The term interstitial lung disease (ILD) includes an enormous amount of parenchymal pulmonary disorders (>200). The appropriate and strict categorization of the underlying process was always considered pivotal for the management, as well as the prediction of outcomes. The vast majority of the ILDs are categorized in some connective tissue disease associated ILD (such as Rheumatoid arthritis, Scleroderma, Sjogren’s). The most well studied and most devastating ILD is Idiopathic Pulmonary Fibrosis (IPF), with other well studied ILDs being chronic hypersensitivity pneumonitis (CHP), Non-specific Interstitial pneumonia (NSIP) and Sarcoidosis-ILD. When the accurate diagnosis cannot be pinpointed the patient may be “classified” as Unclassifiable. To highlight the unknowns around unclassifiable ILD and to allow further research into the condition, a research group established a new diagnostic entity termed interstitial pneumonia with autoimmune features (IPAF). All these different classifications has led to much clinical and translational research, but in fact, there are actually no advances in the pharmacological treatment of ILD patients, other than IPF, compared to 10 or 20 years ago, thus highlighting the major unmet need. ILD dominates the morbidity and mortality in all these individual categories and while in some cases the disease can be self-limited or controlled by immunosuppression and antigen removal in the case of CHP, in other cases the fibrosis can take its own course, become self-sustained, progressive and fatal. Until now, though these patients were not entitled to receive any additional therapy and the novel antifibrotics, Nintedanib and Pirfenidone, were only indicated for IPF. Nintedanib, after showing efficacy in the treatment of Scleroderma ILD , aimed to prove efficacy in patients suffering from progressive lung fibrosis, whichever the etiology. Patients were carefully phenotyped as progressive ILDs(PF-ILD), as assessed by documented FVC decline and CT abnormalities consistent with progressive fibrosis; >20% extent of fibrosis, UIP-like fibrotic pattern. In this innovative trial, Nintedanib proved effective in reducing the rate of progression, as assessed by the annual FVC decline, by 57%. The authors report an absolute difference of 107ml in the FVC decline at week 52 compared to placebo, benefits comparable to the IPF trials.
The two novel antifibrotics changed the landscape of IPF and may have a place in the treatment of other ILDs as well. Nintedanib conclusively proved effective in the treatment of PF-ILDs and Pirfenidone showed some encouraging results in Unclassifiable-ILD patients, which will need to be confirmed with further studies. Those two studies provide evidence for possible shared pathogenic pathways in different categories of ILDs and they have revolutionized our view of Lung Fibrosis. Currently, we are entering a new era of disease classification in ILDs that will probably emphasize on disease behavior rather than the initial insult. Suffice it to say, categorization of the diseases will always play a major role to understand the underlying disease-specific pathogenetic pathways and to prevent the formation of the disease in prone individuals.