Acute Eosinophilic Pneumonia Masquerading as a Lung Abscess.

BACKGROUND: Acute Eosinophilic Pneumonia (AEP) is a rare form of non-infectious pneumonia that is easily missed and misdiagnosed because of its atypical clinical symptoms and misleading laboratory and imaging studies. METHODS: By reporting a case of an initial diagnosis of lung abscess, which was treated with antibiotics and then CT suggesting that the lesion continued to worsen, it was eventually confirmed to be AEP by lung biopsy, A joint literature analysis was conducted to improve clinicians' understanding of the diagnosis and treatment of AEP. RESULTS: Initially, because of the atypical ancillary findings, we thought the disease was a lung abscess, which was eventually confirmed by pathology as AEP. CONCLUSIONS: The presence of AEP needs to be considered when various laboratory findings point to infectious dis-ease, but anti-infection is not effective. Diagnosis can be confirmed by bronchoalveolar lavage and lung tissue biopsy. Prompt treatment can provide rapid relief and reduce the risk of patient death.

Immunophenotypic and Functional Characterization of Eosinophil and Migratory Dendritic Cell Subsets during Filarial Manifestation of Tropical Pulmonary Eosinophilia.

The role of eosinophil and migratory dendritic cell (migDC) subsets during tropical pulmonary eosinophilia (TPE), a potentially fatal complication of lymphatic filariasis, has not been explored. We show that the onset of TPE is characterized by the accumulation of ROS and anaphylatoxins and a rapid influx of morphologically distinct Siglec-Fint resident eosinophils (rEos) and Siglec-Fhi inflammatory eosinophils (iEos) in the lungs, BAL fluid, and blood of TPE mice. While rEos display regulatory behavior, iEos are highly inflammatory cells, as evident in upregulated expression of activation markers CD69 and CD101, anaphylatoxin receptor C5AR1, alarmins s100a8 and s100a9, components of NADPH oxidase, and copious secretion of TNF-α, IFN-γ, IL-6, IL-1ß, IL-4, IL-10, IL-12, and TGF-ß. Importantly, iEos exhibited heightened ROS generation, higher phagocytic and increased antigen presentation capacity, elevated Ca2+ influx, and increased F-actin polymerization but downregulated negative regulators of the immune response, i.e., Cd300a, Anaxa1, Runx3, Lilrb3, and Serpinb1a, underlining their essential role in promoting lung damage during TPE. Interestingly, TPE mice also showed significant expansion of CD24+CD11b+ migDCs, which showed upregulated expression of maturation and costimulatory markers CD40, CD80, CD83, CD86, and MHCII, increased antigen presentation capacity, and higher migratory potential as evidenced by increased expression of cytokine receptors CCR4, CCR5, CXCR4, and CXCR5. CD24+CD11b+ migDCs also upregulated the expression of immunoregulators PD-L1 and PD-L2 and secreted proinflammatory cytokines, suggesting their significant involvement during TPE. Taken together, we document important morphological, immunophenotypic, and functional characteristics of eosinophil and migDC subsets in the lungs of TPE mice and suggest that they contribute to worsening lung histopathological conditions during TPE.

[Clinical analysis of chronic eosinophilic pneumonia in 9 cases].

Objective: To investigate the clinical features, treatment and prognosis of chronic eosinophilic pneumonia. Methods: Nine patients with chronic eosinophilic pneumonia diagnosed in Shandong Provincial Qianfoshan Hospital from January 2014 to December 2020 were enrolled and followed up. The data of clinically proven chronic eosinophilic pneumonia were reviewed. Results: The 9 cases included one male and eight females, aged from 16 to 71 years (median 47 years). Among them, 5 cases were complicated with asthma, 1 case was complicated with allergic rhinitis, and 1 case had an allergic history of pollen. All the patients had cough, expectoration, chest tightness and wheezing, and a few had fatigue (3/9), fever (1/9) and chest pain (1/9). Single or multiple patchy high-density shadows (9/9), mediastinal lymphadenopathy (7/9), air bronchogram (2/9), and reticular shadow (1/9) were observed in chest CT. Peripheral eosinophils (EOS) and serum total IgE increased to varying degrees in the 9 patients. Meanwhile, the bronchoscopy of 5 cases showed elevated percentage of eosinophils in alveolar lavage fluid, and the lung biopsy of remaining 4 cases showed EOS infiltration in lung alveolar and interstitium. After receiving glucocorticoid therapy for 0.5 to 1 month, the clinical symptoms of all 9 patients had been improved and lung lesions on CT scans had been obviously absorbed. Four cases relapsed during follow-up. Conclusions: For patients especially women who have a history of allergy, elevated blood eosinophils and serum total IgE with pulmonary high-density shadow or consolidation, chronic eosinophilic pneumonia should be considered, and bronchoscopy or percutaneous lung biopsy is indicated for a definite diagnosis. Glucocorticoid therapy is effective, but the rate of recurrence is high.

