Should atelectasis be considered a pulmonary complication and indicator of poor prognosis in cystic fibrosis?

OBJECTIVE: This study examined whether bronchoscopy leads to clinicoradiological improvement in cystic fibrosis (CF) and the predictive factors. The study also investigated whether pulmonary atelectasis is a poor prognostic factor in CF. METHODS: This multicenter, case-control, observational, retrospective study included two groups of patients with CF: a case group (patients with persistent atelectasis who were followed-up at least for 2 years) and a control group (patients without atelectasis matched 1:1 by sex and age [±3 years]). We recorded demographic data, lung function test results, pulmonary complications, comorbidities, treatments (including bronchoscopies, surgery and transplantation), and deaths. RESULTS: Each group included 55 patients (case group: 20 men, mean age 25.4 ± 10.4 years; control group: 20 men, mean age 26.1 ± 11.4 years). Bronchoscopy did not lead to clinicoradiological improvement. Allergic bronchopulmonary aspergillosis (ABPA) was more frequent in the case group. Patients in the case group more frequently used inhaled steroids, their pre-atelectasis lung function was statistically worse, and they had more exacerbations during follow-up. CONCLUSION: Moderate-to-severe pulmonary disease and ABPA can favor atelectasis. Pulmonary atelectasis can be a poor prognostic factor in CF because it increases exacerbations. Despite our results, we recommend enhancing treatment, including bronchoscopy, to prevent persistent atelectasis.

Case Report: Allergic Bronchopulmonary Aspergillosis and Tropical Pulmonary Eosinophilia Co-Occurrence Masquerading as Refractory Allergic Bronchopulmonary Aspergillosis.

Pulmonary infiltrates with eosinophilia are a heterogeneous group of disorders that are characterized by pulmonary infiltrates on chest radiograph and elevated levels of eosinophils in the peripheral blood. Among patients with these disorders, reports of either allergic bronchopulmonary aspergillosis (ABPA) or tropical pulmonary eosinophilia (TPE) are common. However, the simultaneous occurrence of ABPA and TPE is not often reported. We present the case of a young man with a history of asthma who was diagnosed with ABPA and TPE. Initially, the patient exhibited a partial response to treatment of ABPA, but persistent symptoms and eosinophilia led to suspicion and subsequent diagnosis of TPE. With implementation of antifilarials and steroids, the patient experienced satisfactory clinical and serological improvements. This case underscores the importance of considering multiple diagnoses in patients with overlapping symptoms and highlights the need for comprehensive management strategies in complex lung diseases.

Polymorphisms in Innate and Adaptive Immune Genes in Subjects with Allergic Bronchopulmonary Aspergillosis Complicating Asthma.

Innate and adaptive immunity play a crucial role in allergic bronchopulmonary aspergillosis (ABPA) pathogenesis. We performed next-generation sequencing using the Illumina TruSight One panel (4,811 human disease-associated genes, at least 20 × coverage) and selected 22 known immune genes (toll-like receptors (TLRs), C-type lectin, interleukin-4 receptor, and others). We included ABPA (n = 18), asthma without ABPA (n = 12), and healthy controls (n = 8). We analyzed 3011 SNPs from 22 genes and identified 145 SNPs (13 genes) that were present only in the disease groups and absent in controls. The SNP frequency overall was significantly higher in ABPA than in asthmatics (89/145 [61.4%] vs. 56/145 [38.6%], p = 0.0001). The SNP frequency in the TLR10 gene was also significantly higher in ABPA than in asthma (p = 0.017). Association analysis further revealed three genes having significant associations. Of these, NOS3 and HLA-DQB1 are associated with antimicrobial activity and adaptive immunity. More extensive studies are required to confirm our findings.

[Allergic bronchopullmonary aspergillosis (ABPA) - an Update]. / Allergische bronchopulmonale Aspergillose (ABPA) ­ ein Update.

