Atopy in people aged 40 years and over: Relation to airflow limitation.

BACKGROUND: Previous studies have reached conflicting conclusions about the role of atopy as a risk factor for COPD. In part, this is attributable to variation in the definitions of airflow limitation and the treatment of people with asthma. OBJECTIVE: To establish whether there is any independent association between atopy and post-bronchodilator airflow limitation in the general population aged 40 years and over. METHODS: A cross-sectional survey was conducted in a general population sample of 2415 people aged 40 years and over in Australia. A history of ever being diagnosed with asthma was elicited by questionnaire. Atopy was defined as any skin prick test weal to common aeroallergens ≥4 mm. Airflow limitation was defined as post-bronchodilator spirometric (FEV1 /FVC) ratio

Omega-3 supplementation during the first 5 years of life and later academic performance: a randomised controlled trial.

BACKGROUND/OBJECTIVES: Consumption of oily fish more than once per week has been shown to improve cognitive outcomes in children. However, it is unknown whether similar benefits can be achieved by long-term omega-3 fatty acid supplementation. The objective was to investigate the effect of omega-3 fatty acid supplementation during the first 5 years of life on subsequent academic performance in children by conducting a secondary analysis of the CAPS (Childhood Asthma Prevention Study). SUBJECTS/METHODS: A total of 616 infants with a family history of asthma were randomised to receive tuna fish oil (high in long-chain omega-3 fatty acids, active) or Sunola oil (low in omega-3 fatty acids, control) from the time breastfeeding ceased or at the age of 6 months until the age of 5 years. Academic performance was measured by a nationally standardised assessment of literacy and numeracy (National Assessment Program Literacy and Numeracy (NAPLAN)) in school years 3, 5, 7 and 9. Plasma omega-3 fatty acid levels were measured at regular intervals until 8 years of age. Between-group differences in test scores, adjusted for maternal age, birth weight and maternal education, were estimated using mixed-model regression. RESULTS: Among 239 children, there were no significant differences in NAPLAN scores between active and control groups. However, at 8 years, the proportion of omega-3 fatty acid in plasma was positively associated with the NAPLAN score (0.13 s.d. unit increase in score per 1% absolute increase in plasma omega-3 fatty acid (95% CI 0.03, 0.23)). CONCLUSIONS: Our findings do not support the practice of supplementing omega-3 fatty acids in the diet of young children to improve academic outcomes. Further exploration is needed to understand the association between plasma omega-3 fatty acid levels at 8 years and academic performance.

Variance components analyses of multiple asthma traits in a large sample of Australian families ascertained through a twin proband.

BACKGROUND: Intermediate phenotypes are often measured as a proxy for asthma. It is largely unclear to what extent the same set of environmental or genetic factors regulate these traits. OBJECTIVE: Estimate the environmental and genetic correlations between self-reported and clinical asthma traits. METHODS: A total of 3,073 subjects from 802 families were ascertained through a twin proband. Traits measured included self-reported asthma, airway histamine responsiveness (AHR), skin prick response to common allergens including house dust mite (Dermatophagoides pteronyssinus [D. pter]), baseline lung function, total serum immunoglobulin E (IgE) and eosinophilia. Bivariate and multivariate analyses of eight traits were performed with adjustment for ascertainment and significant covariates. RESULTS: Overall 2,716 participants completed an asthma questionnaire and 2,087 were clinically tested, including 1,289 self-reported asthmatics (92% previously diagnosed by a doctor). Asthma, AHR, markers of allergic sensitization and eosinophilia had significant environmental correlations with each other (range: 0.23-0.89). Baseline forced expiratory volume in 1 s (FEV(1)) showed low environmental correlations with most traits. Fewer genetic correlations were significantly different from zero. Phenotypes with greatest genetic similarity were asthma and atopy (0.46), IgE and eosinophilia (0.44), AHR and D. pter (0.43) and AHR and airway obstruction (-0.43). Traits with greatest genetic dissimilarity were FEV(1) and atopy (0.05), airway obstruction and IgE (0.07) and FEV(1) and D. pter (0.11). CONCLUSION: These results suggest that the same set of environmental factors regulates the variation of many asthma traits. In addition, although most traits are regulated to great extent by specific genetic factors, there is still some degree of genetic overlap that could be exploited by multivariate linkage approaches.

