The association between transfer coefficient of the lung and the risk of exacerbation in asthma-COPD overlap: an observational cohort study.

BACKGROUND: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) patients experience exacerbations more frequently than those with asthma or COPD alone. Since low diffusing capacity of the lung for carbon monoxide (DLCO) is known as a strong risk factor for severe exacerbation in COPD, DLCO or a transfer coefficient of the lung for carbon monoxide (KCO) is speculated to also be associated with the risk of exacerbations in ACO. METHODS: This study was conducted as an observational cohort survey at the National Hospital Organization Fukuoka National Hospital. DLCO and KCO were measured in 94 patients aged ≥ 40 years with a confirmed diagnosis of ACO. Multivariable-adjusted hazard ratios (HRs) for the exacerbation-free rate over one year were estimated and compared across the levels of DLCO and KCO. RESULTS: Within one year, 33.3% of the cohort experienced exacerbations. After adjustment for potential confounders, low KCO (< 80% per predicted) was positively associated with the incidence of exacerbation (multivariable-adjusted HR = 3.71 (95% confidence interval 1.32-10.4)). The association between low DLCO (< 80% per predicted) and exacerbations showed similar trends, although it failed to reach statistical significance (multivariable-adjusted HR = 1.31 (95% confidence interval 0.55-3.11)). CONCLUSIONS: Low KCO was a significant risk factor for exacerbations among patients with ACO. Clinicians should be aware that ACO patients with impaired KCO are at increased risk of exacerbations and that careful management in such a population is mandatory.

Impact of visceral fat on the prognosis of coronavirus disease 2019: an observational cohort study.

BACKGROUND: Clarification of the risk factors for coronavirus disease 2019 (COVID-19) severity is strongly warranted for global health. Recent studies have indicated that elevated body mass index (BMI) is associated with unfavorable progression of COVID-19. This is assumed to be due to excessive deposition of visceral adipose tissue (VAT); however, the evidence investigating the association between intra-abdominal fat and COVID-19 prognosis is sparse. We therefore investigated whether measuring the amount of intra-abdominal fat is useful to predict the prognosis of COVID-19. METHODS: The present study enrolled 53 consecutive cases of COVID-19 patients aged ≥ 20 years with chest computed tomography (CT) scans. The VAT area, total adipose tissue (TAT) area, and VAT/TAT ratio were estimated using axial CT images at the level of the upper pole of the right kidney. Severe COVID-19 was defined as death or acute respiratory failure demanding oxygen at ≥ 6 L per minute, a high-flow nasal cannula, or mechanical ventilation. The association of VAT/TAT with the incidence of progression to a severe state was estimated as a hazard ratio (HR) using Cox regression analysis. To compare the prediction ability for COVID-19 disease progression between BMI and VAT/TAT, the area under the receiver operating characteristic curve (AUC) of each was assessed. RESULTS: A total of 15 cases (28.3% of the whole study subjects) progressed to severe stages. The incidence of developing severe COVID-19 increased significantly with VAT/TAT (HR per 1% increase = 1.040 (95% CI 1.008-1.074), P = 0.01). After adjustment for potential confounders, the positive association of VAT/TAT with COVID-19 aggravation remained significant (multivariable-adjusted HR = 1.055 (95% CI 1.000-1.112) per 1% increase, P = 0.049). The predictive ability of VAT/TAT for COVID-19 becoming severe was significantly better than that of BMI (AUC of 0.73 for VAT/TAT and 0.50 for BMI; P = 0.0495 for the difference). CONCLUSIONS: A higher ratio of VAT/TAT was an independent risk factor for disease progression among COVID-19 patients. VAT/TAT was superior to BMI in predicting COVID-19 morbidity. COVID-19 patients with high VAT/TAT levels should be carefully observed as high-risk individuals for morbidity and mortality.

Tezepelumab treatment for allergic bronchopulmonary aspergillosis.

