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Biomedical subjects

Won-Jung Koh

Publications and source records attributed to Won-Jung Koh.

At least 19 recordsLinked to original sources

Polymorphisms of interferon-gamma and interferon-gamma receptor 1 genes and non-tuberculous mycobacterial lung diseases.

Interferon-gamma (IFN-gamma) is crucial for host defense against mycobacterial infections. Recent studies have indicated that IFN-gamma and IFN-gamma receptor 1 (IFN-gammaR1) gene polymorphisms are associated with susceptibility to pulmonary tuberculosis. The aim of this study was to test the hypothesis that IFN-gamma and IFN-gammaR1 gene polymorphisms influence susceptibility to lung disease caused by non-tuberculous mycobacteria (NTM). Seventy-six patients with the nodular bronchiectatic form of NTM lung disease (37 patients with Mycobacterium avium complex infection and 39 patients with Mycobacterium abscessus infection) and 80 controls were included. Polymorphisms of the IFN-gamma gene at position +874 were determined by the amplification refractory mutation system (ARMS) polymerase chain reaction assay and IFN-gammaR1 gene at positions -611, -270, -56 and +95 was genotyped by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry using genomic DNA. IFN-gammaR1 -270 and +95 polymorphisms were not present in any of the patients or controls. The patients with NTM lung disease showed no significant difference from controls in genotype and allele frequencies of the IFN-gamma +874 and IFN-gammaR1 -611 and -56 polymorphisms. The IFN-gamma +874 and IFN-gammaR1 -611 and -56 polymorphisms do not appear to be responsible for host susceptibility to NTM lung disease, at least in the Korean population.

Adult↗

Acute pneumonia and empyema caused by Mycobacterium intracellulare.

Nontuberculous mycobacterial infection is rarely accompanied by pleural involvement. We report a very rare case of M. intracellulare pulmonary disease with pleural empyema. A 56-year-old man was admitted to our hospital because of fever, purulent sputum and pleuritic chest pain. A chest radiograph and CT revealed pneumonic consolidation in the left lower lobe and loculated hydropneumothorax. The sputum smear was positive for acid fast bacilli. The aspirated pleural fluid was grossly purulent and the smear of the pleural effusion was also positive for acid fast bacilli. M. intracellulare was identified by culture and PCR from sputum and pleural fluid specimens. The patient improved with percutaneous tube drainage of the purulent effusion and antibiotic treatment including clarithromycin, rifampicin, ethambutol and streptomycin.

Acute Disease↗

Partial interferon-gamma receptor deficiency and non-tuberculous mycobacterial lung disease.

Interferon-gamma (IFN-gamma) plays a key role in the host defense response against mycobacterial disease, and a complete or partial deficiency in IFN-gamma receptor 1 (IFN-gammaR1) or IFN-gamma receptor 2 (IFN-gammaR2) has been reported to contribute to susceptibility to disseminated infection with non-tuberculous mycobacteria (NTM). However, IFN-gammaR1 and IFN-gammaR2 deficiencies have not yet been studied in adult patients with isolated NTM lung disease. The purpose of the present study was to evaluate whether partial IFN-gammaR1 and IFN-gammaR2 deficiency are associated with human susceptibility to NTM lung disease. We studied 40 patients with NTM lung disease (Mycobacterium avium complex infection, 20 patients; Mycobacterium abscessus infection, 20 patients) for partial IFN-gammaR1 and IFN-gammaR2 deficiency. Genomic DNA was amplified by polymerase chain reaction and sequenced for revealing mutations of the IFN-gammaR1 and IFN-gammaR2 gene. None of the patients had previously reported homozygous recessive missense mutation causing an amino-acid substitution in the extracellular domain of the receptor (I87T) and hotspot for small deletions (818delT, 818del4) of the IFN-gammaR1 or homozygous missense mutation (R114C) of the IFN-gammaR2. In conclusion, in adult patients with isolated NTM lung disease, there is no evidence for previously known genetic defects of partial deficiencies of IFN-gammaR1 and IFN-gammaR2 to correlate with disease.

Adult↗

Drug-sensitive tuberculosis, multidrug-resistant tuberculosis, and nontuberculous mycobacterial pulmonary disease in nonAIDS adults: comparisons of thin-section CT findings.

