Allergic Bronchopulmonary Aspergillosis–A Luminal Hypereosinophilic Disease With Extracellular Trap Cell Death

Allergic bronchopulmonary aspergillosis (ABPA) is characterized by an early allergic response and late-phase lung injury in response to repeated exposure to Aspergillus antigens, as a consequence of persistent fungal colonization of the airways. Here, we summarize the clinical and pathological features of ABPA, focusing on thick mucus plugging, a key observation in ABPA. Recent findings have indicated that luminal eosinophils undergo cytolytic extracellular trap cell death (ETosis) and release filamentous chromatin fibers (extracellular traps, ETs) by direct interaction with Aspergillus fumigatus. Production of ETs is considered to be an innate immune response against non-phagocytable pathogens using a “trap and kill” mechanism, although eosinophil ETs do not promote A. fumigatus damage or killing. Compared with neutrophils, eosinophil ETs are composed of stable and condensed chromatin fibers and thus might contribute to the higher viscosity of eosinophilic mucus. The major fate of massively accumulated eosinophils in the airways is ETosis, which potentially induces the release of toxic granule proteins and damage-associated molecular patterns, epithelial damage, and further decreases mucus clearance. This new perspective on ABPA as a luminal hypereosinophilic disease with ETosis/ETs could provide a better understanding of airway mucus plugging and contribute to future therapeutic strategies for this challenging disease

Postharvest Properties of Ultra-Late Maturing Peach Cultivars and Their Attributions to Melting Flesh (M) Locus: Re-evaluation of M Locus in Association With Flesh Texture

The postharvest properties of two ultra-late maturing peach cultivars, "Tobihaku" (TH) and "Daijumitsuto" (DJ), were investigated. Fruit were harvested at commercial maturity and held at 25 degrees C. TH exhibited the characteristics of normal melting flesh (MF) peach, including rapid fruit softening associated with appropriate level of endogenous ethylene production In contrast, DJ did not soften at all during 3 weeks experimental period even though considerable ethylene production was observed. Fruit of TH and DJ were treated with 5,000 ppm of propylene, an ethylene analog, continuously for 7 days. TH softened rapidly whereas DJ maintained high flesh firmness in spite of an increase in endogenous ethylene production, suggesting that DJ but not TH lacked the ability to be softened in response to endogenous and exogenous ethylene/propylene. DNA-seq analysis showed that tandem endo-polygalacturonase (endoPG) genes located at melting flesh (M) locus, Pp-endoPGM (PGM), and Pp-endoPGF (PGF), were deleted in DJ. The endoPG genes at M locus are known to control flesh texture of peach fruit, and it was suggested that the non-softening property of DJ is due to the lack of endoPG genes. On the other hand, TH possessed an unidentified M haplotype that is involved in determination of MF phenotype. Structural identification of the unknown M haplotype, designated as M-0, through comparison with previously reported M haplotypes revealed distinct differences between PGM on M-0 haplotype (PGM-M-0) and PGM on other haplotypes (PGM-M-1). Peach M haplotypes were classified into four main haplotypes: M-0 with PGM-M-0; M-1 with both PGM-M-1 and PGF; M-2 with PGM-M-1; and M-3 lacking both PGM and PGF. Re-evaluation of M locus in association with MF/non-melting flesh (NMF) phenotypes in more than 400 accessions by using whole genome shotgun sequencing data on database and/or by PCR genotyping demonstrated that M-0 haplotype was the common haplotype in MF accessions, and M-0 and M-1 haplotypes were dominant over M-2 and M-3 haplotypes and co-dominantly determined the MF trait. It was also assumed on the basis of structural comparison of M haplotypes among Prunus species that the ancestral haplotype of M-0 diverged from those of the other haplotypes before the speciation of Prunus persica

Recurrence of Atrial Fibrillation within Three Months after Pulmonary Vein Isolation in Patients with Paroxysmal Atrial Fibrillation : Analysis Using an External Loop Recorder with Auto-trigger Function

Pulmonary vein isolation (PVI) via catheter ablation has been shown to be a highly effective option for patients with symptomatic paroxysmal atrial brillation (AF). The recurrence of AF within 3 months after PVI is not considered a failure of the ablation procedure because early recurrence of AF is not always associated with late recurrence. We examined the usefulness of an external loop recorder with auto-trigger function (ELR-AUTO) to detect AF following PVI to characterize early recurrence and determine the implication of AF within 3 months after PVI. The study included 53 consecutive patients with symptomatic paroxysmal AF (age, 61.6 ± 12.6 years ; 77％ male) who underwent PVI, and were fitted with an ELR-AUTO for 7 ± 2 days within 3 months after PVI. Of the 33 patients(62.2％) who did not have AF within the 3-month period, only 1 patient had AF recurrence at 12 months. Seven of 20 patients (35％) who experienced AF within 3 months had symptomatic AF recurrence at 12 months. The sensitivity, specificity, positive predictive value, and negative predictive value of early AF recurrence for late recurrence was 87.5％, 71.1％, 35.0％, and 96.9％, respectively. Thus, AF recurrence detected by ELR-AUTO within 3 months after PVI can predict late AF recurrence. Freedom from AF in the firrst 3 months following ablation significantly predicts long-term freedom from AF. An ELR-AUTO is useful for detecting symptomatic and asymptomatic AF

Plasma Cathepsin S and Cathepsin S/Cystatin C Ratios Are Potential Biomarkers for COPD

Purpose. This study aimed to examine whether plasma levels of cathepsin S or its inhibitor, cystatin C, may serve as biomarkers for COPD. Patients and Methods. We measured anthropometrics and performed pulmonary function tests and chest CT scans on 94 patients with COPD and 31 subjects with productive cough but no airflow obstruction (“at risk”; AR). In these subjects and in 52 healthy nonsmokers (NS) and 66 healthy smokers (HS) we measured plasma concentrations of cathepsin S and cystatin C using an ELISA. Data were analyzed using simple and logistic regression and receiver operating characteristic analyses. Results. Cathepsin S and cystatin C plasma levels were significantly higher in the COPD and AR groups than in the NS and HS groups (p < 0.01). Among the COPD patients and AR subjects, plasma cathepsin S levels and cathepsin S/cystatin C ratios, but not cystatin C levels, were negatively related to severe airflow limitation (% FEV1 predicted < 50%; p = 0.005) and severe emphysema as assessed by low attenuation area (LAA) score on chest CT scans (LAA ≥ 8.0; p = 0.001). Conclusion. Plasma cathepsin S and cathepsin S/cystatin C ratios may serve as potential biomarkers for COPD

Laminin γ2 fragments are increased in the circulation of patients with early phase acute lung injury

Katayama, M., Ishizaka, A., Sakamoto, M. et al. Intensive Care Med (2010) 36: 479. https://doi.org/10.1007/s00134-009-1719-