At the beginning of the school year and with the arrival of winter, young children are prone to illness from upper respiratory tract infections (URTI), which can range between six and eight episodes a year. Most of these colds tend to resolve spontaneously within a week or two. However, 5–10% of patients develop bacterial complications, including acute rhinosinusitis (ARS) and acute otitis media (AOM). It is estimated that between 6% and 13% of children will have had an episode of ARS by three years of age [1
]. Although it is usually a self-limited disease, it becomes one of the most frequent causes of antibiotic prescription in childhood, behind otitis and tonsillitis [3
]. ARS is mainly characterized by the excessive prolongation of the symptoms of the common cold beyond 10 days, with difficulty in nasal breathing, mucopurulent discharge, persistent cough predominantly at night, difficulty in falling asleep, loss of appetite, and sometimes vomiting of phlegm [5
]. Often there is a spontaneous improvement after conservative treatment with hypertonic saline sprays or irrigations [6
]. When the general condition is more affected, or in young children, it may be necessary to use antibiotics [7
]. Some patients lengthen the usual colds over and over again, causing recurrent ARS (RARS), which do not usually cause fever, and thus predisposes some parents not to come to the consultation and ends up turning into chronic rhinosinusitis (CRS). They are patients who have persistent green mucus, significant nasal obstruction, difficulty falling asleep and a persistent cough, although with little effect on the general condition. This persistent inflammatory state contributes to the enlargement of the local lymphatic tissue, such as the palatine tonsils and the adenoids, leading to a space conflict [8
]. They often present with worsening clinical attacks or other complications, such as recurrent acute otitis media (RAOM), otitis media with effusion (OME), persistent nasal obstruction (PNO) and recurrent wheezing or childhood asthma (SR) [9
]. The diagnosis of ARS is not straightforward and can be considered as a clinical challenge, as it is generally performed on subtle clinical grounds, with the absence of specific tests. It is difficult to distinguish when a viral process has become bacterial [11
]. Routine imaging is not recommended precisely because of its lack of specificity [12
]. Pharyngeal exudates are also not useful since they do not correlate with sinus exudates. The most common bacterial species are: streptococcus pneumoniae, Hemophilus influenzae, Moraxella catarrhalis, and streptococcus pyogenes [15
]. The treatment of RARS and CRS is controversial; several types of antibiotics have been used with limited results, since after initial improvement, patients eventually relapse [9
]. Corticosteroid irrigations through the nasal passages and oral corticosteroids have also been used based on the few studies conducted in children with different results [1
]. Mucolytics, expectorants, and antihistamines have not been shown to be helpful [21
]. The pneumococcal vaccine does not appear to have decreased the incidence of ARS [13
]. In the last case and after having failed with the pharmacological treatment, surgical intervention is usually indicated, with the oblation of the adenoids and/or the palatine tonsils, without the results being entirely satisfactory [23
There are more and more studies that demonstrate the anti-inflammatory effects of the Mediterranean diet [24
], which has allowed us to develop the hypothesis that recurrent inflammatory episodes of the respiratory mucosa are closely related to the abandonment of the traditional diet. This anti-inflammatory action is based on the reduction of pathologies related to oxidative stress, chronic inflammation, and the inflammatory system. Our hypothesis is that diet and individual nutrients can influence the resolution of RARS by stabilizing the inflammatory and immune mechanisms. We have previously conducted studies on the effects of the Mediterranean diet on URTI and their frequent bacterial complications [25
], such as recurrent acute otitis media [26
], otitis media with effusion [27
], persistent nasal obstruction [28
], and childhood asthma [29
], with satisfactory results. We have also applied the Mediterranean diet in infants since birth and have observed a lower incidence of habitual inflammatory pathology [30
]. Following our main line of argument in which we relate recurrent inflammatory episodes with the abandonment of the traditional diet, we have carried out this study on the effects of a traditional Mediterranean diet (TMD) in patients diagnosed with recurrent acute and chronic rhinosinusitis.
Participation was proposed in a program called ‘Learning to eat from the Mediterranean’. The families of 131 patients met the RARS and RSC inclusion criteria. Nine refused to participate. From the 122 patients included, eight left the program after the first sessions. Three were due to social or personal difficulties in implementing the diet, two were due to the disagreement with the limitations of certain foods, and three were due to surgical interventions indicated by the otorhinolaryngology service and not coordinated with our team. The study was thus completed with a total of 114 patients (56 girls and 58 boys) with an average age of 2.9 years. All of the patients included in the study were evaluated at 4 and 12 months after the initial visit. The results obtained were similar in both sexes, and are thus collated together (Table 4
shows the evolution of the patients with the number of ARS episodes in the previous year and the following year after the application of the nutritional program; ARS episodes per child and year were assessed. The evolution of other bacterial complications of the oropharynx is also exposed.
