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This international cross-sectional survey examined the potential role of organizational psychological support in mitigating the association between experiencing social discrimination against long-term care (LTC) facilities' healthcare professionals (HCPs) and their intention to stay in the current workplace during the COVID-19 pandemic. Participants included a convenience sample of 2,143 HCPs (nurses [21.5 %], nurse aids or residential care workers [40.1 %], social workers [12.1 %], and others [26.4 %]) working at 223 LTC facilities in 13 countries/regions. About 37.5 % of the participants reported experiencing social discrimination, and the percentage ranged from 15.3 % to 77.9 % across countries/regions. Controlling for socio-demographic and work-related variables, experiencing social discrimination was significantly associated with a lower intention to stay, whereas receiving psychological support showed a statistically significant positive association (p-value=0.015 and <0.001, respectively). The interaction term between social discrimination and psychological support showed a statistically significant positive association with the intention to stay, indicating a moderating role of the psychological support., Competing Interests: Declaration of competing interest None, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To calculate the direct cost of personal protective equipment (PPE) used during the COVID-19 pandemic from the perspective of a Brazilian tertiary public hospital., Methods: We evaluated the cost of PPE during the pandemic to the cost before (2021 vs 2019, respectively) using the microcosting method. Cost estimates were converted into US dollars in 2023, taking inflation into account and using purchasing power parity conversion rates. Our expenses included gloves, disposable gowns, head coverings, masks, N95 respirators, and eye protection. The number of PPE used was determined by the hospital's usual protocol, the total number of hospitalized patients, and the number of days of hospitalization. We used the following variables for uncertainty analysis: PPE adherence, an interquartile range of median length of hospitalization, and variance in the cost of each PPE., Results: In 2021, 26 618 individuals were hospitalized compared with 31 948 in 2019. The median length of stay was 6 and 4 days, respectively. The total and per-patient direct cost of PPE were projected to be 2 939 935.47 US dollar (USD) and 110.45 USD, respectively, during the pandemic, and 1 570 124.08 USD and 49.15 USD, respectively, before the pandemic. The individual cost of PPE was the most influential cost variable., Conclusions: According to the hospital's perspective, the total estimated direct cost of PPE during the COVID-19 pandemic was nearly twice as high as the previous year. This difference might be explained by the 3-fold increase in PPE in the treatment of patients with COVID-19 compared with patients without isolation precautions., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: National and international guidelines on frailty assessment and management recommend frailty screening in older people. This study aimed to determine how Brazilian healthcare professionals (HCPs) identify and manage frailty in practice., Methods: An anonymous online survey on the assessment and management of frailty was circulated virtually through HCPs across Brazil., Results: Most of the respondants used non-specific criteria such as gait speed (45%), handgrip strength (37.6%), and comprehensive geriatric assessment (33.2%). The use of frailty-specific criteria was lower than 50%. The most frequently used criteria were the Frailty Index (19.1%), Frailty Phenotype (13.2%), and FRAIL (12.5%). Only 43.5% felt confident, and 40% had a plan to manage frailty. In the multivariate-adjusted models, training was the most crucial factor associated with assessing frailty, confidence, and having a management plan (p < 0.001 for all). Those with fewer years of experience were more likely to evaluate frailty (p = 0.009). Being a doctor increased the chance of using a specific tool; the opposite was true for dietitians (p = 0.03). Those who assisted more older people had a higher likelihood of having a plan (p = 0.011)., Conclusion: Frailty assessment was heterogeneous among healthcare professions groups, predominantly using non-specific criteria. Training contributed to frailty assessment, use of specific criteria, confidence, and having a management plan. This data informs the need for standardized screening criteria and management plans for frailty, in association with increasing training at the national level for all the HCPs who assist older people., (© 2024. The Author(s).)

