Criteria For Allergic Bronchopulmonary Aspergillosis Research Articles

Cutoffs of diagnostic criteria for allergic bronchopulmonary aspergillosis in asthmatic children

Cutoffs of diagnostic criteria for allergic bronchopulmonary aspergillosis in asthmatic children

Real-World Effectiveness of Anti–IL-5/5R Therapy in Severe Atopic Eosinophilic Asthma with Fungal Sensitization

Severe asthma with fungal sensitization (SAFS) is a complex clinical phenotype associated with poorly controlled type 2 inflammation and significant morbidity from both the disease itself and a high steroid burden. To assess the effectiveness of biologic therapies targeting eosinophilic inflammation in SAFS. We assessed the effectiveness of treatment with mepolizumab or benralizumab in patients with SAFS, and compared outcomes with patients with severe atopic asthma without fungal sensitization and patients with severe nonatopic asthma. Baseline clinical characteristics and clinical outcomes at 48 weeks were evaluated. A subgroup analysis was performed of patients who met the criteria for allergic bronchopulmonary aspergillosis (ABPA) rather than SAFS. A total of 193 patients treated with mepolizumab (n= 63) or benralizumab (n= 130) were included. Patients with SAFS had higher baseline IgE level compared with patients with severe atopic asthma without fungal sensitization and severenonatopic asthma (733 ± 837 IU/mL vs 338 ± 494 and 142 ± 171, respectively; both P < .001). There were no other significant baseline differences in clinical characteristics betweengroups. At 48 weeks, there were significant improvements in 6-item asthma control questionnaire score and exacerbation frequency, and reduction in maintenance oral corticosteroid dose across all groups (all P < .05). No significant between-group differences in outcomes were observed at 48 weeks. Patients with ABPA (n= 9) had a significant reduction in exacerbation frequency (P= .013) with treatment. Treatment with eosinophil-targeting biologics led to improvements in exacerbation frequency, oral corticosteroid requirements, and patient-reported outcomes in patients with SAFS, with a reduction in exacerbations in the subgroup of patients with ABPA. These data highlight the potential clinical utility of targeting eosinophilic inflammation in SAFS and ABPA.

A PATIENT WITH ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS (ABPA) WHO HAD UNDERGONE TUBERCULOSIS TREATMENT TWICE

The case subject was a 19-year-old exchange student from Thailand who had undergone tuberculosis (TB) treatment twice. Upon observing a shadow in the right upper lung, the patient was referred for examination; however, acid-fast bacteria test results were negative. Furthermore, high levels of total IgE and anti-aspergillus IgE and IgG antibodies were found. Bronchoscopy revealed inflammation with stenosis in the right superior lobar bronchus, and there was an outflow of yellow viscous sputum upon suctioning. After applying a localized steroid spray, the patient expectorated a large amount of sputum containing Aspergillus fumigatus. Upon administration of steroids and itraconazole, the conglomerate mass shadow's inner portion disappeared, and dilated bronchi appeared. Even though the diagnostic criteria for allergic bronchopulmonary aspergillosis (ABPA) of Rosenberg and Patterson were not strictly satisfied, ABPA was diagnosed in conjunction with the course of treatment. It was determined that prior tubercle bacilli test results were negative, and thus the patient must have had ABPA from the onset. The symptoms eased, and the patient returned to Thailand. Although pulmonary tuberculosis and ABPA are different illnesses, they share similarities in symptoms and clinical findings. Therefore, past medical history should not be believed blindly, and it is imperative to diagnosis the condition accurately by performing appropriate tests. Furthermore, we had the opportunity to view the computed tomography images of the chest 18 years after the initial examination. In the entire lung region, findings of significant bronchiectasis were presented.

