LAUSR

Diagnosing idiopathic pulmonary fibrosis (IPF) has evolved over the last 10 years as the diagnostic guidelines have been updated, diagnostic modalities have become refined and more accessible and, indeed, as anti-fibrotic medications have become more accessible globally. The current gold standard approach to diagnosis of IPF in patients clinically suspected of having the disease, as recommended in the 2018 American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association (ATS/ERS/JRS/ALAT) guidelines, involves identification of either a usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRCT) or a combination of HRCT and histopathology patterns in patients proceeding to surgical lung biopsy (SLB). The multidisciplinary discussion (MDD) plays a key role in identifying patients who should undergo biopsy and in reaching a consensus diagnosis. Patients with HRCT patterns of probable UIP, indeterminate for UIP or an alternate diagnosis are suggested to undergo SLB. In comparison, the earlier 2011 guidelines categorized patients into having radiology consistent with UIP, possible UIP or inconsistent with UIP. SLB was considered necessary in order to make a definitive diagnosis in patients without UIP on HRCT, including all patients with ‘possible UIP’. In practice, clinicians are often faced with the dilemma of a patient with a non-diagnostic CT who has a contraindication(s) to undergoing lung tissue sampling. How should these patients be managed? In a recent publication in Respirology, Sgalla et al. retrospectively compared the rates of mortality and disease progression in 249 IPF patients receiving anti-fibrotic treatment across three centres in Italy between two diagnostic subgroups: patients with definite UIP on HRCT or SLB and patients with possible UIP on HRCT and no SLB. The major finding of this study was that patients with possible UIP demonstrated similar mortality (log-rank test P = 0.771) and disease progression (log-rank test P = 0.139) as compared to patients with UIP on HRCT or SLB. These findings were confirmed on multivariate analysis. There was also no difference in survival rates or time to disease progression between the two diagnostic categories when stratified by GAP (gender, age and physiology) stage. This supports a pragmatic approach to the diagnosis of IPF where there is sufficient diagnostic confidence based on the incorporation of clinical and radiological data at MDD. Importantly, these findings are consistent with the current literature. Jo et al. reviewed the application of guidelines to 417 patients enrolled in the Australian IPF registry and found that the rate of decline in forced vital capacity (FVC) % predicted and overall survival was similar between patients with guideline-adherent IPF and those with an ‘inconsistent with IPF’ diagnosis. However, unlike Sgalla et al.’s study, the presence of honeycombing on HRCT was associated with increased mortality, translating to higher mortality in the definite IPF group. In a separate study, Raghu et al. published a post hoc analysis of pooled data from the INPULSIS trials demonstrating no difference in the adjusted annual rate of decline in FVC % predicted in patients with definite UIP compared with possible UIP. Similarly, Walsh et al. investigated the diagnostic likelihood at which clinicians prescribe anti-fibrotics without requesting SLB. There was no significant mortality difference between patients with a definite IPF diagnosis and patients with a provisional high confidence IPF diagnosis. What then is the role of SLB in the patient with an indeterminate HRCT? While the results of Sgalla et al.’s study do support the notion of a working IPF diagnosis prior to commencing anti-fibrotic therapy, even within their study, there was one centre in which no patient was treated without clear evidence of UIP on HRCT and/or SLB. This highlights the variability in practice globally with some centres now steering away from SLB or moving to transbronchial cryobiopsy as a less invasive but diagnostically equivalent alternative, with others, perhaps due to local prescribing regulations, maintaining a strict policy to biopsy in all uncertain cases. The results of Sgalla et al.’s study are reassuring for those patients in whom an SLB cannot be performed, indicating that the likely outcomes when receiving anti-fibrotic medications are similar to those patients with confirmed UIP. However, the role of lung biopsy is not yet obviated. While biopsy is perhaps less desirable in the setting of likely IPF as assessed at MDD, it remains a crucial diagnostic tool in the assessment of other fibrosing interstitial lung diseases. One major reason to perform a biopsy is to exclude alternative aetiologies, for example, fibrotic non-specific interstitial pneumonia or fibrosing organizing pneumonia, which exhibit different disease behaviour and treatment responsiveness to IPF. In addition, in patients with truly unclassifiable disease, which constitutes at least 7–10% of patients presented at interstitial lung disease (ILD) MDD, histopathology provides important diagnostic information and increases diagnostic confidence. But, who should be receiving anti-fibrotic therapy? This growing body of evidence suggests that we should consider prescribing anti-fibrotic treatment in all suitable patients with a clinical diagnosis of IPF if there is