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The airborne pollens can produce asthma and rhinoconjuctivitis (pollinosis). Since geographic and climatic factors influence the quality and quantity of pollen counts in various countries and between seasons, the aim of the study was to record major seasonal allergenic pollens; grasses, olive, parietaria and cypress in Athens during five consecutive seasons throughout the years 1995–1999. The daily pollen count was carried out every year from March to October using a Burcard volumetric weekly spore trap, which was placed about 20 m from the ground, in Athens city centre. Daily values were expressed as number of pollen grains/m3 of air. The mean monthly values of pollens/m3 were used to compare the results of the consecutive years. Recording of the major pollen allergens in Athens area for five consecutive years led to the assessment of the pollination period for each of these plants and confirmed the variations in the amount of pollen per plant per year. [ABSTRACT FROM AUTHOR]

Background: Data are sparse regarding the safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with multiple sclerosis (MS)., Objective: To estimate (1) the pooled proportion of MS patients experiencing relapse among vaccine recipients; (2) the rate of transient neurological worsening, adverse events, and serious adverse events; (3) the previous outcomes of interest for different SARS-CoV-2 vaccine types., Methods: Systematic review and meta-analysis of pharmacovigilance registries and observational studies., Results: Nineteen observational studies comprising 14,755 MS patients who received 23,088 doses of COVID-19 vaccines were included. Mean age was 43.3 years (95% confidence interval (CI): 40-46.6); relapsing-remitting, secondary-progressive, primary-progressive MS and clinically isolated syndrome were diagnosed in 82.6% (95% CI: 73.9-89.8), 12.6% (95% CI: 6.3-20.8), 6.7% (95% CI: 4.2-9.9), and 2.9% (95% CI: 1-5.9) of cases, respectively. The pooled proportion of MS patients experiencing relapse at a mean time interval of 20 days (95% CI: 12-28.2) from vaccination was 1.9% (95% CI: 1.3%-2.6%; I 2  = 78%), with the relapse risk being independent of the type of administered SARS-CoV-2-vaccine ( p for subgroup differences = 0.7 for messenger RNA (mRNA), inactivated virus, and adenovector-based vaccines). After vaccination, transient neurological worsening was observed in 4.8% (95% CI: 2.3%-8.1%) of patients. Adverse events and serious adverse events were reported in 52.8% (95% CI: 46.7%-58.8%) and 0.1% (95% CI: 0%-0.2%) of vaccinations, respectively., Conclusion: COVID-19 vaccination does not appear to increase the risk of relapse and serious adverse events in MS. Weighted against the risks of SARS-CoV-2-related complications and MS exacerbations, these safety data provide compelling pro-vaccination arguments for MS patients.

This brief report examined the frequency and characteristics of a significant blood-pressure (BP) increase after Pfizer-BioNTech BNT162b2 vaccination among healthcare workers who were advised to measure their BP at home. A total of 797 participants (mean age 48.1 ± 10.8 years, 63% women, 39% smokers) were included in the analysis. Seven participants reported an increase in their BP (three in the range of grade 2 and four in the range of grade 3 hypertension). Only one participant had a history of treated hypertension. The BP increase was observed at the end of the first week after the first dose, lasted for 3 to 4 days, and recurred promptly after the second dose. Only one case required hospitalization, mainly due to a history of cardiovascular disease (follow-up). Individuals experiencing a BP increase compared with those not reporting issues with their BP had a higher mean age and similar distribution of sex and non-smoking status. In conclusion, a significant BP increase after Pfizer-BioNTech vaccination seems to be rare and of a benign and transient nature. Monitoring the BP before and after vaccination might be advisable only for selected individuals with a high cardiovascular risk.

