<h2>Practice points</h2><ul><li>Andrographis may reduce multiple symptoms in upper respiratory tract infections (URTIs) (cough, expectoration, nasal discharge, headache, fever and sore throat)</li><li>Pelargonium may reduce symptom severity and duration in acute bronchitis in adults and children and acute sinusitis in adults, and is well tolerated</li><li>Ivy leaf may be effective for reducing cough and expectoration in adults and children</li><li>Echinacea may reduce symptoms of the common cold, but evidence is conflicting</li><li>Zinc is important for normal immune function. A deficiency may increase risk for infections, and supplementation may reduce common cold incidence and severity</li><li>Vitamin C is known to be important for immune function. Evidence for benefit in the common cold is mixed, however it may assist some individuals, and is well tolerated</li></ul><h2>Description</h2><ul><li>Respiratory tract infections (RTIs) can occur anywhere in the respiratory tract (i.e. the nose, throat and lungs). The infection can be caused by bacteria, a virus or even fungi1</li><li>Aetiology of coughs, colds and flu is often viral. Antibiotics only work on infections caused by bacteria, not those caused by viruses2</li><li>RTIs account for three to four million visits to general practitioners (GPs) each year in Australia. And cost taxpayers due to absenteeism and loss of productivity3</li><li>Each year, most children get about five colds, and most adults get two or three4</li></ul>

<h2>Management principles</h2>Symptomatic relief is mainstay treatment involving home remedies and over-the-counter (OTC) medicines. However some OTC medicines may be ineffective or unsuitable:5 <ul><li>No benefit and potential harm with OTC cough and cold medications in children</li><li>Inhaled corticosteroids and oral prednisolone are ineffective in children</li><li>Pseudoephedrine, phenylephrine, inhaled ipratropium modestly reduce the severity and duration of symptoms for adults</li><li>Antihistamines are effective for the relief of cold symptoms in the short term (1-2 days) in adults (not children), and are not effective in the medium to long term, and are not beneficial for the symptoms of a blocked or runny nose or sneezing29</li></ul>Use evidence based CMs to prevent, fight and recover from respiratory tract infection

