History Of Respiratory Disease Research Articles

#1708 Mortality and kidney function recovery in patients with sepsis-associated vs non-septic acute kidney injury treated with CRRT

Abstract Background and Aims It was recently suggested that sepsis-associated acute kidney injury (SA-AKI) is characterized by different pathogenesis and outcomes compared to non-Septic AKI (NS-AKI). However, limited data are available focusing on the clinical outcomes of SA-AKI versus NS-AKI. The aim of this study is to examine risk factors and outcomes of SA-AKI vs NS-AKI among critically ill patients who developed AKI requiring renal replacement therapy (RRT). Methods We performed a single-center retrospective analysis, examining all patients admitted to ICU who developed AKI requiring RRT at Policlinico of Bari, from January 2021 to July 2023. We classified patients in two groups based on the leading cause of AKI: NS-AKI and SA-AKI. We collected clinical and laboratory data, including maximum AKI stage reached during hospitalization, RRT indications, modality and duration. The primary outcome was to assess mortality rate between SA-AKI and NS-AKI groups. The cumulative 28-day survival probability was calculated using the Kaplan–Meier method. The analysis of the risk factors associated with in-hospital mortality was performed using Cox's proportional hazard regression models. Kidney Functional Recovery (KFR) from, RRT discontinuation and length of ICU and hospital stay were also analyzed. Results 320 patients were included in the study; 131 patients developed SA-AKI (40.9%), while the remaining 189 were classified as NS-AKI (59.1%). Median age was 67 years (IQR 57-73) with a predominance of male gender (67.8%), without significant differences between groups. A significant percentage of patients had an history of cardiovascular disease in NS-AKI group compared to SA-AKI group (54.5% vs 29%, p < 0.001). Conversely, the proportion of patients with a history of chronic respiratory disease was significantly higher in the SA-AKI group (23.7% vs 9.5%, p = 0.001). 268 patients (83.8%) developed AKI Stage 3 and 40 patients AKI stage 2 (12.5%) at RRT initiation. All patients were treated with continuous modalities (CRRT). There was no significant difference in CRRT duration between groups (median days 5, IQR 2-12) (Table 1). The timing of CRRT initiation from ICU admission was significant different and we reported a late CRRT initiation in the SA-AKI group (3 vs 1 days, p = 0.002). The median length of ICU stay was 12 days (IQR 4-25) and did not differ between groups. 184 patients (57.5%) died at 28 days, with a higher percentage in the SA-AKI (70.2 vs 48.6%, p < 0.001). Similarly, in-hospital mortality was reported in 221 patients (69%), with impressive percentages in the SA-AKI group (82.45 vs 69.3%, p < 0.001) (Fig. 1). KFR at 28 days from CRRT initiation was significantly higher in the NS-AKI (28.5%) compared to the SA-AKI group (13.7%, p = 0.002). Median time of KFR was similar between groups (p = 0.833). Multivariate Cox Regression analysis showed that only SA-AKI (HR 1.442, 95% CI 1.052-1.978, p = 0.023) was independently associated with increased risk of mortality. Conclusions Sepsis-associated AKI was associated with high mortality rate and lower likelihood of renal recovery compared to non-septic AKI in critically ill patients requiring RRT. These findings emphasize the importance of identifying specific AKI phenotypes characterized by different pathophysiology and clinical outcomes.

Knockdown of the SDHB Subunit Induces Mitochondrial Remodeling in Human Airway Smooth Muscle Cells

