Aspergillus Fumigatus-specific IgG Research Articles

Chronic pulmonary aspergillosis in tea population of Assam.

Chronic pulmonary aspergillosis (CPA) is a disease commonly caused by Aspergillus fumigatus and other Aspergillus speciescharacterizedby cavitary lung lesions. Tea garden population is an agrarian population of Assam, mostly associated with tea plantations. Assam is a major tea-producing state with 803 tea gardens producing approximately 50% of the total tea in India, of which 177 are present in the Dibrugarh district alone. Tuberculosis is common in tea garden workers. This community-based cross-sectional study in the tea garden community of Dibrugarh was done to find the prevalence of Aspergillus IgG antibodies and CPA cases in individuals with chronic respiratory symptoms. Patients visiting 3 tea garden hospitals and 2 referral hospitals with chronic cough and/or haemoptysis, weight loss/fatigue, and other respiratory symptoms for a duration of 3 months or more were included in this one-year study. Serum samples were tested by Immunocap Phadia 200 for Aspergillus fumigatus-specific IgG antibodies. CPA cases were diagnosed based on clinical, radiological, and serological criteria. Out of 128 samples, seropositivity was seen in 41 (32.0%) patients (cutoff value: 27 mgA/l). Male preponderance (1.6:1) with a mean age of 41.9 (±15.69) was observed. Haemoptysis and fatigue were significant symptoms seen (p-values: 0.0086 and 0.0098, respectively). Aspergillus fumigatus-specific IgG antibody was found to be significantly high in 29 out of 76 patients (38.1%) with a history of tuberculosis. Amongst them, seropositivity with active TB was 5 out of 27 patients (18.5%), and seropositivity with post-TB was 24 out of 49 patients (48.9%). Chronic cavitary pulmonary aspergillosis was the predominant type (38.1%). Proven CPA (clinically, radiologically, and serologically positive) were 22 (17.1%, 95% CI 10.7%-26.0%), and possible CPA (clinically and serologically positive but without radiological data) were 19 (14.8%, 95% CI 8.9%-23.1%). A high prevalence of CPA (60 per 100 000) was detected. High Aspergillus seropositivity of 48.9% was seen in the post-TB population. Aspergillus-specific IgG antibody testing is the only confirmatory method for diagnosing CPA, which is available in limited centres in India. Aspergillus seropositivity should be detected in post-TB patients presenting with chronic respiratory symptoms.

Clinical applications of immunoglobulin G against different individual Aspergillus species for the diagnosis of chronic pulmonary aspergillosis among at-risk populations

ABSTRACT Aspergillus fumigatus-specific IgG is often used as a diagnostic test for chronic pulmonary aspergillosis (CPA), but few studies have evaluated the performance and serology of IgGs from species other than A. fumigatus. In this study, we evaluated the serology and performance of different Aspergillus species-specific IgG antibodies in patients with CPA and at-risk populations and whether different Aspergillus species-specific IgGs could be of clinical utility and aid in the diagnosis of CPA caused by all Aspergillus species. A total of 187 participants were included between 2020 and 2022 (12 with CPA, 75 with old tuberculosis [TB], 45 with active TB and 55 with bronchiectasis). We measured the serum Aspergillus fumigatus, flavus, terreus, niger-specific, and mixed Aspergillus IgG levels (Phadia ImmunoCap). The correlation was the strongest between A. fumigatus and A. niger (Spearman’s rank: 0.940), followed by A. niger and A. flavus (Spearman’s rank: 0.915). A. terreus-specific IgG was less strongly correlated with the other three Aspergillus species-specific IgG (Spearman’s rank: 0.828–0.849). A. flavus (4 of 6, 67%) was the dominant species. Using the at-least-one-positive approach, the highest performance was obtained when A. fumigatus and A. flavus IgGs were used (sensitivity, 0.75; specificity, 0.84). Significant cross-reactivity exists among different Aspergillus-species IgGs although the correlation may be less significant for A. terreus. In addition to the commonly used A. fumigatus IgG test, IgGs specific to local prevalent Aspergillus species may provide additional clinical utility.

Serum Aspergillus fumigatus-Specific IgG as a Complementary Biomarker in Differentiating Endotypes of Chronic Rhinosinusitis: A Study on Its Role and Diagnostic Efficacy in Type 2 Inflammation.