Background: SARS-CoV-2 mortality rates are significantly higher in patients with lung cancer compared with the general population. However, little is known on their immunization status after vaccination. Methods: To evaluate the humoral response (seroconversion) of patients with lung cancer following vaccination against SARS-COV-2 (Group A), we obtained antibodies against SARS-CoV-2 spike (S) protein both at baseline and at different time points after the first dose of SARS-CoV-2 vaccine (two to three weeks [T1], six weeks ± one week [T2], 12 weeks ± three weeks [T3], and 24 weeks ± three weeks [T4]). Antibodies were also acquired from a control cohort of non-lung cancer patients (Group B) as well as a third cohort containing healthy controls (Group C) at all time points and at T4, respectively, to make comparisons with Group A. Analysis of antibody response at different time points, association with clinicopathologic parameters, and comparisons with control groups were performed. Results: A total of 125 patients with lung cancer were included in the analysis (96 males [74.3%], median age of 68 years [46−91]. All study participants received two vaccine doses (BNT162b2, mRNA-1273, AZD1222). Analysis of anti-SARS-CoV-2 S antibody titers showed minimal response at T1 (0.4 [0.4−48.6] IU/mL). Antibody response peaked at T2 (527.0 [0.4−2500] IU/mL) and declined over T3 (323.0 [0.4−2500] IU/mL) and T4 (141.0 [0.4−2500] IU/mL). Active smokers had lower antibody titers at T2 (p = 0.04), T3 (p = 0.04), and T4 (p < 0.0001) compared with former or never smokers. Peak antibody titers were not associated with any other clinicopathologic characteristic. No significant differences were observed compared with Group B. However, lung cancer patients exhibited significantly decreased antibody titers compared with Group C at T4 (p < 0.0001). Conclusions: Lung cancer patients demonstrate sufficient antibody response six weeks after the first dose of vaccine against SARS-CoV-2 when vaccinated with two-dose regimens. Rapidly declining antibody titers six weeks after the first dose underline the need for a third dose three months later, in patients with lung cancer, and especially active smokers.

Previous data suggested the potential treatment effect of a proprietary quail eggs-based blend on allergic rhinitis (AR) symptoms, induced by allergen challenge. We herein aimed to investigate the efficacy and safety of a similar dietary supplement, comprising the bioactive ingredients of quail eggs and the zinc mineral, in the setting of active AR. Adult patients ( n  = 77), aged 18- 60 years, with mild, intermittent AR were enrolled in this single-arm, open-label trial. Patients' responses were assessed based on peak nasal inspiratory flow (PNIF) measurements at two visits (Day 1/Visit 1 and Day 7/Visit 2) and self-rating of AR-associated symptoms on a Visual Analog Scale (VAS) throughout the entire 7-day study period. PNIF values at 15, 30, 60, 90 and 120 min (Visit 1) following administration of an oral dose of the study product were the primary efficacy endpoint. PNIF values (Visit 1) gradually increased from baseline (pre-treatment), with statistical significance first reached 30 min later ( p  = 0.002). VAS scores (Visit 1) for all AR symptoms gradually decreased with statistical significance first reached at 15 min (rhinorrhea, p  = 0.042; itchy nose, p  = 0.001; sneezing p  < 0.001), 30 min (nasal congestion, p  < 0.001; itchy eyes, p  = 0.003) or 60 min (watery eyes, p  = 0.04). PNIF improvement and decline of VAS scores were significantly more apparent at Visit one vs. Visit 2. Treatment-emergent adverse events were limited to cough and muscle strain (one patient each). Our results support the efficacy, rapid mode of action and tolerability of the investigated product for symptomatic treatment of mild intermittent AR.

Background: Previous clinical trials have demonstrated the efficacy and safety of the anti-IgE monoclonal antibody omalizumab in chronic spontaneous urticaria (CSU) not responding to antihistamine treatment. The primary aim of our study was to describe the response patterns of patients with refractory CSU treated with omalizumab in a real-world clinical setting., Methods: A retrospective analysis of medical records of 20 patients with refractory CSU was performed. Demographic, clinical, and laboratory features were retrieved and analyzed in correlation with treatment data., Results: Mean age of our patient population was 54.5 years, while the majority were females (15/20 cases, 75%). Mean disease duration prior to omalizumab administration was 21.8 months. All patients had a history of chronic urticaria, refractory to high antihistamine and corticosteroid treatment, and responded favorably to omalizumab after administration of 1-5 doses of omalizumab; complete response was observed in 17/20 patients (85%) and well-controlled disease in the remaining 3/20 patients (15%). In a subset of cases (6/20, 30%), best response to omalizumab was achieved after interval administration of a 9-day course of methylprednisolone (total dose of 188 mg). Late response to omalizumab (after three-month treatment) was significantly correlated (P = 0.026) with shorter disease duration before initiation of omalizumab., Conclusion: In the present series, omalizumab, either alone or in combination with a short-term course of corticosteroids, was highly effective in resolution of refractory CSU. Furthermore, disease duration prior to omalizumab had a significant effect on timing of response., (© 2018 The International Society of Dermatology.)

