Chronic Lung Disease Research Articles

Effect of LRRC15 on autophagy in A549 cells.

Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic, and irreversible interstitial lung disease with unknown cause. To explore the role and regulatory mechanism of leucine-rich repeat-containing protein 15 (LRRC15) in IPF, bleomycin (BLM)-induced pulmonary fibrosis in mouse and A549 cells were constructed, and the expression of LRRC15 were detected. Then, MTT, GFP-RFP-LC3 dual fluorescent labeling system and Western blotting were used to investigate the effects of LRRC15 on cell activity and autophagy after transfection of siLRRC15, respectively. The results indicated that the expression of LRRC15 was significantly increased after the BLM treatment in mouse lung tissue and A549 cells. The designed and synthesized siLRRC15 followed by transfection into A549 cells resulted in a dramatic reduction in LRRC15 expression and partially restored the cell damage induced by BLM. Moreover, the expression of LC3-II and P62 were up-regulated, the amount of autophagosome were increased by GFP-RFP-LC3 dual fluorescent labeling assay after BLM treatment. Meanwhile, this study also showed that the key autophagy proteins LC3-II, ATG5 and ATG7 were up-regulated, P62 was down-regulated and autophagic flux were enhanced after further treatment of A549 cells with siLRRC15. The above findings suggest that LRRC15 is an indicator of epithelial cell damage and may participate in the regulation of fibrosis through autophagy mechanism in IPF. This study provides necessary theoretical basis for further elucidating the mechanism of IPF.

The association between six-minute walk test and one minute sit to stand test in patients with acute exacerbations of COPD

ABSTRACT Aim: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a major complication of COPD and a leading cause of hospitalization, detrimentally affecting functional exercise capacity. The 6-minute walk test (6MWT) is a reliable measure of exercise capacity in chronic lung diseases. Conversely, the 1-minute sit-to-stand test (1STST) offers a simpler assessment of physical function. The aim was to demonstrate the association of functional exercise capacity assessed by 1STST and 6MWT in COPD patients with acute exacerbation. Materials and Methods: In this study, 37 hospitalized patients with acute exacerbation COPD (mean age:66 years) underwent assessments including pulmonary function testing, 6MWT, 1STST and modified Medical Research Council (MMRC). Parameters such as heart rate, oxygen saturation, and perceived dyspnea (via the modified Borg scale) were monitored during tests. Results: The results showed a significant correlation between 6MWT and 1STST performance (r=0.656, p<0.001). Notably, end-tidal oxygen saturation differed between tests, with the 6MWT showing higher end-tidal dyspnea scores. During recovery, 1STST induced increased heart rate and decreased oxygen saturation. Both 6MWT and 1STST were negatively associated with age and MMRC. Positive correlations were observed between 6MWT and FEV1(L) and PEF(L). Conclusions: Similar to the 6MWT, the 1STS test may be used to evaluate how well patients with AECOPD perform during functional exercise. We propose that the 1STST is a suitable alternative to the 6MWT for the assessment of functional exercise performance during hospitalization in AECOPD patients.

Long-term outcomes in patients with COPD treated with non-invasive ventilation for acute hypercapnic respiratory failure.

Chronic Obstructive Lung Disease (COPD) remains a major cause of morbidity and mortality across the world. We evaluated survival over 9years in a cohort of patients with COPD requiring acute inpatient non-invasive ventilation (NIV). We analyzed prognostic indices to evaluate if they were associated with mortality. We performed a retrospective chart review of all patients who were admitted to St. James's Hospital respiratory ward with COPD and acute hypercapnic respiratory failure who required NIV over a 12-month period and followed their outcomes over 9years. We investigated the association between survival and potential prognostic variables using univariate analysis and multivariate Cox proportional hazards model. We evaluated the association between survival and the following parameters: age, gender, multiple admissions requiring NIV (> 1 admission in within 12months of index presentation), home NIV use preadmission, initial arterial blood gas pH, days spent on NIV, serum albumin and serum albumin to serum CRP ratio at admission. Ninety-nine patients with COPD and acute hypercapnic respiratory failure were identified over a 12-month period from January to December 2011. Survival at 1, 2, 5 and 9years was 65% (n = 64), 42% (n = 42), 25% (n = 25) and 21% (n = 21), respectively. Increasing age (p value < 0.001) and a lower serum albumin (p value < 0.005) were associated with a higher mortality. There was a trend towards improved survival in the group who were treated with home NIV prior to admission compared to no NIV therapy at home but this did not reach statistical significance (Fig.3, p value = 0.088). This study highlights the long-term mortality in patients with COPD admitted with hypercapnic respiratory failure requiring NIV and correlates with prior studies. Increasing age and lower serum albumin were associated with increased mortality.Home NIV may have a protective long-term survival benefit in patients with COPD who have been admitted for acute NIV.

