High attenuation mucus in bronchi with allergic bronchopulmonary mycosis.

BACKGROUND: High-attenuation mucus (HAM) is a specific manifestation of allergic bronchopulmonary mycosis (ABPM) on chest computed tomography (CT). OBJECTIVES: To compare the diagnostic accuracy of the two definitions of HAM and to clarify the clinical and radiographic characteristics of HAM-positive and HAM-negative ABPM. METHODS: CT images at the diagnosis of ABPM using Asano's criteria were retrospectively analysed. In Study #1, radiographic data obtained using the same CT apparatus in a single institute were analysed to determine the agreement between the two definitions of HAM: a mucus plug that is visually denser than the paraspinal muscles or that with a radiodensity ≥70 Hounsfield units. In Study #2, HAM was diagnosed by comparison with the paraspinal muscles in patients with ABPM reporting to 14 medical institutes in Japan. RESULTS: In Study #1, 93 mucus plugs from 26 patients were analysed. A substantial agreement for HAM diagnosis was observed between the two methods, with a κ coefficient of 0.72. In Study #2, 60 cases of ABPM were analysed; mucus plugs were present in all cases and HAM was diagnosed in 45 (75%) cases. The median A. fumigatus-specific IgE titre was significantly lower in HAM-positive patients than in HAM-negative patients (2.5 vs. 24.3 UA /mL, p = .004). Nodular shadows were observed more frequently in the airways distal to HAM than in those distal to non-HAM mucus plugs (59% vs. 32%, p < .001). CONCLUSION: In conclusion, agreement between the two methods to diagnose HAM was substantial. HAM was associated with some immunological and radiographic characteristics, including lower levels of sensitization to A. fumigatus and the presence of distal airway lesions.

Radiological Diagnosis of Pulmonary Aspergillosis.

Imaging plays an important role in the various forms of Aspergillus-related pulmonary disease. Depending on the immune status of the patient, three forms are described with distinct imaging characteristics: invasive aspergillosis affecting severely immunocompromised patients, chronic pulmonary aspergillosis affecting less severely immunocompromised patients but suffering from a pre-existing structural lung disease, and allergic bronchopulmonary aspergillosis related to respiratory exposure to Aspergillus species in patients with asthma and cystic fibrosis. Computed tomography (CT) has been demonstrated more sensitive and specific than chest radiographs and its use has largely contributed to the diagnosis, follow-up, and evaluation of treatment in each condition. In the last few decades, CT has also been described in the specific context of cystic fibrosis. In this particular clinical setting, magnetic resonance imaging and the recent developments in artificial intelligence have shown promising results.

Value of CT Radiomics Combined with Clinical Features in the Diagnosis of Allergic Bronchopulmonary Aspergillosis.

Objective: Early diagnosis of allergic bronchopulmonary aspergillosis (ABPA) and targeted treatment can block the process of the disease. This study explores the diagnostic value of CT radiomics combined with clinical features in allergic ABPA. Methods: A total of 40 patients with ABPA were studied retrospectively, divided into training set (n = 28) and test set (n = 12). Based on CT imaging, the radiomics features are extracted and combined with clinical features to build a diagnostic model. The diagnosis model was based on support vector machine algorithm. The receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to evaluate the diagnostic efficiency of the model. Results: There was no significant difference in general information and clinical data between the training and test sets (P > 0.05). The AUC of the training set and the test set is 0.896 (95% CI: 0.836-0.963) and 0.886 (95% CI: 0.821-0.952), respectively. Conclusion: Based on the CT radiomics model combined with clinical data, it has high efficiency in the diagnosis of ABPA.