Aims: To (i) assess the adherence of long-term care (LTC) facilities to the COVID-19 prevention and control recommendations, (ii) identify predictors of this adherence and (iii) examine the association between the adherence level and the impact of the pandemic on selected unfavourable conditions., Design: Cross-sectional survey., Methods: Managers (n = 212) and staff (n = 2143) of LTC facilities (n = 223) in 13 countries/regions (Brazil, Egypt, England, Hong Kong, Indonesia, Japan, Norway, Portugal, Saudi Arabia, South Korea, Spain, Thailand and Turkey) evaluated the adherence of LTC facilities to COVID-19 prevention and control recommendations and the impact of the pandemic on unfavourable conditions related to staff, residents and residents' families. The characteristics of participants and LTC facilities were also gathered. Data were collected from April to October 2021. The study was reported following the STROBE guidelines., Results: The adherence was significantly higher among facilities with more pre-pandemic in-service education on infection control and easier access to information early in the pandemic. Residents' feelings of loneliness and feeling down were the most affected conditions by the pandemic. More psychological support to residents was associated with fewer residents' aggressive behaviours, and more psychological support to staff was associated with less work-life imbalance., Conclusions: Pre-pandemic preparedness significantly shaped LTC facilities' response to the pandemic. Adequate psychological support to residents and staff might help mitigate the negative impacts of infection outbreaks., Impact: This is the first study to comprehensively examine the adherence of LTC facilities to COVID-19 prevention and control recommendations. The results demonstrated that the adherence level was significantly related to pre-pandemic preparedness and that adequate psychological support to staff and residents was significantly associated with less negative impacts of the pandemic on LTC facilities' staff and residents. The results would help LTC facilities prepare for and respond to future infection outbreaks., Patient or Public Contribution: No Patient or Public Contribution., (© 2023 The Authors. Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

During the coronavirus disease 2019 (COVID-19) pandemic, the Brazilian long-term care (LTC) sector faced many challenges, which accentuated other common issues experienced by persons living with dementia (PLWD). The current pilot study evaluated staff perspectives regarding the care of institutionalized PLWD during the COVID-19 pandemic. Using an online survey, we collected the perspectives of 24 workers from seven long-term care facilities (LTCFs) located in São Paulo State, Brazil, about the impact of COVID-19 in caring for PLWD. Results highlight concerns about challenges related to following precautionary measures and the negative effects of social distancing on PLWD. Aspects related to workforce and staffing and person-centered care approaches were recognized by staff as important to provide good care for PLWD. Future research is needed to consider how to support LTCFs in achieving a balance between the protection and well-being of PLWD. [ Journal of Gerontological Nursing, 49 (5), 45-52.].

Objective: to evaluate the adherence of Brazilian long-term care facilities to the World Health Organization Infection Prevention and Control guidance, and assess the association of their size with the adherence to these recommendations., Method: cross-sectional study conducted with facilities' managers. Authors developed a 20-item questionnaire based on this guidance, and a global score of adherence, based on the adoption of these recommendations. Adherence was classified as (1) excellent for those who attended ≥14 out of 20 recommendations; (2) good for 10 to 13 items; and (3) low for those with less than ten items. Facilities' sizes were established as small, intermediate, and large according to a two-step cluster analysis. Descriptive statistics and chi-square tests were used at a 5% significance level., Results: among 362 included facilities, 308 (85.1%) adhered to 14 or more recommendations. Regarding its size, adherence to screening COVID-19 symptoms of visitors (p=0.037) and isolating patients until they have had two negative laboratory tests (p=0.032) were lower on larger ones compared to medium and small facilities., Conclusion: adherence to COVID-19 mitigation measures in Brazilian facilities was considered excellent for most of the recommendations, regardless of the size of the units.

This scoping review aimed to explore the characteristics, strengths, and gaps in research conducted in Brazilian long-term care facilities (LTCFs) for older adults. Electronic searches investigating the residents (≥60 years old), their families, and the LTCF workforce in Brazil were conducted in Medline, EMBASE, LILACS, and Google Scholar, within the timescale of 1999 to 2018, limited to English, Portuguese, or Spanish. The reference lists were hand searched for additional papers. The Mixed Methods Appraisal Tool (MMAT) was used for critical appraisal of evidence. Data were reported descriptively considering the study design, using content analysis: 327 studies were included ( n = 159 quantitative non-randomized, n = 82 quantitative descriptive, n = 67 qualitative, n = 11 mixed methods, n = 6 randomized controlled trials, and n = 2 translation of assessment tools). Regardless of the study design, most were conducted in a single LTCF (45.8%), in urban locations (84.3%), and in non-profit settings (38.7%). The randomized trials and descriptive studies presented the lowest methodological quality based on the MMAT. This is the first review to provide an overview of research on LTCFs for older people in Brazil. It illustrates an excess of small-scale, predominantly qualitative papers, many of which are reported in ways that do not allow the quality of the work to be assured.

