Biomarkers in bronchiectasis.

Bronchiectasis is a heterogeneous disease with multiple aetiologies and diverse clinical features. There is a general consensus that optimal treatment requires precision medicine approaches focused on specific treatable disease characteristics, known as treatable traits. Identifying subtypes of conditions with distinct underlying biology (endotypes) depends on the identification of biomarkers that are associated with disease features, prognosis or treatment response and which can be applied in clinical practice. Bronchiectasis is a disease characterised by inflammation, infection, structural lung damage and impaired mucociliary clearance. Increasingly there are available methods to measure each of these components of the disease, revealing heterogeneous inflammatory profiles, microbiota, radiology and mucus and epithelial biology in patients with bronchiectasis. Using emerging biomarkers and omics technologies to guide treatment in bronchiectasis is a promising field of research. Here we review the most recent data on biomarkers in bronchiectasis.

Pathophysiology and genomics of bronchiectasis.

Bronchiectasis is a complex and heterogeneous inflammatory chronic respiratory disease with an unknown cause in around 30-40% of patients. The presence of airway infection together with chronic inflammation, airway mucociliary dysfunction and lung damage are key components of the vicious vortex model that better describes its pathophysiology. Although bronchiectasis research has significantly increased over the past years and different endotypes have been identified, there are still major gaps in the understanding of the pathophysiology. Genomic approaches may help to identify new endotypes, as has been shown in other chronic airway diseases, such as COPD.Different studies have started to work in this direction, and significant contributions to the understanding of the microbiome and proteome diversity have been made in bronchiectasis in recent years. However, the systematic application of omics approaches to identify new molecular insights into the pathophysiology of bronchiectasis (endotypes) is still limited compared with other respiratory diseases.Given the complexity and diversity of these technologies, this review describes the key components of the pathophysiology of bronchiectasis and how genomics can be applied to increase our knowledge, including the study of new techniques such as proteomics, metabolomics and epigenomics. Furthermore, we propose that the novel concept of trained innate immunity, which is driven by microbiome exposures leading to epigenetic modifications, can complement our current understanding of the vicious vortex. Finally, we discuss the challenges, opportunities and implications of genomics application in clinical practice for better patient stratification into new therapies.

Bioelectrical impedance and lung function-associations with gender and central obesity: results of the EpiHealth study.

BACKGROUND: Obesity is a major public health concern associated with various health problems, including respiratory impairment. Bioelectrical impedance (BIA) is used in health screening to assess body fat. However, there is no consensus in healthcare on how body fat should be assessed in relation to lung function. In this study, we aimed to investigate how BIA in relation to waist circumference contribute, using data from a large Swedish population study. METHODS: A total of 17,097 participants (aged 45-75 years) were included in the study. The relationships between fat mass, waist circumference, and lung function were analysed using weighted quantile sum regression. RESULTS: Increased fat mass was significantly associated with decreased lung function (FEV1, FVC) in both sexes. Also, the influence of trunk fat and waist circumference on FVC and FEV1 differed by sex: in males, waist circumference and trunk fat had nearly equal importance for FVC (variable weights of 0.42 and 0.41), whereas in females, trunk fat was significantly more important (variable weights 0.84 and 0.14). For FEV1, waist circumference was more important in males, while trunk fat was more significant in females (variable weights male 0.68 and 0.28 and 0.23 and 0.77 in female). CONCLUSIONS: Our results suggest that trunk fat should be considered when assessing the impact of adipose tissue on lung function and should potentially be included in the health controls.

