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Background Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans. Objective We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness ( BHR), and total and specific IgEs, measured before conception vs. after birth, with offspring asthma and hayfever. Methods The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey ( ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991 to 1993, and data on 9100 offspring born 1972-2012. Adjusted relative risk ratios ( aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions. Results Offspring asthma with hayfever was more strongly associated with parental BHR and specific IgE measured before conception than after birth [ BHR: aRRR = 2.96 (95% CI: 1.92, 4.57) and 1.40 (1.03, 1.91), respectively; specific IgEs: 3.08 (2.13, 4.45) and 1.83 (1.45, 2.31), respectively]. This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11-22 years with information on parental disease activity both before and after birth. Conclusion & Clinical Relevance Parental BHR and specific IgE were associated with offspring asthma and hayfever, with the strongest associations observed with clinical assessment before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hayfever. [ABSTRACT FROM AUTHOR]

RATIONALE: Little is known about the long-term outcomes of individuals with mild/moderate chronic obstructive pulmonary disease (COPD) according to spirometric criteria. OBJECTIVES: To test whether nonsmokers and asymptomatic subjects with a spirometric diagnosis of COPD have a steeper decrease in lung function and higher hospitalization rates than subjects without airway obstruction. METHODS: A total of 5,205 subjects without asthma (20-44 years of age) from the general population, with FEV(1) >or= 50% predicted at baseline, were followed for 9 years in the frame of an international cohort study. Percent decrease in FEV(1) (DeltaFEV(1)%) and the annual hospitalization rate for respiratory causes during the follow-up were assessed for each subject. MEASUREMENTS AND MAIN RESULTS: At baseline, 324 (6.2%) subjects had the prebronchodilator FEV(1)/FVC ratio less than the lower limit of normal (LLN-COPD), and 105 (2.0%) subjects had the same ratio less than 0.70 (modified GOLD-COPD). At follow-up, smokers with LLN-COPD (n = 205) had a greater mean DeltaFEV(1)% (1.7%; 95% confidence interval [CI], 0.8-2.7) and a higher hospitalization rate (rate ratio [RR], 2.52; 95% CI, 1.65-3.86) than normal subjects. Similarly, symptomatic subjects with LLN-COPD (n = 104) had DeltaFEV(1)% (2.0%; 95% CI, 0.8-3.3) and the hospitalization rate (RR, 4.18; 95% CI, 2.43-7.21) higher than the reference group. By contrast, nonsmokers and asymptomatic subjects with LLN-COPD had outcomes that were similar or even better than normal subjects. Among subjects with LLN-COPD, the association of symptoms with DeltaFEV(1)% varied according to smoking habits (P = 0.007); it was particularly strong in symptomatic smokers and disappeared in symptomatic nonsmokers. Similar results were found with the modified GOLD classification. CONCLUSIONS: In relatively young populations, COPD is associated with poor long-term outcomes in smokers and in symptomatic subjects only. [ABSTRACT FROM AUTHOR]