Aspergillus is one of the most common pathogens causing fungal allergy in the respiratory tract. Serum Aspergillus fumigatus-specific immunoglobulin G (Af-sIgG) levels have been used as a biomarker for the diagnosis and treatment response monitoring in airway allergic diseases such as allergic bronchopulmonary aspergillosis and allergic fungal rhinosinusitis. However, its role in common primary chronic rhinosinusitis (CRS) was unclear. This study aims to evaluate whether serum Af-sIgG level could serve as a biomarker for the disease presentation of primary CRS. We obtained serum Af-sIgG levels from patients diagnosed as bilateral primary CRS refractory to medical treatment and evaluated the correlations between serum Af-sIgG levels and disease severity in patients with type 2 (T2) and non-T2 CRS. Patients with T2 CRS exhibited significantly higher serum Af-sIgG levels than non-T2 CRS patients. The cut-off value of serum Af-sIgG in T2 CRS was 20.9 mg/L, with an odds ratio of 3.8 (95% CI 1.17-12.20, P = .026). Furthermore, serum Af-sIgG levels were positively correlated with symptom scores evaluated by the Sino-Nasal Outcome Test-22 (SNOT-22) scores in T2 patients (P = .009). While stratified by SNOT-22 total scores, patients with severe disease had higher serum Af-sIgG levels only in T2 CRS (P = .034). In individual domains of SNOT-22 analysis, serum Af-sIgG levels showed a significant correlation with "ear/facial" symptom scores in the T2 group (P < .001). Serum Af-sIgG levels may serve as a supplementary objective biomarker that correlates with identification and subjective measurements of T2 CRS, and may be associated with symptoms arising from Eustachian tube dysfunction.

Value Evaluation of Quantitative Aspergillus fumigatus-Specific IgG Antibody Test in the Diagnosis of Non-neutropenic Invasive Pulmonary Aspergillosis.

The role of Aspergillus-specific IgG antibody test in the diagnosis of non-neutropenic invasive pulmonary aspergillosis (IPA) is still uncertain, and related studies are also limited. This study aims to evaluate the quantitative test value of Aspergillus fumigatus-specific IgG antibody in non-neutropenic IPA, which could provide additional evidence for related clinical diagnosis. This prospective study collected clinical data of suspected IPA patients from January, 2020 to December, 2022, and patients were divided into two groups, IPA and non-IPA. The study analyzed clinical characteristics and diagnostic value of Aspergillus-specific IgG antibody test, using the receiver operating characteristic (ROC) curve to evaluate diagnostic efficacy. The study enrolled 59 IPA cases and 68 non-IPA cases, the average admission age of IPA group was 63.2±9.6 (33-79), and the gender ratio (male:female) of IPA group was 42:17. The proportion of patients with history of smoking and COPD were higher in IPA group (59.3% vs 39.7%, P=0.027; 33.9% vs 14.7%, P =0.011, respectively). The level of Aspergillus fumigatus-specific IgG antibody in IPA group was significantly higher than non-IPA group (202.1±167.0 vs 62.6±58.0, P<0.001). The area under the ROC curve was 0.799 (95%CI: 0.718, 0.865 P<0.001), and the cut-off with best diagnostic efficacy was 91 AU/mL. Immunological test plays an important role in the diagnosis of pulmonary aspergillosis, and Aspergillus-specific IgG antibody test has the good diagnostic value in non-neutropenic IPA.

Sensitivity and specificity of LDBio Aspergillus ICT lateral flow assay for diagnosing allergic bronchopulmonary aspergillosis in adult asthmatics.