Summary: Data derived from previous clinical trials and real-life studies have shown that omalizumab may represent an effective third-line treatment option for patients with chronic spontaneous urticaria (CSU) refractory to standard antihistamine treatment. Nevertheless, the safety and efficacy of omalizumab treatment for CSU, when administered concurrently with other immunomodulatory agents remains largely unknown. We herein present the case of a female patient with relapsing-remitting multiple sclerosis (RRMS), under treatment with interferon beta-1a, azathioprine and gabapentin, who was successfully treated with omalizumab for refractory CSU. To the best of our knowledge, this is the first reported case attesting to the safety and efficacy of omalizumab for CSU when administered concurrently with other immunomodulatory agents.

Objectives: Previous data have suggested that filaggrin (FLG) and periostin (POSTN) genes may be dysregulated in eosinophilic esophagitis (EoE). We aimed to further evaluate the expression patterns of FLG and POSTN proteins in esophageal tissue samples of patients with EoE, as compared to those of patients with gastroesophageal reflux disease (GERD) and normal controls., Methods: A total of 61 prospectively collected cases, including 40 children with EoE and 21 children with GERD, and a control group of 14 sex- and age-matched healthy children were enrolled. Patients with EoE were treated with skin testing-driven elimination diet and/or corticosteroids. The immunohistochemical expression of FLG and POSTN was evaluated in esophageal biopsies obtained from patients and controls, and the results were correlated with EoE-related clinicopathological parameters., Results: Positive FLG and negative POSTN staining were observed in all esophageal biopsies from normal controls. In contrast, FLG and POSTN stained negative and positive, respectively, in all pretreatment biopsies obtained from patients with EoE, whereas FLG and POSTN stained positive in 57.1% and 95.2% of GERD cases, respectively (P < 0.001). A statistically significant decrease of the proportion of cases with negative FLG and positive POSTN staining was observed from the first (pretreatment) to the second (post-treatment) biopsy in the subgroup of patients with EoE (P < 0.001 in both correlations)., Conclusions: FLG and POSTN expression may be downregulated and upregulated, respectively, in the esophageal mucosa of patients with active EoE, and these changes may be restored with treatment in a significant percentage of cases.

Drug-induced acute generalized exanthematous pustulosis is a rare pustular skin reaction, most commonly triggered by antibiotics. Although its diagnosis is based primarily on the presence of specific clinical and histopathologic features, additional in vivo (patch testing) or in vitro testing may be required, especially in atypical cases, to more accurately determine the causative agent. The authors report a histologically confirmed case of acute generalized exanthematous pustulosis that was induced by amoxicillin/clavulanic acid, as documented by subsequent patch testing, and presented with generalized painful lymphadenopathy, mimicking an acute infectious process. This is a very rare and diagnostically challenging clinical presentation of acute generalized exanthematous pustulosis, which has been reported, to the best of our knowledge, only once previously., (© The Author(s) 2015.)

Background: A combination of PPIs and corticosteroids is the pharmacotherapy mostly used to treat eosinophilic esophagitis (EoE), while dietetic manipulations consist also an efficient option. The aim of this study was to compare the efficacy of allergy-test-driven elimination diet in children with mild symptoms of EoE to a group of children with moderate/severe symptoms., Methods: Thirty-five children, aged 7 months to 12 yr, with EoE were enrolled in the study. They had a clinical history of GERD-like (21 children, Group A) or more severe symptoms (14 children, Group B). The diagnosis had been confirmed after two preliminary months of therapy with PPIs and an esophagogastroduodenoscopy. Soon after diagnosis, they were allergy-tested, using IgE detection (SPT and serum-specific IgE) and atopy patch tests (APTs). A 12-month tailor-made diet was prescribed according to the tests. Patients of Group B continued PPIs for two more months, while swallowed topical steroids were also prescribed to them for the first 5 months after diagnosis, followed by an 'as-needed' use of them for the rest of the study. Endoscopy was repeated at the end of the study., Results: Milk and egg were the most common APT-positive allergens. Thirty-two patients were instructed to follow an elimination diet, which was completed by 15/18 of Group A and 12/14 of Group B. An improvement of symptoms was reported by 26/27 patients that completed the study. The use of swallowed corticosteroids was noticeably decreased during the as-needed period, in Group B. A remarkable reduce of eosinophils was noticed in biopsies; from 42.84 ± 18.08, they decreased to 6.41 ± 3.20, a year after., Conclusion: All children with EoE and mild symptoms had resolution of symptoms and normal eosinophils in the esophageal mucosa a year after an allergy-driven elimination diet. Patients with moderate/severe EoE symptoms had the same improvement, indicating that an elimination diet is an efficient complementary treatment to corticosteroids., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Giant reactions to the tuberculin skin test are extremely rare and have been previously reported almost exclusively in patients with lepromatous leprosy. We herein report a giant tuberculin reaction associated with the homeopathic drug Tuberculinum in a patient with no evidence of active tuberculosis or leprosy.

