Allergic bronchopulmonary aspergillosis

Idiopathic eosinophilic pneumonia (IEP) is a rare and complex disease. It usually presents in the form of acute idiopathic eosinophilic pneumonia (AIEP) or chronic idiopathic eosinophilic pneumonia (CIEP). The common clinical picture of IEP comprises nonspecific respiratory symptoms that can easily be confused with other common conditions. The diversity of differential diagnoses, the subtlety of radiologic findings, and the lack of specific clinical tests can prolong and confuse the clinical course. Much research has been done on the clinical and pathologic features of acute and chronic eosinophilic cases of pneumonia. Conversely, the idiopathic and subacute forms have been the subject of only a handful of published papers, where each only contained a small number of cases. We present and discuss a case of IEP, the challenges involved in this diagnosis. its management and the importance of its recognition.

There remains lack of agreement on diagnostic criteria and approaches to treatment of patients with Allergic Bronchopulmonary Aspergillosis (ABPA). The results of a survey of AAAAI members regarding these 2 issues are presented and compared for concordance with published recommendations. The literature was reviewed for pertinent reports and an electronic survey was conducted of AAAAI members and fellows regarding diagnostic criteria, numbers of patients evaluated for ABPA, and treatment approaches. From 508 respondents to the survey sent to 5155 U. S. physicians in the AAAAI database of members and fellows, 245 (48%) health professionals had treated at least 1 patient with ABPA in the previous year. For the diagnosis of ABPA, there was a difference in the threshold concentration of total serum IgE as 44.9% used ≥ 417 kU/L whereas 42.0% used ≥ 1000 kU/L. These findings suggest that ABPA might be underdiagnosed. Regarding pharmacotherapy, oral steroids were recommended for 97.1% of patients and oral steroids + inhaled corticosteroids + anti-fungal agent were utilized in 41.2% of patients. The armamentarium for treatment of ABPA includes oral corticosteroids as the initial treatment with inhaled corticosteroids used for management of persistent asthma. Azoles remain adjunctive.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease characterized by Aspergillus fumigatus (Af) colonization, IgE and IgG anti-Af antibodies, pulmonary infiltrates, bronchiectasis, and pulmonary fibrosis. Little is known regarding T cell responses and their role in the pathogenesis of ABPA. To examine T cell reactivity to Af antigens, T cell clones (TCC) specific to the Asp f 1 antigen, an 18-kD protein of Af, were established from the peripheral blood of three ABPA patients. The majority of TCC isolated from ABPA patients, and specific for the Asp f 1 allergen of Af, are IL-4 producing CD4 ϩ cells of the Th2 phenotype. Further analysis in this study revealed that the majority of TCC reacted to mainly two epitopes of Asp f 1, while the remaining TCC reacted to three additional "minor" epitopes. Blocking studies using monoclonal antibodies specific for class II HLA-D region gene products showed that most TCC, 19/21, were restricted by HLA-DR molecules, and the remaining two clones by HLA-DP molecules. The use of a panel of HLA-matched and mismatched EBVtransformed B cells as antigen presenting cells revealed that the HLA-DR restriction was mediated exclusively by either the HLA-DR2 or HLA-DR5 alleles. Genotyping of DRB1 gene products showed that class II presentation for most clones was not restricted to a single allele, representing DRB1 gene products of either HLA-DR2 or DR5. These studies offer insight into the cellular and molecular determinants which contribute to the immunopathophysiology of ABPA. ( J.

Background:  Allergic bronchopulmonary aspergillosis (ABPA) is characterized by a heightened Th2 CD4+ T‐cell response to Aspergillus fumigatus allergens and a hyper‐immunoglobulin (Ig)E state compared with cystic fibrosis patients without ABPA. We hypothesize that one reason for this response is increased sensitivity to interleukin (IL)‐4 in ABPA resulting in increased expression of CD23 and CD86 and leading to a positive amplification mechanism that increases Th2 CD4+ T cell responses.Methods:  Peripheral blood mononuclear cells (PBMC) were isolated from seven ABPA CF and 19 non‐ABPA CF patients and 16 nonatopic controls and stimulated with rIL‐4 (range 0.1–10 ng/ml) and rIL‐13 (range 1–10 ng/ml) for 48 h. The number of CD23 molecules and percentages of CD23+ B cells were quantified by flow cytometry. Both phorbol 12‐myristate 13‐acetate (PMA)/ionomycin (IO) and antigen stimulated, toxoid and Asp f2/f3/f4, PBMC were examined for cytoplasmic cytokine synthesis enumerated by cytokine...

