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.

Prognostic factors in patients with miliary tuberculosis.

BACKGROUND AND PURPOSE: Acute respiratory distress syndrome (ARDS) complication has long been considered a factor associated with poor prognosis in patients with miliary tuberculosis. However, few reports exist on the prognostic factors of miliary tuberculosis including those complicating ARDS. SUBJECTS AND METHODS: We retrospectively examined prognoses and other clinical information obtained from medical records of a total of 68 patients diagnosed with miliary tuberculosis. Clinical findings were compared between patients who died within three months (non-survivor group) and those who survived beyond three months (survivor group), and risk factors for death within three months of diagnosis were examined using logistic regression analysis. RESULTS: Fifteen of 68 patients diagnosed with miliary tuberculosis died within three months. Most patients were aged 60 years or older (63 patients; 91.2%), with a peak in the 80 s (32 patients; 47.1%). Of the 68 patients with miliary tuberculosis, 13 (19%) had ARDS. The risk of death within three months increased with increasing age and ARDS onset during the disease course. The results of multivariate analysis revealed that, in addition to age (odd ratio (OR): 15.5) and the presence/absence of ARDS (OR: 12.0), consciousness disturbance (OR: 81.53) and high BUN levels (OR: 5.71) were independent factors for death within three months. CONCLUSION: In patients with miliary tuberculosis, old age, ARDS, consciousness disturbance, and high BUN levels were factors associated with poor prognosis.

Prognostic value of serial serum KL-6 measurements in patients with idiopathic pulmonary fibrosis.

BACKGROUND: The prognostic significance of serial measurements of serum KL-6 levels in patients with idiopathic pulmonary fibrosis (IPF) is unclear; hence, it was assessed in this study. METHODS: Medical records of 66 patients with IPF, who were not treated with pirfenidone prior to enrollment, were retrospectively reviewed for information on clinical progress, forced vital capacity (FVC), survival, and serum KL-6 levels. We assessed initial serum levels of KL-6, serial changes in serum KL-6 levels, yearly decline in FVC (ΔFVC), and the rate of decline (%ΔFVC). RESULTS: Patients with increased serum KL-6 levels during follow-up had a significantly steeper decline in ΔFVC than those with no KL-6 increase (-201 vs. -50.7ml/year; p=0.0001). Patients with both initial serum KL-6 ≥1000U/ml and serial increases in serum KL-6 had the steepest decline, while those with both initial serum KL-6 <1000ml and no serial increases in KL-6 had the least decline in ΔFVC and %ΔFVC. Relative to the non-increased KL-6 group, survival in the increased KL-6 group tended to be poorer (p=0.0530). Patients with both initial serum KL-6 values <1000U/ml and no serial increase in KL-6 had more favorable prognoses than those with serial increases in KL-6 or initial serum KL-6 values ≥1000U/ml (p<0.0044). Prognosis was significantly poorer in patients with serial KL-6 changes >51.8U/ml/year than in those with serial KL-6 changes <51.8U/ml/year (p=0.0009). CONCLUSION: Thus, serial serum KL-6 measurements can be useful for assessing prognosis in patients with IPF.

Patients with MAC Lung Disease Have a Low Visceral Fat Area and Low Nutrient Intake.

OBJECTIVE: This study aimed to examine the nutritional status and nutrient intake of patients with MAC lung disease with a focus on visceral fat area. PATIENTS AND METHODS: Among 116 patients of our hospital with nontuberculous mycobacteriosis who were registered between May 2010 and August 2011, 103 patients with MAC lung disease were included in this study. In all patients, nutritional status and nutrient intake were prospectively examined. RESULTS: Patients were 23 men and 80 women (mean age, 72.3±10.9 years). BMI (kg/m2) at the time of registration was 20.4±2.7 in men and 19.2±2.9 in women. Visceral fat area (cm2) was significantly lower in women (35.7±26.6) than in men (57.5±47.4) (p=0.0111). The comparison with general healthy adults according to age revealed a markedly reduced visceral fat area among patients with MAC lung disease. With respect to nutrient intake, energy adequacy (86.1±15.7%), protein adequacy (82.4±18.2%), lipid adequacy (78.1±21.8%), and carbohydrate adequacy (89.6±19.2%) ratios were all low at the time of registration. BMI was significantly correlated with protein adequacy (p=0.0397) and lipid adequacy (p=0.0214) ratios, while no association was found between visceral fat area and nutrient intake. CONCLUSION: Patients with MAC lung disease had a low visceral fat area and low nutrient intake.

[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.

[A case of Streptomyces pneumonia].

A 85-year-old man who had a past history of gastrectomy but no subsequent chemotherapy was suffering fever and fatigue. The infiltrative shadow with cavitation on his chest X-ray film did not improve despite treatment with several antibiotics after admission. Transcutaneous needle aspiration performed for diagnosis of the cavitated lung lesion yielded Streptomyces. A definitive diagnosis of streptomyces lung infection was established. We believed that this is the first case of streptomyces infection of the lung reported in Japan. The current case was also rare because he did not have any immunosuppressive status, while almost all cases previously reported.

[A case of right paratracheal air cyst].

