Outcomes and prognosis of progressive pulmonary fibrosis in patients with antineutrophil cytoplasmic antibody-positive interstitial lung disease.

Approximately one-third of fibrosing interstitial lung diseases exhibit progressive pulmonary fibrosis (PPF), a clinicopathological condition distinct yet resembling idiopathic pulmonary fibrosis (IPF). PPF in ANCA-positive ILD (ANCA-ILD) is poorly documented. To clarify incidence, predictors of PPF in ANCA-ILD, and their prognostic impact, 56 patients with ANCA-ILD were followed for ≥ 1 year (April 2004 to April 2021). PPF was defined per ATS/ERS/JRS/ALAT PPF 2022 guideline. We compared PPF and non-PPF in 38 patients with pulmonary function tests and ≥ 1 year follow up. ANCA-ILD (19 male, 19 female; mean age 72 years) comprised 21 patients with microscopic polyangiitis ILD (MPA-ILD) and 17 with ANCA-positive IP without systemic vasculitis (ANCA-IP). PPF occurred in 15/38 (39.5%) overall, and 27% of patients with MPA-ILD and 53% with ANCA-IP. Patient characteristics did not differ between PPF and non-PPF, however, the survival was significantly worse in patients with PPF than those with non-PPF. On multivariate regression analysis, higher age, higher serum SP-D level, and lower baseline %FVC were associated with PPF. In ANCA-ILD, 39.5% of patients demonstrated PPF, which is associated with increased mortality. Predictors of PPF were older age, higher SP-D, and lower baseline %FVC.

Novel Effector RHIFs Identified From Acidovorax avenae Strains N1141 and K1 Play Different Roles in Host and Non-host Plants.

Plant pathogenic bacteria inject effectors into plant cells using type III secretion systems (T3SS) to evade plant immune systems and facilitate infection. In contrast, plants have evolved defense systems called effector-triggered immunity (ETI) that can detect such effectors during co-evolution with pathogens. The rice-avirulent strain N1141 of the bacterial pathogen Acidovorax avenae causes rice ETI, including hypersensitive response (HR) cell death in a T3SS-dependent manner, suggesting that strain N1141 expresses an ETI-inducing effector. By screening 6,200 transposon-tagged N1141 mutants based on their ability to induce HR cell death, we identified 17 mutants lacking this ability. Sequence analysis and T3SS-mediated intracellular transport showed that a protein called rice HR cell death inducing factor (RHIF) is a candidate effector protein that causes HR cell death in rice. RHIF-disrupted N1141 lacks the ability to induce HR cell death, whereas RHIF expression in this mutant complemented this ability. In contrast, RHIF from rice-virulent strain K1 functions as an ETI inducer in the non-host plant finger millet. Furthermore, inoculation of rice and finger millet with either RHIF-deficient N1141 or K1 strains showed that a deficiency of RHIF genes in both strains results in decreased infectivity toward each the host plants. Collectively, novel effector RHIFs identified from A. avenae strains N1141 and K1 function in establishing infection in host plants and in ETI induction in non-host plants.

Inhibition of neutral lipid synthesis by avarols from a marine sponge.

The effects of 14 sesquiterpene hydroquinones, including 8 marine sponge-derived avarols (1-8) and 6 semisynthetic derivatives (9-14), on lipid droplet accumulation and neutral lipid synthesis in Chinese hamster ovary (CHO) K1 cells were investigated. In intact CHO-K1 cell assays, avarol (1) markedly decreased the number and size of lipid droplets in CHO-K1 cells and exhibited the most potent inhibitory activity on the synthesis of cholesteryl ester (CE) and triglyceride (TG) with IC50 values of 5.74 and 6.80 µM, respectively. In enzyme assays, sterol O-acyltransferase (SOAT), the final enzyme involved in CE biosynthesis, and diacylglycerol acyltransferase (DGAT), the final enzyme involved in TG biosynthesis, were inhibited by 1 with IC50 values of 7.31 and 20.0 µM, respectively, which correlated well with those obtained in the intact cell assay. These results strongly suggest that 1 inhibited SOAT and DGAT activities in CHO-K1 cells, leading to a reduction in the accumulation of CE and TG in lipid droplets.

Chest High-Resolution CT Findings of Microscopic Polyangiitis: A Japanese First Nationwide Prospective Cohort Study.

