Asthma Adults Science

Inhaled steroids with and without regular salmeterol for asthma: serious adverse events.

Cochrane Database Syst Rev. 2018 Dec 03;12:CD006922

Authors: Cates CJ, Schmidt S, Ferrer M, Sayer B, Waterson S

Abstract
BACKGROUND: Epidemiological evidence has suggested a link between use of beta₂-agonists and increased asthma mortality. Much debate has surrounded possible causal links for this association, and whether regular (daily) long-acting beta₂-agonists (LABAs) are safe, particularly when used in combination with inhaled corticosteroids (ICSs). This is an update of a Cochrane Review that now includes data from two large trials including 11,679 adults and 6208 children; both were mandated by the US Food and Drug Administration (FDA).  OBJECTIVES: To assess risks of mortality and non-fatal serious adverse events (SAEs) in trials that randomised participants with chronic asthma to regular salmeterol and ICS versus the same dose of ICS.
SEARCH METHODS: We identified randomised trials using the Cochrane Airways Group Specialised Register of trials. We checked websites of clinical trials registers for unpublished trial data. We also checked FDA submissions in relation to salmeterol. The date of the most recent search was 10 October 2018.
SELECTION CRITERIA: We included parallel-design randomised trials involving adults, children, or both with asthma of any severity who were randomised to treatment with regular salmeterol and ICS (in separate or combined inhalers) versus the same dose of ICS of at least 12 weeks in duration.
DATA COLLECTION AND ANALYSIS: We conducted the review according to standard procedures expected by Cochrane. We obtained unpublished data on mortality and SAEs from the sponsors, from ClinicalTrials.gov, and from FDA submissions. We assessed our confidence in the evidence according to current GRADE recommendations.
MAIN RESULTS: We have included in this review 41 studies (27,951 participants) in adults and adolescents, along with eight studies (8453 participants) in children. We judged that the overall risk of bias was low for all-cause events, and we obtained data on SAEs from all study authors. All except 542 adults (and none of the children) were given salmeterol and fluticasone in the same (combination) inhaler.DeathsEleven of a total of 14,233 adults taking regular salmeterol and ICS died, as did 13 of 13,718 taking regular ICS at the same dose. The pooled Peto odds ratio (OR) was 0.80 (95% confidence interval (CI) 0.36 to 1.78; participants = 27,951; studies = 41; I² = 0%; moderate-certainty evidence). In other words, for every 1000 adults treated for 25 weeks, one death occurred among those on ICS alone, and the corresponding risk among those taking salmeterol and ICS was also one death (95% CI 0 to 2 deaths).No children died, and no adults or children died of asthma, so we remain uncertain about mortality in children and about asthma mortality in any age group.Non-fatal serious adverse eventsA total of 332 adults receiving regular salmeterol with ICS experienced a non-fatal SAE of any cause, compared to 282 adults receiving regular ICS. The pooled Peto OR was 1.14 (95% CI 0.97 to 1.33; participants = 27,951; studies = 41; I² = 0%; moderate-certainty evidence). For every 1000 adults treated for 25 weeks, 21 adults on ICS alone had an SAE, and the corresponding risk for those on salmeterol and ICS was 23 adults (95% CI 20 to 27).Sixty-five of 4229 children given regular salmeterol with ICS suffered an SAE of any cause, compared to 62 of 4224 children given regular ICS. The pooled Peto OR was 1.04 (95% CI 0.73 to 1.48; participants = 8453; studies = 8; I² = 0%; moderate-certainty evidence). For every 1000 children treated for 23 weeks, 15 children on ICS alone had an SAE, and the corresponding risk for those on salmeterol and ICS was 15 children (95% CI 11 to 22).Asthma-related serious adverse eventsEighty and 67 adults in each group, respectively, experienced an asthma-related non-fatal SAE. The pooled Peto OR was 1.15 (95% CI 0.83 to 1.59; participants = 27,951; studies = 41; I² = 0%; low-certainty evidence). For every 1000 adults treated for 25 weeks, five receiving ICS alone had an asthma-related SAE, and the corresponding risk among those on salmeterol and ICS was six adults (95% CI 4 to 8).Twenty-nine children taking salmeterol and ICS and 23 children taking ICS alone reported asthma-related events. The pooled Peto OR was 1.25 (95% CI 0.72 to 2.16; participants = 8453; studies = 8; I² = 0%; moderate-certainty evidence). For every 1000 children treated for 23 weeks, five receiving an ICS alone had an asthma-related SAE, and the corresponding risk among those receiving salmeterol and ICS was seven children (95% CI 4 to 12).
AUTHORS' CONCLUSIONS: We did not find a difference in the risk of death or serious adverse events in either adults or children. However, trial authors reported no asthma deaths among 27,951 adults or 8453 children randomised to regular salmeterol and ICS or ICS alone over an average of six months. Therefore, the risk of dying from asthma on either treatment was very low, but we remain uncertain about whether the risk of dying from asthma is altered by adding salmeterol to ICS.Inclusion of new trials has increased the precision of the estimates for non-fatal SAEs of any cause. We can now say that the worst-case estimate is that at least 152 adults and 139 children must be treated with combination salmeterol and ICS for six months for one additional person to be admitted to the hospital (compared to treatment with ICS alone). These possible risks still have to be weighed against the benefits experienced by people who take combination treatment.However more than 90% of prescribed treatment was taken in the new trials, so the effects observed may be different from those seen with salmeterol in combination with ICS in daily practice.

PMID: 30521673 [PubMed - as supplied by publisher]

Exposure to Secondhand Smoke Among Nonsmokers - United States, 1988-2014.

