Fungal Sensitization Is Associated with Increased Risk of Life-Threatening Asthma

Medrek, Sarah; Kao, Christina C.; Yang, Danny H.; Hanania, Nicola A.; Parulekar, Amit

doi:10.1016/j.jaip.2016.11.015

Cited by 42 publications

(29 citation statements)

References 30 publications

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“…Our study adds to work reporting the key association between fungal sensitization, frequent exacerbations and life-threatening asthma in a population with severe asthma as defined by medication requirements (GINA step 4 or 5) 23. While O’Driscoll et al6 and others24,25 had reported the association between fungal sensitization and multiple hospital admissions, patients in their study had differing asthma severities (British Thoracic Society guidelines steps 1–4),26 making conclusions difficult to draw, particularly with regard to severe asthma.…”

Section: Discussionmentioning

confidence: 91%

Sensitization to <em>Aspergillus </em>species is associated with frequent exacerbations in severe asthma

Goh¹,

Yii²,

Lapperre³

et al. 2017

JAA

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BackgroundSevere asthma is a largely heterogeneous disease with varying phenotypic profiles. The relationship between specific allergen sensitization and asthma severity, particularly in Asia, remains unclear. We aim to study the prevalence of specific allergen sensitization patterns and investigate their association with outcomes in a severe asthma cohort in an Asian setting.MethodsWe conducted a cross-sectional study of patients receiving step 4 or 5 Global Initiative for Asthma treatment. Univariate and multivariate analyses were performed to assess the association between sensitization to a specific identifiable allergen by skin prick test (SPT) and uncontrolled asthma (defined in our study as the use of ≥2 steroid bursts or hospitalization in the past year, a history of near-fatal asthma or evidence of airflow obstruction on spirometry).ResultsTwo hundred and six severe asthma patients (mean age 45±17 years, 99 [48.1%] male) were evaluated. Of them, 78.2% had a positive SPT to one or more allergens. The most common allergen to which patients were sensitized was house dust mites (Blomia tropicalis, Dermatophagoides pteronyssinus and Dermatophagoides farinae). Also, 11.7% were sensitized to Aspergillus species. On multivariate analysis, Aspergillus sensitization was associated with uncontrolled asthma (odds ratio 6.07, 95% confidence interval 1.80–20.51). In particular, Aspergillus sensitization was independently associated with the use of ≥2 steroid bursts in the past year (odds ratio 3.05, 95% confidence interval 1.04–8.95). No similar associations of uncontrolled asthma with sensitization to any other allergens were found.ConclusionHigh allergen, specifically Aspergillus sensitization was observed in the Asian population with severe asthma by SPT. Aspergillus sensitization was specifically associated with frequent exacerbations and a greater corticosteroid requirement. An improved understanding of the severe asthma with Aspergillus sensitization phenotype is warranted, which is likely a subgroup of severe asthma with fungal sensitization.

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Section: Discussionmentioning

confidence: 91%

Sensitization to <em>Aspergillus </em>species is associated with frequent exacerbations in severe asthma

Goh¹,

Yii²,

Lapperre³

et al. 2017

JAA

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“…Studies have shown that virally mediated inflammatory pathways (acute or quiescent) are implicated in near-fatal asthma and occur in as much as 50% of patients [3]. The association of fungal isolates with near-fatal asthma is a novel finding but consistent with the association of these organisms in acute asthma [4,5]. This finding suggests the possibility of defective antifungal and/or antiviral immune pathways in these patients.…”

Section: Inflammatory and Microbiological Associations With Near-fatamentioning

confidence: 72%

Inflammatory and microbiological associations with near-fatal asthma requiring extracorporeal membrane oxygenation

