Allergic bronchopulmonary aspergillosis (ABPA) sans asthma: A distinct subset of ABPA with a lesser risk of exacerbation.

Allergic bronchopulmonary aspergillosis (ABPA) is a complex immunological disorder complicating asthma. Uncommonly, ABPA presents without underlying asthma. Herein, we describe the outcomes of ABPA with and without asthma. Of the 530 subjects (median follow-up, 39 months), 37 (7%) were ABPA sans asthma. Bronchiectasis was more frequent (97.3% vs. 83.2%, P = .02), and the lung function was significantly better in ABPA sans asthma. The incidence-rate of ABPA exacerbation was higher in those with asthma than without (112 vs. 242 per 1000 person-years, P = .0001). ABPA sans asthma appears to be a distinct subset of ABPA, with a better lung function and fewer exacerbations.

Worsening pulmonary outcomes during sex reassignment therapy in a transgender female with cystic fibrosis (CF) and asthma/allergic bronchopulmonary aspergillosis: a case report.

BACKGROUND: Cystic Fibrosis (CF) is a hereditary pulmonary and extra-pulmonary disease that occurs equally in men and women. However, a difference in morbidity and mortality rates between the sexes has been long documented. Similarly, a sex-disparity in disease severity has been reported in asthma as well. Studies done to date point to estrogen as a possible cause of this sex disparity in pulmonary outcomes in both conditions. CASE PRESENTATION: Here, we describe a case of a patient with CF and asthma/allergic bronchopulmonary aspergillosis (ABPA) undergoing sex reassignment therapy (male-to-female) and the negative impact it had on her lung function and frequency of pulmonary exacerbations in the context of increasing doses of exogenous estrogen. CONCLUSIONS: This case raises the possibility of a link between estrogen and worsening pulmonary outcomes and the need for further studies into transgender individuals with CF and/or asthma/ABPA as well as those undergoing high dose estrogen therapy for other indications.

A case of allergic bronchopulmonary aspergillosis successfully treated with mepolizumab.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is an allergic pulmonary disease comprising a complex hypersensitivity reaction to Aspergillus fumigatus. Clinical features of ABPA are wheezing, mucoid impaction, and pulmonary infiltrates. Oral corticosteroids and anti-fungal agents are standard therapy for ABPA, but long-term use of systemic corticosteroids often causes serious side effects. CASE PRESENTATION: A 64-year-old woman was diagnosed with ABPA based on a history of bronchial asthma (from 40 years of age), elevated total IgE, the presence of serum precipitating antibodies and elevated specific IgE antibody to A. fumigatus, and pulmonary infiltration. Bronchoscopy showed eosinophilic mucoid impaction. Systemic corticosteroid therapy was initiated, and her symptoms disappeared. Peripheral eosinophilia and pulmonary infiltration recurred five months after cessation of corticosteroid treatment. Systemic corticosteroids were re-initiated and itraconazole was added as an anti-fungal agent. The patient was free of corticosteroids, aside from treatment with a short course of systemic corticosteroids for asthma exacerbation, and clinically stable with itraconazole and asthma treatments for 3 years. In 2017, she experienced significant deterioration. Laboratory examination revealed marked eosinophilia (3017/µL) and a chest computed tomography (CT) scan demonstrated pulmonary infiltration in the left upper lobe and mucoid impaction in both lower lobes. The patient was treated with high-dose inhaled corticosteroid/long-acting beta-agonist, a long-acting muscarinic antagonist, a leukotriene receptor antagonist, and theophylline; spirometry revealed a forced expiratory volume in 1 s (FEV1) of 1.01 L. An uncontrolled asthma state was indicated by an Asthma Control Test (ACT) score of 18. Mepolizumab, 100 mg every 4 weeks, was initiated for the treatment of severe bronchial asthma with ABPA exacerbation. Bronchial asthma symptoms dramatically improved, and ACT score increased to 24, by 4 weeks after mepolizumab treatment. Peripheral eosinophil count decreased to 174/µL. Spirometry revealed improvement of lung function (FEV1: 1.28 L). A chest CT scan demonstrated the disappearance of pulmonary infiltration and mucoid impaction. CONCLUSIONS: To our knowledge, this is the first case of ABPA to be treated with mepolizumab. Dramatic improvements were observed in symptoms, lung function, peripheral eosinophil counts, and chest images. Mepolizumab could serve as an alternative treatment with the potential to provide a systemic corticosteroid-sparing effect.

