key: cord-0730449-ow7tovxa
authors: Taw, Malcolm B.; Nguyen, Chau T.; Wang, Marilene B.
title: Complementary and Integrative Treatments: Rhinosinusitis
date: 2013-04-27
journal: Otolaryngol Clin North Am
DOI: 10.1016/j.otc.2013.02.002
sha: 7789852d2607338406c1df13172425c955d0f568
doc_id: 730449
cord_uid: ow7tovxa

Rhinosinusitis is characterized by inflammation of the mucosa involving the paranasal sinuses and the nasal cavity and is one of the most common health care problems, with significant impairment of quality of life. There is a growing amount of interest in the use of complementary and integrative medicine for the treatment of rhinosinusitis. This article focuses on an integrative approach to rhinosinusitis.

The paranasal sinuses are comprised of 4 paired sinuses: maxillary, ethmoid, sphenoid, and frontal. The roof of the ethmoid sinus is the fovea ethmoidalis, which forms the floor of the anterior cranial cavity and slopes upward at an angle from the midline to extend 2 to 3 mm above the cribriform plate. The lateral wall of the ethmoid is the lamina papyracea, which is also the medial wall of the orbit. The ethmoid sinuses are comprised of numerous small air cells, which develop from evaginations of the lateral nasal wall in the embryo. There are an average of 9 ethmoid air cells present, although the number varies widely.

The ethmoid sinus can be divided into anterior and posterior groups of air cells. The anterior group of ethmoid cells includes the frontal recess, bullar, and infundibular cells. The infundibulum is the site of drainage for the frontal sinus and anterior ethmoid cells and is located lateral to the middle turbinate and anterior to the bulla. The bullar cells drain into the middle meatus via the hiatus semilunaris, a large cleft in the lateral nasal wall. The uncinate process, which forms the anterior border of the hiatus semilunaris, is a ridge of bone extending from the ascending process of the maxilla. The remaining anterior ethmoid cells drain into the middle meatus, whereas the posterior cells drain into the sphenoethmoidal recess. The vascular supply for the ethmoid sinuses is from the anterior and posterior ethmoidal arteries, and innervation of the sinuses comes from the orbital division of the fifth cranial nerve.

The maxillary sinuses are roughly triangular in shape, with boundaries of the orbital floor superiorly, the lateral nasal wall medially, and the bony lateral wall. The sinus drains into the natural ostium on the superior medial wall, which flows into the hiatus semilunaris. There may also be accessory maxillary sinus ostia in the medial sinus wall.

The frontal sinus originates from the frontal recess cells of the anterior ethmoid and at birth is often indistinguishable from these cells. The frontal sinus is usually well formed by 12 years of age but does not reach adult size until 18 to 20 years of age. The anterior table is twice as thick as the posterior table when measured in the midsagittal plane inferiorly. An intersinus septum separates the two sinuses. The sinuses drain through a nasofrontal recess into the hiatus semilunaris beneath the middle turbinate. In most adults, this recess is a mucous membrane-lined bony canal measuring 3 mm or greater.

The ostiomeatal complex includes the middle turbinate, uncinate process, middle meatus, hiatus semilunaris, and infundibulum. The drainage pathways for the frontal, anterior ethmoid, and maxillary sinuses all flow through the ostiomeatal complex. Obstruction of this relatively narrow path from polyps or other mass lesions, inflammatory edema, or purulence will result in postobstructive sinusitis involving one or more of the aforementioned sinuses.

The sphenoid sinuses originate as evaginations from the sphenoethmoidal recess. They are present at birth but do not begin to pneumatize until about 3 years of age. The development of the sinuses may continue through adulthood, and the size may vary greatly because of differences in the degree of development. The midline is often an irregularly shaped intersinus septum. Drainage is into the sphenoethmoidal recess medial to the superior turbinate. The superior boundary is the sella and pituitary fossa, whereas the lateral walls contain the optic nerve, carotid artery, and cavernous sinus. There may be bony dehiscence of the lateral wall over these structures.

The paranasal sinuses are lined by respiratory epithelium, which consists of pseudostratified ciliated columnar epithelium with goblet cells. Numerous mucous and serosanguinous glands are present. In addition to mucus, the sinus glands also secrete Complementary and Integrative Treatments: Rhinosinusitis immunoglobulins, interferons, and lysozyme. The anterior portion of the nares and nasal septum are covered by skin with adnexa. The roof of the nasal cavity contains specialized olfactory epithelium with bipolar olfactory neurons.

