The Effects of Violence and Related Stress on Asthma

Abstract

In the United States, people living in deprived urban areas and persons in certain minoritized groups are often exposed to violence and affected with asthma, and epidemiologic studies have shown a link between exposure to violence (ETV) and asthma throughout the lifespan. Indeed, ETV at the individual, intrafamilial and community levels has been linked to asthma in children and adults. In this review, we discuss the evidence for a causal relation between ETV and asthma, emphasizing findings published in the last five years. Interpretation of the available evidence is limited by variable quality of the assessment of ETV or asthma, potential recall and selection bias, inability to estimate the relative contribution of various types of violence to the observed associations, lack of objective biomarkers of asthma or asthma endotypes, and inconsistent consideration of potential confounders or modifiers of the ETV-asthma link. Despite such limitations, the aggregate evidence from studies conducted in different locations and populations suggests that ETV affects asthma and asthma outcomes, and that this is explained by direct physiologic effects of violence-related distress and indirect effects (e.g., through risky health behaviors or co-morbidities). Thus, large prospective studies with careful assessment of specific types of ETV, key covariates and comorbidities (including mental illness), and asthma are needed to advance this field. Such research efforts should not preclude screening for maltreatment in children with asthma and ETV-related depression and anxiety in adolescents and adults with asthma. Further, vigorous policies are needed to curtail violence, as such policies could benefit patients with asthma while saving lives.

INTRODUCTION

Asthma affects approximately 300 million people and is the most common chronic respiratory disease among children worldwide¹. In 2021, 6.5% of children and 8% of adults in the United States (U.S.), comprising approximately 25 million people, were estimated to have current asthma².

Between 1980 and 2020, the U.S. experienced a substantial surge in homicides and homicides perpetrated with firearms, with mass shootings also increasing from 2018 to 2022³. In 2019, gun violence became the number one cause of death in U.S. children⁴, making this extreme form of violence a major public health problem nationwide.

In the U.S., people living below the federal poverty level or in deprived urban areas and members of certain minoritized groups (Puerto Rican, Black, and Indigenous persons) are disproportionately affected with asthma^{2, 5}. In parallel, people in these groups are often directly (as victims) or indirectly (as witnesses) exposed to violence at multiple levels (individual, intrafamilial, community, and global) throughout their lifespans⁶.

Over the last three decades, epidemiologic studies with variable design have reported an association between exposure to violence (ETV) at various life stages and at multiple levels (individual, intrafamilial or community) and asthma or worse asthma outcomes^6–10.

In this focused review article, we first examine and interpret findings linking ETV to asthma, emphasizing those published in the last five years. We then discuss the clinical implications of this evidence and propose future directions for research in this field.

Exposure to violence (ETV) and asthma

Individual-level

Table 1 summarizes the design and findings of recent epidemiologic studies of various types of ETV at the individual level and asthma.

Table 1.

Summary of studies of exposure to violence and asthma at the individual level, published since 2020

