The incidence and prevalence of serious fungal diseases in Tunisia.

With increasing concern about the negative health impact of fungal disease, there is a need to survey what is and is not known about the epidemiology of these infections in Tunisia. We have estimated the incidence and prevalence of the most serious fungal diseases in Tunisia for the first time. Using published literature from Tunisia, or if absent other countries, we have estimated the burden of life-threatening fungal infections and those causing significant morbidity, using deterministic modeling, based on populations at greatest risk. An estimated 250,494 (2.12% of the Tunisian population) are affected by a serious fungal disease annually. Invasive and chronic pulmonary aspergillosis are relatively common with 708 and 2090 patients affected, partly linked to the prevalence of chronic obstructive pulmonary disease (COPD). Fungal asthma (allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization) have an estimated prevalence of 38,264 (5.8% of the adult asthma population). Fungal keratitis probably affects 1,761 eyes annually, often leading to uniocular blindness. Candidaemia and Candida peritonitis probably affect at least 680 people annually, with a high mortality. Recurrent vulvovaginal candidiasis probably affects over 200,000 women. While fungal diseases are regularly diagnosed in Tunisia, epidemiological studies with denominators are uncommon. Some fungal diseases are poorly addressed with the current diagnostic portfolio, and surveillance is lacking. Studies on these diseases and the implementation of a national program of surveillance are required.

Elevated Serum Aspergillus Fumigatus-Specific Immunoglobulin G in Type 2 Chronic Rhinosinusitis.

Background: Aspergillus fumigatus-specific immunoglobulin G (Af-sIgG) has been applied to diagnose allergic bronchopulmonary aspergillosis, a hypersensitivity reaction to the colonization of the fungus in the lower airways. In the upper airways, it has been reported to be involved in allergic fungal rhinosinusitis and local fungal rhinosinusitis. However, in primary chronic rhinosinusitis (CRS), a more common upper airway disease, the role of Af-sIgG remains unclear. Objective: The aim of our study was to investigate the role of serum Af-sIgG levels in primary CRS patients. Methods: We prospectively recruited patients diagnosed with bilateral primary CRS and patients with nasal septal deviation as the non-CRS group. Patients in the primary CRS group were further classified into two endotypes, including type 2 (T2) and non-T2 groups. Serum samples collected were sent for Af-sIgG analysis. Potential factors and surgical outcomes were analyzed. Results: Forty-eight patients with a diagnosis of primary CRS (including 28 with T2 and 20 with non-T2 CRS) and 22 patients in the non-CRS group were recruited. The T2 CRS group had significantly higher serum Af-sIgG levels than the non-T2 CRS group (odds ratio 10.2 with Af-sIgG more than 27.6 mg/L; p < 0.001). Further multivariate logistic regression showed that the serum Af-sIgG level was the independent factor for early disease recurrence within one year in primary CRS patients. The optimal cutoff value of the serum Af-sIgG level to predict postoperative recurrence was 27.1 mg/L (odds ratio 15.1, p = 0.013). Conclusions: We suggest that the serum Af-sIgG level is a practical marker to detect T2 inflammation and the surgical outcome of primary CRS. By applying this feasible test, we may be able to achieve optimal treatment for every individual with primary CRS. This study may provide physicians with a reference for future clinical applications in dealing with primary CRS.

ABPA sans asthma: an entity to remember.

A male patient in his 20s presented with a cough and a small volume of haemoptysis that lasted a year. He had no other constitutional symptoms and a respiratory examination was suggestive of a consolidation. A chronic infection, such as tuberculosis, was suspected. The routine evaluation showed peripheral eosinophilia with raised serum total IgE. Sputum examination for tuberculosis was negative; hence, a high-resolution CT of the thorax was performed, which revealed bilateral bronchiectasis with high-attenuation mucus plugging. The imaging and blood profiles were in favour of allergic bronchopulmonary aspergillosis, but there was no history suggestive of asthma, and the pulmonary function test was normal. The patient underwent a skin prick test and an allergen-specific IgE test for Aspergillus fumigatus, and both were positive. His bronchoalveolar lavage cultures also grew A. fumigatus, and he responded well to antifungal therapy. This case illustrates the presentation of a rare entity-allergic bronchopulmonary aspergillosis sans asthma.

