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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 10  |  Issue : 4  |  Page : 388-392

The diagnostic yield and safety of sputum induction in suspected pulmonary tuberculosis: The experience of a single tertiary care center in Saudi Arabia


1 College of Medicine, King Saud University for Health Sciences; King Abdullah International Medical Research Centre; Department of Medicine, Division of Pulmonary, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia
2 College of Medicine, King Saud University for Health Sciences; King Abdullah International Medical Research Centre;Department of Medicine, Internal Medicine Division, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia
3 College of Medicine, King Saud University for Health Sciences; King Abdullah International Medical Research Centre; Department of Medicine, Internal Medicine Division, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia
4 College of Medicine, King Saud University for Health Sciences; King Abdullah International Medical Research Centre, Riyadh, Saudi Arabia

Date of Submission02-Oct-2021
Date of Decision26-Oct-2021
Date of Acceptance10-Nov-2021
Date of Web Publication13-Dec-2021

Correspondence Address:
Hamdan Al-Jahdali
McGill University, Montreal, Canada; King Saud University for Health Sciences, Riyadh, Saudi Arabia; Division of Pulmonary, Sleep Disorders Center, King Abdulaziz Medical City, Riyadh
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmy.ijmy_203_21

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  Abstract 


Background: Sputum smear microscopy examination and culture for tuberculosis (TB) remain a fundamental tool of diagnosis but may be negative up to 50% case of active pulmonary TB. Bronchoscopy to obtain sputum is invasive and not readily available. Alternative methods of obtaining sputum specimens are crucial in suspected pulmonary TB cases who are unable to expectorate. In this context, it may be beneficial to stimulate sputum production by administering a mist of hypertonic saline produced by ultrasonic nebulization. The aims of the study are to describe the experience of a tertiary center in Saudi Arabia with sputum induction (SI) for the investigation of patients suspected to have sputum scare TB. Methods: A retrospective cohort study was performed. All patients suspected of sputum scare TB and investigated with SI were included. Standard descriptive statistics were used. Categorical data presented as frequency were compared using the Chi square test. Continuous data presented as mean ± standard deviation were compared using Student's t test. Sensitivity, specificity, and predictive values were calculated. Results: Of 252 patients with suspected TB who underwent SI, 78 (31%) were ultimately diagnosed to have TB. Culture of induced sputum confirmed the diagnosis of TB in 44 (56.4%) of these patients. However, the diagnosis of TB would have been missed in 13.5% of the cohort if no further investigations were done. The incidence of complications was low. No patients required hospitalization or specialist intervention. Conclusions: SI is safe well tolerated and inexpensive. It may reduce the need for bronchoscopy in patients with suspected sputum scare TB. However, around 20% of TB can be missed by SI unless further investigations are performed. Hence, patients suspected to have sputum scare TB in whom the risk of bronchoscopy is high, a clinical decision on the appropriateness of empirical therapy is often required.

Keywords: Bronchoscopy, diagnosis, sputum induction, sputum-scarce respiratory disease, tuberculosis


How to cite this article:
Khan MA, Rajendram R, Al-Harbi A, Al-Ghamdi M, Masuadi E, Obaidi M, Al-Jahdali H. The diagnostic yield and safety of sputum induction in suspected pulmonary tuberculosis: The experience of a single tertiary care center in Saudi Arabia. Int J Mycobacteriol 2021;10:388-92

How to cite this URL:
Khan MA, Rajendram R, Al-Harbi A, Al-Ghamdi M, Masuadi E, Obaidi M, Al-Jahdali H. The diagnostic yield and safety of sputum induction in suspected pulmonary tuberculosis: The experience of a single tertiary care center in Saudi Arabia. Int J Mycobacteriol [serial online] 2021 [cited 2022 Jan 23];10:388-92. Available from: https://www.ijmyco.org/text.asp?2021/10/4/388/332360