Repeatability of peak nasal inspiratory flow measurements and utility for assessing the severity of rhinitis.

BACKGROUND: The measurement of peak nasal inspiratory flow (PNIF) provides a simple, cheap, fast and readily available tool for determining the extent of nasal airway patency. However, there are questions regarding its repeatability when used to assess the degree of nasal obstruction in large populations. Therefore, this study aimed to evaluate the repeatability of PNIF measurements and to assess their association with the signs and symptoms of rhinitis. METHODS: The PNIF, rhinitis symptoms, judged by Meltzer questionnaire and rhinitis signs, as determined by anterior rhinoscopy, were assessed in 283 adults representative of the general population. One training and two test PNIF measurements were recorded during the same session. RESULTS: The PNIF was highly reproducible (ICC = 0.92; 95% limits of agreement: +/-36 l/min). The PNIF was strongly correlated with rhinitis signs, measured by anterior rhinoscopy (rs= -0.38, P < 0.0001) but was not correlated with rhinitis symptoms, measured by questionnaire (rs= -0.11, P = 0.057). Differences in PNIF for subjects categorized as asymptomatic, mild or moderate/severe on the basis of rhinitis signs, were highly significant (P < 0.0001), but less significant on the basis of rhinitis symptoms (P = 0.04). A PNIF cut-off of 115 l/min had moderately high specificity (72%) and sensitivity (65%) and a high negative predictive value (90%) for moderate/severe signs of rhinitis. CONCLUSION: In a large general population-based sample of young adults, PNIF was highly reproducible and closely related to the signs of rhinitis, as determined by clinical examination. The PNIF provides information that is qualitatively different to that provided by symptom scores and may be useful to measure the extent of nasal obstruction.

Effects of gas and other fume emitting heaters on the development of asthma during childhood.

BACKGROUND: Several studies have shown adverse effects of gas cookers and heaters on respiratory health. The long term effects of early life exposure to these appliances are not known. This study investigated the effect of exposure to fume emitting heaters, currently and during the first year of life, on the risk of asthma outcomes. METHODS: A cross sectional study of schoolchildren (n = 627) aged 8-11 years was conducted in Belmont, Australia. Information on symptoms and heating types was collected by parent completed questionnaire. Atopy was assessed by skin prick tests and airway hyperresponsiveness (AHR) was assessed by histamine challenge test. RESULTS: There was no association between the current use of fume emitting heaters and any of the asthma outcomes. However, having been exposed to fume emitting heaters during the first year of life was associated with an increased risk of having AHR (relative risk (RR) 1.47, 95% confidence interval (CI) 1.06 to 2.03), recent wheeze (RR 1.44, 95% CI 1.11 to 1.86), and recent wheeze + AHR (RR 2.08, 95% CI 1.31 to 3.31). CONCLUSION: If confirmed in other settings, this finding would require a review of the range of heating types that are appropriate for use in households in which young children live.

Written individualised management plans for asthma in children and adults.

