleep cardiorespiratory monitoring (HSCM). Exclusion criteria: Obesity hypoventilation syndrome (OHS) and other non-respiratory sleep disorders. Results: Sleep time with oxygen saturation below 90% (T90) was negatively correlated with forced expiratory volume in the first second, % of predicted (%FEV1), forced vital capacity, % of predicted (%FVC), forced expiratory flow at 25–75% of the pulmonary volume, % of predicted (%FEF25–75), and, after multivariable linear regression analysis, %FEF25–75 remained an independent factor for T90 with a negative correlation in mild and moderate OSA. Obstructive apnea index (oAI) and FEV1/FVC were negatively correlated in mild and moderate OSA. OVS presented with more severe OSA (higher AHI, oAI, and T90) and SAD (lower FEF25–75) compared to aOVS. Conclusions: This study highlights a possible interdependence between OLD and OSA; obstruction of the large and small airways at PFTs contributes to the worsening of these patients' nocturnal hypoxemia and obstructive events of the upper airway during sleep. Furthermore, this study shows that patients with OVS should be carefully monitored, as they present worse data at HSCM and have greater small airways involvement compared to aOVS. [ABSTRACT FROM AUTHOR]

Objective To explore the effect of stepped rehabilitation nursing in elderly patients with a- cute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods A total of 74 elderly patients with AECOPD admitted to the hospital from January 2022 to January 2023 were divided into two groups by random number table method, 37 cases in each group. The control group was given routine nursing. while the observation group was given routine nursing combined with stepped rehabilitation nursing. The lung function, motor function, degree of dyspnea, daily living ability, psychological status and complications were compared between the two groups. Results After eight weeks of discharge, the forced expiratory volume in the first second (FEV₁) and FEV₁/forced vital capacity of the two groups were higher than those at admission, and the observation group was higher than the control group, the differences were statistically significant (P<0.05). The modified medical research council dyspnea scale scores of the two groups were lower than those at admission, and the observation group was lower than the control group. The six min walking distance and Barthel index scores of the two groups were higher than those at admission, and the observation group was higher than the control group. The differences were statistically significant (P<0.05). The scores of self- rating anxiety scale and self-rating depression scale in the two groups were lower than those at admission, and the scores in the observation group were lower than those in the control group, the differences were statistically significant (P<0.05). There was no significant difference in the incidence of complications between the two groups at hospitalization and follow-up after discharge (P>0.05). Conclusion Stepped rehabilitation nursing for elderly patients with AECOPD can improve lung function. improve daily living ability and exercise ability, and alleviate negative emotions. [ABSTRACT FROM AUTHOR]

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

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

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

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

Objectives: To investigate the mediating role of the activation degree of arginine-proline metabolism in the association of coal dust and decreased lung function. Methods: Cumulative dust exposure (CDE) represented coal dust exposure, whereas the hydroxyproline-to-arginine concentration ratio (Hyp/Arg) in bronchoalveolar lavage fluid gauged arginine-proline metabolism activation. Pulmonary function indicators, including predicted value of forced vital capacity (FVC%pred), forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC%), and the ratio of actual to predicted value of FEV1 (FEV1%pred), diffusing capacity of the lungs for carbon monoxide (DLCO%pred), difference value between alveolar air and arterial partial oxygen pressure (P(A-a) O2), and 6-minutewalking distance test (6MWT), were assessed. Results: Findings revealed a significant association between elevated CDE and increased Hyp/Arg, increased P(A-a) O2, decreased 6MWT, DLCO%pred, and decreased FVC%pred. However, no statistically significant association was found between CDE and FEV1%pred or FEV1/FVC%. The mediating effect of Hyp/Arg was significant for CDE's impact on P(A-a) O2 and DLCO%pred but not on 6MWT and FVC%pred. Conclusions: These results highlight the role of Hyp/Arg in mediating the association between CDE and lung function parameters, shedding light on potential therapeutic avenues for mitigating coal dust-induced lung function impairment. [ABSTRACT FROM AUTHOR]

Background: PM2.5 has been associated with various adverse health effects, particularly affecting lung function and chronic respiratory diseases. However, the genetic causality relationship between PM2.5 exposure and lung function as well as chronic respiratory diseases remains poorly understood. Method: We conducted a two-sample Mendelian randomization analysis to investigate the causal impact of PM2.5 on lung function and chronic respiratory diseases. Instrumental variables were carefully selected, with significance thresholds (P < 5 × 10− 8), and linkage disequilibrium with an r2 value below 0.001. Additionally, SNPs with an F-statistic exceeding 10 were included to mitigate potential bias stemming from weak instrumental variables. The primary analytical approach employed the Inverse Variance Weighted method, supplemented by the Weighted Median, MR-Egger, Simple Model, and Weighted Model. Furthermore, pleiotropy and heterogeneity were evaluated through the MR-Egger intercept test and Cochrane's Q test, with a sensitivity analysis conducted using the leave-one-out method. Results: Eight SNPs significantly associated with PM2.5 exposure were identified as Instrumental variables. Mendelian randomization analysis revealed a significant causal association between PM2.5 exposure and lung function (FEV), with an OR of 0.7284 (95% CI: 0.5799–0.9150). Similarly, PM2.5 exposure demonstrated a substantial causal effect on asthma, with an OR of 1.5280 (95% CI: 1.0470–2.2299). However, no causal association was observed between PM2.5 exposure and chronic obstructive pulmonary disease, with an OR of 1.5176 (95% CI: 0.8294–2.7768). Conclusion: These findings emphasize the necessity for continued research efforts in environmental health to develop effective strategies for the prevention and management of chronic respiratory diseases. [ABSTRACT FROM AUTHOR]

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

To conduct a systematic review and meta-analysis of the association between chorioamnionitis and respiratory outcomes of prematurely born children. Pubmed, Medline and Embase were searched for relevant studies. Studies were included if they assessed prematurely born children, who had been exposed to chorioamnionitis and had either lung function testing or assessment of wheeze or asthma following NICU discharge. Two reviewers independently screened the search results, applied inclusion criteria and assessed methodological quality. One reviewer extracted the data and these were checked by a second reviewer. A total of 1,237 studies were identified, but only eight which included 35,000 infants, fulfilled the inclusion criteria. One study looked at both lung function results and wheeze or asthma in childhood. Four of five studies found an association between wheeze/asthma in childhood and exposure to chorioamnionitis: the overall Odds Ratio (OR) for developing wheeze/asthma in childhood was OR 1.71 (95 % CI: 1.55–1.89). Four studies looked at lung function in childhood, three of which showed no statistically significant association between chorioamnionitis exposure and altered lung function. One study found lower lung function in those exposed to chorioamnionitis and lower expiratory flows with increasing levels of chorioamnionitis (forced expiratory flow at 50 % of exhaled forced vital capacity (=FEF50) p=0.012, forced expiratory flow at 25–75 % of the forced vital capacity is exhaled (=FEF25–75) p=0.014). There was a significant association between chorioamnionitis and the development of wheeze or asthma in childhood, but overall not in impairment of lung function. [ABSTRACT FROM AUTHOR]

