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Dry Cough: Presentation, Causes and Management Algorithm

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INTRODUCTION
Cough is a symptom that has been experienced by
every human and is an essential innate protective
mechanism that ensures the removal of mucus, noxious
substances, and infectious organisms from the larynx,
trachea, and large bronchi. Cough also minimizes the
effects of inhaled toxic materials. Impairment or
absence of coughing can be harmful or even fatal
in disease. Cough may also be a sign of disease outside
the respiratory system and a useful indicator for both
patient and physician for initiating diagnosis and
treatment of disease processes. When cough is persistent
and excessive, it can be harmful and deleterious and
may need to be suppressed.1
In the United States, cough is the most common
complaint for which patients seek medical attention and
the second most common reason for a general medical
consultation; patients with persistent cough constitute
about 10–38% of the chest specialist outpatient practice.
Epidemiologic surveys report that 11–18% of the
general population has a persistent cough, but it
is not known how much this cough is part of a “normal”
clearance process and how much reflects pathology.2
Cough is defined as a deep inspiration followed
by a strong expiration against a closed glottis, which
then opens with an expulsive flow of air, followed by
a restorative inspiration; these are the inspiratory,
compressive, expulsive (expiratory or explosive), and
recovery phases of cough.
Cough can be classified based upon the duration
of the cough; within each category are likely diagnostic
possibilities. Acute cough exists for less than 3 weeks
ABSTRACT
Cough is one of the most common symptoms of respiratory tract infections. A wide range of disease
processes may present with cough and definitive treatment depends on identifying the cause and
diagnosis. Specific treatment of the cause should control the cough, but this may not occur in all cases
and in a sizable proportion of patients, no associated cause can be found. This chapter reviews the
causes, presentation and management of dry cough.
and is most commonly due to an acute respiratory
tract infection. Other considerations include an
acute exacerbation of underlying chronic pulmonary
disease, pneumonia, and pulmonary embolism.
Cough that has been present longer than 3 weeks
is either subacute (3–8 weeks) or chronic (more than
8 weeks).
In this chapter we will discuss mechanism and
etiology of the dry cough, along with recent advances in
the field of cough, highlighting some of the diagnostic
and management challenges.
PHYSIOLOGY OF COUGH
In general, coughing is characterized by a reflex-
evoked modification of the normal breathing pattern.
However, coughing can also be initiated and suppressed
voluntarily. Stimulation of the peripheral sensory
nerves is the first step that drives resultant cough.
This is set off by the irritation of cough receptors that
exist not only in the epithelium of the upper and lower
respiratory tracts, but also those in the pericardium,
esophagus, diaphragm, and stomach.
Mechanical cough receptors are stimulated by
triggers such as touch or displacement. The receptors
in larynx and tracheobronchial tree respond to
both mechanical and chemical stimuli. The efferent
signals are carried from the cough center through the
vagus, phrenic, and spinal motor nerves to expiratory
musculature which results in the production of cough
(Flow chart 1). The cough reflex can be assessed by
various tussive agents such as citric acid, capsaicin and
low-chloride content solutions are used.3
AA Mahashur, R Banka
Dry Cough: Presentation, Causes and
Management Algorithm
76
CHAPTER
Each of us should strive “to rise above the routines of the daily ward round and to see in every patient an
opportunity not only to serve mankind in the best tradition of medical excellence, but to add to the store
of medical knowledge”
A McGehee Harvey
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CHAPTER 76 Dry Cough: Presentation, Causes and Management Algorithm
Flow chart 1 Pathophysiology of cough reex
In its simplest form, clinical cough is a reflex event
beginning with activation of vagal afferent sensory
nerves located in pulmonary and extrapulmonary
sites that project the “signal” centrally, where it
undergoes modulation, resulting in the generation of
the appropriate efferent motor response.
Although the anatomic and neurophysiologic
processes responsible for the initiation and regulation
of cough are complex, knowledge about the mechanism
of cough can help the clinician understand how and
why his/her patient coughs and provide rationale for a
targeted and systematic approach to treatment.
