Mediterranean-Type Diets as a Protective Factor for Asthma and Atopy.

We are currently riding the second wave of the allergy epidemic, which is ongoing in affluent societies, but now also affecting developing countries. This increase in the prevalence of atopy/asthma in the Western world has coincided with a rapid improvement in living conditions and radical changes in lifestyle, suggesting that this upward trend in allergic manifestations may be associated with cultural and environmental factors. Diet is a prominent environmental exposure that has undergone major changes, with a substantial increase in the consumption of processed foods, all across the globe. On this basis, the potential effects of dietary habits on atopy and asthma have been researched rigorously, but even with a considerable body of evidence, clear associations are far from established. Many factors converge to obscure the potential relationship, including methodological, pathophysiological and cultural differences. To date, the most commonly researched, and highly promising, candidate for exerting a protective effect is the so-called Mediterranean diet (MedDi). This dietary pattern has been the subject of investigation since the mid twentieth century, and the evidence regarding its beneficial health effects is overwhelming, although data on a correlation between MedDi and the incidence and severity of asthma and atopy are inconclusive. As the prevalence of asthma appears to be lower in some Mediterranean populations, it can be speculated that the MedDi dietary pattern could indeed have a place in a preventive strategy for asthma/atopy. This is a review of the current evidence of the associations between the constituents of the MedDi and asthma/atopy, with emphasis on the pathophysiological links between MedDi and disease outcomes and the research pitfalls and methodological caveats which may hinder identification of causality. MedDi, as a dietary pattern, rather than short-term supplementation or excessive focus on single nutrient effects, may be a rational option for preventive intervention against atopy and asthma.

[Generalized granuloma annulare: A clinicopathological study]. / Granulome annulaire généralisé : étude anatomoclinique.

BACKGROUND: Granuloma annulare (GA) is a benign granulomatous skin disorder that is generalized (GGA) in 15 % of cases. Although many case reports describe a relationship between GGA and systemic diseases, few large series have been published, and their association is debated. We present herein a series of GGA in order to describe their clinical and histological features. PATIENTS AND METHODS: We included all biopsy-proven cases of GA presenting at the dermatopathology laboratory of Strasbourg where generalized (i.e. over 10 lesions). Clinical features were obtained from patients' medical files. RESULTS: We included 35 GGA, with a sex ratio of 0.5. The mean age was 54 years. Lesions were annular or non-annular in equal measure and were symptomatic in 25 % of cases. Most patients (77 %) had an associated disease, already known in 60 % of cases, including dyslipidemia (27 %), diabetes mellitus (20 %), immunosuppressive drugs (17 %), atopy (17 %), auto-immune disease (17 %), hematological disease (14 %), and cancer (9 %). Histological analysis revealed the predominant pattern to be interstitial (54 %) rather than palisading (20 %), having no correlation with clinical type. Eosinophils were frequent (46 %) in GA but were not correlated with systemic disease or drug taking. Among the 40 % of patients treated, 50 % had a successful outcome on topical corticosteroids, doxycycline, antimalarial drugs or phototherapy. DISCUSSION: GGA differs from localized GA, which is mostly associated with an already known systemic disease, whether metabolic, infectious or neoplastic, uncorrelated with clinical or histological features, and screening is necessary.

The role of antimicrobial treatment during pregnancy on the neonatal gut microbiome and the development of atopy, asthma, allergy and obesity in childhood.

INTRODUCTION: The use of antibiotics prenatally, during pregnancy, or neonatally may have adverse effects on the neonatal gut microbiome, and adversely affect the development of the infant immune system, leading to childhood atopy, asthma, allergy and obesity. AREAS COVERED: Vaginal eubiosis and dysbiosis from molecular-based, cultivation-independent techniques, and how this affects the neonatal gut microbiome and early development of the immune system, the association between maternal antibiotics and the beneficial role of vitamin D in the development of atopy, asthma, allergy and obesity, efforts to reduce the use of antibiotics in pregnancy and therapeutic interventions such as vaginal 'seeding', probiotics, breastfeeding and neonatal dietary supplementation. EXPERT OPINION: Currently available research gives insufficient attention to confounding variables. There remains uncertainty as to whether it is relevant that the mother suffered from the same condition as the purported infant outcome variable, for which she may have received antibiotics. In most studies, there is a lack of control for the number of antibiotic courses administered, the timing of use, the use of broad spectrum or narrow range antibiotics, the indication for antibiotics, the dose-dependent nature of the effect, the class of antibiotics used, or a varying degree of risk.