The aim of this work was to compare thin-section CT (TSCT) findings of drug-sensitive (DS) tuberculosis (TB), multidrug-resistant (MDR) TB, and nontuberculous mycobacterial (NTM) pulmonary disease in nonAIDS adults. During 2003, 216 (113 DS TB, 35 MDR TB, and 68 NTM) patients with smear-positive sputum for acid-fast bacilli (AFB), and who were subsequently confirmed to have mycobacterial pulmonary disease, underwent thoracic TSCT. The frequency of lung lesion patterns on TSCT and patients' demographic data were compared. The commonest TSCT findings were tree-in-bud opacities and nodules. On a per-person basis, significant differences were found in the frequency of multiple cavities and bronchiectasis (P < 0.001, chi-square test and multiple logistic regression analysis). Multiple cavities were more frequent in MDR TB than in the other two groups and extensive bronchiectasis in NTM disease (multiple logistic regression analysis). Patients with MDR TB were younger than those with DS TB or NTM disease (P < 0.001, multiple logistic regression analysis). Previous tuberculosis treatment history was significantly more frequent in patients with MDR TB or NTM disease (P < 0.001, chi-square test and multiple logistic regression analysis). In patients with positive sputum AFB, multiple cavities, young age, and previous tuberculosis treatment history imply MDR TB, whereas extensive bronchiectasis, old age, and previous tuberculosis treatment history NTM disease.

Adult↗

Mycobacterium abscessus pulmonary infection presenting as a solitary pulmonary nodule.

Nontuberculous mycobacterial pulmonary infection is a rare cause of a solitary pulmonary nodule. All previously reported cases were caused by Mycobacterium avium complex, and a solitary pulmonary nodule caused by other NTM species has been very rarely reported. We describe the first case of Mycobacterium abscessus infection presenting as a solitary pulmonary nodule in a 51-year-old asymptomatic adult patient.

Female↗

Tuberculous otitis media: a clinical and radiologic analysis of 52 patients.

OBJECTIVE: This retrospective study reports on the clinical and radiologic features and the treatment outcomes of patients with tuberculous otitis media (TOM). METHODS: We reviewed the medical records of 52 patients (53 ears) with TOM between 1993 and 2005 and analyzed temporal bone computed tomography scans of 23 patients. The diagnosis of TOM was made if a specimen of the middle ear revealed the presence of acid fast bacilli (AFB), grew Mycobacterium tuberculosis (M. Tb) on a culture, revealed characteristic histology, and/or was positive for polymerase chain reaction (PCR) for M. Tb. RESULTS: The highest incidence of the disease was observed among patients in their 30s. The main symptom was otorrhea, and the duration of symptoms was shorter than with nonspecific chronic otitis media. Most patients demonstrated a moderate to severe hearing loss. Five patients (9.6%) demonstrated a peripheral-type facial palsy. Temporal bone CT scans demonstrated relatively well-pneumatized mastoids and occupation by soft tissue of the entire tympanum and mastoid air cells. Six patients demonstrated bone destruction that involved the cortex of the mastoid bone. In most patients, antituberculous medication was effective treatment. The patients who underwent chemotherapy after surgery achieved more rapid healing of the ear and more frequent closure of the tympanic membrane than those who did not receive surgery. CONCLUSIONS: Clinicians should have a high index of suspicion and be aware of the clinical and radiologic characteristics of TOM.

Adolescent↗

Toll-like receptor 2 polymorphisms and nontuberculous mycobacterial lung diseases.

To investigate the occurrence of the Toll-like receptor 2 (TLR2) polymorphisms in patients with pulmonary disease caused by nontuberculous mycobacteria (NTM), TLR2 Arg677Trp and Arg753Gln polymorphisms were examined. TLR2 polymorphisms do not appear to be responsible for host susceptibility to NTM lung disease, at least in the Korean population.

Adult↗

Clinical significance of nontuberculous mycobacteria isolated from respiratory specimens in Korea.

