Pleuroparenchymal Fibroelastosis with a Predominantly Airway-centered Distribution: A Late Complication of Chemotherapy.

Airway-centered fibroelastosis is a distinct entity characterized by prominent airway-centered elastosis of the upper lobe with little or no pleural involvement. Little is known regarding its etiology; however, it was reported to have an idiopathic or asthma-associated etiology. We document, for the first time, 2 women (19 and 60 years old) who developed pleuroparenchymal fibroelastosis with a predominantly airway-centered distribution as a late complication (6 and 9 years later, respectively) of chemotherapy. The disease rapidly progressed following the manifestation of symptoms, and they subsequently died (3 and 2 years later, respectively). Therefore, post-chemotherapy long-term monitoring for this disease is warranted.

Clinical characteristics of COVID-19 in Osaka, Japan: Comparison of the first-third waves with the fourth wave.

BACKGROUND: The fourth wave of COVID-19 in Osaka Prefecture, Japan, caused a medical crisis. Here, we aim to identify the risk factors for COVID-19 severity and compare patients between the first-third waves and the fourth wave. METHODS: We performed an observational retrospective study of COVID-19 cases at the National Hospital Organization Kinki-Chuo Chest Medical Center. RESULTS: We identified 404 patients (median age: 71.0 years [interquartile range: 56.0-80.0]), of whom 199 (49.1%) had mild disease, 142 (35.2%) had moderate disease, and 63 (15.6%) had severe disease. The overall mortality rate was 5.4% (22/404). Based on multivariate logistic regression analysis, cardiovascular disease, fever, dyspnea, and several inflammatory biomarkers were independent risk factors for moderate to severe disease. For every 1 mg/dL increase in C-reactive protein, 10 IU/L increase in lactate dehydrogenase, and 100 ng/mL increase in ferritin, the risk for moderate to severe disease increased by 18.3%, 12.9%, and 8.9%, respectively. Overall disease severity in the fourth wave was higher than in the first-third waves. However, there was no significant difference in mortality. Because of a shortage of beds, four of the 28 severe patients (14.3%) in the fourth wave could not be transferred to the advanced hospital. CONCLUSIONS: Cardiovascular disease, fever, dyspnea, and several inflammatory biomarkers were risk factors for moderate to severe COVID-19 in our cohort. During the fourth wave, COVID-19 severity worsened, increasing the number of patients who could not be transferred to beds for severe cases, resulting in a medical crisis in Osaka.

B cell-activating factors in autoimmune pulmonary alveolar proteinosis.

BACKGROUND: Autoimmune pulmonary alveolar proteinosis (APAP) results from the suppression of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling by a neutralizing autoantibody against GM-CSF. B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are involved in immunoglobulin G production and are overproduced in various autoimmune disorders. We hypothesized that BAFF and/or APRIL levels would be elevated in serum and bronchoalveolar lavage fluid (BALF) and serum and BALF levels of BAFF and APRIL respond to the treatments (whole lung lavage (WLL) or inhalation of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF)) in patients with APAP. SUBJECTS AND METHODS: BAFF and APRIL levels in serum and BALF from 110 patients with APAP were measured at baseline and during and after treatment, using an enzyme-linked immunosorbent assay kit. We enrolled 34 healthy volunteers as serum cytokine controls, and 13 disease controls for BALF. Associations of BAFF and APRIL levels with clinical measures were assessed to clarify their clinical roles. RESULTS: In patients with APAP, serum BAFF and APRIL levels were significantly increased relative to healthy volunteers (p < 0.0001 and p < 0.05, respectively), and BALF BAFF and APRIL levels were significantly increased versus disease controls (p < 0.0001 and p < 0.01, respectively). Serum BAFF levels (but not APRIL levels) were significantly correlated with Krebs von den Lungen-6 (KL-6), surfactant protein (SP)-D, SP-A, and lactate dehydrogenase (p < 0.0001). There was no significant correlation between serum BAFF or APRIL levels and anti-GM-CSF autoantibody. BAFF and APRIL were negatively correlated with single-breath diffusion capacity for carbon monoxide (DLco) (p = 0.004) and forced vital capacity (p = 0.04), respectively. BAFF (but not APRIL) in BALF was negatively correlated with vital capacity (p = 0.04) and DLco (p = 0.006). There were significant correlations between disease severity and BAFF levels in serum (p = 0.04) and BALF (p = 0.007). Serum levels of anti-GM-CSF autoantibody, BAFF, and APRIL were not significantly affected by WLL or inhalation of recombinant human GM-CSF. CONCLUSIONS: BAFF and APRIL levels of sera and BALF in APAP were significantly increased compared with healthy volunteer and disease control, and the BAFF and APRIL pathway might have important specific roles in pathogenesis of APAP. Our data suggest a new perspective of future treatment for APAP.

Seroradiologic prognostic evaluation of acute exacerbation in patients with idiopathic interstitial pneumonia: a retrospective observational study.

BACKGROUND: We previously reported that high-resolution computed tomography (HRCT) patterns and certain serum marker levels can predict survival in patients with acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) and in those with idiopathic interstitial pneumonias (IIPs). The utility of serum marker changes before and during AE has not been previously evaluated. This study aimed to clarify whether changes in serum marker levels could improve the prognostic significance of HRCT patterns in patients with AE-IIPs. METHODS: Seventy-seven patients (60 males, 17 females) with AE-IIP diagnosed between 2004 and 2016 and whose serum Krebs von den Lungen (KL)-6 and surfactant protein (SP)-D levels were measured before and at the onset of AE were enrolled in this study. The HRCT pattern of each patient was classified as diffuse, multifocal, or peripheral. We examined the prognostic significance of the HRCT pattern, increased serum marker levels, and a combination of these parameters using Cox proportional hazard regression analysis. RESULTS: Fifty-three patients had IPF and 24 had non-IPF IIP. A serum KL-6 level that was increased compared with the level in the stable state (ΔKL-6/ST-KL-6: ≤0.211) was a significantly poor prognostic factor in patients with a multifocal pattern. Multivariate Cox analysis identified long-term oxygen therapy, a partial oxygen tension/fraction of inspired oxygen ratio ≤200 Torr, and an elevated SP-D level during a stable state to be significantly poor prognostic factors in all patients. A diffuse HRCT pattern was not a significant prognostic factor in an AE-IIP in multivariate analysis after adjustment; however, a multifocal pattern accompanying a ΔKL-6/ST-KL-6 ≤0.211 or a diffuse pattern was a significantly poor prognostic factor than a peripheral pattern or a multifocal pattern with ΔKL-6/ST-KL-6 >0.211. CONCLUSIONS: Combining the HRCT pattern and the ΔKL-6/ST-KL-6 value can improve our ability to predict the survival of AE-IIP patients.