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Table of Contents
ORIGINAL ARTICLE
Year : 2019  |  Volume : 68  |  Issue : 2  |  Page : 155-158

Transbronchial cryobiopsy in diagnosis of smear-negative pulmonary tuberculosis: validity and safety


1 Chest Medicine Department, Mansoura University, Egypt
2 Pathology Department, Mansoura University, Egypt
3 Microbiology Department, Mansoura University, Egypt

Date of Submission07-Oct-2018
Date of Acceptance09-Jan-2019
Date of Web Publication17-May-2019

Correspondence Address:
Heba Wagih Abdelwahab
Mansoura university
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ejcdt.ejcdt_149_18

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  Abstract 


Background Smear-negative pulmonary tuberculosis (PTB) represents 42% of PTB cases and is responsible for ∼20% of tuberculosis (TB) transmission cases. Early recognition of TB cases is important to limit TB transmission. This study was planned to assess validity and safety of bronchoscopic transbronchial cryobiopsy in diagnosis of patients with smear-negative PTB.
Patients and methods Patients with smear-negative PTB were enrolled. Bronchoalveolar lavage (BAL) and transbronchial cryobiopsy were taken. BAL was sent for microbiological examination (Ziehl–Neelsen for acid-fast bacilli and TB culture).
Results A total of 24 patients were included in the study. BAL Ziehl–Neelsen staining result was positive in four (16.7%) patients, and TB culture finding was positive in five (20.8%) patients. Among those who had a positive cryobiopsy result, the probability of TB disease was 100% (no false-positive results). Among those who had a negative cryobiopsy result, the probability of being TB free was 89.5%. So, sensitivity of transbronchial cryobiopsy in diagnosis of pulmonary TB was 85% and specificity was 100%.
Conclusion Transbronchial lung cryobiopsy is rapid and safe procedures in diagnosis of smear-negative pulmonary TB. However, further studies on a large number of patients are recommended.

Keywords: cryobiopsy, smear-negative tuberculosis, transbronchial biopsy, tuberculosis diagnosis


How to cite this article:
El-badrawy MK, El Shafey MM, Elhadidy T, Shebl AM, MA AE, Wafeik N, Abdelwahab HW, Zalata K. Transbronchial cryobiopsy in diagnosis of smear-negative pulmonary tuberculosis: validity and safety. Egypt J Chest Dis Tuberc 2019;68:155-8

How to cite this URL:
El-badrawy MK, El Shafey MM, Elhadidy T, Shebl AM, MA AE, Wafeik N, Abdelwahab HW, Zalata K. Transbronchial cryobiopsy in diagnosis of smear-negative pulmonary tuberculosis: validity and safety. Egypt J Chest Dis Tuberc [serial online] 2019 [cited 2019 Jun 26];68:155-8. Available from: http://www.ejcdt.eg.net/text.asp?2019/68/2/155/258443




  Introduction Top


The second leading cause of death from an infectious disease, after the HIV, is tuberculosis (TB). According to WHO report (2013), approximately nine million people had TB disease and 1.5 million deaths were caused by TB [1].

Diagnosis of pulmonary tuberculosis (PTB) depends only on clinical examination, sputum smear microscopy, and chest radiography in areas of limited resources, where nucleic acid amplification tests and sputum culture are not routinely available [2]. However, 42% of PTB cases are smear negative. Although smear-positive PTB cases are more infectious than smear-negative PTB cases, ∼20% of TB transmissions are thought to be caused by patients with smear-negative PTB [3].

Early recognition of PTB cases is important to both allow proper isolation and provide a basis for early institution of therapy. On the contrary, appropriate prediction of persons who are unlikely to have TB is essential to limit the cost and toxicity of empiric treatment. Relying on the culture results, which may take weeks, in starting therapy of the TB leads to delayed treatment and subsequent disease transmission [4]. So, this study was planned to assess validity and safety of bronchoscopic transbronchial cryobiopsy in diagnosis of patients with smear-negative PTB.