Succinate dehydrogenase (SDH) is a mitochondrial enzyme that serves a dual role in mitochondrial respiration: catalyzing the oxidation of succinate to fumarate in the tricarboxylic acid (TCA) cycle and transferring electrons from succinate to ubiquinone as complex II in the electron transport chain (ETC). SDH is composed of four subunits (SDHA-SDHD) and the loss of SDHB subunit, specifically, has been shown to increase oxidative stress. As a part of the catalytic core of the SDH complex, the SDHB subunit mediates electron transfer to ubiquinone. In human airway smooth muscle (hASM) cells with siRNA-mediated knockdown of SDHB, the maximum velocity of the SDH reaction (SDHmax) is decreased. Moreover, SDHB-knockdown leads to an increase in mitochondrial volume density, indicating a role of SDH in mitochondrial remodeling. However, the impact of SDHB-knockdown on mitochondrial dynamics has not been explored. Therefore, we hypothesize that SDHB-knockdown promotes mitochondrial fragmentation as part of mitochondrial remodeling in hASM cells. To investigate this hypothesis, bronchiolar tissue samples were collected in female and male patients undergoing lung surgery with no current history of smoking or respiratory diseases, the smooth muscle layer was dissected and hASM cells were dissociated. The targeted knockdown of SDHB was achieved by siRNA-mediated knockdown. Mitochondria in hASM cells were labeled with MitoTracker Green (200 nM) and imaged in 3D with a Z optical slice of 0.5 μm using an oil-immersion ×60/1.4 NA objective on a Nikon Eclipse A1 laser scanning confocal system. Optical slices were deconvolved to enhance contrast and the MitoTracker labeling was thresholded to create binary images, which were then reconstructed in 3D. From these images, the mitochondrial complexity index (MCI) was calculated to quantify the extent of fragmentation. To identify the signaling pathway involved in mitochondrial fragmentation, the expression and phosphorylation of dynamin-related protein 1 (DRP1) was quantified by Western blot. Mitochondrial fragmentation is associated with increased phosphorylation of DRP1 at Ser616 (pDRP1s616). Furthermore, mitophagy was assessed by determining the mitochondrial expression of PINK1 and the phosphorylation of Parkin at Ser65 (pParkinS65). Mitochondrial biogenesis was also evaluated through the expression of PGC1α, NRF1/2 and TFAM. Our results show that SDHB-knockdown increased mitochondrial fragmentation (reduced MCI) in hASM cells, and increased pDRP1s616 phosphorylation and its translocation to mitochondria. SDHB-knockdown also increased mitochondrial expression of PINK1 and pParkins65 phosphorylation indicating activation of mitophagy. We also confirmed that SDHB-knockdown increased expression of PGC1α, NRF1/2 and TFAM consistent with mitochondrial biogenesis. These findings unveil the mechanisms underlying SDHB-knockdown-mediated mitochondrial remodeling. Supported by NIH grant R01-HL157984 (GCS). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Investigation and Analysis of Lung Cancer Risk Factors in the Health Check-Up Population

Objective: To investigate and analyze the risk factors of lung cancer in the population of health checkups. Methods: A total of 500 cases of the health check-up population were selected for data study. Surveyed showed that 19 cases of lung cancer were grouped as the lung cancer group and the remaining 481 cases made up the control group, and the risk factors were analyzed. Results: Among men, there was a significant proportion of individuals aged 60–69 years old, and women aged 30–39 years old. Additionally, individuals aged 60 and above were at increased risk of developing lung cancer. The results of the multifactorial analysis were that the risk factors affecting the detection of lung cancer in healthy people were smoking history, family history of lung cancer, secondhand smoke, history of respiratory diseases, psychosomatic factors, living environment, and kitchen fumes. Conclusion: People over 60 years of age were prone to early lung cancer, followed by individuals aged 30–39 years. It is important to identify the risk factors of lung cancer to strengthen the screening of high-risk groups for early detection and treatment.

Effect of Different Induction Immunosuppression on the Incidence of Infectious Complications after Kidney Transplantation-Single Center Study.

Background/Objectives: Potent immunosuppression lowers the incidence of acute graft rejection but increases the risk of infections. In order to decrease either infectious complications or acute rejection, it is necessary to identify risk groups of patients profiting from personalized induction immunosuppressive treatment. The aim of our analysis was to find whether there were higher incidences of infectious complications after kidney transplantation (KT) in groups with different induction immunosuppressive treatment and also to find independent risk factors for recurrent infections. Materials: We retrospectively evaluated all patients with induction treatment with basiliximab after kidney transplantation from 2014 to 2019 at our center relative to age- and sex-matched controls of patients with thymoglobulin induction immunosuppression. Results: Our study consisted of two groups: basiliximab (39) and thymoglobulin (39). In the thymoglobulin group we observed an increased incidence of recurrent infection in every observed interval; however, acute rejection was seen more often in the basiliximab group. A history of respiratory diseases and thrombocytopenia were identified as independent risk factors for recurrent bacterial infections from the first to sixth month after KT. Decreased eGFR from the first month, infections caused by multi-drug-resistant bacteria, and severe infections (reflected by the need for hospitalization) were identified as independent risk factors for recurrent bacterial infections from the first to the twelfth month after KT. Conclusions: We found that in the group of patients with thymoglobulin induction immunosuppressive treatment, infectious complications occurred significantly more often during the entire monitored period with decreased incidence of acute humoral and cellular rejection occurred more often.