New clinical diagnostic criteria for allergic bronchopulmonary aspergillosis/mycosis and its validation

There are several clinical diagnostic criteria for allergic bronchopulmonary aspergillosis (ABPA). However, these criteria have not been validated in detail, and no criteria for allergic bronchopulmonary mycosis (ABPM) are currently available. This study proposes new diagnostic criteria for ABPA/ABPM, consisting of 10 components, and compares its sensitivity and specificity to existing methods. Rosenberg-Patterson criteria proposed in 1977, the International Society for Human and Animal Mycology (ISHAM) criteria proposed in 2013, and this new criteria were applied to 79 cases with pathological ABPM and the control population with allergic mucin in the absence of fungal hyphae (n= 37), chronic eosinophilic pneumonia (n= 64), Aspergillus-sensitized severe asthma (n= 26), or chronic pulmonary aspergillosis (n= 24). These criteria were also applied to the 179 cases with physician-diagnosed ABPA/ABPM in a nationwide Japanese survey. The sensitivity for pathological ABPM with Rosenberg-Patterson criteria, ISHAM criteria, and this new criteria were 25.3%, 77.2%, and 96.2%, respectively. The sensitivity for physician-diagnosed ABPA/ABPM were 49.2%, 82.7%, and 94.4%, respectively. The areas under the curve for the receiver-operating characteristic curves were 0.85, 0.90, and 0.98, respectively. The sensitivity for ABPM cases that were culture-positive for non-Aspergillus fungi were 13.0%, 47.8%, and 91.3%, respectively. The new diagnostic criteria, compared with existing criteria, showed better sensitivity and specificity for diagnosing ABPA/ABPM.

Measuring total IgE is useful in detecting exacerbations in patients with allergic bronchopulmonary aspergillosis receiving omalizumab

The pathogenesis of allergic bronchopulmonary aspergillosis (ABPA), a hypersensitivity reaction to Aspergillus fumigatus antigens, is complex and not yet fully clarified.Moreover, the diagnosis might sometimes represent a challenge because there is no universal consensus on the diagnostic criteria originally proposed by Rosenberg et al. Nonetheless, IgE plays a key pathogenic role in the disease, and is currently accepted as a marker of both initial diagnosis and disease activity. Systemic corticosteroids are required to suppress the immunological response, but ABPA is a chronic and progressive disease, associated with repeated exacerbations after successful treatment with steroids and/or antifungal agents. The well-known adverse effects of steroids have prompted clinicians to look for other therapeutic options. Hence, omalizumab, an mAb that binds to circulating IgE, has been repeatedly reported to successfully control ABPA within the initial months of treatment, both in retrospective case series and in a recent placebo-controlled registered clinical trial, but no long-term information is currently available. Another problem is that the ability to assess adequate reductions in total IgE levels afterward, or even to detect further exacerbations, on the basis of indicator and predictor value of serum IgE in ABPA, represents a concern in all patients receiving omalizumab. This occurs given that measuring the total IgE level through commercially available methods is considered not quite reliable in patients receiving omalizumab, and measuring free IgE is both controversial and, above all, not available for most clinicians. The aim of this communication was to describe the long-term clinical follow-up and serial measured total and specific IgE levels in 3 adult patients with ABPA while receiving treatment with omalizumab. All 3 patients have severe asthma according to the European Respiratory Society/American Thoracic Society criteria, and central bilateral bronchiectasis on chest computed tomography. The main clinical, laboratory, and spirometric parameters of the 3 patients are summarized in Table I. The pattern of total IgE levels over time is shown in Figure 1. Patient 1 (male, 44 years old) met commonly used criteria for ABPA since 1999, with multiple severe exacerbations requiring systemic corticosteroids and itraconazole (on average 3/year), a mean baseline total IgE level of 1000 KU/L (ImmunoCAP Phadia, Uppsala, Sweden), rising up to 4000 KU/L during exacerbations, and lung function impairment (mean baseline FEV1 70% of predicted, decreasing down to 43% during exacerbations). In 2010, he was started on omalizumab, with clinical and lung function improvement and a decrease in the total IgE level to 315 KU/L within the first year, being stable afterward and without ABPA exacerbations for almost 2 years. Still on omalizumab, in 2013 he had an ABPA relapse consisting of clinical and spirometrical decline, blood eosinophilia up to 1393/mm, increase in specific IgE and IgG levels to Aspergillus fumigatus, and also an almost 10-fold increase (from 400 to 3788 IU/mL) in measured total IgE level, which decreased progressively after initiating treatment with oral corticosteroids and itraconazole, coinciding with clinical improvement and progressive steroid step-down. Patient 2 (female, 50 years old) has aspirin-exacerbated respiratory disease (chronic rhinosinusitis with recurrent nasal polyps, difficult-to-control asthma, and aspirin hypersensitivity) since 1983; therefore, off-label treatment with omalizumab was started in 2008, achieving clinical and spirometrical stability (mean FEV1, 70%-75% of predicted) and no further need of sinus surgery. Every now and then she presented blood eosinophilia up to 900/mm, but the total IgE level was always around 400 KU/L, specific IgE and IgG for Aspergillus spp had always been negative, and Churg-Strauss and other autoimmune vasculitis had also been excluded. Almost 6 years after starting omalizumab, the patient experienced progressively worsening asthma symptoms and FEV1 decline down to 54% predicted. Chest X-ray was normal. The skin prick test performed to A fumigatus was positive (6 8 mm), and blood work revealed a total IgE level of 2402 KU/L, specificAspergillus IgG of 66mgA/L, and r Asp f 4 of 212 KU/L. The total IgE level decreased after starting oral steroids and itraconazole in July 2014, with progressive clinical and spirometric improvement up to previous values (FEV1 79% predicted). One year later (July 2015), she maintains asthma control (Asthma Control Test: 24 points), with no further exacerbations and having suspended oral steroids. Patient 3 (male, 34 years old) has early-onset allergic bronchial asthma. At age 20 years, he was diagnosed with ABPA, experiencing frequent and severe exacerbations, some of them requiring hospital admission. In 2008, he was started on omalizumab with consequent clinical improvement and stability for almost 3 years. In 2011, he was referred for a moderate clinical worsening (Asthma Control Test value decreased from 25 to 19 points). The total IgE level increased from 1132 kU/L to 2425 KU/L. One month after starting oral steroids, the total IgE level decreased to 964 KU/L, and clinical and lung function