Aspergillus fumigatus In-Host HOG Pathway Mutation for Cystic Fibrosis Lung Microenvironment Persistence.

The prevalence of Aspergillus fumigatus colonization in individuals with cystic fibrosis (CF) and subsequent fungal persistence in the lung is increasingly recognized. However, there is no consensus for clinical management of A. fumigatus in CF individuals, due largely to uncertainty surrounding A. fumigatus CF pathogenesis and virulence mechanisms. To address this gap in knowledge, a longitudinal series of A. fumigatus isolates from an individual with CF were collected over 4.5 years. Isolate genotypes were defined with whole-genome sequencing that revealed both transitory and persistent A. fumigatus in the lung. Persistent lineage isolates grew most readily in a low-oxygen culture environment, and conidia were more sensitive to oxidative stress-inducing conditions than those from nonpersistent isolates. Closely related persistent isolates harbored a unique allele of the high-osmolarity glycerol (HOG) pathway mitogen-activated protein kinase kinase, Pbs2 (pbs2C2). Data suggest this novel pbs2C2 allele arose in vivo and is necessary for the fungal response to osmotic stress in a low-oxygen environment through hyperactivation of the HOG (SakA) signaling pathway. Hyperactivation of the HOG pathway through pbs2C2 comes at the cost of decreased conidial stress resistance in the presence of atmospheric oxygen levels. These novel findings shed light on pathoadaptive mechanisms of A. fumigatus in CF, lay the foundation for identifying persistent A. fumigatus isolates that may require antifungal therapy, and highlight considerations for successful culture of persistent Aspergillus CF isolates. IMPORTANCE Aspergillus fumigatus infection causes a spectrum of clinical manifestations. For individuals with cystic fibrosis (CF), allergic bronchopulmonary aspergillosis (ABPA) is an established complication, but there is a growing appreciation for A. fumigatus airway persistence in CF disease progression. There currently is little consensus for clinical management of A. fumigatus long-term culture positivity in CF. A better understanding of A. fumigatus pathogenesis mechanisms in CF is expected to yield insights into when antifungal therapies are warranted. Here, a 4.5-year longitudinal collection of A. fumigatus isolates from a patient with CF identified a persistent lineage that harbors a unique allele of the Pbs2 mitogen-activated protein kinase kinase (MAPKK) necessary for unique CF-relevant stress phenotypes. Importantly for A. fumigatus CF patient diagnostics, this allele provides increased fitness under CF lung-like conditions at a cost of reduced in vitro growth under standard laboratory conditions. These data illustrate a molecular mechanism for A. fumigatus CF lung persistence with implications for diagnostics and antifungal therapy.

Case Report: Allergic Bronchopulmonary Aspergillosis Revealing Asthma.

Allergic bronchopulmonary aspergillosis (ABPA) is an immunological pulmonary disorder caused by hypersensitivity to Aspergillus which colonizes the airways of patients with asthma and cystic fibrosis. Its diagnosis could be difficult in some cases due to atypical presentations especially when there is no medical history of asthma. Treatment of ABPA is frequently associated to side effects but cumulated drug toxicity due to different molecules is rarely reported. An accurate choice among the different available molecules and effective on ABPA is crucial. We report a case of ABPA in a woman without a known history of asthma. She presented an acute bronchitis with wheezing dyspnea leading to an acute respiratory failure. She was hospitalized in the intensive care unit. The bronchoscopy revealed a complete obstruction of the left primary bronchus by a sticky greenish material. The culture of this material isolated Aspergillus fumigatus and that of bronchial aspiration fluid isolated Pseudomonas aeruginosa. The diagnosis of ABPA was based on elevated eosinophil count, the presence of specific IgE and IgG against Aspergillus fumigatus and left segmental collapse on chest computed tomography. The patient received an inhaled treatment for her asthma and a high dose of oral corticosteroids for ABPA. Her symptoms improved but during the decrease of corticosteroids, the patient presented a relapse. She received itraconazole in addition to corticosteroids. Four months later, she presented a drug-induced hepatitis due to itraconazole which was immediately stopped. During the monitoring of her asthma which was partially controlled, the patient presented an aseptic osteonecrosis of both femoral heads that required surgery. Nine months after itraconazole discontinuation, she presented a second relapse of her ABPA. She received voriconazole for nine months associated with a low dose of systemic corticosteroid therapy with an improvement of her symptoms. After discontinuation of antifungal treatment, there was no relapse for one year follow-up.

