The collapse and burning of the World Trade Center (WTC) towers exposed thousands to a complex mixture of dust, debris, and jet fuel combustion byproducts (Landrigan et al., 2004). Physical health consequences for rescue/recovery workers and local community members are documented in multiple and distinct studies (Crowley et al., 2011; Dalton et al., 2010; Izbicki et al., 2007; Prezant et al., 2002; Reibman et al., 2005, 2009). Community members, including children, had potential acute exposures from the fires and dust cloud from collapsing buildings on the September 11, 2001, sub-acute exposures from the fires and resuspended dust within the first week, and/or chronic exposures from resuspended dust and incompletely cleaned homes/schools (Friedman et al., 2011). Exposed pregnant women have been studied for consequences in their children (Berkowitz et al., 2003; Lederman et al., 2004; Wolff et al., 2005), and authors have related psychological stress in children to the disaster (Chemtob et al., 2008). However, little is known about physical health impacts on the nearly 46,000 children who lived and/or attended school in downtown Manhattan (Landrigan et al., 2004), a large number of whom continued to reside near the WTC site in the months after the tragedy.

The WTC Health Registry (WTCHR), a national monitoring program sponsored by the National Institute for Occupational Safety and Health, includes questionnaire-derived parental reports on their children exposure and health consequences. A prior report identified 45% of respondent children with WTC dust cloud exposure, over half of whom reported ≥1 new or worsened respiratory symptom post-exposure; 5.7% reported new post-September 11 asthma, a cumulative prevalence well above expected (Thomas et al., 2008b). Possible etiologic origins include exposure to alkaline dust/smoke in the immediate aftermath (Lioy et al., 2002) and combustion products released by fires burning >3 months after the event (Landrigan et al., 2004). Psychological trauma (Islam et al., 2011), as well as consequent psychopathology, may also contribute.

Physiologic/physician corroboration of these parent-reported, questionnaire-derived findings is lacking. Szema et al. investigated asthma diagnosis, medication use, and limited spirometry data in a group of schoolchildren in Chinatown, reporting increased asthma medication use with greater proximity to the WTC site (Szema et al., 2009). To our knowledge no study has performed comprehensive physiologic assessment of respiratory/other physical health effects in exposed children.

Especially for those children with asthma and other respiratory consequences directly related to the WTC disaster, obesity, insulin resistance and other cardiometabolic consequences may well exist. Increased risk of obesity among children from asthma is well documented, possibly due to decreased reduced functional lung and exercise capacity (Bibi et al., 2004; Figueroa-Muñoz et al., 2001; Gilliland et al., 2003; Shore, 2008; To et al., 2004). Further dietary imbalances may have been produced by exposure to WTC dust or by witnessing the events of September 11, 2011 and experiencing resultant mental health consequences, such as depression, anxiety and post-traumatic stress (Goodman and Whitaker, 2002; Richardson et al., 2003).

The cardiovascular consequences of outdoor air pollutants are best documented in the context of adult exposure, dating to the Six Cities study (Dockery et al., 1993; Krewski et al., 2004). While the cardiovascular consequences in children are not well documented, children's unique vulnerability to these pollutants is well documented for respiratory illnesses (Roy et al., 2011; Sheffield et al., 2011; Trasande and Thurston, 2005). It is within the context of the emerging obesity epidemic (Freedman et al., 1999; Ogden et al., 2008) in the United States in which the plausibility of accelerated and early cardiovascular disease in children arises, through the coupling of oxidative stress from outdoor air pollutant exposures and increased lipid deposition in early life (Ceriello and Motz, 2004; Griendling and FitzGerald, 2003; Heitzer et al., 2001). Indeed, DNA adducts have been identified as a marker of oxidative stress due to air pollution leading to cardiovascular diseases (Autrup et al., 1999; Risom et al., 2003). These same DNA adducts have been identified as elevated among highly exposed newborns born to mothers with increasing proximity to the WTC site (Perera et al., 2005). Adolescence may also mobilize highly lipophilic chemicals absorbed into fatty stores earlier in life, increasing bioavailability and potentially acutely increasing toxicity to multiple organ systems.

