Influence of age, sex and respiratory viruses on the rates of emergency department visits and hospitalisations with respiratory tract infections, asthma and COPD.

BACKGROUND: The importance of age, sex and respiratory virus prevalence in emergency department (ED) visits and hospitalisations for respiratory tract infections (RTIs), asthma and COPD in a whole population over time is not well established. METHODS: This study retrospectively analysed data for daily ED visits and hospitalisations from 2003 to 2013 in Ontario, Canada and the daily number of virus positive tests. Daily numbers of ED visits and hospitalisations with RTIs, asthma and COPD listed as a primary diagnosis were collected from the Canadian Institute for Health Information. Virus data were obtained from the Respiratory Virus Detection Surveillance System. Multiple linear regression was used to assess the association of individual viruses with the daily rates. RESULTS: There were 4 365 578 ED visits and 321 719 (7.4%) admissions for RTIs, 817 141 ED visits and 260 665 (31.9%) admissions for COPD and 649 666 ED visits and 68 626 (10.6%) admissions for asthma. Respiratory syncytial virus and influenza A were associated with male ED visits, whereas human rhinovirus was associated with female ED visits for RTIs in preschool children. 19.2% of males, but only 7.2% of females were admitted. The correlation between the prevalence of each virus and ED visits and hospitalisations for asthma was weak, irrespective of age group and sex. Influenza A was most strongly associated with COPD ED visits and hospitalisations in males and females. CONCLUSIONS: There are significant age and sex differences in the contribution of respiratory viruses to the number of ED visits and hospitalisations for RTIs, asthma and COPD.

Disparate geographic prevalences of asthma, allergic rhinoconjunctivitis and atopic eczema among adolescents in five Canadian cities.

To assess concordance of prevalence rates of asthma, allergic rhinoconjunctivitis and atopic eczema symptoms among adolescents in five Canadian cities. The International Study of Asthma and Allergies in Childhood Phase 3 written questionnaires were answered by 8334 adolescents aged 13 to 14 in Vancouver, Saskatoon, Winnipeg, Hamilton and Halifax, Canada. Prevalence rates of current symptoms ranged from 13.7-33.0% for wheezing, 14.6-22.6% for allergic rhinoconjunctivitis and 8.2-10.4% for atopic eczema. Using Hamilton as reference, the prevalence of wheezing was significantly higher in Halifax (OR = 1.58; 95% CI 1.36-1.84) and Saskatoon (1.27; 1.07-1.50) and significantly lower in Vancouver (0.51; 0.44-0.59). In contrast, allergic rhinoconjunctivitis was significantly more prevalent in Winnipeg (1.39; 1.16-1.68) and Halifax (1.36; 1.14-1.61) and trended lower in Saskatoon (0.81; 0.66-1.00). Atopic eczema was significantly more prevalent in Winnipeg (1.31; 1.01-1.69) and Vancouver (1.28; 1.04-1.58). Multivariable logistic regression analyses showed the region of residence, being born in Canada, recent use of acetaminophen and heavy exposure to traffic exhaust were significantly associated with all three allergic conditions, while obesity and having two or more smokers at home was only associated with increased risk for wheezing. Chinese ethnicity decreased that risk. Among five Canadian centres, the highest prevalence rates of allergic rhinoconjunctivitis or atopic eczema were not observed in the same regions as the highest prevalence rates of wheezing. This disparity in regional variations in the prevalence rates suggests dissimilar risk factors for the development or expression of wheezing (asthma), allergic rhinoconjunctivitis and atopic eczema.

Cats and dogs and the risk of atopy in childhood and adulthood.