que fueron mantenidas en su forma de levadura por repiques semanales en agar caldo glucosado al 2%, incubados a 37°C. Después de una semana de incubación, las células fúngicas fueron suspendidas en agua destilada estéril adicionada de mertiolato borato de sodio y fenilmetilsulfonilfluoruro a la concentración final de 1/5000. Esta suspensión se dejó a temperatura ambiente durante 72 h y el sobrenadante fue liofilizado. Se determinó la concentración total de proteínas y polisacáridos. En las pruebas de inmunodifusión se utilizó el antígeno con una concentración de proteínas de 1,4 mg/ml. El exoantígeno mostró siete bandas en la corrida electroforética en poliacrilamida, pero sólo dos de ellas mostraron actividad antigénica en la inmunotransferencia con una mezcla de sueros de pacientes con histoplasmosis. Los pesos moleculares de estas dos proteínas antigénicas fueron de 97 y 66 kDa respectivamente. Se preparó una γ-globulina de conejo anti-H. capsulatum para ser empleada como control positivo en las reacciones serológicas. Se produjeron en total diez lotes del antígeno para determinar su reproducibilidad y la capacidad antigénica de los mismos fue estudiada mediante pruebas de inmunodifusión en gel de agar (ID) y contrainmunoelectroforesis (CIE) usando muestras séricas de 20 hámsters inoculados experimentalmente por vía intracardíaca con la forma de levadura de H. capsulatum. Todos los sueros obtenidos después de la tercera semana de la infección dieron resultados positivos con los diez lotes del antígeno. Se estudiaron cincuenta sueros de pacientes con histoplasmosis por medio de reacciones ID, CIE y fijación de complemento (FC), comparando los resultados con una histoplasmina patrón. En los pacientes VIH negativos se observaron 7/7 (100 %) reacciones positivas con el exoantígeno en las tres pruebas serológicas, en tanto que la histoplasmina proporcionó 5/7 resultados positivos (71,4 %). Las reacciones de CIE y FC fueron las más sensibles en los enfermos VIH positivos, presentaron 15/43 (34,8 %) resultados positivos con el exoantígeno y 7/43 con la histoplasmina (13,9 %). Se examinaron además 10 sueros de cada una de las siguientes micosis: paracoccidioidomicosis, aspergilosis y candidiasis empleando la prueba de ID para comprobar reacciones cruzadas. No se observó ninguna prueba positiva. El exoantígeno de la fase levaduriforme resultó más sensible que la histoplasmina e igualmente específico.

Background Invasive aspergillosis (IA) is one of the rarest opportunistic fungal infections and has increased in frequency worldwide in recent years. It is a life-threatening infection associated with high mortality rates. Invasive pulmonary aspergillosis (IPA) is the most severe form of the disease. Extrapulmonary forms can develop as a primary infection or occur as part of a disseminated infection from the lung in severely immunocompromised patients. The major limitation in the management of these infections is the challenge of early diagnosis. Case presentation Here we report a case of secondary cutaneous aspergillosis that developed from extensive pulmonary aspergillosis in a 3-year-old female who underwent immunosuppressive therapy for a diagnosed Behçet disease (BD). Aspergillus hyphae were identified on skin biopsies. Cultures grew Aspergillus fumigatus. The diagnosis of cutaneous aspergillosis enabled us to diagnose IPA, although there was no mycopathological proof of lung i...

The rising global prevalence of allergic diseases, particularly conditions like atopic dermatitis, asthma and allergic rhino conjunctivitis, has become a significant public health concern. Contributing factors, including climate change, are altering the distribution and allergenicity of pollen, exacerbating allergic reactions and increasing the burden on healthcare systems.

OBJECTIVE To establish the role of therapeutic bronchoalveolar lavage in addition to conventional treatment among two groups, with allergic bronchopulmonary aspergillosis, in terms of regression in serum IgE levels and clinical recurrence at 3 and 6 months of follow-up. STUDY DESIGN Aquasi-experimental study. PLACE AND DURATION OF STUDY Department of Pulmonology, Fauji Foundation Hospital, Rawalpindi, from July 2010 to December 2013. METHODOLOGY The study was carried out on 132 patients who fulfilled the Greenberger and Patterson criteria and underwent a chest X-ray, an HRCT chest and classified radiologically as with Central Bronchiectasis (CB), High Attenuation Mucus (HAM) or Other Radiological Features (ORF). Baseline serum IgE levels were noted. All patients were given treatment including prednisolone and antifungal agent itraconazole for 4 months. Patients with ORF on HRCTchest and just received the medical treatment were labeled as conventional group. Those patients who had CB...

Two CF patients developed Cushing's syndrome during administration of inhaled budesonide (400 mgyd) with oral itraconazole in one and with clarithromycin in the other patient. Clinical features appeared respectively after 2 and 6 weeks of drug coadministration, with prolonged adrenal suppression, and a slow recovery after ceasing the drugs. Inhibitors of the cytochrome P450 interfere with the metabolism of corticosteroids. Combination of these drugs even with moderate doses of budesonide should be closely monitored.

