Jung-Woo Rhim

Difference of clinical features in childhood Mycoplasma pneumoniae pneumonia

BackgroundM. pneumoniae pneumonia (MP) has been reported in 10-40% of community-acquired pneumonia cases. We aimed to evaluate the difference of clinical features in children with MP, according to their age and chest radiographic patterns.MethodsThe diagnosis of MP was made by examinations at both admission and discharge and by two serologic tests: the indirect microparticle agglutinin assay (≥1:40) and the cold agglutinins titer (≥1:32). A total of 191 children with MP were grouped by age: ≤2 years of age (29 patients), 3-5 years of age (81 patients), and ≥6 years of age (81 patients). They were also grouped by pneumonia pattern: bronchopneumonia group (96 patients) and segmental/lobar pneumonia group (95 patients).ResultsEighty-six patients (45%) were seroconverters, and the others showed increased antibody titers during hospitalization. Among the three age groups, the oldest children showed the longest duration of fever, highest C-reactive protein (CRP) values, and the most severe pneumonia pattern. The patients with segmental/lobar pneumonia were older and had longer fever duration and lower white blood cell (WBC) and lymphocyte counts, compared with those with bronchopneumonia. The patient group with the most severe pulmonary lesions had the most prolonged fever, highest CRP, highest rate of seroconverters, and lowest lymphocyte counts. Thrombocytosis was observed in 8% of patients at admission, but in 33% of patients at discharge.ConclusionsIn MP, older children had more prolonged fever and more severe pulmonary lesions. The severity of pulmonary lesions was associated with the absence of diagnostic IgM antibodies at presentation and lymphocyte count. Short-term paired IgM serologic test may be mandatory for early and definitive diagnosis of MP.

Hyperactive immune cells (T cells) may be responsible for acute lung injury in influenza virus infections: A need for early immune-modulators for severe cases

Summary It has been believed that acute lung injury in influenza virus infections is caused by a virus-induced cytopathy; viruses that have multiplied in the upper respiratory tract spread to lung tissues along the lower respiratory tract. However, some experimental and clinical studies have suggested that the pathogenesis of acute lung injury in influenza virus infections is associated with excessive host response including a cell-mediated immune reaction. During the pandemic H1N1 2009 influenza A virus infections in Korea, we experienced a dramatic effect of immune-modulators (corticosteroids) on the patients with severe pneumonia who had significant respiratory distress at presentation and those who showed rapidly progressive pneumonia during oseltamivir treatment. We also found that the pneumonia patients treated with corticosteroids showed the lowest lymphocyte differential and that the severity of pneumonia was associated with the lymphocyte count at presentation. From our findings and previous experimental and clinical studies, we postulated that hyperactive immune cells (T cells) may be involved in the acute lung injury of influenza virus infections, using a hypothesis of ‘protein homeostasis system’; the inducers of the cell-mediated immune response are initially produced at the primary immune sites by the innate immune system. These substances reach the lung cells, the main target organ, via the systemic circulation, and possibly the cells of other organs, including myocytes or central nerve system cells, leading to extrapulmonary symptoms (e.g., myalgia and rhabdomyolysis, and encephalopathy). To control these substances that may be possibly toxic to host cells, the adaptive immune reaction may be operated by immune cells, mainly lymphocytes. Hyperimmune reaction of immune cells produces higher levels of cytokines which may be associated with acute lung injury, and may be controlled by early use of immune-modulators. Early initiation and proper dosage of immune-modulators with antiviral agents for severe pneumonia patients may reduce morbidity and prevent progressive fatal pneumonia.