Purpose: Over 550 loci have been associated with human pulmonary function in genome-wide association studies (GWAS); however, the causal role of most remains uncertain. Single nucleotide polymorphisms in a disintegrin and metalloprotease domain 19 (ADAM19) are consistently related to pulmonary function in GWAS. Thus, we used a mouse model to investigate the causal link between Adam19 and pulmonary function. Methods: We created an Adam19 knockout (KO) mouse model and validated the gene targeting using RNA-Seq and RT-qPCR. Mouse body composition was assessed using dual-energy X-ray absorptiometry. Mouse lung function was measured using flexiVent. Results: Contrary to prior publications, the KO was not neonatal lethal. KO mice had lower body weight and shorter tibial length than wild-type (WT) mice. Their body composition revealed lower soft weight, fat weight, and bone mineral content. Adam19 KO had decreased baseline respiratory system elastance, minute work of breathing, tissue damping, tissue elastance, and forced expiratory flow at 50% forced vital capacity but higher FEV0.1 and FVC. Adam19 KO had attenuated tissue damping and tissue elastance in response to methacholine following LPS exposure. Adam19 KO also exhibited attenuated neutrophil extravasation into the airway after LPS administration compared to WT. RNA-Seq analysis of KO and WT lungs identified several differentially expressed genes (Cd300lg, Kpna2, and Pttg1) implicated in lung biology and pathogenesis. Gene set enrichment analysis identified negative enrichment for TNF pathways. Conclusion: Our murine findings support a causal role of ADAM19, implicated in human GWAS, in regulating pulmonary function. [ABSTRACT FROM AUTHOR]

Childhood asthma is a prevalent condition with potential impacts on adult life. In a 60-year follow-up study of adults with a history of severe childhood asthma, what are the potential differences in characteristics between individuals with persistent asthma and asthma remission in adulthood? Danish adults with a history of childhood asthma and a 4-month stay at an asthma care facility in Kongsberg, Norway (1950-1979) in childhood were included. Recruitment was carried out through social media and personal invitation letters. Participants completed questionnaires and underwent spirometry, bronchial provocation, and bronchodilator reversibility and blood tests. Asthma remission was defined as no use of asthma medication and no asthma symptoms within the past 12 months, with the remaining participants being classified as having current asthma. Among 1,394 eligible participants, 232 participants completed the follow-up. Ninety percent had current asthma, of whom 26% reported exacerbations in the past year. Only 16% of all the participants were managed in secondary care. Common comorbidities were allergic rhinitis (60%), hypertension (21%), eczema (16%), and cataract (8%). Compared with participants in remission, participants with persistent asthma showed higher total IgE (P =.03) and both lower FEV 1 % predicted (P =.03) and FEV 1 to FVC ratio (P <.001), as well as numerically higher fractional exhaled nitric oxide and blood eosinophil count. Our 60-year follow-up study of adults with a history of severe childhood asthma revealed that nine of 10 participants still had current asthma. Persistent asthma was associated with lower lung function and higher levels of type 2 inflammatory biomarkers compared with asthma remission. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Asthmatic children present variable degrees of airway inflammation, remodeling, and resistance, which correlate with disease control and severity. The chronic inflammatory process of the airway triggers airway remodeling, which reflects the degree of airway resistance. Pro-inflammatory and pro-fibrotic mediators are centrally involved in this process. Objective: To investigate whether the levels of pulmonary and systemic pro-inflammatory and pro-fibrotic mediators present a correlation with the resistance of the respiratory system and of the proximal and distal airways. Methods: 39 Asthmatic children (persistent mild and moderate) and 39 non-asthmatic children (both between 6 and 13 years old) were evaluated for anthropometric characteristics, lung function and mechanics, and pulmonary and systemic immune responses. Results: Asthmatic children showed an increased number of blood eosinophils (p < 0.04), basophils (p < 0.04), monocytes (p < 0.002) and lymphocytes (p < 0.03). In addition, asthmatic children showed impaired lung function, as demonstrated by FEV1 (p < 0.0005) and FEV1/FVC (p < 0.004), decreased total resistance of the respiratory system (R5Hz; p < 0.009), increased resistance of the proximal airways (R20Hz; p < 0.02), increased elastance (Z5Hz; p < 0.02) and increased reactance (X5Hz; p < 0.002) compared to non-asthmatic children. Moreover, the following inflammatory factors were significantly higher in asthmatic than non-asthmatic children: GM-CSF in the breath condensate (BC) (p < 0.0001) and in the serum (p < 0.0001); TGF-beta in the BC (p < 0.0001) and in the serum (p < 0.004); IL-5 in the BC (p < 0.02) and in the serum (p < 0.01); IL-4 in the serum (p < 0.0002). Conclusions: Impulse oscillometry is a sensitive method to detect airway resistance in persistent mild and moderate asthmatic children, an event followed by increased levels of pro-inflammatory and pro-fibrotic mediators. [ABSTRACT FROM AUTHOR]

Objectives: To investigate potential presence and resolution of longer-term pulmonary diffusion limitation and microvascular perfusion impairment in COVID-19 convalescents. Materials and methods: This prospective, longitudinal study was carried out between May 2020 and April 2023. COVID-19 convalescents repeatedly and age/sex-matched healthy controls once underwent MRI including hyperpolarized 129Xe MRI. Blood samples were obtained in COVID-19 convalescents for immunophenotyping. Ratios of 129Xe in red blood cells (RBC), tissue/plasma (TP), and gas phase (GP) as well as lung surface-volume ratio were quantified and correlations with CD4+/CD8+ T cell frequencies were assessed using Pearson's correlation coefficient. Signed-rank tests were used for longitudinal and U tests for group comparisons. Results: Thirty-five participants were recruited. Twenty-three COVID-19 convalescents (age 52.1 ± 19.4 years, 13 men) underwent baseline MRI 12.6 ± 4.2 weeks after symptom onset. Fourteen COVID-19 convalescents underwent follow-up MRI and 12 were included for longitudinal comparison (baseline MRI at 11.5 ± 2.7 weeks and follow-up 38.0 ± 5.5 weeks). Twelve matched controls were included for comparison. In COVID-19 convalescents, RBC-TP was increased at follow-up (p = 0.04). Baseline RBC-TP was lower in patients treated on intensive care unit (p = 0.03) and in patients with severe/critical disease (p = 0.006). RBC-TP correlated with CD4+/CD8+ T cell frequencies (R = 0.61/ − 0.60) at baseline. RBC-TP was not significantly different compared to matched controls at follow-up (p = 0.25). Conclusion: Impaired microvascular pulmonary perfusion and alveolar membrane function persisted 12 weeks after symptom onset and resolved within 38 weeks after COVID-19 symptom onset. Clinical relevance statement: 129Xe MRI shows improvement of microvascular pulmonary perfusion and alveolar membrane function between 11.5 ± 2.7 weeks and 38.0 ± 5.5 weeks after symptom onset in patients after COVID-19, returning to normal in subjects without significant prior disease. Key Points: • The study aims to investigate long-term effects of COVID-19 on lung function, in particular gas uptake efficiency, and on the cardiovascular system. • In COVID-19 convalescents, the ratio of 129Xe in red blood cells/tissue plasma increased longitudinally (p = 0.04), but was not different from matched controls at follow-up (p = 0.25). • Microvascular pulmonary perfusion and alveolar membrane function are impaired 11.5 weeks after symptom onset in patients after COVID-19, returning to normal in subjects without significant prior disease at 38.0 weeks. [ABSTRACT FROM AUTHOR]

