Clinical Relevance of Lepidoglyphus destructor Sensitisation in Allergic Rhinitis: Nasal Provocation Test as in vivo Assessment.

BACKGROUND: Dust mites are the leading cause of respiratory allergic diseases worldwide. Allergy to storage mites (SMs) has mostly been related to occupational exposures. However, recent studies have shown that sensitisation to SM, such as Lepidoglyphus destructor (Lep d), is of considerable importance also in urban populations, with high prevalence in dust samples of domestic environments. Co-sensitisation between house dust mites (HDMs) and SM is now regarded as very frequent in some regions, and cross-reactivity between them seems to be narrow. Therefore, SM allergenic capacity is increasingly a subject of study. The nasal provocation test (NPT), as an in vivo technique, could be considered the gold standard for the clinical relevance assessment of an allergen, in polysensitised rhinitis patients. OBJECTIVE: The objective of this study was to analyse the clinical relevance of the SM Lep d, by assessing the relationship between in vivo sensitisation and expression of allergic respiratory disease in an urban setting. PATIENTS AND METHODS: In our study, we enrolled a total of 32 allergic patients with rhinitis (with or without asthma) with proven sensitisation by skin prick test (SPT) and specific IgE (sIgE) to HDMs and/or SM. Patients underwent NPT with Lep d using subjective (Lebel Symptom Score Scale) and objective measurements (peak nasal inspiratory flow [PNIF]) for assessment of nasal response. RESULTS: Most of the patients with positive SPT and sIgE to Lep d had a positive NPT (24/27; 89%). True Lep d allergy, assessed by a positive NPT, could be predicted by a SPT wheal size >9.7 mm and a sIgE >0.42 kUA/L, with 100%/95.7% sensitivity and 75.0%/83.3% specificity, respectively. Co-sensitisation between Lep d and Der p was high, 75.0%. Asthma was more frequent in the positive Lep d NPT group (54 vs. 12%, p < 0.05). Significantly more patients from this group reported physical exercise, nonspecific irritants, and respiratory infections as relevant triggers of respiratory symptoms (p < 0.01-p < 0.05). CONCLUSIONS: To our knowledge, this is the first study to show that sensitisation to Lep d may have clinical relevance in a non-occupational setting. In this group, there seems to be a relationship between allergy to Lep d and severity of respiratory disease, with more bronchial inflammation, when comparing with mite-allergic patients sensitised only to HDM. Therefore, the authors consider that sensitisation to Lep d should be considered when assessing and treating allergic respiratory disease in urban environments.

Impact of Air Pollution on Daily Asthma Symptoms.

INTRODUCTION: The impact of air pollution on respiratory diseases, particularly in asthma, has been the subject of several studies. The impact of pollution on the daily symptoms of patients with asthma has been less studied. The aim of this study is to assess the association between the intensity of asthma symptoms and the variation of pollution levels. MATERIAL AND METHODS: Patients with a diagnosis of asthma were instructed to record the intensity of their respiratory symptoms daily, expressed on a scale from 0 to 5, in the months of March and April 2018. The website of the Portuguese Environment Agency was consulted in order to obtain the daily levels of pollutants measured by the two local monitoring stations during the same period of time. Data was analyzed using a temporal causal model to study the association between pollutant levels - particulate matter, ozone, nitrogen dioxide and carbon monoxide - and the intensity of respiratory symptoms. RESULTS: From the 135 schedules delivered, 35 were correctly filled out and returned. The patient median age was 47.0 years, 18 being females. The best statistical model obtained identified ozone as the most relevant 'Granger cause' of asthma symptoms. Particulate matter, carbon monoxide and nitrogen also appeared as lower impact factors. The quality of the model was expressed by an R2 of 0.92. The correlation between ozone values and asthma symptoms was more significant after five days. For the other identified factors there was a lag of four to five days. DISCUSSION: Our results support the existence of a daily variation of asthma symptoms that is associated with the pollution levels, even if these are within acceptable limits according to national and international standards. Regretfully, the small number of participants was a limitation in term of the conclusions that could be drawn and did not allow the analysis of clinical or other factors that are potentially involved. CONCLUSION: In the place and period studied the air pollutants behaved as factors of variation in the intensity of asthma symptoms. The ozone level was the best predictive factor of symptom variation. Levels of particulate matter, carbon monoxide and nitrogen were identified as secondary markers. The time lag between the variables with the best correlation suggests there could be a delayed effect of pollutants on respiratory symptoms.