BACKGROUND: Non-adherence to treatment advice is a common phenomenon in asthma and may account for a significant proportion of the morbidity. Comprehensive care that includes asthma education, a written self-management plan and regular review has been shown to improve asthma outcomes, but the contribution of these components has not been established. OBJECTIVES: To determine whether the provision of a written asthma self-management plan increases adherence and improves outcome. SEARCH STRATEGY: We carried out a search on the Cochrane Airways Group trials register. There was no language restriction. The search of the databases used the following terms: action plan OR self OR self-care OR self-manag* OR educ* AND adher* OR comply OR compli*. We contacted authors of included studies for any unpublished or on-going studies and bibliographies of all included studies and reviews were searched for further studies. The most recent search was carried out in May 2003. SELECTION CRITERIA: We only considered randomised controlled trials (RCTs) in patients with asthma. Participants must have been assigned to receive an individualised written asthma management plan (symptom or peak flow based) about the actions required for regular asthma management and/or the actions to take in the event of an asthma exacerbation. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed study quality and abstracted data. MAIN RESULTS: Seven trials met the inclusion criteria. The written management plans were either peak flow or symptom based, which were compared against each other or compared to no written management plan. Reported outcomes included: medication adherence, hospitalisation, emergency department visits, oral corticosteroid use, lung function, days lost from school/work, unscheduled doctor visits and respiratory tract infections. There was no consistent evidence that written plans produced better patient outcomes than no written plan. For some outcomes, there appeared to be an advantage of one type of plan over the other, but there was no consistency - one type of plan was not consistently more effective than another. REVIEWERS' CONCLUSIONS: The available trials are too small and the results too few and inconsistent to form any firm conclusions as to the contribution of written self management plans in the known beneficial effects of a comprehensive asthma care programme.

Childhood factors that predict asthma in young adulthood.

Predicting adult asthma, using childhood characteristics, is important for advising on prognosis and, potentially, for secondary prevention. A novel use of multivariate likelihood ratios (LRs) to quantify prognosis is described here. Of 718 subjects of a community-based cohort, 575 (80%) members were recruited at age 8-10 yrs and were re-assessed 15-17 yrs later. At baseline, information about symptoms, spirometry, histamine challenge and skin-prick tests were collected. At follow-up "asthma symptoms" were defined as wheeze, sleep disturbance from asthma or inhaled steroid use within the previous year. LRs were calculated for significant predictors of this outcome. Shinkage factors were applied to yield multivariate LRs. Childhood characteristics that independently predicted asthma symptoms in adulthood were obstructive spirometry (adjusted (adj)LR 2.9, 95% confidence interval (CI) 1.3-6.5), airway hyperresponsiveness (adjLR 2.6, 95% CI 1.8-3.7), atopy (adjLR 2.0, 95% CI 1.5-2.7), recent wheeze (adjLR 1.9, 95% CI 1.5-2.5) and being female (adjLR 1.29, 95% CI 0.8-2.1). Children with all five characteristics had a cumulative LR of 36.9 for asthma symptoms in adulthood. Most adults who had asthma symptoms did not have manifestations of asthma as children. However, the presence of obstructive spirometry, airway hyperresponsiveness and atopy in childhood identifies individuals with increased likelihood of having asthma in adulthood. Cumulative likelihood ratios are more valuable than odds ratios for quantifying risk in individuals and for identifying people with most to gain from preventive interventions.

Use of a paper disposable cup as a spacer is effective for the first-aid management of asthma.

OBJECTIVE: There are many settings in which a spacer device is not available for the administration of bronchodilator. Therefore, we tested whether a paper disposable cup is as effective as a commercially produced spacer to administer bronchodilator. METHODOLOGY: Randomised controlled trial. 50 subjects aged 16-50 years who had wheeze and a greater than 10% decrease in FEV1 after histamine inhalation test (HIT). Subjects were randomised to either the 150 ml paper disposable cup group (CUP) or the commercially produced spacer group (SPACER). Twenty minutes after 400 microg salbutamol was administered FEV1 was measured. The recovery index measured post-bronchodilator FEV1 as a percentage of baseline FEV1. Also, analysis of covariance tested whether recovery of FEV1 was related to the magnitude of the fall following the HIT. RESULTS: There were no statistically significant differences between CUP and SPACER groups in any characteristics. There was no difference for the recovery index (t48=1.14, P=0.26). Regression analyses showed that the relation between the magnitude of the fall in FEV1 during the HIT and the percent recovery was not different between the CUP and SPACER groups (t=-1.2, P<0.23). CONCLUSIONS: A paper disposable cup was effective for the reversal of mild to moderate bronchoconstriction. Therefore, a paper disposable cup can be used for the first-aid management of asthma when there is concern about cross-infection and a commercially produced spacer is not available.

