Masaki Kawakami

Efficacy of Corticosteroids in the Treatment of Community-Acquired Pneumonia Requiring Hospitalization

BackgroundRecent studies suggested that administration of corticosteroids may improve clinical outcomes in patients with severe pneumonia.ObjectivesThe aim of this study was to assess the effectiveness of corticosteroids as an adjunctive therapy in community-acquired pneumonia (CAP) requiring hospitalization.Design and SettingAn open label, prospective, randomized control study was conducted from September 2003 to February 2004 in a community general hospital in Japan.PatientsThirty-one adult CAP patients who required hospitalization were enrolled.Measurements and ResultsFifteen patients received 40 mg of prednisolone intravenously for 3 days (steroid group). Sixteen patients did not receive prednisolone (control group). Both groups were also evaluated for their adrenal function. The primary endpoint was length of hospital stay. Secondary endpoints were duration of intravenous (IV) antibiotics and time required to stabilize vital signs. Both groups demonstrated similar baseline characteristics and length of hospital stay, and yet a shorter duration of IV antibiotics was observed in the steroid group (p < 0.05). In addition, vital signs were stabilized earlier in the steroid group (p < 0.05). These differences were more prominent in the moderate–severe subgroup but not as significant in the mild–moderate subgroup. The prevalence of relative adrenal insufficiency (RAI) in both groups was high (43%), yet there was no difference in baseline characteristics between patients, with or without RAI. In multiple regression models, RAI seemed to have no influence on clinical courses.ConclusionsIn moderate–severe CAP, administration of corticosteroids promotes resolution of clinical symptoms and reduces the duration of intravenous antibiotic therapy.

Diagnostic and Prognostic Value of Procalcitonin in Community-Acquired Pneumonia

Introduction:The value of measuring procalcitonin (PCT) in patients with community-acquired pneumonia (CAP) is unclear. The aim of this study was to determine the value of PCT as a marker for microbial etiology and a predictor of outcome in CAP patients. Methods:A single-center observational study was conducted with CAP patients. On admission, their leukocyte count, serum C-reactive protein level, and serum PCT level were determined, and microbiological tests were performed. Patients were classified into 4 groups according to the A-DROP scoring system, which assesses the severity of CAP. Results:A total of 102 patients were enrolled. The pathogen was identified in 60 patients, and 31 patients had streptococcal pneumonia. The PCT levels were significantly higher in those patients with pneumococcal pneumonia than in those patients with other bacterial pneumonias (P < 0.0001). Multivariate regression analysis revealed that high PCT levels were associated with a pneumococcal etiology [odds ratio, 1.68; 95% confidence interval (CI): 1.02–2.81; P = 0.04] after adjustment for disease severity and demographic factors. The PCT levels were correlated with the A-DROP score (r = 0.49; P < 0.0001). The area under the curve for predicting mortality was highest for the A-DROP score (0.97; 95% CI: 0.92–0.99), followed by the area under the curve for PCT (0.82; 95% CI: 0.74–0.89) and C-reactive protein (0.77; 95% CI: 0.67–0.84). Conclusions:High PCT levels indicate that pneumococcal pneumonia and PCT levels depend on the severity of pneumonia. PCT measurements may provide important diagnostic and prognostic information for patients with CAP.

The role of CCR7 in allergic airway inflammation induced by house dust mite exposure

House dust mite (HDM), the most common allergen, activate both the IgE-associated and innate immune responses. To clarify the process of sensitization, we investigated the role of the CCL21, CCL19, and CCR7 axis in a mouse model of HDM-induced allergic asthma. HDM inhalation without systemic immunization resulted in a HDM-specific IgE response. CCR7-knockout (CCR7KO) mice exhibited greater airway inflammation and IgE responses compared to wild-type mice. We examined FoxP3 expression in these mice to clarify the contribution of regulatory cells to the responses. FoxP3 expression was higher in the lungs but not in the lymph nodes of CCR7KO mice compared to wild-type mice. In CCR7KO mice, FoxP3-positive cells were found in lung, but we observed higher release of IL-13, IL-5, TGF-β, IL-17, and HMGB1 in bronchoalveolar lavage fluid. We demonstrate here that immuno-regulation through CCR7 expression in T cells plays a role in HDM-specific sensitization in the airway.

Relationships among Smoking Habits, Airflow Limitations, and Metabolic Abnormalities in School Workers

Background Chronic obstructive pulmonary disease is caused mainly by habitual smoking and is common among elderly individuals. It involves not only airflow limitation but also metabolic disorders, leading to increased cardiovascular morbidity and mortality. Objective We evaluated relationships among smoking habits, airflow limitation, and metabolic abnormalities. Methods Between 2001 and 2008, 15,324 school workers (9700 males, 5624 females; age: ≥30 years) underwent medical checkups, including blood tests and spirometry. They also responded to a questionnaire on smoking habits and medical history. Results Airflow limitation was more prevalent in current smokers than in ex-smokers and never-smokers in men and women. The frequency of hypertriglyceridemia was higher in current smokers in all age groups, and those of low high-density-lipoprotein cholesterolemia and diabetes mellitus were higher in current smokers in age groups ≥ 40 s in men, but not in women. There were significant differences in the frequencies of metabolic abnormalities between subjects with airflow limitations and those without in women, but not in men. Smoking index was an independent factor associated with increased frequencies of hypertriglyceridemia (OR 1.015; 95% CI: 1.012–1.018; p<0.0001) and low high-density-lipoprotein cholesterolemia (1.013; 1.010–1.016; p<0.0001) in men. Length of smoking cessation was an independent factor associated with a decreased frequency of hypertriglyceridemia (0.984; 0.975–0.994; p = 0.007). Conclusions Habitual smoking causes high incidences of airflow limitation and metabolic abnormalities. Women, but not men, with airflow limitation had higher frequencies of metabolic abnormalities.

