common cold and flu-like illness - mso-hns · 2019-05-07 · pathophysiology ˙˙ 6 ... urti is a...

Expert Opinion on the Diagnosisand Early Treatment Approach

Common Cold and Flu-like Illness

Teresa Luisa G. Cruz | Ronald Eccles | Anne Goh Eng Neo

Jason Pang Wui Chi | Pham Nhat An | Tran Anh Tuan | Yap Yoke Yeow

ACADEMY OF FAMILY PHYSICIANS OF MALAYSIA (AFPM)Malaysian Society Of Otorhinolaryngologists

Head & Neck Surgeons (MSO-HNS)

Expert Opinion on the Diagnosis and Early Treatment Approach

Common Cold and Flu-like Illness

Teresa Luisa G. Cruz

Ronald Eccles

Anne Goh Eng Neo

Jason Pang Wui Chi

Pham Nhat An

Tran Anh Tuan

Yap Yoke Yeow

ContentsForeword 4

1. Introduction 6

2. Virology 7

3. Symptoms of URTI 8

4. Viral transmission 10

5. Pathophysiology 11

6. Diagnosis of common cold 13

7. Management of the common cold 19

8. Patient case scenarios 26

9. Conclusion 29

References 30

Authors 32

4

ForewordAcute viral upper respiratory tract infection (URTI) is the most frequently observed infectious disease for which patients visit their primary health care provider. Children may have six to eight URTIs per year and adults may experience two to four episodes per year. In the majority of cases, URTI is caused by respiratory viruses such as rhinovirus, coronavirus, parain�uenza, in�uenza, respiratory syncytial virus, adenovirus, enterovirus or metapneumovirus.

The common cold is a syndrome of familiar symptoms caused by viral infection of the upper respiratory tract. Early symptoms of the cold include headache, sneezing, chilliness and sore throat, with later symptoms including nasal discharge, nasal obstruction, cough and malaise. These symptoms result in lost productivity and healthcare resource use.

Despite the enormous economic and social burden of URTI, there remains an unmet need for an e�ective treatment for this disease. In addition, URTI–related clinical practice guidelines relevant to Asian countries are currently lacking.

This compendium gives an overview of the diagnosis and early treatment approaches of common cold based on the consensus points discussed during the 2017 Upper Respiratory Tract Infection Expert Forum & Advisory Board Meeting attended by a group of leading physicians and scientist in the �eld of otorhinolaryngology (ear, nose, and throat – ENT) specialists, paediatricians, and family medicine, from public hospitals, private hospitals and specialty centres.

5

This compendium is meant to be a guide for clinical practice and was developed based on the best available evidence and expert opinion of the authors.

Healthcare professionals can generally apply the recommendations for the management of URTI outlined in this compendium. However, due to the possibility of speci�c complications, unique presentations, or infections with unusual organisms, referral to an ENT specialist may be necessary. Every healthcare provider is responsible for treatment decisions and educating patients to play an active role in self-management and preventive behaviours based on the therapeutic options available locally.

6

Viral upper respiratory tract infection (URTI) is one of the most common health problems encountered in primary care.1 In 2013, 18.8 billion cases of URTI occurred worldwide.2 Adults may have an average of two to four episodes of URTI each year, while school children have an average of six to eight episodes of colds in a year.3

In Singapore, a survey of primary health care clinics found that URTIs constituted 25% of all diagnoses made, and it was the leading condition for which a diagnosis was sought (Figure 1).4 Similarly, problems relating to the respiratory system were one of the most common reasons for an encounter with a primary health care provider in Malaysia.5

URTI is also a common reason for children visiting the doctor.3 A survey of primary medical clinics in Singapore (2001) found that URTI was the main condition for which young patients visited these clinics, accounting for 52% of visits of patients aged 0–4 years and 48% of visits of patients aged 5–17 years.6 In Australia, URTI was the most common respiratory tract infection managed by general practitioners among patients aged ≤5 years.7

URTIs a�ect an individual’s social life, sleep, school or work performance, and impose a substantial economic burden on society.8,9 In the US (2000–2001), it was estimated that the total economic impact of the common cold was around US$ 40 billion annually.8

2017 UPPER RESPIRATORY TRACT INFECTION EXPERT MEETING CONSENSUS

Introduction1

Figure 1. Leading conditions (n=77,342) for which diagnosis was sought in primary health care clinics in Singapore in 2010. The survey included 18 polyclinics and 407 private general practitioners4

Gastritis

Medical ce

rtication

of �tness

Diarrhoeal diseases

Diabetes

Dermatologica

l

Musculoskeletal

Ill-de�ned

Hyperlipidemia

Hypertensio

nURTI

Others0

10

20

30

40

Perce

ntag

e

4%4%3%4% 5% 5% 5% 6% 8%

25%31%

| Introduction

URTI is the top condition seen in

outpatient primary care setting. It accounts for

28% of adult visits and over 50% of pediatric visits.

