Interstitial pneumonia with autoimmune features (IPAF) has emerged as a distinct clinical entity, defined by the presence of interstitial lung disease (ILD) with autoimmune manifestations that do not fulfill the criteria for established autoimmune rheumatic disease (AIRD).¹ While IPAF is increasingly recognized in clinical practice, its natural history remains unpredictable, ranging from long‑term stability to rapid pulmonary decline.² This unpredictability complicates therapeutic decision‑making, especially in the absence of standardized treatment algorithms.³ Moreover, some IPAF patients progress to a defined autoimmune disease, underscoring the importance of long‑term multidisciplinary follow‑up, as lung involvement may be the first or only manifestation of the AIRD.⁴ There is no doubt that the introduction of IPAF offered a much‑needed label for previously unclassified patients, but it left unresolved the critical question of which individuals will progress and which will remain stable.

In this issue of Polish Archives of Internal Medicine, Miądlikowska et al⁵ do not fully answer this question but they nudge us to reconsider the IPAF progression criteria and the value of multimodal patient monitoring. In the single‑center prospective study, the authors explored predictors of IPAF progression using well‑established progression criteria, including INBUILD (Efficacy and Safety of Nintedanib in Patients With Progressive Fibrosing Interstitial Lung Disease) trial definition,⁶ progressive pulmonary fibrosis (PPF),⁷ and absolute forced vital capacity (FVC) decline by at least 10%. They found a substantial 1‑year IPAF progression ranging from 22% to 43%, depending on the applied criteria (22% of the patients had FVC decline ≥10%, 37% met the INBUILD criteria, and 43% met the PPF criteria). When compared with the AIRD‑ILD patients, significant differences were only observed for the PPF definition. Notably, the presence of usual interstitial pneumonia (UIP) and honeycombing on high‑resolution computed tomography (HRCT) as well as elevated baseline peripheral blood neutrophil counts emerged as independent predictors of the disease progression. Surprisingly, antinuclear antibody titers and bronchoalveolar lavage fluid (BALF) lymphocyte percentages were not associated with the disease trajectories. These findings carry a potentially important implication, as they underscore the possibility that the biology of the disease progression is not primarily immune‑driven but instead overlaps with fibrotic pathways similar to those reported in idiopathic pulmonary fibrosis. This does not diminish the relevance of immune features—indeed, they may guide treatment decisions and help to identify overlapping syndromes—but it suggests that fibrosis may determine the outcome. While the findings reported by Miądlikowska et al⁵ must be interpreted with caution—given the limited sample size, short follow‑up period of 12 months, and inter‑reader variability related to classification of HRCT patterns—they nevertheless provide a valuable framework for further discussions on clinical trajectories and predictive biomarkers of IPAF. Importantly, similar observations have been reported by others who noted that defining IPAF exclusively through an autoimmune “lens” fails to capture its granularity, and emphasized that the UIP pattern on imaging, comorbidities such as cardiovascular disease, cerebrovascular accident, diabetes mellitus, lymphoma, or chronic kidney disease, lower baseline lung function, and early decline in FVC carry strong prognostic value.^8-11 Collectively, all these findings underscore the heterogeneity of the disease and clearly show that not all patients fit well into the current classification criteria.

What are the next steps? Undoubtedly, the path forward requires well‑designed, multicenter, prospective studies with longer follow‑up periods and larger, more diverse patient cohorts to overcome the limitations of single‑center trials. Such studies should implement a multidimensional definition of progression, which does not rely solely on the FVC decline. Furthermore, integrating radiological patterns of fibrosis with blood and / or BALF biomarkers, and acknowledging the impact of systemic comorbidities may pave the way for the development of effective risk stratification strategies. These advancements will ultimately facilitate more informed treatment decisions and enable earlier interventions improving IPAF patient outcome. In the long‑term, these coordinated efforts may transform IPAF from a descriptive label into a clinically actionable entity, guiding individualized treatment strategies.