STUDY OBJECTIVES: Precise epidemiologic data regarding nontuberculous mycobacterial (NTM) lung infection in many Asian countries have been relatively unavailable. In order to determine the clinical significance of NTM isolated from respiratory specimens, we reviewed medical records from all patients from whom NTM isolates were recovered within a 2-year period. MATERIALS AND METHODS: We identified all NTM isolates from respiratory specimens at the Samsung Medical Center (Seoul, South Korea) obtained from January 2002 to December 2003. We then reviewed the clinical and radiologic characteristics of the patients from whom NTM was isolated. Patients were classified as having either definite, probable, or unlikely NTM lung disease, as defined by the guidelines of both the American Thoracic Society and the British Thoracic Society. RESULTS: During the study period, 1,548 NTM isolates were recovered from 794 patients. Of these 794 patients, 131 patients (17%) were determined to have definite NTM lung disease, and 64 patients (8%) were designated as probable disease candidates. The most commonly involved organisms in the definite and probable NTM lung disease cases were Mycobacterium avium complex (n = 94, 48%) and Mycobacterium abscessus (n = 64, 33%). In 195 patients with NTM lung disease, 82 patients (42%) manifested the upper lobe cavitary form, 101 patients (52%) exhibited the nodular bronchiectatic form, and 12 patients (6%) exhibited the unclassifiable form. CONCLUSIONS: About one fourth of the patients in whom NTM was isolated from respiratory specimens were found to have clinically significant NTM lung infections. The spectrum of organisms responsible for the NTM lung disease in these Korean patients differed from those reported in other regions of the world. However, the estimates of clinical significance in this study may be underestimates due to the retrospective analysis. Some of the patients might have "true" NTM lung disease that could be diagnosed with continued evaluation and follow-up.

Adult↗

Thoracic actinomycosis: CT features with histopathologic correlation.

OBJECTIVE: Thoracic actinomycosis is a chronic suppurative pulmonary or endobronchial infection caused by Actinomyces israelii, a gram-positive anaerobic organism. We present the CT features of thoracic actinomycosis with histopathologic correlation. CONCLUSION: The typical CT feature of parenchymal actinomycosis is a chronic segmental air-space consolidation containing necrotic low-attenuation areas with frequent cavity formation. A broncholith can be secondarily infected with Actinomyces organisms, resulting in endobronchial actinomycosis. It usually manifests as a proximal endobronchial calcification associated with distal obstructive pneumonia.

Actinomycosis↗

Report of a Korean patient with cystic fibrosis, carrying Q98R and Q220X mutations in the CFTR gene.

Although cystic fibrosis (CF) is one of the most frequently seen autosomal-recessive disorders in Caucasians, it is extremely rare in the Korean population. Recently, a 15-yr-old Korean boy was admitted to our hospital complaining of coughing, sputum, and exertional dyspnea. Chest radiographs and computed tomographic chest and paranasal sinus scans revealed diffuse bronchiectasis and pansinusitis. Pulmonary function tests revealed severe obstructive impairment. The average sweat chloride concentrations on both of the patients' forearms were 63.0 mM/L (reference limit: < 40 mM/L). Upon mutation analysis, two different mutations (Q98R and Q220X) were identified in the cystic fibrosis transmembrane conductance regulator gene, both of which had been previously detected in CF patients, one from France and the other from England. As CF is quite rare in Korea, the diagnosis of CF in this patient might be delayed. Therefore, we recommend that a diagnosis of CF should be suspected in patients exhibiting unexplained chronic respiratory symptoms.

Adolescent↗

Prognostic factors and causes of death in Korean patients with idiopathic pulmonary fibrosis.

The purpose of this study was to investigate the prognostic factors at initial presentation and the causes of death in Korean patients with idiopathic pulmonary fibrosis (IPF), which might be different report wise, in comparison to the western countries. A retrospective review of 88 patients (mean 60.3 years, 69 male) was carried out and they were diagnosed as IPF positive. After diagnosis, the survival rate was 57% and 41% for third and fifth year, respectively (mean follow-up 39.1 months). Mortality was closely correlated with severe dyspnea at presentation (Hazard Ratio [HR], 2.6 per grade; p=0.015), lower initial forced vital capacity (HR, 1.7 per 10% predicted; p=0.004) and lower initial diffusing capacity of the lung (HR, 1.5 per 10% predicted; p=0.033). Treatment with specific drugs was ineffective against the survival when compared with symptomatic supportive care. Thirty-four patients (68%) died of worsened respiratory failure, seven (14%) died of infection and only one patient showed cardiovascular death. In conclusion, our study suggests that the severity of dyspnea and lung function tests at the time of diagnosis are the predictive factors for the survival of patients with IPF. In comparison to the reports from western countries, we observed that respiratory failure and pulmonary infection were more frequent causes of death, while cardiovascular death was rare in Korean patients with IPF.