We have evaluated the degree of clinical involvement of children with RARS and CRS and we have recorded the mean of their total score before and after the treatment. We have also assessed the number of times the patients visited the emergency department in the previous year and the following year, as well as the antibiotic treatment cycles they received during their inflammatory processes and symptomatic treatment, such as paracetamol, saline sprays, anti-inflammatory drugs, or expectorant mucolytics (Figure 2
The clinical evaluation test of the patients is shown in Table 1
, which shows the assessment of the families regarding the evolution of the process and the difficulties of treatment. The anthropometric variables before, at four months, and after intervention, are set out in Table 6
. The mean weight increase the year before the study was 2.33 kg compared to the current 2.64 kg, and the increase in average height was 8.8 cm compared to 9.4 cm today.
The mean value of the KIDMED index at the beginning of the program was 7.7 ± 1.82 points; 24.6% of the patients obtained a qualification according to the KIDMED test of “need to improve” and 69.3% obtained the qualification of “optimal diet”. At the end of the study, 90.4% of the children obtained optimal levels with a mean of 11 points, mean difference of 2.11 ± 0.10 (95% CI: 1.91–2.31 p
< 0.01). According to this data, the average value of the KIDMED index evolved from a score considered medium-high at the beginning of the program to an optimal value at the end of the program (Table 7
, Figure 3
and Figure 4
At the beginning of the study, the mean value of the TMD test was 6.79 ± 1.98, qualifying as a poor-quality diet; 89.5% of the sample obtained a score below eight points (poor-quality diet) and 10.5% obtained a score between eight and fourteen points (need for improvement). At the end of the study, the mean score was 16.78 ± 1.90 points, qualifying as an optimal traditional Mediterranean diet. The TMD test evolved from levels considered to be low quality to optimal levels (Table 8
and Figure 5
). Despite the good score obtained with the KIDMED test, the patients maintained the incidence of ARS. However, when applying the TMD test, we obtained statistically significant results in the evolution of ARS.
In view of these results, we suggest that the traditional Mediterranean diet could help in the prevention and also in the control of RARS and CRS, improve their treatment, and limit pharmacological and surgical intervention. At the end of the year of the intervention, less than 5% of the patients treated met the criteria to be classified as having RARS and CRS. Of the patients, 53.5% did not have any ARS, and 26.3% had only one, when the usual issue with the conventional treatment is that new episodes would have been repeated and would have ended up in the OR service. We had few episodes of CRS, probably because many of the patients already followed an acceptable Mediterranean diet, and because when they reached three to four annual episodes of ARS, we incorporated them into the TMD. RARS and CRS often overlap and it is difficult to know when a new rhinosinusitis episode starts or when it is a relapse of a process that has not yet been resolved [5
]. In our study, most of the patients were diagnosed with RARS.
The number of ARS episodes decreased by 90.5%, from a mean of 3.37 to less than 0.32% episodes per year. Although with age the effectiveness of the immune system increases and recurrent inflammatory episodes tend to disappear spontaneously, such a rapid evolution in the disappearance of symptoms could not be anticipated, which resulted in preventing the patients from having prolonged pharmacological treatments and undergoing surgery. Thus, we deduce that the nutritional intervention was beneficial for them. The degree of intensity of the ARS decreased significantly, so that not only did the total number of ARS episodes decrease, but there was also less involvement and fewer symptoms in the patients who followed the nutritional guidelines. It is important to note that during the time that the patients were enrolled in the study, we were extending the application of the TMD to the entire pediatric population (siblings, relatives, patients with other recurrent pathologies, and infants under two years of age). This led to a progressive decrease in the number of patients diagnosed with ARS, thus delaying the achievement of the sample size [30
]. As we had already verified in previous studies, the URTI [25
], which are one of the precipitating reasons for bacterial involvement of the paranasal sinuses, decreased significantly. In our study, there was 60% less URTI than in the previous year.
