amphotericin-b and Asthma

Severe asthma with fungal sensitisation and allergic bronchopulmonary aspergillosis encompass two closely related subgroups of patients with severe allergic asthma. Pulmonary disease is due to pronounced host inflammatory responses to noninvasive subclinical endobronchial infection with filamentous fungi, usually Aspergillus fumigatus. These patients usually do not achieve satisfactory disease control with conventional treatment of severe asthma, i.e. high-dose inhaled corticosteroids and long-acting bronchodilators. Although prolonged systemic corticosteroids are effective, they carry a substantial toxicity profile. Supplementary or alternative therapies have primarily focused on use of antifungal agents including oral triazoles and inhaled amphotericin B. Immunomodulation with omalizumab, a humanised anti-IgE monoclonal antibody, or "pulse" monthly high-dose intravenous corticosteroid, has also been employed. This article considers the experience with these approaches, with emphasis on recent clinical trials.

Topics: Adrenal Cortex Hormones; Amphotericin B; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Asthma; Clinical Trials as Topic; Humans; Inflammation; Triazoles

Topics: Alveolitis, Extrinsic Allergic; Amphotericin B; Aspergillosis, Allergic Bronchopulmonary; Asthma; Flucytosine; Humans

Antifungal therapy for severe asthma with fungal sensitisation (SAFS) and allergic bronchopulmonary aspergillosis (ABPA) remains poorly studied. We assessed the efficacy and safety of NAB as second and third line therapy in SAFS and ABPA.. 21 adult asthmatics with SAFS (n = 11) and ABPA (n = 10) who had either failed itraconazole (n = 8), voriconazole proceeded by itraconazole (n = 5) or developed adverse events (AEs) to either agent (n = 7) were treated with 10mg of NAB (Fungizone) twice daily. We audited clinical and immunological response, using the Asthma Quality of Life Questionnaire (AQLQ-J) scores, asthma control, FEV1, healthcare utilisation and IgE. Patients were followed up for 12 months.. Twenty-one patients were treated (SAFS, n = 11) and (ABPA, n = 10), M: F = 8:12, median age 65 years (range, 24-78). The median duration of therapy was 30 days (0-1825). Clinical benefit was observed in three (14.3 %) in which overall mean AQLQ-J score improved by + 2.9, mean FEV1 improved by 0.5 L and there was improvement in overall asthma control. Seven (33%) failed initial dose (bronchospasm). Eleven (52.4%) discontinued within 12 months of therapy due to delayed bronchospasm (n = 3, within 4 weeks), equipment problems (n = 2, within 4 weeks) and lack of clinical benefit (n = 4, within 16 weeks).. Our data suggest that the overall efficacy of NAB in this group of patients is poor and associated with bronchospasm. However, the excellent response in 3 patients, suggest it may be considered when other alternatives have been exhausted. Overcoming the initial bronchospasm may improve tolerability.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Asthma; Female; Forced Expiratory Volume; Humans; Itraconazole; Male; Middle Aged; Nebulizers and Vaporizers; Quality of Life; Voriconazole

Inhaled steroids such as fluticasone propionate and beclomethasone dipropionate play a central role in the treatment of bronchial asthma. Fluticasone exhibits excellent clinical effectiveness; however, oral adverse effects can occur.. To compare the frequency of oral candidiasis in asthmatic patients treated with fluticasone and beclomethasone, to evaluate the effect of gargling with amphotericin B, and to measure the inhalation flow rate on candidiasis.. The study consisted of 143 asthmatic patients who were treated with inhaled steroids, 11 asthmatic patients not treated with inhaled steroids, and 86 healthy volunteers. Quantitative fungal culture was performed by aseptically obtaining a retropharyngeal wall swab from these patients. Patients with positive results were treated with gargling using a 1:50 dilution amphotericin B solution. In asthmatic patients treated with fluticasone, the inhalation flow rate was measured using an inspiratory flow meter.. The amount of Candida spp. was significantly greater in asthmatic patients taking inhaled steroids compared with those who were not. It was also significantly greater in patients with oral symptoms than asymptomatic patients and significantly greater in asthmatic patients treated with fluticasone than in those treated with beclomethasone. Although the presence of Candida did not correlate with the inhaled dose of beclomethasone, it did increase with the dose of fluticasone. Gargling with amphotericin B was effective in most asthmatic patients with candidiasis. Candidiasis was not due to inappropriate flow rates during inhalation of steroids.. Fungal culture of a retropharyngeal wall swab may be useful for predicting the risk of developing oral candidiasis in asthmatic patients treated with inhaled steroids. The amount of isolated Candida was significantly greater in asthmatic patients treated with fluticasone than in those treated with beclomethasone. Attention to dosage is required as the amount of Candida increased with dose of fluticasone. Gargling with a 1:50 dilution of amphotericin B is effective in treating oral candidiasis of asthmatic patients treated with inhaled steroids.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Androstadienes; Anti-Inflammatory Agents; Antifungal Agents; Asthma; Beclomethasone; Candidiasis, Oral; Dose-Response Relationship, Drug; Drug Hypersensitivity; Female; Fluticasone; Glucocorticoids; Humans; Japan; Male; Middle Aged; Regression Analysis; Statistics as Topic; Treatment Failure

