Immunotherapy (IT) by injection more readily induces clinical tolerance to stinging insects than to respiratory allergens. However, while systemic immunization induces adaptive responses systemically, the induction of mucosal immunity generally requires local Ag exposure. Taken together, these observations suggest that the poor success rate of systemic IT for asthma could be a consequence of inadequate immune modulation in the airways. In support of this position, investigations presented in this report demonstrate that allergen IT more effectively induces airway allergen tolerance in Th2-sensitized mice, when delivered by the intranasal (i.n.) vs the intradermal (i.d.) route. Moreover, compared with native allergen, allergen immunostimulatory sequence oligodeoxynucleotide conjugate proved to be a more effective i.n. IT reagent for protecting allergic mice from airway hypersensitivity responses. Furthermore, for both native allergen and allergen immunostimulatory sequence oligodeoxynucleotide conjugate, i.n. and i.d. IT delivery were similarly effective in modulating systemic immune profiles in Th2-sensitized mice, while only i.n. IT had significant immunomodulatory activity on B and T cell responses in the airways. The present investigations may be the first to suggest that i.n. IT is more effective than i.d. IT for the treatment of asthma. Furthermore, our results suggest that modulating airway rather than systemic immunity may be the more important therapeutic target for the induction of clinical tolerance to respiratory allergens.

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SUMMARYWhile effective for the prevention and treatment of allergic rhinitis (AR) symptoms, currently available medications do not reverse allergen specific hypersensitivities. Therefore, pharmacotherapeutics are not curative and their daily use is often required for years. These investigations were conducted to determine whether immunostimulatory sequence oligodeoxynucleotide (ISS-ODN) delivery protects previously sensitized mice from AR hypersensitivity responses and modulates their allergen specific immune profiles. Mice were first sensitized with ovalbumin (OVA) and alum, twenty-four hr before beginning a series of seven daily intranasal (i.n.) allergen challenges, subsets of mice received a single i.n. or intradermal (i.d.) dose of ISS-ODN or control oligodeoxynucleotide (C-ODN), a single intraperitoneal (i.p.) injection of dexamethasone (DXM), or no intervention. Mice receiving i.d. or i.n. ISS-ODN were found to have attenuated immediate and late phase effector cell responses to i.n. OVA challenge. Specifically, ISS-ODN treated mice had less histamine and cysteinyl leukotriene release and eosinophilic inflammation in their nasal passages than mice treated with C-ODN. In addition, splenocytes from ISS-ODN but not C-ODN treated mice displayed attenuated OVA-specific interleukin (IL)-4, IL-5, and IL-13 but increased interferon-c responses. Finally, ISS-ODN was generally a more effective treatment than DXM, both in blunting AR hypersensitivity responses and in shifting T helper 2 Th2-biased immune parameters towards Th1 dominance. As ISS-ODN delivery rapidly attenuated effector cell responses in this AR model in an allergen independent manner, the present results suggest that therapy with ISS-ODN alone may be an effective alternative to corticosteroid medications for the clinical management of AR.

Visual Analog Scales for Assessment of Severe Acute Mountain Sickness on Aconcagua Background.-The Lake Louise AMS Self-report Score (LL-Self) is a commonly used, validated method of assessing acute mountain sickness (AMS). Objectives.-Compare a visual analog scale (VAS) method of quantifying AMS with the LLSelf among trekkers to 6962 m for both overall symptoms and the 5 individual constituent categories of the LLSelf. Methods.-Setting: Plaza de Mulas base camp (4365 m), Aconcagua Provincial Park, Argentina. Inclusion criteria: volunteer trekkers to Aconcagua (6962 m) in January 2009 who provided written informed consent. Exclusion criteria: pregnancy, age Ͻ18 years. Study protocol: Subjects were prospectively enrolled while ascending, instructed to complete a questionnaire when symptoms were maximal, and return it upon descent. The questionnaire consisted of maximum altitude reached, the LLSelf, and standard 100-mm VAS for each LLSelf component, as well as overall AMS. Statistics: means with 95% confidence interval (CI), interrater reliability with Cohen's , and correlation of VAS with LLSelf with Spearman's rank correlation coefficient (r) were computed using Stata (Stata Corp, College Station, TX). Results.-A total of 45 subjects completed both VAS and LLSelf. Twenty-two (49%) climbers reached the summit (6962 m). Mean maximum altitude reached was 6467 m. Mean altitude of maximal symptoms was 5859 m. Mean LLSelf was 5.1 (95% CI, 4.3-5.9). Interrater reliability for measurement of VAS was high (ϭ 0.9998). All individual VAS categories were highly correlated with their respective LLSelf symptoms: headache r ϭ 0.85; gastrointestinal symptoms r ϭ 0.57; fatigue r ϭ 0.79; lightheadedness r ϭ 0.72; and difficulty sleeping r ϭ 0.75. Overall VAS was also highly correlated with total LL-Self: r ϭ 0.71. Conclusions.-In this study of VAS and LLSelf at extreme altitude on Aconcagua (6962 m), individual VAS and overall VAS were highly correlated with both individual constituent categories of LLSelf and overall LLSelf. Further studies comparing VAS, LLSelf, and physician assessment of AMS are needed to determine optimal measurement of AMS, especially on expeditions where multiple languages are encountered.