Association between swallowing dynamics, tongue pressure and pulmonary function in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Swallowing is a complex process that requires the coordination of muscles in the mouth, pharynx, larynx, and esophagus. Dysphagia occurs when a person has difficulty swallowing. In the case of subjects with respiratory diseases, the presence of oropharyngeal dysphagia potentially increases lung disease exacerbations, which can lead to a rapid decline in lung function. This study aimed to analyze the swallowing of patients with idiopathic pulmonary fibrosis (IPF). METHODS: Patients with IPF were evaluated using the Eating Assessment Tool (EAT-10), tongue pressure, the Timed Water Swallow Test (TWST), and the Test of Mastication and Swallowing Solids (TOMASS). The findings were related to dyspnea severity assessed by the modified Medical Research Counsil (mMRC) score; the nutritional status screened with Mini Nutritional Assessment (MNA) tool; and pulmonary function tests, specifically spirometry and measurement of the diffusing capacity for carbon monoxide (DLCO), the maximal inspiratory pressure (PImax), and the maximal expiratory pressure (PEmax). RESULTS: The sample consisted of 34 individuals with IPF. Those who exhibited swallowing modifications scored lower on the MNA than those who did not (9.6 ± 0.76 vs. 11.64 ± 0.41 points; mean difference 1.98 ± 0.81 points; p = 0.02). They also showed poorer lung function when considering the predicted force vital capacity (FVC; 81.5% ± 4.61% vs. 61.87% ± 8.48%; mean difference 19.63% ± 9.02%; p = 0.03). The speed of liquid swallowing was altered in 31of 34 of the evaluated subjects (91.1%). The number of liquid swallows correlated significantly with the forced expiratory volume in 1 s (FEV1)/FVC ratio (r = 0.3; p = 0.02). Solid eating and swallowing assessed with the TOMASS score correlated with lung function. The number of chewing cycles correlated negatively with PImax% predicted (r = -0.4; p = 0.0008) and PEmax% predicted (r = -0.3; p = 0.02). FVC% predicted correlated with increased solid swallowing time (r = -0.3; p = 0.02; power = 0.6). Swallowing solids was also impacted by dyspnea. CONCLUSION: Patients with mild-to-moderate IPF can present feeding adaptations, which can be related to the nutritional status, lung function, and the severity of dyspnea.

Effect of flow-optimized pressure control ventilation-volume guaranteed (PCV-VG) on postoperative pulmonary complications: a consort study.

BACKGROUND: Postoperative pulmonary complications (PPCs) after one-lung ventilation (OLV) significantly impact patient prognosis and quality of life. OBJECTIVE: To study the impact of an optimal inspiratory flow rate on PPCs in thoracic surgery patients. METHODS: One hundred eight elective thoracic surgery patients were randomly assigned to 2 groups in this consort study (control group: n = 53 with a fixed inspiratory expiratory ratio of 1:2; and experimental group [flow rate optimization group]: n = 55). Measurements of Ppeak, Pplat, PETCO2, lung dynamic compliance (Cdyn), respiratory rate, and oxygen concentration were obtained at the following specific time points: immediately after intubation (T0); immediately after starting OLV (T1); 30 min after OLV (T2); and 10 min after 2-lung ventilation (T4). The PaO2:FiO2 ratio was measured using blood gas analysis 30 min after initiating one-lung breathing (T2) and immediately when OLV ended (T3). The lung ultrasound score (LUS) was assessed following anesthesia and resuscitation (T5). The occurrence of atelectasis was documented immediately after the surgery. PPCs occurrences were noted 3 days after surgery. RESULTS: The treatment group had a significantly lower total prevalence of PPCs compared to the control group (3.64% vs. 16.98%; P = 0.022). There were no notable variations in peak airway pressure, airway plateau pressure, dynamic lung compliance, PETCO2, respiratory rate, and oxygen concentration between the two groups during intubation (T0). Dynamic lung compliance and the oxygenation index were significantly increased at T1, T2, and T4 (P < 0.05), whereas the CRP level and number of inflammatory cells decreased dramatically (P < 0.05). CONCLUSION: Optimizing inspiratory flow rate and utilizing pressure control ventilation -volume guaranteed (PCV-VG) mode can decrease PPCs and enhance lung dynamic compliance in OLV patients.

Insufficient Pulmonary Rehabilitation Uptake After Severe Exacerbation of COPD: A Multicentre Study in the South West Region of France.

Purpose: Pulmonary rehabilitation (PR) is a type of multidisciplinary care strongly recommended after severe exacerbation of chronic obstructive pulmonary disease (COPD). Recently, a national French study reported a very low rate of PR uptake (8.6%); however, important clinical data were missing. Here, we aimed to identify the main factors associated with insufficient PR uptake after hospitalisation for COPD exacerbation. Patients and Methods: This multicentre retrospective study included patients hospitalised with COPD exacerbation between 1 January 2017 and 31 December 2018, as identified by both coding and a detailed review of medical records. PR was defined as inpatient care in a specialised centre or unit within 90 days of discharge. Multivariate logistic regression was used to identify associations between PR uptake and patient characteristics, such as comorbidities, non-invasive ventilation (NIV), inhaled treatment, and forced expiratory volume in 1 second (FEV1). Results: Among the 325 patients admitted for severe COPD exacerbation, 92 (28.3%) underwent PR within 90 days of discharge. In univariate analysis, relative to those who underwent PR, patients without PR had significantly more comorbidities, were less often treated with triple bronchodilator therapy or NIV, and had a higher FEV1. In multivariate analysis, variables independently associated with the lack of PR uptake were the presence of comorbidities (adjusted odds ratio (aOR) = 1.28 [1.10-1.53], p = 0.003) and a higher FEV1 (aOR = 1.04 [1.02-1.06], p < 0.001). There was no significant correlation between PR uptake and departmental PR centre capacity (notably, some departments had no PR facilities). Conclusion: These data highlight the lack of PR in the early stages of COPD. Collaboration among all healthcare providers involved in patient management is crucial for improved PR uptake.