The prevalence and mortality risks of PRISm and COPD in the United States from NHANES 2007–2012

BackgroundWe estimated the prevalence and mortality risks of preserved ratio impaired spirometry (PRISm) and chronic obstructive pulmonary disease (COPD) in the US adult population.MethodsWe linked three waves of pre-bronchodilator spirometry data from the US National Health and Nutritional Examination Survey (2007–2012) with the National Death Index. The analytic sample included adults ages 20 to 79 without missing data on age, sex, height, BMI, race/ethnicity, and smoking status. We defined COPD (GOLD 1, 2, and 3–4) and PRISm using FEV1/FVC cut points by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). We compared the prevalence of GOLD stages and PRISm by covariates across the three waves. We estimated adjusted all-cause and cause-specific mortality risks by COPD stage and PRISm using all three waves combined.ResultsPrevalence of COPD and PRISm from 2007–2012 ranged from 13.1%-14.3% and 9.6%-10.2%, respectively. We found significant differences in prevalence by sex, age, smoking status, and race/ethnicity. Males had higher rates of COPD regardless of stage, while females had higher rates of PRISm. COPD prevalence increased with age, but not PRISm, which was highest among middle-aged individuals. Compared to current and never smokers, former smokers showed lower rates of PRISm but higher rates of GOLD 1. COPD prevalence was highest among non-Hispanic White individuals, and PRISm was notably higher among non-Hispanic Black individuals (range 31.4%-37.4%). We found associations between PRISm and all-cause mortality (hazard ratio [HR]: 2.3 95% CI: 1.9—2.9) and various cause-specific deaths (HR ranges: 2.0–5.3). We also found associations between GOLD 2 (HR: 2.1, 95% CI: 1.7–2.6) or higher (HR: 4.2, 95% CI: 2.7–6.5) and all-cause mortality. Cause-specific mortality risk varied within COPD stages but typically increased with higher GOLD stage.ConclusionsThe prevalence of COPD and PRISm remained stable from 2007–2012. Greater attention should be paid to the potential impacts of PRISm due to its higher prevalence in minority groups and its associations with mortality across various causes including cancer.

Effects of pulmonary rehabilitation on functional and psychological parameters in post-acute sequelae of SARS-CoV-2 infection (PASC) patients

