Significant Emphysema Linked to Worse ILD Outcomes: Yet Khor, MD, PhD

Emphysema affecting at least 20% of the lung on CT imaging was associated with worse lung function trajectories and transplant-free survival.

A study published in CHEST examined combined pulmonary fibrosis and emphysema (CPFE) across a multicenter cohort of more than 1500 patients with idiopathic pulmonary fibrosis (IPF) and non-IPF fibrotic interstitial lung disease (ILD). The study found that aside from CT imaging, spirometry alone often failed to detect significant emphysema in these patients.

Yet H. Khor, the study’s lead author and a respiratory physician-researcher affiliated with Monash University, the University of Melbourne, and Austin Health in Australia, spoke with The American Journal of Managed Care^® (AJMC^®) about the findings and their clinical implications.

This transcript was lightly edited for clarity.

AJMC: What prompted you and your colleagues to examine CPFE across both IPF and non-IPF fibrotic ILD, rather than focusing primarily on IPF as previous research has done?

Khor: That’s a good question. I think, as you highlighted, most of the existing literature on CPFE focuses on IPF, where interest in this condition first started. But in clinics, we actually do see quite a few patients with non-IPF fibrotic ILD who have coexisting emphysema, and we don't really have a lot of information about this group of patients; we think CPFE is not unique to IPF.

That triggered interest in expanding the research and investigation into this group of patients, especially when we know that there are many different aspects. For instance, disease trajectories and prognostic outcomes vary between patients with IPF and non-IPF fibrotic ILD. Hopefully, this piece of research will add information for us to understand CPFE better.

AJMC: Your study found that emphysema affecting at least 20% of the lung on CT was consistently associated with differences in lung-function trajectories and worse transplant-free survival. What do you think this finding tells us about the clinical significance of coexisting emphysema in patients with fibrotic ILD?

Khor: When we look at the literature previously, there have been many different thresholds used to define CPFE, and there's always been some uncertainty about what the best threshold is to define significant emphysema in this situation. So, we decided to look at the various CT thresholds in this study, ranging from 5% to more than 20%. What we found, as you mentioned, is that the threshold of affecting 20% of the lungs or more is the most consistent one that's associated with significant health outcomes.

I think this finding shows, first, that it confirms emphysema is not just a bystander or another comorbidity that happens to occur in patients with fibrotic ILD. It does carry prognostic significance and identifies a group of patients who perhaps have worse outcomes compared with their peers, and also provides evidence for us to define a threshold for significant emphysema in the context of CPFE that's clinically meaningful.

When a patient has this extent of emphysema, 20% or more of the lungs affected, it does carry clinical significance for patients. I hope that, from a clinical perspective, this finding can help clinicians perhaps stratify patients to identify who may need closer monitoring because they are more likely to do worse.

AJMC: Your findings suggest that both physiologic and radiologic assessments are needed to identify coexisting emphysema. How might this more comprehensive assessment change risk stratification or disease management for individual patients?

Khor: I think it is always about the complementary nature between the radiology assessments and the physiology assessments. The radiology assessment provides a good visual assessment where we can directly judge how much of the lungs are affected by different diseases, emphysema vs fibrosis. But the limitation of radiology is that it doesn't provide the actual functionality of the organ. Even though spirometry has its limitations in terms of quantifying physiological changes in this situation, other physiological assessments, like diffusing lung capacity, are particularly important, especially since both emphysema and lung fibrosis can contribute to the measurements and let us know how much impairment the patient is suffering from the combination of both diseases.

There might be other potential physiological assessments we may consider as well. For instance, the 6-minute walk test, which can provide information about exercise capacity and oxygenation status, since this group of patients, again, is more susceptible to oxygen desaturation, which is another important factor to consider for intervention in this group of patients.

AJMC: One of the striking findings was that conventional measures of airflow obstruction had poor sensitivity for detecting emphysema on CT. What are the implications of this for how clinicians evaluate patients with fibrotic ILD who may also have emphysema?

Khor: It's an interesting situation, because the presence of lung fibrosis and emphysema exert opposing physiological impacts on the measurements. So the lung fibrosis increases the elastic recoil of the lungs, which masks the obstructive effects on the airways caused by emphysema. We see these changes, and I think this highlights to clinicians the inadequacy of relying on spirometry alone in this situation, which is typically the most common parameter we use in the clinic to track patients' trajectories in the care of patients with ILD.

This gives clinicians good information about when we identify a patient with CPFE or coexisting emphysema: the measurements that we get from spirometry are likely to be inaccurate and don't really reflect the disease state as well as they would if there were no emphysema. We might need to think about other parameters. For instance, this might be a group of patients where we may need to do more frequent CT scans of the chest that provide better visualization of the extent of emphysema vs the extent of fibrosis to judge disease progression.

AJMC: The study also has implications for clinical trial design, particularly because fixed forced expiratory volume in 1 second/forced vital capacity (FEV/FVC) criteria may not adequately identify patients with coexisting emphysema. How should future fibrotic ILD trials think about eligibility criteria for patients with COPD or emphysema?

Khor: Currently, most of the fibrotic ILD clinical trials use physiological criteria to define the presence of airway disease or emphysema, and our findings suggest that this approach is likely to miss a large proportion of patients who may have radiologically significant emphysema but normal lung function. But it is also potentially excluding a group of patients who may have apparent airflow obstruction based on the numbers but don't actually have significant emphysema on CT, especially with the fixed FEV1/FVC threshold of 0.7, which is actually less specific than the other parameter we evaluated—the lower limit of normal definition for airflow obstruction, which changes with age and has increased specificity. I think, more broadly, we also need to acknowledge that CPFE is not rare. It affects quite a substantial proportion of patients with fibrotic ILD.

Traditionally, we try to exclude this group of patients from clinical trials, but that, at the same time, also limits the generalizability of the findings, leaving evidence gaps on how to manage this relatively large number of patients with fibrotic ILD. I think, moving forward, in terms of trial design, instead of excluding this group of patients, now with better technology—quantitative CT scan assessments—we can better characterize the amount of emphysema that may be present in this group of patients. That allows us to stratify the trial design or prespecify subgroup analyses so that we can include this group of patients but also perform separate analyses on them to evaluate whether they behave differently in their treatment responses, which can better translate into clinical care.

Reference

McCrear S. CPFE: why spirometry alone misses emphysema in fibrotic ILD. AJMC. August 31, 2026. Accessed September 9, 2026. https://www.ajmc.com/view/cpfe-why-spirometry-alone-misses-emphysema-in-fibrotic-ild