Structural lung disease following allergic bronchopulmonary aspergillosis complicating pediatric cystic fibrosis.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) complicating cystic fibrosis (CF) is frequently associated with significant structural lung damage as assessed by computed tomography (CT) scanning. METHODS: Using a validated CF scoring system (structural lung disease [SLD] score) we examined the degree of structural lung disease in a group of 25 children with CF who had received steroid therapy for ABPA (CF-ABPA) and compared our findings to a matched group of CF patients without ABPA (CF-CON) using both cross-section and longitudinal analysis. Further, we examined the structure-function correlation between CT findings and lung function. RESULTS: Mean SLD score (expressed as a percentage of maximal score) was significantly higher (worse) in the CF-ABPA group than the CF-CON group (29.3% CF-ABPA vs. 18.7% CF-CON p < .05). CF-ABPA patients showed significantly greater rate of development of structural lung disease over time than CF-CON patients (6.8% per year vs 1.4% p < .01). We found no correlation between lung function and the degree of structural lung disease. CONCLUSIONS: ABPA in children with CF is associated with significantly more structural lung disease than that found in children with CF without ABPA. Despite interventive steroid therapy lung disease progresses more rapidly in those patients with ABPA and CF than control patients with CF.

Uncommon presentation of allergic bronchopulmonary aspergillosis during the COVID-19 lockdown: a case report.

BACKGROUND: During the ongoing pandemic of coronavirus disease 2019 (COVID-19), lockdown periods have changed the way that people and communities live, work and interact. CASE PRESENTATION: This case report describes an uncommon but important presentation of allergic bronchopulmonary aspergillosis (ABPA) in a previously healthy male, who decided to live in the basement of his house when Italy entered a nationwide lockdown during the COVID-19 pandemic. As high resolution computed tomography (HRCT) of the chest on admission showed diffuse miliary nodules, a miliary tuberculosis was initially suspected. However, further investigations provided a diagnosis of unusual presentation of ABPA. CONCLUSIONS: This case highlights the importance of maintaining awareness of Aspergillus-associated respiratory disorders during the COVID-19 pandemic, especially because lifestyle changes associated with home isolation carry an increased risk of exposure to mold spores present in some indoor environments.

Bronquiectasias no fibrosis quística: desde la infancia a la adultez: enfoque diagnostico y terapéutico / Bronchiectasis no cystic fibrosis: from childhood to adult: diagnostic and therapeutic approach

Bronchiectasis is a suppurative lung disease with heterogeneous phenotypic characteristics. It is defined as abnormal dilation of the bronchi, losing the existing relationship between bronchial sizes and accompanying artery. According to their form, they can be cylindrical, varicose, saccular or cystic. According to its location, they could be diffuse or localized. The diagnosis of bronchiectasis is usually suspected in patients with chronic cough, mucopurulent bronchorrea, and recurrent respiratory infections. The etiology can be varied, being able to classify in cystic fibrosis bronchiectasis, when there is cystic fibrosis transmembrane regulator (CFTR) gene mutation and not cystic fibrosis, being post infectious the most frequent. Its relationship with childhood is unknown. Severe respiratory infections can predispose in a susceptible subject the so-called theory of the "vicious circle" and the development of these. Persistent bacterial bronchitis in children has been described as a probable cause of not cystic fibrosis bronchiectasis in adults. The treatment is based on the management of symptoms and the prevention of exacerbations. The evidence is poor and many treatments are extrapolated from cystic fibrosis bronchiectasis. We are going to describe the diagnostic and therapeutic approach of non-cystic fibrosis bronchiectasis in adults.

La bronquiectasia es una enfermedad pulmonar supurativa con características fenotípicas heterogéneas. Se define como la dilatación anormal de los bronquios, perdiendo la relación existente entre tamaño bronquial y arteria que acompaña. Según su forma, pueden ser clasificadas en cilíndricas, varicosas, saculares o quísticas y según su etiología presentarse de forma difusa o localizada. El diagnóstico de bronquiectasias se sospecha generalmente en pacientes con tos crónica, broncorrea mucosa, mucupurulenta e infecciones respiratorias recurrentes. La etiología es variada, pudiendo clasificarse en bronquiectasias fibrosis quística, aquellas que se encuentran en el contexto de la mutación del gen regulador transmembrana de fibrosis quística (CFTR) y no fibrosis quística, de etiologías diversas, siendo post infecciosas la gran mayoría. No se conoce con certeza su relación con la infancia, es sabido que infecciones respiratorias severas pueden predisponer en un sujeto susceptible, a la llamada teoría del "circulo vicioso" y el desarrollo de estas. La bronquitis bacteriana persistente en niños se ha descrito como una causa probable del desarrollo de bronquiectasias no fibrosis quística en adultos. El tratamiento se basa en el manejo de los síntomas y la prevención de las exacerbaciones. La evidencia es escasa y la mayoría de las terapias se han investigado en las bronquiectasias tipo fibrosis quística. En este trabajo se explicará el enfrentamiento diagnóstico y terapéutico de los adultos portadores de bronquiectasias no fibrosis quística.

