Classifications of moderate to severe asthma phenotypes in Japan and analysis of serum biomarkers: A Nationwide Cohort Study in Japan (NHOM Asthma Study).

BACKGROUND: Asthma is a heterogeneous disease, and phenotyping can facilitate understanding of disease pathogenesis and direct appropriate asthma treatment. This nationwide cohort study aimed to phenotype asthma patients in Japan and identify potential biomarkers to classify the phenotypes. METHODS: Adult asthma patients (n = 1925) from 27 national hospitals in Japan were enrolled and divided into Global Initiative for Asthma (GINA) steps 4 or 5 (GINA 4, 5) and GINA Steps 1, 2, or 3 (GINA 1-3) for therapy. Clinical data and questionnaires were collected. Biomarker levels among GINA 4, 5 patients were measured. Ward's minimum variance hierarchical clustering method and tree analysis were performed for phenotyping. Analysis of variance, the Kruskal-Wallis, and chi-square tests were used to compare cluster differences. RESULTS: The following five clusters were identified: 1) late-onset, old, less-atopic; 2) late-onset, old, eosinophilic, low FEV1; 3) early-onset, long-duration, atopic, poorly controlled; 4) early-onset, young, female-dominant, atopic; and 5) female-dominant, T1/T2-mixed, most severe. Age of onset, disease duration, blood eosinophils and neutrophils, asthma control questionnaire Sum 6, number of controllers, FEV1, body mass index (BMI), and hypertension were the phenotype-classifying variables determined by tree analysis that assigned 79.5% to the appropriate cluster. Among the cytokines measured, IL-1RA, YKL40/CHI3L1, IP-10/CXCL10, RANTES/CCL5, and TIMP-1 were useful biomarkers for classifying GINA 4, 5 phenotypes. CONCLUSIONS: Five distinct phenotypes were identified for moderate to severe asthma and may be classified using clinical and molecular variables (Registered in UMIN-CTR; UMIN000027776.).

The usefulness of a combination of age, body mass index, and blood urea nitrogen as prognostic factors in predicting oxygen requirements in patients with coronavirus disease 2019.

INTRODUCTION: Risk factors for seriously ill coronavirus disease 19 (COVID-19) patients have been reported in several studies. However, to date, few studies have reported simple risk assessment tools for distinguishing patients becoming severely ill after initial diagnosis. Hence, this study aimed to develop a simple clinical risk nomogram predicting oxygenation risk in patients with COVID-19 at the first triage. METHODS: This retrospective study involved a chart review of the medical records of 84 patients diagnosed with COVID-19 between February 2020 and March 2021 at ten medical facilities. The patients were divided into requiring no oxygen therapy (non-severe group) and requiring oxygen therapy (severe group). Patient characteristics were compared between the two groups. We utilized univariate logistic regression analysis to confirm determinants of high risks of requiring oxygen therapy in patients with moderate COVID-19. RESULTS: Thirty-five patients ware in severe group and forty-nine patients were in non-severe group. In comparison with patients in the non-severe group, patients in the severe group were significantly older with higher body mass index (BMI), and had a history of hypertension and diabetes. Serum blood urea nitrogen (BUN), lactic acid dehydrogenase (LDH), and C-reactive protein (CRP) levels were significantly higher in the severe group. Multivariate analysis showed that older age, higher BMI, and higher BUN levels were significantly associated with oxygen requirements. CONCLUSIONS: This study demonstrated that age, BMI, and BUN were independent risk factors in the moderate-to-severe COVID-19 group. Elderly patients with higher BMI and BUN require close monitoring and early treatment initiation.

Early diagnosis of idiopathic pulmonary haemosiderosis: increased haemosiderin-laden macrophages in repeat bronchoscopy.

Idiopathic pulmonary haemosiderosis (IPH) is a diagnosis of exclusion, which is characterized by persistent or recurrent episodes of alveolar haemorrhage. Early diagnosis of IPH, especially in the case of first-time manifestation, is challenging because previous episodes of alveolar haemorrhage are often difficult to prove. Repeated episodes of alveolar haemorrhage can result in chronic iron-deficient anaemia and irreversible interstitial fibrosis; thus, early recognition and intervention are desirable in terms of clinical outcome. We report a case of IPH that was diagnosed early by confirming the presence of an increased number of haemosiderin-laden macrophages with alveolar haemorrhage in repeat bronchoscopy. We wanted to highlight that decreased but sustained attenuation of ground-glass opacities on high-resolution computed tomography does not always correlate with successful remission in patients with IPH. Repeat bronchoscopy can be useful in the early recognition of IPH, especially in the case of sustained opacities a few months after alveolar haemorrhage.

