Daily global stress is associated with nocturnal asthma awakenings in school-age children

Abstract

Asthma guidelines use nocturnal awakenings to categorize asthma impairment. Even with daily controller therapy in a clinical trial, nocturnal asthma symptoms occurred in the absence of exacerbations and in up to 26% of children at least monthly.1Horner C.C. Mauger D. Strunk R.C. Graber N.J. Lemanske Jr., R.F. Sorkness C.A. et al.Most nocturnal asthma symptoms occur outside of exacerbations and associate with morbidity.J Allergy Clin Immunol. 2011; 128 (e1-2): 977-982Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar Because psychological stress is associated with the risk of asthma exacerbations in children2Sandberg S. Paton J.Y. Ahola S. McCann D.C. McGuinness D. Hillary C.R. et al.The role of acute and chronic stress in asthma attacks in children.Lancet. 2000; 356: 982-987Abstract Full Text Full Text PDF PubMed Scopus (347) Google Scholar and affects sleep quality,3Mezick E.J. Matthews K.A. Hall M. Kamarck T.W. Buysse D.J. Owens J.F. et al.Intra-individual variability in sleep duration and fragmentation: associations with stress.Psychoneuroendocrinology. 2009; 34: 1346-1354Abstract Full Text Full Text PDF PubMed Scopus (166) Google Scholar stress is a potential modifiable predisposing factor for nocturnal asthma symptoms. We hypothesized that acute child and caregiver stress would be associated with increased likelihood of nocturnal asthma symptom occurrence in school-age children. Nocturnal awakenings and measures of parental and child stress were assessed by Daily Diary Card (DDC). After development, pilot study, and revision, the DDC included 42 self-administered items (17 child, 9 caregiver, 16 caregiver with child input). Questions addressed nocturnal awakenings attributed to asthma and to other reasons. The perception of the child's daily global stress was indicated by response to the question “How was your day today?” (question 6 DDC; see Table E1 in this article's Online Repository at www.jacionline.org). Possible responses included very bad, bad, good, or very good and represent decreasing levels of daily global stress. The child circled facial representations of his or her emotions that day (questions 18-22 DDC) and of how specified daily events made him or her feel4Varni J.W. Rapoff M.A. Waldron S.A. Gragg R.A. Bernstein B.H. Lindsley C.B. Effects of perceived stress on pediatric chronic pain.J Behav Med. 1996; 19: 515-528Crossref PubMed Scopus (39) Google Scholar (questions 7-17 DDC). Morbidity measures, including albuterol use, school absence, doctor contacts, and prednisone use (questions 25-28 DDC), were recorded. Daily caregiver stress was assessed by questions about family, home, job/school, and financial demands5Bolger N. DeLongis A. Kessler R.C. Schilling E.A. Effects of daily stress on negative mood.J Pers Soc Psychol. 1989; 57: 808-818Crossref PubMed Google Scholar (questions 36-39 DDC). Child worry and anxiety was assessed at baseline with the T score from the Revised Child Manifest Anxiety Scale-26Reynolds C. Richmond B. Revised Children's Manifest Anxiety Scale, Second Edition (RCMAS-2). Western Psychological Service (WPS), Torrance, CA2008Google Scholar (for instruments and questions used, see this article's Online Repository at www.jacionline.org). Diary cards were completed daily by 46 caregiver-child pairs for a median of 12 weeks (range, 1-12 weeks). Children were 6 to 11 years old, had a physician diagnosis of persistent asthma for 1 or more year, reported 1 or more nocturnal asthma symptoms in the past 6 months, and slept in the same residence as their caregiver on 7 nights in a usual week. Exclusion criteria included other chronic lung disease, prematurity (<34 weeks' gestation), obstructive sleep apnea or sleep-disordered breathing, gastroesophageal reflex disease diagnosis or treatment, attention deficit/hyperactivity disorder or other psychiatric disorder, and psychostimulant or anticonvulsant medication use. This study was conducted in accordance with the institutional review board with written informed consent and assent. Descriptive statistics were performed for baseline characteristics. Comparisons of categorical variables used chi-square tests, and comparisons of continuous variables used Spearman correlation tests. Logistic regressions were also performed. All analyses were performed with SAS version 9.3 (SAS, Cary, NC). At enrollment, children were 8.9 ± 1.7 years