  Introduction Top


Tuberculosis (TB) remains a major public health concern worldwide. In Saudi Arabia, the prevalence of TB ranges from 8.5% in the central region up to 38% in Makkah and the surrounding area.[1]

Active pulmonary TB is the main cause of tuberculous infections, and a prompt and accurate diagnosis is the key to successful outcome. The standard diagnostic approach to pulmonary TB requires sputum microscopy for acid-fast bacilli (AFB) and sputum culture. However, the overall clinical sensitivity is 22%–80% and the positive predictive value of mycobacteria is more than 95% depending on the burden of TB, number of sputum samples, the method of AFB stain used, and the experience of laboratory technicians.[2],[3]

The diagnostic yield can be further increased if bronchial wash, imaging, nucleic acid amplifications tests, and histological examination of biopsy specimens are also performed.[4],[5]

Besides adverse outcomes for individual patients; delays in the diagnosis of pulmonary TB hinder public health initiatives to control the spread of TB.[6],[7] Yet, the isolation of TB remains challenging in patients who are unable to expectorate sufficient sputum for microbiological assessments. In this cohort, treatment decisions are delayed, and hospitalization may be prolonged.[8] It is in this context that sputum induction (SI) may be extremely beneficial.

SI is a simple, safe, and tolerable procedure that uses ultrasonic nebulization to produce a mist of hypertonic saline droplets that, when inhaled, stimulate sputum production.

The smaller droplets are deposited peripherally in the lung. It is suggested that the hypertonicity of the deposited saline draws interstitial fluid into the lower airways by osmosis. The hypertonic fluid also causes bronchial irritation and this stimulates bronchial secretions. After 10–20 min of nebulization, the fluid produced mobilizes the material in the lower airways. Repeated coughing can then help to move this material into trachea to facilitate expectoration.[9]

SI can facilitate the collection of sufficient sputum for microbial analysis in patients who are unable to expectorate. The sensitivity and specificity of SI are similar to those of invasive techniques such as bronchoscopy.[10],[11],[12] Furthermore, the sensitivity is higher than that of self-expectorated sputum, nasopharyngeal aspiration, and gastric lavage.[13] However, there are no previous data on the use of SI in Saudi Arabia.

Our institution is a large tertiary care hospital with over 1600 beds. It has been accredited by Joint Commission International for 2006. The hospital has well-established pulmonology services covered by 8 full time consultants. The pulmonology team work closely with specialists in infectious disease to manage patients with suspected TB.

The facilities available for the diagnosis of TB include bronchoscopy, nucleic acid amplifications tests, and equipment for obtaining histopathological specimens. The aim of this study was to describe the performance of SI for the diagnosis of TB in this setting.


  Methods Top


Ethical approval

This study was approved by the institutional review board of our center.

Study design

This retrospective cohort study was conducted at a tertiary center in Riyadh. Saudi Arabia.

Participants

The electronic medical records of all adult patients (over 18 years old) with suspected TB for whom SI was performed between March 2012 and October 2019 were reviewed. Other indications for SI (e.g., suspected Pneumocystis jirovecii infection or malignancy) were excluded.

The SI program at our institution was started in 2012 to facilitate the timely diagnoses of those patients with suspected TB whom were not producing sufficient sputum for microbial analysis. The validated technique used for SI at our institution has been described previously.[9]

SI was considered for all inpatients and outpatients suspected to have TB but was unable to spontaneously expectorate sufficient sputum for microbial analysis. SI was also considered when logistical issues delayed scheduling of invasive diagnostic procedures (e.g. bronchoscopy) for patients with no or scanty sputum specimens.

Contraindications to SI included uncontrolled asthma or chronic obstructive pulmonary disease, active hemoptysis, recent eye surgery, unstable angina or arrhythmias, and patients already on antituberculous therapy were excluded from the study.

