Chapter 1 Endobronchial Tuberculosis: An Overview
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1 Chapter 1 Endobronchial Tuberculosis: An Overview Gayathri Devi HJ* Department of Respiratory Medicine, MS Ramaiah Medical College, India * Corresponding Author: Gayathri Devi HJ, Department of Respiratory Medicine, MS Ramaiah Medical College, Bangalore , India, Tel: ; Gayathrijoshy@gmail.com First Published March 24, 2017 Copyright: 2017 Gayathri Devi. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source. Abstract Endobronchial tuberculosis (EBTB) is the tuberculous infection of the tracheobronchial tree, with microbial and histopathological evidence, with or without parenchymal involvement. Endobronchial tuberculosis because of the delay in the diagnosis continues to be a health problem. Diagnosis of EBTB is challenging because the disease presents with nonspecific clinical findings and normal Chest x-ray. Bronchoscopic examination with microbiological and histopathological evidence of tuberculosis is essential for the diagnosis. Early diagnosis and prompt treatment are important to prevent the serious complications of EBTB. This article elaborates on the clinical presentation and current treatment options for EBTB. Introduction Tuberculosis remains a major global health problem. Recently there has been an unprecedented resurgence of tuberculosis that may be related to increased incidence of HIV [1]. In 2015, million people around the world were afflicted with tuberculosis. There were 1. 8 million TB related deaths worldwide. Endobronchial tuberculosis was first described in 1689 by an English physician, RichardMorton [2]. EBTB is present in 10-40% of patients with active tuberculosis [3]. The incidence of EBTB varies depending on the population studied and the method of examination. The incidence has been reported to be 60% in autopsies and 10% in routine bronchoscopy [4]. 2 3
2 Diagnosis of endobronchial tuberculosis in endemic areas continues to be a clinical challenge, since it may mimic pulmonary diseases such as bronchogenic carcinoma, pneumonia or bronchial asthma [5]. Chest x-ray may be normal in 20% of the patients. Bronchoscopy is considered as the most reliable method for confirmation of the diagnosis. It should be performed as soon as possible in suspected patients to prevent the serious complications of EBTB such as Broncho stenosis. Pathogenesis and Clinical Features Endobronchial tuberculosis is defined as a tuberculous infection of the tracheobronchial tree with microbial and histopathological evidence, with or without parenchymal involvement [6]. EBTB is present in 10-40% of patients with active tuberculosis [3]. The true incidence of EBTB is likely to be underestimated since bronchoscopy procedure is not performed routinely in patients with tuberculosis [5]. There are studies in the literature in which all patients with active pulmonary tuberculosis were subjected to bronchoscopy and reported an incidence of EBTB as high as 50% [7]. In an another study in Korea 429 patients with pulmonary tuberculosis were prospectively studied to assess the incidence of concomitant EBTB by performing bronchoscopy and EBTB was found in 54. 3% of patients [8]. EBTB is the main complication of pulmonary tuberculosis. It occurs more commonly in patients who are in second or third decade. But Van der Brandeetall [9]have described a second peak in geriatric population. Studies have shown female preponderance of EBTB [10]. The possible cause proposed is longer exposure to tubercle bacilli, because female patients tend to retain sputum containing bacilli due to sociocultural and aesthetic factors. The exact pathogenesis of EBTB is not yet fully understood, the five proposed mechanisms of infection described in literature include (a) direct extension from an adjacent parenchymal focus; (b) implantation of organisms from the infected sputum; (C)haematogenous dissemination; (d) lymph node erosion into a bronchus; and (e) spread of infection via the lymphatics [11]. Research studies have shown elevated interferon -gamma (IFN gamma) and Transforming growth factor beta (TGF beta) in the bronchial wash fluid of the EBTB patients. It may be related to the pathogenesis and progression of EBTB [12]. The clinical course of EBTB is variable and is dependent on the interaction between mycobacteria, host immunity and treatment effects. Clinical features depend on the site and extent of involvement of EBTB. Some patients are asymptomatic, while most complain of cough which is barking in nature, haemoptysis, hoarseness, chest pain and generalized weakness [13]. Dyspnoea is often associated with atelectasis and constitutional symptoms including anorexia, weight loss and night sweats may occur. It may have an acute onset mimicking asthma [1], foreign 4 5
