[The impact of maternal smoking during pregnancy on respiratory disease in children]. / Impact du tabagisme au cours de la grossesse sur les pathologies respiratoires de l'enfant.

Among the causes of abnormal fetal lung development, active and environmental maternal smoking represents a major potential target in preventive medicine. Prevalence of smoking among women, particularly during pregnancy, varies across the different regions of the world. We reviewed the literature on the repercussions of maternal smoking on the lungs of the fetus and the neonate. One of the main consequences is prematurity, leading to pulmonary bronchodysplasia followed by respiratory infections, which particularly affect young children. In the medium- and long-term, smoking in utero leads to asthma and allergies, and is suspected to be associated with impaired respiratory function in children and teenagers. We also report on the potential effects of e-cigarettes, which represent an emerging threat to children's respiratory health.

Evidence of the association between asthma and lung cancer risk from mendelian randomization analysis.

Asthma and lung cancer are both significant public health concerns worldwide. Previous observational studies have indicated a potential link between asthma and an increased risk of lung cancer, whereas the causal relationship remains uncertain. We aimed to investigate the potential causal relationship between asthma and lung cancer risk utilizing Mendelian randomization (MR) design.The present study employed a two-sample MR analysis utilizing summary statistics from genome-wide association studies (GWAS) with European descent of asthma and lung cancer. The MR analysis was performed using inverse variance weighting (IVW), supplemented with MR-Egger regression and weighted median method to investigate the potential causality between asthma and lung cancer. Furthermore, Sensitivity analyses were also conducted to ensure the reliability of the findings. The MR analysis showed that genetically predicted asthma had suggestive causal association with the elevated risk of lung cancer [odds ratio (OR), 1.05 (95%Cl,1.01-1.09), P = 0.01]. The consistent direction of effects observed in the three methods further supported this finding. In addition, sensitivity analyses demonstrated the reliability of the results. This study provided potential evidence supporting a causal association between asthma and lung cancer. These findings highlighted the importance of early detection and prevention strategies for lung cancer in individuals with asthma. Further research was needed to elucidate the underlying mechanisms linking asthma and lung cancer.

Chest CT assess the impact of omalizumab treatment on airway remodeling in refractory asthma.

BACKGROUND: To evaluate the benefits of omalizumab treatment in patients through real-world follow-up and assess the impact of omalizumab treatment on airway remodeling using chest CT. METHODS: This is a single-center prospective, observational study included Chinese patients with refractory asthma who received omalizumab treatment from May 2021 to December 2022. We collected real-world clinical data, including their hospitalization information, pulmonary function, FENO, laboratory assessment, ACT scores, chest CT at baseline and every follow-up month. A comparison was made between the pre-treatment and post-treatment laboratory indicators, pulmonary function, airway parameters, and mucous plug scores under chest CT. RESULTS: This study included a total of 61 patients with refractory asthma treated with omalizumab. The study found that: ①regardless of whether the treatment lasted for a full four months or not, it significantly improved patient asthma control scores and reduced hospitalization costs and length of stay (p < 0.05). ②After four months of treatment, pulmonary ventilation function examination revealed significant improvements (p < 0.05) in MEF75, MEF50, MEF75/25, PEF, and FEV1/FVC. ③After four months of omalizumab treatment, the ratio of wall thickness and outer radius (T/D) and wall area percentage (WA%) of the bronchial wall decreased significantly (p < 0.05). ④After medication, the expression of airway mucous plugs decreased. CONCLUSIONS: Omalizumab treatment can reduce airway wall thickness, decrease the percentage of airway wall area, and the expression of airway mucous plugs, thereby improving airflow limitation. Utilizing chest CT provides a novel and intuitive assessment of the efficacy of omalizumab treatment. TRIAL REGISTRATION: This study was registered in Chinese Clinical Trial Registry, the number is ChiCTR2100046343.

Viral Determinants of Childhood Asthma Exacerbation Severity and Treatment Response.