Topics: Amphotericin B; Antiretroviral Therapy, Highly Active; Aspergillosis, Allergic Bronchopulmonary; Asthma; Hepatitis B; HIV Infections; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive

Fungi can cause a variety of infectious diseases, including invasive mycosis and non-invasive mycosis, as well as allergic diseases. The different forms of mycosis usually have been described as mutually exclusive, independent entities, with few descriptions of overlapping cases. Here, we describe the first reported case of a patient with the complication of pulmonary eosinophilia in the course of invasive mucormycosis.. A 74-year-old Japanese man with asthma-COPD overlap underwent emergency surgery for a ruptured abdominal aortic aneurysm. The surgery was successful, but fever and worsening dyspnea appeared and continued from postoperative day (POD) 10. A complete blood count showed leukocytosis with neutrophilia and eosinophilia, and the chest X-ray showed consolidation of the left upper lung at POD 15. We suspected nosocomial pneumonia together with an exacerbation of the asthma-COPD overlap, and both antibiotics and bronchodilator therapy were initiated. However, the symptoms, eosinophilia and imaging findings deteriorated. We then performed a bronchoscopy, and bronchoalveolar lavage (BAL) fluid analysis revealed an increased percentage of eosinophils (82% of whole cells) as well as filamentous fungi. We first suspected that this was a case of allergic bronchopulmonary mycosis (ABPM) caused by Aspergillus infection and began corticosteroid therapy with an intravenous administration of voriconazole at POD 27. However, the fungal culture examination of the BAL fluid revealed mucormycetes, which were later identified as Cunninghamella bertholletiae by PCR and DNA sequencing. We then switched the antifungal agent to liposomal amphotericin B for the treatment of the pulmonary mucormycosis at POD 29. Despite replacing voriconazole with liposomal amphotericin B, the patient developed septic shock and died at POD 39. The autopsy revealed that filamentous fungi had invaded the lung, heart, thyroid glands, kidneys, and spleen, suggesting that disseminated mucormycosis had occurred.. We describe the first reported case of pulmonary mucormycosis with pulmonary eosinophilia caused by Cunninghamella bertholletiae, which resulted in disseminated mucormycosis. Although it is a rather rare case, two important conclusions can be drawn: i) mycosis can simultaneously cause both invasive infection and a host allergic reaction, and ii) Cunninghamella bertholletiae rarely infects immunocompetent patients.

Topics: Aged; Amphotericin B; Antifungal Agents; Aortic Aneurysm, Abdominal; Asthma; Bronchoalveolar Lavage Fluid; Bronchoscopy; Cross Infection; Cunninghamella; Disease Progression; Fatal Outcome; Humans; Male; Mucormycosis; Postoperative Complications; Pulmonary Disease, Chronic Obstructive; Pulmonary Eosinophilia; Radiography, Thoracic; Tomography, X-Ray Computed

Topics: Administration, Inhalation; Aged; Amphotericin B; Anti-Asthmatic Agents; Asthma; Candidemia; Candidiasis, Oral; Drug Therapy, Combination; Endophthalmitis; Eye Infections, Fungal; Female; Fluconazole; Glucocorticoids; Humans; Nystatin; Risk Factors

A case of lethal invasive mucormycosis (IM), a rare fungal infection which predominantly affects immunocompromised patients, is reported in a 73-year-old female patient who presented with a cervical abscess. The patient had asthma treated with steroids and had previously undiagnosed diabetes mellitus. Despite surgical treatment and parenteral antibiotic therapy, there was fatal progression of the condition. The pathogenesis, histological appearances and treatment of mucormycosis are discussed, particularly the importance of urgent histological examination of debrided tissue to distinguish this condition from necrotizing fasciitis (NF) earlier than microbiological culture alone would allow, thus permitting the early introduction of appropriate antifungal therapy.