MMWR Morb Mortal Wkly Rep. 2018 Dec 07;67(48):1342-1346

Authors: Tsai J, Homa DM, Gentzke AS, Mahoney M, Sharapova SR, Sosnoff CS, Caron KT, Wang L, Melstrom PC, Trivers KF

Abstract
Exposure to secondhand smoke from burning tobacco products can cause sudden infant death syndrome, respiratory infections, ear infections, and asthma attacks in infants and children, and coronary heart disease, stroke, and lung cancer in adult nonsmokers (1). There is no risk-free level of secondhand smoke exposure (2). CDC analyzed questionnaire and laboratory data from the National Health and Nutrition Examination Survey (NHANES) to assess patterns of secondhand smoke exposure among U.S. nonsmokers. The prevalence of secondhand smoke exposure among U.S. nonsmokers declined substantially during 1988-2014, from 87.5% to 25.2%. However, no change in exposure occurred between 2011-2012 and 2013-2014, and an estimated one in four nonsmokers, or approximately 58 million persons, were still exposed to secondhand smoke during 2013-2014. Moreover, marked disparities persisted across population groups. Exposure prevalence was highest among nonsmokers aged 3-11 years (37.9%), non-Hispanic blacks (50.3%), and those who were living in poverty (47.9%), in rental housing (38.6%), or with someone who smoked inside the home (73.0%), or among persons who had less than a high school education (30.7%). Comprehensive smoke-free laws and policies for workplaces and public places and smoke-free rules for homes and vehicles can further reduce secondhand smoke exposure among all nonsmokers.

PMID: 30521502 [PubMed - in process]

Effects of weight loss on dynamic hyperinflation in women obese asthmatics.

J Appl Physiol (1985). 2018 Dec 06;:

Authors: Silva AG, Freitas PD, Ferreira PG, Stelmach R, Pinto RMC, Salge JM, Martins MA, Carvalho CRF

Abstract
Obese adults with asthma are more likely to develop dynamic hyperinflation (DH) and expiratory flow limitation (EFL) than non-obese asthmatics, and weight-loss seems to improve the breathing mechanics during exercise. However, studies evaluating the effect of weight-loss on DH in obese adults with asthma have not been performed.
OBJECTIVE: To evaluate the effect of a weight-loss program on DH in obese adults with asthma.
METHODS: Forty-two asthma patients were enrolled in a weight-loss program (diet, psychological support and exercise) and were subsequently divided into two groups according to the percentage of weight-loss: the ≥5%group (n=19) and the <5%group (n=23). Before and after the intervention, DH and EFL (constant load exercise), health-related quality of life (HRQoL), asthma control, quadriceps muscle strength and endurance, body composition and lung function were assessed.
RESULTS: Both groups exhibited a decrease of ≥10% in inspiratory capacity (DH) before intervention, and only the ≥5%group showed clinical improvement in DH compared to <5%group post-intervention (-9.1±14.5% vs. -12.5±13.5%, respectively). In addition, the ≥5%group displayed a significant delay in the onset of both DH and EFL and a clinically significant improvement in HRQoL and asthma control. Furthermore, a correlation was observed between reduced waist circumference and increased inspiratory capacity (r=-0.45, p=0.05) in the ≥5%group.
CONCLUSION: A weight-loss ≥5% of the body weight improves DH, which is associated with waist circumference in obese adults with asthma. In addition, the group with greater weight-loss showed a delayed onset of DH and EFL during exercise and improved asthma clinical control and HRQoL.

PMID: 30521428 [PubMed - as supplied by publisher]

Amazing pleiotropic effects of azithromycin.

Breathe (Sheff). 2018 Dec;14(4):336-337

Authors: Lahousse L

Abstract
The large randomised, double-blind, placebo-controlled AMAZES trial observed that azithromycin 500 mg given 3-times a week for 48 weeks in adults with persistent uncontrolled asthma decreased asthma exacerbations and improved asthma-related quality of life 
http://ow.ly/WGlz30lLL7z.

PMID: 30519303 [PubMed]

Cross-sectional associations of vitamin D status with asthma prevalence, exacerbations, and control in New Zealand adults.

J Steroid Biochem Mol Biol. 2018 Nov 30;:

Authors: Win SS, Camargo CA, Khaw KT, Lawes CMM, Sluyter J, Waayer D, Toop L, Scragg R

Abstract
BACKGROUND: Previous studies, mostly with children, have reported inconsistent findings on the associations of vitamin D status with asthma prevalence, exacerbations, and control. Because of limited research with adults, we examined these associations in a large community-based sample of New Zealand adults.
METHODS: 5110 participants, aged 50-84 years, were recruited from the community into a clinical trial of vitamin D supplementation. The current analysis is based on baseline blood sample collection to measure serum 25-hydroxyvitamin D (25(OH)D), which was deseasonalized for data analyses; and baseline asthma assessment, which included questions on asthma prevalence, urgent medical care for asthma in the previous 12 months, and control of asthma symptoms in the previous 4 weeks.
RESULTS: 702 (13.2%) of 5088 participants reported having doctor-diagnosed asthma. There was no difference in mean (SE) 25(OH)D concentration between participants with and without asthma: 66 (0.9) and 66 (0.4) nmol/L, respectively, adjusting for sex (p = 0.71). However, in multivariable analyses restricted to participants who reported having asthma, mean (SE) 25(OH)D concentration was 6.3 (2.6) nmol/L lower in those who reported having urgent medical care for asthma in the previous 12 months compared to others (p = 0.02), and 10.4 (3.9) nmol/L lower in those with very poor asthma control compared to those who were well-controlled (p = 0.03).
CONCLUSION: These cross-sectional results suggest that asthmatic adults with lower vitamin D status are more likely to receive urgent asthma medical care and to experience poor asthma control. Clinical trials are needed to determine the role of vitamin D supplementation in asthma management.

PMID: 30508643 [PubMed - as supplied by publisher]