Aged↗

Bilateral bronchiectasis and bronchiolitis at thin-section CT: diagnostic implications in nontuberculous mycobacterial pulmonary infection.

PURPOSE: To determine frequency of nontuberculous mycobacterial (NTM) pulmonary infection in patients with bilateral bronchiectasis and bronchiolitis at chest computed tomography (CT) and whether CT findings are indicative of Mycobacterium avium-intracellulare complex (MAC) infection. MATERIALS AND METHODS: Institutional review board approved this research study; patient informed consent (not required) was obtained from all patients to perform CT. From July 2000 to December 2002, 126 consecutive patients, who were suspected of having NTM pulmonary infection at helical CT (120 kVp, 70 mA, 2.5-mm collimation, pitch of 6) with findings of bilateral bronchiectasis and bronchiolitis, were included. Of these, 105 patients underwent study for diagnosis of NTM disease. Medical records and CT scans were reviewed for final diagnoses. Clinical and chest CT findings in patients with NTM disease and those with other airway diseases were compared (unpaired t test, chi(2) test, or Fisher exact test). RESULTS: NTM pulmonary infection was seen in 36 (34%) of 105 patients; NTM was definite in 32 (30%) and probable in four (4%). In decreasing order of frequency, organisms involved were MAC in 18 patients (50%), with M avium in 10 and M intracellulare in eight, Mycobacterium abscessus in 14 (39%), Mycobacterium kansasii in one (3%), and Mycobacterium fortuitum in one (3%); organisms were unidentifiable in two (6%). Female (P = .031) nonsmokers (P = .037) with history of treatment for Mycobacterium tuberculosis (P = .002), sputum smear positive for acid-fast bacilli (P < .001), and thin-section CT findings of bronchiolitis in more than five lobes with bronchiectasis (P = .011), lobular consolidation (P = .010), and a cavity (P < .001) were related to diagnosis of NTM pulmonary infection. CONCLUSION: About one-third of patients with thin-section CT findings of bilateral bronchiectasis and bronchiolitis have NTM pulmonary infection; in these situations, MAC and M abscessus are two most frequent causative organisms. Thin-section CT findings of bronchiectasis and bronchiolitis involving more than five lobes, especially when associated with lobular consolidation or a cavity, are highly suggestive of NTM pulmonary infection.

Adolescent↗

Comparison of drug resistance genotypes between Beijing and non-Beijing family strains of Mycobacterium tuberculosis in Korea.

The frequency of resistance genotypes among Beijing and non-Beijing strains was compared using a reverse blot hybridization assay to detect mutations within genes associated with rifampicin (rpoB) and isoniazid (katG, inhA, and ahpC) resistance. Of the 743 Mycobacterium tuberculosis isolates, 569 (77%) belonged to Beijing family. The proportion of Beijing strains was significantly higher among MDR-TB isolates than among drug-susceptible strains (82% vs. 72%, p<0.01). Genotype analysis of the rpoB gene revealed significantly lower rates of the Ser531Leu mutation rate among Beijing vs. non-Beijing MDR-TB strains (41% vs. 66%, p<0.005). While the mutation for Ser315Thr in the katG gene was more common among Beijing vs. non-Beijing family strains (65% vs. 50%, p<0.01), the mutation rate of promoter region of the inhA gene was lower among Beijing strains compared with non-Beijing strains (14% vs. 25%, p<0.05). Reverse hybridization successfully detected over 80% of isoniazid-resistant strains and over 92% of rifampicin-resistant strains among Korean isolates. Significant differences in mutation rates in the rpoB, katG, and inhA genes between Beijing strains and non-Beijing strains could explain discrepancies in mutation rates of genotypes in different countries. Reverse hybridization was useful for rapid detection of isoniazid and rifampicin resistant strains.

Antitubercular Agents↗

Recruitment maneuvers attenuate repeated derecruitment-associated lung injury.