Coronary artery calcification score as a prognostic indicator for COVID-19 mortality: evidence from a retrospective cohort study in Iran

Background: Coronary artery calcification (CAC) has been established as an independent risk factor for major adverse cardiovascular events. Nevertheless, the effect of CAC on in-hospital mortality and adverse clinical outcomes in patients with COVID-19 has yet to be determined. Objective: To investigate the association between CAC score and in-hospital mortality of COVID-19 patients Method: This retrospective cohort study was conducted across tertiary hospitals of University of Medical Sciences in Babol, a northern city in Iran, and enroled 551 confirmed COVID-19 patients with definitive clinical outcomes of death or discharge between March and October 2021. Demographic and clinical data, along with chest computed tomography (CT) findings and CAC score on admission, were systematically collected. The study utilized logistic regression analysis and Kaplan-Meier plots to explore the association between CAC score and in-hospital death and adverse clinical outcomes. Results: The mean age was 60.05±12.8. A significant difference regarding CAC score, age, history of hypertension, hyperlipidemia, cardiovascular diseases, and respiratory diseases among survivors and non-survivors was observed; however, gender was not found to be different. Furthermore, in multivariate analysis, CAC score greater than or equal to 400 [odds ratio (OR): 4.2, 95% CI: 1.70–10.33, P value: 0.002], hospitalization time (OR: 1.31, 95% CI: 1.13–1.53, P value < 0.001), length of ICU stay (OR: 2.02, 95% CI: 1.47–2.77, P value < 0.001), severe or critical COVID-19 severity in time of admission (95% CI: 1.79–18.29, P value: 0.003), and history of respiratory diseases (95% CI: 2.18–40, P value: 0.003) were found to be associated with higher odds of in-hospital mortality. Log-rank test also revealed a significant difference regarding the time of admission to death between patients with CAC score greater than or equal to 400 and those with CAC score less than 400 (P value < 0.001). Conclusion: Elevated CAC score is a crucial risk factor linked to in-hospital mortality and unfavourable clinical results in confirmed COVID-19 patients. This finding emphasizes the need for careful monitoring of individuals with high CAC scores.

Safety of a controlled human infection model of tuberculosis with aerosolised, live-attenuated Mycobacterium bovis BCG versus intradermal BCG in BCG-naive adults in the UK: a dose-escalation, randomised, controlled, phase 1 trial.

Mycobacterium tuberculosis is the main causative agent of tuberculosis. BCG, the only licensed vaccine, provides inadequate protection against pulmonary tuberculosis. Controlled human infection models are useful tools for vaccine development. We aimed to determine a safe dose of aerosol-inhaled live-attenuated Mycobacterium bovis BCG as a surrogate for M tuberculosis infection, then compare the safety and tolerability of infection models established using aerosol-inhaled and intradermally administered BCG. This phase 1 controlled human infection trial was conducted at two clinical research facilities in the UK. Healthy, immunocompetent adults aged 18-50 years, who were both M tuberculosis-naive and BCG-naive and had no history of asthma or other respiratory diseases, were eligible for the trial. Participants were initially enrolled into group 1 (receiving the BCG Danish strain); the trial was subsequently paused because of a worldwide shortage of BCG Danish and, after protocol amendment, was restarted using the BCG Bulgaria strain (group 2). After a dose-escalation study, during which participants were sequentially allocated to receive either 1 × 103, 1 × 104, 1 × 105, 1 × 106, or 1 × 107 colony-forming units (CFU) of aerosol BCG, the maximum tolerated dose was selected for the randomised controlled trial. Participants in this trial were randomly assigned (9:12), by variable block randomisation and using sequentially numbered sealed envelopes, to receive aerosol BCG (1 × 107 CFU) and intradermal saline or intradermal BCG (1 × 106 CFU) and aerosol saline. Participants were masked to treatment allocation until day 14. The primary outcome was to compare the safety of a controlled human infection model based on aerosol-inhaled BCG versus one based on intradermally administered BCG, and the secondary outcome was to evaluate BCG recovery in the airways of participants who received aerosol BCG or skin biopsies of participants who received intradermal BCG. BCG was detected by culture and by PCR. The trial is registered at ClinicalTrials.gov, NCT02709278, and is complete. Participants were assessed for eligibility between April 7, 2016, and Sept 29, 2018. For group 1, 15 participants were screened, of whom 13 were enrolled and ten completed the study; for group 2, 60 were screened and 33 enrolled, all of whom completed the study. Doses up to 1 × 107 CFU aerosol-inhaled BCG were sufficiently well tolerated. No significant difference was observed in the frequency of adverse events between aerosol and intradermal groups (median percentage of solicited adverse events per participant, post-aerosol vs post-intradermal BCG: systemic 7% [IQR 2-11] vs 4% [1-13], p=0·62; respiratory 7% [1-19] vs 4% [1-9], p=0·56). More severe systemic adverse events occurred in the 2 weeks after aerosol BCG (15 [12%] of 122 reported systemic adverse events) than after intradermal BCG (one [1%] of 94; difference 11% [95% CI 5-17]; p=0·0013), but no difference was observed in the severity of respiratory adverse events (two [1%] of 144 vs zero [0%] of 97; 1% [-1 to 3]; p=0·52). All adverse events after aerosol BCG resolved spontaneously. One serious adverse event was reported-a participant in group 2 was admitted to hospital to receive analgesia for a pre-existing ovarian cyst, which was deemed unrelated to BCG infection. On day 14, BCG was cultured from bronchoalveolar lavage samples after aerosol infection and from skin biopsy samples after intradermal infection. This first-in-human aerosol BCG controlled human infection model was sufficiently well tolerated. Further work will evaluate the utility of this model in assessing vaccine efficacy and identifying potential correlates of protection. Bill & Melinda Gates Foundation, Wellcome Trust, National Institute for Health Research Oxford Biomedical Research Centre, Thames Valley Clinical Research Network, and TBVAC2020.

