Qualitative and quantitative results of interferon-γ release assays for monitoring the response to anti-tuberculosis treatment

BACKGROUND/AIMS: The usefulness of interferon-γ release assays (IGRAs) in monitoring to responses to anti-tuberculosis (TB) treatment is controversial. We compared the results of two IGRAs before and after anti-TB treatment in same patients with active TB. METHODS: From a retrospective review, we selected patients with active TB who underwent repeated QuantiFERON-TB Gold (QFN-Gold, Cellestis Limited) and T-SPOT.TB (Oxford Immunotec) assays before and after anti-TB treatment with first-line drugs. Both tests were performed prior to the start of anti-TB treatment or within 1 week after the start of anti-TB treatment and after completion of treatment. RESULTS: A total of 33 active TB patients were included in the study. On the QFN-Gold test, at baseline, 23 cases (70%) were early secreted antigenic target 6-kDa protein 6 (ESAT-6) or culture filtrate protein 10 (CFP-10) positive. On the T-SPOT. TB test, at baseline, 31 cases (94%) were ESAT-6 or CFP-10 positive. Most of patients remained both test-positive after anti-TB treatment. Although changes in interferon-γ release responses over time were highly variable in both tests, there was a mean decline of 27 and 24 spot-forming counts for ESAT-6 and CFP-10, respectively on the T-SPOT.TB test (p < 0.05 for all). CONCLUSIONS: Although limited by the small number of patients and a short-term follow-up, there was significant decline in the quantitative result of the T-SPOT. TB test with treatment. However, both commercial IGRAs may not provide evidence regarding the cure of disease in Korea, a country where the prevalence of TB is within the intermediate range.

The Need for a Well-Organized, Video-Assisted Asthma Education Program at Korean Primary Care Clinics / 결핵및호흡기질환

BACKGROUND: The purpose of this study was to assess the effect of our new video-assisted asthma education program on patients' knowledge regarding asthma and asthma control. METHODS: Adult asthmatics who were diagnosed by primary care physicians and followed for at least 1 year were educated via smart devices and pamphlets. The education sessions were carried out three times at 2-week intervals. Each education period lasted at most 5 minutes. The effectiveness was then evaluated using questionnaires and an asthma control test (ACT). RESULTS: The study enrolled 144 patients (mean age, 56.7±16.7 years). Half of the patients had not been taught how to use their inhalers. After participating in the education program, the participants' understanding of asthma improved significantly across all six items of a questionnaire assessing their general knowledge of asthma. The proportion of patients who made errors while manipulating their inhalers was reduced to less than 10%. The ACT score increased from 16.6±4.6 to 20.0±3.9 (p<0.001). The number of asthmatics whose ACT score was at least 20 increased from 45 (33.3%) to 93 (65.3%) (p<0.001). The magnitude of improvement in the ACT score did not differ between patients who received an education session at least three times within 1 year and those who had not. The majority of patients agreed to the need for an education program (95.8%) and showed a willingness to pay an additional cost for the education (81.9%). CONCLUSION: This study indicated that our newly developed education program would become an effective component of asthma management in primary care clinics.

Larger Testicular Volume Is Independently Associated with Favorable Indices of Lung Function / 결핵및호흡기질환