The number of other bacterial complications decreased by 88.8% (4.31 in the previous year versus 0.72 in the year of intervention); 61% of the patients did not have any bacterial complication during the nutritional intervention period, 28% had only one in the entire year, and 10% had two, compared to the more than four episodes they had on average in the previous year. Children with PNO went from a mild-moderate intensity profile to not at all-mild [28
]. Likewise, one of the most frequent reasons for attending pediatric emergencies is the discomfort caused by ARS, with worsening of the URTI and difficulties in breathing through the nose and being able to fall asleep; there was a significant reduction of 88.5% in emergencies compared to the previous year. As a consequence of the decrease in URTI, ARS, and other bacterial complications, symptomatic treatment decreased by 57%. Likewise, antibiotic treatment was reduced by 87.6%, which allows us to verify a greater benignity of the infectious processes. The degree of satisfaction shown by the parents in the clinical evaluation test was high, with scores indicating a good clinical and therapeutic evolution. In the first four months, improvements were already observed compared to the situation of the previous year, so that loyalty increased and monitoring was easier.
There was a good tolerance to the proposed diet, with easy adaptation and without great culinary difficulties. The main difficulty was the fulfillment of the diet, as they were proposed to make a homemade, familiar diet of fresh products that must be prepared, and the parents did not always have the time and dedication to do it properly. The presence of a dietitian-nutritionist was essential to guarantee the compliance with the the TMD. By the end of the program, the dietary habits of the patients had improved in the sample as a whole; an increase in the number of patients consuming fruits, vegetables, nuts, whole grains, and fermented dairy products was observed. In general, the consumption of proteins of animal origin was reduced considerably, especially cow’s milk, red meat, and meat products. The consumption of processed foods also decreased, especially industrial pastries. Prior to the development of our study, we promoted the application of a validated test, such as the KIDMED test [34
], with the intention of preventing and treating inflammatory and recurrent diseases, as well as preventing becoming overweight and obese [33
]. Despite this, we did not obtain satisfactory results, so we decided to implement a new TMD test, which collected information about important aspects of the Mediterranean diet that had not previously been detailed. Many of the children who had an optimal KIDMED test failed on the TMD index. It was only when they began to show improved scores with the new test that we obtained satisfactory results. In the KIDMED test, some variables that we believe are important are not considered. For example, no differences are noted between refined cereals and whole grains, nor are there any references to the consumption of sugar or sugary industrial juices. Additionally, in general, glycemic index/glycemic load is not taken into account. In the lipid section, saturated fat consumption is neither limited nor evaluated. The test does not allow for the detection of an excess consumption of animal proteins. Additionally, no assessment is made of the consumption of raw food, nor is the minimum amount to be taken specified. Serving sizes and schedules are not taken into account. Completing the KIDMED test has not been shown to be effective in our study. We believe that these small nuances that we have proposed in the TMD test are important for obtaining satisfactory results in the examination of recurrent inflammatory diseases, in particular RARS. The patients showed satisfactory predicted growth rates. Their weight, height, and BMI percentile evolved as expected. A positive result was the slight decrease in the BMI and fat mass levels and a small increase in height and lean body mass.
Although these data suggest that the intake of healthy foods and/or the avoidance of non-traditional foods may play an important role in the control of ARS, there are almost no bibliographic references in the scientific literature. We want to highlight that most of the studies published on the treatment of RARS and CRS are based on the application of actions external to the body, such as the use of drugs or surgical intervention. The nutritional factors have not been taken into account, when the deconfiguration of the inflammatory system and the immune system due to inadequate food is likely at the base of these pathologies. The etiology and pathogenesis of this inflammation are often unclear, although this is believed to represent an inappropriate or excessive immune response to an external stimulus inhaled through the nasal airways [1
The research has suggested the protective effect of breastfeeding for at least 6 months, although other risk factors accumulate after that age [39
]. Among them, the early introduction of adapted milk has been noted [40
] as well as the abuse of antibiotics [41
]. A pan-European study has shown that children consuming excessive refined flours and processed animal-based products and having a diet poor in fruit and vegetables have high inflammatory markers, and as a whole, they can be considered to be in a pro-inflammatory state [42
]. Likewise, ARS patients have been shown to have an altered regulation of key immune mediators during good health and pathogenesis and are amenable to treatment by immunomodulatory intervention [43
]. Predominantly eating foods with a low glycemic index/load—typical of the TMD—helps to control insulin levels; this hormone may interfere in the formation of anti-inflammatory eicosanoids, by blocking the ∆-desaturase enzyme [44
