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Abstract

Coughs lasting more than 3 weeks after airway infections are likely regarded as post-infectious coughs. A normal chest radiography unfavors possibility of pulmonary infection. These coughs are self-limited. This study reviews conducted studies in order to identify and define prevalence, pathogenesis, and cure of post-infectious constant coughs. The necessary data and guidelines are gained from English articles in PubMed website. Post-infectious and cough are searched. Post-infectious cough pathogenesis are not known; nevertheless, inflammation, epithelial damages of upper and lower airways, increased mucus secretion , and an increased reactivity of airways can cause these coughs. Despite self-limitedness of these coughs; dextromethorphan, antihistamines, ipratropium bromide, and decongestant are usually prescribed for cure of these coughs. Conversely, antibiotics play no significant role in this regard. These coughs constitutes smaller percentage of chronic coughs and are primarily classified in subacute coughs. Further studies should cover sub-acute and chronic properties of these coughs as well as their prevalence in different age groups and their determinants.
Trends in Phramaceutical Sciences 2016: 2(1)
TIPS
...................................
An overview of post infectious coughs
Samrad Mehrabi
Department of Internal Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Trends in Phramaceutical Sciences 2016: 2(1): 11-16.
.................................................................................................................................
Abstract
Coughs lasting more than 3 weeks after airway infections are likely regarded as post-infectious
coughs. A normal chest radiography unfavors possibility of pulmonary infection. These coughs are self-
limited. This study reviews conducted studies in order to identify and dene prevalence, pathogenesis, and
cure of post-infectious constant coughs. The necessary data and guidelines are gained from English articles
in PubMed website. Post-infectious and cough are searched. Post-infectious cough pathogenesis are not
known; nevertheless, inammation, epithelial damages of upper and lower airways, increased mucus se-
cretion, and an increased reactivity of airways can cause these coughs. Despite self-limitedness of these
coughs; dextromethorphan, antihistamines, ipratropium bromide, and decongestant are usually prescribed
for cure of these coughs. Conversely, antibiotics play no signicant role in this regard. These coughs con-
stitutes smaller percentage of chronic coughs and are primarily classied in subacute coughs. Further stud-
ies should cover sub-acute and chronic properties of these coughs as well as their prevalence in different
age groups and their determinants.
Keywords: Airways, Cough, Post-infectious cough.
.................................................................................................................................
1. Introduction
Cough is a protective reex of airways and
lungs, which reduces risks of infection, atelectasis,
and aspiration. Cough duration is very signicant
to identication of its causes (1):(1) acute cough
(shorter than three weeks) primarily in cases of
infections, aspirations, and stimulative conditions,
(2) subacute cough (3-8 weeks) mostly occurs in
viral infections; (3) chronic cough (longer than
8 weeks) primarily occurs in inammatory, neo-
plasms, and cardiovascular diseases. Most preva-
lent causes of acute and subacute cough are in-
fectious. Monto and Arbor (1995) and Greenberg
(2002) revealed that respiratory infections signi-
cantly affect death rate of children and adults (2-3).
2. Pathogenesis
As Lieberman et al. (1998) point out, vi-
ruses are the most inuential causes of respiratory
...........................................................................................................................
Corresponding Author: Samrad Mehrabi, Department of Internal
Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Email: mehrabis@sums.ac.ir
Recieved:01/11/2015; Accepted:20/12//2015
Review Article
diseases, by which upper and lower airways are in-
volved. Bacteria can also cause respiratory infec-
tions in a lower level of prevalence (4). According
to Mackie (2003), there are many viral pathogens
that cause acute upper respiratory tract infections
and seen in different patients depending on age,
season, and geographical region. Until 1960, inu-
enza and measles were known as viral respiratory
infections while next widely-conducted studies
also revealed rhinoviruses, coronaviruses, adeno-
viruses, parainuenza viruses, and respiratory syn-
cytial virus as causes of respiratory tract infections
(5). Braman (2006), Zimmerman et al. (2000), and
Ryan and Gibson (2008) demonstrate that coughs
lasting 3 weeks or longer or even several months
after primary infections are related to airway in-
fections but their infectious pathogens are hardly
identied (6-8).
