Infant Bronchiolitis Endotypes and the Risk of Developing Childhood Asthma: Lessons From Cohort Studies.

Severe bronchiolitis (i.e., bronchiolitis requiring hospitalization) during infancy is a heterogeneous condition associated with a high risk of developing childhood asthma. Yet, the exact mechanisms underlying the bronchiolitis-asthma link remain uncertain. Birth cohort studies have reported this association at the population level, including only small groups of patients with a history of bronchiolitis, and have attempted to identify the underlying biological mechanisms. Although this evidence has provided valuable insights, there are still unanswered questions regarding severe bronchiolitis-asthma pathogenesis. Recently, a few bronchiolitis cohort studies have attempted to answer these questions by applying unbiased analytical approaches to biological data. These cohort studies have identified novel bronchiolitis subtypes (i.e., endotypes) at high risk for asthma development, representing essential and enlightening evidence. For example, one distinct severe respiratory syncytial virus (RSV) bronchiolitis endotype is characterized by the presence of Moraxella catarrhalis and Streptococcus pneumoniae, higher levels of type I/II IFN expression, and changes in carbohydrate metabolism in nasal airway samples, and is associated with a high risk for childhood asthma development. Although these findings hold significance for the design of future studies that focus on childhood asthma prevention, they require validation. However, this scoping review puts the above findings into clinical context and emphasizes the significance of future research in this area aiming to offer new bronchiolitis treatments and contribute to asthma prevention.

Prevalence of Wheezing and Its Association with Environmental Tobacco Smoke Exposure among Rural and Urban Preschool Children in Mpumalanga Province, South Africa.

BACKGROUND: This study aimed to investigate the prevalence of wheezing and its association with environmental tobacco smoke exposure among rural and urban preschool children in Mpumalanga province, South Africa, an area associated with poor air quality. METHODS: In this study, parents/caregivers of preschool children (n = 3145) completed a modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Data were analysed using multiple logistic regression models. RESULTS: The overall prevalence of Wheeze Ever was 15.14%, with a higher prevalence in urban preschoolers than rural preschoolers (20.71% vs. 13.30%, p < 0.000). Moreover, the total prevalence of Asthma Ever was 2.34%. The prevalence was greater in urban preschoolers than in rural preschoolers (3.92% vs. 1.81%, p < 0.001). In the final adjusted model, both urban- and rural-area children who lived with one or more people who smoked in the same household (WE: OR 1.44, 95% CI 1.11-1.86) (CW: OR 2.09, 95% CI 1.38-3.16) and (AE: OR 2.49, 95% CI 1.12-5.54) were found to have an increased likelihood of having Wheeze Ever, Current Wheeze, and Asthma Ever as compared to those who lived with non-smokers. CONCLUSIONS: The implementation of smoking limits and prohibition is crucial in areas that are frequented or utilized by children. Hence, it is imperative for healthcare providers to actively champion the rights of those who do not smoke within the society, while also endorsing legislative measures aimed at curtailing the extent of tobacco smoke exposure.

The relationship between childhood atopic dermatitis and asthma in an under resourced community.

Background: Atopic dermatitis (AD) is an inflammatory skin disease caused by allergen exposures and estimated to affect ∼20% of children. Children in urban areas have a higher prevalence of AD compared with those living outside of urban areas. AD is believed to lead to asthma development as part of the "atopic march." Objective: Our objective was to determine the sequential and chronological relationships between AD and asthma for children in an under-resourced community. Methods: The progression from AD to asthma in the under-resourced, urban community of Sun Valley, Colorado, was examined by assessing Medicaid data for the years 2016 to 2019 for a diagnosis of AD or asthma in children 6 and 7 years old. Results: Pearson correlations between AD and asthma diagnoses were significant only with respect to AD at age 6 years compared with asthma 1 year later, at age 7 years. Conclusion: By studying a susceptible community with a consistent but mixed genetic background, we found sequential and chronological links between AD and asthma.

Association of factors with childhood asthma and allergic diseases using latent class analysis.

