Outcome of COVID-19 in interstitial lung disease patients treated with anti-inflammatory drugs and antiviral drugs.

A recent study reported that patients with interstitial lung disease (ILD) are at increased risk of death from coronavirus disease 2019 (COVID-19). However, there are no studies on the outcome of COVID-19 patients with preexisting ILD treated with corticosteroids or antiviral drugs. We extracted 26 patients with preexisting ILD by medical records and HRCT pattern. Of 503 patients with COVID-19, we selected 52 patients as control matched for age and sex. Twenty out of the 26 ILD patients (76.9%) received corticosteroid therapy, and 23 patients (88.5%) also received antiviral treatment with remdesivir or favipiravir. Although no statistical difference was found, the proportion of severe patients in ILD group tended to be higher than in non-ILD group (23.1% vs. 42.3%; p = 0.114). Also, mortality rate in ILD group tended to be higher than in non-ILD patients (11.5% vs. 3.8%; p = 0.326). In univariate analysis to evaluate risk factors for severe condition, diagnosis of idiopathic pulmonary fibrosis, usual interstitial pneumonia pattern, and honeycomb lung were not risk factors of severe disease. Treatment with corticosteroids, antiviral drugs, and immunosuppressive agents may affect the outcome of COVID-19 patients with ILD.

Clinical characteristics of Japanese patients with moderate to severe COVID-19.

INTRODUCTION: Although several reports on the risk factors for severe disease of COVID-19 already exist, reports on effective early indicators are still limited, especially from Japan. This study was conducted to clarify the patient's characteristics whose disease progressed to severe status. METHODS: The medical records of all consecutive 300 Japanese patients hospitalized at our institution between February and November 2020 were retrospectively reviewed. The clinical characteristics were evaluated to compare between mild (no oxygen needed), moderate (oxygen needs of 1-4 L/min), and severe diseases (oxygen needs of 5 L/min or more). RESULTS: The median age was 68 years old, with 123 (41.0%) males and 177 (59.0%) females. Of these, 199 patients (66.3%), 55 patients (18.3%), 46 patients (15.3%) patients were in the mild disease, moderate disease, severe disease groups, respectively. Patients with severe disease were more likely to be older, have more comorbidities, and tended to have higher body mass index. In laboratory data, lymphocyte count, levels of C-reactive protein (CRP), LDH, and AST on admission were significantly associated with the severity. In multivariate analysis, age and CRP were the independent risk factors for severe disease (OR = 1.050, 1.130, respectively). The optimal cut-off value for age was 74 years old and that for CRP was 3.15 mg/dL. CONCLUSIONS: Age and CRP were independently associated with disease severity of COVID-19 in multivariate analysis. Additionally, the numbers of underlying disease, lymphocyte count, and inflammatory markers such as LDH and D-dimer may also be related to disease severity.

Baseline lung allograft dysfunction after bilateral deceased-donor lung transplantation: A single-center experience in Japan.

BACKGROUND: Baseline lung allograft dysfunction (BLAD) refers to a condition in which a lung transplant recipient does not achieve normal pulmonary function (i.e., forced expiratory volume in 1 s or forced vital capacity of <80% of predicted values). Although BLAD is reportedly associated with a poor prognosis, the condition has not been examined in Japanese patients. METHODS: In this study, we retrospectively examined 38 Japanese adults who underwent bilateral lung transplantation from 2015 to 2022 in a single center. RESULTS: Twenty-one (55%) patients met the criteria for BLAD. No significant differences were found in recipient or donor factors between the BLAD and non-BLAD groups, but the donor-recipient ratio of the predicted vital capacity was lower in the BLAD group (p = 0.009). The intensive care unit length of stay, ventilator duration, and blood loss during transplant surgery were significantly higher in the BLAD group (p < 0.05). No significant difference was found in survival. The median observation period was significantly shorter in the BLAD than non-BLAD group (744 vs.1192 days, respectively; p = 0.031). The time to reach the normal threshold of pulmonary function after lung transplantation varied among the patients, ranging from 6 months to 4 years. CONCLUSIONS: The characteristics of these Japanese patients with BLAD were similar to those of other patients in previous reports. The effects of the observation period and donor-recipient age discrepancy on BLAD require further exploration.

Living-donor lobar lung transplantation from a hepatitis B surface antigen-positive donor to a negative recipient.

A man in his 40s was diagnosed with interstitial pneumonia at another hospital. He was referred to our hospital for lung transplantation. His lung function was rapidly declining, necessitating semiurgent living-donor lobar lung transplantation (LDLLT). Although he was negative for hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb), one of the candidate donors was proven HBsAg-positive. The risk of hepatitis B virus (HBV) infection at transplantation was considered high; however, after careful discussion about the safety of the recipient and donor, it was decided to conduct LDLLT. For prophylaxis, human anti-HBV surface immunoglobulin and entecavir were administered to the recipient. HBsAg and HBsAb were continuously monitored postoperatively and consistently negative, suggesting no signs of reactivation in the recipient, even after corticosteroid pulse treatment for acute cellular rejection. More than 6 months after LDLLT, there were no signs of HBV reactivation in either the recipient or donor.

