Version May 2024
INTRODUCTION — Asthma and allergic rhinitis (rhinosinusitis) often coexist and may represent similar disease entities (one airway hypothesis) [1,2]. There is also a strong link between asthma and bacterial rhinosinusitis, viral upper respiratory infections (acute viral rhinosinusitis), and nasal polyposis.
Allergic rhinitis is almost ubiquitous in patients with allergic asthma [3-7]. Position papers on allergic rhinitis generated at international workshops in collaboration with the World Health Organization [8-11] and endorsed by the American Academy of Allergy, Asthma, and Immunology and by numerous other professional organizations internationally have supported this view.
Rhinitis is defined as the presence of sneezing, rhinorrhea (anterior and posterior), nasal congestion, and/or nasal itching arising from irritation and inflammation of the nasal passages. Rhinosinusitis describes disorders affecting both the nasal passages and paranasal sinuses. Symptoms of sinus involvement include nasal congestion, posterior nasal drainage, facial pressure and pain, headache, fatigue, and reduced sense of smell.
In most instances, the term "rhinosinusitis" is preferred to "sinusitis" since inflammation of the sinuses rarely occurs without concurrent inflammation of the nasal mucosa. However, rhinitis can occur without sinusitis. Patients with environmental allergies, especially seasonal (eg, pollens), can have rhinitis alone. In contrast, patients with perennial symptoms, usually associated with sensitization to indoor allergens (eg, dust mites, pet danders, fungi), often have prominent nasal congestion and posterior drainage and may be more predisposed to sinus mucosal involvement.
This topic reviews the epidemiologic, physiologic, and therapeutic evidence that supports the one airway hypothesis. Allergic rhinitis, acute and chronic rhinosinusitis, and asthma are covered in detail separately in numerous topics. (See "An overview of rhinitis" and "Pathogenesis of allergic rhinitis (rhinosinusitis)" and "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis" and "Acute sinusitis and rhinosinusitis in adults: Clinical manifestations and diagnosis" and "Pathogenesis of asthma" and "Uncomplicated acute sinusitis and rhinosinusitis in adults: Treatment".)
EPIDEMIOLOGY — Rhinitis occurs in 75 to 90 percent of adult subjects with allergic asthma and 80 percent of those with nonallergic asthma [12]. Conversely, asthma occurs in 25 to 50 percent of individuals with rhinitis. Adults with perennial rhinitis are more likely to have asthma than those without rhinitis [13]. The odds of developing asthma are 8-fold higher in patients with allergic rhinitis and almost 12-fold higher in subjects with nonallergic rhinitis.
Similar data are observed in children [3,6,14,15]. In a prospective study of over 600 urban children and adolescents with asthma, 94 percent had a diagnosis by questionnaire of one of five phenotypic forms of rhinitis [3]. Previous estimates of rhinitis in the general population across all ages have ranged from 10 to 40 percent. The children in this study with perennial allergic rhinitis with seasonal exacerbations had the most severe rhinitis symptoms and were more likely to have difficult-to-control asthma and rhinitis. The prevalence of rhinitis in the general population is reviewed elsewhere. (See "An overview of rhinitis".)
The Copenhagen Allergy Study further illustrates the close relationship between rhinitis and asthma [6]. This population-based study examined the prevalence of allergic rhinitis and allergic asthma in 700 subjects aged 15 to 69 years at two time points eight years apart. Diagnosis of allergy was based upon allergic respiratory symptoms and in vitro-specific immunoglobulin (Ig)E testing. Findings were as follows:
●All 52 subjects with allergic asthma to pollen had concomitant allergic rhinitis to pollen at the second time point. Twenty-eight of these subjects were new cases. All had allergic rhinitis to pollen at baseline or had developed allergic rhinitis to pollen at follow-up.
●Similarly, allergic rhinitis to animals and to dust mites was present in all subjects with allergic asthma to those respective allergens.
TRIGGERS — The same agents can trigger both rhinitis (rhinosinusitis) and asthma. These include:
●Allergens
●Aspirin and other cyclooxygenase 1-inhibiting nonsteroidal antiinflammatory drugs
●Irritants
●Infections (viral and bacterial)
As examples:
●Cysteinyl leukotrienes are released into both nasal and bronchial secretions following aspirin challenge in patients with aspirin-exacerbated respiratory disease (classically referred to as aspirin triad or "Samter's triad") [9,16]. (See "Aspirin-exacerbated respiratory disease".)
●Similarly, occupational rhinitis usually precedes occupational asthma. This is true for both high-molecular-weight agents and low-molecular-weight allergens, such as animal proteins [9]. (See "Occupational rhinitis" and "Occupational asthma: Definitions, epidemiology, causes, and risk factors".)
