Epidemiologic links

Various epidemiologic studies have shown allergic rhinitis to be a common disorder in the United States. Prevalence rates of allergic rhinitis range from 15% to 40% . The variability in the many epidemiologic studies available may be because of sampling issues and differences in case definition. But regardless, allergic rhinitis is a common disorder that is encountered frequently by the practicing otolaryngologist. Similarly, asthma is a prevalent disorder that affects approximately 7% of the United States population . Asthma and allergic rhinitis, however, occur together at rates that greatly exceed what would be expected from the baseline prevalence of each disorder alone ( Fig. 1 ). Between 19% and 38% of patients who have allergic rhinitis also have asthma . In patients who have asthma, rhinitis is extremely common; the vast majority of patients who have asthma have rhinitis. Multiple studies have shown rhinitis to be present in 50% to 85% of asthmatic subjects, with the differences between studies likely caused by differences in methodology. Relying on patient self-reporting of symptoms may be insensitive considering that many patients with asthma may be more bothered by their asthma than any rhinitis symptoms . In a chart review-based study of 1245 asthmatic subjects in Olmstead County, Minnesota, 52% of asthmatic subjects were found to have allergic rhinitis, and 6% had nonallergic rhinitis . In the Copenhagen Allergy Study, which relied on direct questioning and examination of study subjects, 100% of subjects who had allergic asthma induced by pollen had allergic rhinitis from pollen. Eighty-nine percent of subjects who had allergic asthma caused by animals had allergic rhinitis from animals, and 95% of subjects who had allergic asthma caused by mites had allergic rhinitis from mites . The fact that the vast majority of asthma patients suffer from rhinitis has therapeutic implications that will be discussed later.

Venn diagram showing the relative populations with asthma, allergic rhinitis, or a combination of the two.

Allergic rhinitis is a risk factor for the development of asthma; it is much more than just an associated condition. This assertion has been corroborated by multiple studies . In the Finnish Twin Cohort Study , over 11,000 subjects were administered questionnaires in 1975, 1981, and 1990. The study found that men who reported hay fever in 1975 had a fourfold increased risk of reporting asthma in 1990. In women, the effect was even more pronounced, with a sixfold increased risk of developing asthma after reporting hay fever in the earlier survey. Looking at this longitudinal data, the authors also noted that rhinitis nearly always was diagnosed before asthma. This trend, where allergic rhinitis precedes the development of asthma, has been noted by other authors , and sometimes has been referred to as the allergic march. But the natural history of rhinitis and asthma are quite variable between individuals, and asthma sometimes becomes manifest before rhinitis. It is now accepted, however, that rhinitis is an independent risk factor for the development of asthma .

There are multiple variables that influence the linkage between asthma and rhinitis. The association of rhinitis and asthma depends upon the atopic status of the patient, the age of onset of atopy, and the severity of symptoms. Subjects who develop atopy at an earlier age appear more likely to develop asthma. It should be noted that atopy is not required for this relationship . In a nested case–control study of data acquired as part of the Tucson Epidemiologic Study of Obstructive Lung Diseases, Guerra and colleagues showed that both allergic and nonallergic rhinitis increased the risk of developing asthma threefold, and only in allergic rhinitis subjects with the highest IgE levels did atopy strengthen this risk of developing asthma. The association of rhinitis and asthma is independent of allergy, but in allergic patients it is dependent to some extent on the severity and persistence of rhinitis symptoms. The pathophysiological explanation for these observations remains a matter of investigation.

Perennial, nonallergic rhinitis also has been established as an independent risk factor for asthma. Data from young adults participating in the European Community Respiratory Health Survey showed that nonallergic rhinitis was associated strongly with asthma. In this large, multicenter study, 1412 young adults who had perennial rhinitis symptoms were compared with 5198 control subjects by means of a questionnaire, total and specific IgE testing, and spirometric testing with methacholine bronchoprovocation . The odds ratio for current asthma among nonatopic perennial rhinitis subjects was 11.6 (95% CI, 6.2 to 21.9) after multiple logistic regression analysis. Additionally, in this study, nonallergic individuals who had rhinitis but no asthma were found to have increased bronchial hyper-responsiveness to methacholine challenge. (The phenomenon of bronchial hyper-responsiveness in non-asthmatic rhinitics will be discussed later in the article.) So the connection between rhinitis and asthma is not merely a result of atopy.