Allergic bronchopulmonary aspergillosis (ABPA) is a regular occurrence in everyday pneumology. ABPA should be considered in patients with severe asthma, in mould allergic patients with very high serum IgE levels and in patients with cystic fibrosis. The aim should be to make the diagnosis as early as possible in the course of the disease to avoid late complications such as bronchiectasis and fibrotic lung remodelling. Symptoms are highly variable and rather non-specific, overlapping with those of the underlying primary disease. However, clearly defined diagnostic criteria exist, so that the diagnosis can be made relatively easily if one thinks of it. In therapy, systemic steroids and antifungals (mainly azoles) play the leading role. However, biologics have been gaining in importance in recent years, especially in cases of insufficient therapy response or occurrence of side effects to standard therapies, as well as an alternative in permanently steroid-dependent patients.

Epidemiology of the relationship between allergic bronchopulmonary aspergillosis and asthma.

PURPOSE OF REVIEW: Allergic bronchopulmonary aspergillosis (ABPA) can complicate the natural history of asthmatic patients, especially the more severe ones, worsening disease control and increasing the need for therapies, steroids in particular, and medical care. The aim of the present review is to summarize the latest epidemiological data related to the relationship between asthma and ABPA and to offer a summary of the most recent strategies that could potentially facilitate in the identification of ABPA in asthmatic patients. RECENT FINDINGS: In the last years, great efforts have been made by researchers worldwide to provide reliable epidemiological data on fungal sensitization and ABPA, especially in severe asthma patients both in adult and pediatric population. Data differ depending on the geographical area and population studied, but pooled data show a concerning 11% of severe asthma patients having ABPA and one out of four asthmatic patients being sensitized to fungi, Aspergillus fumigatus in particular. SUMMARY: Reliable epidemiological data and advances in the diagnostic procedures can facilitate the detection of ABPA among asthmatic patients, improving the management of a still under-recognized and challenging condition.

Efficacy of omalizumab in adult patients with allergic bronchopulmonary aspergillosis: a multicentre study in China.

Despite conventional glucocorticoid and antifungal therapy, acute exacerbation and hospitalization occur frequently in patients with allergic bronchopulmonary aspergillosis (ABPA). Whether omalizumab is an effective and safe treatment for adult patients with ABPA complicating asthma. Patients with ABPA complicating asthma who were treated with omalizumab from October 2019 to May 2023 were collected from five tertiary hospitals and evaluated. The frequencies of acute exacerbation and hospitalization; the number of eosinophils; the total IgE levels; and the average monthly medical dosages after 3, 6, and 12 months of omalizumab treatment were analysed, and the data before and after treatment (up to one year) were compared. The efficacy and safety of omalizumab treatment were assessed. In total, 26 patients were enrolled. The average monthly glucocorticoid dosage significantly decreased (median 0 vs. 24 mg/m) after 6 months of omalizumab treatment compared with 3 months; 73.68% of patients discontinued glucocorticoids after ≤ 12 months of treatment. Similarly, the average monthly dosage of antifungal agents was significantly decreased (median 0 vs. 3.49 g/m) after 12 months of treatment compared with 3 months. The average monthly glucocorticoid dosage (median 213.75 vs. 65.42 mg/m, P = 0.002) and the frequency of acute exacerbation (median 0.94 vs. 0.44 events, P = 0.033) were considerably reduced after omalizumab treatment. Omalizumab is effective in reducing the frequency of acute exacerbation and the necessary dosage of glucocorticoids in adult patients with ABPA complicating asthma. Patient age and BMI may affect the efficacy of treatment.

Overlap of Chronic Pulmonary Aspergillosis on Allergic Bronchopulmonary Aspergillosis.

An 80-year-old woman who developed allergic bronchopulmonary aspergillosis (ABPA) was admitted to our institution in 2023 for an enlarged pulmonary mass lesion. She had developed ABPA in 2017, and corticosteroid therapy had improved the mucoid impaction of the bronchi. Because part of the lesion remained, increased doses of corticosteroid, antifungals, and biologics were administered, but the pulmonary lesion enlarged in 2022. Bronchoscopy showed necrotic tissue in the bronchial lumen, and bronchial washing fluid showed neutrophilic inflammation and fungal hyphae. We subsequently diagnosed her as having chronic pulmonary aspergillosis overlapping ABPA, and voriconazole was started that resulted in shrinkage of the nodules.

