Air pollution and rhinitis.

Rhinitis arises from either allergic or non-allergic inflammation of the nasal mucosa, characterized by the infiltration of inflammatory cells into the tissue and nasal secretions, along with structural alterations in the nasal mucosa. The pathways through which air pollution affects rhinitis may diverge from those affecting asthma. This article aims to review the effects of diverse air pollutants on the nose, the correlation of climate change and pollution, and how they aggravate the symptoms of patients with rhinitis.

Establishment of a human nasal epithelium model of histamine-induced inflammation to assess the activity of fexofenadine as an inverse agonist and its link to clinical benefit.

Background: Fexofenadine (FEX) is an antihistamine that acts as an inverse agonist against histamine (HIS) receptor 1 (H1R), which mediates the allergic reaction. Inverse agonists may be more potent than neutral antagonists, as they bind the same receptor as the agonist (HIS) but stabilize the inactive form and induce an opposite pharmacological response, suppressing the basal activity of H1R and preventing HIS from binding. This study aims to establish and validate a model of HIS-induced inflammation based on fully reconstituted human nasal epithelial tissue to assess the activity of FEX as an inverse agonist in this model and explore its link to clinical benefit. Methods: The model was developed using nasal MucilAir™ (Epithelix) in vitro epithelium challenged by HIS. Two conditions were assessed in a side-by-side comparison: tissue was exposed to HIS + FEX with or without FEX pre-treatment (one-hour prior to HIS challenge). Tissue functionality, cytotoxicity, H1R gene expression, and inflammatory cytokines were assessed. Results: HIS at 100 µM induced significant 3.1-fold and 2.2-fold increases for inflammatory biomarkers interleukin (IL)-8 and IL-6, respectively (p < 0.0001), as well as rapid upregulation of H1R mRNA. Inflammatory biomarkers were inhibited by FEX and H1R expression was significantly reduced (p < 0.0001). FEX alone decreased H1R expression at all doses tested. With one-hour FEX pre-treatment, there was significantly higher downregulation of IL-8 (p < 0.05) and further downregulation of H1R expression and IL-6 versus without FEX pre-treatment; the effects of FEX were improved from 22% to 40%. Conclusion: A model of HIS-induced airway inflammation was established based on IL-8, IL-6 and H1R gene expression and was validated with FEX. FEX works as an inverse agonist, with a higher effect when used before+during versus only during the HIS challenge. Taking FEX before+during allergen exposure, or when symptoms first occur, may reduce basal activity and H1R gene expression, providing stronger protection against the worsening of symptoms upon allergen exposure.

Pollen respiratory allergy: Is it really seasonal?

Allergic rhinitis (AR) is a highly prevalent respiratory condition that carries a heavy burden and can have a significant impact on patient quality of life. AR is caused by seasonal or perennial exposure to outdoor pollens and molds as well as indoor allergic triggers. In this review article, we discuss the factors associated with the development of AR throughout the year and the fact that patients with AR need continuous treatment rather than seasonal treatment. Conventionally, AR has been mainly categorized into seasonal AR and perennial AR, but these classes do not seem to be well-adapted. Climate changes, temperature changes, and high carbon dioxide (CO2) concentration affect the growth of plants and increase the length of pollen seasons and pollen allergenicity. Air pollution aggravates allergic sensitization symptoms in AR sensitized individuals. Due to increased air pollution and indefinite pollen seasons AR symptoms are present throughout the year. Patients with AR often need continuous treatment, which should be considered while making the strategy for treating allergic rhinitis sufferers. Management of AR involves avoiding the allergen, medications for symptomatic relief, anti-inflammatory therapies, and allergy immunotherapy. Although the first-generation H1-antihistamines reduce AR symptoms, they cause sedation and impair cognitive functions; thus, second-generation antihistamines (ie, levocetirizine, loratadine, bilastine, fexofenadine) are preferred. The efficacy and safety of fexofenadine for the treatment of seasonal allergic rhinitis (SAR) symptoms have been demonstrated by numerous clinical studies, irrespective of the season and underlying allergen. In this review, we discuss the allergic rhinitis classification, the role of climate change, air pollution, and factors contributing to year-round symptoms in patients with AR and the need for continuous pharmacological treatment for management.

Insights into urticaria in pediatric and adult populations and its management with fexofenadine hydrochloride.