The presence of rhinitis appears to be associated with more severe asthma. In a study of hospital admissions in 2961 children from Norway, even when correcting for severity of asthma, children who had allergic rhinitis had a higher risk of hospital readmission and more hospital days per year when compared with asthmatic patients without rhinitis . Similar findings have been noted from the United Kingdom. Using a general practice database, Thomas and colleagues found that asthmatic children who had a recorded diagnosis of allergic rhinitis had more general practitioner visits and were more likely to be hospitalized during the 12-month follow-up period of the study compared with children who had asthma alone. In addition to increased severity of disease, increased costs are seen when asthma and rhinitis are concomitant disorders. In the study of 1245 asthmatic subjects in Olmstead County, Minnesota, yearly medical care charges were 46% higher in those patients who had concomitant asthma and rhinitis . Halpern and colleagues studied a medical claims database, and found when analyzing all patients who had a claim of asthma (n = 27,398), that the presence of allergic rhinitis was associated with more asthma medication prescriptions and higher asthma prescription costs. These studies suggest that clinically diagnosed allergic rhinitis may be more common in individuals who have severe asthma, or that individuals who manifest both rhinitis and asthma symptoms have a more severe disease complex than those who have only upper or lower airway symptoms.

Although the epidemiologic linkage between asthma and rhinitis is now clear, the exact reason for this connection remains under investigation. Rhinitis, which leads to nasal obstruction, may cause inspiration of unfiltered and unconditioned air that theoretically could exacerbate any underlying lung disease. Although experimental data are lacking to support this assertion, there does appear to be some connection between nasal obstruction and asthma symptoms. In fact, improving nasal breathing in asthmatics with a simple nostril dilating device has been shown to reduce nocturnal asthma symptoms . There is also a putative nasobronchial reflex wherein nasal irritation provokes bronchoconstriction. In a study of normal individuals, Fontanari and colleagues showed that nasal, but not oral inhalation of cold dry air increased airway resistance, and this increased resistance could be blocked by nasal anesthesia, nasal anticholinergic treatment, or bronchial anticholinergic treatment. In animal experiments, mechanical or chemical stimulation of the nose may induce bronchoconstriction, and this same phenomenon has been demonstrated in nonasthmatic people . Milqvuist performed warm and cold nasal air challenges in cold-sensitive asthmatic patients and normal control subjects. He found that nasal insufflation of cold air (confined to the nose) caused a decrease in specific airway conductance and forced expiratory volume in 1 second (FEV ₁ ) in the asthmatic patients, but not in normal controls, suggesting an interplay between the nose and the remainder of the airways that is present in cold-sensitive asthmatics, and may represent a trigeminal reflex. Interestingly, warm air insufflation had an opposite effect, increasing the specific airway conductance and FEV ₁ . So potentially there are reflex-like linkages that explain how nasal disease may trigger changes in the pulmonary airways.

Aspiration of infected or inflammatory sinonasal secretions has been invoked to explain the connection between rhinosinusitis and asthma. This mechanistic explanation never has found convincing evidence for its role, and seems highly unlikely in neurologically intact patients. Additionally, studies have been conducted that argue against this phenomenon. In one study, patients taken to the operating room for sinus surgery had radionuclide tracers placed within their maxillary sinuses. They then were followed with scintigraphy for any evidence of pulmonary aspiration of secretions. Two of four patients who had depressed consciousness had evidence of aspiration. None of the neurologically intact individuals who had a history of sinusitis and asthma, or sinusitis alone had any radiotracer localize to the thoracic cavity . Although there is obvious anatomic contiguity between the nose and lower airways, it seems unlikely that direct transfer of inflamed or infected secretions from the upper to lower airways plays a significant role in the connection between asthma and rhinitis.