• Long-lasting deficits in function and cognition persisted for a year post-COVID-19. • Better recovery was associated with higher premorbid mobility, male sex, shorter hospital stays, fewer comorbidities, and higher force expiratory volume in the first second (FEV1 % pred). • Early targeted interventions are crucial for restoring prior functioning. Limited data exist on post-severe COVID-19 functional trajectory, particularly considering premorbid status. We characterized 1-year functional recovery post-hospitalization for COVID-19, highlighting predictors of long-term recovery. We enrolled adult patients with lab-confirmed SARS-CoV-2 infection and hospitalized for COVID-19 sequelae, from five major Ontario, Canada hospitals in a prospective cohort study. Assessments included telephone interviews on admission followed by telephone and in-person assessments at 3-, 6-, 9-, and 12-months post-discharge. The Activity-Measure for Post-Acute Care (AM-PAC) Mobility and Cognition scales were administered at baseline and every 3 months for 1 year. Secondary outcomes included symptoms, spirometry, physical performance, dyspnea, fatigue, distress, anxiety and depression, and quality of life. A total of 254 patients (57.1% male) with a mean age of 60.0 (±13.1) years and an average hospital stay of 14.3 (±19.7) days agreed to participate. At 12 months, 55.3% demonstrated clinically important deficits in mobility and 38.8% had cognitive deficits compared to premorbid levels. Fatigue was reported in 44.2%, followed by difficulty walking long distances in 35.8% and dyspnea in 33.0%. Almost 40% of patients had an FEV1(% Pred) < 80% at 12 months, 60.3% had impairments in physical performance, and 44.5% had problems with anxiety or depression. Predictors of better mobility at 12 months included higher premorbid mobility status, male sex, shorter hospital stay, fewer comorbidities, and higher FEV1 (% pred) at the 3-month follow-up. Our study provides compelling evidence of the long-term impact of COVID-19 on functional and cognitive status 1-year post-infection. [ABSTRACT FROM AUTHOR]

To investigate causal relationships of lung function with risks microvascular diseases among participants with diabetes, type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM), respectively, in prospective and Mendelian randomization (MR) study. 14,617 participants with diabetes and without microvascular diseases at baseline from the UK Biobank were included in the prospective analysis. Of these, 13,421 had T2DM and 1196 had T1DM. The linear MR analyses were conducted in the UK Biobank with 6838 cases of microvascular diseases and 10,755 controls. Lung function measurements included forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). The study outcome was microvascular diseases, a composite outcome including chronic kidney diseases, retinopathy and peripheral neuropathy. During a median follow-up of 12.1 years, 2668 new-onset microvascular diseases were recorded. FVC (%predicted) was inversely associated with the risk of new-onset microvascular diseases in participants with diabetes (Per SD increment, adjusted HR = 0.86; 95%CI:0.83–0.89), T2DM (Per SD increment, adjusted HR = 0.86; 95%CI:0.82–0.90) and T1DM (Per SD increment, adjusted HR = 0.87; 95%CI: 0.79–0.97), respectively. Similar results were found for FEV1 (%predicted). In MR analyses, genetically predicted FVC (adjusted RR = 0.55, 95%CI:0.39–0.77) and FEV1 (adjusted RR = 0.48, 95%CI:0.28–0.83) were both inversely associated with microvascular diseases in participants with T1DM. No significant association was found in those with T2DM. Similar findings were found for each component of microvascular diseases. There was a causal inverse association between lung function and risks of microvascular diseases in participants with T1DM, but not in those with T2DM. • Lung function was prospectively, inversely associated with microvascular disease in type 1 diabetes. • Lung function was prospectively, inversely associated with microvascular disease in type 2 diabetes. • Lung function was causally, inversely associated with microvascular disease in type 1 diabetes. • Lung function was not causally associated with microvascular disease in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Several studies have documented the detrimental impacts of secondhand smoke (SHS) exposure to a range of pediatric respiratory conditions, including asthma, bronchitis, and reduced lung function. The aim of the study was to investigate the influence of SHS exposure on lung function, physical fitness, and body mass index (BMI) in children aged 10 to 14 years. Methods: This cross-sectional study included children aged 10 to 14 years at the Elementary School "Trilj" in Trilj, Croatia. Data on SHS exposure were collected using a questionnaire. Antropometric and spirometry measurements were performed. Physical fitness was assessed using the shuttle run (BEEP) test. Results: This study included 157 children, 89 (56.69%) boys and 68 (43.31%) girls. Children exposed to every day SHS in households had significantly lower values of forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC, peak expiratory flow (PEF) (p < 0.001) and higher z-score BMI levels (p = 0.018) in comparison to unexposed children. Logistic regression showed that children unexposed to SHS had higher odds for better results in the BEEP test (OR 62.45, 95% CI 21.26–179.24, p < 0.001). Children with poorer physical fitness, expressed by lower BEEP score levels, had significantly lower FVC, FEV1, FEV1/FVC, and PEF (p < 0.001). Conclusions: Every day SHS exposure in children was associated with poorer lung function, higher BMI, and poorer physical fitness. [ABSTRACT FROM AUTHOR]

Acute respiratory failure (ARF) is a sudden failure of the respiratory system to ensure adequate gas exchanges. Numerous clinical conditions may cause ARF, including pneumonia, obstructive lung diseases (e.g., asthma), restrictive diseases such as neuromuscular diseases (e.g., spinal muscular atrophy and muscular dystrophy), and albeit rarely, interstitial lung diseases. Children, especially infants, may be more vulnerable to ARF than adults due to anatomical and physiological features of the respiratory system. Assessing respiratory impairment in the pediatric population is particularly challenging as children frequently present difficulties in reporting symptoms and due to compliance and cooperation in diagnostic tests. The evaluation of clinical and anamnestic aspects represents the cornerstone of ARF diagnosis: first level exams (e.g., arterial blood gas analysis) confirm and evaluate the severity of the ARF and second level exams help to uncover the underlying cause. Prompt management is critical, with supplemental oxygen, mechanical ventilation, and the treatment of the underlying problem. The aim of this review is to provide a comprehensive summary of the current state of the art in diagnosing pediatric ARF, with a focus on pathophysiology, novel imaging applications, and new perspectives, such as biomarkers and artificial intelligence. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction is closely linked to obesity and diabetes, with declining lung function in aging increasing diabetes risk, potentially due to elevated serum levels of dioxin-like mitochondria inhibitor substances (MIS) from prolonged exposure to environmental pollutants. However, the mechanisms connecting MIS, mitochondria, lung function, and metabolic disorder remain unclear. In this study, we analyzed data from 1371 adults aged 40–69 years in the 2008 Korean Genome Epidemiologic Study (KoGES) Ansung cohort. We indirectly estimated dioxin-like MIS levels by measuring intracellular ATP (MISATP) and reactive oxygen species (MISROS) in cultured cells treated with the serum of participants. Using correlation analysis and structural equation modeling (SEM), we explored the relationships among MIS, mitochondrial function, body mass index (BMI), and lung function (FEV1 and FVC). Our findings revealed that MISATP was associated with BMI in females and with FVC in males, while MISROS correlated with both BMI and FVC in males, not in females. Significant associations between BMI and FVC were found in the highest MIS subgroup in both sexes. SEM analyses demonstrated that MIS negatively influenced mitochondrial function, which in turn affected BMI and lung function. Age-related declines in lung function were also linked to mitochondrial dysfunction. This study underscores the potential of MIS assays as alternatives for assessing mitochondrial function and highlights the importance of mitochondrial health in metabolic disorders and lung function. [ABSTRACT FROM AUTHOR]

