Young woman after sinusitis smelling flowers in the vase

Sinusitis

Sinusitis

Last Section Update: 11/2012

Contributor(s): Shayna Sandhaus, PhD

1 Overview

Summary and Quick Facts for Sinusitis

  • Sinusitis is inflammation in the sinuses. It causes symptoms such as throbbing facial pain or pressure, headache, runny nose and ear pain.
  • Since sinusitis usually resolves on its own, treatment with medications other than mild anti-inflammatories or pain relievers is often unnecessary. However, antibiotics are often prescribed for sinusitis, potentially contributing to the problem of antibiotic resistance.
  • In this protocol, learn about the different causes of sinusitis and when aggressive treatments like antibiotics are needed. Discover several supplements that can support healthy sinuses.
  • N-acetylcysteine is an amino-acid derivative that has mucus-thinning properties may help keep sinuses healthy.

What is Sinusitis?

Sinusitis is inflammation of the sinuses (ie, small air-filled cavities within the bones of the face surrounding the nose). Inflammation occurs when the drainage opening is blocked and stagnant mucus accumulates in the cavity. Anything that prevents drainage from the sinuses, such as anatomical obstructions or swelling from an infection, can cause sinusitis. Sinusitis should not be confused with rhinitis (ie, inflammation of the mucosal surface of the nasal cavity); however, since most cases of sinusitis include symptoms of rhinitis, the term rhinosinusitis is often used.

Often, acute sinusitis resolves on its own, and so antibiotics are not usually necessary or even desirable.

Natural interventions such as lactoferrin and vitamin C may help prevent and alleviate symptoms of sinusitis.

What are Causes and Risk Factors for Sinusitis?

  • Viral upper respiratory tract infection (ie, common cold)
  • Allergies
  • Cystic fibrosis
  • Facial injury
  • Change in atmospheric pressure
  • Deviated septum
  • Tumor
  • Foreign body, and others

What are the Signs and Symptoms of Sinusitis?

  • Throbbing facial pain or pressure
  • Opaque nasal secretions
  • Headache
  • Postnasal drip
  • Ear pain or pressure
  • Congestion
  • Cough
  • Aching teeth
  • Fever
  • Fatigue

Note: Symptoms usually last up to 10 days for viral sinusitis and 10 – 30 days for acute bacterial sinusitis. Chronic or recurring symptoms may indicate an underlying issue.

What are Conventional Medical Treatments for Sinusitis?

  • Decongestants
  • Mild analgesics such as aspirin, acetaminophen, and ibuprofen
  • Intranasal corticosteroids
  • Antibiotics – but only if symptoms are severe enough or last long enough to suggest a bacterial infection
  • Surgical intervention in the case of chronic sinusitis that does not respond to drug therapy

What Self-Care Strategies Can Be Beneficial for Sinusitis?

  • Get adequate rest
  • Elevate the head while sleeping to allow sinuses to drain
  • Stay hydrated
  • Avoid alcohol and caffeine
  • Eat a healthy, balanced diet with plenty of antioxidants
  • Steam inhalation
  • Warm compresses to the sinuses
  • Nasal irrigation with saline or sea salt solution

What Natural Interventions May Be Beneficial for Sinusitis?

Note: The listed natural interventions have been studied in the context of sinusitis. Those with acute sinusitis should also refer to the Common Cold protocol, as most cases of sinusitis are caused by complications from colds.

  • Lactoferrin. Lactoferrin has antibacterial, antifungal, and antiviral properties. Its production is reduced in people with sinus conditions.
  • Vitamin C. A sufficient intake of vitamin C is essential for the immune system to fight off infections. Vitamin C supplementation has been shown to decrease the risk of catching a cold and reduce the duration of cold symptoms.
  • Zinc. Zinc is required for maintaining healthy immune function. Zinc supplementation can reduce the duration and severity of the common cold when taken within 24 hours of symptom onset.
  • N-acetylcysteine (NAC). NAC may reduce the viscosity of mucus and help restore healthy sinus conditions.
  • Vitamin E. Vitamin E may have a positive effect on the immune system, helping to prevent colds and reduce nasal inflammation.
  • Bromelain. Bromelain is a proteolytic enzyme that can reduce inflammation and loosen mucus. Bromelain-treated sinusitis patients had shorter duration of symptoms than those treated conventionally or with placebo.
  • Eucalyptus. Eucalyptus oil can thin, drain, and reduce mucus secretions. It has also been shown to improve symptoms and reduce the duration of acute rhinosinusitis.
  • Other natural interventions for sinusitis include xylitol nasal irrigation, black cumin seed oil, and various herbs and herbal combinations such as rosemary, gentian root, primula flower, elder flower, sorrel herb, and verbena.

 

2 Introduction

Sinusitis is inflammation of the sinuses, which are small air-filled cavities within the bones of the face surrounding the nose (NIH 2012; NIAID 2012; MedlinePlus 2011; Mayo Clinic 2012a). Sinusitis symptoms include congestion, mucus discharge, and facial pain. The condition affects an estimated 16% of the United States adult population, resulting in millions of primary care office visits each year (Leung 2008; Smith 2012).

Sinusitis should not be confused with rhinitis, which is characterized by inflammation associated with the mucosal surface of the nasal cavity (Hytonen 2012). However, since most cases of sinusitis also include symptoms of rhinitis, the term rhinosinusitis is often used (Fokkens 2005; NIH 2012).

Sinusitis can be acute, subacute, chronic, or recurrent acute; categorization is dependent upon duration and frequency of symptoms (Leung 2008; Radojicic 2010). Acute sinusitis typically causes mild symptoms that resolve on their own, but very rarely may progress into severe or even life-threatening complications, such as a brain abscess (Onisor-Gligor 2012; Boto 2011; Suhaili 2010; Ferri 2012). Chronic sinusitis causes persistent symptoms and is often difficult to treat (Leung 2008).

Conventional pharmaceutical options to reduce inflammation in the sinuses and nasal passages include corticosteroids and decongestants, though some people receive limited, or minimal, symptom relief (Rossberg 2005). Moreover, antibiotics are often needlessly overprescribed since most cases of acute sinusitis are caused by viruses, which do not respond to antibiotics, and chronic sinusitis can be caused by chronic inflammation or anatomic irregularities (Leung 2008; Mayo Clinic 2012c; PubMed Health 2012). The inappropriate use of antibiotics can lead to antibiotic-resistant organisms and an unnecessary increase in antibiotic-related adverse events such as diarrhea (Smith 2012; Guarch Ibanez 2011).

This protocol will describe the human sinuses as well as the causes, risk factors, and symptoms of sinusitis. Conventional treatment options will be examined along with an underutilized drug-free method for relieving sinusitis symptoms. Also, a variety of scientifically studied natural sinusitis therapies will be reviewed.

