Guy A. Settipane’s research while affiliated with Brown University and other places

The purpose of this study is to examine the relationship between the course of asthma and allergic rhinitis among former Brown University students who were diagnosed with these diseases either before or after their freshman year of 1962 or 1963. A total of 738 former students, who were evaluated and underwent skin testing during their freshman year, completed a 23-year follow-up questionnaire inquiring of their history of allergies and asthma and are the focus of this study. The activity of asthma as related to the course of allergic rhinitis (hay fever and/or nonseasonal allergic rhinitis) was examined. Among 44 asthmatic subjects with purely seasonal allergic rhinitis (hay fever and no history of nonseasonal allergic rhinitis), asthma was active in 75% of those with worse hay fever, 70% of those with unchanged hay fever, 50% of those with better (but not symptom-free) hay fever, and 10% of those with symptom-free hay fever. The resolution of asthma symptoms correlated significantly with improvement in hay fever (p = 0.0053). Among 70 asthmatics with any form of allergic rhinitis (hay fever and/or nonseasonal allergic rhinitis), asthma was active in 75.0% of those with worse allergic rhinitis, 66.7% of those with unchanged allergic rhinitis, 53.3% of those with better (but not symptom-free) allergic rhinitis, and 20.0% of those with symptom-free allergic rhinitis. The resolution of asthma symptoms correlated significantly with improvement in allergic rhinitis (p = 0.0052). The activity of allergic rhinitis as related to the course of asthma was also examined. Among 44 asthmatic subjects with purely seasonal allergic rhinitis (hay fever and no history of nonseasonal allergic rhinitis), hay fever was active in 100% of those with worse asthma, 100% of those with unchanged asthma, 90.9% of those with better (but not symptom-free) asthma, and 60.9% of those with symptom-free asthma. The resolution of hay fever symptoms correlated significantly with improvement in asthma (p = 0.0109). Among 71 asthmatic subjects with any form of allergic rhinitis (hay fever and/or nonseasonal allergic rhinitis), allergic rhinitis was active in 91.9% of those with active asthma and 64.7% of those with symptom-free asthma. The resolution of allergic rhinitis symptoms correlated significantly with improvement in asthma (p = 0.0078). In summary, among individuals with asthma and allergic rhinitis, improvement of allergic rhinitis was associated with a resolution of asthma symptoms, whereas a worsening of allergic rhinitis was associated with the persistence of asthma symptoms. Likewise, among asthmatic subjects with allergic rhinitis, improvement of asthma was associated with a resolution of allergic rhinitis symptoms, whereas a worsening of asthma was associated with the persistence of allergic rhinitis symptoms.

The Hygiene Hypothesis helps to explain the increased epidemiology of atopy, especially asthma and hay fever. This hypothesis depends on two major immunological pathways, the Th1 and the Th2 pathways, which are mutually inhibitory, with the Th2 pathway being the dominant one in fetal life and the newborn. The Th1 leads to a cellular delayed hypersensitive response while the Th2 pathway leads to increased IgE, eosinophilia, atopy, and airway/hyperresponsiveness. The ever-increasing vaccines for immunization against viral and bacterial microorganisms together wit better public health hygiene procedures introduce a bias in favor of the inhibition of the Th1 pathway, thereby allowing the Th2 pathway, wit its IgE hypersensitivity, to predominate. We have attempted to correlate this new hypothesis with data from our Brown University college student longitudinal study. In this study, our data have demonstrated that allergen sensitization (positive pollen skin tests reactions) leads to an increased risk factor for developing asthma. Most of our asthmatic patients in our longitudinal study had positive allergy skin tests. Also, students born in months with high concentrations of atmospheric ragweed pollen had an increased risk of developing sensitization to ragweed and late to develop hay fever, which may led to asthma. There is a strong association of asthma with hay fever (a classic IgE disease). Also hay fever patients have three times the risk for developing asthma than controls. There appear to be several factors needed to express the phenotype of allergic asthma: elevated IgE, eosinophilia, airway hyperresponsiveness, exposure to allergens, and the predominance of the Th2 pathway of immunologic reactions.