  Patients and methods Top


The study was conducted at Chest Medicine Department, Mansoura University, after approval of Institutional Research Board and written informed consent from all included patients.

Inclusion criteria

Patient more than 18 years old and diagnosed as having smear-negative PTB according to WHO report 2013 were included:
  1. Either have two sputum smears that is negative for mycobacterium TB.
  2. Or decision by a physician to give anti-TB treatment in patients with radiographic abnormalities suggestive of active pulmonary TB (e.g. upper lobe infiltrates, consolidations, cavities, or pleural effusions) and no improvement in response to broad-spectrum antibiotics.


Exclusion criteria

Patients unfit for bronchoscopy or refused to participate in the study were excluded.

All enrolled patients were subjected to the following:
  1. History taking and clinical examination.
  2. Chest radiography.
  3. ECG.
  4. Laboratory investigations: complete blood count, bleeding profile, arterial blood gas, liver, and kidney function tests.
  5. Computed tomography of chest for localization of the target segment or lobe.
  6. Bronchoscopic procedure:


The bronchoscope (PENTAX Europe GmbH, Hamburg, Germany) was introduced through oral route and advanced to the segmental bronchus that was previously determined by computed tomography of chest. The procedure was conducted after local oropharyngeal anesthesia with three to five puffs of lidocaine spray 10% and under sedation with 2–5 mg midazolam. Monitoring of oxygen saturation was done throughout the procedure.

Bronchoalveolar lavage (BAL) was taken using 150 ml of warm saline 0.9% from the selected segment and sent for microbiological examination [Ziehl–Neelsen (ZN) for acid-fast bacilli and TB culture].

Transbronchial cryobiopsy was done by introduction of a flexible cryoprobe (of 2.8 mm diameter) introduced through the working channel of fiberoptic bronchoscopy to the target segment followed by a freezing cycle for 3–4 s. The cryoprobe was retracted together with fiber optic bronchoscopy (FOB) while the biopsy was attached to its frozen tip ([Figure 1]).
Figure 1 Biopsy attached to the frozen tip of cryobiopsy probe.

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The biopsies were preserved and fixed in 10% buffered formalin and transferred to pathology laboratory for processing and staining. All samples were embedded in paraffin and stained with hematoxylin and eosin in each case. Hematoxylin and eosin-stained sections were reviewed by two pathologists.

Complications of the procedure (bleeding, pneumothorax, etc.) were recorded.


  Results Top


A total of 24 patients were enrolled, where 13 (54.2%) patients were males, three patients presented by pulmonary infiltrates and reticular opacities, 15 patients presented by cavitary lesions ([Figure 2]), 10 patients by consolidation, and one patient presented by miliary shadow in their radiology (chest radiography and CT).
Figure 2 Computed tomography of chest revealed left upper lobe cavitary lesion.

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Bronchoalveolar lavage

ZN staining was positive in four (16.7%) patients and TB culture was positive in five (20.8%) patients ([Table 1]).
Table 1 Microbiological results of bronchoalveolar lavage in the studied patients

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Pathological result of cryobiopsy specimen and relation with bronchoalveolar lavage results

TB granuloma resulted in five (20.8%) patients, interstitial pneumonia in four (16.7%) cases, and inflammatory (nontuberculous) lesions in nine (37.5%) patients and healthy lung tissue was found in six (25%) patients ([Table 2]).
Table 2 Transbronchial cryobiopsy biopsy results among the studied patients

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In the five patients with TB granuloma, three of them were positive by BAL TB culture and two patients were positive by BAL ZN. In six patients with healthy lung tissue, one patient was positive by both BAL ZN and TB culture. However, in nine patients with inflammatory lesion, one of them was positive by BAL ZN and TB culture. On the contrary, the four patients with interstitial pneumonia were negative by BAL TB culture and BAL ZN stain ([Table 3]).
Table 3 Cryobiopsy results in relation to Ziehl–Neelsen and tuberculosis culture results among the studied patients

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Validity of transbronchial cryobiopsy

Positive predictive value of transbronchial cryobiopsy was (12/12) 100% ([Table 4]).
Table 4 Validity of a transbronchial cryobiopsy

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Among those who had a positive cryobiopsy result, the probability of TB disease was 100% (no false-positive results).