The Human Sinuses

The paranasal sinuses are 4 pairs of interconnected, mucous membrane-lined cavities that drain into the nasal cavity and are formed within the skull bones that surround the nose (Ogle 2012; NIAID 2012; AAFP 2011). Each of the sinus cavities are named after the particular facial bone(s) that shape(s) them, including (NIAID 2012):

  Name   Location
Frontal sinuses Above the eyes in the brow area
Maxillary sinuses Inside each cheekbone
Ethmoid sinuses Behind the bridge of the nose, and between the eyes
Sphenoid sinuses Deeper behind the ethmoids, above the nose, and behind the eyes

The sinuses circulate air and are lined with specialized cells that produce mucus and cells that possess tiny hairs called cilia (DeMuri 2009). The sinuses contain a thin layer of watery mucus that traps and filters out pathogens and other harmful particles from inhaled air, while the cilia rhythmically pulsate or “beat”, sweeping the stagnant mucus out of the sinuses and into the nasal cavity (AAFP 2008; NIAID 2012). In addition to catching unwanted material before it reaches the lungs, mucus and cilia also work together to warm and humidify the sinuses and nasal cavities so they remain moist and do not dry out during breathing (NIAID 2012; Jurkiewicz 2011). The sinuses also generate high concentrations of nitric oxide, a free radical and immune-mediator, which may serve to maintain sterility, strengthen immune defense against viruses and bacteria, and enhance the efficiency of cilia in clearing excess mucus (DeMuri 2009; Keir 2009).

3 Causes and Risk Factors

In contrast to the nasal passages that are heavily colonized with bacteria, the paranasal sinuses are generally free from harmful bacteria or other pathogens (DeMuri 2009). However, the drainage openings (ostia) that allow the sinuses to empty into the nasal cavity are relatively small, and are thus vulnerable to becoming blocked easily (Merck 2006; Osguthorpe 2001). When this drainage system is blocked, the stagnant mucus begins to accumulate, allowing bacteria and other pathogens to colonize in the sinus cavity, resulting in inflammation and infection (ie, sinusitis) (NIH 2012A; Merck 2006).

Blockage of the ostia can occur as a result of direct mechanical obstruction, or injury that causes swelling in the nose (NIAID 2012; DeMuri 2009). The following table represents potential causes of ostia blockage (Leung 2008; NIH 2012; DeMuri 2009):

Swelling Factors

  • Viral upper respiratory tract infection (ie, common cold)
  • Allergies (eg, hay fever)
  • Cystic fibrosis
  • Chemical inhalation (eg, tobacco smoke)
  • Immune disorders
  • Facial injury
  • Changes in atmospheric pressure (eg, flying, scuba diving)
  • Overusing nasal decongestant sprays

 Mechanical & Anatomical Obstructions

  • Deviated septum
  • Nasal polyps
  • Foreign body
  • Congenital deformity
  • Tumor
  • Nasal bone spur

Although there are multiple risk factors that can contribute to ostia obstruction, allergic inflammation and viral upper respiratory infections (URIs) are the most significant (DeMuri 2009). Infection with a common cold virus is the most frequent cause of viral sinusitis (Mayo Clinic 2012b; Balkissoon 2010). Bacterial sinusitis is much less common, arising as a complication of viral sinusitis in about 0.5-2% of cases (Piccirillo 2004; Leung 2008).  

Other conditions that reduce the clearance of mucus from the sinuses can also contribute to sinusitis (DeMuri 2009). For instance, the common cold virus appears to impair mucus clearance from the sinuses by disrupting the structure and function of the cilia (AAFP 2008; DeMuri 2009). This increases the chances of developing sinusitis, particularly in the maxillary sinuses where the direction of drainage is against gravity (Leung 2008; AAFP 2008).

Since the function of cilia is largely dependent on the quality and quantity of the surrounding mucosal fluid, diseases that dry out the mucosal layer or affect its viscosity (eg, cystic fibrosis) may also contribute to sinusitis (DeMuri 2009; NIH 2012). Ostia blockage is also associated with an increase in mucosal viscosity because the trapped mucus begins to lose its water content. Likewise, sinus inflammation independently thickens sinus secretions through the release of inflammatory debris (NIAID 2012; DeMuri 2009).

In rare cases, fungi can cause sinusitis (NIAID 2012). People with abnormal sinus structures or those with weakened immune systems are more vulnerable to fungal sinusitis (NIAID 2012; Mayo Clinic 2012b; Riechelmann 2011). Between 6 and 9% of all resistant rhinosinusitis cases that require surgery are attributable to fungal infection (Schubert 2009). Unfortunately, surgical treatment is usually needed, since evidence suggests that antifungal treatment is of little to no benefit in the management of chronic rhinosinuisitis due to fungal infection (Sacks 2011, 2012; Isaacs 2011).

4 Sinusitis Symptoms

Distinguishing between sinusitis and other nasal conditions such as allergic rhinitis and the common cold can be difficult since the symptoms are often similar (Balkissoon 2010). Viral sinusitis is the most common form of sinus infection, and typically produces symptoms similar to those of the common cold that last approximately 10 days (Smith 2012; Leung 2008; Balkissoon 2010). However, symptoms of acute bacterial sinusitis typically last 10-30 days and are more severe than those of the common cold or viral sinusitis (NIAID 2012; Balkissoon 2010; Leung 2008).

Throbbing facial pain or pressure is a prominent feature in many cases of sinusitis. This symptom typically originates in the same location as the affected sinus (eg, in the forehead, cheeks, nose, or between the eyes). The pain associated with sinusitis is a result of increased pressure caused by trapped air and mucus, which pushes on the sinus mucous membrane and bony wall behind it. Sinus pain can also be caused by negative pressure within the sinuses, which occurs due to blocked sinus openings that do not allow air to enter, thus creating a vacuum space (NIAID 2012).

Sinusitis is also often marked by a change in the characteristics of nasal secretions, which progress from clear and watery to thick and opaque (eg, white, yellowish, greenish, or blood-tinged) (DeMuri 2009; NIAID 2012). The mucus becomes thick because it loses its water content while trapped in the sinus cavity. It also becomes saturated with inflammatory mediators (NIAID 2012) and appears discolored as it mixes with neutrophils, a type of white blood cell (Rosenfeld 2007).

Other symptoms linked to sinusitis include (AAFP 2008, 2011; NIH 2012; Mayo Clinic 2012b):

  • Headache
  • Postnasal drip
  • Sore throat
  • Reduced sense of smell and taste
  • Halitosis (ie, bad breath)
  • Ear pain/pressure
  • Nasal congestion and runny nose
  • Cough (may be worse at night)
  • Fever
  • Fatigue
  • Aching teeth

When symptoms of the common cold or viral sinusitis do not improve after 10 days or worsen after 5 days, bacterial sinusitis may be suspected (Balkissoon 2010; DeMuri 2009).

