Quantitative CT analysis in patients with pulmonary emphysema: is lung function influenced by concomitant unspecific pulmonary fibrosis?

Purpose: Quantitative analysis of CT scans has proven to be a reproducible technique, which might help to understand the pathophysiology of chronic obstructive pulmonary disease (COPD) and combined pulmonary fibrosis and emphysema. The aim of this retrospective study was to find out if the lung function of patients with COPD with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages III or IV and pulmonary emphysema is measurably influenced by high attenuation areas as a correlate of concomitant unspecific fibrotic changes of lung parenchyma. Patients and methods: Eighty-eight patients with COPD GOLD stage III or IV underwent CT and pulmonary function tests. Quantitative CT analysis was performed to determine low attenuation volume (LAV) and high attenuation volume (HAV), which are considered to be equivalents of fibrotic (HAV) and emphysematous (LAV) changes of lung parenchyma. Both parameters were determined for the whole lung, as well as peripheral and central lung areas only. Multivariate regression analysis was used to correlate HAV with different parameters of lung function. Results: Unlike LAV, HAV did not show significant correlation with parameters of lung function. Even in patients with a relatively high HAVof more than 10%, in contrast to HAV (p=0.786) only LAV showed a significantly negative correlation with forced expiratory volume in 1 second (r=−0.309, R2=0.096, p=0.003). A severe decrease of DLCO% was associated with both larger HAV (p=0.045) and larger LAV (p=0.001). Residual volume and FVC were not influenced by LAV or HAV. Conclusion: In patients with COPD GOLD stage III-IV, emphysematous changes of lung parenchyma seem to have such a strong influence on lung function, which is a possible effect of concomitant unspecific fibrosis is overwhelmed

Comparison of distinctive models for calculating an interlobar emphysema heterogeneity index in patients prior to endoscopic lung volume reduction

Background: The degree of interlobar emphysema heterogeneity is thought to play an important role in the outcome of endoscopic lung volume reduction (ELVR) therapy of patients with advanced COPD. There are multiple ways one could possibly define interlobar emphysema heterogeneity, and there is no standardized definition. Purpose: The aim of this study was to derive a formula for calculating an interlobar emphysema heterogeneity index (HI) when evaluating a patient for ELVR. Furthermore, an attempt was made to identify a threshold for relevant interlobar emphysema heterogeneity with regard to ELVR. Patients and methods: We retrospectively analyzed 50 patients who had undergone technically successful ELVR with placement of one-way valves at our institution and had received lung function tests and computed tomography scans before and after treatment. Predictive accuracy of the different methods for HI calculation was assessed with receiver-operating characteristic curve analysis, assuming a minimum difference in forced expiratory volume in 1 second of 100 mL to indicate a clinically important change. Results: The HI defined as emphysema score of the targeted lobe (TL) minus emphysema score of the ipsilateral nontargeted lobe disregarding the middle lobe yielded the best predicative accuracy (AUC =0.73, P=0.008). The HI defined as emphysema score of the TL minus emphysema score of the lung without the TL showed a similarly good predictive accuracy (AUC =0.72, P=0.009). Subgroup analysis suggests that the impact of interlobar emphysema heterogeneity is of greater importance in patients with upper lobe predominant emphysema than in patients with lower lobe predominant emphysema. Conclusion: This study reveals the most appropriate ways of calculating an interlobar emphysema heterogeneity with regard to ELVR

α1A-Adrenergic Receptor-Directed Autoimmunity Induces Left Ventricular Damage and Diastolic Dysfunction in Rats

BACKGROUND: Agonistic autoantibodies to the alpha(1)-adrenergic receptor occur in nearly half of patients with refractory hypertension; however, their relevance is uncertain. METHODS/PRINCIPAL FINDINGS: We immunized Lewis rats with the second extracellular-loop peptides of the human alpha(1A)-adrenergic receptor and maintained them for one year. Alpha(1A)-adrenergic antibodies (alpha(1A)-AR-AB) were monitored with a neonatal cardiomyocyte contraction assay by ELISA, and by ERK1/2 phosphorylation in human alpha(1A)-adrenergic receptor transfected Chinese hamster ovary cells. The rats were followed with radiotelemetric blood pressure measurements and echocardiography. At 12 months, the left ventricles of immunized rats had greater wall thickness than control rats. The fractional shortening and dp/dt(max) demonstrated preserved systolic function. A decreased E/A ratio in immunized rats indicated a diastolic dysfunction. Invasive hemodynamics revealed increased left ventricular end-diastolic pressures and decreased dp/dt(min). Mean diameter of cardiomyocytes showed hypertrophy in immunized rats. Long-term blood pressure values and heart rates were not different. Genes encoding sarcomeric proteins, collagens, extracellular matrix proteins, calcium regulating proteins, and proteins of energy metabolism in immunized rat hearts were upregulated, compared to controls. Furthermore, fibrosis was present in immunized hearts, but not in control hearts. A subset of immunized and control rats was infused with angiotensin (Ang) II. The stressor raised blood pressure to a greater degree and led to more cardiac fibrosis in immunized, than in control rats. CONCLUSIONS/SIGNIFICANCE: We show that alpha(1A)-AR-AB cause diastolic dysfunction independent of hypertension, and can increase the sensitivity to Ang II. We suggest that alpha(1A)-AR-AB could contribute to cardiovascular endorgan damage