7

Over 200 types of viruses have been associated with the symptoms of URTI and the common cold.1,3 Rhinoviruses (more than 100 serotypes) account for 30–50% of colds.1,3,10 Other causative viruses include coronavirus, respiratory syncytial virus, adenovirus, parain�uenza, in�uenza, enteroviruses, metapneumovirus and bocavirus (Table 1).1,3,10,11 Bocavirus is commonly associated with nasopharyngeal symptoms in children.12


Virology2

Table 1. Viruses associated with the common cold1,3,10

Virus Proportion of cases

Rhinoviruses 30–50%

Coronavirus 10–15%

Respiratory syncytial virus 10%

Adenovirus <5%

Parain�uenza 5%

In�uenza 5–15%

Enteroviruses <5%

Metapneumovirus Unknown

Bocavirus Unknown

Unknown 20–30%

Virology |

8

URTI is a multisymptom disease, with the symptom pro�le varying from patient to patient in terms of the severity, duration and types.1,3,13 The type of virus as well as the age, physiological state and immunology of the patient will also in�uence what symptoms occur.1 URTIs may occur without symptoms, or may result in death, but most commonly they will manifest as an acute self-limiting illness.1

Since di�erent viruses may be associated with similar symptoms, it is generally not possible to identify the causative virus on the basis of symptoms.1,3 The “common cold” and “�u” are syndromes of familiar symptoms caused by a viral infection of the upper respiratory tract.1

The common cold syndrome has been de�ned as a short, mild illness that predominantly a�ects the nasal part of the upper respiratory system; early symptoms include headache, sneezing, chilliness and sore throat, and later symptoms of nasal may include discharge, nasal obstruction, cough and malaise.1,14 Fever is an infrequent �nding during rhinovirus infections in adults, but it is fairly common in children.3

The period that occurs before symptoms of the common cold appear varies across the di�erent causative viruses.3 For instance, the onset of symptoms may occur as soon as 10–12 hours with a rhinovirus infection,3,15 while the incubation period of in�uenza may range from 1–7 days.3


Symptoms of URTI3

A purulent nasal discharge may occur,

but it does not necessarily indicate a bacterial

infection.3 The discharge colour may change from clear to yellow to green

during the course of an URTI, and this is

thought to be related to the recruitment of leucocytes

into the airway lumen, not the bacterial load.1

| Symptoms of URTI

9

Figure 2. Cold symptom pro�le in healthy school children16

100

80

60

40

20

01

B

2 3 4 5

Day of Illness

Perc

enta

ge re

port

ing

sym

ptom

6 7 8 9 10

100

80

60

40

20

01

A

2 3 4 5

Day of Illness

Perc

enta

ge re

port

ing

sym

ptom

6 7 8 9 10

Cough Sneezing Feverish Congestion Running Nose

Symptoms of URTI |

In adults, the mean symptom duration is usually 7-10 days.1,16 In children, the symptoms

are generally resolved by day 15.13

The severity of cold symptoms increases rapidly, and in general, peaking 2–3 days after infection, followed by a decline over 1–2 weeks (Figure 2).


10

Most viruses associated with URTI are transmitted to susceptible individuals through surface (by direct contact with the viral particles) or aerosol transmission.3,17 Mucus can be deposited on commonly touched surfaces and then transmitted by �nger contamination to the mouth, nose or eye. Mucus expelled during coughing or sneezing may form droplets which are largely responsible for the spread of URTIs. Large droplets infect at close distance by being sprayed near to the nose where they can be inhaled or by being sprayed into the eye. Small droplets may be suspended in the air for many hours and can infect patients at a longer distance.


Viral transmission4

| Viral transmission

11

The pathophysiology of the various respiratory viruses can be very di�erent.3 During rhinovirus and coronavirus infection, viral replication occurs mainly in a small number of nasal epithelial cells.18 For adenoviruses and in�uenza A infections, the primary site of replication is the tracheobronchial epithelium.3 About 90% of rhinovirus serotypes use intercellular adhesion molecule-1 (ICAM-1) as their receptor.19

There is a lack of morphological changes to the epithelial cells during rhinoviral infection, apart from a substantial increase in polymorphonuclear leucocytes early in the course of infection.1,19,20 Consequently, the local and systematic symptoms of the common cold are thought to be largely the result of the immune response (Figure 3).1,19,20

When stimulated by viral particles, macrophages trigger an acute immune response. The surface of the macrophage exhibits toll-like receptors that bind to speci�c viral components and trigger the production of cytokines (eg, interleukin-1, -6, -8).1,21 The cytokines act to recruit other immune cells, trigger in�ammation and generate systemic symptoms such as fever.1,21 In�ammatory mediators such as bradykinin and prostaglandins released during infection are thought to contribute to the local symptoms of the common cold (eg, sneezing, runny nose, nasal congestion, cough and/or sore throat).1,21


Pathophysiology5

Figure 3. The immune response to the viral infection may give rise to local or systemic symptoms.1,21

Pathophysiology |

Viral infection

Viral RNA DNA Cellular damage

Enzyme activation

Blood vessels, glands, nervesCNS, joints, muscles

Immune cells:• Macrophage• Neutrophils

Nasal epithelium

Systemic symptoms Local symptoms

Cytokines BradykininProstaglandins

Headache, fever, muscle aches and pain, anorexia, tiredness, mood changes

Sore throat, sneezing, cough, congested or runny nose, sinus pain, ear ache

12

Table 2. Pathophysiology of symptoms of the common cold

Local Symptom

Proposed pathophysiology

Sore throat Prostaglandins and bradykinin act on sensory nerve endings in the airway. The sensation of pain is mediated by the cranial nerves supplying the nasopharynx and pharynx.

Sneezing Stimulation (prostaglandins and bradykinins may be involved in URTIs) of sensory nerves of the a�erent trigeminal system in the nasal epithelium sends a message to the “sneeze centre” in the medulla that triggers re�ex activation of nasal and lacrimal glands. Rhinorrhoea ensues, facial muscles cause the closure of the eyes and respiratory muscles cause a maximal inspiration followed by an explosive expiration.