BACKGROUND: Although respiratory viruses are common triggers of asthma exacerbations, the influence of viral infection characteristics on exacerbation presentation and treatment response in the pediatric emergency department (ED) is unclear. OBJECTIVE: To assess viral infection characteristics of children experiencing ED asthma exacerbations and to test their associations with severity and treatment response. METHODS: Prospective study of children, 4-18 years, who received standard ED asthma exacerbation treatment with inhaled bronchodilators and systemic corticosteroids. Nasal swabs collected for viral metagenomic analyses determined virus presence, load and species. Outcomes included exacerbation severity (Pediatric Asthma Severity (PAS) score, clinician impression, and vital signs) and treatment response (discharge home without needing additional asthma therapies). RESULTS: Of 107 children, 47% had moderate/severe exacerbations by PAS and 64% demonstrated treatment response. Viral metagenomic analysis on nasal swabs from 73 children detected virus in 86%, with 10 different species identified, primarily rhinovirus A (RV-A), RV-C, and enterovirus D68. Exacerbations involving RV-A were milder (odds ratio [OR]=0.25; 95% CI=0.07-0.83) and tended to be more responsive to treatment compared to non-RV-A infections, whereas exacerbations involving enterovirus D68 were more severe (OR=8.3; 95% CI=1.3-164.7) and had no treatment response association. Viral load was not associated with treatment response but exhibited a strong linear relationship with heart rate (rpartial=0.48), respiratory rate (rpartial=0.25), and oxygen saturation (rpartial=-0.25), indicative of severity. CONCLUSIONS: The majority of ED asthma exacerbations are triggered by respiratory viruses. Viral species are associated with severity and treatment response, suggesting early pathogen detection could inform ED treatment decisions. Additional studies are needed to identify differences in pathobiology underlying exacerbations triggered by different viral species, and how to effectively treat these heterogeneous exacerbations.

A reappraisal of IL-9 in inflammation and cancer.

While much is known about the functional effects of type 2 cytokines interleukin (IL)-4, IL-5 and IL-13 in homeostasis and disease, we still poorly understand the functions of IL-9. Chronic inflammation seen in allergic diseases, autoimmunity and cancer is however frequently accompanied by overproduction of this elusive type 2 cytokine. Initially identified as a T cell and mast cell growth factor, and later as the hallmark cytokine defining TH9 cells, we now know that IL-9 is produced by multiple innate and adaptive immune cells. Recent evidence suggests that IL-9 controls discrete aspects of the allergic cascade, cellular responses of immune and stromal cells, cancer progression, tolerance and immune escape. Despite functioning as a pleiotropic cytokine in mucosal environments, like the lungs, the direct and indirect cellular targets of IL-9 are still not well characterized. Here, we discuss IL-9's cellular senders and receivers, focusing on asthma and cancer. Moreover, we review current research directions and the outlook of targeted therapy centered around the biology of IL-9.

Real-World Studies of Biologics for the Treatment of Moderate-to-Severe Asthma.

Presently, there are 6 biologic agents available for treatment of asthma. Each of these agents has undergone robust clinical trials in their approval programs. Such studies rely upon very rigid entry criteria that may not translate to real-world efficacy. Thus, exploring the efficacy of these agents in a larger, more heterogeneous, population brings a sense of comfort regarding their efficacy in the real-world. This review explores the available literature regarding the use of biologics in the real world, with a focus on markers of likely response to therapy.

Biologics in Asthma: Potential to Achieve Clinical Remission.

Establishing a universal definition for asthma remission has the potential to improve asthma outcomes and advance research. However, there is still no consensus definition despite broad multidisciplinary efforts to achieve this goal. This study explores the evolving concept of asthma remission, emphasizing the potential of biologics to achieve this state. We will discuss various proposed definitions of asthma remission, international guidelines, and studies evaluating the effectiveness of biologics at achieving clinical remission. We highlight the need for a consensus definition of asthma remission to standardize treatment goals and improve patient outcomes.

Biologics in Asthma: Role of Biomarkers.

Our modern understanding of asthma mainly concerns identification of inflammatory endotype to guide management. The distinction mostly concerns identification of type-2 inflammation, for which different biomarkers have been well characterized. Blood eosinophils corroborate activity in the interleukin (IL)-5 axis while fraction of exhaled nitric oxide is indicative of the IL-4/IL-13 axis, giving us an indication of activity in these distinct but complementary pathways. These biomarkers predict disease activity, with increased risk of exacerbations when elevated, and a further, multiplicative increase when both are elevated. Serum immunoglobulin E is also implicated in this pathway, and can represent allergen-related stimulation.

