Мировое сообщество врачей пересмотрело классификацию интерстициальных болезней легких

When the American Thoracic Society (ATS) and European Respiratory Society (ERS) last year came out with their joint statement on the classification of idiopathic interstitial pneumonias, it was the first update of the definitions of the subtypes of interstitial lung disease (ILD) in more than a decade and reflected how the thinking and management of the disease had evolved. The goal was to clearly define disease pathogenesis and biology, said Kerri Johannson, MD, associate professor at the Cumming School of Medicine at the University of Calgary in Calgary, Alberta, Canada, and a member of the statement writing committee. “The updated classification harmonizes the framework for how we think about the interstitial pneumonias/ILDs and broadened the classification to include not only ILDs of unknown cause, but those with presumptively identified cause or etiology,” Johannson said. The 2025 statement reshuffled the classification of ILD into two broad categories — interstitial disorders and alveolar filling disorders — merged secondary and idiopathic subtypes, accounted for disorders with combined patterns of different ILD subtypes, and added a definition for rare alveolar filling disorders. “The most important change is that we are moving away from thinking about ILD as a collection of isolated diagnostic boxes defined primarily by morphology,” said Ayodeji Adegunsoye, MD, MSc, PhD, scientific director of the interstitial lung disease program at the University of Chicago in Chicago and the second author on the 2025 statement. The statement “is trying to bring together” secondary and idiopathic etiologies, said Yet Khor, MBBS, PhD, associate professor at Monash University in Melbourne, Australia, and also a member of the ERS/ATS statement committee. “It comes under one umbrella and then puts together the patterns on radiology and histology alongside the causes because clinically both matter with how we manage patients.” Updated Major Subtypes The 2025 update divides interstitial disorders into six major secondary and primary interstitial disease patterns, each with distinguishing characteristics based on clinical findings, radiologic features, and pathologic findings. They include: Secondary usual interstitial pneumonia (UIP) and idiopathic pulmonary fibrosis (iPF). Chronic onset characterizes UIP, and it carries a high likelihood of progression and rapid worsening. Older males with a smoking history are at high risk, particularly for iPF. Radiologic findings include subpleural and usually lower lung predominance. Pathologically, patients have dense fibrosis, typically with fibroblast foci, and a predilection for subpleural and paraseptal parenchyma. Honeycomb change can also occur. Nonspecific interstitial pneumonia (NSIP). This subtype can also be chronic, but the risk for progression can vary. It can also worsen rapidly, especially if the patient also had organizing pneumonia. It’s more common in younger females with a background of connective tissue disease. Radiology would show a predominance in the lower lobe, often with subpleural sparing, along with ground-glass opacities, fine reticulation, and traction bronchiectasis without honeycombing. On pathology, cellular NSIP would demonstrate a cellular interstitial infiltrate of lymphocytes causing thickening of alveolar walls with no fibrosis or granulomas. Fibrotic NSIP would have diffuse thickening of alveolar walls by fibrosis with traction bronchiolectasis but not centered around the bronchi or with honeycombing or granulomas. Bronchiolocentric interstitial pneumonia (BIP). This newly added subtype manifests in two forms: nonfibrotic and fibrotic. Nonfibrotic BIP has an acute or subacute onset, frequently with respiratory or systemic symptoms. Fibrotic BIP is chronic, and while its risk for progression can vary, it can worsen rapidly, especially with ongoing exposure. It is linked to a history of exposure to hypersensitivity pneumonia-related antigens. Radiologic findings of nonfibrotic BIP show centrilobular ground-glass nodules, a mosaic pattern or lobular air trapping — or all three. Fibrotic BIP will demonstrate ground-glass, traction bronchiectasis, mosaic patterning, lobular air trapping, and a three-density sign around the airways and blood vessels. However, features of fibrotic BIP can overlap with nonfibrotic BIP. Pathologically, nonfibrotic BIP would be centered around the bronchi with or without nonnecrotizing granulomatous inflammation. Fibrotic intraocular pressure would have fibrosis around the bronchi, often with metaplasia but with or without inflammation. Diffuse alveolar damage (DAD). Previously called acute interstitial pneumonia, DAD was adopted “to reflect that this isn’t a unique diagnosis, but rather a manifestation of DAD/acute respiratory distress syndrome (ARDS) without a clearly identified cause,” Johannson said. DAD presents as acutely worsening with a high likelihood of residual fibrosis and the potential for ongoing regression. Risk factors vary with the underlying etiology, such as sepsis, aspiration, pneumonia, or connective tissue disease-ILD. On radiology, DAD can appear as patchy or diffuse ground-glass opacity that can progress to fibrosis, with significant traction bronchiectasis, architectural distortion, and honeycombing. Pathology depends on disease phase. Exudative disease demonstrates thickening of the alveolar septa. In the organizing phase, interstitial involvement emerges with loose organizing connective tissue and pneumocyte proliferation. In the fibrotic phase, DAD can progress to interstitial fibrosis with varying features. Pleuroparenchymal fibroelastosis (PPFE). Chronic and frequently linked to significant weight loss, PPFE will appear on imaging as biapical pleural thickening, dense subpleural confluent fibrosis, and traction bronchiectasis and may include platythorax, deep sternal notch, or tracheal deviation, or all three. It can often coexist with other patterns, particularly UIP. Pathologic findings will include pleural fibrosis in the upper zone with subpleural intra-alveolar fibroelastosis, and the fibrosis can extend into the underlying lung parenchyma. One third or more of cases can coexist with other patterns or findings characteristic of UIP, NSIP, BIP, granulomas, or mycobacterial or fungal infections. Lymphoid interstitial pneumonia. This subtype presents with what the statement described as “insidious onset” and progresses slowly. Risk factors are vague. Radiology will show predominant thin-walled lung cysts with reticulation in the mid-to-lower lobe, ground-glass opacity, and bronchovascular and perilymphatic interstitial thickening. On pathology, a dense and diffuse interstitial infiltrate of lymphocytes and plasma cells expands the alveolar septa. The infiltrate of the lymphocytes and plasma cells can be polyclonal. Alveolar Filling Disorders The statement also separated out four alveolar filling disorders. They are: Organizing pneumonia (OP). OP includes respiratory symptoms with acute or subacute onset that, on radiology, can appear as patchy consolidation with air bronchograms, patchy ground-glass opacities, focal nodules, and/or mass-like lesions. Pathology will reveal intra-alveolar buds of loose connective tissue, but interstitial inflammation can be mild in cryptogenic OP. Respiratory bronchiolitis (RB)-ILD. Mostly occurring in adult male smokers, RB-ILD has a subacute onset with potential for improvement with smoking cessation. On radiology, it will appear as centrilobular ground-glass nodules predominantly in the upper lobe. Pathology includes collections of lightly pigmented macrophages in airspaces. Lymphoid aggregates and fibrosis may also be present. Distribution of findings is centered around the small airways. Alveolar macrophage pneumonia (AMP). This is the new label for desquamative interstitial pneumonia. AMP is also mostly found in adult smokers, predominantly male, but rare cases have been reported in nonsmokers. Onset can be variable. Radiologic findings will show mid-to-lower lung predominance with variable upper lung involvement, patchy and confluent ground-glass opacities with smooth reticulation, and in some cases emphysema and traction bronchiectasis. Pathology findings are similar to RB-ILD, but with diffuse distribution. Rare alveolar disorders. Rare alveolar disorders, including acute and chronic types of eosinophilic pneumonia, cover eosinophilic pneumonia, pulmonary alveolar proteinosis, and lipoid pneumonia. A new “other” category has been added to encompass secondary and primary interstitial pneumonia with combined diagnostic patterns, and the “unclassifiable” category carries over from the previous statement. What Does It All Mean? “The morphology, the underlying patterns that the radiology and histology tell us, will give us information about whether the patient is going to respond to treatment, whether there’s going to be more inflammation or more fibrosis, and what is the prognostic implication for patients,” Khor said. “At the same time, if there are underlying causes, that’s also going to modify how we’re going to treat the patient.” In recent years, evidence has shown ILD is more heterogenous than previously thought, she added. “In the past we knew that under ILD there are many different subtypes and [thought that] within each subtype patients are going to behave relatively similarly in terms of their response to treatment and their outcomes,” Khor explained. “The past decade has proved us wrong in terms of that idea. Even within the [same] subtype there’s going to be heterogeneity within patients in terms of the disease behaviors and their response to treatment.” Differentiating Disease Patterns Distinguishing between fibrotic and nonfibrotic disease patterns matters, Adegunsoye said, “because treatment should follow the integrated diagnosis and disease behavior, not simply the CT pattern.” He noted iPF requires disease-modifying antifibrotic therapy, connective-tissue-disease ILD requires immunomodulation, and hypersensitivity pneumonitis (HP) needs exposure identification and remediation. Inflammatory vs fibrotic behavior can determine the need for additional therapy, he said. “And once a non-iPF fibrotic ILD demonstrates progressive pulmonary fibrosis, that progression itself has therapeutic implications.” BIP: A ‘Controversial’ Addition Johannson said the addition of BIP to the updated classification has been “controversial” because the statement introduced it as both a pattern on CT and histology and idiopathic BIP as a “provisional multidisciplinary diagnosis.” Idiopathic BIP is meant to be used in the context of a “BIP pattern” on CT or biopsy, but in the absence of any identified cause — making it similar to a “primary BIP” as opposed to a “secondary BIP” when an obvious cause has been found, Johannson said. In most scenarios, BIP would replace “HP without an identified exposure,” she said. “This has caused concern for a few reasons, including the fact that the field has understood HP for decades to mean a certain thing,” Johannson continued. In some cases, an exposure is not always found, but the CT and biopsy pattern are identical to HP with an exposure. “Then the diagnosis is still HP, but a cause may truly not exist, may have been remote or may have not been recognized by the clinician or patient,” Johannson said. The use of this new term could pose challenges for research, requiring either starting all research on BIP from scratch or a reclassification of existing data based on the new term, which could introduce “several forms of bias,” she said. “The biggest concern from the community appears to be that if people are ‘provisionally’ diagnosed with idiopathic BIP, then the search for a cause may be stopped and the patients may continue to be exposed to a harmful environmental stimulus that will accelerate disease progression,” Johannson said. Next Steps The next iteration of efforts to classify ILD will likely take into account how genetics and molecular biology drive differences in ILD subtypes as they have in lung cancers, Khor said. “It has come a long way in ILD that we have applied selected important molecular biology or genetics, such as telomere length [the length of protective DNA sequences at the end of chromosomes], but we still haven’t reached the state where it’s the mainstay that can be incorporated into classifications.” That will evolve over the next decade or so, Khor predicted. “The underlying molecular biology and genetics might be the reason why patients behave differently,” she said. “They’re going to tell us which patient will respond to which medication the best.” Adegunsoye reported having financial relationships with Boehringer Ingelheim, AbbVie, Avalyn, Baxter, Brainomix, Gossamer Bio, Insmed, Inogen, PureTech Health, and Roche. Khor reported having financial relationships with AbbVie, Boehringer Ingelheim, Chiesi, and Air Liquide Healthcare. Johannson is a consultant to Boehringer Ingelheim. Richard Mark Kirkner is a medical journalist based in the Philadelphia area.