[Chronic eosinophilic pneumonia: imaging findings]. / Neumonía eosinofílica crónica: hallazgos en imágenes.

Chronic eosinophilic pneumonia (CEP) is a rare disease of unknown cause characterized by alveolar and interstitial eosinophilic infiltration. The tomographic pattern is characterized by consolidations and peripherally distributed ground glass opacities in both upper lobes. Other findings are opacities in bands parallel to the pleura, thickening of the interlobular septa, migratory opacities, and mediastinal lymph nodes. We presented a case of a woman with CEP and described the most relevant clinical and radiological characteristics.

La neumonía eosinofílica crónica (NEC) es una enfermedad rara de causa desconocida caracterizada por infiltración eosinofílica alveolar e intersticial. El patrón tomográfico se caracteriza por consolidaciones y opacidades en vidrio esmerilado de distribución periférica en ambos lóbulos superiores. Otros hallazgos son las opacidades en bandas paralelas a la pleura, engrosamiento de septos interlobulillares, opacidades migratrices y adenomegalias mediastinales. Se presenta el caso de una mujer con NEC y se describen las características clínicas y radiológicas más relevantes.

Label-free imaging and evaluation of characteristic properties of asthma-derived eosinophils using optical diffraction tomography.

Optical diffraction tomography (ODT), an emerging imaging technique that does not require fluorescent staining, can measure the three-dimensional distribution of the refractive index (RI) of organelles. In this study, we used ODT to characterize the pathological characteristics of human eosinophils derived from asthma patients presenting with eosinophilia. In addition to morphological information about organelles appearing in eosinophils, including the cytoplasm, nucleus, and vacuole, we succeeded in imaging specific granules and quantifying the RI values of the granules. Interestingly, ODT analysis showed that the RI (i.e., molecular density) of granules was significantly different between eosinophils from asthma patients and healthy individuals without eosinophilia, and that vacuoles were frequently found in the cells of asthma patients. Our results suggest that the physicochemical properties of eosinophils derived from patients with asthma can be quantitatively distinguished from those of healthy individuals. The method will provide insight into efficient evaluation of the characteristics of eosinophils at the organelle level for various diseases with eosinophilia.

Migration of Lung Resident Group 2 Innate Lymphoid Cells Link Allergic Lung Inflammation and Liver Immunity.

Group 2 innate lymphoid cells (ILC2s) are tissue resident in the lung and activated by inhaled allergens via epithelial-derived alarmins including IL-33. Activated ILC2s proliferate, produce IL-5 and IL-13, and induce eosinophilic inflammation. Here, we report that intranasal IL-33 or the protease allergen papain administration resulted in increased numbers of ILC2s not only in the lung but also in peripheral blood and liver. Analyses of IL-33 treated parabiosis mice showed that the increase in lung ILC2s was due to proliferation of lung resident ILC2s, whereas the increase in liver ILC2s was due to the migration of activated lung ILC2s. Lung-derived ILC2s induced eosinophilic hepatitis and expression of fibrosis-related genes. Intranasal IL-33 pre-treatment also attenuated concanavalin A-induced acute hepatitis and cirrhosis. These results suggest that activated lung resident ILC2s emigrate from the lung, circulate, settle in the liver and promote type 2 inflammation and attenuate type 1 inflammation.

UDP-glucose and P2Y14 receptor amplify allergen-induced airway eosinophilia.

