The Role of Sinus Disease in Asthma

Claus Bachert; Joke Patou; Paul Van Cauwenberge

Disclosures

Curr Opin Allergy Clin Immunol. 2006;6(1):29-36. 

In This Article

Relationship Between Sinus Disease and Asthma

The relationship between sinus disease and asthma may be demonstrated by several means. First, they may be related on an epidemiological basis. Second, demonstration of improvement in asthma after medical or surgical treatment of rhinosinusitis supports such a relationship. Furthermore, some hypotheses have been proposed that could explain this relationship.

In a study comparing patients with mild-to-moderate asthma with corticosteroid dependent asthmatic patients,[34] about 70% of all participants reported symptoms of rhinosinusitis. The total symptom score, however, was significantly higher in patients with severe steroid dependent asthma than in those with mild-to-moderate asthma. In this study the entire corticosteroid dependent (severe asthmatic) group had abnormal CT scans, as compared with about 90% of the mild-to-moderate asthmatic group. Another study,[35] however, demonstrated CT scan abnormalities in about 84% of the severely asthmatic patients, and extensive sinus disease was identified in 24% of those patients. Of asthmatic children, 44-70% exhibit clinical, endosopic, or radiological findings of sinusitis.[36,37,38] In a group of 25 adult patients with CRS who had failed to response to medical treatment, 24% had asthma and 36% had small airway disease.[39*]

In asthma, 7% of patients have nasal polyposis.[40] The proportion is higher in patients with nonatopic asthma (13%) than in those with atopic asthma (5%).[41] Late-onset asthma is associated with development of nasal polyposis in 10-15%.[40] In patients with nasal polyposis, approximately 30% have asthma[42] and 15% have aspirin-intolerance.[43] In approximately 69% of patients with both asthma and nasal polyposis, asthma is the first disease to develop, and nasal polyposis takes between 9 and 13 years to be diagnosed. In only 10% of patients with both asthma and nasal polyposis do both diseases develop simultaneously, and in the remaining patients polyps develop first followed 2-12 years later by asthma.[44] In nasal polyposis the male: female ratio is 2: 1. Women with nasal polyposis, however, are 1.6 times more likely to be asthmatic and 2.7 times more likely to have allergic rhinitis than are men.[45]

Patients with asthma, nasal polyposis and aspirin sensitivity are usually nonatopic and the prevalence increases in those older than 40 years. When parents have asthma, nasal polyposis and aspirin sensitivity, their children more commonly have nasal polyposis and rhinosinusitis than do control children.[46] Of 500 patients with aspirin-induced asthma, almost 80% had symptoms of rhinosinusitis such as nasal blockage and rhinorrhoea. Abnormalities in the paranasal sinuses were detected in 75% of these patients. The combination of air-fluid levels, mucosal thickening and opacification was a characteristic finding in the paranasal sinuses. Nasal polyposis was diagnosed in 62% of aspirin-sensitive patients.[47]

Epidemiological data on sinusitis and lower airway disease, however, must be evaluated with caution because they are mostly based on symptoms only and do not include nasal endoscopic or CT findings. Thus, the diagnosis of or differentiation between CRS and nasal polyposis is impossible, or at least unreliable, affecting any data on the link between these diseases and lower airway comorbidity. Efforts should be made to generate more reliable data, perhaps even including biomarker screening in mucosal tissue, as discussed above.

One way to approach a possible causal relationship between rhinosinusitis and asthma is to demonstrate improvement in asthma after medical or surgical treatment of rhinosinusitis.[48*] Some older studies concluded that there is a correlation between treatment of rhinosinusitis and improvement in asthma. In one study,[49,50] 79% of children with asthma and rhinosinusitis were able to discontinue taking their bronchodilators after receiving antibiotic treatment for their rhinosinusitis. Moreover, pulmonary function tests normalized in 67% of those patients. In addition, improvement in asthma symptoms has been reported.[50] A large group of asthmatic children, both allergic and nonallergic, with rhinosinusitis, exhibited a Th2 polarization at the rhinosinusal level.[51] Treatment for rhinosinusitis in this group with antibiotics and a topical steroid spray plus a short course of oral corticosteroids appears to induce a decrease in IL-4 and an increase in IFN-γ levels.[52]

In 18 asthmatic children, a recent study demonstrated an improvement in severity of asthma and respiratory functioning, together with reduced levels of inflammatory cells and a change from a Th2 cytokine profile to a Th1 profile.[53] In another study,[54] patients with opacified maxillary sinuses at entry and normal sinus X-rays after 30 days of treatment exhibited a decrease in their sensitivity to metacholine, indicating improvement in their bronchial hyperresponsiveness.

