Trinity College Dublin. Dublin, Ireland. References. 1. Watanabe K, Inoue Y, Shimoda T, Watanabe T, Hayashi T, Tsutsumi T,. Dotsu Y, Kohno S, Yamaguchi K, ...
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of 79%, sensitivity of 95%, and specificity of 100% in this high pre-test probability group. The positive and negative predictive value was 100% and 80%, respectively. The microbiologic and cytomorphologic diagnostic accuracy of EBUS-TBNA in patients diagnosed with tuberculosis were 63% and 84%, respectively. Steinfort and coworkers reported one case of mediastinal lymph node tuberculosis diagnosed by EBUS-TBNA in an HIV-positive patient (3), but our series of 19 HIV-negative patients confirms that this procedure is accurate and safe. One center has reported on the utility of EBUS-guided sampling technique and bronchoalveolar lavage without addressing extrapulmonary tuberculosis or EBUSTBNA (4, 5). Studies have shown that transesophageal EUS-FNA is a useful diagnostic modality in extrapulmonary tuberculosis; however, EUS-FNA cannot access the anterior mediastinum due to air interposition from the trachea (6, 7). EBUS-TBNA also outperformed previous FNA studies, which rendered positive smear and culture in 30% and 49%, respectively (8, 9). EBUS-TBNA was not positive in any of the patients who lacked a high pre-test probability, validating the importance of clinical features as a tool in suspecting tuberculosis (10, 11). The majority of our patients (z 85%) were from countries of high tuberculosis prevalence, which is consistent with the epidemiologic findings of others (e.g., subgroup analysis performed in a Somali population revealed a risk of up to 30% of developing extrapulmonary tuberculosis in the first year of immigration [12, 13]). In the era of increasing drug resistance, EBUS-TBNA can deliver clinical isolates which can be tested for drug sensitivity. This provides more effective treatment regimens, and avoids side-effects from drugs to which the disease is resistant. Due to the high pre-test probability of tuberculosis in our study population, our reported predictive values are not applicable to the general population. However, our data suggest that this technique has much to offer the prescribing clinician in a setting where invasive procedures or high-risk empirical treatment is the only other option. Author Disclosure: T.H. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. A.M.M. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. F.O. has received industry-sponsored grants from GlaxoSmithKline ($5,001–$10,000). N.G. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. S.N. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. J.K. has received lecture fees from AstraZeneca (up to $1,000).
TIDI HASSAN ANNE MARIE MCLAUGHLIN, M.D. FINBARR O’CONNELL, M.D. NOEL GIBBONS SIOBHAN NICHOLSON JOSEPH KEANE, M.D. St. James’s Hospital Dublin, Ireland and Trinity College Dublin. Dublin, Ireland
References 1. Watanabe K, Inoue Y, Shimoda T, Watanabe T, Hayashi T, Tsutsumi T, Dotsu Y, Kohno S, Yamaguchi K, Hara K. Diagnostic usefulness of transbronchial aspiration and bronchial lavage for pulmonary tuberculosis. Kekkaku 1990;65:227–239. 2. Chang SC, Lee PY, Perng RP. Clinical role of bronchoscopy in adults with thoracic tuberculous lymphadenopathy. Chest 1988;93:314–317. 3. Steinfort DP, Johnson DF, Connell TG, Irving LB. Endobronchial ultrasound-guided biopsy in the evaluation of thoracic lymphadenop-
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athy in suspected tuberculosis: a minimally invasive technique with a high diagnostic yield. J Infect 2009;58:309–311. Lin SM, Chung FT, Huang CD, Liu WT, Kuo CH, Wang CH, Lee KY, Liu CY, Lin HC, Kuo HP. Diagnostic value of endobronchial ultrasonography for pulmonary tuberculosis. J Thorac Cardiovasc Surg 2009;138:179–184. Lin SM, Ni YL, Kuo CH, Lin TY, Wang TY, Chung FT, Kuo HP. Endobronchial ultrasound increases the diagnostic yields of polymerase chain reaction and smear for pulmonary tuberculosis. J Thorac Cardiovasc Surg 2010;139:1554–1559. Berzosa M, Tsukuyama DT, Davies SF, Debol SM, Cen YY, Li R, Mallery S. Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of extra-pulmonary tuberculosis. Int J Tuberc Lung Dis 2010; 12:578–584. Puri R, Vilmann P, Sud R, Kumar M, Taneja S, Verma K, Kaushik N. Endoscopic ultrasound-guided fine needle aspiration cytology in the evaluation of suspected tuberculosis in patients with isolated mediastinal lymphadenopathy. Endoscopy 2010;42:462–467. Gupta SK, Chugh TD, Sheikh ZA, al-Rubah NA. Cytodiagnosis of tuberculous lymphadenitis: a correlative study with microbiologic examination. Acta Cytol 1993;37:329–332. Radhika S, Gupta SK, Chakrabarti A, Rajwanshi A, Joshi K. Role of culture for mycobacteria in fine-needle aspiration diagnosis of tuberculosis lymphadenitis. Diagn Cytopathol 1989;5:260–262. Snider DE Jr, Roper WE. The new tuberculosis. N Engl J Med 1992;326: 703–705. Talbot EA, Moore M, McCray E, Binkin NJ. Tuberculosis among foreignborn persons in the United States, 193–1998. JAMA 2000;284:2894–2900. Lilleback T, Andersen AB, Dirksen A, Smith E, Skovgaard LT, Kok-Jensen A. Persistent high incidence of tuberculosis in immigrants in a low-incidence country. Emerg Infect Dis 2002;8:679–684. Rock RB, Sutherland WM, Baker C, Williams DN. Extrapulmonary tuberculosis among Somalis in Minnesota. Emerg Infect Dis 2006;12: 1434–1436.