●Rhinoviruses are the major cause of the common cold and are also a trigger of acute asthma exacerbations [17,18]. The combined effects of allergen sensitization, exposure to perennial aeroallergens, and viral infection increase the risk of hospitalization for asthma in adults (odds ratio [OR] 8.4, 95% CI 2.1-32.8) [19].
●More than two-thirds of individuals with asthma have symptoms of rhinosinusitis. Up to 100 percent of adults with severe, glucocorticoid-dependent asthma and up to 90 percent of those with mild-to-moderate asthma have abnormal sinus computed tomography scans [20]. Fifty to 75 percent of children with asthma have abnormal sinus radiographs. Both acute and chronic rhinosinusitis may exacerbate asthma [18].
NATURAL HISTORY — Longitudinal studies suggest that both allergic rhinitis with positive allergy skin tests and nonallergic rhinitis are risk factors for development and persistence of asthma [5,7,21-27].
●One series surveyed 690 individuals as college freshmen and then reevaluated them 23 years later [5]. None of these individuals had a diagnosis of asthma or symptoms compatible with asthma at the time of their first evaluation. However, 162 had a diagnosis of rhinitis. The incidence of asthma over 23 years was 10.5 percent in subjects with rhinitis and 3.6 percent in those without rhinitis. This study suggests that subjects with allergic rhinitis are three times more likely to develop asthma than those without allergic rhinitis.
●The European Community Respiratory Health Survey, a longitudinal, population-based study, found that rhinitis, either allergic or nonallergic, was predictive of the development of adult-onset asthma in 6461 adult subjects without asthma at baseline [24]. The adjusted relative risk of asthma over approximately nine years was 1.63 (95% CI 0.82-3.24) for "atopy only" (positive prick skin tests for one or more allergens; no rhinitis), 2.71 (95% CI 1.64-4.46) for nonallergic rhinitis, and 3.53 (95% CI 2.11-5.91) for allergic rhinitis. Dust mites were the only allergens independently associated with an increased risk of asthma in patients with allergic rhinitis (2.79 [95% CI 1.57-4.96]).
●The Tucson Epidemiologic Study of Obstructive Lung Diseases assessed rhinitis as a potential risk factor for asthma [7]. This study compared 173 adults who developed asthma over 10 years with 2177 control subjects who, during the same approximate period, did not have any chronic lower respiratory tract symptoms. They controlled for several confounding variables, including smoking status and concomitant chronic obstructive pulmonary disease. The odds ratio (OR) for developing asthma was 2.59 (95% CI 1.54-4.34) if rhinitis was present and was 6.28 (95% CI 4.01-9.82) if both rhinitis and rhinosinusitis were present. The risk for asthma increased with the persistence or severity of rhinitis.
●A birth cohort study examined risk factors for persistent wheezing at six years of age [21]. Persistent asthma at six years of age was associated with inhalant allergy, with positive skin tests to aeroallergens and rhinitis independent of colds. These continue to be markers of asthma persistence through adolescence and adult life [22].
COMPARATIVE ANATOMY — The structure of the airway mucosa is similar in the nose and bronchi. Histologically similar respiratory epithelium extends posteriorly from the nasal septum and lateral walls of the nasal fossa to the nasopharynx, larynx, trachea, bronchi, and bronchioles. However, there are several differences. Keratinized and unkeratinized stratified squamous epithelium are present in the nasal vestibule. Cartilage is found from nasal fossa to the bronchi only. There is no muscle present in the nasal cavity. Only skeletal muscle is present in the nasopharynx and larynx and only smooth muscle in the lower airway.
AIRWAY INFLAMMATION — The mucosal cellular infiltrates that characterize rhinosinusitis and asthma are similar (eg, eosinophils, mast cells, macrophages, and T cells). In addition, the same proinflammatory mediators are present in both nasal and bronchial mucosa (eg, histamine; leukotrienes; interleukin [IL] 4; IL-5; IL-13; granulocyte-macrophage colony-stimulating factor; regulated on activation, normal T cell expressed and secreted [RANTES]; and adhesion molecules) [9]. As examples:
●Nasal challenge with allergen can result in bronchial inflammation in patients with allergic rhinitis but no clinical signs of asthma [28,29].
●Eosinophils are found in higher numbers in both nasal and bronchial biopsies in patients with asthma and allergic rhinitis versus patients with asthma alone [30].
●Increased eosinophils are seen in nasal mucosa biopsies in patients with asthma, with or without a history of rhinitis [31].
●Individuals with allergic rhinitis but not asthma who respond to segmental methacholine bronchoprovocation have increased eosinophils in the lamina propria of the nose [32].
