International Journal of Research in Medical Sciences

Luhadia A et al. Int J Res Med Sci. 2020 Dec;8(12):4302-4306

www.msjonline.org

pISSN 2320-6071 | eISSN 2320-6012

Role of fiberoptic bronchoscopy in sputum smear negative suspected cases of pulmonary tuberculosis: a study conducted in Southern part of Rajasthan

Atul Luhadia*, Shanti K. Luhadia, Shubham Jain, Mohammad Hamza Hanfe, Divax Oza, Adit Zota, Trishi Nagda, Deepak Shukla, Sujit Gupta, Vidit Saxena, Monica Bansal, Ronak Kankrecha, Vishal Yadav, Viren Patel


Department of Respiratory Medicine, Geetanjali Medical College and Hospital, Udaipur, Rajasthan, India

Received: 01 November 2020

Revised: 09 November 2020

Accepted: 10 November 2020

*Correspondence:

Dr. Atul Luhadia,

E-mail: atulluhadia124@gmail.com

Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Background: Sputum smear negative pulmonary tuberculosis is a common problem faced by clinicians. Fiberoptic bronchoscopy may be very useful in diagnosing these cases which have no sputum or whose sputum smear is negative for acid fast bacilli. Objective of the current study was to assess the role of fiberoptic bronchoscopy in sputum smear negative under NTEP and radiologically suspected cases of pulmonary tuberculosis.

Methods: Clinico-radiological suspected cases of pulmonary tuberculosis patients in whom two sputum smear for acid fast bacilli by Ziehl Neelsen stain under NTEP was negative were included in the study. Fiberoptic bronchoscopy was performed in all these patients and samples taken were sent for investigations.

Results: Fiberoptic bronchoscopy was performed in 250 patients of suspected pulmonary tuberculosis whose sputum for AFB smear was negative. Cough was the most predominant symptom. Radiologically, right side disease was more common and upper zone was most commonly involved and infiltrates were common radiological finding. During bronchoscopy, congestion and hyperaemia (36%) and mucopurulent/mucoid secretions (32%) was seen in maximum number of cases. BAL was positive in 200 patients (80%), post bronchoscopy sputum was positive in 70 cases (28%) and biopsy was positive in 12 patients out of 16 performed biopsies (75%). The total TB positive cases after combining all the methods were 215 making the overall diagnostic yield of 86%.

Conclusions: Fiberoptic bronchoscopy and post bronchoscopy sputum can be very useful for diagnosing sputum for AFB smear negative but clinico-radiological suspected cases of pulmonary tuberculosis patients.

Keywords: Sputum smear negative-pulmonary tuberculosis, Ziehl Neelsen stain, Mycobacterium tuberculosis, Fiberoptic bronchoscopy, Brocho alveolar lavage

INTRODUCTION

Pulmonary tuberculosis (PTB) is one of the most important problem worldwide.1 India has more new TB cases annually than any other country.2 The most widely used tool of diagnosis of PTB is sputum examination and chest X-ray. The WHO also recommends the detection of acid fast bacilli (AFB) in respiratory specimens as the initial approach in the diagnosis of pulmonary TB.3 Though AFB smear is the most rapid, highly specific (98-99%) and low cost test but has poor sensitivity (30-70%).4,5 Early diagnosis to reduce the period of infectivity is considered to be one of the most effective TB control strategies. Mycobacterial cultures are more sensitive than AFB smears (80-85%) but cultures require 3-8 weeks.6,7

Though sputum smear and culture examinations still remain the gold standard in the diagnosis of PTB, but even in advanced disease it may be negative due to immunosuppression, low bacterial yield, poor quality of the sample collection, inadequate preparation, staining or examination of the smear.8 According to the global tuberculosis report 2013, there were 1.29 million notified tuberculosis cases in India in 2012, out of which about 30% were smear negative cases.9 The diagnosis becomes even more difficult when a patient who is suspected to have active pulmonary TB, both clinically and radiologically, does not produce sputum particularly in HIV positive, miliary tuberculosis or NTM disease situations. If these patients are left untreated then about 70% of them may develop active TB in next 12 months.10 In these suspected sputum smear negative (SSN-PTB) cases, repeat sputum samples are examined after 10-14 days under NTEP, but it may delay or miss the diagnosis.