Evaluation of an Aspergillus IgG/IgM lateral flow assay for serodiagnosis of fungal asthma in Uganda.

BACKGROUND: Diagnosis of fungal allergies in asthma remains problematic in low-and middle-income countries due to non-availability of point-of-care testing. In this study, we aimed to evaluate the performance of an Aspergillus immunochromatographic technology (ICT) IgG/M lateral flow device (LFD) for the serological diagnosis of allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitisation (SAFS) among Ugandan adult asthmatics. METHODS: 374 adult (aged ≥18years) asthmatics in the African Severe Asthma Program study, Ugandan site constituted the study population. ABPA and SAFS were diagnosed according to standard criteria. Asthmatics who did not meet the above criteria constituted a control group. The LFD tests were performed and read according to manufacturer's instructions. RESULTS: ABPA was found in 12/374 (3.2%) and SAFS in 60/374 (16%) participants. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the Aspergillus ICT for the diagnosis of ABPA were 0.0%, 96.4%, 0.0% and 96.7% respectively, and for SAFS 6.7%, 97.1%, 30.8% and 84.5% respectively. False positive and negative rates were 3.5% and 3.2% for ABPA and 2.4% and 14.9% for SAFS, respectively. Patients with a positive LFD significantly had higher median Aspergillus fumigatus-specific IgE levels compared to those with negative LFD (median: 0.06 kUA/l VS 0.03 kUA/L, P = 0.011). CONCLUSION: The Aspergillus ICT IgG/M LFD had a poor diagnostic performance for the diagnosis of both ABPA and SAFS. Its greatest value may be in distinguishing chronic and allergic aspergillosis in Africa.

[Biological Treatments in patients with ABPA]. / ABPA'li hastalarda biyolojik tedaviler.

Allergic Bronchopulmonary Aspergillosis (ABPA) is a pulmonary disease characterized by recurrent pulmonary opacities and bronchiectasis caused by Type 1 hypersensitivity to A. fumigatus. Asthma is an important part of the disease and is generally in severe form. It is thought that immunoglobulins against A. fumigatus, Th2-derived cytokines such as IL-4, IL-5 and IL-13 and eosinophilic inflammation play a role in the pathogenesis of the disease. Monoclonal antibody treatments targeting IL-4, IL-5, IL-13 and IgE, which are involved in pathogenesis, have been used in asthmatic patients before. The main treatment of ABPA for exacerbations and remissions is oral corticosteroids (OCS). However, in cases where the corticosteroid dose cannot be reduced or side effects develop, monoclonal agents may be added to the treatment. Monoclonal agents such as omalizumab, mepolizumab, benralizumab and dupilumab targeting cytokines involved to the patogenesis have been used in patients with ABPA. Omalizumab has shown a reduction in exacerbations and OCS requirements, improvement in asthma symptoms and improvement in pulmonary function parameters. With mepolizumab, a decrease in OCS dose, decrease in blood eosinophil count, clinical improvement and radiological improvement were observed. Benralizumab reduced, the number of eosinophil or even almost nullified as well as clinical recovery alongside with radiological improvement. With dupilumab, improvement in symptoms, discontinuation of OCS, but increase in eosinophil count at the beginning of treatment was reported. As a result, monoclonal antibodies were generally found to be successful and safe in patients with ABPA.

Aspergillus fumigatus Strain-Specific Conidia Lung Persistence Causes an Allergic Broncho-Pulmonary Aspergillosis-Like Disease Phenotype.