Topics: Abscess; Absidia; Aged; Amphotericin B; Antifungal Agents; Asthma; Dermatomycoses; Diabetes Complications; Diagnosis, Differential; Drug Therapy, Combination; Fasciitis, Necrotizing; Fatal Outcome; Female; Humans; Immunocompromised Host; Mucormycosis; Neck

Early use of inhaled steroids is recommended for bronchial asthma. The side effects are rare, but oral discomfort and candidiasis are clinically important complications. Most previous studies reported that the use of spacer and water gargling was necessary to prevent oral complications. However, in some patients, this may fail to prevent such complications.. To compare the effects of water gargling with those of amphotericin B, in the prevention of oral complications in asthmatics using inhaled steroids.. Pharyngeal swab samples were obtained aseptically from the posterior pharyngeal wall of 128 asthmatics who have been using inhaled steroids (beclomethasone dipropionate) for more than 1 year. The amount of Candida albicans in cultured swabs was evaluated based on the following criteria: oral symptoms, method of gargling, dose of inhaled steroids, type of spacer and serum cortisol level.. The number of isolated C. albicans was significantly higher in asthmatics with oral symptoms than in those free of symptoms. It was also significantly higher in patients who gargled with water or 1,000 times dilution than in those who gargled with 100 or 50 times dilutions of amphotericin B. Moreover, it was significantly higher in patients with low levels of serum cortisol than in those with normal serum cortisol.. We demonstrated that at least in a subgroup of asthmatics using steroid inhalers, gargling with water or even weak concentrations of amphotericin B does not prevent colonization of the throat with C. albicans. This group at high risk of developing oral candidiasis should gargle with amphotericin B at concentrations higher than 100 times dilution that can prevent clinically detectable oral candidiasis.

Topics: Administration, Oral; Adult; Amphotericin B; Antifungal Agents; Asthma; Candida albicans; Candidiasis, Oral; Dose-Response Relationship, Drug; Female; Humans; Hydrocortisone; Japan; Male; Middle Aged; Mouthwashes; Respiratory Therapy; Steroids

We describe a 68-year-old asthmatic female patient with multiple pulmonary cavities. A preexisting ecthyma on the left lower leg became erythematous and swollen during exacerbation of her asthma which was under treatment with high-dose steroids. Nonseptate broad hyphae were found in her sputum, pus from the wound, and debrided skin tissue. Hematogenous spread of septic emboli from indolent cutaneous mucormycosis to both lungs was the suspected mechanism of dissemination. High-dose steroid therapy may have been the major contributory factor. The patient was successfully treated with local surgical debridement of the wound and intravenous amphotericin B.

Topics: Aged; Amphotericin B; Antifungal Agents; Asthma; Debridement; Dermatomycoses; Female; Humans; Lung Diseases, Fungal; Mucormycosis