Allerjik bronkopulmoner aspergilloz (ABPA) astım ya da kistik fibrozisli hastalarda görülen ve Aspergillus fumigatus'a karşı gelişen yaygın bir hipersensitivite reaksiyonudur. Astımı olmayan hastalarda da nadiren bildirilmiştir. Burada atipik klinik bulgularla gelen ve "High attenuation mucoid impaction" saptanan bir ABPA olgusu sunulmaktadır. Amaç, ABPA'nın atipik klinik bulgularla ortaya çıkabileceğini vurgulamaktır.

clinical experience of use of two of the newer agents targeted against Gram negative bacteria, Ceftazidime-avibactam and Ceftolozane-tazobactam. These agents were used for the treatment of Carbapenemase Producing Enterobacteriacea (CPE), in a post-op cardiothoracic patient with severe hospital acquired pneumonia and Multi Drug Resistant (MDR) Pseudomonas in a patent with severe burns airlifted to our specialist burns unit from a hospital in Pakistan. Conclusions: Antibiotic resistance is a global problem. Resistance mechanisms are becoming increasingly complex to understand and detect, and are highly mobile via genes on plasmids spread through bacterial populations, augmented by air travel and migration. Collaboration between countries is now more essential than ever. We feel that this should include the sharing of real life clinical data and experience of the newer agents, in order to build up clinicians confidence to use them in the clinical setting, thereby increasing treatment options globally.

Summary This cross-sectional study was designed to investigate the extent of genetic susceptibility by targeting variants in interleukin (IL)−4/IL-13 signalling pathways leading to atopic disease in early childhood. We evaluated involvement of five single nucleotide polymorphisms IL4 C-590T, IL13 C-1055T, IL13 Arg130Gln, IL4RA Ile50Val and IL4RA Gln576Arg, in the control of serum total and antigen-specific immunoglobulin (Ig)E levels. Furthermore, we analysed their association with changes in gene expression of five cytokines having key roles in inflammatory and anti-inflammatory immune response [IL-4, IL-13, interferon (IFN)-γ, IL-8 and IL-10]. Total and antigen-specific IgE levels in serum and gene expression of selected cytokines in peripheral blood were measured in 386 children aged 1–8 years. TaqMan allelic discrimination, amplification refractory mutation system–polymerase chain reaction (ARMS–PCR) and restriction fragment length polymorphisms (RFLP) methods validated by seque...

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Objectives: To examine rates of CF deaths in the intensive care unit (ICU) in France. Methods: Medical records from all CF patients who died in France over four years (2007)(2008)(2009)(2010) were obtained from CF centres and examined by an independent adjudication committee. Site of death (out of hospital, in hospital in the medical ward or in ICU) were determined and justification of ICU admission was determined based on patient's status toward lung transplantation (LTX). Results: Of 245 deaths related to CF, 215 (88%) deaths occurred in hospital, including 148 (60%) deaths that occurred in ICUs. Hospitalization in the ICU was considered always justified for 72/148 (48.7%) patients who were either on waiting list for a first (n = 20) or a second (n = 7) LTX, or who died during first year after LTX (n = 45). Hospitalization in the ICU was considered possibly justified for 44/148 (29.7%) patients who were not listed for LTX at the time of death, but in whom no contraindication to transplantation was identified. Hospitalization in the ICU was considered possibly not justified for 32/148 (21.6%) patients because a first or a second LTX was refused by the patient (n = 9) or was denied by medical staff (n = 23). Conclusion: Death in CF patients in France often occurred in ICU, which appeared justified or possibly justified in most patients, but possibly not justified in 22% of patients who had endstage lung disease and no perspective for LTX. Advance care planning appears important to avoid unjustified ICU care in CF patients at the end of life.

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a type of hypersensitivity reaction to mold Aspergillus fumigatus, especially common in patients with bronchial asthma. However, systemic data regarding the clinicodemographic, radiological, and immunological profiles of patients is sparse, particularly from the eastern India.Methods: This is a prospective observational study done over a year, from January 2021 to December 2021, in patients visiting the pulmonary medicine outpatient department (OPD) with symptoms similar to ABPA. Following the clinical examination, routine blood investigations, serum total immunoglobulin E (IgE) test, Aspergillus-specific IgE test, spirometry, and chest radiology (chest X-ray/high resolution CT scan) were done. ABPA was diagnosed using the 2013 ISHAM-ABPA working group criteria. Data were analyzed using statistical package for the social sciences (SPSS) software version 2021 against different categories of eosinophil count.Results: A tota...

