ERS 2024: Primary Asthma Prevention: Where are we in 2024?
Speaker- Bianca Schaub
Asthma prevention encompasses three levels: primary, secondary, and tertiary. Primary prevention focuses on fostering healthy development to prevent the initial onset of asthma. Secondary prevention targets the early detection and management of asthma manifestations and new sensitizations, aiming to reduce morbidity. Tertiary prevention seeks to manage and mitigate ongoing asthma complications and comorbidities. Environmental exposures, particularly farming-related, play a critical role in asthma risk. The discussion will address various harmful exposures, including aspects of the microbiome, nutrition, and the potential benefits of early immunotherapy. The Benjamin Franklin axiom, "an ounce of prevention is worth a pound of cure," underscores the importance of proactive measures. From 1994 to 2004, the Finnish asthma program significantly reduced the prevalence of severe asthma cases and associated costs by 72% through comprehensive national public health strategies. Similarly, the Finnish allergy program focused on transitioning from allergen avoidance to fostering tolerance.
The Lahti Regional Health and Environmental Programme, set to run until 2032, targets several key areas: enhancing healthy nutrition, advancing sustainable food production, increasing physical activity, promoting healthy housing and living environments, and improving citizens' exposure to nature. This comprehensive action plan addresses asthma, other chronic diseases, disease prevention, and environmental sustainability. Extensive study has explored the interaction between environmental factors and the immune system, revealing that certain harmful exposures may contribute to disease prevention. However, protective exposures are also crucial, mediated through various immune mechanisms, including the innate immune system, T cells, and regulatory cells. These mechanisms are relevant not only for asthma and allergic diseases but also for chronic conditions such as autoimmunity and other exposome-related diseases. Farm exposure stands out as a significant protective factor. For instance, the Martha study by Marcus Egan and Erika von Mutzius investigated the effects of minimally processed milk on asthma prevention, focusing on outcomes up to age five. The study faced challenges due to the COVID-19 pandemic, which impacted intervention but left pending data. Another key protective exposure involves dust extracts from European and Amish farms. Donata Vercelli and Erika Formozios identified 12 transport proteins in these dust extracts, including lipocalins like Bosd2 (bovine) and odorant-binding proteins. These studies have shown that murine models found the asthma-protective component between 28 and 64 kilodaltons. A parallel study involving asthma models on European farms has demonstrated that cows have been linked to beneficial outcomes as part of protective exposure. Analyses revealed shared proteins between distinct exposures, particularly lipocalins and others. Odorant-binding protein BOSD2 and other proteins in the stable serve as carriers for various cargos. Ongoing studies aim to translate these findings into practical applications, deepening our understanding of how environmental factors influence asthma.
Bacterial lysates, including polyvalent chemical bacterial lysates (PCBL) and mechanical bacterial lysates (PMBL), play a significant role in early immune system stimulation. They positively impact innate and adaptive immune responses by activating dendritic and lung epithelial cells, mimicking the natural microbiome. This activation can lead to reduced inflammation, a shift in atopic responses from T-helper 2 (TH2) to T-helper 1 (TH1), and an increase in regulatory T cell (Treg) activity. Clinical studies have demonstrated that bacterial lysates can lower the risk of wheezing episodes and asthma exacerbations. These findings suggest that bacterial lysates hold promise as a potential treatment option for asthma, given their ability to modulate immune responses and improve asthma-related outcomes.
The Broncho-Vaxom Efficacy Assessment Research Study (BEAR) was conducted across 31 centers in six European countries and involved hundreds of children. The study aims to evaluate the efficacy of Broncho-Vaxom, a bacterial lysate, in reducing respiratory tract infections and wheezing frequency. Respiratory tract infections are significant risk factors for wheezing and the development of asthma. The study employs 21 bacterial strains from five pathogenic genera and includes three study arms. The data collected is expected to provide insights into the effectiveness of Broncho-Vaxom in decreasing respiratory infections and wheezing. Meanwhile, four murine studies investigating the prenatal application of OM-85 (a bacterial lysate) have shown trends toward improved resistance to inflammatory and infectious airway challenges. These findings suggest that OM-85 may enhance immune system resilience against respiratory conditions.
The gut microbiome is crucial in regulating immune maturation and resistance to pathogens. Bifidobacterium, a beneficial bacterium, has been shown to have a protective effect against asthma in children, demonstrating a bidirectional interaction between the gut and the lungs. However, the condition can lead to intestinal damage and inflammation in children with asthma. Manipulating the gut microbiome can influence immune maturation by affecting the development and function of immune cells and enhancing resistance to pathogens. Short-chain fatty acids (SCFAs) are key components in this process, contributing to immune regulation and gut health. The chronic exchange of immune cells between the airway and gut epithelial cells is also significant, impacting systemic circulation and overall immune function.
Nutrition plays a vital role in preventing chronic diseases, with extensive data available on preventive strategies, healthy diets, and early dietary introductions. In Sweden, updated guidelines indicate no increase in asthma-related food allergies, eczema, or sensitization. SCFAs, including acetate, propionate, and butyrate, have been associated with a reduced prevalence of wheezing, asthma, and other allergic diseases in early life. These effects are thought to be mediated through anti-inflammatory mechanisms, potentially involving antioxidants or polyunsaturated fatty acids. Vitamin D exposure varies; additional factors such as Caesarean section delivery, exposure to animals, and lack of primary prevention against house dust mites also affect asthma risk. Early immunotherapy is an area of interest for pediatricians but is not widely available before age five in many countries. A systematic review of 24 qualitative and 18 meta-analysis studies suggests a potential preventive effect of early immunotherapy on asthma onset, particularly in children and those with mono-sensitization. However, sensitivity analyses revealed no statistically significant results, likely due to publication bias and moderate study heterogeneity. The risk ratios for asthma prevention are 0.71 for general cases, 0.64 for three years of therapy, and 0.49 for mono-sensitized patients.
Recent data indicates that early allergen immunotherapy can potentially prevent the onset of asthma. Real-world evidence shows that allergen immunotherapy can enhance long-term asthma control and lower the risk of developing asthma. It may also modulate non-targeted allergen-induced immune responses, affecting various immune cells such as interleukin-10 (IL-10)-producing type 2 innate lymphoid cells (ILC2s), regulatory T cells (Tregs), regulatory B cells (Bregs), and T-helper 2 (Th2) cells. Early allergen immunotherapy might also reduce the incidence of lower respiratory tract infections by improving gamma studies, which suggests a protective effect on respiratory tract infections. A recent study suggests that exposure to house dust mites might enhance epithelial antiviral resistance to viral infections. This could help explain the observed efficacy of allergen immunotherapy in reducing exacerbations in allergic asthma. Despite these promising findings, further study is necessary to fully elucidate the benefits and mechanisms of early allergen immunotherapy.
Public health policies are crucial in mitigating harmful influences and promoting a healthy lifestyle. Key protective exposures include innate stimulation through environmental factors, fostering a healthy microbiome, exposure to farming environments, balanced nutrition, early allergen immunotherapy, and maintaining a healthy lifestyle. Notable progress has been made in these areas. The challenge lies in determining the most effective primary and secondary prevention methods. For instance, bacterial lysates are considered a promising approach for primary prevention, while early allergen immunotherapy is more applicable for secondary prevention.
European Respiratory Society Congress 2024, 7–11 September, Vienna, Austria
