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Role of flexible bronchoscopy in patients with sputum-negative pulmonary tuberculosis

  • Satyaprakash Sanjeevaiah
  • Maruti Yamanappa Haranal
  • Shashidhar Buggi
Original Article

Abstract

Background

Pulmonary tuberculosis is one of the major health concerns in the developing countries. Isolation of acid-fast bacilli (AFB) or tuberculosis bacilli from the sputum is required for the diagnosis. A proportion of suspected pulmonary tuberculosis (PTB) cases either clinically or radiologically will not produce sputum or will have sputum negative for AFB. These subsets of cases pose a diagnostic challenge to the treating clinicians. In this study, we present our experience and outcomes with flexible bronchoscopy in patients with sputum-negative pulmonary tuberculosis.

Materials and methods

This was a prospective cross-sectional study, conducted at SDS Tuberculosis research Centre and Rajiv Gandhi Institute of Chest Diseases, Bengaluru, India, from 2010 to 2016. A total of 1095 flexible bronchoscopies were done during this period, out of which 180 were patients with sputum negative for AFB, but were strongly suspected to have pulmonary tuberculosis on clinical examination or radiologically. There were 106 males and 74 females. The age ranged between 11 and 68 years. All patients underwent complete evaluation of the tracheobronchial tree followed by bronchoalveolar lavage (BAL). Microbiological studies used were Ziehl-Neelsen (ZN) staining and culture in Lowenstein-Jensen (LJ) medium. Mucosal lesions suspected of tuberculosis were subjected to biopsy and histopathological confirmation. The data was analyzed.

Results

Out of 180 patients, 106 (58.88%) cases had positive AFB smear on BAL. The culture confirmed the diagnosis of pulmonary tuberculosis in 120 cases (66.66%). Histopathology showed caseous granuloma in 38 (42.22%) cases, nonspecific inflammation in 40 (44.44%) cases, and malignancy in 12 (13.33%) cases out of 90 cases, who underwent biopsy. There were no post-procedural complications.

Conclusion

Bronchoscopy is the useful tool in the diagnosis of pulmonary tuberculosis in patients with sputum-negative pulmonary tuberculosis. It is also helpful in differentiating conditions having the clinical picture that mimics pulmonary tuberculosis.

Keywords

Tuberculosis AFB Sputum negative 

Introduction

Pulmonary tuberculosis (PTB) is one of the major health problems worldwide. PTB is known to the mankind since time immemorial. It is a leading cause of morbidity and mortality globally with an estimated 9 million cases and 1.5 million deaths each year. Every 4 s, an individual contracts tuberculosis and one of them dies every 10 s [1, 2]. The emergence of multidrug TB and increasing number of immunocompromised population are threats to the global TB control.

The most commonly used tools for the diagnosis of PTB are sputum smear for acid-fast bacilli (AFB) and the chest radiography. As per World Health Organization (WHO), detection of AFB in respiratory specimen using acid-fast staining or Ziehl-Neelsen (ZN) staining is a must for the confirmation of PTB [3]. Under Revised National Tuberculosis Control Program (RNTCP), sputum microscopy was considered for the diagnosis of PTB, which is cost effective and highly specific for the diagnosis of PTB. AFB smears of respiratory specimens (at least two or more specimens) are important for the prompt diagnosis of PTB. AFB smears have 30–70% sensitivity and 98–99% specificity.

However, all patients with PTB will not show AFB in their sputum smears. About 40–60% of patients with suspected active PTB either clinically or radiologically may fail to produce sputum, or when it is available AFB may be negative on repeated smear examinations [3]. Even though mycobacterial cultures are more sensitive than AFB smears (80–85%), culture results usually require 3–8 weeks [4]. Chest x-ray is often used for PTB screening, but many cases with sputum smear-negative TB show atypical x-ray patterns or normal findings [5]. Sputum smear-negative PTB may have mild or no respiratory symptoms and clinical manifestations [6].

Strategies to control TB include prompt early diagnosis, notification, and successful treatment of patients with active, transmissible disease. Early diagnosis of active PTB is critical for TB control, which in turn would help in curtailing the mortality and morbidity of the disease.

