ROLE OF FIBEROPTIC BRONCHOSCOPY IN SPUTUM NEGATIVE PATIENTS

Background: Tuberculosis continues to be the one of the most common global health problems for more than a century. Fiberoptic bronchoscopy may be very useful in diagnosing cases who have no sputum or whose sputum smear is negative for Acid-Fast bacilli. The current study aims to assess the role of fiberoptic bronchoscopy in sputum smear negative under NTEP and radiologically suspected cases of pulmonary tuberculosis. Methods: This study was conducted in our institution in clinico-radiological suspected cases of pulmonary tuberculosis patients in whom two sputum smear for acid fast bacilli by Zeihl-Neelsen stain under NTEP was negative. Fiberoptic bronchoscopy was performed in all these patients and samples taken were sent for investigations. Result: Fiberoptic bronchoscopy was performed in a total of 110 patients of presumptive pulmonary tuberculosis whose sputum for AFB smear was negative. Out of 110 patients, 65.45% were male and 35.55% were female. Fever was the most common presenting symptom and was found in 93.64% patients. Radiographically, pulmonary consolidation was bilateral in 63.34% cases while was unilateral in 36.36% cases. The total yield of FOB came out to be 59.1% in which BAL for AFB smear was positive in 43.63% cases, BAL for Mtb culture was positive in 54.54% cases while, BAL for PCR was found to be positive in 59.09% cases. Conclusion: Fiberoptic bronchoscopy may be useful in rapid diagnosis and early treatment initiation thereby, reducing the risk of transmission of the disease. The findings of the study indicated that fiberoptic bronchoscopy is a useful method to diagnose the cases of sputum negative radiologically suspected symptomatic patients of tuberculosis. the of infectious diseases owing to inadequacy of The only diagnostic for TB, to peripheral levels of health is serial sputum smear microscopy with ZiehlNeelsen (ZN) staining .Sputum smear microscopy is not only time consuming but has also shown a high false negative rate ranging from 16 to50% despite the clinical profile and radiological lesions being consistent with diagnosis of pulmonary tuberculosis 4 .Attempts to improve the quality of sputum smear examination have been made from time to time but did not reveal any significant improvement in false positivity as well as false negativity rate the complexity of investigational of

Background:Tuberculosis continues to be the one of the most common global health problems for more than a century. Fiberoptic bronchoscopy may be very useful in diagnosing cases who have no sputum or whose sputum smear is negative for Acid-Fast bacilli. The current study aims to assess the role of fiberoptic bronchoscopy in sputum smear negative under NTEP and radiologically suspected cases of pulmonary tuberculosis. Methods:This study was conducted in our institution in clinicoradiological suspected cases of pulmonary tuberculosis patients in whom two sputum smear for acid fast bacilli by Zeihl-Neelsen stain under NTEP was negative. Fiberoptic bronchoscopy was performed in all these patients and samples taken were sent for investigations. Result:Fiberoptic bronchoscopy was performed in a total of 110 patients of presumptive pulmonary tuberculosis whose sputum for AFB smear was negative. Out of 110 patients, 65.45% were male and 35.55% were female. Fever was the most common presenting symptom and was found in 93.64% patients. Radiographically, pulmonary consolidation was bilateral in 63.34% cases while was unilateral in 36.36% cases. The total yield of FOB came out to be 59.1% in which BAL for AFB smear was positive in 43.63% cases, BAL for Mtb culture was positive in 54.54% cases while, BAL for PCR was found to be positive in 59.09% cases. Conclusion:Fiberoptic bronchoscopy may be useful in rapid diagnosis and early treatment initiation thereby, reducing the risk of transmission of the disease. The findings of the study indicated that fiberoptic bronchoscopy is a useful method to diagnose the cases of sputum negative radiologically suspected symptomatic patients of tuberculosis.