The sinus epithelium forms a mucociliary system, which supplies the nose with a mucous covering to warm and humidify inspired air. Both parasympathetic and sympathetic nerves supply this mucous blanket, which is renewed every 10 to 15 minutes. 36, 37 The cilia beat 10 to 15 times per second and move the mucous blanket toward the natural ostia of the sinuses. Environmental factors influence ciliary function; humidity increases the activity, whereas dehydration and cold temperatures decrease flow. 38 Bacterial and viral proliferation may increase when there is dysfunction of the cilia and relative stasis of the mucous blanket. In addition to mucociliary dysfunction, any condition that obstructs the drainage of the sinuses (eg, polyps, inflammation, or edema of the nasal mucosa) will lead to sinusitis. Benign and malignant tumors of the nasal cavity, paranasal sinuses, and skull base can also lead to a postobstructive sinusitis of one or more of the paranasal sinuses.

A variety of host and environmental factors play a role in the development of RS. Host factors can be divided into general (genetic factors and immune deficiency), local (anatomic abnormalities, mucosal and bone inflammation), and environmental factors (air pollution, smoke, allergens, viruses, bacteria, and fungi). 39 The pathophysiology leading to RS of the maxillary and frontal sinuses usually involves a constellation of changes that lead to the obstruction of the ostiomeatal complex, including mucosal swelling and inflammation, mucous stasis, impaired mucociliary function, and microbial infection.

Lately, several different theories have emerged to describe the pathophysiology involved in chronic RS, especially of a recalcitrant nature, including inflammation, fungal-mediated hypersensitivity, bacterial biofilms, osteitis, and superantigens, with novel therapies targeted toward each of these specific areas. [40] [41] [42] [43] [44] [45] [46] Other conditions to consider that can mimic chronic RS include gastroesophageal reflux disease, adenoiditis, Thornwaldt cyst, dental infection, granulomatous disorders, and neoplasia. 47 

The signs and symptoms of RS can differ depending upon contributing factors and the overall duration. Acute RS often presents with purulent nasal discharge with nasal obstruction and facial pain or pressure. Additional symptoms can include hyposmia/ anosmia, headache, fever, cough, aural fullness, halitosis, fatigue, and dental pain. 32 Because purulent nasal discharge cannot be used as a sole factor to distinguish between viral and bacterial infection, the illness pattern and duration should be used instead, with viral RS usually lasting less than 10 days, but acute bacterial RS being more persistent. 2, 48 Chronic RS exists if these symptoms continue for greater than 12 weeks.

The goals of treatment are to improve drainage, remove obstruction, promote mucociliary function, eradicate infection, reduce inflammation, and prevent complications.

Medical therapies for RS can include any of the following: intranasal or systemic steroids, topical or oral antibiotics, nasal saline irrigation, topical or systemic decongestants, antihistamines, leukotriene antagonists, mucolytics, expectorants, immunotherapy, and analgesics. If these conventional therapies are not effective and symptoms become refractory, other medical options that have been used include antifungals, proton-pump inhibitors, bacterial lysates, immunomodulators, and immunostimulants. 47, [49] [50] [51] [52] Long-term, low-dose macrolide therapy may also have a role in the treatment of chronic RS, given its demonstrated antiinflammatory effects. [53] [54] [55] 

Endoscopic sinus surgery is indicated for 2 reasons: (1) failed medical treatment or (2) potential or actual complications, such as the development of a mucocele, mucopyocele, orbital abscess, invasive fungal sinusitis, anatomic obstruction caused by polyps or mass lesion, or suspicion of malignancy. Substantial evidence exists that supports surgical intervention in reducing symptoms and improving quality of life in patients with RS. 56 

In South Africa, Pelargonium sidoides (P sidoides) has historically been used to treat a variety of ailments, including upper respiratory tract infections like bronchitis and tuberculosis. 57 P sidoides, traditionally known as Umckaloabo, is rich in phenols and flavonoids, consisting of coumarins, tannins, diterpenes, and proanthocyanidins. [58] [59] [60] It has been standardized in Germany as an aqueous ethanolic extract of its root known as EPs 7630.

EPs 7630 has been shown to have significant antibacterial activity against multiresistant Staphylococcus aureus and antiviral effects against seasonal influenza A virus strains (H1N1, H3N2), respiratory syncytial virus, human coronavirus, parainfluenza virus, and Coxsackie virus. 58, 61 Through its immunomodulatory effects, EPs 7630 has been demonstrated to specifically enhance human peripheral blood phagocyte activity as well as have antiadhesive effects through interaction with bacterial surface binding factors. [62] [63] [64] A double-blind, randomized, multicenter trial conducted by Bachert and colleagues 65 enrolled 103 patients with radiographically and clinically confirmed acute RS and compared EPs 7630 (1:8-10; extraction solvent: ethanol 11% at a dosage of 60 drops 3 times daily for up to 22 days) with placebo. EPs 7630 was found to have superior efficacy and tolerance, based on changes in sinusitis severity scores. A Cochrane review concluded that P sidoides may be effective in alleviating symptoms, including headaches and nasal discharge, for acute RS and the common cold in adults. 66 Bromelain Bromelain, a mixture of proteolytic enzymes extracted from pineapples (Ananas comosus), has demonstrated antiinflammatory, antiedematous, antithrombotic, and fibrinolytic effects. 67 Three double-blind, randomized controlled trials were conducted in the 1960s on patients with acute and chronic RS, using similar protocols of 2 parallel treatment arms comparing bromelain with placebo, with each group also receiving conventional management consisting of antibiotics, decongestants, antihistamines, and analgesics. 68-70 A meta-analysis performed by Guo and colleagues 71 showed