Sinusitis can be classified as follows (Radojicic 2010):

  • Acute – Symptoms last less than 4 weeks
  • Subacute – Symptoms last from 4 to 8 weeks
  • Chronic – Symptoms last longer than 8 weeks
  • Recurrent acute – Symptoms occur 3 or more times per year and last less than 2 weeks

5 Diagnosis and Conventional Treatment

Sinusitis is usually diagnosed based upon a physician’s assessment of a patient’s symptoms and medical history. In some cases, when a patient presents with a history of upper respiratory infection and symptoms lasting from 7 to 10 days, a bacterial culture may be obtained. Some other procedures can help aid diagnosis, but are typically not required in uncomplicated cases; these include radiography, computed tomography, endoscopic visualization of ostia secretions, and sinus puncture in cases that have failed other treatments (Fort 2012).

Conventional treatment recommendations for acute sinusitis are largely dependent upon the underlying cause of infection (Mayo Clinic 2012b). The majority of sinusitis cases are caused by viral infection, and antibiotics are generally not needed in these cases (AAFP 2011; Mayo Clinic 2012b; Smith 2012). Since the symptoms of viral sinusitis are mild-to-moderate and typically resolve on their own within 10 days or less, they can often be managed via self-care techniques and/or home remedies (Leung 2008; Mayo Clinic 2012b; Smith 2012; Puhakka 1998).

The following self-care strategies may provide relief from sinusitis symptoms:

  • Adequate rest to help the body fight infection and speed-up recovery (AAFP 2008; Mayo Clinic 2012b).
  • Elevate the head while sleeping by using an extra pillow to reduce congestion and keep the sinuses draining properly (AAFP 2008; Mayo Clinic 2012b).
  • Stay hydrated with water, as this helps to thin out mucus secretions and promote drainage (Mayo Clinic 2012b; NIH 2012). Sipping hot beverages may also help, since they can dilate blood vessels and promote drainage (AAFP 2008; Merck 2008).
  • Avoid alcohol and caffeine consumption, since they can cause dehydration and contribute to nasal and sinus swelling (AAFP 2008; Mayo Clinic 2012b).
  • Eat a healthy, well-balanced diet, which includes plenty of fruits and vegetables; a diet rich in antioxidants may boost immune function and help fight infection (NIH 2012).
  • Try steam inhalation 3-4 times daily to open sinus passages, which can reduce pain and help clear mucus (AAFP 2011). This can be done by draping a towel over the head and inhaling rising steam from a bowl of hot water (Mayo Clinic 2012b). Breathing in the warm, moist air of a hot shower or use of a humidifier may also be beneficial (AAFP 2011; Mayo Clinic 2012b; NIH 2012).
  • Apply a warm, damp towel to painful sinus areas several times a day (AAFP 2008; Mayo Clinic 2012b; NIH 2012).
  • Rinse out nasal passages with a saline nasal spray several times a day. This helps to reduce congestion by loosening mucus and cleaning out sinuses and nasal passages (AAFP 2008, 2011; Balkissoon 2010; Mayo Clinic 2012b; NIH 2012). This technique may also have a moisturizing effect, which can reduce the crusting of nasal secretions (Balkissoon 2010). Nasal irrigation with a sea salt solution appears to be as effective as saline nasal wash and topical nasal steroids for the management of chronic rhinosinusitis (Friedman 2006, 2012).

Treatment with one or more of the following medications may also help:

  • Decongestants – Also known as α-adrenergic agonists, decongestants cause blood vessel constriction, thereby reducing airway resistance by increasing the size of the airway lumen (Balkissoon 2010; DeMuri 2009; Corboz 2008). Oral decongestants such as pseudoephedrine (eg, Sudafed™) are less potent than topical nasal decongestant sprays such as oxymetazoline (eg, Afrin™) and phenylephrine (eg, Neo-Synephrine™) (Balkissoon 2010). Unlike topical nasal decongestants, oral decongestants are associated with systemic side effects, including increased blood pressure, restlessness, insomnia, and urinary retention (Balkissoon 2010; DeMuri 2009). Although topical nasal decongestants are preferred for these reasons, their use should be limited to no more than 3-5 consecutive days. This is because they quickly induce tolerance, which means that higher and higher doses will be needed to achieve the same effect (Balkissoon 2010). Furthermore, if a nasal decongestant spray is overused and then abruptly stopped, an extreme increase in nasal congestion (ie, rebound congestion) may be experienced (Mayo Clinic 2012b; Balkissoon 2010). Similarly, continued overuse of nasal decongestant sprays can cause a phenomenon known as rhinitis medicamentosa, in which congestion worsens despite continued or even increased medication use (Doshi 2009).

  • Mild analgesics – Over-the-counter pain relievers such as aspirin, acetaminophen (Tylenol™), or ibuprofen (Advil™ or Motrin™) may be helpful for temporarily relieving sinus pain and headache (Mayo Clinic 2012b; AAFP 2008). Refer to the Acetaminophen and NSAID Toxicity protocol especially when using acetaminophen over an extended period.

  • Intranasal corticosteroids – Although nasal steroids may decrease the inflammatory response associated with sinusitis, clinical trials have shown conflicting results (DeMuri 2009). The Food and Drug Administration (FDA) has not approved their use for the treatment of acute sinusitis (Leung 2008). However, nasal steroids may still be of benefit, since they are able to decrease swelling of the sinus passages associated with allergies and allow the sinuses to drain (NIAID 2012). As a result, nasal steroids may be of benefit to individuals whose nasal allergies (eg, hay fever) predispose them to developing sinusitis (DeMuri 2009).

  • Antibiotics – Although bacterial sinusitis is less common and more severe than viral sinusitis, it may resolve without the need for antibiotics (Mayo Clinic 2012b). As a result, sinusitis treatment guidelines do not recommend taking antibiotics within the first week of illness, unless the symptoms are particularly severe (eg, high fever or extreme pain). The cautious use of antibiotics for the treatment of sinusitis is warranted because they are not usually helpful, and are also associated with negative side effects, antibiotic resistance, and increased medical costs (Smith 2012). If deemed necessary,  antibiotics that  may be prescribed include amoxicillin, doxycycline, and trimethoprim-sulfamethoxazole (Mayo Clinic 2012b). A typical course of antibiotic treatment for severe bacterial sinusitis will last for 10-14 days, and should not be discontinued early just because the symptoms have resolved (Balkissoon 2010).