…………………………………………………………………………………………………….... Introduction:-
Tuberculosis continues to be the one of the most common global health problems for more than a century. It remains one of the world's leading causes of adult morbidity and mortality resulting in an estimated 10 million incident cases and 1.5 million deaths from the disease in the year 2020, thus showing an incremental trend despite systemic efforts to curb and control the disease. 1 In 2020, thirty high burden countries accounted for 86% of new TB cases, with India leading the count. 1 TB remains a major health problem in India, with the country accounting for nearly 26% of all TB cases reported globally. In 2021, out of the estimated global incidence of 10 million cases 2.64 million cases were estimated to have occurred in India. 1 Early detection, proper treatment and controlling the drug-compliance are the key to success for controlling tuberculosis. 2 Unfortunately, most of the high burden countries are have poor ISSN: 2320-5407 Int. J. Adv. Res. 10(03), 573-578 574 infrastructure for the diagnosis of infectious diseases owing to inadequacy of resources. The only diagnostic technique for TB, suitable to peripheral levels of health services, is serial sputum smear microscopy with ZiehlNeelsen (ZN) staining 3 .Sputum smear microscopy is not only time consuming but has also shown a high false negative rate ranging from 16 to50% despite the clinical profile and radiological lesions being consistent with diagnosis of pulmonary tuberculosis 4 .Attempts to improve the quality of sputum smear examination have been made from time to time but did not reveal any significant improvement in false positivity as well as false negativity rate despite increasing the complexity of investigational procedures. [5][6][7] In the event of negative-sputum in presence of symptoms, it is essential that the diagnostic tool is sensitive enough to provide an accurate diagnosis within a reasonable time. There are alternative approaches like culture sensitivity, however, AFB culture takes around 4-6 weeks, and during this time a false negative patient remains without treatment and thus increases the chance of spread of disease in the community.Anti-tuberculosistreatment (ATT) is frequently started empirically, leading many a time to avoidable risk of drug toxicity, and infructuous expenditure. Diseases like bronchogenic carcinoma and diffuse lung diseases are sometimes missed because cases are put within the grey area of "presumptive tuberculosis''. On the other hand, if not treated, 64% of sputum negative suspects could need chemotherapy within 12 months 8 .
Various methods have been employed to ascertain active TB disease in patients with presumptive sputum negative tuberculosis which includes sputum induction with hypertonic saline, gastric lavage, bronchoscopic procedures such as bronchial aspirate/bronchoalveolar lavage (BAL)/brushing/biopsy and post bronchoscopy sputum. Among various alternative methods, use of fiber-optic bronchoscope (FOB) is one of the most widely studied alternative diagnostic approach among sputum negative patients. [9][10][11][12] The FOB facilitates rapid diagnosis and offers the additional advantage of the diagnosis of several conditions that may mimic PTB. However, FOB is an invasive procedure, and is associated with the risk of transmission of tuberculosis (TB) and other infections. It is costly, and is not widely available in the developing countries. In developed countries with no limitations on resources, early FOB seems to be the best course of action in a patient with suspected SSN-PTB. With the changing economic scenario and availability of fiber-optic bronchoscope facilities in developing countries, the picture is changing fast, hence it is essential that its utility in smear negative situations must be evaluated in our settings. The present study is an attempt in that direction.

Methods:-
This prospective observational study was conducted in Era's Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh from June 2015 to December 2016. All presumptive cases of Pulmonary tuberculosis attending the pulmonary OPD and those admitted in the chest ward with following inclusion and exclusion criteria were included in the study.
Patients aged 18 years or more, with clinic-radiological suspicion of pulmonary TB and in whom sputum was negative for acid fast bacilli on two samples under NTEP or in whom sputum was either not produced or was inadequate for examination were included in the study. Patients younger than 18 years of age, with bleeding diathesis, history of myocardial infarction or arrythmias, history of anti-tubercular treatment for more than one month and patients who were hemodynamically unstable were excluded from the study.

Procedure:-
All patients who gave an informed written consent and fulfilled the inclusion criteria, were subjected to bronchoscopy. Patients were kept nil orally for 8 hours prior to bronchoscopy, which was carried out under local anesthesia and a thorough examination of the bronchial tree was done. BAL was obtained from the radiographically suspected areas/segments in all the patients. BAL obtained was sent for AFB smear by ZN stain method, MTB culture (LJ Medium) and PCR.
Patient was kept under observation for 2 hours after the procedure to watch for any complications and was asked to keep nil orally for 2 hours post procedure.

Results:-
Fiberoptic bronchoscopy was performed in a total of 110 patients of presumptive pulmonary tuberculosis whose sputum for AFB smear was negative. Out of 110 patients, 72(65.45%) were male and 38(35.55%) were females ( Table 1). The mean age of the patients was 39.78±16.31 years. Most common age group was 21-30 years (22.73%) 575 followed by 41-50 years (20.91%), while the least common age group were 61-70 years and >70 years (4.55%) each ( Table 2). Out of 110 patients included in the study, only 24 (21.82%) had positive contact history while rest 86 (78.18%) had no contact history (Table 3). Fever was the most common presenting symptom and was found in 103 (93.64%) patients followed by cough which was present in 88 (80%) patients (Table 4). Radiographically pulmonary consolidation was bilateral in 70 (63.64%) cases while in rest it was unilateral 40 (36.36%) cases (Table 5). Congestion and hyperaemia (38%) were the most common bronchoscopic findings followed by mucopurulent/mucoid secretions (34%). Out of a total of 110 sputum negative patients enrolled in the study, a total of 65 (59.1%) turned out to be positive after fiberoptic bronchoscopy. BAL for AFB smear was positive in 43.63% cases, BAL for MTB culture was positive in 54.54% cases while BAL for PCR was found to be positive in 59.09% cases ( Table 6). The sensitivity of different measures ranged from 73.8% (AFB) to 100% (PCR). All the measures had 100% specificity and 100% positive predictive value. The negative predictive value of different measures ranged from 72.6% (AFB) to 100% (PCR) ( Table 7).