Complementary and Integrative Treatments: Rhinosinusitis a small but statistically significant difference in favor of adjunctive treatment with bromelain for nasal mucosal inflammation, nasal discomfort, breathing difficulty, and overall rating but not for nasal discharge.

A recent multicenter trial enrolling children less than 11 years of age with acute sinusitis had 3 treatment groups (bromelain vs bromelain 1 standard therapy vs standard therapy) and showed a statistically significant recovery time with bromelain monotherapy compared with other treatment groups. 72 Only one mild self-limiting allergic reaction was noted. The 1993 German Commission E monograph concluded that bromelain may be effective for "acute postoperative and post-traumatic swelling, especially of the nose and paranasal sinuses." 73 Caution must be used when prescribing bromelain for patients already on anticoagulants because of the increased risk for bleeding as well as when prescribing various antibiotics, such as penicillin and tetracycline, because bromelain is also known to promote their absorption. 67 Moreover, bromelain strongly inhibits human cytochrome P450 2C9 (CYP2C9) activity and can, thereby, affect metabolism of its substrates. 74 Recommended dosages range from 500 to 2000 mg/d. 75 Cineole Cineole, or more specifically 1,8-cineole, is a monoterpene present in many plantbased essential oils and is commonly derived from Eucalyptus globulus; 1,8-cineole is also one of the main chemical ingredients identified in the Chinese herb Flos magnoliae. 76 It has been shown to enhance mucociliary clearance; block inflammation through inhibiting formation of cytokines, such as tumor necrosis factor (TNF)-alpha and interleukin-1beta; and activate antinociceptive properties, perhaps through a mechanism involving a nonopioid receptor. [77] [78] [79] A prospective, randomized, double-blind study comparing cineole (200 mg 3 times per day) with placebo in 152 patients with acute nonpurulent RS showed a statistically significant difference in symptoms sum scores in the cineole group, in addition to a reduction in secondary symptoms, such as headache on bending, frontal headache, nasal obstruction, and nasal secretion. 80 Mild side effects, including heartburn and exanthema, were noted with cineole. The investigators concluded that cineole may serve as an integrative therapy during the first 4 days of acute RS, but antibiotics should be initiated if symptoms persist. In addition, another prospective, randomized, double-blind study demonstrated that cineole was more effective than an herbal preparation with 5 different components in the treatment of acute viral RS. 81 Cod liver oil Cod liver oil, which is rich in omega-3 fatty acids and vitamin D, was historically used as a remedy for rickets in the 1800s. 82 There is limited evidence for the use of cod liver oil for RS, including a 4-month, open-label study enrolling 4 children with recurrent chronic RS who were given escalating doses of cod liver oil and a multivitamin with selenium. 83, 84 Three patients demonstrated a positive response with decreased sinus symptoms, fewer episodes of acute sinusitis, and fewer physician visits. The investigators concluded that cod liver oil in combination with a multivitamin containing selenium was an inexpensive, noninvasive adjunctive intervention that can be used for selected patients.

Manuka honey is produced from the nectar of flowers native to Australia and New Zealand, particularly from the species of Leptospermum, and has potent antibacterial activity attributed to its high concentration of methylglyoxal, hyperosmolarity, hydrogen peroxide, and low pH. 85, 86 It was found to have bactericidal activity against biofilms formed by Pseudomonas aeruginosa and Staphylococcus aureus, with significantly higher effects than commonly used antibiotics and may have implications for treating chronic RS. 87, 88 Thamboo and colleagues 89 studied the use of manuka honey in patients with allergic fungal RS. Thirty-four patients were treated with a topical combination of manuka honey and saline in one nostril daily for 30 days. Culture results from their ethmoid cavities were unchanged, as was their endoscopic staging. However, there was reported symptomatic improvement using the Sino-Nasal Outcome Test (SNOT)-20 as an outcome measure.