Coexistence of Allergic Bronchopulmonary Aspergillosis and Active Pulmonary Tuberculosis To the Editor:
Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus fumigatus colonization of the tracheobronchial tree (1). ABPA occurs predominantly in patients with underlying chronic airway disorders (1–3). Pulmonary tuberculosis is one of the most common chronic pulmonary infections caused by Mycobacterium tuberculosis in developing countries. Patients with human immunodeficiency virus infection and those requiring immunosuppressive therapies are more susceptible to tuberculosis (4). The occurrence of ABPA in patients with pulmonary tuberculosis has been rarely reported. Some of them are cases of ABPA developed in patients with previous histories of pulmonary tuberculosis (5–7), and the others are cases of ABPA misdiagnosed as pulmonary tuberculosis (8, 9). Some of the results of these studies have been previously reported in the form of an abstract (10). A 69-year-old woman was admitted for evaluation of a consolidation that was detected through a medical check-up. She had no respiratory or systemic symptoms and no previous history of airway diseases. A chest computed tomography (CT) scan showed abrupt narrowing of left upper bronchus by low density materials with central bronchiectasis (Figures 1A and 1B). A chest magnetic resonance imaging (MRI) scan with multiphase enhancement revealed that the lesion in the left upper lobe showed a high signal intensity on pre-contrast image and mild peripheral enhancement, suggesting ABPA (Figures 1C–1F). Laboratory evaluation revealed a white blood cell count of 5,170/mm3 (eosinophil 1.9%) and a serum total immunoglobulin (Ig) E level of 679.5 IU/ml. Serum IgG specific to A. fumigatus was positive (2 kUA/L). Supported by a grant of the Korea Healthcare Technology R&D Project, Ministry for Health and Welfare, Republic of Korea (A084144).
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and treated with antituberculosis drugs for a long time (12). Therefore, pulmonary tuberculosis developed in patients with ABPA may be difficult to recognize radiologically without a clinical suspicion. In the present case, chest CT and MRI showed mucoid impaction and central bronchiectasis, suggesting ABPA. There were no radiographic findings or clinical features of active pulmonary tuberculosis. However, during the evaluation process to confirm the cause for chronic granulomatous inflammation, active pulmonary tuberculosis was incidentally diagnosed through surgical excision. In our case, the lesion of pulmonary tuberculosis was mainly located in the same lobe with ABPA. Because one disease is able to mask the other, it may be hard to detect both pulmonary diseases with similar radiologic features, especially presented as one localized lesion. These findings suggest that a precise diagnosis of pulmonary tuberculosis that occurred concurrently with ABPA in the same lobe is difficult before histological examination. In conclusion, this first case of coexistent ABPA and active pulmonary tuberculosis suggest that pulmonary tuberculosis should be carefully evaluated in patients with ABPA, particularly those in the endemic area. Author Disclosure: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.
KYUNG HOON MIN, M.D., PH.D. SEOUNG JU PARK, M.D., PH.D. SO RI KIM, M.D., PH.D. MIN HEE LEE, M.D. CHI RYANG CHUNG, M.D. HYO JIN HAN, M.D. KYOUNG HWA CHOI, M.D. MYOUNG JA CHUNG, M.D., PH.D. YONG CHUL LEE, M.D., PH.D. Chonbuk National University Medical School Jeonju, South Korea and Chonbuk National University Hospital Jeonju, South Korea
Figure 1. A chest computed tomography (CT) scan showed abrupt narrowing of the left upper bronchus, which was filled with low-density materials with central bronchiectasis (A, mediastinal setting; B, lung setting). A chest magnetic resonance imaging (MRI) scan with multiphase enhancement revealed that the lesion in the left upper lobe showed a high signal intensity on pre-contrast image and mild peripheral enhancement after injection of gadolinium (C, pre-contrast; D, arterial phase; E, equilibrium phase; F, delayed phase). The resection specimen showed bronchiectasis with mucus plug (periodic acid-Schiff stain) and small amount of fungal hyphae, morphologically consistent with Aspergillus species ( Gomori methenamine silver stain, 3400; G). There were small foci of chronic granulomatous inflammation with caseous necrosis; Ziehl-Neelsen staining for acid-fast bacilli was positive in the necrotic area (H ).
