Bronchiectasis is a common pulmonary feature among a subset of patients with antineutrophil cytoplasm antibody (ANCA)-associated vasculitis, French researchers reported.
The ANCA-associated vasculitides -- microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA) -- are a heterogeneous group of diseases characterized by necrotizing inflammation of the small blood vessels. In MPA and EGPA, the ANCAs primarily are directed against myeloperoxidase (MPO), while in GPA, the target is proteinase 3 (PR3).
Action Points
- Note that this small study found that patients with anti-PR3 ANCA vasculitis did not have bronchiectasis, while those with anti-MPO ANCA vasculitis frequently had bronchiectasis.
- While this hints at a potential pathophysiological mechanism, further studies will be needed to determine if anti-MPO antibodies are responsible for interstitial lung disease.
In the French study, which included 58 patients with MPA or GPA, the overall prevalence of bronchiectasis was 37.9%. Among the 39 patients in whom the ANCA target was MPO, 56.4% had evidence of bronchiectasis visible on CT scans and 10% were symptomatic. In contrast, none of the patients whose ANCA target was PR3 showed evidence of bronchiectasis, which is associated with enlargement of the airways, mucus production, and frequent lung infections, reported Antoine Néel, MD, PhD, and colleagues from Nantes University Hospital in .
In GPA, it is recognized that extra-vascular inflammation affects the respiratory tract, and typically develops before the clinical vasculitis. These granulomatous lesions are thought to be the site at which the autoimmune response is initiated. However, in MPA, it was long thought that the respiratory tract inflammation was exclusively vasculitic, with manifestations such as alveolar hemorrhage but without any prodromal extra-vasculitic pulmonary manifestations.
But some reports have suggested that lung involvement may be more widespread than previously appreciated in ANCA-associated vasculitis. In , 97% of patients with MPA showed pulmonary abnormalities on chest CT, including bronchiectasis in 32%.
However, among Asians, as in that study, ANCAs are overwhelmingly anti-MPO and MPA is seen more often than GPA. And although also suggested that bronchiectasis was common among MPO-targeted ANCA-associated vasculitis, the broader prevalence and clinical significance of bronchiectasis in these types of vasculitis is uncertain. It also is not clear whether the presence of bronchiectasis is associated with a distinct disease phenotype.
Therefore, to explore these questions, the researchers examined the records of all patients seen at their hospital from 2005 to 2015 who had either GPA or MPA and who had high-resolution CT of the chest.
Bronchiectasis was defined as a bronchus/artery ratio greater than 1.5, a lack of tapering in the bronchi, or the presence of bronchi within 1 cm of the pleural surface.
Among the 58 patients, 51.7% had MPA and 48.3% had GPA. Median age at the time of vasculitis diagnosis was 65.5 years. Disease features included renal manifestations in 55.2%, arthralgias in 50%, pulmonary involvement in 46.5%, weight loss in 44.8%, ear/nose/throat involvement in 43.1%, and peripheral neuropathy in 29.3%.
The researchers found that a distinct clinical picture was seen among patients with bronchiectasis. Those with bronchiectasis were older (75 versus 60 years, P=0.002) and more often were women (78% versus 39%, P=0.004). In addition, peripheral nervous system involvement was more common (54% versus 17%, P=0.019), whereas renal disease was less frequent (39% versus 63%, P=0.009).
On a multivariate analysis, factors that were independently associated with bronchiectasis included the presence of anti-MPO ANCA, female sex, and age at the time of vasculitis diagnosis. In addition, the association between bronchiectasis and a lack of renal involvement also was independent of age, sex, and type of ANCA.
With regard to outcomes, the researchers noted that the treatments were similar for patients with and without bronchiectasis, consisting of corticosteroids plus an immunosuppressant such as cyclophosphamide or azathioprine.
Similar results also were seen from patients with and without bronchiectasis on overall survival, progression-free survival, and relapse-free survival. This may be explained by the fact that most patients had received cyclophosphamide and therefore were given cotrimoxazole for Pneumocystis jirovecii prophylaxis, lowering their overall infection risk, the authors suggested. Five patients with MPO ANCA died, including three with bronchiectasis.
In discussing their findings, the researchers noted that respiratory involvement in patients with MPO ANCA has primarily included pulmonary infiltrates and diffuse alveolar hemorrhage, while in recent years interstitial lung disease has also been detected. The data in this analysis are similar to what was seen in the study from England, "and confirm that bronchiectasis is a frequent pre-existing respiratory condition in patients with anti-MPO ANCA-associated vasculitis."
Bronchiectasis is known to be more prevalent among women and to increase with age. In this study, therefore, the observation that bronchiectasis was not explained by female sex or age in the multivariate analysis "raises the question of whether airway abnormalities could contribute to the emergence of anti-MPO autoimmunity and ANCA-associated vasculitis, as is already suspected for anti-PR3 ANCA-associated vasculitis."
These observations were "interesting," commented Ulrich Specks, MD, chair of Pulmonary and Critical Care Medicine at the Mayo Clinic in Rochester, Minnesota, who was not involved in the study.
"While we occasionally see patients with bronchiectasis who are MPO-ANCA positive, and occasionally patients who have MPO-ANCA associated vasculitis and bronchiectasis, we do not see these associations at this reported high frequency. In addition, the clinical significance of this observation is also somewhat unclear as only 10% of the patients with bronchiectasis had symptoms," Specks told 榴莲视频.
Nonetheless, "the fact that this association only occurred with MPO-ANCA but not with PR3-ANCA certainly raises questions about potential pathogenesis," he said.
Mechanisms that might be involved in disease pathogenesis and the emergence of ANCA or ANCA-associated vasculitis in the airway include defects in the epithelial barrier and mucosal immunity as well as shifts in the respiratory tract microbiota, but further studies will be needed to explore these factors. "Alternatively, anti-MPO ANCA-induced neutrophil dysfunction could promote infection leading to bronchiectasis," the researchers explained.
Disclosures
The authors reported no conflicts of interest.
Primary Source
Seminars in Arthritis & Rheumatism
Néel A, et al "Bronchiectasis is highly prevalent in anti-MPO ANCA-associated vasculitis and is associated with a distinct disease presentation" Seminars Arthritis Rheum 2017; doi:10.1016/j.semarthrit.2017.12.002.