Furthermore, studies have demonstrated the effect of sinus surgery on asthma. After endoscopic sinus surgery in patients with asthma and concomitant rhinosinusitis, there was an improvement in asthma symptoms and reductions in total dosage of steroids and in the number of days of steroid use in the first year after surgery.[55] Moreover there was an improvement in respiratory functions, including increased peak expiratory flow measurements[56] and a significant decrease in bronchial hyperreactivity,[57] after sinus surgery. According to questionnaires, after functional endoscopic sinus surgery about 70% of patients had less frequent asthma and 65% had less severe asthma, along with a 75% reduction in hospitalizations and an 81% reduction in acute care visits during the year after the surgery.[58] It appears that treatment for rhinosinusitis has a beneficial effect on asthma. It is likely, however, that medical treatment used after surgery, such as oral antibiotics and oral or topical steroids, also have direct pulmonary effects.[59]

Many pathogenic hypotheses have been proposed to explain the link between sinus disease and asthma (Fig. 1).

Link between sinus disease and lower airways disease.

It has been suggested that airway hyperresponsiveness in sinusitis may be caused by the activation of a pharyngobronchial reflex. A postulated neuroanatomical pathway that connects the paranasal sinuses to the lungs consists of receptors in the nose, pharynx and sinuses, which give rise to fibres that form a part of the trigeminal nerve. The trigeminal nerve connects with the dorsal vagal nucleus, which sends parasympatic fibres via the vagus nerve to the bronchi.[60*] In patients with chronic rhinosinusitis the pharyngeal mucosa is damaged, manifesting as epithelial thinning, and there is an increase in pharyngeal nerve fibre density.[61] The pharyngobronchial reflexes may be triggered by drainage of inflammatory mediators and material from infected sinuses into the pharynx.

Another theory to explain the association between sinus disease and asthma pertains to silent dripping of material containing mediators from the nose and aspiration into the bronchial tree. After placing radionuclides into the maxillary sinuses of patients with sinusitis and asthma, however, the radionuclide was visible over a 24-hour period in the maxillary sinuses, the nasopharynx, the oesophagus and the lower gastrointestinal tract, but it was impossible to demonstrate any form of pulmonary aspiration.[62] In contrast to this report, pulmonary aspiration of radionuclide-labelled nasal secretions during sleep has been described,[63] but there was no difference in aspirated amounts between the asthma/chronic sinusitis group and the control group.

The concept with the best supporting evidence involves the blood circulation and the bone marrow and its responses. Sinus diseases involve production of inflammatory mediators, eosinophil precursors, T-helper lymphocytes and cytokines, which may lead to increased generation of eosinophils, mast cells and basophils in the bone marrow and to subsequent recruitment of cells and mediators into the lungs. In patients with allergic rhinitis, segmental bronchial provocation and nasal provocation induced allergic inflammation in both the nasal and bronchial mucosa. In addition, allergen provocation resulted in an increase in circulating inflammatory cells and mediators.[64] Allergic provocation and release of inflammatory mediators (e.g. IL-5 and eotaxin) from inflammatory sites activate a systemic response that may provoke inflammatory cell production by the bone marrow. Progenitors may then migrate to the airways and may differentiate into an eosinophilic phenotype.[65,66] The systemic allergic response is characterized by increased expression of adhesion molecules, such as vascular cell adhesion molecule-1 and E-selectin, on nasal and bronchial endothelium, which facilitates migration of inflammatory cells into the tissue.[67]

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