Type of exposure	References	Study design and study population	Main findings	Strength of the evidence
ETV and related distress	Gaietto, K. et al., 202212	Longitudinal 98 U.S. children aged 9–16 years treated with low-dose ICS in a 48-week randomized clinical trial (VDKA, 2016–2019), and 232 Puerto Rican youth aged 9–20 years resided in Puerto Rico followed by 5.4 years (2009–2010 and 2014–2017)	• 1-point increment in CCDS score was associated with 3.27% decrease in FEV1 %predicted and 2.65% decrease in FVC %predicted in the VDKA cohort • 1-point increment of CCDS score was associated with 0.30 points lower overall PAQLQ score in the VDKA cohort • 1-point increment in CCDS score was associated with 3.50% decrease in FEV1 %predicted and 2.23% decrease in FVC %predicted in the Puerto Rican replication cohort	• Moderate to high
ETV and related distress	Gaietto, K. et al., 202314	Cross-sectional and longitudinal 892 Puerto Rican children and youth aged 6–20 years resided in Puerto Rico, 2009–2010 and 2014–2017	• 742 and 150 participants had high and low Th2 immunity*, respectively • In the cross-sectional analyses, 1-point increment in ETV or CCDS score was associated with 1.13−1.54 times increased odds of asthma in participants with high Th2 immunity • In the longitudinal analyses, a persistently high ETV score was associated with persistent or new-onset asthma in youth with high Th2 immunity (OR= 2.83, 95% CI= 1.10−7.29)	• Moderate to high
Child maltreatment	Ospina, M.B. et al., 202131	Cross-sectional 1,207 Canadian adults living in Alberta, 2013	• Experiencing sexual abuse during childhood was associated with asthma in adulthood (OR=3.23, 95% CI=1.89–5.23) • Childhood verbal or physical abuse, or witnessing violence against mothers was associated with asthma in adulthood (95% CI=1.17–3.38)	• Weak to moderate
Child maltreatment	Han, Y.Y. et al., 202233	Cross-sectional 81,105 British adults aged 40–69 years from the U.K. Biobank, 2006–2010	• In women, any CM (OR=1.24, 95% CI=1.15–1.33) and sexual abuse (OR=1,29, 95% CI=1.16–1.43) were associated with current physician-diagnosed asthma • In men, any CM was associated with current physician-diagnosed asthma (OR=1.19, 95% CI=1.09–1.29) • In all participants, lifetime generalized anxiety disorder and lifetime major depressive disorder explained 21.8% and 32.5%, respectively, of the CM–current asthma association.	• Moderate
Child maltreatment	Kascakova, N. et al., 202230	Cross-sectional, population-based survey (national representative) 1,800 Czech adults aged 15–88 years and 1,018 Slovak adults age 18–85 years, 2016	• Any type of abuse or neglect was associated with 1.5- to 6.6 times increased odds of asthma in all participants • A dose-response relationship was reported, with participants who reported ≥ 3 types of maltreatment having the highest odds of asthma	• Weak to moderate
Child maltreatment	Han, Y.Y. et al., 202335	Cross-sectional 87,891 British adults aged 40–69 years from the U.K. Biobank, 2006–2010	• In women, exposure to ≥ 2 types of CM was associated with 1.26 (95% CI=1.13–1.41) to 1.62 (95% CI=1.44–1.83) times increased odds of current physician-diagnosed asthma after adjusting for adverse events during adulthood • In men, exposure to ≥ 2 types of CM was associated with 1.24 (95% CI=1.07–1.43) to 1.53 (95% CI=1.28–1.84) times increased odds of current physician-diagnosed asthma, after adjusting for adverse events during adulthood. • Similar findings were obtained in analyses stratified by smoking status or peripheral blood eosinophil count	• Moderate
Child maltreatment	Moog N.K. et al., 202325	Meta-analysis of longitudinal data from birth cohorts 4,337 mother-child dyads from 21 cohorts from the ECHO program,1999–2016	• Maternal exposure to CM was associated with asthma in their offspring (OR=1.54, 95% CI=1.34–1.77) • There was a dose-response relationship between the number of types of CM reported the mothers and risk of asthma in their offspring. • The association between maternal CM and asthma in offspring did not differ by child sex	• Moderate
Sexual violence (Rape)	Hancox, R.J. et al., 202041	Longitudinal population-based study 1,037 adults aged 38 years (born in 1972 or 1973), New Zealand	• In women, forced intercourse was associated with asthma (OR=4.47, 95% CI=2.22–8.99), wheeze (OR=2.19, 95% CI=1.23–3.90), and dysfunctional breathing (OR=2.71, 95% CI=1.47–5.01) • In men, forced intercourse was associated with increased dysfunctional breathing only (OR=8.05, 95% CI =2.53–25.70)	• Moderate
Bullying	Curry, C. W. et al., 202144	Cross-sectional, population-based survey 21,789 US youth in grades 9 to 12 in both public and private schools from the Youth Risk Behavior Survey, 2009–2017	• In female students, victimization from bullying (OR=1.54, 95% CI=1.23–1.92) and cyberbullying (OR=1.39, 95% CI=1.10–1.76) was associated with non-remitting asthma • In male students, victimization from bullying was associated with non-remitting asthma (OR=1.39, 95% CI=1.03–1.62).	• Weak to moderate
Bullying	Joseph, S.P. et al., 202245	Cross-sectional, population-based survey 19,766 U.S. children and adolescents aged 6–17 years from the National Survey of Children’s Health, 2018	• Experiencing bullying 1 to 2 times per year was associated with asthma (OR=1.28, 95% CI=1.06–1.55) • Being bullied at least 4 times per month was associated with asthma (OR=1.59, 95% CI=1.22–2.09)	• Weak to moderate

CM=child maltreatment, CCDS= Checklist of Children’s Distress Symptoms, CI=confidence interval; ECHO= Environmental influences on Child Health Outcomes, ETV=exposure to violence, FEV₁= forced expiratory volume in 1 second, FVC= forced vital capacity, ICS=inhaled corticosteroids, OR=odds ratio; PAQLQ= Pediatric Asthma Quality of Life Questionnaire, VDKA= Vitamin D Kids Asthma Study

^*High Th2‐immunity was defined as ≥1 positive allergen specific IgE and/or a total IgE ≥ 100 IU/mL and/or an eosinophil count ≥ 150 cells/μL

Sex-specific associations are shown when reported.