The WTC Survivors Health Program (WTCHP) at Bellevue Hospital is funded to provide clinical care to children who lived/attended school near the WTC site. We describe results from 148 clinical histories, physical examinations, and laboratory data of patients who presented to the WTCHP, and were ≤18 years of age on September 11, 2001. We examined associations of acute exposure to the dust cloud, sub-acute exposure (within the week after the towers fell) and chronic household exposures with respiratory, metabolic and cardiovascular outcomes.

Our sample was ethnically diverse (Table 1). Over one-third of questionnaire respondents (38.5%) were caught in the dust cloud. Many (39.7%) resided <1 mile from the WTC site, while most, 77%, attended school <1 mile from the WTC site. Home dust exposure was identified in 25.7%, with the majority reporting heavy exposure. An increase in a wide range of clinical diagnoses and symptoms was noted, with mean latency onset often within the first 3–4 years.

One-third were overweight, and 15.6% obese (Table 2). Prehypertension or hypertension criteria were met in 45.5% (33% of those <20 years of age), with 10.6% meeting hypertension criteria. An HDL<40 mg/dL was identified in 10%, 24% had triglycerides≥ 100 mg/dL, and 19.4% had elevated ALT. Body mass was similar to normative data from NHANES 2003–8. There was a significant divergence from normative data with respect to other cardiometabolic outcomes. Whereas in 2001–2006 NHANES, 6.9% were prehypertensive and 2.4% were hypertensive, 45.5% and 10.6% in our study population were prehypertensive and hypertensive respectively. Low HDL and elevated triglycerides were similar compared to a reference population (Johnson et al., 2009), while NAFLD prevalence was much higher (19.4%) adult NHANES prevalence (8%) (Clark, 2006). The mean eosinophil count was 168.4/μL and <2% had abnormal TSH. Both were slightly lower than the normative sample from NHANES 2009–10.

As of December 19, 2011, spirometry was completed in 127 (85.8%; Table 3). Four-fifths (82.9%) had normal predicted FEV₁ and FVC, yet mean FEV₁/FVC averaged 84.1%, with 11.3% having FEV₁≤ 5th percentile, and 10.5% with FEV₁/FVC≤5th percentile. Compared with normative data from NHANES 2007–10, the study population appeared to have lower FEV₁ and FVC percent predicted, as well as more frequent abnormal FEV₁, FVC, and MMEF.

Multivariable linear/logistic analyses of clinical and metabolic outcomes (Table 4) included dust cloud, home dust, residence ≥1 day at home between September 11 and 18, 2001, BMI category and age as independent variables. Spirometry outcomes also included categorical heavy dust cloud as a nominal covariate. Older children more frequently reported gastroesophageal reflux symptoms (+16.6% odds/year older, p=0.004) and headaches (+10.2% odds/year older, p= 0.011), while younger children were diagnosed with asthma more frequently (+16.2% odds/year younger, p=0.001). Increased eosinophils (counts and %) were identified among those residing at home ≥1 day in the week following the WTC disaster (p=0.027) and younger children (p=0.023). Prehypertension was positively associated with older age (+9.5% odds/year older, p=0.024).

Home dust exposure was associated with reductions in HDL (−10.3 mg/dL, p=0.027) and elevations in triglycerides (+36.3 mg/dL, p=0.033). Logistic regressions identified OR 7.00 (p=0.059) for elevated triglycerides and OR 2.85 (p=0.162) for low HDL. Exclusion of nonfasting triglycerides>200 mg/dL (suggestive of a genetic dyslipidemia not related to environmental exposure) (Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents: Summary Report, 2011) attenuated association of home dust with trigylcerides to p=0.059 (+22.3 mg/dL). No associations with TSH, anthropometrics or ALT were identified.

Children with dust cloud exposure, but not those with heavy dust cloud exposure, were identified as having reduced FEV₁/FVC (−5.4%, p=0.032) and MMEF (−17.1% predicted, p=0.034). Associations were also identified for dust cloud (but not heavy dust cloud) exposure with subnormal FVC (OR 44.36, p=0.003) and FEV₁/FVC (OR 15.06, p=0.002). Dust cloud exposure was associated with higher odds of abnormal spirometry (OR 24.39, p=0.0002), isolated low FVC (OR 21.16, p=0.011) and obstructive pattern (OR 7.05, p=0.026). No associations were identified either in the group not exposed to dust cloud or in the more heavily exposed dust cloud category (all p>0.05).

