Peptest for diagnosing gastro‑oesophageal reflux

CE marking

The Peptest is classified as an in‑vitro diagnostic medical device, general classification. The manufacturer, RD Biomed, received a CE mark for the Peptest in January 2011.

Description

The Peptest is a non‑invasive, single‑use, in‑vitro diagnostic medical device for detecting pepsin in saliva or sputum. Samples are collected by patients at home in sample tubes, which contain citric acid as a preservative, and can be posted to RD Biomed's laboratories for analysis or processed locally if suitable equipment is available (see costs section for details of test components).

The Peptest is a lateral flow device that contains 2 types of unique proprietary monoclonal antibodies against pepsin, on a nitrocellulose membrane in a plastic case. One antibody is tagged with a colorimetric marker and becomes soluble on application of a test sample. The other antibody is immobilised onto the nitrocellulose membrane, at the test line. Any pepsin in the sample is bound at the test line by the 2 antibodies, and a coloured line is seen through the viewing window in the plastic case.

If the sample is processed locally, a bench‑top vortex mixer and micro‑centrifuge are needed. The sample is centrifuged to remove any insoluble material and mixed with a migration buffer. This diluted sample is then applied to the sample well of the Peptest device. Any pepsin in the sample is bound at the test line by the 2 antibodies and, after 5 to 15 minutes, a coloured line becomes visible through the viewing window in the plastic case, giving a qualitative result. The test line is visible if Pepsin is present at a concentration of 16 ng/ml or more.

A quantitative test result can be obtained by analysing the intensity of the test line using an electronic lateral flow reader. There is currently no consensus in the literature around the concentration of pepsin in saliva that is clinically relevant, and so the value of a quantitative result in guiding clinical management is unclear. The level of pepsin can be quantified if it is present at a concentration of 25 ng/ml or more.

Intended use

The Peptest is designed for use where diagnosing GORD using a saliva sample or laryngopharyngeal reflux using a sputum sample would be advantageous, and where other diagnostic tests are not available, not easily accessed, or not appropriate for a specific patient.

Setting and intended user

The Peptest can be used in primary or secondary care. Samples can be posted to RD Biomed for analysis or processed locally where the necessary laboratory equipment is available. People can also buy the Peptest directly from RD Biomed but this use is outside of the scope of this briefing,

Reflux levels may vary over the course of a day. The manufacturer recommends that 3 samples are taken over 1–2 days to confirm diagnosis.

If the samples are being processed locally, such as in a hospital laboratory, a vortex mixer and a bench‑top centrifuge (and staff trained in their use) must be available. For quantitative analysis of the test results, an electronic lateral flow device reader is also needed. Samples sent to RD Biomed's laboratory by GPs or hospital doctors are processed, tested and quantified, and a report is sent to the patient and doctor.

Current NHS options

NICE guidance on dyspepsia makes recommendations on the diagnosis, management and treatment of GORD. The aims are to control symptoms, heal oesophagitis and prevent recurrent oesophagitis or other complications.

The guideline recommends referral for endoscopy if there are any red‑flag symptoms, which include:

Endoscopy is used to view the oesophagus and take biopsies. The oesophagus is examined for any oesophageal mucosal breaks, which are used to grade any oesophagitis. Oesophageal mucosal breaks are clearly demarcated areas of slough or erythema along the mucosa of the oesophagus.

If a person has GORD but no red‑flag symptoms, no confirmatory tests are done. Treatment is based on advice on lifestyle changes and a medication review, because some drugs such as non‑steroidal anti‑inflammatories can cause GORD. If the symptoms remain uncontrolled then proton pump inhibitors may be offered to control gastric acid secretion. If this is successful, then a step‑down approach is used to lower the dose or return to self‑care. A test for Helicobacter pylori is also offered at this stage in the patient pathway. If symptoms continue despite proton pump inhibitor treatment, further investigations may be necessary.