ETV and related distress

Being witness to or a direct victim of violence at home, school or in the neighborhood has been associated with asthma in cross-sectional studies of school-aged children^{6, 11}. However, little is known about the relation between ETV and specific phenotypes or endotypes of asthma. Further, whether ETV and related distress have any link to new onset or persistence of asthma in children with enhanced T helper (Th)2 immunity is unknown (i.e. Could ETV play a role in the development or persistence of asthma -as opposed to other conditions such as atopic dermatitis- in children at risk of allergic diseases?).

In a recent study, Gaietto et al. reported that lifetime ETV and violence-related distress in the prior six months (both measured using validated scales) were associated with asthma in two cross-sectional studies of Puerto Rican youth aged 9 to 20 years who had positive biomarkers of high Th2 immunity (a high total IgE, a positive IgE to at least one common aero-allergen, or a high eosinophil count)¹². Further, a longitudinal analysis in youth who participated in both studies (conducted approximately 5 years apart) found that those who had persistently high ETV at both timepoints had higher odds of asthma than those who did not, suggesting that ETV and related distress may lead to persistence or new onset of Th2-high asthma among children at risk¹².

Violence-related distress may worsen asthma by promoting resistance to short-acting beta2-agonists and inhaled corticosteroids (ICS). In a cross-sectional study of Puerto Rican children with asthma, those with high violence-related distress in the prior six months had lower bronchodilator responsiveness (BDR) than others¹³. Further, anxiety or related conditions were linked to lower BDR in other diverse cohorts of youth who had or were at risk for asthma, and a genetic variant in the gene for adenylate cyclase activating polypeptide 1 receptor type 1 [(ADCYAP1R1), a candidate gene for childhood anxiety and post-traumatic stress disorder or post-traumatic stress disorder (PTSD) in adults] was associated with reduced BDR and lower expression of the gene for the beta2-adrenergic receptor (ADRB2) in CD4+ lymphocytes from youth and adults with asthma, as well as with a radiologic marker of anxiety in heavily traumatized women with asthma¹³. More recently, Gaietto et al. showed that increased levels of violence-related distress over 1 to 5 years were linked to lower growth rates in forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC) or worse asthma-related quality of life, even among children treated with low-dose ICS, in two longitudinal studies of youth in the U.S. mainland and in Puerto Rico¹⁴.

Child maltreatment

Adverse childhood experiences (ACE) can have lasting effects on physical and mental health and have been linked to asthma¹⁵. Child maltreatment (CM) is an ACE that includes not only physical or emotional neglect but also direct ETV as physical, sexual, or emotional abuse. Although estimates of the prevalence of CM must be cautiously interpreted due to potential under-reporting, at least 13% of children in the U.S¹⁶ and as many as ~25% of adults worldwide may have experienced CM, with sexual abuse more common in girls than in boys and physical abuse more common in boys than in girls^{17, 18}

Three separate cross-sectional studies, each including at least 1,200 participants, reported that children and (in one study) young adults with history of CM had 1.5 to 2.5 times higher odds of lifetime or current asthma than those without CM history^19–21, though one such study only found an association with non-atopic asthma symptoms¹⁹. Similarly, two prospective studies, each including at least 3,700 participants, reported that any CM was associated with lifetime asthma or hospitalizations for asthma in children and adolescents in Brisbane (Australia) and in a city in the U.S. midwest^{22, 23}, compared to no CM. However, the association reported in the Australian study was attenuated after adjustment for confounders²².

CM may have intergenerational effects, perhaps through epigenetic mechanisms, as offspring of mothers who experienced CM may be at increased risk of asthma symptoms in early childhood²⁴ or at school age²⁵. In a recent meta-analysis of data from 4,337 mother-child dyads who participated in 21 of 69 cohorts in a North American consortium, conducted by Moog et al, maternal report of any CM before age 18 years was associated with 1.54 times increased odds of asthma (defined as parental or self-reported asthma illness or physician-diagnosed asthma) in their offspring, even after accounting for the child’s age sex, and race/ethnicity; parental age and income; and maternal education and maternal depression²⁵. Interestingly, there was suggestion of a dose-response relationship but not of an interaction between the child’s sex and maternal CM on childhood asthma.