Allergic bronchopulmonary aspergillosis (ABPA) is an abnormal immune response (hyper-sensitivity) mounted against Aspergillus fumigatus in predisposed immunocompetent hosts. This entity is commonly seen in individuals with bronchial asthma and rarely in cystic fibrosis. Serological and radiological tests help to confirm the diagnosis. High resolution computed tomography (HRCT) is the radiological modality of choice for investigating ABPA subjects. The subjects with ABPA may present variably with no HRCT abnormalities, bronchiectasis, high attenuation mucus (HAM) and chronic fibrotic lung changes. The presence of HAM represents immunological severity and also indicates higher chances of relapse. HAM is pathognomonic for ABPA. HRCT findings of ABPA are reviewed in this article.

Airway infections are a key component of cystic fibrosis (CF) lung disease. Whereas the approach to common pathogens such as Pseudomonas aeruginosa is guided by a significant body of evidence, other infections often pose a considerable challenge to treating physicians. In Part I of this series on the antibiotic management of difficult lung infections, we discussed bacterial organisms including methicillin-resistant Staphylococcus aureus, gram-negative bacterial infections, and treatment of multiple bacterial pathogens. Here, we summarize the approach to infections with nontuberculous mycobacteria, anaerobic bacteria, and fungi. Nontuberculous mycobacteria can significantly impact the course of lung disease in patients with CF, but differentiation between colonization and infection is difficult clinically as coinfection with other micro-organisms is common. Treatment consists of different classes of antibiotics, varies in intensity, and is best guided by a team of specialized clinicians and microbiologists. The ability of anaerobic bacteria to contribute to CF lung disease is less clear, even though clinical relevance has been reported in individual patients. Anaerobes detected in CF sputum are often resistant to multiple drugs, and treatment has not yet been shown to positively affect patient outcome. Fungi have gained significant interest as potential CF pathogens. Although the role of Candida is largely unclear, there is mounting evidence that Scedosporium species and Aspergillus fumigatus, beyond the classical presentation of allergic bronchopulmonary aspergillosis, can be relevant in patients with CF and treatment should be considered. At present, however there remains limited information on how best to select patients who could benefit from antifungal therapy.

Namibia is a sub-Saharan country with one of the highest HIV infection rates in the world. Although care and support services are available that cater for opportunistic infections related to HIV, the main focus is narrow and predominantly aimed at tuberculosis. We aimed to estimate the burden of serious fungal infections in Namibia, currently unknown, based on the size of the population at risk and available epidemiological data. Data were obtained from the World Health Organization (WHO), Joint United Nations Programme on HIV/AIDS (UNAIDS), and published reports. When no data existed, risk populations were used to estimate the frequencies of fungal infections, using the previously described methodology. The population of Namibia in 2011 was estimated at 2,459,000 and 37% were children. Among approximately 516,390 adult women, recurrent vulvovaginal candidiasis (≥4 episodes /year) is estimated to occur in 37,390 (3003/100,000 females). Using a low international average rate of 5/100...

Colistin is a polypeptid antibiotic and it is used to treat infections caused by multidrug-resistant gram-negative bacteria. The intravenous use of colistin has been considered to be associated with considerable nephrotoxicity and neurotoxicity. For this reason, the systemic administration of colistin has been abandoned for about 20 years in most areas of the world. The emergence of multidrug-resistant gram-negative bacteria in parallel with the lack of new antibacterial agents led scientists to understand the importance of colistin. In this manuscript the use of colistin has been discussed in the light of current knowledge.

Sierra Leone is a small, resource-limited country that has a low national prevalence of human immunodeficiency virus (HIV) and a very high burden of tuberculosis (TB). Fungal diseases are probably common, but poorly documented. In this article, we reviewed the existing literature on fungal epidemiology in Sierra Leone using national, regional, and international data, identified knowledge gaps, and propose solutions to address the challenges on the prevention and control of fungal diseases in Sierra Leone and similar countries. In advanced HIV disease, we estimate 300 cryptococcal meningitis, 640 Pneumocystis pneumonia, and over 4000 esophageal candidiasis cases annually. Chronic lung disease is common, with an estimated 6000 cases of chronic pulmonary aspergillosis, many mistaken for TB, 5000 adults with allergic bronchopulmonary aspergillosis complicating asthma, and probably over 6600 cases of severe asthma with fungal sensitization. Invasive aspergillosis is estimated at 478 case...

