The upper airway ranges from the nares to the subglottis and includes diverse anatomic structures with a wide variety of functions. Along with assisting in respiration, the structures of the upper airway contain the nerves for the sensory functions of taste and smell, create a functionally safe swallow by separating deglutition from respiration, and allow for communication through the generation of voice and speech. The nasal cavity has a defined role in filtering and humidifying air for presentation to the lower airway. The glottis performs the functions of protecting the airway to prevent aspiration, regulating airflow and vocalization. The pharynx and oral cavity assist in these functions by controlling and shaping substances to be swallowed and modulating voiced sounds from the glottis into words and speech. The upper airway is controlled by both voluntary and involuntary mechanisms. Therefore respiratory function can be affected through uncoordinated or inefficient muscular activity, centrally mediated neurologic reflex activity, and/or humoral or immunologic responses. The exact function of some areas within the upper airway, such as the paranasal sinuses, is unclear.
Pathologic changes in the upper airway are often associated with lower airway disease. Swallowing disorders may result in aspiration with inflammatory and infectious complications in the lungs. Chronic inflammation of the paranasal sinuses is frequently associated with asthma. Long-standing infection in the sinuses has been implicated as a possible reservoir for recurrent pulmonary infection. Laryngeal dysfunction may create symptoms similar to reactive airway disease. Finally, stenosis of the subglottis or cervical trachea is often misdiagnosed as asthma. In this chapter we discuss the anatomy and clinical conditions of the upper airway and their influence on lower airway function.
Anatomy, Histology, and Physiology
The nose represents the initial site of air entry for the majority of respiration. The external nose has important structural components that, when compromised, may inhibit nasal airflow. The nasal dorsum is made up of three structurally distinct subunits ( Fig. 49-1 ). The upper third of the nasal dorsum is supported by the nasal bones. At their distal end, the nasal bones articulate with the upper lateral cartilages in a region known as the keystone area. The upper lateral cartilages define the middle third of the nose. The structure of the lower third, or nasal tip, is defined primarily by the lower lateral cartilages. The nasal septum divides the right and left sides of the nose and provides additional structural support to the lower two thirds of the nose. The quadrangular cartilage forms the anterior septum. The bone of the vomer, perpendicular plate of the ethmoid, and maxillary crest form the posterior and inferior aspects of the septum.
Airflow through the nose may be limited by the cross-sectional area of the external and internal nasal valves ( Fig. 49-2 ). The relationship between the lower lateral cartilage, the septum, and the inferior turbinate largely determines the external valve area. The angle between the upper lateral cartilage and septum impacts airflow through the internal nasal valve. Facial musculature that attaches to the upper and lower cartilages of the nose can widen these principal areas of resistance, enhancing nasal respiration. Patients with narrowing or structural weakness in these regions may suffer from nasal obstruction. The external and internal nasal valves are frequently the target of nasoseptal reconstructive surgery.
Another common area implicated in narrowing of the nasal cavity and subsequent nasal obstruction is the nasal septum. Deviation of the septum diminishes the cross-sectional area of the affected nasal passage and can significantly impact nasal airflow. Most patients have some degree of septal deviation, so anatomic changes in this area must be correlated with clinical findings when determining if a septal deviation would benefit from treatment. Nasal trauma may lead to septal deviations and spurs; many patients will relate a history of trauma to the nose. Developmental variations are perhaps a more common cause of deviation and spurs of the nasal septum than is trauma. Overgrowth of the quadrangular cartilage may result in bowing of the cartilage or spurs at the junction of the cartilage and bones that make up the nasal septum. Nasal obstruction related to septal deviation may respond either to surgical or to medical treatment. In patients with concomitant turbinate hypertrophy or chronic rhinitis, treatment with intranasal corticosteroids may diminish mucosal swelling and provide an adequate airway despite the septal deviation. Surgery to straighten the septum has few risks and complications and is an effective method for improving the nasal airway in patients with narrowing secondary to septal deviation. Septal deviations have been implicated as a cause for acute or chronic rhinosinusitis. This is a rare cause for inflammatory sinus disease, and caution is advised in diagnosing or treating rhinosinusitis based upon septal findings alone.
Air that enters the nasal sill (or floor of the nose) and passes through the internal nasal valve accelerates as it passes through this area of narrowing. There is also a change in direction of airflow because inspired air shifts from a vertical to a horizontal trajectory at this site. This combination of acceleration and change in flow vector causes the majority of airborne particles to be deposited in the anterior nasal cavity. Airflow through the nose slows as the nasal passages widen beyond the internal nasal valve.
Upon entry into the nasal cavity, the stratified squamous epithelium of the nasal sill quickly transitions to a respiratory epithelium. Located along the lateral nasal wall, the turbinates (or conchae) serve to warm and humidify air passing through the nasal cavity. Rich vasculature, including venous sinusoids, allows the turbinates to enlarge and shrink in response to various stimuli. Fenestrated subepithelial capillaries facilitate heat and gas exchange, enhancing humidification during nasal inhalation. Engorgement of the turbinates increases the surface area and mucosal contact with inspired air. The slowing of airflow beyond the internal nasal valve provides prolonged mucosal contact during nasal inspiration and allows efficient humidification and filtration of inspired air so that even at extremes of ambient temperature and humidity, air that reaches the trachea is very close to body temperature and 98% humidity.
