Long-Term Effectiveness of Benralizumab in Eosinophilic Granulomatosis With Polyangiitis.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystemic disease characterized by eosinophilic tissue inflammation. Benralizumab, an anti-IL-5 receptor (anti-IL-5R) monoclonal antibody, induces rapid depletion of eosinophils; its longer-term effect in EGPA is unknown. OBJECTIVE: To assess the real-world effectiveness and clinical remission rates of anti-IL-5R therapy in EGPA. METHODS: We performed a retrospective cohort analysis of patients with EGPA, who commenced treatment with benralizumab. Clinical remission, assessed at 1 year and 2 years after the initiation of benralizumab, was defined as an absence of active vasculitis (Birmingham Vasculitis Activity Score of 0) and an oral corticosteroid (OCS) dose of ≤4 mg/d of prednisolone. "Super-responders" were defined as patients in remission and free of any significant relapses (asthma or extrapulmonary) over the preceding 12 months. The corticosteroid-sparing capacity of benralizumab, patient-reported outcome measures, and characteristics associated with clinical remission and super-responder status were also analyzed. RESULTS: A total of 70 patients completed at least 1 year of treatment with benralizumab, of whom 53 completed 2 years. Of 70 patients, 47 (67.1%) met the definition for clinical remission at 1 year, with a similar proportion in remission at 2 years. Excluding asthma-related relapses, 61 of 70 (87.1%) patients were relapse free at 1 year, and of the 53 who completed 2 years, 45 (84.9%) were relapse free. A total of 67.9% of patients no longer needed any OCS for disease control. No significant difference was seen between antineutrophilic cytoplasmic antibody (ANCA)-positive and ANCA-negative subgroups. CONCLUSIONS: In this real-world setting of patients with EGPA, treatment with benralizumab was well tolerated and resulted in corticosteroid-free clinical remission for the majority of patients.

Ultrasound-Derived Diaphragm Contractile Reserve as a Marker of Clinical Status in Patients With Cystic Fibrosis.

Introduction: In patients with cystic fibrosis (CF), the monitoring of respiratory muscle activity using electromyography can provide information on the demand-to-capacity ratio of the respiratory system and act as a clinical marker of disease activity, but this technique is not adapted to routine clinical care. Ultrasonography of the diaphragm could provide an alternative, simpler and more widely available alternative allowing the real-time assessment of the diaphragm contractile reserve (DCR), but its relationship with recognized markers of disease severity and clinical outcomes are currently unknown. Methods: Stable patients with CF were prospectively recruited. Diaphragm ultrasound was performed and compared to forced expiratory volume in 1 s (FEV1), residual volume (RV), handgrip strength, fat-free mass index (FFMI), serum vitamin levels, dyspnea levels and rate of acute exacerbation (AE). Diaphragm activity was reported as DCR (the ratio of tidal-to-maximal thickening fractions, representing the remaining diaphragm contractility available after tidal inspiration) and TFmax (representing maximal diaphragm contractile strength). Inter-observer reliability of the measurement of DCR was evaluated using intra-class correlation analysis. Results: 110 patients were included [61 males, median (interquartile range), age 31 (27-38) years, FEV1 66 (46-82)% predicted]. DCR was significantly correlated to FEV1 (rho = 0.46, p < 0.001), RV (rho = -0.46, p < 0.001), FFMI (rho = 0.41, p < 0.001), and handgrip strength (rho = 0.22, p = 0.02), but TFmax was not. In a multiple linear regression analysis, both RV and FFMI were independent predictors of DCR. DCR, but not TFmax, was statistically lower in patients with > 2 exacerbations/year (56 ± 25 vs. 71 ± 17%, p = 0.001) and significantly lower with higher dyspnea levels. A ROC analysis showed that DCR performed better than FEV1 (mean difference in AUROC 0.09, p = 0.04), RV (mean difference in AUROC 0.11, p = 0.03), and TFmax at identifying patients with an mMRC score > 2. Inter-observer reliability of DCR was high (ICC = 0.89, 95% CI 0.84-0.92, p < 0.001). Conclusion: In patients with CF, DCR is a reliable and non-invasive marker of disease severity that is related to respiratory and extra-pulmonary manifestations of the disease and to clinical outcomes. Future studies investigating the use of DCR as a longitudinal marker of disease progression, response to interventions or target for therapy would further validate its translation into clinical practice.

Derivation and Validation of a Diagnostic Prediction Tool for Interstitial Lung Disease.