OBJECTIVE: Repeated derecruitments of previously recruited lungs can exacerbate lung injuries during mechanical ventilation. The aim of this study was to assess lung injury associated with repeated derecruitments and to assess whether this type of injury could be attenuated by recruitment maneuvers. DESIGN: Prospective, randomized, experimental animal study. SETTING: University laboratory. SUBJECTS: New Zealand White rabbits. INTERVENTIONS: Twenty-one rabbits were ventilated in pressure-controlled mode with constant tidal volume (10 mL/kg). After lung injury was induced by repeated saline lavage, positive end-expiratory pressure (PEEP) at a lower inflection point was applied for 3 hrs. The control group (n = 7) received ventilation with the same PEEP for 3 hrs without derecruitments. In the derecruitment group (n = 7), derecruitment was repeatedly induced by intentional disconnection of the ventilatory circuit for 1 min every 10 mins for 3 hrs. In the recruitment maneuver group (n = 7), continuous positive airway pressure of 30 cm H2O was applied for 30 secs after each derecruitment. MEASUREMENTS AND MAIN RESULTS: After PEEP levels were increased to lower the inflection point value, Pao2 increased to >500 mm Hg in all groups. Increased Pao2 persisted at >450 mm Hg in the control and recruitment maneuver groups, whereas progressive declines in arterial oxygen levels were observed in the derecruitment group (median, 381.1 mm Hg [interquartile range, 350.1-466.7 mm Hg] at 2 hrs and 318.2 mm Hg [214.3-414.9 mm Hg] at 3 hrs, p < .05 compared with other groups). Histologically, there was significantly increased hyaline membrane formation in alveolar ducts in the derecruitment group compared with the control group (p = .005). Also, significantly more membranous and respiratory bronchiolar injuries were observed in the derecruitment group compared with the control and recruitment maneuver group (p < .005). CONCLUSIONS: These findings suggest that repeated derecruitments could induce lung injuries during mechanical ventilation, and recruitment maneuvers may attenuate derecruitment-associated lung injuries.

Animals↗

Inactive hepatitis B surface antigen carrier state and hepatotoxicity during antituberculosis chemotherapy.

STUDY OBJECTIVES: To determine whether inactive hepatitis B surface antigen (HBsAg) carriers are at a higher risk of drug-induced hepatotoxicity than control subjects during antituberculosis treatment with standard short-course regimens of isoniazid, rifampin, ethambutol, and/or pyrazinamide. DESIGN: Retrospective case-control study. SETTING: Tertiary university medical center. PATIENTS: One hundred ten inactive HBsAg carriers with newly diagnosed active tuberculosis who had been treated with isoniazid, rifampin, ethambutol, and/or pyrazinamide were included in the study population. Inactive HBsAg carriers were defined as follows: (1) positive for HbsAg; (2) negative for hepatitis B e antigen (HBeAg), positive for antibody to HBeAg; (3) < 10(5) copies per mL of serum hepatitis B virus DNA; and (4) normal pretreatment aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels. Ninety-seven HBsAg-negative patients who received standard antituberculosis medication were selected as control subjects. RESULTS: The baseline characteristics of the 110 inactive HBsAg carriers were similar to those of the 97 noncarriers. A total of 85% of persons in both groups had received an initial treatment regimen that included pyrazinamide. Thirty-eight inactive HBsAg carriers (35%) and 19 control subjects (20%) exhibited elevated liver enzyme levels during antituberculosis treatment (p = 0.016). Drug-induced hepatotoxicity, which was defined as a liver transaminase level of >/= 120 IU/L, occurred more frequently in HBsAg carriers (9 of 110 carriers; 8%) than in control subjects (4 of 97 control subjects; 4%), although this was not a statistically significant discrepancy (p = 0.230). More importantly, HBsAg carriers (n = 9; 8%) who received antituberculosis therapy evidenced a higher proportion of moderate-to-severe drug-induced hepatotoxicity when compared with the control subjects (n = 2; 2%; p = 0.05). Isoniazid and rifampin were reintroduced as therapy after AST/ALT levels returned to baseline values in 10 patients (6 HBsAg carriers and 4 control subjects) among the 13 patients exhibiting drug-induced hepatotoxicity, and these retrials proved to be successful in 7 patients (5 HBsAg carriers and 2 control subjects). CONCLUSIONS: Tuberculosis treatment in HBsAg-positive and HBeAg-negative inactive carriers could be pursued in the usual manner, using standard short-course regimens of isoniazid, rifampin, ethambutol, and/or pyrazinamide, with the condition that monthly liver function tests are performed.