Culture filtrate antigens of Aspergillus fumigatus Ag 534 were purified by preparative isoelectric focusing and affinity chromatography. One of the pooled antigen fractions from the preparative isoelectric focusing step (pool 2) was passed through a concanavalin A column and yielded two components, designated antigens IIa and IIb. Antigen IIb reacted more strongly than antigen IIa with all of the aspergilloma and allergic bronchopulmonary aspergillosis sera tested by enzyme-linked immunosorbent assay. The glycoprotein nature of antigen IIb was shown by the concanavalin A binding properties and staining reactions of the components.

Allergic bronchopulmonary aspergillosis (ABPA) is the result of hypersensitivity to Aspergillus antigens in patients with long-standing atopic asthma. In the present study mycelial and culture filtrate antigens from Aspergillus fumigatus cultures isolated from diverse sources were tested against sera of 10 ABPA patients and 10 control individuals by an ELISA methodology. The results indicate higher antibody reactivity against both antigens in the sera of ABPA patients, while culture filtrate antigens also gave non-specific reactivity with control sera. Mycelial extracts, in general, were useful in the diagnosis of ABPA.

Asthma is a significant health problem worldwide and Allergic Bronchopulmonary aspergillosis (ABPA) complicates the course of 1-2% of patients of asthma. Aspergillus skin hypersensitivity (AH) is the first step for diagnosis of ABPA. This study was conducted to know the correlation of AH with severity and duration of asthma. Patients, age >15 years, of asthma attending this hospital from January 2015 to December 2015 were included. Asthma was diagnosed clinically and confirmed with spirometry. Of 282 patients 206 patients were AH positive. The AST-positivity in patients having severe asthma (96.8%) was higher than that in patients having mild (36.8%) and moderate asthma (80.4%). The median (IQR) duration of asthma of AH positive patients was 5.0 yrs. This study emphasized the need of ABPA screening by intradermal skin test especially in patients having severe asthma and/or those having asthma for longer duration in order for early diagnosis of ABPA.

The idea that a mechanism of autoimmunity could play a role in the pathogenesis of atopic dermatitis gained support from the observation that patients with atopic dermatitis display IgE reactivity to a variety of human protein antigens, several of which have been characterized at molecular level. A broad spectrum of at least 140 IgE-binding self-antigens associated with atopic dermatitis has been demonstrated; they might promote, perpetuate, or both, skin inflammation by binding IgE antibodies or activating specific T cells. Even if the presence of autoreactivity seems to be associated with the severity of the disease and may be used as a parameter reflecting chronic tissue damage, at the state of art the role of autoimmunity in atopic dermatitis is far from clear. Data from the literature show that the use of autoantibodies as biomarkers of atopic dermatitis are still limited by the evidence that the epiphenomenon of autoreactivity is detectable only in a percentage of patients and that the involved selfallergens often are not the same; further longitudinal case-control studies are needed to investigate and to clarify the pathogenethic role of autoimmunity in the course of atopic dermatitis.

Pulmonary hypertension as presenting manifestation of SLE is extremely rare. Here we report a case of 29 year old woman presenting with progressive shortness of breath associated with pedal edema which on detailed examination found to be secondary to pulmonary hypertension .Further examination of patient fulfilled diagnostic criteria of SLE

Aim and Objective: This cadaveric study was performed to describe the variations in the pattern of pulmonary fissures in the Western Kenyan population. Data were sourced from 68 lungs fixed in formalin in the gross anatomy laboratory of the Department of Human Anatomy, Uzima University. The fissures were studied, and the results were compared with the previous studies. Results: In this study, 83.82% of lungs had a classical appearance: three major fissures (horizontal and two oblique fissures) that were complete without any accessory fissures. Out of the 31 right lungs examined, the horizontal fissure was absent in none of the lungs, incomplete in six lungs (16.13%), and complete in 25 lungs (80.64%). Out of the 37 left lungs, the oblique fissure was incomplete in four lungs (10.70%) and complete in 29 lungs (86.30%). The fissure was absent in one left lung (2.70%). Four right lung accessory fissures were observed (12.90%). Six left lungs (16.67%) had accessory fissures. Conclusion: The incidence of the complete oblique fissures was more significant in our present work when compared with other authors' work. Our study's incomplete oblique fissure and horizontal fissure varied compared with other studies. Our study recorded a prevalence of absent oblique fissures in the left lung that was greater in relation to absent horizontal fissures. The superior accessory fissure was significant in our study compared to other studies, as well as when other studies were compared to the inferior accessory fissure prevalence in our study. The left minor fissure was our study's most frequently appearing accessory fissure. Anatomists should note that lung fissure anatomy is more variable than traditionally presented, and clinicians must be aware of the prevalence these variations. Considering these variants, we recommend that more explorative research be done on this topic to increase awareness.

All patients with prolonged cough with a history of atopy, even if not clinically asthmatic, should be evaluated for allergic bronchopulmonary aspergillosis (ABPA); also, we suspect that we may miss the early diagnosis of ABPA if bronchial asthma is considered as a major criteria for the diagnosis of ABPA.