Pulmonary rehabilitation (PR) is multidisciplinary care strongly recommended after severe exacerbation of chronic obstructive pulmonary disease (COPD); however, referral remains very low in France. We have shown, in three French centres, that early-stage COPD and associated comorbidities are the main factors contributing to insufficient PR after hospitalisation for exacerbation. Collaboration among all healthcare providers involved in patient management is crucial to improve PR uptake in the years ahead because physical medicine and rehabilitation professionals play key roles in the promotion and early initiation of PR programs.

First real-time imaging of bronchoscopic lung volume reduction by electrical impedance tomography.

BACKGROUND: Bronchoscopic lung volume reduction (BLVR) with one-way endobronchial valves (EBV) has better outcomes when the target lobe has poor collateral ventilation, resulting in complete lobe atelectasis. High-inspired oxygen fraction (FIO2) promotes atelectasis through faster gas absorption after airway occlusion, but its application during BLVR with EBV has been poorly understood. We aimed to investigate the real-time effects of FIO2 on regional lung volumes and regional ventilation/perfusion by electrical impedance tomography (EIT) during BLVR with EBV. METHODS: Six piglets were submitted to left lower lobe occlusion by a balloon-catheter and EBV valves with FIO2 0.5 and 1.0. Regional end-expiratory lung impedances (EELI) and regional ventilation/perfusion were monitored. Local pocket pressure measurements were obtained (balloon occlusion method). One animal underwent simultaneous acquisitions of computed tomography (CT) and EIT. Regions-of-interest (ROIs) were right and left hemithoraces. RESULTS: Following balloon occlusion, a steep decrease in left ROI-EELI with FIO2 1.0 occurred, 3-fold greater than with 0.5 (p < 0.001). Higher FIO2 also enhanced the final volume reduction (ROI-EELI) achieved by each valve (p < 0.01). CT analysis confirmed the denser atelectasis and greater volume reduction achieved by higher FIO2 (1.0) during balloon occlusion or during valve placement. CT and pocket pressure data agreed well with EIT findings, indicating greater strain redistribution with higher FIO2. CONCLUSIONS: EIT demonstrated in real-time a faster and more complete volume reduction in the occluded lung regions under high FIO2 (1.0), as compared to 0.5. Immediate changes in the ventilation and perfusion of ipsilateral non-target lung regions were also detected, providing better estimates of the full impact of each valve in place. TRIAL REGISTRATION: Not applicable.

Gut-derived immune cells and the gut-lung axis in ARDS.

The gut serves as a vital immunological organ orchestrating immune responses and influencing distant mucosal sites, notably the respiratory mucosa. It is increasingly recognized as a central driver of critical illnesses, with intestinal hyperpermeability facilitating bacterial translocation, systemic inflammation, and organ damage. The "gut-lung" axis emerges as a pivotal pathway, where gut-derived injurious factors trigger acute lung injury (ALI) through the systemic circulation. Direct and indirect effects of gut microbiota significantly impact immune responses. Dysbiosis, particularly intestinal dysbiosis, termed as an imbalance of microbial species and a reduction in microbial diversity within certain bodily microbiomes, influences adaptive immune responses, including differentiating T regulatory cells (Tregs) and T helper 17 (Th17) cells, which are critical in various lung inflammatory conditions. Additionally, gut and bone marrow immune cells impact pulmonary immune activity, underscoring the complex gut-lung interplay. Moreover, lung microbiota alterations are implicated in diverse gut pathologies, affecting local and systemic immune landscapes. Notably, lung dysbiosis can reciprocally influence gut microbiota composition, indicating bidirectional gut-lung communication. In this review, we investigate the pathophysiology of ALI/acute respiratory distress syndrome (ARDS), elucidating the role of immune cells in the gut-lung axis based on recent experimental and clinical research. This exploration aims to enhance understanding of ALI/ARDS pathogenesis and to underscore the significance of gut-lung interactions in respiratory diseases.

