Therapy For Allergic Bronchopulmonary Aspergillosis Research Articles

Expert consensus on the diagnosis and treatment of allergic bronchopulmonary aspergillosis(2022 update)

As an allergic lung disease caused by Aspergillus species, allergic bronchopulmonary aspergillosis(ABPA) is manifested by asthma and recurrent lung infiltrates, often with signs of bronchiectasis. ABPA is not uncommon, but under-diagnosis/misdiagnosis and inappropriate management are common in clinical practice, due to the varied manifestations, inconsistent diagnostic criteria, and the need of complicated laboratory studies. To improve the diagnosis and treatment of ABPA, experts of the Asthma Group of Chinese Thoracic Society proposed an expert consensus on the diagnosis and treatment of ABPA in 2017 (1 st Edition). Its publication has been well received by the Chinese physicians, and promoted the appropriate management of the disease. In the past 5 years, advances have been made in the investigation into the mechanisms, and in the diagnosis and therapy of ABPA, including novel insight into the pathogenesis, more studies of the diagnostic criteria, and more evidence on the efficacy of glucocorticoid, antifungal and/or biologic therapies. Based on new evidence and the clinical practice in China, experts of the Asthma Group of Chinese Thoracic Society updated the consensus.

Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus, and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, and their many side effects are well-documented. A group of compounds, the azoles, have activity against A fumigatus, and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been used in aerosolised form to treat invasive infection with A fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. This is an update of a previously published review. The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis: 1. improve clinical status compared to placebo or standard therapy (no placebo); and 2. do not have unacceptable adverse effects. If benefit was demonstrated, we planned to assess the optimal type, duration, and dose of antifungal therapy. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, and abstract books of conference proceedings. Date of the most recent search of the Group's Trials Register was 28 September 2021. We searched ongoing trials registries, most recently on 11 March 2022. Earlier, we also approached pharmaceutical companies regarding possible unpublished trials. Published or unpublished randomised controlled trials, in which antifungal treatments were compared to either placebo or no treatment, or where different doses of the same treatment were used in the treatment of ABPA in people with cystic fibrosis. The searches identified six trials; none of which met the inclusion criteria for the review. We included no completed randomised controlled trials. There is currently one ongoing trial, which we may find eligible for a future update. At present, there are no randomised controlled trials that evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis, although one trial is currently ongoing. Trials with clear outcome measures are needed to properly evaluate the use of corticosteroids in people with ABPA and cystic fibrosis.

Anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review. To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 09 September 2021. We searched two ongoing trial registries (Clinicaltrials.gov and the WHO trials platform). Date of latest search: 16 August 2021. Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager. Only one study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine(66.67%) and one out of five(20%) participants in omalizumab group and placebo group respectively. There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.

Optimization of antimicrobials in the treatment of cystic fibrosis pulmonary exacerbations: II. Therapies for allergic bronchopulmonary aspergillosis.

This review is the second article in the State-of-the-Art series and aims to evaluate medications used in the treatment of allergic bronchopulmonary aspergillosis (ABPA) in pediatric and adult patients with cystic fibrosis (CF). ABPA is one of several organisms that are found in the airways of CF patients. This review provides an evidence-based summary of pharmacokinetic (PK)/pharmacodynamic (PD), tolerability, and efficacy studies of medications including corticosteroids, amphotericin B, azole antifungals (isavuconazole, itraconazole, posaconazole, and voriconazole), and a monoclonal antibody omalizumab in the treatment of ABPA and identifies areas where further study is warranted.

Molecularly targeted therapy for allergic bronchopulmonary aspergillosis

Molecularly targeted therapy for allergic bronchopulmonary aspergillosis

Anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review. To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 29 September 2017.We searched two ongoing trial registries (Clinicaltrials.gov and the WHO trials platform). Date of latest search: 24 January 2018. Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager. Only one study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine(66.67%) and one out of five(20%) participants in omalizumab group and placebo group respectively. There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.

Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, their many side effects are well-documented. A group of compounds, the azoles, have activity against Aspergillus fumigatus and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been employed in aerosolised form to treat invasive infection with Aspergillus fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. This is an update of a previously published review. The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis:1. improve clinical status compared to placebo or standard therapy (no placebo);2. do not have unacceptable adverse effects.If benefit was demonstrated, we aimed to assess the optimal type, duration and dose of antifungal therapy. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings.In addition, pharmaceutical companies were approached.Date of the most recent search of the Group's Trials Register: 29 September 2016. Published or unpublished randomised controlled trials, where antifungal treatments have been compared to either placebo or no treatment, or where different doses of the same treatment have been used in the treatment of ABPA in people with cystic fibrosis. Four trials were identified by the searches; none of which was judged eligible for inclusion in the review. No completed randomised controlled trials were included. At present, there are no randomised controlled trials to evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis, although trials in people who do not have cystic fibrosis have shown clinical and serological evidence of improvement and a reduction in the use of corticosteroids with no increase in adverse effects. Trials with clear outcome measures are needed to properly evaluate this potentially useful treatment for cystic fibrosis.

Anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review. To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 27 July 2015.We searched the ongoing trial registry clinicaltrials.gov for any ongoing trials. Latest search for clinicaltrials.gov: 23 October 2015. Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager. Only one study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine(66.67%) and one out of five(20%) participants in omalizumab group and placebo group respectively. There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.

Omalizumab, an additional therapy for allergic bronchopulmonary aspergillosis

Omalizumab, an additional therapy for allergic bronchopulmonary aspergillosis

137 Omalizumab therapy for allergic bronchopulmonary aspergillosis patients with cystic fibrosis

Objectives Allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) is characterized by an elevated total serum immunoglobulin E (IgE) level and the presence of IgE antibodies directed against Aspergillus fumigatus antigens. Long term treatment with oral corticosteroids can result in serious adverse effects. As a result, alternative therapies have been sought. One such therapy uses the humanized recombinant anti-IgE monoclonal antibody omalizumab. Method Here we present the clinical profile of six children treated with omalizumab. Monthly omalizumab therapy has been used to six patients with ABPA and CF. Four patients had experienced adverse effects related to long-term use of corticosteroids and two patients had no response to steroid therapy prior to omalizumab. Results Omalizumab treatment was related to significant reduction of Ig E (p = 0.043) and improvement in symptoms of all patients. Corticosteroids were reduced after the omalizumab initiation of one to three months later. However there were no significant difference between the radiological findings and lung function tests (FEV1%) (p = 0.68) after the treatment. The mean duration of omalizumab therapy was 9 months (3–13 months). Conclusion Steroid-sparing effects of omalizumab have been previously reported in patients with ABPA and allergic bronchial asthma, but conflicting reports exist in the CF literature. Here; symptoms improved, FEV1 stability was achieved and clear reductions in IgE with omalizumab therapy were demonstrated. Therefore, omalizumab may be an alternative therapy for ABPA in CF patients who fail to respond to systemic corticosteroids or have serious adverse effects.

Pattern recognition pathways leading to a Th2 cytokine bias in allergic bronchopulmonary aspergillosis patients.

