Socioeconomic status associated with exhaled nitric oxide responses to acute stress in children with asthma

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Abstract

Although psychosocial stress has been linked to clinical asthma outcomes, controlled, laboratory paradigms that test associations between psychosocial stress and markers of airway inflammation in humans are lacking. There is also little known about how individual background characteristics may affect variability across individuals in asthma-relevant inflammatory and pulmonary responses to stress. The goals of this study were to investigate the effects of a laboratory stress paradigm on markers of airway inflammation and pulmonary function in children with asthma, and to determine why some children are more biologically responsive to stress. 38 children physician-diagnosed with asthma, and 23 healthy control children (M age = 15 years) engaged in a conflict discussion task with a parent. Pulmonary function (FEV1) was measured before and immediately after the task. Airway inflammation (indicated by exhaled nitric oxide, FeNO) was measured before and 45 min after the task (to minimize effects from spirometry). Parents were interviewed about family socioeconomic status (SES: income and occupation). In children with asthma only, there was an inverse association of SES with change in FeNO levels in response to the conflict task, meaning that as SES declined, greater increases in FeNO were observed No changes in FEV1 were found in response to the conflict task. This study suggests that lower SES children with asthma may be more vulnerable to heightened airway inflammation in response to stress.

Introduction

Stress has long been thought to contribute to a number of diseases, including asthma. Clinical evidence supports this hypothesis. For example, experiencing an acute negative life event (e.g., death of a close family member) in the context of chronic stress increased the risk of a subsequent asthma attack in children by nearly 3-fold (Sandberg et al., 2000). Parental stress also has been linked to more frequent symptoms, poorer daily functioning, and greater health care service utilization in children with asthma (Shalowitz et al., 2001, Weil et al., 1999).

Researchers have attempted to understand the biological mechanisms underlying these effects by studying real-world stress. For example, stressors such as school exams are associated with greater mobilization of eosinophils into sputum and blood following allergen challenge, greater in vitro production of the Th-2 cytokine IL-5 in patients with asthma, and a decreased Th-1/Th-2 ratio of cytokine production in atopic individuals (Hoglund et al., 2006, Kang et al., 1997, Liu et al., 2002). Children whose caregivers report high levels of stress have greater stimulated production of the pro-inflammatory cytokine TNF-a, as well as reduced production of the Th-1 cytokine IFN-γ (Wright et al., 2004). In addition, stressful experiences such as exposure to violence and parental conflict have been associated with decreased pulmonary function (Suglia et al., 2008). Furthermore, the relationship between daily stress and pulmonary function has been found to be mediated by airway inflammation (Kullowatz et al., 2008).

While these studies are clearly informative, there remain limitations to the conclusions that can be drawn. First, the naturalistic setting, while closer to the real-world, can make alternative confounding explanations difficult to rule out. Second, variability in stress responsiveness across individuals with asthma remains less well-understood. For example, we know that social group characteristics, such as low socioeconomic status (SES), are associated with increased inflammatory signaling, as marked by higher levels of C reactive protein and IL-6, and greater stimulated production of Th-2 cytokines (Chen et al., 2003, Chen et al., 2006, Hemingway et al., 2003, Panagiotakos et al., 2005). SES refers to an individual’s position within a social hierarchy, and can be defined both in terms of the social prestige ascribed to an individual, as well as in terms of the material resources an individual possesses, with both having been associated with health outcomes (Adler et al., 1993, Krieger et al., 1997). Hence social group characteristics such as SES may also determine variability in inflammatory responses in the context of asthma.

In asthma, the fractional concentration of exhaled nitric oxide (FeNO) is a non-invasive marker related to airway inflammation. FeNO is elevated in children with asthma (Kovesi and Dales, 2008, Pijnenburg and de, 2008, Strunk et al., 2003). FeNO levels are related to asthmatic airway inflammation indicated by bronchial wall inflammation (Payne et al., 2001), sputum eosinophilia (Jatakanon et al., 1998), and airway hyper-responsiveness (Strunk et al., 2003). FeNO levels increase as asthma control deteriorates (Jones et al., 2001), and decrease when treatment reduces airway inflammation (Beck-Ripp et al., 2002, Bratton et al., 1999, Kharitonov et al., 2002, Montuschi et al., 2007, Sorkness et al., 2007, Straub et al., 2005a, Straub et al., 2005b).

The present study had two goals: (1) to document the effects of a standardized stressor on markers of airway inflammation (as reflected by FeNO) and pulmonary function in children with asthma vs. healthy children; and (2) to understand which background characteristics may account for variability in FeNO or pulmonary function changes in response to stress. Based on previous research reviewed above, we hypothesized that SES would be associated with changes in pulmonary function and FeNO following an acute laboratory stressor, such that as SES declined, pulmonary function would be reduced and FeNO would increase in children with asthma.

Section snippets

Participants

Thirty-eight children physician-diagnosed with asthma and 23 healthy control children were recruited from Vancouver, BC. Children ranged in age from 10–20 years, were fluent in English, free of acute respiratory illness, had not received prednisone for at least 2 weeks, and had no other chronic illnesses (other than asthma). Asthma severity was determined from the NAEPP/EPR2 Guidelines based on symptoms and medication use, paralleling the approach of previous researchers (Bacharier et al., 2004).

Participant characteristics

Children with asthma and healthy children did not differ in terms of age, sex, or ethnicity (all ps > 0.15). Children with asthma had a range of severity (13% mild intermittent, 45% mild persistent, 29% moderate, 13% severe), and 71% were currently being prescribed inhaled corticosteroid medication. Further details on the characteristics of this sample can be found in Table 1.

There was a main effect of group on FEV1%, such that children with asthma had lower FEV1 % predicted both at baseline and

Discussion

This is the first study that we are aware of to use a laboratory stress paradigm to investigate changes in a marker of airway inflammation (FeNO) in children with asthma. It is also the first to document inverse associations of SES with FeNO change in children with asthma, such that lower SES children showed greater increases in FeNO, whereas higher SES children showed greater decreases in FeNO, after a conflict task with their parents. In contrast, healthy children did not show these patterns.

Conflict of interest

All authors declare that there are no conflicts of interest.

Acknowledgment

This study was supported by NIH grant HL073975 and the William T. Grant Foundation.

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