A 23-year followup study of 1,601 college students who were initially evaluated for evidence of asthma and allergic rhinitis by direct interviews, physical examination, laboratory tests, and repeated questionnaires was conducted. The individuals were located through addresses from the alumnae office. Of these, 1,021 (64%) returned their completed questionnaires and these included 738 (72%) who had allergy skin tests as freshmen. A similar proportion of our total population of 1,021 were skin tested as freshmen compared with the original study population of 1,836 in the freshmen year (72% versus 68%). This difference was not statistically significant. Among these 738 alumnae, with a mean age of 40 years, there were a total of 84 with a history of asthma. At the time of the 23-year followup, 44 (52%) were considered to have active asthma and 40 (48%) were symptom free. A majority (85%) of those with inactive asthma were symptom free for 5 years or longer. Of those with active asthma, 50% felt they were improved, 39% unchanged, 9% felt worse, and 2% were unknown. Atopy was a non-prognostic indicator of asthma outcome as determined by scratch skin testing as college freshmen. New asthma occurred in 36 (5.2%) of those at risk to develop new asthma in this 23-year period for a rate of 0.23% per year. This 23-year followup study demonstrates that the cumulative prevalence of asthma continues to increase as the individuals become older. The asthma symptoms were no longer present or were improved in about three-fourths of the asthma subjects in this 40-year-old age group. Of the remainder, most symptoms were unchanged and a small number felt worse.

The purpose of this study is to examine the co-existence of asthma and allergic rhinitis among former college students who were diagnosed with these diseases either before or after their freshman year. A total of 738 former Brown University students (69% males and 31% females) who were evaluated and underwent skin testing during their freshman year completed a 23-year follow-up questionnaire inquiring of their history of allergies and asthma. The mean age of the participants at the time of the follow-up study was 40 years. In this group, the cumulative incidence of asthma was 11.3% (84/738), hay fever was 41.5% (306/738), and nonseasonal allergic rhinitis was 14.0% (103/738). The cumulative incidence of allergic rhinitis (hay fever) and/or nonseasonal allergic rhinitis (was 45.8% (338/738). Among the 84 individuals with a cumulative incidence of asthma, 63 (75.0%) had a history of hay fever, 27 (32.1%) had a history of nonseasonal allergic rhinitis, and 72 (85.7%) had a history of allergic rhinitis. Among the 306 participants with a cumulative incidence of hay fever, 63 (20.6%) had a history of asthma. Twenty-seven (26.2%) of the 103 individuals with a history of nonseasonal allergic rhinitis had a cumulative incidence of asthma. Among the 338 individuals with a cumulative incidence of allergic rhinitis 72 (21.3%) had a history of asthma. Among the participants with a history of both asthma and hay fever, 44.8% developed hay fever first, 34.5% developed asthma first, and 20.7% developed both diseases at the same time. Among the individuals with a history of asthma and nonseasonal allergic rhinitis, 38.5% developed nonseasonal allergic rhinitis first, 30.8% developed asthma first, and 30.8% developed both diseases at the same time. This study further demonstrates the frequent co-existence of asthma and allergic rhinitis. Among asthmatics, allergic rhinitis occurred in 85.7%. Only 14.3% of asthmatics did not have allergic rhinitis. Among individuals with allergic rhinitis, asthma occurred in 21.3%. Also, allergic rhinitis often precedes or occurs at the same time as asthma.

The purpose of this study is to determine whether a hereditary factor exists for nasal polyps. Fifty patients (27 male, 23 female; age range 14-86 years) had a personal history of nasal polyps. These were confirmed by physician reports, polypectomy pathology reports, or direct visualization. These 50 patients were questioned concerning the existence of a familial history (parents, siblings, or children) of nasal polyps. A control group of 30 patients without nasal polyps was obtained by matching sex, age, personal history of atopy, and allergy skin test results to patients with a personal history of nasal polyps. Familial history of nasal polyps was obtained from the control group by direct interview. Seven of 50 (14%) of the group with nasal polyps had a familial history of nasal polyps. Of those seven, three patients had more than one immediate family member with a positive family history (two patients with two family members (sister, mother; 2 sisters) and one patient with three family members (3 brothers)). Among the control group, 0 of 30 (0%) had a familial history of nasal polyps. This difference is statistically significant (P value is 0.0414). This study suggests that there exists a hereditary factor for development of nasal polyps.

Nasal polyps are found in 36% of patients with aspirin intolerance, 7% of those with asthma, 0.1% in children, and about 20% in those with cystic fibrosis. Other conditions associated with nasal polyps are Churg-Strauss Syndrome, allergic fungal sinusitis, and cilia dyskinetic syndrome, (Kartagener's) and Young Syndrome. Nasal polyps are statistically more common in nonallergic asthma versus allergic asthma (13% vs 5%, P < 0.01). About 40% of patients with surgical polypectomies have recurrences. There appears to be a hereditary factor for developing nasal polyps. A classification system for staging nasal polyps is proposed in order to standardize treatment, consider differential diagnosis, and harvest meaningful comparative research information.