Psychosocial impacts of coughing in public places during the COVID-19 pandemic: a cross-sectional study in the western region of Saudi Arabia

BACKGROUND Dry cough is a prevalent symptom of COVID-19. During the pandemic, people may mistake this cough for symptoms associated with other respiratory diseases. This increases the risk of individuals with a cough being falsely judged as having COVID-19. This study aimed to investigate the impact of coughing in public places on adults’ mental and social well-being during the COVID-19 pandemic and to explore the role of demographic factors in the relationship between coughing and psychosocial life in public places in the western region of Saudi Arabia. METHODS This cross-sectional study was conducted in the western region of Saudi Arabia, targeting healthy adults aged ≥18 years. The participants were randomly selected using a cluster sampling technique. Data were collected through a self-administered validated questionnaire to explore the psychosocial impact of coughing in public places during the COVID-19 pandemic. Additionally, the questionnaire collected demographic information, smoking habits, cough frequency, consumption of cough medications, history of mild respiratory diseases, and family history of chronic respiratory illnesses. The mean and standard deviation were used to calculate continuous variables, and frequency and percentages were used to present categorical variables. We analyzed the relationships between study variables using the analysis of variance test. RESULTS 288 adults participated in the study, with a 67.2% agreement score. 82.0% of the participants avoided people who coughed in public, while 51.8% felt angry and frustrated when someone coughed in public during the pandemic. CONCLUSIONS COVID-19 has changed how people react to coughing in public. Mild coughs can be mistaken for COVID-19, leading to avoidance.

Cohort profile: China undergraduate cohort for environmental health study

The China Undergraduate Cohort (CUC) is an ambispective cohort study with its major purpose to better understand the effects of lifetime environmental exposures on health outcomes. We recruited 5322 college students with an average age of 18.3 ± 0.7 years in China from August 23, 2019 to October 28, 2019. Follow-up surveys were conducted annually. The dataset comprises individual demographic data (e.g. age, sex, height, weight, birth date, race, home address, annual family income, contact information), health-related behavior data (smoking status, smoking cessation, passive smoking exposure, drinking habit, physical activity, dietary status), lifestyle data (physical exercise, dietary habit, length of time spent outdoors), disease history (respiratory disease history, cardiovascular disease history, urinary system disease history, etc.), mental health status data (sleep quality, self-reported stress, anxiety and depression symptoms), lung function and blood samples data. Preliminary results from our cohort have found the association between air pollution, summer heat and mercury exposure and lung function among young adults in China.

Proportions and risk factors of chronic obstructive pulmonary disease and preserved ratio impaired spirometry, and association with small airway disease, in the positive screening older population from China: a cross-sectional study

BackgroundEarly diagnosing Chronic Obstructive Pulmonary Disease (COPD) is relatively difficult. Therefore, the concepts of preserved ratio impaired spirometry (PRISm) and small airway disease (SAD) were proposed to achieve early diagnosis for COPD. Besides, the occurrence of COPD is positively related to age. However, the relationship among COPD, PRISm, and SAD still requires clarification. Thus, we estimated the proportions and risk factors of COPD and PRISm in the positive screening participants, and searched the methods of early diagnosing COPD via the SAD indicators.MethodsA total of 53,641 residents aged more than 60 years old from Shaoxing City, Zhejiang Province, China, completed a series of screening projects. And 2327 of positive screening participants ultimately finished bronchodilator tests. The data were statistically analyzed to figure out the proportions and risk factors of COPD and PRISm, and the efficacy of early diagnosing COPD by the SAD indicators.ResultsTotally 2229 positive screening participants were included, the proportion of PRISm was 6.3% (141/2229), and of COPD was 78.2% (1743/2229). Statistical analyses showed that COPD patients were more likely to be smokers, males, and older. And COPD patients had higher questionnaire scores, meaning that they were more prone to have family history of respiratory diseases and more severe respiratory symptoms. Additionally, COPD patients had lower maximal mid-expiratory flow (MMEF) pred, forced expiratory flow (FEF) 75pred, and FEF50pred. And we found that male sex and presence of respiratory symptoms might lead to COPD and PRISm. Also, the methods of early diagnosing COPD through the SAD indicators might be acceptable.ConclusionThere is a close association between COPD and decreased small airway function (SAF) among the participants included. Age, smoking, male sex, worse SAF, and respiratory symptoms might cause the progressing from normal people to PRISm, then to COPD patients. Besides, the SAD indicators such as MMEFpred, FEF75pred, and FEF50pred were included in lung function tests and bronchodilator tests. Intriguingly, it was found that early diagnosing COPD via the SAD indicators might be feasible. In the future, early diagnosis for COPD requires further research.