The role of the bronchoalveolar lavage fluid (BALF) microbiome in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) remains unclear. The advent of the metagenomic next-generation sequencing (mNGS) has made it possible to reveal the complex microbiome composition of the respiratory tract. This study aimed to explore whether there are differences in the BALF microbiome of AECOPD patients with different lung functions. We enrolled 55 AECOPD patients and divided them into a mild group (n = 31) and a severe group (n = 24) according to their lung function. We collected BALF and submitted it to mNGS and bioinformatics analysis. At the species level, mNGS identified 264 bacteria, 13 fungi and 12 viruses in the mild group, and 174 bacteria, 6 fungi and 6 viruses in the severe group. Mixed bacterial and viral infection occurred in both groups. At the genus level, Rothia and Veillonella were more abundant in the mild group, while Pseudomonas and Staphylococcus were more abundant in the severe group. At the species level, compared with the mild group, the relative abundance of Haemophilus influenzae and Pseudomonas aeruginosa was increased in the severe group. Besides, the BALF microbiome composition was similar between the two groups, and there was no significant difference in α and β diversity. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) (%) showed no significant correlation with the Shannon or Simpson index. The microbiome abundance was different between the mild and severe groups; however, microbiome diversity was similar between the two groups. Based on our findings, Haemophilus influenzae and Pseudomonas aeruginosa may be the pathogenic bacteria that cause the difference in lung function in patients with AECOPD. [ABSTRACT FROM AUTHOR]

Rationale: Declines in percent predicted forced expiratory volume in 1 second (ppFEV1) are an important marker of clinical progression of cystic fibrosis (CF). Objectives: We examined ppFEV1 variability in relation to a combined outcome of lung transplant or death. Methods: We estimated the association between ppFEV1 variability and the combined outcome of lung transplant or death. We included children aged 8 years and older with CF and two prior years of ppFEV1 data before baseline between 2005 and 2021. We defined ppFEV1 increased variability as any relative increase or decrease of at least 10% in ppFEV1 from a 2-year averaged baseline. A marginal structural Cox proportional hazards model was used. We examined a cumulative measure of ppFEV1 variability, defined as the cumulative proportion of visits with ppFEV1 variability at each visit. Kaplan-Meier survival curves were generated on the basis of quartiles of the cumulative distribution of ppFEV1 variability. Results: We included 9,706 patients with CF in our cohort. The median age at cohort entry was 8.3 (interquartile range, 8.2–8.4) years; 50% of patients were female; 94% were White; and the median baseline ppFEV1 was 94.4 (interquartile range, 81.6–106.1). The unadjusted hazard ratio for increased ppFEV1 variability on lung transplant/mortality was 4.13 (95% confidence interval, 3.48–4.90), and the weighted hazard ratio was 1.49 (95% confidence interval, 1.19–1.86). Survival curves stratified by quartile of cumulative variability demonstrated an increased hazard of lung transplant/mortality as the proportion of cumulative ppFEV1 variability increased. Conclusions: We found a strong association between ppFEV1 variability and lung transplant or mortality in a cohort of people with CF in the United States. [ABSTRACT FROM AUTHOR]

Rationale: There is no consensus on criteria to include in an asthma remission definition in real life. Factors associated with achieving remission after biologic initiation remain poorly understood. Objectives: To quantify the proportion of adults with severe asthma achieving multidomain-defined remission after biologic initiation and identify prebiologic characteristics associated with achieving remission that may be used to predict it. Methods: This was a longitudinal cohort study using data from 23 countries from the International Severe Asthma Registry. Four asthma outcome domains were assessed in the 1 year before and after biologic initiation. A priori–defined remission cutoffs were: 0 exacerbations/yr, no long-term oral corticosteroid (LTOCS), partly/well-controlled asthma, and percent predicted FEV1 ⩾ 80%. Remission was defined using two (exacerbations + LTOCS), three (+control or +lung function), and four of these domains. The association between prebiologic characteristics and postbiologic remission was assessed by multivariable analysis. Measurements and Main Results: A total of 50.2%, 33.5%, 25.8%, and 20.3% of patients met criteria for two-, three- (+control), three- (+lung function), and four-domain remission, respectively. The odds of achieving four-domain remission decreased by 15% for every additional 10 years of asthma duration (odds ratio, 0.85; 95% confidence interval, 0.73–1.00). The odds of remission increased in those with fewer exacerbations per year, lower LTOCS daily dose, better control, and better lung function before biologic initiation. Conclusions: One in five patients achieved four-domain remission within 1 year of biologic initiation. Patients with less severe impairment and shorter asthma duration at initiation had a greater chance of achieving remission after biologic treatment, indicating that biologic treatment should not be delayed if remission is the goal. [ABSTRACT FROM AUTHOR]

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

Purpose: Predicting the onset of pulmonary exacerbation for people with cystic fibrosis (CF) is critical to identify those at high risk in advance and allows timely clinical intervention. The FEV1-indicated exacerbation signal (FIES) has been proposed by the CF Learning Network to identify pulmonary exacerbation events, but temporal predictive performance of this marker is unknown. Methods: To assess the epidemiologic impact of secular trends in CF care and treatments on algorithms aimed at prediction of pulmonary exacerbation, we evaluated prediction model "drift" using a longitudinal retrospective cohort of 29,476 individuals from the U.S. CF Foundation Patient Registry (2011–2018). The FIES marker was defined for each clinical encounter using relative drops in lung function, measured as forced expiratory volume in 1 s of % predicted (FEV1pp). We formed predictive probabilities for each FIES event via a target function for a predictive algorithm of FEV1pp. Models were trained using 2 year data windows with prediction performance tested on subsequent years. Results: Year-over-year FIES event discrimination remained consistent (area under the receiver-operator characteristic curve, AUC > 80%). Annual drift was < 1% with actual drop in AUC ~ 3% in 6 years. The model performed best in individuals with moderate-to-low baseline FEV1pp (AUC range: 84–85%). For relatively higher FEV1pp levels, discrimination was slightly lower with higher AUC variability. Conclusion: While model fit improved by accounting for modulator therapy, prediction performance was similar. Most impactful model drifts occurred after 2012 coinciding with increased ivacaftor modulator use. Additional evaluation will be necessary given recent, broad uptake of highly effective modulators. [ABSTRACT FROM AUTHOR]