Sinupret Sinupret (comprised of Gentiana radix, Primula flos, Rumex herba, Sambucus flos, and Verbena herba) is an herbal formula used widely in Germany for the treatment of respiratory infections. Approved by the German Commission E in 1994 for the treatment of acute and chronic inflammation of the paranasal sinuses, Sinupret is available as a coated tablet of 6 mg of Gentiana radix and 18 mg each of Primula flos, Rumex herba, Sambucus flos, and Verbena herba or as a water and alcohol extract in a proportion of 1:3:3:3:3. 73 Sinupret has been shown to have antiviral activity in vitro against certain subtypes of viruses known to cause respiratory infections, including adenovirus, human rhinovirus, and respiratory syncytial virus and to strongly stimulate transepithelial Cl(-) secretion to maintain normal mucociliary clearance in sinonasal epithelium through the hydration of the airway surface liquid. 90, 91 Four randomized controlled trials (RCTs) evaluated Sinupret (either 2 tablets or 30 drops of liquid formula 3 times per day) as adjunctive therapy for acute RS (3 RCTs) and chronic RS (1 RCT) (Berghorn, Langer W, Mä rz RW, Bionorica GmbH, unpublished data, 1991). [92] [93] [94] A systematic review demonstrated that Sinupret may be effective as an adjunctive therapy in acute RS. 71 However, one study found no significant difference in olfactory function between patients treated with Sinupret versus placebo, although an initial therapy of oral prednisolone for 7 days had preceded the treatment intervention. 95 Esberitox Esberitox is an herbal extract containing Thuja occidentalis (white cedar), Echinacea purpurea and pallida (purple coneflower), and Baptisia tinctoria (wild indigo) with demonstrated immunomodulatory properties. 96 A randomized, double-blind, placebo-controlled study showed a dose-dependent efficacy in the treatment of upper respiratory infections and, in particular, certain symptoms like rhinorrhea. 97 Another study that enrolled 90 patients with acute RS compared (1) Esberitox (3 tablets 3 times per day) and doxycycline, (2) Sinupret (5 tablets twice per day) and doxycycline, and (3) doxycycline alone and found that both groups with combination therapies had a significantly higher rate of response. 71, 94 Reported adverse events included photosensitivity and gastrointestinal symptoms, such as nausea.

Myrtol is a standardized phytotherapeutic extract (Gelomyrtol/Gelomyrtol Forte) taken from Pinus spp, Citrus aurantifolia, and Eucalyptus globulus. It is mainly comprised of In a randomized, double-blind, multicenter trial, 330 patients with acute sinusitis were enrolled into one of 3 arms: (1) Myrtol extract (300 mg/d), (2) other unidentified essential oil, or (3) placebo. 99 Myrtol and the other essential oil groups both demonstrated superior efficacy to placebo based on the total symptom score of 7 items (headache, nasal secretion, nasal obstruction, pain on pressure, pain at bending over, general well-being, and fever), although there were insufficient statistical data to support this conclusion. 71 Mild to moderate adverse events that were mostly gastrointestinal in nature were reported.

Nasturtium (Tropaeoli majoris herba) and horseradish root (Armoraciae rusticanae radix) have broad antibacterial activities against several gram-positive and gramnegative organisms, including Haemophilus influenzae, Moraxella catarrhalis, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes. 100 A prospective, multicenter, cohort study performed in children between 4 and 18 years of age with acute RS found that an herbal drug preparation, containing nasturtium and horseradish root, had similar efficacy and fewer adverse events compared with standard antibiotics. 101

Dietary polyphenols are widely available in food and well-known for their antiinflammatory effects. Both ginger and quercetin, a polyphenolic bioflavonoid commonly found in apples and onions, have potent antioxidant and antiinflammatory properties. 102, 103 Mechanisms of action that have been elucidated for quercetin include suppression of the inflammatory mediator cyclooxygenase-2, inhibition of histamine release through downregulation of mast cell activity, and enhanced mucociliary clearance through augmented transepithelial chloride secretion via the cystic fibrosis transmembrane conductance regulator anion channel. [104] [105] [106] A combination of ginger extract and green tea (Camellia sinensis), which is rich in epigallocatechin gallate (EGCG), showed significant antiallergy effects through the suppression of certain cytokines, such as TNF-alpha and MIP-1alpha (macrophage inflammatory protein). 107 The dietary polyphenols of [6]-gingerol, quercetin, and EGCG were found to effectively inhibit excess mucus secretion of respiratory epithelial cells while maintaining normal nasal ciliary movement. 108 Homeopathy Homeopathy, initially developed by German physician Samuel Christian Hahnemann at the end of the eighteenth century, is based on the principle of similars (like cures like) whereby therapeutic effects are achieved by stimulating the body's homeostatic healing response via substances that have been serially diluted and shaken. There is evidence from RCTs that homeopathy may be effective for the treatment of influenza and allergies. 109 In a recent prospective observational trial from Germany, 134 adult patients with treatment refractory chronic sinusitis were tried on different homeopathic remedies. Over the course of 8 years, the investigators found sustained improvements in quality-of-life outcomes (36-Item Short Form Health Survey) and decreased use of conventional medications, with the greatest change noted during the first 3 months of follow-up. 110 Sinfrontal Sinfrontal is a homeopathic remedy (containing Cinnabaris D4, Ferrum phosphoricum D3, Mercurius solubilis D6) that is commonly used in Germany for a variety of upper respiratory tract infections and has shown promise as a treatment for RS without Taw et al the need for antibiotics. A prospective, randomized, double-blind, placebo-controlled, multicenter, clinical trial comparing Sinfrontal with placebo in 113 patients with radiography-confirmed acute maxillary sinusitis found that there was a significant difference in patients treated with Sinfrontal with no recurrence of symptoms 8 weeks after treatment. 111 Patients receiving Sinfrontal were instructed to take 1 tablet every hour until improvement was noted, with a maximum of 12 tablets per day, after which the dosing would change to 2 tablets 3 times per day. An economic analysis demonstrated that Sinfrontal can lead to substantial cost savings with markedly reduced absenteeism from work. 112 