Infection pulmonaire à Mycobacterium abscessus sensu lato chez des patients exempts de mucoviscidose

Infection with Mycobacterium abscessus sensu lato is uncommon in patients without cystic fibrosis. We are interested in these patients and have collected cases in Finistère between 2007 and 2011. Four patients met the infection criteria recommended by the American Thoracic Society in 2007. Among them, all had Aspergillus spp. in sputum, 3 had gastroesophageal reflux and two had the criteria for allergic bronchopulmonary aspergillosis. We identified Mycobacterium massiliense in the single patient in our series whose therapeutic outcome was successful. By comparing these data with those in the literature, we believe that the search for allergic bronchopulmonary aspergillosis and gastroesophageal reflux is necessary in these patients and that species identification is essential for prognosis.

EPS02.2 Fungal colonization in a cystic fibrosis adult population

Fungal colonization is extremely frequent in patients with cystic fibrosis. However, its consequences and implications are still unclear. Aim To determine the prevalence and risk factors of fungal colonization in adult patients with CF. Methods Observational study of 37 adult patients with cystic fibrosis, followed at Hospital de Santa Maria, Lisbon. Clinical files were reviewed in order to collect the following data: demographics, sputum colonization, lung function (FEV1), nutritional status (BMI), pancreatic function and presence of diabetes. The patients were divided according to whether they had fungi in the sputum or not. Results More than two-thirds of the patients (67.6%) were colonized by fungi. The group with fungi was 2 years younger than the group without fungi. The group with fungi had a FEV1 15% lower than the group without fungi (p = 0.062). The group with fungi had also a higher rate of P. aeruginosa chronic infection (77%) than the group without fungi (58%) (p = 0.443). The patients with fungi had a higher prevalence of pancreatic insufficiency and a lower body mass index. However, the results had no statistic significance. The prevalence of cystic fibrosis related diabetes was 10.8% and none of this patients had criteria of allergic bronchopulmonary aspergillosis. Conclusion Fungal colonization is a marker of greater disease severity, as seen by the lower FEV1, higher prevalence of P. aeruginosa chronic infection, lower BMI and higher prevalence of pancreatic insufficiency in these patients. A transversal study with a larger population is essential to determine whether fungal colonization is a cause or a consequence of greater disease severity.