Any effects of CM on asthma may extend into adulthood, as eight cross-sectional studies and one prospective study have reported an association between CM and asthma in adults in different racial or ethnic groups and in diverse geographic locations^26–34, with evidence of a dose-response relationship for the number of types of CM and current asthma in several cross-sectional studies^{28, 30, 32, 33}, including a meta-analysis of data from ten countries³². In the only prospective study of CM and asthma in adults to date, 28,456 African American women aged 21 to 59 years were followed up for 16 years³⁴. In that study, women who reported any physical or sexual abuse during childhood had 24% higher risk of new-onset asthma during follow-up than those who reported no such abuse during childhood, even after adjusting for parental asthma, income, education, hormonal therapy, body mass index (BMI) and health behaviors (physical activity, smoking, alcohol consumption)³⁴.

Two recent cross-sectional studies by Han et al. examined whether mental illness or adverse experiences during adulthood may mediate or account for an association between self-reported CM and asthma in British adults. In the first study, including 81,105 British adults 40 years and older, any CM was associated with 22% increased odds of current asthma (defined as physician-diagnosed asthma and current wheeze) compared to no CM, with a dose-response relationship for the number of types of CM. Moreover, a mediation analysis showed that lifetime generalized anxiety disorder (GAD) and/or major depressive disorder (MDD) explained nearly a third of the estimated effects of CM on asthma, even after accounting for tobacco use and other covariates³³. In the second study, including 87,891 British adults, having at least two types of CM was associated with 1.25 to 1.59 times increased odds of current asthma compared to no CM, independently of adverse events during adulthood and tobacco use³⁵. Interestingly, the estimated effects of CM on asthma were not modified by sex or eosinophil count, suggesting potential long-lasting pre-pubertal effects of CM on eosinophilic and non-eosinophilic asthma into adulthood.

Sexual violence

Sexual violence against women -including rape, sexual assault, sexual harassment, and sexual exploitation- is common, with one study estimating that 7% of women worldwide had experienced non-partner sexual violence^{36 37}. Such violence may have long-lasting health effects including mental disorders such as depression and anxiety, poor quality of life, and chronic conditions such as HIV/AIDS and asthma^{38, 39}.

In a survey of 4,831 American women, unwanted touching, attempted unwanted intercourse, forced unwanted intercourse, and any sexual violence (touching, attempted intercourse, or forced intercourse) were associated with 1.8- to 3.7- fold increased odds of asthma episodes⁴⁰.Further, a study of 1,037 adults in New Zealand showed that rape victimization before age 16 years was associated with 2.2- to 4.5-times increased odds of current asthma, current wheeze, and dysfunctional breathing in women at age 38 years. In that study, rape victimization was associated with dysfunctional breathing but not with asthma or wheeze in men⁴¹. Because sexual violence constitutes one form of intimate partner violence (IPV) and given that IPV occurs at both the individual and intrafamilial levels, we review IPV in the section on intrafamilial violence.

Bullying

Bullying or cyberbullying (physical, verbal, relational or social) of school-aged children is a major public health challenge. In a study of high school students in the U.S., 25% had experienced any bullying, 19.5% reported having been bullied on school property in the prior year, and 15.7% reported having been victims of electronic bullying (through texting, Instagram, Facebook, or other social media) in the prior year⁴².

Children living with chronic conditions such as asthma are at risk of being bullied at school⁴³, and chronic distress from bullying has been linked to childhood asthma. Three cross-sectional nationwide surveys found that, compared with no bullying, cyberbullying or victimization/bullying on school property in the previous year was associated with 27%–59% increased odds of asthma in U.S. children^44–46, with similar findings in a cross-sectional study of Korean youth⁴⁷. Moreover, bullying victimization can lead to cigarette smoking, violent behavior, lack of sleep, physical inactivity, or attempted suicide, all of which may in turn increase the risk of asthma or worse asthma outcomes⁴⁸.

Intrafamilial level

Recent epidemiologic studies of intrafamilial ETV and asthma are summarized in Table 2. Three cross-sectional studies showed that maternal lifetime exposure to IPV, domestic violence, or chronic interpersonal trauma (physical violence, abuse, or forced sex), was associated with 29%–82% increased odds of asthma in their offspring compared to offspring of women reporting none of these adversities^49–51. In one of these studies, a sex-stratified analysis further revealed that this association was seen in boys but not in girls⁵¹.

Table 2.

