Inter-societal Delphi Consensus on the topical nasal treatments in Italy

Abstract

Topical nasal therapy is widely used in clinical practice by different specialists. However, it is multifaceted and still controversial. Namely, there is no consensus about the many aspects, and there needs to be specific guidelines.

Four independent experts involved 14 Italian scientific societies (concerning ENT, allergy, and pediatrics areas) to participate in generating an Intersocietal Delphi Consensus on this matter. Three iterative rounds collected experts (4 in the first round, 20 in the second round, and 45 in the third round) designed by the scientific societies based on their clinical expertise and documented scientific value. Thirty-four statements were discussed and voted on. At the second round, all statements accomplished a very high consensus grade (>95%). At the third round, many statements reached a high or very high grade of consensus (>70%). However, some statements did not obtain sufficient agreement. Consequently, there is a need to implement knowledge about this issue through educational initiatives and new studies conducted with a robust methodology.

In conclusion, topical nasal therapy deserves adequate knowledge as it is widespread and fruitful in managing upper respiratory diseases.

Introduction

The nose serves as the leading organ for respiration and performs many functions, including i) warming, humidifying, and filtering air; ii) guaranteeing innate and adaptive immune response to antigens; iii) smelling; iv) connecting with paranasal sinuses, Eustachian tuba, and nasopharynx; and v) contributing to speech.

The nose is the front door through which microbes, allergens, pollutants, and noxious agents penetrate the body. As a result, inflammation and infection can readily occur, starting from the nose and usually spreading to adjacent tissues. The most important diseases affecting the upper airways are rhinitis, rhinosinusitis, otitis, and nasopharyngitis [1].

The nose is a duct characterized by high resistance and turbulence of the inspired airflow. The nasal turbinate structure guarantees an ideal condition to warm and moisten the inspired air. Together, these mechanisms permit nasal physiological health [2]. However, several pathophysiologic mechanisms, including infection, inflammation, trauma, mechanical abnormalities, iatrogenic and physical stimuli, alter nasal physiology.

The most prevalent rhinitis phenotypes are acute viral rhinitis (the common cold) and allergic rhinitis. Although these nasal diseases have different etiopathogenetic mechanisms, both present similar symptoms, including nasal itching, sneezing, rhinorrhea, and nasal congestion.

The term rhinosinusitis replaced the sinusitis definition, as each sinus disease derives from initial rhinitis [3]. Rhinosinusitis may be acute or chronic if it lasts more than one month. Chronic rhinosinusitis (CRS) may present with nasal polyps (CRSwNP) or without (CRSsNP), as stated by the EPOS guidelines [4].

Acute otitis media (AOM) is a common disease mainly affecting children. It usually follows an acute upper airway infection [5]. Allergic rhinitis and turbinate hypertrophy are relevant risk factors for AOM [6].

Acute nasopharyngitis may also include tonsillitis (pharyngotonsillitis) and adenoiditis. This disease is commonly acute, and the cause is infectious, starting from the nose. Namely, the common cold includes nasopharynx involvement [7].

All these upper airway diseases share pathogenic mechanisms. In particular, mucus hypersecretion and defective mucociliary clearance cause mucus accumulation, interfering with airflow passage [8]. Nasal congestion due to vasodilation and turbinate edema also reduces the airflow passage [9]. Also, chronic inflammation causes turbinate hypertrophy, leading to nasal obstruction [10]. As a result, mucus stagnation promotes microbial overgrowth, favoring infection spreading to the sinuses and the middle ear [11]. Posterior rhinorrhea dripping into the pharynx and larynx triggers cough; this phenomenon is called post-nasal drip and defines the rhino-sinus-bronchial syndrome [12].

Namely, impaired nasal function significantly affects lower airways, mainly asthma and sleeping [13].

Consequently, a close and “dirty” nose favors, keeps and magnifies respiratory infections and inflammatory diseases [14]. As a result, an ideal therapy should “open and clean” the nose to ensure the health of the respiratory airways [14]. Thus, opening and cleaning the nose is the most simple and helpful remedy that may be pursued in everyday practice and at all ages.

Physical, medical, and surgical treatments may control upper airway diseases. Intranasal administration of active products represents the safest and most effective way to quickly obtain normal nasal patency, dampen inflammation, contrast pathogens, and consequently relieve symptoms.

