A randomized controlled trial of effects of open-label placebo compared to double-blind placebo and treatment-as-usual on symptoms of allergic rhinitis.

Placebo effects are known for numerous clinical symptoms. Until recently, deception of placebos was thought to be essential for placebo effects, but intriguing new studies suggest that even placebos without concealment (open-label placebos) may help patients with various clinical disorders. Most of those studies compared open-label placebo treatments with no treatment conditions (or treatment "as usual"). Given that open-label placebo studies obviously cannot be blinded, additional control studies are important to assess the efficacy of open-label placebos. The current study aimed to fil this gap by comparing open-label with conventional double-blind placebos and treatment as usual. Patients with seasonal allergic rhinitis were randomly divided in different groups. The first group received open-label placebos, the second double-blind placebos, and the third was treated as usual. After 4 weeks, results demonstrated that open-label placebos improved allergic symptoms more than treatment-as-usual and even more as double-blind placebos. In addition, we observed that allergic symptoms in general (and also the open-label placebo effects) were reduced by the Covid-19 pandemic. The results suggest that seasonal allergic symptoms may be relieved by open-label placebos. We discuss these results by addressing possible different mechanisms of open-label and conventionally concealed placebo treatments.

Allergen-specific immunotherapy and COVID-19: What happened?

BACKGROUND: The COVID-19 infection played a key role in the discontinuation of patient treatment, such as allergen-specific immunotherapy, in chronic diseases. OBJECTIVES: We conducted a retrospective observational study at Verona University Hospital, Verona, Italy, to assess the level of adherence to sublingual immunotherapy (SLIT) in patients affected by allergic rhinitis and mild asthma. MATERIALS AND METHODS: We compared and analysed data related to first prescription and collection of 5-grass-pollen 300-index of reactivity (IR) SLIT and tablet lyophilisate, containing 75,000 standardized quality tablet units (SQ-T) allergen extract of grass-pollen from Phleum pratense L, for the five-year period 2017-2021.In particular we considered the group of naïve patients from 2017 who completed pre-COVID treatment (2017-2019) and the group of naïve patients from 2019 who completed treatment during the COVID period (2019-2021). The significance test used was Student's t-test, and P ˂ 0.05 was considered as statistically significant. RESULTS: In the three-year period 2017-2019, 264 naïve patients began treatment in 2017, of these 181 continued in 2018, 135 continued in 2019. Instead, for the period 2017-2019, there were 226 naïve patients in 2019; of these 139 continued in 2020, and 102 in 2021. CONCLUSIONS: COVID-19 did not seem to influence adherence to SLIT, which declined independently even in during the pre-pandemic 3-year period.

Online public attention toward allergic rhinitis in Wuhan, China: Infodemiology study using Baidu index and meteorological data.

Background: With the popularization of the Internet and medical knowledge, more and more people are learning about allergic rhinitis (AR) on the Internet. Objective: This study aims to analyze the epidemiological characteristics and online public attention to AR in Wuhan, China, utilizing the most popular search engine in mainland China and meteorological data of Wuhan. Methods: To study the Internet attention and epidemiological characteristics of AR in Wuhan, the search volume (SV) of "Allergic Rhinitis" in Mandarin and AR-related search terms from 1 January 2014 through 31 December 2021 were recorded. For user interest, the search and demand data were collected and analyzed. Results: The yearly average Baidu SV of AR in both Wuhan and China increased year by year but began to decline gradually after the COVID-19 pandemic. Baidu SV of AR in Wuhan exhibited significant seasonal variation, with the first peak was from March to May and the second peak occurring between September and October. Correlation analysis revealed a moderate positive correlation between the monthly average SV of "Allergic Rhinitis" and "Mites" and "Mites + Pollen Allergy" in Wuhan, a weak positive correlation between the monthly average SV of "Allergic Rhinitis" and "Pollen Allergy," and a positive correlation between monthly SV of "Allergic Rhinitis" and the meteorological index of pollen allergy (MIPA). Conclusion: The attention given to the topic on the internet, as measured by the search volume, was reflective of the situation in Wuhan, China. It has the potential to predict the epidemiological characteristics of AR and help medical professionals more effectively plan seasonal AR health education.

Ameliorating Atopy by Compensating Micronutritional Deficiencies in Immune Cells: A Double-Blind Placebo-Controlled Pilot Study.