Management

<h2>Primary recommendations</h2><h2>ANDROGRAPHIS (Andrographis paniculata)</h2>Mechanism of action11<ul><li>Immunomodulatory</li><li>Antibacterial and antiviral activity noted in vitro</li><li>Antipyretic</li><li>Anti-inflammatory</li></ul>Research<ul><li>A randomised, double-blind, placebo-controlled trial in patients with ≥2 common cold symptoms (n=223) found:</li><li> At day 5, treatment decreased cough, expectoration, discharge, headache, fever, sore throat, fatigue sleep disturbance compared to placebo where were unchanged or aggravated</li><li>Overall efficacy over placebo and was 2.1 times higher than placebo (52.7%) (p ≤ 0.05)13</li></ul>Systematic reviews have suggested superiority to placebo in alleviating subjective symptoms of URTIs.14,15,16One trial of 107 subjects reported a protective effect against common cold that became evident during the 3rd month.17Dosage and formulation<ul><li>100 mg twice daily of standardised andrographis extract providing 60 mg andrographolide per day11,13</li><li>Equivalent to 6 g herb daily during infection18</li></ul>Adverse effects<ul><li>Generally well tolerated in clinical trials. Unpleasant chest sensation, intensified headaches and urticaria have been reported18</li><li> A number of case reports of hypersensitivity reactions exist19</li><li> Insufficient evidence to determine safety in pregnancy11</li></ul>Key interactions<ul><li>Immunosuppressants: may decrease drug effect. The interaction is possible. Avoid concomitant use21</li></ul><h2>PELARGONIUM (Pelargonium sidoides)</h2>Mechanism of action11<ul><li>Antibacterial</li><li>Antiadhesive</li><li>Immune enhancement</li><li>Antiviral</li></ul>Research<ul><li>In adults with acute bronchitis, two studies (n=592) found after 7 days, pelargonium significantly decreased the Bronchitis Severity Score (BSS) compared with placebo.7,8 At day 7, 84.4% of patients were assessed by physicians as completely recovered or with major improvement compared to 30% with placebo7</li><li>In children and adolescents 1-17 years with acute bronchitis, pelargonium significantly decreased the BSS from baseline compared to placebo.9 At day 7, 48.5% of the treatment group had returned to kindergarten, school or work, compared to 12.4% of placebo</li></ul>In 103 adults with acute sinusitis there was a greater reduction in Sinus Severity Score and major symptom improvement at day 7 with pelargonium compared to placebo.10 Improvements occurred in the patients’ quality of life and wellbeing and reduced time away from work.Dosage and formulation<ul><li>A proprietary Pelargonium sidoides preparation (EPs® 7630) has been the subject of the majority of clinical trials.</li><li>Acute Bronchitis</li><li>Adults: 30 drops (1.35 ml) 3 times daily</li><li>6-12 years: 20 drops (0.9 ml) 3 times daily</li><li>2-5 years: 10 drops (0.45 ml) 3 times daily</li></ul>Acute sinusitis<ul><li>Adults: 60 drops (2.7 ml) 3 times daily</li></ul>Common cold<ul><li>Adults: 30 drops (1.35 ml) 3 times daily11</li></ul>Adverse effects<ul><li>Mild side effects limited to gastrointestinal symptoms such as nausea, vomiting, diarrhoea or heartburn and rashes. Allergic skin reactions have been report in trials11</li><li> Animal models suggest pelargonium is safe in pregnancy. No human studies11</li></ul>Key interactions<ul><li>Contains coumarin which may reduce platelet aggregation. Theoretically, concomitant use might increase the effects of some anticoagulant and antiplatelet drugs and increase bleeding risk. Until more is known use with caution12</li></ul><h2>ECHINACEA (E. purpurea, E. angustifolia)</h2>Mechanism of action11<ul><li>Immunomodulator</li><li>Anti-inflammatory</li><li>Antibacterial</li><li>Antiviral</li></ul>Research<ul><li>Clinical studies investigating the use of echinacea in the treatment of URTIs have produced inconsistent results due in part to different plant parts and extracts used and methodological problems20</li><li>There is some evidence to support the use of extracts of above-ground parts of E. purpurea if taken soon after the onset of cold symptoms19</li><li>There is mixed data for prevention of the common cold20</li></ul>DosageEquivalent to 3-10 g/d dried herb11 The cold-pressed juice and ethanolic extract of the aerial parts of E. purpurea and the hydroethanolic extracts from the roots of the E. angustifolia are the most studied preparation for URTIs.11Adverse effects<ul><li>Echinacea is well tolerated. Systematic reviews have found a slight risk of transient, reversible and self-limiting gastrointestinal symptoms and rashes11</li><li>No adverse events associated with use in pregnancy. Insufficient evidence to determine safety in lactation11</li></ul>Key interactions<ul><li>Chemotherapeutic agent: May increase drug effect. Interaction is possible. Avoid concomitant use21</li><li>CYP1A2, CYP2D6, CYP3A4 substrates: May increase or decrease drug effect. Interaction is possible. Use with caution under the supervision of a healthcare professional (HCP) and monitor21</li><li>Immunosuppressants: May decrease drug effect. Interaction is possible. Avoid concomitant use21</li></ul>For more information on key interactions visit: <a href="~/link.aspx?_id=4471DACF65C148EA8FD82B23FD6712D4&_z=z">https://www.blackmoresinstitute.org/interactions</a>

