Erik van Spronsen Department of Otorhinolaryngology, Academic Medical Centre, Amsterdam; , Peter W Hellings Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Faculty of Medicine, University of Leuven; , Elisabeth HD Bel Department of Pulmonology, Academic Medical Centre, Amsterdam; , Wytske J Fokkens Department of Otorhinolaryngology, Academic Medical Centre, Amsterdam

Originally printed in:
» European Respiratory Disease 2007 - Issue II

Recently, the revised European Position Paper on Rhinosinusitis and Nasal Polyps (EP3OS) was published.¹ This evidence-based position paper was initiated by the European Academy of Allergology and Clinical Immunology (EAACI) to consider what was known about rhinosinusitis and nasal polyps (NP) and to offer evidence-based recommendations on diagnosis and treatment. The relevance of this document for pulmonologists will be outlined in the following paragraphs.

Inflammation of mucosa in the paranasal sinuses and nasal cavity usually co-exists in individuals with symptoms related to sinus disease. Therefore, the definition of rhinosinusitis is introduced. In view of the fact that the diagnosis of rhinosinusitis is made by a wide variety of practitioners such as allergologists, otolaryngologists, pulmonologists and primary care physicians, an accurate definition of rhinosinusitis is required. The clinical definition of rhinosinusitis is based on sinonasal symptoms in combination with sinonasal mucosal abnormalities evaluated by either nasal endoscopy or a computed tomography (CT) scan (see Figure 1).

Usually, the diagnosis of rhinosinusitis can be based on symptoms. X-ray examination does not contribute to the diagnosis and is discarded. Initially, a CT scan is not recommended unless additional problems such as very severe disease, immunocompromisation or signs of complication are present. Symptom severity is assessed by means of a visual analogue scale (VAS). Mild severity is a VAS score between 0 and 4, moderate between 4 and 7 and severe between 7 and 10. A VAS score of more than 5 has been shown to affect patient quality of life (QOL).² When specified symptoms resolve within 10 days, the episode is defined as a common cold or an acute viral rhinosinusitis. If symptoms persist after 10 days or increase after five days, it is defined as an acute non-viral rhinosinusitis. When symptoms do not completely resolve within 12 weeks, the disease is defined as a chronic rhinosinusitis (CRS) with or without NP (see Figure 2).

CRS with or without NP is often taken together as one disease entity, as it is impossible to differentiate clearly between the two.^3–5 CRS with NP is considered a subgroup of CRS (see Figure 3). Nasal endoscopy allows the visualisation of pedunculated mucosal lesions in the sinonasal cavity, which is crucial for the diagnosis of NP. CRS is a multifactorial disease6 in which several factors contribute to the disease manifestation, for example mucociliairy impairment,^7,8 (bacterial) infection,9 allergy,¹⁰ swelling of the mucosa for another reason or rare physical obstructions caused by morphological/anatomical variations in the nasal cavity or paranasal sinuses.^11,12

Due to its strategic position at the entry of the airway, the nose plays a crucial role in airway homeostasis. By warming up, humidifying and filtering incoming air, the nose is essential in the protection and homeostasis of lower airways.¹³ The nose and bronchi are linked anatomically, lined with a pseudo-stratified respiratory epithelium and equipped with an arsenal of innate and acquired immune defence mechanisms. It is not hard to imagine that nasal conditions such as rhinosinusitis may become a trigger for lower airway pathology in susceptible individuals. Evidence-based effects of CRS with or without NP and its treatment on asthma and chronic obstructive pulmonary disease (COPD) are discussed below.