et al. 2020

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Extracorporeal membrane oxygenation (ECMO) has developed as a critical tool permitting lung protection in severe respiratory failure. Its use was largely confined to acute respiratory distress syndrome [1]; however, as technology has advanced, it is now used in a range of respiratory diseases, including asthma. In the context of near-fatal asthma exacerbations, ECMO provides a management strategy for difficult-to-ventilate patients who would otherwise be unlikely to survive. Importantly, in asthma, traditional mechanical ventilation strategies can be associated with volutrauma and barotrauma due to the high pressures required in the presence of severe bronchospasm [2]. To date, there is a paucity of data for ECMO use in acute asthma and it is unknown whether specific clinical or inflammatory characteristics are associated with the need for ECMO.We performed a retrospective review of all adult asthmatics requiring mechanical ventilatior and/or ECMO for near-fatal asthma admitted to our single large tertiary hospital between 2011 and 2016. Clinical and demographic data including ventilator parameters, biochemical and immunological indices, and microbiology isolates were recorded. We compared patients requiring ECMO with patients requiring conventional mechanical ventilation only, to identify any factors that were significantly associated with the need for ECMO.All data, including demographic, physiological and laboratory data, utilised in this study were collected as part of routine acute asthma care in our intensive care unit (ICU) and tertiary severe asthma centre. No additional ethical approval was required. 76 patients (46% female, mean±SD age 39±16 years) with a primary diagnosis of acute asthma associated with the clinical features of a near-fatal exacerbation requiring ECMO or mechanical ventilation were included in this analysis. 22 patients (29%) required ECMO and 54 (71%) required conventional mechanical ventilation only. Compared to patients requiring mechanical ventilation, those requiring ECMO were more likely to be female (72% versus 35%, p=0.003) and younger (mean age 30±14 versus 43±15 years, p=0.002). Prior to intervention, patients requiring ECMO had a higher total white cell count (15.5±6.4 versus 12.2±4.4×10 9 L −1 , p=0.013), were more acidotic (mean pH 7.12±0.17 versus 7.27±0.09, p<0.001) and hypercapnic (mean carbon dioxide tension 12.8±4.1 versus 7.26±2.1 kPa, p<0.001). No statistically significant differences in oxygenation (oxygen tension), C-reactive protein (CRP), total serum immunoglobulin E or blood eosinophil counts at the time of admission to the ICU were observed between groups. Patients requiring ECMO were more likely to have a positive fungal isolate from bronchoalveolar lavage (BAL) fluid than those requiring mechanical ventilation (36% versus 10%, p=0.026). Rhinovirus was also identified in a greater proportion of respiratory isolates in the ECMO cohort compared to mechanical ventilation (27.2% versus 6.9%, p=0.048) with a strong trend towards a greater likelihood of any respira...

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“…This finding is supported by Oluwole et al [45], who demonstrated that high mold levels in children's play areas are associated with current asthma (adjusted OR = 3.0, 95% CI (1.11-8.0)). Furthermore, additional studies have demonstrated that sensitization to Alternaria increases with higher mold concentration exposure and may lead to a risk of hospitalization, especially in the urban setting [46][47][48][49].…”

Section: Endotoxinmentioning

confidence: 99%

The Impact of Ambient Environmental Exposures to Microbial Products on Asthma Outcomes from Birth to Childhood

Howard

Orhurhu

Huang

et al. 2019

Curr Allergy Asthma Rep

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Purpose of Review Asthma is a chronic respiratory condition with increasing domestic and worldwide prevalence that burdens individuals and the healthcare system with high costs associated with long-term treatments and acute emergency room (ER) visits. It can be triggered by ambient microbes, including bacteria, viruses, and fungi. In this review, we examine the outcomes of asthma patients in relation to environmental exposures to ambient microbe products, focusing on whether exposure leads to asthma development from birth to childhood and if particular microbes are associated with worsened asthma exacerbations. Recent Findings Bacterial endotoxin is more prominent in homes with pets and may cause cytokine cascades that lead to asthma exacerbation. However, some studies have demonstrated a protective effect with early exposure. Patients with positive Aspergillus skin testing are more prone to moderate-severe or severe-uncontrolled asthma. Fungal sensitization is also associated with earlier onset of asthma and demonstrates a dose-dependent relationship of symptom severity and duration. Among viruses, rhinovirus has the greatest association with decreased lung function, severe asthma, and asthma-related hospital admissions. Distribution of microbial products and associated asthma symptoms depends on the geographical climate. Genetic variations among individuals also mitigate the effects of microbial products on asthma development and symptom severity. Summary Microbial products of bacteria, fungi, and viruses are associated with the development of asthma, more severe asthma symptoms, and worse outcomes. However, some early exposure studies have also demonstrated a protective effect. Bacterial and fungal products are related to decreased lung function and earlier onset of asthma. Viral products are related to asthma-associated hospital admissions; and the climate and patient genetics can also temper or intensify the relationships between microbial products, asthma development, and asthma symptom severity. Further research should focus on the effects of early microbe exposure and its interaction with human immune systems and asthma-related outcomes.

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Fungal Sensitization Is Associated with Increased Risk of Life-Threatening Asthma

Cited by 42 publications

References 30 publications

Sensitization to <em>Aspergillus </em>species is associated with frequent exacerbations in severe asthma

Sensitization to <em>Aspergillus </em>species is associated with frequent exacerbations in severe asthma

Inflammatory and microbiological associations with near-fatal asthma requiring extracorporeal membrane oxygenation

The Impact of Ambient Environmental Exposures to Microbial Products on Asthma Outcomes from Birth to Childhood

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