Aspergillus fumigatus-specific IgG estimation is crucial for diagnosing allergic bronchopulmonary aspergillosis (ABPA). A point-of-care LDBio immunochromatographic lateral flow assay (LFA) had 0%-90% sensitivity to detect IgG/IgM antibodies against A. fumigatus. To assess the accuracy of LDBio-LFA in diagnosing ABPA, using the modified ISHAM-ABPA working group criteria as the reference standard. The secondary objective was to compare the diagnostic performance between LDBio-LFA and A. fumigatus-specific IgG (cut-offs, 27 and 40 mgA/L), using a multidisciplinary team (blinded to A. fumigatus-IgG and LDBio-LFA results) diagnosis of ABPA as the reference standard. We prospectively enrolled adult subjects with asthma and ABPA. We performed the LDBio-LFA per the manufacturer's recommendations. We used the commercially available automated fluorescent enzyme immunoassay for measuring serum A. fumigatus-specific IgG. We used the same serum sample to perform both index tests. The tests were performed by technicians blinded to the results of other tests and clinical diagnoses. We included 123 asthmatic and 166 ABPA subjects, with a mean ± SD age of 37.4 ± 14.4 years. Bronchiectasis and high-attenuation mucus were seen in 93.6% (146/156) and 24.3% (38/156) of the ABPA subjects. The sensitivity and specificity of LDBio-LFA in diagnosing ABPA were 84.9% and 82.9%, respectively. The sensitivity of serum A. fumigatus-specific IgG ≥27 mgA/L was 13% better than LDBio-LFA, with no difference in specificity. There was no significant difference in sensitivity and specificity between LDBio-LFA and serum A. fumigatus-IgG ≥40 mgA/L. LDBio-LFA is a valuable test for diagnosing ABPA. However, a negative test should be confirmed using an enzyme immunoassay.

The minimal important difference of six-minute walk test in subjects with chronic pulmonary aspergillosis treated with six-months of oral itraconazole.

The minimal important difference of six-minute walk test in subjects with chronic pulmonary aspergillosis treated with six-months of oral itraconazole.

P408 Evaluation of fungal serum biomarkers in the diagnosis and for monitoring patients with post tuberculosis chronic pulmonary aspergillosis

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PMObjectivesThe evaluation of serum β-D-glucan, galactomannan, and Aspergillus fumigatus specific IgG in the diagnosis and clinical management of patients with chronic pulmonary aspergillosis.MethodsConsecutive 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.ResultsA total of 105 post-TB patients with CPA and 11 controls were enrolled. Aspergillus fumigatus (n = 8) was the most commonly isolated species, followed by A. flavus (n = 4), and A. niger (n = 2). The mean A. fumigatus specific IgG levels, serum galactomannan index and BDG levels were higher among CPA cases vs. controls at 101.4 mgA/l vs. 11.8 mgA/l, P-value: .0001; 0.73 vs. 0.35, P-value: .3134; and 133.7 pg/ml vs. 32.37 pg/ml, P-value: .012, respectively (Figs. 1a, b, c). The serum BDG had an area under curve 0.834 ± 0.044 (95% CI: 0.748-0.920) on the ROC curve with a sensitivity of 57.1% and specificity of 100% at the kit cut-off of 80 pg/ml (Fig. 2a). Comparison between CPA patients with multiple (n = 38) versus single lobe (n = 67) involvement showed comparable A. fumigatus specific IgG levels (112.3 vs. 93.8; P-value: .133 respectively) while galactomannan index and BDG levels were higher in cases with multiple vs. single lobe involvement (0.94 vs. 0.57, P-value: .117), and (174.3 vs. 105.3, P-value: .0071), respectively (Fig. 1d, e, f). There was a significant association of BDG value with the severity of dyspnea (P-value: .002) and a trend of higher A. fumigatus specific IgG was also seen to correlate with the severity of dyspnea (Fig. 2b and 2c).ConclusionBDG assay can serve as an adjunct in the diagnosis of patients with CPA. An association of higher levels of BDG with multiple lobe involvement and severe dyspnea could be due to more extensive tissue damage associated with a greater release of antigen in circulation during progressive disease. More studies with a larger number of control samples, preferably with multi-center coordination can further improve our understanding of this test's applicability in routine practice.

P501 Aspergillus fumigatus complicates one third of the patients with suspected bronchial asthma or pulmonary tuberculosis: Clinical validation of indigenously developed diagnostic kits