Risk Factors of Sarcopenia in COPD Patients: A Meta-Analysis.

Objective: Sarcopenia is a common complication of COPD associated with an age-related reduction in skeletal muscle mass associated with decreased muscle strength and / or reduced mobility. The incidence of sarcopenia in patients with COPD is twice that of non-COPD patients and is associated with poor prognosis, this study aimed to investigate the influencing factors of sarcopenia in COPD patients. Methods: Selected studies from PubMed, Embase, Web of Science, Cochrane Library, Wanfang, Wanfang, CNKI, CBM, and Wanfang databases as of November 12023. Patients aged 18 were selected; data were then independently extracted by two reviewers using a standard data collection form. Results: In total, 17 articles reporting on 5408 patients were included. Age (OR = 1.083; 95% CI, 1.024-1.145), ALB (OR = 0.752; 95% CI, 0.724-0.780), BMI(OR = 0.701; 95% CI, 0.586-0.838), smoking (OR = 1.859; 95% CI, 1.037-3.334), diabetes (OR = 1.361; 95% CI, 1.095-1.692), qi deficiency (OR = 9.883; 95% CI, 2.052, 47.593), GOLD C (OR =2.232; 95% CI, 1.866, 2.670) and GOLD D (OR = 2.195; 95% CI, 1.826-2.637) were factors affecting muscle loss in COPD patients. Conclusion: Sarcopenia is more prevalent in patients with COPD. Age, body mass index, smoking, diabetes mellitus, qi deficiency, ALB, and GOLD grade were the contributing factors for sarcopenia in patients with chronic obstructive pulmonary disease. In the future, medical staff should not only pay attention to the early screening of sarcopenia in high-risk groups, but also provide relevant prevention information.

The relationship between lung function, exercise capacity, oxidant and antioxidant response in primary ciliary dyskinesia and cystic fibrosis.

BACKGROUND: There is a need to identify the complex interplay between various physiological mechanisms in primary ciliary dyskinesia (PCD) and cystic fibrosis (CF). The study investigated the interaction between respiratory function, exercise capacity, muscle strength, and inflammatory and oxidant/antioxidant responses in patients with PCD and CF. METHODS: The study included 30 PCD patients, 30 CF patients, and 29 age and sex-matched healthy subjects. Exercise capacity was assessed using the modified shuttle walk test (MSWT). Handgrip strength (HGS) was used to evaluate general muscle strength. Oxidative stress-inflammatory parameters were also assessed. Pulmonary function test was performed by spirometry. Regarding the forced expiratory volume in 1 second (FEV1) z-score, patients with PCD and CF were subdivided into normal, mild, and severe/moderate groups. RESULTS: Forced vital capacity (FVC) z-scores were lower in PCD and CF patients than controls. FEV1, FEV1/FVC, peak expiratory flow (PEF), and forced mid expiratory flow (FEF25-75%) z-scores were lower in PCD than in the other groups. HGS was lower in both mild PCD and normal CF patients relative to the controls. MSWT distance was lower in severe/moderate PCD patients than controls. Catalase (CAT), glutathione S-transferase (GST), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels did not differ significantly among the study groups, but superoxide dismutase (SOD) level in severe/moderate PCD, and glutathione (GSH) level in normal CF were higher than in controls. Interleukin-6 (IL-6) level was higher in patients with normal PCD and CF compared to the controls. IL-1ß level was higher in PCD compared to controls. Additionally, correlations among these parameters were also determined in some patient groups. CONCLUSION: Homeostasis related to respiratory function, aerobic performance, muscle strength, inflammatory response, and oxidant/antioxidant balance were affected in PCD and CF. Evaluating these mechanisms together may contribute to elucidating the pathophysiology of these rare diseases.

The predictive role of lung clearance index on FEV1 decline in cystic fibrosis.

