Title of the Project

A randomized controlled trial comparing three percent versus seven percent hypertonic saline for sputum induction in adults with presumptive pulmonary tuberculosis, in terms of sputum adequacy and safety at a tertiary care hospital.

Introduction 

Presumptive tuberculosis refers to individuals who present with symptoms suggestive of tuberculosis infection such as cough for more than two weeks, fever, night sweats, weight loss, or radiological findings indicating pulmonary tuberculosis. Diagnosis of pulmonary tuberculosis primarily depends on sputum examination, but many patients are unable to produce sputum spontaneously. Sputum induction using hypertonic saline is a widely accepted method to obtain diagnostic samples in such cases. The optimal saline concentration to achieve maximum sputum yield and quality is not well established. This study will compare the diagnostic yield, sputum quality, and safety of three percent and seven percent hypertonic saline used for sputum induction in presumptive pulmonary tuberculosis patients. The findings may improve diagnostic accuracy and enhance early detection of tuberculosis in patients who cannot produce sputum spontaneously.

Aim

To compare three percent and seven percent hypertonic saline for sputum induction in patients with presumptive pulmonary tuberculosis.

Objectives

Primary Objective:
To compare sputum adequacy and volume between the two saline concentrations using Bartlett score and sample volume.

Secondary Objectives:
To compare the incidence of side effects such as cough, dyspnea, desaturation, and throat irritation during sputum induction.
To assess patient comfort using a one to ten visual analogue scale.
To compare the tuberculosis detection rate by GeneXpert or acid fast bacilli smear positivity between the two groups.

Hypothesis

Null Hypothesis:
There is no significant difference in sputum yield or quality between three percent and seven percent hypertonic saline used for sputum induction in presumptive pulmonary tuberculosis patients.

Alternative Hypothesis:
Seven percent hypertonic saline produces higher sputum yield and better sample quality than three percent hypertonic saline in presumptive pulmonary tuberculosis patients.

Materials and Methods

Type of study: Randomized controlled trial
Study duration: Twelve months
Methodology: Conducted according to CONSORT guidelines

Bias Control

Randomization will be performed using a computer generated list with one to one allocation ratio.
Allocation concealment will be achieved using sequentially numbered, sealed, opaque envelopes.
Outcome assessors, patients, and laboratory personnel will be blinded to the saline concentration.
A uniform sputum induction protocol will be followed for all participants.
All study staff will be trained to ensure standardized procedures.
Sputum adequacy will be evaluated using predefined cytological criteria by blinded personnel.
An intention to treat analysis will be applied.
Missing data will be handled appropriately and all outcomes will be reported as per CONSORT guidelines.

Inclusion Criteria

1. Adults aged eighteen years and above.
2. Patients with clinical or radiological features suggestive of pulmonary tuberculosis as per World Health Organization criteria such as cough for more than two weeks, fever, weight loss, night sweats, and chest radiograph showing infiltrates, cavitation, fibrotic changes, miliary pattern, or mediastinal lymphadenopathy.
3. Patients unable to produce sputum spontaneously.
4. Patients willing to participate and providing written informed consent for sputum induction.

Exclusion Criteria

1. Oxygen saturation less than ninety two percent on room air.
2. Known or uncontrolled asthma or chronic obstructive pulmonary disease.
3. Active hemoptysis at the time of enrolment.

Sample Size

Based on a previous study showing tuberculosis detection rates of twenty five percent and thirty seven point five percent in the two groups, assuming a two sided alpha error of zero point zero five and eighty percent power, the calculated sample size is four hundred and thirty participants, with two hundred and fifteen in each group.
As the study is time bound, all eligible patients during the study period of twelve months will be included. The expected minimum sample size is one hundred and twenty patients.

Statistical Methods

Data will be analysed using IBM SPSS version twenty six. Continuous variables will be expressed as mean with standard deviation or median with interquartile range. Categorical variables will be expressed as frequencies and percentages.
Group comparisons will use independent t test or Mann Whitney U test as appropriate. Chi square test will be used for categorical outcomes. Paired t test and ANOVA will be used for within group and subgroup analyses.

Primary Outcome Measure

Adequacy and volume of sputum sample based on National Tuberculosis Elimination Program criteria defined as at least two millilitres with adequate cellular content as per Bartlett score.

Time Point:
after the procedure.

Secondary Outcome Measures

1. Tuberculosis detection rate by GeneXpert or acid fast bacilli smear positivity.
   Time Point: After processing of the induced sputum sample.
2. Incidence of adverse events such as cough, wheeze, breathlessness, desaturation, or throat irritation.
   Time Point: Before sputum induction, continuously during the procedure, and immediately after completion.
3. Patient comfort score measured by visual analogue scale.
   Time Point: Immediately after the procedure.

Project Timeline

Total study duration: Twelve months from ethics approval.
Last patient enrolment: Eleven months from ethics approval.
Data analysis: One month after last enrolment.
Final report preparation: One additional month.

Conclusion 

This study compares three percent and seven percent hypertonic saline for sputum induction in adults with presumptive pulmonary tuberculosis. It aims to determine the concentration that provides better sputum adequacy, higher diagnostic yield, and acceptable safety. The findings will support improved diagnostic strategies and standardization of sputum induction protocols in tertiary care settings.