BACKGROUND: Exposure to cats and dogs during childhood has been linked to a lower risk of developing allergies. It remains unclear whether this is due to selective avoidance of pets by families with a history of allergies. The effects of pet ownership in adulthood are unknown. OBJECTIVES: We sought to assess the association between cat and dog ownership in childhood and early adulthood and the development of atopy in a population-based birth cohort of 1037 subjects. METHODS: Ownership of cats or dogs between birth and age 9 years and between the ages of 18 and 32 years was reported. Skin prick tests to common allergens were performed at 13 and 32 years. RESULTS: There was no evidence that families with a history of atopy avoided owning pets. There were significant cat-by-dog interactions for the development of atopy in both childhood and adulthood. Children who had owned both a cat and a dog were less likely to be atopic at age 13 years. Living with only one of these animals was not protective against atopy. Among those who were not atopic by age 13 years, having both a cat and a dog in adulthood was associated with a lower risk of new atopy by age 32 years. This association was only significant among those with a parental history of atopy. These effects were independent of a range of potential confounding factors. CONCLUSIONS: There is a synergistic interaction between cat and dog exposure that is associated with a lower risk of developing atopy in childhood and young adulthood.

Emergency department visits and hospitalisations for asthma, COPD and respiratory tract infections: what is the role of respiratory viruses, and return to school in September, January and March?

BACKGROUND: Asthma exacerbations increase in September coinciding with children returning to school. The aim of this study was to investigate whether this occurs 1) for COPD and respiratory tract infections (RTIs); 2) after school resumes in January and March; and 3) identify which viruses may be responsible. METHODS: Emergency department (ED) visits and admissions for asthma, COPD and RTIs and the prevalence of viruses in Ontario, Canada were analysed daily between 2003 and 2013. ED visits and admissions were provided by the Canadian Institute for Health Information. Viral prevalence was obtained from the Centre for Immunisation and Respiratory Infectious Diseases. RESULTS: ED visits and admissions rates demonstrated a biphasic pattern. Lowest rates occurred in July and August and the highest rates in September for asthma, and after December for COPD and RTI. The increase in rates for 30 days before and after school return in September was greatest for children with asthma <15 years (2.4-2.6×). Event rates fell after school return in January for all three conditions ranging from 10-25%, and no change followed March break for asthma and COPD. Human rhinovirus was prevalent in summer with a modest relationship to asthma rates in September. The prevalence of respiratory syncytial virus, influenza A and coronavirus was associated with sustained event rates for COPD and RTIs. CONCLUSIONS: Asthma, COPD and RTIs increase in September but do not occur after return to school in January and March. Human rhinovirus is associated with ED visits and admissions only in September.

Prevalence and contribution of respiratory viruses in the community to rates of emergency department visits and hospitalizations with respiratory tract infections, chronic obstructive pulmonary disease and asthma.

BACKGROUND: The individual and combined contribution of viral prevalence in the community to Emergency Department (ED) visits and hospitalizations with respiratory tract infections (RTIs), chronic obstructive pulmonary disease (COPD) and asthma is unclear. METHODS: A retrospective analysis on daily viral positive tests and daily ED visits and hospitalizations between 01/01/2003 to 31/12/2013 in Ontario, Canada. Viral data was collected from the Centre for Immunization and Respiratory Infectious Diseases (CIRID). The Canadian Institute for Health Information reports daily ED visits and hospitalizations for RTIs, COPD and asthma as a primary diagnosis. RESULTS: There were 4,365,578 ED visits with RTIs of which 321,719 (7.4%) were admitted to hospital; 817,141 ED visits for COPD of which 260,665 (31.9%) were admitted and 649,666 ED visits with asthma of which 68,626 (10.6%) were admitted. The percentage of positive tests to influenza A and B, respiratory syncytial virus (RSV), parainfluenza and adenovirus prevalence explained 57.4% of ED visits and 63.8% of hospitalizations for RTI, 41.4% of ED visits and 39.2% of hospitalizations with COPD but only 1.5% of ED visits and 2.7% of hospitalizations for asthma. The further addition of human metapneumovirus, rhinovirus and coronavirus over the final 3 years accounted for 66.7% of ED visits and 74.4% of hospitalizations for RTI, 52.5% of visits and 48.2% of hospitalizations for COPD, and only 13.3% of visits and 10.4% of hospitalizations for asthma. CONCLUSIONS: Community respiratory viral epidemics are major drivers of ED visits and hospitalizations with RTIs and COPD but only a modest contributor to asthma.