BackgroundCOVID-19 survivors may develop long-term symptoms of fatigue, dyspnea, mental health issues, and functional limitations: a condition termed post-acute sequelae of COVID-19 (PASC). Pulmonary rehabilitation (PR) is a recommended treatment for PASC; however, there is a lack of data regarding PR’s effect on multiple health indices and the factors that influence patient outcomes. The aim of our study is to evaluate the impact of pulmonary rehabilitation on functional and psychological parameters in patients diagnosed with Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), thereby offering insights into the efficacy of such interventions in improving the quality of life and clinical outcomes for these individuals.MethodsWe extracted patient demographic, comorbidity, and outcome data from Allegheny Health Network’s electronic medical records. Functionality test results were compared before and after PR, including 6-minute walk test (6MWT), chair rise repetitions (CR reps), timed up and go test (TUG), gait speed (Rehab gait), modified medical research council scale (MMRC), shortness of breath questionnaire (SOBQ), hospital anxiety and depression scale (HADS) and chronic obstructive pulmonary disease assessment test (CAT) scores. Multiple regression analysis was done to evaluate the effect of comorbidities and patient factors on patient responses to PR.ResultsThe 55 patients included in this study had a mean time of 4 months between the initial COVID-19 diagnosis and the subsequent PASC diagnosis. Following pulmonary rehabilitation (PR), significant improvements were observed across various metrics. The distance covered in the 6-minute walk test (6MWT) increased markedly from a pre-rehabilitation average of 895 feet (SD 290) to 1,300 feet (SD 335) post-rehabilitation, with a mean change of 405 feet (95% CI [333, 477]). Chair rise repetitions (CR reps) saw an increase from 9 (SD 3) reps to 13 (SD 3) reps, with a change of 4 reps (95% CI [3.7, 4.9]). The timed up and go test (TUG) time decreased significantly from 13 s (SD 5) to 10 s (SD 2), reflecting a mean reduction of 3 s (95% CI [-4.5, -2.5]). Rehabilitation gait speed improved from 1.0 m/s to 1.3 m/s, changing by 0.3 m/s (95% CI [0.2, 0.3]). The Modified Medical Research Council (MMRC) dyspnea scale showed a notable decrease from a mean of 2 (SD 1) to 1 (SD 1), a change of -1 (95% CI [-1.5, -1]). The Shortness of Breath Questionnaire (SOBQ) scores reduced significantly from 51 (SD 21) to 22 (SD 18), with a change of -29 (95% CI [-34, -23]). The Hospital Anxiety and Depression Scale (HADS) scores decreased from 11 (SD 7) to 8 (SD 7), a reduction of -4 (95% CI [-5, -2]). Lastly, the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) scores significantly dropped from 18 (SD 7) to 9 (SD 7), changing by -10 (95% CI [-11, -8]). However, the presence of hypertension, diabetes, chronic lung diseases, outpatient status, and receipt of specific pharmacologic treatments (decadron, decadron + remdesivir, and decadron + remdesivir + tocilizumab) were identified as factors associated with a poor response to PR.ConclusionOur study supports PR as an integrated model of care for PASC patients to improve several physical and mental health indices. The long-term effects of PR on patients’ functional status should be investigated in the future.

Maintenance Pulmonary Rehabilitation: An Update and Future Directions.

The Global Initiative for Chronic Obstructive Lung Disease guidelines recommend pulmonary rehabilitation (PR) for individuals with COPD to improve exercise capacity and health-related quality of life (HRQOL) and reduce symptoms of dyspnea. For cost-effectiveness in COPD care, PR is second only to smoking cessation. However, PR programs typically last 9-12 weeks. The benefits of PR in terms of exercise capacity and HRQOL often decrease toward pre-PR levels as early as 3-6 months after completing PR if patients do not continue to engage in exercise. This review will (1) briefly summarize the efficacy data that informed the 2023 American Thoracic Society (ATS) clinical practice guidelines for maintenance PR, (2) discuss exercise components of maintenance PR studied since 2020 when the last papers were included in the ATS guidelines, (3) explore future directions for delivery of maintenance PR using technology-mediated models, and (4) examine the need for behavior change techniques informed by theoretical models that underpin long-term behavior change. This review will focus on persons with COPD who have completed an out-patient core initial PR program as most of the data on maintenance PR have been published in this patient population. Core PR typically implies a facility-based initial intensive structured program. All patients who complete a core initial PR program should be counseled by PR staff at the discharge visit to engage in ongoing exercise. This usual care is equally as important as referral to a formal PR maintenance program. It is critical to emphasize that usual care after core initial PR means all patients should be supported to participate in regular ongoing exercise, regardless of whether supervised maintenance PR is available. Currently, the optimal frequency, exercise and/or physical activity content, and delivery mode for maintenance PR in persons with COPD and other chronic respiratory diseases remain unknown. Patient safety and degree of in-person supervision required due to the severity of the underlying lung disease need to be considered. Future research of maintenance PR should be underpinned by behavior change techniques. Finally, in the setting of finite resources, balancing the competing priorities of core initial programs with those of maintenance PR programs needs to be achieved.

Blood Pressure, Readmission, and Mortality Among Patients Hospitalized With Acute Kidney Injury.

