Shyamali C. Dharmage

Environmental research • October 24, 2024

Albina Gross, Rachel Tham, Shyamali Dharmage, Martin Röösli, Urs Frey, Olga Gorlanova

Background: The association between long-term ambient air pollution and adult lung function has been inconsistently reported. This systematic review and meta-analysis aimed to quantify the impact of long-term (≥1 year) ambient air pollution on adult lung function. Methods: Original articles published between 1 January 2006 and 26 July 2024 were searched in PubMed, Embase and Web of Science. Random-effects models were used to assess the strength of associations of gaseous (nitrogen dioxide and ozone) and particulate matter (PM) pollutants with diameters ≤2.5 and 10 µg, with lung function (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio). Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system (GRADE) approach. Results: Of 25 064 potential papers, 27 were included, of which 12 were meta-analysed. There was low-certainty evidence that a 10 µg·m-3 increase in long-term NO2 exposure was associated with lower FEV1 (-15.6 mL, 95% CI -25.0- -6.2; I 2=86%; p<0.01) and high-certainty evidence for FVC (-25.3 mL, 95% CI -36.7- -14.0; I 2=70%, p<0.01). Similar associations were observed for PM2.5, while long-term exposure to O3 and PM10 were associated with lower FEV1 with high- and moderate-certainty evidence, respectively. Exposure to O3 was associated with lower FEV1/FVC (high-certainty evidence). Conclusions: Long-term exposure to ambient air pollution adversely impacts adult lung function. This emphasises the importance of ongoing commitments to mitigating air pollution levels to preserve optimum lung health and prevent premature lung function decline that can lead to earlier and avoidable respiratory diseases.

Expert Opinion On Drug Discovery • May 16, 2025

Maria Bordukova, Alina Arneth, Nikita Makarov, Robyn Brown, Elena Schneider Futschik, Shyamali Dharmage, Elif Ekinci, Peter Crack, Danny Hatters, Alastair Stewart, David Stroud, Teresa Sadras, Gary Anderson, Fabian Schmich, Raul Rodriguez Esteban, Michael Menden

Patient management strategies have evolved from a one-drug-fits-all approach to precision [Citation1] and personalized medicine [Citation2,Citation3], significantly improving treatment efficacy, safety, and outcomes [Citation2]. However, achieving genuine individualization at the patient level remains a substantial challenge. Generative artificial intelligence (AI) has the potential to revolutionize personalized healthcare by enabling the creation of synthetic data that augments observed data, building a continuum of patients and capturing rare conditions, thereby fundamentally enhancing our understanding of patient characteristics and treatment responses [Citation4]. Generative AI powers the development of digital twins [Citation5]—virtual patient representations capable of simulating the effects of different pharmacological treatments and predicting outcomes in individual patients – marking a paradigm shift toward fully personalized medicine. Conventionally, the one-drug-fits-all approach applies a standard treatment to all patients, irrespective of individual patient characteristics (Figure 1(a)). For instance, amoxicillin is often prescribed to treat chest, ear, or urinary tract bacterial infections [Citation6]. The same antibiotic is used for a broad population of patients, even though they have differences in genetic characteristics and microbiome diversity and hence may have different responses or sensitivities to the drug. This approach, while effective for many, does not account for individual variability or allergic reactions, which can lead to suboptimal outcomes or adverse effects.

Environmental Research • April 05, 2025

Yaoyao Qian, Garun Hamilton, Chamara Senaratna, Caroline Lodge, Michael Abramson, Xin Dai, Dinh Bui, Anurika De Silva, Paul Thomas, Bircan Erbas, Eugene Walters, Jennifer Perret, Shyamali Dharmage