Asthma Biologics: Lung Function, Steroid-Dependence, and Exacerbations.

The development of multiple targeted biologic therapies over the past two decades has revolutionized the management of asthma. Currently, there are 6 monoclonal antibodies that target specific inflammatory mediators involved in the pathophysiology of asthma, and together, they provide the opportunity for personalized treatment options beyond bronchodilators and inhaled or systemic glucocorticoids in severe and difficult-to-control cases of asthma. These agents are the anti-IgE antibody omalizumab, the anti-IL-5 antibodies mepolizumab and reslizumab, the IL-5 receptor alpha antagonist benralizumab, the IL-4 receptor alpha antagonist dupilumab, and the anti-thymic stromal lymphopoietin antibody tezepelumab.

Biologics in Asthma: Emerging Biologics.

Advances in our understanding of asthma pathophysiology have led to the advent of multiple targeted asthma therapies such as biologics. However, partial response to biologics occurs, indicating residual disease activity in some patients. Hence, there exists a need for new therapies that focus on novel pathways, alongside perhaps evaluation of combination biologic therapies and modulators of downstream cytokine activation. Therefore, although our current focus is on biologics; it is critical to take a more holistic approach including consideration for nonbiologic therapies that have the potential to significantly advance asthma care.

[Efficacy and toxicity of short-course corticosteroid therapy in chronic bronchial diseases]. / Efficacité et toxicité de la corticothérapie en cures courtes dans les pathologies bronchiques chroniques.

Chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) are characterized by airway inflammation. While corticosteroids (CS) are frequently prescribed during exacerbations of these conditions, their repeated use is associated with numerous side effects. The aim of this review is to synthesize the recent literature on the indications, benefits, and risks of short-term CS therapy for these two diseases. French guidelines recommend short-term CS as a first-line treatment during asthma exacerbation (0,5 to 1mg/kg/day, not exceeding 60mg/day, for at least 5 to 7 days) or as a second-line treatment for COPD exacerbation (5 days, 30 to 40mg/day). However, these recommendations are not without limitations; they are primarily based on studies conducted in hospital settings, raising questions about the generalizability of their results to primary care, and as they employ a "one size fits all" strategy, they do not take into account the phenotypic heterogeneity of different patients. Moreover, repeated short-term CS courses generate side effects that even at low doses can appear early in young asthma patients, and they can exacerbate pre-existing comorbidities in COPD patients. The concept of a threshold dose should be employed in routine practice in view of accurately assessing the risk of side effects. In the near future, it will be important to consider recently published data supporting the use of predictive biomarkers for responses to CS, particularly in COPD cases.

Examining noncommunicable diseases using satellite imagery: a systematic literature review.

INTRODUCTION: Noncommunicable diseases (NCDs) are the leading cause of morbidity and mortality worldwide, accounting for 74% of deaths annually. Satellite imagery provides previously unattainable data about factors related to NCDs that overcome limitations of traditional, non-satellite-derived environmental data, such as subjectivity and requirements of a smaller geographic area of focus. This systematic literature review determined how satellite imagery has been used to address the top NCDs in the world, including cardiovascular diseases, cancers, chronic respiratory diseases, and diabetes. METHODS: A literature search was performed using PubMed (including MEDLINE), CINAHL, Web of Science, Science Direct, Green FILE, and Engineering Village for articles published through June 6, 2023. Quantitative, qualitative, and mixed-methods peer-reviewed studies about satellite imagery in the context of the top NCDs (cancer, cardiovascular disease, chronic respiratory disease, and diabetes) were included. Articles were assessed for quality using the criteria from the Oxford Centre for Evidence-Based Medicine. RESULTS: A total of 43 studies were included, including 5 prospective comparative cohort trials, 22 retrospective cohort studies, and 16 cross-sectional studies. Country economies of the included studies were 72% high-income, 16% upper-middle-income, 9% lower-middle-income, and 0% low-income. One study was global. 93% of the studies found an association between the satellite data and NCD outcome(s). A variety of methods were used to extract satellite data, with the main methods being using publicly available algorithms (79.1%), preprocessing techniques (34.9%), external resource tools (30.2%) and publicly available models (13.9%). All four NCD types examined appeared in at least 20% of the studies. CONCLUSION: Researchers have demonstrated they can successfully use satellite imagery data to investigate the world's top NCDs. However, given the rapid increase in satellite technology and artificial intelligence, much of satellite imagery used to address NCDs remains largely untapped. In particular, with most existing studies focusing on high-income countries, future research should use satellite data, to overcome limitations of traditional data, from lower-income countries which have a greater burden of morbidity and mortality from NCDs. Furthermore, creating and refining effective methods to extract and process satellite data may facilitate satellite data's use among scientists studying NCDs worldwide.