Rhinorrhoea The nasal discharge is a mixture of material from glands, goblet cells, plasma cells, and capillary plasma exudates. The relative contribution from these sources varies over the duration of the infection and the severity of the in�ammatory response. The colour of the discharge is related to the presence of leucocytes.

Nasal congestion

Results from the dilation of large veins in the nasal epithelium (venous sinuses) in response to vasodilator mediators of in�ammation (eg, bradykinin).

Sinus pain Possible factors include pressure changes in the sinus air space, or pressure changes in the blood vessels draining the sinus.

Watery eyes In�ammation and congestion of blood vessels in the nasal epithelium cause blockage of the nasolacrimal duct. This may result in an accumulation of tears and watery eyes.

Cough Caused by hyper-reactivity of the cough re�ex as a result of in�ammatory mediators acting on airway sensory nerve endings. Cough can also be initiated and inhibited by voluntary control, indicating some level of control from higher centres such as the cerebral cortex.

Systemic Symptom

Proposed pathophysiology

Headache Caused by cytokines acting on central nervous system.

Chills and fever Cytokines released from immune cells may act on vagal nerve endings or enter the brain to cause a resetting of the temperature control centre in the hypothalamus. The hypothalamus causes shivering and constriction of skin blood vessels, and may result in a sensation of chilliness that is perceived in the cerebral cortex.

Malaise and mood changes

Caused by cytokines acting on the central nervous system.

Anorexia Caused by cytokines acting on the feeding centre in the hypothalamus.

Muscle aches and pain

Caused by cytokines acting on the on skeletal muscle.

| Pathophysiology


13

As common cold symptoms may mimic symptoms of other conditions, the expert panel recommended the following practical algorithm (Figure 4) to assist physicians in making a di�erential diagnosis and treating the disease appropriately.

1. An important �rst step in the algorithm is to identify signs and symptoms that may determine if the illness is due to the common cold or in�uenza (see Section 6.1).

2. It is important to identify features that are suggestive of bacterial infection (see Section 6.2 and Table 3). Use of the Centor criteria may be helpful (Figure 6).

3. The physician must also look for any “red �ags” that suggest the condition may not be a common cold (Figure 5).

Diagnosis of the common cold6

Diagnosis of the common cold |


14

Figure 4. Algorithm to diagnose the common cold

Uncomplicated, without bacterial infection

If in�uenza test available

Positive

Positive for bacterial infection

Yes

Yes

No

No

Negative

Signs and symptoms typically include:• headache • nasal obstruction• sneezing • cough• chilliness • malaise• sore throat • fever• nasal discharge

Treat appropriately

Consider antibiotics

Agents with antiviral e�ects

Perform rapid diagnostic

test for in�uenza

Common Cold

Bacterial infection?

Symptoms suggestive of

common cold?

In�uenza

| Diagnosis of the common cold


15

6.1. Diagnosis of uncomplicated common cold

When di�erentiating between URTIs, assessment of the signs and symptoms, and their duration is an important initial step.1 The symptoms of the common cold can be vague and may overlap with those of other, more severe illnesses. It is important to eliminate the possibility that a serious illness is present and look out for ‘red �ags’, in�uenza and allergic rhinitis.

In the majority of adult patients, the diagnosis of the common cold is simple and reliable. However, this diagnosis may be more problematic with a child who cannot e�ectively communicate how they are feeling.3 In the clinic, the judgement of the physician for both adults and children will be based on examination of the ear, nose, throat and lymph nodes, and an assessment of respiratory symptoms, the patient’s temperature and ease of swallowing.

Red �agsClinical features regarded as "red �ags" which suggest that the condition may not be the common cold, or may be compounded by complications, are shown in Figure 5. When red �ags are identi�ed, further investigations are warranted.


Diagnosis of the common cold |

Figure 5. “Red �ags” suggesting that the condition is not a common cold

Fever >4 daysSevere headacheConvulsions/seizuresLethargy/drowsinessPhotophobia

Periorbital swellingPainful eye movement

Facial painOtalgiaBulging tympanic membraneLymph node swellingMedialized tonsils

Severe vomitingPoor food intake

DysphagiaOdynophagia

Drooling

DyspnoeaStridorSevere productive coughChest pain

Severe joint pain

Rash/Vesicles

16

Common cold vs in�uenzaFever is also more commonly present in children, especially in the early phase of an infection, and for patients with in�uenza are usually sicker than those with the common cold —the former having fever, chills, headaches, myalgia and malaise (Table 3). Nevertheless, accurately diagnosing in�uenza infection solely on the basis of clinical criteria is di�cult because of the overlapping symptoms caused by URTI-associated viruses.1 If the infection is caused by an in�uenza virus, this should be determined as early as possible. If available, a rapid in�uenza diagnostic test could be used to determine if the infection was due to an in�uenza virus and the patient could then be treated accordingly.