]. Similarly, the TMD is rich in vitamins, minerals, and antioxidants, many of which are indispensable co-factors in the enzymatic chemical reactions involved in the body’s immune processes. Children with recurrent inflammatory infections have been shown to have poor responses to pro-inflammatory cytokines and antiviral chemokines [45
]. High-mobility group box protein 1 (HMGB1), that acts as a mediator between innate and acquired immunity, is overexpressed and can play a role in the progression of CRS and RARS, acting as an inflammatory marker and cytokine [47
There is a growing interest in understanding the alterations of the naso-sinus microbiome as a causative factor of the disease. Likewise, it has been considered that there is a dysfunctional naso-sinus mucosa, in which defects of the epithelial surface may be the basis of the etiology and pathogenesis of the disorder [48
]. It has been shown that an inadequate diet, away from the traditional diet, can alter the rhino-sinus microbiota and cause intestinal dysbiosis [52
]. Biofilms provide a protected environment for pathogens and can be responsible for persistent or recurrent diseases [1
]. The immune system may not recognize foreign, infrequent, or foreign microbial germs, and cause the cytokines or other cell signaling molecules to react, which alter inflammatory mechanisms and leave the respiratory mucosa in a permanent pro-inflammatory state. In this way, in the face of small stimuli, such as simple catarrhal viruses, hyper-reactivity of the mucous membranes would be triggered, with flowery symptoms, which would end up causing the usual complications and in particular the RARS. Adenoid hypertrophy and adenoiditis contribute significantly to the pathogenesis of RARS, being one of the main differences between the involvement of children and adults [1
]. The mechanisms by which the intestinal flora modulates the immune response are not clear, but it seems prudent to favor an intestinal microbiota typical of the human species, since evolution and genetic coding have had to configure a specific symbiosis between nutrition, the intestinal microbiota, and immunity that we should not modify.
The growing interest in the Mediterranean diet is based on its role in inflammatory diseases [54
]. Several clinical and epidemiological studies, as well as experimental studies, show that the consumption of the TMD reduces the incidence of certain pathologies related to oxidative stress, chronic inflammation, and the immune system, such as cancer, atherosclerosis, or cardiovascular disease [55
]. There is evidence that diet and individual nutrients can influence the systemic markers of immune function and inflammation [56
]. The pro-inflammatory actions of platelet-activating factor (PAF), one of the most potent endogenous mediators of inflammation, can be favorably modulated by the TMD and regulate its metabolism [57
]. The TMD is an ancient diet, dating back to way before documented history, and which has stood the test of time. Many of the foodstuffs eaten as part of the Western diet contain materials not recognized or assimilated by the human body. Many of these products are not absorbed by the intestine, thus encouraging non-specific microflora that is alien to the human intestinal microbiota. The excess “antigenic load” inherent in the Western diet of today—which has multiplied the available foodstuffs by the thousand—may misadjust our immune system, making it weaker and notably hyperplasic.
It has recently been proven that better adherence to the Mediterranean diet may be associated with a lower risk of COVID-19 [58
], demonstrating its effect against virus infections. Secretory IgA antibodies are an important part of the immune defense against viral diseases. People who ingest Okinawan vegetables have high IgA levels and might be more likely to develop immunity against influenza RNA viruses [60
One of the characteristics that every research study should have is that it is easily reproducible, using small groups, and with little economic cost. The work presented here is easy to reproduce in any primary care pediatric consultation, but it is not easy to perform due to the lack of nutritionists and the lack of effective monitoring of the diet.
We could not perform a study with a control group since most of our pediatric space was adhering to the Mediterranean diet and it did not seem ethical to promote a pro-inflammatory Western-type diet in a control group. Our hypothesis is precisely that the standard diet proposed by “Western civilization” is the origin of alterations in the inflammatory and immune mechanisms, and therefore the precipitating factor of most of the inflammatory and recurrent diseases of childhood. It would have been very interesting to perform analyses that measured the response of the immune system, inflammatory markers, and the data on the modification of the microbiota when making the nutritional change.
Most of our patients have been consecutively included in the program “Learning to eat from the Mediterranean” and we have verified how the prevalence of ARS and other inflammatory recurrent diseases has decreased considerably. The change of the “model of medicine” that these research studies entail should not go unnoticed. It is no longer about remedying a disease with external drugs or surgical interventions, but the therapeutic proposal is based on providing the body with everything it needs to solve their needs and eliminate that for which it is not ready.
We can conclude by saying that the application of the traditional Mediterranean diet could have promising effects in the prevention and treatment of acute recurrent and chronic rhinosinusitis, with a notable decrease in associated inflammatory diseases, limiting pharmacological and surgical intervention in many of these patients.