Browsing by Subject "Corticosteroid sensitivity"

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    Determinants of Lung Function Across Childhood in the Severe Asthma Research Program (SARP) 3
    (Elsevier, 2023) Gaffin, Jonathan M.; Petty, Carter R.; Sorkness, Ronald L.; Denlinger, Loren C.; Phillips, Brenda R.; Ly, Ngoc P.; Gaston, Benjamin; Ross, Kristie; Fitzpatrick, Anne; Bacharier, Leonard B.; DeBoer, Mark D.; Teague, W. Gerald; Wenzel, Sally E.; Ramratnam, Sima; Israel, Elliot; Mauger, David T.; Phipatanakul, Wanda; National Heart, Lung and Blood Institute’s Severe Asthma Research Program-3 Investigators; Pediatrics, School of Medicine
    Background: Children with asthma are at risk for low lung function extending into adulthood, but understanding of clinical predictors is incomplete. Objective: We sought to determine phenotypic factors associated with FEV1 throughout childhood in the Severe Asthma Research Program 3 pediatric cohort. Methods: Lung function was measured at baseline and annually. Multivariate linear mixed-effects models were constructed to assess the effect of baseline and time-varying predictors of prebronchodilator FEV1 at each assessment for up to 6 years. All models were adjusted for age, predicted FEV1 by Global Lung Function Initiative reference equations, race, sex, and height. Secondary outcomes included postbronchodilator FEV1 and prebronchodilator FEV1/forced vital capacity. Results: A total of 862 spirometry assessments were performed for 188 participants. Factors associated with FEV1 include baseline Feno (B, -49 mL/log2 PPB; 95% CI, -92 to -6), response to a characterizing dose of triamcinolone acetonide (B, -8.4 mL/1% change FEV1 posttriamcinolone; 95% CI, -12.3 to -4.5), and maximal bronchodilator reversibility (B, -27 mL/1% change postbronchodilator FEV1; 95% CI, -37 to -16). Annually assessed time-varying factors of age, obesity, and exacerbation frequency predicted FEV1 over time. Notably, there was a significant age and sex interaction. Among girls, there was no exacerbation effect. For boys, however, moderate (1-2) exacerbation frequency in the previous 12 months was associated with -20 mL (95% CI, -39 to -2) FEV1 at each successive year. High exacerbation frequency (≥3) 12 to 24 months before assessment was associated with -34 mL (95% CI, -61 to -7) FEV1 at each successive year. Conclusions: In children with severe and nonsevere asthma, several clinically relevant factors predict FEV1 over time. Boys with recurrent exacerbations are at high risk of lower FEV1 through childhood.
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    Responsiveness to Parenteral Corticosteroids and Lung Function Trajectory in Adults with Moderate-to-Severe Asthma
    (American Thoracic Society, 2021) Denlinger, Loren C.; Phillips, Brenda R.; Sorkness, Ronald L.; Bleecker, Eugene R.; Castro, Mario; DeBoer, Mark D.; Fitzpatrick, Anne M.; Hastie, Annette T.; Gaffin, Jonathan M.; Moore, Wendy C.; Peters, Michael C.; Peters, Stephen P.; Phipatanakul, Wanda; Cardet, Juan Carlos; Erzurum, Serpil C.; Fahy, John V.; Fajt, Merritt L.; Gaston, Benjamin; Levy, Bruce D.; Meyers, Deborah A.; Ross, Kristie; Teague, W. Gerald; Wenzel, Sally E.; Woodruff, Prescott G.; Zein, Joe; Jarjour, Nizar N.; Mauger, David T.; Israel, Elliot; Pediatrics, School of Medicine
    Rationale: It is unclear why select patients with moderate-to-severe asthma continue to lose lung function despite therapy. We hypothesized that participants with the smallest responses to parenteral corticosteroids have the greatest risk of undergoing a severe decline in lung function. Objectives: To evaluate corticosteroid-response phenotypes as longitudinal predictors of lung decline. Methods: Adults within the NHLBI SARP III (Severe Asthma Research Program III) who had undergone a course of intramuscular triamcinolone at baseline and at ≥2 annual follow-up visits were evaluated. Longitudinal slopes were calculated for each participant’s post-bronchodilator FEV1% predicted. Categories of participant FEV1 slope were defined: severe decline, >2% loss/yr; mild decline, >0.5–2.0% loss/yr; no change, 0.5% loss/yr to <1% gain/yr; and improvement, ≥1% gain/yr. Regression models were used to develop predictors of severe decline. Measurements and Main Results: Of 396 participants, 78 had severe decline, 91 had mild decline, 114 had no change, and 113 showed improvement. The triamcinolone-induced difference in the post-bronchodilator FEV1% predicted (derived by baseline subtraction) was related to the 4-year change in lung function or slope category in univariable models (P < 0.001). For each 5% decrement in the triamcinolone-induced difference the FEV1% predicted, there was a 50% increase in the odds of being in the severe decline group (odds ratio, 1.5; 95% confidence interval, 1.3–1.8), when adjusted for baseline FEV1, exacerbation history, blood eosinophils and body mass index. Conclusions: Failure to improve the post-bronchodilator FEV1 after a challenge with parenteral corticosteroids is an evoked biomarker for patients at risk for a severe decline in lung function.