Aim: To compare subjective and objective measures of adherence to prophylaxis in haemophilia., Methods: In this cross-sectional study, we compared participants' self-perceived adherence and their estimate of the number of clotting factor concentrates (CFCs) that had been missed over the last period of CFC dispensation with an objective measure of adherence based on counts of CFC vials returned by participants., Results: We included 29 out of 31 eligible patients in the study. There was no significant correlation between self-perceived degree of adherence and the objective classification of adherence (Rho: 0.10, 95% CI: -028 to 0.46, P: 0.61) and between the classification of adherence based on the proportion of missed CFC doses assessed by participants' self-report and objectively (Rho: 0.32, 95% CI: -0.01 to 0.59, P: 0.11). Conversely, we found evidence of moderate correlation between the proportion of missed CFC doses as assessed by participants' self-report and objectively (Rho: 0.56, 95% CI: 0.24 to 0.77, P: 0.003). Participants' self-perceived adherence was 3 times more likely to be rated as very good or good than it was for the objective assessment to be classified as adherent or suboptimally adherent., Conclusion: Our results showed significant discrepancies between subjective and objective measures of adherence, which likely reflect the influence of social desirability bias in self-reported measures and different concepts of adherence between patients/caregivers and haemophilia experts. Additionally, our results allow us to hypothesize that studies on adherence to prophylaxis in haemophilia relying exclusively on information from self-reports and questionnaires may substantially overestimate adherence levels., (© 2019 John Wiley & Sons Ltd.)

Background: infectious diseases in older people are associated with higher mortality rates and probiotics have been hypothesised to reduce the occurrence of infection., Objectives: to assess the effectiveness and safety of probiotics in the occurrence of infections in older adults in comparison to placebo., Methods: a systematic review and meta-analysis of randomised placebo-controlled trials were conducted on 30 December 2016 using Medline, Embase, CENTRAL, Web of Science and LILACS databases. Efficacy outcomes were: occurrence of infection, quality of life, mortality and mean duration of infection per episode. Safety outcomes were adverse events. Data were analysed using relative risk ratios with 95% confidence intervals. Relative risk ratios were pooled where more than three estimates were available., Results: fifteen articles were included, with a total of 5,916 participants with a mean age of 75.21 years. The effect of probiotics was not significantly different from that reported for placebo on the occurrence of infection, adverse events, mortality or mean duration of infection episodes (relative risk (RR) 0.90, 95% confidence interval (CI) 0.76 to 1.08; RR 1.01, 95% CI 0.91 to 1.12; RR 1.09, 95% CI 0.70 to 1.72; MD -0.35, 95% CI -1.57 to 0.87, respectively)., Conclusion: the current low-quality evidence does not support the use of probiotics for the reduction in the occurrence of infection in older adults, however, the safety outcomes were similar between probiotics and placebo. Further research is required to confirm these findings.PROSPERO: CRD42014013707., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Leprosy in children under 15 years of age is a serious public health problem. In this retrospective case series conducted in a Brazilian reference center (2004-2012), we found 18 cases with a mean age of 10.0±3.6 years of age and 16.6% between 0-5 years of age. Almost 56% of the cases were female, with a median time between the first symptoms and diagnosis of 11 months (4-24); 77.8% reported household contact with leprosy patients. Upon hospital admission, 66.7% presented mostly skin symptoms, while 27.8% presented a degree 2 disability. Most were classified as multibacillary (66.7%). Half of the sample developed a reaction (predominantly type 1) during the follow-up period, while 22.2% developed a late disability.

Few studies have described therapeutic options in brachioradial pruritus. We describe a cross-sectional study of brachioradial pruritus patients treated in an outpatient unit. We reviewed medical records and interviewed brachioradial pruritus patients without indication for decompressive surgery, in order to access the perceptions of intensity of pruritus prior to treatment and response to therapy. We found that antidepressants and anticonvulsants were the most frequently prescribed drugs. Best reductions in pruritus were associated with its highest intensities prior to treatment, and with longer periods of therapy.