Adult↗

NRAMP1 gene polymorphism and susceptibility to nontuberculous mycobacterial lung diseases.

STUDY OBJECTIVES: Pulmonary disease caused by nontuberculous mycobacteria (NTM) may occur in patients with no underlying lung disease and no known immunodeficiency. The purpose of this study was to evaluate a potential role for natural-resistance-associated macrophage protein 1 (NRAMP1) gene polymorphisms for human susceptibility to the NTM lung disease. DESIGN: A case-control study. SETTING: Tertiary university medical center. PARTICIPANTS: Forty-one adult patients with NTM lung disease (Mycobacterium avium complex infection, 18 patients; Mycobacterium abscessus infection, 23 patients) were included in the study population. The diagnosis of NTM lung disease was made when the patients fulfilled the diagnostic criteria published by the American Thoracic Society. All patients had findings on high-resolution CT scans, such as bilateral bronchiectasis combined with multiple small nodules and branching linear structures, that were characteristic of the nodular bronchiectatic form of NTM lung disease. Fifty healthy individuals were selected as control subjects. RESULTS: Heterozygotes at intron 4 (469 + 14G/C) [INT4], codon 543 in exon 15 (D543N), and 3' untranslated region (3'UTR) were observed at significantly higher frequencies in patients with NTM lung disease than in control subjects. The odds ratios (ORs) were 2.78 (95% confidence interval [CI], 1.12 to 6.89; p = 0.026) for INT4 G/C, 5.74 (95% CI, 1.48 to 22.30; p = 0.006) for D543 G/A, and 9.54 (95% CI, 2.49 to 36.53; p < 0.001) for 3'UTR TGTG+/del. Subjects who were heterozygous for two NRAMP1 polymorphisms in INT4 and D543N were particularly overrepresented among those with NTM lung disease, compared with those with the most common NRAMP1 genotype (OR, 10.88, 95% CI, 1.18 to 100.45; p = 0.035). There were no significant differences in the frequencies of INT4, D543N, and 3'UTR polymorphisms between the patients with M avium complex infection and those with M abscessus infection. CONCLUSIONS: These findings suggest that the NRAMP1 genetic polymorphisms are associated with human susceptibility to NTM lung disease.

Adult↗

Clinical features of recently diagnosed pulmonary paragonimiasis in Korea.

STUDY OBJECTIVE: Paragonimiasis is a typical food-borne parasitic disease that is common in Southeast Asia, the Far East, Latin American, and Africa. Recently, however, this disease has been seen in many parts of the world, largely due to increases in the numbers of immigrants and overseas travelers. The purpose of this study was to evaluate the clinical and radiologic features of recently diagnosed pulmonary paragonimiasis. PATIENTS: We retrospectively analyzed the clinical and radiologic characteristics of 36 patients (21 men and 15 women; median age 48 years; range, 19 to 75) with pulmonary paragonimiasis whose conditions were diagnosed between October 1994 and September 2004. RESULTS: Thirty-four patients (94%) presented with respiratory symptoms, including hemoptysis (n = 20, 56%) and cough (n = 17, 47%). However, chest pain (n = 5, 14%) and fever (n = 5, 14%) were less frequently reported. Chest radiography revealed intrapulmonary parenchymal lesions (n = 26, 72%), such as nodules (n = 14, 39%), linear opacity (n = 6, 17%), and airspace consolidations (n = 4, 11%), which occurred more commonly than did pleural lesions (n = 10, 28%). Most cases were initially suspected to be lung cancer or tuberculosis. In 13 patients with intrapulmonary parenchymal lesions who underwent bronchoscopy, bronchial luminal narrowing, coupled with congested or edematous mucosal changes, was seen in 7 patients (54%). Bronchial mucosal biopsy specimens exhibited chronic inflammation with eosinophilic infiltrations in three of these seven patients (43%). CONCLUSIONS: Our findings indicate that patients with pulmonary paragonimiasis presented with a variety of clinical and radiologic findings that were different from the classic presentations reported earlier, frequently mimicking those of lung cancer or tuberculosis.

Adult↗