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Table of Contents

Reviewed August 2, 2004

Daniel A.
Culver, DO

Mani S.
Kavuru, MD

Department of
Pulmonary & Critical
Care Medicine

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Cough is a symptom that is experienced by all people at one time or another. In otherwise healthy individuals, self-limited cough may occur as part of local irritation due to a viral rhinitis or respiratory infection. Chronic or persistent cough, with a duration greater than 8 weeks, is a very common presenting symptom in outpatient clinical practice. Although chronic cough is usually not caused by a life-threatening disorder, the frequency of this complaint as a cause for a visit to the physician as well as the patient and family's distress and concern about an underlying cause makes chronic cough an important problem.

Because cough is a symptom that is a common pathway for a variety of diverse conditions and because there are no reliable objective monitoring tools for cough, the management of cough is quite variable by physicians. A number of studies suggest that, in addition to a history and physical examination, a systematic diagnostic approach including a chest radiograph (CXR), spirometry, bronchoprovocation study in a pulmonary laboratory, sinus imaging, and esophageal pH monitoring will yield a specific diagnosis in the vast majority of patients (> 95%) with chronic cough.¹ However, a common situation that clinicians face is the presence of a cough of unclear cause in the setting of a normal CXR and normal spirometry. Whether these patients should undergo a trial of empiric therapy (either sequential or concurrent) or an aggressive and targeted diagnostic evaluation is often unclear. In clinical practice, it is likely that both these approaches are used in conjunction. It is worthwhile to keep in mind that, for a symptom such as cough, simply excluding certain serious causes may go a long way to reassure the patient as well as the clinician and allow a period of observation.

An optimal, cost-effective approach to the management of chronic cough remains controversial. Since chronic cough is rarely progressive, often self-limited, and due to a benign cause in the majority of cases, we recommend a stepwise approach employing empiric therapy targeted at the most common diagnoses, without extensive diagnostic testing (Figure 1).

Definition/
Pathophysiology

Prevalence

Signs and
Symptoms

Etiology

Diagnosis

Treatment

References

Cough is an important physiologic defense mechanism, a protective reflex to augment the mucociliary clearance of airway secretions. The cough reflex is characterized by the generation of high intrathoracic pressures against a closed glottis, followed by forceful expulsion of air and secretions on glottic opening. Intrathoracic pressures of up to 300 mm Hg and expiratory velocities approaching 500 miles per hour may be achieved.¹ Although a typical cough has a characteristic acoustic profile and is universally recognizable, there is no clinical test that can document and confirm the presence of cough. This has hampered progress in the study of cough.

The symptom of cough involves a reflex arc originating in peripheral cough receptors. Cough receptors are most concentrated in the epithelium of the upper and lower respiratory tracts, but are also located in the external auditory meatus, tympanic membrane, esophagus, stomach, pericardium, and diaphragm. Receptors are predominantly of two types. Irritant receptors are stimulated by noxious fumes or liquids, while mechanical receptors are activated by physical triggers such as touch, displacement, or stretch. Signals from the receptors are carried by vagal afferents to a medullary cough center, which then triggers cough activation via efferents mediated by the vagal, phrenic, and spinal motor nerves. Cough modulation is partly under the control of cortical stimuli. Therefore, irritation anywhere along the reflex arc by a disease process can cause cough.

It is useful to classify cough as acute (less than some arbitrary duration of 3 to 8 weeks) or chronic/persistent. Most of the attention by clinicians is devoted to the chronic/persistent variety, since this is the variety that usually prompts patients to seek medical care. Acute cough usually has a self-limited origin, usually viral rhinitis, which does not require specific therapy.

Most patients seek medical attention because of complications of cough, either psychologic or physical. The most common complications include a feeling that something is wrong (98%), exhaustion (57%), feeling self-conscious (55%), insomnia (45%), lifestyle change (45%), musculoskeletal pain (45%), hoarseness (43%), excessive perspiration (42%), and urinary incontinence (39%).¹ A host of other physiologic symptoms occur occasionally, due to the high intrathoracic and intra-abdominal pressures achieved. The most common of these include cough syncope, cardiac dysrhythmias, headache, subconjuctival hemorrhage, inguinal herniation, and gastroesophageal reflux.

It is important to elicit which specific cough-related symptoms are bothersome for the patient, as a guide to the pace and scope of diagnostic testing.

