Occupational respiratory disease in Eastern Slovakia between 1990-2021: a shift from agriculture to industrial manufacturing.

OBJECTIVES: Occupational allergic respiratory diseases frequently occur in individuals working in the agricultural and food production sectors, textile manufacturing, and industries involving exposure to isocyanates. The study aimed to describe trends surrounding the prevalence of occupational asthma (OA), occupational rhinitis (OR), and occupational hypersensitivity pneumonitis (OHP) in Eastern Slovakia between 1990-2021. METHODS: All cases of OA, OR, and OHP registered in a database at the Louis Pasteur University Hospital in Kosice, Slovakia, between 1990 and 2021, were divided into categories based on economic sector (agricultural, food production sectors, textile manufacturing, healthcare, industrial manufacturing, and tertiary sector) and causal agent. Changes in disease prevalence, causal agents, and economic sector association over time were analysed. RESULTS: There were 287 occupational respiratory cases (179 OA, 65 OR, and 43 OHP cases). The annual prevalence of OA declined significantly over the study period (p < 0.05). Overall, there was a significant decrease in cases from the agricultural (p < 0.001) and an increase in the industrial manufacturing (p < 0.01). The number of cases due to farming agents fell markedly over the study period, while metalworking fluids (MWFs) were found to be the most common causes of allergic respiratory diseases since 2018. CONCLUSIONS: This study found a decrease in the number of OA cases, as well as changes in economic sectors and causal agents associated with OA and OHP, specifically, in the agricultural sector, with MWFs from the industrial manufacturing sector now being the most common aetiological agent.

Liquid-liquid phase separation: a new perspective on respiratory diseases.

Liquid-liquid phase separation (LLPS) is integral to various biological processes, facilitating signal transduction by creating a condensed, membrane-less environment that plays crucial roles in diverse physiological and pathological processes. Recent evidence has underscored the significance of LLPS in human health and disease. However, its implications in respiratory diseases remain poorly understood. This review explores current insights into the mechanisms and biological roles of LLPS, focusing particularly on its relevance to respiratory diseases, aiming to deepen our understanding and propose a new paradigm for studying phase separation in this context.

Respiratory adverse effects in patients treated with immune checkpoint inhibitors in combination with radiotherapy: a systematic review and meta-analysis.

BACKGROUND: We conducted a systematic review and meta-analysis to assess the risk of respiratory adverse effects in patients with solid tumors treated with immune checkpoint inhibitors (PD-1, PD-L1 and CTLA-4 inhibitors) in combination with radiation therapy. METHODS: We selected eligible studies through the following databases: PubMed, Embase, Cochrane Library, and Clinicaltrials ( https://clinicaltrials.gov/ ). The data was analyzed by using Rstudio. RESULTS: Among 3737 studies, 26 clinical trials, including 2670 patients, were qualified for the meta-analysis. We evaluated the incidence rates of adverse respiratory events, including cough, pneumonia, upper respiratory tract infections, and others: grades 1-5 cough, 0.176 (95%CI: 0.113-0.274, I2 = 92.36%); grades 1-5 pneumonitis, 0.118 (95%CI: 0.067-0.198, I2 = 88.64%); grades 1-5 upper respiratory tract infection, 0.064 (95%CI: 0.049-0.080, I2 = 0.98%); grades 3-5 cough, 0.050 (95%CI: 0.012-0.204, I2 = 8.90%); grades 3-5 pneumonitis, 0.052 (95%CI: 0.031-0.078, I2 = 83.86%); grades 3-5 upper respiratory tract infection, 0.040 (95%CI: 0.007-0.249, I2 = 45.31%). CONCLUSIONS: Our meta-analysis demonstrated that ICI combined with radiotherapy for solid tumors can produce respiratory adverse effects. ICIs combination treatment, a tumor located in the chest, is more likely to cause adverse reactions, and SBRT treatment and synchronous treatment will bring less incidence of adverse reactions. This study provide insights for clinicians to balance the risks of radiotherapy in the course of treating oncology patients.

Rainfall events and daily mortality across 645 global locations: two stage time series analysis.

