Nonwhite Patients More at Risk for Restrictive Lung Disease, Study Finds

Patients with scleroderma are more likely to develop restrictive lung disease (RLD) — a precursor to interstitial lung disease (ILD) — if they are nonwhite, according to a multicenter U.S. study.

The study, “Baseline characteristics of systemic sclerosis patients with restrictive lung disease in a multi-center US-based longitudinal registry,” was published in International Journal of Rheumatic Diseases.

ILD, characterized by inflammation and scarring in the lungs, is a major possible complication of scleroderma (also called systemic sclerosis, SSc). It occurs in about 40–60% of these patients and accounts for approximately 35–60% of their mortality.

Risk of ILD is greatest early in the course of scleroderma, and identifying the factors associated with lung disease may be important for the care and evaluation of these patients. Although ILD associated with scleroderma has been evaluated in international studies, they may not reflect the U.S. patient population.

To address this knowledge gap, researchers in the U.S. analyzed data from 357 patients with and without RLD who enrolled in the Collaborative National Quality and Efficacy Registry (CONQUER) multicenter registry of adults with scleroderma. Those included were enrolled from June 2018 through April 2020 at 13 expert centers.

Less than half, 45%, of the participants had RLD at baseline (study start). More patients with RLD were Black or African American (21.9%) and had diffuse cutaneous disease, a subtype of scleroderma with skin hardening throughout the body (70%).

Patients with RLD were significantly less likely to have anti-centromere antibodies — self-targeting antibodies associated with scleroderma — as compared with those without RLD, 7.5% versus 15.2%.

Additionally, those with RLD were significantly more likely to have pitting scars in the fingers, 28.8% versus 18.3%.

Lung function, as assessed by mean predicted forced vital capacity (FVC) — how much air a person can exhale forcibly after a deep breath — was worse in those with RLD compared with those without, 67% versus 97%. Also, patients with RLD had worse New York Heart Association functional class — a way of classifying heart failure.

Of the 122 patients with RLD who underwent a high-resolution CT scan of the chest, 35.2% had a larger esophagus, compared with 10.3% of the 117 patients without RLD who underwent HRCT.

The study also showed that 38.5% of the participants without RLD displayed ground glass opacities, a hazy, white-flecked pattern, and 23.9% of them had a reticular pattern, indicative of lung disease.

“Our findings do emphasize the need for careful review of HRCT scans and utilizing both HRCT and PFTs [pulmonary function tests] in the assessment of ILD in SSc subjects,” the scientists wrote.

They further said that these patients may have had other risk factors for ILD, such as diffuse skin disease and being African American, that impacted the decision to order a HRCT scan.

Physician assessments were worse in patients with RLD, with scores on the global assessment of 4.1 for those with RLD as compared to 2.9 in those without.

Measures of difficulty breathing, including the scleroderma health assessment questionnaire breathlessness scores, the modified Medical Research Council (mMRC) dyspnea scale, and the Functional Assessment of Chronic Illness Therapy, were all significantly worse in patients with RLD.

As for medication use, patients with RLD were more likely to be treated with CellCept (mycophenolate mofetil), an immunosuppressant medication, as compared with those without RLD — 63.1% versus 43.1%. Also, 67.5% of RLD patients were treated with proton pump inhibitors (which reduce the amount of stomach acid), as were 53.8% of those without RLD.

A statistical analysis found that those who were nonwhite, those who had higher physician health assessment scores, and those who had higher scores on the mMRC dyspnea scale were more likely to have RLD at baseline.

The researchers further evaluated participants with RLD who had evidence of ILD on their chest scans. A total of 43 patients had findings suggestive of more advanced ILD; 29 of them had diffuse SSc, 19 were positive for Scl-70 autoantibodies (also characteristic of scleroderma), and one had a positive anti-centromere antibody test.

Of the group with baseline HRCT scans, 40 did not have ILD, which the researchers suggest may indicate other causes for RLD.

Statistical testing indicated that having anti-RNA polymerase III autoantibodies — another marker for scleroderma — was associated with a lower likelihood of having ILD.

“In summary, we found that non-White race was independently associated with RLD. Additionally, 45% of subjects in CONQUER with early disease already had RLD, highlighting the importance of screening for ILD at the time of SSc diagnosis,” the investigators wrote. “Ultimately, we hope that data from the CONQUER SSc Registry will allow us to refine care for SSc patients and track patient outcomes that will enable more individualized care for patients with SSc.”