An accurate and early diagnosis of the causative viral infection may be important when pandemic in�uenza or severe acute respiratory syndrome (SARS) is suspected or present in the community as it will allow the appropriate treatment and public health measure to be taken, such as the use of antiviral therapy and the isolation of infected individuals.1

Common cold vs allergic rhinitisAllergic rhinitis may present with similar symptoms to the common cold, but it may have a seasonal component or clear allergic aggravation, and is unlikely to have an accompanying sore throat.23

Table 3. Features suggestive of common cold or in�uenza22

Signs and Symptoms In�uenza Cold

Symptom onset Abrupt Gradual

Fever Usual; lasts 3–4 days Rare

Aches Usual; often severe Slight

Chills Fairly common Sometimes

Fatigue, weakness Usual Sometimes

Sneezing Sometimes Sometimes

Stu�y nose Sometimes Common

Sore throat Sometimes Common

Chest discomfort, cough Common, can be severe Mild to moderate, hacking cough

Headache Common Rare



17Diagnosis of the common cold |

6.2. Diagnosis of bacterial URTIIn most patients with mild URTI symptoms, the infection will be viral.3 However, other ENT conditions due to a bacterial infection, such as a streptococcal throat infection, need to be ruled out. In addition to careful clinical examination, diagnostic tests that may be useful in con�rming a streptococcal throat infection include:

• measurement of C-reactive protein (CRP); in individuals who have been ill for more than 12 hours, very high CRP levels could indicate bacterial infection, whereas very low serum CRP concentrations (<20 mg/L) may indicate that the symptoms are probably due to a viral infection.24,25

• tests for myxovirus resistance protein A (MxA) which is elevated in the presence of viral infections.25

• tests of antigen levels to identify infections by Streptococcus A.26

Centor/McIsaac scores have been used to predict group A streptococcal pharyngitis and the need to treat with antibiotics.27-29 The Centor score, is calculated based on the patient’s age and four signs and symptoms (Figure 6). UK’s National Institute for Health and Clinical Excellence (NICE) guidelines suggest considering antibiotic treatment if the patient’s Centor score is ≥3.30


18


Figure 6. Diagnosis and management of sore throat29

Risk of GABHS pharyngitis

51 to 53%

Negative

Option

Positive

Treatment with antibioticsNo antibiotics indicated

Modi�ed Centor score and mangement options using clinical decision rule. Other factors should be considered (eg, a score of 1, but recent family contact with documented streptococcal infection). GABHS = group A beta-hemplytic streptococcus; RADT = rapid antigen detection testing

Adapted with permission from Mcisaac WJ, White D, Tannenbaum D, Low DE. A clinical score to reduce unnecessary antibiotic use in patients with sore throat. CMAJ. 1998;158(1):79.


28 to 35%


11 to 17%


5 to 10%


1 to 2.5%

Bacterial infection may be present if the symptoms have been present for 7–10 days with no signs of improvement.

Score 4Score = 3Score = 2Score = 1Score 0

Criteria PointsAbsence of cough 1Swollen and tender anterior 1cervical nodesTemperature >100.4°F (38°C) 1Tonsillar exudates or swelling 1Age

3 to 14 years 1 15 to 44 years 0 45 years and older -1

Cumulative score:

Consider empiric treatment with

antibiotics

No further testing or antibiotics indicated

Perform throat culture or RADT

Patient with sore throatApply streptococcal score


19


Management of the common cold7

There is no widely available cure or vaccination for the common cold, and so treatment is focused primarily on alleviating symptoms.1 Various guidelines are available for the management of URTIs,26,30-33 including the common cold.34-36 Some examples include:

World Health Organization. Cough and cold remedies for the treatment of acute respiratory infections in young children. Available at: http://www.who.int/maternal_child_adolescent/documents/fch_cah_01_02/en/

American College of Chest Physicians. Cough and the common cold: ACCP evidence based clinical practice guidelines (2006). Available at: http://journal.chestnet.org/article/S0012-3692(15)52834-1/fulltext

7.1. Agents with antiviral e�ects

Most URTIs are caused by viruses. In some cases, bacteria such as Streptococcus pyogenes may be the primary cause of infection. As several of the clinical manifestations characteristic for bacterial tonsillitis and pharyngitis are similar to the common cold, it is important to manage the conditions at its root causes.

Neuraminidase inhibitorsOseltamivir and zanamivir have been used to treat seasonal and pandemic in�uenza infection. A systematic review of these agents concluded that they have small, nonspeci�c e�ects on reducing the time to alleviation of in�uenza symptoms in adults, but not in asthmatic children.60 Using either drug as prophylaxis reduces the risk of developing symptomatic in�uenza.60 The researchers also noted that the balance between bene�ts and harms should be considered when making decisions about the use of both neuramidase inhibitors for either prophylaxis or treatment of in�uenza.

Management of the common cold |

of antiviral treatment

is greatest when administered early

20

Antiviral treatment is recommended as early as possible for any patient with con�rmed or suspected in�uenza who: is hospitalized; has severe, complicated, or progressive illness; or is at higher risk for in�uenza complications.59

Higher-risk patients include:59

• children aged <2 years

• adults aged ≥65 years

• persons with several systemic diseases

• persons with immunosuppression

• women who are pregnant or postpartum (within 2 weeks after delivery)

• persons aged <19 years who are receiving long-term aspirin therapy

• persons who are morbidly obese (ie, body-mass index ≥40)

• residents of nursing homes and other chronic-care facilities

Iota-carrageenan nasal spray

Iota-carrageenan is a natural ingredient extracted from red seaweed. It is a large polymer which does not permeate the nasal mucosa.61 The early and targeted use of iota-carrageenan nasal spray is thought to trap viruses in a protective layer, thus blocking viral attachment and entry into the mucosal cells. In vivo and in vitro studies showed iota-carrageenan was e�ective against viral respiratory infections resulting from human rhinovirus, human coronavirus, respiratory syncytial virus, adenovirus, parain�uenza virus, and in�uenza viruses.62-66 Iota-carrageenan nasal spray was also showed to be e�ective and safe in randomized, double-blind, placebo-controlled clinical trials in adults and children aged >1 year with early symptoms of the common cold.67-71 Iota-carrageenan treatment has been associated with a reduction in the time to recovery by up to two days p=0.002 (Table 5).71 Iota-carrageenan also increased viral clearance, reducing the viral load in patients with early symptoms of common cold by about 99% (Figure 7).67


| Management of the common cold

21Management of the common cold |

Table 5. Average reduction in duration of the disease with iota-carrageenan compared with placebo in overall intention-to-treat (ITT) population71