OBJECTIVE: To examine the associations between characteristics of daily rainfall (intensity, duration, and frequency) and all cause, cardiovascular, and respiratory mortality. DESIGN: Two stage time series analysis. SETTING: 645 locations across 34 countries or regions. POPULATION: Daily mortality data, comprising a total of 109 954 744 all cause, 31 164 161 cardiovascular, and 11 817 278 respiratory deaths from 1980 to 2020. MAIN OUTCOME MEASURE: Association between daily mortality and rainfall events with return periods (the expected average time between occurrences of an extreme event of a certain magnitude) of one year, two years, and five years, with a 14 day lag period. A continuous relative intensity index was used to generate intensity-response curves to estimate mortality risks at a global scale. RESULTS: During the study period, a total of 50 913 rainfall events with a one year return period, 8362 events with a two year return period, and 3301 events with a five year return period were identified. A day of extreme rainfall with a five year return period was significantly associated with increased daily all cause, cardiovascular, and respiratory mortality, with cumulative relative risks across 0-14 lag days of 1.08 (95% confidence interval 1.05 to 1.11), 1.05 (1.02 to 1.08), and 1.29 (1.19 to 1.39), respectively. Rainfall events with a two year return period were associated with respiratory mortality only, whereas no significant associations were found for events with a one year return period. Non-linear analysis revealed protective effects (relative risk <1) with moderate-heavy rainfall events, shifting to adverse effects (relative risk >1) with extreme intensities. Additionally, mortality risks from extreme rainfall events appeared to be modified by climate type, baseline variability in rainfall, and vegetation coverage, whereas the moderating effects of population density and income level were not significant. Locations with lower variability of baseline rainfall or scarce vegetation coverage showed higher risks. CONCLUSION: Daily rainfall intensity is associated with varying health effects, with extreme events linked to an increasing relative risk for all cause, cardiovascular, and respiratory mortality. The observed associations varied with local climate and urban infrastructure.

Exploring the relationship between sarcopenia and 11 respiratory diseases: a comprehensive mendelian randomization analysis.

BACKGROUND: Sarcopenia (SP) is an aging-related loss of muscle mass and function, affecting the respiratory system. However, the causality of the association between sarcopenia on lung diseases remains elusive. METHODS: The bidirectional univariate Mendelian randomization (UVMR), multivariate MR (MVMR) analysis, and mediation MR were utilized to systematically investigate the genetic causal relationship of SP and 11 respiratory diseases. Independent genomic variants related to sarcopenia or respiratory diseases were identified as instrumental variables (IVs), and the summary level data of genome-wide associated studies (GWAS) were obtained from the UK biobank and FinnGen. MVMR analysis was conducted to explore the mediation effects of body mass index (BMI), Alcohol Use Disorders Identification Test (AUDIT), smoking, education attainment (EA), physical activity, and Type 2 Diabetes Mellitus (T2DM). RESULTS: Forward UVMR analysis based on the primary method revealed that pneumoconiosis was associated with a higher risk of appendicular lean mass (ALM) (OR = 1.01, p = 0.03), and BMI (10.65%), smoking (10.65%), and physical activity (17.70%) had a mediating role in the effect of pneumoconiosis on ALM. In reverse MR analysis, we found that genetically predicted ALM was significantly associated with an increased risk of pulmonary embolism (PE) (OR = 1.24, p = 7.21E-05). Chronic obstructive pulmonary disease (COPD) (OR = 0.98, p = 0.002) and sarcoidosis (OR = 1.01, p = 0.004) were identified to increase the loss of left-hand grip strength (HGS). Conversely, the increase in left- HGS presented a protective effect on chronic bronchitis (CB) (OR = 0.35, p = 0.03), (OR = 0.80, p = 0.02), and asthma (OR = 0.78, p = 0.04). Similarly, the loss of the right-HGS elevated the risk of low respiratory tract infection (LRTI) (OR = 0.97, p = 0.02) and bronchiectasis (OR = 1.01, p = 0.03), which is also an independent protective factor for LRTI and asthma. In the aspects of low HGS, the risk of LRTI was increased after MVMR analysis, and the risk of sarcoidosis and pneumoconiosis was elevated in the reverse analysis. Lastly, asthma was found to be related to the loss of the usual walking pace, and the reverse MR analysis suggested a causal relationship between the usual walking pace and LRTI (OR = 0.32, p = 2.79 × 10-5), asthma (OR = 0.24, p = 2.09 × 10-6), COPD (OR = 0.22, p = 6.64 × 10-4), and PE(OR = 0.35, p = 0.03). CONCLUSIONS: This data-driven MR analysis revealed SP was bidirectional causally associated with lung diseases, providing genetic evidence for further mechanistic and clinical studies to understand the crosstalk between SP and lung diseases.