Schematically, the types of administration of topical nasal treatments may be classified into three main groups: irrigation, nebulization, and drop instillation. The active compounds topically administrable include saline (hypertonic and isotonic) solutions, nonpharmacological agents (e.g., hyaluronic acid, resveratrol, xylitol, glycerol, glycyrrhetic acid, lactoferrin, oligoelements, vitamins, etc.), and drugs (e.g., antihistamine, corticosteroid, α–adrenergic, antibiotics). All upper respiratory diseases may be treated by topical therapy. Indeed, there is valuable evidence that topical nasal therapy is effective and safe.

However, topical nasal treatments are a debated issue. No ad hoc guideline provides general and specific recommendations on this matter, and some doctors are reluctant to prescribe them.

Therefore, an Intersocietal Delphi Consensus faced this theme by proposing a series of statements voted on by a panel of Italian experts on this topic. Namely, the Delphi method was an indirect, anonymous, and iterative way to obtain a consensus [15].

Materials and methods

Delphi method

A modified Delphi method was used to reach a consensus among Italian specialists, including otorhinolaryngologists, pediatricians, and allergologists.

The first round involved a restricted group of independent experts (four) constituting the steering committee that drafted a list of statements to be voted on.

The steering committee requested an interest in participating in a number of Italian scientific societies that are involved in the management of upper airway pathologies, particularly in otorhinolaryngology, pediatrics, and allergology.

The 14 scientific societies that have joined the project are reported in Table 1.

Table 1.

List of Scientific Societies participating to the Delphi Consensus and their Delegates who participated to the second round.

Berardi Carlo	Associazione Italiana Otorinolaringoiatri Libero Professionisti (AIOLP)
Borrelli Paolo	Associazione Allergologi Immunologi Italiani Territoriali e Ospedalieri (AAIITO)
Brunese Francesco P.	Società Italiana di Allergologia e Immunologia Pediatrica (SIAIP)
Casale Manuele	Società Italiana di Otorinolaringoiatria e Chirurgia Cervico Facciale (SIOeChCF)
Ciprandi Giorgio	Società Italiana di Allergologia e Immunologia Pediatrica (SIAIP)
Cristalli Giovanni	Società Italiana di Otorinolaringologia Pediatrica (SIOP)
Di Maria Domenico	Associazione Ospedaliera Italia Centromeridionale Otorinolaringoiatrica (AOICO)
Gelardi Matteo	Accademia Italiana di Citologia Nasale (AICNA)
La Mantia Ignazio	Società Italiana di Otorinolaringologia Pediatrica (SIOP)
Landi Massimo	Società Italiana per le Malattie Respiratorie Infantili (SIMRI)
Macchi Alberto	Accademia Italiana di Rinologia (IAR)
Marchese Ragona Rosario	Società Italiana di Otorinolaringoiatria e Chirurgia Cervico Facciale (SIOeChCF)
Marseglia Gian Luigi	Società Italiana di Allergologia e Immunologia Pediatrica (SIAIP)
Pagella Fabio	Società Italiana di Otorinolaringoiatria e Chirurgia Cervico Facciale (SIOeChCF)
Passali Giulio	Società Italiana di Rinologia (SIR)
Presutti Livio	Società Italiana di Otorinolaringoiatria e Chirurgia Cervico Facciale (SIOeChCF)
Rossi Oliviero	Società Italiana di Allergologia, Asma ed Immunologia Clinica (SIAAIC)
Tosca Maria Angela	Società Italiana di Allergologia e Immunologia Pediatrica (SIAIP)
Varricchio Attilio	Società Italiana di Pediatria Preventiva e Sociale (SIPPS)
Varricchio Alfonso M.	Associazione Italiana Vie Aeree Superiori (AIVAS)

The second round involved a group of 20 experts nominated and delegates by the scientific societies participating in this project (Table 1). These experts participated in a web-based round table discussion that was held in January 2024. During this remote meeting, the statements were discussed, and some changes were made. Subsequently, anonymously, these experts expressed their level of approval.