Artificial Intelligence Applied to Forced Spirometry in Primary Care

IntroductionThis study aims to create an artificial intelligence (AI) based machine learning (ML) model capable of predicting a spirometric obstructive pattern using variables with the highest predictive power derived from an active case-finding program for COPD in primary care. Material and methodsA total of 1190 smokers, aged 30–80 years old with no prior history of respiratory disease, underwent spirometry with bronchodilation. The sample was analyzed using AI tools. Based on an exploratory data analysis (EDA), independent variables (according to mutual information analysis) were trained using a gradient boosting algorithm (GBT) and validated through cross-validation. ResultsWith an area under the curve close to unity, the model predicted a spirometric obstructive pattern using variables with the highest predictive power: FEV1_theoretical_pre values. Sensitivity: 93%. Positive predictive value: 94%. Specificity: 97%. Negative predictive value: 96%. Accuracy: 95%. Precision: 94%. ConclusionAn ML model can predict the presence of an obstructive pattern in spirometry in a primary care smoking population with no prior diagnosis of respiratory disease using the FEV1_theoretical_pre values with an accuracy and precision exceeding 90%. Further studies including clinical data and strategies for integrating AI into clinical workflow are needed.

Associations between long-term ozone exposure and small airways function in Chinese young adults: a longitudinal cohort study

BackgroundIncreasing evidence is appearing that ozone has adverse effects on health. However, the association between long-term ozone exposure and lung function is still inconclusive.ObjectivesTo investigate the associations between long-term exposure to ozone and lung function in Chinese young adults.MethodsWe conducted a prospective cohort study among 1594 college students with a mean age of 19.2 years at baseline in Shandong, China from September 2020 to September 2021. Lung function indicators were measured in September 2020 and September 2021, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flow at the 25th, 50th, and 75th percentile of the FVC (FEF25, FEF50, and FEF75) and mean flow rate between 25% and 75% of the FVC (FEF25-75) were measured. Daily 10 km×10 km ozone concentrations come from a well-validated data-fusion approach. The time-weighted average concentrations in 12 months before the lung function test were defined as the long-term ozone exposure. The associations between long-term ozone exposure and lung function indicators in Chinese young adults were investigated using a linear mixed effects model, followed by stratified analyses regarding sex, BMI and history of respiratory diseases.ResultsEach interquartile range (IQR) (8.9 µg/m3) increase in long-term ozone exposure were associated with a -204.3 (95% confidence interval (CI): -361.6, -47.0) ml/s, -146.3 (95% CI: -264.1, -28.4) ml/s, and − 132.8 (95% CI: -239.2, -26.4) ml/s change in FEF25, FEF50, and FEF25-75, respectively. Stronger adverse associations were found in female participants or those with BMI ≥ 24 kg/m2 and history of respiratory diseases.ConclusionLong-term exposure to ambient ozone is associated with impaired small airway indicators in Chinese young adults. Females, participants with BMI ≥ 24 kg/m2 and a history of respiratory disease have stronger associations.

The ratio of immunocompetent cells, immunoglobulins and cytokines in individuals with a comorbid background after COVID-19 in the Arctic region

BACKGROUND: The level of resistance to the effects of the environmental factors among people living in the North is significantly reduced due to slower development of the immune system in children and a lower reserve capabilities of immune reactions among adults. This is important in the context of a new coronavirus infection. Respiratory diseases are the main causes of morbidity among the residents of the North. Little is known about the state of immune homeostasis after COVID-19 among residents of the Arctic with a history of chronic respiratory diseases.
 AIM: To identify concentrations of immunocompetent cells, immunoglobulins, and cytokines after COVID-19 in individuals with a comorbid background.
 MATERIAL AND METHODS: In total, 45 residents of Arkhangelsk including 25 women and 20 men, aged 18–40 with a history of laboratory confirmed COVID-19 (U07.1) of mild or moderate severity comprised the sample. All the study participants had a history of concomitant chronic bronchitis.
 RESULTS: In women, high values of cellular immunological parameters CD8+ and CD95+, as well as immunoglobulins IgM, IgG, IgE were associated with elevated values of cytokine IL-1β in 17–45% of cases, depending on the indicator (all p 0.01). Only in 10% of cases we observed increased content of IL-10 and TNF-α. In men, high concentrations of CD8+ and CD95+ cells were associated with increased levels of IgA (5%), IgM, IgG, IgE (13–25%). Seventeen percent of cases had high levels of IL-10 and 15% had high concentrations of TNF-α.
 CONCLUSIONS: Young residents of the North with a history of chronic bronchitis after Covid-19 of mild or moderate severity have high concentrations of CD8+ and CD95+ cells, IgM, IgG, IgE, IL-10 and TNF-α c low concentrations combined with CD10+ and IL-4 cells.