old, with 52% being male, 61% white, and 28% Medicaid users (for baseline characteristics, see Table E1 in this article's Online Repository at www.jacionline.org). A total of 66% had baseline Childhood Asthma Control Test (C-ACT) score of more than 20. During the 12 weeks, 59% of the children had 1 or more awakenings from asthma; 80% of children had 1 or more awakenings for another reason besides asthma. Children who had 1 or more awakenings at night from asthma were younger (P = .028) and reported more frequent controller use (P = .038) than did children with no asthma awakenings. There were no significant associations between nocturnal asthma awakenings and sex, insurance, step therapy, baseline C-ACT score, allergic rhinitis diagnosis, or season of enrollment. Daily global stress was rated as very bad on 1.4% of days, bad on 4.2% of days, good on 46.3% of days, and very good on 48.1% of days; 39.1% of the children had 1 or more very bad days, 63.0% had 1 or more bad days, 97.8% had 1 or more good days, and 93.5% had 1 or more very good days. Awakening from asthma that night was similarly frequent after days rated as very bad, bad, or good, but awakening was significantly more likely after days rated as very bad, bad, or good compared with days rated as very good (odds ratio [OR], 2.2; 95% CI, 1.5-3.1) (Figs 1 and 2). This association remained significant when controlling for prednisone use that day (OR, 2.1; 95% CI, 1.5-3.1) or for albuterol use that day (OR, 1.8; 95% CI, 1.19-2.6). There was no association between child daily global stress and awakening for reasons besides asthma that night (P = .69).Fig 2Interrelationships between hypothesized associations; P values are shown for statistical associations between 2 measures connected by a line; for example, child daily global stress was significantly associated with nocturnal awakening from asthma, baseline worry and anxiety, and negative emotions that day. P values without other accompanying values are for χ2 tests. Solid lines represent associations with significant P values. Dotted lines represent associations with P values that are not significant.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Greater child-reported worry and anxiety was associated with higher percentages of days rated very bad (Spearman correlation = 0.48; P = .0025), days the child experienced negative emotions “a lot” (Spearman correlation = 0.61; P = .0011), and days that events made the child feel “very bad” (Spearman correlation = 0.83; P = .011). Although there was no daily measure that included all facets of anxiety, when children responded “today I was worried a lot,” they had a greater likelihood of rating their day as very bad (P < .0001). When children responded “today I was worried not at all,” they had a lower likelihood of rating their day as very good (P < .0001). Children were also more likely to report daily global stress as very bad when they experienced negative emotions “a lot” that day (P < .0001). There was no association between caregiver-reported stressful demands that day and child daily global stress that day (P = .47) or between caregiver-reported stressful demands that day and child awakening from asthma that night (P = .63). Days following awakenings from asthma contained more morbidity events, including daytime albuterol use, doctor contact, missed school day, and prednisone use (all P < .0001). There were no emergency department visits. The only child with hospitalization did not have asthma awakening the previous nights. The main study finding is that greater child-perceived daily global stress significantly increases the odds of an asthma awakening that night, but not of awakening for other reasons. Nights following days rated other than “very good” are more than twice as likely to have awakenings from asthma. This association persists when adjusting for daytime asthma symptom activity reflected by albuterol and prednisone use. Although previous studies have linked chronic stress and negative life events to subsequent asthma symptoms,2Sandberg S. Paton J.Y. Ahola S. McCann D.C. McGuinness D. Hillary C.R. et al.The role of acute and chronic stress in asthma attacks in children.Lancet. 2000; 356: 982-987Abstract Full Text Full Text PDF PubMed Scopus (347) Google Scholar, 7Wright R.J. Mitchell H. Visness C.M. Cohen S. Stout J. Evans R. et al.Community violence and asthma morbidity: the Inner-City Asthma Study.Am J Public Health. 