Keywords

1 Introduction

Nasal polyps (NP) are benign, edematous masses growing into nasal cavity that could have multiple etiological factors [1,2,3,4,5].

Basic etiological factor for polyp formation is chronic inflammatory change and thus stromal nasal and paranasal mucosa edema [6]. All theories about NP formation try to explain the edema formation. Edema and mucosal inflammation may originate from trauma; bacterial, viral, or fungal infections; environmental irritants; or allergens [7].

The prevalence of NP in the general population is unclear. It varies from 0.2% to 5.6%. Different diagnostic measurements and criteria may be responsible for this wide range [1,2,3,4,5]. Additionally, age, gender, and such demographical factors affect the variability. Ethnic and genetic factors should also be taken into consideration.

The prevalence of NP shows a wide range according to etiology. The most important data on the epidemiology of NP are obtained from NP etiology studies. For these reasons, in this chapter, epidemiological data are presented parallel to the etiological reasons and hypotheses of NP. The main hypotheses that lead to the development of NP will be discussed below with the current incidence and prevalence rates.

2 Genetics

There may be hereditary factors for NP but there is limited knowledge in this area. However, we have some evidence for genetic inheritance. Studies reported that up to 14% of patients with NP have a family history [8]. A link has been indicated that NP and asthma have an association with HLA-A1B8 and HLA-A74 genes [9, 10].

Monozygotic twin studies tried to describe genetic pathway for NP. Both or none of identical twins showed NP with asthma and aspirin intolerance [11, 12].

In terms of familiar association, studies have revealed the presence of family history in patients with NP. In a report, 52% of patients with NP showed family history in the last three generations [13]. Another study documented a family history of patients with NP over 14% [14].

NP, most likely has a genetic predisposition, but there is no definite inheritance model. Gene and environment communication is likely at work [15].

In some genetically transmitted disorders the formation of NP is a disease characteristic symptom, such as cystic fibrosis, primary ciliary dyskinesia, and Young’s syndrome.

The association of NP with cystic fibrosis is clearly reported. Studies documented NP prevalence as 10–37% of fibrotic patients [11, 16,17,18]. Transmembrane conductance regulator (CFTR) gene mutations occur in cystic fibrosis as autosomal recessive disorder. These CFTR gene mutations create intestine, liver, lung, and exocrine gland changes by affecting chloride ion channels [11]. Children younger than 16 years old, who have NP, should be investigated for cystic fibrosis.

NP is also related to chronic dyskinetic cilia syndrome, also known as Kartagener’s syndrome, in these cases neutrophils are the predominant cells reveled in nasal mucosa. Primary ciliary dyskinesia has very different genetic circumstances, with an estimated incidence of 0.02% [19, 20]. Kartagener’s syndrome is inherited as an autosomal recessive disease and it is characterized by chronic sinusitis, bronchiectasis, and situs inversus (complete reversal of internal organs). This syndrome affects cilia; there are defects in dynein arms of cilia and microtubule transposition anomalies [21]. The ciliary abnormality involves the entire body, including the respiratory and genital tract.

Both Kartagener’s syndrome and cystic fibrosis patients have sensitivity to Pseudomonas aeruginosa infection. So antibiotic therapy should be taken into consideration against this pathogen [22, 23].

Young’s syndrome is another disorder consisting NP, recurrent respiratory disease, obstructive azoospermia [24]. Young’s syndrome is different from cystic fibrosis and primary ciliary dyskinesia in way of showing normal sweat chloride test. Ciliary function and structures are normal such as normal sperm tails and normal tracheal biopsies. Spermatogenesis is normal but there is a male infertility of about 7.4%, because of epididymis blockage with concentrated secretions [25].

3 Age and Gender

The general consensus is that the incidence of NP increases with age and it is more common in male population [26, 27]. It has been suggested that there is a 2:1 male to female preponderance at least [26]. Recently, Hulse et al. published that male-to-female ratio is changing from 1.3 to 2.2 [28].