Background: Docetaxel (DT) is an extensively used taxane, frequently associated with hypersensitivity reactions. The aim of this study was to record the epidemiological and clinical features of hypersensitivity to DT in non-small cell lung cancer patients in order to obtain useful information concerning the management of these patients. We also developed a desensitization protocol and evaluated its clinical application., Methods: We retrospectively reviewed records of 620 non-small cell lung cancer patients treated with DT-containing regimens in the adjuvant, first-, second- or next-line setting. Data from 102 patients who had exhibited hypersensitivity reactions were analyzed according to the Common Toxicity Criteria for Adverse Events version 3.0. Five patients were chosen for the desensitization protocol. We applied the standard protocol for parenteral desensitization to β-lactam antibiotics, and DT treatment was carried out with a series of 10-fold dilutions in sufficient volume to administer the total dose., Results: One hundred and two patients (16.5%) were recorded as having hypersensitivity to DT. Reactions were observed after approximately 2.5 ± 1.0 cycles. Only 14 patients (14/620, 2%) developed grade 3-4 hypersensitivity. Reactions were more likely in patients during second- or third-line chemotherapy, but no other correlation (age, gender, atopic status) was observed. Five patients completed a parenteral desensitization protocol and continued their treatment uneventfully., Conclusions: Hypersensitivity reactions to DT respond quickly to discontinuation along with appropriate supportive care. Premedication and increased infusion time may allow readministration. The desensitization protocol that we developed provides a reliable alternative to permanent discontinuation of DT., (Copyright © 2011 S. Karger AG, Basel.)

Hypersensitivity reactions to chemotherapy agents are defined as unexpected reactions with signs and symptoms not consistent with known toxicity of these drugs. These reactions range from mild to life-threatening and are difficult to predict. Symptoms include flushing, nausea, difficulty breathing, back pain, hypotension and tachycardia. Hypersensitivity is commonly encountered owing to the increasing use of chemotherapy drugs in clinical practice. The pathogenetic mechanisms are not fully understood but they seem to vary between agents. Reactions to taxanes usually occur during the first few minutes of the first or second infusion, whereas acute reactions to platinum agents usually occur after multiple cycles of therapy. Basic principles that allow management and possible completion of the regimen should be followed. Certain protocols aim to prevent acute reactions by slowing the infusion rate and by administering steroid and histamine receptor antagonists. Skin testing and desensitization protocols have also been successfully used in case of hypersensitivity to various chemotherapy drugs. Knowledge of all available management options assists physicians in making the most appropriate decision regarding further treatment.

Carboplatin is a chemotherapeutic agent approved in the first-line setting of numerous malignancies. Hypersensitivity to carboplatin has been reported in up to 44% of patients receiving this antineoplastic agent, usually occurring after several courses of treatment. The aim of this study was to determine the usefulness of skin tests in ruling out cross-reaction to cisplatin to continue platinum-based chemotherapy in patients who are responsive to these agents. Prick tests and intradermal tests with a series of dilutions of carboplatin and cisplatin were performed on three patients who had exhibited medium and severe hypersensitivity reactions to carboplatin. Prick tests were negative in both the antineoplastic agents. Intradermal tests with carboplatin were positive in all three patients and negative with cisplatin. In all patients, the administration of cisplatin instead of carboplatin was well tolerated without the need of premedication. In conclusion, intradermal skin tests can be a useful tool for detecting a potential cross-reaction between platinum salts. It allows safe administration of a different platinum agent in patients who seem to benefit from platinum-based therapy. Discontinuation of chemotherapy, desensitization protocols and steroid premedication can be avoided.

Platinum-containing chemotherapy agents (cisplatin, carboplatin, oxaliplatin) have been approved in the first-line setting of numerous malignancies, such as ovarian, bladder, head and neck, colorectal, and lung cancer. Their extensive use over the last decade has led to a significant increase in the incidence of hypersensitivity reactions, which are defined as unforeseen reactions whose signs and symptoms cannot be explained by the known toxicity of these drugs. Skin rash, flushing, abdominal cramping, itchy palms, and back pain are common symptoms. Cardiovascular and respiratory complications can prove fatal. Multiple pathogenetic mechanisms have been suggested. Hypersensitivity usually appears after multiple infusions, suggesting type I allergic reactions; however, other types of hypersensitivity also seem to be implicated. Several management options are available to treating physicians: discontinuation of chemotherapy, premedication, prolonging of infusion duration, desensitization protocols, and replacement with a different platinum compound after performing skin tests that rule out cross-reactions among platinum agents.