Airway eosinophilia is a hallmark of allergic asthma and is associated with mucus production, airway hyperresponsiveness, and shortness of breath. Although glucocorticoids are widely used to treat asthma, their prolonged use is associated with several side effects. Furthermore, many individuals with eosinophilic asthma are resistant to glucocorticoid treatment, and they have an unmet need for novel therapies. Here, we show that UDP-glucose (UDP-G), a nucleotide sugar, is selectively released into the airways of allergen-sensitized mice upon their subsequent challenge with that same allergen. Mice lacking P2Y14R, the receptor for UDP-G, had decreased airway eosinophilia and airway hyperresponsiveness compared with wild-type mice in a protease-mediated model of asthma. P2Y14R was dispensable for allergic sensitization and for the production of type 2 cytokines in the lung after challenge. However, UDP-G increased chemokinesis in eosinophils and enhanced their response to the eosinophil chemoattractant, CCL24. In turn, eosinophils triggered the release of UDP-G into the airway, thereby amplifying eosinophilic recruitment. This positive feedback loop was sensitive to therapeutic intervention, as a small molecule antagonist of P2Y14R inhibited airway eosinophilia. These findings thus reveal a pathway that can be therapeutically targeted to treat asthma exacerbations and glucocorticoid-resistant forms of this disease.

Clinical features of acute fibrinous and organizing pneumonia: An early histologic pattern of various acute inflammatory lung diseases.

BACKGROUND: Acute fibrinous and organizing pneumonia (AFOP) is a rare histologic pattern of acute lung involvement with intra-alveolar fibrin deposition. However, the clinical significance of the pathological findings of AFOP remains unclear. This study aimed to explore the clinical significance of AFOP through a comprehensive clinical examination. METHODS: The medical records of patients with lung diseases accompanied by the pathological finding of intra-alveolar organization between January 2010 and December 2019 were retrospectively reviewed. The clinical and radiological findings were compared between the groups with and without the histologic pattern of AFOP. RESULTS: We identified 34 patients with AFOP (AFOP group) and 143 without AFOP (non-AFOP group). The underlying diseases of the AFOP group were as follows: 19 patients had cryptogenic organizing pneumonia (OP), 5 had connective tissue diseases, 3 had radiation pneumonitis, 3 had chronic eosinophilic pneumonia, 2 had myelodysplastic syndromes, and 2 had drug-induced pneumonia. Fever was more common, the time from symptom onset to biopsy was shorter, and the serum C-reactive protein level was higher in the AFOP group than in the non-AFOP group. On high-resolution computed tomography, 85% of patients had OP pattern, and halo sign was more common in the AFOP group. Corticosteroids were effective in 94% of the patients in the AFOP group; however, recurrences were more frequent, and a higher corticosteroid dose was needed during recurrence. CONCLUSIONS: AFOP might be an early phase of a histologic pattern associated with known etiologies. In addition, it could be a marker indicating intense inflammatory diseases with a tendency of recurrence.

Histopathological Correlation of Acute on Chronic Eosinophilic Pneumonitis Caused by Vaporized Cannabis Oil Inhalation.

Whether eosinophilic pneumonitis represents a true manifestation of e-cigarette, or vaping, product use-associated lung injury remains uncertain, and this ambiguity stems from a lack of histopathological data. We present a previously healthy young woman whose asthma-like symptoms and histopathologic finding of eosinophilic pneumonitis were caused by inhalation of vaporized cannabis hash oil concentrates. This report provides compelling evidence that eosinophilic pneumonitis can result from cannabis hash oil inhalation.

Serum sphingolipid profile in asthma.

Sphingolipids metabolism is an important cell process and plays critical roles in asthma. However, the involvement of sphingolipids in the pathogenesis of asthma and its subtypes is unknown. The present study aimed to determine the role of sphingolipids in asthma and its subtypes. Clinical data from 51 asthma patients and 9 healthy individuals were collected and serum samples were performed to analyze the levels of serum sphingolipids by liquid chromatography-mass spectrometry-based targeted metabolomics. Results showed that the levels of sphingomyelin (SM) including SM34:2, SM38:1, and SM40:1 were significantly decreased in asthmatic patients compared to healthy controls. Moreover, serum SM levels were obviously decreased in the blood noneosinophilic asthma (bNEA) group compared with blood eosinophilic asthma group. Similar tendencies of serum SM level changes were observed in the early-onset group compared with late-onset group. Correlation analysis revealed that SM 40:1 was negatively related to sputum IL-17A (r = -0.621, P = 0.042). The present study presented that the SM may be a protective factor of asthma and contributes to the mechanism of asthma, especially bNEA. SM may be a potential biomarker and therapeutic target in asthma.

