Non-invasive Diagnosis of Acid Reflux Cough

Diagnose Acid Reflux Cough in Respiratory Illnesses including:

• Chronic Cough
• Asthma
• Chronic Obstructive Pulmonary Disease

Aeriflux™ is a new non-invasive test which measures acid in the airway and associates acid levels with specific cough episodes to create a profile. The profile of results is interpreted using simple guidelines. Aeriflux is critical for management of Severe Asthma and COPD where the margin for experimentation is low, urgency is high, and multiple disease mechanisms cloud therapeutic outcomes.

Test Description

Non-invasive measurement of Airway Lining Fluid pH by collection and analysis of Exhaled Breath

Test Protocol

• Patient collects six breath samples during symptomatic episodes and two when asymptomatic using simple take-home collection kit
• Samples are sent to Respiratory Research central lab for pH analysis in provided prepaid shipping carton
• Laboratory measures the acid in the breath and faxes the results direct to physician

Test Characteristics

89% Positive Predictive Value for Acid Reflux Cough

Physician Information | Patient Information

Get the Data. Know the Answer. Aeriflux.

• Overview
• Detailed comparison of current diagnostic options
• Algorithm for Use of Aeriflux
• Summary of Clinical Trials
• Selected Case Studies
• Billing and Reimbursement
• FDA Status of the RTube™ and Aeriflux family of products
• Links to Clinical Trial Report and related publications

Overview

Aeriflux provides straightforward answers to a previously difficult to diagnose condition: Acid Reflux induced Cough. At least half the time that a subspecialist physician (Pulmonologist, Allergist, ENT) thinks that Acid reflux could be causing cough, the patients don't get better with a trial or Proton pump inhibition (in other words, the prescribed three-month therapeutic trial fails). By using Aeriflux, long and expensive therapeutic trials with proton pump inhibition can be avoided, for you will know if the patient is likely to respond or not in advance. Furthermore, therapeutic trials of PPI are commonly confounded by placebo effect or spontaneous resolution of the symptoms, in which case one never knows that the medication can be stopped. Importantly, in patients with various respiratory diseases (asthma, COPD and others) symptomatic worsening can occur because of allergy exposure or bacterial or viral infection, making a concurrent therapeutic trial of PPI therapy seem to fail.

Aeriflux provides objective data that overcome these obstacles. The dominant mechanism by which acid reflux causes cough is through aspiration of small amounts of stomach acid. When cough is associated with breath acidification, acid reflux cough is confidently diagnosed, and a positive response to proton pump inhibition can be expected.

Detailed comparison of current diagnostic options

Acid reflux is a cause of transient exhaled breath acidification. Although exhaled breath pH can be low in inflammatory diseases, the transience and intermittent nature of reflux-associated low exhaled breath pH values are clearly seen within the Aeriflux profiles, allowing specificity to be high for acid reflux. Measurement of multi-sample exhaled breath pH profiles, involving samples collected immediately subsequent to a coughing episode, may be used appropriately to direct therapy to those patients with cough who have relevant acid reflux. This method is the only diagnstic which specifically targets acid in the airway, as opposed to acid in the lower esophagus.

Algorithm for Use of Aeriflux

Use of Aeriflux for evaluation of acid reflux as a contributor to respiratory symptoms in severe asthma.

Severe Asthma is a symptom- and lung function-based categorization appropriately used for a minority of patients with asthma. This categorization is not based on underlying pathophysiologic mechanisms. This group consumes the majority of the financial resources devoted to asthma. The diagnosis of severe asthma is difficult because there are so many contributors and mimics to the condition. Patients with Severe Asthma are by their nature harder to manage with standard therapeutic modalities such as inhaled steroids, and more likely to have confounding diagnoses such as vocal cord dysfunction or acid reflux.

At what point acid reflux enters into your thinking depends on the patient and your practice style. Here are some considerations:

1. Acid reflux occurs in over 50% of severe asthmatics, and is a likely contributor to respiratory symptoms in most of these.
2. Esophageal symptoms such as heartburn are often not present. It takes very little acid in the airway to cause cough. But this mild acid reflux may well be insufficient to cause any heartburn.
3. Symptomatic gastroesophageal reflux disease (GERD) and heartburn may be present in some patients with asthma without being relevant to their respiratory symptoms.
4. It is necessary to identify who among the people with heartburn have acid reflux cough. Likewise it is necessary to distinguish who within the asthma population without GERD symptoms have acid reflux cough.
5. It is uncertain in any given patient what dosing of proton pump inhibitor or H2 antagonist is necessary to control acid reflux cough in any given patient.
6. Esophageal pH probes are located in the wrong place to identify airway acidification, trigger coughing on their own by physical stimuli, and importantly suffer from inappropriate interpretation. The airway is not the esophagus, and tiny amounts of acid reflux that are considered "normal" by esophageal pH probe guidelines can be highly relevant for the acid-intolerant airway.