Background: Amoxicillin is a β-lactam antibiotic which is bactericidal for sensitive
gram-positive and gram-negative bacteria and amoxicillin extends the spectrum of
activity of penicillin G.
Method: The literature search was performed using PubMed database as search
engine.
Results: Amoxicillin is active against meningococci, Listeria monocytogenes,
Streptococcus pyogenes, and many strains of Haemophilus influenzae. Some bacteria
possess β-lactamases which destroy the β-lactam ring; thus, amoxicillin is coformulated with clavulanic acid, a β-lactamase inhibitor, and amoxicillin/clavulanate
extends the spectrum of β-lactamase-producing Haemophilus influenzae, Escherichia
coli, Klebsiella, Proteus, Moraxella, and Bacillus fragilis. Amoxicillin is used to treat
sinusitis, otitis media, acute exacerbations of chronic bronchitis, and epiglottitis.
The efficacy, safety, prophylaxis, treatment, and trials with amoxicillin/clavulanate
have been studied, and the penetration of amoxicillin into the cerebrospinal fluid,
treatment of meningitis, transfer across the human placenta, and migration into the
breast milk with amoxicillin have also been studied. In addition, the pharmacokinetics
of amoxicillin and clavulanic acid have been studied.
Conclusion: the aim of this study is to review amoxicillin efficacy and safety,
prophylaxis, treatment, trials, penetration into the cerebrospinal fluid, treatment of
bacterial meningitis, transfer across the human placenta, migration into the breast
milk, and amoxicillin and clavulanic acid pharmacokinetics.

Background Invasive aspergillosis (IA) is one of the rarest opportunistic fungal infections and has increased in frequency worldwide in recent years. It is a life-threatening infection associated with high mortality rates. Invasive pulmonary aspergillosis (IPA) is the most severe form of the disease. Extrapulmonary forms can develop as a primary infection or occur as part of a disseminated infection from the lung in severely immunocompromised patients. The major limitation in the management of these infections is the challenge of early diagnosis. Case presentation Here we report a case of secondary cutaneous aspergillosis that developed from extensive pulmonary aspergillosis in a 3-year-old female who underwent immunosuppressive therapy for a diagnosed Behçet disease (BD). Aspergillus hyphae were identified on skin biopsies. Cultures grew Aspergillus fumigatus. The diagnosis of cutaneous aspergillosis enabled us to diagnose IPA, although there was no mycopathological proof of lung i...

Background: The prevalence of aspergillus sensitization (AS) and allergic bronchopulmonary aspergillosis (ABPA) in asthmatic children remains unclear. Objective: To systematically review the literature to estimate the prevalence of AS and ABPA in children with bronchial asthma. Methods: We searched the PubMed and Embase databases for studies reporting the prevalence of AS or ABPA in pediatric asthma. The primary outcome was to assess the prevalence of AS, while the secondary outcome was to evaluate the prevalence of ABPA. We pooled the prevalence estimates using a random effects model. We also calculated the heterogeneity and publication bias. Results: Of the 11,695 records retrieved, 16 studies with 2468 asthmatic children met the inclusion criteria. Most studies were published from tertiary centers. The pooled prevalence of AS in asthma (15 studies; 2361 subjects) was 16.1% (95% confidence intervals [CI], 9.3–24.3). The prevalence of AS was significantly higher in prospective stud...

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM   Objectives The evaluation of serum β-D-glucan, galactomannan, and Aspergillus fumigatus specific IgG in the diagnosis and clinical management of patients with chronic pulmonary aspergillosis. Methods Consecutive patients with a past history of pulmonary tuberculosis (PTB) with clinical suspicion of chronic pulmonary aspergillosis (CPA) attending the outpatient services of PGIMER, Chandigarh were included from August 2019 to August 2021, and CPA was defined as described by Denning et al. including both radiological and mycological evidence. Age and sex-matched post-PTB individuals selected from a population attending the chest clinic were enrolled as controls. Serum samples were obtained from all participants and testing for serum β-D-glucan (Fungitell, CapeCod), galactomannan (Platelia, BioRad) and Aspergillus fumigatus specific IgG (ImmunoCAP, Phadia) was performed as per manufacturer's instructions. Results A total of ...

