Note from the National Guideline Clearinghouse (NGC): For full context of the major recommendations stated below, please see the National Guideline Clearinghouse (NGC) summary of the American College of Chest Physician's guideline An Empiric Integrative Approach to the Management of Cough: ACCP Evidence-based Clinical Practice Guidelines, which utilizes a comprehensive approach, including algorithms for the clinician to follow in evaluating and treating the patient with acute, subacute, and chronic cough.
Definitions for the level of evidence, strength of recommendation, and net benefit follow the "Major Recommendations."
- In patients with chronic cough due to gastroesophageal reflux disease (GERD), the term acid reflux disease, unless it can be definitively shown to apply, should be replaced by the more general term reflux disease so as not to mislead the clinicians into thinking that all patients with cough due to GERD should improve with acid-suppression therapy. Level of evidence, expert opinion; benefit, substantial; grade of recommendation, E/A
- In patients with chronic cough who also complain of typical and frequent gastrointestinal (GI) complaints such as daily heartburn and regurgitation, especially when the findings of chest-imaging studies and/or clinical syndrome are consistent with an aspiration syndrome, the diagnostic evaluation should always include GERD as a possible cause. Level of evidence, low; benefit, substantial; grade of recommendation, B
- Patients with chronic cough who have GI symptoms that are consistent with GERD or who fit the clinical profile described in the table below, titled "Clinical Profile That Predicts That Chronic Cough Is Likely Due to GERD", should be considered to have a high likelihood of having GERD and should be prescribed antireflux treatment even when they have no GI symptoms. Level of evidence, low; benefit, substantial; grade of recommendation, B
Clinical Profile That Predicts That Chronic Cough Is Likely Due to GERD
Chronic cough
Not exposed to environmental irritants nor a present smoker
Not taking an angiotensin-converting enzyme inhibitor
Chest radiograph is normal or shows nothing more than stable, inconsequential scarring
Symptomatic asthma has been ruled out:
- Cough has not improved with asthma therapy, or
- Methacholine inhalation challenge is negative
Upper airway cough syndrome due to rhinosinus diseases has been ruled out:
- First-generation H1-antagonist has been used and cough failed to improve, and
- "Silent" sinusitis has been ruled out
Nonasthmatic eosinophilic bronchitis has been ruled out:
- Properly performed sputum studies are negative, or
- Cough has not improved with inhaled/systemic corticosteroids
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- In patients with chronic cough, it should not be assumed that GERD has been definitively ruled out as a cause of cough simply because there is a history of antireflux surgery. Level of evidence, low; benefit, substantial; grade of recommendation, B
- In patients with chronic cough, while tests that link GERD with cough suggest a potential cause-effect relationship, a definitive diagnosis of cough due to GERD requires that cough nearly or completely disappear with antireflux treatment. Level of evidence, low; benefit, substantial; grade of recommendation, B
- In patients with chronic cough being evaluated for GERD, the 24-hour esophageal pH-monitoring test is the most sensitive and specific test; however, it is recommended that the test results be interpreted as normal only when conventional indexes for acid reflux are within the normal range and no reflux-induced coughs appear during the monitoring study. Level of evidence, low; benefit, substantial; grade of recommendation, B
- In patients with cough who are undergoing 24-hour monitoring, a low percentage of coughs associated with (or induced by) reflux does not exclude a diagnosis of cough due to GERD. Level of evidence, low; benefit, substantial; grade of recommendation, B
- In patients with cough due to GERD, the degree of abnormality noted in the esophageal pH-monitoring variables, such as the frequency and duration of reflux events, does not directly correlate with the severity of the patients' cough. Level of evidence, low; benefit, substantial; grade of recommendation, B
- In diagnosing nonacid GERD as the cause of cough, barium esophagography may be the only available test to reveal gastroesophageal reflux of potential pathologic significance in this setting (see the discussion regarding esophageal impedance monitoring in the "Laboratory Testing" section of the original guideline document). When this is the case, barium esophagography is the test of choice to reveal gastroesophageal reflux of potential pathologic significance. Level of evidence, low; benefit, substantial; grade of recommendation, B
- In patients with cough due to GERD, normal esophagoscopy findings do not rule out GERD as the cause of cough. Level of evidence, low; benefit, substantial; grade of recommendation, B
- For patients fitting the clinical profile for cough due to GERD, it is recommended that treatment be initially started in lieu of testing. Level of evidence, low; benefit, substantial; grade of recommendation, B
- For patients fitting the clinical profile for cough due to GERD, the performance of 24-hour esophageal pH monitoring is recommended on therapy when cough does not improve or resolve to assist in determining whether the therapy needs to be intensified or if medical therapy has failed. Level of evidence, low; benefit, substantial; grade of recommendation, B
- For patients with chronic cough, the following tests are not routinely recommended to link cough with GERD: (a) assessing for lipid-laden macrophages in bronchoalveolar lavage (BAL) fluid and induced sputum, because this test has not been studied in patients with chronic cough and because a positive test result is not specific for aspiration; (b) exhaled nitric oxide measurements, because they do not appear to be helpful in diagnosing cough due to GERD; (c) a Bernstein test, because a negative Bernstein test result cannot be used to exclude the diagnosis of cough due to GERD; and (d) inhaled tussigenic challenges with capsaicin, because they are not specific for coughs due to GERD and because the test result can be positive in patients with GERD without cough. Level of evidence, low; benefit, conflicting; grade of recommendation, I