OBJECTIVE. The lung is one of the organs possibly involved in microscopic polyangiitis (MPA), and myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA) is commonly found in patients with MPA. The aim of this study was to assess pulmonary lesions in Japanese patients with MPA. SUBJECTS AND METHODS. This prospective study was based on 144 patients with MPA who were enrolled in the Remission Induction Therapy in Japanese Patients With ANCA-Associated Vasculitis and Rapidly Progressive Glomerulonephritis Study and who underwent chest high-resolution CT (HRCT) imaging at the time of diagnosis during 2011-2014. We reviewed the electronic case report forms of patients with MPA who did and did not have interstitial pneumonia (IP), and the clinical features and laboratory findings of these groups were compared. RESULTS. Abnormal HRCT findings were noted in 134 of the 144 patients (93%). Chest HRCT findings included ground-glass opacity (n = 72; 50%), reticulation (n = 69; 48%), traction bronchiectasis (n = 57; 42%), honeycombing (n = 44; 31%), and emphysema (n = 32; 22%). IP was diagnosed radiologically in 74 patients (51%), 38% of whom had the usual IP (UIP) pattern. Ground-glass opacity, reticulation, traction bronchiectasis, honeycombing, and interlobular septal thickening were frequent in patients with IP (p < 0.05). Patients with MPA with the UIP or possible UIP pattern also had minor findings, such as bronchial wall thickening, consolidation, increased attenuation around honeycombing, and traction bronchiectasis. CONCLUSION. IP (51%) was most commonly observed in Japanese patients with MPA, and 38% of these patients exhibited a UIP pattern. Increased attenuation around honeycombing or traction bronchiectasis was also found.

The Utility of Virtual Bronchoscopy Using a Computed Tomography Workstation for Conducting Conventional Bronchoscopy: A Retrospective Analysis of Clinical Practice.

BACKGROUND: Recent clinical trials demonstrated the benefits of several guided-bronchoscopy technologies for the diagnosis of peripheral pulmonary lesions (PPLs). However, introduction of these technologies is expensive. Therefore, in clinical practice, these are unavailable in many hospitals. In contrast, virtual bronchoscopy (VB) using the computed tomography (CT) workstation can be made available immediately without additional cost as many hospitals already have the CT scan facility. However, the effectiveness of VB alone remains to be shown. OBJECTIVES: The aim of this study was to investigate the effect of VB using the CT workstation in hospitals performing conventional bronchoscopy. METHODS: Results from consecutive patients who underwent bronchoscopy for small PPLs (major diameter ≤30 mm) were retrospectively reviewed. Sixty-nine patients who underwent bronchoscopy without VB from April 2014 to March 2015 and 56 patients who underwent bronchoscopy with VB from April 2015 to December 2015 were assigned to non-VB and VB groups, respectively. We compared the two groups and analyzed the factors affecting the diagnostic yield. RESULTS: The VB group had a significantly higher diagnostic yield than the non-VB group (57.1 vs. 33.3%; p = 0.008). In the multivariate analysis, VB was identified as a significant factor affecting the diagnostic yield (odds ratio: 3.30, p = 0.011). CONCLUSIONS: In the conventional bronchoscopy settings, VB using the CT workstation is efficient for the diagnosis of PPLs when other guided-bronchoscopy techniques are unavailable.

Frameshift Mutation Confers Function as Virulence Factor to Leucine-Rich Repeat Protein from Acidovorax avenae.

Many plant pathogens inject type III (T3SS) effectors into host cells to suppress host immunity and promote successful infection. The bacterial pathogen Acidovorax avenae causes brown stripe symptom in many species of monocotyledonous plants; however, individual strains of each pathogen infect only one host species. T3SS-deleted mutants of A. avenae K1 (virulent to rice) or N1141 (virulent to finger millet) caused no symptom in each host plant, suggesting that T3SS effectors are involved in the symptom formation. To identify T3SS effectors as virulence factors, we performed whole-genome and predictive analyses. Although the nucleotide sequence of the novel leucine-rich repeat protein (Lrp) gene of N1141 had high sequence identity with K1 Lrp, the amino acid sequences of the encoded proteins were quite different due to a 1-bp insertion within the K1 Lrp gene. An Lrp-deleted K1 strain (KΔLrp) did not cause brown stripe symptom in rice (host plant for K1); by contrast, the analogous mutation in N1141 (NΔLrp) did not interfere with infection of finger millet. In addition, NΔLrp retained the ability to induce effector-triggered immunity (ETI), including hypersensitive response cell death and expression of ETI-related genes. These data indicated that K1 Lrp functions as a virulence factor in rice, whereas N1141 Lrp does not play a similar role in finger millet. Yeast two-hybrid screening revealed that K1 Lrp interacts with oryzain α, a pathogenesis-related protein of the cysteine protease family, whereas N1141 Lrp, which contains LRR domains, does not. This specific interaction between K1 Lrp and oryzain α was confirmed by Bimolecular fluorescence complementation assay in rice cells. Thus, K1 Lrp protein may have acquired its function as virulence factor in rice due to a frameshift mutation.