Acidic Calcium-Independent Phospholipase A2 Regulates Eosinophil-Mediated Pathology during Filarial Manifestation of Tropical Pulmonary Eosinophilia.

Eosinophils mediate pathological manifestations during tropical pulmonary eosinophilia (TPE), a potentially fatal complication of lymphatic filariasis, by mechanisms that are incompletely understood. Using two-dimensional gel electrophoresis, mass spectrometry, flow cytometry, and pharmacological and functional studies, we identified acidic calcium-independent phospholipase A2 (aiPLA2) as the master regulator of TPE pathogenesis. FACS-sorted lung eosinophils from TPE mice exhibited aiPLA2-dependent activation characterized by heavy calcium influx, F-actin polymerization, increased degranulation, and heightened reactive oxygen species generation. Interestingly, aiPLA2 also promoted alternative activation in lung macrophages and regulated the release of inflammatory intermediates from them. Treatment of TPE mice with MJ33, a nontoxic pharmacological inhibitor of aiPLA2, lowered eosinophil counts in the bronchoalveolar lavage fluid, reduced eosinophil peroxidase and ß-hexosaminidase activity, increased airway width, improved lung endothelial barrier, and lowered the production of inflammatory lipid intermediates, which significantly improved the pathological condition of the lungs. Importantly, ex vivo reconstitution of arachidonic acid to eosinophils from MJ33-treated TPE mice increased eosinophil degranulation and inflammatory lipid intermediates underlining the pivotal role of aiPLA2 in arachidonic acid metabolism. Mechanistically, phosphorylation of JNK-1 regulated phospholipase activity of aiPLA2, whereas IgG cross-linking mediated pathological activation of eosinophils. Taken together, ours is the first study, to our knowledge, to report hitherto undocumented role of aiPLA2 in regulating TPE pathogenesis.

The role of HRCT in Tropical Pulmonary Eosinophilia.

PURPOSE: To determine the pattern of pulmonary involvement in clinically confirmed patients of tropical pulmonary eosinophilia (TPE). METHOD: An observational study on 13 patients with clinically confirmed TPE was performed to determine the CT scan appearances. RESULTS: The predominant CT scan finding is the presence widespread ill-defined bronchocentric nodules, which need to be differentiated from other conditions. CONCLUSION: The pattern of lung involvement on a CT scan can give a clue to the diagnosis of TPE in the correct clinical context. Radiologists in tropical countries should have a high index of suspicion for this diagnosis when reading scans showing widespread ill-defined bronchocentric nodules.

TSLP drives acute TH2-cell differentiation in lungs.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine that is important for the development of type 2 inflammatory responses at mucosal surfaces. OBJECTIVE: In humans, TSLP level has been found to be elevated in the lungs of patients with asthma, and in mouse models, TSLP can promote type 2 airway inflammation, primarily through the activation of dendritic cells. However, the mechanisms underlying its role remain unclear. The objective of this study was to provide a mechanistic analysis of TSLP-mediated type 2 airway inflammation METHODS: To dissect the mechanisms of TSLP-mediated type 2 responses, mice were treated with TSLP and antigen to evaluate cellular immune responses. Flow cytometric analyses were used to follow responses in the airways, and conditional deletion of TSLP receptor and adoptive transfer were used to identify the cellular subsets involved in this inflammatory response. RESULTS: We showed that TSLP can directly promote TH2-cell differentiation in the lung, independent of the draining lymph nodes. We also identified a population of patrolling monocytes/interstitial macrophages (IMs) (CD11c-expressing IMs) that are both necessary and sufficient for TSLP-mediated TH2-cell differentiation and airway inflammation. TH2-cell-driven airway eosinophilia is attenuated by ablation of CD11c-expressing IMs or by selective deficiency of TSLP receptor signaling in these cells. More importantly, CD11c-expressing IMs are sufficient for the induction of acute TH2-cell responses in the lungs that is independent of dendritic cells and T-cell priming in the draining lymph nodes. CONCLUSION: These findings indicate a novel mechanistic role for TSLP and CD11c-expressing IMs in the development of acute TH2-cell-dependent allergic airway inflammation. This work also demonstrates a new role for TSLP in promoting type 2 responses directly in the lung.

Possible Mechanisms of Eosinophil Accumulation in Eosinophilic Pneumonia.