Immediate skin test for A. fumigatus was also positive. Mannitol provocation test revealed bronchial hyperresponsiveness. Percutaneous transthoracic needle biopsy was performed, and histologic examination showed chronic granulomatous inflammation with negative findings for acid-fast bacilli (AFB), periodic acidSchiff (PAS), and Gomori methenamine silver (GMS) staining as well as for polymerase chain reaction (PCR) analysis for Mycobacterium tuberculosis and nontuberculous mycobacterium. We also performed left upper lobectomy to confirm the cause of the chronic granulomatous inflammation in the lesions. The resection specimen showed bronchiectasis with mucus plug and fungal hyphae, morphologically consistent with Aspergillus species (Figure 1G), and small foci of chronic granulomatous inflammation with caseous necrosis with positive for AFB staining and PCR analysis for M. tuberculosis (Figure 1H). On the basis of these findings, we confirmed diagnosis of coexistent ABPA and active pulmonary tuberculosis in the same lobe. Although there are typical radiologic findings of ABPA and pulmonary tuberculosis, it is not easy to diagnose these two diseases when they present with atypical radiologic pattern, especially in asymptomatic patients (8, 9, 11). In areas with a high prevalence of pulmonary tuberculosis, patients with ABPA are often misdiagnosed with pulmonary tuberculosis
GONG YONG JIN MIN HO KIM Chonbuk National University Medical School Jeonju, South Korea
References 1. Tillie-Leblond I, Tonnel AB. Allergic bronchopulmonary aspergillosis. Allergy 2005;60:1004–1013. 2. Maurya V, Gugnani HC, Sarma PU, Madan T, Shah A. Sensitization to Aspergillus antigens and occurrence of allergic bronchopulmonary aspergillosis in patients with asthma. Chest 2005;127:1252–1259. 3. Knutsen AP, Bellone C, Kauffman H. Immunopathogenesis of allergic bronchopulmonary aspergillosis in cystic fibrosis. J Cyst Fibros 2002;1: 76–89. 4. Falagas ME, Voidonikola PT, Angelousi AG. Tuberculosis in patients with systemic rheumatic or pulmonary diseases treated with glucocorticosteroids and the preventive role of isoniazid: a review of the available evidence. Int J Antimicrob Agents 2007;30:477–486. 5. Boz AB, Celmeli F, Arslan AG, Cilli A, Ogus C, Ozdemir T. A case of allergic bronchopulmonary aspergillosis following active pulmonary tuberculosis. Pediatr Pulmonol 2009;44:86–89. 6. Agarwal R, Singh N, Aggarwal AN. An unusual association between Mycobacterium tuberculosis and Aspergillus fumigatus. Monaldi Arch Chest Dis 2008;69:32–34. 7. Yanase K, Nakamura M, Toyoda T, Dote K, Tsunami A, Hisaoka N, Maruyama T, Shikanai K, Maruyama S, Ueno K. A case of allergic bronchopulmonary aspergillosis following active pulmonary tuberculosis. Arerugi 1996;45:1181–1184.
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8. Al-Moudi OS. Allergic bronchopulmonary aspergillosis mimicking pulmonary tuberculosis. Saudi Med J 2001;22:708–713. 9. Agarwal AK, Bhagat R, Panchal N, Shah A. Allergic bronchopulmonary aspergillosis with aspergilloma mimicking fibrocavitary pulmonary tuberculosis. Asian Pac J Allergy Immunol 1996;14:5–8. 10. Kim SR, Park JK, Seo SY, Choung BS, Choi KH, Chung CR, Han HJ, Lee MH, Moon H, Min KH, et al. An unusual coexistence of allergic bronchopulmonary aspergillosis and pulmonary tuberculosis: a case report. Korean J Asthma Allergy Clin Immunol 2010;20:S382. 11. Agarwal R, Aggarwal AN, Gupta D, Bal A, Das A. Case report: a rare cause of miliary nodules - allergic bronchopulmonary aspergillosis. Br J Radiol 2009;82:e151–e154. 12. Shah A. Allergic bronchopulmonary aspergillosis: an Indian perspective. Curr Opin Pulm Med 2007;13:72–80.