Pulmonary involvement in ANCA-associated vasculitis from the view of the pulmonologist.

Microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) are conditions classified under the general heading of antinuclear cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). Lung lesion is a very common and important clinical feature in AAV. In MPA, diffuse alveolar hemorrhage and pulmonary fibrosis (PF) are the most frequent manifestations. High-resolution computed tomography (HRCT) chest findings associated with MPA in PF patients demonstrate a high frequency of usual interstitial pneumonia (UIP), fibrotic-nonspecific interstitial pneumonia (F-NSIP), and combined PF and emphysema (CPFE) pattern with honeycombing, traction bronchiectasis, ground-glass opacity, and emphysema. In most of these cases, the histologic pattern of PF has been classified as UIP and/or fibrotic NSIP. In addition, a high incidence of histological findings, such as extensive interstitial fibrosis, lymphoid hyperplasia, and bronchiolitis, are characteristics observed in PF associated with collagen vascular diseases and which are not observed in idiopathic PF (IPF). In some cases, PF precedes the development of MPA. Indeed, there are some cases of pulmonary-limited MPA in this group. Therefore, clinicians should be aware of MPA as an underlying feature of PF in order to avoid overlooking and misdiagnosing this condition as IPF. The median survival time (MST) in UIP pattern/MPA is comparable with that of IPF. In GPA, almost all patients have either upper airway or lower respiratory tract lesions. Solitary or multiple nodules (frequently cavitated) and masses are the most common findings on chest images. Asthma is a cardinal symptom of Churg-Straus syndrome, often preceded by allergic rhinitis. To induce remission, a severity-based regimen was given to patients according to the appropriate protocol of the Japanese patients with myeloperoxidase (MPO)-ANCA-associated vasculitis (JMAAV) study group: low-dose corticosteroid and, if necessary, cyclophosphamide or azathioprine in patients with mild form; high-dose corticosteroid and cyclophosphamide in those with severe form; severe-form regimen plus plasmapheresis in those with the most severe form.

Cavitary pulmonary infection with Mycobacterium avium observed by bronchoscopy.

A 58-year-old man was admitted to our hospital because of fever and loss of appetite. He had undergone surgery for esophageal cancer. A chest radiography 12 years after the surgery revealed cavitary lesions in the right upper lobe of the lung. The patient was then diagnosed as having Mycobacterium avium infection. The cavitary lesions worsened 2 years after clarithromycin monotherapy. Bronchoscopy was performed to observe the interior of the cavity. Gray debris adhering to the cavitary wall decreased after intensive treatment with Streptomycin, rifabutin, levofloxacin, and ethambutol. This is a rare case in which treatment efficacy of M. avium infection was directly observed by serial bronchoscopy.

Negative pressure pulmonary edema during tracheal Dumon stent implantation.

Negative pressure pulmonary edema (NPPE), or acute postobstructive pulmonary edema, is caused by negative intrathoracic pressure against an obstructed upper airway. Although NPPE is generally a benign condition, several fatal cases attributed to the delay in diagnosis have been reported. We report a case of NPPE experienced during Dumon stent placement. In a 39-year-old man, unilateral NPPE developed upon relief from a right main bronchial obstruction caused by a blood clot within the Dumon. The incident indicates that the "increased preload theory" is unable by itself to explain the pathophysiology of NPPE. Although we preferred spontaneous assisted ventilation for interventional rigid bronchoscopy, the potential risk of NPPE during Dumon stent placement, especially in spontaneously breathing young, healthy patients, needs to be considered.