Chronic Cough due to Gastroesophageal Reflux Disease: Failure to Resolve Despite Total/Near-Total Elimination of Esophageal Acid

doi:10.1378/chest.121.4.1132

Chest

Volume 121, Issue 4, April 2002, Pages 1132-1140

https://doi.org/10.1378/chest.121.4.1132 Get rights and content

Background

While medical therapy may fail to improve cough due to gastroesophageal reflux disease (GERD), it is not known if inadequate esophageal acid suppression is responsible.

Methods

In a prospective, before-and-after interventional trial, we assessed the effects of antireflux surgery in eight patients whose chronic coughs were due to GERD resistant to intensive medical therapy. All patients met a profile predicting that cough was likely due to GERD and had an initial positive 24-h esophageal pH monitoring study, and then underwent serial 24-h esophageal pH monitoring on gradually intensified medical therapy until the percentage of time that esophageal pH was < 4 was zero and there were no acid reflux events > 4 min. The effects of medical and surgical therapy on cough were assessed clinically by a visual analog scale (VAS) and the Adverse Cough Outcome Survey (ACOS).

Results

Before surgery (median, 23.7 days), patients still complained of cough, VAS score was 73.1 ± 6.1, and ACOS score was 15.0 ± 1.1. After surgery (median, 41.2 days and 1 year), cough improved in all, VAS score decreased to 19.1 ± 8.3 and 22.6 ± 8.1 (p = 0.001), respectively, and ACOS score decreased to 2.0 ± 1.3 and 3.6 ± 2.3, respectively (p = 0.002).

Conclusions

Antireflux surgery can improve chronic cough due to GERD resistant to intensive medical therapy. There is a clinical profile that can predict when GERD is the likely cause of cough. GERD cannot be excluded on clinical grounds as the potential cause of cough. The term acid reflux disease, when applied to chronic cough due to GERD, can be a misnomer.

Section snippets

Study Design

The study group consisted of consecutive patients referred for evaluation of chronic cough of unknown etiology that was initially resistant to intensive medical therapy for GERD. The eight patients are a highly selected subgroup of a larger cohort, who are part of an ongoing study assessing the long-term effects of antireflux surgery for chronic cough (ie, cough of at least 8 weeks' duration) due to GERD resistant to intensive medical therapy. Their coughs had resolved/improved following

Characteristics of Patients

From 1997 to 2000, 25 patients were prospectively evaluated according to a systematic, diagnostic protocol⁷ and were thought to have chronic cough due to GERD that had been resistant to intensive medical therapy. Twenty-one patients underwent only one operation by us, four patients underwent antireflux surgery before being reoperated on by us. This report focuses on a cohort of eight patients, because their results provide new insights into the pathogenesis and management of cough due to GERD.

Discussion

Four findings emerged that continue to expand our clinical and pathogenetic understanding of chronic cough due to GERD.

First, we have confirmed that antireflux surgery can improve chronic cough due to GERD that is resistant to intensive medical therapy. While others have come to a similar conclusion,^20,^21,²² the medical treatment regimens used in these previous studies were not as intensive as ours. For instance, Fitzgerald et al²⁰ prescribed dietary and lifestyle changes; cimetidine, 300 mg

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Cited by (108)