Surgical intervention is usually a last resort, and thus reserved for cases of chronic sinusitis that have not responded to drug therapy (DeMuri 2009; NIAID 2012). For example, allergic fungal sinusitis represents up to 9% of all sinusitis cases requiring surgery (Schubert 2009). The goal of surgery is to improve drainage by removing or reducing sinus obstruction (NIAID 2012). Most surgical procedures for sinusitis are aided by endoscopic visualization (DeMuri 2009). Surgery can be performed to enlarge sinus openings, remove nasal polyps, and correct anatomical abnormalities (eg, deviated septum) (DeMuri 2009; NIAID 2012; NIH 2012). For most patients, surgery results in lasting symptom improvement and an increased quality of life (DeMuri 2009; NIAID 2012); however, symptoms may reoccur (NIAID 2012).

Drug-free sinusitis relief with therapeutic ultrasound

Chronic sinusitis is notoriously difficult to treat and causes significant suffering for those it afflicts. Antibiotics and/or corticosteroid therapies may fail to provide relief in some cases, leaving surgery as a last resort (Leung 2008).

Therapeutic ultrasound, in which low-frequency ultrasound waves are applied to the sinuses, appears to be an effective drug-free treatment for chronic, as well as acute sinusitis, with little potential for side effects (Patel 2012).

In a 2010 study on 22 subjects with a history of chronic rhinosinusitis that had failed aggressive medical management, therapeutic ultrasound 3 days per week for 6 sessions lead to a 34% improvement on a standardized assessment of sinusitis symptoms (Young 2010). A 2012 study on 30 chronic rhinosinusitis patients who received therapeutic ultrasound 3 days per week for 10 sessions revealed a reduction of sinusitis symptoms of up to 65% (Ansari 2012). A 2010 case report showed that this same treatment regimen resolved sinusitis symptoms in a patient who had been suffering from chronic sinusitis for a year. After the treatment the patient only experienced mild nasal obstruction (Ansari 2010). In a larger 2010 trial involving 42 subjects with acute sinusitis, therapeutic ultrasound administered for 4 consecutive days provided as much relief from symptoms as the antibiotic amoxicillin (Hosoien 2010).

Therapeutic ultrasound has been shown to disrupt biofilms (Karosi 2012). A Biofilm is a layer of mucus-like film secreted by some pathogens that helps infectious organisms colonize a surface. Organisms embedded in a biofilm are very difficult to eradicate. In the sinus cavities, biofilms appear to contribute to persistent infection and are associated with sinusitis (Biel 2011; Bezerra 2009). Therapeutic ultrasound appears to disrupt biofilm, which may contribute to its efficacy in relieving sinusitis symptoms (Karosi 2012; Patel 2012; Young 2010).

6 Nutrients

In addition to the natural therapies listed below, which have been studied in the context of sinusitis, those with acute sinusitis should refer to the Common Cold protocol, since a majority of sinusitis cases arise from complications of the common cold (Puhakka 1998; Han 2011; NIH 2012).

LactoferrinLactoferrin and its active metabolite, lactoferricin, are multifunctional proteins known to possess antibacterial, antifungal, and antiviral activities, as well as immune regulatory and anti-inflammatory actions (Psaltis 2008). Lactoferrin is a component of whey protein that can also be found in high concentrations within mucosal secretions, such as airway mucus, tears, and breast milk (Roxas 2007; Acioglu 2012). Lactoferrin is produced and stored within the cells of the nasal mucosa and is presumed important as a first line of defense against invading pathogens (Acioglu 2012).

Research suggests that lactoferrin may be beneficial for alleviating the symptoms and complications of the common cold for at least 2 reasons. First, it can kill bacteria through the binding of iron molecules that would otherwise be needed for essential bacterial functions (Acioglu 2012; Roxas 2007). Second, lactoferrin exerts an antioxidant effect by preventing the formation of free radicals, thus decreasing nasal tissue oxidative damage (Acioglu 2012).

Studies suggest that decreased levels of lactoferrin may play a role in the development of chronic sinusitis, especially when nasal polyps, asthma, and/or allergies are involved (Zielinska-Blizniewska 2012; Psaltis 2008). Lactoferrin production is reduced in people with sinus conditions compared to healthy subjects. Moreover, lactoferrin levels are particularly low in sinusitis patients with nasal polyps. The low levels of lactoferrin associated with sinusitis are due to both its decreased expression/down-regulation as well as its increased utilization to fight infection (Acioglu 2012).

Vitamin C - Since the human body cannot synthesize vitamin C, it must be acquired from the diet (Hemavathi 2010). Research shows a sufficient daily intake of ascorbic acid is required for the immune system to defend the body against infections (especially viral infections) (Ely 2007).

Evidence suggests that supplementation with 1000 mg daily of vitamin C can decrease the risk of catching a cold (Holt 2010). When given in doses greater than 200 mg daily, vitamin C has been shown to reduce the duration of cold symptoms by 1-4 days (Khalid 2011). Vitamin C markedly improves immune function by enhancing natural killer cell activity, interferons (signaling proteins that boost immune response), macrophages, T-lymphocyte production, cell movement (ie, chemotaxis), and cell-mediated immunity (Heimer 2009; Khalid 2011).

Individuals with sinusitis typically exhibit decreased serum levels of vitamin C (Cho 2009; Unal 2004). Topical vitamin C may be associated with enhanced mucociliary clearance of the paranasal sinuses, through the loosening of thick mucus secretions, and an increase in ciliary beat frequency (Cho 2009; Zhang 2012). Oral vitamin C supplementation also reliably decreases plasma levels of histamine, a known contributor to inflammation and nasal congestion, especially among people with allergy-induced sinusitis (Helms 2006; Naclerio 2010).

ZincZinc is an essential trace element required for a variety of metabolic processes (Classen 2011), including the maintenance of a healthy immune function (Roxas 2007). Unfortunately, zinc deficiency is prevalent throughout developed Western countries (Maggini 2012). Zinc deficiency, which is common among the elderly and the young, is linked to the impairment of many components of the immune response, including T- and B-lymphocyte function, natural killer cell activity, macrophage phagocytosis, and antibody formation (Maggini 2012; Pae 2012; Nriagu 2007). As a result, zinc deficiency is associated with an increased risk of infection (Maggini 2012; Pae 2012). In one study, children with chronic rhinosinusitis exhibited lower levels of antioxidants, including zinc, than healthy control subjects (Unal 2004). Correcting zinc deficiency through supplementation is efficacious for a variety of viral infections (Pae 2012; Nriagu 2007). This may be partly attributable to zinc’s positive effect on the expression of interleukin-2 and interferon-γ, as well as on natural killer and cytotoxic T cells, which help the immune system kill viruses (Sandstead 2010).