CAUSES OF DRY COUGH
Chronic cough can be caused by a myriad of different
respiratory or nonrespiratory conditions. The common
causes of chronic cough in an immunocompetent
nonsmoking adult with normal chest radiograph
are angiotensin-converting enzyme (ACE) inhibitor
medication, upper airway cough syndrome (UACS),
also known as postnasal drip syndrome, asthma, or
gastroesophageal reflux disease (GERD), alone or in
combination. Chronic cough has two or more causes
in 18–62% of patients, and three causes in up to 42%
of patients. It has been reported that causes of cough
cannot be identified in up to 42% of the patients
presenting at a specialized clinic.4
Upper Airway Cough Syndrome
The American College of Chest Physicians (ACCP) 2006
guidelines has suggested the term ‘UACS’ instead of
the previously described ‘postnasal drip syndrome’.5
This is because UACS more effectively addresses the
possibility that cough in these patients occurs not only
because of postnasal drip, but can occur as a result
of irritation or inflammation of the upper airway
structures that directly stimulate the cough receptors
independently or in addition to the postnasal drip.
The clinical presentation of patients with UACS,
in addition to cough, commonly involves complaints
(or at least an affirmative response to questioning) of
a sensation of something draining into the throat, a
need to clear the throat, a tickle in the throat, nasal
congestion, or a nasal discharge with a cobblestone
appearance of the oropharyngeal mucosa or mucus in
the oropharynx on examination. Patients sometimes
complain of hoarseness of voice, wheeze and a history of
upper respiratory illness. In patients with an atypical
clinical presentation, the diagnosis is often established
only after the response to empirical treatment with oral
first-generation antihistamines/decongestants, which
are preferred over newer agents. Use of intranasal
corticosteroids for 2–8 weeks or oral antihistamines
or nasal ipratropium bromide is also recommended in
selected patients with rhinitis.6,7
Asthma
Asthma is the second leading cause of persistent cough
in adults, and the most common cause in children.
Cough due to asthma is commonly accompanied
by episodic wheezing and dyspnea; with symptoms
typically worse at night; however, it can also be
the sole manifestation of a form of asthma called
“cough variant asthma”. Mechanism of cough in
asthma includes (1) sensitization of cough receptors
by inflammatory mediators such as bradykinin,
tachykinins, or prostaglandins; (2) bronchial smooth
muscle constriction.
Spirometry is the most reliable test for establishing
the diagnosis of asthma which reveals reversible
airflow obstruction. Use of objective tests, such as raised
sputum eosinophil count or increased exhaled nitric
oxide (NO) concentration are important for establishing
diagnosis of cough-variant asthma. Treatment
involves use of inhaled long-acting bronchodilators and
corticosteroids with theophylline and antileukotrienes.8
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SECTION 7Clinical Symptoms and Signs
Eosinophilic bronchitis characterized by cough and
sputum eosinophilia without other symptoms of asthma
or bronchial hyper-responsiveness is another important
cause of dry cough. Treatment involves inhaled
corticosteroid and oral steroids in refractory cases.9
Gastroesophageal Reux Disease
Gastroesophageal reflux disease is reported as a cause
of chronic cough in as many as 40% of the patients.
GERD-associated cough has been postulated to occur
through three major mechanisms: (1) intraesophageal
reflux (stimulation of the esophageal tracheobronchial
cough reflex); (2) laryngopharyngeal reflux; (3)
microaspiration. Each of these three mechanisms may
act directly by triggering cough events or indirectly by
sensitization of the cough reflex. The vagally mediated
esophageal-tracheobronchial cough reflex is the major
mechanism responsible for GERD-associated cough.
Treatment includes lifestyle modification such as
sleeping with an elevated head, smoking cessation,
weight reduction, a diet rich in protein and low in
fat, and in food and beverages that may relax the
lower esophageal sphincter (LES), such as alcohol,
chocolate, mint, onion, coffee, tea, cola and citrus fruits.