Effect of pulmonary rehabilitation on all-cause mortality in patients with chronic respiratory disease: a retrospective cohort study in an Australian teaching hospital.

BACKGROUND: Pulmonary rehabilitation (PR) is widely recommended for short-term benefits in chronic respiratory diseases, yet long-term outcomes remain uncertain. This retrospective cohort study addresses this gap, comparing 20-year mortality rates between PR participants and matched controls, and hypothesizing that the short-term benefits of PR contribute to improved long-term survival. METHODS: The 20-year mortality of stable chronic respiratory patients who participated in an outpatient PR program was compared with a matched control group based on the type of lung disease. Demographic and clinical variables, and the dates of deaths, were extracted and compared between two groups with two sample t-test and chi-square tests. Kaplan-Meier plots and Cox regression analyses were employed to evaluate survival differences. RESULTS: Between 2000 and 2002, 238 individuals enrolled in a pulmonary rehabilitation (PR) program (58% male, mean age ± SD: 69 ± 8 years, mean FEV1% predicted ± SD: 46 ± 21%). An equal number of people with comparable lung disease were selected as controls (88% COPD, 5% ILD). Controls had lower FEV1% predicted values (mean ± SD: 39 ± 17%, P < 0.001), smoked more (mean ± SD: 48 ± 35 pack-years, P = 0.032), and no differences in age, BMI, sex, and Index of Relative Socio-economic Advantage and Disadvantage (IRSAD). Median (IQR) follow-up time was 68 months (34-123), with 371 (78%) deaths. Univariable (HR = 1.71, p < 0.001) and multivariable (HR = 1.64, p < 0.001) Cox regression found higher mortality risk in controls. Subgroup analysis for COPD replicated these findings (HR = 1.70, P < 0.001). DISCUSSION: Despite some methodological limitations, our study suggests that clinically stable patients with chronic respiratory disease who undertake PR may have lower mortality than matched controls. TRIAL REGISTRATION: Retrospectively registered.

Modeling respiratory tract diseases for clinical translation employing conditionally reprogrammed cells.

Preclinical models serve as indispensable tools in translational medicine. Specifically, patient-derived models such as patient-derived xenografts (PDX), induced pluripotent stem cells (iPSC), organoids, and recently developed technique of conditional reprogramming (CR) have been employed to reflect the host characteristics of diseases. CR technology involves co-culturing epithelial cells with irradiated Swiss-3T3-J2 mouse fibroblasts (feeder cells) in the presence of a Rho kinase (ROCK) inhibitor, Y-27632. CR technique facilitates the rapid conversion of both normal and malignant cells into a "reprogrammed stem-like" state, marked by robust in vitro proliferation. This is achieved without reliance on exogenous gene expression or viral transfection, while maintaining the genetic profile of the parental cells. So far, CR technology has been used to study biology of diseases, targeted therapies (precision medicine), regenerative medicine, and noninvasive diagnosis and surveillance. Respiratory diseases, ranking as the third leading cause of global mortality, pose a significant burden to healthcare systems worldwide. Given the substantial mortality and morbidity rates of respiratory diseases, efficient and rapid preclinical models are imperative to accurately recapitulate the diverse spectrum of respiratory conditions. In this article, we discuss the applications and future potential of CR technology in modeling various respiratory tract diseases, including lung cancer, respiratory viral infections (such as influenza and Covid-19 and etc.), asthma, cystic fibrosis, respiratory papillomatosis, and upper aerodigestive track tumors. Furthermore, we discuss the potential utility of CR in personalized medicine, regenerative medicine, and clinical translation.