Persistent cough has variety of pathogen-
esis and airways inammation is the main cause.
If lower airways get involved in the process of in-
ammation, the patient coughs due to an increase
Trends in Pharmaceucal Sciences 2016: 2(1):11-16.
Samrad Mehrabi.
in mucus secretion and impaired mucus clearance.
Upper airway inammation directly stimulates
cough receptors. Cough also may be caused by
inamed sinus secretions that stimulate cough re-
ceptors in larynx- and hypopharynx. Gastro pha-
ryngeal reux caused or worsened by coughs is
one of persistent cough pathogenesis. Cough also
starts and aggravates with multiple factors such as
cigarette smoking, dust, perfumes, chemical gases,
and even eating, drinking, laughing, and breathing
in cold air. Throat irritation is often reported by
patients, which cause bout of coughs (9).
3. Prevalence
As Ryan et al. (2012) showed, although
symptoms of respiratory infections are usually
resolved after control of infection, but sometimes
symptoms such as coughs may continue. As such
40% of adults are aficted with coughs after an
incidence of acute airway infections (10). These
constant coughs are regarded as 11-25% of chronic
coughs. Throat irritation is often reported by pa-
tients, which cause regular coughs (9). Kwon et al.
(2006) revealed occurrence of persistent coughs
after respiratory infections in 50% of cases (11).
Curley et al. (1988) showed that constant coughs
that persists 2 weeks or longer occur in 25% cases
of cold. Fifty percent of cases of whooping cough
and pneumonia are caused by mycoplasma pneu-
monia (12). In a study on 136 patients attending a
pulmonology clinic, 8% of chronic coughs were
post-infectious coughs (13). Findings of Ryan et
al. (2010) during inuenza pandemic (2009) on
136 patients demonstrated rate of 43% of post-
infectious chronic cough in patients suffering
from inuenza virus and 36% in cases suffered
from non-inuenza infection. Inuenza-suffering
patients have cough reex sensitivity nine times
greater as compared with patients not being af-
icted with post-infectious chronic cough (10).
Cough considered post infectious when a
patient complains of cough that lasts greater than
3 weeks but less than 8 weeks after an acute upper
respiratory tract infection and chest x-ray is nor-
mal (1, 14). The frequency of postinfectious cough
has been reported between 11% up to 50% during
outbreaks of Mycoplasma pneumoniae and Borde-
tella pertussis infections (6, 11). H1N1 inuenza
infection is also is a risk factor for persistent cough
that in one study has been reported in 43% of pa-
tients (10). Excessive cough can result in a variety
of complications (table 1) (15).
4. Treatment
Irwin et al. (2006) and Morice et al.
(2006) found that as these persistent coughs do
not cause great incapability and they ignored by
some people. Conversely, educated persons and
some others attend clinics for treatment due to
their jobs (1, 16). Poe et al. (1989) showed that
symptomatic treatments including antihistamines,
decongestants, ipratropium bromide, and some-
times oral and nasal corticosteroids albeit during a
short period are used (17). Braman (2006), Morice
et al. (2006), and Ryan et al. (2010) suggested
antihistamines, narcotics, centrally acting coughs
suppressants, dextromethorphan, corticosteroids,
ipratropium bromide, and bronchodilators for these
coughs (6, 10, 16). Nevertheless, these coughs are
hardly controlled.
Fujimori et al. (1997) followed 22 patients
with post-infectious chronic coughs, without any
history of smoking cigarettes, taking ACE inhibi-
tors, atopy and sinus diseases. They revealed that
Table 1. Some complications of excessive cough.
