What is rhinosinusitis?
1. What is sinus?
A schematic diagram of the paranasal sinus structure
The sinuses are hollow air pockets in the bones of the face and head, opening into the nasal passages, and probably exist to cushion the brain during trauma. The paranasal sinuses are a group of air-filled cavities located within the human skull, divided into four pairs: the frontal sinuses (situated in the forehead), the maxillary sinuses (within the cheekbones), the ethmoid sinuses (between the eyes), and the sphenoid sinuses (at the base of the skull). These cavities are lined with mucous membranes and connect to the nasal cavity through narrow openings known as sinus ostia.
2. The causes of rhinosinusitis
(1) Macroscopic mechanism
Rhinosinusitis is an inflammation or infection of the nasal passages and sinuses, most commonly caused by viruses, but it may also result from bacteria or other factors.
The sinuses are lined with a thin layer of tissue that normally makes a small amount of mucus to keep the sinuses healthy and lubricated and flush away germs.
When the lining of the sinuses becomes infected or irritated, it swells and produces excess mucus. Due to the narrow sinus openings, the swollen tissue blocks the passages connecting the sinuses to the outside, causing mucus to accumulate and leading to sinusitis.
Development of rhinosinusitis
Some people with chronic rhinosinusitis have abnormal soft, jelly-like growths inside their nose or sinuses called nasal polyps. The polyps can become large and numerous enough to clog the sinuses, causing symptoms.
Example of Sinuses with nasal polyps
(2) Molecular mechanism
The molecular mechanism of rhinosinusitis
Sinusitis can be initiated by various factors such as viruses, fungi, physical trauma, or bacterial infections. These pathogenic factors first cause damage to the nasal epithelium, compromising the integrity of the nasal mucosa. Following this injury, KLRG1+ CD27+ CD8+ T cells become activated. These T cells release Granzyme K (GZMK), which subsequently acts on the complement system components C3, C2, and C4. GZMK promotes the cleavage of these complement components, generating a series of active fragments including C3a, C3b, C2a, and C4b. These complement active fragments collectively trigger and amplify the inflammatory response, leading to typical inflammatory symptoms in the sinus mucosa—such as redness, swelling, heat, and pain—ultimately resulting in the development of sinusitis.
3. The symptoms of rhinosinusitis
The common symptoms of sinusitis include:
- Fever
- Pain, pressure, redness, or swelling around the forehead, cheeks, or eyes
- Thick yellow or green discharge from your nose
- Loss of smell or taste
- Dry cough that happens mostly at night or when you lie down
- Headache and face pain that is worse when you lean forward
- Tooth pain, or pain when you chew
Chronic rhinosinusitis is different from the more common form of rhinosinusitis (called acute rhinosinusitis), which is a temporary infection of the sinuses that often occurs following colds. Chronic rhinosinusitis is a more persistent problem that requires a specific treatment approach.
Chronic rhinosinusitis is understood to be predominantly an inflammatory condition rather than an infectious process. The underlying pathophysiology likely involves a combination of epithelial barrier insults (e.g., microbes, allergens) and dysregulation of inflammatory pathways.
Chronic rhinosinusitis refers to a condition that lasts at least 12 weeks despite being treated and causes at least TWO of the following symptoms:
- Nasal congestion
- Mucus discharge from the nose or mucus that drips down the back of the throat
- Facial pain, pressure, or “fullness”
- A decreased sense of smell. (which is especially common among people who have polyps)
4. The incidence rate of rhinosinusitis
Chronic rhinosinusitis has an estimated prevalence of 8% in China, meaning that approximately 107 million individuals have CRS. Expanding our vision to the international landscape, chronic rhinosinusitis is also highly prevalent worldwide, with an estimated prevalence of 10.9% in Europe, 16% in the United States, and 6.95% in Korea.
The severity of sinusitis
In addition to the basic symptoms, rhinosinusitis may also be associated with impaired sleep, severe fatigue, and depression, which can interfere substantially with activities of daily living. In Canada, patients lose an average of 20.6 work days per year because of symptoms as well as time off for surgeries and medical appointments related to the condition, leading to substantial economic costs.