Accelerated decline in lung function in cigarette smokers is associated with TP53/MDM2 polymorphisms.

In vitro studies have shown that p53 mediates a protective response against DNA damage by causing either cell-cycle arrest and DNA repair, or apoptosis. These responses have not yet been demonstrated in humans. A common source of DNA damage in humans is cigarette smoke, which should activate p53 repair mechanisms. As the level of p53 is regulated by MDM2, which targets p53 for degradation, the G-allele of a polymorphism in intron 1 of MDM2 (rs2279744:G/T), that results in higher MDM2 levels, should be associated with a reduced p53 response and hence more DNA damage and corresponding tissue destruction. Similarly, the alleles of rs1042522 in TP53 that encode arginine (G-allele) or proline (C-allele) at codon 72, which cause increased pro-apoptotic (G-allele) or cell-cycle arrest activities (C-allele), respectively, may moderate p53's ability to prevent DNA damage. To test these hypotheses, we examined lung function in relation to cumulative history of smoking in a population-based cohort. The G-alleles in MDM2 and TP53 were found to be associated with accelerated smoking-related decline in lung function. These data support the hypothesis that p53 protects from DNA damage in humans and provides a potential explanation for the variation in lung function impairment amongst smokers.

Cigarette smoking and allergic sensitization: a 32-year population-based cohort study.

BACKGROUND: Cigarette smoke has immunosuppressant effects, but its effect on allergic sensitization is unclear. OBJECTIVE: To investigate associations between parental and personal smoking and skin prick tests (SPTs) for atopy in a population-based birth cohort of 1037 participants followed to adulthood. METHODS: Parental history of atopic disease, parental smoking, and personal smoking were obtained at multiple assessments between birth and age 32 years. Atopy was assessed by SPTs for 11 common inhaled allergens at ages 13 and 32 years. RESULTS: Children of atopic parents were less likely to have positive SPTs at age 13 years if either parent smoked (odds ratio, 0.55; P = .009). This association was not significant after adjusting for breast-feeding history, number of siblings, and childhood socioeconomic status. Subjects with atopic parents were also less likely to develop positive results to SPTs between ages 13 and 32 years if they smoked themselves (odds ratio, 0.18; P < .001). This reduction in risk remained significant after adjusting for multiple potential confounding factors. Neither parental nor personal smoking was significantly associated with allergic sensitization among subjects whose parents did not have a history of atopic disease. Few of those with positive SPT results at age 13 years had negative tests at age 32 years, and there was no evidence that this was influenced by smoking. CONCLUSION: Personal and parental smoking is associated with a reduced risk of allergic sensitization in people with a family history of atopy.

Prevalence of asthma among Chinese adolescents living in Canada and in China.

