Publications by authors named "Nilakshi T Waidyatillake"

Background: The impact of early rapid body mass index (BMI) increase on asthma risk and subsequent lung function remains contentious, with limited prospective studies during a critical window for lung growth.

Objective: We investigated the associations between BMI trajectories in the first 2 years of life, and adolescent asthma and lung function.

Methods: Anthropometric data was collected up to 18 times in the first 24 months on 620 infants from the Melbourne Atopy Cohort Study. BMI trajectories were developed using group-based trajectory modelling. Associations between these trajectories and spirometry, fractional exhaled nitric oxide, and current asthma status at 12 and/or 18 years of age were modelled using multiple linear and logistic regression.

Results: Five BMI trajectories were identified. Compared to the "average trajectory", children belonging to the "early low and catch up" and "persistently high" BMI trajectories were at higher risk of asthma at 18 years (OR=2·2; 95%CI 1·0, 4·8 and 2·4; 1·1, 5·3 respectively). These trajectories were also associated with lower FEV1 by FVC, and higher FeNO levels at 18 years. In addition, children belonging to the "persistently low" trajectory had lower FEV1 (β=-183·9 ml; 95%CI -340·9, -26·9) and FVC (β=-207·8 ml; -393·6, -22·0) at 18 years.

Conclusion: In this cohort, "early low & catch up" and "persistently high" trajectories were associated with asthma and obstructive lung function pattern in adolescence. Having a persistently low BMI at an early age was associated with a restrictive pattern. Thus, maintenance of normal growth patterns may lead to improved adolescent respiratory health.

Background: There is limited information on risk factors for eczema in adults. Recent evidence suggests that air pollution may be associated with increased incidence of eczema in adults. We aimed to assess this possible association.

Methods: Ambient air pollution exposures (distance from a major road, nitrogen dioxide [NO ], fine particulate matter with an aerodynamic diameter ≤2.5 µm [PM ]) were assessed for the residential address of Tasmanian Longitudinal Health Study participants at ages 43 and 53 years. Eczema incidence (onset after age 43 years), prevalence (at 53 years), and persistence were assessed from surveys, while IgE sensitization was assessed using skin prick tests. The presence or absence of eczema and sensitization was classified into four groups: no atopy or eczema, atopy alone, non-atopic eczema, and atopic eczema. Adjusted logistic and multinomial regression models were fitted to estimate associations between ambient air pollution and eczema, and interaction by sex was assessed.

Results: Of 3153 participants in both follow-ups, 2369 had valid skin prick tests. For males, a 2.3 ppb increase in baselineNO was associated with increased odds of prevalent eczema (OR = 1.15 [95% CI 0.98-1.36]) and prevalent atopic eczema (OR = 1.26 [1.00-1.59]). These associations were not seen in females (p for interaction = 0.08, <0.01). For both sexes, a 1.6 µg/m increase in PM exposure at follow-up was associated with increased odds of aeroallergen sensitization (OR = 1.15 [1.03-1.30]).

Conclusion: Increased exposure to residential ambient air pollutants was associated with an increased odds of eczema, only in males, and aeroallergen sensitization in both genders.

Background: The association between grass pollen exposure and early markers of asthma exacerbations such as lung function changes and increase in airway inflammation is limited. We investigated the associations between short-term grass pollen exposure and lung function and airway inflammation in a community-based sample, and whether any such associations were modified by current asthma, current hay fever, pollen sensitization, age, and other environmental factors.

Methods: Cross-sectional and short-term analyses of data from the Melbourne Atopy Cohort Study (MACS) participants (n = 936). Lung function was assessed using spirometry. Airway inflammation was assessed by fractional exhaled nitric oxide (FeNO) and exhaled breath condensate pH and nitrogen oxides (NOx). Daily pollen counts were collected using a volumetric spore trap. The associations were examined by linear regression.

Results: Higher ambient levels of grass pollen 2 days before (lag 2) were associated with lower mid-forced expiratory flow (FEF ) and FEV /FVC ratio (Coef. [95% CI] = -119 [-226, -11] mL/s and -1.0 [-3.0, -0.03] %, respectively) and also 3 days before (lag 3). Increased levels of grass pollen a day before (lag 1) were associated with increased FeNO (4.35 [-0.1, 8.7] ppb) and also at lag 2. Adverse associations between pollen and multiple outcomes were greater in adults with current asthma, hay fever, and pollen sensitization.

Conclusion: Grass pollen exposure was associated with eosinophilic airway inflammation 1-2 days after exposure and airway obstruction 2-3 days after exposure. Adults and individuals with asthma, hay fever, and pollen sensitization may be at higher risk.