Introdução: O impacto da poluição atmosférica nas doenças respiratórias, nomeadamente na asma, tem sido objeto de numerosos estudos. A repercussão da poluição na sintomatologia diária dos doentes asmáticos tem sido menos estudada. Pretendemos estudar a relação entre a intensidade dos sintomas diários de asma e a variação dos níveis de poluição. Material e Métodos: Foram selecionados doentes com diagnóstico de asma, sendo instruídos para anotar diariamente a intensidade dos seus sintomas respiratórios, expressa numa escala de 0 a 5, nos meses de março e abril de 2018. O website da Agência Portuguesa do Ambiente foi consultado e registaram-se os níveis diários de poluentes medidos pelas duas estações locais de monitorização durante o mesmo período. Os dados foram analisados utilizando um modelo causal temporal com a finalidade de relacionar os níveis de poluentes ­ partículas inaláveis com diâmetro menor que 10 µm, ozono, dióxido de nitrogénio e monóxido de carbono - com a intensidade dos sintomas de asma dos doentes. Resultados: Dos 135 calendários entregues, 35 foram corretamente preenchidos e devolvidos. A mediana de idades dos doentes foi de 47,0 anos, sendo 18 do sexo feminino. O melhor modelo estatístico obtido identificou o ozono como a 'causa Granger' mais relevante para os sintomas de asma. A qualidade do modelo traduziu-se por um R2 de 0,92. A correlação entre os valores de ozono e os valores dos sintomas de asma foi mais significativa após cinco dias. Para os outros fatores identificados verificou-se um desfasamento de quatro a cinco dias. Discussão: Os nossos resultados sugerem, de forma significativa, uma relação entre a variação dos sintomas de asma e os níveis de poluição, mesmo dentro dos limites considerados aceitáveis pelos padrões nacionais e internacionais. A reduzida dimensão da amostra foi, no entanto, um fator limitativo das conclusões e não permitiu a análise de outras varáveis potencialmente envolvidas. Conclusão: No período e local estudados, os poluentes atmosféricos comportaram-se como fatores de variação da intensidade dos sintomas de asma. O nível de ozono foi o melhor fator preditivo das variações da sintomatologia. Os níveis de partículas inaláveis, com diâmetro menor que 10 µm, de monóxido de carbono e de dióxido de nitrogénio foram identificados como marcadores secundários. O desfasamento temporal entre as variáveis com melhor correlação sugere um possível efeito retardado dos poluentes sobre os sintomas respiratórios.

Late-Onset Rash from Irbesartan: An Immunological Reaction.

Cutaneous delayed reactions to antihypertensive drugs have been described in a limited number of case reports but the mechanisms remain mostly unknown. We report the case of a 60-year-old female patient with a 3-week history of an itchy erythematous maculopapular eruption. Although the patient was polymedicated, irbesartan was the most likely culprit. Patch tests and a lymphocyte transformation test to irbesartan were both positive, which was useful for diagnosis and suggested an immunological reaction. No new lesions appeared after irbesartan was stopped or after the introduction of candesartan. Despite its similar chemical structure, candesartan may be tried in patients allergic to irbesartan. LEARNING POINTS: Irbesartan can induce immunological cell-mediated skin reactions.Allergy to irbesartan does not imply a class allergy.Patch tests and a lymphocyte transformation test were useful in the diagnosis of irbesartan allergy.

Environmental azole fungicide, prochloraz, can induce cross-resistance to medical triazoles in Candida glabrata.

Acquisition of azole resistance by clinically relevant yeasts in nature may result in a significant, yet undetermined, impact in human health. The main goal of this study was to assess the development of cross-resistance between agricultural and clinical azoles by Candida spp. An in vitro induction assay was performed, for a period of 90 days, with prochloraz (PCZ) - an agricultural antifungal. Afterward, the induced molecular resistance mechanisms were unveiled. MIC value of PCZ increased significantly in all Candida spp. isolates. However, only C. glabrata developed cross-resistance to fluconazole and posaconazole. The increased MIC values were stable. Candida glabrata azole resistance acquisition triggered by PCZ exposure involved the upregulation of the ATP binding cassette multidrug transporter genes and the transcription factor, PDR1. Single mutation previously implicated in azole resistance was found in PDR1 while ERG11 showed several synonymous single nucleotide polymorphisms. These results might explain why C. glabrata is so commonly less susceptible to clinical azoles, suggesting that its exposure to agricultural azole antifungals may be associated to the emergence of cross-resistance. Such studies forward potential explanations for the worldwide increasing clinical prevalence of C. glabrata and the associated worse prognosis of an infection by this species.

Development of cross-resistance by Aspergillus fumigatus to clinical azoles following exposure to prochloraz, an agricultural azole.

BACKGROUND: The purpose of this study was to unveil whether azole antifungals used in agriculture, similar to the clinical azoles used in humans, can evoke resistance among relevant human pathogens like Aspergillus fumigatus, an ubiquitous agent in nature. Additionally, cross-resistance with clinical azoles was investigated. Antifungal susceptibility testing of environmental and clinical isolates of A. fumigatus was performed according to the CLSI M38-A2 protocol. In vitro induction assays were conducted involving daily incubation of susceptible A. fumigatus isolates, at 35°C and 180 rpm, in fresh GYEP broth medium supplemented with Prochloraz (PCZ), a potent agricultural antifungal, for a period of 30 days. Minimal inhibitory concentrations (MIC) of PCZ and clinical azoles were monitored every ten days. In order to assess the stability of the developed MIC, the strains were afterwards sub-cultured for an additional 30 days in the absence of antifungal. Along the in vitro induction process, microscopic and macroscopic cultural observations were registered. RESULTS: MIC of PCZ increased 256 times after the initial exposure; cross-resistance to all tested clinical azoles was observed. The new MIC value of agricultural and of clinical azoles maintained stable in the absence of the selective PCZ pressure. PCZ exposure was also associated to morphological colony changes: macroscopically the colonies became mostly white, losing the typical pigmentation; microscopic examination revealed the absence of conidiation. CONCLUSIONS: PCZ exposure induced Aspergillus fumigatus morphological changes and an evident increase of MIC value to PCZ as well as the development of cross-resistance with posaconazole, itraconazole and voriconazole.