The various diagnostic methods which can help in early diagnosis of suspected Sputum smear negative-pulmonary tuberculosis (SSN-PTB) cases are sputum induction with hypertonic saline, radiologically guided transthoracic needle aspiration, gastric lavage, bronchoscopic procedures bronchial aspirate/brocho alveolar lavage (BAL)/brushing/biopsy and post bronchoscopy sputum. After the availability of flexible fiber-optic bronchoscope (FOB) in 1966, there have been many studies performed for early diagnosis of TB and many advances has occurred in FOB techniques. Bronchoscopy and related procedures such as bronchoalveolar lavage, bronchial brushing, transbronchial biopsy and post bronchoscopy sputum examination may provide alternative ways of reaching an early diagnosis.11-15

Therefore, this study was done to determine the role of bronchoscopy in the diagnosis of SSN-PTB, as no such large study is being done till now in this part of the country i.e. Southern part of Rajasthan.

METHODS

Presented prospective observational study was conducted in Geetanjali hospital, Udaipur, Rajasthan from January 2018 to March 2020. The patients attending the chest OPD and those admitted in chest ward with the following inclusion and exclusion criteria were included in the study.

Patients with age more than 15 years, patients with clinico-radiological suspicion of pulmonary TB and in whom sputum was either not produced or was inadequate for examination (only saliva or sputum quantity <2 ml) or sputum was negative for acid fast bacilli on two samples under NTEP were included in the study. Patients with bleeding diathesis, history of recent myocardial infarction or arrhythmia, hemodynamically unstable patients and patients aged ≤15 years were excluded from the study.

Procedure

After an informed written consent, the bronchoscopy was performed in all the patients who fulfil the inclusion criteria. Patients were kept nil by mouth for 6 hours prior to procedure. Bronchoscopy was carried out under local anesthesia and a thorough examination of the bronchial tree was done. BAL was taken from the radiologically suspicious areas/segments in all patients. Bronchial brushing and biopsy was taken in any patient who had some kind of visible pathological lesion on bronchoscopy and in whom biopsy was feasible.BAL taken was sent for AFB smear by ZN stain method, AFB culture and GeneXpert MTB. Post bronchoscopy sputum samples one taken immediately and other taken 24 hours post bronchoscopy was sent for AFB smear examination by ZN stain.

Post procedure the patient was kept in recovery room for half an hour to watch for any complications and was asked to keep nil by mouth for 1 hour post procedure. Mathematical percentage statistics is used to analyse the results.

RESULTS

Fiberoptic bronchoscopy was performed in 250 patients of suspected pulmonary tuberculosis whose sputum for AFB smear was negative. Out of 250 patients, 174 were males and 76 were females (Table 1). The mean age of the patients was 50±30 years with a higher frequency between 20 to 60 years of age (Table 1). Cough was the most predominant symptom in 96% of patients (Table 2). Majority of patients had multiple symptoms. Radiologically, right side disease was more common on chest X-ray and upper zone was most commonly involved and infiltrates were common radiological finding (Table 3-4). The bronchoscopy findings are as mentioned in table 5 with congestion and hyperaemia (36%) and mucopurulent/mucoid secretions (32%) were seen in maximum number of cases. During bronchoscopy, bronchial aspirate and lavage were collected and sent for all microbiological investigations and cytological examination. In few patients, transbronchial and endobronchial biopsy were taken and sent for histopathological and AFB smear and culture and genexpert examination. After bronchoscopy, post bronchoscopy sputum was sent for AFB smear examination. BAL was positive in 200 patients (80%). Post bronchoscopy sputum was positive in 70 cases (28%) and biopsy was positive in 12 patients out of 16 performed biopsies (75%) (Table 6). 3 of the biopsy positive patients had BAL positive also. And 64 of the post bronchoscopy sputum positive patients had BAL positive. So the total TB positive cases after combining all the methods were 215 making the overall diagnostic yield of 86% by fibreoptic bronchoscopy.

