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Introduction: Cytomegalovirus (CMV) seropositivity has been recently linked to severity and progression of asthma, cystic fibrosis, and chronic obstructive pulmonary disease (COPD). To date, no longitudinal study has addressed the relation of CMV serology to levels and decline of lung function in the general adult population. Methods: We evaluated 403 participants from the Tucson Epidemiological Study of Airway Obstructive Disease (TESAOD) who at enrollment were aged 28–55 years and completed lung function tests. During follow‐up, the 403 participants completed on average 7.2 lung function tests per subject for a total of 2908 observations over a mean period of 14.7 years. We tested CMV serology in serum samples from enrollment and categorized participants into low, medium, and high CMV serology based on tertiles. The relation of CMV serology at enrollment to lung function levels and decline during follow‐up was tested in multivariate random coefficients models. Results: After full adjustment, participants in the highest CMV serology tertile had faster declines of forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) compared with subjects in the lowest tertile (by −7.9 ml/year 95% confidence interval [−13.9 ml/year, −1.93 ml/year], and by −0.13%/year [−0.23%/year, −0.026%/year], respectively). These CMV effects were additive with those of cigarette smoking. No associations were found between CMV serology and FVC, indicating specific effects of CMV seropositivity on airflow limitation. Conclusion: High CMV serology in young to mid‐adult life may be linked to increased COPD risk through an accelerated decline of lung function. [ABSTRACT FROM AUTHOR]

Background: Allergic diseases often occur in combination (multimorbidity). Human blood transcriptome studies have not addressed multimorbidity. Large‐scale gene expression data were combined to retrieve biomarkers and signaling pathways to disentangle allergic multimorbidity phenotypes. Methods: Integrated transcriptomic analysis was conducted in 1233 participants with a discovery phase using gene expression data (Human Transcriptome Array 2.0) from whole blood of 786 children from three European birth cohorts (MeDALL), and a replication phase using RNA Sequencing data from an independent cohort (EVA‐PR, n = 447). Allergic diseases (asthma, atopic dermatitis, rhinitis) were considered as single disease or multimorbidity (at least two diseases), and compared with no disease. Results: Fifty genes were differentially expressed in allergic diseases. Thirty‐two were not previously described in allergy. Eight genes were consistently overexpressed in all types of multimorbidity for asthma, dermatitis, and rhinitis (CLC, EMR4P, IL5RA, FRRS1, HRH4, SLC29A1, SIGLEC8, IL1RL1). All genes were replicated the in EVA‐PR cohort. RT‐qPCR validated the overexpression of selected genes. In MeDALL, 27 genes were differentially expressed in rhinitis alone, but none was significant for asthma or dermatitis alone. The multimorbidity signature was enriched in eosinophil‐associated immune response and signal transduction. Protein‐protein interaction network analysis identified IL5/JAK/STAT and IL33/ST2/IRAK/TRAF as key signaling pathways in multimorbid diseases. Synergistic effect of multimorbidity on gene expression levels was found. Conclusion: A signature of eight genes identifies multimorbidity for asthma, rhinitis, and dermatitis. Our results have clinical and mechanistic implications, and suggest that multimorbidity should be considered differently than allergic diseases occurring alone. [ABSTRACT FROM AUTHOR]

What are the implications of a lower than expected forced expiratory volume in one second (FEV1) in childhood on respiratory health later in adulthood? Lung function is known to track with age, and there is evidence from recent epidemiologic studies that impaired lung function early in life is associated with later chronic airflow limitation, or even chronic obstructive pulmonary disease, COPD. This risk seems particularly strong in subjects with persistent and severe forms of childhood asthma. Can we translate findings from longitudinal cohort studies to individual risk predictions and preventive guidelines in our pediatric care? In this review, we discuss the clinical implementations of recent epidemiological respiratory studies and the importance of preserved lung health across the life course. Also, we evaluate available clinical tools, primarily lung function measures, and profiles of risk factors, including biomarkers, that may help identifying children at risk of chronic airway disease in adulthood. We conclude that translating population level results to the individual patient in the pediatric care setting is not straight forward, and that there is a need for studies specifically designed to evaluate performance of prediction of risk profiles for long‐term sequelae of childhood asthma and lung function impairment. [ABSTRACT FROM AUTHOR]