Epidemiological comparison of three Mycoplasma pneumoniae pneumonia epidemics in a single hospital over 10 years

Purpose Mycoplasma pneumoniae (MP) pneumonia epidemics have occurred in 3- to 4-year cycles in Korea. We evaluated the epidemiologic characteristics of MP pneumonia in Daejeon, Korea, from 2003 to 2012. Methods We retrospectively analyzed 779 medical records of children (0-15 years of old) with MP pneumonia admitted to our institution and compared the data from 3 recent epidemics. Results In 779 patients, the mean age and male-to-female ratio were 5.0±2.2 years and 1:1, and most cases were observed in autumn. There were three epidemics during the study period, in 2003, 2006-2007, and 2011. In our comparison of the three epidemics, we found no differences in mean age, the male-to-female ratio, hospital stay, or the rate of seroconverters during hospitalization. All three epidemics began in early summer and peaked in September 2003 and 2011 and in October 2006 and then gradually decreased until the next years spring season, although the 2006 epidemic extended further into 2007. The peak age groups in the children in 2003 and 2006 were 3-6 year-olds (57.5% and 56%, respectively), but in the 2011 epidemic, the peak group was 1-4 year-olds (46.5%). The proportion of the <2 years of age group was 20%, 15.7% and 28.8%, and >10 years of age group was 5.2%, 13.8%, and 14.8% of total patients, respectively. Conclusion MP pneumonia outbreaks occurred every 3-4 years. The pattern of 3 recent epidemics was similar in demographic characteristics and seasonality with some variations in each outbreak.

Assessment of intravenous immunoglobulin non-responders in Kawasaki disease

The authors compared pre-treatment and post-treatment characteristics of 206 prospectively enrolled patients with Kawasaki disease (KD) responsive to intravenous immunoglobulin (IVIG) with those of 23 (10% of total) IVIG non-responders. Demographic characteristics were similar in both groups. Compared to IVIG responders, non-responders had a longer total duration of fever and a higher incidence of coronary artery lesions. Prior to IVIG, non-responders had higher neutrophil differential and C-reactive protein, and lower cholesterol. 24 hours after the IVIG infusion, a total leucocyte count >13.1×109/l, neutrophil differential >51% and total protein <72 g/l showed reasonable sensitivity (91%, 91% and 64%, respectively) and specificity (89%, 76% and 78%, respectively) as independent characteristics of non-response to IVIG. Laboratory parameters before and shortly after IVIG may reflect the severity of inflammation in KD patients and assist in informing further management.

Atopic Dermatitis and Cytokines: Recent Patents in Immunoregulatory and Therapeutic Implications of Cytokines in Atopic Dermatitis - Part I: Cytokines in Atopic Dermatitis

Atopic dermatitis is a chronic allergic inflammatory disease of the skin. Its pathophysiology involves an orchestrated sequence of allergic provocation by IgE-mediated and non-IgE-mediated Th2 responses to allergens. Allergen sensitization precedes the immunopathogenesis. Th2 cytokines such as IL-4 and IL-5 play a key role in both the sensitization and effector phases of allergic skin inflammation. Recently, the roles of new cytokines including IL-16, IL-17, IL-21, IL-22, IL-23, IL-27, IL-31, IL-33, IL-35 and thymus stromal lymphopoietin (TSLP), and Th2 polarization in the immunopathogenesis of skin inflammation and physically injured skin have been described, in addition to roles for IL-4, IL- 5, IL-9, IL-13, IFN-γ and TGF-β. Sensitization occurs via the skin for aeroallergen including house dust mites and superantigens and through the gastrointestinal tract for food allergens. Alternatively, food allergens can be sensitized through skin. Atopic dermatitis is described under the structure of sensitization phase and effector phase in this review. Especially, the clinically effective applications of cytokines in AD and relevant patents are updated in this review.

