Bullous Parametric Response Map for Functional Localization of COPD

Advanced bronchoscopic lung volume reduction treatment (BLVR) is now a routine care option for treating patients with severe emphysema. Patterns of low attenuation clusters indicating emphysema and functional small airway disease (fSAD) on paired CT, which may provide additional insights to the target selection of the segmental or subsegmental lobe of the treatments, require further investigation. The low attenuation clusters (LACS) were segmented to identify the scalar and spatial distribution of the lung destructions, in terms of 10 fractions scales of low attenuation density (LAD) located in upper lobes and lower lobes. The LACs of functional small airway disease (fSAD) were delineated by applying the technique of parametric response map (PRM) on the co-registered CT image data. Both emphysematous LACs of inspiratory CT and fSAD LACs on expiratory CT were used to derive the coefficients of the predictive model for estimating the airflow limitation. The voxel-wise severity is then predicted using the regional LACs on the co-registered CT to indicate the functional localization, namely, the bullous parametric response map (BPRM). A total of 100 subjects, 88 patients with mild to very severe COPD and 12 control participants with normal lung functions (FEV1/FVC % > 70%), were evaluated. Pearson’s correlations between FEV1/FVC% and LAV%HU-950 of severe emphysema are − 0.55 comparing to − 0.67 and − 0.62 of LAV%HU-856 of air-trapping and LAV%fSAD respectively. Pearson’s correlation between FEV1/FVC% and FEV1/FVC% predicted by the proposed model using LAD% of HU-950 and fSAD on BPRM is 0.82 (p < 0.01). The result of the Bullous Parametric Response Map (BPRM) is capable of identifying the less functional area of the lung, where the BLVR treatment is aimed at removing from a hyperinflated area of emphysematous regions.

Cardiac involvement in cystic fibrosis evaluated using cardiopulmonary magnetic resonance

Cystic fibrosis (CF) transmembrane conductance regulator is expressed in myocardium, but cardiac involvement in CF remains poorly understood. The recent development of a combined cardiopulmonary magnetic resonance imaging technology allows for a simultaneous interrogation of cardiac and pulmonary structure and function. The aim of this study was to investigate myocardial manifestations in adults with CF, both in a stable state and during an acute respiratory exacerbation, and to investigate the relationship between cardiac and pulmonary disease. Healthy adult volunteers (n = 12) and adults with CF (n = 10) were studied using a multiparametric cardiopulmonary magnetic resonance protocol. CF patients were scanned during an acute respiratory exacerbation and re-scanned when stable. Stable CF was associated with left ventricular dilatation and hypertrophy (LVH; left ventricular mass: CF 59 ± 9 g/m2 vs. control 50 ± 8 g/m2; p = 0.028). LVH was predominantly driven by extracellular myocardial matrix expansion (extracellular matrix mass: CF 27.5 ± 3.4 g vs. control 23.6 ± 5.2 g; p = 0.006; extracellular volume [ECV]: CF 27.6 [24.7–29.8]% vs. control 24.8 [22.9–26.0]%; p = 0.030). Acute CF was associated with an acute reduction in left ventricular function (ejection fraction: acute 57 ± 3% vs. stable 61 ± 5%; p = 0.025) and there was a suggestion of myocardial oedema. Myocardial oedema severity was strongly associated with the severity of airflow limitation (r = − 0.726, p = 0.017). Multiparametric cardiopulmonary magnetic resonance technology allows for a simultaneous interrogation of cardiac and pulmonary structure and function. Stable CF is associated with adverse myocardial remodelling, including left ventricular systolic dilatation and hypertrophy, driven by myocardial fibrosis. CF exacerbation is associated with acute myocardial contractile dysfunction. There is also a suggestion of myocardial oedema in the acute period which is related to pulmonary disease severity.

Perilla Leaf Extract (PLE) Attenuates COPD Airway Inflammation via the TLR4/Syk/PKC/NF-κB Pathway In Vivo and In Vitro