This study evaluated the clinical features and treatment outcomes in patients with endogenous Aspergillus endophthalmitis.. The study design was a multicenter retrospective chart review.. Ten patients (12 eyes) with culture-proven endogenous Aspergillus endophthalmitis treated by 1 of the authors were studied.. Intravitreous amphotericin B injection, pars plana vitrectomy, systemic amphotericin B therapy, and oral anti-fungal therapy were performed.. Elimination of endogenous Aspergillus endophthalmitis and Snellen visual acuity, best corrected, were measured.. All patients had a 1- to 3-day history of pain and marked loss of visual acuity in the involved eyes. Varying degrees of vitritis was present in all 12 eyes. In 8 of 12 eyes, a central macular chorioretinal inflammatory lesion was present. Four patients (six eyes) had associated pulmonary diseases and were receiving concurrent steroid therapy. One of these patients with chronic asthma also was abusing intravenous drugs. Overall, six patients (six eyes) had a history of intravenous drug abuse, whereas a seventh patient (one eye) was suspected of abusing intravenous drugs. Blood cultures and echocardiograms were negative for systemic aspergillosis. Management consisted of a pars plana vitrectomy in 10 of 12 eyes. Intravitreous amphotericin B was administered in 11 of 12 eyes. Systemic amphotericin B therapy was used in eight patients. One patient was treated with oral antifungal agents. In three eyes without central macular involvement, final visual acuities were 20/25 to 20/200. In eight eyes with initial central macular involvement, final visual acuities were 20/400 in three eyes and 5/200 or less in four eyes. Two painful eyes with marked inflammation, hypotony, and retinal detachment were enucleated.. Endogenous Aspergillus endophthalmitis usually has an acute onset of intraocular inflammation and often has a characteristic chorioretinal lesion located in the macula. Although treatment with pars plana vitrectomy and intravitreous amphotericin B is capable of eliminating the ocular infection, the visual outcome generally is poor, especially when there is direct macular involvement.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus flavus; Aspergillus fumigatus; Asthma; Endophthalmitis; Eye Infections, Fungal; Female; Fundus Oculi; Humans; Injections; Lung Diseases, Obstructive; Male; Middle Aged; Retrospective Studies; Substance Abuse, Intravenous; Treatment Outcome; Visual Acuity; Vitrectomy; Vitreous Body

Topics: Aged; Amphotericin B; Anaphylaxis; Asthma; Candidiasis; Desensitization, Immunologic; Drug Resistance, Microbial; Emergency Medical Services; Female; Humans; Leukemia, Myeloid, Acute; Neutropenia

Topics: Administration, Inhalation; Aerosols; Agranulocytosis; Amphotericin B; Asthma; Bone Marrow Transplantation; Humans; Immunocompromised Host; Leukemia; Lung Diseases, Fungal; Time Factors

Our institution used an experimental protocol for the use of inhaled amphotericin B as a prophylactic measure to prevent fungal disease in severely immunocompromised patients. We did a prospective study of the physiologic effects of amphotericin B administration. We looked specifically at oxygen saturation levels, peak flow values, and symptoms of patients given amphotericin B. We collected data on a series of 18 patients and of 132 amphotericin B administrations. Four (22%) of the patients stopped treatments because of nausea and vomiting which were believed to be due to the inhaled amphotericin B. For the remaining patients, no treatment was stopped because of symptoms or physiologic changes caused by amphotericin B, although there were 9 instances of clinically significant bronchospasm as defined by a drop in peak flow of 20% or more, 9 clinically relevant increases in cough, and 3 clinically relevant increases in dyspnea. Forty-eight percent of the clinically relevant changes occurred in patient 8. Another 16% occurred in asthmatic subjects who were significantly more likely (p = 0.03) to experience a 20% or more drop in peak flow than were patients without asthma. The physiologic profile of the response to inhaled amphotericin B is acceptable.

Topics: Administration, Inhalation; Adult; Aerosols; Agranulocytosis; Amphotericin B; Asthma; Bone Marrow Transplantation; Cough; Dyspnea; Humans; Immunocompromised Host; Leukemia; Lung Diseases, Fungal; Nausea; Nebulizers and Vaporizers; Oxygen; Prospective Studies; Pulmonary Ventilation; Vomiting

A 28 year old man with asthma, bronchopulmonary aspergillosis, pulmonary thromboembolic disease, and pulmonary hypertension developed Aspergillus fumigatus empyema complicating a pneumothorax. His condition progressively deteriorated despite treatment with intravenous and intrapleural amphotericin B, but improved promptly after substituting nebulised liposomal amphotericin B and oral itraconazole. This experience suggests that nebulised liposomal amphotericin B is well tolerated and merits further assessment in the treatment of pulmonary fungal disease.