The third round consisted of administering the statements approved during the second round. For this purpose, a provider agency (Lingomed) set up a web platform that allowed anonymous voting of all statements. The panel of participants included 45 experts selected based on their clinical practice (at least ten years of specialized activity) and scientific value (at least ten publications in peer-reviewed journals on this topic in the last five years).

The participants anonymously voted using the same platform.

After collecting and analyzing the third round’s results, the steering committee discussed and approved them.

The Delphi consensus process was conducted between January 2024 and April 2024.

Delphi statements

Table 2 presents the list of the (previously approved) statements proposed to the participants in the third round. The statements are 34 and concerned the most common medical conditions that may benefit from intranasal therapy and the indications for diseases and compounds.

Table 2.

Statements, percentages of agreement grades (4+5), and standard deviations of score 4 + 5 concerning the second round.

Statement	% agreement (scores 4 + 5)	Mean score (SD)
1. The most widely adopted guidelines in Europe are ARIA for rhinitis, EPOS 2020 and EUFOREA for rhinosinusitis.	93%	4.7 (0.4)
2. Rhinitis can be classified into three main phenotypes: allergic, non-allergic (inflammatory and non-inflammatory), and infectious (viral and bacterial).	96%	4.6 (0.5)
3. The nasal spray is the most suitable administration device for treating acute rhinitis and rhinosinusitis.	61%	4.5 (0.5)
4. The nasal spray is the most suitable administration device for treating chronic rhinitis and rhino-sinusitis.	84%	4.5 (0.5)
5. The micronized nasal douche is the most suitable administration device for the treatment of nasopharyngitis.	75%	4.4 (0.5)
6. The operating mechanism of devices dedicated to inhalation therapy consists of the nebulization of a pharmacological solution, with subsequent dispersion of the micronized particles in the various anatomical sites of interest, depending on the mass median aerodynamic diameter (MMAD).	96%	4.7 (0.5)
7. Nasal irrigations are not part of inhalation therapy, as they lack dispersion power and cannot nebulize.	81%	4.5 (0.5)
8. Nasal irrigations, on the other hand, are ideal for mechanically removing secretions and activating mucociliary clearance.	94%	4.7 (0.5)
9. If used beforehand, nasal irrigations increase the therapeutic effectiveness of an inhalation treatment.	87%	4.5 (0.5)
10. Nasal irrigations are divided into three main types: i) gravity-fed (Lavonase-type bag dispenser - Nasir); ii) high-pressure and low-volume (Rinaqua nozzle syringe system – Rinoway; and wave bellows system Atomix, Eukin or Linfovir Iperwash and Isowash); iii) low-pressure and high-volume (Rinoway or XNaso).	89%	4.7 (0.5)
11. Inhaler devices dedicated to nasal cavity medication require a MMAD of more than 15 and less than 100 μm.	84%	4.5 (0.5)
12. The MADD of the atomized particles conditions their deposition at the airway anatomical sites, particularly: i) particles from 100 up to 60 μm stop at the Ostium-Meatal Complex (COM); ii) <60 and up to 30 μm arrive at the Spheno-Ethmoidal Complex (RSE); iii) <30 and up to 15 μm reach the Nasopharynx; iv) <15 μm and up to 10 μm reach the Pharyngeal-Laryngeal District; v) <5 μm reach the Lower Airways.	93%	4.6 (0.5)
13. The indication for topical nasal therapy in diseases of the nasal cavity and Nasopharynx is motivated by three main factors: the immunohistochemical characteristics of inflammation, which is superficial; the high bioavailability of the drugs against a reduced systemic absorption; and the reduction in side effects compared to systemic administration.	94%	4.7 (0.5)
