Blackwell Publishing AsiaMelbourne, AustraliaRESRespirology1323-77992006 Blackwell Publishing Asia Pty Ltd200611S4149151MiscellaneousJRS Guidelines for Management of CoughRespirology

(2006)
11

(Suppl. 4)

Respirology (2006) 11 (Suppl. 4) S149–S151 doi: 10.1111/j.1400-1843.2006.00920.x

GENERAL TOPICS: CHAPTER 6

Treatment of cough
The committee for The Japanese Respiratory Society guidelines for management of cough

The Japanese Respiratory Society

This section provides an overview of drugs to sup- 2. BRONCHODILATORS

press or promote cough. Specific use of each drug in
testing or for treatment is described in other sections. The three types of bronchodilators approved for use
Some drugs are not approved for use in paediatric in Japan are theophylline derivatives, β2 agonists and
patients. anticholinergic drugs. Bronchodilators do not have
antitussive effects and are effective only in cough
associated with bronchial asthma, including cough-
1. CENTRAL COUGH SUPPRESSANTS variant asthma. In other words, cough that improves
with bronchodilator treatment is diagnostic of
As mentioned previously in the chapter on the ‘mech- asthma. Oral sustained-release theophylline formula-
anism of cough’, cough is an important host defence tions (e.g. Theolong®, Theodur®, Uniphyl®, Unicon®)
mechanism to clear sputum and foreign bodies from are used, but the range of therapeutic concentrations
the airway. With the exception of psychogenic cough, is narrow, so serum drug levels must be carefully
cough receptors in the airway are stimulated, the monitored. Adverse effects include nausea, vomiting,
impulse is transmitted to the cough centre, then palpitations and headache. In cases of overdose,
cough is elicited through efferent nerves. Antitussives seizures and death may occur. β2 agonists include
are classified depending on where they act in the oral (e.g. Spiropent®, Meptin®), inhaled (e.g. Meptin®,
cough reflex pathway: central antitussives that act on Sultanol®) and transdermal (Hokunalin Tape®) for-
the cough centre, and peripheral antitussives that act mulations. Adverse effects include palpitations and
on cough receptors. At present, agents classified as tremors. Inhaled β2 agonists are the most commonly
peripheral antitussives, including local anaesthetics, prescribed bronchodilator in the world, but care is
expectorants and mouthwashes, primarily have other required, because in severe cough, the stimulation
effects and are broadly classified as antitussives only due to inhalation may actually worsen coughing.
because of their secondary effects on cough recep- Inhaled anticholinergic drugs (e.g. Atrovent®,
tors. Those classified more narrowly as antitussives Flubron®, Tersigan®) are available, but their bron-
are central cough suppressants. chodilator effects are weaker than that of β2 agonists,
Central cough suppressants are classified as nar- and efficacy in cough-variant asthma has not been
cotic (e.g. Codeine Phosphate® ) or non-narcotic reported. Recently, an inhaled β2 agonist (Serevent®)
(e.g. Asverin®, Medicon®, Toclase®). Side-effects and anticholinergic drug (Spiriva®) with a long dura-
commonly seen with narcotic cough suppressants tion of action (12–24 h) have been developed.
include constipation, drowsiness and difficulty in Although effective in asthma and COPD, these drugs
micturition. These side-effects, albeit mild, may have not been established for treatment of cough-
also occur with non-narcotic cough suppressants. variant asthma.
Cough suppressants are not specific therapy for When prescribing bronchodilators for treatment of
cough, and their use should be limited to cough cough associated with asthma, care must be taken
associated with other symptoms such as chest pain, because theophylline derivatives, β2 agonists and
headache, or rib fractures, where patient QOL is anticholinergic drugs can all decrease lower oesoph-
significantly affected. In patients with a productive ageal sphincter (LES) pressure. The result may be
cough, antitussives are contraindicated because worsening of cough due to GERD.1,2
they suppress sputum production and may worsen
infection.
3. CORTICOSTEROIDS