Eosinophilic pneumonia (EP), including acute EP and chronic EP, is characterized by the massive pulmonary infiltration of eosinophils into the lung. However, the mechanisms underlying the selective accumulation of eosinophils in EP have not yet been fully elucidated. We reported that bronchoalveolar lavage fluid (BALF) from EP patients induced the transmigration of eosinophils across endothelial cells in vitro. The concentrations of eotaxin-2 (CCL24) and monocyte chemotactic protein (MCP)-4 (CCL13), which are CC chemokine receptor (CCR) 3 ligands, were elevated in the BALF of EP patients, and anti-CCR3 monoclonal antibody inhibited the eosinophil transmigration induced by the BALF of EP patients. The concentration of macrophage inflammatory protein 1ß (CCL4), a CCR5 ligand that induces eosinophil migration, was increased in the BALF of EP patients. Furthermore, the concentration of interleukin (IL) 5 was increased in the BALF of EP patients, and it has been reported that anti-IL-5 antibody treatment resulted in remission and the reduction of glucocorticoid use in some cases of chronic EP. The concentrations of lipid mediators, such as leukotriene (LT) B4, damage-associated molecular pattern molecules (DAMPs), such as uric acid, or extracellular matrix proteins, such as periostin, were also increased in the BALF of EP patients. These findings suggest that chemokines, such as CCR3/CCR5 ligands, cytokines, such as IL-5, lipid mediators, such as LTB4, DAMPs, and extracellular matrix proteins may play roles in the accumulation or activation of eosinophils in EP.

Real-Life Study of Mepolizumab in Idiopathic Chronic Eosinophilic Pneumonia.

INTRODUCTION: Idiopathic chronic eosinophilic pneumonia (ICEP) is an orphan lung disease characterized by concomitant systemic and local eosinophilia, along with bilateral lung infiltrates. Symptoms include dyspnea of subacute/chronic onset, cough, and general systemic signs. Although all patients do respond to oral corticosteroids, relapse rate is very high, which highlights the need for alternative therapies in case of relapsing ICEP. Mepolizumab is a fully humanized antibody directed against interleukin 5, a key growth factor of eosinophils. In the present study, we retrospectively studied the effect of off-label use of mepolizumab for relapsing ICEP. MATERIALS AND METHODS: All data from patients treated with mepolizumab for relapsing ICEP were included in our database and diagnoses were reviewed. We analyzed the effect of treatment on relapse rate, oral corticosteroids (OCS) use, and lung lesions on high-resolution computed tomography (HRCT). RESULTS: We included ten patients in the final analysis, with a median follow-up of 9 months after initiation of mepolizumab. Beside its expected effect on circulating eosinophils, treatment with mepolizumab was associated with a significant reduction of annual rate of exacerbations and a reduced consumption of corticosteroids. We also observed a remission of lung lesions on follow-up HRCT. CONCLUSIONS: In this open-label retrospective study, treatment of ICEP with mepolizumab was associated with a reduction of relapses, OCS use, and the disappearance of lung infiltrates.

An endothelial microRNA-1-regulated network controls eosinophil trafficking in asthma and chronic rhinosinusitis.

BACKGROUND: Airway eosinophilia is a prominent feature of asthma and chronic rhinosinusitis (CRS), and the endothelium plays a key role in eosinophil trafficking. To date, microRNA-1 (miR-1) is the only microRNA known to be regulated in the lung endothelium in asthma models. OBJECTIVE: We sought to determine the role of endothelial miR-1 in allergic airway inflammation. METHODS: We measured microRNA and mRNA expression using quantitative RT-PCR. We used ovalbumin and house dust mite models of asthma. Endothelium-specific overexpression of miR-1 was achieved through lentiviral vector delivery or induction of a transgene. Tissue eosinophilia was quantified by using Congo red and anti-eosinophil peroxidase staining. We measured eosinophil binding with a Sykes-Moore adhesion chamber. Target recruitment to RNA-induced silencing complex was assessed by using anti-Argonaute2 RNA immunoprecipitation. Surface P-selectin levels were measured by using flow cytometry. RESULTS: Serum miR-1 levels had inverse correlations with sputum eosinophilia, airway obstruction, and number of hospitalizations in asthmatic patients and sinonasal tissue eosinophilia in patients with CRS. IL-13 stimulation decreased miR-1 levels in human lung endothelium. Endothelium-specific overexpression of miR-1 reduced airway eosinophilia and asthma phenotypes in murine models and inhibited IL-13-induced eosinophil binding to endothelial cells. miR-1 recruited P-selectin, thymic stromal lymphopoietin, eotaxin-3, and thrombopoietin receptor to the RNA-induced silencing complex; downregulated these genes in the lung endothelium; and reduced surface P-selectin levels in IL-13-stimulated endothelial cells. In our asthma and CRS cohorts, miR-1 levels correlated inversely with its target genes. CONCLUSION: Endothelial miR-1 regulates eosinophil trafficking in the setting of allergic airway inflammation. miR-1 has therapeutic potential in asthmatic patients and patients with CRS.