Allergic Broncho Pulmonary Aspergillosis Complicated by Nocardiosis

We describe a 70-year-old male with a history of diabetes mellitus, hypertension, and asthma who presented with increasing breathlessness for 5 months. He was diagnosed to have allergic bronchopulmonary aspergillosis (ABPA) by serological and radiographic criteria. He was treated with steroids and itraconazole. After initial improvement, he developed fever with cough and mucopurulent sputum. X-ray chest revealed multiple cavities with air fluid level. Patient was treated with antibiotics without any response. Sputum was negative for acid fast bacilli (AFB). Sputum culture for bacteria and fungus did not reveal any significant growth; however a delayed growth of Nocardia was noted on fungal plates. Modified Ziehl Nelsen stain was positive for AFB. Patient was treated with cotrimoxazole. We discuss the serological and radiological criteria of ABPA, presentation and treatment of nocardia pulmonary infection and other possible causes of necrotizing pneumonia in immunocompromised settings.

Severe Asthma With Fungal Sensitization in a Child: Response to Itraconazole Therapy

People with severe asthma with fungal sensitization may represent an underdiagnosed subset of patients with refractory disease. It is important to know that such patients may benefit from adjunct treatment with antifungal agents. We describe here the case of a child with refractory asthma, persistent airway obstruction, a serum immunoglobulin E level of >20000 IU/mL, and severe eosinophilic airway infiltration. Although he did not meet diagnostic criteria for allergic bronchopulmonary aspergillosis, he demonstrated evidence of sensitization to several fungi and responded dramatically to the addition of itraconazole therapy. We also discuss emerging hypotheses regarding fungal-induced asthma.

Allergic bronchopulmonary aspergillosis in a patient with cystic fibrosis: diagnostic criteria when the IgE level is less than 500 IU/mL

Recently, the Cystic Fibrosis Foundation developed a consensus report recommending diagnostic criteria for allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis that includes a serum IgE level greater than 500 IU/mL as the "minimal diagnostic criterion." To describe a 7-year-old girl with ABPA whose serum IgE level increased to only 398 IU/mL. Total IgE and anti-Aspergillus serologic measurements were performed using enzyme-linked immunosorbent assay and standard laboratory techniques; HLA analysis was performed; interleukin 4 receptor alpha single nucleotide polymorphisms were performed using polymerase chain reaction and DNA sequencing; CD23+ B cells were measured using flow cytometry; and cytokine synthesis to Aspergillus purified antigens was assessed using flow cytometry. A 7-year-old girl with cystic fibrosis who had mild pulmonary disease and well-controlled asthma developed pulmonary infiltrates, increased wheezing, and decreased pulmonary function. Additional studies demonstrated peripheral blood eosinophilia (eosinophil count, 1807 cells/mm3 [19%]) and an increase in IgE and IgG anti-Aspergillus serology; bronchoalveolar lavage revealed septate hyphae with 45 degrees branching subsequently identified as A fumigatus and pulmonary eosinophilia. Previous HLA typing revealed that the patient was HLA-DR2+, DRB*1501, HLA-DQ2-, a pattern associated with increased risk of ABPA. In addition, there was increased up-regulation of CD23 molecules by interleukin 4 stimulation on the patient's B cells, as observed in ABPA. The patient was treated with corticosteroids and itraconazole with resolution of symptoms and pulmonary infiltrates. Examination of the pulmonary inflammatory response using bronchoalveolar lavage, genetic risk with HLA-DR2+DQ2- typing, and increased interleukin 4 sensitivity are useful adjunctive studies in the diagnosis of ABPA.

Allergic Bronchopulmonary Aspergillosis with Normal Serum IgE in a Child with Cystic Fibrosis

Diagnostic criteria for allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis have required an absolute increase in total serum immunoglobulin E (IgE) to > 1000 IU/mL (2400 ng/mL). Current guidelines recommend in depth evaluation for those with IgE > 500 IU/mL (1200 ng/mL), or even for those with lower values if there is clinical suspicion for ABPA. We present a case of a patient who met all criteria for ABPA with the exception of elevation of IgE above the diagnostic level. An increase in serum IgE from the baseline level, but not > 1000 IU/mL, and subsequent return to baseline corresponded to a clinical exacerbation and resolution of presumptive ABPA.