Acute kidney injury (AKI) complicates 20% to 25% of hospital admissions and is associated with long-term mortality, especially from cardiovascular disease. Lower systolic blood pressure (SBP) following AKI may be associated with lower mortality, but potentially at the cost of higher short-term complications. To determine associations of SBP with mortality and hospital readmissions following AKI, and to determine whether time from discharge affects these associations. This retrospective cohort study of adults with AKI during a hospitalization in Veteran Healthcare Association (VHA) hospitals was conducted between January 2013 and December 2018. Patients with 1 year or less of data within the VA system prior to admission, severe or end-stage liver disease, stage 4 or 5 chronic kidney disease, end-stage kidney disease, metastatic cancer, and no blood pressure values within 30 days of discharge were excluded. Data analysis was conducted from May 2022 to February 2024. SBP was treated as time-dependent (categorized as <120 mm Hg, 120-129 mm Hg, 130-139 mm Hg, 140-149 mm Hg, 150-159 mm Hg, and ≥160 mm Hg [comparator]). Time spent in each SBP category was accumulated over time and represented in 30-day increments. Primary outcomes were time to mortality and time to all-cause hospital readmission. Cox proportional hazards regression was adjusted for demographics, comorbidities, and laboratory values. To evaluate associations over time, hazard ratios (HRs) were calculated at 60 days, 90 days, 120 days, 180 days, 270 days, and 365 days from discharge. Of 237 409 admissions with AKI, 80 960 (57 242 aged 65 years or older [70.7%]; 77 965 male [96.3%] and 2995 female [3.7%]) were included. The cohort had high rates of diabetes (16 060 patients [20.0%]), congestive heart failure (22 516 patients [28.1%]), and chronic lung disease (27 682 patients [34.2%]), and 1-year mortality was 15.9% (12 876 patients). Overall, patients with SBP between 130 and 139 mm Hg had the most favorable risk level for mortality and readmission. There were clear, time-dependent mediations on associations in all groups. Compared with patients with SBP of 160 mm Hg or greater, the risk of mortality for patients with SBP between 130 and 139 mm Hg decreased between 60 days (adjusted HR, 1.20; 99% CI, 1.00-1.44) and 365 days (adjusted HR, 0.58; 99% CI, 0.45-0.76). SBP less than 120 mm Hg was associated with increased risk of mortality at all time points. In this retrospective cohort study of post-AKI patients, there were important time-dependent mediations of the association of blood pressure with mortality and readmission. These findings may inform timing of post-AKI blood pressure treatment.

Prospective association between social isolation, loneliness and lung function among Chinese middle-aged and older adults.

Previous research has highlighted a heightened occurrence of social isolation and loneliness in older adults diagnosed with chronic lung diseases. Nevertheless, there exists a dearth of studies that have explored the influence of impoverished social relationships on lung function. This study aimed to examine the longitudinal association between social isolation, loneliness and lung function over 4 years among middle-aged and older Chinese adults. This study employed two waves (2011 and 2015) of data from the China Health and Retirement Longitudinal Study (CHARLS). The analysis was limited to participants aged 45 years and above and stratified based on gender (3325 men and 3794 women). The measurement of peak expiratory flow (PEF) served as an indicator for assessing lung function. Lagged dependent variable regression models, accounting for covariates, were employed to explore the relationship between baseline social isolation and loneliness and the subsequent PEF. For women, social isolation was significantly associated with the decline in PEF at follow-up (β = -.06, p < .001) even after adjusting for all covariates; no significant correlation was observed between loneliness and PEF. Among men, there was no significant association found between either social isolation or loneliness and PEF. Social isolation is prospectively associated with worse lung function in middle-aged and older Chinese women but not men. The results highlight the importance of promoting social relationships in public health initiatives, especially in groups that are more vulnerable.

"Diagnosed with New Health": Social Security Policy Recommendations for People with Cycstic Fibrosis in Ohio Transitioning to a Longer Lifespan

Cystic fibrosis (CF) is a chronic, progressive, genetic, and life-limiting lung disease that impacts approximately 105,000 individuals globally, including 40,000 individuals in the United States. In 2019, a revolutionary new drug, elexacaftor/ivacaftor/tezacaftor (ETI), was approved to manage some of the major symptoms of CF and dramatically increase the lifespan of people with cystic fibrosis (pwCF). Many individuals with CF cannot work full time and require Medicaid, Supplemental Security Income (SSI), Social Security Disability Insurance (SSDI), and other financial assistance programs to pay for treatments and medical expenses. Yet in recent years, pwCF who are on ETI have been increasingly losing benefits. A possible explanation for this is the effectiveness of ETI in improving lung function, creating the perception that pwCF are no longer disabled by their condition. Even with this “miracle" drug, pwCF continue to experience significant complications and vulnerabilities to their physical and mental health as well as limitations on daily living and employment. The compounded vulnerabilities these individuals experience leave them without a safety net. Social Security policies for pwCF require revisions to prevent further biopsychosocial damage to this population. Two policies will be recommended: leniency in redetermination, and CF education for those who make determination decisions.

