Outcomes of chronic lung disease that are of importance to physicians and researchers are not always the same as those for patients. No longer being able to hike, for example, can be a devastating outcome for patients who previously were very active. Declining forced vital capacity (FVC), on the other hand, matters significantly more to investigators.

Whether you are talking about pulmonary function test results or a patient’s ability to maintain a favorite activity, important drivers of decline include inflammation, fibrosis, and vascular disease. And each of these drivers can make variable and independent contributions to progression and outcomes in chronic lung disease. Some patients with scleroderma will develop prominent PH with little or no associated interstitial lung disease (ILD). Conversely, patients who develop progressive ILD may have little to no PH. In the former, addressing the vasculopathy is much more important than addressing the minimal ILD that may be observed.

There are a handful of short-term surrogates for long-term outcome. For instance, the requirement for lung transplant is often used as a surrogate. When a lung transplant is required, survival is not expected to exceed approximately 6 months without the transplant. Drivers of poor outcomes include declines in FVC and respiratory hospitalization, both of which have been strongly linked to mortality risk. Death and respiratory hospitalization are considered composite end points in some newer trials, while degree of change in FVC over time is considered the primary end point in most other trials. An FVC decline from baseline of 10% or greater is considered by many to be a strong predictor of future mortality, and this has been studied by Goh et al with respect to ILD associated with systemic sclerosis.

Comorbidities are also recognized drivers of outcomes, as is exemplified by lung cancer incidence and related mortality. In a recent study, patients with chronic obstructive pulmonary disease have greater incidence of developing lung cancer compared with those who had neither chronic obstructive pulmonary disease nor a history of smoking. In a similar vein, pulmonary fibrosis is associated with an elevated risk of thromboembolic disease, pulmonary embolus, and PH, all of which may also reduce survival. As more antifibrotics are approved, our ability to prolong survival should improve. Pulmonary fibrosis may be a bit like cancer in that very few cancers are treated with a single agent; most are treated with multiple drug regimens. Idiopathic pulmonary fibrosis and fibrosing ILD will likely become similar in that regard in the future.