Rationale: Increased risk for cardiovascular morbidity and mortality has been related to both lung function impairment and metabolic syndrome. Data on the relationship between lung function and metabolic syndrome are sparse. Objectives: To investigate risk for lung function impairment according to metabolic syndrome traits. Methods: This cross-sectional population-based study included 121,965 men and women examined at the Paris Investigations Préventives et Cliniques Center between 1999 and 2006. The lower limit of normal was used to define lung function impairment (FEV(1) or FVC < lower limit of normal). Metabolic syndrome was assessed according to the American Heart Association/National Heart, Lung, and Blood Institute statement. Measurements and Main Results: We used a logistic regression model and principal component analysis to investigate the differential associations between lung function impairment and specific components of metabolic syndrome. Lung function impairment was associated with metabolic syndrome (prevalence = 15.0%) independently of age, sex, smoking status, alcohol consumption, educational level, body mass index, leisure-time physical activity, and cardiovascular disease history (odds ratio [OR] [95% confidence interval], 1.28 [1.20-1.37] and OR, 1.41 [1.31-1.51] for FEV(1) and FVC, respectively). Three factors were identified from factor analysis: 'lipids' (low high-density lipoprotein cholesterol, high triglycerides), 'glucose-blood pressure' (high fasting glycemia, high blood pressure), and 'abdominal obesity' (large waist circumference). All factors were inversely related to lung function, but abdominal obesity was the strongest predictor of lung function impairment (OR, 1.94 [1.80-2.09] and OR, 2.11 [1.95-2.29], for FEV(1) and FVC, respectively). Similar results were obtained for women and men. Conclusions: We found a positive independent relationship between lung function impairment and metabolic syndrome in both sexes, predominantly due to abdominal obesity. Further studies are required to clarify the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Oxidative stress is thought to play a major role in the pathogenesis of chronic obstructive pulmonary disease, characterized by impaired lung function. A large number (> or =33) of GT repeats (L-allele) in the gene of the powerful antioxidant enzyme heme oxygenase-1 has been associated with susceptibility to accelerated lung function decline. In contrast, beta-carotene may help to protect against accelerated decline. To determine whether high serum levels of beta-carotene might counterbalance the greater susceptibility of L-allele carriers, the authors analyzed the annual decline in forced expiratory volume in 1 second (FEV1) in a general population sample of 523 French subjects (20-44 years, 50% men) examined in 1992 and 2000 as part of the European Community Respiratory Health Survey. Analysis of covariance, adjusted for sex as well as baseline age, body mass index, smoking, and FEV1, showed that, among subjects with low beta-carotene levels, L-allele carriers experienced a steeper mean FEV1 decline than did noncarriers (mean = -58.8, 95% confidence interval: -73.2, -44.5 vs. mean = -34.7, 95% confidence interval: -38.9, -29.8 ml/year) (p = 0.009), whereas among subjects with high beta-carotene levels, the FEV1 decline was not different in L-allele carriers and noncarriers (two-sided p = 0.9). The results suggest that high levels of beta-carotene might counterbalance the effects on FEV1 decline of a genetically determined deficiency in antioxidant response. [ABSTRACT FROM AUTHOR]

A number of studies have shown gender differences in the prevalence of wheeze and asthma. The aim of this review was to examine published results on gender differences in childhood and adolescent asthma incidence and prevalence, define current concepts and to identify new research needs. A Medline search was performed with the search words (gender OR sex) AND (child OR childhood OR adolescence) AND (asthma). Articles that reported on abscence or prescence of gender differences in asthma were included and reviewed, and cross-references were checked. Boys are consistently reported to have more prevalent wheeze and asthma than girls. In adolescence, the pattern changes and onset of wheeze is more prevalent in females than males. Asthma, after childhood, is more severe in females than in males, and is underdiagnosed and undertreated in female adolescents. Possible explanations for this switch around puberty in the gender susceptibility to develop asthma include hormonal changes and gender-specific differences in environmental exposures. This aspect needs consideration of the doctors and allergists who diagnose and treat asthmatic individuals. In conclusion, sex hormones are likely to play an important role in the development and outcome of the allergic immune response and asthma in particular. By obtaining functional data from appropriate models, the exact underlying mechanisms can be unravelled. To examine the effect of gender-specific differences in environmental exposures and changes of asthma prevalence and severity in puberty, larger populations may need to be investigated. [ABSTRACT FROM AUTHOR]

Objectives: Occupational exposures have been associated with an increased risk of new-onset rhinitis in apprentices. However, population-based prospective data are scarce and do not cover new onset of rhinitis later in life. The authors studied the association between occupational exposure and adult onset of rhinitis prospectively. Methods: The data of 4994 participants (age at follow-up 28-57 years) from 27 centres of the European Community Respiratory Health Survey II who were symptom-free at baseline were analysed. As outcome at follow-up self- reported (a) nasal allergies ("allergic rhinitis"( and (b( runny, blocked nose for 12 months a year ("perennial rhinitis"( were used. Occupational exposures at any time during follow-up were defined by job title. Results: The cumulative incidence of allergic rhinitis, perennial rhinitis and both conditions was 12%, 11% and 3%, respectively. Compared to office workers, male medical professionals were at increased risk of new onset of allergic rhinitis (OR 3.0; 95% Cl 1.4 to 6.4). Odds ratios were reduced in metal workers not involved in metal making or treating (0.3; 95% Cl 0.1 to 0.7). For perennial rhinitis ORs were significantly increased in cleaners (1.4; 95% Cl 1.0 to 2.1). Conclusions: Cleaners and medical professionals may be at increased risk for adult-onset rhinitis. [ABSTRACT FROM AUTHOR]