NP largely affects adults and mostly presents in patients older than second decades. It usually occurs in middle age, generally between the fourth and fifth decades [29]. NP appears rarely among pediatric population that the prevalence is estimated to be 0.1% [11]. NP is infrequent in children under 10 and may be associated with cystic fibrosis or antrochoanal polyps [11] (Figs. 42.1, 42.2, 42.3, 42.4).

Fig. 42.1
figure 1

Right antrochoanal polyp (courtesy of Fazilet Altin)

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Fig. 42.2
figure 2

Coronal CT view of right antrochoanal polyp (courtesy of Fazilet Altin)

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Fig. 42.3
figure 3

(a–c) Endoscopic view of antrochoanal polyp (courtesy of Fazilet Altin)

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Fig. 42.4
figure 4

(a, b) Operation specimen of antrochoanal polyp (courtesy of Fazilet Altin)

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It has been implied that the incidence of NP increases with age. Settipane et al. published that the frequency of disease achieves a peak in patients who are over 50 years of age [30]. Also he reported asthmatic persons over 40 years of age have about four times tendency to have NP. Johansson et al. indicate that individuals with NP over 60 years of age have a prevalence of 5%; on the other hand, it is 1% in persons younger than 40 years of age [4]. Larsen et al. reported much similar results in Danish population who have NP. They observed that NP patients are between 40 and 60 years of age. The mean age diagnosis was 51 in males and 49 in females [26]. Klossek et al. also reported similar data. They published that NP prevalence is 1.22% between 18 and 24 years of age, and 2.47% in 65 years of age [2].

4 Allergy

Even if in the past nasal allergy was considered to be a key pathology in the NP etiology, today, the role of allergens causing polyps is controversial; in fact several patients with nasal polyps have low seric IgE levels and/or negative skin tests.

The connection between allergy and nasal polyp has not been efficiently explained in literature. NP prevalence in patients with allergic rhinitis is predicted to be between 1.5% [30] and 1.7% [31], a ratio similar to the general population one.

Contrarily, other studies reported a connection with allergy, regarding the relationship between positive skin tests and NP. Different authors published higher frequency of allergic symptoms appearance and food allergy in patients with NP than in the general population.

Rugina et al. carried out a multicenter study, and found that 32.5% of the patients with NP have positive skin tests [13]. Settipane reported 55% positive skin test rate in patients with NP [30]. Klossek recorded 26.1% positive skin tests in patients with NP [2]. Moreover, Bonfils et al. published two studies founding positive phadiatop test results of 19.5% and 16.2% in patients with NP [32]. Sin et al. showed the presence of allergy in patients with NP using skin tests and demonstrating serum-specific IgE levels. With respect to the two tests, 45.2% of the cases were classified as allergic, while the skin tests were positive in 66.3% of the patients [33].

On the other hand, Pastorello et al. conducted a study, and they determined specific IgE in 38% of the serum and in 32% of the nasal secretions of nasal polypectomy-performed patients [34].

It has been suggested that there may be local IgE secretion without increasing level in serum or in the derma to be detected by skin tests [35]. A meta-analysis reviewed nine studies with specific IgE in serum levels and nasal mucosa. Nineteen percent of the patients’ have positive nasal IgE, but negative serum IE; so we can consider that a percentage of patients with NP may show local allergy [36].

5 Asthma

Another associated factor is asthma. The relationship between nasal polyp and asthma can be defined from two different aspects: asthma patients who develop polyps, and patients diagnosed with NP who develop asthma after that. A number of studies are cited below demonstrating strong association between these two clinical entities, while disputing the association between atopy and polyps.

Settipane reported that, on about 2000 patient samples, NP were more prevalent in patients with nonallergic asthma than with allergic asthma (5–13%) [11]. Another large cohort study conducted by Grigoeras et al. evaluated 3,817 patients with asthma and chronic rhinitis; the incidence of NP was 4.2% in this population. The incidence of polyps’ prevalence in nonallergic asthma was 13% and allergic asthma was 2.4%. There was a correlation between NP and allergy and allergic asthma [31]. Also, there are some small group studies supporting this relationship. An epidemiological study, carried out on NP patients diagnosed by endoscopic findings, by Johansson et al. found that 30% of the patients had experienced asthma attacks or breathing difficulties before [4].