All patients were reviewed by consultant-level physicians before the procedure. Written informed consent for SI was obtained from all patients. SI was performed in negative pressure room within the bronchoscopy suite by expert respiratory therapist taking all infection control precautions appropriate for airborne diseases. SI was performed using an ultrasonic nebulizer (DeVilbiss Ultraneb 99; Sunrise Medical, Somerset, PA, USA) to administer a total of 70–90 ml of 3% hypertonic saline through a Venturi nebulizer mask for 15 min. Sputum was collected any time the patient had the urge to cough or at the end of nebulization.

Data collection

Besides standard demographics, comorbidities, and the results of imaging and the microbial analysis of induced sputum, the data collected included that required to determine the final diagnosis for each patient.

The findings on imaging (i.e. chest X-ray and computed tomography of the chest) were considered suspicious for TB if cavitary lung lesions, pleural effusions, nonresolving pulmonary infiltrate, lymphadenopathy, or tree in bud appearance were present.

Study outcomes

The final diagnosis was based on culture of TB, the presence of caseating granuloma in tissue biopsy or clinical presentation and improvement in the patient's condition after antituberculous therapy.

Statistical analysis

Continuous data are presented as mean and standard deviation and were compared using t-tests or analysis of variance. Categorical data are presented as frequency and percentage and were compared using the Chi-squared test. Sensitivity, specificity, and predictive values were calculated. All statistical analyses were performed using IBM SPSS Statistics for Windows, Version 26.0 (IBM Corp, Armonk, New York, USA).


  Results Top


Demographics

This cohort included 252 patients (mean age 54 years ± SD 19.8 years; male 53%). [Table 1] provides information about the cohort's demographic and clinical characteristics. Only two patients were infected with the human immunodeficiency virus (HIV). However, as the prevalence of HIV is low in Saudi Arabia, the vast majority were not screened for this.
Table 1: Patients' demographics and characteristics

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Comorbidities

Three-quarters of the cohort (189 patients; 75%) had comorbidities that are risk factors for TB [Table 2]. However, while the incidence of asthma was significantly higher in those with a final diagnosis of TB (P = 0.048) and a history of contact with TB did not quite achieve statistical significance (P = 0.08), the incidence of the other risk factors did not differ between the patients with and without TB.
Table 2: Risk factors for tuberculosis and the final diagnosis

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Yield of investigations for tuberculosis performed on induced sputum

On culture of induced sputum, 44 patients (17.5%) were diagnosed with TB. Yet, AFB was only detected in the induced sputum of 26 patients (10.3%). Although not done on all specimens, TB polymerase chain reaction (PCR) was positive in 16 patients (6.3%). As shown in [Table 3], the diagnostic yield increased to 78 (32%) if other investigations were performed (e.g. bronchoscopy, biopsies). An atypical mycobacterium was identified in a small number of patients (6; 2%). Thus, culture of induced sputum for TB was falsely negative in 34 of the 78 patients (43.5%) with a final diagnosis of TB based on clinical or tissue biopsy.
Table 3: Final diagnosis of tuberculosis with results of microscopy for acid-fast bacilli, culture and polymerase chain reaction

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The sensitivity, specificity, and predictive values of the investigations for TB performed on induced sputum are presented in [Table 4]. While the specificity of investigations performed on induced sputum approaches 100%, their sensitivity is poor. The sensitivity of microscopy of induced sputum for AFB was only 30%.
Table 4: The sensitivity, specificity, and predictive values of investigations for tuberculosis performed on induced sputum

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Complications of sputum induction

As is shown in [Table 1], 245 patients (97.2%) underwent SI without any complications. A small number 7 (2.8%) experienced recognized complications (bronchospasm and chest discomfort) but none needed hospital admission or specialist input. Only one procedure was abandoned due to bronchospasm.