Bevacizumab-induced tracheoesophageal fistula in a patient suffering from lung cancer with bulky subcarinal lymph node: a case report.

A 66-year-old male with advanced non-small-cell lung cancer (NSCLC) who was previously treated with carboplatin, pemetrexed, and bevacizumab consequently suffered from severe coughing during deglutition. Chest computed tomography (CT) revealed a tracheoesophageal fistula (TEF) between the left main bronchus and esophagus through a subcarinal metastatic lymph node. Given the extreme swelling of the lymph node due to metastatic cancer, it was determined that the walls of the bronchus and esophagus had been injured simultaneously. Delayed and dysfunctional wound healing due to bevacizumab resulted in necrosis of the contact region leading to fistula formation. This case suggests that using bevacizumab for NSCLC in patients with bulky subcarinal lymphadenopathy may increase the risk for TEF.

Salmonella houtenae-induced Empyema Complicated with Chronic Tuberculous Empyema.

Salmonella spp. are food-borne pathogens that usually cause gastroenteritis, although bacteremia and subsequent focal metastatic infection can also occasionally occur. Of the known Salmonella spp., Salmonella houtenae is a rare subspecies, comprising less than 1% of all Salmonella strains. We herein report the first case of S. houtenae-induced empyema complicated with chronic tuberculous empyema, which was successfully treated by antibacterial agents alone. We wish to highlight the importance of being aware that Salmonella spp. can cause empyema in cases suffering from chronic tuberculous empyema; moreover, despite the successful completion of treatment with antibacterial agents, periodical follow-up is mandatory in such cases.

Pediatric pulmonary tuberculoma with a solid pulmonary nodule detected on chest computed tomography.

A 14-year-old girl underwent a medical checkup for Mycobacterium tuberculosis infection because her grandmother had been diagnosed with pulmonary tuberculosis three months earlier. The interferon-gamma release assay (IGRA) showed a positive result. The patient's chest X-ray findings were normal. Chest computed tomography (CT) showed a single mass lesion in the right lower lobe of the lung. A sputum smear of acid-fast bacilli was positive; however, the polymerase chain reaction results for tuberculosis were negative. We diagnosed the patient with pulmonary tuberculosis based on the fact that she had come in contact with a tuberculosis patient. Six weeks later, a liquid culture examination for acid-fast bacilli was found to be positive and the acid-fast bacillus was identified as M. tuberculosis. The use of chest CT is not routinely recommended in all children suspected of having M. tuberculosis infection. However, IGRA-positive children who report frequent contact with infected individuals should undergo CT tomography if chest X-rays do not show any abnormal shadows.

Pulmonary haemodynamic changes in patients with severe COPD.

Worsening gas exchange during exercise and during exacerbations of COPD contributes to systemic hypoxaemia and reduces quality of life. However, pulmonary haemodynamic changes under such conditions are not well understood. Right heart catheterization was performed in six patients with severe COPD (%FEV(1) < 50%) during rest, exercise and during an exacerbation. Pulmonary artery pressure (Ppa) was slightly elevated at rest. The Ppa, as well as pulmonary artery wedge pressure (Pawp) and cardiac index were significantly increased during bicycle ergometer exercise. In contrast, pulmonary vascular resistance increased significantly during an exacerbation accompanied by a slightly increased Ppa. Supplemental oxygen resulted in significant decreases in Ppa and Pawp during exercise and Ppa during exacerbations. In patients with COPD, haemodynamic changes in the pulmonary circulation may differ during exercise and with exacerbations. Supplementary oxygen is beneficial and associated with reductions in pulmonary arterial pressures.

Selective IgM deficiency accompanied with IgG4 deficiency, dermal complications and a bronchial polyp.