Bonfils et al. published a study, evaluating allergy and asthma co-occurrence in patients diagnosed with NP on the basis of the endoscopic and computed tomography findings; a 48.6% incidence of asthma and a 22.8% incidence of bronchial hyperresponsiveness have been reported in these patients [32].

Bronchial hyperresponsiveness has also been reported in patients with NP. In a study patients with NP underwent methacholine challenge testing, the researchers found 35% bronchial hyperresponsiveness in those subjects [37].

6 Aspirin Intolerance

The relationship between NP and aspirin (acetylsalicylic acid) or nonsteroidal anti-inflammatory drugs intolerance is well known in daily clinical practice. In 1968, Samter described the clinical triad of bronchial asthma, aspirin sensitivity, and NP. This “triad” of symptoms is generally referred to as “Samter’s triad” or “ASA triad.” These medications provoke an acute asthmatic response within minutes [38]. A great number of affected patients produce an acute bronchial response with rhinorrhea, nasal obstruction, facial pain, postnasal drip, and anosmia.

Aspirin intolerance is seen in 5–10% of asthmatic patients and NP prevalence in these patients is higher than the general population and also higher than the nonaspirin intolerant asthmatic population. The recorded incidence of NP is changing from 36% to 95% [11, 38].

In the development of ASA triad, first, patients show chronic rhinitis symptoms. After about 5–10 years aspirin-induced asthma will appear. Then the symptoms evolve into NP. The nasal polyps of ASA-triad patients present with increased edema and inflammatory infiltrate were compared to the polyp of aspirin tolerant patients [39].

NP in ASA-triad patients accompanies to severe inflammation, which is more persistent to medical and surgical treatment. The response of ASA-triad patients to surgery is usually poor, and the patients have to undergo endoscopic sinus surgery procedures several times. Moreover, ASA-triad patients have a considerably higher amount of symptom recurrence, and also regrowth of nasal polyps [40, 41].

7 Allergic Fungal Rhinosinusitis

Allergic fungal rhinosinusitis (AFRS) is an old concept many times connected to chronic rhinosinusitis and is greatly related, by several authors, to NP. Safirstein first related NP with Aspergillus collected from the paranasal sinuses in 1976 [42].

The incidence of AFRS has not been well demonstrated, but about 5–10% of NP patients have AFRS [43]. It is typically young adults’ disease, with an age interval of 22 and 28 [44].

Some studies have suggested that there is an increased prevalence of AFRS in more humid climates, and lower socioeconomic status may also play a role [44].

The nature of the immune reaction is not clear but it is a simple type I hypersensitivity reaction. The existence of fungal specific IgG would display a type III reaction that could be involved in the polyps pathogenesis [45]. This may result in a circle of mucosal edema, and chronic rhinosinusitis and NP.

Diagnosis can be made by clinical suspicion and intraoperative observation of eosinophilic mucin and NP. AFRS diagnosis is based on the presence of five characteristic features: type I hypersensitivity reaction, nasal polyps, paranasal sinus CT scan findings; thickened mucus (gray-brown) with calcification, eosinophilic mucus containing Charcot-Leyden crystals, and positive fungal stains from sinus material. The diagnosis of AFRS should be kept in mind in every atopic patient and nasal polyps that is unrelieved by routine therapy. Culture identification, positive skin test to fungus, positive serum markers, elevated specific IgE and IgG antibodies, and biopsy staining for fungal elements would prove the existence of AFRS.

8 Key Points

  • The exact prevalence of nasal polyps is not known. In the literature, it changes between 0.2% and 5.6%, varying according to the diagnostic methods.

  • There is a weak association between NP and allergic rhinitis.

  • Large cohort studies have reported a great relationship between NP and asthma.

  • The incidence of NP increases with age and peaks between the fourth and fifth decades of life. It is somewhat higher in males.

  • Asthma is common (20–48%) in patients with NP. This relationship increases in patients with aspirin intolerance.

  • The genetic-hereditary factors are held responsible for underlying possible etiology of NP but it remains to be clarified.