BACKGROUND: Men with chronic obstructive pulmonary disease, have reduced endogenous testosterone levels, but the relationship between pulmonary function and endogenous testosterone levels, is inconsistent. Testicular volume is a known indicator of endogenous testosterone levels, male fertility, and male potency. In the present study, the authors investigated the relationship, between testicular volume and lung function. METHODS: One hundred and eighty-one South Korean men age 40-70, hospitalized for urological surgery, were retrospectively enrolled, irrespective of the presence of respiratory disease. Study subjects underwent pulmonary function testing, prior to procedures, and testicular volumes were measured by orchidometry. Testosterone levels of patients in blood samples collected between 7 AM and 11 AM, were measured by a direct chemiluminescent immunoassay. RESULTS: The 181 study subjects were divided into two groups, by testicular volume (≥35 mL vs. <35 mL), the larger testes group, had better lung functions (forced vital capacity [FVC]: 3.87±0.65 L vs. 3.66±0.65 L, p=0.037; forced expiratory volume in 1 second [FEV1]: 2.92±0.57 L vs. 2.65±0.61 L, p=0.002; FVC % predicted: 98.2±15.2% vs. 93.8±13.1%, p=0.040; FEV1 % predicted: 105.4±19.5% vs. 95.9±21.2%, p=0.002). In addition, the proportion of patients with a FEV1/FVC of <70%, was lower in the larger testes group. Univariate analysis conducted using linear regression models, revealed that testicular volume was correlated with FVC (r=0.162, p=0.029), FEV1 (r=0.218, p=0.003), FEV1/FVC (r=0.149, p=0.046), and FEV1 % predicted (r=0.178, p=0.017), and multivariate analysis using linear regression models, revealed that testicular volume was a significant predictive factor for FEV1 % predicted (β=0.159, p=0.041). CONCLUSION: Larger testicular volume was independently associated, with favorable indices of lung function. These results suggest that androgens, may contribute to better lung function.

Acute Respiratory Distress Syndrome as the Initial Clinical Manifestation of an Antisynthetase Syndrome / 결핵및호흡기질환

Antisynthetase syndrome has been recognized as an important cause of autoimmune inflammatory myopathy in a subset of patients with polymyositis and dermatomyositis. It is associated with serum antibody to aminoacyl-transfer RNA synthetases and is characterized by a constellation of manifestations, including fever, myositis, interstitial lung disease, mechanic's hand-like cutaneous involvement, Raynaud phenomenon, and polyarthritis. Lung disease is the presenting feature in 50% of the cases. We report a case of a 60-year-old female with acute respiratory distress syndrome (ARDS), which later proved to be an unexpected and initial manifestation of anti-Jo-1 antibody-positive antisynthetase syndrome. The present case showed resolution of ARDS after treatment with high-dose corticosteroids. Given that steroids are not greatly beneficial in the treatment of ARDS, it is likely that the improvement of the respiratory symptoms in this patient also resulted from the prompt suppression of the inflammatory systemic response by corticosteroids.

Spontaneous Pneumomediastinum: An Unusual Pulmonary Complication in Anorexia Nervosa / 결핵및호흡기질환

Spontaneous pneumomediastinum (PM) is an uncommon condition in which free air enters the mediastinum. This usually occurs either through esophageal tears after vigorous vomiting, or after alveolar rupture subsequent to a rapid increase in intra-alveolar pressure. Spontaneous PM is a rare entity in anorexia nervosa (AN) and self-induced vomiting is often the cause of PM in patients with AN. We experienced a case of spontaneous PM in an anorexic adolescent, in whom vomiting was not the cause of PM.

Effect of Inhaled Tiotropium on Spirometric Parameters in Patients with Tuberculous Destroyed Lung / 결핵및호흡기질환

BACKGROUND: In Korea, patients with destroyed lung due to tuberculosis (TB) account for a significant portion of those affected by chronic pulmonary function impairment. The objective of our research was to evaluate the efficacy of inhaled tiotropium bromide in TB destroyed lung. METHODS: We compared the effectiveness of inhaled tiotropium bromide for 2 months between pre- and post-treatment pulmonary function tests performed on 29 patients with destroyed lung due to TB. RESULTS: The mean age of the total number of patients was 63+/-9 years, where 15 patients were male. The pre-treatment mean forced expiratory volume in 1 second (FEV1) was 1.02+/-0.31 L (44.1+/-16.0% predicted). The pre-treatment mean forced vital capacity (FVC) was 1.70+/-0.54 L (52.2+/-15.8% predicted). Overall, the change in FEV1% predicted over baseline with tiotropium was 19.5+/-19.1% (p<0.001). Twenty patients (72%) got better than a 10% increase in FEV1 over baseline with tiotropium, but one patient showed more than a 10% decrease in FEV1. Overall, the change in FVC% predicted over baseline with tiotropium was 18.5+/-19.9% (p<0.001). Seventeen patients (59%) experienced greater than a 10% increase in FVC over baseline with tiotropium; 12 (41%) patients had stable lung function. CONCLUSION: The inhaled tiotropium bromide therapy may lead to improve lung functions in patients with TB destroyed lung. However, the long-term effectiveness of this treatment still needs to be further assessed.