Corticosteroids are potent anti-inflammatory agents

used for treatment of cough-variant asthma and
The Japanese Respiratory Society guidelines for man- atopic cough, which are characterized by airway
agement of cough, Nichinai Kaikan 7F, 3-28-8 Hongo, eosinophilic inflammation. Inhaled steroids (e.g.
Bunkyo-ku, Tokyo 113-0033, Japan. Email: info@jrs.or.jp Flutide®, Pulmicort®, Qvar®), and in more severe
© 2006 The Japanese Respiratory Society
Journal compilation © 2006 Asian Pacific Society of Respirology
S150
cases, oral steroids (e.g. Predonine®, Rinderon®) are
used. In adults, inhaled steroids at standard doses,
with the exception of local side-effects like oral can-
didiasis, are rarely associated with systemic side-
effects. However, oral steroids have many well-known
adverse effects.
Inhaled steroids are contraindicated in cough due
to bronchial tuberculosis. If cough does not improve
with treatment, steroid administration should be
discontinued.
4. ANTIMICROBIALS
Cough is a common symptom in all respiratory tract
infections, so the effect of antimicrobial therapy on
pathogens has a secondary effect on cough. Because
of space considerations, it is impossible to mention
all antimicrobial agents, so the reader is referred to
other guidelines published by the Japanese Respira-
tory Society on selection of appropriate antibiotics for
treatment of community-acquired pneumonia, noso-
comial pneumonia and airway infections.3,4 The com-
mon cold is the most frequent cause of acute cough,
and in more than 90% of cases, the aetiology is a res-
piratory tract virus. Unless complicated by a second-
ary bacterial infection, antibiotics are ineffective. The
indiscriminate use of antibiotics for cold symptoms is
not recommended because this leads to development
of resistant organisms. In SBS with a productive
cough, 14- and 15-member ring macrolides (e.g.
Erythrocin®, Ilotycin®, Clarith®, Klaricid®, Rulid®,
Zithromac®), without antimicrobial effect against
organisms like H. influenzae and Pseudomonas aerug-
inosa that colonize the airway, can still be effective
with low-dose long-term treatment. This may be due
to immunomodulatory effects of these macrolide
agents.5
5. EXPECTORANTS
Expectorants are peripheral antitussives in the broad
sense that they prevent stimulation of cough recep-
tors by clearing sputum from the airway. Expecto-
rants are sometimes classified based on mechanism
of action as mucolytic (decrease viscosity of sputum;
e.g. Bisolvon®), mucus-modifying (restore physiolog-
ical characteristics of sputum; e.g. Mucodyne®),
mucus-lubricant (decrease viscosity of sputum in the
airway mucosa; e.g. Mucosolvan®) and secretory cell
normalizing (prevent proliferation of goblet cells; e.g.
Cleanal®) agents. However, a clear distinction is often
difficult. Expectorants have few adverse effects, but
with thin sputum that is not viscous, the use of muc-
olytic agents may make it more difficult to expecto-
rate.
6. CHINESE TRADITIONAL MEDICINE
(KAMPOYAKU)
The antitussive effects of kampoyaku such as
Bakumondo-to® (Tsuruma, Japan) have been studied,6
© 2006 The Japanese Respiratory Society
Journal compilation © 2006 Asian Pacific Society of Respirology
Respirology (2006) 11 (Suppl. 4)
but large scale double-blind clinical trials in patients
with cough have not been conducted. At present, the
role in treatment of cough has not been established.
7. HISTAMINE H 1 RECEPTOR
ANTAGONISTS
Histamine H1 receptor antagonists (e.g. Azeptin®,
Zyrtec®, Celtect®, Alesion®, Allegra®, Allelock®,
Claritin®, Ebastel®) are effective in treatment of
atopic cough.7 Drowsiness and malaise may occur,
but the incidence of these adverse effects has mark-
edly decreased with recently developed drugs in this
class.
8. ANTIALLERGIC AGENTS
OTHER THAN HISTAMINE H 1
RECEPTOR ANTAGONISTS
Chemical mediators like prostaglandins and leukot-
rienes are increased in sputum from patients with
chronic cough due to various causes.8,9 Although not
considered first-line therapy in all patients with
cough, some antiallergy drugs, including leukot-
riene receptor antagonists (e.g. Onon®, Acolate®,
Singulair®, Kipres®), thromboxane inhibitors (e.g.
Domenan®, Vega®, Bronica®) and Th2 cytokine
inhibitors (e.g. IPD®), may be effective in cough-
variant asthma.10–13
9. HISTAMINE H 2 RECEPTOR
ANTAGONISTS AND PROTON
PUMP INHIBITORS
Oral histamine H2 receptor antagonists (e.g. Gaster®,
Zantac®, Tagamet®) and proton pump inhibitors
(PPIs) (e.g. Takepron®, Omepral®, Omeprazon®,
Pariet®) inhibit gastric acid secretion and can be used
in treatment of cough due to GERD. As previously
reported in Europe and the USA, randomized com-
parative clinical trials in Japan have also shown that
compared with histamine H2 receptor antagonists,
PPIs are associated with higher rates of healing and
symptom resolution in GERD. However, evidence is
scant regarding their effect in cough due to GERD.
Both classes of drugs have few serious adverse effects,
but severe hepatic dysfunction, anaemia and throm-
bocytopenia have been reported. In addition, serum
levels of theophylline are increased by histamine H2
receptor antagonists and decreased by PPIs, so
caution with co-administration is advised.
10. CAPSAICIN
Capsaicin is the principle ingredient in red pepper,
elicits cough when inhaled by stimulating airway
cough receptors, and is used in cough receptor sensi-
tivity testing. Please refer to Allergological and physi-
ological examinations for further details.
JRS Guidelines for Management of Cough
11. ANGIOTENSIN CONVERTING
ENZYME INHIBITORS
As mentioned previously in the chapter on the ‘mech-
anism of cough’, ACE inhibitors are antihypertensive
agents commonly associated with cough as an
adverse event. However, in elderly patients and those
with cerebral vascular injury, a decreased cough reflex
often leads to aspiration pneumonia. In these
patients, treatment with ACE inhibitors increases
the cough reflex and may decrease the incidence of
aspiration.14
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© 2006 The Japanese Respiratory Society