Recurrence of allergic bronchopulmonary aspergillosis after adjunctive surgery for aspergilloma: a case report with long-term follow-up.

BACKGROUND: Coexistence of aspergilloma and allergic bronchopulmonary aspergillosis (ABPA) has rarely been reported. Although the treatment for ABPA includes administration of corticosteroids and antifungal agents, little is known about the treatment for coexisting aspergilloma and ABPA. Furthermore, the impact of surgical resection for aspergilloma on ABPA is not fully understood. Here, we present an interesting case of recurrent ABPA with long-term follow-up after surgical resection of aspergilloma. CASE PRESENTATION: A 53-year-old man with a medical history of tuberculosis was referred to our hospital with cough and dyspnea. Imaging revealed multiple cavitary lesions in the right upper lobe of the lung, with a fungus ball and mucoid impaction. The eosinophil count, total serum immunoglobulin E (IgE), and Aspergillus-specific IgE levels were elevated. Specimens collected on bronchoscopy revealed fungal filaments compatible with Aspergillus species. Based on these findings, a diagnosis of ABPA with concomitant aspergilloma was made. Although treatment with corticosteroids and antifungal agents was administered, the patient's respiratory symptoms persisted. Therefore, he underwent lobectomy of the right upper lobe, which resulted in a stable condition without the need for medication. Twenty-three months after discontinuation of medical treatment, his respiratory symptoms gradually worsened with a recurrence of elevated eosinophil count and total serum IgE. Imaging revealed recurrent bronchiectasis and cavities with mucoid impaction in the right lower lobe, suggesting relapse of aspergilloma and ABPA. Corticosteroids and antifungal agents were re-administered; aspergilloma improved slightly over a 5-year period, and ABPA remained well controlled with low-dose prednisolone (5 mg/day). CONCLUSIONS: We describe the long-term follow-up outcomes of a patient with concomitant ABPA and aspergilloma, who underwent surgical resection for aspergilloma. Physicians should carefully monitor patients with coexisting ABPA and aspergilloma, as the condition may relapse after remission, even despite surgical resection for aspergilloma. Additionally, surgical resection for aspergilloma could result in resolution of ABPA.

[Clinical Analysis of 40 Patients with Eosinophilic Lung Diseases in Peking Union Medical College Hospital].

Objective To summarize the clinical features of eosinophilic lung diseases(ELD). Methods We retrospectively analyzed the clinical manifestations,laboratory findings,accessory examination results,and pathology of 40 patients who were diagnosed with ELD and hospitalized in Peking Union Medical College Hospital from January 2013 to December 2016.Results There were 19 males and 21 females,and the average age was(48.58±18.25) years.The diagnoses included allergic bronchopulmonary aspergillosis(n=20),eosinophilic granulomatosis with polyangiitis(also known as churg-strauss syndrome)(n=10),chronic eosinophilic pneumonia(n=8),parasitic infection(n=1),and drug-induced eosinophilic pneumonia(n=1).Eosinophils counts in peripheral blood were increased in 35 patients(87.5%),and eosinophils counts in bronchoalveolar lavage fluids increased in 17 of 18 patients(94.4%).Arterial blood gas analysis showed varying degrees of hypoxemia in 23 patients(57.5%),and pulmonary function test showed ventilatory dysfunction in 27 patients(67.5%) and defect in diffusion capacity in 12 patients(30.0%).Chest CT revealed bilateral flaky,streaky,or diffuse ground-glass infiltrates and consolidations;in addition,central cylindrical bronchiectasis and mucous plugging with "finger-in-glove" pattern were seen in patients with allergic bronchopulmonary aspergillosis.Diffuse eosinophil infiltration was revealed in lung or other tissue biopsy.Glucocorticoids alone or combined with other therapies were effective in most patients.Conclusions ELD has a wide range of clinical presentations and can easily be misdiagnosed.Increased eosinophils count in peripheral blood and bronchoalveolar lavage fluids combined with infiltration manifestations in chest imaging are helpful for the diagnosis of ELD.Oral administration of glucocorticoids is the primary therapy for ELD.

A randomised trial of glucocorticoids in acute-stage allergic bronchopulmonary aspergillosis complicating asthma.