The respiratory mucosa of the turbinates contains both goblet cells and seromucous glands. These structures combine to produce a mucus blanket that is mobilized by coordinated beating of this ciliated epithelium. Nasal irritants, microbes, and other particles are swept through the nasal cavity by this mucociliary clearance mechanism to be swallowed, preventing exposure of the lower airways. The lower airways are further protected by immune function within the nasal mucosa. Both the innate and humoral immune arms of the immune system function within the nasal mucosa, resulting in the secretion of immunoglobulins (primarily immunoglobulin [Ig] A) and microbial toxins such as lysozyme and lactoferrin. Emerging evidence suggests that commensal microbes inhabiting the mucosal surface or mucus layer of the nasal cavity contribute to host defense mechanisms within the nasal cavity through competitive colonization and perhaps immune regulation.
The turbinates are dynamic structures that swell and shrink in response to multiple stimuli. Gravity, nasal irritants, allergic response, and autonomic neural input all regulate the blood supply and venous drainage of the submucosal tissue of the inferior turbinate, resulting in marked fluctuations in turbinate size. The size of the inferior turbinate fluctuates alternately on the right and left side as part of the normal nasal cycle. Pathologic enlargement of the inferior turbinate is one of the most common causes of nasal congestion and nasal obstruction.
The tubular structure of the turbinates contributes to a laminar air flow pattern through the nasal cavity. Aggressive resection of the turbinates enlarges the cross-sectional area of the nasal cavity but risks a paradoxical worsening of nasal obstruction. The humidification function of the turbinates can also be lost with resection, resulting in possible dryness and crusting. This constellation of symptoms following turbinate resection has been referred to as “empty nose syndrome.” A conservative surgical approach to nasal obstruction due to turbinate hypertrophy is therefore recommended in patients who do not receive adequate relief from medical therapy.
The superior aspects of the nasal septum, middle turbinate, and superior turbinate are lined with olfactory epithelium. Successful olfaction requires that airborne or mucus-soluble particles reach this epithelium. Odorant-specific receptors of the olfactory epithelium send projections intracranially, through the bone of the cribriform plate. Axons from the olfactory epithelium synapse within the olfactory bulb, and these signals are then routed for central processing. Smell disorders may arise from mucosal inflammation and edema that prevent odorant exposure to the olfactory epithelium. This is frequently a reversible condition. Direct viral injury of the olfactory epithelium has also been postulated as a cause for smell loss, which may result in long-term dysfunction.
Sneezing is a nonspecific, involuntary response to nasal irritation. Allergens, microbes, and other nasal irritants may precipitate this reaction when they contact the nasal mucosa and trigger histamine release. The trigeminal nucleus coordinates the sneeze reflex, which involves muscles of the pharynx, larynx, oral cavity, and chest wall. The pressure generated from a sneeze may expel irritants and can contribute to spread of infections conditions. In susceptible individuals, sudden exposure to bright light may trigger the sneeze reflex. This is an autosomal dominant trait impacting approximately one fourth of the human population.
Pathologic Conditions of the Nasal Cavity
Rhinitis, or inflammation of the nasal cavity, may result from multiple causes. Rhinitis may be classified by duration (acute versus chronic) and further segregated as allergic versus nonallergic. Acute rhinitis is a self-limited inflammation, most commonly secondary to viral infection. Many of the clinical features of acute rhinitis may result from the immune response to viral pathogens. Release of inflammatory cytokines and chemokines including interleukin (IL)-6, tumor necrosis factor-α, and interferon-γ results in tissue edema, increased mucus production, and vascular dilation. The clinical manifestations of these changes are well known as symptoms of the “common cold”: nasal congestion and obstruction, increased nasal drainage, and diminished sense of smell. Nasal irritants, including perfumes, smoke, and cleaning products, can cause a similar constellation of symptoms although typically of shorter duration.
Allergic rhinitis (AR) is a common disorder that is estimated to be the sixth most common chronic illness in the United States. The prevalence of AR is 10% to 20% in the United States and Europe. There are an estimated 18 million adults in the United States who suffer from AR, resulting in significant health care expenditures. A diagnosis of allergic rhinitis adds approximately $1500 per patient per year in direct health care costs. A similar prevalence of AR is evident in children, and AR in this population is associated with a significant decrease in both physical and emotional health, as well as sleep disturbance. As many as 13 million Americans in the workforce suffer from AR, and it is estimated that 3.5 million workdays and 2 million school days are lost each year because of this condition. Overall annual direct and indirect costs of AR in the United States have been estimated at $5 to $8 billion and $11 billion, respectively.