BACKGROUND: The lung clearance index (LCI) is a sensitive lung function index that is used to detect early lung disease changes in children with cystic fibrosis (CF). This study aimed to define the predictive role of baseline LCI, along with other potential factors on the change in forced expiratory volume in one second (FEV1) during one-year follow-up in CF patients who had a percent predicted (pp) FEV1≥80. METHODS: LCI was concurrently performed on 57 CF patients who had ppFEV1 ≥80 at month zero. The ppFEV1 decline was evaluated prospectively during the one year follow up. The primary outcome of ppFEV1 decline in the study group in one year was dichotomized according to the median value for the decline in ppFEV1, which was 3.7. The LCI value predicting ppFEV1 decline at the end of one year was calculated with receiver operating characteristic curve analysis. Regression analysis was performed. Furthermore, a decision tree was constructed using classification and regression tree methods to better define the potential effect of confounders on the ppFEV1 decline. RESULTS: The LCI value for predicting ppFEV1 decline >3.7% at the end of one year was 8.2 (area under the curve: 0.80) Multivariable regression analysis showed that the absence of the F508del mutation in at least one allele, LCI >8.2 and initial FEV1 z-score were predictors of a ppFEV1 decline >3.7 (p<0.001). Factors altering ppFEV1 decline>3.7% at the end of one-year evaluated by decision trees were as follows: initial FEV1 z-score, type of CFTR mutation, LCI value and initial weight-for-age z-score. CONCLUSIONS: LCI is sensitive for predicting ppFEV1 decline in patients with ppFEV1 ≥80 along with the initial FEV1-z-score and type of CFTR mutation.

Post-discharge spirometry evaluation in patients recovering from moderate-to-critical COVID-19: a cross-sectional study.

Understanding the prevalence of abnormal lung function and its associated factors among patients recovering from COVID-19 is crucial for enhancing post-COVID care strategies. This study primarily aimed to determine the prevalence and types of spirometry abnormalities among post-COVID-19 patients in Malaysia, with a secondary objective of identifying its associated factors. Conducted at the COVID-19 Research Clinic, Faculty of Medicine, University Technology MARA, from March 2021 to December 2022, this study included patients at least three months post-discharge from hospitals following moderate-to-critical COVID-19. Of 408 patients studied, abnormal spirometry was found in 46.8%, with 28.4% exhibiting a restrictive pattern, 17.4% showing preserved ratio impaired spirometry (PRISm), and 1.0% displaying an obstructive pattern. Factors independently associated with abnormal spirometry included consolidation on chest X-ray (OR 8.1, 95% CI 1.75-37.42, p = 0.008), underlying cardiovascular disease (OR 3.5, 95% CI 1.19-10.47, p = 0.023), ground-glass opacity on chest X-ray (OR 2.6, 95% CI 1.52-4.30, p < 0.001), and oxygen desaturation during the 6-min walk test (OR 1.9, 95% CI 1.20-3.06, p = 0.007). This study highlights that patients recovering from moderate-to-critical COVID-19 often exhibit abnormal spirometry, notably a restrictive pattern and PRISm. Routine spirometry screening for high-risk patients is recommended.

Hypercapnia and lung function parameters in chronic obstructive pulmonary disease.

BACKGROUND: In advanced chronic obstructive pulmonary disease (COPD), hypercapnia may occur due to severe bronchial obstruction with lung hyperinflation. Non-invasive ventilation (NIV) provides the standard of care intended to achieve physiological PCO2 levels, thereby reducing overall mortality. The present study aimed to evaluate pulmonary function parameters derived from spirometry (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1]), body plethysmography (residual volume [RV], total lung capacity [TLC]), and lung diffusion capacity for carbon monoxide (single-breath method [DCO-SB], alveolar-volume corrected values [DCO-VA]) as predictors of chronic hypercapnia in patients with advanced COPD. METHODS: This monocentric, retrospective observational study included 423 COPD patients. Receiver operating characteristic (ROC) curve analysis and cross-validation were used to assess lung function parameters' diagnostic accuracy for predicting chronic hypercapnia, with the resulting performance expressed as area under the ROC curve (AUROC). We performed univariable and multivariable binary logistic regression analysis to determine if these parameters were independently associated with chronic hypercapnia, with probabilities reported as odds ratios [OR] with 95% confidence intervals [95%CI]. RESULTS: FVC% (AUROC 0.77 [95%CI 0.72-0.81], P < 0.01) and FEV1% (AURIC 0.75 [95%CI 0.70-0.79], P < 0.01) exhibited reasonable accuracy in the prediction of chronic hypercapnia, whereas lung diffusion capacity performed poorly (AUROC 0.64 [95%CI 0.58-0.71] for DCO-SB%, P < 0.01). FVC% (OR 0.95 [95%CI 0.93-0.97], P < 0.01) and FEV1% (OR 0.97 [95%CI 0.94-0.99], P = 0.029) were the only parameters associated independently with chronic hypercapnia in logistic regression analysis. FVC and FEV1 thresholds that best separated hypercapnic from normocapnic subjects reached 56% and 33% of predicted values. CONCLUSIONS: Routinely collected pulmonary function parameters, particularly FVC% and FEV1%, may predict chronic hypercapnia during COPD progression.

