Wanjun Wang, Mo Xian, Yongxia Lei, Juhua Yang, Lulu Wu
<p>To the Editor:</p><p>Allergic bronchopulmonary aspergillosis (ABPA) is an immunological pulmonary disorder caused by hypersensitivity to <i>Aspergillus</i>, which colonizes the airways of patients with asthma [<span>1</span>]. Previous studies have shown that fungal colonization in <i>Aspergillus</i>-allergic diseases could lead to more rapid airway obstruction [<span>2</span>], but they lack a direct link to clinical relevance and outcome. Therefore, we aimed to identify <i>Aspergillus fumigatus</i> colonization in ABPA patients and compare their profile without colonization.</p><p>We retrospectively analyzed the clinical data of 116 patients at the Department of Allergy and Clinical Immunology, the First Affiliated Hospital of Guangzhou Medical University, from January 2014 to October 2020, of which 96 cases were diagnosed with ABPA according to the criteria described previously [<span>3</span>]. Twenty patients with the diagnosis of refractory asthma, according to the Global Institute for Asthma (GINA), were enrolled as controls. The definition of ABPA exacerbation was worsening of clinical status, obstructive deterioration of lung function, rising total IgE levels by > 50%, and the appearance of new shallow infiltrates on radiology. All patients underwent a trans-bronchoscopy and bronchial mucosa biopsy. We utilized metagenomic next-generation sequencing for the detection of the <i>A. fumigatus</i> genome from the samples. Details about the methods are in Appendix S1.</p><p>Our study showed that the basic demographic features were similar in subjects with or without tissue colonization, except for the expectoration of mucus plugs. Eosinophil counts; blood <i>A. fumigatus</i>-sIgE, IgG, and total IgE levels; and the rate of <i>Pseudomonas aeruginosa</i> colonization were all higher in ABPA than in severe asthma. In subjects with colonization, an average of 690 ± 530 bp <i>A. fumigatus</i> nucleotide reads were detected, but only 3.9% had a positive sputum culture. The FEV<sub>1</sub>, FVC, and FEV<sub>1</sub>/FVC values were significantly lower in subjects with colonization. Higher bronchiectasis CT values (59.5 ± 7.1 vs. 34 ± 8, <i>p</i> < 0.05) and more numbers of involved lobes and segments were observed in subjects with colonization (4.8 ± 0.6 vs. 3.3 ± 1.2 and 16.2 ± 4.6 vs. 9.6 ± 4.9, both <i>p</i> < 0.05). The presence of HAM was seen in 76.4% of subjects with colonization. The duration of follow-up among the three groups was nearly identical. The ABPA subjects received a higher dosage of ICS and a longer period of oral corticosteroids. More than half of the subjects with colonization (54.9%) were treated with itraconazole. A significantly larger proportion, 24/51 (47.1% vs. 24.4%), of subjects with colonization experienced ABPA exacerbations (Table 1). Twenty-two of these 24 subjects experienced their first exacerbation after 12 months of the initial diagnosis (Appendix S2). The incidence rate of exacerbation was also signi
{"title":"Allergic Bronchopulmonary Aspergillosis (ABPA) With Colonized Aspergillus fumigatus Detected by Metagenomic Next-Generation Sequencing on Tissue Samples: A Distinct Subset of ABPA With a Higher Risk of Exacerbation","authors":"Wanjun Wang, Mo Xian, Yongxia Lei, Juhua Yang, Lulu Wu","doi":"10.1111/crj.13794","DOIUrl":"10.1111/crj.13794","url":null,"abstract":"<p>To the Editor:</p><p>Allergic bronchopulmonary aspergillosis (ABPA) is an immunological pulmonary disorder caused by hypersensitivity to <i>Aspergillus</i>, which colonizes the airways of patients with asthma [<span>1</span>]. Previous studies have shown that fungal colonization in <i>Aspergillus</i>-allergic diseases could lead to more rapid airway obstruction [<span>2</span>], but they lack a direct link to clinical relevance and outcome. Therefore, we aimed to identify <i>Aspergillus fumigatus</i> colonization in ABPA patients and compare their profile without colonization.</p><p>We retrospectively analyzed the clinical data of 116 patients at the Department of Allergy and Clinical Immunology, the First Affiliated Hospital of Guangzhou Medical University, from January 2014 to October 2020, of which 96 cases were diagnosed with ABPA according to the criteria described previously [<span>3</span>]. Twenty patients with the diagnosis of refractory asthma, according to the Global Institute for Asthma (GINA), were enrolled as controls. The definition of ABPA exacerbation was worsening of clinical status, obstructive deterioration of lung function, rising total IgE levels by > 50%, and the appearance of new shallow infiltrates on radiology. All patients underwent a trans-bronchoscopy and bronchial mucosa biopsy. We utilized metagenomic next-generation sequencing for the detection of the <i>A. fumigatus</i> genome from the samples. Details about the methods are in Appendix S1.