The incidence of allergic rhinitis has been rising over the past 3 decades. One explanation for this is the “hygiene hypothesis”: early exposure to antigens allows for proper immune system development and a reduced risk for allergic rhinitis and other atopic disease. Recent data suggest that early microbial exposure may be particularly important in the prevention of not only atopic, but also autoimmune disease.
Allergic rhinitis symptoms may be seasonal or perennial, depending upon the specific allergen. Pollens from trees and grasses are the most common triggers for seasonal symptoms, whereas dust mites and pet dander represent common triggers for perennial disease. Identification of offending allergens may be accomplished through a variety of approaches. Skin reaction to allergens may be measured through either prick testing or intradermal injection using serial end-point dilution techniques. Both of these approaches carry a rare but important risk for anaphylaxis. Testing centers must have personnel and equipment to deal with such emergencies. Immunoassays for allergen-specific IgE such as ImmunoCAP have largely replaced radioallergosorbent test as an alternative to intradermal skin testing. This approach demonstrates a similar sensitivity as skin testing. Efficacy of both dermal testing and immunoassays is dependent upon proper antigen selection. Knowledge of local flora is particularly important in patients with seasonal allergic rhinitis. This knowledge is also critical in identifying clinically significant allergens. Identification of offending allergens allows counseling of allergen avoidance and may be used to initiate immunomodulatory therapy.
Following an initial allergen exposure, inhaled antigens provoke both early- and late-phase reactions in the nasal cavity. The early phase is initiated by the recognition of a specific allergen by IgE subunits on the surface of mast cells and basophils. IgE activation results in antibody cross-linking, which, through a series of downstream mediators, causes degranulation of mast cells and basophils with release of preformed mediators. Histamine is the primary inflammatory mediator released during degranulation. Tryptase release and de novo formation of leukotrienes may also contribute to nasal inflammation and symptoms. Exposure to inflammatory mediators results in marked tissue edema and mucus secretion, which manifests clinically as rhinorrhea and nasal congestion and obstruction, frequently in association with sneezing. These symptoms develop within minutes of allergen exposure.
The late phase of allergic rhinitis typically arises 4 to 8 hours after allergen exposure. Nasal congestion is typically the dominant symptom. Chemoattractants and adhesion molecules released in response to the initial inflammatory mediators promote infiltration of leukocytes, eosinophils, basophils, CD4 + lymphocytes, and monocytes. Activation of these cells results in the release of a second wave of inflammatory mediators. The early- and late-phase reactions in allergic rhinitis mimic those of allergic asthma.
Another important concept in the pathophysiology of allergic rhinitis is that of priming of the immune response. Repeated allergen exposure results in amplification of mucosal hyperresponsiveness. In patients with seasonal allergic rhinitis, the severity of allergic response depends not only on the current pollen count and allergen exposure, but also upon the cumulative exposure for a given allergy season. Because of this phenomenon, severe symptoms of allergic rhinitis may persist late in the allergy season despite a waning pollen count. This increased allergen sensitivity may be secondary to both a neural hyperresponsiveness and amplification of the immune response through recruitment of mast cells and basophils. Immune system priming is not an allergen-specific phenomenon; patients report increased sensitivity to nonspecific nasal irritants, including smoke and perfume.
Association with Asthma.
Allergic rhinitis and asthma are linked through both pathophysiology and epidemiology. Eighty percent of patients with allergic asthma also suffer from allergic rhinitis. The presence of allergic rhinitis is a risk factor for the future development of asthma. Guidelines suggest screening patients with persistent allergic rhinitis for asthma and evaluating asthmatic patients for rhinitis.
The unified airway theory suggests that inflammatory cell migration from an inflamed area within the airway may impact distant airway locations. In patients with allergic rhinitis and asthma, segmental bronchial allergen challenge results in an inflammatory response not only in bronchi, but also in the nasal cavity. When treated with intranasal corticosteroids, these same patients demonstrate a decrease in both nasal and bronchial hyperreactivity.
There are three modalities of treatment for allergic rhinitis: allergen avoidance, pharmacotherapy, and immunomodulatory treatments. Recent consensus panels suggest evaluating the severity and frequency of AR symptoms to guide treatment. Severity of symptoms is categorized as mild or moderate/severe as determined by the level of impact on daily activities and sleep disturbance. Symptoms are classified as intermittent if the duration is less than 4 days per week or for fewer than 4 weeks and as persistent if the duration satisfies both of these criteria. Figure 49-3 depicts a consensus management strategy for allergic rhinitis. The vast majority of patients are effectively treated with pharmacotherapy and allergen avoidance. Saline irrigation results in modest symptomatic improvement and may reduce the need for medications with more significant side effect profiles. Evidence-based AR treatment recommendations for allergen avoidance, individual medications, and immunotherapy were revised in 2010. Allergen avoidance strategies for patients with allergic rhinitis are similar to those for patients with allergic asthma and require identification of offending allergens. Following identification of clinically significant allergens, environmental precautions may be instituted.