Development of atopic sensitization in Finnish and Estonian children: A latent class analysis in a multicenter cohort.

BACKGROUND: The prevalence of atopy is associated with a Western lifestyle, as shown by studies comparing neighboring regions with different socioeconomic backgrounds. Atopy might reflect various conditions differing in their susceptibility to environmental factors. OBJECTIVE: We sought to define phenotypes of atopic sensitization in early childhood and examine their association with allergic diseases and hereditary background in Finland and Estonia. METHODS: The analysis included 1603 Finnish and 1657 Estonian children from the DIABIMMUNE multicenter young children cohort. Specific IgE levels were measured at age 3, 4, and 5 years, respectively, and categorized into 3 CAP classes. Latent class analysis was performed with the statistical software package poLCA in R software. RESULTS: Both populations differed in terms of socioeconomic status and environmental determinants, such as pet ownership, farm-related exposure, time spent playing outdoors, and prevalence of allergic diseases (all P < .001). Nevertheless, we found similar latent classes in both populations: an unsensitized class, a food class, 2 inhalant classes differentiating between seasonal and perennial aeroallergens, and a severe atopy class. The latter was characterized by high total and specific IgE levels and strongly associated with wheeze (odds ratio [OR], 5.64 [95% CI, 3.07-10.52] and 4.56 [95% CI, 2.35-8.52]), allergic rhinitis (OR, 22.4 [95% CI, 11.67-44.54] and 13.97 [95% CI, 7.33-26.4]), and atopic eczema (OR, 9.39 [95% CI, 4.9-19.3] and 9.5 [95% CI, 5.2-17.5] for Finland and Estonia, respectively). Environmental differences were reflected in the larger seasonal inhalant atopy class in Finland, although composition of classes was comparable between countries. CONCLUSION: Despite profound differences in environmental exposures, there might exist genuine patterns of atopic sensitization. The distribution of these patterns might determine the contribution of atopic sensitization to disease onset.

Ragweed allergy immunotherapy tablet MK-3641 (Ragwitek®) for the treatment of allergic rhinitis.

INTRODUCTION: Allergic rhinitis (AR) is among the most common chronic conditions affecting both children and adults. It is the cause of significant morbidity from the symptoms and interference with sleep. It results in major impairment of performance both at school and at work. In the U.S. and certain parts of Europe, ragweed pollen is a major cause of seasonal AR. In 2014, the U.S. Food and Drug Administration (FDA) approved a sublingual ragweed tablet (MK-3641) for use in adults with ragweed-induced AR. Areas covered: This paper will review the impact of ragweed-induced AR and available treatments including subcutaneous immunotherapy and studies with MK-3641. The principal search method was PubMed. Expert commentary: One dosing finding, two 28-day safety and two 52-week safety and efficacy studies have been conducted with MK-3641. The 12-U (12µg Amb a 1) tablet was the most effective. Local application site reactions were common but usually not serious. Only one, non-serious systemic reaction was reported in four safety studies. MK-3641 is a safe and effective treatment for ragweed-pollen-induced AR when treatment is initiated ≥ 12 weeks prior to the onset of the ragweed pollen season.

Allergen variability and house dust mite sensitivity in pre-school children with allergic complaints.

Yazici S, Günes S, Kurtulus-Çokboz M, Kemer Ö, Baranli G, Asik-Akman S, Can D. Allergen variability and house dust mite sensitivity in pre-school children with allergic complaints. Turk J Pediatr 2018; 60: 41-49. The increase in the prevalence of allergic diseases in pre-school children who are often at home may be due to an increase in house dust mite sensitivity, which is rarely expected in this age group. In our study, it was aimed to investigate allergen sensitivities, especially house dust mite sensitivity in pre-school children with allergic disease complaints by skin prick test (SPT). Two hundred and twenty children admitted to the Pediatric Allergy and Asthma Clinic of Balikesir University between October 2015 and October 2016 diagnosed with asthma, allergic rhinitis, food allergy, atopic dermatitis or urticaria were involved in the retrospective cross-sectional study. Allergen groups used in SPT were Dermatophagoides farina (Derf), Dermatophagoides pteronyssinus (Der p), Alternaria alternata, cat epithelium, pollen mixture and food mixture. Average age of the 220 patients was 2.98 years (2.75-3.21). SPT was positive in 55.9% of patients. Sixteen percent were monosensitized and 73.8% were polysensitized. Seventy two children (32.7%) were sensitive to Der f and 67 (30.4%) were sensitive to Der p. There was no difference between SPT positivity and gender (p > 0.05). Ninty-five children were diagnosed with asthma, 38 with asthma and allergic rhinitis, 63 with food allergy and 24 with urticaria and/or atopic dermatitis. SPT positivity was significantly higher in the asthma and allergic rhinitis group than other groups. As the age increased, significant increases in the sensitivities of Der f (p < 0.01), Der p (P < 0.01) and A. alternata (p < 0.05) and a significant decrease for food panel sensitivity (p < 0.01) were detected. Even though skin and food allergies were included in our study, house dust mite sensitivity was found much higher than other studies reporting ranges between 3.5-23% in children of the same age group with mainly respiratory complaints. It is concluded that the probable reasons for this increase, especially geographical features, should be investigated in different areas and in larger number of studies.