Determining to what extent these confounding pathologic processes are contributing to the asthma symptomatology is difficult. As noted above, esophageal pH probes are not an appropriate diagnostic tool for acid reflux cough in most patients. Therapeutic trials of proton pump inhibition are commonly used instead. However, these trials suffer from the following limitations:

1. Require patient adherence/compliance to be accurate.
2. Entail insurance company payment hassles because of the need for twice daily high-dose PPI treatment to assure a sufficient therapeutic trial. This is rarely covered by insurance.
3. Provide little confidence that acid reflux is important.
   • If a patient does not get better, it may result from failure of adherence, a concomitant exacerbating factor (entering allergy season, infection with the common cold).
   • If a patient does get better, the improvement may result from placebo effect, or from decreasing concomitant factors, such as exiting allergy season.
4. Require up to 3 months to adequately complete the therapeutic trial.

Aeriflux overcomes these issues by providing objective evidence of acidification in the airway occurring in association with cough. Obtaining these diagnostic data requires no long-term medication, provides straightforward chemical evidence about whether acid reflux is important in this patient, and samples are readily collected in a day, with data available to the prescribing doctor within 3 - 4 days.

Placing Aeriflux into your diagnostic paradigm for severe asthma.

Aeriflux is used to identify the presence of acid in the airway that occurs in association with cough. Aeriflux consists of a series of 8 simple breath pH measurements, six of which are performed when the patient has been coughing within the previous 10 minutes, and two when they are cough-free for at least a half-hour. These samples are collected by the patient at home, at work or in the clinic, and can be performed over 1 day or as long as a month. It is as safe as playing a clarinet and simpler than blowing up a balloon.

If a patient has one or more breath samples that reveal acid in the airway concurrent with the presence of cough (especially when one or more non-coughing breath samples reveal no breath acidity), this is good evidence that acid reflux occurred with the cough, and likely triggered it. And this in turn predicts likelihood of response to Proton Pump Inhibition. With this evidence available, you will have objective data available to guide treatment, and this can convince those insurance companies to help your patient.

We recommend performing Aeriflux in all patients whom:

1. You suspect as having acid reflux cough.
2. Require chronic systemic corticosteroids.
3. Require high dose inhaled steroids for control.
4. Require immunosuppressive medication.
5. Are not responding to combined therapy of inhaled steroids and leukotriene antagonism.
6. Have been hospitalized or had emergency visits for asthma.
7. Have been intubated for asthma.
8. Have symptomatic GERD as well as asthma.

*Additionally, you may consider Aeriflux valuable in patients with exercise-induced asthma symptoms and patients with vocal cord dysfunction, both of which can be mimicked by acid reflux. You can also use Aeriflux in follow-up to determine if the dosing of acid blockade medication is sufficient.

Summary of Clinical Trials

Chronic cough is a common problem, frequently caused or exacerbated by acid reflux. We wished to determine if multi-sample exhaled breath condensate pH profiles can identify chronic cough patients likely to respond to proton pump inhibitor therapy. 59 subjects were recruited for this study. An additional 404 subjects were recruited for a separate study to determine the normative breath pH baselines for healthy subjects. We obtained multi-sample exhaled breath pH profiles in patients with chronic cough. These samples were timed to occur after coughing episodes. Exhaled breath pH was measured after gas standardization.

Healthy subjects rarely have any low EBC pH values. Patients with chronic cough who subsequently responded well to proton pump inhibition invariably had one or more of their cough episodes associated with EBC acidification. No patient who had normal exhaled breath condensate pH with each of their cough episodes reported a clinically relevant response to proton-pump inhibition. The Aeriflux Breath Test is shown to have a Positive Predictive Value of 89% for Acid Reflux Cough (PPI-resonsive cough).

The full results of both studies discussed above are currently pending publication and shall be made avaialable for download through this site.

Selected Case Studies

Each of the cases outlined below were obtained as part of the clinical trial described above.

Typical Aeriflux Profile: PPI Responder

• 9 y.o. boy with unresolved Chronic Cough for 6 months: not clinically allergic, normal spirometry
• Failed therapeutic trials with amoxicillin, azithromycin, prednisone, inhaled steroids, beta agonists, and montelukast
• Performed initial Aeriflux then initiated Omeprazole BID dosing
• Complete resolution of cough symptoms within 10 days

Initial Aeriflux Profile is POSITIVE with multiple low (<7.4) pH values with cough.

Aeriflux Profile: PPI Non-Responder

• 58 year old male with Chronic Cough: LPR-induced cough suspected
• Aeriflux performed and treatment with BID dosing of PPI initiated
• Follow up at 2½ months revealed no symptomatic improvement
• Aeriflux profile predicted failure of PPI therapy
• Normal airway pH indicated the absence of Airway Acid Stress

Initial Aeriflux Profile is NEGATIVE with all pH values normal.