Recurrent Pseudomonas aeruginosa Infection in Chronic Lung Diseases: Relapse or Reinfection? / 결핵및호흡기질환

BACKGROUND: Pseudomonas aeruginosa infection is particularly associated with progressive and ultimately chronic recurrent respiratory infections in chronic obstructive pulmonary disease, bronchiectasis, chronic destroyed lung disease, and cystic fibrosis. Its treatment is also very complex because of drug resistance and recurrence. METHODS: Forty eight cultures from 18 patients with recurrent P. aeruginosa pneumonia from 1998 to 2002 were included in this study. Two or more pairs of sputum cultures were performed during 2 or more different periods of recurrences. The comparison of strains was made according to the phenotypic patterns of antibiotic resistance and chromosomal fingerprinting by pulsed field gel electrophoresis (PFGE) using the genomic DNA of P. aeruginosa from the sputum culture. RESULTS: Phenotypic patterns of antibiotic resistance of P. aeruginosa were not correlated with their prior antibiotic exposition. Fifteen of 18 patients (83.3%) had recurrent P. aeruginosa pneumonia caused by the strains with same PFGE pattern. CONCLUSION: These data suggest that the most of the recurrent P. aeruginosa infections in chronic lung disease occurred due to the relapse of prior infections. Further investigations should be performed for assessing the molecular mechanisms of the persistent colonization and for determining how to eradicate clonal persistence of P. aeruginosa.

Treatment Outcomes and Prognostic Factors in Patients with Multidrug-Resistant Tuberculosis in Korean Private Hospitals / 결핵및호흡기질환

BACKGROUND: The increasing rate of drug-resistant tuberculosis (TB) is a threat to the public health and TB control. In Korea, about 75~80% of TB patients are treated in private hospitals and the rate has been continuously increasing since 2000. METHODS: On a retrospective basis, we enrolled 170 newly diagnosed with or retreated for multidrug-resistant TB (MDR-TB) in 2004 from 21 private hospitals. We extracted the following demographics and treatment history from patient medical records: initial treatment outcomes, cumulative survival rates, treatment outcomes, and prognostic factors. RESULTS: Of the 170 patients, the majority were male (64.1%), the mean age was 44.5 years old, and mean body-mass-index was 20.2 kg/m2. None of the patients tested positive for HIV. Eleven (6.5%) were confirmed to have extensively drug-resistant TB (XDR-TB) at treatment initiation. Treatment success rates were not different between XDR-TB (36.4%, 4/11) and non-XDR MDR-TB (51.6%, 82/159). Default rate was high, 21.8% (37/170). Far advanced disease on X-ray was a significant negative predictor of treatment success; advanced disease and low BMI were risk factors for all-cause mortality. CONCLUSION: In private hospitals in Korea, the proportion of XDR-TB in MDR-TB was comparable to previous data. The treatment success rate of MDR-/XDR-TB remains poor and the failure rate was quite high. Adequate TB control policies should be strengthened to prevent the further development and spread of MDR-/XDR-TB in Korea.

18F-FDG Positron Emission Tomography in Patients with Concomitant Malignancy and Tuberculoma / 결핵및호흡기질환

BACKGROUND: To analyze the result of 18F-FDG positron emission tomography (PET) in patients with a concomitant malignancy and tuberculoma in a tuberculosis (TB)-endemic area. METHODS: Twelve patients with a concomitant malignancy and tuberculoma, who underwent whole-body 18F-FDG PET, were evaluated retrospectively. The maximal standardized uptake values (SUVmax) of the malignancy and tuberculoma were compared. In 6 patients, 18F-FDG PET was repeated during the anti-TB treatment and the changes in SUVmax were analyzed. RESULTS: Of the 12 patients, 10 were male. The mean age was 67.2+/-7.9 years. Tuberculomas were located in the lung (n=10) and lymph nodes (n=2), and tumors were located in the lung (n=6), colon (n=3), stomach (n=1), ovary (n=1) and liver (n=1). Although the mean SUVmax of malignant lesions was higher than that of tuberculomas (5.2+/-3.2 vs 3.5+/-2.0), the difference was not significant. In 4 patients, the SUVmax was higher in the tuberculoma than the tumor. After anti-TB treatment in 6 patients, the mean SUVmax of the tuberculomas decreased significantly, from 3.5+/-2.0 to 1.6+/-0.9 (p=0.028). CONCLUSION: In patients with a concomitant malignancy and tuberculoma, SUVmax alone could not differentiate between them. However, 18F-FDG PET may be useful in monitoring the response to anti-TB treatment.