Acute Cough:

Acute cough has been defined as one with a duration of less than 3 weeks at presentation.¹ In general, acute cough usually results from respiratory infections, of which the common cold is the most frequent. Some authors have proposed a category of subacute cough, with a duration of 3 to 8 weeks. Postinfectious cough due to irritation of cough receptors accounts for the bulk of these cases. However, there are no case series assessing the relative frequency of causes in either the acute or subacute categories.

The most common causes of acute cough are listed in Table 1. In the presence of a compatible history and examination, further diagnostic testing is not usually necessary. The mainstay of treatment includes nonspecific antitussive therapy. Under-recognized causes for acute or subacute cough include pertussis and mycoplasma infection. Rarely, life-threatening illness may present primarily with acute cough. Examples include pulmonary embolus, cardiogenic pulmonary edema, and pneumonia.

Chronic Cough:

The causes of chronic cough in the general population have not been systematically assessed. Chronic bronchitis, usually due to cigarette smoking, is thought to be the most common overall cause of chronic cough, but most smokers with cough do not seek medical attention. There have been at least nine systematic studies in adults of cough etiology. In the absence of use of angiotensin-converting enzyme (ACE) inhibitors, the pathogenic triad of postnasal drainage (or drip) (PND), asthma, and gastroesophageal reflux (GERD) have consistently accounted for 90% to 100% of cases among immunocompetent adults.^1,3-6 The same triad is relevant in children and the elderly.^1,3 In 18% to 62% of patients, there are two causes, and in up to 42% there are three.^4,5,7 Of note, all these studies involved patients referred to pulmonologists or cough clinics; however, it is likely that a similar spectrum of causes accounts for the majority of patients seen by primary care providers.

Postnasal Drainage
PND is the single most common cause of chronic cough, accounting for 8% to 87% of cases, either exclusively or in combination with other factors.^1,6 Categories of PND include seasonal allergic rhinitis, perennial allergic rhinitis, perennial nonallergic rhinitis, vasomotor rhinitis, chronic sinusitis, postinfectious rhinitis, rhinitis medicamentosa, and pregnancy-associated rhinitis. Associated symptoms include rhinorrhea, nasal congestion, a sensation of drainage or tickle in the oropharynx, and throat clearing. The pathogenesis of cough involves stimulation of afferent receptors in the upper airway rather than runoff of secretions into the lower airway.

Physical examination may reveal nasal congestion or discharge, nasal mucosal bogginess, mucous in the oropharynx, or a "cobblestoning" appearance of the oropharyngeal mucosa. The examination findings are nonspecific, however, and may be present in any of the other major causes of chronic cough. Although most patients will have at least one symptom or sign, PND can be clinically silent up to 20% of the time.⁶ Ultimately, PND is a syndrome without a clear definition, and its role in chronic cough is best proven by a response to therapy.

The presence of copious sputum is associated with an increased likelihood of chronic sinusitis, but neither the clinical examination nor historical features reliably differentiate it from other causes of PND.^3,7 Among patients with chronic cough, up to 38% have some radiologic sinus abnormality.⁸ Thus, a finding of sinus mucosal thickening on radiographs has only a 29% to 81% positive predictive value for predicting that chronic sinusitis is responsible for cough.^1,8 However, one report documented a 100% positive predictive value for the finding of air-fluid levels on four-view sinus radiographs.⁸

Asthma
In most series, asthma is the second most common cause of chronic cough in adults, present in 14% to 55% of cases.^9,10 Historical features of wheezing, chest tightness, or exertional dyspnea in response to triggers such as strong odors or perfumes, cold air, or allergens should suggest the diagnosis. Cough is a feature of nearly all cases of asthma. A subset of asthmatic patients complain exclusively of cough, so-called cough-variant asthma. Cough-variant or cough-predominant asthma accounts for 6.5% to 57% of all asthmatic patients.¹ Many of these patients later develop typical asthma symptoms.¹¹

The presence of asthma does not reliably implicate it as the cause of chronic cough. The positive predictive value of a suggestive history is only 56%.¹¹ A 20% decrement in FEV₁ after methacholine inhalation, while indicative of bronchial hyperresponsiveness, may have a positive predictive value as low as 74% for diagnosing the cause of cough.⁶ Even detailed analysis of methacholine challenge test characteristics cannot reliably enhance specificity. Thus, proof that asthma is the inciting factor in chronic cough requires demonstration of a response to directed therapy.