Table 1: Age wise distribution of male and female patients.
Age groups (years)MFTotal
<21141125
21-30382260
31-40322052
41-5034943
51-60341145
61-7014115
71-80718
81-90112
Total17476250
Table 2: Distribution of patients according to clinical features (symptoms).
SymptomsFrequencyPercentage
Cough24096
Expectoration15060
Chest pain10040
Breathlessness13052
Fever16064
Loss of appetite21084
Weight loss15060
Hemoptysis156
Table 3: Chest X-ray, site of disease.
Chest X-ray siteFrequencyPercentage
Right12550
Left10040
Bilateral2510
Table 4: Distribution of patients according to type of opacity on chest X-ray.
Type of opacityFrequencyPercentage
Infiltration12048
Consolidation7028
Cavity6024
Table 5: Bronchoscopic findings.
Table reproduced from source PDF page 3
Table 6: Total yield of various bronchoscopic aided methods in our study.
Table reproduced from source PDF page 3

DISCUSSION

The challenge in front of chest physicians is to diagnose a patient of pulmonary TB with sputum for AFB smear negative but with symptoms and radiological features suggestive of TB. Though the sputum smear examination is the most reliable and cheap tool for diagnosis of pulmonary TB, but it’s sensitivity is quite low.4,5 It’s sensitivity is further lower if the patient is either not producing sputum or producing scanty sputum and these cases are usually reported as negative for AFB smear. In NTEP these patients are given symptomatic treatment for 10-14 days and then their sputum is re-examined for AFB smear, leading to delay in the diagnosis and increased chances of transmission of tuberculosis. In these kind of patients, early bronchoscopy and BAL examination may help in early diagnosis.

Table 7: Combined yield, comparison of various studies.
Table reproduced from source PDF page 3

Flexible fiberoptic bronchoscopy provides material (BAL, aspirate), as well as biopsy from localized affected areas of lung aiding in early diagnosis of smear negative tuberculosis.11-15 In present study, majority (90, 36%) of cases showed congestion and hyperaemia of bronchial mucosa on bronchoscopy, mucopurulent or mucoid secretions were seen in 80 (32%) cases, 30 (12%) cases showed narrowing of segmental openings, edematous mucosa and caseous material was seen in 18 (7.2%) cases, bleeding from bronchus was seen in 12 (4.8%) cases, endobronchial growth was seen in 10 (4%) cases. 40 (16%) cases had normal bronchial mucosa. Similarly, Purohit et al and Wallace et al reported generalized congestion/hyperaemia in most of the patients.16,17 The positive yield for tuberculosis using different methods during FOB in our study is 80% by BAL fluid, 28% by post bronchoscopy sputum and 75% by biopsy (Table 6). Six patients had only post bronchoscopy sputum for AFB smear positive and nine patients had only biopsy positive for AFB examination. So, the overall positive yield for tuberculosis using FOB in our study has been found in 215 cases (86%) which is comparable with the previously reported studies (48 to 100%) (Table 7).11-15,18-21

As such there was no limitation in the study apart from financial constraints in very few patients that was managed by the hospital.

CONCLUSION

The diagnostic yield of flexible fiberoptic bronchoscope is determined by indication of its use and the skills of bronchoscopist as well as pathologist. In patients where expectoration is negligible or sputum is negative and there is high suspicion of disease, fiberoptic bronchoscopy may help in rapid and precise diagnosis and thereafter early start of treatment that will reduce the risk of transmission of TB. Current study suggests that flexible fiberoptic bronchoscopy along with post bronchoscopy sputum examination is a useful tool in early diagnosis of pulmonary TB in sputum smear negative patients. Bronchoscopy reveals a higher bacteriological confirmation of diagnosis in patients with strong clinical and radiological evidence suggestive of pulmonary TB. Thus bronchoscopic aided procedures should be done in SSN-PTB patients with a high index of clinico-radiological suspicion. However, under NTEP programme, in sputum smear negative patients there is no provision of bronchoscopy based diagnosis of these patients. The financial constraints limit most of the patients to go for this procedure. Hence, there is a need to formulate guidelines where the physician can make a definitive and early diagnosis in these types of patients.

ACKNOWLEDGEMENTS

The authors are thankful to the bronchoscopy unit, departments of respiratory medicine, microbiology and pathology for their support and help.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: The study was approved by the Institutional Ethics Committee