Objective: To observe the effects of inspiratory muscle training under low intensity [20% maximum inspiratory pres- sure (MIP)] and medium intensity (40% MIP) threshold load on diaphragm function, lung function and quality of life in patients with chronic obstructive pulmonary disease (COPD). Methods: 120 COPD patients who were admitted to Heze Hospital of Shandong Provin- cial Hospital from April 2020 to May 2023 were divided into control group, low intensity group and medium intensity group according to the random number table method, with 40 cases in each group. Control group was given routine treatment; On the basis of control group, the low intensity group used 20% MIP as the initial load of inspiratory muscle training; Medium intensity group used 40% MIP as the ini- tial load of inspiratory muscle training. The lung function [forced vital capacity (FVC), MIP, forced expiratory volume in the first second (FEV1), peak expiratory flow (PEF), maximum ventilation volume per minute (MVV)], diaphragm function [diaphragmatic displacement (DE), deep inspiratory diaphragm thickness (DTei) and quiet end-expiratory diaphragm thickness (DTee), diaphragmatic thickness frac- tion (DTF)] and quality of life [COPD quality of life scale (COPD-QOL), St George's respiratory disease questionnaire (SGRQ)] were compared among three groups. Results: After treatment, MIP, FVC, FEV₁, MVV and PEF in control group, low intensity group and medi- um intensity group increased in turn (P<0.05). After treatment, DE, DTei and DTF in control group, low intensity group and medium intensity group increased in turn (P<0.05). After treatment, DTee in control group, low intensity group and medium intensity group decreased in turn (P<0.05). After treatment, the scores of COPD-QOL and SGRQ in control group, low intensity group and medium intensity group decreased in turn (P<0.05). Conclusion: Inspiratory muscle training can effectively improve lung function, diaphragm function and quality of life in COPD patients, and the effect of moderate intensity threshold load is the best. [ABSTRACT FROM AUTHOR]

To observe the effects of ambroxol hydrochloride combined with respiratory muscle strength training on lung function, respiratory muscle strength and serum levels of high mobility group protein 1 (HMGB1), transforming growth factor-ẞ1 (TGF-β1) and serum amyloid A (SAA) in elderly patients with stable stage chronic obstructive pulmonary disease (COPD). Methods: 123 elderly patients with stable stage COPD admitted to our hospital from March 2021 to April 2023 were divided into control group (ambroxol hydrochloride treatment, 61 cases) and observation group (ambroxol hydrochloride combined with respiratory muscle strength training, 62 cases) by random number table method. The efficacy, lung function, respiratory muscle strength, serum HMGB1, TGF-β1, SAA levels and adverse reactions were compared between two groups. Results: Compared with the control group of 78.69%, the clinical total effective rate of the observation group further increased by 93.55% (P<0.05). Compared with control group, the forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC, maximum expiratory pressure (MEP) and maximum inspiratory pressure (MIP) were higher in observation group at 2 months after intervention, and HMGB1, TGF-β1, and SAA were lower (P<0.05). There was no difference in the incidence of adverse reactions between two groups (P>0.05). Conclusion: Ambroxol hydrochloride combined with respiratory muscle strength training in the treatment of elderly patients with stable stage COPD, which can effectively improve the clinical treatment effect, improve the lung function and respiratory muscle strength of patients, and regulate the levels of serum HMGB1, TGF-β1 and SAA without increasing the incidence of adverse reactions. [ABSTRACT FROM AUTHOR]

Objective: This study was to investigate the correlation between airway inflammation and lung function impairment in patients with bronchiectasis with different FEV, and to analyze the influencing factors of lung function impairment. Methods: 80 patients with bronchiectasis admitted to the respiratory department of our hospital from May 2022 to January 2024 were selected as research objects. General data of each group were analyzed, and lung function and airway inflammatory cytokine levels were compared in each group. Pearson linear analysis was used to analyze the relationship between lung function and airway inflammation in patients with bronchiectasis, and multi-factor Logisitic regression was used to analyze the influencing factors of lung function impairment in patients with bronchiectasis. Results: The FVC, FEV1/FVC and DLCO evaluation of the three groups were included in the study and the difference among the groups was compared. The results showed that the FVC, FEV1/FVC and FVC of the high FEV, group and the medium FEV, group were higher than those of the low FEV, group. FVC, FEV1/FVC and FVC in high FEV, group were higher than those in medium FEV, group (P<0.05). The levels of ESR, CRP, WBC, NEUT, PCT, IL-4, IL-6, IL-10 and TNF-a in the three groups were included in the study and the differences between the groups were compared. The levels of ESR, CRP, WBC, NEUT, PCT, IL-4, IL-6 and TNF-a in high and medium FEV, groups were lower than those in low FEV, group, and the levels of IL-10 were higher than those in low FEV₁ group (P<0.05). The levels of ESR, CRP, WBC, NEUT, PCT, IL-4, IL-6 and TNF-a in high FEV₁ group were lower than those in medium FEV₁ group, and the levels of IL-10 were higher than those in medium FEV, group(P<0.05). The results of Pearson linear analysis showed that FEV₁, FVC, FEV1/FVC and DLCO were positively correlated with airway inflammatory factors ESR, CRP, WBC, NEUT, PCT, IL-4, IL-6 and TNF-a, and negatively correlated with IL-10 in patients with bronchiectasis (P<0.05). Independent variables were set as the indicators with differences in comparison in the above data, including FVC, FEV1/FVC, DLCO, ESR, CRP, WBC, NEUT, PCT, IL-4, IL-6, IL-10, and TNF-a. The dependent variable was impaired lung function in patients with bronchiectasis. Multivariate Logisitic regression analysis was performed, and the results showed that The influential factors of impaired lung function in patients with bronchiectasis are FVC, FEV1/FVC, DLCO, ESR, CRP, WBC, NEUT, PCT, IL-4, IL-6, IL-10, TNF-α. Conclusion: Airway inflammation increases with the increase of FEV, level in patients with bronchiectasis, which is closely related to lung function and is an influential factor of lung function impairment. [ABSTRACT FROM AUTHOR]

