Children cough is a common reason leading parents to seek medical and it is a real dare for pediatricians. Cough is probably the most bothersome symptom associated with upper respiratory tract infections for children and their parents. Frequently cough produces distress and sleep disorders to the whole family [1].
In most cases it is self-restrained, but its perseverance sometimes is exasperating and it can worsen quality of life and common social participation [2].
Influence of persistent children cough on family’s life can create growing discomfort. Indeed, children with acute cough may experience transient disability which provokes losing of parents’ work and absence of children during school time, so increasing global community cost [3]. Generally, parents’ concerns increase when children’s cough lasts for more than a week. Consequently, often occurs that parents seek for a medical consult with requirement of drug treatment, though most of antitussive drugs lack of evidence of effectiveness and safety [4].
Despite of the inappropriate prescription of antitussive pharmacological treatment in children has been reduced, pediatrics prescribing attitudes do not still always are reflecting accurate treatment of cough [2]. Furthermore, pediatric approach is always compromised by parental exaggerate perception of symptoms and usual consequent requirement of pharmacological prescription of antibiotics, that they consider the appropriate and effective therapeutic option for cough [5]. Epidemiological data indicate that cough occurring in children produces more anxiety than in adult people, and a lot of people think of this symptom as “a disease”. A recent Italian survey confirms this view suggesting that some inclination of pediatricians therapeutic should be modified in favor to realize a better control of cough in children and to reduce its impact [2]. Moreover, it often happens that attempting to treat cough, children are administered with over-the-counter products having little or no scientific evidence of proven efficacy [6].
The World Health Organization identified honey as a possible demulcent care for cough [7,8]. Demulcent is called a substance which covers the throat and reduces pain when mucous is irritated. Demulcent products are based essentially on sugar and they act as adjuvant to attenuate cough related to dry throat by covering receptors triggering cough or through increase of saliva and swallowing, reducing cough reflex [9].
Administration of honey at time to sleep to relief of cough in child and sleeping difficulty is believed by parents as more desirable than intake of drugs such as diphenhydramine or dextromethorphan or rather than placebo [10,11].
In 2018 the Cochrane Collaboration reviewed six randomized controlled and three not controlled clinical studies carried out in children and boys aging 1-18 years and investigating on use against acute cough of honey, alone or in association with antibiotic drugs in comparison with no treatment, placebo, syrups containing honey or free-honey over the counter antitussive. Authors’ conclusions were that honey alleviates cough with a greater size effect with respect to diphenhydramine, placebo or no treatment and with poor or no difference in comparison to dextromethorphan. Moreover, honey reduced time period of coughing in a batter way compared to salbutamol or placebo with no adverse effects [12].
Due to above assumptions, it seems interesting to evaluate a different approach to treat cough, instead of pharmacological drugs, for instance a mechanical and non-pharmacological intervention. The safeguarding effect of a mechanical barrier at throat level may be considered a well founded therapeutic perspective acting through an indirect anti-inflammatory activity, able to reduce harm produced by irritant agents or microbes. This protective activity can be acquired with the association of natural substances: honey and plant extracts.
On the light of the above considerations and since number of accessible pediatric antitussive products is reduced because of lack of proof of efficacy, a cough syrup for children (KalobaTUSS®) based on acacia honey in combination with moieties derived from Malva sylvestris extract, Inula helenium, Plantago major extract, Helichrysum stoechas to be clinically tested on persisting cough of children, has been developed. This syrup is a Medical Device class IIa, classified in agreement with the Directive 93/42/EC.
Malva sylvestris is a biennial–perennial herbaceous medicinal plant domestic in North Africa, Asia and Europe also called with the name “common mallow”. It has been used along in folk medicine for its mucus formed of flavonoids and polysaccharides.
Traditionally, M. sylvestris is used for the treatment of various infections or diseases, including cold, cough, tonsillitis, bronchitis. The entire plant exhibits beneficial properties, and it has been used along in folk medicine for its mucus due to the leaves and flowers rich of flavonoids and mucillages. Mucilage is present in the percentage of 6-8% in its leaves containing high molecular weighing acidic polysaccharides of the rhamnogalacturonan type with, situated in epidermal cells [13]. European Medicinal Agency (EMA) in 2018 assessed its traditional use as a “demulcent preparation for the symptomatic treatment of oral or pharyngeal irritation and associated dry cough” [14,15].
Inula helenium (Elecampane) is a perennial herbaceous plant of the Asteraceae family, native of England and Europe, growing also in North and East of Unites States, Canada Asia, India and Siberia. This plant was used for its medicinal properties to treat cough [16].
Inula helenium roots are rich of coumarins, flavonoids, polysaccharides (up to 44% inulin and pectic substances), fatty acids and saponins [17]. The sesquiterpene lactones present in the phytocomplex are responsible for the plant's anti-inflammatory and expectorant properties [18]. Traditionally, extracts of the plant have been used for bronchial/tracheal catarrh and dry irritating cough in children [19].
Plantago major is a plant of Plantaginaceae family native of Asian and European temperate areas. Aerial parts contain iridoids as the main constituents, also are present mucilage (up to 12%), flavonoids, carbohydrates, alkaloids, amino acids, tannins, lipids, steroids, saponins, proteolytic enzymes and vitamins. In traditional medicine the plant was employed against cough related to inflammation of upper respiratory airways [20]. The plant is a quite effective soothing, moistening expectorant remedy for a dry irritable cough because the mucous membranes are lacking in their production of immune rich mucous that coats, soothes and protects the membrane - thus it gets dried out, inflamed and easily irritated [21]. Studies demonstrated that plants belonging to the genus Plantago can significantly attenuate cough [22,23].
Helichrysum stoechas is an annual herb belonging to the family of Asteraceae indigenous in the occidental Mediterranean regions [24]. Extract of aerial parts contains mainly isomers of caffeoylquinic and dicaffeoylquinic acids, apigenin glucosides, quercetin and kaempferol. The stems and the flowers of the plant showed to have expectorant, sudorific and laxative properties and they are used for the treatment of common cold [25].
We investigated through a randomized, controlled double blind clinical trial the effects of KalobaTUSS®, an innovative syrup containing acacia honey and herbal extracts of Malva silvestris, Inula helenium, Plantago major and Helichrysum stoechas, on persistent cough in children aging 3-6 years. The extract of Malva silvestris is titrated to 80% on mucillages, and the extracts of Inula, Plantago and Helichrysum are titrated to 30% on polysaccharides. The rich composition of the study syrup makes it suitable for use in the treatment of children’s cough, acting as a mechanical barrier on the mucosa.
Aim of this trial was to evaluate the efficacy and safety of KalobaTUSS® in comparison with placebo on nocturnal and diurnal persistent cough in children.