Early corticosteroid treatment for severe pneumonia caused by 2009 H1N1 influenza virus

A pandemic of the 2009 H1N1 influenza A virus infection occurred worldwide in 2009. Some previously healthy patients experienced rapidly progressive pneumonia leading to acute respiratory distress syndrome (ARDS) and even death. The effect of corticosteroids on these severely affected patients is controversial because of a lack of controlled clinical trials [1]. During the pandemic in South Korea, we observed that early, short-term corticosteroid treatment along with oseltamivir seemed to have a dramatic effect on patients with severe pneumonia, and we proposed a new theory for the pathogenesis of acute lung injury in influenza virus infections [2]. In that study, we wanted to evaluate this beneficial effect of corticosteroid treatment through comparative data based on the use or non-use of corticosteroids at two separate hospitals. The subjects of the study were the pneumonia patients who had severe respiratory distress with hypoxemia at presentation or during admission and who thus required oxygen therapy. The conditions of 17 patients (median of 6 years of age, range of 4 to 9) in our hospital (The Catholic University of Korea, Daejeon St Marys Hospital, Daejeon, South Korea) (use of corticosteroids) and 15 patients (median of 6 years of age, range of 5 to 18) in a neighboring hospital (Chungnam National University Hospital, Daejeon, South Korea) (non-use of corticosteroids) were diagnosed by reverse transcriptase-polymerase chain reaction. The clinical and laboratory characteristics of patients in the two hospitals are shown in Table ​Table1.1. Our results suggested that the severe pneumonia patients who were treated with corticosteroids showed shortened durations of fever and oxygen therapy, rapid resolution of pneumonic infiltrations, and possibly no progression to ARDS. Table 1 Clinical and laboratory characteristics of severe pneumonia patients infected with the 2009 H1N1 virus, with and without corticosteroid treatment It is reported that corticosteroid treatment for adult ARDS patients with 2009 H1N1 virus infection was effective in the improvement of lung injury score [3]. Two recent case series suggest a possible life-saving role of corticosteroids in severely ill adult patients with 2009 H1N1 virus infection unresponsive to other treatments [4,5]. Corticosteroids may not increase the viral load of the patients [4]. To the best of our knowledge, our study may be the first trial addressing an early and preemptive modality before ARDS development in influenza virus infections. Our policy of corticosteroid treatment with a rapid, high-dose (methylprednisolone, 10 mg/kg per day), and short-term (tapered off within a week) schedule did not show any complications in our patients and may avoid the complications that arise from long-term corticosteroid use. Although rapid corticosteroid treatment for patients with severe pneumonia halted clinical and radiographic exacerbation and possibly prevented progression to ARDS in our series, further controlled clinical trials are needed to evaluate the role of corticosteroids for severely affected patients with influenza virus infections.

Epidemiological and clinical characteristics of childhood pandemic 2009 H1N1 virus infection: an observational cohort study

BackgroundThere was a pandemic influenza around the world in 2009 including South Korea since last pandemic occurred four decades ago. We aimed to evaluate the epidemiological and clinical characteristics of this infection in childhood.MethodsWe evaluated the epidemiologic characteristics of all the subjects infected with the 2009 H1N1 influenza A virus (2,971 patients, ≤ 15 years of age), and the clinical and laboratory findings of the inpatients (217 patients, 80 had pneumonia) between 1 September 2009 and 31 January 2010 in a single hospital throughout the epidemic.ResultsThe age distribution of all the subjects was relatively even. Over 90% of cases occurred during a two-month period. Two hundred and five patients (94.5%) received oseltamivir within 48 h of fever onset, and 97% of inpatients defervesced within 48 h of medication. The group with pneumonia included more males than females, and had higher leukocytes counts with lower lymphocyte differentials than the group without pneumonia. The white blood cell count and lymphocyte differential were associated with the severity of pneumonia. Corticosteroid treatment for severe pneumonia patients was highly effective in preventing disease progression.ConclusionChildren of all ages affected with even rates of infection, but males were predominant in pneumonia patients. Pneumonia patients showed lymphopenia and its severity was associated with the severity of illness. Our results suggest that the mechanism of lung injury in 2009 H1N1 virus infection may be associated with the host immune response.

Pandemic 2009 H1N1 virus infection in children and adults: A cohort study at a single hospital throughout the epidemic.