Two cystic fibrosis (CF) rat models, one carrying the common Phe508del mutation and the other a nonsense cystic fibrosis transmembrane conductance regulator (CFTR) mutation (knockout) were previously characterised. Although relevant CFTR mRNA reductions were present in the lung, no overt CF lung disease was observed. This study used flexiVent lung mechanic assessment and regional ventilation assessment via X-ray velocimetry (XV) functional imaging to assess the lung phenotype in both models. To determine the sensitivity of XV regional ventilation imaging, the effect of a localised physical obstruction (delivery of agar beads to part of the lungs) on lung ventilation was examined. At baseline, Phe508del and knockout CF rats had a lower inspiratory capacity, total respiratory system compliance, and static compliance than wildtype rats. Following agar bead delivery all XV ventilation parameters were altered, with substantial increases in poorly ventilated regions and ventilation heterogeneity. XV ventilation maps accurately identified locations of bead-induced airflow changes. Despite unremarkable lung histopathology, this study indicated that CF rats display altered respiratory mechanics, with CF rats needing to exert additional effort to expand and deflate their lungs due to increased stiffness. This study demonstrated the utility of XV imaging providing spatial lung ventilation information. [ABSTRACT FROM AUTHOR]

Introduction: Malnutrition has always been a problem in CF (cystic fibrosis) patients; however, new treatments with CFTR (cystic fibrosis transmembrane conductance regulator protein) modulators have led to weight gain, with some patients at risk of overweight and obesity. Objective: Our study aimed to analyze the evolution of BMI (body mass index) after one year of treatment with triple therapy and the factors associated with weight gain in CF patients undergoing treatment with triple therapy with CFTR protein modulators (ETI) (elexacaftor/tezacaftor/ivacaftor). Methods: We conducted a prospective, observational, longitudinal, multicenter study in patients diagnosed with cystic fibrosis, aged 18 years or older, with at least one F508del allele and who underwent ETI therapy for at least one year, from 2020 to 2023. One hundred and eight patients from two cystic fibrosis units in Spain, Princess University Hospital of Madrid (74 patients) and Central University Hospital of Asturias (HUCA) (34 patients), were included. Demographic data, anthropometric data, lung function, and exacerbations were collected, comparing the data in the previous year to the start of therapy with the results after one year of treatment. Multivariant models were developed to account for repeated weight and BMI measurements, using a mixed effects model approach and accounting for possible modifying factors Results: One hundred and eight patients were included in the study, 58 men (53.7%) and 50 women (46.3%) with a mean age of 29.5 ± 9.4 years (18–59). Patient weight and BMI were recorded at baseline and at 3-month intervals during the study period. The weight increased from 59.6 kg to 62.6 kg and BMI increased from 21.9 kg/m2 to 23.0 kg/m2 after one year of treatment (p < 0.0001 for both). The proportion of underweight individuals decreased after one year of ETI therapy, from 9.3% to 1.9%, while the proportion of overweight or obese individuals increased from 8.3% to 22.9 % at the same time (p < 0.001). In relation to exacerbations, there is a significant increase in the number of patients who did not have any exacerbations after one year of treatment, which increased from 10.2% to 46.2% (p < 0.001), while the number of patients who had >4 exacerbations decreased significantly, from 40.7% to 1.9% (p < 0.001). FEV1% (forced expiratory volume) increased from 63.9 ± 20.9 to 76.8 ± 21.4 (p < 0.001) and the VR/TLC (residual volume/total lung capacity) value decreased from 45.1 ± 10.9 to 34.9 ± 6.2 (p < 0.001). The proportion with FEV1% > 80% increased from 23.1% before ETI therapy to 49.1% one year after ETI therapy. We performed multivariate mixed models to evaluate the evolution of BMI changes with time, accounting for repeated measures and for possible modifying factors. After the introduction of the triple therapy, patients included in the study had significant weight gain during the 12 months, and when including different covariates in the multivariate mixed model, we found that lower baseline BMI, lower baseline FEV1 and FVC (forced vital capacity), and higher VR/TLC value and higher number of exacerbations were associated with higher BMI changes over the study period. Conclusions: CF patients treated with triple therapy experience significant weight gain, increasing the proportion of overweight patients. CF patients who experienced greater weight gain were those with worse BMI at the start of treatment, as well as patients with worse lung function and a greater number of exacerbations in the year before starting ETI therapy. [ABSTRACT FROM AUTHOR]

Background: Identifying mediators between obesity-related traits and lower respiratory tract infections (LRTIs) would inform preventive and therapeutic strategies to reduce the burden of LRITs. We aimed to recognize whether lung function and inflammatory factors mediate their associations. Methods: We conducted a two-step, two-sample Mendelian randomization (MR) analysis. Two-sample MR was performed on (1) obesity-related traits (i.e., body mass index [BMI], waist circumference [WC], and waist-to-hip ratio [WHR]) and LRTIs (i.e., acute bronchitis, acute bronchiolitis, bronchiectasis, influenza, and pneumonia), (2) obesity-related traits and potential mediators, and (3) potential mediators and LRTIs. Next, two-step MR was applied to infer whether the mediation effects exist. Results: We found that C-reactive protein (CRP), interleukin-6 (IL-6), and forced expiratory volume in the first second (FEV1) mediated 32.59% (95% CI: 17.90%, 47.27%), 7.96% (95% CI: 1.79%, 14.14%), and 4.04% (95% CI: 0.34%, 7.74%) of the effect of BMI on pneumonia, and they mediated 26.90% (95% CI: 13.98%, 39.83%), 10.23% (95% CI: 2.72%, 17.73%), and 4.67% (95% CI: 0.25%, 9.09%) of the effect of WC on pneumonia, respectively. Additionally, CRP, forced vital capacity (FVC), and FEV1 mediated 18.66% (95% CI: 8.70%, 28.62%), 8.72% (95% CI: 1.86%, 15.58%), and 8.41% (95% CI: 2.77%, 14.06%) of the effect of BMI on acute bronchitis, and they mediated 19.96% (95% CI: 7.44%, 32.48%), 12.19% (95% CI: 2.00%, 22.39%), and 12.61% (95% CI: 2.94%, 22.29%) of the effect of WC on acute bronchitis, respectively. Conclusions: Health interventions linked to reducing inflammation and maintaining normal lung function could help mitigate the risk of obesity-related LRTIs. [ABSTRACT FROM AUTHOR]