Summary of studies of exposure to intrafamilial violence and asthma, published since 2020

Type of exposure	References	Study design and study population	Main study findings	Strength of the evidence
Intimate partner violence	Kariuki, S.M. et al., 202052	Cross-sectional and longitudinal 762 infants aged 6–10 weeks and 485 infants at 12 months from South African mother‐infant dyads, 2012–1015	• In the cross-sectional analyses, prenatal or postnatal IPV was associated with reduced respiratory resistance at 6–10 weeks (β=−0.13, p=0.02), and lower ratio of tPTEF/tE at 12 months (β=−0.04, p=0.03) • In the longitudinal analyses, prenatal IPV was associated with reduced tPTEF/tE (β=−0.05, p<0.01) and postnatal IPV was associated with decreased FRC (β=−0.09, p<0.01)	• Moderate to high
Intimate partner violence	Gartland, D. et al., 202156	Longitudinal birth cohort 615 mother–child dyads from six public hospitals in Melbourne, Australia, 2003–2005	• Maternal IPV reported when children were aged 1 and/or 4 years was associated with childhood asthma at age 10 years (OR=2.0, 95% CI=1.3–3.2)	• Moderate
Intimate partner violence	Wang, E. et al., 202161	Cross-sectional, population-based survey 2,634 U.S. adults (71.3% women) aged 18 years and older from 14 States from the Behavioral Risk Factor Surveillance System, 2005	• Any IPV was associated with asthma exacerbations (OR=1.75, 95% CI=1.26–2.43), higher burden of asthma symptoms (OR=2.33, 95% CI=1.53–3.55), and worse asthma control (OR=2.23, 95% CI=1.22–4.09) in men and women • Both recent (<12 months) and remote (≥ 12 months) exposure to IPV were associated with asthma-related ED/UC visits, other urgent provider visits, and nocturnal awakenings	• Weak to moderate
Domestic violence and abuse (DVA)	Nash, K. et al., 202359	Retrospective, population-based cohort 62,888 women aged 18 years and older from a large U.K. primary care database, 1995–2019	• A history of DVA was associated with all atopic diseases (HR=1.52, 95% CI=1.41-.1.64), including asthma (HR=1.69, 95% CI=1.44–1.99) • Incident DVA during the study period was associated with asthma (HR=1.57, 95% CI=1.12–2.19)	• Weak to moderate
Adverse childhood experiences	Thompson, L.A. et al., 202067	Cross-sectional, population-based study 29,450 U.S. children and adolescents (50.5% females) aged 6–17 years from the National Survey of Children’s Health, 2016	• Economic hardship (OR=1.5, 95% CI=1.2–1.9) and living with anyone with mental illness, suicidal, or depressed (OR=1.6, 95% CI=1.1–2.3) was associated with current asthma • A dose-response relationship was reported, with youth exposed to 4 and more types of ACE having higher odds of asthma (OR=1.9, 95% CI=1.3–2.8) than those exposed to 1 type of ACE (OR=1.3, 95% CI=1.0–1.7)	• Moderate
Adverse childhood experiences	Lietźen, R. et al., 202169	Longitudinal, population-based study 21,902 Finnish adults (59% women) aged 20–54 years that were followed for 14 years, 1998–2012	• Exposure to multiple ACEs was associated with adult-onset asthma (HR=1.26, 95% CI=1.16–1.38), compared with exposure to ≤1 ACE. • The ACE-asthma association was similar in women (HR=1.27, 95% CI=1.14–1.42) and men (HR=1.23, 95% CI=1.05–1.44) • The excess asthma risk among participants reporting multiple ACEs persisted over 14 years of follow up	• Moderate to high

ACEs=adverse childhood experiences; CI=confidence interval; DVA=domestic violence and abuse, ED=emergency department, UC=urgent care, FRC=functional residual capacity, HR=hazard ratio, IPV=intimate partner violence, OR=odds ratio; tPTEF/tE=time to peak tidal expiratory flow over total expiratory time. Sex-specific associations are shown when reported.

Longitudinal studies further support an association between pre- and post-natal maternal IPV and asthma or lung function in their offspring. In a birth cohort study from South Africa led by Kariuki et al., pre- and post-natal IPV was associated with decreased functional residual capacity and a reduced ratio of time to peak tidal expiratory flow over total expiratory time (tPTEF/tE) in children from ages 6–10 weeks through 12 months⁵². Further, another analysis of data from this cohort showed that, compared with no maternal IPV, maternal IPV was associated with twofold increased odds of recurrent wheeze at age two years⁵³. Moreover, two prospective U.S.-based studies including at least 1,292 mother-child pairs found an association between maternal IPV and childhood asthma at age 36⁵⁴ or 48⁵⁵ months. Similarly, Gartland et al. showed that maternal IPV before their offspring was aged 5 years was linked to a twofold increased risk of childhood asthma at age 10 years⁵⁶.