Aspergillus fumigatus is a filamentous fungus which can cause multiple diseases in humans. Allergic broncho-pulmonary aspergillosis (ABPA) is a disease diagnosed primarily in cystic fibrosis patients caused by a severe allergic response often to long-term A. fumigatus colonization in the lungs. Mice develop an allergic response to repeated inhalation of A. fumigatus spores; however, no strains have been identified that can survive long-term in the mouse lung and cause ABPA-like disease. We characterized A. fumigatus strain W72310, which was isolated from the expectorated sputum of an ABPA patient, by whole-genome sequencing and in vitro and in vivo viability assays in comparison to a common reference strain, CEA10. W72310 was resistant to leukocyte-mediated killing and persisted in the mouse lung longer than CEA10, a phenotype that correlated with greater resistance to oxidative stressors, hydrogen peroxide, and menadione, in vitro In animals both sensitized and challenged with W72310, conidia, but not hyphae, were viable in the lungs for up to 21 days in association with eosinophilic airway inflammation, airway leakage, serum IgE, and mucus production. W72310-sensitized mice that were recall challenged with conidia had increased inflammation, Th1 and Th2 cytokines, and airway leakage compared to controls. Collectively, our studies demonstrate that a unique strain of A. fumigatus resistant to leukocyte killing can persist in the mouse lung in conidial form and elicit features of ABPA-like disease.IMPORTANCE Allergic broncho-pulmonary aspergillosis (ABPA) patients often present with long-term colonization of Aspergillus fumigatus Current understanding of ABPA pathogenesis has been complicated by a lack of long-term in vivo fungal persistence models. We have identified a clinical isolate of A. fumigatus, W72310, which persists in the murine lung and causes an ABPA-like disease phenotype. Surprisingly, while viable, W72310 showed little to no growth beyond the conidial stage in the lung. This indicates that it is possible that A. fumigatus can cause allergic disease in the lung without any significant hyphal growth. The identification of this strain of A. fumigatus can be used not only to better understand disease pathogenesis of ABPA and potential antifungal treatments but also to identify features of fungal strains that drive long-term fungal persistence in the lung. Consequently, these observations are a step toward helping resolve the long-standing question of when to utilize antifungal therapies in patients with ABPA and fungal allergic-type diseases.

Use of monoclonal antibodies for allergic bronchopulmonary aspergillosis in patients with asthma and cystic fibrosis: literature review.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction (HR) mediated by antigens to Aspergillus fumigatus. It is estimated that 2-15% of patients with cystic fibrosis (CF) and between 1% and 5% of asthmatics develop ABPA, affecting approximately 4.8 million people worldwide. The goals of treatment are controlling inflammation, reducing the number of exacerbations and limiting the progression of lung damage. Systemic steroids are therefore used as the mainstay therapy, along with antifungal medications. However, many patients do not respond or develop side effects to treatment. In this scenario, biological drugs such as Omalizumab, Mepolizumab, Benralizumab and Dupilumab have been implemented in clinical practice, even though there is a lack of scientific evidence to support their use. We performed a literature review of the studies carried out which analyzed biologics for the management of ABPA in adult populations with asthma and CF. To our knowledge this is the first literature review that included all biologics. We included a total of 32 studies, all but one were descriptive studies, and the vast majority evaluated the use of Omalizumab. Biologics appeared to have more benefit for patients with ABPA and asthma than CF, specifically at decreasing the frequency of acute exacerbations and by having a steroid-sparing effect. Although a decrease in serum IgE level is considered a measure of therapy success, values may not decline as expected in the context of a significant clinical improvement, highlighting the importance of measuring patient-oriented outcomes. As evidence comes mainly from case series and case reports, randomized controlled trials are needed to evaluate further the safety and efficacy of biologics in ABPA.The reviews of this paper are available via the supplemental material section.

Evaluation of the LDBio Aspergillus ICT lateral flow assay for serodiagnosis of allergic bronchopulmonary aspergillosis.