Objective: The impact of household air pollution (HAP) on obstructive sleep apnoea (OSA) was unclear from the literature. We aimed to investigate the associations between HAP exposure over 10 years and OSA in middle-aged adults. Methods: Using the Tasmanian Longitudinal Health Study (TAHS), seven longitudinal HAP profiles were previously identified using information on household heating, cooking, mould, active and passive smoking exposure collected at two ages spanning 10 years (at mean ages 43 and 53 years). Probable OSA was only measured at 53 years using validated STOP-Bang, Berlin and OSA-50 questionnaires. Medically diagnosed OSA was self-reported. Multivariable logistic regression was used to assess the associations between HAP profiles and each definition of OSA, adjusting for age, sex, socioeconomic status and ambient air pollution. Results: Compared with the "Least exposed" profile, characterised by reverse-cycle air conditioning, electric cooking and no smoking exposure, the "Wood and gas heating/gas cooking/smoking" profile was associated with both probable OSA defined using OSA-50 (aOR=2.39, 95%CI 1.61-3.53) and medically diagnosed OSA (aOR=2.31, 1.06-5.05). The "All gas" and "Wood heating/smoking" profiles were associated with OSA-50-defined probable OSA (aOR=1.35, 1.01-1.79; aOR=1.47, 1.10-1.96 respectively). Additionally, the "All gas" profile was associated with incident medically diagnosed OSA (aOR=2.15, 1.06-4.38). Conclusions: Sustained exposure to wood and gas heating and gas cooking especially when combined with tobacco smoke increased the risk of OSA over 10 years in middle age. Our study strengthens the rationale for including the potential adverse effects of HAP on mid-life OSA within public educational programs and guidelines.

Pediatric Allergy And Immunology : Official Publication Of The European Society Of Pediatric Allergy And Immunology • March 19, 2025

Vikas Wadhwa, Shyamali Dharmage, Danielle Wurzel, Peter Sly, Cecilie Svanes, Adrian Lowe, N Idrose, Nilakshi Waidyatillake, Caroline Lodge, Melissa Russell

Background: Allergic sensitization and respiratory infections commonly occur in childhood. Interplay between them in asthma development is known as the 'two-hit' hypothesis. There has been no previous investigation of this hypothesis on adult lung function. Objective: In a birth cohort at high risk for allergic diseases, we investigated interactions between these two factors and lung function outcomes into adulthood. Methods: Allergic sensitization was assessed at age 24 months by skin prick testing to aero and food allergens. Respiratory infection was defined as cough, rattle or wheeze measured by frequent questionnaires up to age 24 months. Regression models were utilized to identify interactions between these exposures and associations with lung function at ages 12, 18 and 25 years. Results: At age 25 years, those sensitized at age 2 years(n = 118) demonstrated reductions in pre-bronchodilator FEV1 of 0.06(95% CI: -0.12, 0.00, z-score units, p = .055) for each additional month of respiratory infections. Those not sensitized (n = 120) had increases in pre-bronchodilator FEV1 of 0.07 (95% CI: 0.02, 0.13, z-score units, p = .012) for each additional month of respiratory infection(pinteraction = .012). Similar findings were noted for FEV1/FVC ratio(pinteraction = .011), FEF25-75(pinteraction = .007) and absolute change in pre and post bronchodilator lung function. At 18 years, findings were similar; however, there was less evidence for interactions at 12 years. Conclusions: Our study findings support the 'two-hit' hypothesis of interactions between early-life allergic sensitization and increasing respiratory infections, and impairment in lung function up to age 25 years. Early childhood respiratory infections however had different impacts on lung function depending upon the presence or absence of allergic sensitization.

Cancer Epidemiology • December 22, 2024

Simon Cheah, Adrian Lowe, Nina Afshar, Julie Bassett, Fiona Bruinsma, Wendy Cozen, Simon Harrison, John Hopper, Harindra Jayasekara, H Prince, Claire Vajdic, Nicole Doo, Graham Giles, Shyamali Dharmage, Roger Milne

Objective: Multiple myeloma (MM) is responsible for significant morbidity and mortality, yet our knowledge regarding MM aetiology remains limited. We investigated whether a history of allergic conditions is associated with MM risk. Methods: Incident cases (n = 782) of MM were recruited via cancer registries in Victoria and NSW. Controls (n = 733) were siblings (n = 436) or spouses (n = 297) of cases. Unconditional logistic regression was used to estimate odds ratios (OR) and 95 % confidence intervals (CI) for associations between self-reported allergic conditions (asthma, eczema, food allergy, hay fever) and MM risk. Results: Eczema was inversely associated with MM risk (OR = 0.54, 95 %CI = 0.42-0.70), as was a combined history of food allergy and eczema (OR = 0.52, 95 %CI = 0.29-0.93). There was an inverse association between a history of any allergic condition (compared with none) and risk of MM (OR = 0.68, 95 %CI = 0.55-0.84). In the mean-centred dose-risk analysis the OR was 0.87 (95 %CI = 0.73-1.04) per additional allergic condition of interest. No notable associations were identified for food allergy, asthma, or hay fever alone. Conclusions: We found that a history of allergic disease, particularly eczema, was associated with reduced MM risk. Further research is recommended to confirm findings and investigate potential mechanisms.