Allergic bronchopulmonary aspergillosis presumably unmasked by PD-1 inhibition.

Programmed cell death-1 (PD-1) inhibitors stimulate immune recognition of tumour cells in cancer patients, but have significant autoimmune side effects including pneumonitis. We report the case of a patient with asthma and mild eosinophilia who developed unusual pulmonary side effect of bronchiectasis, severe eosinophilia (absolute eosinophil count: 3200 c/mm3) and elevated IgE levels (7050 IU/mL; normal: <164 IU/mL) 4 months into therapy with the PD-1 inhibitor pembrolizumab. Aspergillus fumigatus IgG was elevated at 15.60 U/mL (normal: <12.01 U/mL). He responded to therapy with corticosteroids and voriconazole and was able to resume pembrolizumab thereafter with good clinical response.

CT evaluation of hyperattenuating mucus to diagnose allergic bronchopulmonary aspergillosis in the special condition of cystic fibrosis.

BACKGROUND: Mucus plugging (MP), central bronchiectasis (CB), and consolidation/atelectasia (CA) are conventional CT signs to diagnose allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF). Hyperattenuating mucus (HAM) has recently been described and may improve diagnostic accuracy. The goal of our study was to compare HAM versus conventional CT signs to diagnose ABPA in CF. Secondary objectives were to determine the optimal threshold of HAM quantitatively and to assess the diagnostic value of HAM using chest radiograph (CXR). METHODS: The study was retrospective and included 137 patients with CF, aged >6-year-old. The presence of HAM, CB, MP and CA were determined by two radiologists in consensus. HAM was quantified using an absolute mean density value (AMD) and a ratio between mucus and paraspinal muscle (DRM). Sensitivity (Se), Specificity (Sp) and Youden's J-index were calculated. The Cystic Fibrosis Conference Consensus criteria were chosen as Gold Standard. RESULTS: 23 out of 137 CF patients had ABPA. Using CT, the most sensitive structural alteration was MP (Se = 91%), followed by CB (Se = 87%) and CA (Se = 70%) whereas specificities were 28%, 19% and 58%, respectively. Conversely, HAM had the highest specificity (Sp = 100%) whereas Se was 69%. HAM had the highest Youden's J-index (p < 0.001) Quantitative optimal thresholds were AMD > 78 HU (Se/Sp = 71%/98%) and DRM > 1.3 (Se/Sp = 82%/97%). HAM was unseen using CXR (Se = 0%). CONCLUSION: HAM is the most specific CT biomarker of ABPA in CF, with good sensitivity. Our study suggests that characterization of mucus density may improve the accuracy of imaging criteria to diagnose ABPA early.

Evaluation of 3 T lung magnetic resonance imaging in children with allergic bronchopulmonary aspergillosis: Pilot study.

