Lung function decline predicts death in fibrotic hypersensitivity pneumonitis

A marginal decrease in forced vital capacity (FVC) ≥5 percent and diffusion capacity of the lung for carbon monoxide (DLCO) ≥10 percent appears to raise the risk of mortality in patients with fibrotic hypersensitivity pneumonitis (fHP), suggests a study.

“In light of the very poor survival in a substantial subgroup of patients with fHP, there is a clear need to develop biomarkers of response to treatment (immunosuppressive) without having to wait for worsening,” the researchers said.

To determine the impact of short-term lung function changes in fHP on mortality, the researchers identified and recorded baseline demographics for 145 consecutive patients with a diagnosis of fHP, as well as baseline and 1-year follow-up of lung function, baseline echocardiographic findings, bronchoalveolar lavage (BAL) cellularity, and all-cause mortality.

In addition, the researchers calculated the changes in FVC ≥5 percent and ≥10 percent, as well as DLCO ≥10 percent and ≥15 percent at 1 year. They also assessed associations with mortality by conducting Cox proportional hazards analysis.

The following factors were associated with early mortality: baseline lung function severity, age, presence of honeycombing on computed tomography (CT), and echocardiographic pulmonary systolic pressure (PASP) ≥40 mm Hg. On the other hand, BAL lymphocytosis correlated with better survival. [Respirology 2022;27:202-208]

Univariable and multivariable analyses revealed that a decline in FVC ≥5 percent (hazard ratio [HR], 3.10, 95 percent confidence interval [CI], 2.00‒4.81; p<0.001), FVC ≥10 percent (HR, 3.11, 95 percent CI, 1.94‒4.99; p<0.001), DLCO ≥10 percent (HR, 2.80, 95 percent CI, 1.78‒4.42; p<0.001), and DLCO ≥15 percent (HR, 2.92, 95 percent CI, 1.18‒4.72; p<0.001) at 1 year were predictive of poorer survival after correcting for demographic variables, disease severity, honeycombing on CT and treatment, as well as BAL lymphocytosis and PASP ≥40 mm Hg on echocardiography, in separate models.

The median survival in patients with FVC decline of ≥10 percent within the first year was 26.0 months, which was lower than that in a study by Gimenez and colleagues (median survival 53 months). This could be associated with worse baseline severity in the present cohort. However, the absence of DLCO measurements in the Gimenez study did not allow direct comparisons. [Thorax 2018;4:391-392]

“Additionally, there were a greater proportion of patients without identifiable exposures in our cohort, a subgroup which is known to have a worse outcome,” the researchers said. “We did not however observe a difference in survival according to the history of exposure.” [Pulmonology 2019;2:97-108]

Immunosuppressive therapy

In the present study, most patients were treated with corticosteroids or immunosuppresants. Because of its retrospective nature, the researchers were not able to accurately assess response to treatment. However, they found many patients with stable lung function at 1 year on corticosteroids or immunosuppressive therapy; such finding correlated with significantly improved survival.

“Immunosuppression has been associated with stabilization of lung function in fHP, although corticosteroid treatment was not associated with a survival benefit in a cohort of fHP patients,” the researchers said. [ERJ Open Res 2017;3:00016-02017; Chest 2017;3:619-625; J Clin Med 2018;1:14]

“It is possible that anti-inflammatory/immunosuppressive treatment has an adverse effect on a proportion of fHP patients, including those with shorter telomeres, while having a positive impact on survival in those with normal telomere lengths, as suggested by Adegunsoye et al,” they added. [Eur Respir J 2021;3:2002872]

A prospective study is warranted to confirm this possibility, as telomere studies were not available in this cohort, according to the researchers.

“Early identification of fHP patients likely to have poor responses to immunosuppression is crucial, particularly now that antifibrotic treatments have been shown to reduce FVC decline in patients with a progressive fibrotic phenotype regardless of the interstitial lung disease entity,” they said. [N Engl J Med 2019;18:1718-1727; Lancet Respir Med 2021;5:476-486]