A Case of Pneumocystis Pneumonia Mimicking Acute Eosinophilic Pneumonia in a Patient with AIDS / 결핵및호흡기질환

73-year-old man was admitted with a sudden onset of dyspnea. He had never smoked. The chest radiograph and computed tomography revealed bilateral ground glass opacity and an enlarging perihilar consolidation with lymphadenopathies. There was a higher percentage of eosinophils (72%) in the bronchoalveolar lavage fluid (BALF) than normal. The patient was diagnosed with acute eosinophilic pneumonia and managed with steroid. Pneumocystis pneumonia (PCP) was diagnosed by an examination of the BALF, and the patient was treated with trimethoprim-sulphamethoxazole. The patient tested positive to the HIV antibody and the peripheral blood CD-4 positive lymphocyte count was only 33/microliter. The percentage of eosinophils in the BALF can increase in some cases of PCP that is complicated with AIDS. Only a few cases of eosinophilic pneumonia associated with PCP pneumonia have been reported in patients with AIDS but there are no case reports in Korea. This case highlights the need to consider PCP when the percentage of eosinophils in the BALF is elevated.

Two Cases of Hot Tub Lung in Bodyscrubbers Working in a Public Bath / 결핵및호흡기질환

Hot tub lung has been described as a pulmonary illness associated with exposure to nontuberculous mycobacteria, mainly hot bathtub water contaminated with Mycobacterium avium complex (MAC) and hence the name. Although not entirely clear, its etiology has been thought to involve either an infection or a hypersensitivity pneumonitis secondary to MAC. Herein, we describe 2 female patients (60 and 53 years old) admitted to our hospital with hot tub lung, and both of whom worked in a public bath. Both women were initially admitted following several months of exertional dyspnea and cough. The patients had been working as body-scrubbers in a public bath for several years. Their chest CT scans showed bilateral diffuse ground-glass opacities with multifocal air-trappings and poorly defined centrilobular nodules in both lungs. Pathological findings from lung specimens revealed small non-necrotizing granuloma in the lung parenchyme with relatively normal-looking adjacent alveoli. Discontinuation of working in the public bath led to an improvement in symptoms and radiographic abnormalities, without antimycobacterial therapy.

Clinical Characteristics and Adherence of Patients Who Were Prescribed Home Oxygen Therapy Due to Chronic Respiratory Failure in One University Hospital: Survey after National Health Insurance Coverage / 결핵및호흡기질환

BACKGROUND: Despite the benefits of home oxygen therapy in patients suffering chronic respiratory failure, previous reports in Korea revealed lower compliance to oxygen therapy and a shorter time for oxygen use than expected. However, these papers were published before oxygen therapy was covered by the national insurance system. Therefore, this study examined whether there were some changes in compliance, using time and other clinical features of home oxygen therapy after insurance coverage. METHODS: This study reviewed the medical records of patients prescribed home oxygen therapy in our hospital from November 1, 2006 to September 31, 2008. The patients were interviewed either in person or by telephone to obtain information related to oxygen therapy. RESULTS: During study period, a total 105 patients started home oxygen therapy. The mean age was 69 and 60 (57%) were male. The mean oxygen partial pressure in the arterial blood was 54.5 mmHg and oxygen saturation was 86.3%. Primary diseases that caused hypoxemia were COPD (n=64), lung cancer (n=14), Tb destroyed lung (n=12) and others. After oxygen therapy, more than 50% of patients experienced relief of their subjective dyspnea. The mean daily use of oxygen was 9.8+/-7.3 hours and oxygen was not used during activity outside of their home (mean time, 5.4+/-3.7 hours). Twenty four patients (36%) stopped using oxygen voluntarily 7+/-4.7 months after being prescribed oxygen and showed a less severe pulmonary and right heart function. The causes of stopping were subjective symptom relief (n=11), inconvenience (n=6) and others (7). CONCLUSION: The prescription of home oxygen has increased since national insurance started to cover home oxygen therapy. However, the mean time for using oxygen is still shorter than expected. During activity of outside their home, patients could not use oxygen due to the absence of portable oxygen. Overall, continuous education to change the misunderstandings about oxygen therapy, more economic support from national insurance and coverage for portable oxygen are needed to extend the oxygen use time and maintain oxygen usage.