Difficulties arise when clinicians encounter sputum smear-negative PTB. Different alternative methods have been described in these patients for predicting active disease [7, 8]. Among the various tools available in the armamentarium, fiberoptic bronchoscopy (FOB) is the most widely used diagnostic modality in these patients [9, 10]. This has been also used as a diagnostic tool in patients with miliary tuberculosis [11].

We present our experience in fiberoptic bronchoscopy in patients with sputum smear-negative patients suspected to have pulmonary tuberculosis either clinically or radiologically.

Materials and methods

This study is a prospective cross-sectional study, conducted in SDS Tuberculosis Research Centre and Rajiv Gandhi Institute of Chest Diseases, Bengaluru, India.

Inclusion criteria

  1. 1.

    The patients, who visited the hospital with clinical history, physical findings, and chest X-ray lesions suggestive of PTB.

     
  2. 2.

    Patients with suspected PTB, in whom sputum is inadequate for examination (saliva or very scanty sputum) or those with sputum smear negative for acid-fast bacillus (AFB) on two samples, as per RNTCP guidelines.

     

Exclusion criteria

  1. 1.

    Patients with smear positive for AFB

     
  2. 2.

    Those with extrapulmonary tuberculosis

     
  3. 3.

    Those on antitubercular treatment for suspected PTB (clinical/radiological)

     
  4. 4.

    Those with contraindications to bronchoscopy: significant hypoxemia (SpO2 < 90% at rest), those with bleeding diathesis and those with recent myocardial infarction (MI)

     

During the period of 2010–2016, a total of 1095 patients underwent fiberoptic bronchoscopy at our center, out of which 180 patients were suspected to have sputum smear negative for PTB.

Chest X-ray

On the chest X-ray, the lungs were divided into upper, middle, and lower zones (delimited by the upper border of the second and the fourth anterior ribs). All six zones were assessed for the findings indicative of tuberculosis. The parenchymal disease was categorized as unilateral or bilateral. The parenchymal abnormalities were divided into active or inactive lesions as follows:
  • Inactive lesions—isolated fibrotic abnormalities or calcified and/or sharply defined tuberculomata.

  • Active lesions—consolidation, patchy fluffy shadowing (with or without an admixture of fibrotic changes), a miliary pattern, pleural effusion, or non-calcified opacities with an indistinct border.

  • If previous chest X-rays are available, the serial changes were taken into account.

  • All patients underwent pre-bronchoscopic screening, which included complete blood profile including BT, CT, and PT, platelet count, Chest X-ray PA view, and an ECG.

Bronchoscopy procedure

Informed written consent was obtained from the patients. The procedure was carried out electively with the patient nil orally for 4 to 6 h. Patients were premedicated with atropine (0.6 mg), 30 min prior to the bronchoscopy with nebulization using 2% xylocaine. Bronchoscopy was done with the patient lying supine on the operation table with the operator standing at the head end. Trans-nasal route was used. Bronchoscopy was carried out under local anesthesia. A thorough examination of the tracheobronchial tree was done for any mucosal congestion/hyperemia or mucosal abnormalities or secretions or any stenotic lesions. Washings were obtained by lavage with 20–40 ml of normal saline (0.9%), instilled through the internal channel of the fiberoptic bronchoscope and subsequent aspiration into a trap connected to the suction tubing. The specimen was sent in sterile container for AFB microscopy and the culture (LJ medium). Mucosal lesions suspected of tuberculosis were subjected to biopsy and histopathological confirmation. Post-procedure patients were monitored for pneumothorax, hemorrhage, and cardiac arrhythmias for 24 h.

Results

There were 106 males and 74 females. The age ranged between 11 and 68 years. The predominant symptom was cough with expectoration (negative for AFB). The distribution of various symptoms is summarized in Table 1. The right lung involvement was seen in 101 (56.11%) cases, the left lung in 59 (32.78%) cases, and bilateral involvement in 20 (11.11%) cases. The right upper lobe was the most commonly involved and infiltration was the most commonly seen radiological abnormality. Chest X-ray findings are summarized in Table 2.
Table 1

Patient symptom profile

Symptoms

Number of patients

Cough with expectoration

120 (66.67%)

Fever (night sweats)

101 (56.11%)

Weight loss

98 (54.44%)