Nasal polyps are usually found in nonallergic individuals. However, when nasal polyps and atopy occur together, a special interaction exists. Total and specific immunoglobulin E (IgE) are found in significantly greater concentration in nasal polyp tissue than in serum and tonsil tissue. Immunoglobulin A (IgA) is also more concentrated in nasal polyps than serum. Patients with nasal polyps and allergies seem to have a greater recurrence rate after surgical polypectomy. Frequently, polyp recurrence occurs during specific pollen seasons in sensitive individuals. Upper respiratory infections are also a precipitating factor for recurrence. Nasal ciliary beat frequency is inhibited in patients with chronic sinusitis, allergic nasal reactions, and nonspecific nasal eosinophilia syndromes: nonallergic rhinitis with eosinophils (NARES) and blood eosinophilic nonallergic rhinitis (BENARS). Nasal polyps are frequently associated with these conditions, which may predispose the nasal mucosa to infections and increased risk for developing nasal polyps. When nasal polyps and allergies occur together, it is important to treat the allergic condition. This takes the form of identifying the allergens, eliminating them from the environment (if possible) using antihistamines/decongestants, and nasal antiinflammatory drugs such as topical steroids. Hyposensitization may be considered in resistant cases.

Rhinitis can be classified into allergic and nonallergic etiologies, the latter probably representing the diagnosis of as many as half the patients presenting to the physician with chronic nasal symptoms.42Nonallergic rhinitis is a term that is applied to a large heterogeneous group of nasal diseases which have in common the occurrence of rhinitis symptoms (obstruction/congestion, hypersecretion/rhinorrhea, and hyperirritable symptoms) without an allergic etiology. Because these symptoms are the same as those that occur in rhinitis of allergic etiology, negative testing for IgE sensitivity to all relevant aerollergens is essential to make this diagnosis.Classification of these nonallergic rhinitis disorders may be performed on the basis of immunologic and nasal cytologic features as suggested by Zeiger70(Table 1) or on the basis of etiology/systemic disease association (Table 2). Neither of these classification systems are perfect, however, because many disorders are without distinctive immunologic or cytologic features, and many disorders are without known etiology.In order to put some limitation on the scope of this article, our discussion of nonallergic rhinitis focuses on chronic diseases of the nose, excluding acute infectious etiologies (viral upper respiratory infections and acute bacterial sinusitis). First, we briefly discuss the epidemiology of nonallergic rhinitis. Then the various syndromes that comprise this disorder are individually discussed, focusing more on the nonallergic rhinitis syndromes of common etiology and briefly reviewing uncommon or rare causes as outlined in Table 3

The purpose of this study is to examine the natural history of hay fever among former college students who were diagnosed with this disease either before or after their freshman year. The diagnosis of hay fever or seasonal allergic rhinitis was based on a history of watery, itchy eyes, rhinorrhea, and sneezing occurring for at least 2 consecutive years during the same seasonal period. A total of 738 former Brown University students (69% males and 31% females) who were evaluated and underwent skin testing during their freshman year completed a 23-year follow-up questionnaire inquiring of their history of allergies and asthma. The mean age of this group at the time of the follow-up study was 40 years. During the 23 years subsequent to the original study, 131 developed new hay fever in addition to the 175 who had hay fever as college freshman, totaling 306. At the time of the 23-year follow-up, improvement was noted by 84.8% (28/33) of those with hay fever onset 1-5 years, 63.6% (56/88) of those with onset 6-12 years, 55.6% (40/72) of those with onset 13-19 years, and 38.7% (41/106) of those with onset 20 years and older. Among those with an unknown age of onset, 42.9% (3/7) reported improvement of hay fever symptoms. The trend of increasing percentage of improvement with younger age of onset of hay fever is of statistical significance (p value of < 0.0001) using the chi-squared test for trend. A total of 54.9% (168/306) had noted improvement, of which 22.9% (70/306) reported being symptom free and 32.0% (98/306) reported being better but not symptom free. Of the remaining 45.1% (138/306), the hay fever was unchanged in 33.3% (102/306), worsened in 9.2% (28/306), and unknown in 2.6% (8/306). This study suggests that over a long period of time, hay fever symptoms will improve in the majority of individuals.