Lung disease in RA filled with 'bad players'
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A wide array of potential etiologies can cause lung disease in rheumatoid arthritis patients, according to a presenter at the 2021 Congress of Clinical Rheumatology-East.
“A lot of rheumatologists are interested in lung disease these days,” John J. Cush, MD, director of clinical rheumatology for Baylor Scott & White Research Institute and professor of medicine and rheumatology at Baylor University Medical Center at Dallas, said in his presentation.
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Compared with patients with RA who have no lung complications, those with lung involvement — specifically, RA-associated interstitial lung disease (ILD) — may have two or three times the mortality risk as their counterparts with no ILD. Other types of lung disease in RA addressed by Cush included various types of pneumonia, along with smoking and chronic obstructive pulmonary disorder (COPD).
Of the many types of RA-ILD, Cush highlighted two: a usual interstitial pneumonia-like pattern with bilateral subpleural reticulation with or without honeycombing, and an nonspecific interstitial pneumonia-like pattern with predominant ground-glass opacities. “The NSIP type has more fibrosis,” he said. “It is worse from the standpoint of prognosis.”
Men are at greater risk than women for RA-ILD, as are older patients and those with other types of lung disease or pulmonary outcomes ranging from asthma and COPD to smoking. High RA disease activity as assessed by DAS scores or C-reactive protein have also been shown to correlate with ILD. “These are all important factors in who will get this,” Cush said.
While the risk factors for RA-ILD have begun to take shape, treatment paradigms are a different story. “The real problem is we do not really have treatment for ILD,” Cush said. “The best we can do is halt progression.”
A number of therapies have been used to varying degrees of efficacy for this complication, according to Cush. These include nintedanib, pirfenidone, rituximab (Rituxan, Genentech), azathioprine and mycophenolate mofetil, among others. “Nothing is a clear-cut win,” he said. “Nothing is FDA-approved.”
In addition, Cush noted that steroids may actually exacerbate lung complications in these patients. “Prednisone is the best drug we have and it is the worst drug we have,” he said. “It is acutely wonderful and chronically dangerous.”
But in order to understand the etiology and the possible treatment approaches for RA-ILD, Cush believes it is necessary to understand the “origin story” of this complication.
“The lung is probably involved in RA early,” he said, noting cyclic citrullinated peptide (CCP)-positivity indicates an altered lung microbiome at the outset of the disease course. “The idea is that early on, even when people are asymptomatic, there is activity going on in the lung that is a forerunner to what might later become ILD and might later become RA.”
This relationship may also partially explain the complex association between RA and pneumonia. Cush noted that women, older individuals and those with underlying lung disease risk are at risk for this complication. “Steroids and immunosuppressive drug use are contributory factors,” he said.
Seropositive RA also puts patients at a two-fold risk for pneumonia, according to Cush.
There is a “comorbidity mix” that puts patients with RA at risk for community-acquired pneumonia (CAP), according to Cush. Age is one factor, along with prednisone use, existing lung disease, myocardial infarction or diabetes. “Serious infectious events are bad, bad news in RA patients,” he added. “Bacterial pneumonia is common in RA.”
Overall, pneumonia is the No. 1 cause of infectious death in this patient population.
Cush said that he was “surprised” to learn that COPD and RA are related. “COPD increases your risk of RA, but if you have RA, you have a higher risk of COPD,” he said, but acknowledged that understanding of this relationship is incomplete. “I think this is all inflammation-based.”
Cush stressed that smoking is a “bad player” in RA. Ever smoking raises the risk for RA, while those with RA who quit experience lower disease activity and fewer hospitalizations. He encouraged attendees to encourage their patients to quit.
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Cush JJ. Rheumatoid Arthritis & Lung Disease. Presented at: Congress of Clinical Rheumatology-East annual symposium; August 12-15, 2021 (hybrid meeting).
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