The human respiratory system processes approximately 12,000 litres of air per day, enabling essential gas exchange but also exposing the lungs to harmful agents such as microorganisms, irritant gases, particulate matter, allergens, medications, foreign bodies, and radiation. These can enter primarily via inhalation or aspiration, and less frequently through internal pathways.

Defence mechanisms include physical barriers, mucus production, cough, macrophages, and antimicrobial molecules.

Cough is a protective reflex that expels harmful substances from the airways. However, when persistent, it may lead to physical complications and exacerbate underlying diseases, impairing quality of life.^1,2

Management ranges from traditional herbal preparations to synthetic medicines. Infusions containing honey with lemon, ginger, ivy, and eucalyptus have long been used for their expectorant and soothing properties, while steam inhalation with thyme can promote airway clearance.

Synthetic medicines such as

• dextromethorphan suppress dry cough;
• expectorants like guaifenesin facilitate mucus clearance in productive cough;
• antihistamines may be useful in allergic causes; and
• bronchodilators are essential for obstructive conditions such as asthma and chronic obstructive pulmonary disease (COPD).^3-7

Physiology, Aetiology, and Classification of Cough

Cough is an essential reflex that protects the respiratory tract by expelling foreign material and secretions. It may be voluntary or involuntary, triggered by mechanical or chemical stimulation of receptors in the bronchial tree.⁸

Effectiveness depends on the coordination of the cough reflex, adequate expiratory force, and intact mucociliary function. While usually transient, it may cause complications such as headache, tussive syncope, arterial dissection, splenic rupture, insomnia, and anxiety.⁹

By duration, cough is classified as

• acute (<3 weeks),
• subacute (3-8 weeks), or
• chronic (>8 weeks).¹⁰

Common causes include viral respiratory infections, asthma, COPD, bronchiectasis, and pneumonia.

Subacute cough is often post-infectious, whereas chronic cough is associated with upper airway cough syndrome (UACS), non-asthmatic eosinophilic bronchitis (NAEB), gastro-oesophageal reflux disease (GORD), and cough-variant asthma.

The cough reflex protects the lower airways by preventing the entry of harmful particles (Figure 1). It is triggered when mucosal receptors detect irritants, initiating three phases: deep inspiration, compression with glottic closure, and rapid air expulsion.^11-13

Receptors are located in the larynx, trachea, and bronchi, including rapidly adapting receptors (RAR), slowly adapting receptors (SAR), and C-fibre nociceptors.¹² These respond to chemical stimuli via TRPV1 and TRPA1 channels, releasing neuropeptides that induce bronchoconstriction and secretion.

Sensory input is processed in the nucleus tractus solitarius and cortex, allowing partial voluntary control, while the efferent pathway activates respiratory muscles, the larynx, and pelvic sphincters during cough.^13,14

Acute and subacute cough are often associated with upper respiratory tract infections such as colds, influenza, acute sinusitis, and bronchitis, as well as with asthma or COPD exacerbations, or with irritants such as tobacco smoke, and chemicals.

Viral infections can sensitise cough receptors, prolonging symptoms post-recovery.

Chronic cough is more commonly linked to UACS, GORD, asthma, NAEB, COPD, and use of certain medications such as angiotensin-converting enzyme (ACE) inhibitors, which cause persistent cough in up to 20% of patients.^10,14,15

By character, cough may be dry or productive. A productive cough facilitates mucus clearance, while a dry cough is often more irritative. Expectorated sputum may occasionally contain blood (haemoptysis) or vary in appearance depending on the underlying condition.

Cough Treatment

Management depends on aetiology and may involve synthetic or natural medicines acting at central, peripheral or mixed levels^16-29 (Table 1).

The treatment includes:

• Antitussives, which inhibit the cough reflex and are recommended for dry cough only.
• Expectorants, which stimulate mucus clearance in hypersecretory conditions, though their efficacy remains debated.³⁰
• Mucolytics such as acetylcysteine and carbocisteine, which reduce mucus viscosity to facilitate expulsion.³¹
• Bronchodilators, which relax bronchial smooth muscle, especially in asthma and COPD.³²

Non-pharmacological measures include positive expiratory pressure (PEP) therapy, mechanically assisted cough, and high-frequency chest oscillation, useful in chronic conditions such as cystic fibrosis and COPD.³¹

Home strategies include avoiding environmental pollutants, maintaining a healthy diet, using humidifiers or steam vaporizers, engaging in physical exercise, and nasal irrigation with saline or seawater.²⁸

Paltomiel^® is a syrup indicated as an adjuvant in productive cough, widely used in Chile in adults and children over 2½ years of age. It contains extracts of Eucalyptus globulus, Persea americana leaves, and Pimpinella anisum seeds (the latter absent in the paediatric formula), with honey as a demulcent to enhance respiratory benefits.

