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This epidemiological change requires updated understanding of IPA pathogenesis, clinical manifestations, and management. The rising incidence likely reflects improved diagnostic recognition and additional predisposing factors beyond absolute neutropenia. Even moderate innate or adaptive immune alterations may enable Aspergillus invasion. The review synthesizes advances in diagnosis and treatment, emphasizing early detection, tailored antifungal strategies by severity and comorbidity, and the use of voriconazole with therapeutic drug monitoring.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/invasive-pulmonary-aspergillosis-in-non-neutropenic-patients-an-evolving-clinical-paradigm/465055/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/invasive-pulmonary-aspergillosis-in-non-neutropenic-patients-an-evolving-clinical-paradigm/465055.png","ImageObject",300,407,{"name":92,"@type":93},"Miles","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is IPA increasingly reported in non-neutropenic patients?","Question",{"text":112,"@type":113},"IPA is increasingly documented due to improved diagnostic capabilities and a broader recognition of predisposing conditions. Even without absolute neutropenia, subtle immune alterations can enable Aspergillus invasion.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What does the review recommend regarding diagnosis and early treatment?",{"text":117,"@type":113},"Early diagnosis and prompt antifungal therapy are critical to improve outcomes. Management should integrate updated diagnostic understanding with timely treatment initiation.",{"name":119,"@type":110,"acceptedAnswer":120},"What antifungal options are highlighted for treatment?",{"text":121,"@type":113},"Voriconazole is discussed as first-line therapy with therapeutic drug monitoring to balance efficacy and toxicity. Isavuconazole is presented as an effective alternative, and liposomal amphotericin B is noted for severe or refractory cases, alongside supportive care.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},465055,1791214298,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},13056703019404,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Review  \nInvasive Pulmonary Aspergillosis in Non-Neutropenic Patients: An Evolving Clinical Paradigm  \nRocco Morena 1,2, Helen Linda Morrone 1, Francesca Serapide 1,2 and Alessandro Russo 1,2, *  \nAcademic Editor: Te-Chun Shen  \nReceived: 5 November 2025  \nRevised: 1 December 2025  \nAccepted: 15 December 2025  \nPublished: 22 December 2025  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 Department of Medical and Surgical Sciences,“Magna Graecia” University of Catanzaro,  \n88100 Catanzaro, Italy  \n2 Infectious and Tropical Diseases Unit,“Renato Dulbecco” Teaching Hospital of Catanzaro,  \n88100 Catanzaro, Italy  \n* Correspondence: [a.russo@unicz.it or alessandro.russo1982@gmail.com](a.russo@unicz.it or alessandro.russo1982@gmail.com)  \nAbstract  \nInvasive pulmonary aspergillosis (IPA), traditionally associated with severe immunosuppression and neutropenia, is increasingly reported among non-neutropenic patients. This epidemiological shift highlights the need for a revised understanding of IPA’s pathogenesis, clinical presentation, and management strategies. The rising incidence in these populations likely reflects improved diagnostic capabilities and recognition of additional predisposing factors. Although profound immunosuppression remains a key risk, even moderate alterations in innate or adaptive immunity can promote Aspergillus spp. invasion. This review summarizes current knowledge and recent advances in the diagnosis and treatment of IPA. Specifically, treatment strategies must be tailored to comorbidities, infection severity, and drug tolerance. Early diagnosis and prompt antifungal therapy are crucial for improving outcomes. Voriconazole remains the first-line treatment, though therapeutic drug monitoring is essential to ensure efficacy and minimize toxicity. Isavuconazole represents an effective alternative, offering comparable efficacy, improved safety, predictable pharmacokinetics, and convenient once-daily dosing. Liposomal amphotericin B serves as a valuable option in severe or refractory cases due to its broad-spectrum activity and reduced nephrotoxicity. Supportive measures—such as respiratory optimization, comorbidity management, and immunomodulatory therapies—are integral to care. Prognosis depends on infection extent, immune status, and timeliness of therapy. Emerging antifungal agents, including olorofim, ibrexafungerp, and fosmanogepix, show promise against resistant Aspergillus species, expanding treatment options. Overall, IPA management in nonneutropenic patients requires a multidisciplinary, patient-centered approach integrating established antifungals, supportive care, and novel therapeutic advances.  \nKeywords: invasive aspergillosis; neutropenic; invasive lung infections; IPA  \n1. Introduction  \nInvasive pulmonary aspergillosis (IPA), historically recognized as a hallmark opportunistic infection in severely immunocompromised individuals, particularly those with neutropenia, is increasingly documented in non-neutropenic patient populations [1,2] . This epidemiological shift necessitates a refined understanding of the pathogenesis, clinical manifestations, and diagnostic and therapeutic strategies pertinent to this evolving clinical paradigm. The heightened incidence of IPA in non-neutropenic patients may be attributed to several factors, including advancements in diagnostic modalities and an expanded  \nrecognition of predisposing conditions [3] . While severe immunosuppression remains a significant risk factor, perturbations in innate and adaptive immunity, even in the absence of absolute neutropenia, can facilitate Aspergillus spp. Invasion [4] . In this review we discussed all the aspects and state of the art of management of IPA.  \n2. Epidemiological and Pathophysiological Considerations  \nThe paradigm of IPA has undergone a significant trans","cbCaifHJTLa9qCQM","https://ap.wps.com/l/cbCaifHJTLa9qCQM","pdf",339700,17,"English","# Abstract\n# 1. Introduction\n# 2. Epidemiological and Pathophysiological Considerations\n## 2.1. Compromised Pulmonary Integrity","[{\"question\":\"Why is IPA increasingly reported in non-neutropenic patients?\",\"answer\":\"IPA is increasingly documented due to improved diagnostic capabilities and a broader recognition of predisposing conditions. Even without absolute neutropenia, subtle immune alterations can enable Aspergillus invasion.\"},{\"question\":\"What does the review recommend regarding diagnosis and early treatment?\",\"answer\":\"Early diagnosis and prompt antifungal therapy are critical to improve outcomes. Management should integrate updated diagnostic understanding with timely treatment initiation.\"},{\"question\":\"What antifungal options are highlighted for treatment?\",\"answer\":\"Voriconazole is discussed as first-line therapy with therapeutic drug monitoring to balance efficacy and toxicity. Isavuconazole is presented as an effective alternative, and liposomal amphotericin B is noted for severe or refractory cases, alongside supportive care.\"}]","Invasive Pulmonary Aspergillosis in Non-Neutropenic Patients: An Evolving Clinical Paradigm | PDF",1790769101,43]