Rationale: Patients with allergic rhinitis have more frequent bronchial hyperresponsiveness (BHR) in cross-sectional studies. Objectives: To estimate the changes in BHR in nonasthmatic subjects with and without allergic rhinitis during a 9-year period. Methods: BHR onset was studied in 3,719 subjects without BHR at baseline, who participated in the follow-up of the European Community Respiratory Health Survey. Measurements and Main Results: BHR was defined as a >/=20% decrease in FEV(1) for a maximum dose of 1 mg of methacholine. Allergic rhinitis was defined as having a history of nasal allergy and positive specific IgE (>/=0.35 IU/ml) to pollen, cat, mites, or Cladosporium. The cumulative incidence of BHR was 9.7% in subjects with allergic rhinitis and 7.0% in subjects with atopy but no rhinitis, compared with 5.5% in subjects without allergic rhinitis and atopy (respective odds ratios [OR] and their 95% confidence intervals [95% CI] for BHR onset, 2.44 [1.73-3.45]; and 1.35 [0.86-2.11], after adjustment for potential confounders including sex, smoking, body mass index and FEV(1)). Subjects with rhinitis sensitized exclusively to cat or to mites were particularly at increased risk of developing BHR (ORs [95% CI], 7.90 [3.48-17.93] and 2.84 [1.36-5.93], respectively). Conversely, in subjects with BHR at baseline (n = 372), 35.3% of those with allergic rhinitis, compared with 51.8% of those without rhinitis had no more BHR at follow-up (OR [95% CI], 0.51 [0.33-0.78]). BHR 'remission' was more frequent in patients with rhinitis treated by nasal steroids than in those not treated (OR [95% CI], 0.33 [0.14-0.75]). Conclusions: Allergic rhinitis was associated with increased onset of BHR, and less chance for remission except in those treated for rhinitis. [ABSTRACT FROM AUTHOR]

RATIONALE: The few prospective studies aimed at assessing the incidence of chronic obstructive pulmonary disease (COPD) in relation to the presence of chronic cough/phlegm have produced contrasting results. OBJECTIVES: To assess the incidence of COPD in a cohort of young adults and to test whether chronic cough/phlegm and dyspnea are independent predictors of COPD. METHODS: An international cohort of 5,002 subjects without asthma (ages 20-44 yr) with normal lung function (FEV(1)/FVC ratio >/= 70%) from 12 countries was followed from 1991-2002 in the frame of the European Community Respiratory Health Survey II. Incident cases of COPD were those who had an FEV(1)/FVC ratio less than 70% at the end of the follow-up, but did not report having had a doctor diagnose asthma during the follow-up. MAIN RESULTS: The incidence rate of COPD was 2.8 cases/1,000/yr (95% confidence interval [CI], 2.3-3.3). Chronic cough/phlegm was an independent and statistically significant predictor of COPD (incidence rate ratio [IRR], 1.85; 95% CI, 1.17-2.93) after adjusting for smoking habits and other potential confounders, whereas dyspnea was not associated with the disease (IRR = 0.98; 95% CI, 0.64-1.50). Subjects who reported chronic cough/phlegm both at baseline and at the follow-up had a nearly threefold-increased risk of developing COPD with respect to asymptomatic subjects (IRR = 2.88; 95% CI, 1.44-5.79). CONCLUSIONS: The incidence of COPD is substantial even in young adults. The presence of chronic cough/phlegm identifies a subgroup of subjects with a high risk of developing COPD, independently of smoking habits. [ABSTRACT FROM AUTHOR]