Subject discomfort associated with the histamine challenge in a population study.

BACKGROUND: Many review articles report the safety and lack of serious side-effects associated with the histamine challenge. Even though methacholine and hypertonic saline are more commonly used to measure airway responsiveness, histamine challenges are used in many countries around the world. Levels of subjects discomfort after a challenge have not been quantified. This study quantified the incidence, severity and duration of subject discomfort after histamine challenge. METHODS: Ninety-nine subjects were recruited in an Australian multi-centre population-based study of the genetic epidemiology of asthma. Subjects completed a histamine challenge with final cumulative dose 3.2 micromol. Immediately, and 10 min, after challenge subjects rated their discomfort for cough, headache, throat irritation, hoarse voice and flushed. Research personnel also reported their perception of subjectdiscomfort. RESULTS: Subjects and research personnel reported a small degree of subject discomfort for all symptoms immediately after the histamine challenge. Overall, median symptom scores were less than 1.5 out of 10. Discomfort scores improved 10 min after challenge and cough, throat irritation and flushed improved significantly CONCLUSIONS: This study confirms the tolerability of the histamine challenge.

Particulate masks and non-powdered gloves reduce latex allergen inhaled by healthcare workers.

BACKGROUND: Although allergy to latex is a well-characterized phenomenon, some hospitals continue to provide staff with powdered latex gloves as an option to low- or non-powdered gloves. OBJECTIVE: We aimed to measure the extent to which inhalation of latex particles could be reduced by the use of protective masks or by replacing powdered latex gloves with non-powdered latex gloves. METHODS: Twenty healthcare workers in a hospital setting wore nasal air samplers (NAS) and Institute of Occupational Medicine (IOM) samplers for four 20-min periods. Subjects wore powdered gloves, non-powdered gloves and no gloves during three sampling periods, and in the fourth, subjects applied an aerosol barrier face-mask or a particulate face-mask (N95) while wearing powdered gloves. All samples were stained for particles bearing Hev b 5 allergen by the Halogen assay. RESULTS: All subjects inhaled Hev b 5 bearing particles in all sampling periods. IOM samplers collected particles at 70% of the rate of NAS. The number of particles inhaled while wearing powdered gloves was 23.8-fold higher than when not wearing gloves and 9.7-fold higher than when wearing non-powdered latex gloves (P < 0.0001). Wearing an aerosol barrier mask did not significantly reduce the number of particles inhaled (P = 0.108), while use of particulate masks significantly reduced the number of particles inhaled by 17.4-fold (P = 0.003). CONCLUSIONS: Use of non-powdered gloves is the most effective method of reducing occupational aeroallergen exposure to latex arising from gloves. However, secondary protection using particulate masks is a valid alternative, and may be helpful for preventing respiratory sensitization.

Written individualised management plans for asthma in children and adults.

BACKGROUND: Non-adherence to treatment advice is a common phenomenon in asthma and may account for a significant proportion of the morbidity. Comprehensive care that includes asthma education, written self-management plan and regular review has been shown to improve asthma outcomes, but the contribution of these components has not been established. OBJECTIVES: To determine whether the provision of a written asthma self-management plan increases adherence and improves outcome. SEARCH STRATEGY: A search was carried out on the Cochrane Airways Group trials register. There was no language restriction. The search of the databases used the following terms: action plan OR self OR self-care OR self-manag* OR educ* AND adher* OR comply OR compli*. Authors of included studies were contacted for any unpublished or on-going studies and bibliographies of all included studies and reviews were searched for further studies. SELECTION CRITERIA: Only randomised controlled trials (RCTs) in patients with asthma were considered. Participants must have been assigned to receive an individualised written asthma management plan (symptom or peak flow based) about the actions required for regular asthma management and/or the actions to take in the event of an asthma exacerbation. DATA COLLECTION AND ANALYSIS: Study quality was assessed and data abstracted by two reviewers independently. MAIN RESULTS: Six trials met the inclusion criteria. The written management plans were either peak flow or symptom based, which were compared against each other or compared to no written management plan. Reported outcomes included: hospitalisation, emergency department visits, oral corticosteroid use, lung function, days lost from school/work, unscheduled doctor visits and respiratory tract infections. There was no consistent evidence that written plans produced better patient outcomes than no written plan. For some outcomes, there appeared to an advantage of one type of plan over the other, but there was no consistency - one type of plan was not consistently more effective than another. REVIEWER'S CONCLUSIONS: The available trials are too small and the results too inconsistent to form any firm conclusions as to the contribution of written self management plans in the known beneficial effects of a comprehensive asthma care programmes.