Timeline of Oxygen Demand in Patients with COVID-19 Pneumonia.

Objective In patients with coronavirus disease 2019 (COVID-19), understanding the timeline of oxygen demand and severe respiratory failure, such as intensive care unit (ICU) admission, may clarify the therapeutic window when home-care treatment is possible and help determine the timing of treatment in hospitalized patients to improve the respiratory status. We examined the timeline of respiratory status in hospitalized patients with moderate-to-severe COVID-19 in terms of oxygen demand and ICU admission. Methods We retrospectively assessed all patients with COVID-19 who were admitted to our hospital between February 2020 and February 2021 and required supplemental oxygen. This study included 66 patients who were transferred to the ICU (ICU patients) and 144 patients who were not transferred to the ICU (non-ICU patients). Results In the total cohort, the median duration from symptom onset to the need for supplemental oxygen was 8 [interquartile range (IQR) 6-10] days. This duration was significantly shorter in ICU patients than in non-ICU patients [8 (IQR 6-9) vs. 9 (IQR 6-10) days, p=0.02]. The median duration from symptom onset to ICU admission was 9 (IQR 8-11) days in severely ill patients. The median duration from the initiation of supplemental oxygen to ICU admission was 1.0 (IQR 1-2.75) days. Only 2 of 66 patients (3.0%) were admitted to the ICU six days or later after the initiation of supplemental oxygen. Conclusion Physicians should carefully monitor each patient's condition after eight days from symptom onset. New therapies and their early administration are needed to reduce the frequency of respiratory failure in COVID-19 patients.

Successful treatment with afatinib following the failure of osimertinib rechallenge with osimertinib-induced interstitial lung disease: A case report.

Herein, we report the case of an 84-year-old woman with epidermal growth factor receptor (EGFR) mutation exon 19 deletion postoperative recurrent lung adenocarcinoma. Osimertinib was administered as a first-line treatment; however, she was urgently admitted to our hospital due to dyspnea on the 46th day. Chest computed tomography revealed bilateral diffuse ground-glass opacities (GGOs) suggestive of grade 3 osimertinib-induced interstitial lung disease (ILD). After discontinuation of osimertinib in combination with short-term corticosteroid therapy, widespread GGOs were promptly resolved. As the disease gradually deteriorated after discontinuation of osimertinib, we administered osimertinib (80 mg every other day) followed by careful observation. However, bilateral GGOs re-appeared on the 15th day, and the diagnosis of osimertinib-induced ILD was established. After the improvement in ILD following corticosteroid therapy, afatinib was administered as salvage therapy, resulting in desirable control of lung cancer without any relapse of ILD. Our results indicate that afatinib would be a promising alternative treatment option even in patients who develop osimertinib-induced ILD and experience failure of osimertinib rechallenge.

Serum Krebs von den Lungen-6 levels are associated with mortality and severity in patients with coronavirus disease 2019.

BACKGROUND: The serum Krebs von den Lungen-6 (KL-6) level is a predictive factor for acute respiratory distress syndrome (ARDS). The development of ARDS has been reported in patients with coronavirus disease 2019 (COVID-19). This study aimed to determine whether serum KL-6 levels are associated with mortality and severity in patients with COVID-19. METHODS: Among 361 Japanese patients with COVID-19 who were hospitalized at Kanagawa Cardiovascular and Respiratory Center between February 2020 and December 2020, 356 patients with data on serum KL-6 levels were enrolled and their medical records were retrospectively analyzed. RESULTS: A negative correlation was observed between KL-6 levels and the ratio of the arterial partial pressure of oxygen to the fraction of inspired oxygen on admission. The KL-6 levels on admission and the maximal KL-6 levels were higher in patients with severe disease (n = 60) than in those with nonsevere disease (n = 296). Furthermore, the maximal KL-6 levels were higher in nonsurvivors (n = 6) than in survivors (n = 350). In nonsurvivors, the KL-6 levels increased as the disease progressed. The optimal cutoff value of the maximal KL-6 level for discriminating between survivors and nonsurvivors was 684 U/mL, with a sensitivity of 83.3%, a specificity of 90.5%, and an area under the curve of 0.89. CONCLUSIONS: The serum KL-6 level was associated with disease severity. Patients with KL-6 levels ≥684 U/mL had a significantly poorer outcome than those with KL-6 levels <684 U/mL.

A case of intrathoracic desmoid tumor with pulmonary Mycobacterium abscessus disease.

A 68-year-old man who was on treatment for pulmonary Mycobacterium avium complex complained a worsening of sputum. Although he archived negative sputum culture two months ago, sputum culture tests revealed the newly isolation of Mycobacterium abscessus repeatedly. Chest computed tomography showed newly-appeared extra-pulmonary mass lesion in contact with a cyst at the bottom of his right lung. From the results of contrast-enhanced magnetic resonance imaging, we first suspected loculated pleural effusion due to Mycobacterium abscessus infection. A thoracoscopic examination was performed as the right pneumothorax developed, and the pleural lesion was successfully resected and diagnosed as an intrathoracic desmoid tumor. Intrathoracic desmoid tumor is very rare, and this is the first report of a case with pulmonary Mycobacterium abscessus disease.