Effect of lung volume preservation during spontaneous breathing trial on successful extubation in patients receiving mechanical ventilation: protocol for a multicenter clinical trial.

BACKGROUND: In standard weaning from mechanical ventilation, a successful spontaneous breathing test (SBT) consisting of 30 min 8 cmH2O pressure-support ventilation (PSV8) without positive end-expiratory pressure (PEEP) is followed by extubation with continuous suctioning; however, these practices might promote derecruitment. Evidence supports the feasibility and safety of extubation without suctioning. Ultrasound can assess lung aeration and respiratory muscles. We hypothesize that weaning aiming to preserve lung volume can yield higher rates of successful extubation. METHODS: This multicenter superiority trial will randomly assign eligible patients to receive either standard weaning [SBT: 30-min PSV8 without PEEP followed by extubation with continuous suctioning] or lung-volume-preservation weaning [SBT: 30-min PSV8 + 5 cmH2O PEEP followed by extubation with positive pressure without suctioning]. We will compare the rates of successful extubation and reintubation, ICU and hospital stays, and ultrasound measurements of the volume of aerated lung (modified lung ultrasound score), diaphragm and intercostal muscle thickness, and thickening fraction before and after successful or failed SBT. Patients will be followed for 90 days after randomization. DISCUSSION: We aim to recruit a large sample of representative patients (N = 1600). Our study cannot elucidate the specific effects of PEEP during SBT and of positive pressure during extubation; the results will show the joint effects derived from the synergy of these two factors. Although universal ultrasound monitoring of lungs, diaphragm, and intercostal muscles throughout weaning is unfeasible, if derecruitment is a major cause of weaning failure, ultrasound may help clinicians decide about extubation in high-risk and borderline patients. TRIAL REGISTRATION: The Research Ethics Committee (CEIm) of the Fundació Unió Catalana d'Hospitals approved the study (CEI 22/67 and 23/26). Registered at ClinicalTrials.gov in August 2023. Identifier: NCT05526053.

Clinical features and associated factors of impaired ventilatory efficiency: findings from the ECOPD study in China.

BACKGROUND: Impaired ventilatory efficiency during exercise is a predictor of mortality in chronic obstructive pulmonary disease. However, little is known about the clinical features and associated factors of impaired ventilatory efficiency in China. METHODS: We conducted a cross-sectional community-based study in China and collected demographic and clinical information, cardiopulmonary exercise testing, spirometry, and CT data. Impaired ventilatory efficiency was defined by a nadir ventilatory equivalent for CO2 production above the upper limit of normal. Multivariable linear and logistic regression models were used to explore the clinical features and associated factors of impaired ventilatory efficiency. RESULTS: The final analyses included 941 subjects, 702 (74.6%) of whom had normal ventilatory efficiency and 239 (25.4%) had impaired ventilatory efficiency. Participants with impaired ventilatory efficiency had more chronic respiratory symptoms, poorer lung function and exercise capacity, and more severe emphysema (natural logarithm transformation of the low-attenuation area of the lung with attenuation values below -950 Hounsfield units, logLAA-950: 0.19±0.65 vs -0.28±0.63, p<0.001) and air trapping (logLAA-856: 1.03±0.65 vs 0.68±0.70, p<0.001) than those with normal ventilatory efficiency. Older age (60-69 years, OR 3.10 (95% CI 1.33 to 7.21), p=0.009 and 70-80 years, OR 6.48 (95% CI 2.56 to 16.43), p<0.001 vs 40-49 years) and smoking (former, OR 3.19 (95% CI 1.29 to 7.86), p=0.012; current, OR 4.27 (95% CI 1.78 to 10.24), p=0.001 vs never) were identified as high risk factors of impaired ventilatory efficiency. CONCLUSIONS: Impaired ventilatory efficiency was associated with poorer respiratory characteristics. Longitudinal studies are warranted to explore the progression of individuals with impaired ventilatory efficiency.

Identification of risk factors for acute exacerbation of idiopathic pulmonary fibrosis based on baseline high-resolution computed tomography: a prospective observational study.

