Aspergillus fumigatus-specific IgG is pivotal in making the diagnosis of chronic pulmonary aspergillosis (CPA). However, the cut-off value for A. fumigatus-specific IgG remains unknown. We included consecutive treatment-naïve subjects with chronic cavitary pulmonary aspergillosis (CCPA, cases). The controls were subjects with treated pulmonary tuberculosis, who had residual radiological abnormality and minimal symptoms. The diagnosis of CCPA was based on consistent clinicoradiological features along with demonstration of Aspergillus infection (growth of Aspergillus in sputum or bronchoalveolar lavage fluid [BALF] culture; serum or BALF galactomannan index >0.5 and >1, respectively). For determining the cut-off of A. fumigatus-specific IgG (Phadia), subjects were randomly classified as derivation (two-thirds) and validation (one-third) cohort. One hundred and thirty-seven cases and 50 controls were included. The best cut-off value for A. fumigatus-specific IgG (derivation cohort) was 27.3 mgA/L (AUROC, 0.976) at a sensitivity and specificity of 95.6% and 100%, respectively. Using a cut-off of 27 mgA/L, the sensitivity and specificity in the validation cohort was 91.3% and 100%, respectively. In contrast, the sensitivity of Aspergillus precipitins was only 25.5%. At a cut-off value of 27 mgA/L, A. fumigatus-specific IgG is a reliable test with high sensitivity and specificity in the diagnosis of CPA. More studies are required to confirm our findings.
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 26.9 mg /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.
The value of serum and bronchoalveolar lavage fluid galactomannan (BALF-GM) in diagnosing chronic pulmonary aspergillosis (CPA) remains unclear. Here, we study the diagnostic efficacy of GM in the diagnosis of CPA. We included consecutive treatment-naive subjects with CPA. For calculating the specificity of serum GM, we enrolled diseased controls (minimally symptomatic subjects previously treated for pulmonary tuberculosis, not meeting the criteria for CPA). To calculate the specificity of BALF-GM, subjects with pulmonary disorders other than CPA who underwent bronchoscopy were included. We determined the cutoff of serum and BALF-GM levels using receiver operating characteristic (ROC) curve analysis. We enrolled 243 consecutive treatment-naive subjects (53.5% males) of CPA with a mean (standard deviation) age of 43.6 (14.7) years. Forty-five (60% males; age, 46.7 [15.7] years) and 27 (59.3% males; age, 52.6 [12.8] years) subjects served as controls for serum and BALF-GM, respectively. The best cutoff value for serum and BALF-GM was 0.55 (area under the ROC curve [AUROC], 0.605; sensitivity, 38%; specificity, 87%) and 1.375 (AUROC, 0.836; sensitivity, 68%; specificity, 93%), respectively. At a cutoff value of 2.5, BALF-GM had a sensitivity and specificity of 50% and 100%, respectively. BALF-GM performs better than serum GM and may be helpful in the diagnosis of CPA in selected patients. More studies are required to confirm our findings.
Background The enormous increase in COVID‐19–associated mucormycosis (CAM) in India lacks an explanation. Zinc supplementation during COVID‐19 management is speculated as a contributor to mucormycosis. We conducted an experimental and clinical study to explore the association of zinc and mucormycosis. Methods We inoculated pure isolates of Rhizopus arrhizus obtained from subjects with CAM on dichloran rose Bengal chloramphenicol (DRBC) agar enriched with (three different concentrations) and without zinc. At 24 h, we counted the viable colonies and measured the dry weight of colonies at 24, 48 and 72 h. We also compared the clinical features and serum zinc levels in 29 CAM cases and 28 COVID‐19 subjects without mucormycosis (controls). Results We tested eight isolates of R arrhizus and noted a visible increase in growth in zinc‐enriched media. A viable count percentage showed a significantly increased growth in four of the eight isolates in zinc‐augmented DRBC agar. A time‐ and concentration‐dependent increase in the mean fungal biomass with zinc was observed in all three isolates tested. We enrolled 29 cases of CAM and 28 controls. The mean serum zinc concentration was below the reference range in all the subjects and was not significantly different between the cases and controls. Conclusions Half of the R arrhizus isolates grew better with zinc enrichment in vitro. However, our study does not conclusively support the hypothesis that zinc supplementation contributed to the pathogenesis of mucormycosis. More data, both in vitro and in vivo, may resolve the role of zinc in the pathogenesis of CAM.
Objectives: The treatment response in chronic pulmonary aspergillosis (CPA) is usually assessed based on the improvement in clinical and imaging findings. Herein, we evaluate serum Aspergillus fumigatusspecific IgG, serum galactomannan, weight change, and lung function for assessing treatment response in subjects with CPA. Methods: We 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. Results: One 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 ¼ 119) was similar in those with favourable or unfavourable response (mean ± SD, -26.3 ± 45.5 mgA/L vs. e3.4 ± 65.6 mgA/L; p 0.20). There was no significant change in the serum galactomannan (favourable vs. unfavourable: mean ± SD, e0.11 ± 2.8 vs. -0.62 ± 2; p 0.92) or FEV1 (favourable vs. unfavourable: mean ± SD, 24 ± 250 mL vs. e62 ± 154 mL; p 0.19) after 6 months of treatment. There was significant loss of weight (mean ± SD, e2.5 ± 4.5 kg) in subjects with unfavourable response. Conclusion: Serum 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.
Summary Background 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.ObjectiveWe 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.MethodsWe included 46 consecutive treatment‐naïve subjects with SA. The 81 controls were subjects of treated 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).ResultsUsing 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.ConclusionsA combination of serological tests has the best sensitivity in diagnosing SA. More studies are needed to confirm our findings.
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