We hypothesize that children characterized by deprived factors have poorer health outcomes. We aim to identify clustering of determinants and estimate risk of early childhood diseases. This 1993-2019 longitudinal cohort study combines three Canadian pediatric cohorts and their families. Mothers and children are clustered using latent class analysis (LCA) by 16 indicators in three domains (maternal and newborn; socioeconomic status [SES] and neighbourhood; environmental exposures). Hazard ratios (HR) of childhood asthma, allergic rhinitis (AR), and eczema are quantified with Cox proportional hazard (PH) regression. Rate ratios (RR) of children's health services use (HSU) are estimated with Poisson regression. Here we report the inclusion of 15,724 mother-child pairs; our LCA identifies four mother-clusters. Classes 1 and 2 mothers are older (30-40 s), non-immigrants with university education, living in high SES neighbourhoods; Class 2 mothers have poorer air quality and less greenspace. Classes 3 and 4 mothers are younger (20-30 s), likely an immigrant/refugee, with high school-to-college education, living in lower SES neighborhoods with poorer air quality and less greenspace. Children's outcomes differ by Class, in comparison to Class 1. Classes 3 and 4 children have higher risks of asthma (HR 1.24, 95% CI 1.11-1.37 and HR 1.39, 95% CI 1.22-1.59, respectively), and similar higher risks of AR and eczema. Children with AR in Class 3 have 20% higher all-cause physician visits (RR = 1.20, 95% CI 1.10-1.30) and those with eczema have 18% higher all-cause emergency department visits (RR = 1.18, 95% CI 1.09-1.28) and 14% higher all-cause physician visits (RR = 1.14, 95% CI 1.09-1.19). Multifactorial-LCA mother-clusters may characterize associations of children's health outcomes and care, adjusting for interrelationships.

Effects of apparent temperature on daily outpatient and inpatient visits for cause-specific respiratory diseases in Ganzhou, China: a time series study.

BACKGROUND: Non-optimum temperatures are associated with increased risk of respiratory diseases, but the effects of apparent temperature (AT) on respiratory diseases remain to be investigated. METHODS: Using daily data from 2016 to 2020 in Ganzhou, a large city in southern China, we analyzed the impact of AT on outpatient and inpatient visits for respiratory diseases. We considered total respiratory diseases and five subtypes (influenza and pneumonia, upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), asthma and chronic obstructive pulmonary disease [COPD]). Our analysis employed a distributed lag nonlinear model (DLNM) combined with a generalized additive model (GAM). RESULTS: We recorded 94,952 outpatients and 72,410 inpatients for respiratory diseases. We found AT significantly non-linearly associated with daily outpatient and inpatient visits for total respiratory diseases, influenza and pneumonia, and URTI, primarily during comfortable AT levels, while it was exclusively related with daily inpatient visits for LRTI and COPD. Moderate heat (32.1 °C, the 75.0th centile) was observed with a significant effect on both daily outpatient and inpatient visits for total respiratory diseases at a relative risk of 1.561 (1.161, 2.098) and 1.276 (1.027, 1.585), respectively (both P < 0.05), while the results of inpatients became insignificant with the adjustment for CO and O3. The attributable fractions in outpatients and inpatients were as follows: total respiratory diseases (24.43% and 18.69%), influenza and pneumonia (31.54% and 17.33%), URTI (23.03% and 32.91%), LRTI (37.49% and 30.00%), asthma (9.83% and 3.39%), and COPD (30.67% and 10.65%). Stratified analyses showed that children ≤5 years old were more susceptible to moderate heat than older participants. CONCLUSIONS: In conclusion, our results indicated moderate heat increase the risk of daily outpatient and inpatient visits for respiratory diseases, especially among children under the age of 5.

The Role of Peptides in Asthma-Obesity Phenotype.

The co-occurrence of asthma and obesity is becoming an increasingly common health problem. It became clear that both diseases are closely related, since overweight/obesity are associated with an increased risk of asthma development, and more than half of the subjects with severe or difficult-to-treat asthma are obese. Currently, there are no specific guidelines for the treatment of this group of patients. The mechanisms involved in the asthma-obesity phenotype include low-grade chronic inflammation and changes in pulmonary physiology. However, genetic predispositions, gender differences, comorbid conditions, and gut microbiota also seem to be important. Regulatory peptides affect many processes related to the functioning of the respiratory tract and adipose tissue. Adipokines such as leptin, adiponectin, resistin, and the less studied omentin, chemerin, and visfatin, as well as the gastrointestinal hormones ghrelin, cholecystokinin, glucagon-like peptide-1, and neuropeptides, including substance P or neuropeptide Y, can play a significant role in asthma with obesity. The aim of this article is to provide a concise review of the contribution of particular peptides in inflammatory reactions, obesity, asthma, and a combination of both diseases, as well as emphasize their potential role in the effective treatment of the asthma-obesity phenotype in the future.