Although it may interact with anticoagulants, antidiabetics, and monoamine oxidase inhibitors, and is contraindicated in severe liver disease or hypersensitivity to its components³³, its use is primarily based on traditional knowledge, as no clinical trials have evaluated its efficacy as a mixed formulation. However, its individual components have strong scientific support and are included in medical patents for antimicrobial, expectorant, anti-inflammatory, and antitussive properties.

In the Chilean market, most herbal cough syrups are based on Hedera helix (ivy), but Paltomiel^® differs in its unique combination of active ingredients, offering a distinct therapeutic profile for productive cough.

This study aimed to describe its composition, review the scientific evidence available for its components, and assess the perceptions of physicians and users regarding its effectiveness and tolerability, considering its decades-long presence in the national market.

To gather data on the use of mixed formulations of eucalyptus leaf extract and/or avocado leaves and/or anise seeds and/or honey and similar products. We evaluated Paltomiel^®, and two structured surveys were designed: one for the target public (users) and another for practising physicians in Chile.

Sample Size Calculation

Sample size was determined using the IdSurve eucalyptus leaf extract, avocado leaves, anise seeds, and honey using a simple-size calculator (https://www.idsurvey.com/es/simple-size-calculator/), assuming a 5% margin of error, 95% confidence level, standard deviation of 50, a 5% attrition rate, and a total population of approximately 20 million potential users in Chile.

For the medical group, an estimated population of 1,200 physicians was considered, based on the 2024 report of the Chilean Health Superintendency regarding medical specialties.³⁴ This calculation yielded statistically significant sample sizes of 144 physicians and 385 users.

Survey Administration

Participants were contacted to complete an anonymous, structured questionnaire evaluating their perception of the product’s safety and effectiveness.

Surveys were designed in-house but adapted from established, validated instruments, including the Treatment Satisfaction Questionnaire for Medication (TSQM) and the Medication Satisfaction Questionnaire (MSQ), which assess patient perception of the effectiveness and satisfaction with medical products.^35,36

Survey Structure

The physicians’ survey was divided into five sections:

1. Brief description of the survey’s scope.
2. General physician data (speciality, years of experience, product awareness) - anonymous.
3. Use and prescription of the product.
4. Product evaluation (effectiveness, toxicity, tolerability).
5. General opinion (recommendations and suggestions).

The users’ survey also comprised five sections:

1. Brief description of the survey’s scope.
2. General user data (age, sex, product awareness) - anonymous.
3. Product evaluation (awareness, effectiveness, toxicity, tolerability).
4. Impact of the product on well-being.
5. Overall perception (other effects, satisfaction, comments).

Certain questions allowed for open-text responses, while others employed a 1-to-5 rating scale.

The research team developed draft versions of both questionnaires, based on items from the TSQM and the MSQ.

Face and content validity were assessed by two healthcare professionals with expertise in respiratory medicine and phytotherapeutic products, who independently reviewed the wording, relevance, and completeness of all items. Their comments were incorporated to refine the questionnaires before their online dissemination.

Statistical Analysis

Data from the physicians’ and users’ questionnaires were exported to a spreadsheet and analysed using descriptive statistics. All variables were categorical and are presented as absolute and relative frequencies (%). Missing data were treated as “no response” (NR) and reported as such in the results, tables, and figures. No inferential statistical tests or data imputation procedures were performed.

Ethical Considerations

This study used an anonymous, voluntary online survey and did not collect personally identifiable data. In accordance with national regulations for non-interventional survey-based research, formal ethics committee approval was not required.

All participants provided electronic informed consent before completing the questionnaire and were informed of the study's objectives, the voluntary nature of participation, and the confidentiality of their responses.

The surveys were conducted between December 29^th, 2024, and March 6^th, 2025, targeting physicians and adult users (>18 years) via various direct and digital channels. A total of 144 physicians and 394 users participated.

Physicians’ Perception

Professional profile

Most respondents specialised in general medicine (69,4%), followed by paediatrics (9,0%), family medicine (4,9%), geriatrics (2,8%), and pneumology (2,1%). A further 11,8% represented other specialties less directly associated with respiratory diseases. Regarding professional experience, 67% had more than 10 years of practice, 15% had 5-10 years, and 18% had fewer than 5 years.

Product Awareness and Prescription

Paltomiel^® was known to 96,5% of physicians, and 83,6% had prescribed it—either occasionally (52,9%) or regularly (30,7%). Among non-prescribers, the main reasons cited were a preference for other treatments (63,6%), infrequent management of respiratory cases, or uncertainty regarding the efficacy of these treatments (Figure 2).

Perceived Effectiveness

• For a productive cough, 80% rated the syrup as very effective or extremely effective.
• For dry cough, 75% gave a positive rating, most frequently as moderately effective.
• For respiratory congestion, 67,1% considered it effective, with 29,3% describing it as moderately effective.

Overall effectiveness was rated between moderately and extremely effective by 87,1% of respondents, with the highest category (extremely effective) selected by 33,6% (Figure 3).

Tolerability and Safety

Organoleptic tolerability (taste, sweetness, consistency) was assessed as good or excellent by 81,4% of physicians, and no reports of poor tolerability were recorded. Most (96,4%) reported no relevant adverse effects, with only four cases of mild diarrhoea.