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease characterized by persistent airflow limitation but still lacking effective treatments. Perilla frutescens (L.) Britt., an important traditional medicinal plant with excellent antioxidant and anti-inflammatory properties, is widely used for the treatment of respiratory disease in China. However, its protective activity and mechanism against COPD airway inflammation have not been fully studied. Here, the anti-inflammatory effects of the PLE were investigated, and its underlying mechanisms were then elucidated. The presented results suggested a notable effect of the PLE on airway inflammation of COPD, by significantly ameliorating inflammatory cell infiltration in lung tissue, lessening leukocytes (lymphocytes, neutrophils, and macrophages) and inflammatory mediators (interleukin 4 (IL-4), IL-6, IL-17A, interferon γ (IFN-γ), and tumor necrosis factor α (TNF-α)) in the bronchoalveolar lavage fluid (BALF) of cigarette smoke (CS)/lipopolysaccharide (LPS)-induced COPD mice in vivo and inhibiting the production of inflammatory factors (nitric oxide (NO), IL-6, and TNF-α) and intracellular reactive oxygen species (ROS) in LPS-stimulated RAW264.7 cells in vitro. For further extent, PLE treatment significantly suppressed the expression and phosphorylation of TLR4, Syk, PKC, and NF-κB p65 in vivo and their mRNA in vitro. Subsequently, by co-treating with their inhibitors in vitro, its potential mechanism via TLR4/Syk/PKC/NF-κB p65 signals was disclosed. In summary, the obtained results indicated a noteworthy effective activity of the PLE on COPD inflammation, and partly, the TLR4/Syk/PKC/NF-κB p65 axis might be the potential mechanism.

Gastric motility and pulmonary function in children with functional abdominal pain disorders and asthma: A pathophysiological study

Background An association has been shown between functional abdominal pain disorders (FAPDs) and asthma. However, the exact reason for this association is obscured. The main objective of this study is to identify the possible underlying pathophysiological mechanisms for the association between FAPDs and asthma using gastric motility and lung function tests. Methods This was a cross-sectional comparative study that consisted of four study groups. Twenty-four children (age 7–12 years) each were recruited for four study groups; asthma only, FAPDs only, both asthma and FAPDs, and healthy controls. Asthma was diagnosed using the history and bronchodilator reversibility test. The diagnosis of FAPDs was made using Rome IV criteria. All subjects underwent ultrasound assessment of gastric motility and pulmonary function assessment by spirometry, using validated techniques. Results All gastric motility parameters, gastric emptying rate, amplitude of antral contraction, and antral motility index, were significantly impaired in children with FAPDs only, children with asthma only, and children with both asthma & FAPDs, compared to controls (p<0.05). Pulmonary function parameters indicating airway obstruction (FEV1/FVC ratio, peak expiratory flow rate, FEF25-75%) were not impaired in children with FAPDs only compared to controls (p>0.05), but significantly impaired in children with asthma and children with both disorders. Antral motility index correlated with the FEV1/FVC ratio (r = 0.60, p = 0.002) and FEF25%-75% (r = 0.49, p = 0.01) in children with both asthma and FAPDs. Conclusions Gastric motor functions were significantly impaired in children with asthma, children with FAPDs, and children with both disorders. Motility index, measuring overall gastric motor activity, showed a significant positive correlation with lung function parameters that measure airflow limitation. Therefore, these diseases might arise as a result of primary disturbance of smooth muscle activity in the airways and gastrointestinal wall, which could be a possible pathophysiological mechanism for this association between asthma and FAPDs.

Dysregulated Cell Signaling in Pulmonary Emphysema

Pulmonary emphysema is characterized by the destruction of alveolar septa and irreversible airflow limitation. Cigarette smoking is the primary cause of this disease development. It induces oxidative stress and disturbs lung physiology and tissue homeostasis. Alveolar type II (ATII) cells have stem cell potential and can repair the denuded epithelium after injury; however, their dysfunction is evident in emphysema. There is no effective treatment available for this disease. Challenges in this field involve the large complexity of lung pathophysiological processes and gaps in our knowledge on the mechanisms of emphysema progression. It implicates dysregulation of various signaling pathways, including aberrant inflammatory and oxidative responses, defective antioxidant defense system, surfactant dysfunction, altered proteostasis, disrupted circadian rhythms, mitochondrial damage, increased cell senescence, apoptosis, and abnormal proliferation and differentiation. Also, genetic predispositions are involved in this disease development. Here, we comprehensively review studies regarding dysregulated cell signaling, especially in ATII cells, and their contribution to alveolar wall destruction in emphysema. Relevant preclinical and clinical interventions are also described.

Extended Bacteria Culture-Based Clustering Identifies a Phenotype Associating Increased Cough and Enterobacterales in Stable Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by airflow limitation. This chronic respiratory disease represents the third leading cause of death worldwide. Alteration of the airway microbiota has been reported to be associated with exacerbation frequency in COPD, but its role on the symptoms in patients at stable state is still incompletely described. This study aimed to determine whether bacteria isolated in sputum can be associated with the clinical features of COPD patients within stable state. Our study highlights, for the first time, that altered microbiota with Enterobacterales is associated with pejorative clinical symptoms in stable COPD patients. The airway microbiota of 38 patients was analyzed using an extended culture approach and mass spectrometry identification. Cluster analysis by principal coordinate analysis of the bacterial communities showed that the patients could be classified into three distinct clusters in our cohort. The clusters showed no differences in proportions of the phylum, but one of them was associated with a high prevalence of Enterobacterales (71.4% in cluster 1 vs. 0% in cluster 3), loss of microbiota diversity, and higher bacterial load (107 vs. 105 CFU/ml, respectively) and characterized by predominant cough and impact on mental health. These novel findings, supported by further studies, could lead to modifying the processing of COPD sputum in the everyday practice of clinical microbiology laboratories.