A Familial Case of Hereditary Hemorrhagic Telangiectasia / 결핵및호흡기질환

Hereditary hemorrhagic telangiectasia (HHT, also called Osler-Weber-Rendu Disease) is a rare systemic fibrovascular dysplasia characterized by recurrent epistaxis, cutaneous telangiectasia, and visceral arteriovenous malformations (AVMs). HHT is an autosomal dominant disease with a prevalence of 1 in 5,000~8,000. Recurrent epistaxis is often the first and most common manifestation, and about 30% of patients reveal pulmonary AVM. Presently, we report a familial case of HHT. A 61-year-old male with asymptomatic multiple pulmonary AVMs was successfully treated with embolization. His older brother who presented with recurrent epistaxis and multiple telangiectasias was treated with laser ablation. Their pedigree revealed a family history of recurrent epistaxis.

Pneumocystis jiroveci Pneumonia Mimicking Miliary Tuberculosis in a Kidney Transplanted Patient / 결핵및호흡기질환

Bilateral interstitial infiltration in chest radiography, which may be fine granular, reticular or of ground glass opacity, is the typical radiographic findings of Pneumocystis jiroveci pneumonia. Recently, atypical radiographic features, including cystic lung disease, spontaneous pneumothorax or nodular opacity, have been reported intermittently in patients with P. jiroveci pneumonia. We report the case of a 29-year-old woman with a transplanted kidney whose simple chest radiography and HRCT scan showed numerous miliary nodules in both lungs, mimicking miliary tuberculosis (TB). Under the presumptive diagnosis of miliary TB, empirical anti-TB medication was started. However, Grocott methenamine silver nitrate staining of a transbronchial lung biopsy tissue revealed P. jiroveci infection without evidence of TB. These findings suggest that even in TB-endemic area other etiology such as P. jiroveci as well as M. tuberculosis should be considered as an etiology of miliary lung nodules in immunocompromised patients.

Congenital Cystic Adenomatoid Malformation of Lung in Adults: Clinical, Pathologic and Radiologic Evaluation of Six Patients / 결핵및호흡기질환

BACKGROUND: Congenital cystic adenomatoid malformation of the lung (CCAM) is a rare congenital developmental anomaly of the lower respiratory tract. Most cases are diagnosed within the first 2 years of life, so adult presentation of CCAM is rare. We describe here six adult cases of CCAM and the patients underwent surgical resection, and all these patients were seen during a five and a half year period. The purpose of this study was to analyze the clinical, radiological and histological characteristics of adult patients with CCAM. METHODS: Through medical records analysis, we retrospectively reviewed the clinical characteristics, the chest pictures (X-ray and CT) and the histological characteristics. RESULTS: Four patients were women and the mean age at diagnosis was 23.5 years (range: 18~39 years). The major clinical presentations were lower respiratory tract infection, hemoptysis and pneumothorax. According to the chest CT scan, 5 patients had multiseptated cystic lesions with air fluid levels and one patient had multiple cavitary lesions with air fluid levels, and these lesions were surrounded by poorly defined opacities at the right upper lobe. All the patients were treated with surgical resection. 5 patients underwent open lobectomy and one patient underwent VATS lobectomy. On the pathological examination, 3 were found to be CCAM type I and 3 patients were CCAM type II, according to Stocker's classification. There was no associated malignancy on the histological studies of the surgical specimens. CONCLUSION: As CCAM can cause various respiratory complications and malignant changes, and the risks associated with surgery are extremely low, those patients who are suspected of having or who are diagnosed with CCAM should go through surgical treatment for making the correct diagnosis and administering appropriate treatment.