Topics: Administration, Inhalation; Administration, Oral; Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Asthma; Drug Carriers; Drug Therapy, Combination; Empyema, Pleural; Humans; Hypertension, Pulmonary; Itraconazole; Liposomes; Male; Nebulizers and Vaporizers; Pulmonary Embolism

We describe a perplexing asthmatic patient who had chronic lymphatic leukemia that developed recurrent severe and prolonged attacks of asthma which required almost continuous hospitalization. Clinical findings of fever, leukocytosis, right lower lobe infiltrate and mouth candidiasis were suggestive of bronchopulmonary candidiasis. No further diagnostic tests were done and the patient responded favorably to amphotericin B therapy. A review of bronchopulmonary candidiasis in adults is discussed briefly. Lung biopsy should be reserved only for the most obscure and problematic cases.

Topics: Amphotericin B; Asthma; Candidiasis; Female; Humans; Leukemia, Lymphoid; Lung Diseases, Fungal; Middle Aged

Thirty cases of allergic bronchopulmonary aspergillosis (ABPA) were treated between 1967 and 1981. Developing in patients with a history of chronic asthma (28 of the 30 cases), the initial manifestations of ABPA developed after long periods (an average of 29 years after the onset of the asthma). Chest radiography demonstrated recurrent labile infiltrates in 28 cases, segmental or lobar atelectasis in 7, and proximal bronchiectasis in 16 cases. A circulating eosinophilia was a constant finding, but this varied with time. Immunologic investigations gave positive skin tests, 19 of the 30 patients only presenting a cutaneous reaction delayed until the 6th hour. Total IgE, determined in 18 cases, varied between 600 and 9400 IU/ml (RIST), with identification of specific IgE for Aspergillus in all cases, though to varying degrees. Serial measurements of total IgE levels showed co-existence of an acute progression of the affection and elevated total IgE in 3 cases, but no correlation was found between serum IgE levels and the severity or chronicity of the disease. Physiopathologic features included immediate and partially delayed hypersensitivity to Aspergillus fumigatus. The frequency of ABPA during the course of mucoviscidosis suggests, by analogy, that a local factor may exist which favorizes Aspergillus fumigatus proliferation in patients with ABPA alone.

Topics: Adolescent; Adult; Aged; Amphotericin B; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Asthma; Bronchial Provocation Tests; Bronchoscopy; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Radiography, Thoracic; Skin Tests

Topics: Adrenal Cortex Hormones; Amphotericin B; Asthma; Cryptococcosis; Cryptococcus neoformans; Humans; Male; Meningitis; Middle Aged; Prednisone

Topics: Amphotericin B; Asthma; Histoplasma; Histoplasmosis; Humans; Immunosuppression Therapy; Male; Middle Aged; Prednisone; Skin Diseases, Parasitic

Topics: Adrenal Cortex Hormones; Adult; Aged; Amphotericin B; Aspergillosis; Asthma; Cromolyn Sodium; Female; Humans; Lung Diseases, Fungal; Male; Pleural Diseases; Spondylitis, Ankylosing

Topics: Amphotericin B; Asthma; Coccidioidomycosis; Complement Fixation Tests; Female; Glucocorticoids; Histoplasmosis; Humans; Male; Middle Aged; Mycoses; Nocardia Infections; Prednisone; Sulfadiazine

Topics: Adolescent; Amphotericin B; Aspergillosis; Aspergillus fumigatus; Asthma; Bronchiectasis; Child; Female; Hemoptysis; Humans; Lung Diseases, Fungal; Recurrence; Staphylococcus

Topics: Adolescent; Amphotericin B; Aspergillosis; Asthma; Humans; Lung Diseases, Fungal; Male

Topics: Aerosols; Amphotericin B; Asthma; Bronchial Diseases; Bronchodilator Agents; Cystic Fibrosis; Eosinophilia; Isotonic Solutions; Lung Diseases; Mucus; Polymyxins; Radiography; Sodium Chloride; Spirometry; Sputum; Ultrasonics; Ventilators, Mechanical

Topics: Acremonium; Amphotericin B; Anti-Bacterial Agents; Antigen-Antibody Reactions; Asthma; Bone Diseases; Candidiasis; Diet; Diet Therapy; Drug Therapy; Food Hypersensitivity; Granuloma; Humans; Immunotherapy, Active; Jaw; Mouth Diseases; Palate; Paranasal Sinuses; Pathology; Sinusitis; Skin Tests; Spores; Spores, Fungal