2004; 94: 625-632Crossref PubMed Scopus (268) Google Scholar this study demonstrates a relationship between acute daily stress and proximate nocturnal awakenings. It is possible that corticotropin-releasing hormone (CRH) is released in response to acute stress. CRH outside the brain activates lung mast cells and causes mediator release and other pro-inflammatory effects.8Theoharides T.C. Enakuaa S. Sismanopoulos N. Asadi S. Papadimas E.C. Angelidou A. et al.Contribution of stress to asthma worsening through mast cell activation.Ann Allergy Asthma Immunol. 2012; 109: 14-19Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar This mast cell activation in combination with the circadian variation with lower lung function at night could lead to bronchoconstriction and obstruction that triggers awakening from asthma. CRH also activates the hypothalamic-pituitary-adrenal axis and stimulates cortisol release. Children with altered glucocorticoid receptors and inflammatory cells from chronic stress9Busse W.W. The brain and asthma: what are the linkages?.Chem Immunol Allergy. 2012; 98: 14-31Crossref PubMed Scopus (4) Google Scholar may have a heightened inflammatory response with acute stress as described. Surprisingly, our measures of caregiver stress were not associated with child daily global stress. It is unclear whether caregiver stressors in general do not influence children or whether other unmeasured stressors are more influential. Our baseline anxiety measure was associated with increased daily stress measures and indicates the possibility of identifying candidate children for stress-reduction intervention with a screening measure rather than daily diaries. The associated morbidity after asthma awakenings confirms our previous findings1Horner C.C. Mauger D. Strunk R.C. Graber N.J. Lemanske Jr., R.F. Sorkness C.A. et al.Most nocturnal asthma symptoms occur outside of exacerbations and associate with morbidity.J Allergy Clin Immunol. 2011; 128 (e1-2): 977-982Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar and provides additional clinical utility for addressing nocturnal awakenings outside of exacerbations. The limited observational design with a lack of control participants is appropriate for our proof-of-concept study. The lack of a criterion standard by which to measure daily stressors necessitated our utilization of a newly developed instrument. We used the child rating of his or her day as a surrogate measure of child daily global stress and a general measure of psychological perception of relative daily stress. We cannot specifically state what stressors contributed to or did not contribute to the formation of this perception. This measure correlated with the related measures of anxiety and negative emotions as a rough measure of construct-related validity. An additional limitation is that a child's understanding of questions about stress and anxiety may vary with the age of the child. The main statistical limitation was lack of adjustment for repeated measures based on small sample size. Replication in a larger prospective study is merited. Shortening the diary card to make it less labor-intensive, while maintaining the focus on daily global stress and asthma symptoms, might be more acceptable for use by families in a clinical setting. In conclusion, child-reported greater daily global stress was associated with increased likelihood of awakening from asthma that night but was not associated with awakening for a reason other than asthma. Further investigation is warranted into screening tools that can be used in clinical practice to identify children experiencing or being at risk for stressors related to nocturnal asthma symptoms. These data support the utility of developing and studying interventions that address reduction in acute stress to ultimately decrease nocturnal asthma symptoms and their associated morbidity. We developed the DDC specifically for this study. We formulated the novel questions in the DDC on the basis of available literature and with help from content leaders in the field. Sources of other questions include the validated Children's Hassles Scale (Varni et alE1Varni J.W. Rapoff M.A. Waldron S.A. Gragg R.A. Bernstein B.H. Lindsley C.B. Effects of perceived stress on pediatric chronic pain.J Behav Med. 1996; 19: 515-528Crossref PubMed Scopus (48) Google Scholar) and Children's Sleep Hygiene Scale (Wilson et alE2Wilson K.E. Lumeng J.C. Kaciroti N. Chen S.Y. LeBourgeois M.K. Chervin R.D. et al.Sleep Hygiene Practices and Bedtime Resistance in Low-Income Preschoolers: Does Temperament Matter?.Behav Sleep Med. 2015; 13: 412-423Crossref PubMed Scopus (30) Google Scholar) as well as a daily stress checklist (Bolger et alE3Bolger N. DeLongis A. Kessler R.C. Schilling E.A. Effects of daily stress on negative mood.J Pers Soc Psychol. 