Four cross-sectional studies in women^{40, 57–59} and three cross-sectional studies in men and women^{50, 60, 61} reported an association between a history of IPV or domestic violence and asthma or worse asthma outcomes in adults. Compared with no domestic abuse, domestic abuse was associated with 20%–68% increased prevalence of asthma in women in nationwide studies in the U.K., Australia, and India^{50, 58, 59}. . In two studies, lifetime IPV was also associated with asthma in men, though the strength of such association was weaker than that reported in women⁶⁰. In contrast to the findings summarized above, IPV was not associated with asthma in two cross-sectional studies including at least 1,200 women in South Africa⁶² and Spain⁶³, and domestic abuse was not associated with deaths from asthma in a British case-control study⁶⁴.

Violence, chaos or dysfunction within families can lead to chronic stress and have been linked to asthma. In four cross-sectional studies of children, family chaos and parental depressive symptoms were associated with worse asthma control⁶⁵, and a history of ACEs and household dysfunction (e.g., witnessing domestic violence, parental divorce or having a parent jailed, or extreme economic hardship) were associated with current or lifetime asthma^66–68. Moreover, ACEs may have long-lasting effects on asthma into adulthood, as retrospective report of multiple family-level adversities during childhood (e.g., parental divorce; financial difficulties; family conflicts; fear of, alcohol use, or illness of a family member), compared with report of no or one family-level adversities, was linked to 31% increased risk of new-onset asthma during adulthood in a large Finnish study by Lietźen et al.⁶⁹

Community level

Community violence is more common in deprived urban areas, which often have a higher burden of asthma. Such violence has been linked to asthma or worse asthma outcomes during childhood in seven cross-sectional studies in the U.S.^70–76, Canada⁷⁷, and Brazil ⁷⁸. In Puerto Rico, a U.S. territory, school-aged children who had heard gunshots more than once during their lifetime had 1.8 times higher odds of asthma than those who had heard gunshots no more than once, even after adjustment for income, second-hand smoke, traffic-related air pollution, and other covariates. Interestingly, the estimated effects of hearing gunshots were greater in children who were also afraid to leave their home due to neighborhood violence⁷², perhaps due to greater violence-related distress.

Children who have both asthma and caregivers who perceive their neighborhoods as unsafe are more likely to have poor disease control or increased use of rescue medications^74–76. Consistent with this finding, analyses of data from the Chicago Police Department showed that higher neighborhood rates of violent (homicide, criminal sexual assault, robbery, aggravated assault, or aggravated battery) or property (burglary, theft, motor vehicle theft, arson) crimes were associated with asthma and emergency department (ED) visits for asthma in school-aged children⁷⁰, including Mexican American children⁷¹. Similarly, community rates of crimes including sexual assaults or theft were linked to those for childhood asthma in Winnipeg (Canada)⁷⁷.

Consistent with cross-sectional findings, results from seven longitudinal studies support an association between community violence and asthma or related outcomes^{14, 79–84}. Compared with children living in neighborhoods with low ETV, those who experienced medium-to-high ETV in their neighborhoods were at 56%–60% increased odds of asthma in a study that accounted for individual- or neighborhood-level confounders⁷⁹. Further, community violence was linked to reduced lung function in another study of urban boys⁸⁰, and living in communities with higher crime rates was associated with 23% increased risk of new-onset asthma and ED visits or hospitalizations for childhood asthma, even after accounting for household characteristics and air pollution^{81, 82}.

Scarce evidence links community violence to asthma in adults. One cross-sectional study found that higher rates of violent crime and theft were associated with reduced adherence to ICS in 75 African American adults with asthma, even after adjusting for socioeconomic status (SES) indicators⁸⁵, while another study showed that community violence was associated with lower asthma-related quality of life and ED visits and hospitalizations for asthma in 397 predominantly African American adults with moderate to severe asthma⁸⁶.

Global-level

Global ETV can be due to political conflicts, wars, natural disasters, or trafficking in persons (TIP). In 2020, trafficking for sex (39%) and forced labor (39%) were the most common forms of TIP, with 42% of detected victims being women and 35% being children⁸⁷. Although published evidence is scarce, TIP has been associated with severe adverse effects on physical, sexual, and mental health^{88, 89}, including delayed effects on physical health after sexual victimization of women during trafficking⁹⁰. Given this, future studies should examine whether TIP is linked to increased asthma risk.

Mechanisms and pathways linking violence, stress, and asthma

ETV may cause or worsen asthma through direct physiological effects or through indirect effects (by increasing the risks of adopting health risk behaviors or other conditions associated with asthma [e.g., obesity, depression, and anxiety-related disorders]). Moreover, any effects of ETV on asthma may be modified by heredity, sex or gender, race or ethnicity, SES, pollutants, comorbidities, and social support (Figure 1).

