Clinical significance of high monocyte counts for the continuous treatment with nintedanib

Abstract Background Nintedanib is now widely used to treat interstitial lung disease (ILD). Adverse events, which occur in not a few patients, make it difficult to continue nintedanib treatment, but the risk factors for adverse events are not well understood. Methods In this retrospective cohort study, we enrolled 111 patients with ILDs treated with nintedanib and investigated the factors involved in starting dosage reduction, withdrawal, or discontinuation within 12 months, even with appropriate symptomatic treatment. We also examined the efficacy of nintedanib in reducing the frequency of acute exacerbations and the prevention of pulmonary function reduction. Results Patients with high monocyte counts (> 0.454 × 109/L) had a significantly higher frequency of treatment failure, such as dosage reduction, withdrawal, or discontinuation. High monocyte count was as significant a risk factor as body surface area (BSA). Regarding efficacy, there was no difference in the frequency of acute exacerbations or the amount of decline in pulmonary function within 12 months between the normal (300 mg) and reduced (200 mg) starting dosage groups. Conclusion Our study results indicate that patients with higher monocyte counts (> 0.454 × 109/L) should very careful about side effects with regard to nintedanib administration. Like BSA, a higher monocyte count is considered a risk factor for nintedanib treatment failure. There was no difference in FVC decline and frequency of acute exacerbations between the starting doseage of nintedanib, 300 mg and 200 mg. Considering the risk of withdrawal periods and discontinuation, a reduced starting dosage may be acceptable in the patients with higher monocyte counts or small body sizes

Anti-Ku antibody-positive desquamative interstitial pneumonia

A 66-year-old man, an ex-smoker, was referred to our hospital for slightly progressive respiratory symptoms of cough and dyspnea on exertion and chest abnormal shadow. Chest high-resolution computed tomography showed wide-ranging ground-glass attenuation and reticulation with lower lobe predominance. Bronchoalveolar lavage (BAL) fluid revealed a marked increase in lymphocytes (53.0%), and a surgical lung biopsy revealed a pattern of desquamative interstitial pneumonia (DIP) with hyperplasia of the lymphoid follicles. His serum was positive for anti-Ku and anti-SS-A antibodies, and he had signs (such as Raynaud's phenomenon, joint pain, and mechanic's hand) suspicious of connective tissue disease (CTD) although a definitive diagnosis of CTD had not been established. On the basis of the findings in our patient obtained from the serologic domain, BAL, and pathological examination, clinicians should consider the important correlation of DIP with CTD as well as with smoking. Keywords: Desquamative interstitial pneumonia, Anti-Ku antibody, Connective tissue diseas

Periostin Is a Biomarker of Rheumatoid Arthritis-Associated Interstitial Lung Disease

Periostin was investigated as a biomarker for rheumatoid arthritis-associated interstitial lung disease (RA-ILD). This prospective study measured serum monomeric and total periostin, Klebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), and lactate dehydrogenase (LDH) in 19 patients with RA-ILD, 20 RA without ILD, and 137 healthy controls (HC). All biomarkers were higher in RA-ILD than HC or RA without ILD. KL-6 accurately detected ILD in RA patients (area under curve [AUC] = 0.939) and moderately detected SP-D and monomeric and total periostin (AUC = 0.803, =0.767, =0.767, respectively). Monomeric and total periostin were negatively correlated with normal lung area and positively correlated with honeycombing, reticulation, fibrosis score, and the traction bronchiectasis grade but not inflammatory areas. Serum levels of SP-D, KL-6, and LDH did not correlate with the extent of those fibrotic areas on high-resolution CT. Serum monomeric and total periostin were higher in patients with RA-ILD with definite usual interstitial pneumonia pattern compared with other ILD patterns. Immunohistochemical analyses of biopsy or autopsy lung tissues from RA-ILD during the chronic phase and acute exacerbation showed that periostin was expressed in fibroblastic foci but not inflammatory or dense fibrosis lesions. Periostin is a potential biomarker for diagnosis, evaluating fibrosis, and deciding therapeutic strategies for patients with RA-ILD