Spirometry Reference Values for Navajo Children Ages 6-14 Years

Summary. Spirometry is the most important tool in diagnosing pulmonary disease and is the most frequently performed pulmonary function test. Since respiratory disease is the single greatest cause for morbidity and mortality on the Navajo Nation, the purpose of this study was to create new age and race-specific pulmonary nomograms for Navajo children. Five hundred fifty-eight healthy children, ages 6-14 years, attending Navajo Nation elementary schools in Arizona, were asked to perform spirometry to develop population-specific and tribe-specific nomograms for forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), and FEV1 Ratio (FEV1/FVC). Spirometry tests from 284 girls and 274 boys met American Thoracic Society quality control standards. Lung function values, except for FEV1/FVC, all increased with height. The lower limit of the normal range for FEV1/FVC was 80%. The spirometry reference equations from the healthy boys and girls were developed. Height and the natural log of height were significant predictors of FEV1, FVC, and FEF 25-75% in the gender-specific models. The resulting population-specific spirometry reference equations should be used when testing Navajo children ages 6-14 years. However, the use of the NHANES III spirometry reference equations for Caucasian children may not result in significant misclassification in clinical settings providing that a maximal effort is given by the Navajo child being tested

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics