The updated 2025 classification for interstitial pneumonia: Are we ready for the entity “idiopathic bronchiolocentric interstitial pneumonia?”

Be not the first by whom the new are tried, nor yet the last to lay the old aside. Alexander Pope. INTRODUCTION The 2025 update to the international multidisciplinary classification of the interstitial pneumonias (IPs), introduces ‘bronchiolocentric interstitial pneumonia’ (BIP) as a major pattern and proposes idiopathic BIP as a provisional diagnostic entity.[1] While the histopathological features of BIP, a discrete form of airway-centric IP in patients with no identifiable cause is well known for nearly 25 years,[2] several synonyms, including airway-centred interstitial fibrosis (ACIF), and peribronchiolar metaplasia (PBM)-interstitial lung diseases (ILDs), were subsequently applied to patterns of airway-centred IP indistinguishable from BIP, as defined in the 2025 classification. The reintroduction of BIP has been proposed to improve classification and potentially enhance diagnostic clarity by providing a morphology-based framework that incorporates radiologic and pathologic findings, similar to usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). This minimizes the tendency to overdiagnose hypersensitivity pneumonitis (HP) and supports for a more structured multidisciplinary approach.[3] While continued efforts to refine nomenclature and diagnostic frameworks in ILDs are important, we consider it necessary to articulate several substantive concerns regarding the reclassification of HP patterns under the umbrella of BIP as stated in the new updated classification.[1] The recent proliferation of classification schemes for IPs encompassing proposed multidimensional diagnostic frameworks and redefinition of established entities has highlighted an urgent need for clarity in how we define and diagnose HP. While the updated schemes aim to reflect evolving scientific understanding, these changes can sometimes complicate clinical decision making and introduce chaos rather than clarity in advancing the field. Introduction of the term bronchiolocentric interstitial pneumonia (BIP) In this context, the proposed replacement of ‘HP pattern’ with BIP, especially in conjunction with the designation of idiopathic BIP even if the histopathology features have definitive features of HP, calls for particularly careful review. Studies have consistently demonstrated that a substantial proportion of patients exhibiting HP like radiologic or histologic features are assigned alternative diagnoses, while others remain antigen negative despite comprehensive multidisciplinary assessments.[4-6] The new classification of primary BIP implicitly assumes that clinicians evaluating the patient with new onset Interstitial lung abnormality (ILA)/ILD have adequately excluded environmental exposures or potential inciting agents. In real world practice this remains inherently subjective and relies entirely on the quality of the exposure history elicited, supplemented by serological testing, and in selective cases bronchoprovocation studies. These tests that are often neither validated nor standardized, contribute to misdiagnosis, falsely eliminating the diagnosis of HP. We agree that distinguishing morphologic patterns from final multidisciplinary diagnoses is fundamental to ILD classification, as demonstrated by UIP and NSIP. Our concern, however, is not with this framework but with the premature designation of BIP as an idiopathic entity. We can take the example of the evolution of NSIP which highlighted the need for systematic, multidisciplinary assignment. Initially it was described as a pattern by Anna-Luise Katzenstein and Robert Fiorelli,[7] following which it underwent extensive multidisciplinary characterization, reflecting in the American Thoracic Society workshop in 2008 that defined its clinical features and natural history,[8] before its formal inclusion as idiopathic NSIP in 2013. Importantly, in the presence of similar uncertainties and heterogeneity, interstitial pneumonia with autoimmune features (IPAF) was deliberately not established as a clinical entity, but instead introduced as a research classification in 2015. Importantly, subsequent validation studies have been limited, and IPAF continues to be regarded primarily as a research construct rather than a fully validated clinical diagnosis.[9] In contrast, the 2025 classification introduces ‘idiopathic BIP’ largely by exclusion which is based on unidentified antigen exposure and absence of connective tissue disease thus, relying on subjective and currently unstandardized assessments. As acknowledged in the classification itself, key aspects of BIP, including disease behaviour and management, remain uncertain. We therefore believe that recognizing idiopathic BIP as a distinct entity is still premature and needs some more robust studies that include a structured, multidisciplinary effort, like that undertaken for NSIP that is needed before its routine adoption. Exposure identification-An unresolved diagnostic challenge in hypersensitivity pneumonitis Identifying the offending antigen and ensuring its avoidance are not secondary considerations but remain central components of the prognosis and therapeutic strategy in HP[4,5]. This concern is particularly relevant in regions characterised by high antigenic variability, where environmental exposures are subtle or easily underestimated. In HP, failure to identify a specific antigen or exposure is common, typically in the order of 30–50% in most series.[6] Data from the ILD-India registry highlights this issue from the Indian context. Here, HP emerged as the most frequently encountered diagnosis, accounting for almost half (47%) of the 1,084 patients with new onset ILD encountered.[10] However, objective confirmation of antigen sensitisation and detailed environmental testing were performed in only a small minority of cases. In fact, when the data was reanalysed by the same authors,[11] only 5.3% of patients could be labelled definite HP, with the authors conceding that in 21% of cases the diagnosis of HP had been made with a low level of confidence. In most cases the diagnosis was inferred only based on compatible radiology and clinical probability (exposure to pigeons, Molds, air conditioners, and air coolers). These are often ubiquitous and do not prove cause and effect. Importantly, when clinicians inquire about exposure to “birds” or other known antigens within the home, patients may deny such contact, while overlooking indirect yet significant exposures such as pigeon droppings on windowsills or in contaminated ventilation systems. In this setting, the accuracy of diagnosing HP and idiopathic BIP is challenged by the lack of standardised and validated questionnaires, validated laboratory tests for serology, inspection and testing by environmental hygienists and bronchial provocation testing.