recommended to note the availability of a SLB and the most likely differential diagnosis for patients with unclassifable ILD given the potential investigation and management implications of these features.

Diagnostic Scenarios

There are multiple scenarios that can lead to fbrotic ILD remaining unclassifable, most commonly including an incomplete evaluation or the presence of nonspecifc, overlapping, or seemingly contradictory fndings.

Common clinical scenarios leading to ILD remaining unclassifable include a potential exposure history that is not obviously related to a fbrotic ILD, or the presence of both an exposure history and presence of a CTD with radiological and pathological features that often fail to distinguish between these two possibilities [10, 11]. Similarly, the chest CT scan might show very mild, extensive, or nonspecifc abnormalities that fail to distinguish ILD subtypes, sometimes further confounded by heart failure, respiratory infections, or the effects of previous treatments that might alter typical morphology. In some situations, a high-quality HRCT might even not be available [14, 15].

One of the most frequent reasons for ILD remaining unclassifable is the lack of an adequate SLB, which can occur for several reasons. First, physicians might decide against performing a SLB in patients with increased risk for complications. This is particularly common in elderly or frail patients with signifcant comorbidities or severely impaired pulmonary function, where the potential risk of SLB should be balanced carefully against the expected beneft resulting from the pathological information. Second, some patients decline to undergo this invasive diagnostic procedure given similar concerns about complications of the procedure. Third, if SLB is performed it might be from a non-diagnostic region of the lung [16]. Finally, even when performed, a SLB can be nonspecifc or contradictory to other clinical-­ radiological data such that the ILD remains unclassifable.

ILD diagnosis is ideally based on integration of clinical, radiological, and pathological information in the setting of a multidisciplinary discussion with experts from each domain discussing the importance of all relevant data in a face-to-­ face meeting [17]. Despite this being the ideal approach, multidisciplinary discussion is not available in every centre, and when available there are still situations when members do not agree on a diagnosis because they interpret and weigh fndings differently or because the available information is contradictory [10, 11, 18].

Epidemiology

The prevalence and incidence of specifc ILDs is challenging to estimate: Epidemiological studies frequently base their analyses on International Classifcation of Diseases codes instead of current ILD classifcation [19–21]. Furthermore, most studies originate from ILD referral centres or in-­hospital populations, which introduces referral and selection bias with unrepresentative baseline populations. The most rigorous studies of IPF, the most common IIP subtype, suggest an incidence and prevalence of 9–18.7 and 20–41.8 per 100,000, respectively, depending on whether a narrow or broad defnition is applied [22]. Based on general ILD cohorts from large referral centres, the incidence and prevalence of unclassifable ILD is likely similar to or slightly less than that of IPF; [10, 11] however, there is substantial heterogeneity related to both the defnition of unclassifable ILD and other cohort characteristics. For example, some cohorts have almost no unclassifable cases, [23] while others report a proportion of unclassifable ILD cases up to 45% in a cohort of elderly patients with ILD [24]. On average, the prevalence of unclassifable ILD within specialized ILD centres is estimated at 12%, with a systematic review and meta-­analysis showing important heterogeneity between included studies, mainly in terms of study designs, defnitions, and diagnostic approaches [7]. The conduct of a multidisciplinary discussion is associated with a lower prevalence of unclassifable ILD within cohorts, [7] suggesting that this is partially effective in reducing the percentage of patients who cannot be provided with a confdent ILD diagnosis.

Clinical Presentation

With unclassifable ILD predominantly representing a mixture of patients with atypical presentations of fbrotic ILDs such as IPF, CTD-ILD, and fbrotic HP, it is unsurprising that the clinical manifestations are nonspecifc and re ect an average general ILD population [10]. For example, patients with unclassifable ILD are more frequently female than patients with IPF, and more frequently male compared to patients with CTD-ILD.

Previous cohort studies report a mean age at presentation between 58 and 75 years. Most studies report a balanced sex distribution, with 25% to 71% of patients being current or former smokers [7]. Patients with unclassifable ILD frequently present with dyspnoea, frst on exertion only and potentially at rest later in the course of disease. Dry or pro-