The Diagnosis and Time of Onset of Voice Disorders in Patients with Chronic Cough
2022, Journal of Voice
Citation Excerpt :
Patients who have CC may also present with globus sensation, dysphagia, dyspnea, and hoarseness.11 Although reflux is often considered the cause of the cough, patients may present with a series of failed reflux treatments prior to or after the cough.12 Following a visit to the patient's primary care physician, referrals to otolaryngologists, gastroenterologists, pulmonologists, or allergists are often made.13
Chronic cough is a complaint of up to 46% of patients referred to specialist clinics. Patients with cough often report hoarseness at the time of the cough diagnosis. When the cough fails to resolve with standard medications, referrals to other specialists including otolaryngologists are made. This is the first study to report the specific diagnosis and length of time it took to obtain a specific voice disorder diagnosis in patients with chronic cough.
Case Series
The charts of 105 patients referred to the Loma Linda Voice and Swallowing Center were reviewed. The first complaint of cough and/or hoarseness and the specific voice disorder diagnosis following otolaryngologic evaluation were identified. Voice disorders were divided into neurogenic or other/functional disorders and common comorbidities were identified. Statistical analysis between diagnostic groups, gender, and age were obtained.
The specific voice disorders in the cohort were identified. There was a high prevalence of neurogenic voice disorders (n = 85, 81%). There were significant relationships between chronic cough and the two most common neurogenic voice disorders, vocal fold paresis and vocal fold atrophy. The average length of time between complaint of hoarseness and the specific voice disorder diagnosis was 32.3 months. Most patients (86%) complained of voice problems after diagnosis of chronic cough. A significant association was found in prevalence of asthma (OR = 4.52, P = 0.02) and dyspnea (OR = 4.24, P = 0.02) in the cohort who presented first with voice complaints and later developed chronic cough.
There is a high incidence of neurogenic voice disorders accompanying patients with chronic cough. Understanding the relationship between chronic cough and hoarseness provides the clinician with specific diagnostic information in the treatment of both disorders.
A broader perspective: Functional symptoms beyond Neurology
2022, Epilepsy and Behavior Reports
Citation Excerpt :
There has been suggestion that patients with reflux of non-acid fluids or patients without typical GERD symptoms may have under-recognized reflux-induced cough. It has been reported in small studies that chronic cough improved greatly with reflux related surgery despite failure to demonstrate acidic esophageal pH prior to procedure [23]. However, without clear signs or symptoms of GERD, it is not generally recommended to trial acid suppression with antihistamine or proton-pump inhibitor (PPI) therapy [24].
Burden of Specialist-Diagnosed Chronic Cough in Adults
2020, Journal of Allergy and Clinical Immunology: In Practice
The burden of chronic cough (CC) in patients seeking specialist care is infrequently researched.
To describe patient characteristics and disease burden associated with specialist-diagnosed CC.
Using administrative pharmacy and medical data, we identified patients aged 18 to 85 years with CC diagnosed by pulmonologists, allergists, otolaryngologists, or gastroenterologists. Patients were stratified into 4 subgroups on the basis of the presence or absence of common respiratory diseases or gastroesophageal reflux disease (GERD). Clinical features and health care resource utilization (HCRU) in the baseline and outcome years were compared between the CC subgroups. The baseline factors associated with persistence of CC and a comparison of the CC cohort to a matched noncough cohort were also determined.
The 11,290 patients with specialist-diagnosed CC were aged about 61 years and 66.7% were females. The CC cohort experienced frequent GERD (44.1%), asthma (31.2%), obesity (24.3%), upper airway cough syndrome (20.4%), common cough complications (19.4%), and hospitalizations (9.8%). The patients with CC with both respiratory disease and GERD exhibited at baseline and follow-up the most common cough comorbidities, higher HCRU, specialist care, and dispensed respiratory and nonrespiratory medications including proton pump inhibitors, antitussives, psychotherapeutics, oral corticosteroids, and antibiotics compared with the other subgroups. A 40.6% persistence of CC occurred similarly between CC subgroups. In addition, patients with CC in the matched analysis experienced significantly more comorbidities, laboratory evaluations, HCRU, and antitussives than patients without cough.
Specialist-diagnosed CC was associated with considerable disease burden, particularly among those with both respiratory disease and GERD. In addition, CC burden was more pronounced than in matched patients without cough.
Chronic Cough Due to Gastroesophageal Reflux in Adults: CHEST Guideline and Expert Panel Report
2016, Chest
We updated the 2006 ACCP clinical practice guidelines for management of reflux-cough syndrome.
Two population, intervention, comparison, outcome (PICO) questions were addressed by systematic review: (1) Can therapy for gastroesophageal reflux improve or eliminate cough in adults with chronic and persistently troublesome cough? and (2) Are there minimal clinical criteria to guide practice in determining that chronic cough is likely to respond to therapy for gastroesophageal reflux?