- In patients who meet the clinical profile predicting that silent GERD is the likely cause of chronic cough or in patients with chronic cough who also have prominent upper GI symptoms consistent with GERD, an empiric trial of medical antireflux therapy is recommended. Level of evidence, low; benefit, substantial; grade of recommendation, B
- For treating the majority of patients with chronic cough due to GERD, the following medical therapies are recommended: (a) dietary and lifestyle modifications; (b) acid suppression therapy; and (c) the addition of prokinetic therapy either initially or if there is no response to the first two therapies. The response to these therapies should be assessed within 1 to 3 months. Level of evidence, expert opinion; benefit, substantial; grade of recommendation, E/A
- In patients in which this empiric treatment fails, it cannot be assumed that GERD has been ruled out as a cause of chronic cough; rather, the objective investigation for GERD is then recommended because the empiric therapy may not have been intensive enough or medical therapy may have failed. Level of evidence, expert opinion; benefit, substantial; grade of recommendation, E/A
- In some patients, cough due to GERD will favorably respond to acid suppression therapy alone; proton pump inhibition may be effective when H2-antagonism has been ineffective; prokinetic therapy and diet, when added to proton pump inhibition, may be effective when proton pump inhibition alone has been ineffective. Level of evidence, low; benefit, substantial; grade of recommendation, B
- Patients requiring an intensive medical treatment regimen should be treated with the following: (a) antireflux diet that includes no >45 g of fat in 24 hours and no coffee, tea, soda, chocolate, mints, citrus products, including tomatoes, or alcohol, no smoking, and limiting vigorous exercise that will increase intraabdominal pressure; (b) acid suppression with a proton pump inhibitor (PPI); (c) prokinetic therapy; and (d) efforts to mitigate the influences of comorbid diseases such as obstructive sleep apnea or therapy for comorbid conditions (e.g., nitrates, progesterone, and calcium channel blockers) whenever possible. Level of evidence, expert opinion; benefit, substantial; grade of recommendation, E/A
- In patients with chronic cough due to GERD that has failed to improve with the most maximal medical therapy, which includes an intensive antireflux diet and lifestyle modification, maximum acid suppression, and prokinetic therapy, and the rest of the spectrum of treatment options in the table below, titled "Spectrum of Options for Treating Chronic Cough Due to GERD, " cough may only improve or be eliminated with antireflux surgery. Level of evidence, low; benefit, substantial; grade of recommendation, B
- In patients who meet the following criteria, antireflux surgery is the recommended treatment: (a) findings of a 24-hour esophageal pH-monitoring study before treatment is positive, as defined above; (b) patients fit the clinical profile suggesting that GERD is the likely cause of their cough (see table above, titled "Clinical Profile That Predicts That Chronic Cough Is Likely Due to GERD"); (c) cough has not improved after a minimum of 3 months of intensive therapy (see table below, titled "Spectrum of Options for Treating Chronic Cough Due to GERD "), and serial esophageal pH-monitoring studies or other objective studies (e.g., barium esophagography, esophagoscopy, and gastric-emptying study with solids) performed while the patient receives therapy show that intensive medical therapy has failed to control the reflux disease and that GERD is still the likely cause of cough; and (d) patients express the opinion that their persisting cough does not allow them a satisfactory quality of life. Level of evidence, expert opinion; benefit, substantial; grade of recommendation, E/A
Spectrum of Options for Treating Chronic Cough Due to GERD
| Treatment |
Options |
| Antireflux medical therapy |
Diet
Lifestyle changes
- Smoking
- Exercising
- Consuming alcohol
Medications
- Acid suppression
- Prokinetic
Address risk factors
- Treat other causes of cough
- Treat comorbid conditions
- Obesity
- Obstructive sleep apnea
Consider changing medications for comorbid conditions
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| Antireflux surgery |
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Definitions:
Quality of the Evidence
Good = evidence is based on good randomized controlled trials (RCTs) or meta-analyses
Fair = evidence is based on other controlled trials or RCTs with minor flaws
Low = evidence is based on nonrandomized, case-control, or other observational studies
Expert opinion = evidence is based on the consensus of the carefully selected panel of experts in the topic field. There are no studies that meet the criteria for inclusion in the literature review.
Strength of Recommendations
A = strong recommendation
B = moderate recommendation
C = weak recommendation
D = negative recommendation
I = no recommendation possible (inconclusive)
E/A = strong recommendation based on expert opinion only
E/B = moderate recommendation based on expert opinion only
E/C = weak recommendation based on expert opinion only
E/D = negative recommendation based on expert opinion only
Net Benefit
Substantial = There is evidence of benefit that clearly exceeds the minimum clinically significant benefit and evidence of little harm
Intermediate = Clear evidence of benefit but with some evidence of harms, with a net benefit between that defined for "substantial" and "small/weak"
Small/weak = There is evidence of a benefit that may not clearly exceed the minimum clinically significant benefit, or there is evidence of harms that substantially reduce (but do not eliminate) the benefit such that it may not clearly exceed the minimum clinically significant benefit
None = Evidence shows that either there is no benefit or the benefits equal the harms
Conflicting = Evidence is inconsistent with regard to benefits and/or harms such that the net benefit is uncertain
Negative = Expected harms exceed the expected benefits to the population
Table: Relationship of Strength of the Recommendations Scale to Quality of Evidence and Net Benefits
| |
Net Benefit |
| Quality of Evidence |
Substantial |
Intermediate |
Small/Weak |
None |
Conflicting |
Negative |
| Good |
A |
A |
B |
D |
I |
D |
| Fair |
A |
B |
C |
D |
I |
D |
| Low |
B |
B |
C |
I |
I |
D |
| Expert Opinion |
E/A |
E/B |
E/C |
I |
I |
E/D |