14. Topical nasal therapy does not exclude systemic treatment, which is often synergistic.	98%	4.8 (0.4)
15. The most indicated molecule for treating allergic and non-allergic cell-mediated rhinitis is the topical corticosteroid, administered as a pre-dosed spray.	96%	4.6 (0.5)
16. In allergic and non-allergic rhinitis, topical antihistamines are indicated to reduce ‘irritative’ (i.e., histamine-dependent) symptoms.	78%	4.6 (0.5)
17. In allergic and non-allergic rhinitis, the fixed combination of topical corticosteroid and antihistamine is indicated to treat both ‘irritative’ and ‘inflammatory’ symptoms simultaneously.	83%	4.6 (0,5)
18. In viral infectious rhinitis, the most suitable molecules for treatment are antivirals (e.g., resveratrol and xylitol) during the first 10 days.	66%	4,3 (0.5)
19. The device indicated for viral infectious rhinitis is the pre-dosed spray.	66%	4.3 (0.5)
20. In bacterial infectious rhinitis, when symptoms persist beyond 10 days, or if they worsen after the first 5 days, topical antibiotics are the most indicated molecules, provided they are dose-dependent (quinolones, aminoglycosides, and macrolides).	57%	4.2 (0.4)
21. The device to be used in bacterial infectious rhinitis is the micronized nasal douche, manual and/or pneumatized.	71%	4.3 (0.4)
22. Ipratropium bromide is indicated in the treatment of ‘watery’ rhinorrhoea.	64%	4.6 (0.5)
23. Nasal sprays containing α-adrenergic are indicated in the treatment of nasal obstruction only for a few days (within 7 days) and above 12 years of age.	83%	4.5 (0.5)
24. Nasal sprays containing the topical corticosteroid are indicated in acute rhino-sinusitis, as they are capable of decongesting and reducing oedema at the COM and RSE sites, and of promoting mucociliary clearance and ventilation of the anterior and/or posterior rhino-sinus system.	82%	4.5 (0.5)
25. The molecule most indicated as the first therapeutic approach and as maintenance therapy for CRSwNP and CRSsNP is the topical nasal corticosteroid.	94%	4.6 (0.5)
26. The pre-dosed spray is the most suitable device for topical therapy of CRSwNP and CRSsNP.	89%	4.5 (0.5)
27. Nasal drops can be used in the topical therapy of CRSwNP and CRSsNP.	43%	4.4 (0.5)
28. Nasal irrigations with hypertonic saline solution can be used in the topical therapy of CRSwNP and CRSsNP in synergy with pre-dosed sprays containing topical corticosteroid	85%	4.4 (0.5)
29. In viral infectious rhino-pharyngitis, the most suitable molecule for topical treatment is an antiviral during the first 10 days, nebulized with a micronized, manual or pneumatic nasal douche.	57%	4.2 (0.4)
30. In bacterial infectious rhino-pharyngitis, when symptoms persist beyond 10 days, or if they worsen after the first 5 days, topical antibiotics are the most suitable molecules, provided they are dose-dependent (quinolones, aminoglycosides, and macrolides), nebulized with a micronized nasal douche, manual or pneumatic.	56%	4.2 (0.4)
31. In treating chronic adenoiditis, the most indicated molecule is topical corticosteroid for at least 4 weeks, nebulized with the Micronised Nasal Shower.	71%	4.4 (0.5)
32. High molecular weight hyaluronic acid is the molecule indicated in the treatment of remodeling and reparative regeneration of the nasal mucosa, both after surgery and after chronic inflammatory stress.	85%	4.4 (0.5)
33. To optimize the effectiveness of topical nasal therapies, it is essential to explain to the patient the correct way to use and maintain the various devices and the use of the various molecules.	94%	4.7 (0.4)
34. Patient engagement and personalized therapy are based on engaging the patient in decision-making and sharing the most suitable treatment.	94%	4.8 (0.4)