Cavernous Destruction of an Upper Lung Lobe in a Healthy Young Man: An Unusual Roentgenographic Presentation of Allergic Bronchopulmonary Aspergillosis

We describe a 32-year-old man with no history of pulmonary disease who presented with extensive cavernous destruction of the right upper lobe as an incidental finding on a chest x-ray film. All major criteria of allergic bronchopulmonary aspergillosis (ABPA) were present. Histologic examination of the resected lobe showed the typical features of ABPA. The differential diagnosis of multiple cavitating lesions should include ABPA.

Prevalence of asthma in patients with bronchiectasis in Hong Kong

Eighty five Chinese patients with diffuse or localized bronchiectasis (non-cystic fibrosis) were studied regarding the prevalence of asthma. Twenty three of the 85 had concomitant asthma, diagnosed by history and reversibility on lung function testing either spontaneously or after bronchodilator. None fulfilled the diagnostic criteria of allergic bronchopulmonary aspergillosis (ABPA). Asthma preceded the onset of bronchiectasis in 13 patients and developed after long duration of bronchiectasis in seven, while the temporal onset could not be differentiated in three patients. Patients with both asthma and bronchiectasis had inferior spirometric values, higher prevalence of bronchial hyperresponsiveness to methacholine, higher prevalence of skin atopy, elevated serum immunoglobulin E (IgE), and more sputum eosinophilia, compared with their non-asthmatic counterparts. Possible mechanisms by which asthma and bronchiectasis predispose to each other include asthmatic obstruction contributing to development of bronchiectasis, and sensitization of airways with increased lability due to microbial colonization of the ectatic bronchial tree.

High prevalence of asthma in patients with bronchiectasis in Hong Kong

Eighty five Chinese patients with diffuse or localized bronchiectasis (non-cystic fibrosis) were studied regarding the prevalence of asthma. Twenty three of the 85 had concomitant asthma, diagnosed by history and reversibility on lung function testing either spontaneously or after bronchodilator. None fulfilled the diagnostic criteria of allergic bronchopulmonary aspergillosis (ABPA). Asthma preceded the onset of bronchiectasis in 13 patients and developed after long duration of bronchiectasis in seven, while the temporal onset could not be differentiated in three patients. Patients with both asthma and bronchiectasis had inferior spirometric values, higher prevalence of bronchial hyperresponsiveness to methacholine, higher prevalence of skin atopy, elevated serum immunoglobulin E (IgE), and more sputum eosinophilia, compared with their non-asthmatic counterparts. Possible mechanisms by which asthma and bronchiectasis predispose to each other include asthmatic obstruction contributing to development of bronchiectasis, and sensitization of airways with increased lability due to microbial colonization of the ectatic bronchial tree.

Aspergillosis and atopy in cystic fibrosis.

Forty-six patients with cystic fibrosis (CF) were studied for colonization and sensitization by Aspergillus organisms. The fungus was cultured from 21 of 37 (57%) patients who produced sputum. The non-CF sputum isolation rate was 6.5%. Sputum hyphae were seen in 95% of patients with positive cultures. Sputum eosinophilia accompanied colonization by Aspergillus. Aspergillus precipitins were found in 37% of CF patients; positive immediate skin tests were found in 39%. "Atopy" defined by skin test criteria was found in 46%. All of these findings were more common in patients with more severe disease (p less than 0.05). CF patients had predominant mold sensitivity in contrast to predominant pollen sensitivity in a control group of asthmatic subjects. Serum IgE concentrations were increased in 22% of CF patients. CF patients who had increased serum concentrations of IgE were more likely to have a family history of atopy. Wheezing was more common in those who were atopic, especially the group with predominant mold sensitivity who had more severe disease. Four patients fulfilled the diagnostic criteria for allergic bronchopulmonary aspergillosis (ABPA) during the time of study and follow-up. A fifth patient had ABPA diagnosed before the study. The incidence of ABPA during a 2-yr period in our CF population was 11%.