Blood eosinophils levels in a Colombian cohort of biomass-and tobacco-related COPD patients

IntroductionChronic obstructive pulmonary disease (COPD) is a major cause of illness and death among adults. In 2019, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy incorporated blood eosinophils as a biomarker to identify patients at increased risk of exacerbations which, with the history of exacerbations during the previous year, allows identification of patients who would benefit from anti-inflammatory treatment to reduce the risk of future exacerbations. The aim of this study was to describe demographic and clinical characteristics, eosinophil counts, and exacerbations in a cohort of COPD patients stratified by clinical phenotypes (non-exacerbator, frequent exacerbator, asthma-COPD overlap) in a Colombian cohort at 2600 meters above sea level.MethodsA descriptive analysis of a historical cohort of patients with a confirmed diagnosis of moderate to severe COPD (FEV1/FVC &amp;lt; 0.7 and at least one risk factor for COPD) from two specialized centers with comprehensive disease management programs was performed from January 2015 to March 2019. Data were extracted from medical records 1 year before and after the index date.Results200 patients were included (GOLD B: 156, GOLD E: 44; 2023 GOLD classification); mean age was 77.9 (SD 7.9) years; 48% were women, and 52% had biomass exposure as a COPD risk factor. The mean FEV1/FVC was 53.4% (SD 9.8), with an FEV1 of 52.7% (20.7). No differences were observed between clinical phenotypes in terms of airflow limitation. The geometric mean of absolute blood eosinophils was 197.58 (SD 2.09) cells/μL (range 0 to 3,020). Mean blood eosinophil count was higher in patients with smoking history and frequent exacerbators. At least one moderate and one severe exacerbation occurred in the previous year in 44 and 8% of patients, respectively; during the follow-up year 152 exacerbations were registered, 122 (80%) moderate and 30 (20%) severe. The highest rate of exacerbations in the follow-up year occurred in the subgroup of patients with the frequent exacerbator phenotype and eosinophils ≥300 cells/μL.DiscussionIn this cohort, the frequency of biomass exposure as a risk factor is considerable. High blood eosinophil count was related to smoking, and to the frequent exacerbator phenotype.

Functional availability of medical oxygen for the management of hypoxaemia in Cameroon: A nationwide facility-based cross-sectional survey.

Medical oxygen is essential for managing hypoxaemia, which has a multifactorial origin, including acute and chronic lung diseases such as pneumonia, asthma, and severe malaria. The coronavirus disease 2019 (COVID-19) revealed substantial gaps in the availability and accessibility of safe medical oxygen, especially in low- and middle-income countries (LMICs). This study aimed to assess the availability and sources, as well as the barriers to the availability of functional medical oxygen in hospitals in Cameroon. This was a nationwide cross-sectional descriptive study conducted from 26 March to 1 June 2021. Using a convenient sampling technique, we sampled accredited public and private COVID-19 treatment centres in all ten regions in Cameroon. Representatives from the selected hospitals were provided with a pre-designed questionnaire assessing the availability, type, and state of medical oxygen in their facilities. All analyses were performed using R. In total, 114 hospitals were included in this study, with functional medical oxygen available in 65% (74/114) of the hospitals. About 85% (23/27) of the reference hospitals and only 59% (51/87) of the district hospitals had available functional medical oxygen. Compared to district hospitals, reference hospitals were more likely to have central oxygen units (reference vs. district: 10 vs. 0%), oxygen cylinders (74 vs. 42%), and oxygen concentrators (79 vs. 51%). The most common barriers to the availability of medical oxygen were inadequate oxygen supply to meet needs (district vs. reference hospitals: 55 vs. 30%), long delays in oxygen bottle refills (51 vs. 49%), and long distances from oxygen suppliers (57 vs. 49%). The availability of medical oxygen in hospitals in Cameroon is suboptimal and more limited in districts compared to reference hospitals. The cost of medical oxygen, delays related to refills and supplies, and long distances from medical sources were the most common barriers to availability in Cameroon.