BACKGROUND: Functional iron deficiency facilitates allergy development and amplifies the symptom burden in people experiencing allergies. Previously we selectively delivered micronutrients to immune cells with ß-lactoglobulin as carrier (holoBLG), resulting in immune resilience and allergy prevention. OBJECTIVE: The clinical efficacy of a food for special medical purposes-lozenge containing ß-lactoglobulin with iron, polyphenols, retinoic acid, and zinc (holoBLG lozenge) was assessed in allergic women. METHODS: In a randomized, double-blind, placebo-controlled pilot study, grass- and/or birch pollen-allergic women (n = 51) were given holoBLG or placebo lozenges over 6 months. Before and after dietary supplementation, participants were nasally challenged and the blood was analyzed for immune and iron parameters. Daily symptoms, medications, pollen concentrations, and well-being were recorded by an electronic health application. RESULTS: Total nasal symptom score after nasal provocations improved by 42% in the holoBLG group versus 13% in the placebo group. The combined symptom medication score during the birch peak and entire season as well as the entire grass pollen season improved in allergic subjects supplemented with the holoBLG lozenge by 45%, 31%, and 40%, respectively, compared with the placebo arm. Participants ingesting the holoBLG lozenge had improved iron status with increased hematocrit values, decreased red cell distribution width, and higher iron levels in circulating CD14+ cells compared with the placebo group. CONCLUSIONS: Targeted micronutrition with the holoBLG lozenge seemed to be effective in elevating the labile iron levels in immune cells and reducing the symptom burden in allergic women in this pilot study. The underlying allergen-independent mechanism provides evidence that dietary nutritional supplementation of the immune system is one of the ways to combat atopy.

Approximate or accurate? Efficacy of daily use of weather and air quality mobile applications for pollen allergy sufferers?

Nowadays, technology permeates every aspect of human activity, from the professional to the recreational side, and the recent pandemic crisis has only amplified a clearly defined trend. Through portable devices, people play, work, and get information. The immediacy of information and of many aspects of our life is a condition that, once acquired, is difficult to give up. However, immediate information must also be correct, and not all issues can easily be simplified to the point of being understandable in the absence of basic theoretical notions to a large audience. This aspect is particularly relevant when dealing with issues related to human health and the communication problems encountered in recent months concerning the spread of SARS-CoV-2, and the vaccination campaign is there to prove it. With the intent of clarifying the advantages and disadvantages of fast and accessible information, in this article, some of the most widespread applications for mobile devices, dedicated to pollen allergens, air quality, parks, gardens, and green areas, were examined. A widespread lack of clarity on the sources of the data and on the criteria used to formulate synthetic judgments-that often confuse the final users-was noted.

Environmental factors and mobility predict COVID-19 seasonality in the Netherlands.

BACKGROUND: We recently showed that seasonal patterns of COVID-19 incidence and Influenza-Like Illnesses incidence are highly similar, in a country in the temperate climate zone, such as the Netherlands. We hypothesize that in The Netherlands the same environmental factors and mobility trends that are associated with the seasonality of flu-like illnesses are predictors of COVID-19 seasonality as well. METHODS: We used meteorological, pollen/hay fever and mobility data from the Netherlands. For the reproduction number of COVID-19 (Rt), we used daily estimates from the Dutch State Institute for Public Health. For all datasets, we selected the overlapping period of COVID-19 and the first allergy season: from February 17, 2020 till September 21, 2020 (n = 218). Backward stepwise multiple linear regression was used to develop an environmental prediction model of the Rt of COVID-19. Next, we studied whether adding mobility trends to an environmental model improved the predictive power. RESULTS: Through stepwise backward multiple linear regression four highly significant (p < 0.01) predictive factors are selected in our combined model: temperature, solar radiation, hay fever incidence, and mobility to indoor recreation locations. Our combined model explains 87.5% of the variance of Rt of COVID-19 and has a good and highly significant fit: F(4, 213) = 374.2, p < 0.00001. This model had a better overall predictive performance than a solely environmental model, which explains 77.3% of the variance of Rt (F(4, 213) = 181.3, p < 0.00001). CONCLUSIONS: We conclude that the combined mobility and environmental model can adequately predict the seasonality of COVID-19 in a country with a temperate climate like the Netherlands. In this model higher solar radiation, higher temperature and hay fever are related to lower COVID-19 reproduction, and higher mobility to indoor recreation locations is related to an increased COVID-19 spread.

