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Background: Lipocalin-2 (LCN2) is a secretory glycoprotein upregulated by oxidative stress; moreover, patients with idiopathic pulmonary fibrosis (IPF) have shown increased LCN2 levels in bronchoalveolar lavage fluid (BALF). This study aimed to determine whether circulatory LCN2 could be a systemic biomarker in patients with IPF and to investigate the role of LCN2 in a bleomycin-induced lung injury mouse model. Methods: We measured serum LCN2 levels in 99 patients with stable IPF, 27 patients with acute exacerbation (AE) of IPF, 51 patients with chronic hypersensitivity pneumonitis, and 67 healthy controls. Further, LCN2 expression in lung tissue was evaluated in a bleomycin-induced lung injury mouse model, and the role of LCN2 was investigated using LCN2-knockout (LCN2 -/-) mice. Results: Serum levels of LCN2 were significantly higher in patients with AE-IPF than in the other groups. The multivariate Cox proportional hazards model showed that elevated serum LCN2 level was an independent predictor of poor survival in patients with AE-IPF. In the bleomycin-induced lung injury mouse model, a higher dose of bleomycin resulted in higher LCN2 levels and shorter survival. Bleomycin-treated LCN2 -/- mice exhibited increased BALF cell and protein levels as well as hydroxyproline content. Moreover, compared with wild-type mice, LCN2-/- mice showed higher levels of circulatory 8-isoprostane as well as lower Nrf-2, GCLC, and NQO1 expression levels in lung tissue following bleomycin administration. Conclusions: Our findings demonstrate that serum LCN2 might be a potential prognostic marker of AE-IPF. Moreover, LCN2 expression levels may reflect the severity of lung injury, and LCN2 may be a protective factor against bleomycin-induced acute lung injury and oxidative stress. [ABSTRACT FROM AUTHOR]

Background and Objective: Checkpoint inhibitor pneumonitis (CIP), caused by the anti‐programmed cell death‐1 (PD‐1)/programmed cell death ligand‐1 (PD‐L1) antibody, can be a fatal adverse event in cancer patients. However, no predictive biomarkers for CIP have been identified. Because high‐mobility group box 1 (HMGB1) can aggravate lung injury and potentially increase the immune response, it was investigated as a predictive blood marker. Methods: Blood samples, prospectively stored before anti‐PD‐1/PD‐L1 monotherapy between December 2015 and October 2020, were obtained at two university hospitals from 87 and 43 non‐small cell lung cancer (NSCLC) patients (discovery and validation cohorts, respectively). We retrospectively evaluated the association of serum HMGB1 levels with the incidence of CIP developed within 3 months of initiating anti‐PD‐1/PD‐L1 therapy. Results: CIP was observed in 9 (10.3%) and 6 (14.0%) patients in the discovery and validation cohorts, respectively. In each cohort, serum HMGB1 levels were significantly and reproducibly higher in patients with CIP. In the discovery cohort, an HMGB1 cut‐off level of 11.24 ng/ml was identified by receiver operating characteristic analysis. CIP incidence in the HMGB1high subgroup was significantly higher than that in the HMGB1low subgroup in the discovery (41.2% vs. 2.9%) and validation cohorts (36.4% vs. 6.3%). In an exploratory pooled analysis, three patients died of grade 5 CIP; a 19.29 ng/ml HMGB1 cut‐off level detected grade 5 CIP with 100% sensitivity and 96.85% specificity. Conclusion: Our results suggest that HMGB1 may be a potential blood marker to predict the development and severity of CIP in NSCLC patients. CIP incidence in the patients with high levels of serum HMGB1 (≥ 11.24 ng/ml) was significantly and reproducibly higher than in those with its low levels (< 11.24 ng/ml) in patients with NSCLC. Our results suggest that HMGB1 may be a potential blood marker for the prediction of CIP. [ABSTRACT FROM AUTHOR]

Introduction: Immunoglobulin G4-related disease (IgG4-RD) responds well to glucocorticoids but is often associated with relapses. Interleukin (IL)-4 and IL-13 are involved in the pathogenesis of IgG4-RD. We present the first case in which dupilumab was an effective adjunct treatment for a patient with steroid-dependent IgG4-RD complicated by asthma.Case study: A 57-year-old man was referred to our hospital for further investigation and treatment of proptosis with neck swelling in 2019. He developed a cough and swelling of the neck in 2016. He was diagnosed with asthma in 2017 and started receiving inhaled glucocorticoids and a long-acting beta-agonist. The patient started receiving oral prednisolone at a dose of 20 mg/day. Oral prednisolone reduced his symptoms, but he relapsed when treatment was tapered to less than 10 mg/day. He was diagnosed with IgG4-RD through a parotid gland biopsy.Results: Azathioprine was given to reduce systemic glucocorticoids. The prednisolone dose was gradually tapered to 10 mg/day, resulting in the relapse of proptosis and an asthma attack. We added dupilumab, and his asthma symptoms and proptosis improved. Serum IgG4 levels continued to decrease, and the prednisolone dose was tapered to 2 mg.Conclusion: Dupilumab might be useful as an adjunctive treatment for patients with steroid-dependent IgG4-RD complicated by asthma. Serum IgG4 levels can be used as a marker to monitor dupilumab treatment in IgG4-RD. [ABSTRACT FROM AUTHOR]