Prednisolone Ameliorates Idiopathic Pulmonary Arterial Hypertension To the Editor:
Idiopathic pulmonary arterial hypertension (IPAH) is caused by pulmonary vascular remodeling. The entire mechanism by which pulmonary vascular remodeling develops has not been well elucidated. Inflammation or autoimmune background are implied in many cases (1, 2). However, there are no proven therapies that modulate inflammatory processes to treat IPAH. We have previously reported that prednisolone has an inhibitory effect on the proliferation and migration of pulmonary arterial smooth muscle cells (PASMC) from patients with IPAH (3). Here, we report a case of IPAH coexisting with idiopathic thrombocytopenic purpura (ITP), which was successfully treated with prednisolone. The severity of IPAH was ameliorated by prednisolone therapy. A 34-year-old female, who was diagnosed with IPAH three years earlier, was admitted to our hospital for further evaluation and treatment of thrombocytopenia. After detailed examination by a hematologist, she was diagnosed with ITP. Bone marrow aspiration showed a normal number of megakaryocytes, and platelet-associated IgG was elevated to 135.4 ng/107 cells (normal range: 9.0–25.0 ng/107 cells). A rheumatologist excluded definite diagnosis of any collagen diseases. One mg/kg/day (65 mg/body/d) of oral prednisolone was started as a standard therapy for treatment of ITP (Figure 1). During prednisolone therapy, the dose of epoprostenol (94 ng/kg/min) and diuretics (trasemide, 8 mg/d) were maintained at the same levels. Her condition progressively had improved and she gradually lost 3.3 kg in body weight. She felt less dyspnea, and World Health Organization (WHO) functional class improved from class III to II. Six-minutewalk distance increased to 305 m, although she could not walk for 6 minutes before steroid therapy because of shortness of breath. The cardiothoracic ratio decreased from 64% to 56%. Pericardial effusion decreased from 17 to 4 mm and the Doppler-estimated peak systolic tricuspid regurgitation pressure gradient decreased from 75 to 50 mm Hg. No adverse effects were observed during prednisolone treatment. While tapering prednisolone, she started to feel slight increase in shortness of breath upon exertion. Platelet counts were successfully maintained within normal range after termination of steroid therapy. However, the tricuspid regurgitation pressure gradient again increased, and we resumed increasing the dose of epoprostenol. Although she was discharged from our hospital at that time, she underwent living-donor lobar lung transplantation due to progressive heart failure 5 months later. It is well documented that inflammation is involved in the development of pulmonary vascular remodeling and the pathogenesis of IPAH. Elevated serum levels of interleukin-1b and -6 and circulating monocyte chemoattractant protein-1 are reported in patients (2, 4). T- and B-lymphocytes and macrophages are found to accumulate in plexiform lesions (1, 5). Prednisolone is a drug that has anti-inflammatory, immunosuppressive, and anti-
Figure 1. Time course of laboratory data and pulmonary hypertension before and after prednisolone treatment. Platelet counts (PLT), cardiothoracic ratio (CTR), Doppler-estimated peak systolic tricuspid regurgitation pressure gradient (TRPG), and plasma level of brain natriuretic peptide (BNP) are shown.
proliferative effects (6, 7). The effectiveness of steroid therapy in pulmonary hypertension associated with collagen diseases is already reported (8–10). However, there is no report that demonstrates the effectiveness of prednisolone therapy in IPAH alone, without any association with collagen diseases. We have previously shown that prednisolone significantly inhibited platelet-derived growth factor (PDGF)-induced accelerated proliferation and migration of PASMC from patients with IPAH (3). Moreover, we demonstrated that the effect was caused, at least in part, by inhibiting activation of NF-kB, a key transcription factor that controls immunity, inflammation, cell proliferation, and apoptosis (11). In summary, this case describes the potential effectiveness of prednisolone for the treatment of IPAH. The rationale for such treatment derives from its potent antiproliferative effect on PASMC from patients with IPAH demonstrated in vitro. We recognize that it is still difficult to integrate these results to apply prednisolone to all patients, taking the many side effects of prednisolone into account. However, this case supports the notion that prednisolone can inhibit pulmonary vascular remodeling and could be considered as a new targeted therapy for IPAH. Author Disclosure: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.
AIKO OGAWA, M.D., PH.D. KAZUFUMI NAKAMURA, M.D., PH.D. HIROKI MIZOGUCHI, M.D. NOBUHARU FUJII, M.D., PH.D. HIDEKI FUJIO, M.D., PH.D. KENGO F. KUSANO, M.D., PH.D. TOHRU OHE, M.D., PH.D. HIROSHI ITO, M.D., PH.D. Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama, Japan References 1. Tuder RM, Groves B, Badesch DB, Voelkel NF. Exuberant endothelial cell growth and elements of inflammation are present in plexiform lesions of pulmonary hypertension. Am J Pathol 1994; 144:275–285.