Hypersensitivity reactions to antineoplastic agents are defined as unexpected reactions with signs and symptoms inconsistent with known toxicity of antineoplastic drugs. These reactions are uncommon and usually associated with certain antineoplastic categories, such as taxanes, platinum-containing compounds, epipodofyllotoxins, asparaginase, procarbazine and, more rarely, with doxorubicin and 6-mercaptopurine. The mechanisms that are responsible for hypersensitivity reactions are unclear and vary between agents. Symptoms of these reactions range from mild skin rashes to more severe reactions, such as arthralgia, respiratory arrest or even death in some cases. Once hypersensitivity reactions are observed, basic principles that allow their management and possible continuance and completion of the regimen should be followed.

Although the reported incidence of hypersensitivity reactions (HSR) to antineoplastic agents is considered to be uncommon, it is difficult to evaluate their exact prevalence, mainly because their definition is vast and pathogenic mechanisms are vague. HSR include facial flushing, erythema, pruritus, fever, tachycardia, dyspnea, tongue swelling, rash/hives, headache, chills, weakness, vomiting, burning sensations, dizziness, and edema. Treatment and prevention consists of slowing the infusion rate, steroids, and type 1 and 2 histamine receptor antagonists. Desensitization could allow the small number of patients who experience severe HSR to receive effective therapy for their cancer. Reintroductions have only been reported as single case studies or small cohorts. Large-scale validation on desensitization strategies is still missing. With regard to oxaliplatin, knowledge of its rare but eminent toxicity is paramount, because this drug is widely used in treating colorectal cancer, the second-highest cause of cancer mortality in the United States.

In a prospective cohort study we investigated the course of allergic sensitization from childhood to puberty in a group of children with atopic asthma. An attempt was made to correlate the findings with the persistence of asthma. A total of 150 children with atopic asthma established at 7 years of age were evaluated when 8-10 years of age. A battery of skin-prick tests (SPTs) to common environmental allergens, a detailed clinical history for asthma severity classification, and spirometric analyses, were performed. In 127 of these children a re-evaluation was performed at puberty. A variety of statistical methods were used to analyze the results regarding changes in skin test reactivity to individual aeroallergens and atopic index (degree of atopy), as well as to determine any correlation between these changes and the persistence of asthma in puberty. A wide spectrum of modification in skin reactivity to common environmental allergens was observed, including the complete loss of sensitization to some allergens or the development of a new one to others. Specifically, 34% of asthmatic children sensitive to Dermatophagoides pteronyssinus and 52.7% sensitive to cat lost their sensitivity in puberty, while only 7.5% and 11.1%, respectively, became sensitized (p = 0.03 and p = 0.001, respectively). In contrast, regarding pollen sensitivity, 30.2% and 24% of asthmatic children became sensitive in puberty to olive pollen and grasses mix, respectively, and only 11.7% and 12.5%, respectively, lost their sensitivity to these allergens (p = 0.04). No correlation was shown between the skin test reactivity changes to individual allergens and the persistence of asthma, but a significant correlation was found between atopic index to indoor allergens in childhood and the persistence of asthma at puberty (p = 0.04). Interestingly, multi-sensitivity to allergens (>/= 4 allergens) in childhood was also found to correlate with the persistence of asthma at puberty [p = 0.05, odds ratio (OR) = 2.65, 95% confidence interval (CI) 1.2-7.2]. Our findings indicate that significant modification of skin reactivity to common environmental allergens in atopic children with asthma in puberty can occur. However, no association between these changes and the persistence of asthma could be demonstrated, although children with indoor allergic sensitization and multi-reactivity were found to have a higher probability of maintaining their asthma in puberty.