Prevalence of Atopy following Mass Drug Administration with Albendazole: A Study in School Children on Flores Island, Indonesia.

BACKGROUND: In many rural areas of tropical countries such as Indonesia, the prevalence of soil-transmitted helminths (STH) infections remains high. At the same time, the burden of allergic disorders in such rural areas is reported to be low and inversely associated with helminth infections. To reduce the morbidity and transmission of helminth infections, the world health organization recommends preventive treatment of school children by providing mass drug administration (MDA) with albendazole. Here, we had an opportunity to evaluate the prevalence of skin reactivity to allergens before and after albendazole treatment to get an indication of the possible impact of MDA on allergic sensitization. METHODS: A study was conducted among 150 school children living in an area endemic for STH infections. Before and 1 year after anthelminthic treatment with albendazole, stool samples were examined for the presence of STH eggs, skin prick tests (SPT) for cockroach and house dust mites were performed, blood eosinophilia was assessed, and total immunoglobulin E (IgE) and C-reactive protein (CRP) were measured in plasma. RESULTS: Anthelminthic treatment significantly reduced the prevalence of STH from 19.6 before treatment to 6% after treatment (p < 0.001). Levels of total IgE (estimate: 0.30; 95% CI 0.22-0.42, p < 0.0001), CRP (estimate: 0.60; 95% CI 0.42-0.86, p = 0.006), and eosinophil counts (estimate: 0.70; 95% CI 0.61-0.80, p < 0.001) decreased significantly. The prevalence of SPT positivity increased from 18.7 to 32.7%. Multivariate analysis adjusted for confounding factors showed an increased risk of being SPT positive to any allergen (OR 3.04; 95% CI 1.338-6.919, p = 0.008). CONCLUSIONS: This study indicates that 1 year of MDA with albendazole was associated with a reduced prevalence of STH infections. This study shows that the prevalence of allergic sensitization increases after 1 year of albendazole treatment. Placebo-controlled and larger studies are needed to further substantiate a role of deworming treatment in an increased risk of allergic sensitization.

Immune Components in Human Milk Are Associated with Early Infant Immunological Health Outcomes: A Prospective Three-Country Analysis.

The role of breastfeeding in improving allergy outcomes in early childhood is still unclear. Evidence suggests that immune mediators in human milk (HM) play a critical role in infant immune maturation as well as protection against atopy/allergy development. We investigated relationships between levels of immune mediators in colostrum and mature milk and infant outcomes in the first year of life. In a large prospective study of 398 pregnant/lactating women in the United Kingdom, Russia and Italy, colostrum and mature human milk (HM) samples were analysed for immune active molecules. Statistical analyses used models adjusting for the site of collection, colostrum collection time, parity and maternal atopic status. Preliminary univariate analysis showed detectable interleukin (IL) 2 and IL13 in HM to be associated with less eczema. This finding was further confirmed in multivariate analysis, with detectable HM IL13 showing protective effect OR 0.18 (95% CI 0.04-0.92). In contrast, a higher risk of eczema was associated with higher HM concentrations of transforming growth factor ß (TGFß) 2 OR 1.04 (95% CI 1.01-1.06) per ng/mL. Parental-reported food allergy was reported less often when IL13 was detectable in colostrum OR 0.10 (95% CI 0.01-0.83). HM hepatocyte growth factor (HGF) was protective for common cold incidence at 12 months OR 0.19 (95% CI 0.04-0.92) per ng/mL. Data from this study suggests that differences in the individual immune composition of HM may have an influence on early life infant health outcomes. Increased TGFß2 levels in HM are associated with a higher incidence of reported eczema, with detectable IL13 in colostrum showing protective effects for food allergy and sensitization. HGF shows some protective effect on common cold incidence at one year of age. Future studies should be focused on maternal genotype, human milk microbiome and diet influence on human milk immune composition and both short- and long-term health outcomes in the infant.