Respiratory Subcutaneous emphysema, pneumomediastinum, pneumothorax, exacerbation of asthma, laryngeal trauma
Cardiovascular Arterial hypotension, dislodgment/malfunctioning of intravascular catheters, brady and tachyarrythmias
Gastrointestinal Gastroesophageal reux events, Mallory-Weiss tear, splenic rupture, herniations
Neurological Headache, dizziness, cough syncope, cerebral air embolism, acute cervical radiculopathy, seizures, stroke
due to vertebral artery dissection
Genitourinary Urinary incontinence, invertion of bladder through urethra
Musculoskeletal Rib fractures, diaphragmatic rupture,
Others Fear of serious disease, decreased quality of life, disruption of surgical wounds, petechiae and purpura
12
Trends in Pharmaceucal Sciences 2016: 2(1):11-16.
post-infectious cough
old women are more likely aficted with chron-
ic cough and effectively respond to a mixture of
dextromethorphan, hydrobromide, oxatomide
(H1antihistamine) and bakumondoto (a traditional
Japanese herbal medicine composed of six herbal
components). Nevertheless, they stated that there is
a need for standard treatment (18). Fujimori et al.
(1997) also evaluated the impact of dextrometho-
rphan and oxatomide combination upon cough
severity after 5-7 days, as compared with persons
taking only one of these medicines. They viewed
a combined treatment of dextromethorphan and
oxatomide as an effective cure for chronic cough
caused by upper airway infections (18). Moreover,
these scholars assess a combined treatment of ox-
atomide, antihistamine, bakumondoto (a Japen-
ese medicine controlling activities of C bers in
patients suffering from constant coughs after up-
per airway infections). After a three-week treat-
ment, cough severity is reduced by 50%. Accord-
ingly, they introduced this combined treatment as
an effective cure for constant coughs (19).
Liu et al. (2013) demonstrated in a detailed
review that Chinese herbal medicines are more
effective in post-infectious coughs as compared
with placebos and common Western medicines
(20). Wang et al. (2014) administered montelukast
10 md daily and placebo respectively to 127 and
139 patients aged 16-49 years old suffering from
post-infectious coughs. They followed patients
2 and 4 weeks later. Their ndings suggest that
montelukast does not reduce post-infectious
coughs (21).
Holmes et al. (1992) highlighted
signicant impact of nasal spray ipratropium bro-
mide (320 mcg/d) uponpost-infectious persistent
cough control (22).
Different studies have investigated effects
of nasal corticosteroids on bronchial sensitivity
(23-25). Ewald et al. (1989) view low dosage of
nasal corticosteroids (400 mcg of beclomethasone
once daily) as ineffective in case of non-asthmatic
chronic cough (25).
Pornsuriyasak et al. (2005) administered
either nasal budesonide (400 mcg twice a day) or
placebo to 30 patients suffering from persistent
cough during 4 weeks to examine clinical impacts
of nasal corticosteroid upon persistent cough after
respiratory tract infections. They were followed up
in the second and fourth weeks. The ndings do not
show any signicant effect of nasal corticosteroid
on persistent cough, relative to placebo (26). Gillis-
sen et al. (2007) introduced nasal beclomethasone
dipropionate (400 mcg twice a day for 7 days and
200 mcg twice a day during the next 4 days) as an
effective cure of post-infectious cough (27). Some
uncontrolled studies also suggest a short-term oral
prednisone treatment (30-40 mg) in mornings and
gradual tappering during 2-3 weeks (17). Accord-
ing to two review studies, due to high prevalence
of coughs, their socio-economic burdens, and use
of antibiotics, further studies should be conducted
for management of post-infectious cough (28-29).
5. Conclusion
While post-infectious coughs last sever-
al weeks and months after infections (30), stud-
ies on post-infectious persistent coughs and their
pathogenesis only have considered coughs lasting
between 3 weeks and 8 weeks after infections as
post-infectious coughs. A small number of stud-
ies have investigated anti-inammatory medi-
cines in cases of post-infectious persistent coughs.