Primary

<h2>Secondary recommendations</h2><h2>IVY LEAF (Hedera helix)</h2>Mechanism of action<ul><li>Expectorant26 </li><li>Antispasmodic26 </li></ul>Research<ul><li>Postmarketing survey n=9657 including 5181 children with bronchitis (acute and chronic) were treated with a syrup made from dried ivy leaf. After 7 days of therapy, 95% of patients showed improvement relieving cough and expectoration22 </li></ul>Dosage<ul><li>Adults: 5mL – 7mL three times a day for up to 7 days, a specific Ivy leaf product26</li><li>Children (been used in children &lt;1-5 years): </li><li>2.5mL –16mL three times a day for 20 days</li><li>26</li></ul>Adverse effects<ul><li>Well tolerated with the overall incidence of adverse events of 2.1%22</li></ul>Key interactions<ul><li>None known26</li></ul><h2>ZINC</h2>Mechanism of action<ul><li>Involved in specific and non-specific immune response11 </li><li>Inhibits viral replication and the expression of viral genes11 </li></ul>Research<ul><li>Supplementation may result in a significant decrease in the incidence of infection, particularly in those with low baseline zinc levels23</li><li>A randomised, double-blind, placebo-controlled trial in adults at onset of cold symptoms found high-dose zinc (1 lozenge containing 13.3 mg of zinc every 2-3 hours while awake) shortened mean duration of cold (4.0 vs. 7.1 days), duration of cough (2.1 vs. 5.0 days) and nasal discharge (3.0 vs. 4.5 days)24</li></ul>Dosage<ul><li>Zinc gluconate or acetate lozenge, providing 4.5 – 24 mg elemental zinc, dissolved in the mouth every one to two hours while awake within 48 hours of symptom onset, often for a total dose of &gt;75 mg27</li></ul>Adverse effects<ul><li>Taking on an empty stomach may cause nausea.11 Always advise to have with a meal</li><li>Toxicity signs include nausea, vomiting, diarrhoea, fever and lethargy after ingestion11</li><li>High doses of zinc (100-150 mg/ day) may interfere with copper metabolism and cause hypercuprinaemia, red blood cell microcytosis and neutropenia 11</li></ul>Key interactions<ul><li>ACE inhibitors, angiotensin receptor blockers, and thiazide diuretics: urinary zinc excretion may be increased with long-term use of these drugs (decreasing zinc). Interaction is possible. Assess nutrient status and supplement if indicated21</li><li>Cefalexin: zinc may decrease the absorption of the drug by chelating with the drug. Interaction is possible. The interaction may be minimised by separating the dose of zinc at least 3 hours after taking cephalexin21</li><li>Hypoglycaemic drugs: low zinc status is common in diabetic patients. Zinc supplementation and normalisation of zinc levels have been shown to improve glycaemic control. Assess nutrient status and supplement if indicated. Monitor blood glucose level and alter drug dose if required under the supervision of an HCP21</li><li>Integrase inhibitors: may decrease the blood level of the drug by chelating with the drug. Interaction is likely. Avoid concomitant use21</li><li>Penicillamine: zinc may decrease the activity of penicillamine. Interaction is possible. The interaction may be minimised by separating the dose of medication and zinc by at least 2 hours21</li><li>Tetracycline &amp; quinolone antibiotics: zinc may decrease the absorption and blood levels of these drugs. Interaction is possible. The interaction may be minimised by taking tetracycline at least 2 hours before, or 4-6 hours after zinc supplement21</li></ul><h2>VITAMIN C</h2>Mechanism of action<ul><li>Modulates T-cell gene expression11</li><li>Stimulates the production of interferons (proteins that protect cells against viral attack)11</li><li>Stimulates synthesis of antibodies (IgG, IgM)11</li></ul>Research<ul><li>A 2013 Cochrane review found mixed evidence regarding the effectiveness of vitamin C in reducing symptoms and severity of the common cold25</li><li>In one trial, regular supplementation with 0.2 g/day vitamin C reduced common cold duration by 8% in adults and by 14% in children; 1-2 g/day vitamin C reduced common cold duration by 18% in children25</li><li>Overall, regular use of vitamin C was not effective, however, taking into consideration the low cost and safety profile of vitamin C and its modest, but consistent effect on the common cold duration and severity, the authors suggest it may it may be worthwhile for common cold patients to test on an individual basis25</li></ul>Dosage<ul><li>1-3 g /day. A dose of at least 2 g /day seem to work better than lower doses28</li></ul>Adverse effects<ul><li>Dose-related, doses greater than the tolerable upper limit of 2 g /day can increase the risk of significant adverse effects such as osmotic diarrhea and gastrointestinal upset28</li></ul>Key interactions<ul><li>Aluminium-containing antacids: increases drug side effects. Vitamin C chelates aluminium and increases aluminium absorption. To avoid interaction separate dose of medication by at least 2 hours21</li><li>Antihypertensive drugs: may have an opposing effect to drug a clinical trial 6 weeks in duration with a treatment of both vitamin C 500 mg and grape seed extract 1000 mg increased blood pressure in hypertensive patients. Interaction is possible. Avoid combination of vitamin C and grape seed extract with hypertensive patients21</li><li>Desferrioxamine: opposing drug effect. Vitamin C may cause transient deterioration of cardiac function with desferrioxamine, avoid concomitant use21</li><li>Estrogen: may increase blood levels of the drug. Possible interaction. Use with caution under the supervision of HCP21</li><li>Paracetamol: high doses of vitamin C (&gt;3g) may decrease the elimination rate of paracetamol. Possible interaction. Use with caution21</li></ul>For more information on key interactions visit: <a href="~/link.aspx?_id=4471DACF65C148EA8FD82B23FD6712D4&_z=z">https://www.blackmoresinstitute.org/interactions</a>

Secondary

<h2>Diet and lifestyle recommendations2,5,6</h2><ul><li>Rest</li><li>Drink plenty of water and non-alcoholic fluids</li><li>Avoid exposure to cigarette smoke</li><li>Inhale steam and saline nasal sprays or drops to relieve a blocked nose</li></ul>