This is a cross-sectional study, conducted from May to November/2014, in a dermatology reference unit, through review of medical records and interviews. In a sample of 49 patients with brachioradial pruritus, we observed higher prevalence of Caucasian (81.6%) and women (73.5 %), with a mean age of 56.1 years. Pruritus occurred in the topography of brachioradialis muscle in 87.8% of cases; 59.2% of the sample reported worsening of pruritus with sun exposure; the mean intensity of this symptom before treatment was 8.63. Therapy effectiveness was described as "very good/good" in 79.2% of cases, and for 55.3% relapses were categorized as "uncommon"., Competing Interests: None.

Background: Mycobacterium peregrinum is a rapidly growing mycobacterium (RGM) that rarely causes skin infections. The correct identification of the specific RGM infecting the skin will enhance therapeutic success., Objective: To highlight the importance of rapid and precise identification of the Mycobacterium involved in skin infections in order to enhance therapeutic success., Methods: We describe an RGM skin infection in an immunocompetent patient., Results: Classic methods (biochemical tests and culture) of RGM identification are time-consuming, and the histopathological features are not specific. Some molecular methods are reliable but expensive. The PRAhsp-65 is a simple procedure that is helpful in identifying the specific agent of an RGM., Conclusion: Although skin infections caused by M peregrinum are rare, they represent a substantial clinical challenge. Specific and more effective treatment options depend on the development of precise and rapid methods for identifying mycobacterial species., (© The Author(s) 2015.)

We conducted a transversal retrospective study with secondary data collection from 25 cases of sporotrichosis, treated at a teaching unit in inner São Paulo (Brazil), between the years 2003-2013. We found that the prevalence was higher in men (72%), rural workers (44%) and those living in rural areas (60%), with an average age of 42.48 years. The median between the onset of lesions and diagnosis was six weeks. Lesions predominated in the upper limbs (92%), and were classified as lymphocutaneous (80%) and fixed cutaneous (20%) forms. Clinical cure was observed in 62.5% of the cases treated with potassium iodide and 100% of cases treated with itraconazole.

Exacerbation of the immune response against Mycobacterium leprae can lead to neuritis, which is commonly treated via immunosuppression with corticosteroids. Early neurolysis may be performed concurrently, especially in young patients with a risk of functional sequelae. We report the case of a young patient experienced intense pain in the left elbow one year after the treatment of tuberculoid-tuberculoid leprosy. The pain was associated with paresthesias in the ulnar edge and left ulnar claw. After evaluation, the diagnosis was changed to borderline tuberculoid leprosy accompanied with neuritis of the left ulnar nerve. Early neurolysis resulted in rapid reduction of the pain and recovery of motor function.

Chromoblastomycosis is one of the most frequent deep mycoses found in rural populations. This cross-sectional, retrospective and descriptive study was conducted with cases of chromoblastomycosis diagnosed throughout 20 years. A higher prevalence was observed among White male rural workers, with an average age of 59.69 years. Median time between onset of symptoms and diagnosis was 156 months. Lesions were predominantly located on the lower limbs; 34% of cases reported previous trauma. The most common associated symptoms were itching, pain and burning sensation. Mycological examination was positive in 91% of cases and Fonsecaea pedrosoi was the most prevalent etiologic agent.

Background: Chronic leg ulcer may have an impact on patients' quality of life., Objectives: This study aimed to identify the impact of leg ulcers on patient's quality of life using the Dermatology Life Quality Index and to define the main factors correlated with this perception., Method: Cross-sectional, non-probabilistic sampling study. We included patients with chronic leg ulcers being treated for at least 3 months. A sociodemographic and clinical survey was conducted to assess the profile of the ulcers. We administered a screening for depressive symptoms and the Dermatology Life Quality Index. We performed a descriptive statistical analysis, chi-square test and Mann-Whitney test for categorical data, Pearson for numeric variables, and multiple regression for categorical data., Results: Forty-one patients were assessed. Their mean age was 61.78 years. Venous ulcers (48.8%) were the most prevalent. Seventy-three percent of the sample perceived no impact/low impact on quality of life in the past week, and 26.8% perceived moderate/high impact. A multiple regression analysis identified the causes of lesion, pain related to the ulcers, time of onset, and severity of the depressive symptoms as the variables that had an influence on quality of life., Conclusions: The majority of the sample perceived low or no impact of the condition on the quality of the life. The variables etiology of the lesion (p<0.001), pain related to the ulcers (p=0.001), time of onset (p=0.006), and severity of the depressive symptoms (p<0.001) had an influence on the quality of life, suggesting the need for further studies with more robust designs to confirm the causal relationship between these characteristics and quality of life.

