Small airway disease more common when AAV affects the lungs: Study

Treatment more effective for small lung disease with no other lung symptoms

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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About one-quarter of adults with ANCA-associated vasculitis (AAV) in which their lungs are affected have small airway disease (SAD), which targets the tiny airways in the lungs, according to a study in China.

Younger age, the presence of clumps of inflammatory cells called granulomas in the lungs, and other airway involvement were found to be significant predictors of SAD among AAV patients. In addition, standard AAV treatment regimens were more effective in patients with SAD alone than in those with other lung symptoms.

These findings highlight that “SAD is a unique manifestation of AAV-related lung involvement and exhibits distinct clinical features,” researchers wrote in the study “Clinical features and outcomes of small airway disease in ANCA-associated vasculitis,” which was published in the journal Respirology.

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AAV in the lungs can lead to shortness of breath, coughing up blood, chest pain

AAV is a group of autoimmune diseases marked by inflammation and damage to small blood vessels caused by self-reactive antibodies called antineutrophil cytoplasmic antibodies (ANCAs).

When the disease affects the lungs, the blood vessels that surround the tiny air sacs, called alveoli, responsible for the exchange of gases, are damaged. This leads to shortness of breath, coughing up blood, and chest pain.

A team of scientists at Peking University First Hospital, in China, previously used chest CT scans to describe the clinical features of AAV lung involvement. They found evidence of bleeding into the lungs, lung granulomas, and interstitial lung disease, a condition characterized by scarring of the tissue around the alveoli.

Unexpectedly, they discovered a subset of patients with SAD, a condition that affects the tiny airways — 2 millimeters or less in diameter — and leads to abnormal features on CT scan and poor performance on certain lung function tests.

Given that the frequency, clinical features, and outcomes of people with AAV-related SAD remain unknown, the team set out to fill this knowledge gap by looking back at 10 years of data from 359 AAV patients with lung involvement.

All patients (50.1% women; ages 58-72) were diagnosed at the researchers’ hospital. Most (83.6%) had microscopic polyangiitis (MPA), while the remaining 16.4% had granulomatosis with polyangiitis, the two most common types of AAV. Most patients (81.9%) also had ANCAs against myeloperoxidase, the type of self-reactive antibody typically associated with MPA.

Results showed more than one-third of patients (35.4%) had lower airway involvement — including the windpipe, the two large tubes that carry air from the windpipe to the lungs, and smaller airways — and 20.3% had upper airway involvement affecting the upper throat and voice box.

A total of 92 patients (25.6%) had SAD, 76.1% of whom had other lower airways affected and 23.9% had SAD alone. Among all 610 adult AAV patients assessed at the hospital over a 10-year period, with or without pulmonary involvement, the overall prevalence of SAD was 15.1%.

Those with SAD were more likely to be younger, female, and non-smokers, and have more ear-nose-throat involvement and more AAV activity at diagnosis, as assessed by Birmingham Vasculitis Activity Scores.

Also, bodywide AAV symptoms were significantly more common among SAD patients than among patients with no lung involvement.

A significantly higher proportion of SAD patients showed features of airway involvement on chest CT scans relative to those without SAD (46.7% vs. 3.4%), but were less affected by interstitial lung disease (14.1% vs. 70%).

The non-SAD [small airway disease] group had the worst prognosis with an approximately two-fold increase in mortality.

Obstructed breathing more common among patients with small airway disease

Of the 99 patients with lung involvement and lung function test data, 23 (23.2%) had obstructed breathing due to airway blockages, being significantly more common among patients with SAD than among those without (65% vs. 12.7%). “Indicators of small airway function also decreased significantly,” the researchers wrote.

Most AAV patients with lung involvement (74.4%) were initially treated with glucocorticoids and immunosuppressive agents as part of treatment to induce disease remission.

There were no significant differences in lung function tests and treatments between those with and without SAD, and between those with isolated SAD and those with SAD and other lower airway involvement.

Statistical analyses indicated younger age, lung granulomas, and airway involvement features on CT scans were independent predictors of SAD. No significant links were observed between ANCA or AAV types and SAD.

Data from 15 SAD patients who underwent lung function tests at diagnosis and at a median of one year after treatment showed significant improvements after remission. CT scans of 43 patients showed a reduction in SAD features in 16.3%, no change in 44.2%, and deterioration in 16.3%, mainly due to repeated lung infections.

During follow-up, 107 patients with lung involvement (29.8%) experienced a relapse, with the lungs being the most frequently affected in both SAD and non-SAD groups (61.9% and 54.2%). Relapses associated with the brain and spinal cord and digestive tract were significantly more common in the SAD group.

Nearly all infections affecting 209 (58.2%) patients during follow-up involved the lungs, with an equal proportion of SAD and non-SAD cases (95.5% and 94.3%). A lung infection caused by a type of fungi called Aspergillus was significantly more common among patients with SAD (14.3% vs. 4.5%).

“We … hypothesize that AAV-SAD patients are prone to Aspergillus colonization and develop secondary Aspergillus infection after immunosuppressive therapy,” the researchers wrote.

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Lower risk of infection found in group with small airway disease alone

While there was no difference in infection-free survival with and without SAD, the isolated SAD group had a significantly lower risk of infection compared with those with SAD plus other lower airway involvement.

A total of 65 patients died during follow-up, primarily due to infections and active AAV.

“The non-SAD group had the worst prognosis with an approximately two-fold increase in mortality,” the team wrote.

These findings demonstrate that “SAD is a unique manifestation of AAV and associated with higher disease activity which is more commonly seen in young, non-smoker, female patients,” the researchers wrote.

Since CT scans of airway infections can look similar to SAD, it is “vital to identify the imaging and clinical features of AAV patients with [small] airway involvements, especially SAD, to better balance antibiotics and immunosuppressors, which might be beneficial to long-term outcomes,” the researchers wrote.

In addition, “our results indicate that the clinical benefits of using standard induction remission regimens may be better in AAV patients with isolated SAD compared to those with other lung involvement,” the team concluded.