Lung eosinophils increase vagus nerve-mediated airway reflex bronchoconstriction in mice.

Eosinophils mediate airway hyperresponsiveness by increasing vagally mediated reflex bronchoconstriction. Here, we tested whether circulating or airway eosinophils change nerve function. Airway resistance in response to aerosolized 5-hydroxytryptamine (5-HT, 10-300 mM) was measured in wild-type mice or transgenic mice that overexpress IL5 in T cells (+IL5T), overexpress IL5 in airway epithelium (+IL5AE), or overexpress IL5 but are devoid of eosinophils (+IL5AE/-Eos). Inflammatory cells in bronchoalveolar lavage (BAL), blood, and bone marrow were quantified. Blood eosinophils were increased in +IL5T and +IL5AE mice compared with wild-type mice. +IL5T mice had increased eosinophils in bone marrow while +IL5AE mice had increased eosinophils in BAL. Eosinophils surrounding large airways were significantly increased only in +IL5AE mice. With intact vagal innervation, aerosolized 5-HT significantly increased airway resistance in +IL5AE mice. 5-HT-induced bronchoconstriction was blocked by vagotomy or atropine, demonstrating that it was mediated via a vagal reflex. Airway resistance was not increased in +IL5AE/-Eos mice, demonstrating that it required lung eosinophils, but was not affected by increased bone marrow or blood eosinophils or by increased IL5 in the absence of eosinophils. Eosinophils did not change M3 function on airway smooth muscle, since airway responses to methacholine in vagotomized mice were not different among strains. Eosinophils surrounding large airways were sufficient, even in the absence of increased IL5 or external insult, to increase vagally mediated reflex bronchoconstriction. Specifically blocking or reducing eosinophils surrounding large airways may effectively inhibit reflex hyperresponsiveness mediated by vagus nerves in eosinophilic asthma.

Benralizumab efficacy for patients with fixed airflow obstruction and severe, uncontrolled eosinophilic asthma.

BACKGROUND: Fixed airflow obstruction (FAO) is associated with severe eosinophilic asthma. Benralizumab is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody for patients with severe, uncontrolled eosinophilic asthma. OBJECTIVE: We evaluated FAO influence on benralizumab treatment response. METHODS: We performed a post hoc analysis of pooled phase III SIROCCO (NCT01928771) and CALIMA (NCT01914757) data for patients with severe, uncontrolled asthma with baseline blood eosinophil counts of 300 or more cells/µL who received benralizumab 30 mg every 8 weeks or placebo. Demographics, baseline clinical characteristics, and treatment responses were evaluated by FAO status. FAO+ and FAO- were defined as ratios of postbronchodilator forced expiratory volume in 1 second (FEV1) to forced vital capacity of less than 70% and 70% or more, respectively, at baseline. RESULTS: FAO+ prevalence was 63% (935/1493). With benralizumab, similar annual asthma exacerbation rate (AER) reductions vs placebo were achieved for FAO+ and FAO- patients (rate ratio [95% confidence interval (CI)] = 0.56 [0.44-0.71] and 0.58 [0.41-0.83], respectively), whereas annual AER reductions associated with emergency department visits or hospitalizations were greater for FAO+ vs FAO- patients (rate ratio [95% CI] = 0.55 [0.33-0.91] and 0.70 [0.33-1.48], respectively). Prebronchodilator FEV1 (95% CI) increase from baseline to end of treatment was greater for FAO+ vs FAO- patients receiving benralizumab compared with placebo (0.159 L [0.082-0.236] vs 0.103 L [-0.008 to 0.215]). Other lung function measures, patient-reported outcomes, and symptom improvements were also numerically greater for FAO+ vs FAO- patients. CONCLUSION: Benralizumab improved asthma control across several measures for patients with severe, uncontrolled eosinophilic asthma and FAO. TRIAL REGISTRATION: SIROCCO trial: NCT01928771 (URL: https://clinicaltrials.gov/ct2/show/NCT01928771) CALIMA trial: NCT01914757 (URL: https://clinicaltrials.gov/ct2/show/NCT01914757).