Association between use of heated tobacco products and long-term respiratory effects considering smoking history: internet-based cross-sectional study in Japan.

BACKGROUND: With the use of heated tobacco products (HTPs) becoming more widespread in Japan, interest in the health effects of HTP has grown. Since the majority of HTP users are former smokers, information about the user's smoking history and health status before HTP use is needed when assessing the health effects of HTP use. The limited epidemiological studies available did not consistently consider this information adequately, therefore we conducted a cross-sectional study investigating the association between HTP use and respiratory chronic diseases and symptoms. METHODS: The questionnaires were sent to a research panel members in Japan via the Internet, and individuals who met the study criteria and were either current exclusive HTP users, current exclusive cigarette users or those had never used tobacco products were selected. Information about the participants' smoking history and health status before they used HTPs was obtained. The effects of participant smoking history before HTP use and the impacts on outcomes upon switching to HTP were assessed using a logistic regression model. The odds ratio (OR) for current exclusive HTP users relative to never tobacco users was calculated. The OR was calculated under two scenarios, one in which the smoking history was ignored or one in which the smoking history was considered. RESULTS: Of the participants from whom responses to the questionnaires were obtained, 17,406 participants were included in the analysis. Almost all participating current exclusive HTP users had a history of long-term smoking (mean: 30.8 years), and the occurrence of outcomes both before and after the start using HTP was reported. The ORs, without adjustment and with adjustment for smoking history before HTP use were, 3.23 (95% CI: 1.37-7.61) and 1.85 (95% CI: 0.70-4.89) respectively in COPD, same as other outcomes. CONCLUSIONS: These results suggest that smoking history before HTP using affects the occurrence of outcomes, and underscore the importance of considering smoking history when assessing the health effect of HTP use. Since the duration of HTP use is considerably shorter than that of cigarette use at present, further research, such as follow-up surveys assessing the long-term respiratory effects of HTP use, will be necessary.

Update on the Role of ß2AR and TRPV1 in Respiratory Diseases.

Respiratory diseases (RDs) constitute a common public health problem both in industrialized and developing countries. The comprehension of the pathophysiological mechanisms underlying these conditions and the development of new therapeutic strategies are critical for improving the quality of life of affected patients. ß2-adrenergic receptor (ß2AR) and transient receptor potential vanilloid 1 (TRPV1) are both involved in physiological responses in the airways. ß2AR is implicated in bronchodilation, mucociliary clearance, and anti-inflammatory effects, while TRPV1 is involved in the mediation of pain and cough reflexes. In RDs, such as respiratory infections, asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis, the concentration and expression of these receptors can be altered, leading to significant consequences. In this review, we provided an update on the literature about the role of ß2AR and TRPV1 in these conditions. We reported how the diminished or defective expression of ß2AR during viral infections or prolonged therapy with ß2-agonists can increase the severity of these pathologies and impact the prognosis. Conversely, the role of TRPV1 was pivotal in neuroinflammation, and its modulation could lead to innovative treatment strategies in specific patients. We indicate future perspectives and potential personalized treatments in RDs through a comprehensive analysis of the roles of these receptors in the physiological and pathological mechanisms of these pathologies.

Objectively measured daily steps and health outcomes: an umbrella review of the systematic review and meta-analysis of observational studies.