Protective immune trajectories in early viral containment of non-pneumonic SARS-CoV-2 infection

The antiviral immune response to SARS-CoV-2 infection can limit viral spread and prevent development of pneumonic COVID-19. However, the protective immunological response associated with successful viral containment in the upper airways remains unclear. Here, we combine a multi-omics approach with longitudinal sampling to reveal temporally resolved protective immune signatures in non-pneumonic and ambulatory SARS-CoV-2 infected patients and associate specific immune trajectories with upper airway viral containment. We see a distinct systemic rather than local immune state associated with viral containment, characterized by interferon stimulated gene (ISG) upregulation across circulating immune cell subsets in non-pneumonic SARS-CoV2 infection. We report reduced cytotoxic potential of Natural Killer (NK) and T cells, and an immune-modulatory monocyte phenotype associated with protective immunity in COVID-19. Together, we show protective immune trajectories in SARS-CoV2 infection, which have important implications for patient prognosis and the development of immunomodulatory therapies

Potential Relevance of α1-Adrenergic Receptor Autoantibodies in Refractory Hypertension

-AAB might have a mechanistic role and could represent a therapeutic target. in cardiomyocytes and induce mesentery artery segment contraction.-AAB in hypertensive patients, and the notion of immunity as a possible cause of hypertension

Endobronchial Valve Therapy in Patients with Homogeneous Emphysema: Results from the IMPACT Study

Rationale: Endobronchial valves (EBVs) have been successfully used in patients with severe heterogeneous emphysema to improve lung physiology. Limited available data suggest that EBVs are also effective in homogeneous emphysema. Objectives: To evaluate the efficacy and safety of EBVs in patients with homogeneous emphysema with absence of collateral ventilation assessed with the Chartis system. Methods: Prospective, multicenter, 1:1 randomized controlled trial of EBV plus standard of care (SoC) or SoC alone. Primary outcome was the percentage change in FEV1 (liters) at 3 months relative to baseline in the EBV group versus the SoC group. Secondary outcomes included changes in FEV1, St. George's Respiratory Questionnaire (SGRQ), 6-minute walk distance (6MWD), and target lobe volume reduction. Measurements and Main Results: Ninety-three subjects (age, 63.7 +/- 6.1 yr [mean +/- SD]; FEV1, % predicted, 29.3 +/- 6.5; residual volume, % predicted, 275.4 +/- 59.4) were allocated to either the EBV group (n = 43) or the SoC group (n = 50). In the intention-to-treat population, at 3 months postprocedure, improvement in FEV1 from baseline was 13.7 +/- 28.2% in the EBV group and -3.2 +/- 13.0% in the SoC group (mean between-group difference, 17.0%; P = 0.0002). Other variables demonstrated statistically and clinicallysignificant changes from baseline to 3 months (EBV vs. SoC, respectively: SGRQ, -8.63 +/- 11.25 vs. 1.01 +/- 9.36; and 6MWD, 22.63 +/- 66.63 m vs. -17.34 +/- 52.8 m). Target lobe volume reduction at 3 months was -1,195 +/- 683 ml (P <0.0001). Of the EBV subjects, 97.2% achieved volume reduction in the target lobe (P <0.0001). Procedure-related pneumothoraces occurred in 11 subjects (25.6%). Five subjects required removal/replacement of one or more valves. One subject experienced two valve migration events requiring removal/replacement of valves. Conclusions: EBV in patients with homogeneous emphysema without collateral ventilation results in clinically meaningful benefits of improved lung function, exercise tolerance, and quality of life

Modifying Post-Operative Medical Care after EBV Implant May Reduce Pneumothorax Incidence.

OBJECTIVE Endoscopic lung volume reduction (ELVR) with valves has been shown to improve COPD patients with severe emphysema. However, a major complication is pneumothoraces, occurring typically soon after valve implantation, with severe consequences if not managed promptly. Based on the knowledge that strain activity is related to a higher risk of pneumothoraces, we asked whether modifying post-operative medical care with the inclusion of strict short-term limitation of strain activity is associated with a lower incidence of pneumothorax. METHODS Seventy-two (72) emphysematous patients without collateral ventilation were treated with bronchial valves and included in the study. Thirty-two (32) patients received standard post-implantation medical management (Standard Medical Care (SMC)), and 40 patients received a modified medical care that included an additional bed rest for 48 hours and cough suppression, as needed (Modified Medical Care (MMC)). RESULTS The baseline characteristics were similar for the two groups, except there were more males in the SMC cohort. Overall, ten pneumothoraces occurred up to four days after ELVR, eight pneumothoraces in the SMC, and only two in the MMC cohorts (p=0.02). Complicated pneumothoraces and pneumothoraces after upper lobe treatment were significantly lower in MMC (p=0.02). Major clinical outcomes showed no significant differences between the two cohorts. CONCLUSIONS In conclusion, modifying post-operative medical care to include bed rest for 48 hours after ELVR and cough suppression, if needed, might reduce the incidence of pneumothoraces. Prospective randomized studies with larger numbers of well-matched patients are needed to confirm the data