BACKGROUND: Studies of the prevalence of asthma among migrating populations may help in identifying environmental risk factors. METHODS: We analyzed data from Vancouver, Canada, and from Guangzhou, Beijing and Hong Kong, China, collected during phase 3 of the International Study of Asthma and Allergies in Childhood. We subdivided the Vancouver adolescents according to whether they were Chinese immigrants to Canada, Canadian-born Chinese or Canadian-born non-Chinese. We compared the prevalence of asthma and wheezing among Chinese adolescents born in Canada, Chinese adolescents who had immigrated to Canada and Chinese adolescents living in China. RESULTS: Of 7794 Chinese adolescents who met the inclusion criteria, 3058 were from Guangzhou, 2824 were from Beijing, and 1912 were from Hong Kong. Of 2235 adolescents in Vancouver, Canada, 475 were Chinese immigrants, 617 were Canadian-born Chinese, and 1143 were Canadian-born non-Chinese. The prevalence of current wheezing among boys ranged from 5.9% in Guangzhou to 11.2% in Canadian-born Chinese adolescents. For girls, the range was 4.3% in Guangzhou to 9.8% in Canadian-born Chinese adolescents. The prevalence of ever having had asthma ranged from 6.6% to 16.6% for boys and from 2.9% to 15.0% for girls. Prevalence gradients persisted after adjustment for other environmental variables (odds ratios for ever having had asthma among Canadian-born Chinese compared with native Chinese in Guangzhou: 2.72 [95% confidence interval 1.75-4.23] for boys and 5.50 [95% confidence interval 3.21-9.44] for girls; p < 0.001 for both). Among Chinese adolescents living in Vancouver, the prevalence of ever wheezing increased with duration of residence, from 14.5% among those living in Canada for less than 7 years to 20.9% among those living their entire life in Canada. The same pattern was observed for the prevalence of ever having had asthma, from 7.7% to 15.9%. INTERPRETATION: Asthma symptoms in Chinese adolescents were lowest among residents of mainland China, were greater for those in Hong Kong and those who had immigrated to Canada, and were highest among those born in Canada. These findings suggest that environmental factors and duration of exposure influence asthma prevalence.

A longitudinal, population-based, cohort study of childhood asthma followed to adulthood.

BACKGROUND: The outcome of childhood asthma in adults has been described in high-risk cohorts, but few population-based studies have reported the risk factors for persistence and relapse. METHODS: We assessed children born from April 1972 through March 1973 in Dunedin, New Zealand, repeatedly from 9 to 26 years of age with questionnaires, pulmonary-function tests, bronchial-challenge testing, and allergy testing. RESULTS: By the age of 26 years, 51.4 percent of 613 study members with complete respiratory data had reported wheezing at more than one assessment. Eighty-nine study members (14.5 percent) had wheezing that persisted from childhood to 26 years of age, whereas 168 (27.4 percent) had remission, but 76 (12.4 percent) subsequently relapsed by the age of 26. Sensitization to house dust mites predicted the persistence of wheezing (odds ratio, 2.41; P=0.001) and relapse (odds ratio, 2.18; P=0.01), as did airway hyperresponsiveness (odds ratio for persistence, 3.00; P<0.001; odds ratio for relapse, 3.03; P<0.001). Female sex predicted the persistence of wheezing (odds ratio, 1.71; P=0.03), as did smoking at the age of 21 years (odds ratio, 1.84; P=0.01). The earlier the age at onset, the greater the risk of relapse (odds ratio, 0.89 per year of increase in the age at onset; P<0.001). Pulmonary function was consistently lower in those with persistent wheezing than in those without persistent wheezing. CONCLUSIONS: In an unselected birth cohort, more than one in four children had wheezing that persisted from childhood to adulthood or that relapsed after remission. The factors predicting persistence or relapse were sensitization to house dust mites, airway hyperresponsiveness, female sex, smoking, and early age at onset. These findings, together with persistently low lung function, suggest that outcomes in adult asthma may be determined primarily in early childhood.

Systemic inflammation and lung function in young adults.

BACKGROUND: Impaired lung function is associated with systemic inflammation and is a risk factor for cardiovascular disease in older adults. It is unknown when these associations emerge and to what extent they are mediated by smoking, chronic airways disease, and/or established atherosclerosis. We explored the association between the forced expiratory volume in one second (FEV(1)) and the systemic inflammatory marker C-reactive protein (CRP) in young adults. METHODS: Associations between spirometric lung function and blood CRP were assessed in a population based birth cohort of approximately 1000 New Zealanders at ages 26 and 32 years. Analyses adjusted for height and sex to account for differences in predicted lung function and excluded pregnant women. RESULTS: There were significant inverse associations between FEV(1) and CRP at both ages. Similar results were found for the forced vital capacity. These associations were similar in men and women and were independent of smoking, asthma, and body mass index. CONCLUSIONS: Reduced lung function is associated with systemic inflammation in young adults. This association is not related to smoking, asthma, or obesity. The reasons for the association are unexplained, but the findings indicate that the association between lower lung function and increased inflammation predates the development of either chronic lung disease or clinically significant atherosclerosis. The association between poor lung function and cardiovascular disease may be mediated by an inflammatory mechanism.