BACKGROUND: Interstitial lung disease (ILD) results in high morbidity and health-care utilization. Diagnostic delays remain common and often occur in nonpulmonology settings. Screening for ILD in these settings has the potential to reduce diagnostic delays and improve patient outcomes. RESEARCH QUESTION: This study sought to determine whether a pulmonary function test (PFT)-derived diagnostic prediction tool (ILD-Screen) could accurately identify incident ILD cases in patients undergoing PFT in nonpulmonology settings. STUDY DESIGN AND METHODS: Clinical and physiologic PFT variables predictive of ILD were identified by using iterative multivariable logistic regression models. ILD status was determined by using a multi-reader approach. An ILD-Screen score was generated by using final regression model coefficients, with a score ≥ 8 considered positive. ILD-Screen test performance was validated in an independent external cohort and applied prospectively to PFTs over 1 year to identify incident ILD cases at our institution. RESULTS: Variables comprising the ILD-Screen were age, height, total lung capacity, FEV1, diffusion capacity, and PFT indication. The ILD-Screen showed consistent test performance across cohorts, with a sensitivity of 0.79 and a specificity of 0.83 when applied prospectively. A positive ILD-Screen strongly predicted ILD (OR, 18.6; 95% CI, 9.4-36.9) and outperformed common ILD clinical features, including cough, dyspnea, lung crackles, and restrictive lung physiology. Prospective ILD-Screen application resulted in a higher proportion of patients undergoing chest CT imaging compared with a historical control cohort (74% vs 56%, respectively; P = .003), with a significantly shorter median time to chest CT imaging (5.6 vs 21.1 months; P < .001). INTERPRETATION: The ILD-Screen showed good test performance in predicting ILD across diverse geographic settings and when applied prospectively. Systematic ILD-Screen application has the potential to reduce diagnostic delays and facilitate earlier intervention in patients with ILD.

Ultrasound Evaluation of the Quadriceps Muscle Contractile Index in Patients with Stable Chronic Obstructive Pulmonary Disease: Relationships with Clinical Symptoms, Disease Severity and Diaphragm Contractility.

Rationale: Chronic obstructive pulmonary disease (COPD) is associated with changes in the composition and function of peripheral and respiratory muscles, which can negatively impact quality of life. Ultrasonography can provide a non-invasive evaluation of the integrity of both peripheral muscles and diaphragm, but its use in patients with COPD is still being investigated. We aimed at evaluating the relationship between quadriceps size, using ultrasonography and symptoms, lung function and diaphragm contractility in a cohort of patients with COPD. Methods: COPD patients were prospectively recruited and ultrasonography of the dominant quadriceps and of the diaphragm was performed. Quadriceps size was evaluated using three measurements: 1) cross-sectional area of the rectus femoris (Qcsa), 2) thickness (Qthick) and 3) contractile index (Qci), defined as the ratio of quadriceps thickness/total anterior thigh thickness. Diaphragm contractility was evaluated using thickening fraction (TFdi). Clinical characteristics and number of moderate-to-severe exacerbations in the previous year were retrieved from medical files. Dyspnea (mMRC scale) and disease impact on health status (COPD Assessment Test (CAT)) were measured at inclusion. Fat-free mass index (FFMI) was assessed using bioelectrical impedance. Results: Forty patients were recruited (20 males, mean age and FEV1 66±6 years and 49±17%predicted, respectively). Mean Qcsa, Qthick and Qci were 336±145 mm2, 1.55±0.53 cm and 64±16%, respectively, and mean TFdi was 91±36%. Qci was significantly correlated with FFMI (rho=0.59, p=0.001), TFdi (rho=0.41, p=0.008), FEV1 (rho=0.43, p=0.001) but not with age (rho=0.18, p=0.28). Qci was significantly correlated to CAT score (rho=-0.47, p=0.002), even when controlled for FEV1, and was lower in patients with an mMRC score ≥2 (55±15 vs 70±14%, p=0.002). Qcsa and Qci were significantly lower in patients with frequent exacerbations. In a multiple linear regression analysis that included age, gender, FFMI, FEV1 and TFdi, only FFMI and TFdi were found to be significantly related to lower Qci values. Conclusion: In patients with COPD, ultrasound evaluation of the quadriceps contractile index is feasible and related to disease severity, clinical symptoms, exacerbation history and diaphragm contractility. As such, it may provide a novel tool for the evaluation of the severity and burden of the disease in this population. Further studies are required to better delineate its potential role as a prognostic marker in this population.