The association between tobacco and the risk of asthma, rhinoconjunctivitis and eczema in children and adolescents: analyses from Phase Three of the ISAAC programme.

Thorax. 2012 Jun 12;

Authors: Mitchell EA, Beasley R, Keil U, Montefort S, Odhiambo J,

Abstract
BACKGROUND: Exposure to parental smoking is associated with wheeze in early childhood, but in 2006 the US Surgeon General stated that the evidence is insufficient to infer a causal relationship between exposure and asthma in childhood and adolescents. AIMS: To examine the association between maternal and paternal smoking and symptoms of asthma, eczema and rhinoconjunctivitis. METHODS: Parents or guardians of children aged 6-7 years completed written questionnaires about symptoms of asthma, rhinoconjunctivitis and eczema, and several risk factors, including maternal smoking in the child's first year of life, current maternal smoking (and amount) and paternal smoking. Adolescents aged 13-14 years self completed the questionnaires on these symptoms and whether their parents currently smoked. RESULTS: In the 6-7-year age group there were 220 407 children from 75 centres in 32 countries. In the 13-14-year age group there were 350 654 adolescents from 118 centres in 53 countries. Maternal and paternal smoking was associated with an increased risk of symptoms of asthma, eczema and rhinoconjunctivitis in both age groups, although the magnitude of the OR is higher for symptoms of asthma than the other outcomes. Maternal smoking is associated with higher ORs than paternal smoking. For asthma symptoms there is a clear dose relationship (1-9 cigarettes/day, OR 1.27; 10-19 cigarettes/day, OR 1.35; and 20+ cigarettes/day, OR 1.56). When maternal smoking in the child's first year of life and current maternal smoking are considered, the main effect is due to maternal smoking in the child's first year of life. There was no interaction between maternal and paternal smoking. CONCLUSIONS: This study has confirmed the importance of maternal smoking, and the separate and additional effect of paternal smoking. The presence of a dose-response effect relationship with asthma symptoms suggests that the relationship is causal, however for eczema and rhinoconjunctivitis causality is less certain.

PMID: 22693180 [PubMed - as supplied by publisher]

Genome-wide association studies of asthma indicate opposite immunopathogenesis direction from autoimmune diseases.

J Allergy Clin Immunol. 2012 Jun 11;

Authors: Li X, Ampleford EJ, Howard TD, Moore WC, Torgerson DG, Li H, Busse WW, Castro M, Erzurum SC, Israel E, Nicolae DL, Ober C, Wenzel SE, Hawkins GA, Bleecker ER, Meyers DA

Abstract
BACKGROUND: Genome-wide association studies (GWASs) of asthma have consistently implicated the ORM1-like 3 and gasdermin B (ORMDL3-GSDMB), IL33, IL-1 receptor-like 1 and IL-18 receptor 1 (IL1RL1-IL18R1), RAD50-IL13, thymic stromal lymphopoietin and WD repeat domain 36 region (TSLP-WDR36), and HLA-DR/DQ regions. OBJECTIVE: A GWAS of asthma was performed in a non-Hispanic white population. METHODS: A GWAS was performed in 813 Severe Asthma Research Program/Collaborative Studies on the Genetics of Asthma/Chicago Asthma Genetics Study cases and 1564 control subjects. The GWAS results were compared with those of the published GWASs of autoimmune diseases. RESULTS: Multiple single nucleotide polymorphisms in the TNFAIP3 interacting protein 1 (TNIP1) gene, which interacts with TNFAIP3 and inhibits the TNF-α-induced nuclear factor κB inflammation pathway, were associated with asthma: rs1422673 (P = 3.44 × 10(-7)) and rs10036748 (P = 1.41 × 10(-6), r(2) = 0.67). rs1422673 was also associated with asthma in the published GABRIEL (P = .018) and EVE (P = 1.31 × 10(-5)) studies. The minor allele T of rs20541 in IL13 is the risk allele for asthma but the protective allele for psoriasis. The minor allele T of rs2395185 in HLA-DRA is the risk allele for asthma but the protective allele for ulcerative colitis. The minor allele A of rs2872507 in GSDMB is the protective allele for asthma but the risk allele for rheumatoid arthritis, Crohn disease, and ulcerative colitis. The T allele of rs10036748 in the TNIP1 gene is the minor protective allele for asthma but the minor or major risk allele for systemic lupus erythematosus and systemic sclerosis in non-Hispanic white or Chinese subjects, respectively. CONCLUSIONS: Our study suggests that single nucleotide polymorphisms associated with both asthma and autoimmune diseases might have opposite effects on immunopathogenesis.

PMID: 22694930 [PubMed - as supplied by publisher]

Patients with severe or difficult-to-treat asthma are an understudied population but account for considerable asthma morbidity, mortality, and costs.

The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study was a large, 3-year, multicenter, observational cohort study of 4756 patients (n = 3489 adults ≥18 years of age, n = 497 adolescents 13-17 years of age, and n = 770 children 6-12 years of age) with severe or difficult-to-treat asthma. TENOR's primary objective was to characterize the natural history of disease in this cohort. Data assessed semiannually and annually included demographics, medical history, comorbidities, asthma control, asthma-related health care use, medication use, lung function, IgE levels, self-reported asthma triggers, and asthma-related quality of life.

We highlight the key findings and clinical implications from more than 25 peer-reviewed TENOR publications. Regardless of age, patients with severe or difficult-to-treat asthma demonstrated high rates of health care use and substantial asthma burden despite receiving multiple long-term controller medications. Recent exacerbation history was the strongest predictor of future asthma exacerbations. Uncontrolled asthma, as defined by the 2007 National Heart, Lung, and Blood Institute guidelines' impairment domain, was highly prevalent and predictive of future asthma exacerbations; this assessment can be used to identify high-risk patients.

IgE and allergen sensitization played a role in the majority of severe or difficult-to-treat asthmatic patients.

Treatment of chronic diseases such as chronic obstructive pulmonary disease (COPD) is complicated by the presence of comorbidities. The objective of this analysis was to estimate the prevalence of comorbidity in COPD using nationally-representative data.

METHODS: This study draws from a multi-year analytic sample of 14,828 subjects aged 45+, including 995 with COPD, from the National Health and Nutrition Examination Survey (NHANES), 1999-2008. COPD was defined by self-reported physician diagnosis of chronic bronchitis or emphysema; patients who reported a diagnosis of asthma were excluded. Using population weights, we estimated the age-and-gender-stratified prevalence of 22 comorbid conditions that may influence COPD and its treatment.

RESULTS: Subjects 45+ with physician-diagnosed COPD were more likely than subjects without physician-diagnosed COPD to have coexisting arthritis (54.6% vs. 36.9%), depression (20.6% vs. 12.5%), osteoporosis (16.9% vs. 8.5%), cancer (16.5% vs. 9.9%), coronary heart disease (12.7% vs. 6.1%), congestive heart failure (12.1% vs. 3.9%), and stroke (8.9% vs. 4.6%). Subjects with COPD were also more likely to report mobility difficulty (55.6% vs. 32.5%), use of >4 prescription medications (51.8% vs. 32.1), dizziness/balance problems (41.1% vs. 23.8%), urinary incontinence (34.9% vs. 27.3%), memory problems (18.5% vs. 8.8%), low glomerular filtration rate (16.2% vs. 10.5%), and visual impairment (14.0% vs. 9.6%). All reported comparisons have p<0.05.

CONCLUSIONS: Our study indicates that COPD management may need to take into account a complex spectrum of comorbidities. This work identifies which conditions are most common in a nationally-representative set of COPD patients (physician-diagnosed), a necessary step for setting research priorities and developing clinical practice guidelines that address COPD within the context of comorbidity.