An 82-year-old man had been diagnosed with asthma. He experienced repeated exacerbations requiring treatment with a systemic corticosteroid despite being treated with medications including high-dose fluticasone furoate/umeclidinium/vilanterol, montelukast sodium, and theophylline; treatment with mepolizumab was then initiated. The patient had been free from exacerbations for 15 months; however, he suffered from post-obstructive pneumonia and atelectasis secondary to mucoid impaction in the right middle lobe of the lung, accompanied by a productive cough, wheezing, dyspnea, and right chest pain. In addition to the development of mucus plugs, the levels of serum IgE specific to Aspergillus spp. became positive; a definite diagnosis of allergic bronchopulmonary aspergillosis (ABPA) was established. The patient underwent treatment with tezepelumab. Over 3 months, the mucus plugs and pulmonary opacities diminished gradually in parallel with the improvement in the control of asthmatic symptoms. Tezepelumab might provide a novel steroid-sparing strategy for the management of ABPA, although further studies are required.

Combination immunotherapy of nivolumab plus ipilimumab in a lung cancer patient with Werner syndrome; a case report.

Werner syndrome (WS) is a rare progressive disorder that is characterized by premature aging of all organs. Malignancy is a frequent complication of WS, however, lung cancer patients with WS are much rare. In patients with WS, the treatment for malignancy is often limited due to other complications of severe skin ulcer, diabetes mellitus and cardiovascular disease. Currently, immune-checkpoint inhibitors (ICIs) are standard therapy for several cancer patients and the combination of nivolumab plus ipilimumab has also been approved for the treatment of non-small cell lung cancer (NSCLC). Recent studies have also reported that serious immune-related adverse events (irAEs) induced by ICIs may correlate with elderly or more vulnerable patients. However, the efficacy and safety of ICIs in NSCLC patients with WS remain unclear. To the best of our knowledge, this is the first case describing a NSCLC patient with WS receiving the combination immunotherapy of nivolumab and ipilimumab. Our case showed objective response to ICIs, however, several immune-related adverse events (irAEs) including hypothyroidism, adrenal insufficiency, hard rash and interstitial lung disease occurred, thus resulted in early treatment discontinuation. Our case suggests that immunotherapy for NSCLC patients with WS could be effective, but physicians may be aware of the possibility of multiple irAEs undergoing immunotherapy for NSCLC patients with WS.

The Prognostic Performance of Lung Diffusing Capacity in Preserved Ratio Impaired Spirometry: An Observational Cohort Study.

Purpose: Similar to chronic obstructive pulmonary disease (COPD), the diffusing capacity of the lung (DLCO) might be decreased and associated with poor prognosis in preserved ratio impaired spirometry (PRISm), a clinical entity as a prodromal phase of COPD. The aims of the present study were to evaluate the distributions of DLCO and to assess the association between DLCO and mortality among subjects with PRISm. Patients and Methods: We conducted an observational cohort study at the National Hospital Organization Fukuoka National Hospital. We classified the 899 patients ≥ 40 years of age with an assessment of DLCO into five groups based on spirometry: preserved spirometry, PRISm, mild COPD, moderate COPD, and severe/very severe COPD. The prevalence of low DLCO (< 80% per predicted) was compared among the five groups. Using PRISm patients with follow-up data, we further investigated the association of low DLCO with all-cause mortality. Results: The prevalence of low DLCO in the PRISm group (58.8%) was significantly higher than that in the preserved-spirometry group (21.8%), the mild-COPD group (23.5%), and the moderate-COPD group (36.0%) (all P < 0.01), and it was comparable to that in the severe/very severe-COPD group (63.2%). The results remained unchanged after adjusting for potential confounders. Among the PRISm subjects, the overall survival rate was significantly lower in the low-DLCO group than in the preserved-DLCO group (P < 0.01). The multivariable-adjusted hazard ratio (HR) for all-cause mortality was significantly higher in the low-DLCO group than in the preserved-DLCO group (HR = 10.10 (95% confidence interval 2.33-43.89)). Conclusion: Diffusing capacity was more impaired in PRISm subjects than in those with preserved spirometry or mild to moderate COPD. Regarding PRISm, low DLCO was a significant risk factor for all-cause mortality. Clinicians should assess DLCO in the management of PRISm to predict the future risk of overall death.

Efficacy of steroid pulse therapy for miliary tuberculosis complicated by acute respiratory distress syndrome.

