[Allergic Broncho-Pulmonary Aspergillosis (ABPA) in cystic fibrosis: Mechanisms, diagnosis and therapeutic options]. / Aspergillose bronchopulmonaire allergique (ABPA) et mucoviscidose : mécanismes, diagnostic et alternatives thérapeutiques.

INTRODUCTION: Fungal aspergillosis colonization and allergic bronchopulmonary aspergillosis (ABPA) can have a strong impact on the prognosis in cystic fibrosis (CF). We conducted round table discussions involving French experts from pediatric and adult centers caring for patients with CF, microbiologists, radiologists and pharmacists. The aim was to explore the current state of knowledge on: the pathophysiological mechanisms of Aspergillus and other micromycetes infections in CF (such as Scedosporium sp.), and on the clinico-biological diagnosis of ABPA. In perspective, the experts explored the role of imaging in the diagnosis of APBA, specifically CT and MRI; as well as the role of bronchoscopy in the management. We also reviewed the therapeutic management, including different corticosteroid regimens, antifungals and anti-IgE antibodies. CONCLUSION: The diagnosis of ABPA in CF should be based on more standardized biological assays and imaging to optimize treatment and follow-up.

Azole-Resistant Aspergillosis: Epidemiology, Molecular Mechanisms, and Treatment.

Aspergillus fumigatus remains the most common species in all pulmonary syndromes, followed by Aspergillus flavus which is a common cause of allergic rhinosinusitis, postoperative aspergillosis and fungal keratitis. The manifestations of Aspergillus infections include invasive aspergillosis, chronic pulmonary aspergillosis and bronchitis. Allergic manifestations of inhaled Aspergillus include allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization. Triazoles are the mainstay of therapy against Aspergillus infections for treatment and prophylaxis. Lately, increased azole resistance in A. fumigatus has become a significant challenge in effective management of aspergillosis. Earlier studies have brought to light the contribution of non-cyp51 mutations along with alterations in cyp51A gene resulting in azole-resistant phenotypes of A. fumigatus. This review highlights the magnitude of azole-resistant aspergillosis and resistance mechanisms implicated in the development of azole-resistant A. fumigatus and address the therapeutic options available.

Respiratory Allergic Disorders.

Allergic asthma refers to a chronic reversible bronchoconstriction influenced by an allergic trigger, leading to symptoms of cough, wheezing, shortness of breath, and chest tightness. Allergic bronchopulmonary aspergillosis is a complex hypersensitivity reaction, often in patients with asthma or cystic fibrosis, occurring when bronchi become colonized by Aspergillus species. The clinical picture is dominated by asthma complicated by recurrent episodes of bronchial obstruction, fever, malaise, mucus production, and peripheral blood eosinophilia. Hypersensitivity pneumonitis is a syndrome associated with lung inflammation from the inhalation of airborne antigens, such as molds and dust.

Aspergilosis broncopulmonar alérgica en pediatría / Allergic bronchopulmonary aspergillosis in childhood

La aspergilosis broncopulmonar alérgica (ABPA) es una complicación importante en niños portadores de asma atópica, fibrosis quística (FQ) y otras enfermedades pulmonares crónicas asociadas a bronquiectasias. Esta afección es el resultado de la colonización de la vía aérea por Aspergilus, habitualmente fumigatus, produce una reacción de hipersensibilidad tipo Th2CD4 con la producción de IgE total y específica. El diagnóstico debe sospecharse en pacientes que presenten secreciones bronquiales en moldes café, aparición o aumento de sibilancias, infiltrados pulmonares y reducción de la función pulmonar. Si esta afección no es tratada precozmente puede conducir a un severo deterioro de la función pulmonar y a largo plazo llegar a la fibrosis. El diagnóstico es difícil debido a la sobreposición de las manifestaciones clínicas y radiológicas de la ABPA con exacerbaciones pulmonares producidas por bacterias o virus. Se han sugerido criterios para establecer el diagnóstico; en este sentido la IgE total y específica son los más importantes. Últimamente han sido desarrollados nuevos test serológicos con el objeto de mejorar la detección precoz y monitorización de la ABPA, presentando gran sensibilidad y especificidad. El tratamiento consiste en el uso de corticoides sistémicos. El itraconazol parece mejorar el control de la enfermedad y reducir la dosis de corticoides.