Factors affecting exhaled nitric oxide measurements: the effect of sex.

BACKGROUND: Exhaled nitric oxide (F(E)NO) measurements are used as a surrogate marker for eosinophilic airway inflammation. However, many constitutional and environmental factors affect F(E)NO, making it difficult to devise reference values. Our aim was to evaluate the relative importance of factors affecting F(E)NO in a well characterised adult population. METHODS: Data were obtained from 895 members of the Dunedin Multidisciplinary Health and Development Study at age 32. The effects of sex, height, weight, lung function indices, smoking, atopy, asthma and rhinitis on F(E)NO were explored by unadjusted and adjusted linear regression analyses. RESULTS: The effect of sex on F(E)NO was both statistically and clinically significant, with F(E)NO levels approximately 25% less in females. Overall, current smoking reduced F(E)NO up to 50%, but this effect occurred predominantly in those who smoked on the day of the F(E)NO measurement. Atopy increased F(E)NO by 60%. The sex-related differences in F(E)NO remained significant (p < 0.001) after controlling for all other significant factors affecting F(E)NO. CONCLUSION: Even after adjustment, F(E)NO values are significantly different in males and females. The derivation of reference values and the interpretation of FENO in the clinical setting should be stratified by sex. Other common factors such as current smoking and atopy also require to be taken into account.

Associations between respiratory symptoms, lung function and gastro-oesophageal reflux symptoms in a population-based birth cohort.

BACKGROUND: Several studies have reported an association between asthma and gastro-oesophageal reflux, but it is unclear which condition develops first. The role of obesity in mediating this association is also unclear. We explored the associations between respiratory symptoms, lung function, and gastro-oesophageal reflux symptoms in a birth cohort of approximately 1000 individuals. METHODS: Information on respiratory symptoms, asthma, atopy, lung function and airway responsiveness was obtained at multiple assessments from childhood to adulthood in an unselected birth cohort of 1037 individuals followed to age 26. Symptoms of gastro-oesophageal reflux and irritable bowel syndrome were recorded at age 26. RESULTS: Heartburn and acid regurgitation symptoms that were at least "moderately bothersome" at age 26 were significantly associated with asthma (odds ratio = 3.2; 95% confidence interval = 1.6-6.4), wheeze (OR = 3.5; 95% CI = 1.7-7.2), and nocturnal cough (OR = 4.3; 95% CI = 2.1-8.7) independently of body mass index. In women reflux symptoms were also associated with airflow obstruction and a bronchodilator response to salbutamol. Persistent wheezing since childhood, persistence of asthma since teenage years, and airway hyperresponsiveness since age 11 were associated with a significantly increased risk of heartburn and acid regurgitation at age 26. There was no association between irritable bowel syndrome and respiratory symptoms. CONCLUSION: Reflux symptoms are associated with respiratory symptoms in young adults independently of body mass index. The mechanism of these associations remains unclear.

Asthma in remission: can relapse in early adulthood be predicted at 18 years of age?