Combination of conservative and lifestyle measures
with proton pump inhibitors (PPIs) and/or prokinetic
agents for a period of 3 months resolves GERD induced
cough in 70–100% of patients, and increases the cough in
patients with reflux esophagitis. Surgical management
(laparoscopic fundoplication) is required when medical
therapy has failed.10
Angiotensin-converting Enzyme
Inhibitor Cough
A dry, persistent cough is a well-described class
effect of the ACE inhibitor medications. Mechanism
involves accumulation of bradykinin and substance
P accumulation in the upper respiratory tract which
is otherwise degraded by ACE. The incidence of ACE
inhibitor-induced cough has been reported to be in the
range of 5–35% among patients treated with these
agents. The onset of ACE inhibitor-induced cough
ranges from within hours of the first dose to months
after the initiation of therapy. Resolution typically
occurs within 1–4 weeks after the cessation of therapy,
but cough may linger for up to 3 months. The only
uniformly effective treatment for ACE inhibitor-
induced cough is the cessation of treatment with the
offending agent. The incidence of cough associated with
therapy with angiotensin-receptor blockers appears to
be similar to that of the control drug. In a minority of
patients, cough will not recur after the reintroduction of
ACE inhibitor therapy.11
Interstitial Lung Disease
Dry cough is an important symptom in patients with
interstitial lung disease (ILD) and at times can be
very bothersome. It occurs due to inflammation of the
interstitium due to various cytokines. It is seen in
almost 80–90% patients. Early in the disease, dry cough
may be the sole manifestation of the disease.
Other Causes
Laryngopharyngeal Reux
This entity has gained attention in the recent years.
Symptoms are nonspecific with a chronic cough.
Examination of larynx reveals erythema, edema and
thickening of the posterior pharynx. Treatment options
are limited and a trial of PPIs is warranted.
Obstructive Sleep Apnea
Several recent studies have suggested a possible
association between chronic cough and obstructive
apnea, with a reported prevalence of 33–44%. A trial of
continuous positive airway pressure therapy is reported
to reduce or resolve the cough in patients with OSA.12,13
Vocal Cord Dysfunction
These patients generally present with stridor, but can
occasionally present with cough. Diagnosis is by direct
laryngoscopy and flattening of the inspiratory flow-
volume loop on spirometry. In acute cases, continuous
positive airway pressure can be used to treat vocal
cord dysfunction, while in longer-term voice therapy,
psychological counseling along with reassurance,
irritant avoidance, and supportive care are useful.14
Somatic Cough Syndrome and Tic Cough
Somatic cough syndrome (earlier referred as psychogenic
cough) is a diagnosis of exclusion. The diagnosis should
be made only after an extensive evaluation is done that
includes ruling out uncommon causes of chronic cough,
and when cough improves with behavior modification or
psychiatric therapy.
Tic cough (earlier referred as habit cough) is seen
in school children especially after a respiratory tract
infection. According to the ACCP guidelines, diagnosis
of tic cough be made when the patient manifests the
core clinical features of tics that include suppressibility,
distractibility, suggestibility, variability, and the
presence of a premonitory sensation whether the cough
is single or one of many tics. Behavioral therapy has
been useful in few cases.15
Idiopathic Cough
When no cause of cough is found after extensive
investigations and evaluation, the patient is said to
have unexplained or idiopathic cough. It is associated
with airway inflammation. It is more common in
postmenopausal females. Differential diagnosis
includes somatic cough syndrome.16
MANAGEMENT
Treatment of cough mainly consists of treating the
underlying cause. An algorithm to the approach to
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CHAPTER 76 Dry Cough: Presentation, Causes and Management Algorithm
Flow chart 2 Approach to patient with chronic dry cough
a patient with chronic dry cough is illustrated in
Flow chart 2.
Other drugs used for treatment of dry cough include:
Antitussives: Antitussive therapies should be
considered in patients with chronic dry cough when the
cause of the increased cough reflex is unexplained and
treatment against the potential aggravating factors
is not satisfactory. These drugs may be centrally or
peripherally acting.
Centrally Acting Antitussives
Centrally acting antitussives inhibit or suppress the
cough reflex by depressing the medullary cough center
or associated higher centers. The most commonly used
drugs in this group are dextromethorphan and codeine.17
Dextromethorphan, a congener of the narcotic
analgesic levorphanol, has no significant analgesic
or sedative properties, does not depress respiration
in usual doses, and is nonaddictive. No evidence of
tolerance has been found during long-term use.
