Pulmonary function and chest CT abnormalities 3 months after discharge from COVID-19, 2020-2021: A nation-wide multicenter prospective cohort study from the Japanese respiratory society.

BACKGROUND: No comprehensive analysis of the pulmonary sequelae of coronavirus disease 2019 (COVID-19) in Japan based on respiratory function tests and chest computed tomography (CT) has been reported. We evaluated post-COVID-19 conditions, especially focusing on pulmonary sequelae assessed by pulmonary function tests and chest CT. METHODS: For this prospective cohort study, we enrolled 1069 patients who presented pneumonia at the time of admission in 55 hospitals from February 2020 to September 2021. Disease severity was classified as moderateⅠ, moderate II, and severe, defined primarily according to the degree of respiratory failure. The data on post-COVID-19 conditions over 12 months, pulmonary function, and chest CT findings at 3 months were evaluated in this study. Additionally, the impact of COVID-19 severity on pulmonary sequelae, such as impaired diffusion capacity, restrictive pattern, and CT abnormalities, was also evaluated. RESULTS: The most frequently reported post-COVID-19 conditions at 3 months after COVID-19 were muscle weakness, dyspnea, and fatigue (48.4%, 29.0%, and 24.7%, respectively). The frequency of symptoms gradually decreased over subsequent months. In pulmonary function tests at 3 months, the incidence of impaired diffusion capacity and restrictive pattern increased depending on disease severity. There also were differences in the presence of chest CT abnormalities at the 3 months, which was markedly correlated with the severity. CONCLUSION: We reported a comprehensive analysis of post-COVID-19 condition, pulmonary function, and chest CT abnormalities in Japanese patients with COVID-19. The findings of this study will serve as valuable reference data for future post-COVID-19 condition research in Japan.

Retrospective investigation on diagnostic process for benign asbestos pleural effusion (BAPE) using checklist.

OBJECTIVES: In Japan, benign asbestos pleural effusion (BAPE) has been eligible for industrial accident compensation since 2003 as an asbestos-related disease despite the lack of good criteria. We compiled a criteria into a checklist of essential items and for excluding other diseases inducing pleural effusion as a diagnosis process. METHOD: Thoracentesis was performed in order to confirm the presence of pleural effusion at the initial diagnosis, and 105 suspected BAPE patients were retrospectively examined. We complied a checklist comprising the following diagnostic items: (a) occupational asbestos exposure; (b) confirmation of exudate of pleural effusion; (c) exclusion of pleural effusion with malignant tumors based on negative results of CEA and hyaluronic acid, and cytology of pleural effusion; (d) exclusion of rheumatic, bacterial, and tuberculous pleuritis; (d) radiological findings for exclusion of malignancies; and (e) histopathological findings based on thoracoscopy that exclude malignancies (when thoracoscopy was not performed, there was confirmation that no malignancies were present during 3-month follow-up observation). Cases that satisfied all items were defined as BAPE. RESULTS: Among the 105 suspected cases, there were five cases that had no occupational asbestos exposure; six cases in which transudate of on pleural effusion; one case each of rheumatoid pleuritis and tuberculous pleuritis; and five cases of pleural mesothelioma based on chest radiography and histopathological findings within 3 months after initial diagnosis. Therefore, we excluded 18 cases from the 105 candidates and determined 87 cases of BAPE. CONCLUSION: We consider that six items described above are suitable for diagnosing BAPE.

[Outcome of patients with acute exacerbation of idiopathic interstitial fibrosis (IPF) treated with sivelestat and the prognostic value of serum KL-6 and surfactant protein D].