Purification and characterization of a 93 kDa Aspergillus fumigatus antigen with diagnostic potential.

A glycoprotein with an apparent molecular weight of 93 kDa was purified from a water-soluble extract of Aspergillus fumigatus NCPF 2109 by single step affinity chromatography using the mannose-specific snowdrop (Galanthus nivalis) lectin coupled to agarose. The carbohydrate moiety contained only mannose and galactose. Partial sequencing of cyanogen bromide fragments of the antigen yielded two sequences, KQNKP and GEIPMKF?PQL, with no homology to any reported proteins. In a preliminary evaluation of its diagnostic potential the 93 kDa antigen was recognized by the sera of four patients with allergic bronchopulmonary aspergillosis, in addition to a monoclonal antibody raised against a partially purified fraction of the A. fumigatus water-soluble extract.

Diagnostic value of recombinant Aspergillus fumigatus allergen I/a for skin testing and serology.

BACKGROUND: We report a clinical study comparing the recombinant Aspergillus fumigatus allergen I/a (rAsp f I/a) to two commercial A. fumigatus extracts in skin prick tests, intradermal tests, and serologic assays. METHODS: Patients with allergic bronchopulmonary aspergillosis and A. fumigatus-allergic patients with asthma, and control subjects, including allergic patients with asthma without allergy to A. fumigatus and healthy subjects, were investigated. RESULTS: All patients with allergic bronchopulmonary aspergillosis (n = 15) reacted to skin prick tests with the commercial extracts, and eight were sensitized to rAsp f I/a. Of 10 patients with well-characterized A. fumigatus-allergic asthma nine showed positive skin prick test results to at least one of the commercial extracts, and five reacted to rAsp f I/a. There was a strong correlation between skin test reactivity to rAsp f I/a and rAsp f I/a-specific serum IgE as determined by an antigen-specific ELISA. The healthy control subjects (n = 7) and allergic patients with asthma without A. fumigatus allergy (n = 6) did not react in skin prick and intradermal tests to rAsp f I/a, nor did they have detectable amounts of rAsp f I/a-specific IgE. In addition, patients with allergic bronchopulmonary aspergillosis showed significant elevated levels of rAsp f I/a-specific IgG4 and IgG1 but no significant differences in rAsp f I/a-specific serum IgA levels when compared with the healthy control subjects. CONCLUSIONS: The data show that rAsp f I/a is a major allergen with biologic relevance in some A. fumigatus-allergic individuals as evaluated by skin prick tests, intradermal tests, or serologic methods. Furthermore, no discrepancies were observed between skin test results and rAsp f I/a-specific IgE. Hence the correlation between rAsp f I/a skin test results and serologic data indicates the potential of recombinant allergens for clinical applications and diagnosis of allergies.

Tratamiento médico de la aspergilosis pulmonar intracavitaria (API) no quirúrgica / Medical treatment for intracavitary aspergillosis pulmonary non surgical

En la aspergilosis pulmonar intracavitaria (API), el tratamiento de elección es el quirúrgico, aunque no siempre es posible por causas relacionadas con patologías pulmonares preexistentes o por asociaciones morbosas. Entre 1979 y l989 se registraron en el Hospital "San Juan de Dios" de La Plata (Pcia. de Buenos Aires) 37 casos de API no quirúrgica , que fueron tratados con una o dos drogas antifúngicas bajo cuatro esquemas de tratamiento: 1)anfotericina B en nebulizaciones, 2)flucitosina oral, 3)ketoconazol oral y 4)anfotericina B nebulizaciones y flucitosina por vía oral. Todos los pacientes presentaron lesiones radiólogicas bilaterales con cavidad (BCC). La mayoría presentó un patrón ventilatorio mixto o restrictivo, y se registró la mayor incidencia de API no quirúrgica en los grupos etarios más afectados por tuberculosis pulmonar (TBC), además se detectó un elevado número de aspergilomas (35,l4%). Se obtuvo el aislamiento de Aspergillus fumigatus en el 83,8% de los casos, con un excelente rendimiento tanto de los cultivos cuanto de la serología. La mortalidad general fue del 10.81% y la atribuible a API del 2,70%. El abandono del tratamiento alcanzó el 35,l4% y se logró la negativización en 7 pacientes (33,40% de los tratamientos cumplidos). Los factores principales que influyeron en el resultado exitoso fueron: la duración prolongada del tratamiento y el esmero por parte del grupo de trabajo en la asistencia y seguimiento de los pacientes