Introduction: Acute respiratory distress syndrome (ARDS) is considered a poor prognostic factor for miliary tuberculosis (MTB), but little is known about the effectiveness of steroid pulse therapy for MTB complicated by ARDS. Patients and methods: Medical records were used to retrospectively investigate the prognosis and clinical information of 13 patients diagnosed with MTB complicated by ARDS among 68 patients diagnosed with MTB at our hospital between January 1994 and October 2016. None of the patients had multidrug resistant tuberculosis (TB). MTB was diagnosed by 1 radiologist and 2 respiratory physicians based on the observation of randomly distributed, uniformly sized diffuse bilateral nodules on chest computed tomography and the detection of mycobacterium TB from clinical specimens. ARDS was diagnosed based on the Berlin definition of ARDS. The effect of steroid pulse therapy on death within 3 months of hospitalization was examined using Cox proportional hazards models. Variables were selected by the stepwise method (variable reduction method). Results: Six of 8 patients with MTB complicated by ARDS were alive 3 months after hospitalization in the steroid pulse therapy group, whereas only 1 of 5 patients was alive in the non-steroid pulse therapy group. Analysis of factors related to the survival of patients with MTB complicated by ARDS revealed that steroid pulse therapy was the strong prognostic factor (hazard ratio = 0.136 (95 % CI: 0.023-0.815)). Conclusion: Our findings suggest that steroid pulse therapy improves the short-term prognosis of patients with MTB complicated by ARDS.

[Clinical review of 8 patients with tuberculous peritonitis].

OBJECTIVE: With the progress of anti-tuberculous therapy, tuberculous peritonitis (TBP) has become a rare manifestation of active tuberculosis. Its early diagnosis is difficult due to lack of pathognomonic findings and specific symptoms. However, early diagnosis is important for effective treatment and for reducing fatality. MATERIALS AND METHOD: We retrospectively reviewed medical records of eight patients who were hospitalized with TBP in National Hospital Organization Omuta National Hospital during the periods between 2001 and 2009. RESULTS: Three patients were males and five were females. The age of the patients ranged between 28 and 80 years old (average 67.3 years). The most common presenting findings were abdominal distention seen in four patients and loss of appetite in five patients. Blood examination suggested that most patients were in poor nutrition. Three patients were diagnosed based on bacteriological examination, two based on histopathological findings of caseating granulomas, two based on the elevation of adenosine deaminase activity in ascitic fluid and one based on clinical diagnosis. The most common CT findings were thin lines along mesenteric vessels representing thickened mesenteric leaves and smooth uniform peritoneal thickening. Most patients were treated with isoniazid, rifampicin and ethambutol for 9 months with/without pyrazinamide initially. Seven patients completed anti-tuberculous therapy successfully and were cured. However, one patient died of the deterioration of tuberculosis. CONCLUSION: TBP should be considered for diagnosis, in patients with non-specific abdominal symptoms. Adenosine deaminase activity in ascitic fluid and CT images are considered to be useful for the diagnosis of TBP in patients in whom bacteriological and histopathological examinations are difficult to perform.

[A case of pulmonary tuberculosis with diminished lung function whose paradoxical reaction led to death].

Paradoxical reaction in tuberculosis treatment is not generally fatal. On rare occasion it can lead a patient with diminished lung function and poor general condition to death. A 60-year-old man with history of left upper lobe resection from tuberculosis was referred to our hospital due to the recurrence of tuberculosis. Sputum examination showed a positive smear with a Gaffky score of 10, and the chest X-ray and CT revealed pulmonary infiltrate with many cavities (bII2) on the whole left lung field. Anti-tuberculosis drugs (isoniazid, rifampicin, ethambutol and pyrazinamide) were administered, but his high fever persisted, and the infiltrate on the chest X-ray deteriorated. While the positive sputum smear persisted, the culture became negative after one month. The tuberculous bacilli were susceptible to all anti-tuberculosis drugs in vitro. Though we performed examinations and trial treatments for non-tuberculous conditions such as pneumonia and drug-induced pneumonia, the patient died after 6 months. A necropsy specimen taken from the worsening lesion (the right upper lobe) as shown on the chest X-ray revealed many epithelioid granulomas. The patient had malnutrition, diabetes, alcoholic hepatic disorder, and insanity. It is supposed that although antituberculosis drugs were effective, a large quantity of killed organisms was continuously excreted from many cavities in the left lung toward the right lung. Lesions in the right lung thus newly produced in this paradoxical reaction seemed to reduce the remaining lung function. In addition, poorly controlled diabetes caused deteriorated heart function. These multiple factors contributed to the poor prognosis of the patient and his ultimate death.