Environmental factors and mobility predict COVID-19 seasonality (preprint)

BackgroundWe recently showed that seasonal patterns of COVID-19 incidence and Influenza-Like Illnesses incidence are highly similar, in a country in the temperate climate zone, such as the Netherlands (latitude: 52{degrees}N). We hypothesize that in The Netherlands the same environmental factors and mobility trends that are associated with the seasonality of flu-like illnesses are predictors of COVID-19 seasonality as well. MethodsWe used meteorological, pollen/hay fever and mobility data from the Netherlands with its 17.4 million inhabitants. For the reproduction number of COVID-19 (Rt), we used data from the Dutch State Institute for Public Health. This Rt metric is a daily estimate that is based on positive COVID-19 tests in the Netherlands in hospitals and municipalities. For all datasets we selected the overlapping period of COVID-19 and the first allergy season: from February 17, 2020 till September 21, 2020 (total number of measurements: n = 218), the end of pollen season. Backward stepwise multiple linear regression was used to develop an environmental prediction model of the Rt of COVID-19. Next, we studied whether adding mobility trends to an environmental model improved the predictive power. ResultsBy means of stepwise backward multiple linear regression four highly significant (p value < 0.01) predictive factors are selected in our combined model: temperature, solar radiation, hay fever incidence, and mobility to indoor recreation locations. Our combined model explains 87.5% of the variance of Rt of COVID-19 and has a good and highly significant fit: F(4, 213) = 374.2, p-value < 0.00001. The combined model had a better overall predictive performance compared to a solely environmental model, which still explains 77.3% of the variance of Rt, and a good and highly significant fit: F(4, 213) = 181.3, p < 0.00001. ConclusionsWe conclude that the combined mobility and environmental model can adequately predict the seasonality of COVID-19 in a country with a temperate climate like the Netherlands. In this model higher solar radiation, higher temperature and hay fever are related to lower COVID-19 reproduction, and mobility to indoor recreation locations with increased COVID-19 spread. HighlightsO_LIThe seasonality of COVID-19 can be well-explained by environmental factors and mobility. C_LIO_LIA combined model explains 87.5% of the variance of the reproduction number of COVID-19 C_LIO_LIInhibitors of the reproduction number of COVID-19 are higher solar radiation, and seasonal allergens/allergies. C_LIO_LIMobility, especially to indoor recreation locations, increases the reproduction number of COVID-19. C_LIO_LITemperature has no direct effect on the reproduction number of COVID-19, but affects mobility and seasonal allergens. C_LIO_LIAdding mobility trends to an environmental model improves the predictive value regarding the reproduction number of COVID-19. C_LI

The effect of face mask usage on the allergic rhinitis symptoms in patients with pollen allergy during the covid-19 pandemic.

PURPOSE: The study aims to evaluate the use of face masks on allergic rhinitis symptoms in pollen allergy patients who were compulsorily using face masks due to the covid-19 pandemic. MATERIALS AND METHODS: A 15-item questionnaire was developed following the study goals by a team experienced in allergic rhinitis. Then the records of patients who underwent allergy tests in our hospital between 2013 and 2019 were retrospectively analyzed. Fifty participants with isolated pollen allergy were included in the study. Patients who agreed to participate in the research answered the questions over the phone. RESULTS: Of the 50 participants, 30 (60%) were female and 20 (40%) were male, with a mean age of 34.34 ± 9.41 years. While the rate of participants who defined their nasal symptoms as severe-moderate in the pre-pandemic period was 92% (46 patients), this rate decreased to 56% (28 patients) during the pandemic when they used face masks. In ocular symptoms, the same rate decreased from 60% (30 patients) to 32% (16 patients). A statistically significant decrease was found in both nasal and ocular symptoms of patients after mask use (p < 0.001). The most regression in allergy symptoms was observed in sneezing (p = 0.029) and nasal discharge (p = 0.039). CONCLUSIONS: This study observed that the use of face masks reduced both nasal and ocular allergic rhinitis symptoms in individuals with pollen allergy. These results support the hypothesis that the use of face masks would reduce the severity of allergic rhinitis symptoms.