OBJECTIVE: The present narrative review provides a comprehensive update of the current knowledge on urticaria, both in adult and pediatric populations, and on the safety and efficacy of fexofenadine hydrochloride (HCl) as a treatment option. DATA SOURCE: A literature search was conducted on Embase and Medline. STUDY SELECTION: Clinical studies published in English and published between 1999 and 2020 were selected. RESULTS: Although the exact pathogenesis of urticaria is not fully understood, multiple pathways of mast cell activation are discussed to explain the existence of phenotypically different clinical manifestations of urticaria. An overview of the worldwide prevalence of chronic urticaria, including disease burden and patient's quality of life is provided. The impact of urticaria on patient's life differs on the basis of whether its form is acute or chronic, but pharmacological approaches are most often needed to control the disabling symptoms. A summary of the current management of urticaria recommended by different guidelines across countries (Global; European; American; Australian; Asian; Japanese) is presented. Non-sedating, second-generation H1-antihistamines are the preferred choice of treatment across several guidelines worldwide. Herein, the efficacy and safety of fexofenadine HCl, a representative second-generation H1-antihistamine approved for the treatment of urticaria, is discussed. The occurrence of urticaria manifestations in COVID-19 patients is also briefly presented. CONCLUSION: The burden of acute and chronic urticaria is high for patients. Second generation anti-histamines such as fexofenadine HCl can help managing the symptoms.

Effect of fexofenadine hydrochloride on allergic rhinitis aggravated by air pollutants.

In recent decades, seasonal allergic rhinitis (SAR) prevalence has increased and recent studies have shown that air pollutants, such as diesel exhaust particles (DEP), can increase inflammatory and allergic biomarkers. The aim of this study was to investigate the effects of DEP on SAR symptoms induced by ragweed and to evaluate the efficacy and safety of fexofenadine HCl 180 mg versus placebo. This phase 3, single-centre, sequential, parallel-group, double-blind, randomised study (NCT03664882) was conducted in an environmental exposure unit (EEU) during sequential exposures: Period 1 (ragweed pollen alone), Period 2 (ragweed pollen+DEP), and Period 3 (ragweed pollen+DEP+single-dose fexofenadine HCl 180 mg or placebo). Efficacy and safety were evaluated in Period 3. Primary endpoints were the area under the curve (AUC) of total nasal symptom score (TNSS) from baseline to hour 12 (AUC0-12) during Period 1 and Period 2; and the AUC of the TNSS from hour 2 to 12 (AUC2-12) during Period 3. 251 out of 257 evaluable subjects were included in the modified intent-to-treat population. Least squares mean difference (95% CI) for TNSS Log AUC0-12 in Period 2 versus Period 1 was 0.13 (0.081-0.182; p<0.0001). Least squares mean difference in TNSS Log AUC2-12 for fexofenadine HCl versus placebo during Period 3 was -0.24 (-0.425--0.047; p=0.0148). One fexofenadine HCl-related adverse event was observed. SAR symptoms evoked by ragweed were aggravated by DEP. Fexofenadine HCl 180 mg was effective in relieving pollen-induced, air pollution-aggravated allergic rhinitis symptoms.

Air pollution and indoor settings.

Indoor environments contribute significantly to total human exposure to air pollutants, as people spend most of their time indoors. Household air pollution (HAP) resulting from cooking with polluting ("dirty") fuels, which include coal, kerosene, and biomass (wood, charcoal, crop residues, and animal manure) is a global environmental health problem. Indoor pollutants are gases, particulates, toxins, and microorganisms among others, that can have an impact especially on the health of children and adults through a combination of different mechanisms on oxidative stress and gene activation, epigenetic, cellular, and immunological systems. Air pollution is a major risk factor and contributor to morbidity and mortality from major chronic diseases. Children are significantly affected by the impact of the environment due to biological immaturity, prenatal and postnatal lung development. Poor air quality has been related to an increased prevalence of clinical manifestations of allergic asthma and rhinitis. Health professionals should increase their role in managing the exposure of children and adults to air pollution with better methods of care, prevention, and collective action. Interventions to reduce household pollutants may promote health and can be achieved with education, community, and health professional involvement.

Thunderstorm allergy and asthma: state of the art.

Thunderstorm-triggered asthma (TA) can be defined as the occurrence of acute asthma attacks immediately following a thunderstorm during pollen seasons. Outbreaks have occurred across the world during pollen season with the capacity to rapidly inundate a health care service, resulting in potentially catastrophic outcomes for allergic patients. TA occurs when specific meteorological and aerobiological factors combine to affect predisposed atopic patients with IgE-mediated sentitization to pollen allergens. Thunderstorm outflows can concentrate aeroallergens, most commonly grass pollen but also other pollens such as Parietaria and moulds in TA, at ground level to release respirable allergenic particles after rupture by osmotic shock related to humidity and rainfall. Inhalation of high concentrations of these aeroallergens by sensitized individuals can induce early asthmatic responses which can be followed by a late inflammatory phase. There is evidence that, during pollen season, thunderstorms can induce allergic asthma outbreaks, sometimes also severe asthma crisis and sometimes deaths in patients suffering from pollen allergy. It has been observed that changes in the weather such as rain or humidity may induce hydratation of pollen grains during pollen seasons and sometimes also their fragmentation which generates atmospheric biological aerosols carrying allergens. Asthma attacks are induced for the high concentration at ground level of pollen grains which may release allergenic particles of respirable size after rupture by osmotic shock. In other words, it is a global health problem observed in several cities and areas of the world that can strike without sufficient warning, inducing sometimes severe clinical consequences also with deaths of asthma patients. Due to constant climate change, future TA events are likely to become more common, more disastrous and more unpredictable, as a consequence it is important to have deep knowledge on this topic to prevent asthma attacks. Other environmental factors, such as rapid changes in temperature and agricultural practices, also contribute to causing TA.