Background: In general, T cells from normal, nonatopic individuals respond to aeroallergens with synthesis and release of IFN-gamma. In contrast, release of T(H)2-type cytokines by activated lymphocytes is a feature of allergic rhinitis and atopic asthma., Objective: The purpose of this study was to determine differences in T-cell recognition of epitopes within allergenic sequences, in terms of proliferation and cytokine production, in subjects with atopic asthma compared with subjects with allergic rhinitis and normal controls., Methods: Proliferative responses and IL-5/IFN-gamma release patterns from PBMCs from cat-allergic asthmatic, cat-allergic rhinitic, and non-cat-allergic asthmatic subjects and nonatopic normal controls were determined in primary cultures. Cells were challenged with 7 overlapping peptides spanning chain 1 of the major cat allergen, Fel d 1., Results: The 4 groups did not differ with respect to the ability to mount proliferative responses to Fel d 1 peptides. In all groups, the IFN-gamma responses were predominantly to the amino terminus peptides. Cat-allergic and non-cat-allergic asthmatic subjects (and not cat-allergic rhinitic subjects and normal controls) made IL-5 responses to most of the Fel d 1 peptides, the result being a mixed (T(H)0) cytokine response at the N-terminus and a restricted (T(H)2) response at the C-terminus., Conclusion: Proliferative and IL-5/IFN-gamma responses of T cells from asthmatic and atopic rhinitic subjects and normal controls to allergen peptides can be dissociated. Furthermore, differing cytokine responses to peptides derived from a single antigen suggest that certain domains of the molecule might preferentially induce IL-5 rather than IFN-gamma and as a result could be more important in disease pathogenesis.

For evaluation of the efficacy and the safety of specific sublingual immunotherapy with high allergen dose, 66 children with seasonal asthma, rhinitis, and conjunctivitis due to sensitization to olive pollen were enrolled in a double-blind, randomized, placebo-controlled study between October 1994 and October 1996 in Greece. Thirty-four patients were randomly allocated to the active group, and 32 received placebo. Immunotherapy consisted of olive-allergen extracts (Stallergènes SA) administered sublingually pre- and coseasonally from January to July for 2 consecutive years. Serial concentrations from 1 to 300 IR. were used up to the maintenance dose of 20 drops of 300 IR daily. The cumulative dose for each patient was 300 times higher than in parenteral immunotherapy, and the cumulative dose of the major allergen Ole e 1 was 8.1 mg/2 years. The patients were assessed by clinical parameters (symptom and medication scores from patients' daily diaries) and immunologic measurements (specific IgE, IgG4, eosinophil cationic protein [ECP]) were performed. The actively treated patients had a significantly lower score for dyspnea (P<0.04 during the first season; P<0.03 during the second season). At the pollinic peak during the second year, a lower score of conjunctivitis was recorded (P<0.05) in the actively treated patients. The analysis of intragroup evolution showed that the total score of rhinitis increased significantly during the pollinic peak in the group under placebo, whereas there was no symptomatic peak for the same period in the group under active treatment. However, the difference between the groups was not significant. The medication score did not differ significantly between the groups. Oral steroids were the only variables with a P value near the significance level (P=0.06) in favor of the actively treated group. A significant decrease in skin reactivity was recorded in the active group after 2 years of treatment. No significant variation in specific IgE and IgG4 was detected. A significantly lower level of serum ECP was observed at the pollinic peak in the actively treated patients during the first pollen season (P=0.01), but this was not confirmed the second year when the ECP levels doubled in both groups without correlation to the clinical findings. Tolerance was excellent with only a few minor side-effects reported. In conclusion, high-dose specific sublingual immunotherapy appears to be safe and effective in improving mild seasonal asthma and conjunctivitis linked to olive-pollen sensitization.

Age at menarche is one of the few established risk factors for breast cancer; identification of its exogenous determinants could throw light on the origins of breast cancer. We have undertaken an epidemiologic study in Greece to ascertain whether: 1) energy intake, an indicator of physical activity, is associated with later age at menarche; 2) energy-adjusted fat intake is related to earlier age at menarche; and 3) other macronutrients and anthropometric variables are predictors of age at menarche. Anthropometric, socio-economic, familiar, nutritional and lifestyle predictors of age at menarche were studied by interviewing in person 345 female students 9 to 16 years old attending 8 schools of Greater Athens. Menarche was the outcome variable in a proportional hazards model assessing the mutually adjusted incidence rate ratio by a series of predictor variables. In a complementary analysis, age at menarche was the dependent variable among menstruating girls. Consistent results were derived from the main and the complementary analysis. Increased height and body mass index accelerate the occurrence of menarche. Maternal and daughter's ages at menarche are correlated, but there is no evidence of an association with paternal education. Various measures of moderate physical activity as well as increased total energy intake were associated with a delay in age at menarche. Energy-adjusted macronutrients were not associated with age at menarche. It appears that an alteration of energy balance in early life through increased physical activity could delay age at menarche and reduce the risk for breast cancer in later life.