The Effect of Aspergillus fumigatus Infection on Vitamin D Receptor Expression in Cystic Fibrosis

Coughlan, Catherine A.; Chotirmall, Sanjay H.; Renwick, J. A. A.; Hassan, Tidi; Low, Teck Boon; Bergsson, Gudmundur; Eshwika, Ahmed; Bennett, Kathleen; Dunne, Katie; Greene, Catherine M.; Gunaratnam, Cedric; Kavanagh, Kevin; Logan, P M; Murphy, Philip G.; Reeves, Emer P.; McElvaney, Noel G.

doi:10.1164/rccm.201203-0478oc

Cited by 93 publications

(64 citation statements)

References 37 publications

(43 reference statements)

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“…A. fumigatus polymerase chain reaction, a more sensitive method for its detection compared to culture alone, was positive in 70% of severe asthma with Aspergillus sensitization (SAAS) patients 40. Subgroup analysis revealed that A. fumigatus polymerase chain reaction became negative following treatment with itraconazole,40 a finding which was also illustrated in CF 39. Taken together, it is therefore plausible that antifungal therapy may be of benefit in patients with SAFS or SAAS; however, due to different methodologies in prior studies (including patient selection, duration of antifungal treatment and end points), strong conclusions cannot be drawn 41–44…”

Section: Discussionmentioning

confidence: 95%

“…There is a growing body of evidence to suggest a significant degree of airway colonization in patients sensitized to A. fumigatus ; however, importantly, colonization by this thermotolerant fungus is unrelated to its allergic manifestations 38,39. Importantly, ~60% of patients with moderate to severe asthma and IgE sensitization to A. fumigatus have positive sputum culture 7…”

Section: Discussionmentioning

confidence: 99%

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Sensitization to Aspergillus 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: 95%

Section: Discussionmentioning

confidence: 99%

Sensitization to Aspergillus species is associated with frequent exacerbations in severe asthma

Goh¹,

Yii²,

Lapperre³

et al. 2017

JAA

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“…Classifying patients into proposed subgroups and delineating those with ABPA from those who are AF sensitised, AF non-sensitised and those with aspergillus bronchitis [11]. Some studies have provided valuable insights into how AF may influence the progression of CF lung disease [9, 12, 13] however the true extent of the impact on disease progression is unknown.…”

Section: Introductionmentioning

confidence: 99%

Co-colonisation with Aspergillus fumigatus and Pseudomonas aeruginosa is associated with poorer health in cystic fibrosis patients: an Irish registry analysis

et al. 2017

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BackgroundPulmonary infection is the main cause of death in cystic fibrosis (CF). Aspergillus fumigatus (AF) and Pseudomonas aeruginosa (PA) are the most prevalent fungal and bacterial pathogens isolated from the CF airway, respectively. Our aim was to determine the effect of different colonisation profiles of AF and PA on the clinical status of patients with CF.MethodsA retrospective analysis of data from the Cystic Fibrosis Registry of Ireland from 2013 was performed to determine the effect of intermittent and persistent colonisation with AF or PA or co-colonisation with both microorganisms on clinical outcome measures in patients with CF. Key outcomes measured included forced expiratory volume in one second (FEV1), number of hospitalisations, respiratory exacerbations and antimicrobials prescribed, and complications of CF, including CF related diabetes (CFRD) and allergic bronchopulmonary aspergillosis (ABPA).ResultsThe prevalence of AF and PA colonisation were 11% (5% persistent, 6% intermittent) and 31% (19% persistent, 12% intermittent) in the Irish CF population, respectively. Co-colonisation with both pathogens was associated with a 13.8% reduction in FEV1 (p = 0.016), higher levels of exacerbations (p = 0.042), hospitalisations (p = 0.023) and antimicrobial usage (p = 0.014) compared to non-colonised patients and these clinical outcomes were comparable to those persistently colonised with PA. Intermittent and persistent AF colonisation were not associated with poorer clinical outcomes or ABPA. Patients with persistent PA had a higher prevalence of CFRD diagnosis (p = 0.012).ConclusionsCF patients co-colonised with AF and PA had poor clinical outcomes comparable to patients persistently colonised with PA, emphasising the clinical significance of co-colonisation with these microorganisms.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-017-0416-4) contains supplementary material, which is available to authorized users.

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“…Simultaneous production of Th2 cytokines is concurrently promoted including IL-4, IL-5, and IL-10 in this setting [154, 162]. Our group and others have shown that elevated Th2 cytokine levels correlate with A. fumigatus positivity in people with CF (IL-5 and IL-13) and the development of IPA with particularly unfavorable outcomes in immunocompromised patients (IL-10) [70, 163]. In addition, Th2-associated cytokines suppress ROS production and hyphal damage of the fungi [164].…”

Section: Cytokines In the Innate Pulmonary Defense Against Aspergimentioning

confidence: 98%

“…Treatment with itraconazole decreases BAL gliotoxin concentrations, restoring VDR expression. Concurrently, a diminished systemic level of the Th2 cytokines IL-5 and IL-13 is detectable with concomitant improvement in clinical and radiological parameters [70]. Despite effective treatment options, an early diagnosis of ABPA with rapid initiation of therapy is key to prevent irreversible pulmonary damage irrespective of the underlying pulmonary condition [71].…”

Section: Allergic Bronchopulmonary Aspergillosis (Abpa)mentioning

confidence: 99%

Aspergillus-Associated Airway Disease, Inflammation, and the Innate Immune Response

Chotirmall

Al‐Alawi

Mirković

et al. 2013

BioMed Research International

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102

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Aspergillus moulds exist ubiquitously as spores that are inhaled in large numbers daily. Whilst most are removed by anatomical barriers, disease may occur in certain circumstances. Depending on the underlying state of the human immune system, clinical consequences can ensue ranging from an excessive immune response during allergic bronchopulmonary aspergillosis to the formation of an aspergilloma in the immunocompetent state. The severest infections occur in those who are immunocompromised where invasive pulmonary aspergillosis results in high mortality rates. The diagnosis of Aspergillus-associated pulmonary disease is based on clinical, radiological, and immunological testing. An understanding of the innate and inflammatory consequences of exposure to Aspergillus species is critical in accounting for disease manifestations and preventing sequelae. The major components of the innate immune system involved in recognition and removal of the fungus include phagocytosis, antimicrobial peptide production, and recognition by pattern recognition receptors. The cytokine response is also critical facilitating cell-to-cell communication and promoting the initiation, maintenance, and resolution of the host response. In the following review, we discuss the above areas with a focus on the innate and inflammatory response to airway Aspergillus exposure and how these responses may be modulated for therapeutic benefit.

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The Effect of Aspergillus fumigatus Infection on Vitamin D Receptor Expression in Cystic Fibrosis

Cited by 93 publications

References 37 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

Co-colonisation with Aspergillus fumigatus and Pseudomonas aeruginosa is associated with poorer health in cystic fibrosis patients: an Irish registry analysis

Aspergillus-Associated Airway Disease, Inflammation, and the Innate Immune Response

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