OBJECTIVE: To evaluate the diagnostic performance of 3 T lung magnetic resonance imaging (MRI) in children with allergic bronchopulmonary aspergillosis (ABPA). MATERIALS AND METHODS: This study protocol was approved by the institutional ethics committee. From October 2015 to January 2018, we prospectively evaluated twenty-seven consecutive children with ABPA. The diagnosis of ABPA was made on the ISHAM-ABPA working group criteria. High resolution computed tomography (HRCT) and 3 T MRI of the chest was performed on the same day. Bronchiectasis, consolidation, nodules, and mucus impaction were assessed in all segments. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of MRI were calculated using HRCT findings as the reference standard. Interobserver agreement was calculated using the kappa statistic. RESULTS: The mean age of the patients was 9.89 years (range: 5-16 years). There were 20 males and 7 females. The sensitivity, specificity, PPV, and NPV for bronchiectasis was 68%, 100%, 100% and 71.43% respectively. The sensitivity, specificity, PPV, and NPV for consolidation was 80%, 100%, 100% and 96% respectively. For detection of nodules, the sensitivity, specificity, PPV, and NPV was 75%, 100%, 100% and 88.46% respectively. There was 100% sensitivity, specificity, PPV and NPV for mucus impaction. There was a high degree of interobserver agreement for MRI findings (k = 0.9-1) as well as agreement (k = 0.7-1) between CT and MRI for all the four findings. CONCLUSION: With the currently available routine MR sequences, MRI demonstrates high specificity but less sensitivity and negative predictive value to HRCT scan in children with ABPA. Newer MR sequences need to be explored and validated to enhance the potential of lung MRI in ABPA.

Allergic Bronchopulmonary Aspergillosis-A Luminal Hypereosinophilic Disease With Extracellular Trap Cell Death.

Allergic bronchopulmonary aspergillosis (ABPA) is characterized by an early allergic response and late-phase lung injury in response to repeated exposure to Aspergillus antigens, as a consequence of persistent fungal colonization of the airways. Here, we summarize the clinical and pathological features of ABPA, focusing on thick mucus plugging, a key observation in ABPA. Recent findings have indicated that luminal eosinophils undergo cytolytic extracellular trap cell death (ETosis) and release filamentous chromatin fibers (extracellular traps, ETs) by direct interaction with Aspergillus fumigatus. Production of ETs is considered to be an innate immune response against non-phagocytable pathogens using a "trap and kill" mechanism, although eosinophil ETs do not promote A. fumigatus damage or killing. Compared with neutrophils, eosinophil ETs are composed of stable and condensed chromatin fibers and thus might contribute to the higher viscosity of eosinophilic mucus. The major fate of massively accumulated eosinophils in the airways is ETosis, which potentially induces the release of toxic granule proteins and damage-associated molecular patterns, epithelial damage, and further decreases mucus clearance. This new perspective on ABPA as a luminal hypereosinophilic disease with ETosis/ETs could provide a better understanding of airway mucus plugging and contribute to future therapeutic strategies for this challenging disease.

Radioaerosol Imaging Predicts the Utility of Aerosolized Antifungal Therapy in Allergic Bronchopulmonary Aspergillosis.

A 10-year-old girl with a history of complicated cystic fibrosis was hospitalized for pulmonary exacerbation with allergic bronchopulmonary aspergillosis and severe right upper lobe bronchiectasis diagnosed with chest radiograph and CT. She was started on itraconazole during the hospitalization in attempt to decrease her systemic steroid dose, but she had ongoing coughing and wheezing. The possibility was raised that the right upper lobe bronchiectasis may be a nidus for ongoing aspergillosis. Radioaerosol imaging was performed to determine whether the aerosolized antifungals would reach the area of bronchiectasis.

"Fleeting pulmonary infiltrates in allergic bronchopulmonary aspergillosis" Misdiagnosed as tuberculosis.

Allergic bronchopulmonary aspergillosis (ABPA) is underdiagnosed and underevaluated routinely because of clinical and radiological overlap with tuberculosis (TB), especially in tropical setting with high TB burden countries like India. ABPA is the best-recognized manifestation of Aspergillus-associated hypersensitivity to Aspergillus antigens in patients with long-standing atopic asthma. ABPA with varied clinical presentation has been reported to occur in 20% of asthmatic patients admitted to hospitals and in 5% of all rhinitis cases. In this case report, we documented middle age male with known asthma case for many years with constitutional symptoms such as cough, fever, and shortness of breath diagnosed as TB and received anti-TB treatment for 4 weeks. Finally, we confirmed as a case of ABPA and documented complete clinical and radiological response to medical treatment with antifungals and systemic corticosteroids.