Delay in time from the onset of symptoms to a diagnosis has been recognized as a risk factor for increased mortality in interstitial lung disease (ILD), acknowledged even prior to the first consensus statement for the classification of idiopathic interstitial pneumonias.1, 2 The prognostic implications of delayed diagnosis in idiopathic pulmonary fibrosis (IPF) have remained constant through subsequent iterations and refinement of the classification schema, derived from increasingly larger and more well-defined patient databases.3-6 Presenting symptoms in IPF are non-specific and do not correlate well with the onset of fibrosis. Advances in diagnostic imaging and genomics have opened the door to earlier detection of IPF, including pre-symptomatic and familial disease. Furthermore, the implementation of lung cancer screening in some regions has increased the identification of interstitial lung abnormalities, a risk factor for mortality and subsequent IPF.7 In parallel, antifibrotics have become the standard of care for retarding IPF progression, including demonstration that early intervention can ameliorate the establishment of extensive, irreversible disease.8 Yet in clinical practice, our potential to expediently detect and treat early IPF frequently remains stagnant, as highlighted in a recent publication in Respirology by Lancaster et al.9

Lancaster et al. present the clinical journey from diagnosis to treatment of 1249 IPF patients (predominantly males, mean age 67.8 years, 40%–68% ex-smokers), as reported by 244 physicians across France, Germany, Japan and the United States. Self-reported data from 739 patients are also included. Using prospective, quantitative, point-in-time surveys, the authors identify a mean time from first symptoms to seeking medical care of 6 months (range 0–60 months), first symptoms until diagnosis of 7 months (range 0–90 months) and diagnosis to treatment ranged from 0.3 to >1 year. As expected, antifibrotic use increased over the study period from 2016 to 2019. Notably, only 56% (range 36%–81%) of IPF patients with physician-perceived mild disease were receiving antifibrotic medication by study conclusion in 2019.

Cumulative time delays in diagnosis and treatment initiation in IPF have been similarly identified in prior studies.10 Substantial interest in candidate biomarkers, genomics, proteomics and artificial intelligence has been explored as early diagnostic modalities. However, amid the search for tools to identify early disease, the unmet need for adequate risk stratification and healthcare systems to allow the successful implementation and maintenance of treatment must not be neglected.

In the context of early IPF diagnosis, the assessment of disease severity by forced vital capacity (FVC) alone is problematic even if subsequent decline in FVC is often accepted as a de facto indication of disease progression. In the study by Lancaster et al., physician-perceived severity did not correspond with FVC-defined severity in approximately 50% of cases. In regions where publicly funded antifibrotic therapy is restricted above an arbitrary FVC limit (e.g., >80% predicted in England), the inability to support early, disease behaviour-modifying pharmacotherapy risks negating initiatives to detect early disease. Such regulatory restrictions specifically discriminate against patients with supranormal lung capacity at baseline due to pre-morbid fitness, physiologically large lung volumes or concomitant emphysema. At a time when the benefits of antifibrotic therapy for non-IPF, progressive-fibrosing ILD are increasingly recognized, the call to reshape how we stratify risk and stage disease severity in ILD grows increasingly louder.

However, regional differences in prescribing regulations alone cannot account for inequalities in access to antifibrotic treatment. Lancaster et al. propose that the large disparity in treatment rates in their mild-IPF cohort (36% in Japan vs. 81% in the United States) may be attributable to the higher rate of gastrointestinal side effects observed in prior Japanese cohorts.11 Indeed, if we are to recommend treatment of early disease, with consequently longer treatment durations and a greater proportion of treatment recipients with minimal or asymptomatic disease, a better understanding of long-term adherence in diverse, real-world populations is needed.

Finally, how does early diagnosis fit in with the goal of improving the quality of life of those affected by this devastating disease? Nearly half of IPF patients in Lancaster et al.'s study were misclassified or investigated for alternative diseases, and underwent seven to 10 investigations prior to diagnosis. Patient satisfaction was reduced across all disease severities. Early diagnosis may allow healthcare givers to engage with the patient and their family in a more focused manner earlier on, potentially reducing the sense of isolation and anxiety associated with a protracted diagnostic process. With more time to synchronize services, including referral to pulmonary rehabilitation, transplantation assessment and palliative care, the hope is that early diagnosis positively impacts the patient's experience in the context of receiving a life-changing diagnosis.

In summary, early IPF diagnosis and timely access to antifibrotic treatment have the potential to improve clinical outcomes. However, the recommendation for early diagnosis will remain an unfulfilled ambition without dedicated and harmonized efforts from healthcare systems, physicians and their associates to initiate, maintain and enhance treatment adherence in all individuals with IPF. Crucially, there must be a collective impetus to define the patient variables that predict a better antifibrotic treatment response.