Although pharmacologic treatment of allergic rhinitis may be quite effective in managing symptoms, immunotherapy offers the only approach known to impact the natural history of the disease. Subcutaneous immunotherapy (SCIT) regimens involve once or twice weekly subcutaneous antigen injections with gradual escalation of the antigen dose. This is the most well-studied and commonly used approach in the United States. More recently, sublingual immunotherapy (SLIT) has emerged as an option that avoids injection appointments. This approach has been primarily studied and is frequently used in Europe but has not yet been approved for use in the United States. The overall treatment course for SCIT or SLIT is 2 to 3 years.
With repeated allergen exposure, a shift in allergen-specific T cells to a regulatory phenotype results in suppression of type 2 T helper inflammatory cytokines and enhanced production of IL-10 and antigen-specific IgG4. This results in suppression of allergen-specific IgE and mast cells and appears to inhibit antigen capture and presentation to T cells. This immune modulation may diminish the onset of additional atopic disorders such as asthma in patients with allergic rhinitis.
Systemic responses to immunotherapy are rare and typically mild. Nevertheless, deaths have been reported from anaphylactic response during immunotherapy, and vigilance is required. SCIT has a higher (although still very low) incidence of systemic response than SLIT; SLIT has a high rate of mild local (mucosal) side effects, which rarely impact the treatment regimen. Practitioners who administer allergy shots require appropriate training and access to emergency equipment to address the rare systemic response. With sublingual administration, patients often self-administer the allergen, and proper patient selection and education is critical. Multiple trials demonstrate efficacy of both SLIT and SCIT; they appear to have similar efficacy, but head-to-head trials are lacking. Use of SLIT in the United States is limited by a lack of approval of the U.S. Food and Drug Administration and limited insurance coverage.
Nonallergic Chronic Rhinitis
Overall, nonallergic rhinitis is poorly characterized. Vasomotor rhinitis is a subgroup of nonallergic patients thought to suffer from aberrant parasympathetic innervation in the nose. Patients frequently note rhinorrhea in association with eating or a change in the weather. This disorder is more common in elderly patients and may respond well to ipratropium nasal spray. Additional noninflammatory disorders of the nasal cavity, including nonallergic rhinitis with eosinophilia, may improve with nasal steroid treatment. Symptomatic treatment with saline irrigation is another popular treatment for nonallergic rhinitis.
The Paranasal Sinuses
Anatomy, Histology, and Physiology
The paranasal sinuses are aerated cavities within the skull that connect to the nasal cavity. There are four sets of paired sinuses: the maxillary, ethmoid, frontal, and sphenoid sinuses. The sinuses are lined with a pseudostratified, ciliated epithelium. Goblet cells within the epithelium produce mucus, and the coordinated action of the cilia moves this mucus through the sinus cavities and into the nose. Once thought to be sterile, it is now known that bacterial communities inhabit the mucosal surfaces of the paranasal sinuses in both health and disease.
The function of the sinuses has not been clearly established. They may serve a protective role in force dissipation with blunt trauma to the head or face. The paranasal sinuses can impact vocal resonance, which may have aided their evolution. The sinuses may allow for enhanced facial aesthetics. They may play a role in mucus production and immune surveillance in the nasal cavity.
The four paired sinuses are named after the bones that they aerate. The maxillary and ethmoid sinuses are the first to develop and are present at birth. The frontal and sphenoid sinuses develop more slowly. A visible frontal sinus is often not present until age 4 or 5, and continued aeration and development persist throughout the teenage years. Asymmetric aeration of the sinuses is common, particularly in the later-developing frontal and sphenoid sinuses. The frontal sinus may be absent in up to 10% of normal patients. An increased incidence of frontal sinus aplasia and diminished overall paranasal sinus aeration is seen in patients with congenital disorders that impact the sinuses such as cystic fibrosis.
Mucus produced in the sinuses is propelled into the nasal cavity by coordinated ciliary motion. The maxillary ( Fig. 49-4 ) and sphenoid sinuses are connected to the nasal cavity by discrete ostia, which often have a diameter of no more than 4 mm. The ethmoid sinuses are made up of a labyrinth of small cavities called air cells that sit between the orbit and the nasal septum. The ethmoid sinus typically drains through clefts between air cells rather than discrete ostia. The anterior ethmoid air cells drain through the middle meatus, between the middle turbinate and the lateral nasal wall. The posterior ethmoid cells drain through the superior meatus, between the superior turbinate and lateral nasal wall. The frontal sinus drainage tract is determined by the variable anatomy of the underlying anterior ethmoid air cells and eventually leads to the middle meatus.