An 87-year-old female was being examined by her primary care doctor during a follow-up of 4 to 5 years after a diagnosis of non-tuberculous mycobacterial infection. An exacerbation of a shadow was suspected on a chest X-ray film, and therefore the patient was referred to our hospital. Her chief clinical symptom was mild occasional coughing, but no clearly abnormal findings were observed on the clinical examination. On chest CT, a cystic lesion was detected in the right posterodorsal side of the trachea at the level of the thoracic aperture, resulting in the diagnosis of a right paratracheal air cyst. Right paratracheal air cyst is a relatively rare disease, but it is believed that such a diagnosis can be made easily based on its localization and the CT findings, and it is a disease to which attention should be paid, which is why we are reporting it.

Increased expression of gp91phox homologues of NAD(P)H oxidase in the aortic media during chronic hypertension: involvement of the renin-angiotensin system.

Although vascular cells express multiple members of the Nox family of nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase, including gp91phox, Nox1, and Nox4, the reasons for the different expressions and specific roles of these members in vascular injury in chronic hypertension have remained unclear. Thus, we quantified the mRNA expressions of these NAD(P)H oxidase components by real-time polymerase chain reaction and evaluated superoxide production and morphological changes in the aortas of 32-week-old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wistar Kyoto rats (WKY). The aortic media of SHRSP had an approximately 2.5-fold greater level of Nox4 mRNA and an approximately 10-fold greater level of Nox1 mRNA than WKY. The mRNA expressions of gp91phox and p22phox in SHRSP and WKY were comparable. SHRSP were treated from 24 weeks of age for 8 weeks with either high or low doses of candesartan (4 mg/kg/day or 0.2 mg/kg/day), or a combination of hydralazine (30 mg/kg/day) and hydrochlorothiazide (4.5 mg/kg/day). The high-dose candesartan or the hydralazine plus hydrochlorothiazide decreased the blood pressure of SHRSP to that of WKY, whereas the low-dose candesartan exerted no significant antihypertensive action. Media thickening and fibrosis, as well as the increased production of superoxide in SHRSP, were nearly normalized with high-dose candesartan and partially corrected with low-dose candesartan or hydralazine plus hydrochlorothiazide. These changes by antihypertensive treatment paralleled the decrease in mRNA expression of Nox4 and Nox1. These results suggest that blood pressure and angiotensin II type 1 receptor activation are involved in the up-regulation of Nox1 and Nox4 expression, which could contribute to vascular injury during chronic hypertension.

Risk factors for the progression of early carotid atherosclerosis in a male working population.

Increased intima-media thickness (IMT) of the carotid artery may represent early atherosclerosis. Although several studies have evaluated risk factors for carotid IMT, only limited information is available concerning risk factors for the progression of carotid IMT. The present study was designed to determine risk factors for the progression of carotid IMT in a male working population. Male employees of a regional transport company (n = 220, 50.9 +/- 4.4 years) underwent baseline physical and laboratory examinations, and ultrasonographic assessment of the maximum common carotid IMT between 1992 and 1994, and they were reexamined 5 years later. In a multivariate analysis at baseline, carotid IMT was positively associated with age, diastolic blood pressure and total cholesterol, and negatively with high density lipoprotein (HDL) cholesterol. During the follow-up period, carotid IMT increased from 0.669 +/- 0.135 mm to 0.784 +/- 0.229 mm, or at a rate of 0.023 +/- 0.039 mm/year. In a multivariate regression analysis using baseline values of carotid IMT, age, body mass index, diastolic blood pressure, total cholesterol, HDL cholesterol and HbA1c as independent variables, the progression of carotid IMT was associated only with baseline total cholesterol. These findings suggest that in middle-aged men, although age, blood pressure, and total cholesterol were associated with baseline carotid IMT, total cholesterol level appeared to be the strongest determinant of the progression of carotid IMT, a result which underscores the importance of maintaining lower cholesterol levels to prevent early atherosclerosis.

Relationship between p38 mitogen-activated protein kinase and small GTPase Rac for the activation of NADPH oxidase in bovine neutrophils.

Superoxide production by NADPH oxidase is essential for bactericidal properties of neutrophils. However, molecular mechanisms underlying the activation of this enzyme remain largely unknown. Here, using bovine neutrophils we examined the role of p38 mitogen-activated protein kinase (p38 MAPK) in the signaling pathways of the NADPH oxidase activation. Superoxide production was induced by stimulation with serum-opsonized zymosan (OZ) and attenuated by p38 MAPK inhibitor, SB203580. OZ stimulation induced the translocation of p47(phox) and Rac to the plasma membrane and SB203580 completely blocked the translocation of Rac, but only partially blocked that of p47(phox). Furthermore, SB203580 abolished the OZ-elicited activation of Rac, which was assessed by detecting the GTP-bound form of this protein. Phosphatidylinositol 3-kinase (PI3K) inhibitors, wortmannin and LY294002, blocked not only p38 MAPK activation but also Rac activation. However, SB203580 showed no effect on the PI3K activity. These results suggested that PI3K/p38 MAPK/Rac pathway was present in the activation of NADPH oxidase in bovine neutrophils.