Discussion:-
Tuberculosis is one of the unresolved diseases that has remained untamed despite concerted efforts by health professionals throughout the world. Primary treatment of tuberculosis is sometimes started on symptomatic manifestation itself. Sputum smear positivity is the criteria for screening; however, it is often marred with false negativity 4,13 . On the other hand there are a number of conditions including malignancy that often have clinical manifestations similar to tuberculosis and are clinically misdiagnosed as pulmonary tuberculosis [14][15][16] . In such a situation, a clinically suspected sputum negative tuberculosis patient needs further exploration for the underlying disease responsible for the clinical manifestation. In such a scenario advanced and confirmatory diagnostic methods like PCR and fiberopticbronchoscopy play an instrumental role.
Hence the present study was planned to evaluate the role of fiberoptic bronchoscopy in sputum negative pulmonary tuberculosis cases.  18 found maximum number of their cases to be aged 40-49 years (41.7%). These differences in age profile of patient might be incidental and as such except for role of intermediate reactors old age, no other association with age was seen.Majority of the cases enrolled in the study were males (65.45%), thus showing a male preponderance with a male to female ratio of 1.9:1. One of the reasons for this high male preponderance could be the gender-biased health services utilization pattern in a country like India where women most often fail to avail the services of formal healthcare system.The findings of present study seem to endorse the observations of Rhines (2013) 19 who while commenting on the epidemiology of tuberculosis found that in some regions, cases among men exceed those found in women by a ratio of 2:1 and attributed this to underreporting and latent variables undoubtedly bias the observed differences in prevalence between males and females to some degree while at the same time also found that there is also strong evidence that sex-based differences in TB prevalence represent real epidemiological differences.In present study, a total of 21.82% patients had a positive contact history. Contact history is a high risk for tuberculosis positivity with a prevalence ranging from 4.7%-26.8% among smear-negative patients 20 . The findings in present study were consistent with this observation.The symptomatic profile of the patients was dominated by presence of fever (93.64%) and cough (80%)two of the primary symptomatic conditions of tuberculosis.In consonance with the inclusion criteria, chest X-ray findings indicated consolidation in all the cases of which majority (63.64%) had bilateral consolidation.These findings are suggestive of active tuberculosis as suggested by Joshi et al. (2012) 21 , however, in yet another study; Joshi et al. (2007) 22 expressed doubts regarding the specificity of chest X-ray and were of the view that chest radiography for TB lacks specificity.Radiologic lesions suggestive of TB are also noticed in conditions such as histoplasmosis, tropical eosinophilia, pneumoconiosis, siderosis, sarcoidosis, ABPA, hypersensitivity pneumonitis and vasculitisError! Bookmark not defined.. Hence, although the radiological picture corroborated the clinical diagnosis yet they cannot be considered confirmatory.
In present study too, we carried out BAL AFB assessment and found that 36 (43.64%) cases were positive whereas L-J medium confirmed the diagnosis of pulmonary tuberculosis in 54.55% cases.BAL AFB assessment is one of the useful modalities for confirming sputum negative tuberculosis as pulmonary tuberculosis as indicated in previous studies 9, 10,12,17,23,24,25,26 and findings of present study confirmed that.In present study, BAL fluid PCR assessment was most sensitive and provided a positivity rate of 59.09%. BAL PCR is a highly sensitive tool for assessment of sputum negative tuberculosis.In a study by Wong et al. (1998) 27 it was found to be 97.2% sensitive. However, specificity of PCR is often questioned. In present study, specificity of all the techniques could not be assessed as there was no definitive false positive criteria and the focus of evaluation was only on sensitivity of the technique.
In present study, in a total of 45 (40.91%) cases tuberculosis could not be confirmed even after fiberoptic bronchscopy. There are many other conditions that mimick pulmonary tuberculosis. Sometimes conditions like, lung cancer can mimic the pulmonary tuberculosis which can also be diagnosed in fiberoptic bronchoscopy 14 18 . A treatment response to antibiotic regimen in these cases confirmed this etiology.
In present study, through the help of fiberoptic bronchoscopy, confirmed diagnosis could be established in 65 out of 110 (59.09%). Thus, showing that bronchoscopy is useful modality for diagnosis in suspect cases.In present study, all the cases were radiologically positive. As already stated, radiological findings are often confusing and most of the time have a high rate of false positivity. The clinical suspicion in these cases was based on chest radiography findings and has been the reason for positive findings in all the cases. Owing to radiological consolidation being the inclusion criteria its assessment was based only on laterality but did not yield a significant association with the outcome. Also, in present study, the resistance pattern studied showed that 17.46% of patients diagnosed to be tuberculosis had resistance to one or more tubercular drugs. It is an issue of concern and shows that sputum negativity can deteriorate the condition of patient and can result in acquired resistance.
The findings in present study highlighted the usefulness of fiberoptic bronchoscopy in sputum negative pulmonary tuberculosis cases. However, we focused on the diagnosis of pulmonary tuberculosis only and ruled out diagnosis and confirmation of other conditions.