Heterozygous CARD9 mutation favors the development of allergic bronchopulmonary aspergillosis / 中华医学杂志(英文版)

BACKGROUND@#Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA.@*METHODS@#A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease.@*RESULTS@#The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production.@*CONCLUSION@#Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.

Tabaquismo y aspergilosis broncopulmonar alérgica: una mala combinación / Smoking habit and allergic bronchopulmonary aspergilosis: a bad combination

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Uso de biológicos para asma grave en otras indicaciones fuera de ficha técnica (off label) / Use of biologic agents for severe asthma in other indications that are off label

En la última década, hemos asistido a la introducción de los anticuerpos monoclonales para el tratamiento del asma grave, lo que ha supuesto una auténtica revolución en la vida de muchos de nuestros pacientes. Existen algunas patologías que a menudo, vemos asociadas al asma grave y con las que debemos hacer un adecuado diagnóstico diferencial como son: granulomatosis eosinofílica con poliangeitis (GEPA), síndromes hipereosinofílicos (SHE), neumonías eosinófilas crónicas (NEC) y aspergilosis broncopulmonar alérgica (ABPA) en las que se han probado dichos tratamientos con buenos resultados en la práctica clínica, pero cuya indicación se encuentra actualmente fuera de ficha técnica. Estas patologías suelen precisar para su control de tratamiento con corticoides sistémicos y/o inmunosupresores durante un tiempo prolongado, con los importantes efectos secundarios que conllevan. Las nuevas terapias están permitiendo un importante ahorro de corticoides sistémicos e incluso su retirada en muchos casos. Hemos realizado una revisión de estas enfermedades y de los resultados clínicos de dichos tratamientos biológicos en cada una. Otra situación en la que se dispone de nueva evidencia, es la utilización de biológicos para el asma alérgico grave durante el periodo de embarazo

In the last decade we have attended to the introduction of monoclonal antibodies for the treatment of severe asthma, which have supposed a real revolution in the lives of many of our patients. There are some pathologies that we often see associated with severe asthma and with which we must make an adequate differential diagnosis such as: eosinophilic granulomatosis with polyangiitis (EGPA), hypereosinophilic syndromes (HES), chronic eosinophilic pneumonia (cep) and allergic bronchopulmonary aspergillosis (ABPA). These treatments have been tested with good results in clinical practice, but being used off label. These pathologies usually require treatment with systemic corticosteroids and/or immunosuppressants for a long time producing important side effects. New therapies are allowing significant dose reduction of systemic corticosteroids and even their withdrawal in many cases. We have carried out a review of these diseases and the clinical results of biological treatments in each one of them. Another situation in which new evidence is available, is the use of biologicals for severe allergic asthma during pregnancy

Fungal allergens in a saxophonist who had never smoked with allergic bronchopulmonary aspergillosis previously diagnosed as COPD

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Cystic fibrosis, atopy, asthma and ABPA

The role of atopy on cystic fibrosis (CF) progression remains unclear but evidence suggests that it may influence the appearance of co-morbid conditions such as CF asthma or allergic bronchopulmonary aspergillosis (ABPA).Recognising asthma in patients with CF is not always easy but the identification of atopic markers favours the diagnosis. Physicians should be aware of this fact in order to achieve a better control of respiratory symptoms in patients with CF.Bronchial mucosa inflammation and abnormal mucus predispose to mould colonisation. These patients are at higher risk of allergic sensitisation, especially when atopic susceptibility is present. In the particular case of A. fumigatus, allergic sensitisation precedes ABPA development, which occurs in up to 10% of CF patients. Progression of lung function deterioration is most strikingly pronounced in patients with ABPA. Therefore, sensitisation with A. fumigatus should be regularly tested in patients with CF, especially those at higher risk.Recombinant allergens constitute an important advance in differentiating Aspergillus sensitisation from ABPA itself

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Caso clínico: aspergilosis pulmonar invasiva tratada con Voriconazol en paciente con Síndrome de Inmunodeficiencia Adquirida / Clinical case: invasive pulmonary aspergillosis treated with Voriconazol in an AIDS patient