BACKGROUND: IgM deficiency is a rare primary immunodeficiency. As few studies of selective IgM deficiency have been reported among the various other types of primary immunodeficiencies, the detailed pathogenesis of this disorder remains to be elucidated. CASE SUMMARY: We clinically analyzed a 37-year-old woman who presented with IgM and IgG4 deficiency and ectopic bronchial pneumonia, and investigated immunological functions. Occlusive pneumonia was repeatedly observed in the right S6 area, and bronchoscopy revealed a polyp in the right B6 orifice, which was later identified as a fibroepithelial polyp after transbronchial endoscopic polypectomy. Two months later, pneumonia involving the right inferior lobe developed. Systemic erythema and pigmentation with bleb formation were also observed on the skin, and were thought to be drug-induced exanthema following a biopsy. Serum levels of IgM and IgG4 were extremely low at 3.0mg/dl and less than 2.0mg/dl, respectively. Circulating CD20 positive B cells were mildly reduced and memory B cells were markedly decreased. The majority of B cells expressed IgM on their surface. There were no abnormalities in cell counts of neutrophils, T cells, NK cells and monocytes. Chemotaxins, bactericidal activity and phagocytosis of neutrophils were normal. DISCUSSION: There have been no case reports of selective IgM deficiency with concurrent IgG4 deficiency, various dermal symptoms and a bronchial polyp, as demonstrated in our patient.

Interstitial lung disease associated with amyopathic dermatomyositis: review of 18 cases.

Interstitial lung disease (ILD) associated with amyopathic dermatomyositis (ADM) is a rare and sometimes fatal condition whose clinical features are not well understood. The goal of this study was to clarify the characteristics of ILD based on its development. Eighteen patients diagnosed with ILD associated with ADM were assigned to 1 of 2 groups: (1) a rapidly progressing group, which included patients who developed abnormal lung findings within 1 month of being diagnosed with ADM (n=9); or (2) a slowly progressing group, which including patients who developed lung findings greater than 1 month after diagnosis of ADM (n=9). Serum creatine phosphokinase and C-reactive protein levels were higher in the rapidly progressing group than in the slowly progressing group. Further, arterial pH was higher and PaO(2)/F(I)O(2) was lower in the rapidly progressing group than in the slowly progressing group. On thoracic high-resolution CT, traction bronchiectasis was present in 4 of the 9 rapidly progressing patients but not in any patients of the slowly progressing group. All 9 slowly progressing patients survived with proper treatment, but only 4 of the 9 rapidly progressing patients survived. In ADM, appropriate investigations are likely required for the early diagnosis of ILD. Our data suggest that ILD associated with ADM can be classified into 2 clinical subtypes based on the time course of pulmonary involvement. Patients with rapid progression in respiratory symptoms should undergo intensive treatment as soon as possible to promote favorable outcomes.

[A case of acute eosinophilic pneumonia with a disassociation between the KL-6 level and SP-A and SP-D levels in the serum and BAL fluid].

A 45-year-old Japanese electrical engineer was admitted to our department of internal medicine on August 12, 2003, because of a sudden high fever and severe hypoxic respiratory failure. At a barbecue with his family on August 3 beside a nearby river, he had been exposed to the smoke. From August 4 to 11, he had suffered fatigue, fever, dry cough and progressive dyspnea. On admission, his SpO2 was 84%, and computed tomography scanning showed patchy ground glass opacity, thickened bronchial walls, and bilateral pleural effusions. The eosinophil count in the bronchoalveolar lavage fluid (BALF) was increased to 52.4%. Noticeably, the KL-6, SP-A and SP-D levels in the serum were elevated to 197 U/ml, 188 ng/ml and 137 ng/ml, and their levels in BALF had also increased to 225 U/ml, 890 ng/ml and 1110 ng/ml, respectively. The lymphocyte stimulation test was negative, and the cultures of blood and BALF did not grow any pathogens. The patient had smoked 1 pack of per cigarettes day for 25 years and showed no sign of atopic illness. Acute eosinophilic pneumonia (AEP) was diagnosed, and responded dramatically to treatment with oxygen and corticosteroids. The dissociation between the normal KL-6 levels and the elevated SP-A and SP-D levels in the serum and BAL fluid may play an important role in cases of AEP.