BackgroundIn allergic bronchopulmonary aspergillosis (ABPA), prolonged nebulised antifungal treatment may be a strategy for maintaining remission.MethodsWe performed a randomised, single-blind, clinical trial in 30 centres. Patients with controlled ABPA after 4-month attack treatment (corticosteroids and itraconazole) were randomly assigned to nebulised liposomal amphotericin-B or placebo for 6 months. The primary outcome was occurrence of a first severe clinical exacerbation within 24 months following randomisation. Secondary outcomes included the median time to first severe clinical exacerbation, number of severe clinical exacerbations per patient, ABPA-related biological parameters.ResultsAmong 174 enrolled patients with ABPA from March 2015 through July 2017, 139 were controlled after 4-month attack treatment and were randomised. The primary outcome occurred in 33 (50.8%) out of 65 patients in the nebulised liposomal amphotericin-B group and 38 (51.3%) out of 74 in the placebo g...

A 32-year-old male presented with complaints of fever, dry cough, breathlessness and right sided chest pain of two months duration. Chest radiograph showed right sided hydropneumothorax which revealed frank pus on diagnostic thoracocentesis, for which tube thoracostomy was done. Despite vigorous broad spectrum antibiotic coverage, postural drainage and chest physiotherapy, there was no clinical improvement. Further work up included serology, pleural fluid culture, closed as well as thoracoscopic guided pleural biopsy revealed growth of Aspergillus fumigatus. Patient was prescribed antifungal medication (Voriconazole) and subsequent thoracotomy with right sided pneumonectomy showed good clinical recovery.

Background and Aim: Allergic bronchopulmonary aspergillosis (ABPA) is classified radiologically based on the findings of central bronchiectasis (CB) and other radiologic features (ORF). However, the long-term clinical significance of these classifications remains unknown. We hypothesized that the immunological activity and outcomes of ABPA could be predicted on HRCT chest finding of high-attenuation mucus (HAM), a marker of inflammatory activity. In this study, we evaluate the severity and clinical outcomes of ABPA with different radiological classifications. Methods: Patients were classified based on CT chest findings as: (a) serologic ABPA (ABPA-S) and ABPA-CB; (b) ABPA-S, ABPA-CB, and ABPA-CB-ORF; and, (c) ABPA-S, ABPA-CB and ABPA-CB-HAM. The clinical, spirometric and serological (total and A fumigatus specific IgE levels, eosinophil count) severity of the disease and clinical outcomes in various classifications were analyzed. Results: Of the 234 (123 males, 111 females; mean age, 34.1 years) patients, 55 (23.5%) had normal HRCT, 179 (76.5%) had CB, 49 (20.9%) had HAM, and 27 (11.5%) had ORF. All immunological markers were consistently higher in the HAM classification, while in other classifications these findings were inconsistent. On multivariate analysis, the factors predicting frequent relapses were presence of HAM (OR 7.38; 95% CI, 3.21-17.0) and CB (OR 3.93; 95% CI, 1.63-9.48) after adjusting for ORF. Conclusions: The classification scheme based on HAM most consistently predicts immunological severity in ABPA. Central bronchiectasis and HAM are independent predictors of recurrent relapses in ABPA. Hence, HAM should be employed in the radiological classification of ABPA.

Background: supplementation with n-3 polyunsaturated fatty acids (PUFA) leads to production of leukotriene (LT) B5, which is biologically less active than LTB4. LTB4 is important chemoattractant in neutrophilic inflammation in CF lung disease. Methods: nine F508del homozygous CF patients (5 females) aged 25.6±3.3 (mean±SD) years were treated for 6 weeks with n-3 PUFA (dosis corresponding to 1.3% of energy intake). Exhaled breath condensates (EBC) were collected before and after treatment. pH and LTB4 concentration (pg/ml) were measured in EBC samples. Results: pH was increased (from 6.08±0.39 to 6.32±0.18; p = 0.013) and LTB4 concentration was decreased (from 227.3±195.0 to 134.9±67.3 pg/ml; p = 0.075) in EBC after n-3 PUFA treatment. Conclusion: LTB4 concentration in EBC tend to be lower after n-3 PUFA treatment and EBC is significantly less acidified, which may reflect less intense neutrophilic inflammation.

A model of allergic bronchopulmonary aspergillosis was developed by exposing BALB/c mice to Aspergillus fumigatus (AF) Ag. Animals immunized intranasally (i.n.) with soluble AF Ag produced low levels of serum IgE compared to animals given alum precipitated AF Ag i.p. The latter treatment also produced higher levels of serum IgG1 and AF-specific IgG1 than soluble AF given i.p. or i.n.. Blood and lung eosinophilia was detected in mice repeatedly exposed to AF by i.n. but not in the groups injected i.p. Particulate AF Ag-induced striking blood and lung eosinophilia and elevated levels of serum IgE in mice preexposed to AF Ag. The results indicate that route of inoculation and physical nature of Ag determine the immune response and can be manipulated to obtain enhanced IgE, eosinophils, or both in the animal model.