Zinc supplementation has long been considered an effective therapy for reducing the duration of the common cold (Roxas 2007; Nriagu 2007). A 2011 study concluded that zinc supplementation significantly reduced both duration and severity of the common cold when administered within 24 hours of the onset of symptoms. This study also revealed that zinc supplementation over 5 months was helpful for preventing infection by common cold viruses (Singh 2011). Likewise, a clinical study involving zinc nasal gel (given within 1-2 days of illness onset) found that zinc was able to reduce the severity and duration of common cold symptoms among healthy adults (Mossad 2003). In a 2012 study, researchers found that the combination of zinc plus vitamin C was more efficacious than placebo at reducing runny nose, and it also appeared to accelerate recovery in common cold patients (Maggini 2012).

N-acetyl cysteineN-acetyl cysteine (NAC) may reduce the viscosity and improve the clearance of mucus. NAC has antioxidant properties, which can help protect against free radical damage. It may also help restore healthy sinus conditions that have deteriorated due to sinusitis (Clinical Pharmacology 2012).
A 2010 study found that NAC is capable of fighting infections, such as those that cause sinusitis, through its ability to break down biofilms. Biofilms are essentially a community of bacteria that adhere to surfaces, including moist mucus membranes. These biofilms are known to produce resistant communities of bacteria and are estimated to be involved in at least 60% of all chronic and/or recurrent infections. NAC has been shown to reduce the adhesion of biofilms to mucus membranes (eg, antibiotics or nasal steroids) (Pintucci 2010).

Vitamin E – Numerous studies have demonstrated that vitamin E may have a positive effect on the human immune system. For instance, elderly patients who took 200 IU of vitamin E daily for 1 year were 20% less likely to catch a cold (Burton 2004). In one study, children with chronic rhinosinusitis were found to have lower serum levels of several antioxidants, including vitamin E, than healthy children (Unal 2004). A 2011 study found that topical vitamin E (in combination with other antioxidant oils) was able to persistently reverse oxidative stress and nasal inflammation, similar to that by viral infections, chronic sinusitis, and allergic disease (Gao 2011). Furthermore, animal studies show that vitamin E may affect the risk and severity of viral respiratory infections (Hemila 2006).

Rosmarinic acid – Rosmarinic acid is an antioxidant compound found in rosemary (Kelsey 2010). In experimental animal models, rosmarinic acid has been shown to reduce allergic inflammatory reactions by decreasing histamine release and inhibiting the expression of interleukin (IL)-1β, IL-6 and tumor necrosis factor-alpha (TNF-α) (Oh 2011). This mechanism of action may be significant for individuals suffering from chronic sinusitis caused by allergies.  

Bromelain – Bromelain, which is a proteolytic enzyme complex found in pineapple, is frequently used to treat sinusitis because it reduces inflammation and loosens mucus. Specifically, bromelain may inhibit pro-inflammatory prostaglandin biosynthesis and prostaglandin E1 accumulation. This in turn inhibits the release of leukocyte enzymes. Among sinusitis patients, bromelain has been shown to hasten symptom recovery and resolve inflammation better than standard treatment or placebo. Typical oral doses of bromelain are between 500-2000 mg daily (Helms 2006).

Eucalyptus – Cineole is the main ingredient of eucalyptus oil. It has anti-inflammatory and antimicrobial properties, and it also affects ciliary beat frequency (Tesche 2008). Studies have confirmed that cineole can thin, drain, and reduce mucus secretions. In a clinical study involving 152 patients with acute rhinosinusitis, cineole was associated with significant symptom improvement at 4 and 7 days when compared to placebo. The authors concluded that cineole is safe and effective for the treatment of acute rhinosinusitis, and suggested that it be utilized prior to the initiation of antibiotics (Kehrl 2004). In 2008, a similar study was conducted among 150 patients with acute and viral rhinosinusitis. These authors also found that treatment with cineole resulted in reduced symptoms at 4 and 7 days, and concluded that this treatment effect was clinically relevant (Tesche 2008).

Herbal combination formula – A combination of Gentian root, Primula flower, Elder flower, Sorrel herb, and Verbena herb is frequently used in the treatment of acute and chronic rhinosinusitis (Glatthaar-Saalmuller 2011; Rossi 2012). Results from a 2011 laboratory study demonstrated that this formula shows a broad spectrum of antiviral activity against viruses commonly known to cause respiratory infections (Glatthaar-Saalmuller 2011). A more concentrated version of the formula (ie, dry extract) reduced exudate volume and leukocyte numbers in an animal study. It also reduced the expression of cyclooxygenase-2 protein and lowered prostaglandin E2 levels. Therefore, the rationality for using the combination formula to manage sinusitis is partly based on its significant anti-inflammatory effects (Rossi 2012). Since inflammation of the mucosa can often lead to a loss of smell, researchers theorize that this combination of herbs may be useful for this indication as well (Reden 2011).

Xylitol nasal irrigation – Xylitol is a sugar alcohol that appears to enhance the body’s natural defense against bacterial pathogens. An animal model showed that administering xylitol solution simultaneously with a bacterial pathogen reduced the amount of bacteria detectable upon a later examination of the sinuses (Brown 2004). In one trial, 20 subjects with chronic rhinosinusitis were randomized and instructed to rinse their sinuses daily with either a xylitol or saline solution. Fifteen subjects completed the study. Nasal irrigation with the xylitol solution was associated with a significant improvement on a standardized assessment of sinusitis symptoms (Weissman 2011). Another trial designed to assess the effects of xylitol nasal irrigation compared to placebo in the treatment of chronic sinusitis is recruiting participants as of November 2012 (ClinicalTrials.gov NCT00924404).

Black cumin seed oil – Nigella sativa, also known as black cumin, is a flowering plant that grows in Eastern Europe, the Middle East, and Western Asia. The small black seeds of nigella sativa have a rich history of medical use in the Middle East and Asian countries. Modern scientific inquiry has examined the potential benefit of black cumin seeds and the oil derived from them in a variety of contexts ranging from cardiovascular disease to cancer (Shabana 2012; Randhawa 2011; Woo 2012; Butt 2010). Several lines of evidence suggest that black cumin seed oil and some of its active constituents are powerful anti-inflammatory agents and also combat oxidative stress (Inci 2012; Umar 2012; Ammar el 2011). In an animal model of rhinosinusitis, an active constituent derived from black cumin seed was found to be as effective as antibiotic therapy in reducing manifestations of sinusitis such as vascular congestion, inflammation, and epithelial injury in sinus tissue (Cingi 2011).

2012

  • Nov: Comprehensive update & review

Disclaimer and Safety Information

This information (and any accompanying material) is not intended to replace the attention or advice of a physician or other qualified health care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a physician or other qualified health care professional. Pregnant women in particular should seek the advice of a physician before using any protocol listed on this website. The protocols described on this website are for adults only, unless otherwise specified. Product labels may contain important safety information and the most recent product information provided by the product manufacturers should be carefully reviewed prior to use to verify the dose, administration, and contraindications. National, state, and local laws may vary regarding the use and application of many of the therapies discussed. The reader assumes the risk of any injuries. The authors and publishers, their affiliates and assigns are not liable for any injury and/or damage to persons arising from this protocol and expressly disclaim responsibility for any adverse effects resulting from the use of the information contained herein.