Neumonía eosinofílica en pediatría, a propósito de dos casos clínicos / Pneumonia eosinofilic in pediatrics, clinical cases

INTRODUCCIÓN: La Neumonía Eosinofílica (NE) es una entidad muy poco frecuente en pediatría y se caracteriza por infiltración de eosinófilos en el intersticio pulmonar y alveolar, pudiendo ser primaria o secundaria, así como también presentar un curso agudo o crónico. OBJETIVO: Presentar dos casos clínicos de NE diagnosticados en el período 2014-2017 en una Unidad de Cuidados Intensivos pediátricos. CASOS CLÍNICOS: Dos lactantes mayores, ambos con antecedente de madre asmática, hospitalizados por in suficiencia respiratoria y diagnóstico de neumonía viral en Clínica Indisa, Santiago, Chile. Ambos presentaron síndrome febril, imágenes de condensación persistentes en la radiografía de tórax y eosinofilia periférica en el transcurso de su enfermedad. Uno de ellos con requerimiento de oxígeno por más de un mes, sin eosinofilia en el lavado broncoalveolar (LBA), al que se le hizo el diagnóstico de NE por biopsia pulmonar. El otro niño requirió ventilación mecánica por 28 días y se hizo diag nóstico de NE por eosinofilia mayor a 20% en LBA. Los dos casos presentaron excelente respuesta a corticoides sistémicos. CONCLUSIÓN: La NE se debe sospechar en el niño con diagnóstico de neumonía con síntomas persistentes sin respuesta al tratamiento, habiéndose descartado otras causas, sobre todo si se asocia a eosinofilia periférica. El diagnostico de NE en pediatría se confirma por eosinofilia mayor a 20% en LBA y en algunos casos es necesaria la biopsia pulmonar.

INTRODUCTION: Eosinophilic Pneumonia (EP) is a very rare disorder in Pediatrics. It is characterized by the infiltra tion of eosinophils in the pulmonary and alveolar interstitium, and may be primary or secondary as well as present an acute or chronic progress. OBJECTIVE: to present 2 pediatric EP clinical cases which were diagnosed at the pediatric intensive care unit of Clinica Indisa in Santiago, Chile between 2014 and 2017. CLINICAL CASES: Two older infants, who were hospitalized due to respiratory failure with a diagnosis of viral pneumonia. Both have asthmatic mothers. Additionally, they both had febrile syn drome, persistent condensation images in the chest x-rays, and peripheral eosinophilia throughout the course of the disease. One of the infants required oxygen for more than one month, and there was no eosinophilia in the bronchoalveolar lavage (BAL). In this case, the diagnosis of EP was reached via pulmonary biopsy. The other infant required mechanic ventilation for 28 days, and was diagnosed due to eosinophilia greater than 25% in the bronchoalveolar lavage. Both patients had excellent res ponse to systemic corticosteroids. CONCLUSION: After ruling out other causes, EP should be suspected in children with pneumonia diagnosis, and persistent symptoms that do not respond positively to treatment, especially if associated with peripheral eosinophilia. The diagnosis of EP in pediatrics is confirmed with eosinophilia greater than 20% in BAL and, in some cases, it is necessary to perform a lung biopsy.

Advances in eosinophilic diseases in 2018.

Interest in eosinophil biology and eosinophilic diseases is increasing, as reflected in a doubling of the number of annual articles focused on this topic published in the Journal of Allergy and Clinical Immunology over the past decade. Although the majority of these publications relate to eosinophilic asthma, a growing proportion of them focus on breakthroughs in the diagnosis, treatment, and pathogenesis of other eosinophilic disorders, most notably eosinophilic esophagitis. This review highlights advances in our understanding of eosinophilia and eosinophilic disorders (excluding asthma) published in the Journal in 2018.