Allergic bronchopulmonary aspergillosis (ABPA) is characterised by an exaggerated Th2 response to Aspergillus fumigatus, but the immunological pathways responsible for this effect are unknown. The aim of this study was to decipher the pattern recognition receptors (PRRs) and cytokines involved in the Aspergillus-specific Th2 response and to study Aspergillus-induced responses in healthy controls and ABPA patients. Peripheral blood mononuclear cells (PBMCs) were stimulated with heat-killed Aspergillus conidia, various other pathogens, or PRR ligands. PRRs and cytokine pathways were blocked with PRR-blocking reagents, anti-TNF (Etanercept or Adalimumab), IL-1Ra (Anakinra) or IFNγ (IFN-gamma). ELISA and FACS were used to analyse cytokine responses. Aspergillus was the only pathogen that stimulated the Th2 cytokines IL-5 and IL-13, while Gram-negative bacteria, Gram-positive bacteria, Candida albicans, chitin, β-glucan or Toll-like receptor (TLR) ligands did not. Depletion of CD4(+) cells abolished IL-13 production. Blocking complement receptor 3 (CR3) significantly reduced IL-5 and IL-13, while blocking TLR2, TLR4 or dectin-1 had no effect. ABPA patients displayed increased Aspergillus-induced IL-5 and IL-13 and decreased IFNγ production compared with healthy controls. All biological agents tested showed the capability to inhibit Th2 responses, but also decreased Aspergillus-induced IFNγ. Aspergillus conidia are unique in triggering Th2 responses in human PBMCs, through a CR3-dependent pathway. ABPA patients display a significantly increased Aspergillus-induced Th2/Th1 ratio that can be modulated by biologicals. These data provide a rationale to explore IFNγ therapy in ABPA as a corticosteroid-sparing treatment option, by dampening Th2 responses and supplementing the IFNγ deficiency at the same time.

Antifungals in severe asthma.

Despite guideline-based treatment, many patients with severe asthma continue to have uncontrolled disease. Fungal allergy is being increasingly recognized in the pathogenesis of severe asthma. Limited data exist on the approach to treatment of fungal asthma. This review summarizes existing evidence on the use of antifungal agents in allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS), and highlights needed areas of future investigation. Recent studies evaluating oral triazole therapy in ABPA appear to support triazole use in a carefully considered clinical setting, whereas studies assessing triazole use in SAFS have yielded mixed results. Despite early encouraging findings that oral triazole use may improve asthma symptoms, stabilize lung function, decrease inhaled and systemic corticosteroid requirements, and alter serum biomarkers, overall data are limited. Appropriate patient selection, as well as choice of the optimal drug, dose, frequency, and duration of therapy, remains poorly defined. The role of antifungal therapy in severe asthma remains unclear. Early studies have suggested a possible benefit of some antifungal agents, such as oral triazoles in ABPA and SAFS; however, routine clinical use of these agents in severe asthma without ABPA is not currently recommended. Further research is needed to better delineate the potential utility of antifungal medications in severe asthma and identify the asthma populations who benefit from such treatment.

Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, their many side effects are well-documented. A group of compounds, the azoles, have activity against Aspergillus fumigatus and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been employed in aerosolised form to treat invasive infection with Aspergillus fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis:1. improve clinical status compared to placebo or standard therapy (no placebo);2. do not have unacceptable adverse effects.If benefit was demonstrated, we aimed to assess the optimal type, duration and dose of antifungal therapy. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings.In addition, pharmaceutical companies were approached.Date of the most recent search of the Group's Trials Register: 17 March 2014. Published or unpublished randomised controlled trials, where antifungal treatments have been compared to either placebo or no treatment, or where different doses of the same treatment have been used in the treatment of ABPA in people with cystic fibrosis. Four trials were identified by the searches; none of which was judged eligible for inclusion in the review. No completed randomised controlled trials were included. At present, there are no randomised controlled trials to evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis, although trials in people who do not have cystic fibrosis have shown clinical and serological evidence of improvement and a reduction in the use of corticosteroids with no increase in adverse effects. Trials with clear outcome measures are needed to properly evaluate this potentially useful treatment for cystic fibrosis.

Anti-IgE therapy for allergic bronchopulmonary aspergillosis

Allergic bronchopulmonary aspergillosis (ABPA) is a severe type of asthma. Some cases are resistant to treatment, even with regular use of antiasthmatic drugs and antifungal agents. The diagnosis of ABPA was made in a 40-year-old patient with ABPA according to the Rosenberg-Patterson criteria. Symptoms were not controlled despite regular use of antiasthmatic drugs, daily systemic steroids, and antifungal agents. Omalizumab, administered in an attempt to stabilize these uncontrolled symptoms, was effective with no adverse events. Our experience suggests omalizumab is a potential candidate drug for controlling steroid-dependent ABPA.