The protocols raise many issues that are subject to change as new data emerge. None of our suggested protocol regimens can guarantee health benefits. Life Extension has not performed independent verification of the data contained in the referenced materials, and expressly disclaims responsibility for any error in the literature.

AAFP (American Academy of Family Physicians) Patient Education: Sinusitis. Copyright © 2008.

AAFP (American Academy of Family Physicians) Sinus infections (sinusitis): Am Fam Physician. 2011 May 1;83(9):1064-5.

Acioglu E, Yigit O, Alkan Z, Azizli E, Gelisgen R, Uzun H. The effects of corticosteroid on tissue lactoferrin in patients with nasal polyposis. Am J Rhinol Allergy. 2012;26(1):e28-31.

Ammar el SM, Gameil NM, Shawky NM, Nader MA. Comparative evaluation of anti-inflammatory properties of thymoquinone and curcumin using an asthmatic murine model. International immunopharmacology. Dec 2011;11(12):2232-2236.

Ansari NN, Fathali M, Naghdi S, Hasson S, Jalaie S, Rastak MS. A randomized, double-blind clinical trial comparing the effects of continuous and pulsed ultrasound in patients with chronic rhinosinusitis. Physiotherapy theory and practice. Feb 2012;28(2):85-94.

Ansari NN, Fathali M, Naghdi S, Hasson S. Effect of pulsed ultrasound on chronic rhinosinusitis: a case report. Physiotherapy theory and practice. Nov 2010;26(8):558-563.

Balkissoon R. (2010) Chapter 43: Disorders of the Upper Airways (pg. 1047). In: Mason R. (Ed.), Murray and Nadel's Textbook of Respiratory Medicine (5th ed). Saunders, An Imprint of Elsevier.

Bezerra TF, Padua FG, Ogawa AI, Gebrim EM, Saldiva PH, Voegels RL. Biofilm in chronic sinusitis with nasal polyps: pilot study. Brazilian journal of otorhinolaryngology. Nov-Dec 2009;75(6):788-793.

Biel MA, Sievert C, Usacheva M, Teichert M, Balcom J. Antimicrobial photodynamic therapy treatment of chronic recurrent sinusitis biofilms. International forum of allergy & rhinology. Sep-Oct 2011;1(5):329-334.

Boto LR, Calado C, Vieira M, et al. [Subdural empyema due to gemella morbillorum as a complication of acute sinusitis]. Acta Med Port. 2011;24(3):475-480.

Brown CL, Graham SM, Cable BB, Ozer EA, Taft PJ, Zabner J. Xylitol enhances bacterial killing in the rabbit maxillary sinus. The Laryngoscope. Nov 2004;114(11):2021-2024.

Burton A. Fewer colds with increased vitamin E intake: Lancet Infect Dis. 2004 Oct;4(10):600.

Butt MS, Sultan MT. Nigella sativa: reduces the risk of various maladies. Critical reviews in food science and nutrition. Aug 2010;50(7):654-665.

Cho DY, Hwang PH, Illek B. Effect of L-ascorbate on chloride transport in freshly excised sinonasal epithelia. Am J Rhinol Allergy. 2009;23(3):294-299.

Cingi C, Eskiizmir G, Burukoglu D, Erdogmus N, Ural A, Unlu H. The histopathological effect of thymoquinone on experimentally induced rhinosinusitis in rats. American journal of rhinology & allergy. Nov-Dec 2011;25(6):e268-272.

Classen HG, Grober U, Low D, Schmidt J, Stracke H. [Zinc deficiency. Symptoms, causes, diagnosis and therapy]. Med Monatsschr Pharm. 2011;34(3):87-95.

Clinical Pharmacology. Acetylcysteine: drug monograph. 2012.

ClinicalTrials.gov NCT00924404. Xylitol Versus Saline in Chronic Sinusitis. Accessed 11/2/2012 at: http://clinicaltrials.gov/ct2/show/NCT00924404?term=sinusitis&rank=31Dabrowska K, Kozlowski Z, Durko T, Stanczyk R, Pietruszewska W. [Fungal rhinosinusitis - still unsolved problem]: Otolaryngol Pol. 2011 Sep-Oct;65(5):369-76.

Corboz MR, Rivelli MA, Mingo GG, McLeod RL, Varty L, Jia Y, Hey JA. Mechanism of decongestant activity of alpha 2-adrenoceptor agonists. Pulmonary pharmacology & therapeutics. 2008;21(3):449-454.

DeMuri G. (2009) Chapter 58: Sinusitis (pg. 839). In: Mandell G. (Ed.), Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases (7th ed). Churchill Livingstone, An Imprint of Elsevier

Doshi J. Rhinitis medicamentosa: what an otolaryngologist needs to know. European archives of oto-rhino-laryngology: official journal of the European Federation of Oto-Rhino-Laryngological Societies. May 2009;266(5):623-625.

Ely JT. Ascorbic acid role in containment of the world avian flu pandemic. Exp Biol Med. 2007;232(7):847-851.

Ferri FF. Sinusitis. In: Ferri: Ferri’s Clinical Advisor 2013, 1st ed. Copyright © 2012 Mosby, An Imprint of Elsevier. Available at: http://www.mdconsult.com/books/page.do?sid=1374951423&eid=4-u1.0-B978-0-323-08373-7..00028-5--sc0115&isbn=978-0-323-08373-7&uniqId=378286358-1596. Accessed November 2, 2012.

Fokkens W, Lund V, Bachert C, et al. EAACI position paper on rhinosinusitis and nasal polyps executive summary. Allergy. 2005;60(5):583-601.

Fort GG, Mikolich DJ. Sinusitis. Ferri: Ferri's Clinical Advisor 2013, 1st ed.: ®©Mosby, An Imprint of Elsevier 2012. Accessed 11/8/2012 at: http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-0-323-08373-7..00028-5--sc0115&isbn=978-0-323-08373-7&sid=1377899512&uniqId=379998037-7#4-u1.0-B978-0-323-08373-7..00028-5--sc0115

Friedman M, Hamilton C, Samuelson CG, et al. Dead Sea salt irrigations vs saline irrigations with nasal steroids for symptomatic treatment of chronic rhinosinusitis: a randomized, prospective double-blind study. Int Forum Allergy Rhinol. 2012;2(3):252-257.

Friedman M, Vidyasagar R, Joseph N. A randomized, prospective, double-blind study on the efficacy of dead sea salt nasal irrigations. Laryngoscope. 2006;116(6):878-882.

Gao M, Singh A, Macri K, et al. Antioxidant components of naturally-occurring oils exhibit marked anti-inflammatory activity in epithelial cells of the human upper respiratory system. Respir Res. 2011;12:92.

