A recent case series from the University of Pittsburgh Medical Center (UPMC) underscores how little is known about the overlap between asthma and rheumatoid arthritis (RA) — two chronic inflammatory diseases that may share immunologic pathways but remain poorly studied together.

Richard P. Ramonell, MD, assistant professor of medicine at the University of Pittsburgh School of Medicine and a pulmonary and critical care specialist at the Asthma Institute within the UPMC Comprehensive Lung Center, Pittsburgh, said the analysis arose from clinical observations that some patients with established asthma later developed RA.

Ramonell and colleagues conducted a retrospective chart review of patients seen by a single physician at the UPMC Comprehensive Lung Center between 2006 and 2023. The analysis included adults with confirmed asthma who were subsequently diagnosed with RA by a rheumatologist. Severe asthma was classified according to European Respiratory Society-American Thoracic Society criteria.

Nine patients met inclusion criteria including diagnostic criteria for asthma: characteristic symptoms and either a positive bronchodilator response or historical documentation of one in combination with a confirmed diagnosis of RA. Eight of the nine had severe asthma. The median age was 71 years; five developed asthma later in life (median age of onset, 28 years). The median age at RA onset was 60 years, and the median interval between the two diagnoses was 20 years. Two thirds of patients were never smokers, and the median BMI was 28.5.

Mixed Evidence in the Literature

Although asthma and RA are both immune-mediated disorders, research examining their coexistence has yielded conflicting results.

“The evidence base investigating the relationship between asthma and RA is somewhat sparse and often contradictory,” Ramonell told Medscape Medical News. “At present, the literature does not show strong, consistent relationships between these two conditions across all studies.”

For instance, a Minnesota population-based case-control study found that asthma was associated with a higher odds ratio of RA (odds ratio, 1.74; 95% CI, 1.05-2.9), Ramonell said. In contrast, a cross-sectional study using data from the Israeli Defense Force database found RA was more frequently diagnosed in individuals without asthma, he noted.

Heterogeneity among patient populations, differences in asthma phenotypes between individuals with mild-to-moderate and severe asthma, and confounding factors likely contribute to these inconsistencies, as does the fact that larger cohort studies largely feature individuals with milder asthma. This contrasts with the population reported by Ramonell, where nearly all patients had severe asthma. “More mechanistic work needs to be done to explore this relationship in much greater detail,” he added.

Exploring Shared Pathways

The UPMC researchers aimed to better understand how chronic airway inflammation might contribute to the development of autoimmunity.

“In our manuscript, we ascribe to the mucosal origin theory of RA,” Ramonell explained. “This theory generally states that chronic mucosal inflammation — such as airway inflammation — could induce loss of self-tolerance against citrullinated proteins. Through epitope spreading, these self-targeted adaptive immune responses could begin to target citrullinated proteins in joints.”

Although the study was not designed to assess whether RA affects asthma severity or treatment response, Ramonell emphasized the need for heightened clinical awareness. “We have a lower threshold to ask about joint symptoms, perform joint examinations, order RA serologic testing, and refer to rheumatology,” he said. “Communication between services remains paramount.”

Co-Management Care Model

To date, no formal guidelines or consensus recommendations exist for the management of patients with both asthma and RA. Ramonell said the goal of the case series was to call attention to these evidence gaps and encourage further investigation into shared mechanisms and management strategies.

He also advocated for a multidisciplinary approach to care. “Using a co-management model with aligned treatment goals — such as pursuing corticosteroid-sparing treatments for both diseases where possible — tends to result in better overall care for individuals with comorbid asthma and RA,” he said.

Ramonell declared receiving consulting fees from GSK and Regeneron.