BACKGROUND: Early recognition and diagnosis of allergic bronchopulmonary aspergillosis (ABPA) is critical to improve patient symptoms, and antifungal therapy may prevent or delay progression of bronchiectasis and development of chronic pulmonary aspergillosis. OBJECTIVE: A recently commercialized lateral flow assay (Aspergillus ICT) (LDBio Diagnostics, Lyons, France) detects Aspergillus-specific antibodies in <30 minutes, requiring minimal laboratory equipment. We evaluated this assay for diagnosis of ABPA compared to diseased (asthma and/or bronchiectasis) controls. METHODS: ABPA and control sera collected at the National Aspergillosis Centre (Manchester, UK) and/or from the Manchester Allergy, Respiratory and Thoracic Surgery research biobank were evaluated using the Aspergillus ICT assay. Results were read both visually and digitally (using a lateral flow reader). Serological Aspergillus-specific IgG and IgE, and total IgE titres were measured by ImmunoCAP. RESULTS: For 106 cases of ABPA versus all diseased controls, sensitivity and specificity for the Aspergillus ICT were 90.6% and 87.2%, respectively. Sensitivity for 'proven' ABPA alone (n = 96) was 89.8%, and 94.4% for 'presumed' ABPA (n = 18). 'Asthma only' controls (no bronchiectasis) and 'bronchiectasis controls' exhibited 91.4% and 81.7% specificity, respectively. Comparison of Aspergillus ICT result with Aspergillus-specific IgG and IgE titres showed no evident immunoglobulin isotype bias. Digital measurements displayed no correlation between ImmunoCAP Aspergillus-specific IgE level and ICT test line intensity. CONCLUSIONS: The Aspergillus ICT assay exhibits good sensitivity for ABPA serological screening. It is easy to perform and interpret, using minimal equipment and resources; and provides a valuable simple screening resource to rapidly distinguish more serious respiratory conditions from Aspergillus sensitization alone.

Pleural effusion. An unfamiliar presentation of ABPA.

Pleural effusion is rarely encountered in patients of allergic bronchopulmonary aspergillosis (ABPA). We report the case of a 17-year-old male who presented with complaints of fever, cough and increasing shortness of breath for 3 weeks. Patient had breathlessness with seasonal variation. Patient had right lower lobe consolidation with pleural effusion which did not respond to antibiotics. Pleural fluid was exudate with neutrophilic predominance and low ADA. Skin prick test for Aspergillus fumigatus was positive, both total IgE and specific IgE against Aspergillus fumigatus were raised.

Molecular allergen sensitization of Aspergillus fumigatus between allergic bronchopulmonary aspergillosis and A fumigatus-sensitized asthma in Guangzhou, Southern China.

BACKGROUND: Few studies have assessed the sensitization of mycotic allergens and Aspergillus fumigatus molecular allergens. This study aimed to investigate the relationships of A fumigatus components and mycotic allergens in allergic bronchopulmonary aspergillosis (ABPA) patients and A fumigatus (Af)-sensitized asthma patients. METHODS: Serum sIgE levels of Penicillium chrysogenum, Cladosporium herbarum, Mucor racemosus, Candida albicans, Alternaria alternata, Helminthosporium halodes, and A fumigatus allergen components (Asp f 1, Asp f 2, Asp f 3, Asp f 4, and Asp f 6) were measured via the ImmunoCAP assay in 18 ABPA and 54 Af-sensitized asthma patients in Guangzhou city, China. RESULTS: 94.44% of ABPA patients and 87.04% of Af-sensitized asthma patients were co-sensitized to at least one other fungal allergen. The positive rates of Asp f 1 (88.89% vs 59.26%, P < .05), Asp f 2 (66.67% vs 33.33%, P < .05), Asp f 4 (61.11% vs 33.33%, P < .05), and Asp f 6 (66.67% vs 14.81%, P < .001) in ABPA patients were higher than those in Af-sensitized asthma patients. IgE levels of Asp f 1 (P < .05), Asp f 4 (P < .05), and Asp f 6 (P < .001) were higher in ABPA patients than in Af-sensitized asthma patients. Optimal scale analysis showed that ABPA was more relevant to Af components (Cronbach's alpha = 90.7%). CONCLUSION: The A fumigatus components and their relationships with various mycotic allergens were different in ABPA and Af-sensitized asthma patients. This finding may help local doctors in the diagnosis and immunotherapy of fungal allergies.