STUDY OBJECTIVE: To determine the frequency of relapse of asthma in young adults in remission at 18 years of age, during a follow-up period of 8 years, and to identify possible prognostic markers for relapse. DESIGN: Longitudinal study of birth cohort (n = 1,037) born in New Zealand in 1972-1973. SETTING: University hospital research clinic. MEASUREMENTS: Participants were assessed at 9, 11, 13, 15, 18, 21, and 26 years of age using a respiratory questionnaire (all ages), spirometry (all ages), bronchodilator response (18 years and 26 years of age), methacholine challenge (9, 11, 13, 15, and 21 years of age), and allergen skin-prick testing (13 years and 21 years of age). RESULTS: Approximately one third of study members (35%) with asthma in remission at 18 years of age relapsed by 21 years or 26 years of age. Atopy and lower FEV(1)/FVC ratio at 18 years of age were significant independent prognostic factors for relapse in multiple logistic regression analyses. Increased responsiveness to methacholine (provocative concentration < 8 mg/mL) or bronchodilator (improvement in FEV(1) >/= 10%) at 21 years of age were more common among those with relapse, but the positive and negative predictive values for a previous positive methacholine challenge test result at 15 years of age were low. Asthma after relapse was generally mild (mean FEV(1) 97.1% predicted). Totally new adult asthma developed by 26 years of age in 9% of study members who had no asthma or wheezing at any time up to 18 years of age. CONCLUSIONS: Subsequent relapse of previously diagnosed asthma in remission at 18 years of age occurs in one in three young adults. Such relapse is not easily predicted, especially by measurements of airway responsiveness. A history of asthma currently in remission should not be used to prejudice employment opportunities for young adults.

Outcome in adulthood of asymptomatic airway hyperresponsiveness in childhood: a longitudinal population study.

The clinical outcome of asymptomatic airway hyperresponsiveness (AHR) first detected in childhood is sparsely reported, with conflicting results. We used a birth cohort of 1,037 children followed to age 26 years to assess the clinical outcome of asymptomatic AHR to methacholine first documented in study members at age 9 years. Of 547 study members who denied wheezing symptoms ever at age 9 years, 41 (7.5%) showed AHR. Forty showed methacholine responsiveness, with a provocation concentration of methacholine that elicited a 20% drop in forced expired volume in 1 sec (PC(20)) < or = 8 mg/mL, and one had baseline airway obstruction with a bronchodilator response exceeding 10%. Of these 41 study members, 18 (44%), 11 (27%), and 4 (10%) maintained AHR in 1, 2, and 3 later assessments, respectively, while 23 (56%) manifested AHR only at age 9. Compared with asymptomatic study members without AHR, those with asymptomatic AHR at age 9 years were more likely to report asthma and wheeze at any subsequent assessment, were more likely to have high IgE levels and eosinophils at ages 11 and 21, and more often demonstrated positive responses to skin allergen testing at ages 13 and 21 years. Persistent AHR at later assessments increased these likelihoods further.In conclusion, asymptomatic children with AHR are more likely to develop asthma and atopy later in life compared with asymptomatic children without AHR. Persistent AHR, even though initially asymptomatic, was associated with an even greater increased risk of development of asthma. We suggest that rather than considering AHR as a marker of asthma, it should be regarded as a parallel pathological process that may lead to subsequent symptoms and clinical evidence of asthma.

The Christmas season as a risk factor for chronic obstructive pulmonary disease exacerbations.

BACKGROUND: Epidemics of hospitalization for chronic obstructive pulmonary disease (COPD) occur annually during the Christmas holidays, and COPD exacerbations commonly coincide with respiratory viral infections. OBJECTIVE: To compare the incidence and determinants of COPD exacerbations occurring between the Christmas holiday period and the remainder of the winter season. METHODS: Seventy-one subjects with COPD of mixed severity faxed daily symptom diaries to a computer monitoring system from December 1, 2006, to April 30, 2007. Possible exacerbations prompted a home visit for assessment, spirometry and specimen collection for virological testing. RESULTS: Study subjects submitted a total of 95.4% of possible daily symptom diary sheets by fax. Of 114 possible COPD exacerbations detected using the faxed diaries, 110 met the Anthonisen criteria for true exacerbations. A total of 47 exacerbations (mean 6.7/week) occurred during the Christmas holiday period, while 63 exacerbations (mean 4.3/week) occurred during the remainder of winter. Of the Christmas period exacerbations and of those in the balance of winter, 21 (44%) and 20 (32%), respectively, coincided with respiratory viral infections. CONCLUSIONS: The incidence of COPD exacerbations during the Christmas period was greater than during the rest of winter in 2006/2007 and peaked immediately before Christmas - in contrast to hospital presentation for COPD, which peaked during the Christmas week. No clear role of respiratory viral infections in the increased rate of exacerbations during the Christmas period was established in the present study. COPD patients were highly compliant with daily symptom reporting using faxed daily diaries, which permitted nearly complete detection of all exacerbations that occurred at incidence.