OBJECTIVES: The purpose of this review is to summarise the evidence from a systematic review and meta-analysis of observational studies that objectively measure daily steps and health outcomes. DESIGN: This is an umbrella review. DATA SOURCES: PubMed, Embase, Scopus, the Cochrane Library and Web of Science databases were searched through 31 January 2024. ELIGIBILITY: We included systematic reviews of observational studies (with or without meta-analysis) that assessed the association of objectively measured daily steps with human health-related outcomes. Methodological quality was assessed using 'A MeaSurement Tool to Assess systematic Reviews 2'. RESULTS: A total of 10 systematic reviews and 6 health outcomes were included after excluding irrelevant and duplicate studies. Higher daily steps were associated with more benefits than harms for a range of health-related outcomes, including all-cause mortality, cardiovascular event, skeletal muscle lesions, metabolic diseases and respiratory disease. A dose-response analysis showed that an increase of 500-1000 steps per day was associated with lower all-cause mortality and cardiovascular events. Beneficial associations were also found in patients with asthma and acutely hospitalised older adults. Conversely, one study within a systematic review suggested that higher daily steps (≥10 000) might be associated with an increased 52% risk of meniscal pathologies in individuals without knee osteoarthritis. However, one study within a systematic review suggested a potential increased risk of meniscal pathologies in individuals without knee osteoarthritis. Specifically, those exceeding 10 000 steps per day showed a 52% increase in risk. CONCLUSION: The results of this study suggest that daily steps are associated with a lower risk of all-cause mortality and cardiovascular events. Future research could focus on identifying specific populations that may benefit most from increased daily steps and exploring potential mechanisms to enhance our understanding of how daily steps contribute to improved health outcomes. PROSPERO REGISTRATION NUMBER: CRD42022347055.

Psychological comorbidities: Impact on respiratory health.

Respiratory diseases are commonly associated with mental health issues, which add to morbidity and mortality. However, this association has never received sufficient attention. There is an urgent need to sensitize the health care workers for early identification of psychological comorbidities, and their basic management. Mental health should be an integral part of the teaching curriculum. Simple, quick and easy to use screening questionnaires should be used on a routine basis for identifying stigma, psychological distress and poor health related quality of life. Psychiatrist should be a vital part of the multidisciplinary teams. Extensive collaborative research needs to be carried out in this field to devise clear-cut recommendations for day-to-day practise.

Health status of Italian children living close to cultivations sprayed with pesticides.

Pesticides are used to control pests, but they are toxic and may severely harm children's health. We assessed health outcomes in Italian children living close to cultivations sprayed with pesticides.In 2011-2012, 2,367 schoolchildren (6-14 years) living in eight Italian cities participated in the Indoor-School observational study. Parents filled in a standardised questionnaire on children's health and related risk factors. Children were classified as exposed to pesticides if living close to cultivations sprayed with pesticides. The association between the last three months of respiratory, allergic or systemic symptoms and pesticide exposure was assessed by multinomial logistic regression models, accounting for host/environmental risk factors.Overall, 14% of children were exposed to pesticides, with significant differences among geographical areas: 21.2% in Northern Italy, 11.6% in Central Italy, and 9.7% in Southern Italy. Pesticide exposure was significantly associated with having: 1) 'often': eye symptoms (OR 3.81, 95% CI 2.06-7.05), skin symptoms (OR 2.60, 95% CI 1.34-5.03), lower airway symptoms (OR 2.38, 95% CI 1.41-4.01), systemic symptoms (OR 1.56, 95% CI 0.96-2.53, borderline); 2) 'daily': upper airways symptoms (OR 2.25, 95% CI 1.25-4.07) and systemic symptoms (OR 2.76, 95% CI 1.43-5.34).Self-reported pesticide exposure was associated with respiratory, allergic or systemic symptoms in children. Public authorities should be aware of and intervene to mitigate this health risk..

CLINICAL MANAGEMENT OF CHRONIC ORANGUTAN RESPIRATORY DISEASE SYNDROME IN THREE ADULT MALE BORNEAN ORANGUTANS (PONGO PYGMAEUS).

Orangutan respiratory disease syndrome (ORDS) is a disease unique to orangutans (Pongo sp), characterized by chronic bacterial infection and inflammation of any region or combination of regions of the respiratory tract, including the sinuses, air sacs, cranial bones, airways, and lung parenchyma. Aggressive early intervention during a first episode may prevent progression to chronic disease. However, in the setting of an established chronic disease, intermittent acute exacerbations are associated with worsening symptoms and increased infection and inflammation. ORDS is ultimately fatal due to loss of respiratory function resulting from chronic structural damage. Utilizing potentially lifelong medications to slow the progression of chronic, destructive inflammation in the respiratory tract, chronic treatment is aimed at stabilizing the animals' respiratory function, decreasing the frequency of recurrent exacerbations, and improving their general well-being. Three adult male Bornean orangutans (Pongo pygmaeus) housed at an orangutan rehabilitation and reintroduction center in Indonesia have long histories of recurrent respiratory disease. Each underwent CT scans confirming ORDS with chronic airway disease prior to initiation of a long-term treatment protocol. Based on data-driven medical management of bronchiectasis in humans, the three orangutans have been treated with long-term combination regimens of oral azithromycin, nebulized salbutamol, and nebulized hypertonic saline. Follow-up CT scans in all three animals at least 1 yr following treatment initiation showed improvements throughout their respiratory tracts. The duration of each exacerbation period decreased, and the orangutans have longer symptom-free periods compared to before the start of treatment. At an average of 5 yr into the long-term treatment protocol, all three orangutans are thriving. Chronic medical management of ORDS modeled after human treatment of bronchiectasis has been efficacious in these three orangutans and encourages further study of this approach.