Asthma and Chronic Rhinosinusitis without Nasal Polyps

Bronchial asthma is considered to be a co-morbid condition of CRS. In some centres, around 50% of patients with CRS have clinical asthma.^14,15 CRS was found to be a self-reported complaint in 70% of asthma patients.¹⁶ Asthmatic patients who reported concomitant CRS had more asthma exacerbations, worse asthma scores and worse cough and sleep quality. Others report that 60% of patients with CRS have lower airway involvement, pulmonary function and histamine provocation test scores.¹⁷ Interestingly, most patients with CRS who do not report having asthma show bronchial hyper-reactivity when given a metacholine challenge test.¹⁵

Histopathological features of CRS and asthma largely overlap. Heterogeneous eosinophilic inflammation and features of airway remodelling such as epithelial shedding and basement membrane thickening are found in the mucosa of CRS and asthma patients.¹⁵ Cytokine patterns in the sinus tissue of CRS patients highly resemble those of bronchial tissue in asthma patients,¹⁸ explaining the presence of eosinophils in both conditions. Therefore, eosinophil degranulation proteins may cause damage to the surrounding structures and induce symptoms at their location in the airway. The interaction between rhinosinusitis and asthma is not always clinically present. Ragab et al.¹⁹ found no correlation between rhinosinusitis and asthma severity. However, patients with asthma showed more CT scan abnormalities than non-asthmatic patients,²⁰ and CT scan abnormalities in severely asthmatic patients correlated with sputum eosinophilia and pulmonary function.²¹

Asthma and Chronic Rhinosinusitis with Nasal Polyps

In general, NP is thought to be hereditary or due to shared environmental factors. Several studies show positive family history of NP in various incidences (14 and 52%).^22,23 Recent genetic studies found a significant correlation between certain human leukocyte antigen (HLA) alleles and NP.^24,25 The role of environmental factors in the development of NP is unclear; neither the patient’s habitat nor pollution at work has been found to influence the prevalence of NP. Surprisingly, a significantly smaller proportion of the population with polyps were smokers compared with an unselected population (15 versus 35%).²²

Around 7% of asthmatic patients and 5% of atopic asthmatics have NP.²⁶ In non-atopic asthma and late-onset asthma, polyps have been reported more frequently (10–15%). Asthma develops first in approximately 69% of patients with both asthma and NP. After onset of asthma, NP can take up to nine to 13 years to develop. Ten per cent develop both polyps and asthma simultaneously, and the remainder develop polyps first and then asthma, between two and 12 years later.²⁷ However, not all patients with NP have lower respiratory tract symptoms.²⁸

Aspirin-induced asthma is a distinct clinical syndrome as these patients tend to suffer from more extensive sinus disease, and it is characterised by the triad of aspirin sensitivity, asthma and nasal polyposis. It has an estimated prevalence of 1% in the general population and 10% among asthmatics.²⁹ In patients with aspirin sensitivity, 36–96% have NP^30–37 and up to 96% have radiographic changes affecting their paranasal sinuses.³⁸

At the cellular level, differences between asthmatic and non-asthmatic patients suffering from CRS with NP are evident. An example of these differences can be seen in patients with NP, where a more severe eosinophilic influx is seen in those who have concomitant asthma, especially in those who have aspirin-intolerant asthma. This finding suggests that a more aggressive inflammatory response is present in asthmatics than in non-asthmatics.^19,39–46

Increased nasal colonisation by Staphylococcus aureus and the presence of specific immunoglobulin E (IgE) directed against S. aureus enterotoxins were found in NP patients.⁴⁷ Interestingly, rates of colonisation and IgE presence in NP tissue were increased in subjects with NP and co-morbid asthma or aspirin sensitivity. The level of IgE against the S. aureus antigen was also found to be higher in patients with severe asthma compared with mild asthma.⁴⁸ Because of their superantigenic activity, enterotoxins may activate inflammatory cells in an antigen-non-specific way. Indeed, nasal application of S. aureus enterotoxin B is capable of aggravating experimental allergic asthma.⁴⁹ Besides bacterial enterotoxins, Ponikau et al. have reported on the potentially important role of fungi, especially Alternaria, in the generation of chronic sinus disease with NP.⁵⁰ Due to their capacity to induce eosinophils degranulation,⁴⁹ Alternaria may contribute to the inflammatory spectrum of CRS with or without NP and asthma.