Omalizumab therapy for allergic bronchopulmonary aspergillosis in children with cystic fibrosis: A synthesis of published evidence

Allergic bronchopulmonary aspergillosis (ABPA) complicating cystic fibrosis (CF) is treated with corticosteroids. Since elevated IgE is a cardinal abnormality, anti-IgE has been used sporadically as adjuvant treatment. In eight case reports, 13 children with CF and ABPA received anti-IgE resulting in improved FEV1 , fewer respiratory symptoms and decreased corticosteroid use.

Prolonged Role of Itraconazole in the Treatment of Allergic Bronchopulmonary Aspergillosis

Journal of Case Reports in Medicine,2013,2,1,1-3.Published:April 2013Type:Case ReportAuthors:Marie Nguyen, and John R. Cohn Author(s) affiliations:Marie Nguyen1 and John R. Cohn2 Department of Medicine, University of Florida, Gainesville, FL 32610, USA. Division of Allergy and Immunology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA. Abstract:Oral corticosteroids are first-line therapy for allergic bronchopulmonary aspergillosis (ABPA), however, itraconazole has been recognized as an adjunctive treatment. This paper describes the prolonged use of itraconazole in an asthmatic patient with a diagnosis of ABPA. This case report features a patient who showed benefit with a longer duration of itraconazole therapy without demonstrating adverse events related to treatment over nearly eight years. Prolonged treatment with itraconazole may serve as a corticosteroid sparing option for ABPA patients. Keywords:Allergic bronchopulmonary Aspergillosis; ItraconazoleView:PDF (94.39 KB) PDF Images Prolonged Role of Itraconazole in the Treatment of Allergic Bronchopulmonary Aspergillosis

Progress in the Diagnosis and Treatment of Pulmonary Aspergillosis

Aspergillus is the most common fungal pathogen of the respiratory mycosis. The respiratory diseases caused by Aspergillus are mainly classified into four clinical types, namely allergic bronchopulmonary aspergillosis, invasive aspergillosis, aspergilloma, and chronic pulmonary aspergillosis. Among the four clinical types of pulmonary aspergillosis, invasive aspergillosis is the most dangerous and difficult to treat disease. The diagnosis of invasive aspergillosis is established initially on clinical aspects and confirmed by the finding of pathogen in culture and histopathology. A number of methods can be conducted to obtain tissue samples from patients with invasive aspergillosis, chronic pulmonary aspergillosis or aspergilloma. Besides BAL detection and transbronchial biopsy, a fine-needle biopsy can be performed and guided by CT to diagnose these diseases. Antifungal agents including those with activity against Aspergillus have been developed. Several agents such as voriconazole, amphotericin B lipid complex, caspofungin, micafungin and anidulafungin are promising in the treatment of the pulmonary aspergillosis in the future. Moreover, under certain condition, surgical intervention is needed to combine with antifungal therapy to deal with aspergilloma or chronic pulmonary aspergillosis, and the use of glucocorticoids to control the inflammatory response is also very important in therapy of allergic bronchopulmonary aspergillosis besides antifungal agents. Keywords: Allergic bronchopulmonary aspergillosis, aspergilloma, chronic pulmonary aspergillosis, invasive aspergillosis.