Population Treatment Group

Duration of illness depending on virus

Rhinovirus Coronavirus

ITT Population Iota-carrageenan 8.8 ± 0.6 9.02 ± 0.7

Placebo 10.7 ± 0.7 12.95 ± 0.99

Reduction of duration of common cold 1.9 days* 3.9 days**

*p<0.05 **p<0.01


Figure 7. Change in viral load in patients with early symptoms of common cold (n=35) at day 3–4 versus day 167

6005004003002001000

% viral load of �rst visit

Decreasedviral loadwith Iota-

carrageenan nasal spray

Iota-carrageenan nasal spray

Placebo

Increased viral load with placebo

Topical antiseptic agents (antiviral e�ects)

Antiseptic gargles, lozenges or throat sprays with a broad spectrum of activity represent another option for the treatment and prevention of URTI, especially in those with pharyngitis.72 Examples include povidone-iodine (PVP-I),72,73 chlorhexidine gluconate74 and benzalkonium chloride.75 By providing a local killing e�ect on the pathogen, these agents may spare or prevent the use of antibiotics.

PVP-I is e�ective against a wide variety of pathogens, including the viruses which commonly cause URTIs, such as coronavirus, adenovirus, in�uenza virus A and rhinovirus.72,76

Virucidal e�ects have been demonstrated in in vitro studies as rapid as 15 to 30 seconds.77-80

22


7.2. Symptomatic treatments

Analgesics/non-steroidal anti-in�ammatory drugs

Aspirin, paracetamol and ibuprofen are commonly used in adults for the treatment of pains and fever associated with colds.37,38 Paracetamol and ibuprofen, but not aspirin, are recommended for children.37 A systematic review found that non-steroidal anti-in�ammatory drugs (NSAIDs) were e�ective for relieving pain and myalgic symptom in people with the common cold, but there was no clear evidence of their e�ect in relieving respiratory symptoms.38 The review concluded that the balance of bene�ts and harms needs to be considered when NSAIDs are used for colds.

Antihistamines

First-generation sedating antihistamines, eg, chlorphenamine, have central e�ects on the sneeze centre and anticholinergic e�ects that a�ect the nasal and lacrimal glands. However, the sedation can reduce academic and/or work performance and these drugs are not recommended for day-time use.23 A systematic review of antihistamine monotherapy concluded that there was insu�cient evidence to support the prescription or use of over-the-counter antihistamines to alleviate symptoms of the common cold.39 Antihistamines are not recommended for use in children.36

Decongestants

These agents are typically used to relieve nasal symptoms through vasoconstriction and reduced nasal in�ammation, and can be administered in topical or oral form.40 Multiple doses of nasal decongestant monotherapy appear to have a small positive e�ect on subjective measures of nasal congestion in adults with the common cold.40 The e�ectiveness and safety of nasal decongestant monotherapy in children is not clear.40

Combinations of antihistamine/decongestant/analgesic

Antihistamine-analgesic-decongestant combinations may have some general bene�t in adults and older children, but their e�ect on individual symptoms is minimal.41,42 The bene�ts of such combinations must be weighed against the risk of adverse e�ects. There is no evidence of e�ectiveness of these combinations in young children.41

The effectiveness and safety of

nasal decongestant monotherapy in

children is not clear

Antihistamines are not recommended for

use in children


23

Intranasal corticosteroids are

not recommended for the symptomatic relief

of the common cold

Intranasal corticosteroids

The anti-in�ammatory actions of intranasal corticosteroids on the nasal mucosa could potentially reduce the symptoms and duration of the common cold.43 However, current evidence does not support the use of intranasal corticosteroids for symptomatic relief of the common cold.43

Saline spray/drops/irrigation

Saline solution has been used to clear excess mucus, reduce congestion and improve breathing.44 It may also remove infectious material from the sinuses and reduce cough associated with postnasal drip. These actions are supported by limited evidence from clinical trials in patients with colds.45 Saline irrigation/drops may be an e�ective and well-tolerated means to clear blocked nose in children.36

Zinc acetate

At doses of about greater than 75 mg/day, and when started within 24 hours of the �rst symptoms, zinc acetate may shorten the duration of the common cold.46,47 Side e�ects include the bad taste of the medication and nausea.46

Vitamin C

Vitamin C supplementation does not appear to prevent the common cold.48 However, a systematic review concluded that vitamin C supplementation appeared to have a consistent e�ect on the duration and severity of colds. The low cost and safety of vitamin C suggests that individual patients with the common cold should test out vitamin C to see if it is e�ective for them.48

Herbal preparations/alternative medications

Herbal preparations and alternative remedies (eg, tea with honey, tamarind, ginger or eucalyptus) are frequently used for the purpose of managing or preventing the symptoms of the common cold.36,49,50 However, the evidence for the e�ectiveness of these traditional remedies from well-designed trials is varied (Table 4).50,51 There is a wide variation in the recipes used to prepare these remedies.35 Safe and soothing remedies (eg, simple linctus) prepared commercially, mixed at a health centre or at home, are recommended by the WHO for cough and sore throat in children.36



24

Topical analgesics and lozenges are not recommended

in children.