Traditional Chinese medicine (TCM) is a whole medical system that has been used for several millennia. The therapeutics used in TCM, such as Chinese herbal medicine and acupuncture, have grown in popularity with a parallel increase in scientific understanding and elucidation of mechanisms. 113 Specifically, the use of TCM for the treatment of disorders involving the ears, nose, and throat can be traced back as early as the fifth century BC, with several therapies that may be beneficial for RS. 114 

The therapeutic effects of acupuncture primarily stem from reestablishing homeostasis of multiple physiologic cascades, whether through modulation of the immune system, inflammatory response, autonomic nervous system, neuroendocrine axis, limbic system, or pain pathway. [115] [116] [117] [118] [119] [120] Although acupuncture may modulate many of these cascades during treatment of patients with RS, specific effects of improved mucociliary clearance and airway surface liquid have also been demonstrated. 121 In a prospective randomized study, patients with nasal congestion and hypertrophic inferior turbinates were treated with acupuncture and found to have significant improvement on visual analog scale and in nasal airflow as measured by active anterior rhinomanometry. 122 Another study demonstrated a 60% reduction in sinus-related pain compared with only 30% in the placebo group. 123 Acupuncture also demonstrated beneficial results in the treatment of children with chronic maxillary sinusitis. 124 A research team in Norway conducted 2 different studies using a similar protocol, whereby 65 patients with chronic RS were randomized into 3 arms: (1) traditional Chinese acupuncture, (2) sham acupuncture, or (3) conventional medical management with antibiotics, oral steroids, nasal saline irrigation, and local decongestants. 125, 126 In both studies, there was improvement in health-related quality-of-life symptom scores in all 3 groups, although there was no overall statistically significant difference among them.

Xanthii fructus (Chinese herbal name: Cang Er Zi) and Flos magnoliae (Chinese herbal name: Xin Yi Hua) are commonly used herbs in traditional Chinese medicine to treat RS. Xanthii fructus is also known as Xanthium sibiricum because the former is simply the fruit of the latter. From a TCM perspective, Xanthii fructus disperses wind and dampness and treats thick, viscous nasal discharge and sinus-related headaches, whereas Flos magnoliae is used to expel wind-cold and treat nasal discharge, hyposmia, sinus congestion, and headaches. 127 In fact, these two herbs are often combined and are key components of the Chinese herbal formula Cang Er Zi Wan or Cang Er Zi San, which are the pill and powder preparations, respectively. 128 It is important to note that Chinese herbs should be used under the guidance of TCM theory. When Chinese herbs are not used according to TCM principles, severe

Complementary and Integrative Treatments: Rhinosinusitis adverse events can occur. One such example was the inappropriate use of Ephedra (Chinese name: Ma Huang) for weight loss, increased energy, and performance enhancement, when traditionally this is used only for upper respiratory infections for a short period of time, much like how pseudoephedrine is used only briefly for symptoms related to upper respiratory infections. 129 Xanthii fructus (Chinese name: Cang Er Zi) In a murine model, Xanthii fructus was found to exhibit (1) antiinflammatory effects through inhibiting interferon-gamma, TNF-alpha, and lipopolysaccharide-induced nitric oxide synthesis; (2) antiallergic effects through blocking mast cell-mediated histamine release; and (3) antioxidant effects through increased activities of catalase, superoxide dismutase, and glutathione peroxidase in the liver with enhanced radical scavenging and reducing activity. [130] [131] [132] Sesquiterpene lactone and xanthatin, specific components of Xanthium sibiricum, displayed significant antibacterial activity against methicillin-resistant Staphylococcus aureus while also inhibiting other bacteria like Staphylococcus epidermidis, Klebsiella pneumoniae, Bacillus cereus, Pseudomonas aeruginosa, and Salmonella typhi. 133 Zhao and colleagues 134, 135 found that Xanthii fructus was able to modulate proinflammatory cytokines through inhibition of human mast cells and peripheral blood mononuclear cells and demonstrated that Shi-Bi-Lin, a modified version of the Chinese herbal formula Cang Er Zi San, ameliorated nasal symptoms, such as sneezing and nasal scratching, in a guinea pig model through reduced nasal thromboxane B2, eosinophil infiltration, and endothelial nitric oxide synthase activity. A double-blind, RCT enrolling 126 patients with allergic rhinitis with equal cohorts receiving Shi-Bi-Lin and placebo found that Shi-Bi-Lin significantly improved symptoms with a sustained response for at least 2 weeks after treatment. 136 However, caution must be exercised when using either Xanthii fructus or Cang Er Zi Wan because they have been shown to lead to certain side effects like muscle spasm and hepatotoxicity and nephrotoxicity. 137, 138 Flos magnoliae (Chinese herbal name: Xin Yi Hua)