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Background and objective Exercise capacity decline is a predictor of mortality in patients with chronic obstructive pulmonary disease ( COPD). Static pulmonary hyperinflation is a key determinant of exercise performance, but its effect on the longitudinal decline in exercise capacity remains unknown. We aimed to study the relationship between the inspiratory capacity-to-total lung capacity ( IC/ TLC) ratio and exercise capacity decline in COPD. Methods We measured IC/ TLC and other relevant clinical and functional variables in 342 clinically stable patients with COPD. The 6-min walk distance ( 6MWD) was determined at recruitment and after a mean ± SD of 1.7 ± 0.3 years. The annual rate of change in 6MWD was calculated. Multiple imputation to account for losses during follow up was implemented, and multivariate regression was used to analyze predictive factors of 6MWD decline. Results Mean decline rate in the 6MWD was 21.9 ± 34.1 m/year. In the bivariate analysis, patients with lower levels of IC/ TLC had greater 6MWD decline (−27.4 ± 42.5, −24.9 ± 36.5 and −13.4 ± 39.9 m/year in the first, second and third tertile of IC/ TLC, respectively; P-for-trend = 0.018). From other potential risk factors considered, dyspnoea, health status, serum C-reactive protein and Borg dyspnoea score at the end of the exercise test were related to exercise capacity decline. In the multivariate regression model, only IC/ TLC (β = 0.7 m/year per each percentage unit of IC/ TLC; P = 0.007) and dyspnoea ( mMRC ≥ 2) (β = −14.6 m/year; P = 0.013) were associated with the annual rate of 6MWD change. Conclusion IC/ TLC and dyspnoea in clinically stable patients with COPD predict their exercise capacity decline and may help to guide early therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background and objective Club cell secretory protein ( CC-16) is a sensitive biomarker of airways epithelium integrity. It has gained interest as a biological marker in chronic lung diseases because of its presumed relationship to inflammation. Little is known about the association between CC-16 serum level and asthma, lung function and airway responsiveness ( AR). Methods Serum CC-16 level was determined by latex immunoassay in 1298 participants from the French Epidemiological case-control and family-based study on Genetics and Environment of Asthma ( EGEA) (mean age 43 years; 49% men, 38% with asthma). Pre-bronchodilator lung function (forced expiratory volume in 1 s ( FEV1), forced vital capacity ( FVC) and FEV1/ FVC) and degree of AR, expressed as a function of the dose-response slope to methacholine test were measured. Standardized residuals CC-16 z-scores were obtained by regressing CC-16 level on the glomerular filtration rate. CC-16 z-scores were correlated with asthma, lung function and AR in participants with and without asthma. Results CC-16 geometric mean level was 12.4 μg/L (range: 2.2-70.6 μg/L). In participants without asthma, lower CC-16 z-scores was associated with impaired FEV1/ FVC% (β = 0.50 (95% CI: 0.06, 0.95) and with higher degree of AR (β = 0.24 (95% CI: 0.09, 0.39)). CC-16 was not associated with impaired lung function or AR in participants with asthma. Conclusions Lower CC-16 serum level was associated with impaired lung function and AR, suggesting that serum CC-16 level may reflect early damages to the lung epithelium in adults without asthma. [ABSTRACT FROM AUTHOR]

Background: Maternal prepregnancy obesity has been linked to the offspring's risk for subsequent asthma. We determined whether maternal obesity is associated with increased risk of wheezing phenotypes early in life. Methods: We used data on 1107 mother-child pairs from two birth cohorts from the INMA-INfancia y Medio Ambiente project. Maternal height was measured and prepregnancy weight self-reported at enrolment (on average at 13.7 ± 2 weeks of gestation). Maternal prepregnancy body mass index was categorised as underweight, normal, overweight and obese according to WHO recommendations. Information on child's wheezing was obtained through questionnaires up to the age of 14 (±1) months. Wheezing was classified as infrequent (<4 reported wheezing episodes) or frequent (≥4 episodes). Weight and length of infants were measured by trained study staff at 14.6 (±1) months of age and weight-for-length z-scores computed. Results: Although maternal obesity did not increase the risk of the child to have any or infrequent wheezing, children of obese mothers were more likely to have frequent wheezing than children of normal-weight mothers (11.8% vs. 3.8%; P = 0.002). In fully adjusted multinomial logistic regression models, including infants' weight-for-length z-scores and other covariates, maternal prepregnancy obesity was associated with increased risk of frequent [adjusted relative risk (RR) 4.18, 95% confidence interval (CI) 1.55, 11.3] but not infrequent (RR 1.05 [95% CI 0.55, 2.01]) wheezing in their children. Conclusions: Maternal prepregnancy obesity is independently associated with an increased risk of frequent wheezing in the infant by the age of 14 months. These findings add evidence on the potential effects of in utero exposures on asthma-related phenotypes. [ABSTRACT FROM AUTHOR]