Delphi assessment

The Delphi Consensus Panel was requested to rate their agreement with each questionnaire statement using a 5-point Likert scale, ranging from 1 (strongly disagree) to 5 (strongly agree). Each expert provided individual and anonymous feedback on the statements, considering routine RRIs practice and clinical evidence. The number and percentage of participants scoring each item as 1–2 (disagreement) or 4–5 (agreement) was calculated.

The scientific committee then discussed the results in a virtual meeting. For each questionnaire statement, the consensus was considered to have been achieved based on the agreement (score 4–5) of at least 70% of the Consensus Panel and the successive acceptance of the steering committee.

The statistical analysis was descriptive and a mean score of the sum of 4+5 scores was calculated also considering the standard deviation.

Results

The first round served to draft a list of statements to administer to the panel of experts designed by the 14 Italian scientific societies involved in the management of upper respiratory disorders. This round included five independent experts who constituted the steering committee. The agreement among these steering committee members was entire, i.e., a 100 percent complete agreement (score 5) was reached for all 34 statements.

The second round included 16 other experts, designed by the scientific societies, who discussed and voted on the 34 statements. The agreement among these experts was very high: 90% complete agreement (score 5) for all statements and 95% considering also score 4, the results are reported in Table 2 and Figures 1–5.

Figure 1.

Distribution of agreement grades for the statements 1–8.

Figure 2.

Distribution of agreement grades for the statements 9–16.

Figure 3.

Distribution of agreement grades for the statements 17–24.

Figure 4.

Distribution of agreement grades for the statements 25–32.

Figure 5.

Distribution of agreement grades for the statements 33–34.

The third round considered a panel of experts selected by the steering committee. The voting results are reported in Figures 1–5.

Ten statements (1, 2, 6, 8, 13, 14, 15, 25, 33, and 34) obtained an agreement level >90%.

Nine statements (4, 9, 10, 17, 23, 24, 26, 28, and 32) obtained an agreement level between 80% and 89%.

Five statements (7, 11, 12, 16, 21, and 31) obtained an agreement level between 70% and 79%.

Consequently, 24 statements reached a positive consensus, such as >70%. Contrarily, ten statements did not achieve a sufficient agreement.

Discussion

Topical nasal therapy is ideal for administering solutions and active compounds in managing patients with upper airway diseases. In this regard, the prototypical model is the nasal lavage. The nasal lavage removes mucus, inflammatory cells, mediators, cytokines, pathogens, and harmful substances by washing the nasal cavity away. In addition, nasal lavage includes different administration methods, such as pre-dosed spray, nasal shower, irrigation, insuffiation, fumigation, and nebulization [16]. Therefore, nasal lavage is an umbrella definition that encompasses many methods and active compounds’ use. However, nasal lavage does not medicate nasal diseases, but simply washes. To medicate, other tools should be used, but there is congeries of devices and substances that are used in clinical practice, seldom inappropriately.

Consequently, this matter is complex and discussed. For these reasons, an Intersocietal Delphi Consensus may help define and clarify controversial aspects and suggest a pragmatic approach in clinical practice.

This document may be relevant as it was shared by a group of particularly qualified experts representing as many as 14 Italian Scientific Societies. Therefore, the results obtained can be applied at a national and interdisciplinary level. This opportunity also represented a virtuous, integrated, and multidisciplinary management model of prevalent diseases.

In particular, most statements achieved a good level of agreement, but as expected, some statements had a low consensus level. This fact is not surprising, as some aspects are controversial and require adequate attention.

The results of the vote at the third round of each statement is presently discussed in this document.

Statement 1 declared that the most widely adopted guidelines in Europe are ARIA for rhinitis, EPOS 2020, and EUFOREA for rhinosinusitis [3,4,17,18]. This statement had a 93% consensus, attesting that these guidelines are widely accepted and shared.

Statement 2 stated that rhinitis can be classified into three main phenotypes: allergic, non-allergic (inflammatory and non-inflammatory), and infectious (viral and bacterial), as reported in the literature [4,17]. This statement reached 96% agreement, confirming the high grade of consensus.

Statement 3 proposed that nasal spray is the most suitable administration device for treating acute rhinitis and rhinosinusitis [4,19,20]. However, this statement obtained only 61% of the consensus. This low agreement level conflicts with guidelines and the results of the second round. This discrepancy could depend on the belief that acute rhinitis is substantially the common cold most people retain and is self-resolving without treatment.

Statement 4 defined nasal spray as the most suitable administration device for treating chronic rhinitis and rhinosinusitis [4]. This statement obtained 84% agreement. This outcome might mean there is confidence in the need for a nasal spray for chronic conditions but not acute ones.

Statement 5 concerned the micronized nasal douche is the most suitable administration device for the treatment of nasopharyngitis [21–24]. The agreement was 75%. Probably, this low consensus depends on the fact that there is poor knowledge concerning the actual value of micronized douche in topically treating nasopharyngitis despite published studies [21–24].

Statement 6 proposed that the operating mechanism of devices dedicated to inhalation therapy consists of the nebulization of a pharmacological solution, with subsequent dispersion of the micronized particles in the various anatomical sites of interest, depending on the mass median aerodynamic diameter (MMAD). This statement was 95% agreed upon. The literature on this topic is well-known and accepted [25–27].