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PMObjectives Aspergillus fumigatus, an opportunistic fungus, causes complications in about 5%-20% of bronchial asthma and about 26% of pulmonary tuberculosis patients. Detection of Aspergillus fumigatus specific IgG and IgE antibodies in the patient serum is an excellent tool to screen for Aspergillus sensitization early on to employ anti-fungal drugs in the clinical management to stall the progression of lung fibrosis.MethodsNovel indigenous AfuPEPLISA assays were developed for the detection of specific IgG and IgE, based on the 12 amino acid long synthetic peptide epitope of Asp f1, an 18 kDa major allergen/antigen. The novel diagnostic kits were manufactured at a licensed GMP facility under a test license. Independent validation of the kits was pursued at PGIMER and VPCI hospitals in suspected bronchial asthma patients (n = 1307), and the diagnostic efficiency was compared with currently used ImmunoCAP assay.ResultsThe diagnostic specificity and sensitivity were found to be 95.7% and 89.8%, respectively, for IgG; and 94.2% and 70%, respectively for IgE AfuPEPLISA, and were not significantly different from ImmunoCAP assay. Screening of the suspected patients of pulmonary tuberculosis (PTB) at RBIPMT Hospital for the presence of A. fumigatus specific IgG and IgE antibodies was pursued using AfuPEPLISA kits. A total of 82 out of 254 suspected PTB patients (32.3%) were seropositive in agreement with the previous reports.See Figures 1 and 2 below.ConclusionThe study inferred that indigenously developed AfuPEPLISA kits are an economically viable option to integrate in the clinical management of patients with suspected bronchial asthma or PTB for efficient diagnosis of Aspergillus sensitization.

Significance of aspergillus fumigatus-specific IgG in the diagnosis of allergic bronchopulmonary aspergillosis

The data of 18 patients with allergic bronchopulmonary aspergillosis (ABPA) who received aspergillus fumigatus-specific IgG detection from 2015 to 2021 in Peking University Third Hospital were retrospectively analyzed. Among them, 11 were male and 7 were female, aged 18-79 years. All patients had a history of asthma or symptoms of cough and asthma, and aspergillus fumigatus-specific IgE was positive; 16 patients had total serum IgE>500 U/ml, of which 13 patients had total serum IgE>1 000 U/ml. Among other diagnostic indicators, peripheral blood eosinophils were >0.5×109/L in 16 cases; lung CT showed bronchiectasis in 15 cases; serum aspergillus fumigatus-specific IgG was positive (>120 AU/ml) in 10 cases. There was no significant difference in serum total IgE level, peripheral blood eosinophil count, and bronchiectasis ratio between positive and negative cases of aspergillus fumigatus-specific IgG (all P>0.05). In this study, the positive rate of aspergillus fumigatus-specific IgG in patients with ABPA was more than 50%, which has auxiliary value in the diagnosis of ABPA.

Establishing Aspergillus-Specific IgG Cut-Off Level for Chronic Pulmonary Aspergillosis Diagnosis: Multicenter Prospective Cohort Study.

Objectives: Aspergillus-specific IgG (Asp-IgG) cut-off level in diagnosing chronic pulmonary aspergillosis (CPA) remains unknown. Methods: We prospectively recruited participants with clinical suspicion of CPA in three centers in Taiwan during 2019 June to 2020 August. Serum Aspergillus fumigatus-specific IgG (Asp-IgG) (Phadia, Uppsala, UPPS, Sweden) was examined. Optimal cut-off level was determined by Youden’s index and validated. Results: A total of 373 participants were recruited. In the derivation cohort (n = 262), Asp-IgG had an area under the receiver-operating-characteristic curve (AUC) of 0.832. The optimal cut-off level was 40.5 mgA/L. While applying this cut-off level to the validation cohort (n = 111), the sensitivity and specificity were 86.7% and 80.2%. Lowering the cut-off level from 40.5 to 27 mgA/L, the sensitivity was steady (30/36, 83.3% to 31/36, 86.1%) while specificity dropped from 81.9% (276/337) to 63.5% (214/337). Restricting CPA diagnosis to only chronic cavitary pulmonary aspergillosis (CCPA) and chronic fibrosing pulmonary aspergillosis (CFPA) yielded a cut-off level of 42.3 mgA/L in the derivation cohort with a sensitivity of 100% and specificity of 84.4% in the validation cohort. Conclusions: Serum Asp-IgG performs well for CPA diagnosis and provides a low false-positive rate when using a higher cut-off level (preferably around 40 mgA/L).

