Alan L. James’s research while affiliated with Sir Charles Gairdner Hospital and other places

Background: Individuals with Preserved Ratio Impaired Spirometry (PRISm), defined as FEV1/FVC ≥0.7 and FEV1 <80% predicted, are at higher risk of developing COPD. However, data for Australian adults are limited. We aimed to describe prevalence of PRISm and its relationship with clinical characteristics in Australia. Method: Data from the Burden of Lung Disease (BOLD) Australia study of randomly selected adults aged ≥40 years from six sites was classified into airflow limitation, PRISm, or normal spirometry groups. Demographic, clinical characteristics, and lung function were compared between groups. Results: Of the study sample (n = 3518), 387 (11%) had PRISm, 549 (15.6%) had airflow limitation, and 2582 (73.4%) had normal spirometry. PRISm was more common in Indigenous Australian adults. Adults with PRISm had more frequent respiratory symptoms, more comorbidities, greater health burden and poorer quality of life than those with normal spirometry. Pre- and post-bronchodilator FEV1 and FVC were lower in adults with PRISm than those with airflow limitation. Adults with PRISm were less likely to use respiratory medicine than those with airflow limitation (OR = 0.56, 95% CI 0.38–0.81). Conclusions: PRISm was present in 11% of adults in this study and they had similar respiratory symptoms and health burden as adults with airflow limitation.

From the results of well‐performed population health studies, we now have excellent data demonstrating that deficits in adult lung function may be present early in life, possibly as a result of developmental disorders, incurring a lifelong risk of obstructive airway diseases such as asthma and chronic obstructive pulmonary disease. Suboptimal fetal development results in intrauterine growth restriction and low birth weight at term (an outcome distinct from preterm complications), which are associated with subsequent obstructive disease. Numerous prenatal exposures and disorders compromise fetal development and these are summarized herein. Various physiological, structural, and mechanical abnormalities may result from prenatal disruption, including changes to airway smooth muscle structure–function, goblet cell biology, airway stiffness, geometry of the bronchial tree, lung parenchymal structure and mechanics, respiratory skeletal muscle contraction, and pulmonary inflammation. The literature therefore supports the need for early life intervention to prevent or correct growth defects, which may include simple nutritional or antioxidant therapy. © 2024 American Physiological Society. Compr Physiol 14:5729‐5762, 2024.

Background Historical data on smoking can enhance our comprehension of the effectiveness of past tobacco control policies and play a key role in developing targeted public health interventions. This study was undertaken to assess trends in smoking initiation and cessation in Australia for the period 1910–2005. Methods Rates of smoking initiation and cessation were calculated for participants in two population-based cohorts, the Busselton Health Study and the Tasmanian Longitudinal Health Study. The effects of time trends, gender and age group were evaluated. Results Of the 29,971 participants, 56.8% ever smoked. In males, over the period 1910–1999, the rate of smoking initiation in young adolescents remained high with a peak in the 1970s; in older adolescents it peaked in the 1940s and then declined; in young adults it showed a steady decline. In females, the rate of smoking initiation in young adolescents rose sharply in the 1960s and peaked in the 1970s, in older adolescents it increased throughout the period, and in young adults it declined after 1970. In the period 1930–2005, 27.3% of 9,605 people aged 36–50 years who smoked ceased smoking. Rates of cessation in this age group increased throughout but decreased in males after 1990 and plateaued around 2000 in females. Conclusion Our findings show substantial variation in the efficacy of tobacco control policies across age groups, with a notable lack of success among the younger population.

Microbial communities at the airway mucosal barrier are conserved and highly ordered, in likelihood reflecting co-evolution with human host factors. Freed of selection to digest nutrients, the airway microbiome underpins cognate management of mucosal immunity and pathogen resistance. We show here the initial results of systematic culture and whole-genome sequencing of the thoracic airway bacteria, identifying 52 novel species amongst 126 organisms that constitute 75% of commensals typically present in heathy individuals. Clinically relevant genes encode antimicrobial synthesis, adhesion and biofilm formation, immune modulation, iron utilisation, nitrous oxide (NO) metabolism and sphingolipid signalling. Using whole-genome content we identify dysbiotic features that may influence asthma and chronic obstructive pulmonary disease. We match isolate gene content to transcripts and metabolites expressed late in airway epithelial differentiation, identifying pathways to sustain host interactions with microbiota. Our results provide a systematic basis for decrypting interactions between commensals, pathogens, and mucosa in lung diseases of global significance.

Quantifying airway smooth muscle (ASM) in patients with asthma raises the possibility of improved and personalized disease management. Endobronchial polarization-sensitive optical coherence tomography (PS-OCT) is a promising quantitative imaging approach that is in the early stages of clinical translation. To date, only animal tissues have been used to assess the accuracy of PS-OCT to quantify absolute (rather than relative) ASM in cross-sections with directly matched histological cross-sections as validation. We report the use of whole fresh human and pig airways to perform a detailed side-by-side qualitative and quantitative validation of PS-OCT against gold standard histology. We matched and quantified 120 sections from five human and seven pig (small and large) airways and linked PS-OCT signatures of ASM to the tissue structural appearance in histology. Notably, we found that human cartilage perichondrium can share with ASM the properties of birefringence and circumferential alignment of fibers, making it a significant confounder for ASM detection. Measurements not corrected for perichondrium overestimated ASM content several-fold (p<0.001, paired t-test). After careful exclusion of perichondrium, we found a strong positive correlation (r=0.96, p<0.00001) of ASM area measured by PS-OCT and histology, supporting the method's application in human subjects. Matching human histology further indicated that PS-OCT allows conclusions on the intra-layer composition and in turn potential contractile capacity of ASM bands. Together these results form a reliable basis for future clinical studies.