Sex and age characteristics of thunderstorm asthma emergency department visits.

Severe asthma has been shown to occur in the combined presence of high pollen and thunderstorm conditions, also known as 'thunderstorm asthma.' First studied as severe epidemic events, recent longitudinal work studied less dramatic but more frequent occurrences. We explore thunderstorm asthma-related emergency department visits in the Minneapolis-St. Paul metropolitan area and evaluated risk differences by sex and age. We define a thunderstorm asthma exposure event as the daily occurrence of 2 or more lightning strikes during high pollen periods, and use daily counts of asthma-related emergency department visits to estimate relative and absolute risk of severe asthma during thunderstorm asthma events for the full population and for sex and age subgroups. The overall population had a 1.06 (95 % CI: 1.02, 1.09) times higher risk of asthma-related ED visits during thunderstorm asthma events compared to days without thunderstorm asthma events. Children under 18 show no higher risk (RR 1.02; 95 % CI: 0.97 1.08), but adults 18-44 years (RR 1.08; 95 % CI: 1.02, 1.13) and 45 and up (RR 1.08; 95 % CI 1.02, 1.15) show higher relative risk. Absolute risk measures show similar patterns to the age and sex results, but age-sex subgroups show more variation in absolute vs relative risk. Our results support an association between ED visits and thunderstorm asthma and provide evidence of varying risks by sex across the life course. These differences in risk have implications for clinical treatment of this allergic type of asthma and for future research into this poorly recognized environmental exposure. Plain Language Summary: Recent research has highlighted the existence of Thunderstorm asthma events, a phenomenon in which pollen grains rupture in the conditions that occur with a thunderstorm, releasing subpollen particles that are capable of triggering severe asthma in susceptible populations. Where severe asthma is a disease that usually impacts children, we find in this study that asthma ED visits associated with thunderstorm asthma events more frequently impact adults, particularly males 18-44 and females 45 and up.

Cross-species comparison of airway epithelium transcriptomics.

Studies of lung transcriptomics across species are essential for understanding the complex biology and disease mechanisms of this vital organ. Single-cell RNA sequencing (scRNA-seq) has emerged as a key tool for understanding cell dynamics across various species. However, comprehensive cross-species comparisons are limited. Therefore, the aims of this study was to investigate the transcriptomic similarities and differences in lung cells across four species-humans, monkeys, mice, and rats-in healthy and asthma conditions using scRNA-seq. The results revealed significant transcriptomic similarities between monkeys and humans and significant cross-species conservation of cell-specific marker genes, transcription factors (TFs), and biological pathways. Additionally, we explored sex differences, identifying distinct sex-specific expression patterns that may influence disease susceptibility. These insights refine our understanding of the mechanism underlying airway cell biology across species and have important implications for studying lung diseases, particularly the mechanisms of mucus clearance in asthma.

Efficacy and Safety of Mepolizumab in Patients With Eosinophilic Granulomatosis With Polyangiitis: A Single-Center Experience.

Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss syndrome, is a systemic vasculitis characterized by eosinophil-rich, necrotizing granulomatous inflammation primarily affecting the respiratory tract with necrotizing vasculitis of small- to medium-sized arteries. In this case series, we retrospectively evaluated the efficacy and safety of mepolizumab in seven patients diagnosed with EGPA who presented to the Department of Allergy and Clinical Immunology at Cleveland Clinic Abu Dhabi. The variables assessed before and after mepolizumab treatment included Birmingham Vasculitis Activity Score (BVAS), prednisolone dose, Asthma Control Test (ACT) score, and blood eosinophil count (BEC). We found a significant reduction in BVAS and prednisolone dosage with clinical improvements in asthma symptoms after treatment with mepolizumab. Our case series, the first from the Middle East on the use of mepolizumab in EGPA, demonstrates that mepolizumab is a safe and effective treatment for patients with EGPA.

[Highlights 57th SEPAR Congress]. / Highlights del 57.° Congreso de la Sociedad Española de Neumología y Cirugía Torácica (SEPAR).