Stimulators of coughs should be identied before
treatment due to multiple pathogenetic factors of
coughs (increased reactivity of airways, increased
mucus secretions, mucociliary system disorders,
gastro pharyngeal reux, etc.). The best treatment
method is unknown inadults suffering from post-
infectious cough which is not caused by bacterial
sinusitis and whooping cough. Dextromethorphan,
antihistamines, ipratropium bromide, and decon-
gestants are usually administered for treatment
of these coughs. Conversely, antibiotics do not
play any role in this regard. With regard to dif-
ferent studies on post infectious cough and their
cure, further studies on corticosteroids and their
role in control of post-infectious coughs would be
suggested.
Conict of Interest
None declared.
.................................................................................................................................
13
Trends in Pharmaceucal Sciences 2016: 2(1):11-16.
Samrad Mehrabi.
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15
... Cough may impact patient's quality of life [1] and result in several complications [2] (Table 1). Postinfectious cough (PIC) is a cough that begins during an acute respiratory tract infection, lasts more than 3 weeks but less than 8 weeks, is not complicated by pneumonia, and usually is self-limited [3]. PIC may be due to airway hyperresponsiveness as a result of airway inflammation [1,3,4]. ...
... Postinfectious cough (PIC) is a cough that begins during an acute respiratory tract infection, lasts more than 3 weeks but less than 8 weeks, is not complicated by pneumonia, and usually is self-limited [3]. PIC may be due to airway hyperresponsiveness as a result of airway inflammation [1,3,4]. Chest radiograph (CXR) findings are usually normal [3]. ...
... PIC may be due to airway hyperresponsiveness as a result of airway inflammation [1,3,4]. Chest radiograph (CXR) findings are usually normal [3]. ...
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To determine whether the cough of the common cold arises from upper respiratory stimuli and whether antihistamine-decongestant therapy is an effective treatment for this cough, we prospectively evaluated volunteers with uncomplicated common colds in a randomized, double-blind, placebo-controlled study. After completing a standardized questionnaire and undergoing a physical examination, throat-culturing, and pulmonary function testing, subjects took the active drug or identical-appearing placebo for 7 days while they kept a diary in which they ranked the severity of 17 symptoms for 14 days. Pulmonary function testing was repeated, on average, on Days 4, 8, and 14. Forty-six percent of the variation in cough severity could be explained by throat-clearing and 47% of the variation in throat-clearing severity by postnasal drip. FIF50%, the only physiologic parameter that significantly correlated with cough, rose as cough severity fell. Antihistamine-decongestant therapy reduced postnasal drip and significantly decreased the severity of cough, nasal obstruction, nasal discharge, and throat-clearing during the first few days of the common cold. In addition, cough was 20 to 30% less prevalent in the active drug group within 3 days of starting therapy. We conclude that the cough of the common cold arose from upper respiratory tract stimuli and that cough and other cardinal symptoms of the common cold were reduced with antihistamine-decongestant therapy when these symptoms were at their worst.
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H1 antihistamines have been shown to have antitussive effects in patients with asthma and postnasal drip. In Japan, no study has been performed to determine whether orally administered oxatomide, H1 antihistamine, can reduce the chronic cough seen in patients with post-upper-airway infection (postinfection). Patients who had chronic cough of more than three weeks' duration and a history of post-upper-airway infection took part in the study. None had any history of nasal disease, gastroesophageal reflux, bronchial asthma, or other chronic pulmonary disease. All patients were non-smokers, and none used ACE inhibitors. They had normal CRP concentrations, peripheral white blood cell and eosinophil counts, serum IgE concentrations, titers of cold agglutinins and antibodies to Mycoplasma pneumoniae, chest roentgenograms, and respiratory function tests. A prospective randomized, open design was used. The effect of one week of treatment with dextromethorphan (D) or with D plus oxatomide (D + O) on the severity of cough, as estimated by cough diary, were examined. Twenty-two patients entered the study, and 20 were eligible for efficacy and side-effect analyses. Nine patients receiving D and 11 receiving D + O completed the protocol. Patients' characteristics before the start of the study, such as severity and duration of cough, and laboratory data, were not significantly different between the two groups. From trial day 5 to 7, improved rates of cough were significantly higher with D + O than with D alone (p < 0.05). Combination therapy with oxatomide and dextromethorphan reduces subjective perception of cough as estimated by cough diary. These results suggest that oxatomide, H1 antihistamine may improve chronic cough in patients with post-upper-airway infection.
