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Step-Up Therapy in Black Children and Adults with Poorly Controlled Asthma

Author/s: 
Wechsler, ME, Szefler, SJ, Ortega, VE, Pongracic, JA, Chinchili, V, Lima, JJ, Krishnan, JA, Kunselman, SJ, Mauger, D, Bleecker, ER, Bacharier, LB, Beigelman, A, Benson, M, Blake, KV, Cabana, MD, Cardet, JC, Castro, M, Chmiel, JF, Covar, R, Denlinger, L, DiMango, E, Fitzpatrick, AM, Gentile, D, Grossman, N, Holguin, F, Jackson, DJ, Kumar, H, Kraft, M, LaForce, CF, Lang, J, Lazarus, SC, Lemanske, RF Jr, Long, D, Lugogo, N, Martinez, F, Meyers, DA, Moore, WC, Moy, J, Naureckas, E, Olin, JT, Peters, SP, Phipatanakul, W, Que, L, Raissy, H, Robison, RG, Ross, K, Sheehan, W, Smith, LJ, Solway, J, Sorkness, CA, Sullivan-Vedder, L, Wenzel, S, Israel, E, NHLBI AsthmaNet

BACKGROUND:

Morbidity from asthma is disproportionately higher among black patients than among white patients, and black patients constitute the minority of participants in trials informing treatment. Data indicate that patients with inadequately controlled asthma benefit more from addition of a long-acting beta-agonist (LABA) than from increased glucocorticoids; however, these data may not be informative for treatment in black patients.

METHODS:

We conducted two prospective, randomized, double-blind trials: one involving children and the other involving adolescents and adults. In both trials, the patients had at least one grandparent who identified as black and had asthma that was inadequately controlled with low-dose inhaled glucocorticoids. We compared combinations of therapy, which included the addition of a LABA (salmeterol) to an inhaled glucocorticoid (fluticasone propionate), a step-up to double to quintuple the dose of fluticasone, or both. The treatments were compared with the use of a composite measure that evaluated asthma exacerbations, asthma-control days, and lung function; data were stratified according to genotypic African ancestry.

RESULTS:

When quintupling the dose of fluticasone (to 250 μg twice a day) was compared with adding salmeterol (50 μg twice a day) and doubling the fluticasone (to 100 μg twice a day), a superior response occurred in 46% of the children with quintupling the fluticasone and in 46% of the children with doubling the fluticasone and adding salmeterol (P = 0.99). In contrast, more adolescents and adults had a superior response to added salmeterol than to an increase in fluticasone (salmeterol-low-dose fluticasone vs. medium-dose fluticasone, 49% vs. 28% [P = 0.003]; salmeterol-medium-dose fluticasone vs. high-dose fluticasone, 49% vs. 31% [P = 0.02]). Neither the degree of African ancestry nor baseline biomarkers predicted a superior response to specific treatments. The increased dose of inhaled glucocorticoids was associated with a decrease in the ratio of urinary cortisol to creatinine in children younger than 8 years of age.

CONCLUSIONS:

In contrast to black adolescents and adults, almost half the black children with poorly controlled asthma had a superior response to an increase in the dose of an inhaled glucocorticoid and almost half had a superior response to the addition of a LABA. (Funded by the National Heart, Lung, and Blood Institute; BARD ClinicalTrials.gov number, NCT01967173.).

Keywords 
asthma African Americans glucocorticoids randomized control trial

Electronic Nicotine Delivery Systems (ENDS)

Electronic nicotine delivery systems (ENDS), also called electronic cigarettes, e-cigarettes, vaping devices, or vape pens, are battery-powered devices used to smoke or “vape” a flavored solution which usually contains nicotine. The American Academy of Family Physicians (AAFP) recognizes the alarmingly increased use of ENDS, especially among youth and young adults, as well as its use by those attempting to quit smoking tobacco.

The AAFP calls for further research to assess ENDS’ safety, quality, and efficacy as a potential cessation device. The AAFP also recommends that the marketing and advertising of ENDS to children and youth cease immediately. The AAFP encourages members to screen for ENDS use starting with school-age children, to discuss the potential harms of ENDS, and to recommend cessation interventions with e-cigarette users. The AAFP encourages members to inform patients who use ENDS, especially children, that the majority of these products contain nicotine and are addictive.  (2014 COD) (April 2019 BOD)

Keywords 
adolescent adult child nicotine tobacco vaping family electronic protocol U.S.

Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents

Author/s: 
Hayden, Frederick G., Sugaya, Norio, Hirotsu, Nobuo, Lee, Nelson, de Jong, Menno D., Hurt, Aeron C., Ishida, Tadashi, Sekino, Hisakuni, Yamada, Kota, Portsmouth, Simon, Kawaguchi, Keiko, Shishido, Takao, Arai, Masatsugu, Tsuchiya, Kenji, Uehara, Takeki, Watanabe, Akira, Baloxavir Marboxil Investigators Group

BACKGROUND:

Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains resistant to current antiviral agents.

METHODS:

We conducted two randomized, double-blind, controlled trials involving otherwise healthy outpatients with acute uncomplicated influenza. After a dose-ranging (10 to 40 mg) placebo-controlled trial, we undertook a placebo- and oseltamivir-controlled trial of single, weight-based doses of baloxavir (40 or 80 mg) in patients 12 to 64 years of age during the 2016-2017 season. The dose of oseltamivir was 75 mg twice daily for 5 days. The primary efficacy end point was the time to alleviation of influenza symptoms in the intention-to-treat infected population.

RESULTS:

In the phase 2 trial, the median time to alleviation of influenza symptoms was 23.4 to 28.2 hours shorter in the baloxavir groups than in the placebo group (P<0.05). In the phase 3 trial, the intention-to-treat infected population included 1064 patients; 84.8 to 88.1% of patients in each group had influenza A(H3N2) infection. The median time to alleviation of symptoms was 53.7 hours (95% confidence interval [CI], 49.5 to 58.5) with baloxavir, as compared with 80.2 hours (95% CI, 72.6 to 87.1) with placebo (P<0.001). The time to alleviation of symptoms was similar with baloxavir and oseltamivir. Baloxavir was associated with greater reductions in viral load 1 day after initiation of the regimen than placebo or oseltamivir. Adverse events were reported in 20.7% of baloxavir recipients, 24.6% of placebo recipients, and 24.8% of oseltamivir recipients. The emergence of polymerase acidic protein variants with I38T/M/F substitutions conferring reduced susceptibility to baloxavir occurred in 2.2% and 9.7% of baloxavir recipients in the phase 2 trial and phase 3 trial, respectively.

CONCLUSIONS:

Single-dose baloxavir was without evident safety concerns, was superior to placebo in alleviating influenza symptoms, and was superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza. Evidence for the development of decreased susceptibility to baloxavir after treatment was also observed. (Funded by Shionogi; JapicCTI number, 153090, and CAPSTONE-1 ClinicalTrials.gov number, NCT02954354 .).

Keywords 
baloxavir marboxil oseltamivir influenza
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