The primary bioactive components of Flos magnoliae include terpenoids, lignans, neolignans, epimagnolin, and fargesin. 139 Neolignans have been found to have antiinflammatory effects through mechanisms of action different from steroids, while epimagnolin and fargesin decrease production of nitric oxide, a potent mediator in inflammation, through inhibition of inducible nitric oxide synthase expression. 140, 141 Flos magnoliae also demonstrates antiallergy activity via inhibition of immediatetype hypersensitivity reactions through blocking mast cell degranulation. 142 As an essential oil, its main chemical ingredients have been identified as 1,8-cineole, sabinene, beta-pinene, alpha-pinene, and transcaryophyllene. 76 

Bi Yuan Shu is a Chinese herbal liquid mixture comprised of an unknown number of herbs but is reported to include at least Magnolia liliflora, Xanthium strumarium, Astragalus membranaceus, Angelica dahurica, and Scutellaria baicalensis. A multicenter RCT divided 340 postoperative patients with chronic RS and nasal polyps who had undergone endoscopic sinus surgery into 2 groups, with both groups receiving antibiotics and topical steroids; the test group was also treated with Bi Yuan Shu (10 mL 3 times per day). 143 Adjunctive treatment with Bi Yuan Shu was found to have significantly higher response rates on days 7, 14, 30, and 60 for purulent nasal discharge, breathing difficulty, pain, hyposmia, and halitosis, with positive trends noted for fever and cough. 71 Another study assessing the efficacy of Chinese herbal medicine in the care of patients after undergoing endoscopic sinus surgery enrolled 97 patients into one of 3 treatment arms: (1) Tsang-Erh-San extract granules and Houttuynia extract powder, (2) oral amoxicillin, or (3) placebo. The study found no benefit of either treatment group over placebo. 144 

A multicenter, nonrandomized study of 63 patients with acute RS comparing multiple conventional (antibiotics, secretolytics and sympathomimetics) with combination complementary (Sinupret and homeopathic remedy, Cinnabaris 3X) therapies demonstrated similar effectiveness based on patients' self-assessment score, physicians' score, and HCG-5 questionnaire. 145 However, the only validated outcome parameter was the HCG-5 quality-of-life instrument. Other limitations with this study included a small sample size and lack of randomization and blinding.

Recently, a pilot study at the University of California, Los Angeles was conducted using integrative East-West medicine to treat patients with recalcitrant chronic RS. 146 Eleven patients underwent 8 weekly sessions of sequential acupuncture ( Table 1 ) and therapeutic acupressure style massage and had received education consisting of dietary modification, lifestyle changes, and self-acupressure. Four items on the SNOT-20 (need to blow nose, runny nose, reduced concentration, and frustrated/restless/irritable) and 3 of 8 domains on the SF-36 (role physical, vitality, and social functioning) showed a statistically significant difference, whereas trends of improvement were noted in most other elements on both quality-of-life instruments. Although the data looks promising, this study was also limited by its small size and lack of randomization and control group.

Lifestyle modifications can also be conducive toward achieving optimal sinus health and function. These modifications include regular aerobic exercise, adequate hydration, steam inhalation, stress management, and good-quality sleep. Minimizing exposure to pollution, smoke, and environmental toxins as well as incorporating nutritional changes, such as consuming an antiinflammatory diet and avoiding dairy products, refined sugars, and processed foods, are important. 147 A regular spiritual practice, such as prayer, is also beneficial, along with anger management and attitudes of forgiveness, gratitude, and optimism. 148 Self-acupressure of certain acupoints can also be helpful to reduce sinus-related symptoms (see Table 1 ).