Gastroesophageal Reflux
GERD accounts for up to 40% of chronic cough.⁹ It has been recognized as a contributor to cough with increasing frequency in observational studies; in recent investigations it has often surpassed other causes of chronic cough.^1,9 Recognition, diagnosis, and treatment of GERD are among the most challenging of all cough considerations, with a number of as-yet unclarified issues.

In a minority of cases, reflux-mediated irritation of laryngeal receptors or episodic microaspiration underlie GERD-induced cough. However, cough is usually attributable to a reflex loop involving vagal afferents in the distal esophagus, and proximal reflux is unnecessary in the pathogenesis.¹² Symptomatic heartburn or water brash occurs in only a minority (25% to 50%) of affected individuals.¹ Other historical features, such as exacerbation at night, in the supine position, or after eating, do not reliably differentiate GERD-induced cough from other causes.⁹

GERD frequently accompanies other causes of cough; up to 80% of asthmatic patients have abnormal 24-hour pH probe findings.¹ Recurrent elevations in abdominal pressure may contribute to this phenomenon. A self-perpetuating cycle of cough and GERD may ensue, making identification and treatment of GERD crucial in the integrated management of all cough syndromes.

Ambulatory 24-hour esophageal pH monitoring is the most reliable test for GERD. It is important to include a temporal symptom log when conducting pH monitoring in order to document the causality of reflux events vis-à-vis cough. Frequently, close examination will reveal that cough preceded the reflux event. A temporal symptom log may also substantiate GERD as a cause for cough even when pH probe scores lie within the "normal" range. The finding of an abnormal pH probe carries a 90% to 100% sensitivity, but the positive predictive value may be as low as 35% when using therapeutic response as a gold standard.^1,13

Angiotensin-converting Enzyme Inhibitors
Angiotensin-converting enzyme normally degrades proinflammatory mediators such as bradykinins and substance P. Inhibition of this action lowers the threshold for cough sensitivity. Cough due to ACE inhibitors is a class effect and has been documented with all ACE inhibitors in use; switching to another agent will not ameliorate the symptoms. Usually, cough onset occurs within 1 week of starting the medication, but may occur as late as 1 year. Approximately 10% to 20% of patients develop cough, but in many it is not bothersome. Interestingly, asthmatic patients are not at increased risk. Cough resolution may be delayed for up to 1 month after discontinuation of the drug. Angiotensin II receptor blockers do not cause cough and therefore are useful therapeutic alternatives.

Eosinophilic Bronchitis
Recently, a subset of patients with increased sputum eosinophils in the absence of demonstrable bronchial hyperresponsiveness has been recognized. The frequency of this syndrome has been reported to be as high as 13%.¹⁴ Diagnosis is usually made by demonstration of induced sputum eosinophilia (> 3%).

Chronic Bronchitis
Chronic bronchitis (CB) is characterized by a productive cough on most days for 3 months in 2 consecutive years. It may be caused by irritant-induced inflammation or by the need to mobilize excessive secretions. Although CB is a frequent cause of cough in the population, it is present in only 5% of those seeking medical attention for cough.^4,5 Cigarette smoke is the most common irritant, but occupational exposures or inflammatory bowel disease may also trigger this syndrome. The mainstay of treatment is avoidance of the offending agents. Particular vigilance is warranted when there is a change in the character of the cough or sputum, since this may be the presenting feature of a superimposed bronchogenic carcinoma.

Bronchiectasis
The prevalence of bronchiectasis has decreased considerably, and it is now present in less than 4% of individuals with chronic cough.^4,5,7 It develops when chronic inflammation or infection leads to progressive airway damage. Bronchi become dilated, with chronic inflammatory cells in the mucosa and mucous pooling within the airway lumen. Most patients produce large volumes of sputum, eg, 2 tbsp/day. However, a history of excessive mucoid sputum production is not specific for the diagnosis, and a few individuals have "dry bronchiectasis," in which there is no sputum production. CXR may reveal evidence of tubular or cystic structures representing dilated, mucus-filled bronchi. Computed tomography of the chest is a more sensitive tool for evaluating patients with equivocal or negative CXR findings. In published series, nearly all patients diagnosed with bronchiectasis as the cause of chronic cough had suggestive CXR findings.^4,5