Regulation of the Expression of SARS-CoV-2 Receptor Angiotensin-Converting Enzyme 2 in Nasal Mucosa.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused a global pandemic. Higher expression of the virus receptor angiotensin-converting enzyme 2 (ACE2) in the nasal mucosa may be associated with high transmissibility and asymptomatic infection. In COVID-19, the elucidation of the determinants of ACE2 expression at nasal tissue level is crucial. The development of strategies to downregulate ACE2 expression in nasal epithelial cells might reduce transmission and be useful as a novel therapeutic approach. OBJECTIVE: To verify ACE2 expression in the nasal mucosa of patients with seasonal allergic rhinitis induced by Japanese cedar pollen (SAR-JCP) and chronic rhinosinusitis with nasal polyp (CRSwNP) and to examine the effects of short-chain fatty acids (SCFAs) on ACE2 expression in airway epithelial cells. METHODS: We assessed ACE2 expression in the nasal mucosa of control subjects, patients with SAR-JCP, and those with CRSwNP using real-time polymerase chain reaction. We also quantified ACE2 gene expression in cultured airway epithelial cells. RESULTS: Although ACE2 expression was greatly increased in a few patients with SAR-JCP during the Japanese cedar pollen season, mean levels were not significantly increased. ACE2 mRNA expression was significantly decreased in nasal polyp tissue from patients with chronic rhinosinusitis compared with the expression in that from control subjects. SCFAs generated by gastrointestinal microbiota significantly reduced resting ACE2 expression in cultured airway epithelial cells. SCFAs also significantly suppressed the dsRNA-dependent upregulation of ACE2 expression in airway epithelial cells. CONCLUSION: Inflammatory endotype affects ACE2 expression in the nasal mucosa and influences susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In particular, type 2 inflammation could downregulate ACE2 expression in the nasal mucosa and reduces susceptibility to SARS-CoV-2 in patients with CRSwNP. Although in vivo experiments are required, administration of SCFAs to the nasal cavity might be worthy of consideration as a preventative or therapeutic strategy for the early-stage COVID-19.

COVID-19 lockdown and seasonal allergic rhinitis: our experience in 40 patients.

INTRODUCTION: The aim of this article was to study the course of seasonal allergic rhinitis during COVID-19 lockdown in order to understand if being quarantined at home for a long time can constitute a protective factor for allergic patients. MATERIALS AND METHODS: Telehealth consultations were performed by the departments of Otolaryngology of Foggia and Bari University Hospitals. Participants took part in a phone interview and were asked about their sinonasal symptoms during the COVID-19 lockdown, by answering the sinonasal outcome test (I-SNOT-22) questionnaire. Further data concerning the medications used to treat allergy and the number of days per month in which they were used were collected. The responses about the COVID-19 lockdown were compared to those obtained by the same patients in our clinics the previous year. The statistical analysis was executed by using the paired sample t-test and the Bartlett test considering as significant values with p values <0.05. RESULTS: Forty patients affected by cypress pollen allergy visited at Foggia and Bari University Hospitals were enrolled in this study. All I-SNOT-22 scores concerning the COVID-19 lockdown were lower than those of the previous year; moreover, 18 (81.8%) clinical parameters were statistically significant (p<0.05). Also, in regard to the treatment, results about COVID-19 lockdown were overall better than those of 2019, with 50% (n=3) of the investigated drugs, reporting statistical significance (p<0.05). CONCLUSIONS: The present study was able to evidence the fundamental role of primary prevention in Allergology. Paradoxically, the home quarantine ordered by the Italian Government appeared to be an effective measure not only in the fight against COVID-19 but also against pollen exposure.

Pollen likely seasonal factor in inhibiting flu-like epidemics. A Dutch study into the inverse relation between pollen counts, hay fever and flu-like incidence 2016-2019.

There is uncertainty if current models for the Covid-19 pandemic should already take into account seasonality. That is because current environmental factors do not provide a powerful explanation of such seasonality, especially given climate differences between countries with moderate climates. It is hypothesized that one major factor is overlooked: pollen count. Pollen are documented to invoke strong immune responses and might create an environmental factor that makes it more difficult for flu-like viruses to survive outside a host. This Dutch study confirms that there is a (highly) significant inverse correlation between pollen count and weekly changes in medical flu consults, and that there is a highly significant inverse correlation between hay fever incidence, as measured by prescribed medication revenues, and weekly flu consults. This supports the idea that pollen are a direct or indirect factor in the seasonality of flu-like epidemics. If seasonality will be observed during the covid-19 spread as well, it is not unlikely that pollen play a role.