Immunopathological features of air pollution and its impact on inflammatory airway diseases (IAD).

Air pollution causes significant morbidity and mortality in patients with inflammatory airway diseases (IAD) such as allergic rhinitis (AR), chronic rhinosinusitis (CRS), asthma, and chronic obstructive pulmonary disease (COPD). Oxidative stress in patients with IAD can induce eosinophilic inflammation in the airways, augment atopic allergic sensitization, and increase susceptibility to infection. We reviewed emerging data depicting the involvement of oxidative stress in IAD patients. We evaluated biomarkers, outcome measures and immunopathological alterations across the airway mucosal barrier following exposure, particularly when accentuated by an infectious insult.

The effects of climate change on respiratory allergy and asthma induced by pollen and mold allergens.

The impact of climate change on the environment, biosphere, and biodiversity has become more evident in the recent years. Human activities have increased atmospheric concentrations of carbon dioxide (CO2 ) and other greenhouse gases. Change in climate and the correlated global warming affects the quantity, intensity, and frequency of precipitation type as well as the frequency of extreme events such as heat waves, droughts, thunderstorms, floods, and hurricanes. Respiratory health can be particularly affected by climate change, which contributes to the development of allergic respiratory diseases and asthma. Pollen and mold allergens are able to trigger the release of pro-inflammatory and immunomodulatory mediators that accelerate the onset the IgE-mediated sensitization and of allergy. Allergy to pollen and pollen season at its beginning, in duration and intensity are altered by climate change. Studies showed that plants exhibit enhanced photosynthesis and reproductive effects and produce more pollen as a response to high atmospheric levels of carbon dioxide (CO2 ). Mold proliferation is increased by floods and rainy storms are responsible for severe asthma. Pollen and mold allergy is generally used to evaluate the interrelation between air pollution and allergic respiratory diseases, such as rhinitis and asthma. Thunderstorms during pollen seasons can cause exacerbation of respiratory allergy and asthma in patients with hay fever. A similar phenomenon is observed for molds. Measures to reduce greenhouse gas emissions can have positive health benefits.

Prescription patterns of analgesics, antipyretics, and non steroidal anti-inflammatory drugs for the management of fever and pain in pediatric patients: a cross-sectional, multicenter study in Latin America, Africa, and the Middle East.

OBJECTIVE: To evaluate the daily practice of pediatricians, physician-perceived reasons for unsatisfactory effects of treatment, and unmet needs in the management of acute pain and/or fever. METHODS: This was a multinational (n=13), multicenter, non interventional, cross-sectional study conducted in Latin America, Africa, and the Middle East in children under 16 years of age with fever (defined as a central body temperature ≥38°C) and/or acute pain (defined as pain lasting ≤6 weeks). Data were collected during a single visit using a structured physician-administered questionnaire and case report forms. RESULTS: A total of 2125 patients were recruited by 178 physicians between September 2010 and September 2011. From the 2117 analyzed patients, 1856 (87.7%) had fever, 705 (33.3%) had acute pain, and 446 (21.1%) had both. Of 1843 analyzed patients with fever, 1516 (82.3%) were previously prescribed a pharmacological treatment for the management of fever concomitantly with a non pharmacological approach, while 1817/1856 patients (97.9%) were currently receiving a prescribed pharmacological treatment for fever. Paracetamol/acetaminophen was the most commonly prescribed antipyretic medication during both previous (70.8%) and current (64.1%) consultations. With regard to acute pain management, 67.2% of the patients received previous and 93.9% received current treatment for pain. The most frequently prescribed analgesic during previous consultations was paracetamol/acetaminophen (53.7%), and the current most commonly prescribed analgesics were non steroidal anti-inflammatory drugs (55.2%). Treatment patterns for patients with both fever and acute pain were similar. Overall, 53.4% of the physicians reported poor treatment compliance as a reason for the unsatisfactory effect of the pain/fever treatment, and the most common unmet need was the availability of new drugs (according to 63.5% of the physicians). CONCLUSIONS: Adequate management of fever was observed; however, due to the complex etiology of pediatric pain, better evaluation and management of pain in pediatrics is necessary.