Eosinophilia is a prominent feature of the cellular response in allergic and parasitic diseases. Allergic bronchopulmonary aspergillosis due to colonization of the lungs of some asthmatics with Aspergillus fumigatus is characterized by high levels of serum immunoglobulin E and peripheral blood (PB) and lung eosinophilia. This study investigates the role of eosinophils in the pathogenesis of allergic bronchopulmonary aspergillosis by using a mouse model. BALB/c mice were immunized intranasally and intraperitoneally with A. fumigatus antigens (Ag), and the eosinophils in PB and bone marrow (BM) were enumerated. Eosinophilopoiesis in BM cultures was studied in the presence of murine recombinant interleukin-5 (mrIL-5) and supernatants from pokeweed mitogen-stimulated spleen cells as the source of eosinophil differentiation factors. Eosinophils were quantitated by direct counting and by estimating eosinophil peroxidase activity. The results indicate that the percentage of eosinophils in ...

ABSTRACTAsp f 2 is a majorAspergillus fumigatusallergen involved in allergic bronchopulmonary aspergillosis. Knowledge of the B-cell epitopes may contribute to the understanding of immunoregulation and immunodiagnosis. To elucidate the immunoglobulin E (IgE) binding epitopes in the linear sequence of Asp f 2, we synthesized decamer peptides spanning the whole molecule of Asp f 2 on derivatized cellulose membranes and evaluated IgE binding in ABPA patient and control sera. Peptides three to five amino acids long were synthesized based on amino acid sequences within the IgE binding regions and evaluated for the specificity of epitope antibody interactions. Nine IgE binding regions were recognized in this protein of 268 amino acid residues. Of the nine epitopes, seven (ATQRRQI, RKYFG, HWR, YTTRR, DHFAD, ALEAYA, and THEGGQ) are present in the hydrophilic regions of Asp f 2. Immunologic evaluation of the three recombinant fragments, Asp f 2A encompassing the N-terminal epitope region, As...

ABSTRACTThe 37-kDa recombinant protein Asp f 2, encoding an allergen ofAspergillus fumigatus, was expressed in a prokaryotic expression system and immunologically evaluated for its functional and structural properties. The open reading frame for a 310-amino-acid-long protein was shown to encode a signal peptide of 31 amino acids. A native 37-kDa culture filtrate protein and a 55-kDa mycelial glycoprotein (gp55) exhibited complete N-terminal sequence homology to Asp f 2. A GenBank search for homologous proteins revealed 60 and 44% sequence homologies to the cytosolic protein ASPND1 fromAspergillus nidulansand fibrinogen binding protein fromCandida albicans, respectively. The glycosylation sites and cysteine molecules are conserved in all the three proteins. The extracellular matrix protein laminin showed a dose-dependent interaction with Asp f 2. This protein, expressed as a major cell-associated protein within 24 h of in vitro fungal culture, comprises 20 to 40% of total fungal prot...

Sera from patients with allergic bronchopulmonary aspergillosis (ABPA) or aspergilloma and normal sera were analyzed for specific antibodies by Western (immuno-) blotting with Aspergillus fumigatus antigens transferred electrophoretically onto polyvinylidene difluoride membranes. Western blot analysis demonstrated consistent reactivity of low-molecular-weight A. fumigatus antigens against ABPA sera but not against uncomplicated aspergilloma or normal sera. None of these low-molecular-weight components had any lectin-binding activity. Sera from patients with aspergilloma, however, frequently reacted with high-molecular-weight components of A. fumigatus. The majority of these high-molecular-weight antigenic components demonstrated concanavalin A-binding activity. The low-molecular-weight bands were discernible in Western blots with sera from all ABPA patients irrespective of disease activities, such as relapse, flare, or treatment. Antibodies detected by methods such as immunodiffusio...

Exposure of BALB/c mice to Aspergillus fumigatus (Af), the antigen responsible for causing allergic bronchopulmonary aspergillosis in humans, caused elevated levels of serum immunoglobulin E (IgE) and peripheral blood and lung eosinophilia similar to that observed in the human disease. We have investigated the role of interleukin-4 (IL-4), IL-5 and interferon-γ in regulating IgE and eosinophilia in the mouse model. Animals were immunized by intraperitoneal injections of soluble Af antigens adsorbed to alum. These animals developed elevated IgE and Af specific IgG1 and were then treated with anticytokine monoclonal antibodies before the final exposure to particulate Af antigens by the intranasal route. The results showed that anti-IL-5 abrogated eosinophilia in mice, while those treated with anti-IL-4 retained the same or reduced IgE levels compared to pretreatment levels. All anti–IL-5, anti–IFN-γ, and control antibody–treated animals showed enhanced IgE levels. Anti–IFN-γ treatment...