The Clinical Utility of Forced Oscillation Technique (FOT) during Hospitalisation in patients with exacerbation of COPD

BackgroundForced Oscillation Technique (FOT) is an innovative tool to measure within-breath reactance at 5 Hz (ΔXrs5Hz) but its feasibility and utility in acute exacerbations of COPD (AECOPD) is understudied.MethodsA prospective observational study was conducted in 82 COPD patients admitted due to AECOPD. FOT indices were measured and the association between these indices and spirometry, peak inspiratory flow rate, blood inflammatory biomarkers and patient-reported outcomes including assessment of dyspnoea, quality of life; anxiety and depression and frailty at admission and discharge were explored.ResultsAll patients were able to perform FOT in both sitting and supine position. The prevalence of expiratory flow limitation (EFL) in the upright position was 39% (32/82) and increased to 50% (41/82) in the supine position. EFL (measured by ΔXrs5Hz) and resistance at 5 Hz (Rrs5Hz) negatively correlated with FEV1; those with EFL had lower FEV1 (0.74±0.30 versus 0.94±0.36 L, p=0.01) and FVC (1.7 ±0.55 versus 2.1 ±0.63 L, p= 0.009) and higher BMI [27 (21–36) versus 23 (19–26) kg/m2, p=0.03] compared to those without EFL. During recovery from AECOPD, changes in EFL was observed in association with improvement in breathlessness.ConclusionFOT was easily used to detect EFL during hospitalisation due to AECOPD. The prevalence of EFL increased when patients moved from a seated to a supine position and EFL was negatively correlated with airflow limitation. Improvements in EFL were associated with a reduction in breathlessness. FOT is of potential clinical value by providing a non-invasive, objective, and effort-independent technique to measure lung function parameters during AECOPD requiring hospital admission.

The annual adult asthma review

Asthma is a chronic inflammatory lung condition characterised by variable respiratory symptoms (wheeze, shortness of breath, cough, and chest tightness) and variable expiratory airflow limitation, usually associated with airway inflammation. It affects 1-in-11 people in the UK and is the cause of over 75 000 hospital admissions per year. Given its prevalence, and the fact that patients are mainly cared for in the community, this article aims to highlight the need for a thorough annual asthma review and what that review entails. When carried out effectively, an asthma review will improve quality of life for those living with the condition, reduce their likelihood of hospital admission and reduce the cost to the NHS as a whole.

Standard spirometry to assess emphysema in patients with chronic obstructive pulmonary disease: the Emphysema Severity Index (ESI)

Background: Chronic obstructive pulmonary disease (COPD) is a generic term identifying a condition characterized by variable changes in peripheral airways and lung parenchyma. Standard spirometry cannot discriminate the relative role of conductive airways inflammatory changes from destructive parenchymal emphysema changes. The aim of this study was to quantify the emphysema component in COPD by a simple parameter (the Emphysema Severity Index - ESI), previously proved to reflect CT-assessed emphysema.Methods: ESI was obtained by fitting the descending limb of MEFV curves by a fully automated procedure providing a 0 to 10 score of emphysema severity. ESI was computed in COPD patients enrolled in the CLIMA Study.Results: the vast majority of ESI values ranged from 0 to 4, compatible with no-to-mild/moderate emphysema component. A limited proportion of patients showed ESI values >4, compatible with severe-to-very severe emphysema. ESI values were greatly dispersed within each GOLD class indicating that GOLD classification cannot discriminate emphysema and conductive airways changes in patients with similar airflow limitation. ESI and diffusing capacity (DLCO) were significantly correlated (p<0.001). However, the great dispersion in their correlation suggests that ESI and DLCO reflect partially different anatomo-functional determinants in COPD.Conclusions: airflow limitation has heterogenous determinants in COPD. Inflammatory and destructive changes may combine in CT densitometric alterations that cannot be detected by standard spirometry. ESI computation from spirometric data helps to define the prevailing pathogenetic mechanism underlying the measured airflow limitation. ESI could be a reliable advancement to select large samples of patients in clinical or epidemiological trials, and to compare different pharmacological treatments.