Codeine, which has antitussive, analgesic, and
slight sedative effects, is especially useful in relieving
painful cough and is considered the gold standard for
treatment of dry cough. There is a linear relationship
between a codeine dosage of 7.5–60 mg/d and a decrease
in the frequency of chronic cough.17 Codeine (60 mg)
significantly reduced the cough frequency compared
to placebo (p < 0.001), and also produced a greater
reduction in cough intensity than placebo and lower
doses of codeine (20 and 30 mg; p < 0.001). It also exerts
a drying action on the respiratory mucosa that may be
useful (e.g. in bronchorrhea) or deleterious (e.g. when
bronchial secretions are already viscous). Nausea,
vomiting, constipation, tolerance to antitussive as well
as analgesic effects, and physical dependence can occur,
but potential for abuse is low.
Other centrally acting antitussives include
chlophedianol, levopropoxyphene, and noscapine in the
nonnarcotic group and hydrocodone, hydromorphone,
methadone, and morphine in the narcotic group.
Peripherally Acting Antitussives
Peripherally acting antitussives may act on either the
afferent or the efferent side of the cough reflex. They
are grouped as demulcents, local anesthetics, and
humidifying aerosols.
Demulcents are useful for coughs originating above
the larynx. They form a protective coating over the
irritated pharyngeal mucosa. They are usually given as
syrups or lozenges and include acacia, licorice, glycerin,
honey, and wild cherry syrups.
Benzonatate is a peripherally acting antitussive
agent that presumably acts by anesthetizing stretch
receptors in the lungs and pleura. There are case
reports of effective use of benzonatate in the palliative
treatment of cough in advanced cancer.
Thalidomide has been evaluated as an antitussive
agent, due to its anti-inflammatory and antifibrotic
properties for patients with cough due to idiopathic
pulmonary fibrosis (IPF). Although it was useful
additional studies are needed due to serious side effects
including teratogenicity.
Nebulized lidocaine may be helpful in a minority of
patients with refractory chronic cough.
Combinations
Single agents may not be effective, combination may
be essential for better control. Many antitussive
preparations are available including combinations of
codeine or dextromethorphan with antihistamines,
decongestants, expectorants, and/or antipyretics. In
India, several such cough mixtures containing an
antihistaminic and an opioid derivative claiming
Abbreviations: ACE-I, angiotensin-converting enzyme inhibitor; Rx, Treatment.
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SECTION 7Clinical Symptoms and Signs
increased efficacy are available. However, whatever
knowledge is available on these cough mixtures is mostly
based on the experience of the practicing clinicians and
there is a paucity of published clinical trials.
An Indian study that compared pholcodine
plus promethazine with dextromethorphan plus
chlorpheniramine and codeine plus chlorpheniramine
in pediatric population concluded that all three
combinations studied were equiefficacious in providing
relief of signs and symptoms of cough.18
Other Agents for Specic Cause
Antihistaminics: First generation antihistamines like
chlorpheniramine reduce the cholinergic transmission
of nerve impulses in the cough reflex, hence, reduce
the frequency of cough and dry up the secretions,
making them ideal for treating cough concomitant with
rhinorrhea. Additionally, sedation, which otherwise
is considered a side-effect of these drugs can be
valuable in this situation, particularly if the cough is
disturbing the sleep. Advantages of first generation
antihistaminics over second generation includes:
additional anticholinergic receptor blockage and ability
to cross blood brain barrier.19
They are the first line of treatment in conjunction
with a decongestant for postnasal drip.
Inhaled glucocorticoids: The observation that chronic
cough is associated with airway inflammation even in
nonasthmatic patients, has prompted use of inhaled
glucocorticoids (GCs) for nonspecific management of
chronic cough. However, studies of inhaled GCs for
the treatment of cough in the absence of asthma have
yielded conflicting results.
Ipratropium bromide: The anticholinergic agent,
inhaled ipratropium bromide, has been used as an
antitussive agent by blocking the efferent limb of
the cough reflex and decreasing stimulation of cough
receptors by alteration of mucociliary factors. It has
been used in patients with persistent cough following
upper respiratory tract infection.
Nonpharmacologic interventions: Modalities
such as speech therapy, breathing exercises, cough
suppression techniques, and patient counseling have
been tried in the management of chronic cough.