1989; 57: 808-818Crossref PubMed Scopus (708) Google Scholar). We obtained permission from the appropriate authors to use these instruments. We did not use the entire instruments and items were modified for use on our diary card. Please see Table E1 for details on the source of the question and who completed it over the study interval. Note that each question was used individually as opposed to grouping with other questions in most cases. The questions regarding caregiver stress (questions 36-39) were analyzed as a group. After the initial draft was developed, we conducted key informant interviews for diary card feedback. Then, cognitive laboratory interviews were conducted in a small group of caregivers and children to identify possible problems with the diary card. We then performed a pilot study for 4 weeks with 26 child/caregiver pairs. We assessed completion rate, understanding of individual diary card items, and ability to measure item variability. Analyses of item nonresponse rates and nondiscriminating questions, as well as content evaluation, were used for item reduction. We also conducted study personnel debriefings to collect personnel perceptions of diary card problems. We revised the diary card on the basis of these analyses and feedback from exit interviews. In the final study, the card was completed daily by both caregivers and children. Caregivers completed questions 1 to 6, 23, and 36 to 39. Children completed questions 6 to 22. Caregivers completed questions 24 to 35 with child input. At a baseline visit, caregivers completed the Night-time Asthma Questionnaire that we developed. The C-ACT (Liu et alE4Liu A.H. Zeiger R. Sorkness C. Mahr T. Ostrom N. Burgess S. et al.Development and cross-sectional validation of the Childhood Asthma Control Test.J Allergy Clin Immunol. 2007; 119: 817-825Abstract Full Text Full Text PDF PubMed Scopus (657) Google Scholar), a validated measure of asthma control over the past 4 weeks, was completed at baseline and at 4-week intervals. At baseline, the child also completed the Revised Child Manifest Anxiety Scale-2, a validated measure of anxiety that was purchased.Table E1Source of questions and who completed them during the studyDDC question no.How formulatedInspiring source validatedWho completed1-5Literature review/key informantNACaregiver6Literature review/key informantNAChild7-12, 14, 16, 17Adapted from Children's Hassles Scale∗Permission obtained from author.YChild13, 15Inspired by Children's Hassles Scale∗Permission obtained from author.YChild18-22Literature review/key informantNAChild23Literature review/key informantNACaregiver24-31Inspired by Childhood Asthma Research and Education Network questionnairesNCaregiver with child input32-35Adapted from Children's Sleep Hygiene Scale∗Permission obtained from author.YCaregiver with child input36-39Adapted from Bolger's Daily Stressors∗Permission obtained from author.NCaregiverN, No; NA, not applicable/available; Y, yes.∗ Permission obtained from author. Open table in a new tab Table E2Baseline characteristics of study participants (N = 46)CharacteristicValueCaregiver Relationship to child, % Mother93 Education, % Some college or higher80 Household annual income, % <$20,00020 Insurance, % Medicaid28 Room where sleeps relative to child, % Same11 Next room46 Down hall41Child Age (y), mean ± SD8.9 ± 1.7 Sex: male, %52 Race, % White61 Ethnicity, % Non-Hispanic98 C-ACT score Median (range)21 (6-27) % ≥20 (well controlled)66 Diary card weeks completed, median (range)12 (1-12) Revised Childhood Manifest Anxiety Scale 2∗A total of 96% fell within the categories of “less problematic than for most students (≤39)” and “no more problematic than for most students (score, 40-60).” T score, median (range)44.5 (29-62) Biological parent with asthma, %52 Other allergic disease diagnosis, % Nasal allergies57 Food allergies20 Step therapy, % Step 235 Step 333 Step 426 Step 52∗ A total of 96% fell within the categories of “less problematic than for most students (≤39)” and “no more problematic than for most students (score, 40-60).” Open table in a new tab N, No; NA, not applicable/available; Y, yes.