Background: The epidemiology and clinical features of brachioradial pruritus are variably described in the literature. We sought to analyze these features in a large group of Brazilian patients., Patients and Methods: In a descriptive, observational study, we identified all patients with a final diagnosis of brachioradial pruritus seen over a one-year period and re-trospectively reviewed their records. The diagnosis was made after clinical-laboratory investigation had ruled out other causes of chronic pruritus. Demographic and clinical variables were collected along with pruritus characteristics, and analyzed using des-criptive statistics., Results: Forty-three patients were identified; their mean age was 55.9 years, with predominance of women (81.4%) and Caucasians (86%). In 52%, the pruritus worsened with heat and sun exposure; 58.1% had intermittent complaints; the ice-pack sign was present only in 20.9%. The arms involving dermatomes C5-C6-C7-C8 (62.8%) were the most affected sites, while psychoactive drugs were the most frequently prescribed therapy., Conclusions: Although uncommon, brachioradial pruritus should not be neglected in dermatological diagnosis. This case series analysis indicated that Brazilian patients from a tropical climate show characteristics similar to those described in other series from more temperate regions., (© The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.)

Objective: to investigate pre-frailty and the factors associated with this condition, taking into account the measurements of the older adults' gait speed., Method: participants were selected by means of inclusion/exclusion criteria and a cognitive tracking test. The sample was calculated based on the estimation of populational proportion and made up of 195 older adults who were using a Primary Health-Care Center in Curitiba in the state of Paraná. Data was collected using a socio-demographic/clinical questionnaire and the gait speed test., Results: pre-frailty for gait speed has moderate prevalence (27.3%), and is associated with the 60 - 69 years age range, a low level of schooling, not feeling oneself to be alone, using anti-hypertensives, having cardiovascular disease and being overweight., Conclusion: it is considered relevant to identify those older adults with pre-frailty, as this creates the possibility for immediate intervention with the aim of stabilizing the picture. There is a significant shortage of studies on the syndrome of frailty in Brazilian older adults, principally referring to components in isolation. Given that gerontological nursing is at an early stage regarding this issue, it is understood that the identification of the prevalence must be the key point of the research on the matter.

Background: Grass pollen immunotherapy for allergic rhinitis is a disease-modifying treatment that results in long-term clinical tolerance lasting years after treatment discontinuation. Active treatment is associated with generation of inhibitory grass pollen-specific IgG antibodies capable of blocking allergen-IgE interactions., Objectives: We sought to investigate the involvement of IgG-associated inhibitory antibodies with long-term clinical tolerance after discontinuation of grass pollen immunotherapy., Methods: We conducted a 4-year study in which patients who had moderate-to-severe allergic rhinitis underwent a randomized, double-blind, placebo-controlled discontinuation of subcutaneous grass pollen immunotherapy. All subjects received grass pollen immunotherapy injections for 2 years (n = 13), followed by a further 2 years of either active (n = 7) or placebo (n = 6) injections. Clinical outcomes included seasonal symptoms and use of rescue medication. Serum specimens were collected at baseline and after 2 and 4 years for quantification of allergen-specific IgG antibodies. Sera were also tested for IgG-dependent inhibitory bioactivity against IgE-allergen binding in cellular assays by using flow cytometry and confocal microscopy to detect binding of IgE-grass pollen allergen complexes to B cells., Results: Clinical improvement was maintained after 2 years of discontinuation. Although immunotherapy-induced grass pollen-specific IgG1 and IgG4 levels decreased to near-preimmunotherapy levels during discontinuation, inhibitory bioactivity of allergen-specific IgG antibodies was maintained unchanged., Conclusion: Grass pollen immunotherapy induces a subpopulation of allergen-specific IgG antibodies with potent inhibitory activity against IgE that persists after treatment discontinuation and that could account for long-term clinical tolerance., (Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