Blood supply to the paranasal sinuses is provided through both the internal and external carotid systems. The sphenopalatine artery (SPA) is the terminal branch of the internal maxillary artery, which originates from the external carotid artery. The SPA enters the nasal cavity through the sphenopalatine foramen just behind the posterior wall of the maxillary sinus. The majority of the blood supply to the nasal cavity is provided by the SPA. The blood supply to the superior nasal cavity, and much of the ethmoid system, arises from the anterior and posterior ethmoid arteries. These vessels are branches from the ophthalmic artery of the internal carotid system and typically run within the skull base along the roof of the ethmoid sinuses. All of these vessels may contribute to refractory or “posterior” nosebleeds. Epistaxis originating from the SPA is amenable to embolization or surgical ligation of the SPA. The anterior and posterior ethmoid arteries are not amenable to embolization due to their origin from the ophthalmic artery and the associated risk for blindness. These vessels are amenable to surgical ligation in cases of refractory epistaxis.
Paranasal Sinus Disease
Overall, inflammatory disease of the paranasal sinuses is poorly understood. Sinusitis likely represents a wide variety of pathologic conditions that may cause either acute or chronic inflammation. Paranasal sinus inflammation is almost inevitably accompanied by inflammation of the nasal cavity, or rhinitis. Thus the term rhinosinusitis is typically used to describe this condition.
Diagnosis of rhinosinusitis is based upon the presence of both clinical symptoms and objective evidence of sinus inflammation. Table 49-1 demonstrates the diagnostic criteria for acute, chronic, and recurrent acute rhinosinusitis. The duration of symptoms is the primary factor used to differentiate between acute and chronic rhinosinusitis. Acute sinusitis lasts up to 4 weeks. Patients with signs and symptoms for 12 weeks or longer are diagnosed with chronic sinusitis. Whereas the duration of symptoms is used to distinguish between acute and chronic disease, the pathophysiologic features, symptoms, and treatment of these entities are different. Acute rhinosinusitis is most commonly an acute infectious disorder, and patients present with fever and facial pain as characteristic symptoms. Chronic rhinosinusitis (CRS) is primarily an inflammatory disorder in which the role of microbes is not well established. Patients with CRS typically note nasal congestion, thick nasal drainage, and facial pressure, but fever and pain are uncommon in the absence of acute exacerbations.
|Acute rhinosinusitis||Up to four (4) weeks of purulent nasal drainage (anterior, posterior, or both) accompanied by nasal obstruction, facial pain-pressure-fullness, or both: |
|Viral rhinosinusitis (VRS)||Acute rhinosinusitis that is caused by, or is presumed to be caused by, viral infection. A clinician should diagnose VRS when: |
|Acute bacterial rhinosinusitis (ABRS)||Acute rhinosinusitis that is caused by, or is presumed to be caused by, bacterial infection. A clinician should diagnose ABRS when: |
|CHRONIC AND RECURRENT|
|Chronic rhinosinusitis (CRS)||Twelve (12) weeks or longer of two or more of the following signs and symptoms: |
|Recurrent acute rhinosinusitis||Four (4) or more episodes per year of ABRS without signs or symptoms of rhinosinusitis between episodes: |
Objective findings of rhinosinusitis may be present on routine physical examination during evaluation of the anterior nasal cavity or anterior rhinoscopy. Acute rhinosinusitis may be diagnosed by history and anterior rhinoscopy alone; imaging studies are not recommended for uncomplicated acute sinusitis. Objective evidence of inflammation in patients with chronic sinusitis is often difficult to establish on anterior rhinoscopy, so nasal endoscopy or imaging of the sinuses is often required to establish the diagnosis. Computed tomography (CT) (see Fig. 49-4 ) is the preferred method of imaging for the paranasal sinuses; radiographs of the paranasal sinuses lack sufficient specificity and sensitivity and have little clinical utility.
Acute rhinosinusitis is extremely common and typically of viral etiology. It is estimated that adults suffer two to five episodes of viral rhinosinusitis (common cold) annually. School-age children may suffer 7 to 10 colds per year. In the United States, upper respiratory tract infection is the third most common reason for a primary care provider consultation, with approximately a third of these attributed to acute rhinosinusitis. Gwaltney and colleagues demonstrated that 60% of viral upper respiratory infections demonstrate radiologic evidence of inflammation within the ethmoid and maxillary sinuses on CT imaging. This study also highlights the futility of CT imaging for distinguishing between acute viral and acute bacterial rhinosinusitis.
Between 0.5% and 2% of viral rhinosinusitis episodes will progress to acute bacterial rhinosinusitis (ABRS). The proposed pathophysiology is that virally mediated mucosal inflammation and edema result in ciliary dysfunction and obstruction of the sinus ostia. This disruption of mucociliary clearance results in mucus stasis and a vulnerability to bacterial superinfection. The most common organisms seen in ABRS are noted in Table 49-2 .
