IgE Sensitization to<i>Aspergillus fumigatus</i>Is Associated with Reduced Lung Function in Asthma

Fairs, Abbie; Agbetile, Joshua; Hargadon, Beverley; Bourne, Michelle; Monteiro, William; Brightling, Christopher E.; Bradding, Peter; Green, Ruth H.; Mutalithas, Kugathasan; Desai, Dhananjay; Pavord, Ian D.; Wardlaw, Andrew J.; Pashley, Catherine H.

doi:10.1164/rccm.201001-0087oc

Cited by 225 publications

(225 citation statements)

References 31 publications

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“…Notably, however, our analysis identified a novel cluster characterized by asthma occurring in nonobese males who develop asthma in childhood and who have sensitivity to Alternaria. Male children frequently have sensitization to Alternaria, and epidemiologic studies suggest that, unlike other forms of male childhood asthma, it does not remit (42)(43)(44). Thus, adult males with asthma and Alternaria sensitivity may represent a cohort of males whose asthma persists from childhood.…”

Section: Discussionmentioning

confidence: 99%

A Large Subgroup of Mild-to-Moderate Asthma Is Persistently Noneosinophilic

McGrath

Icitovic

Boushey

et al. 2012

Am J Respir Crit Care Med

440

313

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Rationale: Airway eosinophilia is typical of asthma, and many controller treatments target eosinophilic disease. Asthma is clinically heterogeneous, however, and a subgroup of people with asthma do not have airway eosinophilia. The size of this subgroup is uncertain because prior studies have not examined repeated measures of sputum cytology to determine when people with asthma have intermittent versus persistent sputum eosinophila and when they are persistently noneosinophilic. Objectives: To determine the prevalence and clinical characteristics of the noneosinophilic asthma phenotype. Methods: We analyzed sputum cytology data from 995 subjects with asthma enrolled in clinical trials in the Asthma Clinical Research Network where they had undergone sputum induction and measures of sputum cytology, often repeatedly, and assessment of responses to standardized asthma treatments. Measurements and Main Results: In cross-sectional analyses, sputum eosinophilia (>2% eosinophils) was found in only 36% of subjects with asthma not taking an inhaled corticosteroid (ICS) and 17% of ICS-treated subjects with asthma; an absence of eosinophilia was noted frequently, even in subjects with asthma whose disease was suboptimally controlled. In repeated measures analyses of people with asthma not taking an ICS, 22% of subjects had sputum eosinophilia on every occasion (persistent eosinophilia); 31% had eosinophilia on at least one occasion (intermittent eosinophilia); and 47% had no eosinophilia on every occasion (persistently noneosinophilic). Two weeks of combined antiinflammatory therapy caused significant improvements in airflow obstruction in eosinophilic asthma, but not in persistently noneosinophilic asthma. In contrast, bronchodilator responses to albuterol were similar in eosinophilic and noneosinophilic asthma. Conclusions: Approximately half of patients with mild-to-moderate asthma have persistently noneosinophilic disease, a disease phenotype that responds poorly to currently available antiinflammatory therapy.Keywords: asthma; eosinophil; noneosinophilic; obesity; neutrophil Asthma is a common disease affecting people across the lifespan; the cost to US society is $56 billion annually (1). Airway eosinophilia is well-described in asthma (2-4), and currently available antiinflammatory treatments for asthma almost exclusively target eosinophilic airway inflammation (5, 6). Many people with asthma respond suboptimally to currently available eosinophil-directed treatments, however, most likely because they do not have airway eosinophilia (7-13).Increased attention is focusing on the clinical heterogeneity of asthma and the argument that failure to recognize and discover the underlying mechanisms of different asthma subtypes is a major limitation to progress (14). Continued uncertainly about the prevalence of eosinophilic versus noneosinophilic subtypes of asthma and about the relationship between airway eosinophilia and treatment responses relates to limitations in previous studies of these issues. The principal limitatio...

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Section: Discussionmentioning

confidence: 99%

A Large Subgroup of Mild-to-Moderate Asthma Is Persistently Noneosinophilic

McGrath

Icitovic

Boushey

et al. 2012

Am J Respir Crit Care Med

440

313

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“…Patients with severe asthma are also more commonly cosensitized to multiple fungi [32]. People with moderate to severe asthma who are sensitized to Aspergillus have impaired lung function, as shown by reduced FEV 1 , more severe airway obstruction, and the need for higher corticosteroid doses [99,100]. A 22% reduction in lung function was associated with fungal sensitization and fungus-positive sputum culture in patients with moderate to severe asthma [101].…”

Section: Asthmamentioning

confidence: 99%

“…The majority of recovered fungi were isolates of A fumigatus, although more than 20 other taxa were also detected [101]. Tissue damage and inflammation were also more frequent in Aspergillus-sensitized asthmatics, as more cases of bronchiectasis and higher eosinophil counts and IgE levels have been detected [99,100]. Culture of Aspergillus was significantly more frequent in patients with moderate-tosevere asthma who were IgE-sensitized to A fumigatus (63%) than nonsensitized asthmatics (31%) and healthy controls (7%) [100].…”