The Effect of Long-Term Particulate Matter Exposure on Respiratory Mortality: Cohort Study in China.

Background: Particulate matter (PM), which affects respiratory health, has been well documented; however, substantial evidence from large cohorts is still limited, particularly in highly polluted countries and for PM1. Objective: Our objective was to examine the potential causal links between long-term exposure to PMs (PM2.5, PM10, and more importantly, PM1) and respiratory mortality. Methods: A total of 580,757 participants from the Guangzhou area, China, were recruited from 2009 to 2015 and followed up through 2020. The annual average concentrations of PMs at a 1-km spatial resolution around the residential addresses were estimated using validated spatiotemporal models. The marginal structural Cox model was used to estimate the associations of PM exposure with respiratory mortality, accounting for time-varying PM exposure. Results were stratified by demographics and lifestyle behaviors factors. Results: Among the participants, the mean age was 48.33 (SD 17.55) years, and 275,676 (47.47%) of them were men. During the follow-up period, 7260 deaths occurred due to respiratory diseases. The annual average concentrations of PM1, PM2.5, and PM10 showed a declining trend during the follow-up period. After adjusting for confounders, a 6.6% (95% CI 5.6%-7.6%), 4.2% (95% CI 3.6%-4.7%), and 4.0% (95% CI 3.6%-4.5%) increase in the risk of respiratory mortality was observed following each 1-µg/m3 increase in concentrations of PM1, PM2.5, and PM10, respectively. In addition, older participants, nonsmokers, participants with higher exercise frequency, and those exposed to a lower normalized difference vegetation index tended to be more susceptible to the effects of PMs. Furthermore, participants in the low-exposure group tended to be at a 7.6% and 2.7% greater risk of respiratory mortality following PM1 and PM10 exposure, respectively, compared to the entire cohort. Conclusions: This cohort study provides causal clues of the respiratory impact of long-term ambient PM exposure, indicating that PM reduction efforts may continuously benefit the population's respiratory health.

Thermal Comfort Conditions and Mortality in Brazil.

Conventional temperature-based approaches often overlook the intricate nature of thermal stress experienced by individuals. To address this limitation, climatologists have developed thermal indices-composite measures designed to reflect the complex interaction of meteorological factors influencing human perception of temperature. Our study focuses on Brazil, estimating the association between thermal comfort conditions and mortality related to respiratory and circulatory diseases. We examined four distinct thermal indices: the discomfort index (DI), net effective temperature (NET), humidex (H), and heat index (HI). Analyzing a comprehensive dataset of 2,872,084 deaths from 2003 to 2017, we found significant variation in relative risk (RR) based on health outcomes, exposure lag, percentile of exposure, sex/age groups, and specific thermal indices. For example, under high exposure conditions (99th percentile), we observed that the shorter lags (3, 5, 7, and 10) had the most robust effects on all-cause mortality. For example, under lag 3, the pooled national results for the overall population (all ages and sexes) indicate an increased risk of all-cause mortality, with an RR of 1.17 (95% CI: 1.13; 1.122) for DI, 1.15 (95% CI: 1.12; 1.17) for H, 1.15 (95% CI: 1.09; 1.21) for HI, and 1.18 (95% CI: 1.13; 1.22) for NET. At low exposure levels (1st percentile), all four distinct thermal indices were linked to an increase in all-cause mortality across most sex and age subgroups. Specifically, for lag 20, we observed an estimated RR of 1.19 (95% CI: 1.14; 1.23) for DI, 1.12 (95% CI: 1.08; 1.16) for H, 1.17 (95% CI: 1.12; 1.22) for HI, and 1.18 (95% CI: 1.14; 1.23) for NET. These findings have important implications for policymakers, guiding the development of measures to minimize climate change's impact on public health in Brazil.

