Respiratory tract infections

| Practice points|

• Andrographis may reduce multiple symptoms in upper respiratory tract infections (URTIs) (cough, expectoration, nasal discharge, headache, fever and sore throat)• Pelargonium may reduce symptom severity and duration in acute bronchitis in adults and children and acute sinusitis in adults, and is well tolerated• Ivy leaf may be effective for reducing cough and expectoration in adults and children• Echinacea angustifolia and Echinacea purpurea may reduce symptoms of the common cold, but evidence is confl icting• Zinc is important for normal immune function. A defi ciency may increase risk for infections, and supplementation may reduce common cold incidence and severity• Vitamin C is known to be important for immune function. Evidence for benefi t in the common cold is mixed, however it may assist some individuals, and is well tolerated

| Description |

• 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• Aetiology of coughs, colds and fl u is often viral. Antibiotics only work on infections caused by bacteria, not those caused by viruses2

• 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

• Each year, most children get about fi ve colds, and most adults get two or three4

| Management principles |

Symptomatic relief is mainstay treatment involving home remedies and over-the-counter (OTC) medicines. However some OTC medicines may be ineffective or unsuitable:5• No benefi t and potential harm with OTC cough and cold medications in children• Inhaled corticosteroids and oral prednisolone are ineffective in children• Pseudoephedrine, phenylephrine, inhaled ipratropium modestly reduce the severity and duration of symptoms for adults• Antihistamines, intranasal corticosteroids, codeine are ineffective for cold symptoms in adults

Complementary medicines

| Primary recommendation |

ANDROGRAPHIS (Andrographis paniculata)

Mechanism of action11

ImmunomodulatoryAntibacterial and antiviral activity noted in vitroAntipyreticAnti-infl ammatory

ResearchA randomised, double-blind, placebo-controlled trial in patients with ≥2 common cold symptoms (n=223) found:• At day 5, treatment decreased cough, expectoration, nasal discharge, headache, fever, sore throat, fatigue

and sleep disturbance compared to placebo where symptoms were unchanged or aggravated• Overall effi cacy over placebo and was 2.1 times higher than placebo (52.7%) (p ≤ 0.05)13

Systematic reviews have suggested superiority to placebo in alleviating subjective symptoms of URTIs. 14,15,16

One trial of 107 subjects reported a protective effect against common cold that became evident during the 3rd month.17

Dosage and formulation• 100 mg twice daily of standardised andrographis

ANDROGRAPHIS (Andrographis paniculata)

INFECTIONS AND IMMUNITY

| INFECTIONS AND IMMUNITY | 2

extract providing 60 mg andrographolide per day11,13

• Equivalent to 6 g herb daily during infection18

Adverse effects• Generally well tolerated in clinical trials. Unpleasant chest sensation, intensifi ed headaches and urticaria have been reported.18 • A number of case reports of hypersensitivity reactions exist19

• Insuffi cient evidence to determine safety in pregnancy11

Interactions• No interactions reported11

• Inhibition of platelet aggregation observed in vitro, although the clinical effect is uncertain. Suspend use 1 week before high risk surgery11

PELARGONIUM (Pelargonium sidoides)

Mechanism of action11

AntibacterialAntiadhesiveImmune enhancementAntiviralResearchRandomised, double-blind, placebo-controlled trials indicate pelargonium may signifi cantly improve recovery time and relieve symptoms in acute bronchitis and acute sinusitis:• In adults with acute bronchitis, two studies (n=592) found after 7 days, pelargonium signifi cantly 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

• In children and adolescents 1-17 years with acute bronchitis, pelargonium signifi cantly 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 placeboIn 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 awayfrom workDosage and formulationProprietary extract Kaloba® has been the subject of the majority of clinical trialsAcute Bronchitis• Adults: 30 drops (1.35 ml) 3 times daily• 6-12 years: 20 drops (0.9 ml) 3 times daily• 2-5 years:10 drops (0.45 ml) 3 times daily

Acute sinusitis• Adults: 60 drops (2.7 ml) 3 times dailyCommon cold• Adults: 30 drops (1.35 ml) 3 times daily11

Adverse effects• Mild side effects limited to gastrointestinal symptoms such as nausea, vomiting, diarrhoea or heartburn and rashes. Allergic skin reactions have been report in trials11

• Animal models suggest pelargonium is safe in pregnancy. No human studies11

Interactions• 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

ECHINACEA (E. purpurea, E. angustifolia)

Mechanism of action11

• Immunomodulator• Anti-infl ammatory• Antibacterial• AntiviralDue to the wide assortment of constituents found in Echinacea, it has varied pharmacological and clinical uses.11

Research• 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 problems.20

• 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

• There is mixed data for prevention of the common cold20

Dosage and formulationEquivalent 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.11

Adverse effects• Echinacea is well tolerated. Systematic reviews have found a slight risk of transient, reversible and self-limiting gastrointestinal symptoms and rashes11

• No adverse events associated with use in pregnancy. Insuffi cient evidence to determine safety in lactation11

Interactions• Theoretical interaction with immunosuppressant medications21

PELARGONIUM (Pelargonium sidoides)

ECHINACEA (E. purpurea, E. angustifolia)

REFERENCES 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 & 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 effi cacy. 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;14:515 20. 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 infl ammatory 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.

| Diet and lifestyle recommendations 2,5,6 |

• Rest

• Drink plenty of water and non-alcoholic fl uids

• Avoid exposure to cigarette smoke

• Inhale steam and saline nasal sprays or drops to relieve a blocked nose

| Secondary recommendations |

• Ivy leaf: May relieve cough and expectoration in acute and chronic bronchitis in adults and children (from 2 years of age). Well tolerated with overall incidence of adverse events of 2.1%22

• Zinc: Supplementation may result in a signifi cant decrease in the incidence of infection, particularly in those with low baseline zinc levels.23 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

• Vitamin C: A 2013 Cochrane review found mixed evidence regarding the effectiveness of vitamin C in reducing symptoms and severity of the common cold. 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 children. Overall, regular use of vitamin C was not effective, however, taking into consideration the low cost and safety profi le 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

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