Idiopathic interstitial fibrosis (IPF) is a chronic, usually fatal lung disease of unknown etiology. There are few specific therapies for acute exacerbation of IPF and factors predicting the onset or severity of this syndrome are not clearly understood. A neutrophil elastase inhibitor, sivelestat (ONO-5046) has been commercially available in Japan since 2002. This inhibitor has a potent effect in the treatment of ALI/ARDS. To evaluate the outcome of patients with acute exacerbation of IPF treated with sivelestat and estimate prognostic factors, we investigated 10 patients with acute exacerbation of IPF who were intubated and mechanically ventilated. We analyzed the outcome of patients with acute exacerbation of IPF until day 180 and measured the P/F ratio, PEEP levels, the values of peripheral white blood cell number, and C-reactive protein (CRP) on day 0, 3, 7 after admission. Serum KL-6 and surfactant protein D (SP-D) concentration on day 0 were also analyzed. All patients were treated with sivelestat and methylprednisolone (mPSL) pulse therapy for 3 days from day 0 and maintenance therapy with prednisone (0.5 mg/kg/day) were continued. Of the 10 patients. 4 patients had survived (40%) and 6 patients had died (60%) at day 180 from the onset of acute exacerbation of IPF. In survivors, P/F ratio, PEEP levels, and CRP values significantly improved on day 7 (p<0.05). Serum KL-6 and SP-D were lower in survivors on day 0 (p<0.05). Taken together, serum KL-6 and SP-D may prove valuable as biochemical markers of prognosis in acute exacerbation of IPF. Sivelestat may have potential in the treatment of acute exacerbation of IPF.

[Familial occurrence of bronchiolitis obliterans associated with pulmonary aspergillosis].

We report the familial occurrence of bronchiolitis obliterans (BO) associated with pulmonary aspergillosis. A mother and daughter admitted for dyspnea after taking Sauropus androgynus both had overfiltration of both lungs in chest X-ray and severe obstructive impairment in lung function tests. They were initially diagnosed with severe asthma and treated with high-dose prednisolone (0.5mg/kg/day) for 1 month to no effects. They did not show reversibility in lung function test. They were difinitively diagnosed with BO associated with Sauropus androgynus. Six months later, the mother's symptoms worsened with productive sputum and severe dyspnea, and her chest X-ray showed patty shadow in both upper lung fields. Precipitating antibodies to aspergillus antigen were positive and aspergillus fumigatus was detected from her sputum culture. She was diagnosed with aspergillosis and treatment with Micafungin (MCFG) and Itraconazole (ITCZ) was started. The daughter's symptoms also worsened and her chest tomography showed multiple cavities in both lung fields. Precipitating antibodies to aspergillus were positive. She was diagnosed with Invasive aspergillosis. She was treated unsuccessfully with MCFG and Amphotericin B (AMPH) and ITCZ. Few reports cover BO with aspergillus infection without organ impairment. In these 2 cases, treatment with steroids' or immune suppression of the lung with BO may a trigger aspergillus infection.

[Familial occurrence of bronchiolitis obliterans associated with sauropus androgynus].

We experienced familial occurrence of bronchiolitis obliterans (BO) associated with Sauropus androgynus. The cases were a mother and daughter and both were admitted to our hospital because of dyspnea after taking Sauropus androgynus. Both cases had hyperinflation of both lungs in chest x-ray and lung function test showed severe obstructive impairment. At first, they were given a diagnosis of severe asthma and treated as such. However, neither their symptoms nor lung function improved. They did not show any reversibility on lung function tests. Although we did not perform histological examination of the lung, they were given a diagnosis of BO associated with Sauropus androgynus (SABO), because of the following reasons. Cases of SABO in Taiwan have already been demonstrated in the 1990's, and there were no other reasons to explain their severe airflow obstruction. Neither bronchodilators nor steroid treatment improved airflow obstruction. BO is rare and can mimic asthma and chronic obstructive pulmonary disease (COPD). We should inquire about the intake of food or medication in cases suspected BO.

[Effectiveness of pneumococcal polysaccharide vaccine in older patients with chronic respiratory diseases].

To evaluate effectiveness of pneumococcal polysaccharide vaccine, we recommended 1378 outpatients aged over 60 with chronic respiratory diseases to be vaccinated from August to October 2002, and 647 patients were vaccinated from August to November 2002. In the 1229 patients without respiratory failure, the incidence of antimicrobial treatment for bacterial respiratory infections in 547 vaccinated patients significantly decreased from 7.9% in the 2001/02 winter season to 5.7% in the 2002/03 winter season, although that in the 682 unvaccinated patients increased from 3.8% to 5.7%. The incidence of antimicrobial treatment for bacterial respiratory infections in 229 vaccinated patients with pneumococcal and influenza vaccines together significantly decreased from 10.5% in the 2001/02 winter season to 5.2% in 2002/03 winter season although that in 110 subjects vaccinated with influenza vaccine only increased from 2.7% to 7.2%. These findings suggest the effectiveness of the pneumococcal polysaccharide vaccine for the prevention of bacterial respiratory infections and the additive effectiveness of pneumococcal and influenza vaccines together.