Pulmonary infection due to Acrophialophora fusispora in a patient with underlying mixed connective tissue disease and chronic pulmonary aspergillosis

BACKGROUND Acrophialophora fusispora is an emerging opportunistic fungus rarely implicated in human infections. Here, we report the first case of pulmonary infection due to A. fusispora from India. CASE DESCRIPTION A 59-year-old male, farmer by occupation was admitted to AIIMS, Jodhpur, Rajasthan, India, with complaints of cough and expectoration of yellowish sputum for last one month and gradually progressive shortness of breath for 20 days. He had past history of pulmonary tuberculosis and was a known case of COPD for last five years. He was diagnosed with mixed connective tissue disease (MCTD) for which he had been receiving treatment with azathioprine and prednisolone for 3 months. CECT of chest revealed cystic bronchiectatic changes with findings suggestive of aspergilloma. Serum Aspergillus fumigatus specific IgG levels were elevated suggestive of chronic pulmonary aspergillosis (CPA). He was tested positive for influenza A (H1N1) by RT-PCR and received treatment with oral oseltamivir but to no clinical benefit. Culture of sputum on two subsequent occasions showed growth of a fungus which was identified as Acrophialophora fusispora based on characteristic microscopic morphology and rDNA ITS sequencing. Treatment with oral itraconazole showed marked symptomatic improvement. He was discharged from the hospital with oral itraconazole to be continued for 6 months. Follow-up visit after 3 months showed significant clinical and radiological improvement. CONCLUSION Molecular sequencing can reliably identify A. fusispora which is crucial for initiating specific antifungal therapy. Further studies are encouraged to determine the prevalence of such infections so as to plan optimal management and improve patient outcomes.

Diagnostic cut-off value for Aspergillus fumigatus- and flavus-specific IgG with clinical relevance in chronic pulmonary Aspergillus infection: A pilot study in Taiwan.

The diagnostic cut-off value for chronic pulmonary Aspergillosis (CPA) by Aspergillus fumigatus-specific IgG has never been evaluated In Taiwan. The cut-off value for Aspergillus flavus-specific IgG has not been evaluated worldwide. Evaluate diagnostic cut-off value of Aspergillus IgG and its application characteristics. Blood from control groups and treatment-naïve patients with CPA infections was collected for Aspergillus-specific IgG measurements. Controls were patients who had chest radiographic abnormalities and signs of respiratory tract infection, but were negative for Aspergillus and resolved without anti-mould therapy. Confirmation and probability of CPA were defined according to radiological features and positivity for an Aspergillus or galactomannan index. Chest computer tomography patterns were recorded for the presence of aspergilloma or nodules, subacute invasive aspergillosis, chronic cavitary pulmonary aspergillosis and chronic fibrotic pulmonary aspergillosis. A total of 35 cases and 50 disease controls were included. The levels of A.fumigatus- and A.flavus-specific IgG correlated with CPA progression (P<.05) but not with the presence of Aspergillus species from clinical specimens (P>.05). The best cut-off value for A.fumigatus IgG was 21.7mg/L with area under curve (AUC) for receiver operating characteristic curve (ROC) 0.934 and had 85.7% sensitivity and 92.0% specificity. For A.flavus IgG, the best cut-off value was 22.1mgA/L and the AUC was 0.928 with 88.2% sensitivity and 94.1% specificity. The level of Aspergillus-specific IgG correlated with radiographic characteristics in patients with CPA and the best cut-off values compared to controls were 21.7mgA/L for A.fumigatus-specific IgG and 22.1mgA/L for A.flavus-specific IgG.

Pulsed echinocandin therapy in azole intolerant or multiresistant chronic pulmonary aspergillosis: A retrospective review at a UK tertiary centre.

Chronic pulmonary aspergillosis (CPA) is a fungal disease with high mortality and morbidity. Guidelines suggest treatment with azoles as first-line therapy. However, patients often develop treatment intolerance or increasingly azole resistance. This retrospective review assesses outcomes in azole resistant or intolerant patients with CPA treated with cyclical echinocandin therapy. We retrospectively examined records of 25 patients with CPA treated with cyclical caspofungin, 6 of whom were either azole-resistant or azole intolerant. Baseline characteristics, high-resolution computed tomography severity scores, forced expiratory volume after 1 minute (FEV1), forced vital capacity (FVC), body mass index and serology (Aspergillus fumigatus-specific IgG, Aspergillus fumigatus-specific IgE, total IgE and CRP) were assessed before and after caspofungin. Of the six patients, four (66%) started caspofungin due to intolerance and two (33%) due to pan-azole resistance. On treatment, there was stability in FEV1 with an overall mortality of 33% during the follow-up period with a median survival of 875.5days (IQR 529-1024). No significant change in serology (A. fumigatus-specific IgG and CRP was seen. With pulsed echinocandin therapy, azole-intolerant or pan-resistant CPA patients have similar mortality rates to azole-naïve CPA patients. Pulsed echinocandin therapy may present a strategy to stabilize CPA in patients with pan resistance or intolerance to, azole therapy.