Changes in exhaled nitric oxide related to estrogen and progesterone during the menstrual cycle.

BACKGROUND: Significant changes in asthma and atopy occur throughout the menstrual cycle. We hypothesized that the characteristics of asthma (eg, symptoms, exhaled nitric oxide [eNO] levels as a marker of airway inflammation, pulmonary function, and atopy) vary throughout the menstrual cycle in relation to changes in the levels of estrogen or progesterone and that this variation is attenuated in women using oral contraception (OC). METHODS: Seventeen women with asthma were studied over the course of their menstrual cycle through daily measurements of symptoms, eNO, spirometry, 17beta-estradiol, and progesterone levels, and through the performance of alternate-day allergy skin-prick tests (SPTs). RESULTS: Of 534 potential daily visits, 526 (98.5%) were completed. Women not using OC (n = 8) had higher mean eNO levels (48.2 parts per billion [ppb]; 95% CI, 43.1 ppb to 53.3 ppb) than women using OC (27.0 ppb; 95% CI, 24.2 ppb to 29.7 ppb; p

Interactions between breast-feeding, specific parental atopy, and sex on development of asthma and atopy.

BACKGROUND: The influence of breast-feeding on the risk of developing atopy and asthma remains controversial. OBJECTIVE: To examine asthma and atopy outcomes by sex, reported specific parental history of atopy, and breast-feeding. METHODS: In a birth cohort, we examined childhood asthma and atopy (positive skin prick tests) by sex and breast-feeding in relation to maternal and paternal atopy. Interactions were explored in logistic regression models. RESULTS: For boys, breast-feeding (odds ratio [OR], 1.63; 95% CI, 0.93-2.87; P = .09) and maternal atopy (OR, 1.95; 95% CI, 0.93-4.08; P = .08) were each associated with atopy at age 13 years. Breast-feeding increased the risk for atopy among boys with paternal atopy (OR, 7.39; 95% CI, 2.21-24.66) compared with non-breast-fed boys with paternal atopy, but did not significantly further increase risk among subjects with maternal atopy. For girls, breast-feeding (OR, 0.74; 95% CI, 0.41-1.31) and maternal and paternal atopy were not independent risk factors for atopy at age 13 years. However, breast-feeding increased the risk for atopy in girls with maternal atopy (OR, 3.13; 95% CI, 1.20-8.14) compared with non-breast-fed girls with maternal atopy. There was no such effect among subjects with paternal atopy. Results for the outcome of asthma followed a similar pattern. CONCLUSION: The influence of breast-feeding on development of atopy and asthma differs by sex and by maternal and paternal atopy, and is most significant among subjects at lower baseline risk. CLINICAL IMPLICATIONS: Analyses of environmental risk factors for asthma and atopy should be stratified by specific parental atopy and sex.

Attenuation of the September epidemic of asthma exacerbations in children: a randomized, controlled trial of montelukast added to usual therapy.