A systematic review reported that studies of such
interventions showed improved cough severity and
frequency, but few of them used validated cough
measurement tools. Thus, the robustness of these
studies’ findings is limited.20
CONCLUSION
Chronic cough is often viewed as a difficult clinical
problem. It can be physically and psychologically
debilitating, occasionally leading to serious
complications. Although there are many etiologies,
an organized approach including focused history and
physical examination, directed testing in select cases,
and treatment trials lead to accurate, safe, and cost-
effective diagnoses in most patients.
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Gastro-oesophageal reflux, either singly or in association with postnasal drip and/or asthma is considered to be a cause of chronic cough. The amount and nature of gastro-oesophageal reflux however is often normal with acid suppression having very little, if any therapeutic effect in these patients. This review examines the challenges posed when exploring the reflux-cough link, and discusses the merits and limitations of the proposed mechanisms of reflux leading to cough.
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Cough is one of the commonest symptoms of respiratory tract infections and is a frequent problem encountered in general practice as well as in hospital practice. A wide range of disease processes may present with cough and definitive treatment depends on identifying the cause and diagnosis. Specific treatment of the cause should control the cough, but this may not occur in all cases and in a sizeable proportion of patients, no associated cause can be found. An increased sensitivity of the cough reflex can be observed in patients with dry cough. Symptomatic relief must be considered when the cough interferes with the patient's daily activities and this is effectively treated with antitussive preparations which are available as combinations of codeine or dextromethorphan with antihistamines, decongestants and expectorants Antitussives are used for effective symptomatic relief of dry or non-productive cough. First generation antihistamines like chlorpheniramine and centrally acting opioid derivatives like codeine are often used alone or in combination in the management of nonspecific cough. Sedation caused by these is valuable, particularly if the cough is disturbing the sleep. Although there is extensive experimental data on single agent antitussives and antitussive combinations, there is a major paucity of published literature on these combinations in nonspecific cough. Treatment of dry cough remains a challenge in some patients and this article reviews the scope of the current drugs and combination of Codeine and Chlorpheniramine in the effective management of dry cough.
Article
For people with refractory chronic cough, nonpharmacological interventions are emerging as alternatives to antitussive medications. These treatments generally are delivered by physiotherapists and speech and language therapists and consist of education, breathing exercises, cough suppression techniques, and counselling. Although the number of studies investigating these treatment options has increased in recent years there has not been a systematic review of the efficacy of these treatment options. Studies were searched for in EMBASE, AMED, Medline, CINAHL, and PsycINFO databases. Bibliographies of studies and reviews were searched by hand. Critical appraisal was carried out by one reviewer using the SIGN appraisal tools and Cochrane handbook for systematic reviews. From a total of 184 studies, 5 full-text English language articles were included in the review. Nonpharmacological interventions were found to significantly reduce cough reflex sensitivity, improve quality of life, and lead to reductions in cough severity and frequency. However, few studies used validated and reliable tools to measure cough severity and frequency thereby limiting the robustness of these findings. Present data support the use of two to four sessions of education, cough suppression techniques, breathing exercises, and counselling in order to achieve improvements in cough sensitivity and cough-related quality of life for people with chronic refractory cough. Due to the lack of validated outcome measures, results for other aspects of cough should be interpreted with caution. There is a need for additional larger-powered comparative studies investigating nonpharmacological interventions for refractory chronic cough.
Article
There has been significant progress in the field of cough in the past 10 years. Obstructive sleep apnoea, tonsillar enlargement and environmental fungi have recently been described as causes of chronic cough. The advances in the assessment of gastro-oesophageal reflux (GOR) have led to a greater understanding of the relationship between cough and GOR and are likely to change the approach to managing patients with GOR-cough. The investigation of the phenotype of patients with idiopathic chronic cough has provided novel insights. Patients with an idiopathic chronic are predominantly female, have an onset of cough around the menopause and have a high prevalence of organ specific autoimmune disease, particularly hypothyroidism. The presence of bronchoalveolar lymphocytosis suggests there is homing of inflammatory cells from primary sites of autoimmune inflammation to the lungs. A heightened cough reflex is a key feature of most patients with chronic cough and has led some investigators to suggest that chronic cough be recognised as a unique entity called Cough Hypersensitivity Syndrome (CHS). A number of subjective and objective tools have been developed recently to assess cough severity. Antitussive drug development is an emerging and exciting area of cough research.