Topical analgesics

The first step in the development of URTIs is the adherence and colonisation of the respiratory pathogen to the oropharyngeal mucosa. Topical anaesthetic agents and lozenges (eg, benzydamine) may temporarily relieve a sore throat in adults, but their use is not recommended in children.36

Table 4. Herbal remedies used in the treatment of the common cold

Treatment Strength of evidence

Findings

Andrographis paniculata preparations

Strong52 E�ective against cough symptoms

Chinese medicines

Poor53,54 May have a positive e�ect on the symptoms of colds, but evidence from well-designed trials is lacking

Echinacea preparations

Poor55 Most products are not e�ective; however, there may be some symptomatic bene�t if the aerial section of the plant is used early in the illness.

May have some preventative e�ect

Garlic Poor56 A single trial suggested that garlic may prevent occurrences of the common cold

Honey Poor57 Honey may be better than ‘no treatment’, but there is insu�cient evidence for or against e�ectiveness in relief from cough

Ivy/primrose/thyme-based preparations

Moderate to strong52,58

E�ective against cough and other respiratory symptoms

Pelargonium sidoides preparations

Poor to moderate52

Relief from respiratory symptoms



25

7. 3 Management of common colds complicated by bacterial infection

Topical antiseptic agents (antibacterial e�ects)

URTIs complicated by a bacterial infection may bene�t from treatment with medicated antiseptic gargle and throat spray.72 PVP-I has demonstrated broad-spectrum antibacterial e�cacy against Gram positive, Gram negative bacteria, spores and fungi. PVP-I containing products have not been associated with any increase in bacterial resistance.81

There have been no clinical reports of microbial resistance development in response to PVP-I treatment despite its long heritage of use (>60 years).72 No signi�cant changes were observed between parent strains and 20th subcultures in terms of: (i) killing times; (ii) minimal inhibitory concentration (MIC); (iii) minimal bactericidal concentration (MBC).81

Antibiotics

Antibiotics are commonly prescribed for the treatment of viral URTIs,82 despite the problem of increasing antimicrobial resistance.83,84 Such prescription practice is contrary to evidence indicating that antibiotics are ine�ective for the treatment of a viral URTI.26,85,86 Nevertheless, there are a few clinical instances when antibiotics are appropriate,30,87-89 and these are outlined by the American College of Physicians (ACP) and the Centers for Disease Control and Prevention.26

Based on a literature review of evidence about the appropriate use of antibiotics in adults, the ACP advise:26

• Clinicians should not prescribe antibiotics for patients with the common cold.

• Clinicians should note when antibiotics are not indicated. For instance, antibiotics do not �ght infections caused by viruses like colds, �u, most sore throats, and bronchitis. Inappropriate use of antibiotics can lead to the development of resistance.

• Clinicians should test patients with symptoms suggestive of group A Streptococcal pharyngitis (eg, persistent fevers, anterior cervical adenitis, and tonsillopharyngeal exudates or other appropriate combination of symptoms) by rapid antigen detection test and/or culture for group A Streptococcus. Clinicians should treat patients with antibiotics only if they have confirmed streptococcal pharyngitis.

• Clinicians should reserve antibiotic treatment for acute rhinosinusitis for patients with persistent symptoms for more than 10 days, onset of severe symptoms or signs of high fever (>39 °C) and purulent nasal discharge or facial pain lasting for at least 3 consecutive days, or onset of worsening symptoms following a typical viral illness that lasted 5 days that was initially improving (double sickening).



26


Patient case scenarios8

A mother brings her 14-month-old child to a paediatric clinic, complaining that he has been having fever and blocked nose for a day. He is still able to drink his milk but she is worried as his fever is quite high (39°C). On examination, his throat is slightly infected but lungs are clear. His 4-year old sister is also sick with fever, cough and runny nose and is on antibiotics.

DiagnosisBased on the above �ndings, the child could be diagnosed as having an acute URTI, with symptoms likely indicating a common cold.

TreatmentHe should be prescribed paracetamol to relieve the fever and normal saline nasal drops to relieve nasal symptoms. The mother should be advised to keep the child hydrated. Antibiotics should not be prescribed as there are no “red �ags”. Given that the child developed symptoms only a day prior, iota-carrageenan nasal spray may be considered for him.

Case 1

| Patient case scenarios

27

A mother brings her 7-year-old daughter to her family physician complaining that she has been having fever, cough, runny nose and sore throat for the past 4 days. The cough and runny nose are mild. She is not eating as normal and, on examination, her temperature is 39°C. Her lungs are clear, but throat is in�amed.

DiagnosisBased on the above �ndings, it is likely that she has acute URTI with viral or bacterial pharyngitis. Since the child has a high temperature and is not eating, routine diagnostic tests for bacterial pharyngitis should be carried out (rapid antigen test [RAT]; C-reactive protein [CRP] for group A Streptococcus; complete blood count [CBC]).

TreatmentIf a bacterial infection is con�rmed, then antibiotics are indicated. Paracetamol should be used to reduce the patient’s temperature. Since this patient is over 6 years old, antiseptic gargle may be considered to relieve the symptoms of the sore throat. Povidone iodine gargle may be a suitable option due to its wide spectrum of action, with no clinically reported antimicrobial resistance.

Case 22017 UPPER RESPIRATORY TRACT INFECTION EXPERT MEETING CONSENSUS

Patient case scenarios |

Note: CBC, as well as tests for CRP and erythrocyte sedimentation rate (ESR) should not be performed during the first two days of illness as results can be difficult to interpret.