Background In 2009, there was an influenza pandemic in South Korea. The aim of this study was to evaluate the epidemiological, clinical and laboratory characteristics of this infection in children and adults. Methods We evaluated the epidemiologic characteristics of patients infected with the 2009 H1N1 influenza A virus (4,463 patients, age range from 2 mo to 86 y), and the clinical and laboratory findings of 373 inpatients (80/217 children, ≤ 15 y, had pneumonia and 36/156 adults, > 16 y, had pneumonia) in a single hospital during the epidemic. Results The majority of infected patients (94%) were less than 40 y, and greater than 90% of cases occurred during a two-month period. The rates of admission and pneumonia were 8.4% (373/4,463) and 2.5% (116/4,463), respectively. The rates of admission and pneumonia, total duration of fever, the frequency of underlying diseases, and the values of C-reactive protein and erythrocyte sedimentation rate tended to increase as age increased; highest rates were found in the ≥ 65 y group. Pneumonia was founded more boys than girls in children, but more female than male in adults. The adult patients with pneumonia had higher leukocyte counts with lower lymphocyte differentials than the group without pneumonia, as shown in children group. Conclusion Our results suggest that the immunologic reaction to viral insults may be associated with age, sex and underlying diseases, and that unknown herd immunity may affect populations. The patients with underlying diseases, especially in older patients may have immunologic insufficiency that is associated with immunologic consumption by the underlying diseases.

Outbreaks of mumps: an observational study over two decades in a single hospital in Korea

Purpose The introduction of the mumps vaccine has dramatically reduced the number of mumps cases, but outbreaks have recently occurred among highly vaccinated populations in developed countries. Epidemiological and clinical characteristics of patients with mumps admitted between 1989 and 2012 in a single hospital in Korea are described in the present study. Methods We retrospectively evaluated inpatients with mumps between 1989 and 2012 and outpatients and inpatients with mumps in 2011-2012. Results A total of 152 patients with mumps were admitted between 1989 and 2012, and 163 patients were recorded in 2011-2012. The highest number of admitted cases occurred in 1998 and 2012 (35 and 34 cases, respectively). Among the patients admitted in 2011-2012, the highest frequency was observed among people aged 15-19 years, and low frequency was observed in those aged <4 years and >20 years, compatible to the city data and national data. In patients admitted to our department in 1998 (35 cases) and in 2010-2012 (27 cases), there were significant differences in the mean age and the rate of secondary measles-mumps-rubella (MMR) vaccination, but had similar clinical features, including complications, except aseptic meningitis. Antimumps immunoglobulin (Ig) G was positive in 83% and 100%, and IgM was positive in 67% and 41%, respectively, in the two periods. Conclusion In Korea, recent mumps outbreaks have occurred mainly among secondary school students who received two doses of the MMR vaccine. The vaccinees might have a modified immune reaction to viral insults, manifesting modified epidemiological and clinical features.

Changes in Kawasaki disease during 2 decades at a single institution in Daejeon, Korea.

Background: The goal of this study is to evaluate the changes in the epidemiologic and clinical features of Kawasaki disease (KD) in a period of 20 years. Methods: We compared the epidemiologic features of 3 KD patient groups: those admitted from 1987 to 1990 (122 cases), from 1997 to 2000 (137 cases) and from 2007 to 2010 (102 cases). For clinical features, we reviewed the medical records of patients admitted from 1996 to 2000 (141 cases) and from 2006 to 2010 (121 cases). Results: There were a total of 772 KD patients during the study period (mean age: 27.2 months; male-to-female ratio: 1.6:1). There were some variations in the mean ages (23.8, 27.8 and 30 months), in the male-to-female ratios (1.9:1, 1.3:1 and 1.8:1) and in the age distributions, including the patients of ages <6 months and >5 years, but the differences were not statistically significant across the groups. The seasonal distributions were relatively consistent with some variations. In clinical features, the preadmission and total fever durations were shorter (P < 0.001, respectively), and the proportions of incomplete KD tended to increase, and the rates of coronary artery aneurysm tended to decrease in recently admitted patients. Conclusions: There were no significant changes in the demographic and seasonal features of KD, although the evaluation of the clinical features showed shorter fever duration suggestive of improved identification and treatment of KD over time.