Vitamin D supplementation during pregnancy and infancy reduces aeroallergen sensitization: a randomized controlled trial.

BACKGROUND: Vitamin D has immune-modulating effects. We determined whether vitamin D supplementation during pregnancy and infancy prevents aeroallergen sensitization and primary care respiratory illness presentations. METHODS: A randomized, double-blind, placebo-controlled parallel-group trial. We assigned pregnant women, from 27-week gestation to birth, and then their infants, from birth to 6 months, to placebo or one of two dosages of daily oral vitamin D. Woman/infant pairs were randomized to: placebo/placebo, 1000 IU/400 IU or 2000 IU/800 IU. When the children were 18 months old, we measured serum-specific IgE antibodies and identified acute primary care visits described by the doctor to be due to a cold, otitis media, an upper respiratory infection, croup, asthma, bronchitis, bronchiolitis, a wheezy lower respiratory infection or fever and cough. RESULTS: Specific IgE was measured on 185 of 260 (71%) enrolled children. The proportion of children sensitized differed by study group for four mite antigens: Dermatophagoides farinae (Der-f1, Der-f2) and Dermatophagoides pteronyssinus (Der-p1, Der-p2). With results presented for placebo, lower dose, and higher dose vitamin D, respectively (all P < 0.05): Der-f1 (18%, 10%, 2%), Der-f2 (14%, 3%, 2%), Der-p1 (19%, 14%, 3%) and Der-p2 (12%, 2%, 3%). There were study group differences in the proportion of children with primary care visits described by the doctor as being for asthma (11%, 0%, 4%, P = 0.002), but not for the other respiratory diagnoses. CONCLUSIONS: Vitamin D supplementation during pregnancy and infancy reduces the proportion of children sensitized to mites at age 18 months. Preliminary data indicate a possible effect on primary care visits where asthma is diagnosed.

Aeroallergens, atopy and allergic rhinitis in the Middle East.

The literature on the nature and prevalence of indoor and/or outdoor aeroallergens, atopy and symptoms of rhinitis and asthma in the Middle East region (defined here as Bahrain, Egypt, Iran, Iraq, Israel, Jordan, Kuwait, Lebanon, Oman, Palestine, Qatar, Kingdom of Saudi Arabia - KSA, Syria, United Arab Emirates and Yemen) was reviewed. Although documentation was poor in all countries other than Iran and the KSA, a wide range of "global" and "local" aeroallergens (grass, weed and tree pollens, fungal spores, insect allergens, dander, and house dust mites) has been observed across the region. The prevalence of current self-reported or parent-reported symptoms of rhinitis ranged from 9% to 38%. Researchers have suggested that the high atopy rates and self-reported rhinitis rates are associated with an on-going shift towards a "western" lifestyle.

Identification of putative kunitz-type proteinase inhibitor as an allergenic protein in potato

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Prevalence of ragweed allergy in rural Geneva - a pilot study.

OBJECTIVE: The prevalence of ragweed allergy is increasing worldwide. Ragweed distribution and abundance is spreading in Europe in a wide area ranging from the Rhone valley in France to Hungary and Ukraine, where the rate of the prevalence can peak at as high as 12%. Low-grade ragweed colonisation was seen in Geneva and Ticino, less than two decades ago. There were fears that allergies to ragweed would increase Switzerland. The intent of this study was to assess the rate of prevalence of sensitisation and allergy to ragweed in the population living in the first rural Swiss setting where ragweed had been identified in 1996, and to evaluate indirectly the efficacy of elimination and containment strategies. MATERIAL AND METHODS: In 2009, 35 adults in a rural village in the Canton of Geneva were recruited. Data were collected by means of questionnaires and skin-prick tests were done on each participant. The study was approved by the local Ethics Committee. RESULTS: Based on questionnaires, 48.6% had rhinitis (95% confidence interval [CI] 32.9-64.4; n = 17/35) and 17.1% asthma (95% CI 8.1-32.6; n = 6/35). Atopy was diagnosed in 26.4% (95% CI 12.9-44.4) of the sample (n = 9/34). Ragweed sensitisation was found in 2.9% (95% CI 0.7-19.7; n = 1/34), mugwort sensitisation in 2.9% (95% CI 0.1-14.9; n = 1/35), alder sensitisation in 17.1% (95% CI 6.6-33.6; n = 6/35), ash sensitisation in 12.5% (95% CI 3.5-29.0; n = 4/32) and grass sensitisation in 22.9% (95% CI 10.4-40.1; n = 8/35). Ragweed (95% CI 0.1-14.9; n = 1/34) and mugwort allergies (95% CI 0.1-14.9; n = 1/35) were both found in 2.9% of the population. CONCLUSION: This study showed a surprisingly low incidence of ragweed sensitisation and allergy, of 2.9% and 2.9%, respectively, 20 years after the first ragweed detection in Geneva. The feared rise in ragweed allergy seems not to have happened in Switzerland, compared with other ragweed colonised countries. These results strongly support early field strategies against ragweed.