Risk factors for onset and remission of atopy, wheeze, and airway hyperresponsiveness.

BACKGROUND: Although many children with asthma may have a remission as they grow and other children who did not have asthma may develop asthma in adult life, knowledge about the factors that influence the onset and prognosis of asthma during adolescence and young adulthood is very limited. METHODS: A cohort of 8-10 year old children (n=718) living in Belmont, New South Wales, Australia were surveyed six times at 2 yearly intervals from 1982 to 1992, and then again 5 years later in 1997. From this cohort, 498 subjects had between three and seven assessments and were included in the analysis. Atopy, airway hyperresponsiveness (AHR), and wheeze in the last 12 months were measured at each survey. Late onset, remission, and persistence were defined based on characteristics at the initial survey and the changes in characteristics at the follow up surveys. RESULTS: The proportion of subjects with late onset atopy (13.7%) and wheeze (12.4%) was greater than the proportion with remission of atopy (3.2%) and wheeze (5.6%). Having atopy at age 8-12 years (OR 2.8, 95% CI 1.5 to 5.1) and having a parental history of asthma (OR 2.0, 95% CI 1.02 to 4.13) were significant risk factors for the onset of wheeze. Having AHR at age 8-12 years was a significant risk factor for the persistence of wheeze (OR 4.3, 95% CI 1.3 to 15.0). Female sex (OR 1.9, 95% CI 1.01 to 3.60) was a significant risk factor for late onset AHR whereas male sex (OR 1.9, 95% CI 1.1 to 2.8) was a significant risk factor for late onset atopy. CONCLUSIONS: The onset of AHR is uncommon during adolescence, but the risk of acquiring atopy and recent wheeze for the first time continues during this period. Atopy, particularly present at the age of 8-10 years, predicts the subsequent onset of wheeze.

Continuing the debate about measuring asthma in population studies.

The reasons for measuring atopy and airway hyperresponsiveness (AHR) and the methods of validating measurements of asthma in population studies continue to be debated. The debate has centred around standards against which to validate asthma measurements but the absence of a "gold standard" makes the criterion validation of measurements difficult. Questionnaires will always be useful but cannot be validated against a doctor diagnosis because of self-selection and recall biases. In practice, measurements should be selected on the merits of what they measure rather than being regarded as validated or non-validated alternatives. The measurement of AHR is invaluable because it is reliable, not influenced by variations in symptom perception or diagnostic trends, and is closely related to the underlying mechanisms of asthma. The value of AHR lies in its high specificity (rate of true negatives) and low sensitivity (rate of false positives) against asthma symptoms which gives additional information about symptomatic subjects. Atopy is also a useful test and, in quantifying its association with asthma, we should not place any currency on ecological evidence. Atopy is a strong risk factor for asthma in the presence of regionally specific allergens and ecological analyses that ignore these effects are diversionary rather than productive. For preventing asthma, we need to identify the group at greatest risk of developing it, measure the risk factors with precision, and develop interventions that are effective in changing environmental exposures and homogeneous outcomes. This is the only approach that has the potential to lead to significant public health benefits.

Problems and possibilities in understanding the natural history of asthma.

In early life, asthma symptoms can occur intermittently or may not be severe enough to limit normal activities, which makes it difficult for the clinician to make reliable predictions and administer therapy with some precision. In the case of pediatric asthma, the identification of children who will experience the development of a clinically important illness that will impair their quality of life can be a complex process. The usual methods for describing this information include the prognostic statistics of sensitivity, specificity, likelihood ratio, and positive predictive value. The sensitivity, specificity, and likelihood ratio of various early markers of asthma have been calculated from several cohort studies. (J Allergy Clin Immunol 2000;106:S144-52.)