Relationship between concentration of air pollutants and frequency of hospitalisations due to respiratory diseases.

INTRODUCTION AND OBJECTIVE: Smog, which contains fine dusts, non-metal oxides, metals and organic compounds can have irritating, allergenic and immunomodulatory effects leading to the development of respiratory diseases and their exacerbations. The aim of the study was to search for a relationship between concentrations of air pollutants and the frequency of hospitalizations due to exacerbation of asthma, chronic obstructive pulmonary disease, or abnormalitis in breathing. MATERIAL AND METHODS: Hospital admission data was accessed from the hospital digital in-formation system. From the publicly available database of the Chief Inspectorate for Environmental Protection, data concerning the concentrations of pollutants, such as PM2.5 and PM10, sulphur oxide IV (SO2), nitric oxide IV (NO2), carbon monoxide II (CO), benzene and ozone (O3), measured daily with hourly accuracy was used. The results of the average concentrations of air pollutants were compared with the rates of hospitalization in the corresponding time intervals. RESULTS: A number of statistically significant correlations were shown indicating the role of increased concentrations of each of the tested contaminants in the frequency of hospitalizations. In particular, strongly positive correlations were shown between the frequency of hospitalizations due to COPD and PM2.5 and PM10, asthma with benzene and NO2, and for respiratory disorders in general with benzene, CO and SO2. CONCLUSIONS: The results indicate that air pollution can be a significant modifiable risk factor for exacerbations of respiratory diseases and therefore its avoidance plays an important role in primary prevention.

House dust mite SCIT reduces asthma risk and significantly improves long-term rhinitis and asthma control-A RWE study.

BACKGROUND: The German Therapy Allergen Ordinance (TAO) triggered an ongoing upheaval in the market for house dust mite (HDM) allergen immunotherapy (AIT) products. Three HDM subcutaneous AIT (SCIT) products hold approval in Germany and therefore will be available after the scheduled completion of the TAO procedure in 2026. In general, data from clinical trials on the long-term effectiveness of HDM AIT are rare. We evaluated real-world data (RWD) in a retrospective, observational cohort study based on a longitudinal claims database including 60% of all German statutory healthcare prescriptions to show the long-term effectiveness of one of these products in daily life. Aim of this analysis was to provide a per product analysis on effectiveness of mite AIT as it is demanded by international guidelines on AIT. METHODS: Subjects between 5 and 70 years receiving their first (index) prescription of SCIT with a native HDM product (SCIT group) between 2009 and 2013 were included. The exactly 3:1 matched control group received prescriptions for only symptomatic AR medication (non-AIT group); the evaluation period for up to 6 years of follow-up ended in February 2017. Study endpoints were the progression of allergic rhinitis (AR) and asthma, asthma occurrence and time to the onset of asthma after at least 2 treatment years. RESULTS: In total, 892 subjects (608 adults and 284 children/adolescents) were included in the SCIT group and 2676 subjects (1824 adults and 852 children/adolescents) in the non-AIT group. During the follow-up period after at least 2 years of SCIT, the number of prescriptions in the SCIT group was reduced by 62.8% (p < .0001) for AR medication and by 42.4% for asthma medication (p = .0003). New-onset asthma risk was significantly reduced in the SCIT vs non-AIT group by 27.0% (p = .0212). The asthma-preventive effect of SCIT occurred 15 months after start of the treatment. In the SCIT group, the time to onset of asthma was prolonged compared to the non-AIT group (p = .0010). CONCLUSION: In this first product based RWD analysis on SCIT with a native HDM product, patients aged 5 to 70 years benefited from AIT in the long term in terms of reduced progression of AR and asthma after at least 2 years of treatment. The effects seemed to last for up to 6 years after treatment termination. A significantly reduced risk of asthma onset was observed, starting after 15 months of treatment.