Objective: To investigate the correlation between serum Rac1 enzyme (Rac1) level with asthma control, airway inflammatory response and lung function in asthmatic children. Methods: A retrospective analysis was performed on 79 children with asthma who were diagnosed and treated in our hospital from June 2020 to January 2023. According to the severity of the disease, the children were divided into mild group (25 cases), moderate group (30 cases) and severe group (24 cases). 36 healthy children who underwent physical examination at the same period in our hospital were selected as the control group. The state of an illness, control level, serum mRNA Rac1, inflammatory factors, and lung function of the children in two groups were compared between the control group and the observation group. Results: The Rac1 mRNA levels, forced vital capacity (FVC), forced expiratory volume in one second/FVC (FEV1/FVC), peak expiratory flow (PEF), and maximum mid-expiratory flow (MMEF) in the observation group were significantly lower than these in the control group (P < 0.05). The tumor necrosis factor-alpha (TNF-α), interleukin-5 (IL-5), IL-6, and IL-33 in the observation group were markedly higher than these in the control group (P < 0.05). As the state of an illness worsened, the Rac1 mRNA levels, FVC, FEV1/FVC, PEF, and MMEF gradually reduced (P < 0.05), while the levels of TNF-α, IL-5, IL-6, and IL-33 increased (P < 0.05). As the degree of disease control improved, the Rac1 mRNA levels, FVC, FEV1/FVC, PEF, and MMEF gradually elevated (P < 0.05), and the levels of TNF- α, IL-5, IL-6, and IL-33 showed the opposite trend (P < 0.05). Rac1 was negatively related to the levels of TNF-α, IL-5, IL-6 and IL-33 (P < 0.05), and positively to the levels of FVC, FEV1/FVC, PEF and MMEF (P < 0.001). Rac1 mRNA levels, FVC, FEV1/FVC, PEF and MMEF were protective factors, while TNF-α, IL-5, IL-6 and IL-33 were risk factors for the prognosis of children with asthma (P < 0.05). Conclusion: Children with asthma have obviously lower serum Rac1 mRNA levels, higher inflammatory factor levels and lower lung function. Serum Rac1 mRNA level may be associated with better asthma control, lower airway inflammatory response, better lung function and lower disease severity. It has important reference value for the evaluation of the state of an illness, efficacy and prognosis of children with bronchial asthma. [ABSTRACT FROM AUTHOR]

Observational studies indicate that Aspergillus colonization and allergic bronchopulmonary aspergillosis (ABPA) in people with cystic fibrosis (CF) are associated with poorer lung health and increased disease severity. We performed a longitudinal observational cohort study to analyse long-term outcomes of Aspergillus colonization and ABPA in children with CF. Anonymised UK CF Registry data from 2009 to 2019 for patients aged 8–17 years in 2009–2010 were collected. For the baseline cohort analysis, patients were classified based on the presence of Aspergillus colonization and ABPA in 2009 and/or 2010. For the longitudinal analysis, patients were categorised according to annual Aspergillus colonization and ABPA status. Comparisons made were (1) Aspergillus positive vs. negative; (2) excluding those with ABPA: Aspergillus positive vs. negative; and (3) ABPA positive vs. negative. Primary outcome was percentage predicted FEV1 decline and secondary outcomes included BMI decline, mortality, lung transplant, and IV antibiotic use. Of the 1675 children, 263 had Aspergillus colonization in the baseline cohort, 260 were diagnosed with ABPA, and 80 had both. Baseline cohort analysis showed significantly lower lung function (p < 0.0001) and increased antibiotic treatment (p < 0.001) in those with Aspergillus colonization and in those with ABPA. Longitudinal analysis showed ABPA was associated with increased decline in lung function (p < 0.00001) and BMI (p < 0.00001). Aspergillus colonization was associated with increased decline in BMI (p = 0.005) but not lung function (p = 0.30). ABPA was associated with increased decline in long-term lung function and BMI in children and young people with CF. Aspergillus colonization was associated with lower lung function at baseline, but no increased rate of decline was observed long-term. [ABSTRACT FROM AUTHOR]

Introduction: Reactance inversion (RI) has been associated with impaired peripheral airway function in persistent asthma. However, there is little to no data about the difference between asthmatic children with and without RI. This study aimed to detect clinical and lung function differences in moderate-severe asthmatic children with and without RI. Methods: This study was conducted between 2021 and 2022 in asthmatic school-age children. Impulse oscillometry (IOS) and spirometry were performed according to ATS/ERS standards. Results: A total of 62 patients, with a mean age of 8.4 years, 54.8% were males and were divided into three groups: group 1 (32.3%) with no RI, group 2 (27.4%) with RI but disappearing after bronchodilator test and group 3 (40.3%) with persistent RI after bronchodilator test. Children in groups 2 and 3 had significantly lower birth weights than in group 1. Group 2 had lower gestational age compared to group 1. FEV1 and FEF25-75 of forced vital capacity were significantly lower in groups 2 and 3. In group 3, R5, AX, R5-20, and R5-R20/R5 ratios were significantly higher. Bronchodilator responses (BDR) in X5c, AX, and R5-R20 were significantly different between groups and lower in group 3. Conclusion: RI is frequently found in children with moderate-severe persistent asthma, particularly in those with a history of prematurity or low birth weight. In some patients, RI disappears after the bronchodilator test; however, it, persists in those with the worst pulmonary function. RI could be a small airway dysfunction marker. [ABSTRACT FROM AUTHOR]

Introduction: Clinical remission is a relatively new concept in asthma but recent research initiatives suggest it could be an ambitious and achievable therapeutic target for patients with asthma. Methods: In this modified Delphi study (comprising two online surveys, completed either side of a virtual scientific workshop), the opinions of a panel of respiratory physicians were evaluated to summarize perspective statements on key therapeutic outcomes and criteria for on-treatment clinical remission in patients with moderate asthma. An agreement threshold was pre-defined as agreement by ≥ 75% of participants. Results: Surveys 1 and 2 were completed by 20 and 18 participants, respectively. Most participants (95%) agreed with the concept of clinical remission in moderate asthma and that this should be a desirable treatment goal (90%). Based on a composite measure of 4–6 desirable therapeutic outcomes, current understanding of clinical remission was considered as 12 months with no exacerbations, no oral corticosteroids, no daytime or night-time asthma symptoms (Asthma Control Test score ≥ 20 or Asthma Control Questionnaire score ≤ 0.75), stable lung function, and no treatment-related adverse events. No agreement was reached on the role of relievers in defining therapeutic outcomes or on the wider use of biomarkers and airway hyperresponsiveness for defining asthma remission in clinical practice. Conclusions: In line with recent consensus statements from the United States and Europe, there was a high level of agreement on the elements of clinical remission among a panel of respiratory physicians from Asia, the Middle East, and South America. Extension of the concept of clinical remission to patients with moderate asthma was considered aligned with the potential of clinical remission as a goal of therapy. [ABSTRACT FROM AUTHOR]

This retrospective study analysed a series of investigations on lung function in military divers and the importance of computed tomography (CT) scans concerning fitness to dive. We examined the incidence of blebs and bullae in a population of military divers with large lungs prompted by six cases of pulmonary barotrauma. All of these divers' medicals were normal apart from having large lungs (FVC > 120% predicted). A subsequent survey of the database of all divers and submariners of the Royal Netherlands Navy (RNLN) found another 72 divers/submariners with large lungs who were then evaluated by a CT scan. This resulted in the identification of three further individuals with blebs and/or bullae, who were then declared unfit to dive. In total, the incidence of these lung abnormalities in this cohort was 11.5%. We discuss the possible consequences for fitness to dive with regard to the current literature on the subject, and also consider the most recent standards of reference values for pulmonary function indices. Based on our results and additional insights from other studies, we advise using the Global Lung Initiative reference values for pulmonary function, while performing high resolution CT scans only in divers with clinical indications. [ABSTRACT FROM AUTHOR]