The synthesis of allergen-specific IgE is required for the development of allergic diseases including allergic rhinitis and allergic asthma (patients), but many individuals with allergen-specific IgE do not develop symptoms (asymptomatic subjects). Differences may exist between asymptomatic subjects and patients. Whether the presence of allergen-specific IgE translates into clinical allergy most likely depends on a complex interplay of multiple factors. These include a family history of atopy, the levels of total serum IgE and, allergen-specific IgE or IgG, epitope-specificity of IgE and their degree of polyclonality (mono- vs polysensitized), as yet unidentified serum factors, the balance of T regulatory cells (Treg) and Th1/Th2 cells, the polymorphisms of the high affinity receptor for IgE (Fc ℇRI) and other factors regulating the activation of Fc ℇRI-bearing cells. Asymptomatic subjects may be more often monosensitized than patients who may be more often polysensitized. There are many unanswered important questions that need to be addressed in order to better understand how IgE sensitization translates into clinical allergy. The assessment of differences between the asymptomatic and symptomatic groups of subjects represent one of the scientific programs of Global Allergy and Asthma European Network funded by the European Union and the hypotheses underlying these differences are presented in this paper. [ABSTRACT FROM AUTHOR]

Rationale: Bronchial responsiveness (BHR) has been found to be associated with smoking, atopy, and lower lung function in cross-sectional studies, but there is little information on determinants of change in adults.Objectives: To analyze change in bronchial responsiveness in an international longitudinal community study.Methods: The study was performed in 3,993 participants in the European Community Respiratory Health Survey who had bronchial responsiveness measured in 1991-1993, when aged 20 to 44 yr, and in 1998-2002.Measurements: Bronchial responsiveness was assessed by methacholine challenge. Serum samples were tested for total IgE, and for specific IgE to four common allergens. Smoking information was obtained from detailed administered questionnaires. Change in bronchial responsiveness was analyzed by change in IgE sensitization, smoking, and lung function, with tests of interaction terms with age and sex.Main Results: Continuing and restarting smokers had increasing bronchial responsiveness, approximately equivalent to a mean reduction in PD[20] of 0.68 and 0.75 doubling doses, respectively, over 10 yr, in addition to a small increase explained by decline in FEV[1]. No other risk factor for change in bronchial responsiveness was identified.Conclusions: Smoking is a risk factor for increasing bronchial responsiveness over and above the effect of decreasing lung function. Neither baseline IgE sensitization nor change in sensitization was shown to be a risk factor for increasing BHR, the latter possibly due to little overall increase or decrease in sensitization. [ABSTRACT FROM AUTHOR]

An association between impaired lower respiratory function and cardiovascular risk factors, such as hypertension, is often reported but it is unknown whether there is a relationship between upper airway disorders and cardiovascular risk factors, despite evidence that upper and lower respiratory tract disorders are closely linked. Our objective was to assess whether rhinitis is associated with arterial blood pressure and hypertension. In a population-based study of 330 adults aged 28-56 years, as part of the European Community Respiratory Health Survey, rhinitis was assessed by means of a questionnaire, and cardiovascular data were obtained using a questionnaire and by measuring blood pressure. Systolic blood pressure (SBP) was higher in men with rhinitis than in men without rhinitis (130.6 +/- 12.7 mm Hg versus 123.5 +/- 13.9 mm Hg; p = 0.002), and it was still the case after adjustment for cardiovascular and respiratory confounding factors. Hypertension was more frequent in men with rhinitis than in men without rhinitis, even after multivariate adjustment (odds ratio = 2.6, 95% confidence interval = [1.14-5.91]). The observation of SBP levels according to whether men have no rhinitis, seasonal rhinitis, or perennial rhinitis was compatible with a dose-response relationship (p for trend = 0.02). In conclusion, rhinitis is strongly associated with SBP and hypertension in men. Blood pressure should be regularly checked in men with rhinitis. [ABSTRACT FROM AUTHOR]