Outcomes of Extracorporeal Life Support (ECLS) in Acute Severe Asthma: A Narrative Review.

BACKGROUND: In this narrative review we aimed to explore outcomes of extracorporeal life support (extracorporeal membrane oxygenation (ECMO) and extracorporeal carbon dioxide removal (ECCO2R)) as rescue therapy in patients with status asthmaticus requiring mechanical ventilation. METHODS: Multiple databases were searched for studies fulfilling inclusion criteria. Articles reporting mortality and complications of ECMO and ECCO2R in mechanically ventilated patients with acute severe asthma (ASA) were included. Pooled estimates of mortality and complications were obtained by fitting Poisson's normal modeling. RESULTS: Six retrospective studies fulfilled inclusion criteria thus yielding a pooled mortality rate of 17% (13-20%), pooled risk of bleeding of 22% (7-37%), mechanical complications in 26% (21-31%), infection in 8% (0-21%) and pneumothorax rate 4% (2-6%). CONCLUSION: Our review identified a variation between institutions in the initiation of ECMO and ECCO2R in patients with status asthmaticus and discrepancy in the severity of illness at the time of cannulation. Despite that, mortality in these studies was relatively low with some studies reporting no mortality which could be attributed to selection bias. While ECMO and ECCO2R use in severe asthma patients is associated with complication risks, further studies exploring the use of ECMO and ECCO2R with mechanical ventilation are required to identify patients with favorable risk benefit ratio.

Maternal dietary indexes are not linked to early childhood wheezing or atopic eczema.

BACKGROUND: Several recent studies have investigated the association between maternal diet during pregnancy and wheezing or asthma in children. However, whether a specific dietary pattern during pregnancy protects children from wheezing or atopic diseases remains unclear. This study investigated the association between The Alternative Healthy Eating Index for Pregnancy (AHEI-P), the Dietary Inflammatory Index (DII), and the risk for wheezing and atopic eczema in children during the first year of life. METHODS: This study included 1330 mother-child pairs who attended the Kuopio Birth Cohort (KuBiCo) study and had dietary information during the last trimester and information on children's health in the first year of life. AHEI-P and DII indicate a healthy diet and dietary inflammation potential during pregnancy. The AHEI-P and DII were compared with reported wheezing and doctor-diagnosed atopic eczema in children during the first year of life. RESULTS: Neither AHEI-P nor DII is associated with wheezing or atopic eczema in children when analyzed by continuous variables and by tertiles. The odds ratio (95% CI) for AHEI-P and wheezing was 0.99 (0.98-1.01), for AHEI-P and atopic eczema1.01 (0.99-1.02), for DII and wheezing 1.02 (0.95-1.09), and for DII and atopic eczema 0.97 (0.91-1.04). CONCLUSION: In this cohort study, AHEI-P and DII during pregnancy were not associated with wheezing or atopic eczema in the offspring during the first year of life.

Impact of particulate air pollution on airway injury and epithelial plasticity; underlying mechanisms.

Air pollution plays an important role in the mortality and morbidity of chronic airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Particulate matter (PM) is a significant fraction of air pollutants, and studies have demonstrated that it can cause airway inflammation and injury. The airway epithelium forms the first barrier of defense against inhaled toxicants, such as PM. Airway epithelial cells clear airways from inhaled irritants and orchestrate the inflammatory response of airways to these irritants by secreting various lipid mediators, growth factors, chemokines, and cytokines. Studies suggest that PM plays an important role in the pathogenesis of chronic airway diseases by impairing mucociliary function, deteriorating epithelial barrier integrity, and inducing the production of inflammatory mediators while modulating the proliferation and death of airway epithelial cells. Furthermore, PM can modulate epithelial plasticity and airway remodeling, which play central roles in asthma and COPD. This review focuses on the effects of PM on airway injury and epithelial plasticity, and the underlying mechanisms involving mucociliary activity, epithelial barrier function, airway inflammation, epithelial-mesenchymal transition, mesenchymal-epithelial transition, and airway remodeling.