Role of recombinant Aspergillus fumigatus antigens in diagnosing Aspergillus sensitisation among asthmatics.

BACKGROUND: The diagnosis of Aspergillus-sensitised asthma (ASA) and allergic bronchopulmonary aspergillosis (ABPA) is made using IgE against crude antigens of A fumigatus (cAsp). However, the IgE against cAsp has limitations due to cross-reactivity with other fungi. OBJECTIVE: To evaluate the utility of recombinant A fumigatus (rAsp) antigens in detecting ASA and their role in differentiating true from cross-sensitisation. METHODS: We performed IgE against rAsp (f 1, f 2, f 3, f 4 and f 6), cAsp and other fungal (Alternaria, Candida, Cladosporium, Malassezia and Trichophyton) antigens in subjects with A fumigatus-unsensitised asthma (Af-UA [n = 51]), ASA (n = 71) and ABPA (n = 123). The diagnoses were made using cAsp-IgE and compared using rAsp-IgE. Subjects with elevated cAsp-IgE, but negative rAsp f 1 and f 2, were presumed to lack true A fumigatus sensitisation. RESULTS: The prevalence of any rAsp antigen positivity (cut-off, 0.35 kUA/L) varied from 2%-22%, 32%-73% and 84%-98% for Af-UA, ASA and ABPA, respectively. The prevalence of sensitisation to other fungi ranged from 29%-65%, 59%-85% and 87%-95%, respectively, among subjects with Af-UA, ASA and ABPA. Nineteen subjects of ASA and one subject with ABPA were positive with cAsp-IgE but negative for rAsp f 1 and f 2 and were also cross-sensitised to at least one of the other fungi. Five subjects of Af-UA (cAsp-IgE negative) were rAsp f 1 or f 2 positive. CONCLUSIONS: Crude Aspergillus antigens may misclassify Aspergillus sensitisation among asthmatics. IgE against rAsp antigens (f 1 and f 2) potentially detect true Aspergillus sensitisation and could be used for this purpose.

Invasive Pulmonary Aspergillosis in Chronic Obstructive Pulmonary Disease Exacerbations.

Nowadays, reports in the literature support that patients with severe chronic obstructive pulmonary disease (COPD) are at higher risk to develop invasive pulmonary aspergillosis (IPA). However, the interpretation of Aspergillus-positive cultures from the airways in critically ill COPD is still a challenge. Indeed, as the patient could be merely colonized, tissue samples are required to ascertain IPA diagnosis but they are rarely obtained before death. Consequently, diagnosis is often only suspected on the basis of a combination of three elements: clinical characteristics, radiological images (mostly thoracic CT scan), and microbiological, and occasionally serological, results. To facilitate the analysis of these data, several algorithms have been developed, and the best effectiveness has been demonstrated by the Clinical algorithm. This is of importance as IPA prognosis in these patients remains presently very poor and using such an algorithm could promote prompter diagnosis, early initiation of treatment, and subsequently improved outcome.While the most classical presentation of IPA in critically ill COPD patients features a combination of obstructive respiratory failure, antibiotic-resistant pneumonia, recent or chronic corticosteroid therapy, and positive Aspergillus cultures from the lower respiratory tract, the present article will also address less typical presentations and discuss the most appropriate treatments which could alter prognosis.

Screening for triazole resistance in clinically significant Aspergillus species; report from Pakistan.