Whether use of high-dose steroids in acute-stage allergic bronchopulmonary aspergillosis (ABPA) is associated with superior outcomes is not known. Herein, we compare the efficacy and safety of two glucocorticoid protocols in ABPA.Treatment-naive ABPA subjects randomly received either high-dose or medium-dose oral prednisolone. The primary outcomes were exacerbation rates and glucocorticoid-dependent ABPA after 1 and 2 years, respectively, of treatment. The secondary end-points were composite response rates after 6 weeks, improvement in lung function, time to first exacerbation, cumulative dose and adverse effects.92 subjects (high-dose n=44, medium-dose n=48) were included in the study. The numbers of subjects with exacerbation after 1 year (high-dose 40.9% versus medium-dose 50%, p=0.59) and glucocorticoid-dependent ABPA after 2 years (high-dose 11.4% versus medium-dose 14.6%, p=0.88) were similar in the two groups. Although composite response rates were significantly higher in the high-dose group, improvement in lung function and time to first exacerbation were similar in the two groups. Cumulative glucocorticoid dose and side-effects were significantly higher in the high-dose group.Medium-dose oral glucocorticoids are as effective and safer than high-dose in treatment of ABPA.

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

BACKGROUND AND AIM: Nebulized amphotericin B (NAB) has been used in the management of acute stage and exacerbations of allergic bronchopulmonary aspergillosis (ABPA). Whether NAB can prevent exacerbations of ABPA is not known. Herein, we evaluate the efficacy and safety of NAB in subjects with ABPA complicating asthma. METHODS: Consecutive subjects of ABPA with recurrent exacerbations were randomized to receive either NAB plus nebulized budesonide (NEB) or NEB alone. The primary outcome was the time-to-first exacerbation of ABPA. The secondary outcomes were the number of subjects with ABPA exacerbations, ACQ7 scores, lung function, IgE levels, and adverse effects of treatment. RESULTS: Twenty-one subjects (14 men; mean age, 32.3 years) were randomized to either the NAB (n = 12) or the NEB (n = 9) arm. The baseline characteristics were similar in the two groups. The time-to-first exacerbation was similar in the two groups. At one year, the numbers of patients experiencing exacerbation was significantly lower in the NAB arm (1/12 [8.3%] vs. 6/9 [66.7%]; p = 0.016). The other secondary end points were not different between the two groups. There were no major adverse events leading to discontinuation of any of the study drugs. Three patients experienced bronchospasm after first dose of NAB; however, the subsequent doses were well tolerated. CONCLUSIONS: NAB seems to be beneficial in decreasing the frequency of exacerbations in patients with ABPA complicating asthma. Larger trials are required to confirm our study results.

Utility of IgE (total and Aspergillus fumigatus specific) in monitoring for response and exacerbations in allergic bronchopulmonary aspergillosis.

The role of total and specific IgE in monitoring treatment responses in allergic bronchopulmonary aspergillosis (ABPA) remains poorly studied. Here in, we evaluate the utility of total and Aspergillus fumigatus specific IgE in the follow-up of ABPA. Eighty-one consecutive treatment-naïve patients of ABPA (acute stage) with pulmonary infiltrates and bronchiectasis underwent measurement of total and A. fumigatus specific IgE at baseline, after 8 weeks of glucocorticoid therapy, and during exacerbations. There was clinical and radiological improvement after treatment with median decline of total IgE by 51.9%. The total IgE declined by at least 35%, 25% and 20% in 69 (85.2%), 76 (93.6%) and 78 (96.3%) patients, respectively. On the other hand, the A. fumigatus specific IgE increased in 42 (51.9%) subjects, and the mean increase was 1.4%, after 8 weeks. Among 13 patients with exacerbation, 12 (92.3%) had a rise of total IgE by >50%. The A. fumigatus specific IgE increased in only five (38.5%) subjects during exacerbation. Thus, the total IgE is a useful test in monitoring treatment responses in ABPA while A. fumigatus specific IgE has limited utility.

Molecular-based allergy diagnosis of allergic bronchopulmonary aspergillosis in Aspergillus fumigatus-sensitized Japanese patients.