Intra-breath changes in respiratory mechanics are sensitive to history of respiratory illness in preschool children: the SEPAGES cohort

BackgroundIntra-breath oscillometry has been proposed as a sensitive means of detecting airway obstruction in young children. We aimed to assess the impact of early life wheezing and lower respiratory tract illness on lung function, using both standard and intra-breath oscillometry in 3 year old children.MethodsHistory of doctor-diagnosed asthma, wheezing, bronchiolitis and bronchitis and hospitalisation for respiratory problems were assessed by questionnaires in 384 population-based children. Association of respiratory history with standard and intra-breath oscillometry parameters, including resistance at 7 Hz (R7), frequency-dependence of resistance (R7 − 19), reactance at 7 Hz (X7), area of the reactance curve (AX), end-inspiratory and end-expiratory R (ReI, ReE) and X (XeI, XeE), and volume-dependence of resistance (ΔR = ReE-ReI) was estimated by linear regression adjusted on confounders.ResultsAmong the 320 children who accepted the oscillometry test, 281 (88%) performed 3 technically acceptable and reproducible standard oscillometry measurements and 251 children also performed one intra-breath oscillometry measurement. Asthma was associated with higher ReI, ReE, ΔR and R7 and wheezing was associated with higher ΔR. Bronchiolitis was associated with higher R7 and AX and lower XeI and bronchitis with higher ReI. No statistically significant association was observed for hospitalisation.ConclusionsOur findings confirm the good success rate of oscillometry in 3-year-old children and indicate an association between a history of early-life wheezing and lower respiratory tract illness and lower lung function as assessed by both standard and intra-breath oscillometry. Our study supports the relevance of using intra-breath oscillometry parameters as sensitive outcome measures in preschool children in epidemiological cohorts.

Therapeutic mitigation of measles-like immune amnesia and exacerbated disease after prior respiratory virus infections in ferrets

Measles cases have surged pre-COVID-19 and the pandemic has aggravated the problem. Most measles-associated morbidity and mortality arises from destruction of pre-existing immune memory by measles virus (MeV), a paramyxovirus of the morbillivirus genus. Therapeutic measles vaccination lacks efficacy, but little is known about preserving immune memory through antivirals and the effect of respiratory disease history on measles severity. We use a canine distemper virus (CDV)-ferret model as surrogate for measles and employ an orally efficacious paramyxovirus polymerase inhibitor to address these questions. A receptor tropism-intact recombinant CDV with low lethality reveals an 8-day advantage of antiviral treatment versus therapeutic vaccination in maintaining immune memory. Infection of female ferrets with influenza A virus (IAV) A/CA/07/2009 (H1N1) or respiratory syncytial virus (RSV) four weeks pre-CDV causes fatal hemorrhagic pneumonia with lung onslaught by commensal bacteria. RNAseq identifies CDV-induced overexpression of trefoil factor (TFF) peptides in the respiratory tract, which is absent in animals pre-infected with IAV. Severe outcomes of consecutive IAV/CDV infections are mitigated by oral antivirals even when initiated late. These findings validate the morbillivirus immune amnesia hypothesis, define measles treatment paradigms, and identify priming of the TFF axis through prior respiratory infections as risk factor for exacerbated morbillivirus disease.

Farm animal exposure, respiratory illnesses, and nasal cell gene expression

BackgroundFarm exposures in early life reduce the risks for childhood allergic diseases and asthma. There is less information about how farm exposures relate to respiratory illnesses and mucosal immune development. ObjectiveWe hypothesized that children raised in farm environments have a lower incidence of respiratory illnesses over the first two years of life than non-farm children. We also analyzed whether farm exposures or respiratory illnesses were related to patterns of nasal cell gene expression. MethodsThe Wisconsin Infant Study Cohort included farm (n=156) and non-farm (n=155) families with children followed to age 2 years. Parents reported prenatal farm and other environmental exposures. Illness frequency and severity were assessed using illness diaries and periodic surveys. Nasopharyngeal cell gene expression in a subset of 64 children at age two years was compared to farm exposure and respiratory illness history. ResultsFarm vs. non-farm children had nominally lower rates of respiratory illnesses (rate ratio 0.82 [0.69,0.97]) with a stepwise reduction in illness rates in children exposed to 0, 1, or ≥2 animal species, but these trends were non-significant in a multivariable model. Farm exposures and preceding respiratory illnesses were positively related to nasal cell gene signatures for mononuclear cells and innate and antimicrobial responses. ConclusionsMaternal and infant exposure to farms and farm animals was associated with nonsignificant trends for reduced respiratory illnesses. Nasal cell gene expression in a subset of children suggests that farm exposures and respiratory illnesses in early life are associated with distinct patterns of mucosal immune expression.