BACKGROUND: This study aimed to investigate risk factors for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) based on baseline high-resolution computed tomography (HRCT). METHODS: This prospective observational study enrolled patients with IPF treated at the General Hospital of Ningxia Medical University between January 2019 and January 2021. HRCT-derived quantitative parameters at baseline were analyzed. RESULTS: A total of 102 patients [92 (90.2%) males with a mean age of 67 years] with IPF were included, with a median follow-up of 32 (24-40.5) months. AE occurred in 30 (29.4%) IPF patients. Multivariable logistic regression analysis identified Doppler transthoracic echocardiography suggestive of pulmonary hypertension (PH) (13.43; 95% CI: 4.18-41.09; P < 0.001), honeycombing (OR 1.08; 95% CI: 1.02-1.14; P = 0.013), and whole lung volume (OR 0.99; 95% CI: 0.99-1.00; P = 0.037) as independent risk factors for AE-IPF. The combination of PH, honeycombing, whole lung volume, and the percentage of predicted forced vital capacity (FVC% pred) showed a high area under the curve from receiver operating characteristic curves of 0.888, with a sensitivity of 90% and specificity of 78%. CONCLUSIONS: This study emphasizes that quantitative CT parameters (honeycombing, whole lung volume) may serve as risk factors for AE-IPF. The combination of honeycombing, whole lung volume, FVC% pred, and PH may aid in predicting AE-IPF.

Modeling lung endothelial dysfunction in sepsis-associated ARDS using a microphysiological system.

Endothelial dysfunction is a critical feature of acute respiratory distress syndrome (ARDS) associated with higher disease severity and worse outcomes. Preclinical in vivo models of sepsis and ARDS have failed to yield useful therapies in humans, perhaps due to interspecies differences in inflammatory responses and heterogeneity of human host responses. Use of microphysiological systems (MPS) to investigate lung endothelial function may shed light on underlying mechanisms and targeted treatments for ARDS. We assessed the response to plasma from critically ill sepsis patients in our lung endothelial MPS through measurement of endothelial permeability, expression of adhesion molecules, and inflammatory cytokine secretion. Sepsis plasma induced areas of endothelial cell (EC) contraction, loss of cellular coverage, and luminal defects. EC barrier function was significantly worse following incubation with sepsis plasma compared to healthy plasma. EC ICAM-1 expression, IL-6 and soluble ICAM-1 secretion increased significantly more after incubation with sepsis plasma compared with healthy plasma. Plasma from sepsis patients who developed ARDS further increased IL-6 and sICAM-1 compared to plasma from sepsis patients without ARDS and healthy plasma. Our results demonstrate the proof of concept that lung endothelial MPS can enable interrogation of specific mechanisms of endothelial dysfunction that promote ARDS in sepsis patients.

Pulmonary function trajectories in COVID-19 survivors with and without pre-existing respiratory disease.

A significant proportion of COVID-19 survivors still experience a reduced diffusion capacity three and twelve months after discharge. We aimed to compare pulmonary function trajectories between hospitalized COVID-19 patients with pre-existing respiratory disease (PRD) and patients without pre-existing respiratory disease (Non-PRD) at three and twelve months after hospital discharge. This single-centre retrospective cohort study included COVID-19 patients admitted to the VieCuri Medical Centre (Venlo, the Netherlands) between February and December 2020 that were invited to the outpatient clinic at three and twelve months after discharge. During this visit, pulmonary function tests were performed and impairments were based on lower limit of normal. Data of 239 patients were analysed (65% male, 66 ± 10 years, and 26% with a history of respiratory disease). Three months after discharge, 49% and 64% of the Non-PRD patients (n = 177) and PRD patients (n = 62) had a low diffusion capacity, respectively. This improved over time in Non-PRD patients (p = 0.003), but not in PRD patients (p = 0.250). A low diffusion capacity was still observed in 34% and 57% of the Non-PRD and PRD group, respectively, twelve months after discharge. Pulmonary function impairments, mainly a reduced diffusion capacity, are observed among hospitalized COVID-19 patients with PRD and Non-PRD, at three and twelve months follow-up. Although diffusion capacity impairments restore over time in Non-PRD patients, poor recovery was observed among PRD patients.

High-resolution Computed Tomography Thorax Volumetric Assessment in Coronavirus Disease 2019 Patients and Correlation with Pulmonary Function Tests.