3 body aspiration or pneumonia or an insidious onset simulating lung carcinoma [14]. Physical examination may be normal. Examination of the respiratory system may detect persistent unilateral wheeze and decreased air entry. Nonspecific respiratory symptoms along with chest radiograph being normal in 20-30% of cases may be the reason for diagnostic delay in EBTB patients [15]. Laboratory abnormalities are non-specific in EBTB. Normal chest x-ray does not exclude the diagnosis of EBTB. Chest x-ray may be normal in 10% of the patients. If there is airway obstruction it can cause distal atelectasis. Classical radiological features of tuberculosis such as cavitation, pleural effusion, hilar and mediastinal lymphadenopathy may be seen. CT scan may reveal the extent of tracheobronchial lesions and the location of stenosis [16]. High resolution computed tomography is more sensitive in demonstrating the early endobronchial spread of tuberculosis. The findings are non specific or it may show endobronchial involvement of both large and small airways [17]. Involvement of the small airways leads to findings on CT which includes poorly defined nodules, centrilobularnodules, bronchial wall thickening and tree in bud appearance [18](Figure 1). 1 (a) 1 (b) Figure 1a and Figure 1b: Showing tree in bud appearance. 6 7
4 It is difficult to demonstrate tubercle bacilli on smear or culture in EBTB. The reason could be expectoration of sputum is difficult because of entrapment of mucus by proximal endobronchial granulation tissue. Ulceration of the mucosa may be necessary for a positive AFB smear result [10]. Polymerase chain reaction (PCR) for mycobacterium tuberculosis is used to improve the diagnosis of EBTB [13]. Endobronchial tuberculosis may result in significant limitation of airflow. That could be due to initial lesion or subsequent stricture formation [19]. Spirometry in EBTB is usually restrictive [15]. Bronchoscopy is mandatory for the diagnosis of endobronchial tuberculosis. Chung et all [1] study showed that the lesions in EBTB usually does not involve the bronchial mucosa circularly. The normal mucosa is partly spared, giving the appearance of a crushed water drop shape. The pathologic changes of EBTB are believed to begin as simple erythema with edema and lymphocytic cell infiltration. As the disease advances submucosal tubercles develop giving it a granular appearance. It can undergo caseous necrosis or progress to ulceration. These ulcerative lesions can evolve into hyperplastic -inflammatory polyp or heal by fibrosis leading to Broncho stenosis [20]. Retrospective study of 121 patients with EBTB by Lee et all [10] has shown that right upper and right main bronchus were the most frequently involved in %. Endobronchial tuberculosis is classified into seven subtypes by Chung [21] according to bronchoscopic features: actively caseating, edematous-hyperemic(figure 2), fibrostenotic, (Figure 3) tumorous(figure4), granular, ulcerative(figure 5), and nonspecific bronchitic type. Rikimaru et al. [22] have further classified bronchial ulcer into three stages(i)active stage ( stage A) before TB treatment commenced, (II) Healing stage (stage H) and (III) Scarring stage (stage S). Figure 2: Oedematous EBTB. 8 9
5 Figure 3: Bronchostenosis Pin Hole Opening(L) Main Bronchus. Figure 4: Tumorous EBTB. Figure 5: Ulcerative EBTB. Early diagnosis and treatment with antituberculous drugs are essential to prevent the development of fibrostenosis [19]. Treatment The treatment of EBTB involves two most important goals. First and foremost is to eradicate tubercle bacilli and to prevent bronchial stenosis [23]. The treatment of EBTB involves 6 months of treatment with antitubercular drugs and is the same as that for pulmonary tuberculosis. Hoheisel et al [6] have described that bronchial stenosis may occur despite adequate antituberculous treatment. The role of corticosteroids in EBTB is not completely defined. Some authors have advocated it and some have 10 11