BACKGROUND: Distinguishing between patients with allergic bronchopulmonary aspergillosis (ABPA) and Aspergillus fumigatus (Af)-sensitized asthmatic patients without ABPA is sometimes difficult owing to the IgE-cross-reactivity between Af and other fungal allergens. OBJECTIVE: To establish the usefulness of molecular-based allergy diagnostics using allergen components from Af in distinguishing ABPA from Af-sensitized asthma without ABPA. METHODS: Sera from Japanese patients with ABPA (n = 53) and Af-sensitized asthma without ABPA (n = 253) were studied. The levels of IgE and IgG antibodies to allergen components from Af and IgE antibodies to different fugal allergen extracts were measured by ImmunoCAP. Comorbid atopic dermatitis (AD) was taken into consideration in the sensitization profile analysis. RESULTS: Patients with ABPA possessed significantly higher levels of IgE antibodies to Asp f 1, and Asp f 2 than asthmatic patients without ABPA. The areas under the receiver operating characteristic curves for the levels of IgE to Asp f 1 and Asp f 2 as diagnostic markers of ABPA were 0.75 and 0.78, respectively. The presence of IgE positivity to Asp f 1 and/or Asp f 2 resulted in increased sensitivity while losing little specificity. Comorbid AD was associated with higher levels of IgE to Asp f 6 (manganese superoxide dismutase from Af, a ubiquitous pan-allergen in fungi) and low but positive levels of IgE to other Af-components, which hampered the serological discrimination of ABPA. CONCLUSIONS AND CLINICAL RELEVANCE: The levels of IgE to Asp f 1 and/or Asp f 2 can effectively differentiate ABPA from Af-sensitized asthma, suggesting that the amounts of IgE specific for these molecules are markers for genuine Af-sensitization in ABPA. However, comorbid AD must be taken into consideration in the interpretation of high IgE to Asp f 6. Establishing of IgE-sensitization profiles using panel of Af-allergen components provides valuable information for distinguishing genuine vs. cross-reactive sensitization in Af-sensitized patients.

Allergic fungal airway disease: pathophysiologic and diagnostic considerations.

PURPOSE OF REVIEW: Fungal spores are ubiquitously present in indoor and outdoor air. A number can act as aeroallergens in Immunoglobulin E (IgE)-sensitized individuals and some thermotolerant fungi germinate in the lung where they can cause a combined allergic and infective stimulus leading to a number of clinical presentations characterized by evidence of lung damage. We discuss which biomarkers are useful in helping to guide diagnosis, prognosis and treatment of allergic fungal airway disease (AFAD). RECENT FINDINGS: Diagnostic biomarkers, such as specific IgEs and fungal culture, for AFAD are limited by sensitivity, although this may be improved with novel agents such as specific IgEs to fungal components and quantitative PCR. Total IgE and hypereosinophilia are nonspecific and do not clearly relate to disease activity. High attenuation mucus and proximal bronchiectasis are specific, albeit insensitive markers of AFAD. Biomarkers that predict prognosis and treatment response are yet to be defined. SUMMARY: This review summarizes the fungi involved and the current debate regarding the diagnostic criteria to define fungal-associated lung disease. We advocate the phasing out of the term allergic bronchopulmonary aspergillosis and the use of a more inclusive term such as AFAD, together with a more liberal set of criteria based largely on IgE sensitization to thermotolerant fungi, which identifies those patients at risk of developing lung damage.

Omalizumab in the treatment of allergic bronchopulmonary aspergillosis: One center's experience with 14 cases.

BACKGROUND: Omalizumab has been a valuable option for patients with severe allergic asthma, but there are only case reports regarding effectiveness of omalizumab in patients with allergic bronchopulmonary aspergillosis (ABPA). OBJECTIVE: To evaluate the clinical and functional effectiveness of omalizumab in patients with asthma and ABPA in long-term follow-up. METHODS: The study was conducted as a retrospective chart review of patients with ABPA who were treated with omalizumab injections between December 2008 and June 2014. Once treatment with omalizumab was started, data were collected at three time points: at baseline, after 1 year, and, in June 2014, at the last follow-up. RESULTS: Fourteen patients with ABPA (seven women and seven men; mean [± standard deviation (SD)] age, 44.21 ± 13.01 years) were included. The treatment period was 31.5 ± 3.99 months (mean ± SD). The difference between the baseline and the last evaluation of the mean percentage of forced expiratory volume in 1 second (FEV1) was significant (p = 0.02). The mean asthma control test score was increased at all-time points compared with the basal score (p = 0.001). After omalizumab treatment was initiated, the patients' mean oral corticosteroid dosage significantly decreased (p = 0.001). The baseline exacerbation rate was 2.7 ± 1.5/y (mean ± SD), and the hospitalization rate was 1.4/y, and both were zero at the last assessment (p = 0.001). Eleven of the patients (78.6%) responded perfectly, and three (21.4%) partially responded to treatment. The patients who had a total immunoglobulin E level of <1000 IU/mL seemed to be more responsive than those whose total immunoglobulin E level was >1000 IU/mL (p = 0.05). CONCLUSION: Omalizumab provided a clinically important reduction in exacerbations and steroid requirement, and improved asthma symptoms and pulmonary function parameters in patients with asthma and ABPA who had previously shown an unsatisfactory response to Global Initiative for Asthma step 4 treatment.