INTRODUCTION: Years after SARS coronavirus disease 2019 (COVID-19) recovery, residual pulmonary abnormalities may still exist. This brings on the question of whether or not COVID-19 could have comparable late consequences. Structural changes in the lungs after recovery can be better visualized using computed tomography (CT) thorax. Computed Tomography Lung Parenchymal changes during hospitalization by COVID-19 and after 4 months of follow-up to correlate with the volumetric high-resolution computed tomography thorax indices, Pulmonary function tests (PFTs) indices, SpO2, and 6 min Walking Test (6MWT). MATERIALS AND METHODS: This is a Hospital based cross-sectional study, with a follow-up among 100 Patients from 2020 to 2022. Each patient's different CT parameters and HRCT volumetric indices Normal Lung (NL), Normal Lung Percentage (NL%), Whole Lung (WL) were correlated with the PFT indices (Forced expiratory volume in 1s [FEV1], forced vital capacity [FVC], FEV1/FVC), Oxygen Saturation (SpO2) and 6-Minute Walking Test (6MWT). RESULTS: The mean NL (L) and NL% during COVID were significantly lower than the mean values 4 months post-COVID. Architectural distortion, bronchiolar dilatation, interstitial thickening, and parenchymal bands were reduced considerably after 4 months post-COVID, compared to during COVID. PFTs results, such as PFT indices, were not significantly different after 4 months post-COVID, compared to during COVID. SpO2 (%) and 6 MWT (m) were significantly increased. During COVID and post-COVID, the values of NL (L) and NL (%) had a significant positive correlation with PFT indices, SpO2, and 6MWT (m). CONCLUSION: Hence, the different CT indices (NL and NL%) can be used as a surrogate for functional recovery of COVID patients since it correlates with the PFT indices (FEV1 and FEV1/FVC), SpO2, and 6MWT post-COVID.

Résumé Introduction:Des années après la guérison du SRAS Covid-19, des anomalies pulmonaires résiduelles peuvent encore exister. Cela amène à se demander si le Covid-19 pourrait ou non avoir des conséquences tardives comparables. Les changements structurels dans les poumons après la récupération peuvent être mieux visualisés à l'aide de CT-Thorax. Étudier les changements CT post-Covid pendant l'hospitalisation et après quatre mois de suivi de l'infection, et corréler les indices volumétriques du thorax HRCT avec les indices des tests de la fonction pulmonaire (PFT), la SpO2 et le test de marche de 6 min (6MWT).Matériels et méthodes:Il s'agit d'une étude transversale en milieu hospitalier, avec un suivi de 100 patients de 2020 à 2022. Les différents paramètres CT et indices volumétriques HRCT de chaque patient Poumon normal (NL), Pourcentage pulmonaire normal (NL%), Les poumons entiers (WL) étaient corrélés avec les indices PFT (volume expiratoire forcé en 1 s [FEV1], capacité vitale forcée [FVC], FEV1/FVC), saturation en oxygène (SpO2) et test de marche de 6 minutes (6MWT).Résultats:Les moyennes NL (L) et NL% pendant le Covid étaient significativement inférieures aux valeurs moyennes 4 mois post-covid. La distorsion architecturale, la dilatation bronchiolaire, l'épaississement interstitiel et les bandes parenchymateuses ont été considérablement réduits après 4 mois post-covid, par rapport à pendant Covid. Les résultats des tests de la fonction pulmonaire, tels que les indices PFT, n'étaient pas significativement différents après 4 mois post-covid, par rapport à pendant Covid. SpO2 (%) et 6 MWT (m) ont été significativement augmentés. Pendant Covid et post-covid, les valeurs de NL (L) et NL (%) avaient une corrélation positive significative avec les indices PFT, SpO2 et 6 MWT (m).Conclusion:Ainsi, les différents indices CT (NL, NL %) peuvent être utilisés comme substitut de la récupération fonctionnelle des patients Covid car ils sont corrélés aux indices PFT (FEV1, FEV1/FVC), SpO2, 6-MWT post-covid.

Microplastic and plastic pollution: impact on respiratory disease and health.

Throughout their lifecycle, from production to use and upon disposal, plastics release chemicals and particles known as micro- and nanoplastics (MNPs) that can accumulate in the environment. MNPs have been detected in different locations of the human body, including in our lungs. This is likely a consequence of MNP exposure through the air we breathe. Yet, we still lack a comprehensive understanding of the impact that MNP exposure may have on respiratory disease and health. In this review, we have collated the current body of evidence on the implications of MNP inhalation on human lung health from in vitro, in vivo and occupational exposure studies. We focused on interactions between MNP pollution and different specific lung-resident cells and respiratory diseases. We conclude that it is evident that MNPs possess the capacity to affect lung tissue in disease and health. Yet, it remains unclear to which extent this occurs upon exposure to ambient levels of MNPs, emphasising the need for a more comprehensive evaluation of environmental MNP exposure levels in everyday life.