6 claimed no benefit. The beneficial effects of corticosteroids are seen in early stages when hypersensitivity is the predominant mechanism. It is unlikely to be helpful in advanced cases of Broncho stenosis with extensive fibrosis [10]. Verhaeghe et al [24] have used local injection of corticosteroids in different sittings and demonstrated rapid healing and complete resolution of endobronchial tuberculosis. Some authors have used aerosol therapy consisting of streptomycine and corticosteroid along with standard chemotherapy and found beneficial effect [25]. Interventional bronchoscopy is used in the management of stenosis resulting from EBTB. Bronchoscopy techniques used to relieve airway stenosis are balloon dilatation, stent insertion, laser photoresection, cryosurgery and argon plasma coagulation(apc). Airway dilatation procedures may be accomplished through rigid and flexible bronchoscopy. Advantages of balloon dilatation over other methods is, it is simple, rapid, well tolerated, minimally invasive and it provides immediate symptomatic relief [26]. (Figure 6 a,b,c) Patients who require more than one session of balloon dilatation usually need stenting or ablative procedures. Tracheobronchial stents can be broadly divided into metal or silicone stents. Self expanding metallic stents are Gianturco-z, the wallstent and the Nitinol. Figure 6a: Left Main Bronchus Stenosis. Figure 6b: Balloon Dilatation
7 stent should be easy to place and remove without causing significant complications. Biodegradable stents may be beneficial [29]. Figure 6c: Left Main Bronchus Open After Balloon Dilatation. Balloon expandable metallic stents are Palmaz stent and Strecker stent. Insertion of Stent is indicated in patient s refractory to balloon dilatation. Silicone stent is preferred to metallic stent because of easy placement and removal [27](Figure 7 a,b,c)silicone stents can be left in place for several years. Complications related to balloon dilatation as well as stenting include airway wall perforation, stent migration leading to obstruction and hemoptysis [28]. The metallic stents remain relatively stable in position but the disadvantage is excessive granulation tissue formation and difficulty of removal once the stent has been epithelialized (Figure 8 a,b,c). Many authors have discussed the characteristics of an ideal stent. The future Figure 7a: RT Main Bronchus TB Bronchostenosis. Figure 7b: Silicone Stent Placed, Proximal View After Balloon Dilatation
8 Figure 8b: Left Main Bronchus Completely Covered Metal Stent. Figure 7c: Silicone Stent, Distal View. Figure 8C: CXR showing left main bronchial metal stent. Figure 8a: Left Main Bronchostenosis, Fish Mouth Like Left Main Bronchus. Ablative techniques are also used to re-establish the patency of the airway. These methods can be applied singly or in combination to achieve the desired outcome. Cryotherapy with video bronchoscopy exhibits favourable effects but it needs to be repeated several times to get good results. Mu D et al [30] have analysed the effect of 16 17
9 cryotherapy in granular EBTB that did not have luminal narrowing of the bronchus at the time of diagnosis. The rate of disappearance of the lesions was faster in patients who received bronchoscopic cryotherapy and anti-tuberculosis chemotherapy when compared to the patients who received only anti tuberculosis treatment. When Argon Plasma Coagulation is used the growth of granulation tissue leads to undesirable effects. Surgical resection may be indicated for patients not responding to interventional bronchoscopy. Lobectomy, pneumonectomy, sleeve resection with end to end anastomosis are the different techniques used to treat airway stenosis. Conclusion High index of suspicion for EBTB is required in a patient with pulmonary tuberculosis presenting with symptoms and signs suggestive of obstruction. For early diagnosis, bronchoscopy to be performed in suspected patients to prevent the serious complications of EBTB such as brocho stenosis. Early diagnosis and treatment helps in reducing the significant morbidity and potential mortality associated with the irreversible fibro stenotic Stage of the disease. Acknowledgement Dr. Ravindra M Mehta Consultant Interventional Pulmonologist, Apollo Hospitals Bangalore for providing bronchoscopy images. Mrs. DivyaDavis Respiratory therapist MS Ramaiah Memorial hospital for technical assistance. References 1. Chung HS, Lee JH. Bronchoscopic assessment of the evolution of endobronchial tuberculosis. Chest. 