Respiratory allergy in immigrants to a highly industrialised area in Italy according to area of origin and time period

BACKGROUND: Migrants from developing to Western countries tend to become more sensitised to host than to origin country allergens, although substantial changes in migration patterns have occurred in recent decades. Methods We investigated adult immigrants with respiratory allergy, first tested for allergic sensitisation between 1985 and 2012 in a highly industrialised area in Italy. A comparison was made of the sensitisation pattern between immigrants and a random sample of native-born subjects affected by a respiratory allergy, and among immigrants according to macro-region of origin and time period. RESULTS: Between 1985 and 2012, 480 immigrants with respiratory allergy had a first positive allergy test. Immigrants were sensitised mainly to grass (67.1%), house dust mites (HDM) (38.5%) and birch (27.5%), with a pattern of sensitisation very similar to that observed in Italians (native-born). An increase in the proportion of subjects with asthma and of subjects with polysensitisation was observed from the first (1985-2002) to the middle (2003-2007) and the most recent period (2008-2012). In recent years, the proportion of subjects with polysensitisation in immigrants is higher than in Italians (native-born) (53.3% vs. 40.1%). Among immigrants, the risk of sensitisation to grass was higher in those from Sub-Saharan Africa (odds ratio, OR = 2.76) and Latin America (OR = 2.49), whereas risk of sensitisation to HDM was higher among immigrants from South Asia (OR = 2.71), compared to immigrants from Eastern Europe. CONCLUSIONS: Immigrants develop multiple sensitisations more frequently than native-born people, and are especially sensitised to local allergens; the country of origin seems to play a role

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Neonatal vitamin A supplementation associated with increased atopy in girls.

BACKGROUND: Neonatal vitamin A supplementation (NVAS) is currently being considered as policy in countries at risk of deficiency. A previous study suggested that NVAS may be associated with increased atopy. We examined the effect of NVAS on atopy by conducting long-term follow-up of a previous randomized controlled trial in Guinea-Bissau. METHODS: In 2002-2004, we randomized 4345 normal birthweight neonates to NVAS (50 000 IU retinyl palmitate) or placebo together with their Bacillus Calmette-Guérin vaccination. In 2013, we visited the 1692 (39%) children now aged 8-10 years who were still living in the study area, and 1478 (87%) were found at home. Provided consent, a skin prick test was performed, and history of allergic symptoms was recorded. Associations of NVAS and atopy (defined as skin prick test reaction of ≥3 mm) were analysed using binomial regression. RESULTS: Of the 1430 children with a valid skin prick test, 228 (16%) were positive (more boys (20%) than girls (12%), P-value < 0.0001). NVAS did not increase the overall risk of atopy (RR 1.10 [95% CI 0.87-1.40]). However, NVAS was associated with significantly increased risk among females (RR 1.78 [1.17-2.72]) but not among males (0.86 [0.64-1.15], P-value for interaction between NVAS and gender = 0.005). Furthermore, NVAS was associated with increased risk of wheezing among females (RR 1.80 [1.03-3.17], but not among males, P-value for interaction = 0.05). CONCLUSION: The study corroborated previous observations; NVAS was associated with increased risk of atopy and wheezing, in this study only among females. Further studies on NVAS and atopy are warranted.

Food consumption and risk of childhood asthma.