Loss of appetite

85 (47.22%)

Breathlessness

60 (33.33%)

Hemoptysis

20 (11.11%)

Chest pain

08 (4.44%)

Table 2

Distribution of radiological abnormalities

Radiological lesion

Zone

Side

Right (n = 121)

Left (n = 59)

Bilateral (n = 20)

Infiltration (n = 115)

Upper zone

36

20

02

Middle zone

11

04

00

Lower zone

14

06

01

Combined

13

05

03

Consolidation (n = 47)

Upper zone

03

03

01

Middle zone

07

04

00

Lower zone

10

04

02

Combined

05

05

03

Cavity (n = 21)

Upper zone

04

01

02

Middle zone

01

02

00

Lower zone

02

00

01

Combined

06

01

01

Fibrosis (n = 17)

Upper zone

03

02

02

Middle zone

02

01

00

Lower zone

02

00

01

Combined

02

01

01

All patients underwent fiberoptic bronchoscopy. Out of 180 patients, 106(58.89%) cases had positive AFB smear on bronchoalveolar lavage (BAL) (Table 3). The culture confirmed the diagnosis of pulmonary tuberculosis in 120 cases (66.67%) (Table 4). Histopathology showed caseous granuloma in 38 (42.22%) cases, nonspecific inflammation in 40 (44.44%) cases, and malignancy in 12 (13.33%) cases out of 90 cases, who underwent biopsy. There were no post-procedural complications.
Table 3

Distribution of patients according to bronchial wash (BAL) for AFB

Bronchial wash for AFB

Number of patients

Positive

106 (58.89%)

Negative

74 (41.11%)

Table 4

Distribution of patients according to bronchial wash for culture

Bronchial wash for culture

Number of patients

Positive

120 (66.67%)

Negative

60 (33.33%)

Discussion

The sputum smear microscopy for AFB for the diagnosis of PTB is cost effective and highly specific. However, all patients with pulmonary tuberculosis will not reveal AFB in the sputum. Also, there are other factors, such as lack of sputum production, low bacterial yield, and improper or incorrect sampling. A smear-negative culture-positive state has been observed in 22–61% of cases [12]. Mycobacterial culture takes 3–8 weeks for the diagnosis of PTB, which delays the treatment [10]. Serological immune markers are also not reliable indicators for the diagnosis of PTB. Early diagnosis and treatment of pulmonary tuberculosis is the vital step in preventing the disease mortality and the morbidity.

Patients with smear-negative PTB can act as a means of transmitting the disease in the community and preclude the early diagnosis and the treatment, often leading to irreversible lung complications in the infected individuals [4]. If these patients were left untreated, 64% of them would require chemotherapy within 12 months [13]. This subset poses a real challenge to the pulmonologists [14]: delayed diagnosis can lead to spread of the disease or irreversible pulmonary complications and the empirical treatment can result in unwanted therapy with its side effects or the emergence of multidrug-resistant strains. According to the Global Tuberculosis report 2013, there were 30% smear-negative PTB cases in India in 2012 [15].

Studies have used scoring systems for the diagnosis of sputum smear-negative PTB based on the clinical characteristics [16, 17, 18]. Samb et al. [16] reported independent predictors of active PTB including a chronic cough lasting longer than 3 weeks, chest pains longer than 15 days, absence of sputum, and absence of dyspnea, and Lee et al. [18] reported that the lack of sputum was a positive predictor of active PTB. The specificity of the clinical predictors or scoring system was low and the positive predictive value was reported to be as low as 50%.

The advent of flexible bronchoscope in 1965 revolutionized the practice of pulmonary tuberculosis. It provides various specimens for smear examination and culture such as bronchial aspirate, bronchial washing, bronchial brushing, and bronchoalveolar lavage fluid. Its magnified telescopic view and extended reach to the disease site by brush or biopsy forceps even beyond the segmental orifices of the gigantic bronchial tree assist in greater diagnostic accuracy [19]. FOB is also useful in the diagnosis of endobronchial TB, which can be seen as normal in high-resolution computerized tomogram (HRCT ). It helps to differentiate tuberculosis with other commonly encountered diseases such as pneumonia or lung cancer [20]. However, its use on a large scale is limited considering the cost, feasibility, and applicability.