Abstract Background Respiratory symptoms are common in the general population, and their presence is related to Health-related quality of life (HRQoL). The objective was to describe the association of respiratory symptoms with HRQoL in subjects with and without asthma or COPD and to investigate the role of atopy, bronchial hyperresponsiveness (BHR), and lung function in HRQoL. Methods The European Community Respiratory Health Survey (ECRHS) I and II provided data on HRQoL, lung function, respiratory symptoms, asthma, atopy, and BHR from 6009 subjects. Generic HRQoL was assessed through the physical component summary (PCS) score and the mental component summary (MCS) score of the SF-36. Factor analyses and linear regressions adjusted for age, gender, smoking, occupation, BMI, comorbidity, and study centre were conducted. Results Having breathlessness at rest in ECRHS II was associated with mean score (95% CI) impairment in PCS of -8.05 (-11.18, -4.93). Impairment in MCS score in subjects waking up with chest tightness was -4.02 (-5.51, -2.52). The magnitude of HRQoL impairment associated with respiratory symptoms was similar for subjects with and without asthma/COPD. Adjustments for atopy, BHR, and lung function did not explain the association of respiratory symptoms and HRQoL in subjects without asthma and/or COPD. Conclusion Subjects with respiratory symptoms had poorer HRQoL; including subjects without a diagnosis of asthma or COPD. These findings suggest that respiratory symptoms in the absence of a medical diagnosis of asthma or COPD are by no means trivial, and that clarifying the nature and natural history of respiratory symptoms is a relevant challenge. Several community studies have estimated the prevalence of common respiratory symptoms like cough, dyspnoea, and wheeze in adults 123. Although the prevalence varies to a large degree between studies and geographical areas, respiratory symptoms are quite common. The prevalences of respiratory symptoms in the European Community Respiratory Health Study (ECRHS) varied from one percent to 35% 1. In fact, two studies have reported that more than half of the adult population suffers from one or more respiratory symptoms 45. Respiratory symptoms are important markers of the risk of having or developing disease. Respiratory symptoms have been shown to be predictors for lung function decline 678, asthma 910, and even all-cause mortality in a general population study 11. In patients with a known diagnosis of asthma or chronic obstructive pulmonary disease (COPD), respiratory symptoms are important determinants of reduced health related quality of life (HRQoL) 12131415. The prevalence of respiratory symptoms exceeds the combined prevalences of asthma and COPD, and both asthma and COPD are frequently undiagnosed diseases 161718. Thus, the high prevalence of respipratory symptoms may mirror undiagnosed and untreated disease. The common occurrence of respiratory symptoms calls for attention to how these symptoms affect health also in subjects with no diagnosis of obstructive airways disease. Impaired HRQoL in the presence of respiratory symptoms have been found in two population-based studies 619, but no study of respiratory sypmtoms and HRQoL have separate analyses for subjects with and without asthma and COPD, and no study provide information about extensive objective measurements of respiratory health. The ECRHS is a randomly sampled, multi-cultural, population based cohort study. The ECRHS included measurements of atopy, bronchial hyperresponsiveness (BHR), and lung function, and offers a unique opportunity to investigate how respiratory symptoms affect HRQoL among subjects both with and without obstructive lung disease. In the present paper we aimed to: 1) Describe the relationship between respiratory symptoms and HRQoL in an international adult general population and: 2) To assess whether this relationship varied with presence of asthma and/or COPD, or presence of objective functional markers like atopy and BHR.

Abstract Background Endothelin-1 (EDN1) has been involved in the development of airway obstruction and inflammation in asthma. Several polymorphisms have been identified among the genes encoding for preproET1, an inactive precursor of ET-1, and for ETA (EDNRA) and ETB (EDNRB), the two receptors for EDN1. In the present work, we hypothesised that molecular variation in these genes could be a major determinant of the degree of bronchial obstruction. The purpose of this study was to investigate whether the genetic polymorphisms of preproET-1, EDNRA and EDNRB genes were associated with the degree of airway obstruction, assessed by FEV1. Methods Polymorphisms of preproET-1, EDNRA and EDNRB were first studied in a population of adult asthmatic patients. Results were confirmed in a large population of adults from the general population from the ECRHS II study. Results In our population of adult asthmatic patients, the EDNRB-30G>A (Leu277Leu) polymorphism (GG genotype) is strongly associated with a low FEV1 and with a higher percentage of patients with FEV1 < 80% of predicted value. No relationship was found between pulmonary function and EDNRA-1363C>T (His323His) or preproET-1-595G>T (Lys198Asp) polymorphism. In the adult population from the ECRHS II, we found a similar association between GG genotype and a low FEV1 or a higher percentage of subjects with FEV1 < 80% predicted, especially in the subgroups of asthmatics subjects (OR = 4.31 (95%CI 1.03 – 18.04)) and smokers (OR = 7.42 (95%CI 1.69 – 32.6)). Conclusion the EDNRB-30G>A polymorphism could be a determinant of airway obstruction in humans with predisposing factors such as tobacco smoke exposure or asthma.