High altitude air pollution and respiratory disease: Evaluating compounded exposure events and interactions.

Today, air pollution remains a significant issue, particularly in high-altitude areas where its impact on respiratory disease remains incompletely explored. This study aims to investigate the association between various air pollutants and outpatient visits for respiratory disease in such regions, specifically focussing on Xining from 2016 to 2021. By analysing over 570,000 outpatient visits using a time-stratified case-crossover design and conditional logistic regression, we assessed the independent effects of pollutants like PM2.5, PM10, SO2, NO2, and CO, as well as their interactions. The evaluation of interactions employed measures such as relative excess odds due to interaction (REOI), attributable proportion due to interaction (AP), and synergy index (S). We also conducted a stratified analysis to identify potentially vulnerable populations. Our findings indicated that exposure to PM2.5, PM10, SO2, NO2, and CO significantly increased outpatient visits for respiratory disease, with odds ratios (ORs) of 2.40 % (95 % CI: 2.05 %, 2.74 %), 1.07 % (0.98 %, 1.16 %), 3.86 % (3.23 %, 4.49 %), 4.45 % (4.14 %, 4.77 %), and 6.37 % (5.70 %, 7.04 %), respectively. However, exposure to O3 did not show a significant association. We found significant interactions among PM2.5, SO2, NO2, and CO, where combined exposure further exacerbated the risk of respiratory diseases. For example, in the combination of PM2.5 and SO2, the REOI, AP, and S were 0.07 (95 % CI: 0.06, 0.09), 0.07 (0.06, 0.07), and 1.07 (1.05, 1.09), respectively. Additionally, elderly individuals and females were more sensitive to these pollutants, but no statistically significant interaction effects were observed between different age and gender groups. In conclusion, our study highlights the strong link between air pollution and respiratory disease in high-altitude areas, with combined pollutant exposure posing an even greater risk. It underscores the need for enhanced air quality monitoring and public awareness campaigns, particularly to protect vulnerable populations like the elderly and females.

Exhaled breath condensate (EBC) in respiratory diseases: recent advances and future perspectives in the age of omic sciences.

Exhaled breath condensate (EBC) is used as a promising noninvasive diagnostic tool in the field of respiratory medicine. EBC is achieved by cooling exhaled air, which contains aerosolized particles and volatile compounds present in the breath. This method provides useful information on the biochemical and inflammatory state of the airways. In respiratory diseases such as asthma, chronic obstructive pulmonary disease and cystic fibrosis, EBC analysis can reveal elevated levels of biomarkers such as hydrogen peroxide, nitric oxide and various cytokines, which correlate with oxidative stress and inflammation. Furthermore, the presence of certain volatile organic compounds in EBC has been linked to specific respiratory conditions, potentially serving as disease-specific fingerprints. The noninvasive nature of EBC sampling makes it particularly useful for repeated measures and for use in vulnerable populations, including children and the elderly. Despite its potential, the standardization of collection methods, analytical techniques and interpretation of results currently limits its use in clinical practice. Nonetheless, EBC holds significant promise for improving the diagnosis, monitoring and therapy of respiratory diseases. In this tutorial we will present the latest advances in EBC research in airway diseases and future prospects for clinical applications of EBC analysis, including the application of the Omic sciences for its analysis.

Parental smoking and respiratory outcomes in young childhood cancer survivors.