Cigarette smoke-induced dysbiosis: comparative analysis of lung and intestinal microbiomes in COPD mice and patients

BackgroundThe impact of cigarette smoke (CS) on lung diseases and the role of microbiome dysbiosis in chronic obstructive pulmonary disease (COPD) have been previously reported; however, the relationships remain unclear.MethodsOur research examined the effects of 20-week cigarette smoke (CS) exposure on the lung and intestinal microbiomes in C57BL/6JNarl mice, alongside a comparison with COPD patients’ intestinal microbiome data from a public dataset.ResultsThe study found that CS exposure significantly decreased forced vital capacity (FVC), thickened airway walls, and induced emphysema. Increased lung damage was observed along with higher lung keratinocyte chemoattractant (KC) levels by CS exposure. Lung microbiome analysis revealed a rise in Actinobacteriota, while intestinal microbiome showed significant diversity changes, indicating dysbiosis. Principal coordinate analysis highlighted distinct intestinal microbiome compositions between control and CS-exposed groups. In the intestinal microbiome, notable decreases in Patescibacteria, Campilobacterota, Defferibacterota, Actinobacteriota, and Desulfobacterota were observed. We also identified correlations between lung function and dysbiosis in both lung and intestinal microbiomes. Lung interleukins, interferon-ɣ, KC, and 8-isoprostane levels were linked to lung microbiome dysbiosis. Notably, dysbiosis patterns in CS-exposed mice were similar to those in COPD patients, particularly of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 4 patients. This suggests a systemic impact of CS exposure.ConclusionIn summary, CS exposure induces significant dysbiosis in lung and intestinal microbiomes, correlating with lung function decline and injury. These results align with changes in COPD patients, underscoring the important role of microbiome in smoke-related lung diseases.

Pharmaceutical treatment status of patients with COPD in the community based on medical Internet of Things: a real-world study

This study aimed to investigate the real-world standardisation and adherence of medical treatment regimens in patients with chronic obstructive pulmonary disease (COPD) in the community for making future management strategy. The follow-up data and treatment information of patients with COPD, which were collected through the Management Information Center of COPD (MICCOPD) in 21 community health service centres in Songjiang District, a countryside region of Shanghai. Concordance between the pharmaceutical treatment plan and recommendation of 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) report during the follow-up management period, as well as the medication adherence by patients,were analysed. Out of the 2044 patients diagnosed with COPD, 814 patients (39.8%) who had an initial record of medication use were found to meet the inclusion criteria. The most common medication regimens were long-acting beta-agonist plus inhaled corticosteroids (35.9%) and oral bronchodilators (41.9%). Among these 814 patients, 45.7%, 38.0%, 31.6% and 14.6% adhered to the treatment after 6, 12, 18 and 24 months of follow-up, respectively. The concordance rate with the regimens recommended by the 2017 GOLD guidelines was 35.5% at baseline, 35.5% at 6 months, 32.7% at 12 months, 35.4% at 18 months and 37% at 24 months. The compliance and guideline consistency rates of patients with COPD in the community under the management of general practitioners need to be improved. Enhancing general practitioner proficiency in the prevention and management of COPD and increasing patient awareness of the condition, are crucial standardising and improving adherence to initial and follow-up COPD treatments.

Age, sex, and lung volume dependence of dissolved xenon-129 MRI gas exchange metrics.

To characterize the dependence of Xe-MRI gas transfer metrics upon age, sex, and lung volume in a group of healthy volunteers. Sixty-five subjects with no history of chronic lung disease were assessed with 129Xe-MRI using a four-echo 3D radial spectroscopic imaging sequence and a dose of xenon titrated according to subject height that was inhaled from a lung volume of functional residual capacity (FRC). Imaging was repeated in 34 subjects at total lung capacity (TLC). Regional maps of the fractions of dissolved xenon in red blood cells (RBC), membrane (M), and airspace (Gas) were acquired at an isotropic resolution of 2 cm, from which global averages of the ratios RBC:M, RBC:Gas, and M:Gas were computed. Data from 26 males and 36 females with a median age of 43 y (range: 20-69 y) were of sufficient quality to analyze. Age (p = 0.0006) and sex (p < 0.0001) were significant predictors for RBC:M, and a linear regression showed higher values and steeper decline in males: RBC:M(Males) = -0.00362 × Age + 0.60 (p = 0.01, R2 = 0.25); RBC:M(Females) = -0.00170 × Age + 0.44 (p = 0.02, R2 = 0.15). Similarly, age and sex were significant predictors for RBC:Gas but not for M:Gas. RBC:M, M:Gas and RBC:Gas were significantly lower at TLC than at FRC (plus inhaled volume), with an average 9%, 30% and 35% decrease, respectively. Expected age and sex dependence of pulmonary function concurs with 129Xe RBC:M imaging results, demonstrating that these variables must be considered when reporting Xe-MRI metrics. Xenon doses and breathing maneuvers should be controlled due to the strong dependence of Xe-MRI metrics upon lung volume.