Article
The clinical effects of inhaled ipratropium bromide were studied in 14 non-smoking patients with persistent post-viral infective cough employing a controlled double-blind, cross-over trial. Patients were selected if they demonstrated no apparent underlying cause for their persistent cough after appropriate radiological and respiratory function tests including methacholine reactivity and bronchoscopic examination. Inhaled ipratropium bromide (320 micrograms day-1) produced significantly less day and night time cough (P < 0.05) with overall clinical improvement in 12 cases, five of whom had total resolution of their cough. We conclude that ipratropium bromide is an effective treatment in non-smoking adults with protracted cough following clinical upper respiratory tract infection.
Bronchial hyperresponsiveness (BHR) and asthma symptoms are linked to chronic inflammation in the airway. Corticosteroids reduce BHR and asthma symptoms and, although their precise mode of action is not yet certain, it is likely that they suppress the allergic inflammatory response. They may act on macrophages, eosinophils, lymphocytes, and airway microvascular leak to inhibit the late response and BHR that follows allergen exposure, whereas chronic administration may also reduce the number of mast cells in airways to decrease the immediate response to allergen and exercise. In view of the safety of administration, inhaled corticosteroids should be considered as first line therapy for chronic asthma, with the aim of suppressing inflammation and reducing the need for bronchodilator therapy.
Article
Thirty-one patients with a dry cough for at least 1 h duration in more than half of the last 30 days and with no recent respiratory infection participated in a clinical trial to evaluate the effect of inhaled beclomethasone dipropionate (BDP). Lung function was normal and reversibility was excluded by spirometry before and after bronchodilator and by no diurnal variation in home peak flow monitoring. Only one had significant eosinophilia and only three were mildly hyperreactive by bronchial provocation with histamine. After a 1-week run-in period the patients were randomly allocated to receive either BDP 4 puffs of 50 micrograms b.i.d., or placebo. After 2 weeks the patients were crossed over and received the alternative treatment for another 2-week period. The degree of cough, disturbance of night sleep and peak expiratory flow morning and evening were recorded daily in a diary. Spirometry was performed at each control visit. A significant period effect from run-in to period 1 and/or from period 1 to period 2 was demonstrated for cough and disturbance at night but not for peak flow or spirometry. However, no significant treatment effect was found for any of the measured variables.
Article
Irwin and co-workers have designed an anatomic approach to the diagnosis and treatment of cough. In their hands, diagnosis was consistently determined and treatment successful almost without exception, if sustained. We reviewed the results of a similar approach in 139 consecutive and unselected patients referred to pulmonary specialists in two community hospitals. Thirty-nine patients demonstrated hyperreactive airways (HA) by carbachol inhalation and/or eucapnic hyperventilation of cold air. Twenty-seven of 78 without HA had postnasal drip, and 13 of 78 had a persistent cough following acute upper airway inflammation. Other less common diagnoses included chronic bronchitis, gastro-esophageal reflux, occupational bronchitis, interstitial lung disease, and psychologic causes. We were able to find the cause of cough 88 percent of the time. Treatment adjusted for noncompliance was not always a success. While all patients with HA improved, 8 percent of patients without HA or specific diagnosis did not have an improvement in their cough upon retrospective inquiry. Based on this analysis, we find that the diagnosis and treatment of cough may not be as successful as originally reported using Irwin's approach.