A pilot randomized trial of nebulized amphotericin in patients with allergic bronchopulmonary aspergillosis

Ram, Babu; Aggarwal, Ashutosh N.; Dhooria, Sahajal; Sehgal, Inderpaul Singh; Garg, Mandeep; Behera, Digambar; Chakrabarti, Arunaloke; Agarwal, Ritesh

doi:10.3109/02770903.2015.1127935

Cited by 56 publications

(35 citation statements)

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“…While itraconazole is widely used as an adjunct to steroid therapy, azole resistance [10] is now a potential problem and there are no large studies available showing a direct benefit of using antifungals in the management of ABPA in patients with CF or any steroid-sparing effect. A case report and a small study of nebulised amphotericin B (AMB) in this condition suggests that nebulised liposomal AMB could represent a possible strategy in ABPA management in CF patients [11, 63], and in asthmatics with ABPA, a further small study suggests that nebulised amphotericin may be beneficial in decreasing the frequency of exacerbations in patients with ABPA complicating asthma [65]. Again, in asthmatics, ABPA has been shown to progress to invasive pulmonary aspergillosis which is a fulminant disease, and in a recent systematic review, only three of the nine patients survived [44].…”

Section: Introductionmentioning

confidence: 99%

Pathogenesis of Fungal Infections in Cystic Fibrosis

Williams

Ranjendran

Ramage

2016

Curr Fungal Infect Rep

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For a long time, the microbiology of cystic fibrosis has been focussed on Pseudomonas aeruginosa and associated Gram-negative pathogens. An increasing body of evidence has been compiled demonstrating an important role for moulds and yeasts within this complex patient group. Whether or not fungi are active participants, spectators or transient passersby remain to be elucidated. However, functionally, they do appear to play a contributory role in pathogenesis, albeit we do not know if this is a direct or indirect effect. The following review examines some of the key evidence for the role of fungi in CF pathogenesis.

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Section: Introductionmentioning

confidence: 99%

Pathogenesis of Fungal Infections in Cystic Fibrosis

Williams

Ranjendran

Ramage

2016

Curr Fungal Infect Rep

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“…A pilot randomised controlled trial involving twenty one subjects with ABPA who were randomised to receive either nebulised amphotericin B plus nebulised budesonide or nebulised budesonide alone reported significantly lower exacerbations in the amphotericin B arm after 1 year . Interestingly, three patients developed bronchospasm after the first dose of nebulised amphotericin B;however, subsequent doses were well tolerated and none of the study drugs were discontinued in all 21 patients . There have been a few case reports describing the use of amphotericin B in the setting of ABPA .…”

Section: Discussionmentioning

confidence: 99%

“…We found high intolerance rates among this cohort who received Interestingly, three patients developed bronchospasm after the first dose of nebulised amphotericin B;however, subsequent doses were well tolerated and none of the study drugs were discontinued in all 21 patients. 19 There have been a few case reports describing the use of amphotericin B in the setting of ABPA. 20 Laoudi and colleagues reported good clinical, biological and functional response following a combination of nebulised amphotericin B (at 5 mg twice a day) with nebulised budesonide for treatment of ABPA in three patients with cystic fibrosis aged 7, 12 and 13 years of age.…”

Section: Discussionmentioning

confidence: 99%

“…14 There has been sustained interest in defining the role of nebulised amphotericin in the treatment of ABPA. A pilot randomised controlled trial involving twenty one subjects with ABPA who were randomised to receive either nebulised amphotericin B plus nebulised budesonide or nebulised budesonide alone reported significantly lower exacerbations in the amphotericin B arm after 1 year 19.…”

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An evaluation of nebulised amphotericin B deoxycholate (Fungizone^®) for treatment of pulmonary aspergillosis in the UK National Aspergillosis Centre