Allergic bronchopulmonary aspergillosis presenting as lobar or total lung collapse.

INTRODUCTION: Allergic bronchopulmonary aspergillosis (ABPA) is a T-helper cell 2 (Th2) mediated hypersensitive lung disorder in response to Aspergillus that usually affects asthmatic and cystic fibrosis (CF) patients. ABPA rarely presents as lung collapse and such kind of presentation is very rare in non asthmatic patients. We are presenting a series of three cases in which ABPA presented as lobar or total lung collapse. ABPA presenting as opaque hemithorax is a rarity with only a few of them reported in the literature. CASE SERIES: the first case described is a 45-year non-smoker with history suggestive of bronchial asthma and on chest radiological examination was found to have opaque right hemithorax. The second case is of 62-year non-smoker non-asthmatic patient who presented to us as left lung collapse. The last case is of middle lobe collapse in asthmatic male. All cases ultimately were proved to be having ABPA and after treatment showed marked clinical and radiological improvement. CONCLUSIONS: The present case series highlights the need for aggressive approach in diagnosing this treatable condition in cases presenting as segmental or total lung collapse. The condition has a good prognosis if detected early.

Antifungal treatment in allergic bronchopulmonary aspergillosis with and without cystic fibrosis: a systematic review.

Allergic bronchopulmonary aspergillosis (ABPA) is a rare disease that affects patients with asthma or cystic fibrosis. Its debilitating course has led to the search for new treatments, including antifungals and monoclonal antibodies. To evaluate the efficacy and safety of antifungal treatments in patients with ABPA and either asthma or cystic fibrosis, we performed a systematic review of the literature on the effects of antifungal agents in ABPA using three biomedical databases. Quality assessment was performed using the GRADE methodology and, where appropriate, studies with comparable outcomes were pooled for meta-analysis. Thirty-eight studies - four randomized controlled trials and 34 observational studies - met the eligibility criteria. The antifungal interventions described were itraconazole, voriconazole, posaconazole, ketoconazole, natamycin, nystatin and amphotericin B. An improvement in symptoms, frequency of exacerbations and lung function was reported in most of the studies and was more common with oral azoles. Antifungals also had a positive impact on biomarkers and radiological pulmonary infiltrates, but adverse effects were also common. The quality of the evidence supporting these results was low or very low due to a shortage of controlled studies, heterogeneity between studies and potential bias. Antifungal interventions in ABPA improved patient and disease outcomes in both asthma and cystic fibrosis. However, the recommendation for their use is weak and clinicians should therefore weigh up desirable and undesirable effects on a case-by-case basis. More studies with a better methodology are needed, especially in cystic fibrosis, to increase confidence in the effects of antifungal treatments in ABPA.

Aspergillus and cystic fibrosis: old disease - new classifications.

PURPOSE OF REVIEW: Aspergillus pulmonary infection has traditionally been recognized as a clinical spectrum of increasing pathogenicity, encompassing saprophytic airways colonization historically regarded of doubtful clinical significance, to allergic bronchopulmonary aspergillosis, chronic cavitatory and life-threatening invasive disease in the immunocompromised host. Whilst the latter two categories are rarely encountered in cystic fibrosis (CF), there is recognition of an extending spectrum of disease yet to be reflected in consensus management guidelines. The purpose of this review is to provide an up-to-date overview of this extending spectrum, with a focus on disease categories and their clinical significance. RECENT FINDINGS: Conflicting evidence regarding the clinical significance of Aspergillus colonization and sensitization in CF, alongside the emergence of a novel disease category 'Aspergillus bronchitis', has led to proposals for the reclassification of Aspergillus disease. In addition, lack of standardization and poor sensitivity of culture-dependent mycology techniques renders clinical and epidemiological interpretation of these isolates challenging. SUMMARY: The role of Aspergillus in the absence of established CF-allergic bronchopulmonary aspergillosis remains unclear. The following review discusses new approaches proposed to categorise the extended spectrum of CF Aspergillus disease, highlighting the need for enhanced microbiological investigation and serological monitoring of patients in light of evidence which differentiates colonization from categories of greater pathogenic potential.