Our sensitivity analysis confirmed decrements in MMEF Z-score (−7.8% predicted, p=0.069) and FEV₁/FVC (−1.75%, p=0.110) among the heavily exposed group, as well as below normal FVC (OR 5.30, p=0.107) and FEV₁/FVC (OR 4.49, p=0.057). Higher odds of abnormal spirometry (OR 4.20, p=0.027), low FVC (OR 3.92, p= 0.194) and obstructive pattern (OR 2.92, p=0.188) were also identified. No increase in triglycerides was identified in the highly exposed sub-sample (+2.30 mg/dL, p=0.700) though a near-significant decrement in HDL was identified (−7.82 mg/dL, p=0.107). Increases in total and percent eosinophils persisted among younger children (+0.090% or +6.4/μL per year younger). Older age was still associated with prehypertension (+9.3% odds/year older, p=0.010), new GERD (OR +17.1% odds/year older, pb0.001), and headaches (+9.2% odds/year older, p=0.015), while younger children developed asthma more frequently (OR +14.1% odds/year younger, p=0.001). New-onset rash was identified in the most-exposed group (OR 3.88, p=0.023) with reduced latency (−3.4 years compared with least-exposed, p=0.010), and reduced latency to allergies was identified among the most heavily exposed (−1.9 years, p=0.032).

These findings suggest a wide range of potential health effects in children with WTC dust exposure. Strengths of this study include: use of clinical testing on pulmonary function, anthropometry, and blood pressure, and metabolic evaluations in addition to exposures and symptoms obtained via clinical history. Most of the clinical tests performed were standardized by age and gender according to national standards.

Absent a reference group or baseline data, the increased risks observed could be due to pre-existing, unknown risk factors in downtown New York City rather than to WTC dust exposure. Additionally, data obtained from a clinic population may not apply to the entire population of exposed children. As the initial clinical visit occurred on average 7.83 years after the WTC tragedy, recall bias of symptoms and exposures is also a concern. Our sensitivity analysis diminishes but does not preclude such concerns. Our clinical measurements are also from a single time point quite distant in time from 2001, and other interceding/confounding events represent plausible alternative explanations for the effects identified.

White coat hypertension is also well documented, and the present study is limited by the existence of a “first reading” effect with oscillometric devices. The present analysis also does not control for psychological stress and related symptoms of posttraumatic stress disorder and depression, an important covariate for the outcomes we studied (Wright, 2005; Wright et al., 2002, 2005). Possible confounding of dust cloud by coexistent stressful exposures known to independently influence pulmonary consequences of air pollution exposure (Islam et al., 2011; Wright, 2005) further limits statements regarding causation. The study area may have had high rates of aerodigestive, cardiometabolic, and high eosinophilia rates even before September 11, 2001. The demographics of our sample are similar to WTCHR children (Thomas et al., 2008b) alleviating this concern somewhat.

Recognizing these limitations, our findings of abnormal FEV₁, obstructed pattern, and low vital capacity, mirror those identified in adults exposed to the dust cloud (Banauch et al., 2006; Friedman et al., 2011; Kleinman et al., 2011). The absence of an association of heavy dust cloud exposure with decrements in spirometry is counterintuitive. Children covered in dust may have been more likely to limit ongoing exposure in the days after September 11, 2001. We did not ask about eye irritation from the dust cloud as a proxy for severity of exposure, as the WTCHR did (Thomas et al., 2008a), and so there is limited comparability with those results. We may also have suffered from low statistical power to detect effects among this relatively small subpopulation of children in our study. Yet an acquired deficit in lung growth such as the one we identified has been associated with an accelerated decline in lung function and the development of chronic obstructive pulmonary disease in adulthood (Martinez, 2009) and it is therefore even more important to interrogate the possibility of physiologic decrements in a larger, more representative sample with a diversity of WTC exposures and compare them with a control group.