[Display omitted] Months after infection with severe acute respiratory syndrome coronavirus 2, at least 10% of patients still experience complaints. Long-COVID (coronavirus disease 2019) is a heterogeneous disease, and clustering efforts revealed multiple phenotypes on a clinical level. However, the molecular pathways underlying long-COVID phenotypes are still poorly understood. We sought to cluster patients according to their blood transcriptomes and uncover the pathways underlying their disease. Blood was collected from 77 patients with long-COVID from the Precision Medicine for more Oxygen (P4O2) COVID-19 study. Unsupervised hierarchical clustering was performed on the whole blood transcriptome. These clusters were analyzed for differences in clinical features, pulmonary function tests, and gene ontology term enrichment. Clustering revealed 2 distinct clusters on a transcriptome level. Compared with cluster 2 (n = 65), patients in cluster 1 (n = 12) showed a higher rate of preexisting cardiovascular disease (58% vs 22%), higher prevalence of gastrointestinal symptoms (58% vs 29%), shorter hospital duration during severe acute respiratory syndrome coronavirus 2 infection (median, 3 vs 8 days), lower FEV 1 /forced vital capacity (72% vs 81%), and lower diffusion capacity of the lung for carbon monoxide (68% vs 85% predicted). Gene ontology term enrichment analysis revealed upregulation of genes involved in the antiviral innate immune response in cluster 1, whereas genes involved with the adaptive immune response were upregulated in cluster 2. This study provides a start in uncovering the pathophysiological mechanisms underlying long-COVID. Further research is required to unravel why the immune response is different in these clusters, and to identify potential therapeutic targets to create an optimized treatment or monitoring strategy for the individual long-COVID patient. [ABSTRACT FROM AUTHOR]

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Rationale: The definition of the lower limit of normal (LLN) of spirometric variables is not well established. Objectives: To investigate the relationship between spirometric abnormalities defined with different thresholds of the LLN and clinical outcomes and to explore the possibility of using different LLN thresholds according to the pretest probability of disease. Methods: We studied the associations between prebronchodilator spirometric abnormalities (forced expiratory volume in the first second [FEV1] < LLN, forced vital capacity [FVC] < LLN, airflow obstruction, spirometric restriction) defined with different thresholds of the LLN (10th, 5th, 2.5th, 1st percentile) and multiple outcomes (prevalence of spirometric abnormalities, respiratory symptoms, all-cause and respiratory mortality) in 26,091 30- to 46-year-old men who participated in a general population survey in Norway in 1988–1990 and were followed for 26 years. Analyses were performed with both local and Global Lung Function Initiative (GLI)-2012 reference equations, stratified by pretest risk (presence or absence of respiratory symptoms), and adjusted for age, body mass index, smoking, and education. Results: In the total population, the prevalence of airflow obstruction was 11.6% with GLI-LLN10, 11.0% with Local-LLN5, 6.1% with GLI-LLN5, 7.6% with Local-LLN2.5, and 3.5% with GLI-LLN2.5. The prevalence of spirometric restriction was 5.9% with GLI-LLN10, 5.2% with Local-LLN5, and 2.8% with GLI-LLN5. Increasingly lower thresholds of the LLN were associated with increasingly higher odds of respiratory symptoms and hazard of mortality for all spirometric abnormalities with both reference equations. Spirometric abnormalities defined with Local-LLN2.5 in asymptomatic subjects were associated with lower hazard of all-cause mortality (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.15–1.95 for FEV1 < LLN) than those defined with Local-LLN5 in the general population (HR, 1.67; 95% CI, 1.50–1.87 for FEV1 < LLN) and symptomatic subjects (HR, 1.67; 95% CI, 1.46–1.91 for FEV1 < LLN). Overall, the prevalence of spirometric abnormalities and associations with outcomes obtained with Local-LLN5 were comparable to those obtained with GLI-LLN10 and those obtained with Local-LLN2.5 to GLI-LLN5. Conclusions: There is a relationship between statistically based thresholds of the LLN of spirometric variables and clinical outcomes. Different thresholds of the LLN may be used in different risk subgroups of subjects, but the choice of the threshold needs to be evaluated together with the choice of reference equations. [ABSTRACT FROM AUTHOR]

Yu Yang,1,2 Shuqi Wang,1,3 Boying Jia,1,3 Shuchun Chen1,3 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 3Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, 348 heping West Road, Shijiazhuang, Hebei, 050051, People’s Republic of China, Tel/Fax +86 311 85988406, Email chenshuc2014@163.comPurpose: To investigate the relationship between the triglyceride-glucose (TyG) index and pulmonary function metrics among the general population undergoing health examinations.Materials and Methods: The enrollment totaled 696 participants. Fasting triglycerides and glucose levels were used to calculate the TyG index. Participants were divided into two categories according to their median TyG: one with high TyG and the other with low TyG. A portable spirometer was used to assess lung function. Fundamental clinical features and lung function indicators were compared between the two groups, and the relationship between the TyG index and lung function parameters was explored.Results: Compared with the low TyG group, the high TyG group exhibited significantly reduced levels of FEV1/FVC, FVC% pred, FEV1% pred, FEV3% pred, FEV3/FVC, FEF75, FEF75% pred, FEF25-75% pred, and MVV% pred, suggesting poor pulmonary function. The TyG index was significantly inversely correlated with multiple pulmonary function metrics, including FVC% pred, FEV1% pred, FEV3% pred, FEV1/FVC, FEV3/FVC, FEF75, FEF75% pred and FEF25-75% pred, which persisted even after accounting for confounding variables.Conclusion: In summary, the present study establishes a correlation between the TyG index and some lung function indicators, offering a new indicator of metabolic abnormalities related to lung functionality.Keywords: triglyceride-glucose index, lung function, insulin resistance, FEV1, FVC

Abstract Background Foundry workers are occupationally exposed to a variety of inhalable chemical substances. Occupational exposure to vapors, gases, dusts, and fumes can lead to adverse health effects on the respiratory system and cause chronic respiratory diseases, such as interstitial lung diseases (ILDs), chronic obstructive lung disease (COPD), chronic bronchitis, and emphysema. Research on respiratory symptoms, diseases, and lung function in foundry workers over the past few decades has been limited. The aim of this cross-sectional study was to assess the prevalence of respiratory symptoms and diseases and declined lung function of current foundry workers, ex-foundry workers, and unexposed controls. Methods We assessed respiratory symptoms, diseases, and lung function among 335 current foundry workers, 64 ex-foundry workers, and 161 unexposed controls. The cumulative dust exposure (mg-y) of each participant was calculated, and the median cumulative dust exposure according to the main places of exposure was determined. Results A higher prevalence of chronic bronchitis, as reported in a questionnaire, was found among current and ex-foundry workers compared to unexposed controls, even after adjusting for pack-years of smoking (p = 0.009). Additionally, cough and wheezing in adulthood without respiratory infection, and chronic rhinitis symptoms were more common among current and ex-foundry workers compared to unexposed controls. These differences remained significant even after adjusting for pack-years of smoking and body mass index (BMI) (p = 0.007 and p