The British Society for Gastroenterology Guidelines for Oesophageal Manometry and pH Monitoring (Bodger and Trudgill 2006) state that flexible endoscopy or contrast radiology (such as barium swallow) should be used for people with suspected oesophageal symptoms, and if these tests are not conclusive then oesophageal manometry should be considered. Oesophageal manometry is used to evaluate dysphagia, and to diagnose primary oesophageal motility disorders (achalasia and diffuse oesophageal spasm). Manometry is carried out via a naso‑gastric tube and assesses how well the lower oesophageal sphincter is working by measuring pressure levels inside the sphincter muscle. Oesophageal pH monitoring is also done using a naso‑gastric tube over 24 hours. Manometry can rule out oesophageal motility disorders and pH monitoring can confirm acid reflux.

Oesophageal pH monitoring may be used to investigate:

During this procedure, pH electrodes for ambulatory oesophageal 24‑hour pH monitoring are placed in the oesophagus, and the patient wears a data recorder to record symptomatic episodes of reflux. Data can be analysed for any correlation of decreased oesophageal pH with episodes of reflux.

In general, manometry and oesophageal pH monitoring are relatively uncommon investigations which tend to be done only in specialist gastroenterology settings.

These symptoms are non‑specific and there is no reference test for such 'extra‑oesophageal reflux'. If GORD is suspected in chronic cough, patients can be treated in the same way as for typical presentations (Irwin, 2006).

GORD also occurs in children. However the NICE guideline on gastro-oesophageal reflux (GOR) in children highlights the difference between GOR, which is a normal physiological process associated with eating, and GORD, for which medical attention should be sought. The guideline describes the further investigations needed if GOR is present with 'red flags' and recommendations for treating symptomatic GORD that is causing distress or pain. Although GORD in children and adolescents often arises in similar ways to GORD in adults, premature babies and children with complex and severe neuro‑disabilities are at increased risk of GORD.

In children, an oesophageal pH study (or combined oesophageal pH and impedance monitoring if available) should be considered. This can be used to confirm the GORD diagnosis where there is:

In these less common presentations, a definitive rather than symptomatic diagnosis is needed.

Recognising GORD in infants, children and young people with a severe neuro‑disability who have limited ability to communicate presents a particular challenge.

NICE is not aware of other CE‑marked devices that have a similar function to the Peptest.

Costs of near‑patient or local testing

A kit of 10 Peptest devices with associated equipment and consumables costs £170. Each kit includes:

A kit of 50 Peptest devices with sufficient consumables costs £500.

Additional items are available from the manufacturer:

The lateral flow device reader is under warranty for 12 months and has an expected lifetime of 3–5 years depending on the level of use. A reference device is provided with each reader that allows for calibration every 250 readings. The manufacturer is planning to make an annual service contract available for the lateral flow device reader, but the planned costs are currently not available. RD Biomed provides full training in the use of the reader, free of charge.

Samples may be processed locally (both a vortex mixer and a centrifuge are needed) or by RD Biomed at its central laboratory.

Costs of performing tests at a central laboratory

For Peptest analyses conducted at RD Biomed's laboratory, 2 samples cost £41.66 and 3 samples cost £60. This price includes sample tubes, instructions, and postage and packaging. The samples are tested before the results are quantified and results sent back to the doctor. As the level of pepsin in saliva varies between people and over the course of the day, the manufacturer recommends that 3 saliva samples are collected over the course of 1–2 days.

Likely place in therapy

In most cases, GORD is diagnosed through patient‑reported symptoms alone without any tests being done. Further investigation is needed only if the patient has dysphagia (an inability to swallow), or if medication and lifestyle changes have not improved symptoms. The Peptest would therefore not be used on all patients who present with GORD symptoms, but could be used when a non‑invasive diagnosis of reflux is needed. For example, a positive Peptest result after the failure of first‑line treatment may confirm a diagnosis of GORD, without needing further invasive diagnostic tests such as endoscopy. Peptest could also be used as an additional test in patients with ear, nose and throat symptoms where GORD is suspected. It could be used in patients with atypical symptoms that have not responded to lifestyle changes or treatment with proton pump inhibitors.

The manufacturer's instructions for use state that test results should be evaluated in conjunction with other clinical data available.