Figure 1.

Conceptual model for pathways connecting exposure to violence, chronic stress, and asthma or asthma outcomes. Dotted lines represent indirect pathways. Adapted from Han et al.⁹¹ HPA, hypothalamic-pituitary-adrenal; PTSD, posttraumatic stress disorder.

Physiological mechanisms

Distress from acute ETV could reduce inflammation by activating the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic–adrenal–medullary (SAM) system, leading to cortisol-induced suppression of pro-inflammatory cytokines such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α. However, chronic distress from prolonged ETV could trigger inhibitory pathways for secretion of cortisol and catecholamines, enhancing Th2 immune responses and allergic airway inflammation^91–94. Consistent with this hypothesis, ETV was recently associated with asthma among Puerto Rican youth with biomarkers of enhanced Th2 immunity¹².

Violence-related distress may also affect asthma through neuro-hormonal pathways leading to abnormal expression of genes that regulate the HPA axis, SAM system, and immune responses, directly or via epigenetic mechanisms such as DNA methylation^{10, 95, 96}. Indeed, stressful experiences have been linked to increased DNA methylation in white blood cells from subjects with asthma and/or reduced expression of genes affecting BDR and corticosteroid response, including NR3C1 (nuclear receptor subfamily 3 group C member 1), ADRB2, and CRHR1 (corticotropin releasing hormone receptor 1)^{10, 97}. Moreover, ETV was associated with methylation of a CpG site in the ADCYAP1R1 promoter (cg11218385), which was then linked to asthma^{11, 13}.

Indirect effects

Violence-related distress could affect asthma by leading to adoption of risk factors such as tobacco use, obesity from unhealthy dietary habits and inactivity, and reduced treatment adherence^{7, 98}.

Lifetime ETV, IPV and a history of CM have been linked to marijuana use, cigarette smoking, and nicotine dependence in youth and adults^{30, 62 99}. Further, self-report of two or more types of CM has been associated with excessive screen time and intake of sugar beverages or fast food in males and females¹⁰⁰, community violence has been linked to reduced physical activity in youth, and dating violence or CM fosters weight gain in female adolescents and in young adults¹⁰¹, all promoting overweight or obesity (a risk factor for asthma)^{6, 102}. Moreover, lower ICS adherence has been reported in African American adults with asthma living in areas with high crime rates, even after adjusting for SES indicators⁸⁵.

Violence-related stressors could cause or worsen asthma through mental disorders such as depression, GAD, and PTSD^{38, 103, 104}, which can in turn cause airway inflammation via abnormal neurohormonal and immune responses or reduce treatment response^105–109. In U.S. adolescents, depressive symptoms and suicidal behaviors were shown to mediate 14% to 21% of the association between any victimization at school and asthma¹¹⁰, and lifetime GAD and MDD mediated 21.8% and 32.5%, respectively, of an association between self-reported CM and asthma in British adults³³. Similarly, depressive symptoms partly mediated the estimated effects of ACEs (e.g., peer bullying and physical abuse) on asthma in a retrospective study of older Chinese adults¹¹¹.

Effect modifiers

ETV can potentially interact with other risk factors for asthma. Two studies, one including a subset of participants in a birth cohort study in East Boston (MA) and another using data on community crime rates in New York City (NY) for a case-crossover analysis, have shown that outdoor pollutants such as nitrogen dioxide (NO₂) and ozone are only associated with asthma or ED visits for asthma among youth highly exposed to violence^{112, 113}. Extending these findings to the indoor environment, chronic maternal IPV has been shown to be more strongly associated with childhood asthma at age 3 years among families living in disarrayed or poor housing conditions (and thus likely exposed to indoor allergens and pollutants). Taken together, current evidence suggests that ETV may increase susceptibility to asthma in those exposed to outdoor or indoor pollutants.

Sex or gender may modify any effects of ETV on asthma^{6, 114}. Females are more often victims of sexual abuse, IPV, and bullying, while also being more susceptible to the adverse effects of violence because adaptive feedback of the HPA axis in response to chronic stress may be less efficient in females than in males across the lifespan^{115, 116}, perhaps due to hormonal effects¹¹⁷. In two birth cohort studies including a total of 1,182 mother-child pairs, pre- and post-natal maternal negative life events (NLE) were associated with asthma or wheeze in children aged 2 or 6 years, but the estimated effects of maternal post-natal NLE on asthma or wheeze were stronger in girls than in boys^{118, 119}. Consistent with an interaction between sex and ETV on asthma, a cross-sectional nationwide survey of U.S. high school students reported that forced sex and cyberbullying were associated with non-remitting asthma in females but not in males⁴⁴.