28

A 47-year-old man comes to an ENT clinic with complaints of mild fever and sore throat for the past 5 days. He mentions that he has recurrent “colds” especially when there are changes in the weather. He is a frequent business traveller and decided to get a second opinion as his next trip is scheduled for the following week. He requests treatment with antibiotics and analgesics, and also for medication to carry while travelling. On examination, his temperature is 38°C and physical examination is otherwise normal. Throat examination reveals mildly enlarged tonsils and congested pharynx.

DiagnosisTo di�erentiate between viral or bacterial infection, the Centor criteria can be applied. This patient has enlarged tonsils (+1 point), fever (+1 point), presence of cough (-1 point), enlarged lymph nodes (+1) and age group >45 years (-1 point). Thus, it is likely that the patient has a viral infection given his other stable physical characteristics.

TreatmentSince the throat symptoms are still persisting, antiseptic gargle such as povidone iodine gargle can be prescribed. Iota-carrageenan nasal spray is not likely to be e�ective for the current infection, but the patient could carry this medication while travelling to be used when the �rst symptoms of a cold appear. Paracetamol may be recommended to reduce the fever.

Case 32017 UPPER RESPIRATORY TRACT INFECTION EXPERT MEETING CONSENSUS

| Patient case scenarios

29

Overall management points that were outlined by the expert panel include:

1. Common colds are caused by more than 200 viruses and rhinoviruses are the most common, accounting for around 30–50% of colds. Other common cold viruses include coronaviruses and in�uenza viruses.

2. Viruses causing respiratory infections usually spread through di�erent routes, including direct contact transmission, airborne transmission and surface transmission.

3. The usual manifestations of a common cold may include local symptoms such as sneezing, nasal congestion, sinus pain and ear ache. Systemic symptoms such as headache, fever, anorexia, muscle aches and pain may also be present.

4. In general, the severity of the cold symptoms increases rapidly, peaking 2–3 days after infection, followed by a decline in symptoms over 1–2 weeks. The mean duration of symptoms is usually 7–10 days.

5. The generation of common cold symptoms can be divided into two components: (i) a local response to cellular damage caused by viruses that lead to the local synthesis of in�ammatory mediators such as bradykinin and prostaglandins; (ii) a systemic response caused by cytokines activated by macrophages and neutrophils, which are immune cells, in response to infection.

6. The diagnosis of the common cold is based on an examination of the ear, nose, throat and lymph nodes, and an assessment of the patient’s signs and symptoms. Rapid diagnostic tests are available for in�uenza infection or bacterial infection such as Streptococcus but there is no diagnostic test for the common cold.

7. Antibiotics are not e�ective against common cold. Treatment of common cold may be achieved with antiviral iota-carrageenan nasal spray which has shown to: (i) shorten the duration of the common cold by up to 2 days; (ii) eliminate 99% of viruses from the nasal secretions; and (iii) reduce the severity of the symptoms.

In closing, Common Cold and Flu-like Illness: Expert Opinion on the Diagnosis and Early Treatment Approach is a simple, practical guide to provide a general understanding of the current treatment and management approaches critical to tackling URTIs, particularly the common cold. We hope this booklet will help you with your day-to-day practice.

Conclusion92017 UPPER RESPIRATORY TRACT INFECTION EXPERT MEETING CONSENSUS

Conclusion |

30


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References |

32


Authors (in alphabetical order, by surname)

A/Prof Teresa Luisa G. CRUZ MD, MHPEd

University of the Philippines–Philippine General Hospital Manila, Philippines

A/Prof Teresa Luisa G. Cruz graduated from the University of the Philippines–College of Medicine in 1992, and subsequently trained in Otorhinolaryngology & Head and Neck Surgery at the University of the Philippines–Philippine General Hospital (UP–PGH) from 1993 to 1996. She had her fellowship training at the International Hearing Foundation and the Department of Otolaryngology at the University of Minnesota. On returning to the Philippines in 1998, she was appointed Attending Otorhinolaryngologist at UP–PGH, and commenced research into Otology at the National Institutes of Health–University of the Philippines, Manila (NIH–UPM).

A/Prof Cruz has held a faculty appointment in the College of Medicine at the University of Philippines since 1998, and was a Research Assistant Professor at NIH–UPM in 2000 until 2014. She also �nished her Masters in Health Professions Education in the same university in 2002. In addition to her academic commitments, teaching and training medical students, Otorhinolaryngology residents and postgraduate students of the Master of Clinical Audiology, she has had clinical practice in General Otorhinolaryngology in three tertiary hospitals. Her main research interests are focused on the science of hearing and balance, particularly hearing screening and management of hearing impairment in neonates and school children.

| Authors

33


Professor Ronald ECCLES PhD, DSc

Cardi� University Wales United Kingdom

Prof Ronald Eccles is a Professor at the School of Biosciences, Cardi� University, and Director of the Common Cold Centre and Healthcare Clinical Trials, Cardi�, United Kingdom. He started his career as a lecturer with the Physiology Department at Cardi� University in 1973, and was subsequently promoted to Senior Lecturer and then Professor. His research interests and leadership were instrumental in the establishment of the Common Cold Centre at Cardi� University in 1988. Since then, he has continued his commitment to clinical care and research on the common cold and other acute URTIs.

Prof Eccles has been involved in conducting phase II through phase IV clinical trials for over 30 years, during which he acted as Principal Investigator on over 120 clinical trials. To date, Prof Eccles has published some 270 articles on rhinology and the treatment of cough, colds and �u. He is also a sought-after lecturer in cough treatments at international conferences, and acts as a consultant to the pharmaceutical industry on the development of new treatments for cough and colds.