●Computed tomography-graded sinusitis severity is positively associated with sputum and peripheral blood eosinophilia, exhaled nitric oxide levels, and functional residual capacity [33].
●Airway remodeling is an ongoing characteristic of allergic asthma, but a study comparing 46 subjects with severe persistent allergic rhinitis to 17 healthy control subjects observed increased levels of proinflammatory mediators in the rhinitis group but no structural changes or evidence of airway remodeling of nasal tissues compared with the control group [34].
AIRWAY HYPERRESPONSIVENESS AND PULMONARY FUNCTION — Airway hyperresponsiveness (AHR) is common in individuals with allergic rhinitis, even in the absence of a history of wheezing [35]. As examples:
●Endobronchial challenge in patients with allergic rhinitis induces nasal and bronchial symptoms as well as reductions in nasal and pulmonary function [32].
●Patients with allergic rhinitis have increased bronchial sensitivity to methacholine and histamine compared with nonatopic subjects [36,37].
●Patients with seasonal allergic rhinitis develop seasonal bronchoconstriction that may be unassociated with clinical symptoms [38].
●One study associated sensitization to aeroallergens with AHR to methacholine challenge in seven-year-old children at high risk for atopic disease [39]. In another report, young adults with moderate-to-severe persistent allergic rhinitis and no clinical asthma also demonstrated AHR to methacholine challenge [40].
●Patients with persistent allergic rhinitis and no clinical asthma may nonetheless show significant increases in forced expiratory volume in one second (FEV1) from their basal level after treatment with a bronchodilator compared with patients without allergic rhinitis or asthma [41].
●Children with both asthma and allergic rhinitis may have delayed recovery of pulmonary function after an acute asthma exacerbation. Of 57 children consecutively evaluated for moderate/severe asthma exacerbations, 42 percent recovered within seven days. Logistic regression analysis determined that allergic rhinitis (both intermittent and persistent classifications) and severe asthma exacerbation were significant factors in those children whose pulmonary function tests (FEV1, forced expiratory flow at 25 to 75 percent [FEF25-75], and peak expiratory flow) recovered after more than seven days [42].
●AHR was greater in patients with both asthma and allergic rhinitis compared with those with asthma alone in another study [43].
●In a study of 605 nonasthmatic adult patients with allergic rhinitis, 8 percent had abnormal FEV1, 25 percent had reduced FEF25-75, and 65 percent had spirometric improvement after bronchodilator [44].
INTERACTIONS BETWEEN THE UPPER AND LOWER AIRWAYS — Postulated mechanisms through which the upper and lower airway may interact include:
●Neural interaction (nasal bronchial reflex) – Animal studies demonstrate reflexes arising from receptor sites in the nose and nasopharynx. These reflexes are mediated by the afferent sensory components of the trigeminal and glossopharyngeal nerves and the efferent bronchoconstrictor fibers of the vagus nerve.
●Disturbance of nasal mucosa conditioning (warming and humidification) of the air entering the respiratory tree – Air warming and humidification are the basic functions of the nasal airway and sinuses. Nasal breathing appears to have a protective effect on exercise-induced bronchospasm. Exercise treadmill tests were conducted with 12 children with mild-to-moderate asthma who were instructed to breathe only through their nose, only through their mouth, or breathe "naturally" (resulted in oral breathing in most patients) [45]. Spontaneous breathing during the exercise challenge resulted in bronchoconstriction, with a decrease in FEV1. Oral breathing exaggerated the airway hyperreactivity, and nasal breathing abrogated the bronchoconstrictive response. A study of eight adult females with asymptomatic mild asthma demonstrated a slight, progressive decrease in FEV1 over a one-hour period during exclusive oral breathing [46]. Patients also perceived increased difficulty in breathing, and three patients experienced coughing/wheezing after oral breathing. Similar findings were not seen with enforced nasal breathing in the same subjects.
●Effects of nitric oxide on both upper and lower airways – Nitric oxide is formed in multiple cell types by various mechanisms. It serves a protective function. It has strong antiviral and bacteriostatic activity, bronchodilatory effects, and modulatory effects on lower airway responsiveness. In addition, it improves oxygenation. Decreased nitric oxide levels are found in patients with inflammatory conditions, such as chronic rhinosinusitis with or without nasal polyposis [4]. (See "Exhaled nitric oxide analysis and applications".)
