Half of adults with AAV have interstitial lung disease at diagnosis, study finds
Early signs of ILD linked to higher risk of death, 'should be investigated'
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At diagnosis, half of adults with ANCA-associated vasculitis (AAV) already have signs of interstitial lung disease (ILD), a condition marked by inflammation and progressive scarring of lung tissue, according to a new single-center study in Italy.
Evidence of lung disease was particularly prevalent among those with microscopic polyangiitis (MPA), a common type of AAV, and was associated with a higher risk of death, the study found.
“ILD should be investigated at diagnosis in all patients with AAV, since early detection might impact the prognosis of these patients,” the researchers wrote, noting that “respiratory symptoms (i.e. [shortness of breath], cough), though often subtle, were reported in all the patients.”
The study, “Prevalence and clinical outcomes of fibrotic interstitial lung disease in ANCA associated vasculitis: a single-centre, retrospective, cohort study,” was published in the journal Respiratory Research.
AAV is a group of rare autoimmune conditions marked by inflammation and damage to small blood vessels, most often in the lungs and kidneys. Most cases are associated with self-targeting antibodies known as ANCAs, which overactivate a type of immune cell called neutrophils, leading to an abnormal attack on small blood vessels.
Lung involvement in AAV may involve asthma-like breathing problems, small spots (nodules) in the lungs, or diffuse alveolar hemorrhage (DAH), a form of lung bleeding.
Most patients with ILD have fibrotic form, with scarring
ILD is also a common lung manifestation of AAV, affecting the connective tissue that supports the alveoli — tiny air sacs that facilitate gas exchange — and the surrounding small blood vessels. The disease can either be fibrotic, where it’s marked by permanent lung scarring, called fibrosis, or nonfibrotic, which is characterized by inflammation without significant scarring.
Despite the frequent findings of ILD among people with AAV, there are limited, inconsistent real-world data on how common the condition is for these patients. There’s also little information on what it looks like on imaging scans and the outcomes patients experience.
Now, a team led by researchers from the Università Degli Studi Di Milano in Milan sought to fill that knowledge gap. The scientists aimed to determine the prevalence of AAV-related ILD in adults treated at a university hospital in Northern Italy, and to evaluate their clinical features and long-term outcomes.
The team retrospectively analyzed data from 71 AAV patients with a mean age at diagnosis of 60.3 years. Slightly more than half of the individuals were women. MPA was the most common AAV type (42%), followed by granulomatosis with polyangiitis (GPA), affecting 31%, and eosinophilic granulomatosis with polyangiitis (EGPA), diagnosed for 24%.
All patients reported respiratory symptoms such as shortness of breath or cough, although these were often mild. ILD was present in half (51%) of the patients at diagnosis. Of these, nearly two-thirds (64%) had the fibrotic form of ILD.
Interstitial lunch disease found in nearly 70% with EGPA
ILD was significantly more common among those with MPA (67%) than those with EGPA (about 40%) or GPA (approximately 30%). This was especially true for fibrotic ILD, which was significantly more frequent in the MPA group (60%) compared with the EGPA (11.7%) and GPA (9%) groups. No significant differences in nonfibrotic ILD rates were found between groups by AAV type.
On CT scans, fibrotic patterns — usual interstitial pneumonia (UIP) and fibrotic non-specific interstitial pneumonia (NSIP) — were most common in the MPA group. In fact, 100% of UIP patterns and two-thirds of fibrotic NSIP patterns occurred in people with MPA.
Inflammatory (nonfibrotic) patterns were more common in EGPA patients (44%) and GPA patients (33%). Lung nodules were detected in 13% of scans, with half occurring in GPA patients. DAH occurred in 6% of patients, mainly in the GPA and MPA groups, with no cases among those with EGPA.
In addition, a positive ANCA test was significantly associated with ILD on CT scans. The researchers noted that perinuclear ANCAs (p-ANCAs) were seven times more common in patients with fibrotic ILD than in those with nonfibrotic lung disease (49% vs. 11%).
p-ANCAs, or those detected around the cell’s nucleus — where all genetic information is stored — typically target the myeloperoxidase protein, one of the two most common targets of ANCAs.
Among potential risk factors for ILD, there were no significant associations between ILD and smoking, other medical conditions (comorbidities), age, sex, and ANCA test results. While having MPA appeared to more than double the odds of developing ILD, the result didn’t reach statistical significance, meaning the finding could have occurred by chance.
The presence of interstitial lung disease resulted in a worse prognosis in patients with AAV.
Further statistical analyses showed that AAV patients with ILD had significantly worse survival than those without ILD, according to the researchers.
“This result highlighted how the presence of interstitial lung disease resulted in a worse prognosis in patients with AAV,” the team wrote.
Although death rates were higher among people with fibrotic ILD than those with nonfibrotic ILD, the difference was not statistically significant, the data showed.
Across AAV types with ILD, there was a trend toward worse survival in those with MPA. A direct comparison showed significantly worse survival in MPA patients than in EGPA patients. However, GPA versus EGPA and GPA versus MPA did not differ significantly with respect to survival.
“Our study confirms that ILD is a common and significant clinical manifestation in patients with AAV, particularly in the MPA subgroup,” the researchers concluded. “These data support the need to systematically include radiological assessment of the lung [tissue] in the initial diagnostic workup of each patient with AAV, for an early detection of cases at increased risk of progression.”