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

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

Particles in Exhaled Air (PExA): Clinical Uses and Future Implications

Access to distal airway samples to assess respiratory diseases is not straightforward and requires invasive procedures such as bronchoscopy and bronchoalveolar lavage. The particles in exhaled air (PExA) device provides a non-invasive means of assessing small airways; it captures distal airway particles (PEx) sized around 0.5–7 μm and contains particles of respiratory tract lining fluid (RTLF) that originate during airway closure and opening. The PExA device can count particles and measure particle mass according to their size. The PEx particles can be analysed for metabolites on various analytical platforms to quantitatively measure targeted and untargeted lung specific markers of inflammation. As such, the measurement of distal airway components may help to evaluate acute and chronic inflammatory conditions such as asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, and more recently, acute viral infections such as COVID-19. PExA may provide an alternative to traditional methods of airway sampling, such as induced sputum, tracheal aspirate, or bronchoalveolar lavage. The measurement of specific biomarkers of airway inflammation obtained directly from the RTLF by PExA enables a more accurate and comprehensive understanding of pathophysiological changes at the molecular level in patients with acute and chronic lung diseases.

Clinical characteristics and the prognostic impact of acute kidney injury in critically ill patients with invasive pulmonary Aspergillosis in the intensive care unit: A retrospective, single-center study

Introduction: The incidence and impact of acute kidney injury (AKI) in patients with invasive pulmonary aspergillosis (IPA) admitted to the intensive care unit (ICU) are unknown. Methods: This retrospective study included 140 patients who were diagnosed IPA and admitted to the medical ICU of China–Japan Friendship Hospital in Beijing, China. AKI was defined according to the kidney disease improving global outcomes guidelines. Data on demographic characteristics, comorbidities, laboratory tests, treatments, and prognosis at ICU admission were collected. Results: The rate of AKI was 71.4% (n = 100), and approximately 30% of the patients had preadmission acute kidney dysfunction. Of the 100 patients with AKI, 19, 8, and 73 patients had stage I, II, and III AKI, respectively, and 64 (87.6%) patients required continuous renal replacement therapy. Overall ICU mortality rate was 52.1%. Irreversible AKI was a strong independent risk factor for ICU mortality (odds ratio 13.36, 95% confidence interval 4.52–39.48, p &amp;lt; 0.001), followed by chronic lung disease, use of intermittent positive-pressure ventilation, and long-term corticosteroid treatment within 1 year prior to ICU admission. Higher cardiac troponin I levels at admission and worse volume control during the first 7 days of ICU stay were potential predictive factors of irreversible kidney dysfunction. Patients with irreversible AKI and those who died during the ICU stay had greater volume overload during the first 14 days of ICU stay. Patients who survived received earlier renal replacement therapy support after ICU admission compared to those who died (median, 2 vs. 5 days; p = 0.026). Conclusion: Compared to the patients with IPA in the absence of AKI, those with AKI presented with more volume overload, worse disease burden, and required stronger respiratory support, while experiencing worse prognosis. Irreversible AKI was a strong predictor of mortality in patients with critical IPA. Better volume control and earlier CRRT initiation should be considered key points in AKI management and prognostic improvement.

Respiratory pathogen and clinical features of hospitalized patients in acute exacerbation of chronic obstructive pulmonary disease after COVID 19 pandemic