The IgE-facilitated allergen binding (IgE-FAB) assay represents an in vitro model of facilitated allergen presentation. Allergen-IgE complexes are incubated with an EBV-transformed B cell line and complexes bound to CD23 on the surface of cells are detected by flow cytometry. The addition of serum from patients who have received allergen-specific immunotherapy has been shown previously to inhibit allergen-IgE complex binding to CD23 on B cells. In this study, we describe the characterisation and analytical validation of the grass pollen-specific IgE-FAB assay according to guidelines from the International Conference on Harmonisation. We established the intra- and inter-assay variability of IgE-FAB and have defined the detection limits of this assay. We have also demonstrated assay linearity and robustness. Using the results from a randomised double-blind placebo-controlled trial of grass pollen immunotherapy (n=33), we have defined the clinical sensitivity and specificity of the IgE-FAB assay using ROC curve analysis. In conclusion, the IgE-FAB assay is reproducible, robust, sensitive and a specific method suitable as a tool for monitoring inhibitory antibody function from patients receiving allergen immunotherapy.

Allergen-specific IgE production is the central event in the pathogenesis of atopic disorders and increases in specific IgE serum antibodies are an indicator of immediate hypersensitivity responses in humans and in animal models of allergy. Consequently, accurate and user-friendly methods are needed to measure serum levels of allergen-specific IgE. This review examines historical and recent developments in in vivo and in vitro methods for the detection of allergen-specific IgE in humans and in animal models. Routinely, in vitro methods such as enzyme-linked immunosorbant assays or radioallergosorbant tests and in vivo methods such as the skin prick test (SPT) for humans and the passive cutaneous anaphylaxis assay (PCA) used in animals are utilized to detect allergen-specific IgE. While in vivo assays are usually more accurate than in vitro assays since they provide a functional readout of IgE activity, they are relatively costly and require considerable expertise. On the other hand in vitro assays are limited by the fact that the amount of allergen-specific serum IgG exceeds IgE antibody by several orders of magnitude, resulting in competition for allergen binding. Consequently, methods that use allergen as a direct capture step are limited by the availability of free allergen binding sites for IgE. In order to circumvent this problem, in vitro methods usually require prior depletion of IgG or use high amounts of allergen in order to facilitate availability of free binding sites for IgE detection. Clearly, these approaches are limited for small sample volumes and allergens that are in short supply. New methods such as protein microarray could potentially overcome this problem by providing high allergen concentrations in a relatively small reaction volume. Currently, in vitro methods are rarely used in isolation for prognosis but are used primarily to complement the information obtained from in vivo assays. With the emergence of new technologies it is conceivable that in vitro assays may in the future replace in vivo assays, however until then in vivo assays remain the gold standard of allergen-specific IgE detection.

Purpose of Review: This paper will review historical and recent evidence for the induction of 'blocking' IgG antibodies during successful specific immunotherapy., Recent Findings: Specific immunotherapy is frequently associated with a rise in allergen-specific IgG4 antibodies and a modest reduction in specific IgE titres, although this does not always correlate with clinical efficacy. There is accumulating evidence that specific immunotherapy also influences the blocking activity on IgE-mediated responses by IgG4, and cellular assays are commonly used to investigate these changes. Recently, a novel assay, which detects allergen-IgE binding using flow cytometry, has been used to detect 'functional' specific immunotherapy-induced changes in IgG antibody activity. Results suggest that successful specific immunotherapy is associated with an increase in IgG blocking activity that is not solely dependent on the quantity of IgG antibodies., Summary: Successful immunotherapy is associated with quantitative and qualitative changes in the allergen-specific IgG antibody response. The induction of IgG antibodies with blocking activity may have a protective role not only through the inhibition of allergen-induced, IgE-mediated release of inflammatory mediators from mast cells and basophils, but also through the inhibition of IgE-facilitated antigen presentation to T cells. Qualitative changes in the allergen-specific IgG antibody response may possibly be an important mechanism underlying the clinical efficacy of specific immunotherapy. Monitoring changes in blocking activity using cellular assays may give an early indication of the potential success of treatment.