REFERENCES

  1. 1. Dye C, Scheele S, Dolphin P, Pathania V, Raviglione MC. Global burden of tuberculosis: estimated incidence and mortality by country, WHO global surveillance and monitoring project. JAMA. 1999;282:667-86.
  2. 2. TB INDIA 2012, annual status report. Available at: https://tbcindia.gov.in/index1.php?lang=1&level=1&sublinkid=4160&lid=2807&theme=Blue. Accessed on 20 October 2020.
  3. 3. Treatment of tuberculosis: guidelines for national programs. Available at: https://www.who.int/tb/features_archive/new_treatment_guidelines_may2010/en/. Accessed on 20 October 2020.
  4. 4. Swai HF, Mugusi FM, Mbwambo JK. Sputum smear negative pulmonary TB: sensitivity & specificity of diagnostic algorithm. BMC Res Notes. 2011;4:475.
  5. 5. Cattamanchi A, Dowdy DW, Davis JL, Worodria W, Yoo S, Joloba M, et al. Sensitivity of direct versus concentrated sputum smear microscopy in HIV-infected patients suspected of having pulmonary tuberculosis. BMC Infect Dis. 2009;9:53.
  6. 6. Foulds J, O’Brien R. New tools for the diagnosis of tuberculosis; the perspective of developing countries. Int J tuberc Lung Dis. 1998;2:778-83.
  7. 7. Ramachandran V, Pachamuthu B, Esaki SM, Kailapuri MG, Settu H, Anitha CJ, et al. Value of single acid-fast bacilli sputum smears in the diagnosis of tuberculosis in HIV-positive subjects. J Med Microbiol. 2007;56:1709-10.
  8. 8. Truffot PC. Cambau E. Bacteriological diagnosis of tuberculosis. Rev Pneumol clin. 1994;50(5):240-6.
  9. 9. Global tuberculosis report 2013. https://apps.who.int/iris/bitstream/handle/10665/91355/9789241564656_eng.pdf;jsessionid=0FE10F5906C4664944E4047B5A31D263?sequence=1. Accessed on 20 October 2020.
  10. 10. Hong Kong chest service, tuberculosis research center, Madras, British research council. A study of the character and course of sputum smear negative pulmonary tuberculosis. Tubercle. 1981;62:155-67.
  11. 11. Stenson W, Aranda C, Bevelaqua FA. Transbronchial biopsy culture in pulmonary tuberculosis. Chest. 1983;83:883-4.
  12. 12. Kulpati DDS, Hira HS. Diagnosis of smear negative pulmonary tuberculosis by flexible fibre-optic bronchoscopy. Indian J Tub. 1986;33:179-82.
  13. 13. Wongthim S, Udompanich V, Limthongkul S, Charoenlap P, Nuchproyoom C. Fibre-optic bronchoscopy in diagnosis of patients with suspected active pulmonary tuberculosis. J Med Assoc Thai. 1989;72:154-9.
  14. 14. Zainudin BM, Wahab SA, Rassip CN, Tay AM. The role of diagnostic fibre-optic bronchoscopy for rapid diagnosis of pulmonary tuberculosis. Med J Malaysia. 1991;46:309-13.
  15. 15. Fujii H, Ishihara J, Fukaura N, Kashima N, Tazawa H, Nakajima H, et al. Early diagnosis of tuberculosis by fibre-optic bronchoscopy. Tubercle Lung Dis. 1993;73:167-9.
  16. 16. Purohit SD, Sisodia RS, Gupta PR, Sarkar SK, Sharma TN. Fibreoptic bronchoscopy in the diagnosis of sputum smear negative pulmonary tuberculosis. Lung India. 1983;1:143-6.
  17. 17. Wallace JM, Deutsch AL, Harsell JH, Moser KM. Bronchoscopy and transbronchal biopsy in evaluation of patients with suspected active tuberculosis. Am J Med. 1981;70:1189-94.
  18. 18. Danek SJ, Bower JS. Diagnosis of pulmonary tuberculosis by flexible fibre-optic bronchoscopy. Am Rev Respir Dis. 1979;119:677-9.
  19. 19. Sarkar SK, Sharma GS, Gupta PR, Sharma RK. Fibre-optic bronchoscopy in the diagnosis of pulmonary tuberculosis. Tubercle. 1980;61:97-9.
  20. 20. Bachh AA, Gupta R, Haq I, Varudkar HG. Diagnosing sputum smear negative pulmonary tuberculosis: Does fibre-optic bronchoscopy play a significant role?. Lung India. 2010;27(2):58-62.
  21. 21. Choudhary S, Tayade BO, Kharbade S, Sontakke A, Khan S, Abraham R. Outcome of fibreoptic bronchoscopy in sputum smear negative pulmonary tuberculosis. Panacea J Med Sci. 2015;5(1):33-9.