Vocal cord dysfunction (VCD) often coexists with asthma and exacerbates respiratory symptoms. A noninvasive method could be considered beneficial for the detection and follow-up of VCD complicated by asthma. Here, we report a case of VCD complicated by asthma, highlighting the effectiveness of colored three-dimensional (3-D) imaging of respiratory impedance using a broadband frequency forced oscillation technique (MostGraph). A 74-year-old woman with difficult-to-treat asthma, in whom mepolizumab treatment was ineffective, was referred to our hospital. Stridulous sounds were loudest over the anterior neck. Pulmonary function tests' results were normal; however, a flattening of the inspiratory flow-volume curve was detected. Remarkably, prominent spikes were observed in the inspiratory phase in the colored 3-D imaging of respiratory resistance, which was superimposed on increased respiratory resistance in the expiratory phase. Flexible laryngoscopy revealed the adduction of vocal cords on inspiration. The patient was diagnosed with asthma complicated by VCD. After successful treatment of VCD by speech therapy, inspiratory spikes of respiratory resistance disappeared, and normal vocal cord movement was observed on laryngoscopy. The present case report indicates the effectiveness of forced oscillometry in evaluating dynamic changes in respiratory resistance for detecting and monitoring VCD complicated by asthma. [ABSTRACT FROM AUTHOR]

Objectives: Bronchoscopy is frequently performed for patients suspected of having lung cancer; however, we sometimes fail to make a definitive diagnosis, resulting in additional invasive testing. Many studies indicate that microRNAs (miRs) are abnormally expressed in cancers. We examined the diagnostic value of 4 miRs (miR-21, miR-31, miR-182, and miR-183) extracted from liquid-based cytology (LBC) samples and validated whether they were diagnostically useful.Methods: We collected 18 surgically resected tissue samples and 136 LBC specimens obtained during bronchoscopic examination at Hiroshima University Hospital. We extracted RNA from these samples and compared the expression of 4 miRs by reverse transcription-quantitative polymerase chain reaction.Results: We confirmed that expression of the 4 miRs was significantly higher in cancer tissues than in tumor-adjacent normal tissues. We examined the expression of these miRs in 125 (cancer cases, 83; noncancer cases, 42) of 136 cytologic samples. Expression of all 4 miRs was significantly higher in patients with lung cancer than in those without lung cancer. Among samples judged as benign or indeterminate, levels of these miRs were also significantly higher in patients with lung cancer than in those without lung cancer.Conclusions: The analysis of miR expression in LBC samples might be helpful for primary lung cancer diagnosis. [ABSTRACT FROM AUTHOR]

Early detection and appropriate management of treatment-related interstitial lung disease (ILD) are important in cancer treatment. We established an algorithm for quantifying fine crackles using machine learning and reported that the fine crackle quantitative value (FCQV) calculated by this algorithm was more sensitive than chest radiography for detecting interstitial changes. Using this algorithm, we periodically analyzed respiratory sounds in two patients with lung cancer who developed treatment-related ILDs and found that the FCQV was elevated before the diagnosis of ILD. These cases may indicate the usefulness of the FCQV in the early diagnosis of treatment-related ILDs.

Background: A significant number of children with asthma show remission in adulthood. Although these adults are often diagnosed with COPD in later life, the effect of clinically remitted childhood asthma on the decline in lung function during adulthood is uncertain. We examined whether clinical remission of childhood asthma was associated with an accelerated decline in lung function in apparently nonasthmatic adults., Methods: 3584 participants (mean (range) age 48.1 (35-65) years) who did not have adulthood asthma and other lung diseases and had normal lung function at the baseline visit were included. They were categorised as those with remitted childhood asthma (n=121) and healthy controls (n=3463) according to their self-reported childhood asthma history. Spirometry was performed at baseline and follow-up visits., Results: The mean follow-up was 5.3 years. Multivariate regression analysis showed that remitted childhood asthma and smoking were independently associated with a rapid decline in forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC). Smoking was an independent predictor of a rapid decline in FEV 1 /FVC. The annual decline in FEV 1 and FVC was significantly greater in participants with remitted childhood asthma than in healthy controls, and the differences remained significant after adjusting for the propensity score., Conclusions: A history of clinically remitted childhood asthma is an independent risk factor for accelerated decline in lung function in adults. Remitted childhood asthma and smoking may additively accelerate the development of obstructive lung disease., Competing Interests: Conflict of interest: S. Miura has nothing to disclose. Conflict of interest: H. Iwamoto has nothing to disclose. Conflict of interest: K. Omori has nothing to disclose. Conflict of interest: K. Yamaguchi has nothing to disclose. Conflict of interest: S. Sakamoto has nothing to disclose. Conflict of interest: Y. Horimasu has nothing to disclose. Conflict of interest: T. Masuda has nothing to disclose. Conflict of interest: S. Miyamoto has nothing to disclose. Conflict of interest: T. Nakashima has nothing to disclose. Conflict of interest: K. Fujitaka has nothing to disclose. Conflict of interest: H. Hamada has nothing to disclose. Conflict of interest: A. Yokoyama has nothing to disclose. Conflict of interest: N. Hattori reports grants from Teijin Pharma Co., Japan, during the conduct of the study. All other authors have nothing to disclose., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)