Short-course subcutaneous treatment with PQ Grass strongly improves symptom and medication scores in grass allergy.

BACKGROUND: A modified grass allergen subcutaneous immunotherapy (SCIT) product with MicroCrystalline Tyrosine and monophosphoryl lipid-A as an adjuvant system (Grass MATA MPL [PQ Grass]) is being developed as short-course treatment of grass-pollen allergic rhinitis (SAR) and/or rhinoconjunctivitis. We sought to evaluate the combined symptom and medication score (CSMS) of the optimized cumulative dose of 27,600 standardized units (SU) PQ Grass in a field setting prior to embarking on a pivotal Phase III trial. METHODS: In this exploratory, randomized, double-blind, placebo-controlled trial subjects were enrolled across 14 sites (Germany and the United States of America). Six pre-seasonal subcutaneous injections of PQ Grass (using conventional or extended regimens) or placebo were administered to 119 subjects (aged 18-65 years) with moderate-to-severe SAR with or without asthma that was well-controlled. The primary efficacy endpoint was CSMS during peak grass pollen season (GPS). Secondary endpoints included Rhinoconjunctivitis Quality of Life Questionnaire standardized (RQLQ-S) and allergen-specific IgG4 response. RESULTS: The mean CSMS compared to placebo was 33.1% (p = .0325) and 39.5% (p = .0112) for the conventional and extended regimens, respectively. An increase in IgG4 was shown for both regimens (p < .01) as well as an improvement in total RQLQ-S for the extended regimen (mean change -0.72, p = .02). Both regimens were well-tolerated. CONCLUSIONS: This trial demonstrated a clinically relevant and statistically significant efficacy response to PQ Grass. Unprecedented effect sizes were reached for grass allergy of up to ≈40% compared to placebo for CSMS after only six PQ Grass injections. Both PQ Grass regimens were considered equally safe and well-tolerated. Based on enhanced efficacy profile extended regime will be progressed to the pivotal Phase III trial.

Natural history of asthma: a 23-year followup of college students.

OBJECTIVE: 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. METHODS AND RESULTS: 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. CONCLUSION: 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 course of asthma parallels that of allergic rhinitis: a 23-year follow-up study of college students.

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.

Natural history of hay fever: a 23-year follow-up of college students.

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.

Co-existence of asthma and allergic rhinitis: a 23-year follow-up study of college students.

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.

Hereditary factor for nasal polyps.

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.