Risk Factors for RA-Related Interstitial Lung Disease

Much is still not known about the connection between RA and ILD, but recent research has identified new risk factors.

• Male sex Although more women get RA than men, men have a higher risk of developing RA-ILD, according to the Arthritis Foundation. “We need more research to find out why this is so,” says Jeffrey A. Sparks, MD, a coauthor of the Rheumatology study mentioned above and an associate professor of medicine in the division of rheumatology, inflammation, and immunity at Brigham and Women’s Hospital and Harvard Medical School in Boston. “It could be genetic or that men tend to have a more aggressive severity of RA.”
• Long-term history of smoking In research published in May 2021 in the Journal of Rheumatology, the Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study (BRASS) found that smoking above a threshold of 30 pack-years (for example, one pack per day for 30 years or two packs per day for 15 years) was strongly associated with RA-ILD. Dr. Sparks was a member of this research team.
• Genetics A review published in June 2022 in the journal Biomedicines noted that “a link has been established” between RA-associated ILD and the mutation of the MUC5B gene. According to the review, other genetic variations have also been associated with the development of ILD in RA patients. Research is ongoing.
• Obesity The study published in the Journal of Rheumatology found that obesity was associated with an over twofold higher risk of future RA-ILD risk.
• Biomarkers Some biomarkers, including antibodies such as ACPA, cytokines and chemokines, and lung epithelial or surfactant markers, have been found to be associated with RA-ILD, according to the Biomedicines review.
• Age Older age is associated with higher risk of RA-ILD, notes a review of research in the December 2019 Journal of Clinical Medicine.
• Duration of RA Longer duration of RA is associated with higher risk of RA-ILD, but patients with early RA can still develop RA-ILD as well.
• Higher disease activity Patients with active joint disease were at increased risk for RA-ILD compared with those with inactive joint diseases, according to a study published in Arthritis Rheumatology in September 2019.

Signs and Symptoms of RA-ILD

RA-ILD may cause breathlessness and dry cough, but in many cases it causes no symptoms at all, making early detection difficult.

RELATED: Costochondritis and Rheumatoid Arthritis: What You Need to Know

Medication and Treatment for RA-ILD

The search for an effective treatment is ongoing, and management of the disease depends on whether the ILD is acute or chronic and whether there is evidence of inflammation or fibrosis (scarring or damage) in the lungs. According to research published in the Journal of Clinical Medicine in September 2021, in the case of chronic RA-ILD, “the arthritis of RA itself should first be stabilized without delay, and afterward, the activity of ILD itself can be stabilized, considering the safety of each antirheumatic drug for use in RA-ILD.”

Traditional DMARDs such as sulfasalazine and tacrolimus are “thought to provide some safety for the lungs” noted the researchers in the Journal of Clinical Medicine. Biologics such as abatacept (Orencia) and rituximab (Rituxan) may also be used. A JAK inhibitor, tocilizumab (Actemra), and a tumor necrosis factor inhibitor might be considered as well. A class of drugs called antifibrotics, which includes nintedanib, may be used in cases of fibrosis.

According to the Arthritis Foundation, depending on how advanced the ILD is, other treatment options may include corticosteroids and oxygen therapy. In some cases, a lung transplant may be necessary.

A Risk for Pulmonary Fibrosis

Inflammation, like the kind caused by RA-ILD, can lead to pulmonary fibrosis, or permanent scarring of the respiratory tissues. This can cause shortness of breath, since healthy air sacs are replaced by scar tissue that is not fully functional. Supplemental oxygen can help make breathing easier but will not reverse the damage done by pulmonary fibrosis.

Nodules May Form in the Throat, on Vocal Cords, and in Lungs

Rheumatoid arthritis can also cause nodules to form in the throat and on the vocal cords, causing complications like hoarseness, shortness of breath, and other changes. Nodules can develop in the lungs as well but usually don’t cause symptoms, notes the Mayo Clinic, and patients may never notice them.

RELATED: What Are Lung Nodules?

Risk for Other RA-Related Lung Complications

According to the abovementioned European Respiratory Review, people living with rheumatoid arthritis also face a risk of:

• Bronchiectasis, or damage to the airways
• Bronchiolitis obliterans, or inflammation in small bronchial tubes
• Pleural effusion, a buildup of fluid between the lung and chest wall
• Pleurisy or pleuritis, or inflammation of the lining of the lung and chest wall
• Pulmonary hypertension, high blood pressure in the heart and lungs

How to Prevent Lung Complications With RA

Don’t wait for experts to understand the “why” behind RA-related lung problems. Get your protective action plan in gear now with these eight tips:

1. Get Early Treatment for RA

“We are still working to understand the natural history of lung involvement in RA and how exactly medication may be involved. At this point, I would encourage early screening for lung involvement for patients with signs and symptoms,” says Sparks. “If you have RA and are experiencing shortness of breath, coughing, or other respiratory symptoms, talk to your doctor. These are potentially serious symptoms that warrant prompt attention.”

RELATED: Early Rheumatoid Arthritis Treatment: Why Is It So Important?

2. Don’t Smoke, and Avoid Secondhand Smoke

According to the Arthritis Foundation, people with RA who smoke are more apt to develop ILD. To get help with quitting, go to the SmokeFree.gov website.

RELATED: The Best and Worst Ways to Quit Smoking

3. Limit Exposure to Pesticides, Airborne Chemicals, and Air Pollution

There seems to be a tight connection between the lungs and joints in RA, so it's very important to eliminate inhalants, such as pesticides, airborne chemicals, and air pollution as much as possible. “Most of the research has focused on the detrimental effects of cigarette smoking on both the joints and lungs, but it makes sense that the others are likely unhealthy as well,” says Sparks.

4. Ask Your Doctor About Vaccines

Have you gotten a flu shot this year? Have you discussed the pneumonia vaccine with your doctor? Preventing infection is better than treating infection, since there may be damage to the lungs. Sparks explains: “The flu, pneumonia, and COVID-19 vaccines are effective, and all patients with RA are strongly advised to receive them, particularly if on immunosuppressive medication, which might make them more susceptible to infection. If infected, [lung disease] could become more severe,” notes Sparks, while the vaccines will make infections milder.

RELATED: The Facts on Flu Shot Side Effects and Risks

5. Get Your Body Moving!

Exercise for lung health in RA has not been extensively studied yet, but regular exercise provides health benefits for your whole system.

6. Be Aware of Possible RA Drug Risks and Side Effects

Some RA drugs are immunosuppressive and may cause infections in the lungs. “No one really knows for sure how treatment for RA affects the lungs, either positively or negatively. Patients are encouraged to talk with their provider to make sure that the medications are optimal for their joint symptoms and their lung health,” says Sparks.

7. Tell Your Doctor Right Away if You Have Shortness of Breath or Dry Cough

Persistent cough can be caused by any of the lung diseases and conditions mentioned above. If you let it go and it turns out to be due to infection, the infection will get worse.

8. Gather a Good Support System of Friends and Family

“A supportive environment is essential to encourage physical activity, smoking cessation, and helping to lead a full and fulfilling life,” says Sparks.

Additional reporting by Deborah Shapiro.