Interstitial Lung Disease
Interstitial Lung Disease: Overcoming the Drivers of Poor Outcomes
Disease trajectories and outcomes in interstitial lung disease (ILD) are shaped by factors that include progressive fibrosis, comorbidities, and the development of pulmonary hypertension (PH) as a complication. There is hope that, with continued therapeutic advancements, an increasingly multimodal treatment approach will emerge for these patients.
“Although ILDs have distinct etiologies and prognoses, there seems to be a final common pathway involving PH where the disease trajectories become similar. This typically occurs late in the disease course when PH might be a more important driver of poor outcomes than the pulmonary fibrosis itself.”
Since ILD is a group of more than 150 conditions affecting the lungs, establishing an accurate diagnosis is an important focus of our efforts and a critical first step in regard to optimizing outcomes. In our own clinic, approximately 30% of ILD cases are idiopathic pulmonary fibrosis (IPF), perhaps 20% to 30% of our patients with ILD have connective tissue disease–related ILD (CTD-ILD), 10% to 15% have chronic hypersensitivity pneumonitis (CHP), approximately 5% have sarcoidosis, with other idiopathic interstitial pneumonias, occupational lung diseases, and ILD due to drug toxicities comprising the remainder. Drivers of prognoses in ILD depend on the type of lung disease; in fact, our counseling and treatment of patients are very different depending on the type of ILD they have. In addition to the type of ILD, other prognostic factors include certain demographic factors, the extent of the fibrosis, and the presence of comorbidities, both pulmonary and extrapulmonary. In particular, PH is a complication in ILD that is associated with worse outcomes.
IPF tends to be progressive, whereas in patients with CHP, you can potentially achieve disease stability if one can eliminate exposure to the offending antigen. CTD-ILD tends to have a more protracted course compared with IPF; however, ILD in rheumatoid arthritis tends to behave more like IPF than do the other CTD-ILDs. IPF is accompanied by a number of comorbidities that have a higher prevalence, even if you correct for age, exposures, and cigarette smoking. Pulmonary and extrapulmonary comorbidities are important factors, with examples of the former including lung cancer, emphysema, pulmonary embolism, and PH. Extrapulmonary comorbidities include entities such as obstructive sleep apnea, gastroesophageal reflux disease, coronary artery disease, and congestive heart failure, all of which may significantly affect outcomes.
Although these fibrotic lung diseases have different prognoses based on the etiology, patients with different ILDs appear to follow a similar trajectory once they reach a certain point in their disease course. When we look at PH-complicating ILDs such as CHP and nonspecific interstitial pneumonitis (NSIP), the prevalence of PH appears to be about the same as in IPF. Take NSIP, for example. Although NSIP has a significantly better prognosis than IPF, many patients with NSIP whose diffusing capacity for carbon monoxide (DLCO) is below 30% are likely to have developed PH, and the disease trajectory then becomes very similar to that of IPF. The same is true for patients with CHP. DLCO levels less than 30% may be considered as a physiologic biomarker for the presence of PH. Although ILDs have distinct etiologies and prognoses, there seems to be a final common pathway involving PH where the disease trajectories become similar. This typically occurs late in the disease course when PH might be a more important driver of poor outcomes than the pulmonary fibrosis itself.
Our goal with treatment is, of course, to modify these outcomes. As a result, ILD treatment will increasingly rely on multimodal therapy to overcome the drivers of poor outcomes. In addition to the antifibrotics, data are accumulating to support the use of therapies to treat or ameliorate PH, as well as to utilize immunosuppressive therapy for those ILDs that are accompanied by inflammation (eg, CTD-ILD). Supportive interventions such as pulmonary rehabilitation are also extremely important to maintain or improve exercise tolerance and quality of life in these patients.
ClinicalTrials.gov. A safety and efficacy study of pulsed inhaled nitric oxide in pulmonary hypertension associated with pulmonary fibrosis. Accessed June 25, 2020. https://clinicaltrials.gov/ct2/show/NCT03267108
ClinicalTrials.gov. Safety and efficacy of inhaled treprostinil in adult PH with ILD including CPFE. Accessed June 25, 2020. https://clinicaltrials.gov/ct2/show/NCT02630316
Cottin V, Schmidt A, Catella L, et al. Burden of idiopathic pulmonary fibrosis progression: a 5-year longitudinal follow-up study. PLoS One. 2017;12(1):e0166462. doi:10.1371/journal.pone.0166462
Hoffmann-Vold AM, Weigt SS, Saggar R, et al. Endotype-phenotyping may predict a treatment response in progressive fibrosing interstitial lung disease. EBioMedicine. 2019;50:379‐386. doi:10.1016/j.ebiom.2019.10.050
Nathan SD, Barbera JA, Gaine SP, et al. Pulmonary hypertension in chronic lung disease and hypoxia. Eur Respir J. 2019;53(1):1801914. doi:10.1183/13993003.01914-2018
Nathan SD. Hypersensitivity pneumonitis and pulmonary hypertension: how the breeze affects the squeeze. Eur Respir J. 2014;44(2):287‐288. doi:10.1183/09031936.00061214
Wong AW, Ryerson CJ, Guler SA. Progression of fibrosing interstitial lung disease. Respir Res. 2020;21(1):32. doi:10.1186/s12931-020-1296-3