In our study, bronchoscopic visualization yielded mucopurulent secretion in 20 (16.67%) cases, mucosal hyperemia in 41 (34.16%) cases. Histopathology showed caseous granuloma in 38 (42.22%) cases, nonspecific inflammation in 40 (44.44%) cases, and malignancy in 12 (13.33%) cases out of 90 cases, who underwent biopsy. Kulapati et al. observed the coating of mucosa of involved segments with yellowish white secretions in almost all patients and also revealed mild to moderate hyperemia after bronchial wash. Purohit et al. reported generalized congestion in most of the patients. They have also reported ulceration in 64% of patients; 60% had frothy secretion of the bronchus [22]. Wallace et al. (1981) reported congestion of mucosa in 86% with no significant correlation of endoscopic findings with mycobacterial positivity [23]. According to the study by Panda et al., 44% had normal bronchial mucosa, 21% had unhealthy mucosa with granulations, 35% had discharge of mucous from the bronchus, 5% had growth, 3% had external compression, and 3% had bleeding from the bronchus and some cases had multiple findings [9].

In our study, patients with positive biopsy for malignancy had history of blood-stained sputum and none of them showed frank obstructive growth on bronchoscopy. These patients were referred to a cancer center for further evaluation and management.

In our study, radiologically, infiltrative opacities were seen in cases 63.88% (115) cases, consolidation in 26.11% (47) cases, cavity in 11.67% (21) cases, and fibrosis in 9.44% (17) cases. Unilateral involvement was dominant in our cases. The right side was more commonly involved, 101 (56.11%) cases as compared to the left side, 59 (32.78%) cases. Bilateral involvement was seen in 20 (11.11%) cases. In a study by Biswas et al., an exclusive upper zone involvement was seen in 67% of patients, while 16% of other patients had multi-lobar involvement including upper zones radiologically [24].

In our study, BAL smear for AFB was positive in 58.89% (106/180) cases. Sarkar et al. [25] and So et al. [26] reported the smear (aspirate/washing/brush) positivity in 67 and 38%cases respectively and are much higher compared to the study of Wallace et al., who reported it as 13% [23].

In this study, BAL culture was positive in 66.67% (120/180) cases. Kulpati et al. [21] and Kvale et al. [27] could grow acid-fast bacilli only in one third of the patients of suspected tuberculosis. The results of stained smear examination of bronchial washing was confirmed by culture in all cases in our study and is comparable to the studies by Kulpati et al. [21] (100%), Danek and Bower [28] (95%), Sarkar et al. [25] (87%), and Uddenfeldt and Lundgren (83%) [29].

Patients who are negative for both BAL smear and culture, and suspected of having sputum-negative pulmonary tuberculosis were treated symptomatically. They were also kept under regular follow-up.

In our study, there was no major complication or mortality. A study by Pereira et al. reported a major complication rate of 1.7% and a mortality of 0.1% [30].

All patients with positive AFB result (smear/culture) were treated with antitubercular treatment (ATT) as per national tuberculosis control program.

The flexible bronchoscopy is a useful tool in the diagnosis of pulmonary tuberculosis in sputum smear-negative patients. Bronchoscopy gives a higher bacteriological confirmation of diagnosis in patients with strong clinical and radiological evidence suggestive of pulmonary tuberculosis. It also helps in differentiating other conditions, which clinically mimic pulmonary tuberculosis. This study re-emphasizes the safety and utility of flexible bronchoscopy in the diagnosis of pulmonary tuberculosis.

Notes

Compliance with ethical standards

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Indian Association of Cardiovascular-Thoracic Surgeons 2018

Authors and Affiliations

  • Satyaprakash Sanjeevaiah
    • 1
  • Maruti Yamanappa Haranal
    • 2
  • Shashidhar Buggi
    • 1
  1. 1.Department of AnesthesiaSDS Tuberculosis Research Centre and Rajiv Gandhi Institute of Chest DiseasesBengaluruIndia
  2. 2.Department of Cardio-Thoracic and Vascular SurgerySDS Tuberculosis Research Centre and Rajiv Gandhi Institute of Chest DiseasesBengaluruIndia

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