＜Editors' Choice＞ Comparison of clinical features between patients with acute exacerbation of idiopathic interstitial pneumonia and collagen vascular disease-associated interstitial pneumonia.

Acute exacerbation (AE) of interstitial pneumonia (IP) shows poor prognosis, due to the typical histological pattern of diffuse alveolar damage superimposed upon lung fibrosis. The previous reports comparing clinical features between AE of idiopathic interstitial pneumonias (IIPs) and those of IPs with known etiology are limited. We retrospectively compared clinical parameters including age, sex, Charlson Comorbidity Index score (CCIS), blood biomarkers at diagnosis of AE, treatment, and 3-month mortality between patients with AE of IIPs and collagen vascular disease-associated interstitial pneumonia (CVD-IP). We assessed 85 patients, comprising 66 patients with AE of IIPs (78%) and 19 patients with AE of CVD-IP (22%). The least absolute shrinkage and selection operator regression selected CCIS (hazard ratio, 1.281; 95% confidence interval, 1.055-1.556; P = 0.012) and log serum lactate dehydrogenase (LDH) (hazard ratio, 6.267; 95% confidence interval, 2.172-18.085; P < 0.001) as significant predictors of 3-month mortality among these patients. Also, the adjusted survival curves using sex, CCIS, and serum LDH showed no significant differences between these two groups. In conclusion, among AE patients, CCIS and serum LDH level may be more important prognostic factors for 3-month mortality rather than two classification of IP subtypes: IIPs and CVD-IP.

Limited efficacy of low-dose dexamethasone for the treatment of severe COVID-19 pneumonia: A retrospective study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2. Its symptoms range from mild to severe, with the latter often being life-threatening. This study aims to assess the effects of low-dose dexamethasone (DEX) in mild-to-severe COVID-19 pneumonia and examine the final clinical outcomes to identify the optimal therapeutic dose. METHODS: Clinical data from 132 patients hospitalized for COVID-19 pneumonia between January and October 2021 at Yamato Municipal Hospital were retrospectively analyzed. Based on the ratio of peripheral arterial oxygen saturation (SpO2) to inspired fraction of oxygen (FiO2), patients were categorized into the mild (>450, n = 65), moderate (315-450, n = 55), and severe (<315, n = 12) pneumonia groups. The event of interest was defined as the worsening of the patient's condition during treatment (need to increase FiO2 > 0.1). Patients were treated with low-dose DEX (6.6 mg/day) for 10 days. RESULTS: The event-free survival rate decreased significantly in patients with severe pneumonia compared with in those with mild and moderate pneumonia (Bonferroni-adjusted p < 0.02). A total of 16 patients were treated with high-dose corticosteroids because of severe hypoxia. Recovery was observed in all discharged patients with respiratory condition improvement. Low SpO2/FiO2 at admission was significantly associated with serum C-reactive protein levels. CONCLUSIONS: For Japanese patients with COVID-19, severe pneumonia, and SpO2/FiO2 of <315, it may be necessary to administer a dose of corticosteroids of >6.6 mg DEX.

ALK-Rearranged NSCLC With Concomitant HER2-Mutant Breast Cancer Patient Treated With Alectinib, Trastuzumab, and Pertuzumab: A Case Report.

Multiple cancers are a common occurrence, and the choice of treatment can be a challenging decision. The current case report describes a 71-year-old woman with overlapping anaplastic lymphoma kinase (ALK)-rearranged lung adenocarcinoma and HER2-mutant breast cancer, who achieved improvement with concurrent use of the molecularly targeted agents Alectinib, Trastuzumab, and Pertuzumab. A 71-year-old woman was diagnosed with lung adenocarcinoma and brain metastases, and invasive ductal carcinoma of the right breast, HER2-mutant type. In March 2021, a biopsy confirmed the presence of the ALK fusion gene in lung cancer. In April 2021, he started Alectinib and showed shrinkage of lung cancer; in December 2021, a metastatic liver tumor was found, and a liver biopsy diagnosed liver metastasis of breast cancer. Therefore, Alectinib was discontinued in February 2022, and Trastuzumab, Pertuzumab, and Docetaxel were started as chemotherapy for breast cancer. She continued treatment with Trastuzumab and Pertuzumab, but in July 2022, she developed an increase in lung cancer. Her metastatic liver tumor continued shrinking, and she was started on Trastuzumab, Pertuzumab, and Alectinib. After six months of treatment, the patient showed a sustained reduction in both lung cancer, breast cancer, and brain metastases with no adverse events. ALK rearrangement lung cancer often develops in young women, and similarly, breast cancer often develops in women. Therefore, those cancers may occur simultaneously. In such cases, the choice of treatment can be difficult, as both cancers require different approaches. Alectinib has been shown to have a high response rate and prolonged progression-free survival in ALK-rearranged non-small cell lung cancer (NSCLC). Trastuzumab and Pertuzumab are commonly used for the treatment of HER2-mutant breast cancer and have been shown to significantly improve progression-free survival and overall survival. This case report provides evidence that the concurrent use of Alectinib, Trastuzumab, and Pertuzumab can be an effective treatment for patients with overlapping ALK-rearranged NSCLC and HER2-mutant breast cancer. It is important to consider concurrent treatment in patients with multiple cancers to optimize treatment outcomes and improve quality of life. However, further studies are needed to establish the safety and efficacy of this combination of drugs for the treatment of overlapping cancers.