BACKGROUND: Burden of aspergillosis is reported to be significant from developing countries including those in South Asia. The estimated burden in Pakistan is also high on the background of tuberculosis and chronic lung diseases. There is concern for management of aspergillosis with the emergence of azole resistant Aspergillus species in neighbouring countries in Central and South Asia. Hence the aim of this study was to screen significant Aspergillus species isolates at the Microbiology Section of Aga Khan Clinical Laboratories, Pakistan, for triazole resistance. METHODS: A descriptive cross-sectional study, conducted at the Aga Khan University Laboratories, Karachi, from September 2016-May 2019. One hundred and fourteen, clinically significant Aspergillus isolates [A. fumigatus (38; 33.3%), A. flavus (64; 56.1%), A. niger (9; 7.9%) A. terreus (3; 2.6%)] were included. The clinical spectrum ranged from invasive aspergillosis (IA) (n = 25; 21.9%), chronic pulmonary aspergillosis (CPA) (n = 58; 50.9%), allergic bronchopulmonary aspergillosis (ABPA) (n = 4; 3.5%), severe asthma with fungal sensitization (SAFS) (n = 4; 3.5%), saprophytic tracheobronchial aspergillosis (n = 23; 20.2%). Screening for triazole resistance was performed by antifungal agar screening method. The minimum inhibitory concentration (MIC) of 41 representative isolates were tested and interpreted according to the Clinical and Laboratory Standards Institute broth microdilution method. RESULTS: All the isolates were triazole-susceptible on agar screening. MICs of three azole antifungals for 41 tested isolates were found to be ≤1 ml/L; all isolates tested were categorized as triazole-susceptible, including 4 isolates from patients previously on triazole therapy for more than 2 weeks. The minimum inhibitory concentration required to inhibit the growth of 90% organisms (MIC90) of itraconazole, voriconazole and posaconazole of the representative Aspergillus isolates was 1 mg/L, 1 mg/L and 0.5 mg/L, respectively. CONCLUSION: Triazole resistance could not be detected amongst clinical Aspergillus isolates from the South of Pakistan. However, environmental strains remain to be tested for a holistic assessment of the situation. This study will set precedence for future periodic antifungal resistance surveillance in our region on Aspergillus isolates.

Treatment of allergic bronchopulmonary aspergillosis: from evidence to practice.

Allergic bronchopulmonary aspergillosis (ABPA) is a complex pulmonary disorder caused by dysregulated immune responses against Aspergillus fumigatus. The disorder usually complicates the course of patients with asthma and cystic fibrosis. Patients with ABPA most often present with asthma that is poorly controlled despite inhaled corticosteroids and long-acting ß2 agonists. The treatment of ABPA is complicated due to the occurrence of recurrent exacerbations and spontaneous remissions. The drugs used for treating ABPA include systemic glucocorticoids, antifungal agents and biologics, each with its own benefits and drawbacks. In this review, we illustrate the treatment pathway for ABPA in different situations, using a case-based approach. In each case, we present the options for treatment based on the available evidence from recent clinical trials.

[Aspergillus-related respiratory conditions and COPD: Diagnostic challenges]. / Affections aspergillaires respiratoires et BPCO : difficultés diagnostiques.

INTRODUCTION: The relations between chronic obstructive pulmonary disease (COPD) and respiratory diseases due to Aspergillus spp. are not well understood. METHODS: We analysed a retrospective series of patients hospitalized with a diagnosis of COPD and respiratory disease due to Aspergillus. Patients were identified between 2010 and 2015 from the medico-administrative database of Cochin hospital, Paris. Historical, clinical, biological, microbiological and imaging data were collected and described. Diagnoses were reclassified based on reference definitions and classifications from the literature. Patients were classified according to the type of Aspergillus-related diseases and risk factors were described. RESULTS: Forty patients were identified. Classifiable Aspergillus-related respiratory conditions were confirmed in 26 of them including 12 allergic bronchopulmonary aspergillosis (ABPA), 8 chronic pulmonary aspergillosis (CPA), 1 invasive pulmonary aspergillosis (IPA) and 3 diagnostic associations ABPA/CPA. Other respiratory comorbidities were present in all cases of CPA and immunodepression was recorded for semi-invasive and invasive forms. Finally, 16 patients could not be classified, among whom Aspergillus related lung disease was considered as likely in one-half. CONCLUSION: The complexity of the diagnosis of pulmonary aspergillosis is related to its multiple types with sometimes unclear distinctions. Any type of pulmonary aspergillosis can be observed in patients with COPD, depending on associated risks factors. It would be helpful to establish specific classifications adapted to patients with COPD. This will require larger, prospective, multicentre studies.