We found no high-quality studies pertinent to either question. From available randomized controlled trials (RCTs) addressing question #1, we concluded that (1) there was a strong placebo effect for cough improvement; (2) studies including diet modification and weight loss had better cough outcomes; (3) although lifestyle modifications and weight reduction may be beneficial in suspected reflux-cough syndrome, proton pump inhibitors (PPIs) demonstrated no benefit when used in isolation; and (4) because of potential carryover effect, crossover studies using PPIs should be avoided. For question #2, we concluded from the available observational trials that (1) an algorithmic approach to management resolved chronic cough in 82% to 100% of instances; (2) cough variant asthma and upper airway cough syndrome (UACS) (previously referred to as postnasal drip syndrome) from rhinosinus conditions were the most commonly reported causes; and (3) the reported prevalence of reflux-cough syndrome varied widely.
The panelists (1) endorsed the use of a diagnostic/therapeutic algorithm addressing causes of common cough, including symptomatic reflux; (2) advised that although lifestyle modifications and weight reduction may be beneficial in suspected reflux-cough syndrome, PPIs demonstrated no benefit when used in isolation; and (3) suggested that physiological testing be reserved for refractory patients being considered for antireflux surgery or for those in whom there is strong clinical suspicion warranting diagnostic testing.
Gastro-esophageal reflux and chronic respiratory diseases
2015, Revue des Maladies Respiratoires
Le reflux gastro-œsophagien (RGO) est fréquemment associé aux pathologies respiratoires chroniques sans qu’un lien de causalité puisse être affirmé. Plusieurs éléments, d’ordre physiopathologique et expérimental, plaident en faveur du rôle pathologique du RGO dans les maladies respiratoires. À l’inverse, les affections respiratoires ainsi que les traitements tels que les bronchodilatateurs peuvent favoriser le RGO. Dans le bilan d’une toux ou d’un asthme sévère, il n’y a plus d’indication à rechercher de façon systématique un RGO ni à avoir toujours recours au test thérapeutique par inhibiteurs de la pompe à protons. La pH-impédancemétrie s’impose désormais comme l’examen diagnostique de référence permettant de mettre en évidence le reflux non acide sur lequel les inhibiteurs de la pompe à protons sont inefficaces. Des données récentes ont montré le rôle potentiel du RGO dans la fibrose pulmonaire idiopathique et dans la bronchiolite post-greffe pulmonaire, faisant discuter la place de la chirurgie. Des études utilisant notamment l’impédancemétrie couplée à la pHmétrie restent cependant nécessaires afin de mieux appréhender et prendre en charge l’association entre RGO et pathologies respiratoires chroniques.
Gastroesophageal reflux disease (GERD) frequently occurs in association with chronic respiratory diseases although the casual link is not always clear. Several pathophysiological and experimental factors are considered to support a role for GERD in respiratory disease. Conversely, respiratory diseases and bronchodilator treatment can themselves exacerbate GERD. When cough or severe asthma is being investigated, GERD does not need to be systematically looked for and a therapeutic test with proton pump inhibitors is not always recommended. pH impedance monitoring is now the reference diagnostic tool to detect non acid reflux, a form of reflux for which proton pump inhibitor treatment is ineffective. Recent data have shown a potential role of GERD in idiopathic pulmonary fibrosis and bronchiolitis obliterans following lung transplantation, leading to discussions about the place of surgery in this context. However, studies using pH impedance monitoring are still needed to better understand and manage the association between GERD and chronic respiratory diseases.
Detecting laryngopharyngeal reflux in patients with upper airways symptoms: Symptoms, signs or salivary pepsin?
2015, Respiratory Medicine
Citation Excerpt :
Twenty-four hour oesophageal pH monitoring detects changes in pH associated with reflux however it is invasive and labour intensive, and simultaneous intraluminal impedance monitoring is required to detect episodes of weakly- or non-acidic reflux [13,14]. Studies in patients with persistent symptoms despite maximal acid suppressive therapy have established a positive symptom and temporal association between non-acid reflux episodes and symptoms such as chronic cough [15,16]. The presence of pepsin in the laryngopharynx has also been shown to correlate with reflux events [17] and has been found in the laryngeal epithelial mucosa of patients with reflux-attributed laryngeal disease [18,19].
Laryngopharyngeal reflux (LPR) can induce laryngeal hyper-responsiveness, a unifying feature underlying chronic cough and vocal cord dysfunction. The diagnosis of LPR currently relies on invasive oesophageal pH impedance testing. We compared symptoms, laryngeal signs and salivary pepsin as potential diagnostic methods for identifying LPR in patients with upper airway symptoms.
Symptoms were assessed using the Reflux Symptom Index (RSI) and signs of laryngeal inflammation quantified using the Reflux Finding Score (RFS) during laryngoscopy. Saliva samples were analysed for the presence of pepsin. A sub-group of patients with severe symptoms and signs of LPR were investigated with oesophageal pH monitoring and impedance study.
Seventy eight patients with chronic cough and/or suspected vocal cord dysfunction were recruited, mean (SD) age, 54.6 (15.6) years. The majority (87%) had significant symptoms of reflux (RSI > 13). There were clinical signs of LPR (RFS > 7) in 51% of cases. Pepsin was detected in the saliva of 63% of subjects and 78% of those with a high RFS. Salivary pepsin had a sensitivity of 78% and specificity of 53% for predicting a high RFS. There was a correlation between the RSI and RFS (r = 0.51, p < 0.001) and between the severity of laryngeal inflammation and the concentration of pepsin (r = 0.28, p = 0.01). All cases investigated with pH-impedance study had objective evidence of proximal reflux.
Salivary pepsin may be used as a screening adjunct to supplement the RFS in the clinical workup of patients with extra-oesophageal symptoms and upper respiratory tract presentations of reflux.