The relatively high frequency of cardiometabolic risks is also of great concern, and has biologic plausibility. Increased risk of obesity among children from asthma is well documented, possibly due to decreased reduced functional lung and exercise capacity (Bibi et al., 2004; Figueroa-Muñoz et al., 2001; Gilliland et al., 2003; Shore, 2008; To et al., 2004). Further chronic dietary imbalances may have been produced by exposure to WTC dust or by witnessing the events of September 11, 2011 as well as experiencing resultant mental health consequences, such as depression, anxiety and post-traumatic stress (Goodman and Whitaker, 2002; Richardson et al., 2003). While the cardiovascular consequences in children are not well documented, it is within the context of the emerging obesity epidemic (Freedman et al., 1999; Ogden et al., 2008) in the United States in which the plausibility of accelerated and early cardiovascular disease in children arises, through the coupling of oxidative stress from outdoor air pollutant exposures and increased lipid deposition in early life (Ceriello and Motz, 2004; Griendling and FitzGerald, 2003; Heitzer et al., 2001). Indeed, DNA adducts have been identified as a marker of oxidative stress due to air pollution leading to cardiovascular diseases (Autrup et al., 1999; Risom et al., 2003). These same DNA adducts have been identified as elevated among highly exposed newborns born to mothers with increasing proximity to the WTC site (Perera et al., 2005). Although selection bias limits extrapolation, the high prevalence of new-onset GERD (29.1%), compared with 1.0% annual prevalence identified in one study (Sorof et al., 2001), raises the need to consider aerodigestive effects more carefully in this population.

In light of the potential clinical significance of accelerated and adverse pulmonary and cardiometabolic risks in WTC-exposed children, additional research is needed to ensure that longer-latency health conditions do not go unrecognized in this younger and vulnerable population. A comparable control group is needed to exclude other environmental triggers in NYC, high baseline rates due to poor disease management, and limited health care access, as potential confounders.

Finally, we note that this manuscript does not present analyses of depression, post-traumatic stress disorder (PTSD) and anxiety as potential risk factors. We note that a substantial literature indicates that PTSD is associated with increased allostatic load resulting in significant physical and psychological morbidity (Chemtob et al., 2008; Juster et al., 2010). Effects include increased cardiovascular reactivity, disturbed sleep physiology, obesity, autonomic hyperarousal, and altered hypothalamic–pituitary axis activity. Similarly, PTSD symptoms have been found to be associated with a significantly increased likelihood of asthma among 9/11 exposed adults. For example, a recent study examining twins found that those in the highest quartile of PTSD symptoms were 2.3 times as likely to have asthma compared with those in the lowest quartile, even taking into account familial/ genetic factors and other potential confounds (Goodwin et al., 2007).

Brackbill and his colleagues studied consequences of WTC exposure on new asthma case prevalence and also examined the prevalence of PTS symptoms (Brackbill et al., 2009). Among those with post 9/11 asthma, 36% had probable PTSD 5–6 years after the disaster. Although younger age was associated with increased vulnerability among children in the WTCHR (Thomas et al., 2008a), there appeared to be no relationship between event witnessing or PTSD symptoms and increased asthma. The association of younger age with vulnerability both to exposure-related asthma and PTSD suggests the importance of re-examining these associations among children and adolescents directly exposed to the WTC dust cloud. Clearly, such re-examination should include (1) better measures of child and adolescent exposure to trauma other than the WTC attacks, (2) assess exposure to stressful life events, and (3) measure actual diagnosis (nearly all prior studies used self-report) (Perlman et al., 2011).

The accurate assessment of exposure–outcome relationships is a critical challenge in this, as in all studies of WTC-exposed populations. Because the event was a disaster with few immediate studies and exposure assessments, personal exposure cannot be reconstructed completely. Modeling of the plume has provided some information (Stenchikov et al., 2006). Exposure categories as previously described (Thomas et al., 2008b) and analyses of acute/chronic exposures in area residents and workers (Friedman et al., 2011) may be useful in developing composite scales for children as well.

This cross-sectional, clinically-based study represents relatively brief follow-up in the context of chronic conditions with a longer latency, especially cardiometabolic outcomes. Thus, additional research is needed to ensure that longer-latency health conditions do not go unrecognized in this younger and vulnerable population. Although findings from this help-seeking clinic sample may not generalize to children exposed to the WTC disaster, our results confirm and extend previously-documented respiratory implications, and suggest possible aerodigestive and cardiovascular effects that require longitudinal study in a larger, more representative sample compared with a control group.