●Irritant and inflammatory effects of nasal secretions directly draining into the lower airway, including particles and irritants entrapped in the mucociliary blanket – Studies in a rabbit model of acute rhinosinusitis provided strong evidence that drainage of nasal inflammatory mediators into the lung may precipitate asthma [47]. There is evidence that pharyngeal aspiration occurs in healthy humans as well as in those with decreased consciousness [48]. However, one study in which radioactively labeled technetium was injected into the maxillary sinuses of subjects with chronic rhinosinusitis and moderate-to-severe asthma failed to detect radioactive material in the lung fields despite the ability to trace it in the gastrointestinal tract [49]. Some investigators have countered that substances produced during allergic reactions can enter the gaseous phase, become aerosolized, and disseminate throughout the lower respiratory tract, thus potentially producing bronchoprovocation [4].
●Systemic propagation of inflammation via effects of mediators and inflammatory cells – Systemic propagation of inflammation may be a principal connection between the upper and lower airways in patients with allergic respiratory disease. Studies suggest that allergic airway inflammation leads to recruitment of eosinophils into the systemic circulation, which then leads to inflammation of respiratory mucosa not exposed to the culprit allergen [28,50]. Specifically, allergen provocation can lead to inflammatory cell production in the bone marrow [51]. The systemic increase in inflammatory cells can also be detected outside of the airway. Patients with asthma and allergic rhinitis have increased numbers of eosinophils, mast cells, and T cells in duodenal biopsies [52].
CLINICAL IMPLICATIONS — The relationship between upper and lower airway disease has clinical relevance. Patients with chronic or recurrent rhinosinusitis should be evaluated for asthma, including pulmonary function studies with bronchodilator if indicated. Patients with persistent asthma should be questioned for symptoms suggestive of rhinitis and acute or chronic rhinosinusitis. Upper airway disease is thought to aggravate or cause lower airway disease, and treatment of upper airway disease can improve lower airway disease [9,11].
●Treatment of allergic rhinitis with intranasal glucocorticoids can prevent or improve asthma symptoms and lower airway hyperresponsiveness (AHR) [53]. Two large, retrospective studies evaluated more than 25,000 subjects and found that intranasal glucocorticoids decrease emergency department visits and hospitalizations for asthma in a dose-dependent manner [54,55]. However, no change was seen in pulmonary function, sputum eosinophils, or methacholine responsiveness in another study in which patients with asthma were treated with intranasal glucocorticoids [56].
●A meta-analysis of 18 trials concluded that the favorable effects of intranasal glucocorticoids on asthma outcomes were most prominent in patients with asthma and allergic rhinitis who did not also use orally inhaled glucocorticoids [57].
●Oral H1 antihistamines also lower the rates of asthma-related emergency department visits and hospitalizations [58].
●Leukotriene modifiers are effective in controlling symptoms of mild-to-moderate asthma and seasonal allergic rhinitis [59].
●Allergen immunotherapy reduces the progression to asthma in children and adults with allergic rhinoconjunctivitis [60-66]. (See "Subcutaneous immunotherapy (SCIT) for allergic rhinoconjunctivitis and asthma: Indications and efficacy", section on 'Prevention of asthma'.)
●Omalizumab (humanized anti-IgE) is effective in treating patients with moderate-to-severe allergic asthma and is also effective in treating patients with seasonal and perennial allergic rhinitis [67].
●Other biologics (eg, mepolizumab and reslizumab, both humanized monoclonal anti-interleukin [IL] 5) have efficacy in treating patients with eosinophilic asthma and nasal polyposis [68-71].
●Multiple studies have examined whether surgical treatment of rhinosinusitis may improve asthma, but high-quality evidence is lacking [72-74].
SUMMARY
●One airway hypothesis – Asthma and rhinosinusitis often coexist and likely represent a spectrum of the same disease entity. Rhinitis occurs in 75 to 90 percent of adult subjects with asthma, and asthma occurs in 25 to 50 percent of individuals with rhinitis. The upper and lower airways are contiguous and have anatomic and physiologic similarities. In addition, the cellular infiltrates and inflammatory mediators present in rhinitis and asthma are similar, and both disorders have the same triggers. (See 'Epidemiology' above and 'Comparative anatomy' above and 'Airway inflammation' above and 'Triggers' above.)
●Rhinitis is a risk factor for asthma – Longitudinal studies suggest that both allergic rhinitis with positive allergy skin tests and nonallergic rhinitis are risk factors for development and persistence of asthma in children and adults. (See 'Natural history' above.)
●Interactions between the upper and lower airway – Postulated mechanisms through which the upper and lower airway may interact include the nasal bronchial reflex, disturbance of nasal mucosa conditioning, nitric oxide effects, drainage of irritant and inflammatory material, and systemic propagation of inflammation. (See 'Interactions between the upper and lower airways' above.)
●Clinical implications – Patients with persistent asthma should be evaluated for rhinitis and rhinosinusitis because detection and treatment of nasal disease improves asthma. (See 'Clinical implications' above.)
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