Effect of three modalities on emergence agitation among post-traumatic stress disorder patients undergoing laparoscopy: a randomized controlled study

Background and aimEmergence agitation (EA) after general anesthesia is common in patients with post-traumatic stress disorder (PTSD). Due to the recent worldwide events such as the Covid-19 pandemic and wars, PTSD is not rare. Accordingly, a reliable, cost-effective anesthetic protocol to lower the incidence of EA is crucial. Therefore, we aimed to compare three different interventions for avoiding EA in PTSD patients undergoing gynecological laparoscopic surgery. Participants were divided into four groups: 1: performing pre-operative relaxation techniques (deep breathing exercise and progressive muscle relaxation [PMR]); 2: administrating intra-operative Ketamine; 3: applying both previously mentioned strategies and 4 as controls.MethodsThis study was carried out on 144 adult women scheduled for gynecological laparoscopy, randomly allocated into four groups: three intervention groups and a control group (36 each). Women aged 18-45 years old, with a diagnosis of PTSD were included in the study. Patients with a positive history of major neurological, cardiovascular, metabolic, respiratory, or renal disease were excluded. Any patient who reported the use of psychiatric drugs were also excluded from the study. Data was analyzed using IBM SPSS Statistics software version 26. Kolmogorov- Smirnov was used to verify the normality of the distribution of variables. Odds ratio was calculated to clarify the strength and direction of the association between intervention groups and control. Data was deemed significant at a p-value ≤0.05.ResultsHeart rate (HR) and Mean Arterial Blood Pressure (MABP) intra-operative and post-operative till 24 hours were significantly lower in groups 1, 2, and 3 compared to group 4 (p<0.001). There was a significant statistical difference in the intraoperative HR percentage decrease. MABP percentage decrease post-operative was higher in all the intervention groups with no statistically significant difference, except for group 1 compared to group 4, which was statistically significant (12.28 ± 11.77 and 6.10 ± 7.24, p=0.025). Visual Analogue Scale measurements were significantly less in the intervention groups 1, 2, and 3 compared to group 4. On Riker sedation–agitation scores, group 1 was 85 times more likely to be non-agitated (85 (15.938 – 453.307), p<0.001), group 2 was 175 times more likely to be non-agitated (175 (19.932–1536.448), p<0.001) and group 3 was protected against agitation.ConclusionPre-operative relaxation techniques (breathing exercises and PMR) significantly lowered HR, MABP, VAS score, and EA than controls. These effects were not significantly different from intra-operative ketamine injection or the combination of both (relaxation techniques and ketamine). We recommend routine pre-operative screening for PTSD and the application of relaxation techniques (breathing exercises and PMR) in the pre-operative preparation protocol of PTSD-positive cases as well as routine practical application of preoperative relaxation techniques. Further studies on using pre-operative relaxation techniques in general could be cost-effective.

Analysis of a Cohort of 165 Pediatric Patients with Human Bocavirus Infection and Comparison between Mono-Infection and Respiratory Co-Infections: A Retrospective Study.

Human Bocavirus (HBoV) is mainly associated with respiratory tract infections. However, its role as respiratory pathogen is not fully understood for a high co-infection rate in symptomatic patients and a significant HBoV detection rate in asymptomatic subjects. This study aimed to describe a large cohort of children with HBoV infection and to compare HBoV mono-infection and co-infections. We retrospectively reviewed data from 165 children admitted to Meyer Children's Hospital IRCCS from March 2022 to March 2023 with the diagnosis of HBoV infection, detected using Reverse Transcription qPCR from nasal swabs. Thereafter, we compared patients with HBoV mono-infection (Group A) and those with HBoV co-infections (Group B) in terms of disease severity, established by the length of stay (LOS), the requirement of Pediatric Intensive Care Unit (PICU), and advanced respiratory support (ARS). The median age was 1.5 years; 80% of patients presented with respiratory symptoms. The discharge rate from the emergency department (ED) within 24 h was 42.4%. Most cases (57.6%) were hospitalized, and 7.3% were admitted to PICU due to respiratory failure. Group A comprised 69 patients, and Group B 96 children (95% viral co-infections, 2% bacterial, 3% viral and bacterial). Group A and Group B were similar in hospitalization rate but differed significantly in LOS (median 3 vs. 5 days) and requirement of PICU admission (0 vs. 12 patients, p < 0.001). Patients with a respiratory disease history (17.5%) showed significantly longer LOS and more necessity of inhaled bronchodilator therapy. HBoV should be considered a relevant respiratory pathogen especially in viral co-infections. Patients with HBoV co-infections have a higher risk of necessitating advanced respiratory support with more PICU admission and longer LOS; a previous respiratory disease puts them at a higher risk of longer hospitalization.