Billing and Reimbursement

Aeriflux is billed as four codes:

• The initial supervised collection in the office/clinic may be billed under code 94250 "Exhaled Breath Conde" Expired gas collection, quantitative, single procedure (separate procedure)".
• The reamining 7 collections performed by the patient at home may be billed under code 94799 may be useful: "Unlisted pulmonary service or procedure"
• Additionally a trainig code may be used in conjunction with 94250 for patient training in the use of Aeriflux
• The pH assay is billed directly to the patient by Respiratory Research, Inc. under a Catetgory III code 0140T "Exhaled Breath Condensate pH"

The prescribing institution would stock the kits and keep them available to provide patients as needed. The laboratory service would be billed and managed completely independent of the prescribing institution and would involve only the patient and Respiratory Research, Inc.

FDA Regulatory Status of the RTube and Aeriflux family of products

RTube is registered with the United States Food and Drug Administration as a Class I device for the collection of expired gas. The proprietary gas-standardized pH assay, when performed by Respiratory Research, Inc., is considered a "home brew" assay. The RTube and gas-standardized pH assay, if used for the purpose of differentiating Acid Reflux-induced respiratory symptoms from airway inflammation, and used in accordance with the protocol for the RTube Breath Test, together comprise the Aeriflux diagnostic allowed for clinical use in the management of patients with respiratory disease.

Links to Clinical Trial Report and related publications

Manage Your Respiratory Disease With Aeriflux

• Aeriflux Diagnoses Acid Reflux Cough
• Costs of Untreated Acid Reflux Cough
• What do I need to know about Aeriflux?
• What will it cost me?
• Link to Detailed Patient Instructions

Aeriflux Diagnoses Acid Reflux Cough

• Over 12 million US Asthmatics, COPD patients, and Chronic Coughers seek health care annually
• 1/3 to ½ of these have Acid Reflux Cough, but current diagnostics are unable to identify these patients
• Initiation or continuation of standard anti-inflammatory treatments do not resolve their Acid Reflux Cough
• Acid control therapy with Proton Pump Inhibition (PPI) does does resolve Acid Reflux Cough
  • "Acid Reflux Cough" = "PPI Responsive Cough"
  • Most patients do not receive proper PPI therapy when needed
• Aeriflux directs the right therapy to the right patients

Costs of Untreated Acid Reflux Cough

• Degraded patient quality of life, lost productivity, increased ER visits, hospitalizations and complications
• Continuation of unneeded standard anti-inflammatory therapy costs $8,628 more per patient over 5 years
  • Standard anti-inflammatory therapy typically uses high-dose steroids, a leukotriene antagonist, and often fails
  • Proper acid control therapy combines PPI and low-dose steroid

What do I need to know about Aeriflux?

Aeriflux consists of 8 special breath collection tubes, known as RTubes. Each RTube is a disposable device through which the patient breathes for 5 minutes. While the patient breathes, the RTube condenses their breath into a liquid. After eight samples are collected (usually within a day or two), the patient simply mails them in a pre-paid mailer to one of our centralized laboratories which measures the acid in the breath with a highly validated patented process. Within 3 days, we will fax the results of the tests to the requesting prescriber, along with guidelines for interpretation. It is as simple as that.

From the patient's point of view, providing breath samples is very easy and completely safe. Within 10 minutes of a coughing episode, the patient begins breathing through the RTube collector for 5 minutes. They cap the collector tube, write their name, birthdate, and today's date and time on the RTube label, check off the box next to the word "Cough", and put the tube in their freezer. Six samples are collected in this manner. Additionally, if possible, two samples are collected during the day when the patient has not been coughing in the previous 30 minutes. They check off the box for "No Symtoms" on the RTube label for these two samples. After eight samples are collected (usually within a day or two), the patient places all the samples in the pre-labeled express shipping box, calls the supplied phone number for Fedex or UPS to pick up the box, and we take it from there.

What will it cost me?

The Aeriflux is a collection kit and a laboratory service. Your doctor will bill your insurance directly for the cost of the collection kit at the associated procedures done in his office under the normal terms of your current plan. Your deductible, out of pocket, and copay should all apply as with any other medical care you are currently receiving.

The laboratory service, however, will be billed directly to you independent of your doctor. Respiratory Research, Inc. will require a credit card authorization or enclosed check accompanying your samples in order to perform the laboratory analysis. Without completion of the laboratory analysis, no results can be provided your doctor and therefore no diagnosis can be made. Respiratory Research charges $160.00 for the assay service. This service will be billed to you under a category III CPT code 0140T "Exhaled Breath Condensate pH". You may on your own initiative run this through your insurer for reimbursement. However, Respiratory Research does not expect this code to be reimbursed by many insurers due to the "emerging technology" designation of this code.

Link to Detailed Patient Instructions