|Organism||Range of Prevalence (%)|
Distinguishing the self-limited, viral-induced inflammation of the common cold from ABRS is a challenge often faced by primary care physicians. Clinical guidelines suggest that a detailed history is somewhat effective in making this distinction. Patients who fail to demonstrate significant clinical improvement after 10 days or experience a worsening of symptoms after 5 days of the onset of symptoms, also referred to as “double sickening,” are more likely to suffer from ABRS. Additionally, facial pain beyond what is expected from a viral upper respiratory infection or evidence of extrasinus extension of infection such as periorbital edema may be used to diagnose ABRS. Although patients who meet these clinical criteria demonstrate decreased duration and severity of symptoms when treated with antibiotics, the magnitude of improvement is relatively small. For patients with severe symptoms, antibiotic treatment is recommended. In patients with moderate symptoms beyond 10 days or who worsen after 5 days, antibiotic treatment is an option. Amoxicillin has been recommended as a first-line treatment for uncomplicated ABRS with trimethoprim-sulfamethoxazole encouraged for penicillin-allergic patients. However, with the emergence of resistant pathogens, the Infectious Diseases Society of America now recommends amoxicillin-clavulanate as first choice in adults, followed by doxycycline or a respiratory fluoroquinolone. Diagnostic imaging, including both radiographs and CT images of the sinuses, do not adequately distinguish between ABRS and acute viral rhinosinusitis and are not recommended unless extrasinus spread of infection is suspected.
Recurrent acute rhinosinusitis, defined as four or more episodes of ABRS per year, may arise in the context of predisposing anatomic variations, exacerbations of CRS, immune compromise, or without identifiable predisposing factors. Surgical intervention with widening of sinus ostia and removal of ethmoid septations may decrease the frequency and severity of symptoms. Although uncommon, complications arising from rhinosinusitis are seen more frequently in acute than chronic rhinosinusitis. Infection may spread to the orbit or intracranial cavity, a complication more common in children. Group B streptococcus is the most likely pathogen. Urgent evaluation and treatment, often including surgical drainage of affected sinuses and associated abscesses, is required to minimize the risk for visual loss, seizures, meningitis, and even death.
Invasive fungal sinusitis is a life-threatening condition that develops in patients with significant immune compromise. Diabetics with poorly controlled blood glucose levels and patients undergoing bone marrow transplantation are at highest risk. The diagnosis is suspected in this patient population with the development of facial pain, swelling, cranial neuropathies, or unexplained fevers. Imaging studies (CT and magnetic resonance imaging) are sensitive, but not specific, for invasive fungal sinusitis. The diagnosis is established by biopsy results demonstrating fungal invasion into the sinus tissues. Frozen section of diseased tissue may expedite this analysis. Cultures may be helpful to guide antifungal treatment; the morphologic features of fungal elements seen on pathologic evaluation may also assist in identifying the offending fungi. Extrasinus invasion is most common with mucormycosis. Treatment involves surgical débridement, systemic antifungal medications, and, when possible, reversal of underlying immune dysfunction. Even with appropriate medical care, mortality for this condition approaches 50%. Aggressive surgical débridement must therefore be considered in the context of the patient’s goals of care.
A slowly progressive, indolent form of invasive fungal sinusitis is seen in patients with less severe immune compromise. Solid organ transplant recipients and patients with chronic corticosteroid use are at risk for this disorder. Aspergillus is the most common pathogen. The treatment principles are the same as for patients with acute invasive fungal sinusitis.
Chronic rhinosinusitis (CRS) has an uncertain incidence because the diagnosis often requires both subjective symptoms and nasal endoscopy or CT evaluation. Surveys, which rely only on patient symptom reports, suggest that more than 15% of the U.S. population suffers from CRS, likely a significant overestimation of the true incidence. The prevalence of physician-diagnosed CRS using diagnostic coding reporting in a limited geographic area was closer to 2%. The impact of CRS on overall quality of life is estimated to be similar to that of chronic obstructive pulmonary disease (COPD) and congestive heart failure. In the United States the overall cost burden for chronic sinusitis is estimated at $8.6 billion/year.
CRS is characterized by persistent mucosal inflammation of the paranasal sinuses. The cause of this inflammation is variable and often poorly understood. Numerous theories have been proposed, including systemic immune dysfunction, staphylococcal superantigens, pathologic bacterial biofilms, aberrant immune response to fungus, and dysbiosis (e.g., imbalance of the resident microbial population). Several subtypes of CRS have been well established.
The bacteriology of CRS differs from that of acute sinusitis. Staphylococcus aureus, Pseudomonas aeruginosa, and anaerobic bacteria are more commonly cultured from patients with chronic disease than with acute disease. Recent studies using culture-independent bacterial identification demonstrate that healthy sinuses contain diverse bacterial communities, which may serve a protective role in the sinuses. Chronically inflamed sinuses are characterized by a loss of bacterial diversity with overgrowth of a pathologic species. Corynebacterium tuberculostearicum may represent a previously unrecognized bacterial pathogen. Furthermore, in a mouse model of sinusitis, the pathogenic potential of bacteria is enhanced with depletion of native bacterial communities through antibiotic treatment. Coinstillation of presumed probiotic microbes appears to protect against the inflammatory changes induced by exposure to pathologic bacteria.
Association with Allergy and Asthma
The role of allergy and atopy in CRS is unclear. Studies suggest a higher rate of positive skin tests in patients with CRS but may be confounded by selection bias. Although a causal role for allergy in patients with CRS has not been demonstrated, treatment of allergy in atopic patients with CRS improves patient outcomes.