Pulmonary infection due to Acrophialophora fusispora in a patient with underlying mixed connective tissue disease and chronic pulmonary aspergillosis

BACKGROUND Acrophialophora fusispora is an emerging opportunistic fungus rarely implicated in human infections. Here, we report the first case of pulmonary infection due to A. fusispora from India. CASE DESCRIPTION A 59-year-old male, farmer by occupation was admitted to AIIMS, Jodhpur, Rajasthan, India, with complaints of cough and expectoration of yellowish sputum for last one month and gradually progressive shortness of breath for 20 days. He had past history of pulmonary tuberculosis and was a known case of COPD for last five years. He was diagnosed with mixed connective tissue disease (MCTD) for which he had been receiving treatment with azathioprine and prednisolone for 3 months. CECT of chest revealed cystic bronchiectatic changes with findings suggestive of aspergilloma. Serum Aspergillus fumigatus specific IgG levels were elevated suggestive of chronic pulmonary aspergillosis (CPA). He was tested positive for influenza A (H1N1) by RT-PCR and received treatment with oral oseltamivir but to no clinical benefit. Culture of sputum on two subsequent occasions showed growth of a fungus which was identified as Acrophialophora fusispora based on characteristic microscopic morphology and rDNA ITS sequencing. Treatment with oral itraconazole showed marked symptomatic improvement. He was discharged from the hospital with oral itraconazole to be continued for 6 months. Follow-up visit after 3 months showed significant clinical and radiological improvement. CONCLUSION Molecular sequencing can reliably identify A. fusispora which is crucial for initiating specific antifungal therapy. Further studies are encouraged to determine the prevalence of such infections so as to plan optimal management and improve patient outcomes.

Efficiency of A fumigatus-specific IgG and galactomannan testing in the diagnosis of simple aspergilloma.

An early diagnosis of chronic pulmonary aspergillosis (CPA) at the stage of simple aspergilloma (SA) remains a challenge in low- and middle-income countries, where imaging may not be routinely available. We investigate the role of Aspergillus fumigatus-specific IgG in serum, and galactomannan (GM) in bronchoalveolar lavage fluid (BALF) and serum for the diagnosis of SA. We included 46 consecutive treatment-naïve subjects with SA. The 81 controls were subjects oftreated pulmonary tuberculosis with residual radiological abnormality and minimal symptoms; and subjects with pulmonary disorders other than CPA who underwent bronchoscopy. The diagnosis of SA was based on consistent clinical features along with radiological manifestations (cavity with fungal ball). Using receiver operating characteristic (ROC) curve analysis, the best cut-off value for A fumigatus-specific IgG was 27.3 mgA/L (AUROC, 0.839; sensitivity, 63.5%; specificity, 98.3%). The best cut-off value for serum and BALF-GM was 0.7 (AUROC, 0.636; sensitivity, 32%; specificity, 96.2%) and 2.5 (AUROC, 0.833; sensitivity, 63.7%; specificity, 97.1%), respectively. A combination of A fumigatus-specific IgG (>27 mgA/L) or serum GM (≥0.7) or BALF-GM (≥2.5) had a sensitivity and specificity of 82.6% and 96%, respectively. A combination of serological tests has the best sensitivity in diagnosing SA. More studies are needed to confirm our findings.

P165 Prospective evaluation of Aspergillus fumigatus-specific IgG in patients with cystic fibrosis

P165 Prospective evaluation of Aspergillus fumigatus-specific IgG in patients with cystic fibrosis

Monitoring treatment response in chronic pulmonary aspergillosis: role of clinical, spirometric and immunological markers