Pediatric asthma and altitude: a complex interplay between different environmental factors.

Asthma is one of the most common non-communicable diseases, and its prevalence and morbidity are influenced by a wide array of factors that are only partially understood. In addition to individual predisposition linked to genetic background and early life infections, environmental factors are crucial in determining the impact of asthma both on an individual patient and on a population level.Several studies have examined the role of the environment where asthmatic subjects live in the pathogenesis of asthma. This review aims to investigate the differences in the prevalence and characteristics of asthma between the pediatric population residing at higher altitudes and children living at lower altitudes, trying to define factors that potentially determine such differences. For this purpose, we reviewed articles from the literature concerning observational studies assessing the prevalence of pediatric asthma in these populations and its characteristics, such as spirometric and laboratory parameters and associated sensitization to aeroallergens.Despite the heterogeneity of the environments examined, the hypothesis of a beneficial effect of residing at a higher altitude on the prevalence of pediatric asthma could be confirmed, as well as a good profile on airway inflammation in asthmatic children. However, the possibility of a higher hospitalization risk for asthma in children living at higher altitudes was demonstrated. Moreover, a positive association between residing at a higher altitude and sensitization to pollens and between lower altitude and sensitization to house dust mites could be confirmed in some pediatric patients, even if the results are not homogeneous, probably due to the different geographical and climatic regions considered. Nonetheless, further studies, e.g., extensive and international works, need to be conducted to better understand the complex interplay between different environmental factors, such as altitude, and the pathogenesis of asthma and how its prevalence and characteristics could vary due to climate change.

Advances in co-pathogenesis of the united airway diseases.

According to the concept of "united airway diseases", the airway is a single organ in which upper and lower airway diseases are commonly comorbid. A range of inflammatory factors have been found to play an important role in the chain reaction of upper and lower airway diseases. However, the amount of research on this concept remains limited. The underlying mechanism of the relationship between typical diseases of the united airway, such as asthma, allergic rhinitis, and chronic sinusitis, also needs to be further explored. This review highlights the interaction between upper and lower respiratory diseases gathered from epidemiological, histoembryology, neural mechanistic, microbiological, and clinical studies, revealing the relationship between the upper and lower respiratory tracts.

Obesity-related asthma: new insights leading to a different approach.

PURPOSE OF REVIEW: Obesity is a growing global health threat that significantly contributes to the burden of asthma by increasing the risk of developing asthma and exerting a distinct effect on lung function and inflammation. The treatment of obesity-related asthma is hindered by a poor response to standard asthma treatments, leading to worse asthma control. Weight loss strategies have a significant effect on asthma symptoms but are not feasible for a large proportion of patients, underscoring the need for a better understanding of the pathophysiology and the development of additional treatment options. RECENT FINDINGS: Recent literature focusing on pathophysiology particularly delved into nontype 2 inflammatory mechanisms, associations with the metabolic syndrome and small airway impairment. Additionally, several new treatment options are currently investigated, including biologics, weight reduction interventions, and novel antiobesity drugs. SUMMARY: Obesity-related asthma is a highly prevalent asthma phenotype for which weight loss strategies currently stand as the most specific treatment. Furthermore, novel pharmacological interventions aiming at metabolic processes are on the way.

Recent Insights into the Environmental Determinants of Childhood Asthma.

PURPOSE OF REVIEW: Ubiquitous environmental exposures, including ambient air pollutants, are linked to the development and severity of childhood asthma. Advances in our understanding of these links have increasingly led to clinical interventions to reduce asthma morbidity. RECENT FINDINGS: We review recent work untangling the complex relationship between air pollutants, including particulate matter, nitrogen dioxide, and ozone and asthma, such as vulnerable windows of pediatric exposure and their interaction with other factors influencing asthma development and severity. These have led to interventions to reduce air pollutant levels in children's homes and schools. We also highlight emerging environmental exposures increasingly associated with childhood asthma. Growing evidence supports the present threat of climate change to children with asthma. Environmental factors play a large role in the pathogenesis and persistence of pediatric asthma; in turn, this poses an opportunity to intervene to change the course of disease early in life.

Rhinovirus-induced wheeze was associated with asthma development in predisposed children.