[12] While a pattern-based framework such as BIP may appear useful in settings with a high prevalence of hypersensitivity pneumonitis, frequent uncertainty in antigen identification, and overlap with airway-centred processes (including fungal-related disease). Real-world evidence suggests that these challenges arise not from a lack of structured frameworks, but from inherent difficulties in accurately identifying exposures, along with the multifactorial interactions between environmental factors and individual host responses. To address this critical gap, Singh and colleagues have recently published a structured and validated questionnaire, HP-SAQE (HP–Specific Assessment of Questionnaire for Exposure) through a detailed systematic review and Delphi consensus process. This rigorous methodology resulted in 14-point structured exposure assessment tool designed to systematically capture potential antigen exposures in patients with suspected HP.[13] The importance of such questionnaires can never be underestimated as it has been repeatedly shown that the absence of identifiable exposure has been associated with worse prognosis among patients with HP.[14] Also, in countries and regions with elevated levels of background air pollution, these environmental exposures may alter disease phenotype and undermine conventional clinicopathological frameworks, thereby complicating the distinction between HP and BIP.[15] The diagnostic and management problems for idiopathic BIP stems from several unknowns [Figure 1]Figure 1: Diagnostic Uncertainty of bronchiolocentric interstitial pneumonia and hypersensitivity pneumonitis with current knowledge and consequences. Left panel indicates diagnostic problems and right panel indicates its consequences. (UIP = Usual Interstitial Pneumonia; NSIP = Nonspecific interstitial pneumonia; SARD-ILD = Systemic Autoimmune Rheumatic disease-associated interstitial lung disease; ILD = Interstitial lung disease; HP = Hypersensitivity Pneumonitis; BIP = Bronchiolocentric Interstitial Pneumonia; MDD = Multidisciplinary Discussion; BAL = Bronchoalveolar Lavage)Several key uncertainties remain in idiopathic BIP, including its genotype–phenotype relationship, clinical demographics, imaging spectrum, bronchoalveolar lavage characteristics, and precise histopathologic criteria like BIP with granulomas. Furthermore, the natural history, disease behaviour, and optimal treatment strategy, including the role of corticosteroids, immunomodulatory therapy, and antifibrotic agents remain poorly defined. Future studies are needed to clarify these aspects and establish evidence-based management strategies. Figure 1, represents the diagnostic uncertainty of BIP and HP with current knowledge and consequences in detail. Cryptogenic hypersensitivity pneumonitis-better suited for diagnostic uncertainty In patients with established connective tissue disease (CTD) who demonstrate a HP pattern in the absence of identifiable antigen exposure, caution is warranted before attributing the findings to CTD-associated interstitial lung disease. Accurate classification depends largely on the clinician’s ability to obtain a comprehensive exposure history and, when appropriate, to undertake additional investigations aimed at identifying occult environmental sources. Such evaluations may include environmental assessment by trained hygienists and serologic testing for IgG antibodies directed against antigens known to cause HP. A significant limitation in routine clinical practice, however, is the lack of standardized and validated diagnostic tools capable of reliably identifying or excluding relevant exposures. Importantly, the presence of CTD does not preclude the development of HP, as patients may develop antigen-driven disease following exposure to common inciting agents such as avian proteins or environmental Molds. Consequently, a systematic evaluation for potential environmental triggers remains essential even in patients with underlying CTD.[16] We, therefore, need to acknowledge that at present the proposed term BIP remains, at best, a concept with several unknowns. Thus, we would argue that it is more appropriate to retain the previously suggested terminology ‘cryptogenic HP’ that more accurately reflects diagnostic uncertainty, whilst acknowledging the current limitations in exposure identification.[17,18] CONCLUSION In summary, we have many reservations about bringing up the term BIP as a major pattern and idiopathic BIP as an entity in the update to the 2013 classification of Idiopathic interstitial pneumonia (IIP) in the 2025 classification.[19] Idiopathic BIP is appropriate as a concept and in principle as a hypothesis generating. Several nuances need to be considered and worked through before the acceptance of BIP as a major pattern and labelling the diagnosis as idiopathic BIP when the cause is not identified. Future studies are warranted to investigate the several unknowns and diagnostic uncertainties and to develop standardized and validated questionnaires and diagnostic tools accepted by the broader chest community world-wide. A lot is known about HP, and clinicians are just beginning to gain confidence in applying the diagnostic criteria and algorithm provided in the recent HP guidelines.[4,5] While UIP and NSIP are both well-known entities that have evolved over a decade, the introduction of new terminology may risk premature cessation of the diagnostic assessment leading to diagnostic uncertainty being relabelled or falsely labelled rather than resolved, resulting in inaccurate diagnosis which ultimately leads to more confusion than clarity for the average clinician. The answer to this diagnostic uncertainty is not another reflex change in the terminology but a more careful search for environmental triggers. The existing HP framework, although imperfect, remains adequate for current clinical practice while ongoing evidence continues to evolve. Like the entity ‘Cryptogenic organizing pneumonia’ that has withstood longstanding clinical practice, and the term ‘cryptogenic HP’ will remind and alert the clinician and patient to keep searching for an occult source of triggers. Such triggers, when identified early and avoided, have the potential to cure non fibrotic HP and decrease the rate of progression of fibrotic HP. We therefore see no justification in the use of additional terminology as proposed in the new classification and would urge that the term Cryptogenic HP as recently refined in two HP guidelines not be abandoned. The older terminology retains value for research consistency, clinical communication, longitudinal patient assessment, and treatment strategies. Financial support and sponsorship Nil. Conflict of interest The authors have no conflicts of interest associated with this report to declare.