Risk Factors for Acute Exacerbation in ANCA-ILD ID’d in New Study

More inflammation, poor lung function linked to worse symptoms

Teresa Carvalho, MS avatar

by Teresa Carvalho, MS |

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Poor lung function and high levels of inflammatory biomarkers in the bloodstream were found to be risk factors for acute exacerbation — an episode of sudden symptom worsening — in patients with antineutrophil cytoplasmic antibody (ANCA)-associated interstitial lung disease.

That’s according to a new study, “Acute exacerbation in antineutrophil cytoplasmic antibody-associated interstitial lung disease: Clinical features and risk factors,” published in the journal Respiratory Medicine.

Interstitial lung diseases, or ILDs, are a group of inflammatory disorders characterized by fibrosis, or scarring, in the lungs. Scar tissue makes the lungs stiffer and hampers their ability to transfer oxygen to the bloodstream.

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Idiopathic pulmonary fibrosis (IPF) is the most common form of ILD that has no clear cause. Acute exacerbations — potentially life-threatening episodes characterized by sudden symptom worsening, such as difficulty breathing — that occur over the course of the disease are the most common cause of death in IPF patients.

ILD can sometimes also affect patients with ANCA — a condition then known as ANCA-ILD. However, the incidence, clinical presentation, and risk factors for acute exacerbations in ANCA-ILD are not well known. Further, the main causes of death in these patients are still not fully understood.

Investigating acute exacerbations in ANCA-ILD

Now, a team of researchers in Japan conducted a retrospective study, analyzing these parameters in 54 ANCA-ILD patients relative to 304 people with IPF.

“The aim of this study was to investigate the incidence of AE [acute exacerbation] and the clinical manifestation of ANCAILD patients with AE and to clarify the risk factors for AE in ANCAILD patients,” the team wrote, adding that they “also investigated differences in post-AE prognoses and causes of death between ANCAILD and IPF patients.”

A total of 26 of the ANCA-ILD patients (48%) included in the study had been diagnosed with ANCA-associated vasculitis (AAV) and were considered to have AAV-ILD. The remaining 28 (52%) did not fulfill the criteria for vasculitis, or blood vessel inflammation.

The study showed that acute exacerbations occurred in 14 ANCA-ILD patients (25.9%), and were seen in 84 people (27.6%) with IPF.

The ANCA-ILD patients had a median age of 74.5 when they started experiencing acute exacerbations.

The predicted forced vital capacity (FVC) — a lung function parameter that measures the total amount of air a person can exhale after taking a deep breath — and blood biomarkers were evaluated and compared between patients with and without exacerbations.

FVC values were found to be significantly lower in the ANCA-ILD patients with exacerbations than in those without. That suggests that a poorer lung function is a risk factor for these episodes of acute symptom worsening. Subsequent statistical analyses also confirmed that patients who had a poorer lung function were at an increased risk of experiencing exacerbations.

High blood levels of KL-6 and C-reactive protein — biomarkers of ILD and acute inflammation, respectively — also were considered potential risk factors, as they were elevated in ANCA-ILD patients who experienced exacerbations compared with those who did not. Specifically, high C-reactive protein levels were linked to a 2.2 times higher risk of exacerbations.

“These results suggest that ANCA-ILD patients with more advanced ILD are more susceptible to AE,” the researchers wrote.

The study also compared ANCA-ILD patients who survived acute exacerbations with those who did not. Of the 14 patients with ANCA-ILD who experienced exacerbations, only three recovered (survivors).

In the remaining 11 who did not recover (non-survivors), the number of patients with a smoking history was significantly higher than in the group of those who survived. Patients in the non-survivor group also had higher levels of C-reactive protein in the bloodstream than those in the survivor group.

All but one of the ANCA-ILD patients with exacerbations died during the study. Acute exacerbations were the most frequent cause of death in these patients, occurring in 55.5% of the cases, as compared with 44.4% in those with IPF.

As such, researchers stressed that “ANCA-ILD patients should be followed up with attention to [acute exacerbations] in the clinical course.”

High blood levels of C-reactive protein and lower FVC values also were found to be potentially poor prognostic factors in ANCA-ILD patients. Additionally, ANCA-ILD patients had lower median survival times after an acute exacerbation compared with IPF patients (35.5 vs. 60 days).

Overall, these results showed that “the overall survival of ANCA-ILD patients is better than that of IPF patients; however, the prognosis of ANCA-ILD patients after [acute exacerbation] is poor, as is that of IPF patients,” the researchers wrote.

Given that, screening for ANCA “should be considered at ILD onset and during the clinical course for all ILD patients,” they wrote.

Researchers also noted that further studies with a larger sample size will be needed to confirm these results, as only three people recovered from exacerbations.