BACKGROUND: The consumption of foods rich in n-3 polyunsaturated fatty acids has been proposed to protect against childhood asthma. This study explores the association of food consumption (including cow's milk (CM)-free diet) in early life and the risk of atopic and non-atopic asthma. METHODS: Food intake of 182 children with asthma and 728 matched controls was measured using 3-day food records, within the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition Study cohort. The diagnoses of food allergies came both from the written questionnaire and from the registers of the Social Insurance Institution. Conditional logistic regression with generalized estimating equations framework was used in the analyses. RESULTS: The diagnosis of cow's milk allergy (CMA) led to multiple dietary restrictions still evident at 4 yr of age. Even after adjusting for CMA, higher consumption of CM products was inversely associated with the risk of atopic asthma and higher consumption of breast milk and oats inversely with the risk of non-atopic asthma. Early consumption of fish was associated with a decreased risk of all asthma. CONCLUSIONS: Dietary intake in early life combined with atopy history has a clear impact on the risk of developing asthma. Our results indicate that CM restriction due to CMA significantly increases and mediates the association between food consumption and childhood asthma risk.

The prevalence of the oral allergy syndrome and pollen-food syndrome in an atopic paediatric population in south-west Sydney.

AIM: Oral allergy syndrome (OAS) and pollen-food syndrome (PFS) are regarded as uncommon manifestations of paediatric atopic disease. However, little Australian data exist. The aim of this study was to examine the prevalence of OAS in an atopic, paediatric population. METHODS: This cross-sectional study assessed 163 patients aged 4-17 years from the Paediatric Allergy & Immunology Clinic at Campbelltown Hospital, which serves a population base >250,000 with approximately 28% under the age of 18 years. A questionnaire was administered and skin prick tests (SPTs) were performed utilising commercial extracts and fresh and frozen fruit samples. Frozen samples were created by reducing fresh fruit to a semi-solid state and storing at -20 degrees Celsius for up to 6 months. RESULTS: Within the studied population, the prevalence of OAS was 14.7%, PFS 4.9%, PFS in those with allergic rhinitis 6.25% and PFS in those with allergic rhinitis and pollen sensitisation 12.1%. All PFS-implicated fruits were tropical fruits with watermelon the most common. The prevalence of OAS caused by food allergy was 13.6%, implicating peanut most frequently. The most common cause of OAS was immunoglobulin E-mediated food allergy (57.9%). Only frozen samples of watermelon, pineapple and rockmelon produced results consistent with the 'gold standard' of fresh fruit SPT. CONCLUSION: This study suggests the prevalence of OAS and PFS are more common in paediatric populations than previously described, with tropical fruits predominantly implicated in PFS. Further research is required to determine whether frozen fruits are a reliable alternative to fresh fruit in SPT.

Cypress pollen: an unexpected major sensitizing agent in different regions of Italy.

OBJECTIVES: In this multicenter survey, we assessed the impact of sensitization to cypress in atopic patients in Italy and determined whether cypress pollen concentration changed over time. METHODS: Allergists were required to collect the results of 100-200 consecutive skin prick tests (SPTs) performed during 2012. Seasonal symptoms were also recorded, as were airborne cypress pollen concentrations (data from the Italian Aerobiology Association) in 1998-2000 and 2010-2012. RESULTS: We examined 2258 atopic outpatients (56% females; age, 2-84 years) sensitized to at least 1 of the aeroallergens tested (Dermatophagoides species, grass, pellitory, olive, cypress, birch, Alternaria tenuis, and dog and cat dander). We found that 62.9%, 16.1%, and 32.7% of patients living in central, northern, and southern Italy, respectively, were sensitized to cypress (P < .0001). The cypress pollen concentration peak was delayed from February to March in 1998-2000 and 2010-2012 in all 3 regions, with a shift in pollination towards spring. Patients who were monosensitized to cypress reported mainly rhinitis (90.7%-97.6%) and conjunctivitis (38.1%-100%). In polysensitized patients, the prevalence of rhinitis, conjunctivitis, and asthma increased progressively (P < .0001) from southern to northern Italy. The same trend was observed for the prevalence of reported winter symptoms typical of cypress allergy (28%-65%). CONCLUSIONS: Today, cypress pollen is the most frequent sensitizing aeroallergen (assessed by SPT) in several areas of central Italy. Variations in the timing of the cypress pollination period may have favored this increased sensitization. Rhinitis and conjunctivitis are the predominant symptoms. The clinical impact of this allergy was poor in southern Italy and increased in central areas before reaching its peak in northern regions.