Middle lobe syndrome: a rare presentation of allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a disease predominantly seen in susceptible asthmatic subjects, due to a hypersensitivity phenomenon caused by colonisation of the airways by Aspergillus species. Although collapse, both lobar and segmental due to mucoid impaction, is not uncommon in ABPA, a middle lobe syndrome (MLS) secondary to ABPA is rather an uncommon association. We report this rare and unusual clinical presentation in a 36-year-old male, who presented for evaluation of a "non resolving pneumonia". Imaging suggested the presence of a MLS and central bronchiectasis. Further investigations revealed that the patient met 6/8 of the essential diagnostic criteria for ABPA. Appropriate therapy with oral corticosteroids resulted in remarkable symptomatic improvement.

Differential effects of dexamethasone and itraconazole on Aspergillus fumigatus-exacerbated allergic airway inflammation in a murine model of mite-sensitized asthma.

BACKGROUND: Fungal exposure is associated with particularly severe asthma. Nevertheless, the effects of anti-fungal treatments on fungus-exacerbated asthma need to be determined. OBJECTIVES: The present study aimed to compare the effects of itraconazole (ITCZ) and dexamethasone (Dex) on Aspergillus fumigatus (Af)-exacerbated preexisting Dermatophagoides farinae (Df) allergen-sensitized allergic airway inflammation. METHODS: Four groups of BALB/c mice were prepared: control, Df-sensitized plus Af-infected mice (Df-Af), and Df-Af mice treated with Dex (Df-Af-Dex) or with ITCZ (Df-Af-ITCZ). Pulmonary pathology and cytokine profiles in the airway were evaluated. In a different set of experiments, the effects of Dex on alveolar macrophage (AM) phagocytosis of Af conidia were determined in Df-sensitized mice. RESULTS: Af infection significantly increased the level of eosinophils and neutrophils in the airway of Df-sensitized mice. While Dex significantly decreased eosinophils, ITCZ significantly decreased both eosinophils and neutrophils in Df-Af mice. Dex significantly decreased IL-5, whereas ITCZ significantly reduced MIP-2 in the airway. Compared to controls, AM isolated from Df-sensitized mice had significantly reduced phagocytotic activity of Af conidia. However, Dex significantly improved phagocytotic activity of AM in Df-sensitized mice. CONCLUSIONS: The present study showed that Dex and ITCZ differently regulated Af-exacerbated allergic airway inflammation; the former inhibits eosinophilic inflammation and the latter inhibits neutrophilic as well as eosinophilic inflammation by regulating different cytokines. Additionally, Dex enhanced the phagocytotic activity of AM in allergic asthma. Thus, a combination of Dex and ITCZ might be effective for the management of fungus-exacerbated asthma.

The basidiomycetous yeast Trichosporon may cause severe lung exacerbation in cystic fibrosis patients - clinical analysis of Trichosporon positive patients in a Munich cohort.

BACKGROUND: The relevance of Trichosporon species for cystic fibrosis (CF) patients has not yet been extensively investigated. METHODS: The clinical course of CF patients with Trichosporon spp. in their respiratory secretions was analysed between 2003 and 2010 in the Munich CF center. All respiratory samples of 360 CF patients (0 - 52.4 years; mean FEV1 2010 81.4% pred) were investigated. RESULTS: In 8 patients (2.2%, 3 male, mean age 21.8 years) Trichosporon was detected at least once. One patient carried T. asahii. One patient carried T. mycotoxinivorans and one patient T. inkin as determined by DNA sequencing. As potential risk factors for Trichosporon colonization steroid treatment, allergic bronchopulmonary aspergillosis (ABPA) and CF associated diabetes were identified in 6, 5, and 2 patients respectively. For one patient, the observation period was not long enough to determine the clinical course. One patient had only a single positive specimen and exhibited a stable clinical course determined by change in forced expiratory volume in one second (FEV1), body-mass-index (BMI), C-reactive protein (CRP) and immunoglobulin G (IgG). Of 6 patients with repeatedly positive specimen (mean detection period 4.5 years), 4 patients had a greater decline in FEV1 than expected, 2 of these a decline in BMI and 1 an increase in IgG above the reference range. 2 patients received antimycotic treatment: one patient with a tormenting dry cough subjectively improved under Amphotericin B inhalation; one patient with a severe exacerbation due to T. inkin was treated with i.v. Amphotericin B, oral Voriconazole and Posaconazole which stabilized the clinical condition. CONCLUSIONS: This study demonstrates the potential association of Trichosporon spp. with severe exacerbations in CF patients.