A potentially very important connection that exists between the lung and nose is the bloodstream. Systemic propagation of nasal or bronchial inflammation, by means of the bloodstream, may be the most important connection that exists between the upper and lower airways. This connection has been investigated in experimental clinical studies, and the findings of these studies are discussed later in this article.

The inflammation in rhinitis and asthma are similar

The pathologic similarity of rhinitis and asthma begins with similar tissues. The nasal and bronchial mucosa are histologically similar. Both nasal and bronchial mucosa have ciliated pseudostratified columnar epithelium. Underlying a basement membrane within the submucosa are mucus glands, vessels, inflammatory cells, and nerves. The nasal submucosa contains numerous capacitance vessels: arteries, venous sinusoids, and capillaries. Changes in this vasculature can lead to nasal obstruction. The bronchial airways, in contrast, do not have such an extensive blood supply or capacitance vessels, but do contain smooth muscle that strongly influences the luminal area of the lower airways .

The inflammation in rhinitis is similar to that seen in the bronchial mucosa of subjects who have asthma. The inflammatory cell infiltrate of mononuclear cells, lymphocytes, and eosinophils in both diseases demonstrates marked pathologic similarity in both the bronchial and nasal mucosa . Additionally, the cytokines, adhesion molecules, and other inflammatory mediators are the same in both diseases . These include a preponderance of the so-called TH2 cytokines, interleukin (IL)-5, regulated upon activation, normal T-cell expressed, and secreted (RANTES), eotaxin, and the cysteinyl leukotrienes. There are differences of course. For example, the nasal obstruction from rhinitis is largely caused by engorged capacitance vessels in the nose and mucosal edema, while in asthma, epithelial disruption, basement thickening, and smooth muscle hypertrophy are pathologic developments . The similarity of histologic features, inflammatory cell infiltrates, and soluble inflammatory mediators suggests that the basic underlying pathogenic factors in asthma and rhinitis are the same. The same triggers, whether viral, irritant, or allergen can trigger both rhinitis and asthma. These common features suggest that asthma and rhinitis are intimately linked disorders, and it is becoming increasingly obvious that practitioners are dealing with one airway disease that has various end-organ manifestations.

The inflammation in rhinitis and asthma are similar

The pathologic similarity of rhinitis and asthma begins with similar tissues. The nasal and bronchial mucosa are histologically similar. Both nasal and bronchial mucosa have ciliated pseudostratified columnar epithelium. Underlying a basement membrane within the submucosa are mucus glands, vessels, inflammatory cells, and nerves. The nasal submucosa contains numerous capacitance vessels: arteries, venous sinusoids, and capillaries. Changes in this vasculature can lead to nasal obstruction. The bronchial airways, in contrast, do not have such an extensive blood supply or capacitance vessels, but do contain smooth muscle that strongly influences the luminal area of the lower airways .

The inflammation in rhinitis is similar to that seen in the bronchial mucosa of subjects who have asthma. The inflammatory cell infiltrate of mononuclear cells, lymphocytes, and eosinophils in both diseases demonstrates marked pathologic similarity in both the bronchial and nasal mucosa . Additionally, the cytokines, adhesion molecules, and other inflammatory mediators are the same in both diseases . These include a preponderance of the so-called TH2 cytokines, interleukin (IL)-5, regulated upon activation, normal T-cell expressed, and secreted (RANTES), eotaxin, and the cysteinyl leukotrienes. There are differences of course. For example, the nasal obstruction from rhinitis is largely caused by engorged capacitance vessels in the nose and mucosal edema, while in asthma, epithelial disruption, basement thickening, and smooth muscle hypertrophy are pathologic developments . The similarity of histologic features, inflammatory cell infiltrates, and soluble inflammatory mediators suggests that the basic underlying pathogenic factors in asthma and rhinitis are the same. The same triggers, whether viral, irritant, or allergen can trigger both rhinitis and asthma. These common features suggest that asthma and rhinitis are intimately linked disorders, and it is becoming increasingly obvious that practitioners are dealing with one airway disease that has various end-organ manifestations.