Otu

Langridge

Denning

2019

Mycoses

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Summary Antifungal treatment options for allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitisation (SAFS) are largely limited to itraconazole based on the outcome of randomised controlled trials. It is unclear if nebulised amphotericin B deoxycholate (Fungizone®) is a viable therapeutic option. We evaluated the safety and efficacy of nebulised Fungizone® in the long‐term treatment of various forms of pulmonary aspergillosis. We assessed the records of 177 patients with various forms of pulmonary aspergillosis attending the National Aspergillosis Centre in Manchester who had received Fungizone®. Patients first received a challenge test with nebulised Fungizone® in hospital with spirometry pre/post‐Fungizone® and nebulised salbutamol given pre‐Fungizone®. Tolerability and changes in Aspergillus IgE, Aspergillus IgG and total IgE were evaluated. Sixty‐six per cent (117/177) were able to tolerate the test dose of Fungizone® and in all cases, the reason for discontinuation of the first test dose was worsening breathlessness. Twenty six (21%) stopped therapy within 4‐6 weeks, and the commonest reason cited for discontinuation of therapy was increased breathlessness, hoarseness and cough. Eighteen (10.2%) patients continued the Fungizone® for >3 months of which 5 (27.8%) recorded an improvement in total IgE, Aspergillus‐specific IgE and Aspergillus IgG. Eleven had ABPA, four had SAFS, two had Aspergillus bronchitis and one had Aspergillus sensitisation with cavitating nodules. Among these 18 patients, sputum fungal culture results went from positive to negative in five patients, became positive in one patient, remained positive in three patients, and remained negative in seven patients. Nebulised Fungizone® appears to be a poorly tolerated treatment for pulmonary Aspergillosis with high dropout rates. There appears to be both clinical and serological benefits following sustained treatment with nebulised Fungizone® in some patients.

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“…Asthmatics without ASA or ABPA (unsensitised asthma or UA) are usually managed with inhaled corticosteroids and bronchodilators. Whereas patients with ABPA additionally require oral glucocorticoids or antifungal azoles, 7‐9 itraconazole has been found to benefit patients with severe ASA 2 . There is an unmet need for investigations that can reliably differentiate ABPA from ASA.…”

Section: Introductionmentioning

confidence: 99%

The utility of the basophil activation test in differentiating asthmatic subjects with and without allergic bronchopulmonary aspergillosis

Prasad

Muthu

Sehgal

et al. 2020

Mycoses

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Summary Background Asthma with Aspergillus sensitisation (ASA) and allergic bronchopulmonary aspergillosis (ABPA) are distinct clinical conditions, with different management strategies. Objective To determine the utility of the basophil activation test (BAT) in differentiating between asthmatic subjects with and without ABPA. Methods We performed the BAT using flow cytometry for the basophil activation markers CD63, CD193, and CD203c in consecutive subjects with unsensitised asthma (UA), ASA and ABPA. The BAT was performed unstimulated (baseline) and after stimulation with peanut and Aspergillus fumigatus antigens. Stimulation indices (SI) for CD63, CD193 and CD203c were compared between the study groups. Results We enrolled 82 (UA [n = 25], ASA [n = 25], ABPA [n = 32]) subjects. Only those subjects without peanut sensitisation on serological testing were included in further analyses (n = 50). The receiver operating characteristic analysis of SI for CD63, CD193 and CD203c for the diagnosis of ABPA vs other asthmatics (UA and ASA) showed an area under the curve of 0.577, 0.317 and 0.625, respectively. The SI CD203c at a cut‐off of 1.2 (sensitivity 50.0%, specificity 88.9%) and the SI CD63 at a cut‐off of 1.3 (sensitivity 42.9%, specificity 91.7%) also had limited utility for the diagnosis of ABPA. Conclusion The BAT cannot be used as a diagnostic test in distinguishing ABPA complicating asthma from ASA and UA.

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A pilot randomized trial of nebulized amphotericin in patients with allergic bronchopulmonary aspergillosis

Cited by 56 publications

References 53 publications

Pathogenesis of Fungal Infections in Cystic Fibrosis

Pathogenesis of Fungal Infections in Cystic Fibrosis

An evaluation of nebulised amphotericin B deoxycholate (Fungizone^®) for treatment of pulmonary aspergillosis in the UK National Aspergillosis Centre

The utility of the basophil activation test in differentiating asthmatic subjects with and without allergic bronchopulmonary aspergillosis

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A pilot randomized trial of nebulized amphotericin in patients with allergic bronchopulmonary aspergillosis

Cited by 56 publications

References 53 publications

Pathogenesis of Fungal Infections in Cystic Fibrosis

Pathogenesis of Fungal Infections in Cystic Fibrosis

An evaluation of nebulised amphotericin B deoxycholate (Fungizone®) for treatment of pulmonary aspergillosis in the UK National Aspergillosis Centre

The utility of the basophil activation test in differentiating asthmatic subjects with and without allergic bronchopulmonary aspergillosis

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An evaluation of nebulised amphotericin B deoxycholate (Fungizone^®) for treatment of pulmonary aspergillosis in the UK National Aspergillosis Centre