2000;117: DBehera. Text Book of Pulmonary Medicine, 2 nd edition. New Delhi: Jaypee Brothers Medical Publishers (P) Ltd C Tetikkurt. Current perspectives on endobronchial tuberculosis. Pneumon. 2008; 21: Albert RK, Petty TL. Endobronchial tuberculosis progressing to bronchial stenosis. Chest. 1976; 70: SevketOzkayaSalihBilgin, SerhatFindik, HayriyeÇeteKök, CananYuksel, AtillaGüvenAtıcı. Endobronchial tuberculosis: histopathological subsets and microbiological results. Multidiscip- Respir Med. 2012; 7: Hoheisel G, Chan BK, Chan CH, Chan KS, Teschler H, et al. Endobronchial tuberculosis: diagnostic features and therapeutic outcome. Respir Med. 1994; 88: Kurasawa T, Kuze F, Kawai M, Amitani R, Murayama T, et al. Diagnosis and management of 18 19
10 endobronchialtuberculosis. Intern Med. 1992; 31: Jung SS, Park HS, Kim JO, Kim SY. Incidence and clinical predictors of endobronchial tuberculosis in patients with pulmonary tuberculosis. Respirology. 2015;20: [Crossref] [PubMed] 9. Brande PM Vanden, Mierop FV, VerbekenEK, Demedts M. Clinical spectrum of endo-bronchial tuberculosis in elderly patients. Arch Intern Med. 1990;150: Lee JH, Park SS, Lee DH, Shin DH, Yang SC, et al. Endobronchial tuberculosis: clinical and bronchoscopic features in 121 cases. Chest. 1992;102: Smart J. Endo-bronchial tuberculosis. Br J Tuberc Dis Chest. 1951;45: Kim Y, Kim K, Joe J, Park H, Lee M, et al. Changes in the levels of interferon-gamma and transforming growth factor-beta influence bronchial stenosis during the treatment of endobronchial tuberculosis. Respiration. 2007;74: Mehta, Atul C, Jain, Prasoon, Gildea, et al. Diseases of the Central Airways-A Clinical Guide. 2016; Matthews JI, Matarese SL, Carpenter JL. Endobronchial tuberculosis simulating lung cancer. Chest. 1984;86: Kashyap S, Solanki A. Challenges in endobronchial tuberculosis: from diagnosis to. management. Pulm Med. 2014;2014: Cary C, Jhaji M, Cinicola J, Evans R, Cheriyath P, et al. A rare case of fibro stenotice ndobronchial tuberculosis of trachea. Ann Med Surg(Lond). 2015;4: Sharma SK. Tuberculosis. New Delhi: Jaypee Brothers Medical Publishers (P) Ltd Muller NL, Fraser RS, Colman NC, Pare PD. Radiologic Diagnosis of Diseases of the Chest. Philadelphia: W. B. Saunders Co. 2001; Michael A Grippi, Jack A Elias, Jay A Fishman, Allan I Pack, Robert M Senior, et al. Fishman s Pulmonary Diseases and Disorders, 5th edn. New York: McGraw Hill Medlar EM. The behavior of pulmonary tuberculous lesions; a pathological study. Am Rev Tuberc. 1955;71: Chung HS, Lee JH, Han SK, et al. Classification of endobronchial tuberculosis by the bronchoscopic features. TubercRespir Dis. 1991; 38: Rikimaru T, Tanaka Y, Ichikawa Y, Oizumi K. Endoscopic classification of tracheobronchi
11 al tuberculosis with healing processes. Chest. 1994;105: Park IW, Choi BW, Hue SH. Prospective study of corticosteroid as an adjunct in the treatment of endobronchial tuberculosis in adults. Respirology. 1997; 2: Verhaeghe W, Noppen M, Meysman M, Monsieur I, Vincken W, et al. Rapid healing of endobronchial tuberculosis by local endoscopic injection of corticosteroids. Monaldi Arch Chest Dis. 1996;51: Rikimaru T, Koga T, Sueyasu Y, Ide S, Kinosita M, et al. Treatment of ulcerative endobronchialuberculosis and bronchial stenosis with aerosolized streptomycin and steroids. Int J Tuberc Lung Dis. 2001; 5: Y Iwamoto, T Miyazawa, N. Kurimoto et al. Interventional bronchoscopy in the management of airway stenosis due to tracheobronchial tuberculosis. Chest. 2004; 126: ShimaaNourMoursi Ahmed, PotjaneeKorrungruang, Hideo Saka, GyoAsai, Yuko Ise, et al. Balloon Dilatation of a Case oftuberculous Tracheobronchial Stenoses during the Course of Antituberculous Treatment. Case Reports in Medicine Wen Ting Siow, Pyng Lee. Tracheobronchial tuberculosis: a clinical review. Journal of Thoracic Disease John E McClay, Arlen D Meyers. Laryngeal and Tracheal Stents. Medscape emedicine Mu D, Nan D, Li W, Fu E, Xie Y, et al. Efficacy and safety of bronchoscopiccry otherapy for granular endobronchial tuberculosis Respiration. 2011;82:
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