Postinfectious Cough
Airway inflammation may follow any respiratory tract infection; up to one quarter of such infections may be complicated by persistent cough.¹ Increased cough receptor sensitivity and/or temporary bronchial hyperresponsiveness, probably related to epithelial damage, likely account for this phenomenon. By definition, postinfectious cough eventually resolves, but its duration may be prolonged. For this reason, 8 weeks is a more clinically useful working definition of chronic cough than 3 weeks. Postinfectious cough is usually caused by respiratory viruses, Mycoplasma species, Chlamydia pneumonia TWAR, or Bordatella pertussis. One investigation found a 21% incidence of pertussis in a group of patients with a cough duration of 2 weeks to 3 months.¹⁵

Cancer
Bronchogenic carcinoma is an infrequent cause of chronic cough (0% to 2%), although most patients with intrathoracic malignancies will develop cough at some point in the course of their disease. Cough receptors are more highly concentrated in the larger airways; thus, cough is more frequent in malignancies with a predilection for central airways, such as squamous cell and small cell cancers. A history of tobacco use should heighten clinical suspicion. Prospective trials of chronic cough have found a 100% negative predictive value for a normal or unchanged CXR, but the numbers in these studies were small.¹ However, in the presence of such a CXR, an unrevealing fiberoptic bronchoscopic examination essentially excludes the diagnosis.

Psychosomatic Cough
Psychosomatic cough is rare, especially in adults. It is a diagnosis of exclusion and should not be entertained until all other potential causes have been investigated, including therapeutic trials of adequate intensity and duration. There are no distinguishing historical features to reliably differentiate it from other causes.⁹ Habit cough is a syndrome of persistent, habitual throat clearing that may respond to biofeedback. In contrast, psychogenic cough usually implies an underlying psychiatric disorder. Most patients with psychogenic cough harbor an intractable fear of serious underlying medical disease.

Rare Causes of Chronic Cough:

• Interstitial lung disease (eg, idiopathic pulmonary fibrosis, sarcoidosis)
• Occult aspiration
• Pulmonary abscess
• Foreign body
• Occult congestive heart failure
• Occult pulmonary emboli
• Nasal polyps
• Disorders at any of the locations of cough receptors (external auditory canal, tracheobronchial tree, pleura, pericardium, diaphragm, esophagus, stomach)
  

DIAGNOSIS

The management of chronic cough typically involves some combination of simple screening studies (CXR and spirogram), additional specific diagnostic studies (methacholine provocation, sinus imaging, or a pH probe), and empiric therapy for the three most common entities (rhinitis, asthma, and GERD) (Figure 1, 2). Patients with chronic persistent cough in whom there are no specific clues by history and examination and who have a normal CXR and spirogram represent the common management dilemma for the clinician. A major decision involves the extent of specific diagnostic testing as opposed to trials of empiric therapy. There is no adequate guidance from randomized clinical trials to help the clinician choose between these two strategies. The approach is usually "negotiated" with the patient, partly based on the level of subjective distress and the level of exasperation felt by the patient as well as the clinician.

Pinpointing the cause of chronic cough is often difficult. Cough may be the sole manifestation of disorders such as asthma, GERD or PND, with a paucity of other historical features to suggest the correct diagnosis. Features of cough, such as timing, associated sputum production, and cough character (eg, brassy) are not helpful in distinguishing causes.⁹ A high proportion of patients have two or more responsible causes. Finally, there are no diagnostic tests with a sufficiently high positive predictive value to reliably implicate any condition as the cause of cough. Thus, diagnosis hinges on demonstration of a response to a specific therapy.

Evaluation and treatment using our algorithm (Figure 1, 2) assume that failure to remedy the cough using trials of empiric therapy will precipitate appropriate diagnostic testing. It is important to remember that treatment fails in a significant proportion of nonresponders due to inadequate intensity or duration of treatment. One study found that 14% of referred patients had been correctly diagnosed but treated with insufficient regimens.⁵ In these cases, diagnostic testing will facilitate appropriate narrowing and intensification of treatment. Since the overwhelming majority of patients will have PND, asthma, or GERD, it is crucial to assiduously investigate the roles of each prior to further investigations.

Common causes for diagnostic frustration include:

• Diagnostic testing suggestive of an underlying etiology does not ensure that cough is caused by that etiology. All tests used for evaluation of chronic cough have a poor positive predictive value.
• Eighteen percent to 62% of chronic coughs are due to two or more causes.
• Inadequate treatment regimens are a common reason for failure to alleviate symptoms.
• Historical features or cough characteristics should not be overrelied upon, since these are often misleading. The cause of cough may otherwise be clinically silent.
• Pressurized metered-dose inhalers may exacerbate cough-variant asthma.
• Eradication of related symptoms (heartburn, nasal congestion) does not ensure that an underlying cause is sufficiently treated.