Problems and possibilities in understanding the natural history of asthma.

In early life, asthma symptoms can occur intermittently or may not be severe enough to limit normal activities, which makes it difficult for the clinician to make reliable predictions and administer therapy with some precision. In the case of pediatric asthma, the identification of children who will experience the development of a clinically important illness that will impair their quality of life can be a complex process. The usual methods for describing this information include the prognostic statistics of sensitivity, specificity, likelihood ratio, and positive predictive value. The sensitivity, specificity, and likelihood ratio of various early markers of asthma have been calculated from several cohort studies.

Lung function growth and its relation to airway hyperresponsiveness and recent wheeze. Results from a longitudinal population study.

To evaluate the association between growth in height and growth in lung function, and to identify the potential temporal relationships between airway hyperresponsiveness (AHR), respiratory symptoms, and lung function growth during adolescence and young adulthood, we analyzed data collected from the Belmont cohort. Among the 718 schoolchildren initially studied at 1982 (aged 8-10 yr), 557 were studied between two times and six times at 2-yr intervals until 1992. Baseline lung function, AHR by histamine inhalation test, and recent wheeze by questionnaires, were measured at each visit. We found that between 17 and 19 yr of age, when growth in height had stopped, growth in FEV(1) was approximately 200 ml/yr in boys and 100 ml/yr in girls. Peak growth velocity of height occurred at age 13 both in boys and in girls, whereas peak growth velocity of FEV(1) occurred at the same age only in girls and 1 yr later in boys. Having AHR and recent wheeze at the previous study time were both associated with lower subsequent growth in FEV(1), but not with subsequent growth in FVC. We conclude that lung function continues to grow after the cessation of height growth and that growth in FEV(1) is reduced in subjects with AHR and/or recent wheeze.

The effect of parental smoking on presence of wheez or airway hyper-responsiveness in New South Wales school children.

BACKGROUND AND AIMS: To assess accurately the effect of parental smoking on the respiratory health of New South Wales (NSW) school children, we obtained a large data set by pooling data from seven cross-sectional studies conducted in NSW between 1991 and 1993. METHODS: A random sample of 6394 children age eight to 11 years was studied. Respiratory symptoms, family history of asthma and parental smoking history were measured by questionnaire, atopy by skin prick test and airway hyper-responsiveness (AHR) by histamine inhalation test. RESULTS: In total, 58.3% of children had at least one parent who smoked; 38.5% were exposed to maternal smoking. After adjusting for potential confounders, such as atopy, parental history of asthma and bronchitis in the first two years, children who were exposed to maternal smoking had a significantly increased risk of recent wheeze but not of AHR (odds ratios 1.33; 95% CI: 1.2-1.5 and 1.00; 95% CI: 0.9-1.2). CONCLUSIONS: The positive association with wheeze and the lack of an association with AHR suggests that exposure to parental smoking leads to wheezing, but does not increase airway responsiveness.

Comparison of three definitions of asthma: a longitudinal perspective.

In epidemiological studies, defining "current asthma" as the presence of both wheeze in the last year and airway hyperresponsiveness (AHR) identifies children with more severe abnormality compared with children with either measure alone. The predictive value of this definition of asthma and other commonly used definitions have not been compared. In 1982, we enrolled a random sample of 718 schoolchildren aged 8-10 years, and in 1992, we restudied a representative sample of 407. On both occasions, we measured wheeze, medication use, morbidity, AHR, and atopy. We compared three asthma definitions-"current asthma," recent wheeze, and doctor-diagnosed asthma. Approximately 70% of subjects classified by each definition remained consistently classified in 1992. However, the current asthma definition distinguished a group with more severe illness after 10 years than did the other asthma definitions. The current asthma definition not only differentiates children with more severe asthma, but also differentiates those with a more severe prognosis.