AIM: This study explored whether early-life factors, such as rhinovirus-induced wheeze and allergic sensitisation, were related to asthma at 11 years of age. METHODS: We focused on 107 children aged 6-48 months, who attended the paediatric emergency department at Astrid Lindgren's Children's Hospital in Stockholm, Sweden, with acute wheeze in 2008-2012. They also attended follow-up visits at 11 years of age and were compared with 46 age-matched healthy controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated with logistic regression. RESULTS: We found that 62.6% of the acute wheeze cases had asthma at 11 years of age. Rhinoviruses at inclusion were the only common airway viruses associated with an increased asthma risk (OR 2.4, 95% CI 1.02-5.6). Other increased risks were parental heredity for asthma and/or allergies (adjusted OR 3.4, 95% CI 1.1-9.9) and allergic sensitisation at 2 years of age (adjusted OR 3.0, 95% CI 1.02-8.7). The highest prevalence of asthma was when children had both rhinovirus-induced wheeze at inclusion and allergic sensitisation at 7 years of age. CONCLUSION: Our findings highlight the importance of hereditary factors and allergic sensitisation on the development of asthma and suggest that rhinoviruses are associated with asthma development in predisposed children.

Early-Life Exposure to Air Pollution and Childhood Asthma Cumulative Incidence in the ECHO CREW Consortium.

Importance: Exposure to outdoor air pollution contributes to childhood asthma development, but many studies lack the geographic, racial and ethnic, and socioeconomic diversity to evaluate susceptibility by individual-level and community-level contextual factors. Objective: To examine early life exposure to fine particulate matter (PM2.5) and nitrogen oxide (NO2) air pollution and asthma risk by early and middle childhood, and whether individual and community-level characteristics modify associations between air pollution exposure and asthma. Design, Setting, and Participants: This cohort study included children enrolled in cohorts participating in the Children's Respiratory and Environmental Workgroup consortium. The birth cohorts were located throughout the US, recruited between 1987 and 2007, and followed up through age 11 years. The survival analysis was adjusted for mother's education, parental asthma, smoking during pregnancy, child's race and ethnicity, sex, neighborhood characteristics, and cohort. Statistical analysis was performed from February 2022 to December 2023. Exposure: Early-life exposures to PM2.5 and NO2 according to participants' birth address. Main Outcomes and Measures: Caregiver report of physician-diagnosed asthma through early (age 4 years) and middle (age 11 years) childhood. Results: Among 5279 children included, 1659 (31.4%) were Black, 835 (15.8%) were Hispanic, 2555 (48.4%) where White, and 229 (4.3%) were other race or ethnicity; 2721 (51.5%) were male and 2596 (49.2%) were female; 1305 children (24.7%) had asthma by 11 years of age and 954 (18.1%) had asthma by 4 years of age. Mean values of pollutants over the first 3 years of life were associated with asthma incidence. A 1 IQR increase in NO2 (6.1 µg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.25 [95% CI, 1.03-1.52]) and children younger than 11 years (HR, 1.22 [95% CI, 1.04-1.44]). A 1 IQR increase in PM2.5 (3.4 µg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.31 [95% CI, 1.04-1.66]) and children younger than 11 years (OR, 1.23 [95% CI, 1.01-1.50]). Associations of PM2.5 or NO2 with asthma were increased when mothers had less than a high school diploma, among Black children, in communities with fewer child opportunities, and in census tracts with higher percentage Black population and population density; for example, there was a significantly higher association between PM2.5 and asthma incidence by younger than 5 years of age in Black children (HR, 1.60 [95% CI, 1.15-2.22]) compared with White children (HR, 1.17 [95% CI, 0.90-1.52]). Conclusions and Relevance: In this cohort study, early life air pollution was associated with increased asthma incidence by early and middle childhood, with higher risk among minoritized families living in urban communities characterized by fewer opportunities and resources and multiple environmental coexposures. Reducing asthma risk in the US requires air pollution regulation and reduction combined with greater environmental, educational, and health equity at the community level.

Thunderstorm Asthma and Climate Change.

This JAMA Insights in the Climate Change and Health Series defines thunderstorm asthma, describes its effects and increased rate of occurrence, and highlights recommendations for improved response during future events.