Assessment of Aspergillus sensitization or persistent carriage as a factor in lung function impairment in cystic fibrosis patients.

BACKGROUND: Cystic fibrosis (CF) patients presenting with persistent carriage of, or sensitization to, Aspergillus fumigatus are often treated with antifungal therapies because the presence of the fungus is commonly thought to impede lung function, even in the absence of allergic bronchopulmonary aspergillosis (ABPA). The aim of this study was to assess Aspergillus-related status modulating the forced expiratory volume in 1 s (FEV1) of CF patients. METHODS: From 1995 to 2007, 251 patients were evaluated. Demographic data, cystic fibrosis transmembrane conductance regulator gene (CFTR) mutations, body mass index, and FEV(1) were recorded. The presence of A. fumigatus and Pseudomonas aeruginosa in sputum and the levels of A. fumigatus precipitin, total IgE (t-IgE), and specific anti-A. fumigatus IgE (Af-IgE) were determined. Patients were divided into 3 groups: (1) ABPA: A. fumigatus precipitin ≥3 lines, Af-IgE > 0.35 IU/ml, and t-IgE ≥500 IU/ml; (2) sensitization: Af-IgE > 0.35 IU/ml but t-IgE < 500 IU/ml; and (3) persistent carriage: Af-IgE ≤ 0.35 IU/ml with either an A. fumigatus persistent positive culture or an A. fumigatus precipitin ≥3 lines, provided this serological finding had been found associated with at least 1 A. fumigatus-positive culture. The remaining patients represented the control group. A multivariate analysis was carried out with FEV(1) as the outcome variable. RESULTS: ABPA, sensitization, and persistent carriage were significantly associated with a larger decline in FEV1 compared with the control group, with odds ratios of 15.9, 14.9, and 10.7, respectively. This association was independent of other associated factors (P. aeruginosa transient detection, age, being underweight, and low FEV1 at baseline). CONCLUSIONS: In addition to ABPA, sensitization and persistent carriage appear to have an impact on pulmonary function in CF patients.

Allergic bronchopulmonary aspergillosis and related allergic syndromes.

While allergic bronchopulmonary aspergillosis (ABPA) is well recognized as a fungal complication of asthma, severe asthma with fungal sensitization (SAFS) is not. In ABPA the total immunoglobulin E (IgE) is usually >1,000 IU/mL, whereas in SAFS it is <1,000 IU/mL, and either skin prick tests or fungus-specific IgE tests are positive. ABPA may present with any severity of asthma, and occasionally with no asthma or cystic fibrosis, the other common underlying disease. SAFS is a problem in patients with poorly controlled asthma and occasionally presents in the intensive care unit (ICU). Production of mucous plugs and coughing paroxysms is more common in ABPA. Certain underlying genetic defects seem to underpin these remarkable phenotypic differences. From a management perspective both ABPA and SAFS respond to both high doses of corticosteroids and oral antifungal agents, with ∼60% response rate in both ABPA and SAFS with itraconazole. In 50% of patients itraconazole boosts inhaled corticosteroid exposure, sometimes leading to cushingoid features. Second-line therapy data are scant, but we have shown that 70 to 80% of patients who tolerate either voriconazole or posaconazole also respond. Other useful therapies include nebulized hypertonic saline to aid expectoration of thick sputum and long-term azithromycin for its anti-inflammatory effect on the airways. Omaluzimab is useful in some patients with SAFS and occasionally in ABPA. Complications of ABPA include bronchiectasis, typically central in distribution, and chronic pulmonary aspergillosis. Most patients with ABPA and SAFS can be stabilized for long periods with inhaled corticosteroids and itraconazole or another antifungal agent. Novel immunotherapies are on the horizon.