  Discussion Top


In the 21st century, the diagnosis of sputum-scare TB remains a significant clinical conundrum. The standard diagnostic approach to pulmonary TB requires analysis of sputum. Thus, the use of ultrasonic nebulization to induce sputum in this cohort is appealing. An adequate sample can be obtained from 93% to 97% of patients with SI.[9],[11],[14],[15]

Culture of induced sputum confirmed the diagnosis of TB in 17.5% of the present cohort. No further investigations were required for this subgroup. Thus, SI can expedite the diagnosis of TB in select patients producing little or no sputum. Furthermore, the present study confirms that SI is a safe procedure with a very low risk of complications (<3%). For contextualization, although the risk of mortality from fiberoptic bronchoscopy is very low (0%–0.1%), rates of complications of up to 11% have been reported.[16]

Thus, the authors recommend that the potential benefits of developing a SI service should be considered in centers where the management of smear-negative cases currently relies upon the index of clinical suspicion, X-ray findings, and tuberculin testing.

However, SI is not a panacea. While the specificity was nearly 100%, the sensitivity of investigations performed on induced sputum (i.e., AFB, PCR, and culture) for the diagnosis of pulmonary TB was poor [Table 4]. The positive predictive values of staining a smear for AFB, PCR, and culture of SI were very high. Yet, as the negative likelihood ratios (LR−) are in the range 0.5–1.0, a negative result only slightly decreases the risk of TB.[2] Thus, the negative LR of AFB, PCR, culture [Table 4] suggests that the discriminatory value of a negative result from SI is poor.

Our observations are consistent with previous studies which report that the yield of sputum smear positivity varies between 26% and 74%.[14],[15] The relative yield of SI is higher for those patients who have nonproductive cough compared to previously smear-negative sputum cases.[15]

In the present study, of the 78 patients ultimately diagnosed with TB, culture of induced sputum for TB was falsely negative in 34 (43.5%). Thus, the diagnosis of TB would have been missed in 13.5% of the present cohort if no further investigations were performed. Therefore, if AFB, PCR, and culture are negative in induced sputum, TB should not be excluded.

Furthermore, in the present study, the discriminatory value of traditional risk factors for TB was poor. In view of these observations, the authors strongly recommend that further investigations should be considered if analyses of induced sputum are negative.

Nonetheless, the present study and others demonstrate that SI can increase the yield in the diagnosis of smear-negative pulmonary TB.[17] A role for SI in pleural TB is well established even in the absence of lung parenchymal changes.[18] In addition, SI can also facilitate the identification of the microbial cause of community-acquired pneumonia.[18],[19] The present study also identified a significant number atypical mycobacteria and other organisms in patients who were finally diagnosed with pneumonia.

McWilliams et al.[20] even showed that the yield of SI was superior to that of bronchoalveolar lavage (96.3% vs. 51.9%) and was three times cheaper.[20] SI has several other advantages over bronchoscopy. It is less invasive, safer, better tolerated and is less time consuming to perform. Furthermore, SI does not require fasting and has no age restriction. Moreover, nurses and respiratory technicians can perform this procedure successfully with minimal additional training. However, contamination of induced sputum with saliva is major concern. This can be decreased by blowing the nose, wearing nose clips or by washing the mouth.

Although the present study reports the findings of only one tertiary center, patients are referred to KAMC from other centers throughout Saudi Arabia. Thus, the large sequential sample of all patients with suspected TB who underwent SI at KAMC is likely to be representative of the whole Saudi population.

In the present study, SI was performed by experienced respiratory therapists. This provides good internal validity. However, while this does limit external validity somewhat, technicians and nurses can successfully perform SI after minimal additional training. Thus, this study provides a proof of concept.


  Conclusions Top


Induction of sputum for microbial analysis is a low-cost, safe intervention that is well tolerated and can be performed in the outpatient setting. The need for invasive investigations (e.g. bronchoscopy) in patients with suspected sputum-scare TB may be reduced by SI. However, around 20% of cases of TB may be missed by SI alone. Hence, further investigations must be considered if analysis of induced sputum is negative. In settings where bronchoscopy is not available or is not appropriate, SI may increase the diagnostic yield for TB and other mycobacterial infections.

Ethical clearance

This study was approved by the institutional review board of our center. IRBC/0143/20.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

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



 

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