Statement 7 reported that nasal irrigations are not part of inhalation therapy, as they lack dispersion power and cannot nebulize. The agreement was 81%; inhalation therapy implies that a liquid should be transformed so that it can be dispersed and thus inhaled. This modality, therefore, requires the nebulization of a compound, which usually takes place using special instruments: nebulizers. Nasal irrigation consists of administering a given volume of liquid that is not changed in its state, i.e., always remains liquid [28]. Thus, irrigation does not belong to inhalation therapy. Some participants may not know this information.

Statement 8 declared that nasal irrigations, on the other hand, are ideal for mechanically removing secretions and activating mucociliary clearance. The consensus was 93%, which confirmed widespread belief about the benefit of nasal irrigation [29–31].

Statement 9 declared that nasal irrigations increase the therapeutic effectiveness of an inhalation treatment if used beforehand. This statement achieved 86% agreement, confirming the widely documented benefit of this method [32–34].

Statement 10 stated that nasal irrigations are divided into three main types: i) gravity-fed (Lavonase-type bag dispenser - Nasir); ii) high-pressure and low-volume (Rinaqua nozzle syringe system – Rinoway; and wave bellows system Atomix, Eukin or Linfovir Iperwash and Isowash); iii) low-pressure and high-volume (Rinoway or XNaso). The consensus was 89%. There was good knowledge concerning the types of irrigation, as also evidenced by several studies [4,35–37].

Statement 11 declared that inhaler devices dedicated to nasal cavity medication require an MMAD of over 15 and less than 100 μm. The agreement was 83%. There was probably incomplete knowledge about the physics of mass median aerodynamic diameters despite the topic being investigated adequately [25–27,38,39].

Statement 12 defined that the MADD of the atomized particles conditions their deposition at the airway anatomical sites, particularly: i) particles from 100 up to 60 μm stop at the Ostium-Meatal Complex (COM); ii) <60 and up to 30 μm arrive at the Spheno-Ethmoidal Complex (RSE); iii) <30 and up to 15 μm reach the nasopharynx; iv) <15 μm and up to 10 μm reach the Pharyngeal-Laryngeal District; v) <5 μm reach the Lower Airways. This statement had 83% of consensus. Although there is evidence about the relevance of the mass diameters, this matter still requires adequate information for some specialists [25–27,38,39].

Statement 13 stated that the indication for topical nasal therapy in diseases of the nasal cavity and nasopharynx is motivated by three main factors: the superficial immunohistochemical characteristics of inflammation, the high bioavailability of the drugs against a reduced systemic absorption, and the reduction in side effects compared to systemic administration. The agreement was 93%, attesting that these concepts are well-documented in the literature [40–43].

Statement 14 reported that topical nasal therapy does not exclude systemic treatment, which is often synergistic. The agreement was almost full (97%). This statement effectively proposed a concept that is rather obvious and shared [4,17].

Statement 15 asserted that the most indicated molecule for treating allergic and non-allergic cell-mediated rhinitis is the topical corticosteroid, administered as a pre-dosed spray. Consistent with the previous statement, this statement also had a high agreement (95%) and is well recognized by guidelines [4,17,18].

Statement 16 expressed that in allergic and non-allergic rhinitis, topical antihistamines are indicated to reduce ‘irritative’ (i.e., histamine-dependent) symptoms. The consensus was 78%. Some participants believe symptom occurrence depends on several mediators that exceed the mere histamine effects. However, there is a consideration of the relevance of antihistamines as a valuable option in managing “histaminedependent” symptoms [44,45].

Statement 17 stated that in allergic and non-allergic rhinitis, the fixed combination of topical corticosteroid and antihistamine is indicated to simultaneously treat both ‘irritative’ and ‘inflammatory’ symptoms. The agreement was 82%. There is consolidated evidence that this association is effective, but some experts are not very convinced about its complete effectiveness despite several studies [17,47,48].

Statement 18 expressed that in viral infectious rhinitis, the most suitable molecules for treatment are antivirals (e.g., resveratrol and xylitol) during the first ten days. The consensus was 66% A considerable number of experts considered that the use of topical antivirals is not indicated in this clinical condition. The robustness of the evidence is likely not particularly high in studies that have explored this aspect because they were all conducted in Italy, and the methodology was not particularly robust [49–52].

