Case Report: Eosinophilic Bronchiolitis With Eosinophil ETosis in Mucus Plugs Successfully Treated With Benralizumab

Eosinophilic bronchiolitis is a rare allergic disorder caused by eosinophilic inflammation in the bronchioles of the lungs. An effective treatment strategy is needed in cases resistant to steroids. However, its pathophysiology remains unclear owing to the limited number of cases. We herein present the case of a 31-year-old man who experienced eosinophilic bronchiolitis with eosinophil ETosis (EETosis) in the mucus plugs. The patient was diagnosed with asthma. His respiratory symptoms worsened with eosinophilia when treated with the standard asthma regimen, including inhaled corticosteroids, long-acting β2-agonist, long-acting muscarinic antagonist, and leukotriene receptor antagonist. Chest computed tomography revealed bronchial wall thickening and centrilobular nodules in the lower lobes of both lungs. Bronchoscopy showed obstruction of the subsegmental bronchus with mucus plugs. Histological analysis demonstrated abundant eosinophils in the mucus plugs. Cytolytic eosinophils together with Charcot–Leyden crystal formations and deposition of major basic proteins were also observed, indicating the occurrence of EETosis. Introduction of benralizumab, an anti-interleukin-5 receptor α antibody, successfully controlled the patient’s condition and reduced the amount of systemic corticosteroids administered. Our findings confirm that this antibody strongly decreases airway eosinophils in patients with severe asthma. Thus, benralizumab might be an optimal therapeutic agent for the treatment of mucus plug-forming and/or EETosis-occurring eosinophilic lung diseases, including eosinophilic bronchiolitis.

Severe pediatric asthma with a poor response to omalizumab: a report of three cases and three-dimensional bronchial wall analysis

Omalizumab is used for the treatment of persistent severe allergic asthma in adults and children. However, some patients remain symptomatic even after omalizumab treatment. In bronchial asthma, chronic inflammation of the bronchial wall causes thickening of the airway wall, resulting from irreversible airway remodeling. Progression of airway remodeling causes airflow obstruction, leading to treatment resistance. We report three Japanese children with severe asthma who had a poor response to omalizumab treatment. They had a long period of inadequate management of asthma before initiating omalizumab. Even after omalizumab treatment, their symptoms persisted, and the parameters of spirometry tests did not improve. We hypothesized that omalizumab was less effective in these patients because airway wall remodeling had already progressed. We retrospectively evaluated the bronchial wall thickness using a three-dimensional bronchial wall analysis with chest computed tomography. The bronchial wall thickness was increased in these cases compared with six responders. Progressed airway wall thickness caused by airway remodeling may be associated with a poor response to omalizumab in children with severe asthma.

SB203580—A Potent p38 MAPK Inhibitor Reduces the Profibrotic Bronchial Fibroblasts Transition Associated with Asthma

Subepithelial fibrosis is a component of the remodeling observed in the bronchial wall of patients diagnosed with asthma. In this process, human bronchial fibroblasts (HBFs) drive the fibroblast-to-myofibroblast transition (FMT) in response to transforming growth factor-β1 (TGF-β1), which activates the canonical Smad-dependent signaling. However, the pleiotropic properties of TGF-β1 also promote the activation of non-canonical signaling pathways which can affect the FMT. In this study we investigated the effect of p38 mitogen-activated protein kinase (MAPK) inhibition by SB203580 on the FMT potential of HBFs derived from asthmatic patients using immunocytofluorescence, real-time PCR and Western blotting methods. Our results demonstrate for the first time the strong effect of p38 MAPK inhibition on the TGF-β1-induced FMT potential throughout the strong attenuation of myofibroblast-related markers: α-smooth muscle actin (α-SMA), collagen I, fibronectin and connexin 43 in HBFs. We suggest the pleiotropic mechanism of SB203580 on FMT impairment in HBF populations by the diminishing of TGF-β/Smad signaling activation and disturbances in the actin cytoskeleton architecture along with the maturation of focal adhesion sites. These observations justify future research on the role of p38 kinase in FMT efficiency and bronchial wall remodeling in asthma.

Chest CT findings in COVID-19

RT-PCR is the gold standard in the diagnosis of COVID-19 infections, due to its high specificity. However, there are clinical situations in which chest CT may prove vital, for example in patients with high clinical and epidemiologic suspicion towards COVID-19 before positive RT-PCR conversion or in detecting complications. Researchers have developed scales that, based on the findings in chest CT, help predict the severity of the disease. There are three main pathologic patterns of lung injury that correlate with the duration of COVID-19 symptoms. Epithelial pattern with diffuse alveolar damage and desquamation/reactive hyperplasia of pneumocytes; vascular pattern with capillary congestion and (micro)thrombi and fibrotic pattern with interstitial fibrous changes. The epithelial pattern and vascular pattern appear early, even before the symptoms of the disease, whereas the fibrous pattern appears approximately three weeks after the onset of the disease. Typical findings on chest CT in COVID-19 infection are: GGO, consolidation, GGO mixed with consolidation, interlobular septal thickening, air bronchogram sign, crazy paving, bronchial wall thickening and vascular enlargement. Findings that may suggest a different etiology include multiple nodules, tree-in-bud opacities, bronchiectasis, pleural and pericardial effusion, extensive consolidations.