As we gain a greater understanding of the complex pathogenesis of RS, what is becoming apparent is a shift in philosophic paradigm. Our previous reductionist models of disease and health are being replaced by holism, systems biology, and complex, nonlinear dynamics. [149] [150] [151] Holism is a central philosophic underpinning of integrative medicine and many CIM modalities, such as TCM.

We now see this paradigm shift in our approach to RS. No longer is the medical community looking at the diagnosis of RS as solely an infectious process but rather as complex and multifactorial. 152 For example, Palmer 41 elegantly describes this transition whereby "generations of doctors and scientists were taught to envision bacteria as single cells that float or swim through some fluid . in fact, rhinologists continue to foster this view"; however, "biofilms are not just single cells, but are structurally and metabolically heterogeneous multicellular communities." 153 Biofilms demonstrate cell-to-cell signaling, a phenomenon known as "quorum sensing." 154 Such is an example of complexity science and holism.

The therapeutic repertoire, likewise, has broadened significantly from antibiotics alone as the mainstay of treatment to the use of multiple therapies to act on different pathophysiological facets of RS. Integrative medicine provides an expanded approach and armamentarium to help patients with RS, whether acute, chronic, or recalcitrant. 

Adult rhinosinusitis defined

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Immunomodulatory principles of Pelargonium sidoides

Extract of Pelargonium sidoides (EPs 7630) improves phagocytosis, oxidative burst, and intracellular killing of human peripheral blood phagocytes in vitro

Evaluation of an aqueous-ethanolic extract from Pelargonium sidoides (EPsÒ 7630) for its activity against group A-streptococci adhesion to human HEp-2 epithelial cells

Treatment of acute rhinosinusitis with the preparation from Pelargonium sidoides EPs 7630: a randomized, double-blind, placebo-controlled trial

Pelargonium sidoides extract for acute respiratory tract infections

Bromelain: biochemistry, pharmacology and medical use

Adjunctive use of bromelains in sinusitis: a controlled study

A double-blind clinical evaluation of bromelains in the treatment of acute sinusitis

The use of bromelains in sinusitis: a double-blind clinical evaluation

Herbal medicines for the treatment of rhinosinusitis: a systematic review

Therapeutic use, efficiency and safety of the proteolytic pineapple enzyme bromelain-POS in children with acute sinusitis in Germany

Rational phytotherapy: a physicians' guide to herbal medicine

Inhibitory effects of fruit juices on cytochrome P450 2C9 activity in vitro

Bromelain: a literature review and discussion of its therapeutic applications

GC-MS analysis of chemical components in essential oil from Flos magnoliae

Effect of a secretolytic and a combination of pinene, limonene and cineole on mucociliary clearance in patients with chronic obstructive pulmonary disease

Inhibitory activity of 1,8-cineol (eucalyptol) on cytokine production in cultured human lymphocytes and monocytes

Antiinflammatory and antinociceptive effects of 1,8-cineole a terpenoid oxide present in many plant essential oils

Therapy for acute nonpurulent rhinosinusitis with cineole: results of a double-blind, randomized, placebo-controlled trial

The value of herbal medicines in the treatment of acute non-purulent rhinosinusitis. Results of a double-blind, randomised, controlled trial

Vitamin D, cod-liver oil, sunlight, and rickets: a historical perspective

Complementary ENT': a systematic review of commonly used supplements

Nutritional supplements as adjunctive therapy for children with chronic/recurrent sinusitis: pilot research

The antibacterial activity of honey derived from Australian flora

Antibacterial components of honey

Effectiveness of honey on Staphylococcus aureus and Pseudomonas aeruginosa biofilms

Methylglyoxal-infused honey mimics the anti-Staphylococcus aureus biofilm activity of manuka honey: potential implication in chronic rhinosinusitis

Single-blind study of manuka honey in allergic fungal rhinosinusitis

Antiviral activity in vitro of two preparations of the herbal medicinal product Sinupret against viruses causing respiratory infections

The bioflavonoid compound, Sinupret, stimulates transepithelial chloride transport in vitro and in vivo

Treatment of chronic sinusitis with Sinupret

Placebo-controlled, randomized double-blind clinical trial with Sinupret sugar coated tablets on the basis of a therapy with antibiotics and decongestant nasal drops in acute sinusitis

Gezielte konservative Therapie der akuten Sinusitis in der HNO-Praxis

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

Efficacy and mode of action of an immunomodulator herbal preparation containing Echinacea, wild indigo, and white cedar

A randomized, double-blind, placebo-controlled, clinical dose-response trial of an extract of Baptisia, Echinacea and Thuja for the treatment of patients with common cold

Interference of myrtol standardized with inflammatory and allergic mediators

Effects of standardized Myrtol in therapy of acute sinusitis-results of a double-blind, randomized multicenter study compared with placebo