Negative predictive value of transbronchial cryobiopsy was (17/19) 89.5%.

Among those who had a negative cryobiopsy result, the probability of being TB free was 89.5%.

So, sensitivity of transbronchial cryo biopsy in diagnosis of pulmonary TB was 85% and specificity was 100%.

Complications

Two (8.3%) patients were complicated with pneumothorax: one of them was treated with conservative measures, and in the other patient, pneumothorax was drained by intercostals tube. Twenty-three (95.8%) cases had mild bleeding that was controlled by maintained FOB suction.


  Discussion Top


The diagnosis of patients with TB is difficult when their sputum smear results are negative for acid-fast bacilli. In patients with a high clinical suspicion, physicians must choose between empirically treating and waiting the results of culture for up to 8 weeks. Rapid and recent laboratory investigations are available now in most medical centers, but they are expensive, and have low specificity and sensitivity for smear-negative sputum samples [4]. Many previous studies were conducted to find a rapid diagnostic tool for smear-negative PTB. The study by Kanaya et al. [4] was aimed to create a prediction rule for TB, and it concluded that the TB prediction score can help physicians decide if smear-negative patients should start empiric antituberculous treatment or wait for culture results. However, these results need further evaluation. Linguiss et al. [5] studied the diagnosis of smear-negative PTB based on clinical signs. Moreover, Bachh et al. [6] concluded that fibreoptic bronchoscopy can provide good tool to reach the diagnosis of smear-negative PTB. In this study, we assessed the validity and safety of transbronchial cryobiopsy in patients with smear-negative PTB. Our results showed that sensitivity of transbronchial cryo biopsy in diagnosis of pulmonary TB was 85% and specificity was 100%. However, one of the cryobiopsy false-negative cases was diagnosed by BAL TB culture, which takes many weeks. We recommend further studies on a large number of patients.


  Conclusion Top


Transbronchial lung cryobiopsy is a rapid and safe procedure in diagnosis of smear-negative pulmonary TB with specificity of 100% and sensitivity of 85%. However, further studies on a large number of patients are needed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
World Health Organization, UNICEF, United Nations Fund for Population Activities, World Bank, United Nations, Department of Economic and Social Affairs, et al.. Trends in maternal mortality, 1990 to 2013: estimates by WHO, UNICEF, UNFPA, The World Bank estimates, and the United Nations Population Division. 2014.  Back to cited text no. 1
    
2.
Piatek AS, van Cleeff M, Alexander H, Coggin WL, Rehr M, van Kampen S et al. GeneXpert for TB diagnosis: planned and purposeful implementation. Glob Health Sci Pract 2013; 1:18–23.  Back to cited text no. 2
    
3.
Tostmann A, Kik SV, Kalisvaart NA, Sebek MM, Verver S, Boeree MJ et al. Tuberculosis transmission by patients with smear-negative pulmonary tuberculosis in a large cohort in The Netherlands. Clin Infect Dis 2008; 47:1135–1142.  Back to cited text no. 3
    
4.
Kanaya AM, Glidden DV, Chambers HF. Identifying pulmonary tuberculosis in patients with negative sputum smear results. Chest 2001; 120:349–355.  Back to cited text no. 4
    
5.
Linguiss L, Vouvoungui C, Poulain P, Essassa G, Sylvie K, Francine N. Diagnosis of smear-negative pulmonary tuberculosis based on clinical signs in the Republic of Congo. BMC Res Notes 2015; 8:804.  Back to cited text no. 5
    
6.
Bachh A, Gupta R, Haq I, Varudkar H. Diagnosing sputum/smear-negative pulmonary tuberculosis: does fibreoptic bronchoscopy play a significant role? Lung India 2010; 27:58–62.  Back to cited text no. 6
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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Abstract
Introduction
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