Complete Genome Sequencing of Mycobacterium heckeshornense Strain JMUB5695, Isolated from Necrotizing Granulomatous Lesions.

We report the complete genome sequence of Mycobacterium heckeshornense strain JMUB5695, which was isolated from necrotizing granulomatous lesions in a lung cancer patient. The complete genome consists of a 4,865,109-bp chromosome with a GC content of 65.9% and contains no plasmids.

[Case of angioimmunoblastic T-cell lymphoma with eosinophilia and interstitial shadows].

A 76-year-old woman was admitted because of respiratory failure with bilateral multiple interstitial shadows and mediastinal adenopathy on chest CT images. Blood examination revealed eosinophilia without leukocytosis and elevated C-reactive protein levels. Corticosteroids were administered before diagnosis because of rapid respiratory failure. Although her symptoms and pulmonary lesions disappeared with steroid therapy, they recurred 4 days later. A definitive diagnosis was not obtained until bronchofiberoptic examination. At the time of recurrence 6 months later, angioimmunoblastic T-cell lymphoma (AITL) was diagnosed with axillary lymph node biopsy. AITL is rare, and shows rapid deterioration of respiratory failure with poor prognosis. Lymph node biopsy is necessary to establish a definitive diagnosis.

Evaluation of SNP calling methods for closely related bacterial isolates and a novel high-accuracy pipeline: BactSNP.

Bacteria are highly diverse, even within a species; thus, there have been many studies which classify a single species into multiple types and analyze the genetic differences between them. Recently, the use of whole-genome sequencing (WGS) has been popular for these analyses, and the identification of single-nucleotide polymorphisms (SNPs) between isolates is the most basic analysis performed following WGS. The performance of SNP-calling methods therefore has a significant effect on the accuracy of downstream analyses, such as phylogenetic tree inference. In particular, when closely related isolates are analyzed, e.g. in outbreak investigations, some SNP callers tend to detect a high number of false-positive SNPs compared with the limited number of true SNPs among isolates. However, the performances of various SNP callers in such a situation have not been validated sufficiently. Here, we show the results of realistic benchmarks of commonly used SNP callers, revealing that some of them exhibit markedly low accuracy when target isolates are closely related. As an alternative, we developed a novel pipeline BactSNP, which utilizes both assembly and mapping information and is capable of highly accurate and sensitive SNP calling in a single step. BactSNP is also able to call SNPs among isolates when the reference genome is a draft one or even when the user does not input the reference genome. BactSNP is available at https://github.com/IEkAdN/BactSNP.

A 63-Year-Old Woman With Progressive Dyspnea After Remission of Lymphoma.

CASE PRESENTAION: A 63-year-old woman visited our hospital for a further evaluation of progressive dyspnea. She had developed a progressive airflow obstruction after 3 years' remission of non-Hodgkin's lymphoma (follicular mixed cell type), which had been treated with chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). The patient's primary care physician had diagnosed her as having COPD and bronchial asthma and had treated her with medications including inhaled corticosteroids, tiotropium, and oral erythromycin. Her dyspnea had gradually worsened, however, and she had a score of 4 on the modified Medical Research Council dyspnea scale at the time of admission to our hospital.

Draft Genome Sequences of Five Rapidly Growing Mycobacterium Species, M. thermoresistibile, M. fortuitum subsp. acetamidolyticum, M. canariasense, M. brisbanense, and M. novocastrense.

We report here the draft genome sequences of five rapidly growing Mycobacterium (RGM) species potentially pathogenic to humans, M. thermoresistibile, M. fortuitum subsp. acetamidolyticum, M. canariasense, M. brisbanense, and M. novocastrense As the clinical importance of RGMs is increasingly being recognized worldwide, these sequences would contribute to further advances in RGM research.