[Gefitinib as a first-line therapy in patients with advanced non-small cell lung cancer].

BACKGROUND: The objective of this study was to evaluate the efficacy and toxicity of gefitinib as a first-line therapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: We analyzed 19 patients with advanced NSCLC retrospectively, who were treated with gefitinib as a first-line therapy. These patients were not considered for systemic chemotherapy secondary to co-morbid conditions, poor performance status (PS) or refusal of chemotherapy. RESULTS: Median age 68 years, male/female 10/9, stage III/IV 7/12, smoker/non-smoker 12/7, adenocarcinoma/non-adeno 13/6, PS 0/1/2/3/4 0/4/7/5/3. Four patients had a partial response and the overall response rate was 21.0%. The median survival time was 6.8 months and 1-year survival was 27%. Overall toxicities were mild. Grade (G) 3 diarrhea was observed in one patient and G1 interstitial pneumonia in one. CONCLUSIONS: These results demonstrate that gefitinib is active as a first-line therapy in patients with advanced NSCLC.

[Combination chemotherapy with carboplatin and weekly Paclitaxel in patients with advanced non-small cell lung cancer].

BACKGROUND: The objective of this study was to evaluate the efficacy and toxicity of carboplatin plus weekly paclitaxel as first-line therapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Forty-nine patients were analyzed retrospectively. Every 4 weeks patients received 70 mg/m(2)paclitaxel on days 1, 8, and 15, and AUC 5-6 carboplatin on day 1. RESULTS: A median of four cycles (range, 1-7) was administered. Twenty-four patients had a partial response, and the overall response rate was 48.9%. The median survival time was 12.8 months and the 1-year survival was 50.7%. Overall toxicities were mild. The most common toxicity was neutropenia, grade 3/4 in 32% of the patients. Grade 3/4 hematologic toxicities included anemia (16%) and thrombocytopenia (8%). Grade 3/4 non-hematologic toxicities included febrile neutropenia (2%), pneumonia (10%) and interstitial pneumonia (2%). Grade 2 peripheral neuropathy was seen in one patient (2%). CONCLUSIONS: These results demonstrate that this regimen is an active and tolerable treatment for patients with advanced NSCLC. It is suggested that this weekly regimen should be considered as one of the standard therapies for future chemotherapy in advanced NSCLC.

[Eighty cases of chronic respiratory failure treated with home noninvasive positive pressure ventilation].

We studied the clinical features and efficacy of home noninvasive positive pressure ventilation (NPPV) therapy in 80 patients to ascertain its indications and problems. The causes of chronic respiratory failure were restrictive thoracic diseases of post-tuberculosis sequelae (40 cases) and kyphoscoliosis (9 cases), COPD (8 cases), bronchiectasis (7 cases), and interstitial pneumonia (4 cases). One year survival rate of the patients with post-tuberculosis sequelae was 76% and most of the patients who started NPPV at their acute exacerbation died within several months. About half of the patients of COPD improved their quality of life (QOL) through NPPV. However, their survival rate 3 months later was only 69%. More than half of the patients with bronchiectasis felt that their QOL was improved by NPPV. Most of the patients with interstitial pneumonia died within 3 months indicating that NPPV is less useful for improving QOL of interstitial pneumonia PaCO2, after home NPPV, decreased significantly in the responder group (70.0 +/- 15.4 vs. 57.6 +/- 10.7[SD]Torr, p < 0.05), while PaCO2 in the non-responder group was unchanged (65.4 +/- 12.1 vs. 64.2 - 10.4 [SD] Torr). Body Mass Index (BMI) in the responder group tended to be higher than in the non-responder group. In conclusion, the restrictive thoracic diseases with post-tuberculosis sequelae and kyphoscoliosis are a good indication for NPPV and the therapy is also useful for patients with bronchiectasis who can dispose of their sputum by themselves. Home NPPV is suitable for patients whose PaCO2 decreases through NPPV and whose BMI is relatively high. QOL of interstitial pneumonia barely improves through NPPV, because interstitial pneumonia with hypercapnia is at the terminal stage.