Rinite alérgica na visão do paciente / Allergic rhinitis from a patient's perspective

Os sintomas nasais têm impacto na vida dos pacientes com rinite alérgica. A maioria das pessoas alérgicas relata impacto negativo dos sintomas de alergia no trabalho e no desempenho escolar. Dentre todos os sintomas de alergia, o mais incômodo é a obstrução nasal, embora outros sintomas também tenham impacto na qualidade de vida dos pacientes, especialmente no sono. Os anti-histamínicos orais e corticosteroides nasais são as medicações mais frequentemente utilizadas para o tratamento de rinite, seguidos por descongestionantes orais ou intranasais. Os pacientes alérgicos frequentemente compram medicações sem prescrição médica nas farmácias, e nem sempre estão satisfeitos com o tratamento que lhes é oferecido. Os médicos devem trabalhar mais na comunicação com os pacientes alérgicos para atender às suas necessidades, abordando medo de efeitos colaterais, preocupações quanto aos sintomas de alergia e como estes interferem na qualidade de vida. Desse modo, a educação do paciente baseada em melhor comunicação pode facilitar o controle da rinite alérgica.

Nasal symptoms have an impact on the daily lives of patients with allergic rhinitis. Most allergic individuals report a negative impact of allergy symptoms on work and school performance. Among all allergy symptoms, the most bothersome is nasal congestion, although other symptoms also have an impact on patients' quality of life, especially on their sleep. Oral antihistamines and intranasal corticosteroids are the most frequently used medications for rhinitis, followed by oral or intranasal decongestants. Allergic patients frequently purchase different over-the-counter medications and sometimes are not satisfied with proposed treatments. Physicians should improve the communication with allergic patients to meet their needs, addressing fear of side effects, concerns about allergy symptoms and how they impact quality of life. Thus, educating patients through better communication may improve the control of allergic rhinitis.

The international survey on the management of allergic rhinitis by physicians and patients (ISMAR).

Epidemiologic studies suggest that the prevalence of allergic rhinitis (AR) is rising worldwide. Several reports, in fact, indicate increasing trends in the prevalence of AR especially in developing countries, likely related to the environment and climate changes and the adoption of an urbanized Western lifestyle. The primary objective of the present study was to collect information about management in real-life settings, including a characterization of typical patients' profile referring to physicians, the disease features, the common approaches to diagnostic assessments and therapeutic decisions. This was an international, multicenter, cross-sectional study conducted in adults or children (≥6 years) suffering from rhinitis confirmed by physician's diagnosis for at least one year. The 234 physicians who participated in the study included a total of 2778 patients in Egypt, Mexico, Brazil, Colombia, Guatemala, Iran, Venezuela, Argentina, Israel, Kuwait and United Arab Emirates. It was found that clinical history was the selected tool to diagnose and categorize AR patients (97.1%), with less than half of patients undergoing allergy testing, may be explaining the scarce use of immunotherapy on management of disease. Out of 2776 patients, 93.4% had somehow received a recommendation to avoid allergens and irritant agent exposure. Notably, 91.4% were receiving at least one treatment at the time of the survey, mostly oral antihistamines (79.7%) and intranasal corticosteroids (66.3%). Oral antihistamines, intranasal steroids and decongestants were considered both safe and effective by patients and physicians, preferring oral and nasal route of administration. The ISMAR registry was designed according to the most accepted epidemiological recommendations, and provides interesting information regarding the management of rhinitis from a patient and physician points of view, with many similarities between the participating countries. Further efforts are required to better manage AR and its comorbidities.

Mizolastine in primary acquired cold urticaria.

BACKGROUND: Treatment of primary acquired cold urticaria (CU) is quite difficult because of variable clinical effectiveness and side effects of classic antihistamines. OBJECTIVE: The objective of the study was to assess the efficacy and safety of mizolastine, an antihistaminic with antiallergic properties, versus placebo in primary acquired CU. METHODS: This study was a phase II, multicenter, randomized, double-blind, crossover, placebo-controlled study of mizolastine (10 mg, once daily) versus placebo in 28 patients with primary acquired CU. Efficacy was measured by the cold-stimulation time test, the wheal response, and pruritus intensity after an ice-cube test. RESULTS: Mizolastine delayed the cold-induced wheal reaction, reduced wheal response at 3 and 10 minutes, and reduced pruritus intensity. Statistically significant differences were observed versus placebo for the cold-stimulation time test, wheal response at 3 and 10 minutes, and pruritus intensity (P =.006,.015,.009, and.005, respectively). No clinically relevant adverse events were reported. CONCLUSIONS: Mizolastine (10 mg, once daily) was shown to be superior to placebo for both delaying and reducing the cold-induced wheal reaction without significant adverse events. Results suggest that mizolastine may be effective in the treatment of CU.