The Spanish Society of Pneumology and Thoracic Surgery (SEPAR) has held its 57th Congress in Valencia from 6 to 8 of June 2024. The SEPAR Congress is the leading meeting for the entire respiratory scientific community, which allows learning about the main scientific advances in this area and provides the ideal situation to create and strengthen ties. This year, under the title "Respiratory Health for everybody", the SEPAR Congress stressed the importance of raising awareness about the importance of caring for and protecting our respiratory system. In this review, we offer a summary of some notable issues addressed in six selected areas of interest: chronic obstructive pulmonary disease (COPD), asthma, interstitial lung diseases (ILDs), pulmonary vascular diseases, sleep and breathing disorders and respiratory physiotherapy.

Multifaceted roles of mitochondria in asthma.

Mitochondria are essential organelles within cells, playing various roles in numerous cellular processes, including differentiation, growth, apoptosis, energy conversion, metabolism, and cellular immunity. The phenotypic variation of mitochondria is specific to different tissues and cell types, resulting in significant differences in their function, morphology, and molecular characteristics. Asthma is a chronic, complex, and heterogeneous airway disease influenced by external factors such as environmental pollutants and allergen exposure, as well as internal factors at the tissue, cellular, and genetic levels, including lung and airway structural cells, immune cells, granulocytes, and mast cells. Therefore, a comprehensive understanding of the specific responses of mitochondria to various external environmental stimuli and internal changes are crucial for elucidating the pathogenesis of asthma. Previous research on mitochondrial-targeted therapy for asthma has primarily focused on antioxidants. Consequently, it is necessary to summarize the multifaceted roles of mitochondria in the pathogenesis of asthma to discover additional strategies targeting mitochondria in this context. In this review, our goal is to describe the changes in mitochondrial function in response to various exposure factors across different cell types and other relevant factors in the context of asthma, utilizing a new mitochondrial terminology framework that encompasses cell-dependent mitochondrial characteristics, molecular features, mitochondrial activity, function, and behavior.

Tezepelumab for severe asthma: elevating current practice to recognize epithelial driven profiles.

BACKGROUND: An increasing amount of evidence supports the relevance of epithelium across the wide spectrum of asthma pathobiology. On a clinical ground tezepelumab, selectively binding TSLP, a major epithelial cytokine, has demonstrated to be effective in asthma patients regardless their specific phenotype. In order to avoid the risk of considering tezepelumab as a not-specific option, the present perspective aims to sketch the tezepelumab best eligible patient profile and to propose some hallmarks of epithelial-driven disease by reviewing the published evidence on the drug mechanism of action and efficacy data. MAIN BODY: Although it cannot rely on standardised or exclusive "markers", the relationship between environment and poor asthma control might suggest a major relevance of the epithelial barrier dysfunction. In that light, allergy and asthma exacerbations concomitant with specific exposures (pathogens, pollutants, chemicals), as well as increased susceptibility to infections can be considered as the hallmark of an impaired epithelial immune response. Tezepelumab is effective in allergic patients, being able to reduce asthma exacerbations precipitated by the exposure to seasonal or perennial aeroallergens, including fungi. In addition, tezepelumab reduced the incidence of co-occurring respiratory illness and asthma exacerbations. In terms of inflammation, epithelial immune response has been related to an impaired mucus hypersecretion and plugging. A placebo-controlled trial demonstrated a significant reduction of mucus plugging in treated patient. Airways hyperreactivity (AHR), airways obstruction and remodelling have been described as an expression of epithelial orchestrated immunological activation. Of note, a significantly higher incidence of mannitol negative test in patients treated with tezepelumab when compared to placebo group has been observed. In addition, A 130 mL improvement in pre-BD FEV1 has been described in patients assuming Tezepelumab. The above-mentioned data suggest that bronchial reversibility and AHR can be considered "functional biomarkers" supporting patients' phenotyping and the identification of tezepelumab best responders. CONCLUSION: Integrating "functional biomarkers" to the inflammatory ones and a better characterization of asthma exacerbations might pave the way to a different and more transversal phenotyping, which overcomes the "restrictive" labels including T2 high, allergic/atopic or T2 low asthma. Precisely defining the disease characteristics and potential targets for a better control even in tezepelumab eligible subjects is essential to avoid the block buster temptation and optimize the personalized medicine approach according to each patient's individuality.