Diet & lifestyle

<h2>References</h2>1. NPS Medicinewise. Respiratory tract infections. http://www.nps.org.au/conditions/respiratory-problems/respiratory-tract-infections2. NPS 2014. Patient brochure ;Colds, Coughs and Flu: What you can do’ http://www.nps.org.au/__data/assets/pdf_fi le/0004/211567/NPS-Cold-and-Flu-Brochure-May-2014.pdf 3. Respiratory Infectious Disease Burden in Australia. The Australian Lung Foundation. 2007. http://lungfoundation.com.au/wp-content/uploads/2014/03/2007-RID-Case-Statement.pdf 4. BMJ Publishing Group Limited 2009. Patient leafl et. Common Cold 5. Fashner J, Ericson K, Werner S. Treatment of common cold in children and adults. Am Fam Physician. 2012;86(2):153-159. 6. NPS Symptomatic Management plan. http://www.nps.org.au/__data/assets/pdf_fi le/0007/316285/Respiratory-tract-infections-manage-your-symptoms.pdf 7. Chuchalin AG, Berman B, Lehmacher W. Treatment of acute bronchitis in adults with a Pelargonium sidoides preparation (EPs 7630): a randomized, double-blind, placebo controlled trial. Explore. 2005;1:437-45. 8. Matthys H, Heger M. Treatment of acute bronchitis with a liquid herbal drug preparation from Pelargonium sidoides (EPs 7630): a randomised, double-blind, placebo-controlled, multicentre study. Curr Med Res &amp; Opinion. 2007; 23(2):323-31. 9. Kamin W, Ilyenko LI, Malek FA, Kieser M. Treatment of acute bronchitis with EPs 7630: Randomized, controlled trial in children and adolescents. Paed Int. 2012;54:219-26. 10. Bachert C, Schapowal A, Funk P, Kieser M. Treatment of acute rhinosinusitis with the preparation from Pelargonium sidoides EPs 7630: A randomized, double-blind, placebo-controlled trial. Rhinology. 2009;47:51-8. 11. Braun L, Cohen M. Herbs and Natural Supplements 4th ed. Elsevier 2015 12. Natural Medicines 2016. Umckaloabo Professional Monograph 13. Saxena RC, Singh R, Kumar P, Yadav SC, Negi MP, Saxena VS, Joshua AJ, Vijayabalaji V, Goudar KS, Venkateshwarlu K, Amit A. A randomised double blind placebo-controlled clinical evaluation of extract of Andrographis paniculata (KalmColdTM) in patients with uncomplicated upper respiratory tract infection. Phytomed 2010;17:178-85 14. Poolsup N, Suthisisang C, Prathanturarug S, Asawamekin A, Chanchareon U. Andrographis paniculata in the symptomatic treatment of uncomplicated upper respiratory tract infection: systematic review of randomised controlled trials. J Clin Pharm Ther 2004;29:37-45 15. Coon JT, Ernst E. Andrographis paniculata in the treatment of upper respiratory tract infections: a systematic review of safety and efficacy. Planta Med 2004;70:293-98 16. Kliger B, Ulbricht C, Basch E, DeFranco Kirkwood C, Abrams TR, Miranda M, Singh Khalsa KP, Giles M, Boon H, Woods J. Andrographis paniculata for the treatment of upper respiratory infection: a systematic review by the Natural Standard Research Collaboration. EXPLORE 2006;2(1):25-2917. Caceres DD, Hancke JL, Burgos RA, Wikman GK. Prevention of common colds with Andrographis paniculata dried extract. A pilot double-blind trial. Phytomed 1997;4(2):101-04 18. Mills S, Bone K. Principles and Practice of Phytotherapy - Modern Herbal Medicine. Churchill Livingstone Edinburgh 2013 19. Suwankesawong W, Saokaew S, Permsuwan U, Chaiyakunapruk N. Characterisation of hypersensitivity reactions reported among Andrographis paniculata users in Thailand using Health Product Vigilance Center (HPVC) database. BMC Comp Altern Med 2014;14:51520. Natural Medicines 2016. Echinacea Professional Monograph 21. Blackmores Institute 2015. Complementary Medicines Interactions Guide 7th ed. 22. Fazio S. Tolerance, safety and effi cacy of Hedera helix extract in inflammatory bronchial diseases under clinical practice conditions: a prospective, open, multicentre post marketing study in 9657 patients. Phytomedicine. 2009 Jan;16(1):17-24. 23. Prasad A, Beck F, Bao B, Fitzgerald J, Snell C, Steinberg J, Cardozo L. Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress. The American Journal of Clinical Nutrition 2007; 85:837-44 24. Prasad A, Beck F, Bao B, Snell D, Fitzgerald J. Duration and Severity of Symptoms and Levels of Plasma Interleukin-1 Receptor Antagonist, Soluble Tumor Necrosis Factor Receptor, and Adhesion Molecules in Patients with Common Cold Treated with Zinc Acetate. Journal of Infectious Diseases 2008:197 25. Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database of Systematic Reviews 2013, Issue 1. Art. No.: CD000980. DOI: 10.1002/14651858.CD000980.pub4.26. Natural medicines database. English Ivy leaf monograph. https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=465 Accessed 22nd February 201927. Natural Medicines database. Zinc monograph. https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=982 Accessed 22 February 201928. Natural medicines database. Vitamin C monograph. https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=1001 Accessed 22 February 201929. Sutter D et al. Antihistamines for the common cold. Cochrane Library. 28 November 2015 Immune health

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