Glatthaar-Saalmuller B, Rauchhaus U, Rode S, Haunschild J, Saalmuller A. Antiviral activity in vitro of two preparations of the herbal medicinal product Sinupret(R) against viruses causing respiratory infections. Phytomedicine. 2011;19(1):1-7.

Guarch Ibanez B, Bunuel Alvarez JC, Lopez Bermejo A, Mayol Canals L. [The role of antibiotics in acute sinusitis: a systematic review and meta-analysis]. Anales de pediatria (Barcelona, Spain : 2003). Mar 2011;74(3):154-160.

Han JK, Hendley JO, Winther B. Bacterial pathogens of acute sinusitis in the osteomeatal complex during common colds and wellness. Int Forum Allergy Rhinol. 2011;1(5):356-360.

Heimer KA, Hart AM, Martin LG, Rubio-Wallace S. Examining the evidence for the use of vitamin C in the prophylaxis and treatment of the common cold. J Am Acad Nurse Pract. 2009;21(5):295-300.

Helms S, Miller A. Natural treatment of chronic rhinosinusitis. Altern Med Rev. 2006;11(3):196-207.

Hemavathi, Upadhyaya CP, Akula N, et al. Enhanced ascorbic acid accumulation in transgenic potato confers tolerance to various abiotic stresses. Biotechnol Lett. 2010;32(2):321-330.

Hemila H, Virtamo J, Albanes D, Kaprio J. The effect of vitamin E on common cold incidence is modified by age, smoking and residential neighborhood. J Am Coll Nutr. 2006;25(4):332-339.

Holt S. Hype around high-dose vitamin C is unjustified: N Z Med J. 2010 Oct 15;123(1324):109-10.

Hosoien E, Lund AB, Vasseljen O. Similar effect of therapeutic ultrasound and antibiotics for acute bacterial rhinosinusitis: a randomised trial. Journal of physiotherapy. 2010;56(1):29-32.

Hytonen M, Suvilehto J. [Sinusitis or rhinosinusitis?]. Duodecim. 2012;128(2):230-231.

Inci M, Davarci M, Inci M, et al I. Anti-inflammatory and antioxidant activity of thymoquinone in a rat model of acute bacterial prostatitis. Human & experimental toxicology. Aug 7 2012.

Isaacs S, Fakhri S, Luong A, Citardi MJ. A meta-analysis of topical amphotericin B for the treatment of chronic rhinosinusitis. International forum of allergy & rhinology. Jul-Aug 2011;1(4):250-254.

Jurkiewicz D, Rapiejko P. [Use of isotonic NaCl solution in patients with acute rhinosinusitis]. Otolaryngol Pol. 2011;65(1):47-53.

Karosi T, Sziklai I, Csomor P. Low-frequency ultrasound for biofilm disruption in chronic rhinosinusitis with nasal polyposis: In vitro pilot study. The Laryngoscope. Aug 14 2012.

Kehrl W, Sonnemann U, Dethlefsen U. Therapy for acute nonpurulent rhinosinusitis with cineole: results of a double-blind, randomized, placebo-controlled trial. Laryngoscope. 2004;114(4):738-742.

Keir J. Why do we have paranasal sinuses? J Laryngol Otol. 2009;123(1):4-8.

Kelsey NA, Wilkins HM, Linseman DA. Nutraceutical antioxidants as novel neuroprotective agents. Molecules. 2010;15(11):7792-7814.

Khalid U, Saleem T, Shah S. Therapeutic and prophylactic use of vitamin C for the common cold: J Pak Med Assoc. 2011 Dec;61(12):1252.

Leung RS, Katial R. The diagnosis and management of acute and chronic sinusitis. Prim Care. 2008;35(1):11-24.

Maggini S, Beveridge S, Suter M. A combination of high-dose vitamin C plus zinc for the common cold. J Int Med Res. 2012;40(1):28-42.

Mayo Clinic. Chronic sinusitis. Causes. Available at: http://www.mayoclinic.com/health/chronic-sinusitis/DS00232/DSECTION=causes. Last updated January 20, 2012c. Accessed November 2, 2012.

Mayo Clinic. Chronic sinusitis. Symptoms. Available at: http://www.mayoclinic.com/health/chronic-sinusitis/DS00232/DSECTION=symptoms. Last updated January 20, 2012a. Accessed November 2, 2012.

Mayo Clinic. Health Information: Acute sinusitis. Updated Jan 20, 2012b. Accessed 8/20/12 at: http://www.mayoclinic.com/health/acute-sinusitis/DS00170/METHOD=print

Medline Plus. Nasal discharge. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/003051.htm. Last updated August 12, 2011. Accessed November 2, 2012.

Merck Manual Home Health Handbook. Sinusitis. Last Reviewed July 2006. Accessed on 8/19/12. Available at: http://www.merckmanuals.com/home/ear_nose_and_throat_disorders/biology_of_the_ears_nose_and_throat/nose_and_sinuses.html

Merck Manual Home Health Handbook. Sinusitis. Last Reviewed July 2008. Accessed on 8/18/12. Available at: http://www.merckmanuals.com/home/ear_nose_and_throat_disorders/nose_and_sinus_disorders/sinusitis.html#v796315

Mossad SB. Effect of zincum gluconicum nasal gel on the duration and symptom severity of the common cold in otherwise healthy adults. Qjm. 2003;96(1):35-43.

Naclerio RM, Bachert C, Baraniuk JN. Pathophysiology of nasal congestion. Int J Gen Med. 2010;3:47-57.

NIAID (National Institute of Allergy and Infectious Diseases). Sinusitis. Last Updated January 2012. Available at: http://www.niaid.nih.gov/topics/sinusitis/Documents/sinusitis.pdf

NIH (National institutes of Health) Medline Plus: Sinusitis. Last Updated August 8, 2012. Accessed 8/15/12. Available at: http://www.nlm.nih.gov/medlineplus/sinusitis.html

Nriagu J. Zinc Deficiency in Human Health. In: Nriagu J, Encyclopedia of Environmental Health. University of Michigan, MI: Elsevier; 2007.

Ogle OE, Weinstock RJ, Friedman E. Surgical anatomy of the nasal cavity and paranasal sinuses. Oral and maxillofacial surgery clinics of North America. May 2012;24(2):155-166, vii.

Oh HA, Park CS, Ahn HJ, Park YS, Kim HM. Effect of Perilla frutescens var. acuta Kudo and rosmarinic acid on allergic inflammatory reactions. Exp Biol Med. 2011;236(1):99-106.

Onisor-Gligor F, Lung T, Pintea B, Muresan O, Pop PB, Juncar M. Maxillary odontogenic sinusitis, complicated with cerebral abscess--case report. Chirurgia. 2012;107(2):256-259.