View all citing articles on Scopus

: Presented in part at the annual meeting of the American Thoracic Society, April 28, 1999, San Diego, CA.

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Chest

Clinical InvestigationsCOUGHChronic Cough due to Gastroesophageal Reflux Disease: Failure to Resolve Despite Total/Near-Total Elimination of Esophageal Acid

Background

Methods

Results

Conclusions

Section snippets

Study Design

Characteristics of Patients

Discussion

Chest

Chest

Am J Gastroenterol

Med Clin North Am

Am J Gastroenterol

Chest

Am J Gastroenterol

Lancet

Gastroenterology

Eosinophilic bronchitis is an important cause of chronic cough

Am J Respir Crit Care Med

Chronic cough with eosinophilic bronchitis: examination for variable airflow obstruction and response to corticosteroid

Clin Exp Allergy

Persistent acid secretion during omeprazole therapy: a study of gastric acid profiles in patients demonstrating failure of omeprazole therapy

Am J Gastroenterol

Chronic cough: the spectrum and frequency of causes, key components of the diagnostic evaluation and outcomes of specific therapy

Am Rev Respir Dis

Treatment of cough due to gastroesophageal reflux disease (GERD): a double-blind, randomized, placebo-controlled trial comparing diet and/or cisapride [abstract]

Am Rev Respir Crit Care Med

The impact of chronic cough on quality of life

Arch Intern Med

Upper gastrointestinal tract: technical aspects

When is esophagitis healed?

Dig Dis Sci

Clinical Investigations
COUGH
Chronic Cough due to Gastroesophageal Reflux Disease: Failure to Resolve Despite Total/Near-Total Elimination of Esophageal Acid