Cough is classified as acute or chronic. Acute cough is a very common symptom resolving in the short term, while chronic cough lasts for more than three weeks . Acute cough in children is a common reason why parents seek medical treatment and it is a real challenge for paediatricians. Cough is probably the most bothersome symptom associated with upper respiratory tract infections for children and their parents. Cough frequently produces distress and sleep disorders in the whole family .
In most cases, acute cough is self-restrained, but its perseverance can be exasperating and can worsen the quality of life and common social participation .
The effect of cough experienced by children on the family’s life may create increasing discomfort. Indeed, children with acute cough may experience a transient disability, prompting parents to miss work and children to miss school, thus increasing the global community cost . Generally, parents’ concerns increase when their children’s cough lasts for more than a week. Consequently, parents often seek for a medical consultation with a requirement for drug treatment, although most antitussive drugs lack evidence of effectiveness .
In recent years, the inappropriate prescription of antitussive pharmacological treatments in children has decreased; however, paediatricians’ prescriptions currently do not always reflect an accurate treatment of cough . According to epidemiological data, cough occurring in children produces more anxiety than in cough occurring in adults, and many people view this symptom as “a disease”. A recent Italian survey confirms this view, suggesting that some inclinations of paediatricians’ therapeutic practice should be modified to achieve better control of cough in children and to reduce its impact . Moreover, when attempting to treat cough, children are administered over-the-counter products with little or no scientific evidence of proven efficacy .
The World Health Organization has identified honey as a possible demulcent treatment for cough [7,8]. Demulcent is a substance that is usually based on polysaccharides, covers the throat and reduces pain when the mucosa is irritated by increasing saliva production to reduce the cough reflex .
Parents often believe that the administration of honey to relieve cough and improve sleep quality at night is more desirable than the administration of drugs such as diphenhydramine or dextromethorphan. Moreover, evidence from some clinical studies support the use of honey to relieve cough. Results from a study comparing a single dose of honey, dextromethorphan and no treatment indicated that parents view honey as the most favourable treatment for symptomatic relief of nocturnal cough due to upper respiratory tract infection in children aged 2-18 years .
Another study in which the effects of honey on the nightly cough and sleep quality of children and their parents were compared with dextromethorphan and diphenhydramine showed that the administration of honey before sleep produced a greater effect on alleviating cough induced by an upper respiratory infection in children aged 24-60 months .
In 2018, the Cochrane Collaboration reviewed six randomized controlled clinical studies that investigated the use of honey to treat acute cough in children. The authors concluded that honey alleviates cough with a greater size effect than diphenhydramine, an antihistamine drug classified as a cough suppressant in the United States, placebo or no treatment and with little or no difference compared to dextromethorphan .
Due to assumptions described above, an evaluation of a different approach to treat cough, instead of synthetic drugs, appears to be interesting. The safeguarding effect of a mechanical barrier in the throat may be considered a well-founded therapeutic approach that indirectly exhibits anti-inflammatory activity and is able to reduce the damage produced by irritant agents or microbes. This protective activity may be acquired from natural substances such as honey and plant extracts.
Based on the considerations listed above and the lack of effective paediatric antitussive products, a cough syrup for children (KalobaTUSS®) based on acacia honey in combination with Malva sylvestris, Inula helenium, Plantago major and Helichrysum stoechas extracts has been developed for acute cough in children. This syrup is a Medical Device class IIa, classified in accordance with Directive 93/42/EC.
Malva sylvestris is a biennial–perennial herbaceous medicinal plant known as “common mallow” that is indigenous to North Africa, Asia and Europe. It has been used in folk medicine for its mucus formed of flavonoids and polysaccharides. Traditionally, M. sylvestris has been used to treat upper respiratory tract infections. The entire plant possesses beneficial properties, and it has been used in folk medicine for its mucus because the leaves and flowers are rich in flavonoids and mucilage. Mucilage is present at a percentage of 6-8% in M. sylvestris leaves and is composed of high-molecular weight acidic polysaccharides of the rhamnogalacturonan type that are also observed in epidermal cells . In 2018, the European Medicinal Agency (EMA) assessed the traditional use of M. sylvestris as a “demulcent preparation for the symptomatic treatment of oral or pharyngeal irritation and associated dry cough” [14,15]. The extract used in the syrup is a Malva sylvestris leaf aqueous extract, containing no less than 80% mucilage.
Inula helenium (Elecampane) is a perennial herbaceous plant of the Asteraceae family that is native to England and Europe, but it also grows in the northern and eastern United States, Canada Asia, India and Siberia. This plant was used to treat cough based on its medicinal properties .
Inula helenium roots are rich in coumarins, flavonoids, polysaccharides (up to 44% inulin and pectic substances), fatty acids and saponins . The sesquiterpene lactones present in the phytocomplex are responsible for the expectorant properties of this plant . Traditionally, extracts of the plant have been used to treat bronchial/tracheal catarrh and dry irritating cough in children . The extract used in the syrup is an Inula helenium roots aqueous extract, containing no less than 30% polysaccharides.
Plantago major is a plant of the Plantaginaceae family that is native to temperate areas of Asia and Europe. Aerial parts contain mucilage (up to 12%). In traditional medicine, the plant was employed as a treatment for cough related to inflammation of the upper respiratory airways . The plant is a quite effective soothing, moistening, expectorant for a dry irritable cough, because the mucous membranes are unable to produce the immune factor-rich mucous that coats, soothes and protects the membrane; thus, it becomes dry, inflamed and easily irritated . Plants belonging to the genus Plantago significantly attenuate cough [22,23]. The extract used in the syrup is a Plantago major aerial part aqueous extract, containing no less than 30% polysaccharides.
Helichrysum stoechas is an annual herb belonging to the family Asteraceae and is indigenous to the occidental Mediterranean regions . The extract used in the syrup is a Helichrysum stoechas aerial part aqueous extract, containing no less than 30% polysaccharides.
We performed a randomized, controlled double blind clinical trial to investigate the effects of KalobaTUSS®, an innovative syrup containing acacia honey and herbal extracts of Malva sylvestris, Inula helenium, Plantago major and Helichrysum stoechas, on acute cough in children aging 3-6 years. The extract of Malva sylvestris is titrated to 80% based on mucilage, and the extracts of Inula, Plantago and Helichrysum are titrated to 30% based on polysaccharides. The rich composition of the study syrup makes it suitable for use as a treatment for cough in children, because it forms a mechanical barrier on the mucosa. Mucilage is a complex of polysaccharide molecules that is part of different organs of the plant, mainly the aerial parts. When in contact with water, mucilage tends to swell and to create a jelly-like film on the contact surface. When mucilage contacts the respiratory mucosa, it adsorbs moisture present in the mucus, gels and forms bonds with the structure of the mucosa . In the presence of an inflammatory state, this film exerts a soothing and emollient effect on irritated mucosa: this action is defined as “demulcent” activity. Demulcent indicates a soothing and protective effect on the irritated or inflamed mucosal tissue .
The aim of this trial was to evaluate the efficacy and safety of KalobaTUSS® compared with the placebo on nocturnal and diurnal acute cough in children.