Section: Asthmamentioning

confidence: 99%

Allergic Fungal Airway Disease

Rick¹,

Woolnough²,

Pashley³

et al. 2016

J Investig Allergol Clin Immunol

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Fungi are ubiquitous and form their own kingdom. Up to 80 genera of fungi have been linked to type I allergic disease, and yet, commercial reagents to test for sensitization are available for relatively few species. In terms of asthma, it is important to distinguish between species unable to grow at body temperature and those that can (thermotolerant) and thereby have the potential to colonize the respiratory tract. The former, which include the commonly studied Alternaria and Cladosporium genera, can act as aeroallergens whose clinical effects are predictably related to exposure levels. In contrast, thermotolerant species, which include fungi from the Candida, Aspergillus, and Penicillium genera, can cause a persistent allergenic stimulus independent of their airborne concentrations. Moreover, their ability to germinate in the airways provides a more diverse allergenic stimulus, and may result in noninvasive infection, which enhances inflammation. The close association between IgE sensitization to thermotolerant filamentous fungi and fixed airflow obstruction, bronchiectasis, and lung fibrosis suggests a much more tissue-damaging process than that seen with aeroallergens. This review provides an overview of fungal allergens and the patterns of clinical disease associated with exposure. It clarifies the various terminologies associated with fungal allergy in asthma and makes the case for a new term (allergic fungal airway disease) to include all people with asthma at risk of developing lung damage as a result of their fungal allergy. Lastly, it discusses the management of fungirelated asthma. Key words: Thermotolerant fungi. Allergic fungal airway disease (AFAD). ABPA. SAFS. Asthma. Allergic fungal rhinosinusitis (AFRS). Immune responses. Diagnosis. Treatment. ResumenLos hongos son obicuos y forman su propio reino. Hasta 80 géneros de hongos han sido asociados con la enfermedad alérgica tipo I; sin embargo, los reactivos comerciales para testar las sensibilizaciones a los mismos, se encuentran disponibles para un número relativamente pequeño de especies. En cuanto al asma, es importante distinguir entre especies incapaces de crecer en temperatura ambiente y aquellas que son termotolerantes y que, por lo tanto, tienen una capacidad potencial para colonizar el tracto respiratorio. Los primeros, que incluyen los géneros comúnmente estudiados Alternaria y Cladosporium, pueden actuar como aeroalérgenos y sus efectos clínicos están relacionados con los niveles de exposición. En contraste, las especies termotolerantes, que incluyen hongos del género Candida, Aspergillus y Penicillium, pueden causar un estímulo alergénico persistente independiente de su concentración en el aire. Además, su capacidad para germinar en las vías aéreas da lugar a estímulos alergénicos más diversos y puede dar como resultado infecciones no invasivas que facilitan la inflamación. La estrecha asociación entre sensibilización dependiente de IgE a hongos filamentosos termotolerantes y la obstrucción del flujo aéreo, bronquiectasias y fib...

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“…São importantes alérgenos, e em grandes quantidades, podem afetar gravemente as pessoas asmáticas e com doenças respiratórias, pois, a exposição prolongada pode enfraquecer o sistema imunológico (Fairs et al, 2010).…”

Section: Introductionunclassified

Cladosporium spp: Morfologia, infecções e espécies patogênicas

2017

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ResumoO gênero Cladosporium spp compreende grande número de fungos dematiáceos com distribuição mundial e que estão entre os fungos de ambiente mais comuns. São frequentemente isolados como contaminantes, no entanto, algumas espécies são patogênicas e toxigênicas para os seres humanos, estando associados a infecções superficiais da pele e dos tecidos moles e incluem sepse disseminada com elevada mortalidade. Cladoporium spp são aero-alérgenos e causam graves doenças alérgicas do trato respiratório, bem como lesões intrabrônquicas. Atualmente, as espécies de Cladosporium spp de interesse médico associadas com doença humana são C. cladosporioides, C. herbarum, C. oxysporum e C. sphaerospermum. No caso de infecções por Cladosporium spp, a terapia é prolongada e varia de acordo com a síndrome clínica. Sendo essencial o conhecimento a cerca desse gênero, para melhor diagnóstico e tratamento adequado. Esta revisão de literatura teve como objetivo reunir informações sobre as características gerais e morfológicas, patologias, aspectos clínicos e principais espécies patogênicas das infecções causadas por esse gênero. Palavras-chave: Feo-hifomicoses, Fungos dematiáceos, Micoses oportunistas. Cladosporium spp: Morphology, infections and pathogenic species AbstractThe genus Cladosporium spp comprises a large number of dematiaceous fungi with a world-wide distribution and are among the most common air-borne fungi. They are frequently isolated contaminants and some species are pathogenic and toxigenic to humans and are associated with superficial infections of the skin and soft tissues, including disseminated sepsis with high mortality. In addition, Cladoporium spp. are aero-allergens and cause serious allergic diseases of the respiratory tract, as well as intrabronchial lesions. Currently, the Cladosporium spp species of medical interest associated with human disease are C. cladosporioides, C. herbarum, C. oxysporum and C. sphaerospermum. In the case of Cladosporium spp infections, the therapy is prolonged and varies according to the clinical syndrome. Knowledge about this genre is essential for better diagnosis and appropriate treatment. This literature review to gather information about the general and morphological characteristics, pathologies, clinical aspects and main pathogenic species of the infections caused by this genus.

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IgE Sensitization toAspergillus fumigatusIs Associated with Reduced Lung Function in Asthma

Cited by 225 publications

References 31 publications

A Large Subgroup of Mild-to-Moderate Asthma Is Persistently Noneosinophilic

A Large Subgroup of Mild-to-Moderate Asthma Is Persistently Noneosinophilic

Allergic Fungal Airway Disease

Cladosporium spp: Morfologia, infecções e espécies patogênicas

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