Tratamiento médico de la aspergilosis pulmonar intracavitaria (API) no quirúrgica / Medical treatment for intracavitary aspergillosis pulmonary non surgical

En la aspergilosis pulmonar intracavitaria (API), el tratamiento de elección es el quirúrgico, aunque no siempre es posible por causas relacionadas con patologías pulmonares preexistentes o por asociaciones morbosas. Entre 1979 y l989 se registraron en el Hospital "San Juan de Dios" de La Plata (Pcia. de Buenos Aires) 37 casos de API no quirúrgica , que fueron tratados con una o dos drogas antifúngicas bajo cuatro esquemas de tratamiento: 1)anfotericina B en nebulizaciones, 2)flucitosina oral, 3)ketoconazol oral y 4)anfotericina B nebulizaciones y flucitosina por vía oral. Todos los pacientes presentaron lesiones radiólogicas bilaterales con cavidad (BCC). La mayoría presentó un patrón ventilatorio mixto o restrictivo, y se registró la mayor incidencia de API no quirúrgica en los grupos etarios más afectados por tuberculosis pulmonar (TBC), además se detectó un elevado número de aspergilomas (35,l4%). Se obtuvo el aislamiento de Aspergillus fumigatus en el 83,8% de los casos, con un excelente rendimiento tanto de los cultivos cuanto de la serología. La mortalidad general fue del 10.81% y la atribuible a API del 2,70%. El abandono del tratamiento alcanzó el 35,l4% y se logró la negativización en 7 pacientes (33,40% de los tratamientos cumplidos). Los factores principales que influyeron en el resultado exitoso fueron: la duración prolongada del tratamiento y el esmero por parte del grupo de trabajo en la asistencia y seguimiento de los pacientes

[Symptoms and functional disorders of the respiratory system caused by exposure to tea dust]. / Objawy i zaburzenia czynnosciowe ukladu oddechowego wywolane ekspozycja na pyl z herbaty.

A case report is presented of a female worker of a tee packing factory, with a 5 years history of tea dust exposition and symptoms of reversible airway obstruction and early allergic alveolitis. The results of spirometric and lung mechanics demonstrated reversible airway obstruction with co-existent restrictive changes, lowering of CO diffusing capacity (DLc0). Bronchial provocation tests with tea dust were carried out thrice and all were positive. The authors believe that the etiological factor of above mentioned changes were Aspergillus niger spores found in tea dust. Tea dust and the patient's sputum cultured for fungi revealed massive growth of A. niger. Serological tests revealed additionally, antibodies to A. niger and tea dust extracts. The authors discuss the possible mechanisms of airway disturbances in this patient.

The many faces of pulmonary aspergillosis.

The recognition of aspergillus in all its clinical disguises remains a challenge to clinicians in all fields of medicine. Fortunately, aspergillus has low pathogenicity for humans and requires very heavy inoculum of spores (aspergillary pneumonitis) in order to infect those whose pulmonary defense mechanisms, inherent structure, and physiology are intact. Patients with problems from aspergillus may be seen in either inpatient or outpatient clinical practice. The patient with fibrotic or cavitary lung disease finds himself at risk to be colonized and develop an aspergilloma (fungus ball). Conservative therapy (that is, antibiotics, pulmonary hygiene) or simple observation is often all that is required. With significant hemoptysis, surgical removal could be definitive treatment; but these patients often have such compromised pulmonary function that alternative therapies like infusion of antifungal agents locally are tempting. Part of the problem of the patient with asthma or COPD may actually be secondary to hypersensitivity to aspergillus (ABPA), which exacerbates bronchospasm and adds "pulmonary infiltrates" to the underlying disease. The recognition of this entity and then the judicious use of corticosteroids to control the symptoms will stabilize the clinical course of the disease. The immunocompromised patient may be relatively free of pulmonary disease.; but aspergillus, waiting until cytotoxic agents, corticosteroids, granulocytopenia, broad-spectrum antibiotics, and previous pneumonias destroy the local lung defense mechanisms, will then attack with a vengeance. The resultant invasive pulmonary aspergillosis requires treatment with amphotericin B, along with its own inherent toxicity.