Although most investigators recommend CXR early in the evaluation of chronic cough, only 4% to 11% of nonsmokers have culpable abnormalities.^4,5 The yield of fiberoptic bronchoscopy is similarly low, with only 4% of those with normal CXRs having endobronchial abnormalities. Even with a finding of endobronchial disease, the positive predictive value is only 50% to 89%.¹ In assessing for the presence of uncommon causes of chronic cough, chest CT has a relatively higher diagnostic yield and should be performed prior to cardiac tests in the absence of cardiac symptoms.

Postnasal Drainage
Initial therapy for most postnasal drainage syndromes should include an antihistamine-decongestant combination (Table 2). Older-generation antihistamines, such as dexbrompheniramine maleate or azatadine maleate, have been demonstrated to be superior to second-generation (nonsedating) drugs because of their additional anticholinergic activity.¹ If drowsiness is problematic, therapy may be initiated at bedtime, with escalation to BID dosing at a later time. Second-generation antihistamines are useful primarily in allergic rhinitis syndromes. The role of bacteria in perpetuating chronic sinusitis is controversial, and treatment regimens are not well defined. Except for chronic sinusitis, most patients will have a symptomatic response within 1 week.

Asthma
Cough-equivalent asthma is particularly challenging and response to therapy is not as predictable or certain as in typical asthma. Beta-agonist metered-dose inhalers (MDIs) are frequently utilized and maximal responses may be delayed for 6 to 8 weeks.^1,4 The addition of inhaled corticosteroids may be required to optimize therapy for most patients. Mast cell stabilizers, such as cromolyn sodium, may also be effective. A few patients may require oral corticosteroids for symptom control. Use of a pressurized MDI alone may aggravate cough, and we recommend a dry-powder device or the addition of a spacer.

The presence of bronchial hyperresponsiveness should be demonstrated by provocation testing or reliable history prior to the use of oral steroids and when bronchodilators alone are ineffective in the presence of high clinical suspicion. Caution is warranted when interpreting the results of empiric therapeutic success with asthma therapy-eosinophilic bronchitis and postinfectious cough may respond similarly. For this reason, we recommend an attempt to taper therapy in patients who have not undergone bronchoprovocation testing.

Gastroesophageal Reflux
Treatment of GERD should begin with maximal therapy. Avoidance of reflux-predisposing foods (fatty foods, chocolate, caffeine, alcohol), tobacco cessation, elevation of the head of the bed, and not eating within 2 to 3 hours prior to lying down are important lifestyle adaptations that may significantly diminish cough. Proton pump inhibitors should be used as the mainstay of medical therapy. We recommend commencement of treatment with twice-daily proton pump inhibitors, dosed just prior to the morning and evening meals; later, therapy may be de-escalated if proven effective. Onset of response may take up to 3 months to be manifest, with maximal effects of treatment delayed for up to 6 months.¹ Response rates of 70% to 100% have been reported when the end point is improvement in cough.¹ However, the true response rate is unknown, since there is no objective gold standard to prove GERD is the cause except for therapeutic response. The role of non-acid reflux in cough pathogenesis is also currently unknown, but probably accounts for a proportion of nonresponders.

Ambulatory pH monitoring should be performed when maximal therapy fails. Documentation of persistent symptomatic acid reflux should prompt consideration of esophageal fundoplication. The operative risk and morbidity of fundoplication have diminished considerably in recent years due to the expanding use of laparoscopy. Success rates approaching 85% may be expected for improvement of cough after surgical management.¹⁶

Eosinophilic Bronchitis
Inhaled corticosteroids (ICS) are usually effective, but a few patients will require a short course of oral steroid therapy.¹⁴ A 2- to 3-week course of prednisone at 30 mg/d is sufficient; a few patients may require maintenance therapy, generally with ICS.

Chronic Bronchitis
Smoking cessation markedly reduces symptoms in more than 50% of patients within 1 month. Cough frequency as well as sputum production are most effectively decreased by ipratropium MDI (2 puffs QID). Mucolytics are not helpful, and a symptomatic benefit of ICS has not been demonstrated.