Intention to Continue Prescribing the Syrup

A total of 80,7% stated they were very likely or likely to continue prescribing the product, and 80% would recommend it to colleagues. Among those who did not recommend it (17,9%), the most common reasons were the absence of specific scientific evidence and limited demonstrated efficacy.

Users’ Perception

Demographics and Respiratory History

Among 394 respondents, 65,4% were female, with a mean age of 43,5 ± 14,2 years. The most frequently reported respiratory conditions were bronchitis (62,4%), asthma (13,7%), pneumonia (6.6%), and COPD (1,0%).

Product Awareness

A total of 95,7% were aware of the syrup, and 69,8% were aware of both adult and paediatric formulations.

Perceived Efficacy

The syrup was considered useful for reducing cough by 93,9% of respondents, with 77,2% rating it as very or extremely effective.

Regarding cough improvement, 82% reported a moderate or significant improvement, while only 3,4% perceived no change.

For throat discomfort relief, 93,1% gave a positive assessment, with 44,4% rating it extremely effective.

In mucus expulsion, 91,5% found it effective, and 88,1% rated it positively for overall relief of respiratory symptoms (Figure 4).

Adverse Events and Tolerability

The findings were the following:

• 1,3% reported any adverse reaction,
• 97,9% indicated no side effects,
• 54,2% reported improved sleep quality during respiratory illness episodes when using the syrup.

Overall Satisfaction

Satisfaction was high, with 80,4% describing themselves as very or extremely satisfied and only 2,1% expressing dissatisfaction.

Open-ended comments frequently praised the syrup’s effectiveness, natural composition, and regular use within families, though some noted excessive sweetness or greater benefit in early stages of cough.

In both the Chilean and international markets, there is a wide range of standardized natural pharmaceutical products and mixed formulations marketed for various pathologies, either as first-line treatments or as adjuvants. Many of these products lack robust scientific support or clinical studies to substantiate their efficacy and/or safety. Nonetheless, they are widely used and highly valued by the public due to long-standing traditional use.

For such products, it is essential to compile supporting scientific evidence, obtain expert-opinion certifications, conduct perception studies, and, where feasible, conduct at least limited clinical trials to strengthen confidence in their therapeutic role.

In Chile, most herbal cough syrups are based on Hedera helix (ivy).⁵ Paltomiel^® combines several natural active ingredients, each with documented efficacy, although no specific clinical trials have evaluated the exact formulation.

The natural components in the studied formulation have traditionally been used for respiratory conditions due to their anti-inflammatory, expectorant, antitussive, and antispasmodic properties:

• Eucalyptus globulus contains eucalyptol (1,8-cineole), which has mucolytic, anti-inflammatory, and bronchodilatory effects that improve lung function and relieve cough.^37,38
• Pimpinella anisum provides carminative, antioxidant, and antitussive effects that can help reduce bronchial irritation.^39,40
• Persea americana contributes flavonoids with anti-inflammatory and antioxidant activity, although it has been less extensively studied.
• Honey enhances therapeutic action through antimicrobial and demulcent properties, reducing night-time cough and improving sleep.⁴¹
• Hedera helix, although not an ingredient in Paltomiel^®, is referenced for comparison, as its triterpenic saponins act as mucolytics and bronchodilators.⁷

Survey findings strongly support these properties, indicating high levels of awareness and acceptance among physicians: 96,5% were familiar with the product, and more than 80% had prescribed it.

Effectiveness was remarkably well rated for productive cough (80%) and to a slightly lesser extent for dry cough (75%).

Organoleptic tolerability was judged good or excellent by 81,4%, and adverse events were rare.

Willingness to continue prescribing was also high (80%).

The main barrier to broader recommendation was the absence of formulation-specific clinical evidence, which aligns with the recognised need for formal validation of phytotherapeutic combinations.

From the users’ perspective, perceptions were similarly positive. Almost all knew the product, and over 93% considered it effective against cough. It was also valued for relieving throat discomfort (93,1%), aiding mucus clearance (91,5%), and improving general respiratory symptoms (88,1%). Notably, 54,2% reported improved sleep quality during illness episodes, highlighting honey's demulcent properties. Adverse effects were minimal, with 97,9% reporting none.

These findings position the formulation as a well-tolerated, widely accepted phytotherapeutic alternative for productive cough and related respiratory symptoms. However, the absence of randomised controlled trials (RCTs) means that its efficacy cannot yet be quantitatively compared with other available treatments, such as Hedera helix-based syrups or synthetic expectorants.

Conducting RCTs across Phases I-IV would allow rigorous evaluation of its safety, efficacy, and comparative effectiveness.

In addition, given its anti-inflammatory and expectorant properties, future research could explore its role as a complementary treatment for viral respiratory infections, including post-viral cough syndromes and post-COVID-19 bronchial inflammation, in which persistent cough and airway irritation are common.^42,43