Pneumothorax in a COVID-19 Pneumonia Patient without Underlying Risk Factors.

Coronavirus disease 2019 (COVID-19) has been recognized as a worldwide pandemic. However, the clinical course of COVID-19 remains poorly characterized. Although some cases of pneumothorax have been reported, they all had pulmonary complications or were managed with mechanical ventilation. We herein report a case of pneumothorax that developed even though the patient had no pulmonary underlying diseases and had never been managed with mechanical ventilation. In the present case, a lung bulla was found on chest computed tomography during treatment for COVID-19. We concluded that COVID-19 affected the formation of the lung bulla and induced the complication of pneumothorax.

Correction to: Ultra-high-resolution computed tomography can demonstrate alveolar collapse in novel coronavirus (COVID-19) pneumonia.

The correct caption is given below.

Ultra-high-resolution computed tomography can demonstrate alveolar collapse in novel coronavirus (COVID-19) pneumonia.

PURPOSE: To review the chest computed tomography (CT) findings on the ultra-high-resolution CT (U-HRCT) in patients with the Novel coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: In February 2020, six consecutive patients with COVID-19 pneumonia (median age, 69 years) underwent U-HR CT imaging. U-HR-CT has a larger matrix size of 1024 × 1024 thinner slice thickness of 0.25 mm and can demonstrate terminal bronchioles in the normal lungs; as a result, Reid's secondary lobules and their abnormalities can be identified. The distribution and hallmarks (ground-glass opacity, consolidation with or without architectural distortion, linear opacity, crazy paving) of the lung opacities on U-HRCT were visually evaluated on a 1 K monitor by two experienced reviewers. The CT lung volume was measured, and the ratio of the measured lung volume to the predicted total lung capacity (predTLC) based on sex, age and height was calculated. RESULTS: All cases showed crazy paving pattern in U-HRCT. In these lesions, the secondary lobules were smaller than those in the un-affected lungs. CT lung volume decreased in two cases comparing predTLC. CONCLUSION: U-HRCT can evaluate not only the distribution and hallmarks of COVID-19 pneumonia but also visualize local lung volume loss.

Five cases of BRAF V600E-mutant lung adenocarcinoma with high expression of programmed death ligand 1.

We reported consecutive five patients with BRAF V600E-mutant recurrent or advanced non-small cell lung cancer who were identified between April 2016 and June 2019. All five patients had high programmed death ligand 1 (PD-L1) tumor proportion scores (50, 55, 75, 95 and 100%). Four of the five patients received regimens including pembrolizumab. Of them, one patient experienced a partial response, but two patients experienced progressive disease and one patient was not evaluable. Three of the four patients received regimens including pemetrexed were able to continue long-term treatment. The presence of a BRAF mutation may be associated with higher levels of PD-L1 expression. The effect of immune checkpoint inhibitors therapy in patients with BRAF mutation was similar to the previous reports in patients with previously treated advanced non-small cell lung cancer with PD-L1 tumor proportion score ≥50%. Chemotherapy regimens including pemetrexed may have a positive effect in patients with BRAF V600E-mutant lung adenocarcinoma. Accumulation of additional Case series is necessary to confirm our results.

Outcome of early-stage combination treatment with favipiravir and methylprednisolone for severe COVID-19 pneumonia: A report of 11 cases.

Although the use of corticosteroids is not recommended in the World Health Organization statement for the treatment of coronavirus disease 2019 (COVID-19), steroid therapy may be indicated for critical cases in specific situations. Here, we report the successful treatment of 11 cases of severe COVID-19 pneumonia with favipiravir and methylprednisolone. All cases were severe and patients required oxygen administration or had a blood oxygen saturation ≤93% on room air. All were treated with favipiravir and methylprednisolone, and 10 of 11 patients responded well and required no further oxygen supplementation or ventilator management. This study shows the importance of the early-stage use of a combination of favipiravir and methylprednisolone in severe cases to achieve a favorable clinical outcome.

Pembrolizumab-associated bronchiolitis in an elderly lung cancer patient required the treatment with an inhaled corticosteroid, erythromycin and bronchodilators.

Immune checkpoint inhibitors (ICIs) have been used to treat lung cancer. Several types of ICI-related interstitial lung diseases have been reported, including organizing pneumonia, non-specific interstitial pneumonia, and diffuse alveolar damage. However, pembrolizumab-associated bronchiolitis requiring treatment for persistent cough has not yet been reported. Here, we describe a patient who developed dry cough while being treated with pembrolizumab for lung adenocarcinoma. Radiography and lung biopsy findings indicated bronchiolitis. His cough improved after the discontinuation of pembrolizumab and treatment with erythromycin, an inhaled corticosteroid, a long-acting muscarinic antagonist, and a long-acting ß2 agonist.