Statement 19 declared that the device indicated for viral infectious rhinitis is the pre-dosed spray. The agreement was 66%. Also, in this case, some panelists believed that this statement had no sufficient evidence and, consequently, expressed their perplexity on this issue, as recently outlined [53].

Statement 20 affirmed that in bacterial infectious rhinitis, when symptoms persist beyond ten days or if they worsen after the first five days, topical antibiotics are the most indicated molecules, provided they are dose-dependent (quinolones, aminoglycosides, and macrolides). The agreement was low: 56%. Many participants may have misunderstood the meaning of the statement, believing that topical therapy should substitute systemic treatment. Severe infections require adequate systemic antibiotics, but there is evidence that topical antibiotics could also effectively treat this condition [54,57].

Statement 21 stated that the device to be used in bacterial infectious rhinitis is the micronized nasal douche, manual and/or pneumatized. The consensus was 71%. This matter is strictly the domain of the ENT specialist; in fact, studies have been conducted in that field [54,55,58]. As a result, the other specialists need to familiarize themselves with this subject.

Statement 22 stated that ipratropium bromide is indicated in the treatment of ‘watery’ rhinorrhoea. The consensus was 64%. For some participants, little is known about this molecule, and few studies have been conducted on it. However, a recent meta-analysis has again reconsidered this molecule [59].

Statement 23 proposed that nasal sprays containing a-adrenergic are indicated for treating nasal obstruction only for a few days (within seven days) and for children above 12 years of age. The agreement was 82%. There is awareness that decongestants are effective, but they are burdened with significant side effects, and the Italian regulatory agency (AIFA) has proscribed them for children under the age of 12. However, use must be limited in time to avoid even irreversible damage [60,61].

Statement 24 declared that nasal sprays containing the topical corticosteroid are indicated in acute rhinosinusitis, as they can decongest and reduce edema at the COM and RSE sites and promote mucociliary clearance and ventilation of the anterior and/or posterior rhinosinus system. The consensus was 82%. This point has been underlined in the EPOS guidelines [4]. However, some participants (not ENT) may not know this recommendation.

Statement 25 stated that the topical nasal corticosteroid is the molecule most indicated as the first therapeutic approach and as maintenance therapy for CRSwNP and CRSsNP. The agreement was 94%. This high consensus endorsed the widespread dissemination of EPOS guidelines and literature [4,62].

Statement 26 reported that the pre-dosed spray is the most suitable device for topical therapy of CRSwNP and CRSsNP. The agreement was 89%. Also, for this statement, the EPOS recommendations are well-known and adopted [4].

Statement 27 affirmed that nasal drops can be used in the topical therapy of CRSwNP and CRSsNP. The agreement was 43%. However, this statement had to be considered adversely. Namely, there is evidence that nasal drops quickly slide out of the nasal cavity after instillation, so they cannot exert a local therapeutic effect [21]. However, nasal drops are still popular, as many doctors continue to prescribe them without knowing this drawback.

Statement 28 expressed that nasal irrigations with hypertonic saline solution can be used in the topical therapy of CRSwNP and CRSsNP in synergy with pre-dosed sprays containing topical corticosteroid. The consensus was 85%. Indeed, the EPOS guidelines recommend nasal irrigations for treating both CRS phenotypes [4].

Statement 29 stated that in viral infectious rhino-pharyngitis, the most suitable molecule for topical treatment is an antiviral during the first ten days, nebulized with a micronized, manual or pneumatic nasal douche. The agreement was 56%. This result consisted of other outcomes concerning the use of topical antivirals. There is widespread belief that viral infections do not require specific treatments, and antivirals, such as xylitol or resveratrol, are not indicated despite positive literature [49–52,63].

Statement 30 expressed that in bacterial infectious rhino-pharyngitis when symptoms persist beyond ten days or if they worsen after the first five days, topical antibiotics are the most suitable molecules, provided they are dose-dependent (quinolones, aminoglycosides, and macrolides), nebulized with a micronized nasal douche, manual or pneumatic. The consensus was 56%. Likewise, statements 20 and 21 need to be revised for a better agreement. This statement might generate a misunderstanding about the use of antibiotics, as systemic antibiotics use is settled in clinical practice. A recent review pointed out that solid evidence was lacking for nebulized antibiotics for treating upper respiratory infections [64]. However, there is conflicting evidence for systemic antibiotics, as recently considered by a meta-analysis [65].