Se reporta un caso clínico de aspergilosis pulmonar invasiva en un paciente de 29 años VIH(+) en etapa SIDA, sin antecedentes mórbidos conocidos, con diagnóstico inicial de neumonía por Pneumocystis jirovecii. Fue tratado con éxito, pero sin asistir a controles posterior a su alta . Tres meses después ingresa al servicio de Urgencias del Hospital Gustavo Fricke con tos productiva mucopurulenta, disnea progresiva, fiebre intermitente y compromiso del estado general. La radiografía de tórax sugirió neumonía atípica, detectándose en los exámenes Pneumocystis jirovecii y Enterobacter aerógenes , por lo que se inicia tratamiento con Cotrimoxazol y Ertapenem. En los cultivos en agar Sabouraud se detectó abundante desarrollo de Aspergillus fumigatus , por lo que se empieza tratamiento con anfotericina B en dosis crecientes hasta alcanzar 50 mg/día, sin embargo, por reacciones adversas severas se decidió tratamiento con Voriconazol intravenoso y luego oral, con buena respuesta clínica, radiológica y de laboratorio. Es dado de alta con tratamiento con Voriconazol oral, además de profilaxis secundaria para P. jirovecii y Mycobaterium avium.

A clinical case of an invasive pulmonary aspergillosis in a 29 aged VIH (+) patient, at an AIDS stage, lacking any known morbid data, and bearing an initial diagnosis of pneumonia by Pneumocystis jirovecii is herein described. Was successfully treated even though he failed to attend subsequent health controls. Three months later he is admitted in the Hospital Gustavo Fricke, showing productive mucupurulent cough, progressive disnea, intermittent fever and his overall health condition resulting deeply compromised. Thorax X-ray revealed an atypical pneumonia together with the presence of P. jirovecii and Enterobacter aerogenes, and decided to treat him with Cotrimoxazol and Ertapenem. Meanwhile in agar cultures a heavy development of Aspergillus fumigatus was detected, thus the patient was given Anfotericina B in increasing doses up to reach 50mg/day; however due to some severe adverse reactions, the treatment with intravenous and later oral Voriconazol, which rendered satisfactory clinical, radiological and laboratory responses was ultimately preferred. The patient is discharged from the hospital and advised to continue with oral Voriconazol besides undergoing secondary profilaxis for P. jirovecii and Mycobaterium avium.

Aspergilosis bronopulmonar alérgica, diagnóstico previo de una fibrosis quística / Allergic bronchopulmonary aspergillosis, previous diagnosis of a cystic fibrosis

La aspergilosis broncopulmonar alérgica es una enfermedad pulmonar de base inmune frente a diversas especies de Aspergillus. En los pacientes con fibrosis quística, la aspergilosis broncopulmonar alérgica cursa con clínica respiratoria de tos, sibilancias, disnea de esfuerzo que no mejora tras tratamiento antibiótico, a lo que se suman alteraciones radiológicas como bronquiectasias o infiltrados y pruebas que muestran sensibilización al hongo. Presentamos a una paciente con aspergilosis broncopulmonar alérgica que posteriormente fue diagnosticada de fibrosis quística (AU)

The allergic bronchopulmonar aspergillosis is an immunology lung disease produced by Aspergillus. In cystic fibrosis patients, allergic bronchopulmonar aspergillosis deals with a respiratory clinic of cough, wheezes and dyspnea which do not improve after antibiotic treatment, and radiological alterations as bronchiectasis or infiltrators. We present a patient with allergic bronchopulmonar aspergillosis who was diagnosed as cystic fibrosis (AU

Allergic Bronchopulmonary Aspergillosis Coupled with Broncholithiasis in a Non-asthmatic Patient

Allergic bronchopulmonary aspergillosis (ABPA), an asthmatic disease, is caused primarily by hypersensitivity to Aspergillus species. ABPA is rarely observed in the absence of asthma, which is, in fact, the principle criterion for its diagnosis. Here, we report the case of a 36-yr-old woman without a history of bronchial asthma, who manifested a localized pneumonic consolidation, coupled with broncholithiasis. Pathologic examinations of bronchoscopic biopsy specimens and resected surgical specimens revealed features typical of ABPA. This is a very rare case of ABPA coupled with broncholithiasis in a non-asthmatic individual.