Are environmental factors for atopic eczema in ISAAC Phase Three due to reverse causation?
J Invest Dermatol. 2018 Dec 03;:
Authors: Rutter C, Silverwood RJ, Williams HC, Ellwood P, Asher I, Garcia-Marcos L, Strachan DP, Pearce N, Langan SM, ISAAC Phase Three Study Group, Aït-Khaled N, Anderson HR, Asher MI, Beasley R, Björkstén B, Brunekreef B, Crane J, Ellwood P, Flohr C, Forastiere F, García-Marcos L, Foliaki S, Keil U, Lai CKW, Mallol J, Robertson CF, Mitchell EA, Montefort S, Odhiambo J, Pearce N, Shah J, Stewart AW, Strachan D, von Mutius E, Weiland SK, Weinmayr G, Williams H, Wong G
Some previously described environmental associations for atopic eczema (AE) may be due to reverse causation. We explored the role of reverse causation by comparing individual- and school-level results for multiple AE risk factors. ISAAC Phase Three surveyed children within schools (the sampling unit) on AE symptoms and potential risk factors. We assessed the effect of these risk factors on AE symptoms using mixed-effect logistic regression models, first with individual-level exposure data and second with school-level exposure prevalence. 546,348 children from 53 countries were included. At age 6-7 the strongest individual-level associations were with current paracetamol use (odds ratio=1.45, 95% confidence interval 1.37-1.54), which persisted at school-level (1.55, 1.10-2.21), antibiotics (1.41, 1.34-1.48) and early life paracetamol use (1.28, 1.21-1.36) with the former persisting at school-level while the latter was no longer observed (1.35, 1.00-1.82 and 0.94, 0.69-1.28 respectively). At age 13-14 the strongest associations at individual-level were with current paracetamol use (1.57, 1.51-1.63) and open-fire cooking (1.46, 1.33-1.62); both were stronger at school-level (2.57, 1.84-3.59 and 2.38, 1.52-3.73 respectively). Association with exposure to heavy traffic (1.31, 1.27-1.36) also persisted at school-level (1.40, 1.07-1.82). Most individual- and school level effects were consistent tending to exclude reverse causation.
PMID: 30521836 [PubMed - as supplied by publisher]
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
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
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]
Acupuncture Regulates the Balance of CD4+ T Cell Subtypes in Experimental Asthma Mice.
Chin J Integr Med. 2018 Dec 05;:
Authors: Dong M, Wang WQ, Chen J, Li MH, Xu F, Cui J, Dong JC, Wei Y
OBJECTIVE: To evaluate the involvement of different CD4+ T cell subtypes in the anti-asthmatic effects of acupuncture in asthmatic mice.
METHODS: BALB/c mice were challenged by ovalbumin (OVA) for the establishment of experimental asthma model. Mice were divided into 4 groups by a random number table including the normal control, asthma model, acupuncture and sham acupuncture groups (14 per group). Acupoints Dazhui (GV 14), bilateral Fengmen (BL 12) and Feishu (BL 13) were selected for manual acupuncture treatment every other day for 4 weeks and Huantiao (GB 30) was selected for sham acupuncture. Airway hyperresponsiveness was examined by Buxco Pulmonary System. Pulmonary histopathology analysis was performed for inflammatory cell infiltration and mucus hypersecretion by haematoxylin eosin staining and periodic acid-Schiffstaining. Inflammatory mediators assays of serum were investigated by enzyme-linked immunosorbent assay and Bio-Plex. CD4+ T cell subpopulations including the expression levels of important factors in T lymphocyte polarization in lung tissue were examined by flow cytometric and Western blot analyses. Related pathways were detected by Western blot assay.
RESULTS: Compared with the OVA-induced asthma model group, acupuncture could attenuate airway hyperresponsiveness, inhibit inflammatory cell infiltration and mucus hypersecretion (P<0.05 or P<0.01). Furthermore, acupuncture increased the expressions of T-bet and Foxp3+, the cell numbers of CD4+ interferon gamma (IFN-γ)+ and CD4+ Foxp3+ in lung tissue and the level of Treg type cytokine interleukin (IL)-10 in serum (P<0.05 or P<0.01). Meanwhile, acupuncture reduced the RAR-related orphan receptor gamma t (RORγt) level, the cell numbers of CD4+ IL-17A+ as well as the levels of IL-5, IL-13 and IL-17A in serum (P<0.05 or P<0.01). In addition, both acupuncture and sham acupuncture could inhibit the phosphorylation of p38 and p44/42 (P<0.01).
CONCLUSION: Acupuncture could alleviate allergic airway inflammation by strengthening the activities of Th1 and Treg, thus regulating the balance of CD4+ T cell subtypes in experimental asthmatic mice.
PMID: 30519873 [PubMed - as supplied by publisher]
RISK EFFECTS OF NEAR-ROADWAY POLLUTANTS AND ASTHMA STATUS ON BRONCHITIC SYMPTOMS IN CHILDREN.
Environ Epidemiol. 2018 Jun;2(2):
Authors: Urman R, Eckel S, Deng H, Berhane K, Avol E, Lurmann F, McConnell R, Gilliland F
Background: Bronchitic symptoms in children pose a significant clinical and public health burden. Exposures to criteria air pollutants affect bronchitic symptoms, especially in children with asthma. Less is known about near-roadway exposures.
Methods: Bronchitic symptoms (bronchitis, chronic cough, or phlegm) in the past 12 months were assessed annually with 8 to 9 years of follow-up on 6757 children from the southern California Children's Health Study. Residential exposure to freeway and non-freeway near-roadway air pollution was estimated using a line-source dispersion model. Mixed-effects logistic regression models were used to relate near-roadway air pollutant exposures to bronchitic symptoms among children with and without asthma.
Results: Among children with asthma, a two standard deviation increase in non-freeway exposures (odds ratio [OR]: 1.44; 95% confidence interval [CI]: 1.17-1.78) and freeway exposures (OR: 1.31; 95% CI: 1.06-1.60) were significantly associated with increased risk of bronchitic symptoms. Among children without asthma, only non-freeway exposures had a significant association (OR: 1.14; 95% CI: 1.00-1.29). Associations were strongest among children living in communities with lower regional particulate matter.
Conclusions: Near-roadway air pollution was associated with bronchitic symptoms, especially among children with asthma and those living in communities with lower regional particulate matter. Better characterization of traffic pollutants from non-freeway roads is needed since many children live in close proximity to this source.
PMID: 30519674 [PubMed]