Osguthorpe JD. Adult Rhinosinusitis: Diagnosis and Management. Am Fam Physician. 2001;63(1):69-77.

Pae M, Meydani SN, Wu D. The role of nutrition in enhancing immunity in aging. Aging Dis. 2012;3(1):91-129.

Patel ZM, Hwang PH, Chernomorsky A, Bravo DT, Nguyen BL, Nesterova K, Nayak JV. Low-frequency pulsed ultrasound in the nasal cavity and paranasal sinuses: a feasibility and distribution study. International forum of allergy & rhinology. Jul-Aug 2012;2(4):303-308.

Piccirillo JF. Clinical practice. Acute bacterial sinusitis. The New England journal of medicine. Aug 26 2004;351(9):902-910.

Pintucci JP, Corno S, Garotta M. Biofilms and infections of the upper respiratory tract. Eur Rev Med Pharmacol Sci. 2010;14(8):683-690.

Psaltis AJ, Wormald PJ, Ha KR, Tan LW. Reduced levels of lactoferrin in biofilm-associated chronic rhinosinusitis. Laryngoscope. 2008;118(5):895-901.

PubMed Health. Sinusitis. Available at: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001670/. July 30, 2012. Accessed November 2, 2012.

Puhakka T, Makela MJ, Alanen A, et al. Sinusitis in the common cold. J Allergy Clin Immunol. 1998;102(3):403-408.

Radojicic C. Sinusitis. In: Cleveland Clinic: Current Clinical Medicine, 2nd ed. Copyright © 2010 Saunders, An Imprint of Elsevier. Accessed 11/2/2012 at: http://www.mdconsult.com/books/page.do?sid=1374956842&eid=4-u1.0-B978-1-4160-6643-9..00006-0&isbn=978-1-4160-6643-9&uniqId=378358841-38

Randhawa MA, Alghamdi MS. Anticancer activity of Nigella sativa (black seed) - a review. The American journal of Chinese medicine. 2011;39(6):1075-1091.

Reden J, El-Hifnawi D, Zahnert T, Hummel T. The effect of a herbal combination of primrose, gentian root, vervain, elder flowers, and sorrel on olfactory function in patients with a sinonasal olfactory dysfunction. Rhinology. 2011;49(3):342-346.

Riechelmann H. [Fungal sinusitis] [Article in German]. Laryngorhinootologie. Jun 2011;90(6):374-81.

Rosenfeld RM, Andes D, Bhattacharyya N, et al. Clinical practice guideline: adult sinusitis. Otolaryngol Head Neck Surg. 2007;137(3 Suppl):S1-31.

Rossberg E, Larsson PG, Birkeflet O, Soholt LE, Stavem K. Comparison of traditional Chinese acupuncture, minimal acupuncture at non-acupoints and conventional treatment for chronic sinusitis. Complement Ther Med. 2005;13(1):4-10.

Rossi A, Dehm F, Kiesselbach C, Haunschild J, Sautebin L, Werz O. The novel Sinupret(R) dry extract exhibits anti-inflammatory effectiveness in vivo. Fitoterapia. 2012;83(4):715-720.

Roxas M, Jurenka J. Colds and influenza: a review of diagnosis and conventional, botanical, and nutritional considerations. Altern Med Rev. 2007;12(1):25-48.

Sacks PL, Harvey RJ, Rimmer J, Gallagher RM, Sacks R. Antifungal therapy in the treatment of chronic rhinosinusitis: a meta-analysis. American journal of rhinology & allergy. Mar-Apr 2012;26(2):141-147.

Sacks PL, Harvey RJ, Rimmer J, Gallagher RM, Sacks R. Topical and systemic antifungal therapy for the symptomatic treatment of chronic rhinosinusitis. Cochrane database of systematic reviews. 2011(8):CD008263.

Sandstead HH, Prasad AS. Zinc intake and resistance to H1N1 influenza: Am J Public Health. 2010 Jun;100(6):970-1. Epub 2010 Apr 15.

Schubert MS. Allergic fungal sinusitis: pathophysiology, diagnosis and management. Med Mycol. 2009;47(1):27.

Shabana A, El-Menyar A, Asim M, Al-Azzeh H, Al Thani H. Cardiovascular Benefits of Black Cumin (Nigella sativa). Cardiovascular toxicology. Aug 22 2012.

Singh M, Das RR. Zinc for the common cold. Cochrane Database Syst Rev. 2011;16(2).

Smith SR, Montgomery LG, Williams JW, Jr. Treatment of mild to moderate sinusitis. Archives of internal medicine. Mar 26 2012;172(6):510-513.

Suhaili DN, Goh BS, Gendeh BS. A ten year retrospective review of orbital complications secondary to acute sinusitis in children. Med J Malaysia. 2010;65(1):49-52.

Tesche S, Metternich F, Sonnemann U, Engelke JC, Dethlefsen U. The value of herbal medicines in the treatment of acute non-purulent rhinosinusitis. Results of a double-blind, randomised, controlled trial. Eur Arch Otorhinolaryngol. 2008;265(11):1355-1359.

Umar S, Zargan J, Umar K, Ahmad S, Katiyar CK, Khan HA. Modulation of the oxidative stress and inflammatory cytokine response by thymoquinone in the collagen induced arthritis in Wistar rats. Chemico-biological interactions. Apr 15 2012;197(1):40-46.

Unal M, Tamer L, Pata YS, et al. Serum levels of antioxidant vitamins, copper, zinc and magnesium in children with chronic rhinosinusitis. J Trace Elem Med Biol. 2004;18(2):189-192.

Weissman JD, Fernandez F, Hwang PH. Xylitol nasal irrigation in the management of chronic rhinosinusitis: a pilot study. The Laryngoscope. Nov 2011;121(11):2468-2472.

Woo CC, Kumar AP, Sethi G, Tan KH. Thymoquinone: potential cure for inflammatory disorders and cancer. Biochemical pharmacology. Feb 15 2012;83(4):443-451.

Young D, Morton R, Bartley J. Therapeutic ultrasound as treatment for chronic rhinosinusitis: preliminary observations. J Laryngol Otol. May 2010;124(5):495-499.

Zhang N, Van Crombruggen K, Holtappels G, Bachert C. A Herbal Composition of Scutellaria baicalensis and Eleutherococcus senticosus Shows Potent Anti-Inflammatory Effects in an Ex Vivo Human Mucosal Tissue Model. Evid Based Complement Alternat Med. 2012;673145:5.

Zielinska-Blizniewska H, Sitarek P, Milonski J, et al. Association of the -33C/G OSF-2 and the 140A/G LF gene polymorphisms with the risk of chronic rhinosinusitis with nasal polyps in a Polish population. Mol Biol Rep. 2012;39(5):5449-5457.