ObjectivesThe treatment response in chronic pulmonary aspergillosis (CPA) is usually assessed based on the improvement in clinical and imaging findings. Herein, we evaluate serum Aspergillus fumigatus-specific IgG, serum galactomannan, weight change, and lung function for assessing treatment response in subjects with CPA. MethodsWe categorized treatment response as favourable (improved or stable clinical response with radiologically improved or stable disease) or unfavourable (worsening of symptoms or radiological progression) after 6 months of treatment with antifungal azoles. We measured A. fumigatus-specific IgG, serum galactomannan, weight, and lung function at baseline, 3 months, and 6 months in those with favourable and unfavourable treatment response. ResultsOne hundred and twenty-six consecutive treatment-naïve subjects (53.2% (67/126) males; mean ± SD age, 42.3 ± 14.7 years) with CPA were included. One hundred and six and 20 were classified as having favourable and unfavourable response, respectively. After 6 months of treatment, the decline in serum A. fumigatus-specific IgG (n = 119) was similar in those with favourable or unfavourable response (mean ± SD, -26.3 ± 45.5 mgA/L vs. –3.4 ± 65.6 mgA/L; p 0.20). There was no significant change in the serum galactomannan (favourable vs. unfavourable: mean ± SD, –0.11 ± 2.8 vs. -0.62 ± 2; p 0.92) or FEV1 (favourable vs. unfavourable: mean ± SD, 24 ± 250 mL vs. –62 ± 154 mL; p 0.19) after 6 months of treatment. There was significant loss of weight (mean ± SD, –2.5 ± 4.5 kg) in subjects with unfavourable response. ConclusionSerum A. fumigatus-specific IgG and serum galactomannan inconsistently decrease following treatment and may not be useful indicators for monitoring treatment response in CPA. Similarly, there is little change in pulmonary function following treatment. A gain in body weight is seen in those with favourable response.

Role of Aspergillus fumigatus-specific IgG in diagnosis and monitoring treatment response in allergic bronchopulmonary aspergillosis.

Few studies have evaluated the utility of Aspergillus fumigatus-specific IgG in allergic bronchopulmonary aspergillosis (ABPA). Herein, we evaluate the role of specific IgG in diagnosis and monitoring treatment response in ABPA. Forty-eight control subjects with A.fumigatus-associated asthma underwent A.fumigatus-specific IgG measurements at baseline, while specific IgG was assayed in 102 treatment-naïve subjects of ABPA at baseline, after eight weeks of glucocorticoid therapy, and during exacerbations. For determining the cut-off of A.fumigatus-specific IgG, we randomly classified two-thirds of the study subjects (cases and controls) as the derivation cohort, while the remaining one-thirds were labelled as the validation cohort. The best cut-off value of A.fumigatus-specific IgG in the derivation cohort was 26.9mgA /L (sensitivity: 88%; specificity: 100%). Using this limit, the sensitivity and specificity of A.fumigatus-specific IgG in diagnosis of ABPA was 89% and 100%, respectively, in the validation cohort. In contrast, the sensitivity of Aspergillus precipitins was only 27.4%. Following treatment, the A.fumigatus-specific IgG increased in 38 (37.2%) subjects, while it decreased in three (23.1%) of the 13 subjects experiencing an exacerbation. The A.fumigatus-specific IgG was found to be an extremely useful test in the diagnosis and differential diagnosis of ABPA but is unreliable in monitoring treatment response in this disorder.

New Commercially Available IgG Kits and Time-Resolved Fluorometric IgE Assay for Diagnosis of Allergic Bronchopulmonary Aspergillosis in Patients with Cystic Fibrosis.

Allergic bronchopulmonary aspergillosis (ABPA) is difficult to diagnose; diagnosis relies on clinical, radiological, pathological, and serological criteria. Our aim was to assess the performance of two new commercially available kits and a new in-house assay: an Aspergillus fumigatus enzyme-linked immunosorbent assay (ELISA) IgG kit (Bordier Affinity Products), an Aspergillus Western blotting IgG kit (LDBio Diagnostics), and a new in-house time-resolved fluorometric IgE assay (dissociation-enhanced lanthanide fluorescent immunoassay, or DELFIA) using recombinant proteins from an Aspergillus sp. recently developed by our laboratory for ABPA diagnosis in a retrospective study that included 26 cystic fibrosis patients. Aspergillus fumigatus-specific IgG levels measured by a commercial ELISA kit were in accordance with the level of precipitins currently used in our lab. The ELISA kit could accelerate and help standardize ABPA diagnosis. Aspergillus fumigatus-specific IgE levels measured by ImmunoCAP (Phadia) with A. fumigatus M3 antigen and by DELFIA with a purified protein extract of A. fumigatus were significantly correlated (P < 10(-6)). The results with recombinant antigens glucose-6-phosphate isomerase and mannitol-1-phosphate dehydrogenase were encouraging but must be confirmed with sera from more patients. The DELFIA is an effective tool that can detect specific IgE against more fungal allergens than can be detected with other commercially available tests.