To cite this article: Kurzius-Spencer M, Guerra S, Sherrill DL, Halonen M, Elston RC, Martinez FD. Familial aggregation of allergen-specific sensitization and asthma. Pediatric Allergy Immunology 2012: 23: 21-27. Abstract Background: Familial aggregation of specific response to allergens and asthma adjusted for age and sensitization to multiple allergens was assessed in two large population cohorts. Methods: Allergen skin prick tests (SPTs) were administered to 1151 families in the Tucson Children's Respiratory Study (CRS) and 435 families in the Tucson Epidemiological Study of Airway Obstructive Disease (TESAOD). Sensitization was defined by wheal size ≥3 mm; physician-diagnosed asthma at age ≥8 yr was based on questionnaires. Using s.a.g.e. 6.1 software assoc and fcor, familial correlations of crude and adjusted phenotypes were evaluated. Results: Crude estimates of parent-offspring (P-O) and sibling correlations were statistically significant for most allergens, ranging from 0.03 to 0.29. After adjusting for age of assessment and 'other atopy' (SPT-positive response to additional allergens), correlations were reduced by 14-71%. Sibling correlations for specific response to allergens were consistently higher than P-O correlations, but this difference was significant only for dust mite and weed mix in the TESAOD population. Familial correlation for atopic status (any positive SPTs vs. none) tended to be higher than for specific allergens. Asthma, with and without adjustment, showed greater familial correlation than either specific or general SPT response and significantly higher sibling correlation in TESAOD than in CRS, probably due to the older age of the siblings and the longer period of ascertainment. Conclusions: Significant familial aggregation of specific response to allergen after adjustment for other atopy appears to reflect a genetic propensity toward atopy, dependent on shared familial exposures. Results also suggest that inheritance of asthma is independent of atopic sensitization. [ABSTRACT FROM AUTHOR]

The ratio of forced expiratory volume in 1 s and forced expiratory volume in 6 s (FEV1/FEV6) has been proposed as an alternative for FEV1/forced vital capacity (FVC) to diagnose obstructive diseases with less effort during spirometry; however, its prognostic value is unknown. We evaluated whether FEV1/FEV6 is a significant predictor of mortality in elderly subjects and compared its prognostic value with that of FEV1/FVC and FEV1. One thousand nine hundred and seventy-one subjects, aged >65 years, participated in the population-based SA.R.A. study. During the baseline exam, a multidimensional assessment included spirometry. Vital status was determined during 6 years of follow-up. Association of all-cause, cardio-pulmonary (CP) and non-CP mortality with a low FEV1/FEV6, FEV1/FVC and FEV1 was evaluated. Among subjects with both survival data and acceptable spirometry including FEV6, all-cause unadjusted mortality rates were 7·00 and 2·46 per 100 person-years in subjects with FEV1/FEV6 less than and greater than or equal to lower limit of normal (LLN), respectively (mortality rate ratio: 2·84, 95%CI: 2·12-3·84). After adjustment for age, gender, FVC, smoke exposure and main comorbidities, the risk of all-cause mortality remained significantly increased in subjects with FEV1/FEV6 < LLN [hazard ratio (HR): 1·87, 95%CI: 1·35-2·58] as well as in subjects with FEV1/FVC < LLN (HR: 2·01, 95%CI: 1·51-2·90) and FEV1 < LLN (HR: 2·17, 95%CI: 1·32-3·57). Similar results were found for CP mortality, but not for non-CP mortality. A low FEV1/FEV6 is a significant predictor of mortality in older individuals. Its prognostic value is comparable to that of a low FEV1/FVC and FEV1. [ABSTRACT FROM AUTHOR]

PROBLEM: The protein CD14 is a pattern recognition receptor for bacterial lipopolysaccharide (LPS). Whether genetic variation has the same influence on soluble CD14 (sCD14) levels in human plasma and milk remains to be determined. METHOD OF STUDY: We measured sCD14 levels in plasma during pregnancy (n = 196) and in milk in the postpartum (n = 152) for women genotyped for the single nucleotide polymorphisms (SNPs) at positions -1619, -550, and -159 from the transcription start site of the CD14 gene. RESULTS: Plasma-and milk-sCD14 levels differed significantly both by CD14/-1619 and CD14/-550 genotypes and by haplotypes. Most interestingly, sCD14 levels were regulated differentially by the same genetic variants in plasma and milk, with the CD14/)550T allele and the corresponding are ATC haplotype associated with high sCD14 in milk but low sCD14 in plasma. A correlation between sCD14 levels in plasma and milk was absent (r = 0.091, P = NS). CONCLUSIONS: Our findings suggest the existence of cell-specific regulation mechanisms of CD14 gene expression. [ABSTRACT FROM AUTHOR]