Respiratory infections are common causes of acute exacerbation of chronic obstructive lung disease (AECOPD). We explored whether the pathogens causing AECOPD and clinical features changed from before to after the coronavirus disease 2019 (COVID-19) outbreak. We reviewed the medical records of patients hospitalized with AECOPD at four university hospitals between January 2017 and December 2018 and between January 2021 and December. We evaluated 1180 patients with AECOPD for whom medication histories were available. After the outbreak, the number of patients hospitalized with AECOPD was almost 44% lower compared with before the outbreak. Patients hospitalized with AECOPD after the outbreak were younger (75 vs. 77 years, p = 0.003) and more often stayed at home (96.6% vs. 88.6%, p < 0.001) than patients of AECOPD before the outbreak. Hospital stay was longer after the outbreak than before the outbreak (10 vs. 8 days. p < 0.001). After the COVID-19 outbreak, the identification rates of S. pneumoniae (15.3 vs. 6.2%, p < 0.001) and Hemophilus influenzae (6.4 vs. 2.4%, p = 0.002) decreased, whereas the identification rates of P. aeruginosa (9.4 vs. 13.7%, p = 0.023), Klebsiella pneumoniae (5.3 vs. 9.8%, p = 0.004), and methicillin-resistant Staphylococcus aureus (1.0 vs. 2.8%, p = 0.023) increased. After the outbreak, the identification rate of influenza A decreased (10.4 vs. 1.0%, p = 0.023). After the outbreak, the number of patients hospitalized with AECOPD was lower and the identification rates of community-transmitted pathogens tended to decrease, whereas the rates of pathogens capable of chronic colonization tended to increase. During the period of large-scale viral outbreaks that require quarantine, patients with AECOPD might be given more consideration for treatment against strains that can colonize chronic respiratory disease rather than community acquired pathogens.

Insights from Chilean NCDs Hospitalization Data during COVID-19

The COVID-19 pandemic has affected the lifestyles of people of all ages, conditions and occupations. Social distance, remote working, changes in diet and a lack of physical activity have directly and indirectly affected many aspects of mental and physical health, particularly in patients with many comorbidities and non-communicable diseases (NCDs). In our paper, we analyzed COVID-19 hospitalized and non-hospitalized cases according to comorbidities to assess the average monthly percentage change (AMPC) and monthly percentage change (MPC) using open access data from the Chilean Ministry of Science, Technology, Knowledge and Innovation. As expected, the infection mainly affected patients with comorbidities, including cardiovascular risk factors. The hospitalized cases with obesity and chronic lung disease increased throughout the period of June 2020–August 2021 (AMPC = ↑20.8 and ↑19.4%, respectively, p &lt; 0.05), as did all the non-hospitalized cases with comorbidities throughout the period (AMPC = ↑15.6 to ↑30.3 [p &lt; 0.05]). The increases in hospitalizations and non-hospitalizations with comorbidities may be associated with physical inactivity. A healthy lifestyle with regular physical activity may have had a protective effect on the COVID-19 severity and related events in the post-pandemic period, especially for the NCD population.

Association between threat-related adverse childhood experiences and chronic lung diseases in a middle and older aged population: A cross-sectional and longitudinal study in China

ObjectivesWe investigated the association between threat-related adverse childhood experiences (ACEs) and the risk of chronic lung diseases (CLDs). MethodsThe data used for this study were extracted from the China Health and Retirement Longitudinal Study (CHARLS), a nationally representative survey of respondents recruited from 450 villages/urban communities in 28 provinces. Threat-related ACEs were constructed using five adverse factors: household substance abuse, physical abuse, domestic violence, unsafe neighbourhood, and bullying). Participants were divided into three groups according to their number of threat-related ACEs at baseline and at follow-up. The association between threat-related ACEs and CLD prevalence in the cross-sectional study was calculated using logistic regression models. The association between threat-related ACEs and CLD onset was evaluated using Cox proportional regression models in the cohort study. Potential confounders were considered in both the cross-sectional and cohort studies. ResultsThe CLD prevalence in the total population, no exposure group, exposure to one threat-related ACE, and exposure to at least two threat-related ACEs were 10.07% (1320/13104), 9.20% (665/7232), 10.89% (421/3865), and 11.66% (234/2007), respectively. Exposure to one threat-related ACE (OR: 1.23, 95% CI: 1.07–1.41) and exposure to at least two threat-related ACEs (OR: 1.31, 95% CI: 1.11–1.55) were significantly associated with higher CLD prevalence rates. The cohort study included 11,645 participants. During the 7-year follow-up, 738 CLD incidents were identified. Similarly, exposure to one threat-related ACE (HR: 1.20, 95% CI: 1.01–1.43) and at least two threat-related ACEs (HR: 1.64, 95% CI: 1.35–2.00) were significantly associated with a higher CLD incidence risk. ConclusionsExposure to threat-related ACEs was significantly associated with a higher CLD prevalence risk and onset. It is crucial to identify individuals who have encountered childhood threats and prioritise the monitoring of their pulmonary function.