Statement 31 declared that in treating chronic adenoiditis, the most indicated molecule is topical corticosteroid for at least 4 weeks, nebulized with the Micronized Nasal Shower. The agreement was 71%. The degree of consensus was not particularly high despite the fact that many studies and documents support this recommendation [66–69].

Statement 32 declared that high molecular weight hyaluronic acid is the molecule indicated in the treatment of remodeling and reparative regeneration of the nasal mucosa, both after surgery and after chronic inflammatory stress. The agreement was 84%. Evidence shows that hyaluronic acid at high volume effectively restores mucosal structure and function [4,70–73].

Statement 33 stated that to optimize the effectiveness of topical nasal therapies, it is essential to explain to the patient the correct way to use and maintain the various devices and the use of the various molecules. The agreement was 93%. Indeed, there is convinced belief that correct use and adequate compounds are fundamental requirements for treatment efficacy and safety [74–76].

Statement 34 expressed that patient engagement and personalized therapy are based on engaging the patient in decision-making and sharing the most suitable treatment. The consensus was 93%. Patient engagement is of paramount relevance in managing every disease, so this aspect is critical for nasal conditions [78,79].

The comparison of the results obtained during the second round and the third allows to draw some relevant considerations. The second round achieved a very high consensus probably as it derived from a face-to-face interaction and the possibility to discuss and modify the initial proposal (first round). An in depth evaluation of the statement and the possibility to reflect on the contents probably was determinant for obtaining very high agreement. Contrarily, the third round reflected an immediate evaluation of the statement that was based on clinical practice. Moreover, it has to be underlined that this initiative involved specialists belonging to different areas so it is likely that some specialists are unfamiliar with some practical aspects or do not adequately know the peculiar literature on some topics. As a result, it is not particularly surprising to note this discrepancy between second and third round outcomes. Surely, these findings obligate to think that there is the need to implement the knowledge grade on specific issues, such as topical antibiotics, antiviral agents, and devices. Indeed, these results underscored a relevant gap between participants. However, there is the need to increase the level of evidence on these topics by performing new studies conducted with robust methodology. Effectively, some topics were investigated by a few studies performed only in Italy and usually monocentric.

This Delphi Consensus did not, furthermore, consider specific issues, including bacteriotherapy (administration of “good” bacteria), halotherapy (dry salt inhalation), thermal therapy, dilators, intranasal filters, and other topical remedies. Further studies should address these topics.

The present Delphi Consensus had strength because 14 scientific societies endorsed this project and cover three main specialized areas: ENT, allergy, and pediatrics. In addition, the participants’ documented clinical expertise and scientific value were considered when selecting them. As a result, the outcomes represented valuable experts’ opinions. In addition, the Delphi method consisted of three iterative rounds, guaranteeing a more careful evaluation of the statements.

However, this Delphi Consensus had limitations, including the results reflecting participants’ personal knowledge and clinical expertise, the need for a systematic review of the literature concerning this issue, and the limited number of participants to the third round. On the other hand, the present statements may be fruitful in clinical practice as there are no specific guidelines on this topic. In this regard, further detailed studies on administration devices, molecules, and schedules should follow the present initiative. This new information should serve to implement Intersocietal guidelines and promote educational initiatives. In addition, another aspect deserving adequate attention is the role of topical nasal therapy in the self-management. This aspect is relevant as there is growing interest in this approach [79]. Also, telemedicine could implement a medical supervision of self-administered topical remedies [80].

Conclusion

In conclusion, topical nasal therapy is a complex and debated matter, but it is widespread and applied to various medical conditions managed by different specialists. There is also the need to implement the knowledge of this topic and provide new and robust evidence about this therapy. There is a shared belief that topical nasal therapy is a meaningful option in managing upper respiratory diseases as it may significantly improve other therapeutical strategies.

Availability of data and material

For the current study, the data are available from the corresponding author upon reasonable request from the requester(s).