T regulatory cells and IL-10 have been implicated in the mechanism of immunotherapy in patients with systemic anaphylaxis following bee stings. We studied the role of IL-10 in the induction of clinical, cellular, and humoral tolerance during immunotherapy for local mucosal allergy in subjects with seasonal pollinosis. Local and systemic IL-10 responses and serum Ab concentrations were measured before/after a double-blind trial of grass pollen (Phleum pratense, Phl P) immunotherapy. We observed local increases in IL-10 mRNA-positive cells in the nasal mucosa after 2 years of immunotherapy, but only during the pollen season. IL-10 protein-positive cells were also increased and correlated with IL-10 mRNA(+) cells. These changes were not observed in placebo-treated subjects or in healthy controls. Fifteen and 35% of IL-10 mRNA signals were colocalized to CD3(+) T cells and CD68(+) macrophages, respectively, whereas only 1-2% of total CD3(+) cells and 4% of macrophages expressed IL-10. Following immunotherapy, peripheral T cells cultured in the presence of grass pollen extract also produced IL-10. Immunotherapy resulted in blunting of seasonal increases in serum allergen Phl p 5-specific IgE, 60- to 80-fold increases in Phl p 5-specific IgG, and 100-fold increases in Phl p 5-specific IgG4. Post-immunotherapy serum exhibited inhibitory activity, which coeluted with IgG4, and blocked IgE-facilitated binding of allergen-IgE complexes to B cells. Both the increases in IgG and the IgG "blocking" activity correlated with the patients' overall assessment of improvement. Thus, grass pollen immunotherapy may induce allergen-specific, IL-10-dependent "protective" IgG4 responses.

Background: Among atopic individuals, levels of allergen-specific IgG antibodies have been inversely associated with the degree of allergen sensitization. Additionally, allergen-specific IgG antibodies are markedly increased by allergen injection immunotherapy. These observations have led to proposals that allergen-specific IgG antibodies might have protective properties in atopic individuals., Objective: We hypothesized that after grass pollen immunotherapy, these antibodies disrupt IgE-dependent allergen processing by antigen-presenting cells., Methods: We have developed a novel flow cytometric assay based on detection of allergen-IgE binding to the low-affinity IgE receptor on B cells to examine the blocking effects of sera collected from 18 patients who participated in a double-blind, controlled trial of grass pollen immunotherapy for 1 year., Results: In all 10 patients who received active therapy, there was induction of activity that inhibited allergen-IgE binding to B cells (P =.02, vs placebo subjects), as well as subsequent allergen presentation to T cells. This activity copurified with IgG and was allergen specific, because sera taken from patients treated with grass pollen immunotherapy but who were also birch pollen sensitive did not inhibit IgE-birch pollen allergen binding to B cells., Conclusion: We conclude that allergen-specific IgG antibodies induced by immunotherapy can disrupt formation of allergen-IgE complexes that bind to antigen-presenting cells and facilitate allergen presentation.

Grass pollen immunotherapy is the only treatment for hayfever that is both effective and confers long-term benefit. Immunotherapy may act by altering the local nasal mucosal T helper type 2 (Th2) to type 1 (Th1) cytokine balance either by down-regulation and/or immune deviation of T-lymphocyte responses. There is controversy as to whether these changes are detectable in peripheral blood. We therefore examined both local nasal and peripheral T-cell responses to allergen exposure in the same subjects before and after immunotherapy. In a double-blind trial of grass pollen immunotherapy, nasal biopsies were obtained at baseline and during the peak pollen season following 2 years of immunotherapy. Placebo-treated patients showed a seasonal increase in CD3(+) T cells (P = 0.02) and in interleukin-5 (IL-5) mRNA(+) cells (P = 0.03) and no change in interferon-gamma (IFN-gamma ) mRNA(+) cells (P = 0.2) in the nasal mucosa. In contrast, in the immunotherapy-treated group, there were no changes in the number of CD3(+) T cells (P = 0.3) and IL-5 mRNA+ cells (P = 0.2) but a significant increase in the number of IFN-gamma mRNA(+) cells (P = 0.03). Furthermore, clinical improvement in the immunotherapy-treated group was accompanied by a seasonal increase in the ratio of IFN-gamma to IL-5 mRNA(+) cells in the nasal mucosa (P = 0.03). In contrast, there were no significant changes in peripheral T-cell proliferative responses or cytokine production for IFN-gamma or IL-5 in response to grass pollen either within or between the two treatment groups. We conclude that successful grass pollen immunotherapy was associated with an increase in the ratio of IFN-gamma to IL-5 mRNA(+) cells in the nasal mucosa, whereas these changes were not reflected by alterations in peripheral blood T-cell proliferative responses or cytokine production before/after treatment.