Delayed bronchial perforation after bulla cauterization with soft coagulation system

Background Soft coagulation is widely used for hemostasis because of its significant advantage in inducing tissue coagulation and denaturation without carbonization. However, a few cases of airway damage have been reported at the site, where soft coagulation was directly applied. Case presentation We encountered an unusual case of delayed perforation of the intermediate bronchial trunk observed on 24 days after cauterization of the right S6 bulla adjacent to the bronchus. Chest computed tomography revealed a large fistula between the intermediate bronchial trunk and the cauterized bulla in the right S6. Bronchoscopy showed a large fistula at the membranous portion of the intermediate bronchial trunk. We presumed that the bronchial perforation resulted from thermal damage to the intermediate bronchial trunk during bulla cauterization and the bronchial perforation induced infection in the bulla. Resection of the infectious bulla and the intermediate bronchial trunk, followed by end-to-end bronchial anastomosis and a pedicled intercostal muscle flap coverage, was performed. Conclusions The severe airway damage resulting in perforation developed even without direct contact between the electrode tip and the bronchial wall, provoking the need for special attention to the duration of cauterization and location, where it is used.

Kerley A-lines represent thickened septal plates between lung segments in patients with lymphangitic carcinomatosis: confirmation using 3D-CT lung segmentation analysis

Purpose Kerley A-lines are generally apparent in patients with pulmonary edema or lymphangitic carcinomatosis. There are two main thoughts regarding the etiology of Kerley A-lines, but no general agreement. Specifically, the lines are caused by thickened interlobular septa or dilated anastomotic lymphatics. Our purpose was to determine the anatomic structure represented as Kerley A-lines using 3D-CT lung segmentation analysis. Materials and methods We reviewed 139 charts of patients with lymphangitic carcinomatosis of the lung who had CT and X-ray exams with a maximum interval of 7 days. The presence of Kerley A-lines on X-ray was assessed by a radiologist. The A-lines on X-ray were defined as follows: dense; fine (< 1 mm thick); ≥ 2 cm in length, radiating from the hilum; no bifurcation; and not adjacent to the pleura. For cases with Kerley A-lines on X-ray, three radiologists agreed that the lines on CT corresponded with Kerley A-lines. The incidence of A-lines and the characteristics of the lines were investigated. The septal lines between lung segments were identified using a 3D-CT lung segmentation analysis workstation. The percentage of agreement between the A-lines on CT and lung segmental lines was assessed. Results On chest X-ray, 37 Kerley A-lines (right, 16; left, 21) were identified in the 22 cases (16%). Of these, 4 lungs with 12 lines were excluded from analysis due to technical reasons. Nineteen of the 25 lines (76%) corresponded to the septal lines on CT. Of these, 11 lines matched with automatically segmented lines (intersegmental septa, 4; intersubsegmental septa, 7) by the workstation. Two lines (8%) represented fissures. Four lines corresponded to the bronchial wall/artery (3 lines, 12%) or vein (1 line, 4%). Conclusion Kerley A-lines primarily represented thickened and continued interlobular septal lines that corresponded to the septa between lung segments and subsegments.

Similarities in Quantitative Computed Tomography Imaging of the Lung in Severe Asthma with Persistent Airflow Limitation and Chronic Obstructive Pulmonary Disease

Background: Severe asthma with persistent airflow limitation (SA-PAL) and chronic obstructive pulmonary disease (COPD) are characterised by irreversible airflow limitation and the remodelling of the airways. The phenotypes of the diseases overlap and may cause diagnostic and therapeutic concerns. Methods: There were 10 patients with SA-PAL, 11 patients with COPD, and 10 healthy volunteers (HV) enrolled in this study. The patients were examined with a 128-multislice scanner at full inspiration. Measurements were taken from the third to ninth bronchial generations. Results: The thickness of the bronchial wall was greater in the SA-PAL than in the COPD group for most bronchial generations (p < 0.05). The mean lung density was the lowest in the SA-PAL group (−846 HU), followed by the COPD group (−836 HU), with no statistical difference between these two groups. The low-attenuation volume percentage (LAV% < −950 HU) was significantly higher in the SA-PAL group (15.8%) and COPD group (10.4%) compared with the HV group (7%) (p = 0.03). Conclusion: Severe asthma with persistent airflow limitation and COPD become similar with time within the functional and morphological dimensions. Emphysema qualities are present in COPD and in SA-PAL patients.

Eosinophilic bronchiolitis successfully treated with benralizumab

A 53-year-old non-smoking Japanese woman was admitted to our hospital with a 20-year history of wet cough and dyspnoea on exertion. Bronchial asthma (BA) had been diagnosed 20 years earlier. Although she has been treated with high-dose inhaled corticosteroid, she had experienced frequent exacerbation of BA, and short-term oral corticosteroid bursts were occasionally administered. High-resolution CT of the chest revealed diffuse centrilobular nodules with bronchial wall thickening and patchy ground-glass opacities in both lungs. Lung biopsy specimens showed widespread cellular bronchiolitis with follicle formations in the membranous and respiratory bronchioles, accompanied by marked infiltration of plasma cells and eosinophils. In addition, immunohistochemical immunoglobulin G4 (IgG4) staining revealed many IgG4-positive plasma cells, and the ratio of IgG4-positive cells to IgG-positive cells exceeded 40%. The final diagnosis was eosinophilic bronchiolitis with marked IgG4-positive plasma cell infiltration in association with BA. With benralizumab therapy, her clinical condition dramatically improved.