In vitro study to evaluate the antibacterial activity of a combination of the haulm of nasturtium (Tropaeoli majoris herba) and of the roots of horseradish (Armoraciae rusticanae radix)

On-going investigations on efficacy and safety profile of a herbal drug containing nasturtium herb and horseradish root in acute sinusitis, acute bronchitis and acute urinary tract infection in children in comparison with other antibiotic treatments

Comparative antioxidant and antiinflammatory effects of [6]-gingerol

The role of quercetin, flavonols and flavones in modulating inflammatory cell function

Quercetin suppresses cyclooxygenase-2 expression and angiogenesis through inactivation of P300 signaling

Flavonoids inhibit histamine release and expression of proinflammatory cytokines in mast cells

Quercetin increases cystic fibrosis transmembrane conductance regulator-mediated chloride transport and ciliary beat frequency: therapeutic implications for chronic rhinosinusitis

In vitro and in vivo anti-allergic effects of 'benifuuki' green tea containing O-methylated catechin and ginger extract enhancement

Dietary polyphenols affect MUC5AC expression and ciliary movement in respiratory cells and nasal mucosa

A critical overview of homeopathy

Homeopathic treatment of patients with chronic sinusitis: a prospective observational study with 8 years follow-up

Efficacy of a complex homeopathic medication (Sinfrontal) in patients with acute maxillary sinusitis: a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial

Economic evaluation of Sinfrontal in the treatment of acute maxillary sinusitis in adults

Acupuncture: theory, efficacy, and practice

The root and development of otorhinolaryngology in traditional Chinese medicine

Acupuncture and immunomodulation

Anti-inflammatory actions of acupuncture

The acute effects of acupuncture upon autonomic balance in healthy subjects

Neuroendocrine mechanisms of acupuncture in the treatment of hypertension

Acupuncture, the limbic system, and the anticorrelated networks of the brain

Neural mechanism underlying acupuncture analgesia

Effect of needle puncture and electro-acupuncture on mucociliary clearance in anesthetized quails

Acupuncture for nasal congestion: a prospective, randomized, double-blind, placebo-controlled clinical pilot study

Effect of acupuncture on sinus pain and experimentally induced pain

The effects of treatment with antibiotics, laser and acupuncture upon chronic maxillary sinusitis in children

Health-related quality of life in a trial of acupuncture, sham acupuncture and conventional treatment for chronic sinusitis

Comparison of traditional Chinese acupuncture, minimal acupuncture at non-acupoints and conventional treatment for chronic sinusitis

Chinese herbal medicine: Materia Medica

Chinese herbal medicine: formulas & strategies

Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids

Xanthii fructus inhibits inflammatory responses in LPS-stimulated mouse peritoneal macrophages

Inhibitory effects of Xanthii fructus extract on mast cell-mediated allergic reaction in murine model

Antioxidant, antinociceptive, and antiinflammatory activities of Xanthii Fructus extract

A xanthanolide with potent antibacterial activity against methicillin-resistant Staphylococcus aureus

The effects of Fructus Xanthii extract on cytokine release from human mast cell line (HMC-1) and peripheral blood mononuclear cells

Effect of a Chinese herbal formula, Shi-Bi-Lin, on an experimental model of allergic rhinitis

Treatment of perennial allergic rhinitis using Shi-Bi-Lin, a Chinese herbal formula

Muscle spasm associated with therapeutic use of Cang Er Zi Wan

The study of intoxication and toxicity of Fructus Xanthii

Chemistry and bioactivity of Flos Magnoliae, a Chinese herb for rhinitis and sinusitis

Extracts of Magnoliae flos inhibit inducible nitric oxide synthase via ERK in human respiratory epithelial cells

Anti-inflammatory effect of neolignans newly isolated from the crude drug "Shin-i" (Flos magnoliae)

Magnoliae flos inhibits mast cell-dependent immediatetype allergic reactions

Multi-centre randomized controlled trial of bi yuan shu liquid on patients with chronic nasal sinusitis or nasal polyp after endoscopic sinus surgery

Postoperative care with Chinese herbal medicine or amoxicillin after functional endoscopic sinus surgery: a randomized, double-blind, placebo-controlled study

A non-randomised pilot study to compare complementary and conventional treatments of acute sinusitis

Treatment of recalcitrant chronic rhinosinusitis with integrative East-West medicine: a pilot study

Natural treatment of chronic rhinosinusitis

Chronic sinusitis

Evolving from reductionism to holism: is there a future for systems medicine?

Systems biology, proteomics, and the future of health care: toward predictive, preventative, and personalized medicine

What is physiologic complexity and how does it change with aging and disease?

Chronic rhinosinusitis: preface

The application of biofilm science to the study and control of chronic bacterial infections

What's in a name? The semantics of quorum sensing