Coping mechanisms may attenuate any detrimental effects of ETV and related distress on asthma¹²⁰ or on adoption of risk behaviors for asthma such as smoking and unhealthy dietary habits^{99, 100, 121}. For example, mother-child activities or availability of educational or recreational toys have been shown to decrease the risk of asthma in the children of mothers exposed to chronic IPV⁵⁴.

CONCLUSION

Interpretation of the evidence for a causal link between various types of ETV and asthma is limited by differing quality of exposure assessment, potential recall bias and selection bias, inability to estimate the relative contributions of each type of ETV to the observed associations, lack of data on objective biomarkers of asthma and asthma phenotypes or endotypes, potential misclassification of transient wheeze (in young children) or chronic obstructive pulmonary disease (COPD, in adults) as asthma. Regarding the exposure, some studies have directly assessed ETV through self-report (by the parents in studies of children or by adults themselves), while others have relied on information extracted from databases, which may in turn have data at the community but not at the individual level. Further, many studies rely on retrospective assessment of various types of ETV by the participants or their parents, causing potential recall bias for non-severe events, and the severity of the exposure (ETV) and the outcome (asthma) may influence study entry or retention, leading to selection bias. In addition to what is discussed above, published studies have not consistently measured, adjusted, or tested for interaction with potential confounders or effect modifiers that commonly co-occur with ETV, including sex or gender, indoor and outdoor pollutants, overweight or obesity, preterm birth, healthcare access, mental disorders, and treatment and treatment adherence.

Despite such limitations, findings from recent studies and the aggregate body of literature support an association between ETV and violence-related distress and asthma. Although the mechanisms underlying these findings are insufficiently understood, preliminary evidence suggests that ETV may affect asthma through direct effects of violence-related distress on neuro-hormonal pathways or indirectly by leading to adoption of other risk factors for asthma (e.g., tobacco use) or co-morbidities such as obesity.

While there has been much progress over the last decade, large studies with a prospective design and careful direct assessment not only of specific types of ETV but also of key covariates (including structural and social determinants of health) and comorbidities (including mental illness), coping mechanisms, and asthma phenotypes and endotypes are needed to advance the field of ETV and asthma, in conjunction with clinical trials to test whether pharmacological and non-pharmacological interventions^{122, 123} to treat ETV-related MDD or GAD benefits adolescents and adults with asthma. In parallel, analyses of data from both epidemiologic and experimental studies should help advance our understanding of the causal pathways for the ETV-asthma link and thus improve the prevention, diagnosis, and treatment of asthma.

Ongoing and future research, while important, should not preclude screening for CM and for ETV- related depressive and anxiety disorders in children and adults with asthma, which can be done using tools validated for general medical practice (e.g., ACE questionnaire¹²⁴ for CM, PHQ-9 for depression, GAD-7 for anxiety). In parallel, future studies should aim to develop much needed screening tools for IPV or sexual violence with robust psychometric properties^{125, 126}.

Persons with asthma who have been exposed to violence, particularly women, children, and members of minoritized and disadvantaged groups¹²⁷ may benefit from trauma-informed care (TIC), which recognizes and responds to the signs, symptoms, and risks of trauma to better support the health needs of patients who have experienced adversities or traumatic events. Beyond this or other interventions at the individual or intrafamilial level, vigorous efforts are needed to develop and implement public health policies aiming to improve neighborhood or community-level safety and curtail the ongoing epidemic of gun violence, as such policies could benefit patients with chronic conditions such as asthma¹²⁸ and, more importantly, save lives.

Abbreviations:

ACE

adverse childhood experience

ADCYAP1R1

adenylate cyclase activating polypeptide 1 receptor type 1

ADRB2

beta2-adrenergic receptor

BDR

bronchodilator responsiveness

BMI

body mass index

CI

confidence interval

CM

child maltreatment

ED

emergency department

ETV

exposure to violence

FEV₁

forced expiratory volume in 1 second

FVC

forced vital capacity

GAD

generalized anxiety disorder

HPA

hypothalamic-pituitary-adrenal

ICS

inhaled corticosteroid

IgE

immunoglobulin E

IL

interleukin

IPV

intimate partner violence

MDD

major depressive disorder

NLE

negative life events

OR

odds ratio

PTSD

post-traumatic stress disorder

SAM

sympathetic–adrenal–medullary

SES

socioeconomic status

Th2

T helper 2

TIC

trauma-informed care

TIP

trafficking in person

TNF

tumor necrosis factor

tPTEF/tE

time to peak tidal expiratory flow over total expiratory time

TRAP

traffic-related air pollution

US

United States