Bronchiectasis
The excessive secretions of bronchiectasis mandate persistent cough for mobilization. Complete cough suppression is neither achievable nor desirable. Chest physiotherapy techniques are useful for patients who produce large volumes of sputum and during disease flares. Flares may also require prolonged antibiotic courses. A beneficial role in treating chronic cough for beta-agonists or theophylline has not been demonstrated.

Postinfectious Cough
Postinfectious cough usually responds to treatment that is analogous to asthma. Alternatively, ipratropium MDIs have proven efficacy. Ongoing pertussis or mycoplasma infections should be treated with appropriate antibiotic therapy (Table 1).

Evaluation of cough depends on a systematic evaluation of potential causes. A recent consensus statement from the American College of Chest Physicians¹ outlines a diagnostic and therapeutic protocol for chronic cough. This schema focuses on using diagnostic tests to systematically exclude potential etiologies for cough. The basis for this approach lies in a consideration of the anatomic location of all cough receptors. A particular strength of this algorithm is that it forces clinicians to maintain a comprehensive differential diagnostic perspective during evaluation. Ultimately, however, delineation of the underlying cause (or causes) can be accomplished only by demonstrating a response to therapy. For this reason, we believe that systematic empiricism is an acceptable alternative approach, with serial assessments of treatment response.

Return to Medicine Index

1. Irwin RS, Boulet LP, Cloutier MM, et al. Managing cough as a defense mechanism and a symptom. A consensus panel report of the American College of Chest Physicians. Chest. 1998;114(suppl 2):133S-181S. Also at www.chestjournal.org/cgi/reprint/114/2/133S.pdf. Accessed February 28, 2002.

2. Cherry DK, Burt CW, Woodwell DA. National ambulatory medical care survey: 1999 results. www.cdc.gov/nchs/about/major/ahcd/officevisitcharts.htm. Accessed February 28, 2002.

3. Smyrnios NA, Irwin RS, Curley FJ, French CL. From a prospective study of chronic cough: diagnostic and therapeutic aspects in older adults. Arch Intern Med. 1998;158:1222-1228.

4. Irwin RS, Curley FJ, French CL. Chronic cough. The spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy. Am Rev Respir Dis. 1990;141:640-647.

5. Irwin RS, Corrao WM, Pratter MR. Chronic persistent cough in the adult: the spectrum and frequency of causes and successful outcome of specific therapy. Am Rev Respir Dis. 1981;123:413-417.

6. Pratter MR, Bartter T, Akers S, DuBois J. An algorithmic approach to chronic cough. Ann Intern Med. 1993;119:977-983.

7. Smyrnios NA, Irwin RS, Curley FJ. Chronic cough with a history of excessive sputum production. The spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy. Chest. 1995;108:991-997.

8. Pratter MR, Bartter T, Lotano R. The role of sinus imaging in the treatment of chronic cough in adults. Chest. 1999;116:1287-1291.

9. Mello CJ, Irwin RS, Curley FJ. Predictive values of the character, timing, and complications of chronic cough in diagnosing its cause. Arch Intern Med. 1996;156:997-1003.

10. Poe RH, Harder RV, Israel RH, Kallay MC. Chronic persistent cough. Experience in diagnosis and outcome using an anatomic diagnostic protocol. Chest. 1989;95:723-728.

11. McGarvey LP, Heaney LG, Lawson JT, et al. Evaluation and outcome of patients with chronic non-productive cough using a comprehensive diagnostic protocol. Thorax. 1998;53:738-743.

12. Ing AJ, Ngu MC, Breslin AB. Pathogenesis of chronic persistent cough associated with gastroesophageal reflux. Am J Respir Crit Care Med. 1994;149:160-167.

13. Ours TM, Kavuru MS, Schilz RJ, Richter JE. A prospective evaluation of esophageal testing and a double-blind, randomized study of omeprazole in a diagnostic and therapeutic algorithm for chronic cough. Am J Gastroenterol. 1999;94:3131-3138.

14. Brightling CE, Ward R, Goh KL, Wardlaw AJ, Pavord ID. Eosinophilic bronchitis is an important cause of chronic cough. Am J Respir Crit Care Med. 1999;160:406-410.

15. Wright SW, Edwards KM, Decker MD, Zeldin MH. Pertussis infection in adults with persistent cough. JAMA. 1995;273:1044-1046.

16. Allen CJ, Anvari M. Gastro-oesophageal reflux related cough and its response to laparoscopic fundoplication. Thorax. 1998;53:963-968.
    

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