BACKGROUND: Passive exposure to cigarette smoke has negative effects on respiratory health. Childhood cancer survivors (CCS) are at increased risk for respiratory disease due to treatment regimens that may harm the respiratory system. The objective of this study was to assess the prevalence of parental smoking among CCS and investigate its association with respiratory outcomes. PROCEDURE: As part of the Swiss Childhood Cancer Survivor Study, between 2007 and 2022, we sent questionnaires to parents of children aged ≤16 years who had survived ≥5 years after a cancer diagnosis. Parents reported on their children's respiratory outcomes including recurrent upper respiratory tract infections (otitis media and sinusitis), asthma, and lower respiratory symptoms (chronic cough persisting >3 months, current and exercise wheeze), and on parental smoking. We used multivariable logistic regression to investigate associations between parental smoking and respiratory outcomes. RESULTS: Our study included 1037 CCS (response rate 66%). Median age at study was 12 years (interquartile range 10-14 years). Eighteen percent of mothers and 23% of fathers reported current smoking. CCS exposed to smoking mothers were more likely to have recurrent upper respiratory tract infections (OR 2.1; 95%CI 1.1-3.7) and lower respiratory symptoms (OR 2.0; 95%CI 1.1-3.7). We found no association with paternal smoking. CONCLUSIONS: A substantial proportion of CCS in Switzerland have parents who smoke. Exposure to maternal smoking was associated with higher prevalence of upper and lower respiratory problems. Healthcare providers can support families by addressing caregiver smoking behaviors and providing referrals to smoking cessation programs.

A protein risk score for all-cause and respiratory-specific mortality in non-Hispanic white and African American individuals who smoke.

Protein biomarkers are associated with mortality in cardiovascular disease, but their effect on predicting respiratory and all-cause mortality is not clear. We tested whether a protein risk score (protRS) can improve prediction of all-cause mortality over clinical risk factors in smokers. We utilized smoking-enriched (COPDGene, LSC, SPIROMICS) and general population-based (MESA) cohorts with SomaScan proteomic and mortality data. We split COPDGene into training and testing sets (50:50) and developed a protRS based on respiratory mortality effect size and parsimony. We tested multivariable associations of the protRS with all-cause, respiratory, and cardiovascular mortality, and performed meta-analysis, area-under-the-curve (AUC), and network analyses. We included 2232 participants. In COPDGene, a penalized regression-based protRS was most highly associated with respiratory mortality (OR 9.2) and parsimonious (15 proteins). This protRS was associated with all-cause mortality (random effects HR 1.79 [95% CI 1.31-2.43]). Adding the protRS to clinical covariates improved all-cause mortality prediction in COPDGene (AUC 0.87 vs 0.82) and SPIROMICS (0.74 vs 0.6), but not in LSC and MESA. Protein-protein interaction network analyses implicate cytokine signaling, innate immune responses, and extracellular matrix turnover. A blood-based protein risk score predicts all-cause and respiratory mortality, identifies potential drivers of mortality, and demonstrates heterogeneity in effects amongst cohorts.

Temporal variations in the short-term effects of ambient air pollution on cardiovascular and respiratory mortality: a pooled analysis of 380 urban areas over a 22-year period.

BACKGROUND: Ambient air pollution, including particulate matter (such as PM10 and PM2·5) and nitrogen dioxide (NO2), has been linked to increases in mortality. Whether populations' vulnerability to these pollutants has changed over time is unclear, and studies on this topic do not include multicountry analysis. We evaluated whether changes in exposure to air pollutants were associated with changes in mortality effect estimates over time. METHODS: We extracted cause-specific mortality and air pollution data collected between 1995 and 2016 from the Multi-Country Multi-City (MCC) Collaborative Research Network database. We applied a two-stage approach to analyse the short-term effects of NO2, PM10, and PM2·5 on cause-specific mortality using city-specific time series regression analyses and multilevel random-effects meta-analysis. We assessed changes over time using a longitudinal meta-regression with time as a linear fixed term and explored potential sources of heterogeneity and two-pollutant models. FINDINGS: Over 21·6 million cardiovascular and 7·7 million respiratory deaths in 380 cities across 24 countries over the study period were included in the analysis. All three air pollutants showed decreasing concentrations over time. The pooled results suggested no significant temporal change in the effect estimates per unit exposure of PM10, PM2·5, or NO2 and mortality. However, the risk of cardiovascular mortality increased from 0·37% (95% CI -0·05 to 0·80) in 1998 to 0·85% (0·55 to 1·16) in 2012 with a 10 µg/m3 increase in PM2·5. Two-pollutant models generally showed similar results to single-pollutant models for PM fractions and indicated temporal differences for NO2. INTERPRETATION: Although air pollution levels decreased during the study period, the effect sizes per unit increase in air pollution concentration have not changed. This observation might be due to the composition, toxicity, and sources of air pollution, as well as other factors, such as socioeconomic determinants or changes in population distribution and susceptibility. FUNDING: None.