BACKGROUND: A recurring epidemic of asthma exacerbations in children occurs annually in September in North America when school resumes after summer vacation. OBJECTIVE: Our goal was to determine whether montelukast, added to usual asthma therapy, would reduce days with worse asthma symptoms and unscheduled physician visits of children during the September epidemic. PATIENTS AND METHODS: A total of 194 asthmatic children aged 2 to 14 years, stratified according to age group (2-5, 6-9, and 10-14 years) and gender, participated in a double-blind, randomized, placebo-controlled trial of the addition of montelukast to usual asthma therapy between September 1 and October 15, 2005. RESULTS: Children randomly assigned to receive montelukast experienced a 53% reduction in days with worse asthma symptoms compared with placebo (3.9% vs 8.3%) and a 78% reduction in unscheduled physician visits for asthma (4 [montelukast] vs 18 [placebo] visits). The benefit of montelukast was seen both in those using and not using regular inhaled corticosteroids and among those reporting and not reporting colds during the trial. There were differences in efficacy according to age and gender. Boys aged 2 to 5 years showed greater benefit from montelukast (0.4% vs 8.8% days with worse asthma symptoms) than did older boys, whereas among girls the treatment effect was most evident in 10- to 14-year-olds (4.6% [montelukast] vs 17.0% [placebo]), with nonsignificant effects in younger girls. CONCLUSIONS: Montelukast added to usual treatment reduced the risk of worsened asthma symptoms and unscheduled physician visits during the predictable annual September asthma epidemic. Treatment-effect differences observed between age and gender groups require additional investigation.

Adiposity, asthma, and airway inflammation.

BACKGROUND: Several studies have found obesity to be associated with an increased prevalence of asthma. For reasons that remain unclear, this association has often been reported to be stronger in women than in men. One possible explanation might be that these studies have used body mass index to identify adiposity, which might be a less reliable measure of body fat in men than in women. OBJECTIVE: We sought to explore the association between body fat percentage measured by means of bioelectrical impedance analysis and asthma, airflow obstruction, and airway inflammation in men and women. METHODS: Respiratory questionnaires, spirometry, bronchodilator response, exhaled nitric oxide level, and percentage of body fat were measured in a population-based cohort of approximately 1000 individuals at age 32 years. RESULTS: There was a significant association between the percentage of body fat and asthma in women (P = .043) but not in men (P = .75). Airflow obstruction was associated with percentage of body fat in women (P = .046), but there was an inverse association in men (P = .010). Bronchodilator responsiveness was also associated with lower body fat in men (P = .004). Airway inflammation, measured by means of exhaled nitric oxide, was not associated with body fat in either women (P = .17) or men (P = .25). CONCLUSION: Adiposity is associated with asthma and airflow obstruction in women. This does not appear to be mediated by airway inflammation. In men airflow obstruction and bronchodilator responsiveness are associated with a lower percentage of body fat. CLINICAL IMPLICATIONS: In women, but not in men, obesity is associated with asthma and airflow obstruction, but there was no association with airway inflammation.

Association between exhaled nitric oxide and systemic inflammatory markers.

BACKGROUND: Asthma is an inflammatory condition of the airways, and there is some evidence to suggest that it is associated with a systemic inflammatory response, as measured by C-reactive protein (CRP) and fibrinogen. Exhaled nitric oxide is a noninvasive measure of asthmatic airway inflammation. OBJECTIVE: To determine if there is an association between exhaled nitric oxide and these systemic inflammatory markers. METHODS: The Dunedin Multidisciplinary Health and Development Study is a birth cohort of approximately 1,000 individuals born between April 1, 1972, and March 31, 1973. At the age of 32 years, study members were assessed for diagnosis of asthma, atopy by skin prick testing, smoking, body mass index, exhaled nitric oxide, high-sensitivity serum CRP, and plasma fibrinogen level. RESULTS: There was no significant association between exhaled nitric oxide and CRP (P = .99). There was a trend to an inverse association between exhaled nitric oxide and fibrinogen (P = .049), but this was not significant after adjusting for smoking and use of corticosteroids or after further adjustment for body mass index and atopy (P = .71). CONCLUSION: In this population-based sample of young adults, there was no association between airway inflammation, as measured by exhaled nitric oxide, and systemic inflammation, as measured by either CRP or fibrinogen.