Diagnostic criteria for chronic rhinosinusitis: (Table 1)
| Criterion |
Symptom or sign |
| At least 2 symptoms |
Nasal obstruction or congestion |
| Anterior or posterior nasal drainage |
| Decreased sense of smell |
| Facial pressure, pain, or fullness |
| At least 1 sign |
Polyps, edema, or mucopurulence on nasal endoscopy or anterior rhinoscopy |
| Sinus mucosal thickening on computed tomography |
The current diagnosis plans for sinusitis
1. Differential diagnosis
The differential diagnosis of chronic rhinosinusitis includes allergic rhinitis, septal deviation, and neoplasms of the sinonasal cavity.
2. Clinical examination
The diagnosis of chronic rhinosinusitis requires objective findings of sinonasal inflammation (Table 1). The phenotypic distinction of whether or not the patient has polyps can guide treatment. Nasal polyps may be suspected on anterior rhinoscopy or computed tomography (CT), but endoscopy by an otolaryngologist is currently considered the gold standard, particularly for detecting smaller polyps. When compared with the nasal turbinates, nasal polyps often have a watery, edematous, translucent quality.
(1) Sinus Computed Tomography (CT) scan
A sinus CT scan is a procedure that takes about 15 minutes and involves a series of radiographs of the head and face. The radiographs give a detailed picture of the linings of the sinuses and any mucus or polyps within the space of the sinuses.
The standard imaging modality used in chronic rhinosinusitis is noncontrast CT of the sinuses. Chronic inflammation appears as mucosal thickening or opacification (lack of aeration) of the sinuses on CT.
A radiograph of the linings of the sinuses and the mucus or polyps within the space of the sinuses
(2) Adopt a procedure called sinus endoscopy
During the sinus endoscopy, a clinician uses a thin tube attached to a camera to see inside the sinuses.
Endoscopy also allows the clinician to take a sample of mucus from inside the sinuses to examine under the microscope, and identify bacteria, fungi, and other contributing factors.
Schematic diagram of sinus endoscopy
The current treatment plans for sinusitis
Medication
Long-term topical intranasal corticosteroids are the first-line treatment. A Cochrane review of 18 randomized controlled trials (RCTs) compared intranasal steroids to placebo and concluded that intranasal corticosteroids improved patient symptoms, reduced inflammation in the sinonasal mucosa (including the reduction of nasal polyps), and addressed related conditions such as allergic rhinitis.
Topical saline sprays and irrigations are effective adjuvant treatments for chronic rhinosinusitis (both with and without nasal polyps). A systematic review demonstrated that high-volume saline irrigations (squeeze bottle or pot) had greater distribution to the sinus cavities than saline sprays.
Oral Medication
Short bursts of oral steroids such as prednisone can reduce the size of known nasal polyps and provide rapid symptomatic relief, including improved sense of smell. A Cochrane review that included 8 RCTs showed that the benefits of oral steroids were generally limited to a few months.
Surgical Treatment
Endoscopic sinus surgery is known to be an effective and safe treatment for patients with chronic rhinosinusitis for whom standard medical therapy has not been beneficial. This minimally invasive procedure is done through the nostrils with endoscopes, without external incisions. Inflamed tissue, polyps, and small pieces of bone can be delicately removed to improve the drainage and ventilation of the sinus cavities. Several studies have demonstrated the ability of endoscopic sinus surgery to improve quality of life while reducing the inflammatory burden in the sinuses. Perhaps most importantly, surgery facilitates an improved delivery of topical medications to the paranasal sinuses, which is an essential component of long-term management and symptom control.
However, endoscopic sinus surgery cannot definitively change the underlying pathophysiology of this disease, and patients may require further procedures.
Monoclonal Antibody Therapy for Chronic Rhinosinusitis with Nasal Polyps
Several monoclonal antibody therapies, also known as biologics, can improve both symptoms and signs among patients with severe chronic rhinosinusitis with polyps.The targets of various monoclonal antibodies differ, but they primarily focus on IL-4, IL-13, IL-5, IgE, and other related targets, which is dictated by the mechanisms of inflammatory responses. GZMK drives inflammatory processes through the complement cascade. Compared to other targets, GZMK is located further upstream, which is the fundamental reason it can serve as an earlier biomarker.
A 2021 Cochrane review demonstrated the efficacy of biologics in the treatment of chronic rhinosinusitis with polyps. Therapeutic effects include reduction in nasal congestion, reduction in polyp size, improvement in smell and disease-specific quality-of-life score, and minimization of the need for oral steroids and surgical revisions.
However, short-term risks of systemic biologic use include arthralgias, rash, and conjunctivitis. Moreover, the cost of these medications will be prohibitive for many patients.