Клинико-анамнестические факторы риска развития преэклампсии как осложнения гестационного сахарного диабета

Aim. To identify the clinical and anamnestic risk factors of preeclampsia (PE) in gestational diabetes mellitus (GDM). Design. Open-label observational prospective study. Materials and methods. The study enrolled 204 pregnant women with GDM, 70 of which had their pregnancy complicated with PE (study group) and 134 patients did not have PE (controls). In the study group, clinical and anamnestic risk factors were searched for by tracing data from primary medical records. The age of participants was 21 to 46 years old. Extragenital conditions were studied as possible risk factors of PE in GDM. Results. It has been established that GDM with PE was more likely to be associated with chronic arterial hypertension (CAH) (χ2 = 7.72, р = 0.006, odds ratio (OR) = 8.52, 95% confidence interval (CI): 1.76–41.29); a history of respiratory diseases — severe sore throat (χ2 = 6.2, р = 0.01, OR = 3.98, 95% CI: 1.40–11.27), chronic tonsillitis (χ2 = 12.84, р &lt; 0.001, OR = 4.81, 95% CI: 2.03–11.40), acute bronchitis (χ2 = 6.0, р = 0.02, OR = 7.33, 95% CI: 1.48–36.32) than GDM without PE. Conclusion. Clinical and anamnestic risk factors of PE in women with GDM are CAH, a history of respiratory diseases (acute bronchitis, severe sore throat, chronic tonsillitis). Keywords: gestational diabetes mellitus, preeclampsia, risk factors.

COPD in Never-Smokers: BOLD Australia Study.

Tobacco smoking is the major risk factor for COPD, and it is common for other risk factors in never-smokers to be overlooked. We examined the prevalence of COPD among never-smokers in Australia and identified associated risk factors. We used data from the Australia Burden of Obstructive Lung Disease (BOLD) study, a cross-section of people aged ≥40 years from six sites. Participants completed interviews and post-bronchodilator spirometry. COPD was primarily defined as an FEV1/FVC ratio <0.70 and secondarily as the ratio less than the lower limit of normal (LLN). The prevalence of COPD in the 1656 never-smokers who completed the study was 10.5% (95% CI: 9.1-12.1%) [ratio<LLN 4.6%]. The likelihood of having COPD increased with advancing age [odds ratio (OR) 4.11 in those 60-69 years and OR 8.73 in those 70 years and older], having attained up to 12 years of education (OR 1.75) compared to those with more than 12 years, having a history of asthma (OR 2.30), childhood hospitalization due to breathing problems before age 10 years (OR 2.50), or having a family history of respiratory diseases (OR 2.70). Being overweight or obese was associated with reduced prevalence of COPD compared with being normal weight. In males and females, advanced age, a history of asthma, and childhood breathing problems before age 10 were factors that elevated the likelihood of COPD. However, in males, additional factors such as a higher body mass index and a family history of respiratory diseases also contributed to increased odds of COPD. COPD was prevalent in this population of never-smokers aged 40 years and over. This finding highlights the significance of risk factors other than smoking in the development of COPD.

Pulmonary hypertension within individuals suffering from chronic obstructive pulmonary disease.

Objective: To establish the frequency in regards to pulmonary hypertension within individuals suffering from chronic obstructive pulmonary disease. Study Design: Cross-sectional study. Setting: Pulmonology Division of Jinnah Hospital Lahore. Period: January, 2023 to April, 2023. Material &amp; Methods: A total of 200 patients of both male and female patients with age from 40 to 70 years having chronic obstructive pulmonary disease were included by nonprobability consecutive sampling. Patients with history of other respiratory disease like interstitial lung disease, bronchiectasis, allergic broncho-pulmonary aspergillosis (ABPA), sarcoidosis, occupational lung diseases, asthma, ischemic heart disease, pulmonary hypertension, collagen vascular disease were factored out of the study. Cardiac echocardiography was performed in all the patients and pulmonary hypertension as assessed. Results: In this study, 87 (43.5%) were between 40-55 years of age while 113 (56.5%) were within the ages of 56-70, and thus the mean age was 57.28±8.44 years. 131 (65.5%) patients were male and 69 (34.5%) were females. 49 (24.5%), 103 (51.5%) and 48 (24%) patients had mild, moderate and severe COPD respectively. Pulmonary hypertension was found in 105 (52.5%) patients. Pulmonary hypertension is more prevalent in severe cases of COPD than mild and moderate patients with p-value = 0.0001. Conclusion: Patients with chronic obstructive lung disease have a high prevalence of pulmonary hypertension. This is shown to be more common within patients suffering from severe cases of COPD.