Buruli ulcer (BU) is a subcutaneous necrotic infection of the skin caused by Mycobacterium ulcerans. It is the third most common human mycobacterial disease after tuberculosis (TB) and leprosy. The available methods for detection of the bacilli in lesions are microscopic detection, isolation and cultivation of the bacterium, histopathology, and polymerase chain reaction (PCR). These methods, although approved by the World Health Organization (WHO), have infrastructural and resource challenges in medical centres and cell-mediated immunity (CMI) and/or serology-based tests have been suggested as easier and more appropriate for accurate assessment of the disease, especially in remote or underdeveloped areas. This study systematically reviewed and conducted a meta-analysis for all research aimed at developing cell-mediated immunity (CMI) and/or serology-based tests for M. ulcerans disease. Information for this review was searched through PubMed and Web of Science databases and identified up to June 2019. References from relevant articles and reports from the WHO Annual Meeting of the Global Buruli Ulcer Initiative were also used. Twelve studies beginning in 1952, that attempted to develop CMI and/or serology-based tests for the disease were identified. These studies addressed issues of specificity and sensitivity in context of antigen composition as well as study heterogeneity and bias. The two main types of antigenic preparations considered were pathogen-derived and recombinant protein preparations. There was slight difference in test performance when M. ulcerans recombinant proteins [positivity: 67.5%; 32.5%] or pathogen-derived [positivity: 76.0%; 24.0%] preparations were used as test antigens among BU patients. However, pathogen-derived preparations were better at differentiating between patients and control groups [odds ratio (OR) of 27.92, 95%CI: 5.05-154.28]. This was followed by tests with the recombinant proteins [OR = 1.23, 95%CI: 0.27-5.62]. Overall, study heterogeneity index, I2 was 92.4% (p = 0.000). It is apparent from this review that standardisation is needed in any future CMI and/or serology-based tests used for M. ulcerans disease.

Background: Glutathione S-transferase (GST) genes are involved in the management of oxidative stress in the lungs. We aimed to determine whether they modify the associations between early life smoke exposure and adverse lung health outcomes.

Methods: The Melbourne Atopy Cohort study (a high-risk birth cohort) enrolled 620 children and followed them prospectively from birth. We recorded perinatal tobacco smoke exposure, asthma, and lung function at 12 (59%) and 18 years (66%) and genotyped for GSTM1, GSTT1, and GSTP1 (69%).

Results: GST genotypes were found to interact with tobacco smoke exposure on lung function outcomes (P interaction ≤ .05). Only among children with GSTT1 null genotypes was exposure to mother's, father's, or parental tobacco smoke in early life associated with an increased risk of reductions in prebronchodilator (BD) FEV and FVC at both 12 and 18 years. These associations were not seen in children with GSTT1 present. Similarly, only among children with GSTM1 null genotypes was exposure to father's or parental smoking associated with reductions in pre- and post-BD FEV and FVC at 18 years. Only among children with Ile/Ile genotypes of GSTP1 was exposure to mother's smoking associated with increased risk of reduced FEV at 18 years, but this was not the case among children with Val/Val or Ile/Val genotypes.

Conclusions: Our study provides evidence of interaction between early tobacco smoke exposure and GST genotypes on lung function. Carriers of GST null mutations and GSTP1 Ile/Ile alleles may be more susceptible when exposed to tobacco smoke in early life. These findings support stronger recommendations to protect all infants from tobacco smoke exposure.

Trial Registry: Australian and New Zealand Clinical Trials Registry; No.: ACTRN12609000734268; URL: http://www.anzctr.org.au/.

Early identification of people at risk of developing COPD is crucial for implementing preventive strategies. We aimed to systematically review and assess the performance of all published models that predicted development of COPD. A search was conducted to identify studies that developed a prediction model for COPD development. The Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies was followed when extracting data and appraising the selected studies. Of the 4,481 records identified, 30 articles were selected for full-text review, and only four of these were eligible to be included in the review. The only consistent predictor across all four models was a measure of smoking. Sex and age were used in most models; however, other factors varied widely. Two of the models had good ability to discriminate between people who were correctly or incorrectly classified as at risk of developing COPD. Overall none of the models were particularly useful in accurately predicting future risk of COPD, nor were they good at ruling out future risk of COPD. Further studies are needed to develop new prediction models and robustly validate them in external cohorts.

The objective was to assess associations between duration of total and exclusive breastfeeding and lung function up to adolescence.A birth cohort (Melbourne Atopy Cohort Study) of 620 infants with a family history of allergic disease was recruited. Mothers were encouraged to breastfeed exclusively for 6 months. Lung function was assessed at 12 and 18 years of age. Associations between breastfeeding and lung function were investigated using multivariable linear regression and path analysis was used to assess the potential mediating factors.Duration of breastfeeding (total and exclusive) was not associated with most assessed lung function outcomes. However, there was a trend for increased pre-bronchodilator mid-expiratory flow (MEF) at both 12 (adjusted mean difference (95% CI) per week of breastfeeding of 10 (-1-20) mL·s(-1)) and 18 years (11 (-1-22) mL·s(-1)) (p-values of 0.07 and 0.08, respectively). There was a strong indirect effect of height on these observed associations.Duration of breastfeeding does not appear to greatly influence lung function outcomes in children with a family history of allergic diseases. Longer duration of exclusive breastfeeding may be associated with an increase in MEF, partly due to greater attained height of the child.

With the global trend of increasing asthma and allergic disorders there is strong interest regarding early life nutrition as a potentially modifiable risk factor for lung disease. This systematic review includes 10 studies that assessed the effect of breastfeeding on lung growth and function. The review found breastfeeding to be beneficial for lung function, with the most consistent effect on increased forced vital capacity. There was no clear evidence that the relationship between breastfeeding and lung function was mediated through other factors. Furthermore, the findings from the few studies that investigated if maternal asthma modified the effect of breastfeeding on lung function were inconsistent. Further research is needed to determine the specific details such as duration and type (exclusive vs partial) of breastfeeding that leads to improved lung function.