Nonspecific elevation of serum Aspergillus galactomannan antigen levels in patients with rheumatoid arthritis

BACKGROUND Infections are an important cause of morbidity and mortality in patients with rheumatoid arthritis. Patients receiving immunosuppressive or anti-tumor necrosis factor (TNF) agents are vulnerable to fungal infections, including those derived from Aspergillus species. Detection of the Aspergillus galactomannan antigen in serum is useful for the early diagnosis of invasive aspergillosis in patients with hematological malignancies. However, its usefulness for detecting early invasive aspergillosis in rheumatoid arthritis patients remains unestablished. METHODS Galactomannan antigen levels were measured in 340 patients (311 female patients). For patients who exhibited galactomannan antigen levels ≥0.5 during the initial examination, a second examination was performed 3-6 months later. Conventional blood tests and chest radiography were also performed. RESULTS Elevated galactomannan antigen levels (≥0.5) were observed in 62 (18.2%) of 340 patients during the initial examination. A second examination was performed in 56 of 62 patients, 50 of whom exhibited elevated antigen levels. Elevated antigen levels were not associated with the use of any drug including anti-TNF agents. Serum galactomannan antigen levels were correlated with the albumin/globulin ratio (r=-0.19, p<0.001), γ-globulin (%; r=0.17, p=0.001), and hemoglobin concentration (r=-0.15, p=0.005). No patient was clinically diagnosed with invasive aspergillosis during the study period. CONCLUSIONS Serum galactomannan antigen levels are frequently elevated in a nonspecific manner in patients with rheumatoid arthritis.

Primary Malignant Pericardial Mesothelioma Mimicking Pericardial Metastasis from Adenocarcinoma

An 85-year-old man was admitted with dyspnea on exertion and general fatigue. He was a retired school teacher without obvious history of asbestos exposure. Chest radiograph revealed cardiomegaly, and a large pericardial effusion was found from echocardiogram, which was subsequently drained by ultrasound-guided needle aspiration. Its hyaluronic acid level was 32,000 ng/ml (within normal range). Cytologic examination was positive, suggesting adenocarcinoma. The F-18 fluorodeoxyglucose positron emission tomography scan detected abnormal aggregations around the ascending aorta, pulmonary artery, and pericardium, but no primary focus was found (Figure 1). Pleural thickening and pleural plaques were not detected. A diagnosis of adenocarcinoma and pericardial metastasis of unknown origin was made. He died about 3 months after diagnosis due to right cardiac failure resulting from constrictive pericarditis. Autopsy revealed tumor had infiltrated and proliferated in the pericardium and myocardium and invaded the pericardial cavity (Figure 2a). Tumor was not found in the pleura. Pleural plaques were found, but asbestos bodies were not observed. Histologic examination revealed atypical proliferation of epithelioid cells (Figure 2b) and spindle cells (Figure 2c). Immunologic staining for calretinin was positive in the epithelioid and sarcomatous tumor cell nuclei and cytoplasm (Figure 2d). We diagnosed diffuse and biphasic primary malignant pericardial mesothelioma (PMPM). PMPM is extremely rare and represents 0.7% of all mesotheliomas.1 In this case, the patient was originally misdiagnosed with adenocarcinoma by pericardial effusion cytology. The reliability of body cavity fluid cytology is low for malignant mesothelioma; its sensitivity is reported to be 33 to 84%.2 Thus, histologic and immunohistochemical studies should be performed when PMPM is clinically suspected, even if adenocarcinoma is diagnosed by pericardial effusion cytology.

Severity of community-acquired pneumonia treated with low-dose adjunctive corticosteroid

We read with interest the report of the randomized double-blind controlled trial by Fernandez-Serrano and colleagues [1] suggesting that the administration of methyl-prednisolone (MPDN) with ceftriaxone plus levofl oxacin improves clinical variables in communityacquired pneumonia (CAP). Compared with randomly controlled studies in which patients benefi ted from corticosteroid treatment [2-4], all patients of this study received the same antibiotics. It is striking that this study has overcome the problem that choice and dose of antibiotics may infl uence results. However, several points should be discussed. First, it would be better to consider the severity of CAP because adjunctive corticosteroid treatment should not be routinely administrated to patients with any severity of CAP. In fact, the results of our study suggest that cortico steroid treatment lacks effi cacy in cases of mild to moderate CAP [3]. Although additional subgroup analysis may lead to similar results to those of our study because more than 50% of patients in both studies had a pneumonia severity index [5] rating of IV or V [1,3], the target population for corticosteroid treatment should be precisely identifi ed. Moreover, although the authors administrated 620 mg MPDN per patient, we [3] and Meijvis and colleagues [4] showed a benefi cial eff ect with lower doses of corticosteroids over shorter periods. Th e authors should consider lower doses and shorter periods of MPDN treatment in a future study. Although this study could clearly provide signifi cantly benefi cial evidence of the value of MPDN treatment, the severity of pneumonia should be addressed because of the potential risk associated with corticosteroid treatment.