A Case of Recurrent Pneumonitis Caused by Bojungikgitang(Bu-Zhong-Yi-Qi-Tang) / 결핵및호흡기질환

Many classes of drug, such as antineoplastic drugs and antiarrhythmic drugs, have potential to induce interstitial lung disease. Herbal medicines are also believed to have the potential to induce pneumonitis. However, to our knowledge, there are no reports of pneumonitis caused by herbal medications in the Korean medical database. We report a case of recurrent pneumonitis caused by a self rechallenge of the Herbal medicine Bojungikgitang (Bu-Zhong-Yi-Qi-Tang : Hochu-ekki-to).

A Case of Tuberculous Pleural Effusion Developed after Percutaneous Needle Biopsy of a Solitary Pulmonary Nodule / 결핵및호흡기질환

A tuberculous pleural effusion may be a sequel to a primary infection or represent the reactivation of pulmonary tuberculosis. It is believed to result from a rupture of a subpleural caseous focus in the lung into the pleural space. It appears that delayed hypersensitivity plays a large role in the pathogenesis of a tuberculous pleural effusion. We encountered a 52 years old man with pleural effusion that developed several days after a CT guided percutaneous needle biopsy of a solitary pulmonary nodule. He was diagnosed with TB pleurisy. It is believed that his pleural effusion probably developed due to exposure of the parenchymal tuberculous focus into the pleural space during the percutaneous needle biopsy. This case might suggest one of the possible pathogeneses of tuberculous pleural effusion.

A Case of Pulmonary Edema by Idiopathic Rupture of Mitral Chordae Tendinae / 결핵및호흡기질환

The typical radiographic findings of pulmonary edema from the increased hydrostatic pressure shows centrally localized consolidation, which is known as a "butterfly or bat's wing" pattern. These terms describe the anatomic distribution of edema that uniformly involve the hilum and medulla of the lung but not the peripheral region of the lung parenchyma (cortex). We present a case of butterfly wing-like pulmonary edema on a chest radiograph by mitral regurgitation due to an idiopathic chordal rupture.

A Case of Delayed Response of Tumorous type of Endobronchial Tuberculosis to Antituberculosis Treatment / 결핵및호흡기질환

Pulmonary tuberculomas show variable responses to treatment, with some even increasing in size after treatment. To date, however, no data have been reported on the response of tumorous type of endobronchial tuberculosis (EBTB-T) to treatment observed both bronchoscopically and histologically. We report a case of bacteriologically- and biopsy-proven EBTB-T that showed delayed response to anti-tuberculosis treatment. Even after EBTB-T was treated with antituberculosis drugs for 15 months, the bronchoscopic findings and the histologic findings of chronic granulomatous inflammation with caseation necrosis still remained. However, in fourteen months after the completion of treatment, the lesioneventually disappeared without further treatment.

A case of Transverse Myelitis due to Multidrug-Resistant Tuberculosis / 결핵및호흡기질환

Acute transverse myelitis (TM) is a neurological syndrome caused by inflammation of the spinal cord. TM is rare but is frequently caused by viral or bacterial infections. TM caused by tuberculosis (TB) is extremely rare and there are no reports of TM caused by multidrug-resistant TB (MDR-TB). We report a case of acute TM due to MDR-TB in a 40-year-old man. The patient had been diagnosed with pulmonary TB and was started on the first-line anti-TB treatment. However, the chest radiographic findings were aggravated and neurological symptoms such as weakness in both lower extremities, sensory changes, and voiding difficulty were newly developed. The T2-weighted magnetic resonance image of the spine showed diffusely increased signal intensity in the spinal cord, particularly at the lower cervical and upper thoracic levels, without any definite evidence of myeloradicular compression, which is consistent with a diagnosis of TM. A drug susceptibility test revealed MDR and second-line anti-TB drugs were prescribed. The chest radiographic findings showed improvement after treatment, the mycobacterial culture converted to negative, the MRI findings improved, and there was partial improvement in the low extremity weakness. The patient has been prescribing second-line anti-TB medications for 14 months.