</p><p>Our study showed that the basic demographic features were similar in subjects with or without tissue colonization, except for the expectoration of mucus plugs. Eosinophil counts; blood <i>A. fumigatus</i>-sIgE, IgG, and total IgE levels; and the rate of <i>Pseudomonas aeruginosa</i> colonization were all higher in ABPA than in severe asthma. In subjects with colonization, an average of 690 ± 530 bp <i>A. fumigatus</i> nucleotide reads were detected, but only 3.9% had a positive sputum culture. The FEV<sub>1</sub>, FVC, and FEV<sub>1</sub>/FVC values were significantly lower in subjects with colonization. Higher bronchiectasis CT values (59.5 ± 7.1 vs. 34 ± 8, <i>p</i> < 0.05) and more numbers of involved lobes and segments were observed in subjects with colonization (4.8 ± 0.6 vs. 3.3 ± 1.2 and 16.2 ± 4.6 vs. 9.6 ± 4.9, both <i>p</i> < 0.05). The presence of HAM was seen in 76.4% of subjects with colonization. The duration of follow-up among the three groups was nearly identical. The ABPA subjects received a higher dosage of ICS and a longer period of oral corticosteroids. More than half of the subjects with colonization (54.9%) were treated with itraconazole. A significantly larger proportion, 24/51 (47.1% vs. 24.4%), of subjects with colonization experienced ABPA exacerbations (Table 1). Twenty-two of these 24 subjects experienced their first exacerbation after 12 months of the initial diagnosis (Appendix S2). The incidence rate of exacerbation was also signi","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 6","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13794","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pulmonary heart disease (PHD) involves altered structure and function of the right ventricle caused by an abnormal respiratory system that causes pulmonary hypertension. However, the association between changes in plasma proteomics and PHD remains unclear. Hence, we aimed to identify causal associations between genetically predicted plasma protein levels and PHD. Mendelian randomization was performed to test the target proteins associated with PHD. Summary statistics for the human plasma proteome and pulmonary heart disease were acquired from the UK Biobank (6038 cases and 426 977 controls) and the FinnGen study (6753 cases and 302 401 controls). Publicly available pQTLs datasets for human plasma proteins were obtained from a largescale genome-wide association study in the INTERVAL study. The results were validated using a case–control cohort. We first enrolled 3622 plasma proteins with conditionally independent genetic variants; three proteins (histo-blood group ABO system transferase, activating signal cointegration 1 complex subunit 1, and calcium/calmodulin-dependent protein kinase I [CAMK1]) were significantly associated with the risk of pulmonary heart disease in the UK Biobank cohort. Only CAMK1 was successfully replicated (odds ratio: 1.1056, 95% confidence interval: 1.019–1.095, p = 0.0029) in the FinnGen population. In addition, the level of CAMK1 in 40 patients with PHD was significantly higher (p = 0.023) than that in the control group. This work proposes that CAMK1 is associated with PHD, underscoring the importance of the calcium signaling pathway in the pathophysiology to improve therapies for PHD.
{"title":"Association between plasma proteome and pulmonary heart disease: A two-stage Mendelian randomization analysis","authors":"Shiyang Li, Haifeng Ding, Qi Li, Xiaobin Zeng, Yanyu Zhang, Chengyi Lai, Xiaoshuang Xie, Yongjiang Tang, Jianjun Lan","doi":"10.1111/crj.13775","DOIUrl":"10.1111/crj.13775","url":null,"abstract":"<p>Pulmonary heart disease (PHD) involves altered structure and function of the right ventricle caused by an abnormal respiratory system that causes pulmonary hypertension. However, the association between changes in plasma proteomics and PHD remains unclear. Hence, we aimed to identify causal associations between genetically predicted plasma protein levels and PHD. Mendelian randomization was performed to test the target proteins associated with PHD. Summary statistics for the human plasma proteome and pulmonary heart disease were acquired from the UK Biobank (6038 cases and 426 977 controls) and the FinnGen study (6753 cases and 302 401 controls). Publicly available pQTLs datasets for human plasma proteins were obtained from a largescale genome-wide association study in the INTERVAL study. The results were validated using a case–control cohort. We first enrolled 3622 plasma proteins with conditionally independent genetic variants; three proteins (histo-blood group ABO system transferase, activating signal cointegration 1 complex subunit 1, and calcium/calmodulin-dependent protein kinase I [CAMK1]) were significantly associated with the risk of pulmonary heart disease in the UK Biobank cohort. Only CAMK1 was successfully replicated (odds ratio: 1.1056, 95% confidence interval: 1.019–1.095, <i>p</i> = 0.0029) in the FinnGen population. In addition, the level of CAMK1 in 40 patients with PHD was significantly higher (<i>p</i> = 0.023) than that in the control group. This work proposes that CAMK1 is associated with PHD, underscoring the importance of the calcium signaling pathway in the pathophysiology to improve therapies for PHD.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 6","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13775","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}