352 Minocycline in CF patients: beware of myopericarditis!

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a common complication among patients with CF that produces significant respiratory morbidity. Standard therapy for ABPA includes systemic corticosteroids for a prolonged period of time with potentially severe side effects and use of antifungal agents. Omalizumab is a humanized monoclonal antibody directed against IgE that prevents its binding to receptors on effector cells. It has been shown to be effective in improving asthma control in patients with a strong allergic component. Recently, sporadic reports of omalizumab use against ABPA have been reported. Methods: We present our long term experience of omalizumab in three children with CF and ABPA who were steroid dependent. Results: Five (3.4%) out of 148 children and adolescents with CF followed in our Unit over a seven year period, developed ABPA (75% females, mean age at start of therapy 14.3 years). Omalizumab was given to 3 of them (2 males, mean age 17.1 years, mean FEV1 35%). All three were already experiencing significant side effects from chronic steroid therapy (invasive aspergillosis, diabetes mellitus, depression, relapse of ABPA and severe osteoporosis) and received regular antifugal therapy. Omalizumab treatment was given for a period of 12−18 months. Oral steroids were gradually stopped. Omalizumab resulted in significant improvement of respiratory symptoms and lung function (mean FEV1 52%, p: 0.01). Conclusion: According to our results in a small number of patients, omalizumab has a significant potential as a strategy to control ABPA in steroid dependent patients. However, more studies are needed to confirm these findings.

351 Effectiveness of omalizumab for treatment of allergic bronchopulmonary aspergillosis (ABPA) among children and adolescents with cystic fibrosis

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a common complication among patients with CF that produces significant respiratory morbidity. Standard therapy for ABPA includes systemic corticosteroids for a prolonged period of time with potentially severe side effects and use of antifungal agents. Omalizumab is a humanized monoclonal antibody directed against IgE that prevents its binding to receptors on effector cells. It has been shown to be effective in improving asthma control in patients with a strong allergic component. Recently, sporadic reports of omalizumab use against ABPA have been reported. Methods: We present our long term experience of omalizumab in three children with CF and ABPA who were steroid dependent. Results: Five (3.4%) out of 148 children and adolescents with CF followed in our Unit over a seven year period, developed ABPA (75% females, mean age at start of therapy 14.3 years). Omalizumab was given to 3 of them (2 males, mean age 17.1 years, mean FEV1 35%). All three were already experiencing significant side effects from chronic steroid therapy (invasive aspergillosis, diabetes mellitus, depression, relapse of ABPA and severe osteoporosis) and received regular antifugal therapy. Omalizumab treatment was given for a period of 12−18 months. Oral steroids were gradually stopped. Omalizumab resulted in significant improvement of respiratory symptoms and lung function (mean FEV1 52%, p: 0.01). Conclusion: According to our results in a small number of patients, omalizumab has a significant potential as a strategy to control ABPA in steroid dependent patients. However, more studies are needed to confirm these findings.

Efficacy of nebulised liposomal amphotericin B in the attack and maintenance treatment of ABPA: Figure 1–

To the Editors: Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder that results from a hypersensitivity reaction to Aspergillus spp. It has been estimated to occur in 1–3% of people with chronic asthma and 2–15% of those with cystic fibrosis [1]. The natural history of ABPA is characterised by exacerbations that can threaten the patient’s survival and prognosis [1]. Repetition of such exacerbations is responsible for the development of bronchiectasis, permanent obstructive ventilation defect or fibrotic lung lesions. Prognosis mainly depends on the very early treatment of exacerbations before bronchiectasis sets in. In 2008, the guidelines of the Infectious Diseases Society of America advised combination therapy in ABPA [2]: systemic glucocorticoids to limit the inflammatory component and antifungals to limit mycelium proliferation. However, even though glucocorticoid therapy and antifungals are the treatment of choice for acute-stage ABPA and exacerbations, there are no data to guide the duration of this treatment. Therefore, the current objectives for the management of ABPA are a decrease in the frequency and duration of exacerbations, and a limited solicitation of glucocorticoids. Consequently, the maintenance treatment in the management of ABPA remains a current and progressive problem for pneumologists. We describe a case of ABPA that was difficult to control using the standard treatment regimen, but which improved dramatically and durably following administration of nebulised liposomal amphotericin B (LAmB). In May 2010, a 67-yr-old female presented with fever and productive cough, with sputum plugs and a history of epilepsy treated with phenobarbital. In the preceding 3 months, she had presented recurrent chest infections resistant to amoxicillin and ciprofloxacin; glucocorticoids (1 mg·kg−1·day …