Estimated health effects from domestic use of gaseous fuels for cooking and heating in high-income, middle-income, and low-income countries: a systematic review and meta-analyses.

BACKGROUND: Exposure to household air pollution from polluting domestic fuel (solid fuel and kerosene) represents a substantial global public health burden and there is an urgent need for rapid transition to clean domestic fuels. Gas for cooking and heating might possibly affect child asthma, wheezing, and respiratory health. The aim of this review was to synthesise the evidence on the health effects of gaseous fuels to inform policies for scalable clean household energy. METHODS: In this systematic review and meta-analysis, we summarised the health effects from cooking or heating with gas compared with polluting fuels (eg, wood or charcoal) and clean energy (eg, electricity and solar energy). We searched PubMed, Scopus, Web of Science, MEDLINE, Cochrane Library (CENTRAL), Environment Complete, GreenFile, Google Scholar, Wanfang DATA, and CNKI for articles published between Dec 16, 2020, and Feb 6, 2021. Studies eligible for inclusion had to compare gas for cooking or heating with polluting fuels (eg, wood or charcoal) or clean energy (eg, electricity or solar energy) and present data for health outcomes in general populations. Studies that reported health outcomes that were exacerbations of existing underlying conditions were excluded. Several of our reviewers were involved in screening studies, data extraction, and quality assessment (including risk of bias) of included studies; 20% of studies were independently screened, extracted and quality assessed by another reviewer. Disagreements were reconciled through discussion with the wider review team. Included studies were appraised for quality using the Liverpool Quality Assessment Tools. Key health outcomes were grouped for meta-analysis and analysed using Cochrane's RevMan software. Primary outcomes were health effects (eg, acute lower respiratory infections) and secondary outcomes were health symptoms (eg, respiratory symptoms such as wheeze, cough, or breathlessness). This study is registered with PROSPERO, CRD42021227092. FINDINGS: 116 studies were included in the meta-analysis (two [2%] randomised controlled trials, 13 [11%] case-control studies, 23 [20%] cohort studies, and 78 [67%] cross-sectional studies), contributing 215 effect estimates for five grouped health outcomes. Compared with polluting fuels, use of gas significantly lowered the risk of pneumonia (OR 0·54, 95% CI 0·38-0·77; p=0·00080), wheeze (OR 0·42, 0·30-0·59; p<0·0001), cough (OR 0·44, 0·32-0·62; p<0·0001), breathlessness (OR 0·40, 0·21-0·76; p=0·0052), chronic obstructive pulmonary disease (OR 0·37, 0·23-0·60; p<0·0001), bronchitis (OR 0·60, 0·43-0·82; p=0·0015), pulmonary function deficit (OR 0·27, 0·17-0·44; p<0·0001), severe respiratory illness or death (OR 0·27, 0·11-0·63; p=0·0024), preterm birth (OR 0·66, 0·45-0·97; p=0·033), and low birth weight (OR 0·70, 0·53-0·93; p=0·015). Non-statistically significant effects were observed for asthma in children (OR 1·04, 0·70-1·55; p=0·84), asthma in adults (OR 0·65, 0·43-1·00; p=0·052), and small for gestational age (OR 1·04, 0·89-1·21; p=0·62). Compared with electricity, use of gas significantly increased risk of pneumonia (OR 1·26, 1·03-1·53; p=0·025) and chronic obstructive pulmonary disease (OR 1·15, 1·06-1·25; p=0·0011), although smaller non-significant effects were observed for higher-quality studies. In addition, a small increased risk of asthma in children was not significant (OR 1·09, 0·99-1·19; p=0·071) and no significant associations were found for adult asthma, wheeze, cough, and breathlessness (p>0·05). A significant decreased risk of bronchitis was observed (OR 0·87, 0·81-0·93; p<0·0001). INTERPRETATION: Switching from polluting fuels to gaseous household fuels could lower health risk and associated morbidity and mortality in resource-poor countries where reliance on polluting fuels is greatest. Although gas fuel use was associated with a slightly higher risk for some health outcomes compared with electricity, gas is an important transitional option for health in countries where access to reliable electricity supply for cooking or heating is not feasible in the near term. FUNDING: WHO.