CRS with nasal polyps (CRSwNP) demonstrates a more clear association with asthma. Nearly 30% to 40% of patients with polyps describe wheezing and respiratory discomfort. In addition, 26% of patients with polyps report a diagnosis of asthma, compared to 6% of control patients. Patients with asthma also demonstrate a high incidence of sinus mucosal thickening on CT imaging. Although asthmatic patients demonstrate a high incidence of nasal polyps, nonatopic asthma is more strongly associated (13%) with nasal polyps than atopic asthma (5%). Asthmatic patients who undergo endoscopic sinus surgery for CRSwNP demonstrate clinical improvement in both upper and lower airway disease.
Chronic Rhinosinusitis with Nasal Polyposis
CRSwNP is frequently seen in combination with asthma, and the pathologic findings in these two disorders are similar. Nasal polyp tissue classically demonstrates an eosinophilic infiltrate with a predominance of type 2 T helper inflammatory mediators. CT findings include extensive opacification of the paranasal sinuses and nasal cavities (see Fig. 49-4 ). Although nasal polyps may be visible on anterior rhinoscopy and may even extend to or beyond the nasal vestibule, more frequently nasal endoscopy is required to visualize nasal polyps. Patients typically present with nasal congestion, obstruction, thick nasal drainage, and anosmia. Facial pressure is common. Severe pain, headache, and fever are unusual in the absence of acute exacerbations of chronic disease. Fatigue and difficulty sleeping are also common symptoms.
Patients with asthma and nasal polyps should be queried regarding sensitivity to aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). Aspirin-exacerbated respiratory disease is found in a subset of CRSwNP patients and is characterized by nasal polyps, asthma, and NSAID sensitivity. Patients with aspirin-exacerbated respiratory disease demonstrate abnormalities in arachidonic acid metabolism, characterized by increased production of proinflammatory products of the 5-lipoxygenase pathway, and exposure to cyclooxygenase-1 inhibitors, such as aspirin and NSAIDs, results in shunting through the lipoxygenase pathway and in upper and lower airway inflammation. Patients often develop persistent rhinitis in their late teenage years with asthma and sinusitis developing over the next several years. Aspirin and NSAID sensitivity may develop at any point along the course of the disease. Aspirin-exacerbated respiratory disease represents a significant proportion of patients with asthma (9%) and CRSwNP (13%). These patients demonstrate a more refractory clinical course in the treatment of their sinus disease. Aspirin desensitization improves both asthma and sinus disease in this patient population.
Patients with unilateral nasal polyps should be evaluated for sinonasal neoplasms with imaging and consideration of biopsy. Before performing a biopsy of a sinonasal mass, the clinician should evaluate the relationship of the mass to the skull base to rule out an encephalocele. Assessment of surrounding vasculature is also critical because both aneurysms of the carotid artery and juvenile nasal angiofibromas may present as a nasal mass. Biopsy of these entities may lead to severe hemorrhagic complications.
Allergic fungal rhinosinusitis (AFRS) is a distinct category of chronic sinusitis. Unlike the majority of chronic inflammatory sinus disease, AFRS is often unilateral. This diagnosis is established by the presence of nasal polyps, eosinophilic mucus with Charcot-Leyden crystals, and skin or blood testing demonstrating allergy to fungus. The incidence of AFRS is higher in African American patients, and the disorder is more common in humid regions, including the southern United States. Bone expansion and erosion may result in initial difficulty distinguishing AFRS from sinonasal neoplasms. In such cases, magnetic resonance imaging findings are also helpful in the diagnosis of AFRS ( Fig. 49-5 ).
Congenital disorders that result in impairment of mucociliary clearance have a high incidence of CRS. Because nasal polyps are unusual in pediatric patients, their presence should trigger evaluation for cystic fibrosis and ciliary dyskinesia. Pathologic evaluation of polyps in these patients is more likely to demonstrate a neutrophilic infiltrate and a predominately type 1 T helper cell–mediated inflammatory process.
Treatment of CRSwNP is challenging. Most patients receive temporary, if any, benefit from antibiotic therapy. Topical steroid sprays often provide improvement but rarely provide adequate symptomatic relief for patients with a significant polyp burden. Systemic steroid therapy frequently provides significant symptomatic improvement. Unfortunately, systemic side effects limit long-term use of this medication, and symptoms often recur quickly following cessation of exogenous glucocorticoids. Initial enthusiasm for antifungal irrigations has waned with the publication of trials that demonstrate not only a lack of efficacy, but worsened symptoms when compared to placebo saline irrigations. Endoscopic sinus surgery with removal of polyps and cleaning of mucus and debris from within the sinuses results in significant symptomatic improvement. Systemic corticosteroids are frequently initiated before surgery for CRSwNP to decrease mucosal inflammation, which improves hemostasis and endoscopic visualization during surgery. Corticosteroids also enhance control of asthma during endotracheal anesthesia and the postoperative period. Even in the setting of appropriately performed endoscopic sinus surgery, recurrence of polyps is common. Combining medical and surgical interventions is critical in this patient population. Surgery enhances postoperative access to the sinuses, allowing enhanced penetration of topical steroid irrigations. Steroid-impregnated implantable materials have also been used to extend the duration of symptomatic improvement following surgery.