Assessment of diagnostic utility of serum hemeoxygenase-1 measurement for acute exacerbation of interstitial pneumonias.

The present study aimed to evaluate whether serum heme oxygenase (HO)-1 could be a reliable blood biomarker for diagnosing acute exacerbations (AEs) of both idiopathic interstitial pneumonia (IIP) and secondary interstitial pneumonia (SIP). Serum HO-1 levels of newly diagnosed patients with IP were measured, and the relationships between serum HO-1 and other serum biomarkers and high-resolution CT scores, were evaluated. Blood samples were collected from 90 patients with IIP, including 32 having an AE, and 32 with SIP, including 9 having an AE. The patients having an AE had significantly higher HO-1 levels than those not having an AE (35.2 ng/mL vs. 16.4 ng/mL; p < 0.001). On receiver operating characteristics (ROC) curve analysis for serum HO-1 ability to detect an AE, the area under the ROC curve (AUC) was 0.87 in patients with IIPs and 0.86 in those with SIPs. Also, in patients with both IIPs and SIPs, the combination of the serum HO-1 level and the GGO score showed favorable AUCs (IIPs: 0.92, SIPs: 0.83), though HO-1-not-including model (combination of LDH and GGO) also showed acceptable AUCs. Serum HO-1 could be a clinically useful biomarker for the accurate diagnosis of patients with AEs.

Entrectinib-Induced Heart Failure in a Patient With Metastatic Lung Adenocarcinoma: A Case Report.

Entrectinib is a recently approved multikinase inhibitor to treat advanced c-ros oncogene1 (ROS1) positive non-small cell lung cancer (NSCLC). Although molecular targeted therapy is generally well tolerated, cardiovascular adverse events have been described in recent years. We report a case of NSCLC with ROS1 rearrangement where the patient developed drug-induced heart failure after receiving entrectinib. A 74-year-old non-smoker female patient was diagnosed with stage IVB lung adenocarcinoma with ROS-1 positive and right breast cancer stage I. We started on entrectinib as the first-line therapy for lung cancer. Five days after, she developed oral dysesthesia and blood creatinine increased. These findings gradually worsened, so we temporarily discontinued entrectinib. After withholding the drug for 14 days, these findings improved, and we resumed entrectinib at a reduced dose. On day 19 of the reduced entrectinib dose, she presented to the outpatient with shortness of breath and bilateral lower extremity edema, accompanied by respiratory failure. Laboratory evaluation revealed elevated N-terminal pro-brain natriuretic peptide (NT-pro BNP), troponin I, creatine kinase (CK), and C reactive protein (CRP), and transthoracic echocardiogram showed congestive heart failure (CHF) with a preserved ejection fraction (HFpEF). She did not complain of chest pain and fever, so we did not consider ischemic heart disease and viral myocarditis in the initial evaluation. There was no other causative cause of CHF. Therefore, we suspected entrectinib-related heart failure. Her symptoms improved and she recovered her cardiac function to baseline within a week of discontinuation of entrectinib and standard heart failure treatment. She developed heart failure after a one-step dose reduction and was prone to cardiotoxicity due to entrectinib. Considering that she could be treated with crizotinib, we decided discontinuation of entrectinib permanently. This case report highlights the potential cardiotoxicity of entrectinib and suggests the need for close monitoring of the cardiac functions of patients receiving entrectinib.

[A CASE OF SUMMER-TYPE HYPERSENSITIVITY PNEUMONITIS ACCOMPANIED BY THE SYNDROME OF INAPPROPRIATE SECRETION OF ANTIDIURETIC HORMONE].

A 47-year old man presented to our hospital with a 6-month history of malaise, cough and dyspnea on exertion. Laboratory testing revealed the severe hyponatremia. A chest X-ray showed bilateral diffuse micronodules. Anti-Trichosporon asahii antibody and environmental provocation test were positive. Bronchoalveolar lavage fluid showed lymphocytosis and low CD4/8 ratio. The specimens obtained by transbronchial lung biopsy revealed alveolitis. Based on these findings, the patient was diagnosed as having summer-type hypersensitivity pneumonitis (SHP). The patient was treated with antigen avoidance and oral corticosteroid. The hyponatremia caused by syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was treated with normal saline and water restriction. Serum sodium level was improved with treatment of SHP, which suggested the relevance between SHP and SIADH.

[FAMILIAL SUMMER-TYPE HYPERSENSITIVITY PNEUMONITIS INDUCED IN SUMMER AND WINTER AT THE WORK PLACE].

We report two family members, a 64-year-old woman (patient 1) and her 37-year-old son (patient 2) diagnosed with summer-type hypersensitivity pneumonitis (SHP). Both patients had high serum titers of anti-Trichosporon asahii antibody. The patients lived in the same house and worked in the same barbershop. Patient 1 was diagnosed with SHP in the summer, and she reacted positively to the provocation test at the work place, but not in the house. Patient 2 was diagnosed with SHP in the winter. Generally, SHP develops and is diagnosed in the summer. The home environment is responsible for most cases of familial SHP. Therefore, our cases of familial SHP are unusual and may suggest that the clinical characteristics of SHP have changed, due to alterations in social and environmental conditions.