Authors |

34


A/Prof Anne GOH Eng Neo MBBS, MMed (Paed)(S’pore), FRCPCH (UK), FAMS

KK Women’s and Children’s Hospital Singapore

A/Prof Anne Goh is Head of the Allergy Service at KK Women’s and Children’s Hospital from 2007 till date. She is also a senior consultant with the Respiratory Medicine Service. She did her training in Respirology in the Hospital for Sick Children, Toronto under Dr Hugh O’Brodovitch. Under her lead, paediatric �exible bronchoscopy was introduced into the service and is now regularly performed for both diagnostic and therapeutic indications. Paediatric lung function services have also been expanded and allergy tests have been included to improve services for patients under her leadership. Food and drug challenge tests are now also performed for better management of patients with food and drug allergies.

A/Prof Anne Goh’s subspecialty interests include asthma and allergic diseases, neuromuscular diseases and its lung complications, paediatric interstitial lung diseases, respiratory infections and sleep-disordered breathing.

| Authors

35


Dr Jason PANG Wui Chi MBBS, GDFM

Yong Loo Lin School of Medicine, National University of Singapore Singapore

Dr Jason Pang is a family physician at the Health Partners Medical Clinic (HPMC) in Singapore, where he has practiced for the past 20 years. Prior to joining HPMC, he served as a medical o�cer at various healthcare institutions, including the Singapore General Hospital. He graduated with a Bachelor of Medicine and Bachelor of Surgery degree from the National University of Singapore (NUS) in 1991, and went on to complete a Graduate Diploma of Family Medicine (NUS) in 2008.

An active teacher, Dr Jason Pang has been serving in residency and medical student teaching, and providing comprehensive training in family medicine as an adjunct lecturer/clinical tutor at NUS and the National University Hospital since 2012. Additionally, he regularly contributes to increasing knowledge about public health issues, and translation of this new knowledge into improved services and support for patients.

Authors |

36


Professor PHAM Nhat An MD, PhD

Vietnam Society of Infectious Diseases Vietnam Pediatric Association Vietnam

Prof Pham Nhat An obtained his MD from the Hanoi University of Medicine, and completed his Pediatrics Level 1 and Level 2 residency training at the same university. Prof Pham successfully completed his doctoral studies from the Medical Academy in So�a, Bulgaria, and subsequently received a research fellowship with the Boston University Medical Center under the Educational Commission for Foreign Medical Graduates (ECFMG) Fellowship Program. A former Chair of the Pediatric Faculty at the Hanoi Medical University, Prof Pham has also been the recipient of several teaching awards, including the People’s Professor.

During the course of his career, Prof Pham has served as the Vice Director and Head of the Infectious Disease Clinics at the Vietnam National Hospital of Pediatrics; Chair of the Department of Pediatrics, Department of Infectious Diseases and Department of Family Medicine; and Vice Rector of Hanoi Medical University. He currently serves as Vice Chairman of the Vietnam Society of Infectious Diseases, and Vice Chairman cum General Secretary of the Vietnam Pediatric Association.

| Authors

37


Dr TRAN Anh Tuan MD, PhD

Ho Chi Minh City Paediatrics Hospital No. 1 Vietnam

Dr Tran Anh Tuan is the Head of Department of Pediatrics at the Children’s Hospital No. 1 in Vietnam. He obtained his MD and PhD in Paediatrics from the University of Medicine and Pharmacy, Ho Chi Minh City. Dr Tran also completed clinical rotations at established university hospitals in Paris, and received AFS and AFSA degrees in Paediatrics and Paediatric Emergency Care from the University René Descartes, Paris-France.

In addition to his clinical roles, Dr Tran has strong interest in research and evidence-based treatment. He has published opinion articles and co-authored numerous peer-reviewed papers and book chapters. He currently holds a number of executive positions including Head of Department of Respiratory Medicine at the Children’s Hospital No. 1, Vice President and Vice Chairman of the HCMC Respiratory Society.

Authors |

38


Dr YAP Yoke Yeow MD (USM), MMed (ORL-HNS) (USM)

KPJ Johor Specialist Hospital Malaysia

Dr Yap Yoke Yeow completed his medical training in Universiti Sains Malaysia (USM) in 1997 and his Masters in Otorhinolaryngology (ORL) and Head and Neck Surgery in USM in 2004. Since then, he served as a consultant ENT surgeon in Hospital Kuala Lumpur and Hospital Serdang where he was also the visiting consultant to the Radiotherapy and Oncology Institute in Hospital Kuala Lumpur. He was the Head of ENT in University Putra Malaysia and is now practicing in KPJ Johor Specialist Hospital. He specialises in head and neck surgery, nasopharyngeal carcinoma and sleep apnoea, and was the �rst ENT surgeon to become a Registered Polysomnographic Technologist in the USA in 2013.

Known for the originality and rigor of his research, Dr Yap has sat on various multispecialty guideline, writing committees, such as that for the for URTIs, and the Management of In�ammatory Diseases of the Nose by the Malaysian Society of Otorhinolaryngologists–Head & Neck Surgeons (MSO–HNS). His latest contribution is to The Global Council on Brain Health’s Recommendations on Sleep and Brain Health. Dr Yap has authored numerous papers on di�erent aspects of nasopharyngeal carcinoma, and conducted numerous courses and training on nasopharyngeal carcinoma and surgery for nasopharyngeal carcinoma, allergy and sinusitis, both locally and internationally. Dr Yap was President of the MSO–HNS from 2011–2012, and led the �rst ever ASEAN Sleep Congress in Kuala Lumpur in 2012. He currently sits on the Subspecialty Committee of the National Specialist Registry for ORL in Malaysia.

| Authors

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