New biologic treatments hold promise for the treatment of CRS. Omalizumab (anti-IgE) has been used to treat refractory asthma and, although clinical data are limited, early trials suggest that omalizumab may reduce polyp burden and symptoms in CRSwNP patients. Interleukin-5 is an important driver of eosinophil differentiation and survival, and an anti–IL-5 (mepolizumab) has shown promise in early trials as a treatment for CRSwNP. A recently completed randomized, controlled trial evaluating anti–IL-4 (dupilumab) as a treatment for refractory asthma demonstrated improvement in CRS symptoms as assessed by a validated, disease-specific CRS outcome score. Availability and cost currently limit both clinical use and investigational studies into the efficacy of these biologic agents as treatments for CRS.
The Oral Cavity, Oropharynx, Hypopharynx, and Larynx
Anatomy, Histology, and Physiology
The oral cavity is defined as the space from the lips to the end of the hard palate. It contains the teeth, the buccal and gingival mucosa, the mandible and hard palate, the floor of the mouth and the tongue anterior to the circumvallate papilla ( Fig. 49-6 ). The oral cavity structures are mostly under voluntary control. The oral cavity functions to control the ingestion of substances. The structures control the substance during mastication and preparation of a bolus suitable for presentation to the oropharynx for reflexive swallowing. This involves the muscles of mastication for opening and closing of the jaws as well as the muscles in the lips and cheeks to control the size of the cavity and the muscles of the tongue to move the food particles around the mouth and shape them into the required bolus. In addition to controlling the intake of substances, the structures in the oral cavity are responsible for voluntary modulation of air exhaled from the lungs. This voluntary control is used to control the rate of the air exhaled, as well as to shape the noises created by air flow into speech and song.
The oropharynx is defined as the space from the end of the hard palate to a plane parallel to the top of the epiglottis (see Fig. 49-6 ). This space includes the structures of the lateral pharyngeal walls made up by the middle constrictors, the palatoglossus and the palatopharyngeus, the palatine tonsils, the soft palate and uvula, the vallecula, and the base of the tongue. Although these muscles and structures are under voluntary control for assistance in the rate of exhaled air from the lungs and shaping sounds released from the vocal tract, they are under reflexive control for swallowing. Once the sensory nerves are triggered by the exposure to a bolus of solids or liquids, the central nervous system sends a reflexive response to swallow. This reflex results in orderly contraction of the tongue base, soft palate, and lateral pharyngeal walls to propel the bolus posteriorly, seal off the nasopharynx, and propel the bolus to the hypopharynx, respectively. Again, the skeletal muscles of these structures are under both voluntary and reflexive central nervous system control.
The hypopharynx is defined as the space from a plane perpendicular to the tip of the epiglottis to the superior and lateral aspect of the larynx down to the esophageal inlet (see Fig. 49-6 ). This includes the structure of the lateral pharyngeal walls, including the inferior constrictors and mucosal membranes, as well as the bilateral pyriform sinuses. As for the oropharynx, the skeletal muscles that make up these structures are under voluntary control for assisting in regulation of airflow out of the lungs and shaping the airflow into speech as well as reflexive central nervous system control for swallowing. The distal end of the hypopharynx culminates in the upper esophageal sphincter. This is a region of the pharynx that controls opening of the proximal esophagus to allow passage of food into the alimentary track and to prevent the inadvertent regurgitation of food or secretions back into the pharynx and upper airway. Although the upper esophageal sphincter is several centimeters in length, the primary portion is made up of the cricopharyngeus muscle (see Fig. 49-6 ). This circumferential, slinglike skeletal muscle is maintained in a tonic contracted and closed state. The act of swallowing initiates reflexive inhibition of the neural input, resulting in muscular relaxation. As the larynx and pharynx are pulled upward and forward by the actions of other muscles, the relaxed upper esophageal sphincter is stretched open. This allows the passage of the food bolus. The bolus can fail to pass either because of failure of relaxation of the cricopharyngeus muscle segment or failure to stretch the area open through pull of coordinated muscles on the relaxed upper esophageal sphincter segment. Either will result in the retention of foods and secretions, which can then spill into the upper airway.
The larynx is made of the bone, cartilage, muscular, and mucosal structures from the epiglottis to the bottom of the cricoid ring. It is divided into three regions based on the lymphatic drainage patterns. These regions include (1) the supraglottis from the tip of the epiglottis to the top of the vocal folds (also known as the “vocal cords”), including the upper part of the arytenoid; (2) the glottis, which includes the tissue from the top of the vocal fold to 1 cm below the top of the vocal folds; and (3) the subglottis, which is below the vocal fold to the first ring of trachea ( Fig. 49-7 ).